Title of Invention	DIHYDRO-BENZO [b] [1, 4] DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II
Abstract	This invention is concerned with dihydro-benzo[b] [l,4]diazepin-2-one derivatives of the general formula wherein R1, R2, R3, X and Y are as defined in the specification. The invention further relates to medicaments containing these compounds, a process for their preparation as well as their use for preparation of medicaments for the treatment or prevention of acute and/or chronic neurological disorders.

Title of Invention

DIHYDRO-BENZO [b] [1, 4] DIAZEPIN-2-ONE DERIVATIVES AS MGLUR2 ANTAGONISTS II

Abstract

This invention is concerned with dihydro-benzo[b] [l,4]diazepin-2-one derivatives of the general formula wherein R1, R2, R3, X and Y are as defined in the specification. The invention further relates to medicaments containing these compounds, a process for their preparation as well as their use for preparation of medicaments for the treatment or prevention of acute and/or chronic neurological disorders.

Full Text	Case 20871 Dihydro-benzo[b] [l,4]diazepin-2-one derivatives as mGluR2 antagonists II The present invention relates to compounds of general formula I selected from the group consisting of halogen, lower alkyl, fluoro-lower alkyl, C3-C6-cycloalkyl, lower alkoxy and fluoro-lower alkoxy; R2 is -NR'R-, fluoro4ower alkoxy or S-oxo-piperazin-l-yl, pyrrolidin-l-yl or piperidm-l-}d, which rings are optionally substituted by R-; R' is hydrogen, lower alkyl, C3-C6-cycloalkyl, fluoro-lower alkyl or 2-lower alkoxy lower alkyl; R- is hydrogen, lower alkyl, and to their pharmaceutically acceptable addition salts. It has surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists. Compounds of formula I are distinguished by valuable therapeutic properties. In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, which is sent out by a neuron, with a neuroreceptor. . L-glutamic acid, the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms hgand-controUed ion channels. The metabotropic glutamate receptors (mGluR) form the second main group and, furthermore, belong to the family of G-protein-coupled receptors. At present, eight different members of these mGluR are known and of these some even have sub-types. On the basis of structural parameters, the different influences on the synthesis of secondary metabolites and the different affinity to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGluRl and mGluRS belong to group I, mGluR2 and mGluR3 belong to group II and mGluR4, mGluR6, mGluR7 and mGluRS belong to group III. Ligands of metabotropic glutamate receptors belonging to the group II can be used for the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications in this connection are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are chronic and acute pain, Himtington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutarnate-defidency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, opiate addiction, anxiety, vomiting, dyskinesia and depressions. Objects of the present invention are compounds of formula I and their pharmaceutically acceptable salts per se and as pharmaceutically active substances, their manufacture, medicaments based on a compound in accordance with the invention and their production, as well as the use of the compounds in accordance with the invention in the control or prevention of illnesses of the aforementioned kind, and, respectively, for the production of corresponding medicaments. The compounds of formula I can also be used in form of their prodrugs. Examples are esters, N-oxides, phosphate esters, glycoamide esters, glyceride conjugates and the like. The prodrugs may add to the value of the present compounds advantages in absorption, pharmacokinetics in distribution and transport to the brain. All tautomeric forms of the compounds of the invention are also embraced herewith. Preferred are compounds of formula I, wherein X is a single bond. Exemplarly preferred are compovmds, wherein R^ is trifluoromethyl, and especially those wherein R is cyano, for example the following compounds: 4-(4-oxo-8-pyTrolidin-l-yl-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-pyridine-2-carbonitrile, 4-[8-(cyclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ l,4]diazepin-2-yl] -pyridine-2-carbonitrile, 4-[8-(cyclopropylmethyl-amino)-4-oxo-7-trifiuoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl]-pyridine-2-carbonitrile, 4-[4-oxo-8-(2,2,2-trifluoro-ethoxy)-7-trifluoromethyI-4,5-dihydro-3H-ben2o[b] [l,4]diazepin-2-yl]-pyridine-2-carbonitrile, and 4-[8-(isopropyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ 1,4] diazepin-2-yl] -pyridine-2-carbonitrile. Further preferred are compounds, wherein X is a single bond, R^ is trifluoromethyl and R is an optionally substituted five-membered aromatic heterocyde, which may be substituted by halogen, fluoro-lower alkyl, fluoro-lower alkoxy, cyano, -(CH2)n-NR'R-, -(CH2)n-C(O)-0R-, -(CH2)n-C(O).NR'R-, .(CH2)n-S02-NR'R-, -(CH2)„-C(NH2)=NR-, hydroxy, lower alkoxy, lower alkyithio, or by lower alkyl, which is optionally substituted by fluoro, hydroxy, lower alkoxy, cyano or carbamoyloxy. Examples of such compounds are the following: 7-dimethylamino-4-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimethylaimnO-4-[3-(2-metiiyl-2H-pyra2ol-3-yl)-phenyi]-8-tri dihydro-benzo [b] [ 1,4] diazepin-2-one, 7-dimethylamino-4-(3-imidazol-1 -yl-p}ienyl)-8-trifluoromethyl- 1,3-dihydro- benzo[b] [l,4]diazepin-2-one, 4-[3-(3-methyHsoxa2ol-5-yl)-phenyl]-7-(methyl-propyl-ainino)-8-trifluoromethyl-1,3-dLhydro-benzo [b] [ 1,4] diazepin-2-one, 7-(isobutyl-methyl-amino)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-8-trifluorom l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-(isopropyl-inethyl-ainmo)-4- [3-(3-methyl-isoxa2ol-5-yl)-phenyl] -8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-(isobu1yl-methyl-amino)-4-(3-{5-[(isopropyl-methyI-ainino)-inethyl]- [ 1,2,3] triazol-1-yl}-phenyl)-8-trifluoromethyl-l,3-dihydro-ben2o [b] [ 1,4] diazepin-2- one, 7-(isopropyl-methyl-amino}-4-[3-(5-pyrroKdin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl] -8-txifluorometliyl-l,3-dihydro-benzo [b] [1,4] diazepin-2-one, 7-(methyl-propyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-8-trifluoromethyl-l,3 dihydro-benzo[b][l,4]diazepin-2-one, 7-(isobutyl-methyl-amino)-4-(3-[l,2,3]tria2ol-l-yl-phenyl)-8-trifluoromethyl-1,3 dihydro-benzo [b] [ l,4]diazepin-2-one, 4-(3-imidazol-l-yl-phenyl)-7-isobutylaniino-8-trifluoroinethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimeliiylaiiuno-4-[3-(4-hydroxymethyl-liiiazol-2-yl)-phenyl]-8-trifluoronieA^ l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-dimethylamino-4-[3-(4-hydroxyniethyl-Oxazol-2-yl)-phenyl]-8-1xifluoronieli^ l,3-dihydxo-ben2o[b] [1,4] diazepin-2-one, 4-[3-(4-hydroxynxethyl-thiazol-2-yl)-phenyl]-7-(niethyl-propyl-anriino)-8-trifluoroniethyl-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one, and 4-[3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-phenyl]-7-(niethyl-propyI-aniino) trifluoromethyl-1,3-dihydro-ben2o [b] [ 1,4] diazepin-2-one. Also preferred are compounds, wherein X is a single bond, and R is chloro, tor example the following compounds: 8-diloro-7-isobutyla,in-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro- ben2o[b] [l,4]diazepin-2-one, 8-cUoro-7-(methyl-propyl-amino)-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydrO-benzo[b] [l,4]diazepin-2-one, 8-chloro-7-(isopropyl-methyl-amino)-4-[3-(5-pyrrolidin«l-ylmethyI-[l,2,3]triazoI-l-yl)-phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one, 8-cHoro-7-(isobutyl-methyl-amino)-4-[3-(5-pyrroHdin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one, 8-chloro-4-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-8-chloro-7-(isopropyl-methyl-amino)-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one, 4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazl-yl)-phenyl]-8-chloro-7-(isobutyl-methyi-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 8-chloro-7-(isobutyl-methyI-amino)-4-[3-(5-piperidin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one, 8-chlorO-7-(isopropyl-methyl-amino)-4-(3-{5-[(isopropyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-13-dihydro-benzo[b][l,4]diazepin-2-one, 8-chloro-4-(3-{5-[(isobutyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-7-(isopropyl-methyl-amino)- 1,3-dihydro-benzo [b] [1,4] diazepin-2-one, 8-chloro-7-isopropylamino-4-[3-(3-methyl-isoxazol-5-yl)-phenyi]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 8-chloro-7-(isobutyl-methyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 8-chIoro-4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-1,3-dihydro-benzo [b] 11,4] diazepin-2-one, 8-chloro-7-(ethyl-methyl-amino)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one 8-chloro-4-[3-(4-hydroxymethyi-thiazol-2-yl)-phenyl]-7-(methyl-propyl-amino)-13-dihydro-benzo[b]l [l,4ldiazepin-2-one 7-(ethyl-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimethylamino-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-(isobutyi-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one> 7-(isobutyl-methyl-amino)-8-methyi-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, and 4-(3-{5-[(cyclopropylmethyl-amino)-methyI]-[l,2,3]triazol-l-yl}-phenyl)-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one. Preferred are further compounds, wherein R is -N(CH3)2 or pyrrolidine. Also preferred are compounds, wherein R2 is isopropyl-amino, isopropyl-methyl-amino, isobutyl-amino or isobutyl-methyl-amino. Preferred compounds of formula I in the scope of the present invention are further those, wherein R is cyano or an optionally substituted five-membered aromatic heterocycle, which may be substituted by -CH2OH or -CH2N(CH3)2. The term -lower alkyl- used in the present description denotes straight-chain or branched saturated hydrocarbon residues with 1-7 carbon atoms, preferably with 1-4 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl and the like. The term 'lower alkoxy- denotes a lower alkyl residue in the sense of the foregoing definition bound via an oxygen atom. Examples of'lower alkoxy- residues include methoxy, ethoxy, isopropoxy and the like. The term -halogen- embraces fluorine, chlorine, bromine and iodine. The term -fluoro-lower alkyl- means a lower alkyl residue, wherein one or more hydrogen-atoms may be replaced by fluoro. The term -fluoro-lower alkoxy- denotes a lower alkoxy residue in the sense of the definition herein before, wherein one or more hydrogen-atoms may be replaced by fluoro. The term -C3-C6-cycloalkyl- means a cycloalkyl group containing 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The term -lower alkylthio- denotes a lower alkyi residue in the sense of the foregoing definition bound via an sulfur atom, for example methylsulfanyl. The expression -five-membered aromatic heteroqrde' embraces fiirane, thiophene, thiazole, pyrrole, imidazole, pyrazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole and tetrazole. Preferred heterocycles are 1,2,3-triazole, 1,2,4-triazole, isoxazole, l,3-oxa2ole, 1,3-thiazole, 1,3,4-oxadiazole or imidazole, -Optionally substituted- means that a group may or may not be substituted with one or more, preferably one or two substituents independently selected from the specified group. The term -pharmaceutically acceptable addition salt- refers to any salt derived from an inorganic or organic acid or base. The compounds of general formula I and their pharmaceutically acceptable salts can be manufactured according to methods, which process comprises a) reacting a compound of formula II which subsequently undergoes deprotection of the amino group and cyclization, to obtain a compound of formula 1 According to scheme A, compounds of general formula I, in which X, Y, R1 R2 and R3 are as described above, can be prepared from compounds of general formula II via an acyiation-deprotection-cyclization sequence; For example reacting compounds of general formula II with a dioxinone IV, in which Y and R3 are as described above> in an inert solvent such as toluene or xylene at elevated temperatures, preferably between 80 °C and 160 °C gives rise to compounds of general formula III. Alternatively, compounds of general formula III can also be prepared by for example reaction of a compound of general formula II with a p-ketoester (general formula rVa), in which Y and R^ are as described above using the same conditions as described for the reaction with the dioxinones. Afterwards, deaving the BOC protecting group in compounds of general formula III and concomitant cydization of the deprotected compound yidds the desired compounds of general formula I. Any other suitable amino protecting group, such as e.g- Fmoc or benzyloxycarbonyl (Z), can be altemativdy used instead of the BOC group. The deprotection-cyclization step can be carried out by treating the compounds of general formula III with for example a Bronsted add such as trifluoroacetic add in an inert solvent such as dichloromethane (DCM). The reaction is preferably carried out at temperatures between 0°C and 50 °C- It may be advantageous to use also anisole or 1,3-dimethoxybenzene as a carbocation scavenger in the reaction mixture. According to scheme B, compounds of general formula 11 in which R^ is phenyl optionally substituted as described above for compounds where X is a single bond and R is as described above, can be prepared by different routes depending on the nature of R3 from the iodo-compounds of general formula V, in which R3 is as described above. As shown in scheme B, the key step is a coupling reaction of Suzuki-type to produce compounds of the general formula Via. Compounds of general formula II, in which R1, R3 and X are as described above can be prepared according to scheme B, by reducing the nitro group in compounds of general formula Via to the amino group. The reduction can for example be carried out using hydrogen gas in presence of a suitable catalyst like for example Raney-Nickel or Palladium on carbon. Another possible reduction method is using stannous (II) chloride (SnCl2-2H2O) in ethanol at temperatures between 70 --C and 80 °C (as described in Tetrahedron Lett, 1984,25,839), or alternatively in polar aprotic solvents, like DMF, DMA or NMP and the like, optionally in the presence of bases, like for example pyridine or triethylamine and the like, at temperatures between 0°C and 80 °C. Another suitable method is using zinc-powder in the presence of ammonium chloride in protic solvents like for example water or ethanol at temperatures between 20 °C and 80 °C. The exact conditions for the respective compounds of general formula II can be found in the experimental part. Compounds of general formula V, in which R1 is as described above, can be prepared by different routes depending on the individual residue R2: As shown in scheme C, compound Bl can be prepared from the commercially available 5-chloro-2-nitroaniline by iodination to give the synthetic intermediate Al, which in turn can be protected to yield the compound BL The iodination step can be carried out by for example using iodine monochloride in acetic acid in the presence of sodium acetate. The reaction can be for example carried out at temperatures between 20°C and 80 °C. The protection of the amino function can be applied to a number of commercially available starting materials or compounds synthesized by anyone skilled in the art to produce the corresponding 2-nitroanilines with the general formula VII, in which X is a single bond and R1 is as described above. This transformation leads to the key intermediates of the general formula VIb, and the exact conditions for the respective compounds used in this invention can be foimd in the experimental part. ) One possibility for the protection of the amino function is for example reacting compounds of general formula VII with di-tert-butyl-carbonate in the presence of a base such as cesium carbonate. The reaction can be carried out in polar solvents such as acetone or butanone and the like at temperatures between 20 °C and 60 °C. Alternatively, the protection of the amino group can be achieved by preparing the intermediate isocyanate by treatment of compoimds of the general formula VII with diphosgene, preferably in aprotic solvents such as ethyl acetate or 1,4-dioxane at temperatures from 0 °C to 100 °C, and subsequent treatment of the isocyanate with tert. butanol in solvents such as dichloromethane or 1,2-dichloroethane and the like at temperatures between 20 °C and 85 °C to give the desired compoimds of general formula Vlb. Another suitable method to achieve this protection step is the intermediate formation of a di-BOC compound by treatment of compounds of the general formula VII with di-tert.-butyl-carbonate in the presence of DMAP in an aprotic solvent such as tetrahydrofuran and the like, followed by selective removal of a single BOC-group by treatment with a Bronsted-acid, like e.g. TFA, in aprotic solvents such as dichloromethane, chloroform or 1,2-dichloroethane at temperatures between 0 °C and 20 °C to give the desired compounds of general formula VIb. According to scheme D, compounds of general formula VII in which R1 is pyrrol- 1-yl optionally substituted as described above, X is a single bond and R is chloride, can be prepared from known 5-chloro-2-nitro-l,4-phenylenediamine [CAS-No. 26196-45-2] by selective condensation of the 4-amino-group with a suitable substituted 2,5-dimethoxytetrahydrofuran with the general formula VIII, as described in/. Heterocycl Chem, 1988,25,1003. The reaction is preferably carried out in acidic media, like for example acetic acid or propionic add and the like, at temperatures between 40 °C to 100 °C. The exact conditions for the respective compounds can be found in the experimental part The corresponding substituted 2,5-dimethoxytetrahydrofurans -with the general formula VIII, in which Ra, Rb and Rc are as described above in the general claim for the pyrrol-1-yl compounds, are either commercially available, or synthesized from the suitable substituted furan, as shown in scheme E. The corresponding substituents can optionally be protected with suitable protecting groups, known to someone skilled in the art, or alternatively can be introduced after the pyrrol ring synthesis. The two-step sequence consists of reacting the furan with bromine in MeOH at low temperature, like for example -35 '°C, followed by treatment with base, like for example triethylamine and the like or potassium carbonate or sodium hydrogen carbonate and the like. The resulting 2,5-dimethoxydihydrofuran with the general formula VIII, in which Ra, Rb and Rc are as described above, can be reduced by catalytic hydrogenation, preferably in MeOH with catalysts like for example Palladium on carbon or Raney-Nickel and the like, to produce the desired 2,5-dimethoxytetrahydrofurans with the general formula VIII. An example for this sequence can be found in Tetrahedron 1971,27, 1973-1996. The exact conditions for the individual compounds to be synthesized can be found in the experimental part. As shown in scheme F, compounds of general formula VIc, in which R2 is attached via a nitrogen-atom and is as described above, can be prepared from the intermediate compounds with the general formula VIb - which individual synthesis can be found in the experimental part - by a nucleophilic substitution reaction with the respective amines in the presence of a suitable base. The reaction is preferably carried out in a polar, aprotic solvent such as dimethyl formamide, N-methyl-pyrrolidone or dimethyl sulfoxide and the like. The base can be selected from the sterically hindered amines such as triethylamine or Hiinig's base, alkoxides such as sodium methoxide and tert.-butoxide, or hydrides such as sodium hydride. The reaction can be performed at temperatures between 20 C and 110 ^C, depending on the individual compounds to be synthesized. According to scheme G> compounds of general formula II in which R^ is as described above for compounds where X is an ethynediyl group can be prepared by different routes from the iodo-compounds V, depending on the nature of R and R As shown in scheme G, the transformation can for example be carried out a) by directly attaching the R1-alkynediyl-substituent to a compound of general formula V via a Sonogashira-type coupling to produce compounds of the general formula VId followed by the reduction of the nitro group or b) by two stepwise Sonogashira-type couplings, in which first trimethylsilyi-acetylene is coupled to a compound of general formula V to yield, after desilylation with sodium hydroxide in methanol, the intermediate X which then can be transformed via a second Sonogashira-type coupling with the appropriate reactant R1-I, R1-Br or R1-OSO2CF3 into compounds of the general formula VId and reduction of the nitro group leads to the desired compounds of general formula IL The exact conditions for the respective compounds can be found in the experimental part. According to Scheme H, the dioxinones and 6-keto esters building blocks with the general formula TV and IVa can be prepared by methods known to someone skilled in the art from the corresponding carboxylic acid derivatives R -COR, i.e. free acids, methyl or ethyl esters and acid chlorides. The exact conditions for the corresponding compounds can be found in the experimental part. The pharmaceutically acceptable salts can be manufactured readily according to methods known per se and taking into consideration the nature of the compound to be converted into a salt. Inorganic or organic adds such as, for example, hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid or citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric add, methanesulphonic add, p-toluenesulphonic add and the like are suitable for the formation of pharmaceutically acceptable salts of basic compounds of formula I. The compounds of formula I and their pharmaceutically acceptable salts are metabotropic glutamate receptor antagonists and can be used for the treatment or prevention of acute and/or chronic neurological disorders, such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are acute and chronic pain, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate-deficient functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, dyskinesia and depression. The compounds of formula I and pharmaceutically acceptable salts thereof can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, the administration can also be effected rectally, e.g. in the form of suppositories, or parenterally, e.g. in the form of injection solutions. The compounds of formula I and pharmaceutically acceptable salts thereof can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical preparations. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like; depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules- Suitable carriers for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose and the like. Adjuvants, such as alcohols, polyols, glycerol, vegetable oils and the like, can be used for aqueous injection solutions of water-soluble salts of compounds of formula I, but as a rule are not necessary. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like. In addition, the pharmaceutical preparations can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. As mentioned earlier, medicaments containing a compound of formula I or a pharmaceutically acceptable salt thereof and a therapeutically inert excipient are also an object of the present invention, as is a process for the production of such medicaments which comprises bringing one or more compounds of formda I or pharmaceutically acceptable salts thereof and, if desired, one or more other therapeutically valuable substances into a galenical dosage form together with one or more therapeutically inert carriers. The dosage can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, the effective dosage for oral or parenteral administration is between 0.01-20 mg/kg/day, with a dosage of 0.1-10 mg/ kg/day being preferred for all of the indications described. The daily dosage for an adult human being weighing 70 kg accordingly lies between 0.7-1400 mg per day, preferably between 7 and 700 mg per day. The present invention relates also to the use of compounds of formula I and of pharmaceutically acceptable salts thereof for the production of medicaments, especially for the control or prevention of acute and/or chronic neurological disorders of the aforementioned kind. The compounds of the present invention are group II mGlu receptor antagonists. The compounds show activities, as measured in the assay described below, of 10μM or less, typically 1μM or less, and ideally of 0.3μM or less. In the table below are described some specific Ki values of preferred compounds. Transfection and cell culture cDNA encoding the rat mGlu2 receptor protein in pBluescript II was obtained from Prof. S. Nakanishi (Kyoto, Japan), and subcloned into the eukaryotic expression vector pcDNA I-amp from Invitrogen (NV Leek, The Netherlands). This vector construct (pcDlmGR2) was co-transfected with a psvNeo plasmid encoding the gene for neomycin resistance, into CHO cells by a modified calcium phosphate method described by Chen & Okayama (1988), The cells were maintained in Dulbecco's Modified Eagle medium with reduced L-glutamine (2 -mM final concentration) and 10 % dialysed foetal calf serum from Gibco BRL (Basel, Switzerland). Selection was made in the presence of G-418 (1000 ug/ml final). Clones were identified by reverse transcription of 5 μg total RNA, followed by PCR using mGlu2 receptor specific primers 5'-atcactgcttgggtttctggcactg-3' and 5'-agcatcactgtgggtggcataggagc-3' in 60 mM Tris HCl (pH 10), 15 mM (NH4)2SO4,2 mM MgCl2, 25 units/nil Taq Polymerase with 30 cycles annealing at 60 oC for 1 min., extention at 72 °C for 30 s, and 1 min. 95 °C denaturation. Membrane preparation Cells, cultured as above, were harvested and washed three times with cold PBS and frozen at -80 °C. The pellet was resuspended in cold 20 mM HEPES-NaOH buffer containing 10 mM EDTA (pH 7.4), and homogenised with a polytron (Kinematica, AG, Littau, Switzerland) for 10 s at 10 000 rpm. After centrifugation for 30 min. at 4 °C, the pellet was washed once with the same buffer, and once with cold 20 mM HEPES-NaOH buffer containing 0.1 mM EDTA, (pH 7.4). Protein content was measured using the Pierce method (Socochim, Lausanne, Switzerland) using bovine serum albumin as standard. [3H]'LY354740 binding After thawing, the membranes were resuspended in cold 50mM Tris-HCl buffer containing 2 mM MgClo and 2 mM CaCl2, (pH 7) (binding buffer). The final concentration of the membranes in the assays was 25°Cg protein/ml. Inhibition experiments were performed with membranes incubated with 10 nM [3H]-LY354740 at room temperature, for 1 hour, in presence of various concentrations of the compound to be tested. Following the incubations, membranes were filtered onto Whatmann GF/C glass fiber filters and washed 5 times with cold binding buffer. Non specific binding was measured in the presence of 10°CM DCG IV. After transfer of the filters into plastic vials containing 10 ml of Ultima-gold scintillation fluid (Packard, Zurich, Switzerland), the radioactivity was measured by liquid scintillation in a Tri-Carb 2500 TR counter (Packard, Zurich, Switzerland), Data analysis. The inhibition curves were fitted with a four parameter logistic equation giving K1 values, and Hill coefficients. EXAMPLES General procedure A Preparation of 4-iodo-2-nitroanilines by iodination of 2-nitroanilines [according to Wilson, J. Gerald; Hunt, Frederick C Aust /, Chem. 1983,36^ 2317-25] To a stirred solution of the Z-nitroanilinc (LO mol) in HOAc (500 mL) containing anhydrous NaOAc (93-103 g, 1.125-1.25 mol), iodine monochloride (59-66 mL, 1.125-1.25 mol) in HOAc (300 mL) was added over 60 min. The reaction mixture was heated to the given temperature until thin layer chromatography (tic) indicated complete conversion of the starting material, stirred for another 30 min at 23 oC, then diluted slowly with H2O (1000 mL) which caused the separation of the crystalline product. Stirring was continued for 1 h and the product was filtered off, washed free of HOAc and dried in vacuum at 60 oC. Example A1 5-Chloro-4-iodo-2-nitro-phenylamine The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80oC). Obtained as an orange solid. MS (EI) 298 (M^) and 300 [(M-f2)^]; mp 202-203 C (dec). General procedure B: Preparation of ('2-nitro-phenvl)-carbamic acid tert.-butyl esters from 2-nitroanilines Method a (from 2-nitroanilines): To a solution of diphosgene (4.1 mL, 34,1 mmol) in EtOAc (40 mL) at 0 °C was added a solution of the 2-nitroaniline (45.5 mmol) in EtOAc (200-500 mL), and the mixture was heated to reflux for 18 h. The solvent was removed in vacuum to leave a brown solid, which was triturated with hot hexane (200 mL). The solid material was filtered off and the filtrate was concentrated xmder reduced pressure to leave the pure 2-nitrophenylisocyanate as a yellow soild This material was refluxed in a mixture of excess terL-BuOH in CH2CI2 for 2.5 h. Removal of the solvent left an orange solid which was pmified by silica gel colunm chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbainic acid tert-butyl ester as a yellow solid Method b (from 2-nitroanilines): To a mixture of the 2-nitroaniline (142 mmol) and cesium carbonate (55.5 g, 170 mmol) in 2-butanone (740 mL) was dropwise added a solution of BOC2O (37.8 g, 173 mmol) in 2-butanone (170 mL) and the resulting mixture was stirred at 50 ^C to 80 *C until tic indicated complete conversion. The solvent was removed in vacuxun, the residue was treated with a mixture of H2O (240 mL) and MeOH (240 mL) and extracted with hexane (3 x 500 mL). The combined hexane layer was washed with brine (200 mL) and all aqueous layers were reextracted with hexane (300 mL). All combined hexane layers were dried over MgSO4, filtered and the solvent was removed in vacuum to give an orange solid, which was purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid. Method c (fi-om 2'nitroanilines): To a solution of the 2-nitroaniline (550 mmol) and DMAP (1.22 g, 10 mmol) in THF (1000 mL) at 23 °C was dropwise added within 70 min a solution of Boc2O (246 g, 1128 mmol) in THF (500 mL) and stirring was continued at 23 °C for 75 min. The entire mixture was evaporated to dryness and dried at HV to leave a dark brown solid. This material was dissolved in DCM (1100 mL), cooled to 0 --C and TFA (84 mL, 1100 mmol) was added dropwise. The mixture was stirred at 0 °C for 2 h2 poured into icecold sat. NaHCO3-sol, extracted with DCM, washed with brine and dried over MgSO4. Removal of the solvent in vacuum left a dark brown solid which was coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid. Method d (firom 2'nitroacetanilides): To a solution of the 2-nitroacetanilide (100 mmol) and DMAP (122 mg, 1mmaol) in THF (100 mL) at 23 X was dropwise added within 15 min a solution of B0C2O (22.92 g, 105 mmol) in THF (100 mL) and stirring was continued at 23 oC until tic indicated completed conversion. The entire mixture was evaporated to dryness and dried at HV to leave a yellow to dark brown solid. This material was dissolved in THF (200 mL) and 25 % NH4OH (77 mL, 500 mmol) was added dropwise. The mixture was stirred at 23 oC until tic indicated complete conversion, poured into IN HCl-sol, extracted with EtOAc, washed the organic layer with sat. NaHC03-soL and brine, dried over MgSO4. Removal of the solvent in vacuum left an yellow to brown solid which was generally pure enough for fiirther transformation or - if necessary - coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert-butyl ester as a yellow solid. Example Bl f 5-Chloro-4-iodo-2-nitrO'phenvlVcarbamic acid tert.-butyl ester The title compound was prepared via the isocyanate from 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (7.0 g> 23.45 mmol) with diphosgene (2.12 mL, 17.6 mmol) in EtOAc (30 mL), followed by treatment with tert.-BuOH (100 mL) in CH3CI2 (100 mL) according to the general procedure B (method a). Obtained as a yellow solid (7.1 g, 76%). MS (EI) 398 (M^) and 400 [(M-f2)^]; mp 82-84 °C Example B2 f4,5-Dichloro-2-nitro-phenvlVcarbamic acid tert.-butyl ester The title compound was prepared via the di-Boc-compound from commercially available 4,5-dichlorO-2-nitroaniline (15 g, 72.5 mmol) and BOC2O (32.4 g, 148.5 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained as abrown solid (21.63 g, 97 %). MS (ISN) 305 [(M-H)-]; mp 68-73 °C. Example B3 (5-Fluoro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared via the di-Boc-compound from 5-fluoro-2-nitro-4-trifluoromethyl-phenylamine; prepared from commercially available 4-amino-2-fluorobenzotrifluoride by acetylation with Ac2O in toluene at 23 °C, nitration with 100 % nitric acid from 10-23 °C and deacetylation with 2N NaOH in THE at 50 °C] (5.21 g, 23.2 mmol) and Boc2O (10.63 g, 48.7 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a light yellow solid(6.33 g, 84 %). MS (ISN) 323 [(M-H)-]; mp 104 °C Example B4 [4-Iodo-2-nitrO'5-f2,2.2-trifluoro-ethoxy)-phenvll-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenyiamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (8.95 g, 30 mmol), 2,2,2-trifluoroethanol (30 mL) and KOH (4.36 g, 66 mmol) in DMSO (60 mL) at 23 °C for 35 days.] (10.41 g, 29 mmol) and BOC2O (12,87 g, 59 mmol), followed by treatment with 2 eq. TFA in CR2CL2 according to the general procedure B (method c). Obtained as a yellow solid (13.34 g, 100 %), MS(ISN)461[(M-H)-]. Example B5 (5-Chloro-2-nitro-4-trifIuoromethvl-phenvl)-carbamic acid tert,-butyl ester The title compound was prepared via the di-Boc-compound from commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (22.61 g, 94 mmol) and BOC2O (42.06 g, 193 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (31,82 g, 99%). MS (ISN) 339.1 [(M-H)-]and 341 [(M+2-H)-];mp 113-115 °C. Example B6 (5-Chloro-4-fluoro-2-nitro-phenvl')-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from commercially available 3'-chloro-4'-fluoro-6'-nitroacetanmde [CAS-No. 81962-58-5] (59 g, 254 mmol), and BOC2O (58.13 g, 266 mmol), followed by treatment with NH4OH (25%, 77.5 mL, 507 mmol) according to the general procedure B (method d). Obtained as a yellow solid(73,53 g, 100 %). MS (ISN) 289 [(M-H)-] and 291 [(M+2-H)-]; mp 73-74 °C Example B7 [2-Nitro-5-(2,2,2-trifluoro-ethoxv)-4-trifluoromethyl-phenvn-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenylamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al), 2,2,2-trifluoroethanol and KOH in DMSO at 23 °C for 32.5 days.] and BOC2O, followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (18.955 g). MS (ISN) 403 [(M-H)-]. Example B8 (5-Chloro-4-methyl-2-nitro-phenyl)-carbamic add tert-butyl ester The title compound was prepared via the di-Boc compound from commercially available 5-chloro-4-methyl-2-nitroaniline (10.0 g, 53.6 mmol) and BOC2O (23.9 g, 109 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (toluene/ethylacetate 19:1) as a yellow solid (14.6 g, 95%). MS (ISN) 285.1 [(M-H)'l. Example B9 (4-Cyano-5-fluoro-2-nitro-'phenyl)-Carbamic acid tert-butyl ester The tide compound was prepared via the di-Boc compound from 4-cyano-5-fluoro-2-nitroaniline (24.9 g, 137 mmol) [Ohmori et al. J, Med. Chem. 1994,37,467 - 475] and BOC2O (61,5 g, 282 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (hexane/ethylacetate 4:1) as a light yellow solid (14.5 g, 39%). MS (ISN) 280.1 [(M-H)']. General procedure C: Preparation of 5-N-substituted-(2-nitro-phenyl)-carbamic acid tert.-butylesters: (5-Chloro or -fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester was stirred with the desired amine optionally with DMSO, DMF, DMA, NMP or THF and/or DIPEA or Et3N at temperatures from 23 °C to 130 °C until tic indicated complete disappearance of the chloride or fluoride. The reaction was cooled to 23 °C poured into ice-water, the precipitate was filtered off, washed with water and dried in vacuum. In cases were the product did not precipitate, the mixture was extracted with EtOAc, washed with water and brine, dried over Na2SO4. Filtration and removal of the solvent in vacuum left a crude product, which was - if necessary - purified by silica gel column chromatography with hexane/EtOAc to give the pure title compound. Example CI (4-Chloro-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butylester The tide compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and dimethylamine (5.6 N in EtOH, 8.7 mL, 48.8 mmol) in DMSO (35 mL) at 23 o'C according to the general procedure C. Obtained as a yellow solid (2.81 g). MS (ISP) 316 [(M+H)--] and 318 [(M-h2+H)']; mp 136-138 °C Example C2 (5-DimethylaminO-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic acid tert,-butyl ester (Example Bl) (399 mg, 1 mmol) and dimethylamine (5.6 N in EtOH, 0.36 mL, 2 mmol) in THE (3 mL) at 65 °C for 18 h in a sealed tube according to the general procedure C. Obtained as a yellow solid (386 mg). MS (EI) 407 (M+); mp 120-122 °C. Example C3 (4-Chloro-5- rr2-methoxv-ethyl)-methyl-amino1-2-nitro-phenyl}-carbamic add tert,-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol), N-(2-methoxyethyl)methylamine (2.43 mL, 23 mmol) and Et3N (4.2 mL, 30 mmol) in DMSO (20 mL) at 23 °C according to the general procedure C. Obtained as a brown oil (3,57 g), MS (ISP) 360 [(M+H)+_] and 362 [(M+2-i-H)^]. Example C4 (5-Dimethylamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (5-fluoro-2-mtro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B3) (1.62 g, 5.0 mmol) and dimethylamine (5.6 N in EtOH, 4.47 mL, 25.0 mmol) in DMSO (10 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(1,48 g). MS (ISN) 348 [(M-H)-]; mp 110 X. Example C5 r \|4-Chloro-5-(ethvI-methyI-aminoV2-nitro-phenvi]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-ethyl-methylamine (2.89 g, 48.8 mmol) in DMSO (35 mL) at RT according to the general procedure C. Obtained as a pale brown solid(3.21 g). MS(ISP)330.3 [(M+H)1;mp94oC. Example C6 f4-Chloro-5-(methyl-propyl-aminoV2-nitro-phenyl-carbamic acid tert-butylester The title compound was prepared from (4,5-dichlorO-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-methyl-propyl-amine (2,50 g, 34.2 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a pale brown solid (3.58 g), MS (ISP) 344.3 [(M+H)+]; mp 68 °C, Example C7 f4--Chloro-5'(dietfavl-amino)-2-nitro-phenyn-carbamic acid tert-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and diethyl-amine (3.57 g, 48.8 mmol) in DMSO (35 mL) at 60°C according to the general procedure C. Obtained as a yellow solid (2.63 g). MS (ISP) 344.3 [(M+H)--]; mp 95 °C. Example C8 (4-Chloro-2-nitro-5-pyrrolidin-l'yl'phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and pyrrolidine inDMSO at 23 -€ according to the general procedure C. Obtained as a yellow solid (6.65 g). MS (ISP) 342 [(M+H)--] and 344 [(M+2+H)']; mp 157-158 °C. Example C9 [4-Chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and EtsN (6.97 mL, 50 nunol) in DMSO (30 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.25 g). MS (ISP) 342.2 [(M+H)+ and 344 [(M+2+H)-']; mp 104-106 °C. Example CIO (2-Nitro-5-pyrrolidin-l-yl-4-trifluoromethyl'-phenyl)_-carbamic acid tert-butyl ester The tide compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5) (6,81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) inDMSO (70 mL) at 23 --C according to the general procedure C. Obtained as a yellow solid (7.35 g). MS (ISN) 374 [(M-H)-]; mp 138-141 °C . Example CI 1 f 5-DimethylaminO-4'fluoro-2-nitro-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (5-chloTO-4-fluoro-2'nitro-phenyl)~carbamic acid tert-butyl ester (Example B6) (4.94 g, 17 mmol) and MeaNH (40% in H2O, 7.9M, 10.9 mL, 86 mmol) inDMSO (35 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.93 g), MS (ISP) 303 [(M+H)+]; mp 144-148 X. Example C12 ('4-Chloro-2-nitro-5-piperidin-l-yl-phenylVcarbamic acid tert,-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and piperidine inDMSO at 23 oC according to the general procedure C. Obtained as a yellow solid (1.173 g). MS (ISP) 356 [(M+H)+] and 358 [(M+2+H)']; mp 132-133 °C. Example CI 3 (4-Fluoro-2-nitro-5-pvrrolidin-l-yl-phenylVcarbamic acid tert.-butylester The title compound was prepared from (5-chloro-4-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B6) (5.81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (6.42 g). MS (ISP) 326 [(M+H)--]; mp 188-193 °C. Example C14 (5-A2etidin'l-yi-4-chloro-2-nitro-phenyl')-carbamic acid tert.-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyi ester (Example B2) (6.14 g, 20 mmol), azetidine (2.33 mL, 34 mmol) and Et3N (8.4 mL, 60 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as an orange solid (5.85 g). MS (H) 327 (M+) and 329 [(M+2)+]. Example CI 5 (5-Azetidin-l-yl-2-nitro-4-trifluoromethyl-phenylVcarbaniic acid tert.-butyl ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5), azetidine and Et3N in DMSO at 23 °C according to the general procedure C. Obtained as a yellow solic (6.925 g). MS (ISN) 360 [(M-H)-]. Example C16 (5-(CvclopropylmethyI-methyl-amino)-2-nitro-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B5) (5.11 g 15 mmol), cyclopropylmethyl-methyl-amine hydrochloride (5.47 g, 45 mmol) and Et3N (10.5 mL, 75 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(5.73 g). MS (ISN) 388 l(M-H)']; mp 5 1°C . Example C17 (5-(CycIopropvI-methyI-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamicacid tert.-but\4 ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl) carbamic acid tert-butyl ester (Example B5) (3.40 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and Et3N (6.97 mL, 50 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.74 g). MS (ISP) 374.2 [(M+H)1, Example C18 (2-Dimethylamino-2'-fluoro-5'nitro-biphenyl-4-yl)-carbamic acid tert.-butylester The title compound was prepared from (2-chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example D3) (9,568 g, ca. 26 mmol) and Me2NH (60% in H20,12 mL) inDMSO (87 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.54 g). MS (ISP) 376.3 [(M+Hrj. Example C19 (5-Dimethylamino-4-methyl-2-nitro-phenylVcarbamic acid tert-butyl ester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and dimethylamine (11 ml, 33% in EtOH, 61.0 mmol) in DMSO (35 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid (3.50 g, 97%). MS (ISP) 296.3 [(M+H)-]. Example C20 f4-Cvano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7.11 mmol) and dimethylamine (6.3 ml, 33% in EtOH, 35.0 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.87 g, 86%). MS (ISP) 307.3 [(M+H)'], Example C21 [4-methyl-5-(methyl-propyl-aminol-2'mtro-phenyn-Carbamic acid tert-butylester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-methylpropylamine (6.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (3.89 g, 98%). MS (ISP) 324.4 [(M+H)--]. Example C22 (5-fEthyl-metfayl-amino)-4-methyl-2-nitro-phenyl-carbamic add tert-butyl ester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-ethylmethylamine (5.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.58 g, 95%). MS (ISP) 310.3 [(M+H)--]. Example C23 f4-Chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isopropyl-methyiamine (5.95 g, 81.4 mmol) in DMSO (50 mL) at 75 °C according to the general procedure C. Obtained as a yellow solid (4.07 g, 73%). MS (ISP) 344.3 [(M+H)+]. Example C24 [4-Chloro-5-(isobutyl-methyl-amino)-2-nitro--phenyl]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isobutyl-methylamine (7.09 g, 81,4 mmol) in DMSO (50 mL) at RT according to the general procedure C. Obtained as a brown oil (5.79 g, 99%). MS (ISP) 358.2 [(M+H)--]. Example C25 f4-Cvano-2-nitro-5-pyrrolidin-l'yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7,11 mmol) and pyrrolidine (2.94 ml, 35.6 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.97 g, 83%). MS (ISP) 331.2 [(M-H)-]. Example C26 f4-Cvano-5-fmethyl-propyl-amino)-2-nitro-phenyl-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-methyl-propylamine (3.72 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.75 g, 75%). MS (ISP) 333.3 [(M-H)']. (4-Cyano-5-diethylamino-2-nitro-phcn>i>-carbamic add tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and NJSI-diethyiamine (3.60 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.78 g, 77%). MS (ISP) 333.2 [(M-H)-]. Example C28 [4-Cvano-5-(isopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butyl ester The title compound was prepcured from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isopropyl-N-methylamine (3.60 ml, 34.7 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.84 g, 79%). MS (ISP) 333.3 [(M-H)']. Example C29 f4-Cvano-5-(isobutyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isobutyl-N-methylamine (3.02 g, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C Obtained as a yellow solid (1.87 g, 77%). MS (ISP) 347,4 [(M-H)-]. Example C30 f4-Cyano-2-nitro-5-piperidin-l--'yi-phenyl)-carbamic acid tert-butylester The title compoimd was prepared from (4-cyano-5-£luoro-2-nitro-phenyi)-carbamic acid tert-butyl ester (Example B9) (2.0 g> 7.11 mmol) and piperidine (3.51 ml, 35.6 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.94 g, 79%). MS (ISP) 345.3 [(M-H)-]. Example C31 (4-Chloro-5-isobutylamino-2-nitro-phenyl--carbamic acid tert-butyl ester The title compound was prepared from (4>5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and isobutylamine (3.57 g, 48.8 mmol) in DMSO (20 mL) at 55°C according to the general procedure C. Obtained as a brown solid (2.26 g, 67%). MS (ISP) 344.2 [(M+H)--]. Example C32 [5-fMethyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-methyl-propyl-amine (1.89 ml, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.04 g, 91%). MS (ISP) 378.3 [(M+H)-]. Example C33 f 5-(Isobutyl-methyl-amino V2-nitro-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol),N-isobutyl-methyl-amine (L54 g, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.18 g, 91%). MS (ISP) 390.3 [(M-H)-]. Example C34 f 5-f Isopropyl-methyl-aminoV2-nitro-4-trifluoromethyl-phenyn -carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-isopropyl-methyl-amine (3.67 ml, 35.2 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid(3.27 g, 74%). MS (ISP) 376.3 [(M-H)']. Example C35 (5-(IsobutvI-methyl-aminoV4-methyl-2-nitro-phenyl-carbamic acid tert-butylester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and N-isobutyl-methylamine (4.56 g, 52.3 nunol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (1.84 g, 52%). MS (ISP) 336.3 [(M-H)']. Example C36 (4-MethyI-2-nitro-5-pvTrolidin-l-yl-phenyl Vcarbamic acid tert-butylester The title compound was prepared from (5-chlorO-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and pyrrolidine (4.33 ml, 52.3 mmol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.27 g, 97%). MS (ISP) 320.3 [(M-H)-]; mp 145 °C Example C37 (4-Chloro-5-isopropylamino-2-nitro-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert.-butyl ester (Example B2) (5,0 g, 16,3 mmol) and isopropylamine (7,0 ml, 81.4 mmol) in DMSO (35 mL) at 55 o'C according to the general procedure C. Obtained as a brown solid (3.95 g, 73%). MS (ISP) 330.2 [(M+H)--]. ' Example C38 (5-Isobmylamino-2-mtro-4-trifluoromethyl-phenylVcarbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (5.00 g, 14.7 mmol), isobutyl-amine (7.36 mL, 73.4 mmol) in DMSO (35 mL) at RT according to the general procedure C Obtained as a yellow solid (5.39 g, 97%). MS (ISP) 376.3 [(M-H)-], General procedure D: Preparation of (4-arvI-2-nitro-phenyl)-carbamic acid tert.-butyl esters by direct Suzuki-coupling of ('4-iodo-2-nitro-phenyl)carbamic acid tert.-butylesters with arylboronic acids A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (3.0 mmol), the arylboronic acid (4.5 mmol) and PdCl2(PPh3)2 (2 mol%) was refluxed in 1,4-dioxane (25 mL) and 2M NaaCO2-sol. (7.5 mL) [or alternatively with IM NaHCOa-sol. (7.5 mL), LiCl (6.0 mmol) and (Ph3P)4Pd (3 mol%) in DME (30 mL); also possible with EtaN (9,0 mmol), Pd(0Ac)2 (3 mol%), PPhs (6 mol%) in DMF (10 mL) at 100 °C] until tic indicated complete conversion of the iodide. The mixture was transferred into a separating funnel, H2O (25 mL) was added and the product was extracted with ether or EtOAc (3 x 30 mL). The combined organic layers were washed with brine (50 mL) and dried over Na2S04. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound Example Dl (2-Dimethylamino-2\3'-difluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester The tide compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C2) and 2,3-difluorophenylboronic acid according to the general procedure D. Obtained as a yellow solid (3,096 g). MS(ISN)392[(M-H)-]. Example D2 f2'-Fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yll-carbamic acid tert,-butylester The title compound was prepared from [4-iodO-2-nitro-5-(2,2,2-trifluoro-ethox7)-phenyl]-carbamic add tert-butyl ester (Example B4) and 2-fluorophenylboronic add according to the general procedure D. Obtained as a yeDow solid (1.39 g). MS (ISP) 491 [(M+H)--]; mp 73-75 °C. Example D3 (2-Chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic add tert-butyl ester (Example Bl) (30 g, 75.3 mmol) and 2-fIuorophenylboronic acid (13.82 g, 98.8 nrniol) according to the general procedure D. Obtained as a yellow gum (1.39 g). MS (ISN) 365.0 [(M-H)-]. General procedure E: Preparation of (4-aryl-2-nitro-phenyl)-carbamic acid tert.-butyl esters by Suzuki-coupling of (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butylesters with bisfpinacolato)diboron and subsequent reaction with aryl halides A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (2,0 mmol), bis(pmacolato)diboron (2,2 mmol), KOAc (6.0 mmol) and PdCl2(PPh3)2 (3 mol%) in 1,4-dioxane (25 mL) was stirred at 100 °C until tic indicated complete conversion of the iodide [cf. Tetr. Lett. 1997,38,3841-3844]. After addition of the aryl halide (4.0 mmol), PdCl2(PPh3)2 (3 mol%) and 2M Na2CO3-soL (7.5 mL) the mixture was stirred at 100 oC until tic indicated complete conversion of the intermediate boronic ester. The mixture was transferred into a separating furnnel, H2O (30 mL) was added and the product was extracted with ether or EtOAc (3 x 50 mL). The combined organic layers were washed with brine (100 mL) and dried over Na2SO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound. General procedure F: Preparation of 5-chIoro-2'-nitro-4-pyrroI-l-yl-phenylamines by condensation of 5-chlorO-2-nitro-l,4-phenylenediamine with 2,5-dimethoxvtetrahydrofurans [cf. /. Heterocycl Chem 1988,25y 1003-1005]: A mixture of the 5-chloro-2-nitro-l,4-phenylenediamine (4.69 g, 25 mmol), the 2,5-dimethoxytetrahydrofuran (26 - 32,5 mmol) in HOAc (150 mL) was stirred at 60-120 °C until tic indicated complete conversion of the phenylenediamine. After cooling to 23 °C, the mixture was poured into brine (500 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (300 xriL) and dried over MgSO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/EtOAc to give the title compound. General procedure G: Preparation of 23-dimethoxvdihvdrofurans by bromination of furans in MeOH [cf. Tetrahedron 1971,27,1973-1996]: To a solution of the furan (177.5 mmol) in a mixture of anhydrous ether (54 mL) and abs. MeOH (79 mL) kept at -35 °C bromine (10.0 mL, 195 mmol) in MeOH (105 mL) was added gradually with stirring. The reaction mixture was stirred for 30 min, saturated with gaseous NH3 to pH 8, and allowed to warm up to 23 °C. Poured into ice-water, extracted with ether (3 x 400 mL), washed with brine, dried over Na2So4. Evaporation of the solvent left a yellow liquid, which was purified by vacuum distillation to give the title compound. General procedure H: Preparation of (4-alkynyl-2-nitro-phenyll-carbamic acid tert,-butylesters by Sonogashira-coupling of f4-iodo-2-nitro-phenyI)-carbamic acid tert.-butylesters with acetylenic compounds; also Sonogashira-coupling of (4-ethynyl-2-nitro-phenyl)-carbamic acid tert-butyl esters with aryl halides: A mixture of the halide (3.0-4.5 mmol), acetylenic compound (3.0-4.5 mmol), Et3N (13.5 mmol), PdCl2(PPh3)2 (5 mol%) and PPh3 (2.5 mol%) in THF (12 mL) [with very insoluble material DMF (up to 12 mL) could be added] was stirred for 20 min at 23 °C while being purged with Argon. Cul (1.2 mol %) was added and stirring was continued at 60 °C under Argon atmosphere until tic indicated complete conversion of the minor component [cf. /. Org. Chenu 1998,63,8551]. The mixture was transferred into a separating funnel, 5% citric add (50 mL) was added and the product was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with sat. NaHCOs-sol. (50 mL) and brine (50 mL), followed by drying over MgSO4. Removal of the solvent left a yellow residue, which was purified by silica gel colunm chromatography with hexane/EtOAc and/or triturated with hexane or aqueous EtOH to give the title compound. Example Hi (5-Hydroxymethyl-2-nitro-4-phenylethvnyl-phenyl)'Carbamic acid tert.-butylester The title compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C2) (386 mg, 0.97mmol) and phenylacetylene (149 mg, 1.46 mmol) according to the general procedure H. Obtained as an orange solid (370 mg). MS (EI) 381 (M+); mp 141-149 °C. General procedure T: Preparation of the (2-amino-phenyl)-carbamic acid tert.-butylesters bv reduction of (2-nitro-phenyl)-carbamic acid tert.-butylesters: Method a: Catalytic hydrogenation A mixture of the nitro compound (1.0 mmol) in MeOH or EtOH and THF (1:1 ca. 20 mL) [or solely EtOAc for aromatic chlorides] and 10% Palladium on carbon (20 mg), Raney-Ni (20 mg) or 5% Platinum on carbon was stirred vigorously at 23 °C under hydrogen atmosphere until tic indicated complete conversion. The catalyst was filtered off, washed thoroughly with MeOH or EtOH and THF (1:1) [or EtOAc], the solvent was removed in vacuum to give the title compound, which was generally pure enough for further transformations, but could be crystallized firom hot hexane if necessary. Method b: Reduction with SnCl2'2H2O A mixture of the nitro compound (1.0 mmol) and SnCl2'2H2O (5.0 mmol) was either stirred in EtOH (30 mL) at 70-80 °C or alternatively in pyridine (3 mL) and DMF (12 mL) at 23 °C under Argon atmosphere until tic indicated complete conversion [cf. Tetr. Lett. 1984,25, 839]. The reaction mixture was brought to pH 8 by addition of sat NaHC03-sol. and extracted with EtOAc (2 X 100 mL). The combined organic layer were washed with brine and dried over Na2SO4. Removal of the solvent left a yellow solid, which - if necessary - can be purified by silica gel column chromatography. Method c: Reduction with Zn and NH°Cl To a mixture of the nitro compound (1.0 mmol) in EtOH/THF/sat NH4CI-S0I. (1:1:1> 30 mL) was added Zinc dust (3.0 mmol) and the mixture was stirred at 70 °C imder Argon atmosphere until tic indicated complete conversion. Aqueous workup as described in method b. Example Tl (2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-chlorO-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example CI) (2,76 g, 8.74 nunol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid(2.3 g). MS (ISP) 286 [(M+H)--] and 288 [(M+2+H)+]; mp 96-101 °C. Example T2 f2-Amino-5-dimethylamino-4-phenylethynyl-phenvD-carbamic acid tert.-butyl esr T The title compound was prepared from (5-dimethylaminO-2-nitro-4-phenylethynyl-phenyl)-carbamic acid tert.-butyl ester (Example Hi) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a brown solid (1.927 g). MS(ISP)352[(M+H)+]. Example T3 (5-Amino-2-dimethylamino--2,3'-difluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-dimethylamino-2',3'-di£luoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example Dl) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (2,206 g), MS(ISP)364[(M+H)-'], Example T4 {2-AminQ-4-chloro-5- f f 2-methoxv-ethyl-methyl-amino1 -phenyll-carbamic acid tert.-butyl ester The title compound was prepared from {4-chloro-5-[(2-methoxy-ethyl)-methyi-amino]-2-nitro-phenyl}-carbamic acid te t-butyl ester (Example C3) (3.46 g, 9,62 mmol) by reduction with SnCl22H2O according to the general procedure J.(method b). Obtained as a yellow solid (2.25 g). MS (ISP) 330 [(M+H)1 and 332 [(M+2+H)']; mp 112 X. Example T5 [5-Amino-2-fluoro-2-(2.2.2-trifluoro-ethoxyVbiphenyl-4-yl1 -carbamic acid tert.-butyl ester The title compound was prepared from [2'-fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert,-butyl ester (Example D2) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (U7g). MS(ISP)401[(M+H)1. Example T6 (2-Amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert^-butylester The title compound was prepared from (5-dimethyiamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C4) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as an amorphous yellow substance (1.34 g), MS (ISP) 320 [(M+H)1. Example T7 [2-Amino-4-chloro-5-(ethyl-methvI-aminoVphenyl]-carbamic acid tert-butylester The title compoimd was prepared from [4-chloro-5-(ethyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C5) (3.0 g, 9.09 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.64 g). MS (ISP) 300.3 [(M+H)']; mp 81 X. Example T8 f2-Amino-4-chloro-5-(methyl-propyl-aminQVphenyl-carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C6) (3.15 g, 9.16 mmol) by reduction with SnClf 2H2O accordmg to the general procedure J (method b). Obtained as a pale brown solid (2.58 g). MS (ISP) 314.3 [(M+H)-']; mp 92 X. Example T9 f2'Amino-4'-chIoro-5-fdiethyl-amino)-phenyn'Carbamic add tert-butyl ester The title compound was prepared from [4-chloro-5-(diethyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example G7) (2.25 g, 6.54 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (1.55 g). MS (ISP) 314.3 [(M+H)+]; mp 110 °C. Example TIP (2-Amino-4-chloro-5-pyrrolidin-l-yl-phenylVcarbamic acid tert.-butyl ester The tide compound was prepared from (4-chloro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (&cample C8) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a red solid (4.80 g). MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']; mp 136-138 °C Example Til f 2-Amino-4-chloro-5-(cyclopropyl-methvI-amino')-phenyl1 -carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert.-butyl ester (Example C9) (3.2 g, 9.36 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as brown solid (2.00 g), MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']. Example T12 (2-Amino-5-pvrrolidin-l-yl-4-trifluoromethyl-phenylVcarbamic acid tert.-butylester The title compound was prepared from (2-nitro-5-pyrroHdin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example CIO) (7.35 g, 19.75 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light orange solid (6.75 g). MS (ISP) 346 [(M+H)--]; mp 101-103 °C Example T13 (2-Amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester The title compoiond was prepared from (5-dimethylamino-4-fluoro-2-nitro-phenyI)-carbamic acid tert.-butyl ester (Example C11) (4.88 g, 16 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a green solid(4.55 g). MS (ISP) 270 [(M+H)+]; mp 120-123 °C. Example T14 (2-Amino-4-chlorO-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-chloro-2-nitro-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C12) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as light brown solid (747 mg). MS (ISP) 326 [(M+H)+] and 328 [(M+2+H)1;mp 149-151 °C Example Tl 5 (2-Amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-fluoro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example C13) (6,37 g, 20 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (5.92 g). MS (ISP) 296 [(M+H)--]; mp 75-76 °C Example 116 (2-Amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (5-azetidin-l-yl-4-chloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C14) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (3.664 g). MS (ISP) 298 [(M+H)--] and 300 [(M+2+H)-']; mp 176-179 -C Example T17 (2-Amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic add tert.-butylester The title compound was prepared from (5-a2etidin-l-yl-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C15) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (5.173 g). MS (ISP) 332 [(M+H)+]; mp 166-167 °C Example Tl 8 f2-Amino-5-(cyclopropylmethyl-methyl-aminoV4-trifluoromethyl-phen\d1-carbamic acid tert.'butyl ester The title compoimd was prepared from [5-(cyclopropylmethyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C16) (5.66 g, 14.5 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as yellow solid (4.7 g). MS (ISP) 360 [(M+H)+]; mp 56 X. Example T19 [2-Amino-5--rcvclopropvI-methyl-amino)-4-trifluoromethyl-phenyn-carbamicacid tert,-butyl ester The title compound was prepared from [5-(cyclopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C17) (3.74 g, 9.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange semisolid (2.00 g). MS (ISP) 346.4 [(M+H)--]. Example 120 (5-Amino-2-dimethylamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butylester The title compound was prepared from (2-dimethylamino-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert-butyl ester (Example CIS) (4.54 g, 12.1 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light brown solid (3.324 g). MS (ISP) 346.4 [(M+H)+]. Example T21 [2-Amino-5-f2.2.2-trifluoro-ethoxyV4-trifluoromethyl-phenvIl-carbamic acid tert-butyl ester The title compound was prepared from l2-nitro-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tcrt-butyl ester (Example B7) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a yellow solid (17.374 g). MS(ISP)375[(M+Hr]. Example 22 (2-Amino-5-dimethylamino-4-methyl-phenyl)-Carbamic acid tert-butylester The title compound was prepared from (5-dimeth>1amino-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C19) (3.22 g, 10.9 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a gray solid (2.05 g, 58%). MS (ISP) 266.3 I(M+H)+]; mp 78 X. Example 123 (2-Amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C20) (3.9 g, 12.7 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.05 g, 58%). MS (ISP) 277.2 [(M+H)+]; mp 120 -C Example T24 (2-Amino-4-methyl-5-(methyl-propyI-amino)-phenyl1-carbamic acid tert-butylester The title compound was prepared from [4-methyl-5-(methyi-propyi-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C21) (3.59 g, 11.1 namol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (3.23 g, 99%). MS (ISP) 294.4 [(M+H)--]. Example T25 (2-Amino-5-(ethyl-methyl-amino)=4-methyl-phenvIl-carbamic acid tert-butyl ester The title compound was prepared from [5-(ethyl-methyI-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C22) (3.28 g, 10.6 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (2.94 g, 99%). MS (ISP) 280.3 [(M+H)1. Example T26 [2-Amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl1 -carbamic add tert-butylester The title compoimd was prepared from [4-chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C23) (4.07 g, 11.8 mmol) by reduction with SnClf 2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.08 g, 83%). MS (ISP) 314.3 [(M+H)1; mp 116 °C. Example T27 [2-Amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl1-carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C24) (5.55 g, 15.5 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.98 g, 78%). MS (ISP) 328.3 [(M+H)1. Example T28 (2-Amino-4-cyano-5-pvrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester The tide compound was prepared from (4-cyano-2-mtro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C25) (1.82 g, 5.48 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a pale brown solid (1.27 g, 77%). MS (ISP) 303.2 [(M+H)--]. Example T29 (2-Amino-4-cyano-5-fmethyl-propyl-aminoVphenyl1-carbamic acid tert-butylester The title compound was prepared from [4-cyano-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C26) (1.64 g, 4.90 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a dark red oil (1.24 g, 83%), MS (ISP) 305.3 [(M+Hf], Example T30 (2-Amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-diethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C27) (1.66 g, 4.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.38 g, 91%). MS (ISP) 305.3 [(M+H)+]; mp 151 °C Example T31 (2-Amino-4-cyano-5-(isopropyl-methyl-aminoVphenyl1 -carbamic acid tert-butylester The title compound was prepared from [4-cyano-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C28) (1.73 g, 5.17 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.56 g, 99%). MS (ISP) 305.3 [(M+H)--]; mp 77 °C. Example T32 [2-Amino-4-cyano-5-(isobutyl-methyl-amino)-phenyn-carbamic acid tert-butyl ester The title compound was prepared from [4-cyano-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C29) (1.76 g> 5.05 mmol) by reduction with SnCV2H2O according to the general procedure J (method b). Obtained as a light brown solid (1.55 g, 96%). MS (ISP) 319.5 [(M+H)--]; mp 88 oC. Example T33 (2-Amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-2-nitro-5-piperidin-l-yi-phenyl)-carbamic acid tert-butyl ester (Example C30) (2.08 g, 5.71 mmol) by reduction with SnCl2'2H2O according to the general procedure I (method b). Obtained as an off-white solid (L67 g, 99%). MS (ISP) 317.2 l(M+H)+]; mp 86 oC Example 134 (2-Amino-4-chloro-5-isobutylamino-phen\1)-carbamic acid tert-butylester The title compound was prepared from (4-chloro-5-isobutylainino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C31) (1.93 g, 5.61 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a brown solid (1.30 g, 74%). MS (ISP) 314.3 [(M+H)^. Example 135 (2-Amino-5-(methyl-propyl-aminoV4-trifluoromethyl-phenyl1 -carbamic acid tert-butyl ester The title compound was prepared from [5-(methyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C32) (3.78 g, 10.0 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a red oil (3.40 g, 98%). MS (ISP) 248.4 [(M+H)+]. Example T36 [2-Amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C33) (3.88 g, 9,91 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.70 g, 75%). MS (ISP) 362.3 [(M+H)--]. Example T37 (2-Amino-5-(isopropyl-methyl-aminoV4-trifluoromethyl-phenyn-carbamic acid tert-butyl ester The title compound was prepared from [5-(isopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C34) (2.98 g, 7.90 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.42 g, 88%). MS (ISP) 348.5 [(M-hH)--]. Example T38 (2-Amino-5-fisobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-methyl-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C35) (1.48 g, 4.39 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a white solid (1.08 g, 80%). MS (ISP) 308.3 [(M+H)']; mp 71 °C Example T39 (2-Amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester The tide compound was prepared from (4-methyl-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C36) (3.27 g, 10.2 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale brown solid (2.48 g, 83%). MS (ISP) 292.3 [(M+H)--]; mp 115 °C Example T40 j (2-Amino-4'Chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-chloro-5-i$opropylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C37) (3.75 g> 11.3 mmol) by reduction with SnCl3 2H2O according to the general procedure J (method b). Obtained as a brown solid (2.90 g, 86%). MS (ISP) 303.3 [(M+H)--]. Example T41 f 2-Amino-5-f isobutyl-amino V4-trifluoroir.ethyl-phenyl -carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic.acid tert-butyl ester (°Cample C38) (5.28 g, 13.99 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale yellow solid (3.69 g, 76%). MS (ISP) 348.5 [(M+H)--]; mp 141 °C. The following examples relate to the preparation of the ethyl or tert.-butyl 3-aryl-3-oxo-propionates (general formula IVa), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H): General procedure K Method a) Preparation of ethyl or tert.-butyl3-aryl-3-oxo-propionates The ethyl or tert.-butyl 3-aryl-3-oxo-propionates were prepared from the aryl acid chlorides and ethyl or tert.-butyl malonate potassium salt [CAS-no. 6148-64-7 and 75486-33-8] with Et3N and MgCla in CH3CN at 0 °C to 23 °C according to Synthesis 1993,290. If the free aryl carboxylic acid was employed in this reaction, it was activated by treatment with ethyl chloroformate and Et3N in THF/CH3CN at 0 °C prior to reaction with the malonate salt. Method b) Preparation of tert.-butyl3-aryI-3-oxo-propionates The tert.-butyl 3-aryl-3-oxo-propionates were alternatively prepared from the methyl or ethyl aryl esters by treatment with lithium tert.-butyl acetate [prepared by treatment of tert.-butyl acetate with lithium diisopropylamide in THF at -78 °C] in the prese- :e of lithium tert.-butoxide according to Synthesis 1985,45. If the product contained residual starting material after workup, thus could be removed by selective saponification with LiOH in THF/MeOH/H2O at 23 °C. Method c) Preparation of 3-aryl-3--oxo-propionic acids The 3-aryl-3-oxo-propiomc acids were prepared from the aryl acid chlorides and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 °C according to Synth Commun. 1985,15,1039 (method cl) or with n-BuLi in ether at -60°C o 0 °C according to Synthesis 1979,787 (method c2). Example Kl 3-Oxo-3'(3-f L23ltria2ol-l-yl-phenyl)-propionic acid ethyl ester The title compound was prepared from 3-[l,2,3]tria2ol-l-yl-ben2oic acid, prepared by refluxing of methyl 3-azidobenzoate [CAS-No. 93066-93-4] in trimethylsUyl-acetylene, followed by saponification with aqueous NaOH in refluxing EtOH] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with EtaN and MgCl2 in CH3CN according to general procedure K (method a). Obtained as a light yellow solid(2.22 g). MS (EI) 259 (W); mp 72-74°C, Example K2 3-(3-cyano-phenyl)-3-oxo-propiQnic acid tert.-butyl ester The title compound was prepared from methyl 3-cyanobenzoate [CAS-No, 13531-48-1] by treatment with lithium tert--butyl acetate according to general procedure K (method b). Obtained as a light brown oily semisolid. MS (EI) 245 (M+). Example K3 3-(2-Cyano-pvridin-4-yl)-3-oxo-propiomc acid tert.-butyl ester The title compound was prepared from 2-cyano-isonicotinic acid ethyl ester [CAS-No. 58481-14-4] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light brown solid (7.70 g). MS(ISN)245[(M-H)1. Example K4 3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionic acid tert.-butylester The title compound was prepared from ethyl 3-(3-methyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, acetaldoxime, Et3N and cat amount of pyridine in CHCI3 at 50 'C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (2.54 g). MS (ISP) 302 [(M+H)1; mp 50-56 -C. Example K5 fRSV3-Oxo-3-B45-ftetrahvdro-pvran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phneyl}- propionic acid tert.-butylester The title compound was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-l-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) methyl 3-azidobenzoate [CAS-No. 93066-93-4] (15.55 g, 88 mmol) and (RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-l-ynyl]-silane [CAS-No. 135294-85-8] (33.50 g, 132 mmol) were heated to 60 --C for 10 days; ii.) The obtained material (48.2 g, ca. 88 mmol) was stirred in TBAF (300 mL, IM in THF) at 70°C for 6 days and subsequently refluxed in IN HCl (400 mL) for 2 h; iii.) The obtained material (16.15 g, 74 mmol) was stirred in MeOH (400 mL) and cone. H2S04 (30 mL) at 23 °C for 11 days, iv.) Part of the obtained material (4.60 g, 19.7 mmol) was reacted with 3,4-dihydro-2H-pyran (2.67 mL, 29.5 mmol) and cat. amount p-TsOH.H2O in DCM (38 mL) at 23 -°C for 20 h.] (6.20 g, 19.5 mmol) by treatment with lithium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (8.47 MS(ISP)402[(M+H)-']. Example K6 3-[2-(3-methyl-isoxazol-5-yl)-pvridin-4-yn-3-oxo-propionic acid tert.-butylester The title compound was prepared from 2-(3-methyl-isoxazol-5-yl)-isonicotinic acid methyl ester [prepared by i.) reaction of 2-iodo-isonicotinic acid methyl ester [CAS-No. 134579-47-8] with trimethylsilylacetylene according to general procedure H; ii.) desilylation by reaction with cat. K2CO3 in MeOH at 0 -°C for 4 h; iii.) cycloadditon with a mixture of NCS, acetaldoxime, Et3N and cat. amount of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a brown solid (5.17 g). MS (EI) 302 (M^); mp 59-67 °C Example K7 3-[3-(2-methyl-2H-pyTazol-3-yl)-phenyl1-3-oxo-propionic acid tert.-butylester The title compound was prepared from 3-(2-methyi-2H-pyrazol-3-yl)-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyi)-3-dimethylamino-propenone [CAS-No. 163852-04-81 with methylhydrazine in EtOH at 23 °C for 2.5 days; ii.) chromatographic separation of the obtained isomers; iii.) treatment of the dean isomer -with n-BuLi in THF at -78 °C for 1 h, followed by quenching with a stream of CO2 and subsequent esterification with MeOH and cone, H2SO4 at 23 °C for 48 h.] by treatment with Uthium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.96 g), MS (EI) 300 (M+), Example K8 3- [3-f 5-Dimethylaminomethyl- [ 12,31 triazol- l-yl)-phenyll -3-oxo-propionic acid tert.-butylester The title compound was prepared firom 3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-benzoic acid methyl ester [prepared from methyl 3-azidobenzoate following the synthetic steps i.) to iii.) as described in the preparation of Example K5 and reacting the obtained product with SOCI2 in THF at 0 to 23 °C for 1 h, followed by acidition of dimethylamine (7.9 M in H2O) and stirring at 23 to 70 'C fori h.] (2.14 g, 8.22 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (2.90 g). MS(ISP)345[(M+H)-']. Example K9 3-[3-f3-Methoxvmethyl-isoxazol-5-yl)-phenyl1-3-oxo-propionic acid tert.-butylester The title compound was prepared from methyl 3-(3-methoxymethyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, 2-methoxyacetaldoxime [CAS-No. 71494-93-4], Et3N and cat, amoimt of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40^ 2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow liquid (1.548 g). MS (EI) 331 (M+), Example KlO (RSV3-Oxo-3-{3-f4-(tetrahvdro-pvran-2-yloxvmethyl)-thiazol-2-yl1-phenyll-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yioxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 13-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 °C for 24 h. The reaction mixture was cooled to 20°C and acided to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL), Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii,) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g). MS (ISP) 418.2 [(M+H)1. Example K11 (RS)-3-Oxo-3-{3-F4-ftetrahvdro-pvran-2-yloxvmethyl)-oxazol-2-\yl]-phenyl]-propionic acid tert-butylester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-carbamoyl-benzoic acid methyl ester [CAS-No. 106748-24-7] (17.9 g) and l,3-dichloro-2-propanone (14.0 g) was heated to 140 °C for 1.5 h. The mixture was cooled to 20 °C and cone, sulfuric acid (12 mL) was carefully acided. The mixture was stirred for 10 min. and then poured into ice-water. The product was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as duent to give 3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methyl ester (11.8 g) as a pale-yellow oil. MS (ISP) 252.2 [(M+H)--]. ii.) I A solution of this material (7.6 g) and lithium hydroxide monohydrate (5.0 g) in DMSO (30 mL) was heated to 60 -°C for 7 h. The cooled reaction mixture was poured into ice-water and the mixture was extracted with diethyl ether. The aqueous layer was acidified to pH 1 by the acidition of 6N HCl and the precipitate formed was collected by filtration and crystallized from dichloromethane/hexane. The pale-yellow crystals 5 (5.5 g) were dissolved in DMSO (25 mL), and after the acidition of N,N,N'N'- tetramethyl-guanidine (4.4 mL) and methyl iodide (2.2 mL), the mixture was stirred at 20 ^°C for 1 h. Ethyl acetate was acided and the mixture was washed successively with water, IN HCl and brine. The organic layer was dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as eluent and the purified product was crystallized firom diethyl ether/hexane to give 3-(4-hydroxymethyl-oxazol-2-yl)-benzoic acid methyl ester (2.1 g) as white crystals, mp 118-119 °C. iii.) A mixture of this material (2,1 g), dihydropyrane (1.2 mL) and p-toluenesulfonic acid hydrate (0.1 g) in ethyl acetate (15 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester (3,5 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g). MS (ISP) 402.5 [(M+H)1. Example K12 (RS')-3-Oxo-3-(3-r3-rtetrahvdro-pvran-2-yloxvmethyl)-isoxazol-5-vn-phenyl-propionic acid tert,-butylester The title compound was prepared from (RS)-3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (7.55 g, 23 mmol) and hydroxylamme hydrochloride (4.74 g, 68 mmol) were refluxed in EtOH for 1 h; ii.) The obtained ester (5.94 g, 20 nrniol) was reduced with LiAlH4 (761 mg, 20 mmol) in THF at -10 °C for 1 h; iii.) The obtained alcohol (4.90 g, 19 mmol) was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH.HaO in DCM at 23 °C for 20 h. iv.) The obtained THP-ether (5.24 g, 15 mmol) was treated with n-BuLi at -78 'C for 45 min, followed by a stream of CO2- v.) The obtained crude acid was stirred in MeOH (90 mL) and cone, H2SO4 (6.5 mL) at 50 X for 12 h. vi.) The obtained material (2.01 g, 8.62 mmol) was reacted with 3,4-dihydro-2H-pyran (1.17 mL, 12.9 mmol) and cat, amount p-TsOH.H2O in DCM (17 mL) at 23 °C for 5 h.] (2.44 g, 7.7 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.06 g). MS(ISP)402((M+H)-']. Example K13 (RS)3-(3-f3-Methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phneyl}-3-oxo-propionic acid tert,-butyl ester The title compound was prepared from (RS)-3-[3-methyi-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yi]-benzoic acid methyl ester [prepared by the following sequence: i.) (3-bromO-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 21575-91-7], pyrrolidine and TMSOTf in benzene were refluxed for 16 h {Org. Synth, 53y 59); ii.) The obtained 3-(3-bromo-phenyl)-3-pyrrolidin-l-yl-acrylic acid ethyl ester was reacted with nitroethane, POCI3 and Et3N at 23 °C; iii,) The obtained 5-(3-bromo-phenyI)-3-methyl-isoxazole-4-carboxylic acid ethyl ester was reduced with LiAlHH4 in THF at -10 -°C for 1 h iv.) The obtained [5-(3-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol was reacted with 3,4-dihydrO'2H-pyran and cat amount p-TsOH-HiO in DCM at 23 -C for 20 h. iv.) The obtained THP-ether was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vi.) The obtained 3-(4-hydroxymethyI-3-methyl-isoxazol-5-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (972 mg). MS(EI)416[(M+H)1. Example K14 (RSV3-[3'-[2-methyl-5-(tetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl]-phenylt-3-oxo-propionic acid tert.-butylester The title compound was prepared from (RS)-3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (6.135 g, 21 mmol), MeNHNH2 (1.296 mL, 25 mmol) and HCl (4M in dioxane, 6.25 mL, 25 mol) in EtOH (35 mL) were refluxed for 1.5 h; ii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyrazole-3-carboxylic acid ethyl ester (7.02 g, 22.7 mmol) was reduced with LiAlH4 (862 mg, 22.7 mmol) in THF (60 mL) at -10 °C for 1 h; iii.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-3-yi]-methanol (6.34 g, 24 mmol) was reacted with 3,4-dihydro-2H-pyran (3.25 mL, 36 mmol) and cat amount p-TsOH.H2O in DCM (50 mL) at 23 X for 23 h. iv.) The obtained (RS)-[5-(3-bromo-phenyl)-l-methyl-3-(tetrahydro-pyran-2-yloxymethyl)-lH-pyrazole(8.64 g, 25 mmol) was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. V.) The obtained crude acid was stirred in MeOH (90 mL) and cone. H2SO4 (6.5 mL) at 50 °C for 5 h. vi.) The obtained 3-(5-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (3.41 g, 13.85 mmol) was reacted with 3,4-dihydro-2H-pyran (1.75 mL, 20.77 mmol) and cat amount p-TsOH.H2O in DCM (28 mL) at 23 --C for 18 L] (3.93 g, 11.9 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (4.90 g). MS(ISP)415[(M+H)']. Example K15 propionic acid tert.-butylester The title compound was prepared from (RS)-3-(5-(tctrahydro-pyran-2-yloxymethyI)-isoxazol-3-yl]-benzoic acid methyl ester [prepared from (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] by treatment with NCS, cat amount pyridine in CHCI3 followed by acidition of (RS)-tetrahydro-2-(2-propynyloxy)-2H-pyran and slow acidition of Et3N in CHQ3 at 23 oC-] by treatment with hthium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g). MS (ISN) 400.5 [(M-H)-], Example Kl 6 3-Oxo-3-(3-pyrazol-l-yl-phenyl)-propiQnic acid tert-butvi ester The title compound was prepared from 3-pyrazol-l-yl-benzoic acid methyl ester [CAS-No. 168618-35-7] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.00 g). MS (EI) 286 (M+), Example K17 fRS)-3-Oxo-3-{3-[4-ftetrahvdro-pyran-2-yloxymethyl)-pvrazol-l-yl1-phenyl-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-1-yl]-benzoic acid methyl ester [prepared by the following sequence: L) A mixture of 3-hydrazino-benzoic acid methyl ester hydrochloride [CAS-No. 167626-26-8] (15.14 g, 75 mmol), 2-cyano-3-ethoxy-acryiic acid benzyl ester [CAS-No. 32016-27-6] (17.36 g, 75 mmol) and Et3N (10.5 mL, 75 mmol) in isopropanol (115 mL) was refluxed for 1.5 h. ii.) The obtained 5-amino-l-(3-methoxycarbonyl- phenyl)-lH-pyra2ole-4-carboxylic acid benzyl ester (26.0 g, 74 mmol) was refluxed with isopentyl nitrite (30 mL, 225 mmol; 10 mL) in THF (200 mL) for 22 h. iii.) The obtained l-(3-methoxycarbonyl-phenyl)-lH-pyrazole-4-carboxylic acid benzyl ester (18.98 g, 56 mmol) was hydrogenated in the presence of Pd/C (10% Pd/C, 600 mg, 1 mol%) in EtOAc (350 mL) and THF (250 mL) at 23 oC for 16 h. iv.) The obtained 1-(3-methox7carbonyl-phenyl)-lH-pyrazole-4-carboxylic acid (13.70 g, 55.6 mmol) was reduced with BH3.SMea (28.46 mL, 278.2 mmol) m THF (364 mL) at 5 to 23 °C for 16 h. V.) The obtained 3-(4-hydroxymethyl-pyrazol-l-yl)-benzoic acid methyl ester (10.66 g, 45.9 mmol) was reacted with 3,4-dihydro-2H-pyran (6.24 mL, 68.9 mmol) and cat. amount p-TsOH-HaO in DCM (91 mL) at 23 °C for 22 h.] (14.18 g, 44.8 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (15.87 g), MS(ISN)399[(M.H)-]. Example K18 (RS)-3-Oxo-3-{3-[4'(tetrahvdro-pyran-2yloxvmethyl)-isoxazol-3-yn-phenyll-propionic acid tert.'butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] was treated with NCS, cat amount pyridine in CHCI3 followed by acidition of (E)-3-pyrrolidin-l-yl-acryhc acid tert.-butyl ester [CAS-No. 340257-76-3] and slow acidition of Et3N in CHCI3 at 23 -°C. ii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid tert-butyl ester was stirred in formic acid at 50 °C for 18 h. iii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid was reduced with BH3SMe2 in THF at 5 to 23 'C for 16 h. iv.) The obtained 3-(4-hydroxymethyl-isoxazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH-HzO in DCM at 23 °C for 1L] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (1.817 g). MS(ISN)400[(M-H)-]. Example Kl 9 fRS)-3-l3-(2-methyl-4-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl 3'OXo-propionic acid tert--butyl ester The title compound was prepared from (RS)-3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyra2ol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 3-bromobenzoyl chloride and 3-isopropylamino-acrylic acid methyl ester [CAS-No. 89895-40-9] were reacted in toluene and Et3N according to Synthesis 1982, 318. ii.) The obtained 2-(3-bromo-benzoyl)-3-isopropylamino-acrylic acid methyl ester was reacted with methylhydrazine in ether at 23 °C according to Synthesis 1982, 318. iii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyra2ole-4-carboxylic acid methyl ester was reduced with LiAlH4 in THF at -10 °C for 1 h. iv.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-4-yl]-methanol was reacted with 3,4-dihydro-2H-pyran and cat. amoimt p-TsOH-HaO in DCM at 23°C for 20 h. v.) The obtained (RS)-5-(3-bromo-phenyl)-l-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-iH-pyrazole was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. vi.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vii.) The obtained 3-(4-methoxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with IM BBrs-sol. in DCM at -78 to 23 -°C for 1 h. viii.) The obtained crude bromide was reacted with KOAc in DMF at 60 °C for 30 min. ix.) The obtained crude acetate was reacted with NaOMe-sol. In MeOH at 23 °C for 20 min. X-) The obtained 3-(4-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (11.106 g). MS(ISN)413[(M-H)-]. Example K20 (RS)-3-Oxo-3-(3-{2-(2-ftetrahvdrQ-pyran-2-yloxvVethyl1-2H-pvrazol-3-yl}-phenyl)-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyl)-3-dimethylamino-propenone [CAS-No. 163852-04-8] with 2-hydroxy-ethylhydrazine in EtOH at 23 °C for 2.5 days, ii.) The obtained mixture of pyrazoles (12.36 g, 35.19 mmol) was reacted with 3,4-dihydro-2H-pyran (4.79 mL, 52.8 mmol) and cat amount p-TsOH-H2O in DCM (70 mL) at 23 °C for 20 h iii.) chromatographic separation of the obtained isomers, iv.) treatment of the clean isomer (7.35 g, 73.7 mmol) was treated with n-BuLi (13.08 mL, 20,9 mmol) in THF (42 mL) at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid was reacted (4.56 g, 14.1 mmol) was reacted with KHCO3 (2.89 g, 28.8 mmol) and Mel (0.99 mL, 15.9 mmol) in DMF (29 mL) at 23 °C for 2 h,] (2.96 g, 8.96 mmol) by treatment with Uthium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g). MS(ISP)415[(M+H)+]. Example k21 (RSV3-Oxo-3-f3-{5-r2-ftetrahvdro-p\Tan-2-\dox\'Vethyll-rL23ltriazol-l--vil-phenyl-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-{5-[2-(tetrahydro-pyran-2-yioxy)-ethyl]-[l,2,3]triazol-l-yl}-benzoic acid methyl ester (prepared by the following sequence: L) methyl 3-azidobenzoate [CAS-No. 93066-93-4] and (RS)-tert-butyl-dimethyl-[4-(tetrahydro-pyran-2-yioxy)-but-l-ynyi]-silane [CAS-No. 198411-20-0] were heated to 60 °C for 10 days; ii.) The obtained material was stirred in TBAF (IM m THF) at 70 °C for 6 days and subsequently refluxed in IN HCl for 2 h; iii.) The obtained 3-[5-(2-hydroxy-ethyl)-[l,2,3]triazol-l-yl]-benzoic acid was stirred in MeOH and cone. H2SO4 at 23 °C for 11 days, iv.) The obtained 3-[5-(2-hydroxy-ethyl)-[ 1,2,3]triazol-l-yl]-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH'H2O in DCM at 23 °C for 20 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (6.748 g). MS(ISP)416[(M+H)-']. Example K22 (RS)-3-Oxo-3-l3-(5-rtetrahvdro-pyran-2-yloyvmethyl)-pvrazol-l-yll-phenyll-propionic acid ethyl ester The title compoxmd was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yioxymethyl)-pyrazol-l-yl]-benzoic acid [prepared by the following sequence: i.) A mixture of 3-hydrazino-benzoic acid [CAS-No. 38235-71-1], 4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester [CAS-No. 67751-14-8] in acetic acid was refluxed for 15.5 h. ii.) The obtained 2-(3-carboxy-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was stirred DMF-di-tert-butyl acetal in toluene at 80 X for 45 h. iii.) The obtained 2-(3-terL-butoxycarbonyl-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was saponified 150°C Cristallisation from water and ethyl acetate/hexane (1:1) yielded a light brown solid (24.3 g, 54%) mp 164°C; ii,) The obtained material (24-3 g, 104 mmol) was reacted with 3,4-dihydro-2H-pyran (29.3 mL, 320 mmol) and cat amount p-TsOH-H2O in dichloromethane (360 mL)/ THF (300 ml) at 23 °C for 20 L Purification by column chromatography on silica gd (toluene/ethyl acetate 1:1) gave a light brown oil.] (16.6 g, 52.3 mmol) by treatment with hthiimi tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (14.3 g, 68%). MS (ISP) 400.4 [(M-H)-]. Example K25 3-Oxo-3-(3-[1.2.4]triazol-yl-phenyl)-pTopionic acid tert-butylester The title compound was prepared from methyl 3-[l,2,4]triazol-1-yl-benzoate [CAS-No. 167626-27-9] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange liquid (2.41 g), MS (EI) 287 (M^). Example K26 3-(3-Imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butylester The title compound was prepared from methyl 3-(lH-imida2ol-l-yl)benzoate [prepared from 3-(lH-imidazol-l-yl)benzoic acid (/. Med, Chetn. 1987,30,1342; CAS-No. [108035-47-8] by reflioxing in cone. H2SO4/MeOH] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange-brown oil. MS (ISP) 287 [(M+H)+]. Example K27 3-0X0-3-f3-f4-ftetrahydro-pyran-2-yloxvmethyl')-thia2ol-2-yl]-phenyl]-propionic acid tert-butylester al 3-f4-Hvdroxymethyl-thiazol-2-yl)-benzoic acid methyl ester A mixture of 3-thiocarbamoyl-benzoic acid methyl ester (7,8 g), l,3-dichloro-2-propanone (8.4 g) and NaHCOs (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 -°Cfor 24 h. The reaction mixture was cooled to 20 °C and acided to a stirred solution of NaOMe (5.4 g) in MeOH (200 mL). Stirring was continued for 0,5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ACOEL The organic layer was washed with brine, dried and evaporated in vacuum- The residue was crystallized from CH2Cl2/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-ben2oic acid methyl ester (7.5 g) as light-brown crystals, mp 115-117 °C. b) 3-f4-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-2-yn-benzoic acid methyl ester A mixture of the material prepared in a) (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in AcOEt (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried over Na2SO4 and evaporated in vacuo. The residual oil was purified by chromatography on silica gel using AcOEt /hexane (1:2) as eluent to give 3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil. c) 3-Oxo-3-f3-r4-ftetrahvdro-pyran-2-yloxvmethyD-thiazoI-2-yI1-phenyl]-propionic acid tert-butylester A sample of the material prepared in b) (3.3 g) was treated with lithium tert,-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (3.25 g) as a pale-yeUow oil, MS (ISP) 418.2 [(M-fH)--]. Example K28 3-Oxo-3-f3-(2-bromo-lJ-dimethoxy-ethyl')-phenyll-propionic acid tert-butylester a) 3-(2-Bromo-Ll-dimethoxy-ethyl')-ben2oic acid methyl ester A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-No 62423-73-8] (2.43 g), 4-toluenesulfonic acid hydrate (0.38 g) and trimethyl orthoformiate (5.5 ml) in MeOH (40 mL) was heated at reflux for 20 h. The cooled solution was diluted with AcOEt (0.15 L), washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum to give 3-(2-bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.0 g) as a pale-yellow oil. b) 3-Oxo-3-[3-(2-bromo-l,1-dimethoxv-ethyl)-phenyl1-propionic acid tert-butylester 3-(2-Bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.9 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyi]-propionic acid tert-butyl ester (2.8 g) as a yellow oil. Example K29 3-Oxo-3-r3-(2-methyl-oxazol-4-yl)-phenyn-propionic acid tert-butyl ester a) 3-(2-methyl-oxazol-4-yl)-benzoic acid A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g) and acetamide (1.77 g) was heated with stirring to 130 'C for 40 min. The mixture was cooled and diluted with H2O (30 mL) and the precipitate formed was collected by filtration to give 3-(2-methyl-oxa2ol-4-yl)-ben2oic acid (1.51 g) as brown solid. b) 3-(2-methyl-oxazol-4'yl')-benzoic acid methyl ester A solution of 3-(2^methyl-oxazol-4-)d)-benzoic acid (1.42 g) in a mixture of MeOH (30 mL) and 4NHC1/Et20 (6 mL) was heated to 40 -°C for 4 h. The solution was evaporated in vacuum and the residual oil was stirred with H2O (30 mL), the pH of the mixture being set to about 6 by the acidition of sat NaHCOa solution. The precipitate was isolated by filtration to give 3-(2-methyl-oxa2ol-4-yl)-benzoic acid methyl ester (1.18 g) as light-brown solid, MS (ISP) 218.2 [(M+H)-^]. c) 3-Oxo-3-f3-('2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester 3-(2-Methyl-oxazol-4-yl)-benzoic acid methyl ester (1.02 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (1.50 g) as a pale-yellow oil. Example K30 3-Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3.4lthiadiazol-2'yl1-phenyll-propionic acid tert-butyl ester a) 3-rN'-tert-butoxvcarbonyl-hvdra2inocarbothioyl)-benzoic acid methyl ester A mixture of 3-(N'-tert-butoxycarbonyl-hydrazinocarbonyl)-benzoic acid methyl ester (1.47 g) and Lawesson reagent (1.62 g) in toluene (30 mL) was heated to 70 °C for L5 h. The mixture was concentrated in vacuum and then subjected to chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-(N'-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (1.31 g) as a yellow solid, MS (ISP) 328.3 [(M+NH4)1. b) 3-Hvdra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate A solution of 3-(N1-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (0.93 g) in TFA (9 mL)/anisole (2 mL) was stirred at 0 X for 1 h. The solvents were evaporated in vacuum to give crude 3-hydrazinothiocarbonyl-ben2oic acid methyl ester trifluoroacetate (0.98 g) as a crystallizing oil. c) 3-(5-Hydroxymethyl-[L3,4lthiadiazoI-2-yl)-benzoic acid methyl ester A mixture of 3-hydrazinothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.49 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.47 g) in EtOH (6 mL) was heated to 80 °C for 2.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated. The residual oil (0.8 g) was dissolved in MeOH (5 mL), MeONa (0,08 g) was acided and the solution was heated to 65 °Cfor 0.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (0.15 g) as a white soHd, MS (ISP) 25L2 [(M+H)+]. d) 3'(5-fTetrahvdro-pyran2-yloxvmethyl)-fL3,4lthiadiazol-2-ylUbenzoicacid methyl ester A mixture of 3-(5-hydxoxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (7.8 g), dihydropyrane (5.6 mL) and p-toluenesulfonic acid hydrate (0.59 g) in AcOEt (80 mL) was stirred at 20 °Cfor 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on sihca gel using AcOEt/hexane (1:2) as eluent to give 3-[5-{tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5,85 g) as a pale-yellow oil. e)3'Oxo-3-B-r5-ftetrahvdrO'pyran-2-vIoxvmethyl)-fl3.4lthiadiazQl-2-yl]-phenyl-propionic acid tert-butylester 3-[5-(Tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5.85 g) was treated with lithium tert,-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (8.9 g) as a pale-yellow oil. Example K31 3-Oxo-3-(3-(5-r2-ftetrahvdro-pyran-2-vIoxy)-ethyl14L3.4lthiadia2ol-2-yl}-phenyl)-propionic acid tert-butylester a) 3-[5-(2-Hydroxy-ethyl)-ri3,4lthiadiazol-2-yl1-benzoic acid methyl ester A mixture of 3-hydra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.45 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (0.35 g) in pyridine (5 mL) was heated to 100 °C for 1.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was chromatography on siUca gel using AcOEt/hexane (1:1) as eluent to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]thiadiazol-2-yl]-ben2oic acid methyl ester (0.37 g) as a white solid, MS (ISP) 265.3 [(M+H)+]. b) 3-15- [2-fTetrahydro-pyran-2-yloxy)-ethyl1 - [ 1,3>4]thiadiazol-2-yn-benzoic acid methyl ester A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3>4]thiadia2ol-2-yl]-ben2oic acid methyl ester (1.86 g), dihydropyrane (0.95 mL) and p-toluenesulfonic acid hydrate (0.13 g) in AcOEt (25 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyI]-[l,3,4]thiadia2ol-2-yl}-benzoic acid methyl ester (1.60 g) as a pale-yellow oil. c)3-Oxo-3-r3-l5-r2-ftetrahvdro-pyran-2-vIoxv)-ethyl]-rL3.4lthiadiazoI-2-yl?-phenyD-propionic acid tert-butylester 3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadia2ol-2-yl}-benzoicacid methyl ester (1.60 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phen}i)-propionic acid tert-butyl ester (2.1 g) as a pale-yellow oil. Example K32 3-Oxo-3-(3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3,4loxadiazol-2-yl]-phenyll-propionic acid tert-butyl ester z) 3-(5-HvdrQXvmethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester A mixture of 3-hydrazinocarbonyl-benzoic acid methyl (0.97 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.95 g) in EtOH (20 mL) was heated to 80 -°C for 1 h. The mixture was diluted with AcOEt and washed with IN HCI and with brine. The organic layer was dried and evaporated and the residual oil (1.1 g) was dissolved in DMF (4 mL). Upon acidition of AcOK (0.59 g) and KI (0.07 g), the mixture was stirred at 100 Xfor 0.5 h. After cooling to 20 °C, MeOH (10 mL) and NaOMe (0.14 g) were acided and stirring was continued for 0.5 h at 65 °C. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester (0.72 g) as a white solid, MS (ISP) 235.3 [(M+H)--]. b) 3-(5-(Tetrahvdro-pyran-2-yloxvmethyl)-[ 1.3.4lthiadiazol-2-vn -benzoic acid methyl ester A mixture of 3-(5-hydroxymethyl-[l,3>4]oxadiazol-2-yl)-benzoic acid methyl ester (9.8 g), dihydropyrane (7.7 mL) and p-toluenesulfonic acid hydrate (0.80 g) in AcOEt (100 mL) was stirred at 20 € for 1 h. The solution was diluted with AcOEt, washed with 5% NaHC03 solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-[5-(tetrahydrO-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (12.6 g) as a pale-yellow oil. c)3-Oxo-3-{3-[5-(tetrahydro-pyran-2-yloxvmethvD-fl3,4loxadiazol-2-yn-phenyll-propionic acid tert-butylester 3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,3,4]thiadiazol-2-yl] -benzoic acid methyl ester (12,6 g) was treated with Uthium tert.-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (17.0 g) as a pale-yellow oil. Example K33 3-Oxo-3-f3-{5-[2-ftetrahvdro-pyran-2-yloxvVethyl]-[L3.4loxadiazol-2-yll-phenyl)-propionic acid tert-butylester 2L) 3-[5-(2-Hvdroxv-ethyl)-ri3,4l6xadiazol-2-yl1-benzoic acid methyl ester A mixture of crude 3-hydrazinocarbonyl-ben2oic acid methyl (2,90 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (2.76 g) in pyridine (10 mL) was heated to 100 °Cfor 2 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was crystallized from Et20 to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yI]-benzoic acid methyl ester (2.5 g) as a white solid, MS (ISP) 249.1 [(M+H)--], b)3-l5-(2-fTetrahydro-pyran-2-yloxvVethyl]-fL3,4lthiadiazol-2-vU-benzoicacid methyl ester A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yl]-benzoic acid methyl ester (7.45 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0,57 g) in AcOEt (80 mL) was stirred at 20 'Cfor 2 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoic acid methyl ester (8.2 g) as a pale-yellow oil. cl3-Oxo-3-(3-(5-(2-(tetrahvdro-pyran-2-yloxv)-ethyl]-rL3.4loxadiazol-2-vU-phenyl)-propionic acid tert-butylester 3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoicacid methyl ester (8.2 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (11.6 g) as a pale-yellow oil. Example K34 3-(3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester a) 3-Oxazol-4-yl-benzoic acid methyl ester A mbcture of 3-(2-bromo-acetyl)-benzoic acid (1.94 g) and formamide (1.08 g) was heated with stirring to 130 ^'Cfor 3 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was dissolved in a mixture of MeOH (30 mL) and 4NHC1/Et20 (8 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOs solution and brine, dried and evaporated. The residue was chromatographed on sihca gel using AcOEt/hexane (1:3) as eluentto give 3-oxazol-4-yl-benzoic acid methyl ester (0.85 g) as off-white solid, MS (ISP) 204.1 [(M+H)--]. b) 3-r3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester 3-Oxazol-4-yl-benzoic acid methyl ester (0.85 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (1.46 g) as a pale-yellow oil. Example K35 3-Oxo-3-f3-thiazoI-4-vI-phenyl)-propionic acid tert-butylester a) 3-Thiazol-4-yl-benzoic acid methyl ester A solution of 3-(2-bromo-acetyi)-benzoic acid (L22 g) and thioformamide (0.46 g) in EtOH (5 mL) was heated to 80 •C for 1 L The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was dissolved in a mixture of MeOH (20 mL) and 4NHCl/Et20 (5 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOj solution and brine, dried and evaporated. The residue was chromatographed on siUca gel using AcOEt/hcxanc (1:3) as eluent to give 3-thiazol-4-yl-benzoic acid methyl ester (0,98 g) as off-white solid, MS (ISP) 220.2 [(M+H)--]. b) 3-Oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butylester 3-Thiazol-4-yl-benzoic acid methyd ester (0.91 g) was treated with lithitun terL-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (1.54 g) as a pale-yellow oil. Example K36 3-f3-(5-Methyl-oxazol-4-yI)-phen)d]-3-oxo-propionic acid tert-butylester a) 3-tert-Butoxvcarbonylacetyl-benzoic acid methyl ester Dimethyl isophthaiate (67.9 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give crude 3-tert-butoxycarbonyiacetyi-benzoic acid methyl ester (74.5 g) as a pale-yellow oil. b) 3-Propionyl-benzoic acid methyl ester To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (ILl g) and Mel (2.2 mL) m DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil> 1.4 g). Stirring was continued at 0 ®C for 15 min and at 20 °C for 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated The residue was stirred in a mixture of CH2Cl2 (30 mL) and TEA (30 mL) for 40 min at 20 °C. After the evaporation of the solvents, the solution of the residue in AcOEt was extracted with ice-cold sat NaaCOs solution and the aqueous extracts were immediately acidified with 3N HQ and extracted with AcOEt The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HCl (3 mL) to 100 °C for 1 h. The cooled mixture was diluted with AcOEt, washed with sat. NaHCOs and brine, dried and evaporated to give 3-propionyi-benzoic acid methyl ester (3.87 g) as white solid, MS (ISP) 193.2 [(M+H)--]. c) rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester A mixture of 3-propionyl-benzoic acid methyl ester (3.6 g) and CuBri (7.45 g) in AcOEt (45 mL) was heated at reflux for 2 h. Unsoluble material was filtered oflFfrom the cooled mixture and the clear solution was washed with brine, dried and evaporated to give crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (5.0 g) as pale-yeUow oO. d) 3-r5'methyl-oxazol-4-yl)-benzoic acid methyl ester rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester (5.42 g) and formamide (3.6 ml) were heated together to 130 °C for 5 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as eluent to give 3-(5-methyI-oxazol-4-yl)-benzoic acid methyl ester (2.52 g) as white solid. e) 3-[3-(5-Methyl-oxazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester 3-(5-methyl-oxazol-4-yl)-beruoic acid methyl ester (0.87 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (L46 g) as a pale-yellow oil. Example K37 3-[3-(2-methyl'5-propyl-oxazol-4-yl)-phenyl-3-oxo-propionic acid tert-butyl ester al 3-Pent-4-enoyl-benzoic acid methyl ester To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (11.1 g) and allyl bromide (3.0 mL) in DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil, 1.44 g). Stirring was continued at 0 °C for 20 min and at 20 °Cfor 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated. The residual oil was stirred in a mixture of CH2Cl2 (30 mL) and TFA (30 mL) for 40 min at 20 'C. The solvents were evaporated. The solution of the residue in AcOEt was extracted with ice-cold saL NaaCOa solution and the aqueous extracts were immediately acidified with 3N HCl and extracted with ACOEL The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HQ (2 mL) to 100 ^'C for 1 h. The cooled mbcture was diluted with AcOEt, washed with saL NaHCOs and brine, dried and evaporated to give 3-pent-4-enoyi-ben2oic acid methyl ester (5.11 g) as a pale-yellow oil, MS (ISP) 236.2 [(M+NH4)']. b) rac-3-(2-Bromo-pentanoyl)-benzoic acid methyl ester A sample of 3-pent-4-enoyl-benzoic acid methyl ester (3.93 g) was hydrogenated in AcOEt (50 mL) in the presence of 5% Pd-C (190 mg) for 30 min at 20 ^'C. The catalyst was filtered off, CuBr2 (4.44 g) was acided to the solution and the mixture was heated at reflux for 1 h. Unsoluble material was filtered off from the cooled mixture and the clear solution was washed with IN HCl and brine, dried and evaporated to give crude rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (3.6 g) as pale-yellow oil. c) 3-(2-methyl-5-propvI-oxazol-4-yl)-benzoic acid methyl ester A sample of rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (1.50 g) and acetamide (0.89 g) were heated together to 130 C for 15 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oE was chromatographed on silica gel using AcOEt/hexane (1:3) as duent to give 3-(2-methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0.47 g) as a light-yellow oil. d) 3-f3-(2-methyl-5-propyl-oxazol-4-yl')-phenyl1-3-oxO'propionic acid tert-butylester 3-(2-Methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0,47 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(2-methyl-5-propyl-oxazol-4-yl)-phenyl]-3-oxo-propiomc acid tert-butyl ester (0.58 g) as a light-brown oil. Example K38 3-[3-(5-methyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butylester z) 3-(5-methyl-thia2Ql-4-yl)-benzoic acid methyl ester A solution of crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (2,71 g) and thioformamide (1.83 g) in EtOH (20 ml) was heated at reflux for 1 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as duent to give 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (2.41 g) as white solid. h) 3-[3-(5-methyl-Aiazol-4-yl)-phenyll-3-oxo-propiQnic acid tert-butylester A sample of 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g) was treated with Uthium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-thia2ol-4-yi)-phcnyl]-3-oxo-propiomc acid tert-butyl ester (L9 g) as a pale-yellow oil Example K39 3-f3-(23-Dimethyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester z) 3-(2,5-Diinethyl-thiazol-4-yl)-ben2oic acid methyl ester A mixture of rac-3-(2-bromo-propionyl)-bcn2oic acid methyl ester (6.78 g) and thioacetamide (5.63 g) was heated to 130 ^'Cfor 20 min. The mixture was partitioned between AcOEt and H2O, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gd using AcOEt/hcxane (1:4) as duent to give 3-(2,5-dimethyl-thia2;ol-4-yl)-benzoic acid meth>1 ester (4.97 g) as yellow oil. b) 3-r3-(2>5-Dimethyl-thiazol-4-y!)-phen\i]-3-oxo-propionic acid tert-butyl ester A sample of 3-(2,5-dimethyl-thia2ol-4-yl)-ben2oic acid methyl ester (0.99 g) was treated with lithiimi tert-butyl acetate according to the general procedure K (method b) to give 3-[3-(2,5-dimethyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (1.12 g) as a pale-yellow oil. Example K40 3-Oxo-3-[3-(5-methyl-4-(tetrahvdro-pyran-2-yloxvmethyl)-thia2ol-4-yl]-phenyi1-propionic acid tert-butyl ester a) 3-(2-HydroxymethyI-5-methyl-thia2ol-4-yl)-ben2oic acid methyl ester A solution of rac-3-(2-bromo-propionyI)-ben2oic acid methyl ester (2 Jl g) and 2-(tert.-butylcarbonyloxy)thioacetanude (2.1 g) in EtOH (20 mL) was heated at reflux for 6 h. The mixture was partitioned between AcOEt and brine, and the organic layer was dried and evaporated. A solution of the residual oil and NaOMe (0.54 g) in MeOH (20 mL) was stirred at 60 °C for 1 h. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (1.17 g) as white crystals, MS (ISP) 264.1 [(M+H)^. h) 3-(5-methyl-4-ftetrahvdro-pyran-2-yloxymethyl')-thiazQl-4-yl1-benzoic acid methyl ester A mixture of 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g), dihydropyrane (0.73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 -°C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCO3 solution and with brine, dried and evaporated The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-l5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1,45 g) as a pale-yellow oil. c) 3-0x0-3- [3 r5-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-4-yll -phenyl] -propionic acid tert-butyl ester 3-[5-Methyl-4-(tetrahydro-pyran-2--yloxymethyl)-thiazol-4-yl]-ben2oic acid methyl ester (1.45 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl]-propionic acid tert-butyl ester (2.13 g) as a pale-yellow oil. Example K41 3-Oxo-3-[3[5-propyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-2-yl]-phenyl-propionic acid tert-butyl ester a) 3-(2-Hydroxvmethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester A sample of rac- 3-(2-bromo-pentanoyl)-benzoic acid methyl ester (0.60 g) and and 2-(tert.-butylcarbonyloxy)thioacetamide (0.36 g) in EtOH (4 mL) was heated at reflux for 5 h. The mixture was partitioned between AcOEt and 5% NaHCOs solution, the organic layer was washed with brine, dried and evaporated. A solution of the residual oil and of NaOMe (0.13 g) in MeOH (10 mL) was stirred at 60 °C for 30 min. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.44 g) as an oil. b) 3-f 5-Propyl-4-(tetrahydro-pyran-2-yloxymethyl)-tfaiazol-2-yl1-benzoic acid methyl gster 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (0,73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 ^'C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as duent to give 3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (0.36 g) as a pale-yellow oil. c)3'Oxo-3-f3-(5-propyl-4-(tetrahvdro-pyran-2-yloxyme&yl)-tfaiazol-2-yl]-pheny^ propionic acid tert-butyl ester 3-l5-Propyl-4-(tetrahydro-pyran-2-yloxymeth)d)-thia2ol-2-yl]-benzoic acid methyl ester (0-34 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.42 g) as a pale-yellow oil. Example K42 3-Oxo-3-f3-r2-methyl-5-ftetrahydro-pyran-2-yloxvmetfayl)-thiazQl-4'yl]-phenyl-propionic acid tert-butyl ester al 3-(5-Bromomethyl-2-methyl-thia2oI-4-yl)-benzoic acid methyl ester A mixture of 3-(2,5-dimethyl-thiazol-4-yl)-benzoic acid methyl ester (3.96 g), N-bromosuccinimid (3.13 g) and (X,a'-bis(isobutyronitrile) (0.02 g) in CCI4 (60 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-ben2oic acid methyl ester (6,2 g) as an oil. h) 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-ben2oic acid methyl ester 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-benzoic acid methyl ester was stirred in DMF (16 mL) together with KOAc (2.35 g) at 20 °C for 20 min. MeOH (32 mL) and naOMe (0.86 g) were acided and stirring was continued at 50 '°C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:1) as eluentto give 3-(5-hydroxytnethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (2,93 g) as a white solid. c) 3-[2-methyl-5-ftetrahydro-pyran-2-yloxymethyl)-thiazol-4-yll-benzoic acid methyl ester 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (2.01 mL) and p-toluenesulfonic acid hydrate (0.21 g) in AcOEt (25 mL) was stirred at 20 °Cfor 1 h. The solution was diluted AcOEt, washed with 5% NaHCOa solution and with brine, dried and evaporated. The residual oil was purified by chromatography on siUca gd using AcOEt/hexane (1:3) as eluent to give 3- [2-methyl-5-(tetrahydro-pyran-2-)doxymethyl)-tiuazol-4-yl]-benzoic acid methyl ester (3.8 g) as a pale-ydlow oiL d) 3-0x0-3-r3-r2-methyI-5'rtetrahydro-pyran-2-vIoxvmethyI)-tHazol-4-yl^ propionic acid tert-butyl ester 3-[2-Methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-ben2oic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (methodb) to give crude 3-oxo-3-[3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)' thiazol-4-yl]-phenyl]-propionic acid tert-butyl ester (5.45 g) as a pale-yellow oil. Example K43 3--OXO-3-I [5-(tetrahydro-pyTan'2-yloxymethyl)-thiazol-4-vn -phenyl!-propionic acid tert-butyl ester a) 3-f 5-Bromomethyl-thiazol-4-yl')-benzoic acid methyl ester A mixture of 3-(5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (2.40 g), N-bromosuccinimid (2.01 g) and oc,a'-bis(isobutyronitrile) (0.02 g) in CCU (40 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-thia2ol-4-yl)-benzoic acid methyl ester (3.36 g) as an oil. b^ 3-f 5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester 3-(5-Bromomethyl-thiazol-4-yl)-benzoic acid methyl ester was stirred in DMF (10 mL) together with KOAc (1.52 g) at 20 ^'C for 30 min, MeOH (20 mL) and NaOMe (0.84 g) were acided and stirring was continued at 50 °C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:2) as eluent to give 3-(5-hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (1.43 g) as a white solid. c) 3-[5-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-4-yl]-benzoic acid methyl ester 3-(5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (L25 g), dihydropyrane (0,84 mL) and p-toluenesulfonic acid hydrate (0.10 g) in AcOEt (12 mL) was stirred at 20 °Cfor 3 h. The solution was diluted AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-[5-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1.60 g) as a pale-yellow oil. d) 3-Oxo-3-( (5-(tetrahvdro-pyran-2-yloxyTnethyl)-thia2ol-4-yl]-phenyll-propionic acid tert-butyl ester 3-[5-(Tetrahydro-pyran-2-yioxymethyl)-thiazol--4-yi]-beiizoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-{[5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionic acid tert-butyl ester (2.3 g) as a pale-yellow oil. Example K44 3-[3-(2-Isopropyi-3H'imida2ol-4-yl')-phenyll-3-oxo-propionic acid tert-butyl ester 3) 3-Dihydroxyacetyl-benzoic acid methyl ester A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g), DMSO (17 mL) and 48% HBr (3.4 mL) was heated to 55 °C for 30 min. The mixture was partitioned between AcOEt and H2O and the organic layer was washed with brine, dried and evaporated to give 3-dihydroxyacetyl-benzoic acid methyl ester (1.06 g) as a white solid. h) 3'(2-I$opropyl-3H-imidazol-4-yl)-benzoic acid methyl ester A solution of 3-dihydroxyacetyl-benzoic acid methyl ester (0.36 g) and 2-methyl-propionaldehyde (0.24 ml) in 5% aqueous NH3 (6 mL) was heated to 100 °C for Ih, The mixture was evaporated in vacuum and the solution of the residue in a mixture of MeOH (10 mL) and 4NHC1/Et20 (2 mL) was heated to 40 °C for 18 h. The solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaaCOa solution and brine, dried and evaporated. The residue was chromatographed on silica gel using AcOEt as eluent to give 3-(2-isopropyl-3H-imidazol-4-yl)'ben2oic acid methyl ester (0.37 g) as a pale-yellow oil. c) 3'f3-(2-Isopropyl-3H-imidazol-4-yl)-phenyll-3-oxo-propionic acid tert-butylester 3-(2-Isopropyl-3H-imidazol-4-yl)-benzoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give cmde 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (0.25 g) as a pale-yellow oil. The following examples relate to the preparation of the 6-aryl-2,2-diniethyl-[l,3]dioxin-4-ones (general formula IV), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H): General procedure L Preparation of 6-aryl-2,2-dimethyl-fL3]dioxin-4-ones Method a) The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from 3-aryl-3-oxo-propionic acids and catalytic amount of cone. H2SO4 or trifluoroacetic acid (TFA) in isopropenyl acetate at 23 -€ according to Chem, Pharm, Bull 1983,3J, 1896. The final products were purified by silica gel coliunn chromatography with hexane/EtOAc. Method b) The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from the tert.-butyl 3-aryl-3-oxo-propionates by treatment with trifluoroacetic anhydride (TFAA) in a mixture of TFA and acetone at 23 -°C according to Tetrahedron Lett. 1998,39,2253. The final products were if necessary purified by silica gel column chromatography with hexane/EtOAc. Example LI 3-(2,2-Dimethyl-6-oxo-6H-ri.3ldioxin-4'vD-benzonitrile The 3-(3-cyano-phenyl)-3-oxo-propionic acid was prepared from 3-cyanobenzoyl chloride (828 mg, 5 mmol) and bis(trimethylsilyl)malonate (2.56 mL, 10 mmol) with n-BuLi (1,6M in hexane, 6.25 mL) in ether at-60 °C to 0 °C according to general procedure M (method c2). The crude material (1.04 g) was transformed into the title compound by stirring in isopropenyl acetate and TFA according to general procedure L (method a). Obtained as a light yellow solid (0.8 g). MS (EI) 229 (M^); mp 138 °C (dec). Example L2 4-(2.2-Dimethyl-6-oxo-6H-fL3ldioxin-4-yl1-pvridine-2-carbonitrile The title compound was prepared from 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example MlO) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a brown solid (3.30 g). MS (H) 230 (M^); mp 132 X (dec). Example L3 6'f3'Imidazol-l-yl-phenyi)-2.2-dimethyl-fh3ldioxin-4-one The 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid was prepared from 3-(lH-imidazol-l-yl)ben2oyl chloride hydrochloride [prepared by treatment of 3-(lH-imidazoM-yl)-benzoic acid (/. Med. Chem. 1987,30,1342; CAS-No. [108035-47-8] with SOCI2) and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 ^'C according to general procedure K (method cl). The crude material was transformed into the title compound by stirring in isopropenyl acetate and cone. H2SO4 according to general procedure L (method a). Obtained as an orange semisolid (617 mg). MS (EI) 270 (M^). Example L4 2.2-Dimethyl-6-f3-fL23ltriazol-l-vI-phenyl)-rL3ldioxin-4-one The tide compound was prepared from 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K23) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a beige solid (7.80 g). MS (EI) 271 (M--); mp 144-147 °C (dec). General procedure M: Preparation of {2-[3-aryI-3-oxo-propionylamino]-phenyl}-carbamic acid tert.-butyl ester by reaction of (2-amino-phenyl)-carbamic acid tert-butyl esters with ethyl or tert.-butyi 3-aryl-3-oxo-propionates or 6-aryl-2^-dimethyl-[l,3]dioxin-4-ones: A mixture of the (2-amino-phenyl)-carbamic acid tert.-butyl ester or (1.0-1-2 mmol) and (1.0-1-5 mmol) of the ethyl or tert.-butyl 3-aryl-3-oxo-propionate or 6-aryl-2,2-dimethyl-[l,3]dioxin-4-one was heated in toluene (4-8 mL) to 80 *€ to 120 'C until tic indicated complete consumption of the minor component. The solution was allowed to cool to 23 °C, whereupon the product generally crystallized (in cases where crystallization failed to appear it was induced by acidition of hexane or ether, alternatively the reaction mixture was directly subjected to silica gel column chromatography). The solid was filtered off, washed with ether or mixtures of ether/hexane and dried in vacuum to give the {2-[3-aryl-3-oxo-propionylamino]' phenyil-carbamic acid terL-butyl esters, which was used direcdy in the following step or - if necessary - was purified by recrystallization or by silica gd column chromatography. Example Ml {4-Chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimethylamino-phenyll-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (0.5 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 62088-13-5; prepared from 3-cyanobenzoyl chloride according to general procedure K, method a] (0.55 mmol) according to the general procedure M. Obtained as a white solid (160 mg). MS (ISP) 457 [(M+H)--]; mp 159-163 °C. Example M2 l4-Chloro-5-dimethylamino-2-r3-oxo-3-r3-rh23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) (150 mg> 0.58 mmol) according to the general procedure M. Obtained as a beige solid (160 mg). MS (ISP) 499 [(M+H)--] and 501 [(M+2+H)1; mp 136-137 °C. Example M3 fRS)-r4-Chloro-5-dimethylamino-2-f3-oxo-3-^3-[5-ftetrahvdro-pyran-2- yloxvmethyl)-fL2.3ltria2ol-l-yll-phenyl}-prQpionylaminoVphenyl-carbamicacid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow oil (257 mg). MS (ISP) 613 [(M+H)'] and 615 [(M+2+H)']. Example M4 (243-f3-cyano-phenvD-3-oxo-propiQnylamino1-5-dime1hylamino-4-phenvIethvnyl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carbamic acid tert.-but7l ester (Example J2) and 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-ben2onitrile (Example LI) according to the general procedure M. Obtained as an orange solid (108 mg). MS(ISP)523[(M+H)1. Example M5 /5-Dimethylamino-2-r3'Oxo-3-r3-fL2.3ltriazol-l-yI-phenyD-propionylamino1-4' phenylethvnyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylaminO-phenyl)-carbamic acid tert.-butyl ester (Example J2) and 3-oxo-3-(3-[l,2,3]tria2oM-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as an orange solid (148 mg). MS(ISP)565[(M+H)']. Example M6 f4-Chloro-5-dimetfaylamino-2-l3-[3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylamino I-phenyl) - carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(3-methyi-isoxa2ol-5-yI)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (450 mg, 075 mmol) according to the general procedure M. Obtained as a white solid (136 mg). MS (ISP) 513 [(M-hH)--] and 515 [(M+2+H)']; mp 109-114 °C Example M7 fRS)-r2-Dimethylamino-2'3'-diflu6ro-5-r3-oxo-3-l^-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23]triazoM-yl1-phenvU-propionylamino)-biphenyl-4-yll-carbamic add tert.-butylester The title compound was prepared from (5-amino-2-dimethyiamino-2,3'-difluoro-biphenyl-4-yl)-carbamic acid terL-butyl ester (Example J3) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2^]tria2ol-l-yl]-phenyi}-propionic acid tert- butyl ester (Example K5) according to the general procedure M. Obtained as a yellow solid (253 mg). MS (ISP) 691 [(M+H)--]. Example M8 (2-Dimethylamino-2\3'-difluoro-5-r3-oxo-3-f3-rL23ltria2ol-l-yl-phenyl)-propionylamino1-biphenyl-4'yll-carbamic acid tert.-butylester The title compoimd was prepared from (5-amino-2-dimethylamino-2',3-difIuoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J3) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as a yellow solid (253 mg), MS (ISP) 577 [(M+H)--], Example M9 {5-f3-(3-cyano-phenyl')-3-oxo-propionylaminol-2-dimethylamino-2\3'-difluorO' biphenyl-4-yll-Carbamic acid tert.-butylester The title compound was prepared from (5-amino-2-dimethylantiino-2',3'-difluoro-biphenyl-4-yl)-Carbamic acid tert.-butyl ester (Example J3) 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-benzonitrile (Example LI) according to the general procedure M. Obtained as a yellow solid (145 mg). MS(ISP)535[(M+H)1. Example MlO (4-Chloro-5-dimethylamino-2'{3-(2-f3-methyl-isoxazol-5-vIVpvridin-4-yn-3-oxo-propionylaminol-phenyD-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-Carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yl]-3-oxo-propionic acid tert.-butyl ester (Example K6) (170 mg, 0.56 mmol) according to the general procedure M. Obtained as a brown solid (206 mg). MS (ISP) 514 [(M+H)+] and 516 [(M+2+H)+]; mp 181-183 °C. Example Mil (4-CMoro-5-r(2-metfaoxy-ethyl)-methyl-aminol-2-l3-f3-(3-methyl-isoxa2ol-5-yD-phenyl]-3-oxO'propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (165 mg, 0.55 nrniol) according to the general procedure M. Obtained as an amorphous yellow substance (207 mg), MS (ISP) 557 [(M+H)1 and 559 [(M+2+H)-']. Example M12 (4-Chloro-5-f(2-methoxy-etfavi)>methyl-aminol-2-l3-(2-f3-methvMsoxazoI-5-yl)-pvridin-4-yI1-3-oxo-propionylaminol-phenyIVcarbamic acid tert.-butylester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert,-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yI]-3-oxo-propionic acid tert.-butyl ester (Example K6) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (190 mg). MS (ISP) 558 [(M+H)1 and 560 [(M+2+H)']; mp 148 °C Example M13 (RS)-f4-Chloro-5-f(2-methoxv-ethyl)-methyl-amino1-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-vIoxvmethyl)- f 1,2,31 triazol-1 -yl] -phenyl-propionylamino)-phenyl -carbamic acid tert.-butvi ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyi)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyi ester (Example K5) (200 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg). MS (ISP) 657 [(M+H)+] and 659 [(M+2+H)1. Example M14 U-Chloro-5-[(2-methoxv-ethyl)-methyl-amino1-243-oxo-3-f3Jl,23ltriazol-l-v^ phenyl)-propionylamino]'phenvH-carbamic acid tert--butyl ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-eth7l)-methyl-amino]-phenyl}-carbamic acid tcrt-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-oxo-3-(3-[l,23]tria2oM->1-phenyl)-propionicacid ethyl ester (Example Kl) (165 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (167 mg). MS (ISP) 543 [(M-hH)--] and 545 [(M+2^H)1. tompl^Ml? {4-Chloro-2-f3-(2-cyano-p)Tidin-4-\i)-3-oxo-propionylaminoV5-dimethylamino-phenylj-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethyiamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (155 mg). MS (ISP) 458 [(M+H)--] and 460 [(M+2+H)+];mp llO°C Example M16 (4-Chloro-5-dimet3aylamino-2-{3-f3-(2-methyl-2H-pvrazol-3-vD-phenvi1'3oxO-propionyiaminol-phenyl)-carbamic acid tert.-butylester The title compoimd was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K7) (180 mg, 0,6 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg). MS (ISP) 512 [(M+H)--] and 514 [(M+2+H)+]. - Example M17 (RS)-(5-Dimethylamino-2-(3-oxo-3-(3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23ltriazol-l'yl]-phenvU-propionylamino)-4-trifluoromethyl-phen'vdl-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (160 mg, 03 mmol) and (RS)-3 -oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (201 mg, 0-5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (247 mg). MS (ISP) 647 [(M+H)--]. Example Ml8 (5-Dimethylamino-2-J3-f3-f3-methyl-isoxazol'5-vD-phenyl1-3-oxo-propionylaminoU4'trifluoromethyl-phenyl')-Carbamic acid tert,-butylester The title compoimd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid terL-butyl ester (Example K4) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (94 mg). MS (ISP) 547 [(M+H)+]. Example M19 f4-ChlorO'5-dimethylamino-2-{3-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0,5 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionicacidtert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (176 mg). MS (ISP) 556 [(M+H)--] and 558 [(M+2+H)+]. Example M20 f4-Chloro--5'dimethylamino--2-B-f3-f3-methoxvmethyl-isoxazol-5-yl)-phenyl)-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compotmd was prepared from (2-ainino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (Example K9) according to the general procedure M. Obtained as a yellow solid (205 mg). MS (ISP) 543 [(M+H)T and 545 [(M+2-fH)--]. Example M21 (2-r3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino]-5-dimethylamino-4-trifluoromethyl-phenyll-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromet]iyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, LO mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example K3) (246 mg, 1.0 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (297 mg). MS(ISP)492[(M+H)+]. Example M22 (2'-Fluoro-5-[3-(3-imidazol-l-yl-phenyD-3-oxo-propionylamino1-2-(2,2.2-trifluoro-ethoxv)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 6-(3-imidazoH-yl-phenyl)-2,2-dimethyl-[l,3]dioxin-4-one (Example L3) (160 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous brown substance (167 mg). MS(ISP)492[(M+H)-']. Example M23 (2'-Fluoro-5-(3-r3-(3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-2-f 2.2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (160 mg, 0.53 mmol) according to the general procedure M. Obtained as a white solid (40 mg). MS (ISN) 626 [(M-H)-]; mp 121-123 °C. Example M24 (2'-FIuoro-5-f3-oxo-3-(34h23ltriazol-l-yl-phenyl)-propiQnylamino1-2-(2,2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The title compoxmd was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifiuoro-ethoxy)-biphen)d-4-yl]-carbamic acid tert-butyl ester (Example J5) (200 mg, 0-5 mmol) and 3-oxo3-(3-[l^,3]triazol-l-yl-phenyl)-propionicacid ethyl ester (Example Kl) (150 mg, 0.57 mmol) according to the general procedure M. Obtained as a light yeUow solid (110 mg). MS (ISP) 614 [(M+H)--]; mp 54-56 °C Example M25 (RS)-[2^-Fluoro-5-(3-oxo-3-{345-ftetrahvdro-pwan-2-ylox\nmethyl)-fL23ltria2o^ yl1-phenyl}-propionvIamino)-2-('2.2.2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester The title compound was prepared from [5-amino-2'-fluorO-2-(2,2>2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (220 mg, 0.55 mmol) according to the general procedure M. Obtained as a yellow oil(100 mg). Example M26 (RS)-[4-Chloro-5-fethyl-methyl-aminoV2-(3-oxo-3-(3-r5-ftetrahydro-pyran-2-yloxymethyl)-rL23ltriazol-l-yll-phenyll-propionylamino)-phenyl1-carbamicadd tert-butylester The titlt ipound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)' phenyl]-curbamic acid tert-butyl ester (Example J7) (300 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl\|-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (500 mg), MS (ISP) 627.1 [(M+H)--]. Example M27 (RSVf4-Chloro-5-(methyl-propyl-amino)-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-yIoxvTnethyl]-fl,23ltriazol-l-yl1-phenyIt-propionylamino)-phenyl-carbamicadd tert'butylester The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (402mg, I.O mmol) according to the general procedure M. Obtained as a yellow foam (410 mg). MS (ISP) 641.3 [(M+H)1. Example M28 (RS)-r4-Chloro-5-fdiethyl-ammQV2-f3-oxo-3-(3-r5-ftetrahvdro-pyran-2-yloxymethvD- \ 1.231 triazol-1 -yll -phenyl-propionylamino Vphenyll -carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(diethyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J9) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yI]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg). MS (ISP) 64L3 [(M+H)+]. Example M29 fRSVI'4-Chloro-5-dimethylamino-2-(3-oxo-3-i3-f3-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol'5-yll-phenyU-propionylamino)-phenyl1-carbamicacidtert.-butyl ester The title compotind was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3- [3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl] -phenyl}-propionic acid tert.-butyl ester (Example K12) (201 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg). MS (ISP) 613.1 [(M+H)--] and 615 [(M+2H-H)+]. Example M30 (RS)-r4-CHoro-2-f3-oxo-3-l345-ftetrahvdro-pyran-2-yloxvmetfayl)-[L2,3ltriazol'l-yll -phenyll-propionylaminoV5-pvrrolidin-l'yl-phenyl1 -carbamic acid tert.-butylester The tide compoimd was prepared from (2-amino-4-chloro-5-pyrrolidin-l-yl-phenyl)-carbaniic acid tert.-butyl ester (Example JIO) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.' butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (228 mg), MS (ISP) 639 [(M+H)--] and 641 [(M+2+H)+]. Example M31 (5-Dimethylamino-2-^3-r3-(2-metfayl'2H-pvrazol-3-yl)-phenyll-3-oxo-propionylaminQl-4-trifluoromethyI-phenyD-carbainic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K7) (150 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (90 mg). MS (ISP) 546.2 [(M+H)--], Example M32 fRS)-r4-Chloro-5-dimethylamino-2-f3-B-F3-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol-5-yl] -phenAd}-3-oxo-propionylamino)-phenyl1 -carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethyIamino-phenyO-carbamic acid terL-butyl ester (Example Jl) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]'phenyl}-3-oxo-propionic acid tert-butyl ester (Example K13) according to the general procedure M, Obtained as a light yellow solid (187 mg). MS (ISN) 626 [(M-H)-] and 628 [(M+2-H)']. Example M33 fRS)-r4-Chloro-5-fcvclopropvI-methyl-amino)-2-f3-oxo-3-l3-r5-rtetrahvdro-pyran-2-yloxvmethyl)-fl.2.3ltriazol-l-yl]-phenvU-propionylaminoVphenyl]-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example JU) (156 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2oH-yl]-phenyll-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow solid (215 mg). MS (ISN) 637.1 [(M-H)'] and 639 [(M+2-H)-]; mp 47-49 °C. Example M34 (5-Dimethylamino-2-l3-f3-(5-dimethylaminomethyl-ri.23ltriazoM-yl)-phenyl-3-oxo-propionvIaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (160 mg, 0.5 rQmol)and3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (195 mg). MS (ISN) 588 [(M-H)-]. Example M35 (RS)-[4-Chloro-5-dimethylamino-2-f3-l3-(2-methyl'5-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pyrazol-3-yn-phenvU-3-oxo-propionylaminoVphenyn-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chIoro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (200 mg, 0.7 mmol) and (RS)-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K14) (290 mg, 07 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (329 mg). MS (ISN) 624.0 [(M-H)-] and 626 [(M+2-H)']. Example M36 {2-[3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino1-5-pvrrolidin-l-yl-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-pyTrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J12) (173 mg, 0.5 nrniol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (150 mg, 0,61 mmol) according to the general procedure M. Obtained as a yellow solid (140 mg). MS(ISP)518[(M+H)1- Example M37 fRS)42-r3-Oxo-3-i3-(5-(tetrahvdro-pyran-2-yloxvmethvD4L23ltriazol-l-yl1-phenvU-propionylamino)-5--pvrrolidin-l-yl'4-trifluorometfayl-phenyl]-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifIuoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J12) (173 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-I-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as an orange foam (168 mg). MS(ISP)673[(M-hH)+]. Example M38 f RS)- (5-Dimethylamino-4'fluoro-2-(3-0X0-3-13- f 5-f tetrahydro-pyran-2-yloxvmethyl)-fL23ltriazol-l-yn-phenyll-propionylamino)-phenyn-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-fiuoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1,0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid terL-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (417 mg). MS(ISN)595[(M-H)-]. Example M39 (5-Dimethylammo-2-l3-[3-(5-dimethylaminomethyl'[L2.3ltria2ol-l-vD-phenyl-3-oxo-propionylamino}-4-fluoro-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-anfiino-5-dimethylamino-4-£luoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (344 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (211 mg). MS(ISN)538[(M-H)-]. Example M40 fRSVr5-Dimetfaylamino-4-fluoro-2-(3-oxo-3-B-r3-(tetrahvdro-pyran-2-yloxymetfavD-isoxazol'5-yl]-phenyl}-propionylamino)-phenyncarbamic acid tert.-butyl ester The tide compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example KI2) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (360 mg). MS(ISN)595[(M-H)-]. Example M41 (RS)-(5-DimethylaminO'2-f3-oxo-3-{3-f3-ftetrahvdro-pyran-2-yloxvmethyl)-isoxazol-5-yll -phenyl}-propionylamino)-4-trifluoromethyl-phenyl1 -carbamic acid tert.-butyl ester The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (565 mg, L77 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example K12) (710 mg, 1,77 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (721 mg), MS(ISN)645[(M-H)']. Example M42 (RSV(5-Dimethylamino-4-fluoro-2-r3>oxQ-3-{3-f3-ftetrahvdro-pyran-2-yloxymethyl)-isoxa2ol-5-yn-phenyl}-propionylamino)-phenyiVcarbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M- Obtained as a yellow amorphous substance (273 mg). MS(ISP)497l(M-f-H)-']. Example M43 fRSVf4-ChloTu-5-dimethylamino-2-f3-oxo-3-B45-rtetrahvdro-pyran-2-yloxvmethyl)-isoxazol-3-vn -phenyll-propionylamino)-phenyll -carbamic acid tert.* butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionic acid tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (232 mg). MS (ISN) 611.1 [(M-H)-] and 613 [{M+2-Hr]. Example M44 (RSVf4-ChIoro-2-(3-oxo-3-l3-r5-ftetrahvdro-pyran-2-yIoxvmethyl)-[L23ltriazol-l-yIl-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl1-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-4-chloro-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example J14) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (257 mg). MS (ISP) 653.2 [(M+H)+] and 655 [(M+2+H)1. Example M45 (RS)-f5'Dimethylamino-2-(3-oxQ-3-l3-r5-(tetrahydro-pyran-2-yloxymethyD-isoxazol-3-yl1 -phenyll-propionylamino)-4-trifluoromethyl-phenyn -carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl] -phenyl}-propionic acid tert.-butyl ester (Example K15) according to the general procedure M. Obtained as a light yellow foam (224 mg). MS (ISP) 647.2 KM+H)--]. Example M46 {4-ChIoro-5-dimethylamino-2-f3-OXo-3-(3-pyrazol-lyl-phenyl)-propionyIamino]-phenyl}-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K16) according to the general procedure M. Obtained as a light yellow solid (135 mg). MS (ISP) 498 [(M-hH)--] and 500 [(M+2+Hr]; mp 148-149 °C. Example M47 {2-r3-(2-Cyano-pyridin-4-yI)-3-oxo-propionyIaminol-4-fluoro-5'pyrrolidin-l-yl-phenyU-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert,-butyl ester (Example 115) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (196 mg). MS (ISP) 468 [(M+H)']; mp 231 °C (dec). Example M48 (4-Fluoro-2-l3-[3-(3-methyl-isoxa2oI-5-yl')-phenvI1-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-fiuoro-5-pyrrolidin-l-yl-phenyl)-carbamic acidtert,-butyl ester (Example Jl5) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propiomc acid tert.-butyl ester (Example K4) according to the general procedure M. Obtained as a light yellow solid (126 mg). MS (ISP) 468 [(M+H)+]; mp 186 °C Example M49 fRS)-[4-Fluoro-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-rL23ltria2ol-l-yl1-phenvU-propionylamino)-5-pyrroIidin-l-yl-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidiQ-l-yl-phenyl) carbamic acid tert-butyl ester (Example Jl5) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>23]triazol-l-yi]-phenyl}-propionic acid terL-but)i ester (Example K5) according to the general procedure M. Obtained as an orange viscous oU (268 mg). MS(ISP)623[(M+Hr]. Example M50 l5-Azetidin-l-yl-4-chloro-2-[3-r2-cyano-pyridin-4-vI)-3-oxo-propionylamino]-phenvU-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butyl ester (Example J16) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (142 mg). MS (ISP) 470 [(M+H)--] and 472 [(M+2+H)']; mp 168 °C (dec). Example M51 fRSV(2-f3-Oxo-3-l3-[5-(tetrahydro-pyran'2-ylQxymethyD-isoxazol-3-yll'phenyll-propionylaminoVS-pyrrolidin- l-yl'4-trifluoromethylphenyl -carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI2) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yIoxymethyI)-isoxa2oI-3-yl]-phenyl}-propionicadd tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (522 mg). MS (ISN) 671.2 [(M-H)-], Example M52 l5'Azetidin-l-yl-2-(-3-(2-cyano-pvridin-4-yl)-3-oxo-propionylamino1'4-trifluoromethyl-phenylt-carbamic acid tert.-but\^ ester The title compound was prepared from (2-aminO-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J17) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light yellow solid(131 mg). MS (ISP) 470 [(M+H)--]; mp 166-167 °C. Example M53 (5-Azetidin-l-yl-2-B-r3-f3-m€thyl-isoxa2ol'5-yl>>phenyll-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.'butylester The tide compound was prepared from (2-amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Lxamplc J17) and 3-[3-(3-methyHsoxazol-5-yl)-phenyl]-3-oxo-propionic acid tcrL-but)1 ester (Example K4) according to the general procedure M. Obtained as a light ycUow foam (218 mg). MS (ISN) 557.2 [(M-H)']; mp 83-84 C fRSV[5-Azetidin-l-yl-2-(3-oxo>3- fh23ltria2ol-l-yl1-phenyll-propionylamino)-4-trifluoromethyl-phenyll'Carbamic acid tert.-butylester ——.^1 ,11-1. , The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI7) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoI-l-yi]-phen)d}-propionic acid tert-butyl ester (Example K5) according to the general procedure M, Obtained as a yellow foam (450 mg). MS (ISN) 657.1 [(M-H)']; mp 76-77 X. Example M55 {5-Dimethylamino-2-[3-OXO'3-(3-pyra2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl'phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (485 mg), MS (ISN) 530 [(M-H)+]. Example M56 t5-Dimethylamino-2-f3-QXo-3-f3-fl.2.4ltriazol-4-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoromethyl-phenyi)-carbamic acid tert-butyl ester (Example J6) (383 mg, 1.2 mmol) and 3-oxO-3-(3-[l,2,4]triazol-4-yl-phenyl)-propionic acid ethyl ester [CAS-No. 335255-97-5] (259 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow solid (290 mg). MS (ISP) 533.3 [(M-i-H)l; mp 58-62 °C. Example M57 (5-Dimethylamino-2-f3-r3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)--Carbamic acid tert-butyl ester (Example J6) and 6-(3-imidazol-l-yl-phenyl)-2>2-dimethyl-[l,3]dioxin-4-one (Example L3) according to the general procedure M. Obtained as an orange oil (238 mg). MS(ISP)432[(M+H)']. Example M58 (RS)-f4-Chloro-5-dimethylamino-2-f3-oxo-3-(3--f4-(tetrahydrQ-pyran-2-ylQxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyI]-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (429 mg, L5 mmol) and (RS)-3-oxo-3- {3- [4- (tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl} -propionic acid tert.-butyl ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (710 mg). MS (ISN) 610 [(M-H)-] and 612 [(M+2-H)'l. Example M59 fRSV(5-Dimethylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-yloxvmethvD-pyrazol-l-yl'\|-phenvU-propionylamino)-4-trifluoromethyl-phenyIl-carbamicacid tert.-butyl ester The title compoimd was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (479 mg, 1.5 mmol) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yioxymethyi)-pyrazol-l-yl]-phenyl}-propionic acid tert-butyi ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M. Obtained as a piiik amorphous substance (641 mg). MS (ISN) 644 [(M'H)-]. Example M60 fRS)'[5-Dimethylamino-2-(3-B-[3-methyl-4-('tetrahvdrO'pyran-2-vIoxymethyl)-isoxa2ol-5'yI]-phenyn3-oxo-propionylamino)-4-trifluoromethyl-phenyI1-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K13) according to the general procedure M. Obtained as a red oil (424 mg). MS (ISN) 626 [(M-H)-]. Example M61 fRSV(5-Dimetfaylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-vioxvmetfayl)-isoxazol-S-yll -phenyl KpropionylaminoV4-trifluoromethyl-phenyn -carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionicadd terL-butyl ester (Example K18) according to the general procedure M. Obtained as a light yellow solid(145 mg). MS(ISP)647[(M+Hn. Example M62 (RSV(5-DimethyIamino-2-(3'[3-(2-methylsuIfanvI-imidazoI-l-yl)-phenyl-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-tri£luoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (319 mg, 1-0 mmol) and 3-[3-(2-methylsulfanyI-imida2oI-l-yl)-phenyI]-3-oxo-propiomcadd tert-butyl ester [CAS-No. 335256-01-4] (432 mg, 1.3 mmol) according to the general procedure M. Obtained as a light brown amorphous substance (493 mg). MS (ISP) 333.2 [(M+H)--]. Example M63 fRSVr5-Dimethylamino-2-(3-(3-(2-methyl-4-(tetrahvdro-pyran-2-ylQXvmethyl)-2H-pyra2o]-3-yl1-phenyil-3'OXopropionylaminoV4'trifluorometfayl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-{3-[2-methyl-4-(tetrahydro-pyran-2-ylox)Tneth>1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert-butyl ester (Example K19) according to the general procedure M. Obtained as a light red solid (576 mg). MS (ISN) 658 [(M-H)-]. Example M64 l4-Chloro-5-dimethylamino-2-f3-oxo-3-f 3-\| 1 >2,4]tria2ol-l-yl-phenyl) propionylamino1-phenyllcarbamic acid tert.-butyl ester The title compo d was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carban. dcid terL-but)d ester (Example Jl) and 3-oxo-3-(3-[l>2,4]tria2ol-l-yl-phenyl)-propionic acid tert-but)d ester [G\S-No, 335255-88-4] according to the general procedure M. Obtained as a light yellow solid (427 mg). MS (ISN) 497 [(M-H)-] and 499 [(M+2-H)-]. Example M65 {5-Dimethylamino-2-f3-oxo-3-(3-[l,2,4]triazoM-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-anuno-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and 3-oxo-3-(3' [l>2,4]triazol-l-yl-phenyi)-propionic acid tert-butyl ester [CAS-No. 335255-88-4] according to the general procedure M. Obtained as a light red solid (502 mg). MS(ISN)531[(M-H)-]. . Example M66 {2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimeth^amino-4-trifluorometh^^-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (320 mg, 1-0 mmol) and 3-(2,2-dimethyi-6-oxo-6H-[13]dioxin-4-yl)-benzonitrile (Example LI) (275 mg, 1.2 mmol) according to the general procedure M. Obtained as a reid viscous oil (196 mg). MS (ISN) 489.1 [(M-H)-]. Example M67 fRS)-r5-fCvcIopropvImethyl-methyl-amino)-2-f3-oxo-3-{3-(5-ftetrahvdrO'pyran-2-yloxvinethyD - [ 1,231 triazol- l-yl1 -phenyl! -propionylamino V4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-anmio-5-(cyclopropylmethyl-methyl-amino)-4-trxfluoromethyI-phenyl]-carbamicacid tert,-butyl ester (Example JIS) (719 mg, 2.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (803 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (985 mg). MS (ISP) 687 [(M+H)+]. Example M68 [2-f3-(2-Cyano-pyridin-4-yl)-3-oxo-propiQnvIamino]-5-fcyclopropylmethyI-metfayl' amino)-4-trifluorometfayl-phenyl-carbamic acid tert.-butylester The title compound was prepared from [2-amino-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example JIB) (180 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (206 mg). MS (ISP) 532 [(M+H)+]. Example M69 (RS)-l5-Dimethylamino-2-r3-oxo-3-f3-{2-r2-(tetrahvdro-pyran-2-yloxvVethyl1-2H-pvrazoI-3-yll-phenyl)-propionylaminol-4-trifluoromethyl-phenyn-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifiuoro-methyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (639 mg, 2.0 mmol) and (RS)-3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-phenyl)-propionic acid tert-butyl ester (Example K20) (829 mg, 2.0 mmol) according to the general procedure M. Obtained as a pink amorphous substance (272 mg). MS (ISN) 658 [(M-H)-]. Example M70 (2-r3-(2-cyano-pvridin-4-yl)-3-OXo-propionylaminoV5-fcvclopropyl-methyl-aminoV4-trifluoromethyl-phenyl-carbamic acid tert.-butyl ester The title compound was prepared from [2-amino-5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example J19) (259 mg, 0.75 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert,-butyl ester (Example K3) (192 mg, 0.78 mmol) according to the general procedure M. Obtained as a yellow solid (228 mg). MS (ISN) 516.2 [(M-H)-]; mp 114-116 °C. Example M71 {2-Dimethylamino-2'-fluoro-5-f3-oxo-3-f3-fL23ltriazQl-l-yl-phenyl)-propionylamino1-biphenyl-4-yU-carbamic acid tert-butyi ester The title compound was prepared from (5-amino-2-dimethyIamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J20) (691 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazoM-yl-phenyl)-[l,3]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow solid (820 mg). Mp 125-135 °C. Example M72 (RSyl5-Dimethylamino-2-[3-oxo-3-(3-l5-(2-ftetrahvdro-pyran-2-yloxvVethyll-fl.23ltria2ol-l-yll-phenyl)-propionvIamino1-4-trifluoromethyl-phenvU-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,2,3]triazol-l-yl}-phenyl)-propionicacid tert-butyl ester (Example K21) according to the general procedure M. Obtained as a light red oil (527 mg). MS (ISP) 577 [(M+H)--]. Example M73 fRS)-[5-Dimethylamino-2-(3-oxo-3-f3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-pyrazol-l-yl]-phenyll-propionylamino)-4-trifluoromethyl-phenyl1-carbamicacid tert.-butylester The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionic acid ethyl ester (Example K22) according to the general procedure M. Obtained as a brown oil (179 mg). MS (ISP) 646 [(M+H)-]. Example M74 (5-Dimetfaylamino-2-f3-oxo-3-('3-[L23ltriazoM-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (639 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazol-l-yl-phenyl)-[13]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a red solid (915 mg). MS (ISP) 533,3 [(M+H)+]; mp 79-81 °C. Example M75 [2-f3-(2-cyano-pyridin-4-yl)'3-oxo-propionylamino1-5-(2,2.2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J21) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light brown s.olid (262 mg). MS (ISN) 545.0 [(M-H)']; mp 158 °C (dec). Example M76 l2-[3-(3-cyano-phenyl)-3-oxQ-propionyIamino1-4-dimethylaminO'5-methyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (300 mg, 1.0 mmol) and 3-(3-cyano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (250 mg> 57%). MS (ISP) 437.4 [(M+H)--]. Example M77 (RSV[5-DimethylaminO'4-methyl'2-(3-oxo-3-{3'[5-(tetrahydro-pyran-2-yloxvmethyl)-fl.2.3ltria2ol-l-yl1-phenyU-propionylaminoVphenyl]-carbamicadd tert-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic add tert-butyl ester (Example K5) (402 mg, 1-0 mmol) according to the general procedure M. Obtained as a yellow foam (420 mg, 71%). MS (ISP) 593.5 [(M+H)--]. Example M78 {5-Cyano-2-f3-(3-cyano-phenyl)-3-oxo-propionylamino1-4-dimethylamino-phenyl}-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butyi ester (Example J23) (276 mg, 1.0 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a brown foam (290 mg, 65%). MS (ISP) 448.3 [(M+H)--]. Example M79 [2-f3-f3-cyano-phenvD-3-oxo-propionylamino]-5-methyI-4fmethyl-propyl-amino)phenv]]-carbamic acid tert-butylester The title compound was prepared from [2-aminO-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (293 mg, 1.0 mmol) and 3-(3-qrano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (170 mg, 37%). MS (ISP) 463.3 [(M-H)-], Example M80 (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-l3-(5-(tetrahvdropyran-2-yloxymethvD-[l,2,3ltriazoI-l-vI]-phenvU-propionylamino)-phenyl'Carbamicacid tert-butylester The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-pheiiyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (350 mg, 56%). MS (ISP) 621.2 [(M+H)1. Example M81 fRSV[5-fEthyl-methyl-aminoV4'methyl-2-(3-QXo-3-(3-(5-(tetrahvdro-pyran-2-yloxymethvD-fL2.3ltriazol-l-yl]-phenyI}-propionylamino)-phenyl-carbamicacid tert-butylester The title compound was prepared from [2-amino-5-(ethyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J25) (279 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (400 mg, 66%). MS (ISP) 607.1 [(M+H)1. Example M82 (RSVf4-cyano-5-dimethylamino-2-(3-oxo-3-(3-(5-ftetrahvdro>pyran-2-yloxvmethyl)-fl.23ltriazol-l-yl1-phenyU-propionylamino)-phenyll-carbamicadd tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-dimethylaminO-phenyl)-carbamic acid tert-butyl ester (Example J23) (276 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyi}-propionicadd tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to tiie general procedure M. Obtained as a light brovm foam (360 mg, 59%). MS (ISP) 602.1 [(M-H)1. Example M83 fRS)-[4-Chloro-5-fisopropyl-methyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyl)-Fl,2,3ltriazol-l-yll-phenyl}-propionylamino)-phenyl)-carbamicadd tert-butyl ester The title compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J26) (300 mg, 0.96 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (383 mg, 0.96 mmol) according to the general procedxire M. Obtained as a light yellow oil (530 mg, 86%). MS (ISP) 639.2 [(M-H)-]. Example M84 [4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionylaminol-5-(methyl-propyl-amino)-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyi]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 65%)! MS (ISP) 519.3 [(M-H)'], &tapiple M?5 (4-Cyano-5-dimethylamino-2- The tide compound was prepared from (2-amino-4-q^ano-5-dimethylaxnino-phenyl)-carbamic acid tert-butyl ester (Example ]23) (276 mg, 1.0 mmol) and 3-[3-(3methyl-isoxazol-5-yl)-phenyI]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (320 mg, 64%). MS (ISP) 504.3 [(M+H)+]. (5-(£thyl-methyl-amino)-4-methv'i-2-(3'[3-(3-methyi-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester The title compoiund was prepared from {2-amino-5-(cthyl-methyi-amino)-4-methyl-phenyl]-carbamic acid tert-but)d ester (Example J25) (279 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M, Obtained as a brown foam (390mg,77%). MS (ISP) 505.3 [(M-H)']. Example M87 (5-Dimethylamino-4-methyI-2-l3-[3-f3-methyl-isQxazol-5-yl)-phenyll-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-5-dimethyiamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phen)d]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M. Obtained as a brown foam (330 mg, 67%). MS(ISP)49L3[(M.H)']. Example M88 fRS)-f4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxymethyl)-fh23ltria2ol-l-yl]-phenyn-propionylamino)-phenyl]-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-cliloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,3]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 50%). MS (ISP) 655.1 [(M+H)--]. Example M89 (4-Chloro-5-fisobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl')-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carban[iic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (360 mg, 65%). MS (ISP) 555.1 [(M+H)1. Example M9Q fRS)-[4-cyano-2-(3-oxo-3-B-(5-ftetrahvdro-pyran-2-yloxvmethyl)-ri.23ltriazol-l-ylj-phenvD-propionylaminoVS-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-)doxymethyi)-[l,2,3]tria2ol-l-yl]-phenyl}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light orange foam (380 mg, 60%). MS (ISP) 630.1 [(M+H)--]. Example M91 (4-cyano-2-(3-f3-f3-methyl-isoxazol-5-vD-phenvI1-3-oxo-propionylamino}-5-pvrrolidin-1-yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-ph€nyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 79%). MS (ISP) 530.2 [(M+H)+]. Example M92 (RSV[4-cyano-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvTnethyl)-fL2.3ltriazol-l-yn-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (440 mg, 70%). MS (ISP) 630-1 [(M+H)+]. Example M93 f4-cyano-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-5-(methyl-propyl-aminoVphenyll-carbamic acid tert-butylester The title compoimd was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 namol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (370 mg, 70%). MS (ISP) 532.3 [(M+H)+]. Example M94 (4-cyano-5-diethylamino-2-{3-[3-f3-methyl-isoxazol-5-yl)-phenyl-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butyl ester (Example J30) (304 mg, LO mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butj^l ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (360 mg, 68%). MS (ISP) 530.2 [(M+H)--]. Example M95 (4-Cyano-5-(isopropyl-methyl-aminoV2-l3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 71%). MS (ISP) 530.2 [(M-H)']. Example M96 (RS)-f4-Cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-r5-(tetrahvdro-pyran-2-yIoxvTnethyl]-[L2.3ltriazol-l-yl]-phenyl}-propion)damino)-phenyl]-carbamicadd tert-butylester The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (460 mg, 73%). MS(ISP)630.1[(M-H)-]. Example M97 (4-cyano-5-fisobutyl-methyl-amino)-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M, Obtained as a light brown foam (400 mg, 73%). MS (ISP) 544.3 [(M-H)']. Example M98 (RSVT4-cyano-5-(isobutyI-methyl-aminoV2-(3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fl,2.3ltriazol-l-yll-phenvU-propionylamino)-phenyll-carbamicacid tert-butyl ester —■'■■> - The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (470 mg, 73%). MS (ISP) 644.2 [(M-H)-]. Example M99 (4-cyano-2-(3-f3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-5-piperidin-l-yl-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J33) (316 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 77%). MS (ISP) 544.2 [(M+H)+]. Example MlOO (4-Chloro-5-isobutylamino-2-l3-f3-f3-methyl-isoxazol-5-vD-phenyl-3-oxo-propionylaminol-phenvD-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-isobut7lamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M, Obtained as an off-white foam (340 mg, 63%). MS (ISP) 542.2 [(M+H)--]. Example MlOl fRSVf4-Chloro-5-isobutylamino-2-f3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxymethyl)-FL2.3ltriazol-l-yl'\|-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyI}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a red oU (180 mg, 28%). MS (ISP) 640.2 [(M-H)-]. Example Ml02 (RS)-[5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxvmethyl) - [ 1,231 triazol-1 -yll -phenyll -propionylamino) -4-trifluoromethyl-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (380 mg, L09 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (439 mg, 1.09 mmol) according to the general procedure M. Obtained as a red foam (150 mg, 20%). MS (ISP) 675.4 [(M-H)']. Example M103 (2-{3-f3-f3-methyl-isoxazol-5-vI)-phenyl1-3-Qxo-propionylaminol-5-fmethyl-propyl-aminQV4-trifluoromethyl-phenyl'\|-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]'Carbamic acid tert-butyl ester (Example J35) (360 mg, L04 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (312 mg, 1.04 mmol) according to the general procedure M-Obtained as a light red foam (270 mg, 45%), MS (ISP) 573.2 [(M-H)-]. Example M104 (RSV[5-(I$obutyl-methyl-aminoV2-(3'Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxymethyl')'[L2^3ltriazol-l-yll-phenvU-prQpionylamino)-4-trifluorometh\d-phenyl]-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutjd-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J36) (370 mg, 1.02 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (411 mg, 1.02 mmol) according to the general procedure M. Obtained as a light brown foam (520 mg, 74%). MS (ISP) 687.2 [(M-H)']. Example M105 (5-fIsobutyl-methyl-aminQV2-{3'f3-(3-methyl-isoxa2ol'5-yl)-phenyl)-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)--carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(i$obutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J36) (360 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (302 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (430 mg, 73%). MS (ISP) 587.3 [(M-H)-]. Example M106 fRSV(5-fIsopropyl-methyl-amino)-2-f3-oxQ-3-{3-(5-ftetrahvdrO'pyran-2-yloxvmethyl)-fL23ltria2oM-yl]-phenyll-propionylaminoV4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isopropyl-methyl-ancuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (340 mg, 0.98 mmol) and (RS)-3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)- [ l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (393 mg, 0.98 mmol) according to the general procedure M. Obtained as alight yellow foam (510 mg, 77%). MS (ISP) 673,3 [(M-H)-]. Example M107 ('5-(Isopropyl-metfayl-aminoV2-(3-f3-(3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isopropyl-methyl-anuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (350 mg, 1.01 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (304 mg, 1.01 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 66%). MS (ISP) 573.2 [(M-H)-]. Example M108 (RSV(5-(Isobutyl-methyl-aminoV4-methyl-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxvmethyl)-[L2.3ltriazol-l-yl1-phenyll-propionylamino)-phenyl]-carbamicacid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenylj-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and (RS)-3-oxo-3-(3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 52%). MS (ISP) 635.2 [(M+H)--]. Example M109 (5-fIsobutyl-methyl-aminoV4-methyl-2-{3-[3-f3-methyl'isoxazol-5-yl)-phenyl1-3-oxo-propionylamino}'phenyl)-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 62%). MS (ISP) 535.4 [(M+H)1. Example Ml 10 (RS)-[4-methyl-2-(3-oxo-3-f3-(5-(tetrahvdro-pyran-2-yloxvmethvD-rL2,3ltriazol-l-yI]-phenyl}-propionylaminoV5-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester The title compoimd was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester acid tert-butyl ester (Example J39) (292 mg, 1.0 imnol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (410 mg, 66%). MS (ISP) 619,3 [(M+H)1. Example Mill (4-Methyl-2-{3-f3-(3-methyl-isoxazol-5-yiVphenyl]-3-oxo-propionylaminol-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J39) (291 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 64%). MS (ISP) 517.3 [(M-H)1. Example Ml 12 (4'-Chloro-5-isQprQpylamino-2-{3-[3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester The title compoimd was prepared from (2-amino-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brovm foam (169 mg, 32%). MS (ISP) 525.2 [(M-H)-]. Example Ml 13 fRS)-f4-Chloro-5-isopropylamino-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyD-ri,23]triazol-l'-yl1-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compoxmd was prepared from (2-andno-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, LO nunol) according to the general procedure M. Obtained as a light yellow foam (375 mg, 60%). MS (ISP) 625.1 [(M-H)-]. Example Ml 14 (RS)-r4-Chloro-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyD-[l,2,4ltriazol-l-yl]-phenyll-propionylamino)-phenyll-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (LOg, 3,19 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (L28 g, 3.19 mmol) according to the general procedure M. Obtained as a yellow foam (L48 g). MS (ISP) 641.3 [(M+H)--]. Example Ml 15 fRSVr4-Chloro-5-fisobutyl-methyl-aminoV2-(3-oxo-3-l3-(5-ftetrahydro-pyran-2-yloxymethyl)-[L2,4ltriazol-l-yl]-phenyl}-propionviamino)-phenyl1-carbamicacid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (1.0 mg, 3.05 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.22 g, 3.05 mmol) according to the general procedure M. Obtained as a light brown foam (620 mg, 31%). MS (ISP) 655.1 [(M+H)1. Example Ml 16 fRS)-l'5-(Isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-J3-(5-(tetrahvdro-pyran-2- yIoxvmethyl)-fl.2,4ltriazol-l-yl1-phenyU-propionylamino')-phenyl1-carbamicacid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (1.0 g, 3.25 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.31 g> 3.25 mmol) according to the general procedure M. Obtained as a light yellow foam (970 mg> 47%). MS (ISP) 635.2 [(M+H)1. Example Ml 17 {5-(methyl-propyl-aminoV2-F3-oxo-3-f3-fL2.4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvD-carbamic acid tert-butylester The title compound was prepared from [2-ainino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (320 mg, 57%). MS (ISP) 561.4 [(M+H)1. Example M118 i5-(Methyl-propyl-aminQV2-f3-oxo-3-(3-fl,23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvU-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxO-3-(3-[l>2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (340 mg, 61%). MS (ISP) 561.3 [(M+H)1. Example Ml 19 l5-fIsobutyl-methyl-amino)-2-[3-oxo-3-r3-pvra2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J40) (361 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, LO mmol) according to the general procedure M. Obtained as a light brown foam (500 mg, 87%). MS (ISP) 574.2 [(M+H)1. Example M120 r2-f3-('2-cyano-pyridin-4-yl)-3-oxo-propionylamino1-5-fisopropyl-methyl-amino)-4-trifluoromethyl-phenyl1-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isoproyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J37) (500 mg, 1,44 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (355 mg, 1.44 mmol) according to the general procedure M. Obtained as a light orange oil (670 mg, 90%). MS (ISP) 518.1 [(M-H)-]. Example M121 U-Chloro-5-fisobutyl-methyl-aminoV2-[3-oxo-3-f3-fL2,4ltriazol-l-yl-phenvi)-propionylaminol-phenvU-carbamic acid tert-hutyl ester The title compound was prepared from [2-amino-4-chloro-5-(isobutyi-methyi-amino)-phen)i]-carbamic acid tert-butyl ester (Example J27) (500 mg, 1.53 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yi-phenyl)-propionic acid tert-butyl ester (Example K25) (438 mg, L53 mmol) according to the general procedure M. Obtained as a light orange foam (700 mg, 85%). MS (ISP) 539.2 [(M-H)-]. {5-(Isobutyl-methyI-amino)-2-f30!(o-3'f3-fl.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluorometh>i-phen\il'Carbamic acid tert-butyl ester The title compound was prepared from l2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example J36) (361 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2oM->1-phcn>'l)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (490 mg, 85%). MS (ISP) 575.2 [(M+H)-]. Example Ml23 l4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-f3-fh2.3]triazol-I-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chioro-5-(isobutyl-methyI-amino)-phenyl]-Carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as an orange oil (250 mg, 46%). MS (ISP) 539.2 [(M-H)-]. Example Ml24 {5-fIsobutyl-methyl-aminoV2-f3-QXo-3-f3-[L2.3ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvmcarbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (460 mg, 1.27 mmol) and 3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionic acid tert-butjd ester (Example K23) (364 mg, 1.27 mmol) according to the general procedxire M. Obtained as ahght brown oil (480 mg, 69%). MS (ISP) 573.1 [(M-H)-]. Example M125 (2-f3-r3-Imidazol-l-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg> 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 iiunol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 77%). MS (ISP) 558.2 [(M-H)-]. Example M126 {4-Chloro-2-[3-f3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-5-isobutylamino-phenyll-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 63%). MS (ISP) 524.1 [(M-H)']. Example M127 {4-Chloro-5-fisobutyl-aminoV2-r3-oxo-3-f3-[1.23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-ainino)-phenyl]-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a pale brown foam (220 mg, 42%). M^:iSP) 525.1 [(M-H)1. Example M128 (5-fIsobutyl-aminQV2-f3-oxO'3-(3-fL23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyU-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoro-methyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg, LO mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 60%). MS (ISP) 559.2 [(M-H)-]. Example Ml29 H-Chloro-5-('isobutyl-aminoV2-f3-oxo-3-f3-fL2,4ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M, Obtained as a light ydlow foam (390 mg, 74%). MS (ISP) 525.1 [(M-H)-]. Example Ml30 {5-('Isobutyl-aminoV2-f3-oxo-3-f3-[1.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 11%). MS (ISP) 559.2 [(M+H)--], General procedure N: Preparation of 4-aryl-13-dihvdro-benzofb1 f L4ldiazepin-2-ones: A solution or suspension of the {2-[3-arj4-3-oxo-propionylamino]-phenyl}-carbamic acid tert-butyl ester or {2-[3-aryi-3-oxo-propionyIamino]-phenyl}-carbamic acid tert-butjd ester (1.0 mmol) in CH2Cl2 (5 mL) (anisolc or l^-dimethoxybenzene (5-15 mmol) can be acided if necessary] was treated with TFA (0.5-5.0 mL) at 0 '°C and stirring was continued at 23 °C until tic indicated complete consumption of the starting material. Worlcup procedure a: The solvent was removed in vacuum, the residue treated with little ether, whereupon it crystallized. The solid vas stirred with sat. NaHCOs-sol. or IM NaaCOs-sol., filtered, washed with H2O and ether or mixtures of ether/THF/MeOH and was dried to give the tide compound, which if necessary can be purified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cyclohexane/EtOAc or EtOAc/EtOH. Workup procedure b: The reaction mixture was diluted with DCM or EtOAc, washed with sat. NaHCOs-sol. or IM Na2C03-soL, brine and dried over MgSO4 or Na2S04. Removal of the solvent in vacuum left a material, which could be triturated with ether or mixtures of ether/THF/MeOH to give the title compound, or which if necessary can be pmified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cycIohexane/EtOAc or EtOAc/EtOH. Example 1 3-f7-Chloro-8-dimethylamino-4-oxo-4,5-dihvdro-3H-benzo[blfl.4]diazepin-2-yl)-benzonitrile The tide compoimd was prepared firom {4-chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example Ml) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (85 mg). MS (ISP) 339 [(M+H)--] and 341 [(M+2+H)']; mp >250 »C. Example 2 8-Chloro-7-dimethylamino-4-f3-fl,2,3ltriazol-l-yl-phenyl)-l,3-dihydro-benzofbl f L4ldiazepin-2-one The title compoxmd was prepared from {4-chloro-5-dimethylamino-2-[3-OXo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert.-butyl ester (Example M2) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (87 mg). MS (ISP) 381 [(M+H)--] and 383 [(M+2+H)-']; mp 222-225 °C. Example 3 8-Chloro-7-dimethylamino-4- r3-(5-hvdroxvmethyl-1- 1.2,3ltriazol- 1-yD-phenyll -1,3-dihydro-benzo f b1 \ 1,4] diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl] -carbamic acid tert.-butyl ester (Example M3) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (60 mg). MS (ISP) 411 [(M+H)--] and 413 [(M+2+H)']; mp 210-214 X, Example 4 3-(8-Dimethylamino-4-oxo-7-phenylethynyl-4,5-dihydro-3H-benzofbl \ 1,41 diazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-phenylethynyl-phenyl}-carbamic acid tert.-butyl ester (Example M4) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg). MS (ISP) 405 [(M+H)--]; mp 215-216 °C. Example 5 7-Dimethylamino-8-phenylethvnyl-4-f3-rL23ltriazol-l-yl-phenvi)-K3-dihvdro-benzofbl f 1.41 diazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyi)-propionylamino]-4-phenylethynyl-phenyi}-carbantiicadd tert-butyi ester (Example M5) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (76 mg). MS (ISP) 447 [(M+H)--]; mp 185-186 °C. Example 6 8-Chloro-7-dimethylamino-4-r3-f3-methyl-isoxazol-5-yl')-phenyl1-L3-dihvdro-benzoFb1fl,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacidtert.-butyl ester (Example M6) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (68 mg). MS (EI) 394 (M^) and 396 [(M+2r]; mp 212-215 °C Example 7 8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-('5-hvdroxymethyl-[1.23ltria2ol-l-yl)-phenyl-1.3-dihvdro-benzofb]fL4ldiazepin-2-one The title compound was prepared from (RS)-[2-dimethylamino-2',3'-difluoro-5-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-biphenyl-4-yl]-carbamic acid tert-butyl ester (Example M7) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (26 mg). MS(ISP)489[(M+H)']. Example 8 8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-fL23ltriazQl-l-yl-phenylyl3-dihvdrO'benzo l-b] [ 1.41 diazepin'2-one The title compound was prepared from {2-dimethylamino-2\3-difluoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert-butyl ester (Example M8) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (47 mg). MS (ISP) 459 [(M+H)--]; mp 197-199 °C. Example 9 3-r7-(23-Difluoro-phenyl)-8-dimethylamino-4-QXO-4.5-dihydro-3H-benzofbl \ 1,41 diazepin-2-vn -benzonitrile The title compound was prepared from {5-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-2-dimethylamino-2\3-difluoro-biphenyi-4-yl}-carbamic acid terL-butyl ester (Example M9) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a light yellow solid (75 mg). MS (ISP) 417 [(M+H)--]; mp 228-229 ^'C Example 10 8-CMoro-7-dimethylamino-4-(2-(3-metfayl-isoxazol-5-yl)-pvridin-4-yl1-1.3-dihvdrO-benzofbl f 1.4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimetiiylanuno-2-{3- [2-(3-methyl-isoxazol-5-yI)-pyridin-4-yl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example MIO) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (111 mg). MS (ISP) 396 [(M+H)+] and 398 [(M+H-f 2)--]; mp >250 X. Example 11 8-Chloro-7-[(2-methoxy-ethyl)-methyl-amino1-4'f3-(3-methyl-isoxazol-5-yI')-phenyll -13-dihvdro-benzo [bl f 1 A] diazepin-2-one The title compound was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-2-{3-[3-(3-methyi-isoxazol-5-yl)-phenyl]-3-OXO-propionylamino}-phenyl)-carbanciic acid tert.-butyl ester (Example Ml 1) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg). MS (EI) 438 (M*-) and 440 [(M+2)+]; mp 182 °C. Example 12 8-Chloro-7-f(2-methQxy-ethyl)-methyl'amino1-4-[2-f3-methyl-isoxazoI-5-yl)-pyridin-4-ylyl3-dihydro-benzofb]fl.4ldiazepin'2-one The title compoimd was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-ainino]-2-{3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4~yl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M12) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (106 mg). MS (ISP) 440 [(M+H)'] and 442 [(M+H+2)1; mp 213 °C Example 13 8-ChlorQ-4-r3-(5-hvdroxvmethyl-rL23ltriazol-l-yl]-phenyl-7-r(2-methoxv-ethyl)-methyl-amino1-l3-dihvdro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-[(2-methoxy-ethyl)-methyL amino]-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M13) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (50 mg). MS (ISP) 4.55 [(M+H)'] and 457 [(M+H+2)']; mp 185 X. Example 14 8-Chloro-7-r(2-methoxv-etfayl)-methyl-amino1-4-f3-fl.23]triazol-l-yl-phenylyl.3-dihydro-benzofb] rL4ldiazepin-2-one The title compotmd was prepared from {4-chIoro-5-[(2-methoxy-ethyl)-methyl-amino] -2- [3-oxo-3-(3- [ l,2,3]triazoM-yl-phenyl)-propionylamino] -phenyl}-carbamic acid tert.-butyl ester (Example M14) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg). MS (ISP) 425 [(M+H)--] and427 [(M+H+2)+]; mp 156 °C. Example 15 4-f7-Ch]orO-8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb]fl,4ldiazepin-2-vI)-pyridine-2-carbonitrile The title compoimd was prepared from {4-chlorO-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert.-butyl ester (Example M15) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (50 mg). MS (ISP) 340 [(M+H)--] and 342 [(M+2+H)-^]; mp 216 X. Example 16 8-ChlorO-7-dimethylamino-4-f3-(2-methyI-2H-pvrazol-3-yl)-phenyl]-1.3-dihvdro- benzofbl f l,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert.-butyl ester (Example M16) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofiF-white solid (67 mg). MS (ISP) 394 [(M+H)--] and 396'{(M+2+H)']; mp 225 X. Example 17 7-Dimethylamino-4-f3-(5-hydrox\TOethyl4l,2,3ltria2ol>l'yl)-phenyll'8-trifluoromethy[-L3-dihydro-benzofblfL4ldiazepin-2one The title compound was prepared torn (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester (Example M17) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (62 mg). MS (ISP) 445 [(M+H)+]; mp 210 '°C. Example 18 7-Dimethylamino-4-f3-(3-methyl-isoxa2oI-5-yl)-phenyI]-8-trifluoromethyM.3-dihydro-benzofb] [1,41 diazepin-2'One The title compound was prepared from (5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-OXo-propionylamino}-4-trifiuoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example Ml8) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (28 mg). MS (ISP) 429 [(M+H)+]; mp 223 °C, Example 19 8'Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-l,3-dihvdro-benzo f b] f 1,41 diazepin-2-one The title compound was prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-thiobenzamide (prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [1,4] diazepin-2-yl)-benzonitrile (Example 1) as follows: To a solution of hexamethyldisUthiane (0.55 mL, 2.6 mmol) in l,3dimethyl-2-inaida2olidinone (2.6 mL) was acided at 20 X sodium methoxide (0.13 g, 2.5 mmol). The mixture was stirred for 15 min. and the blue solution formed was then acided to a solution of 3-(7-chloro-8-dimethyIamino-4-oxo-4,5-dihydro-3H-benzo[b][l,4ldiazepin-2-yi)-ben2omtrile (Example 1) (0.34 g, 1.0 mmol) in 1,3-dimethyl-2-imida2olidinone (2 mL). The mixture was stirred for 3 h at 20 °C and then poured into water. The precipitate was isolated by filtration and triturated with acetone to give 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [l,4]diazepin-2-yi)-thiobenzamide (035 g) as yellow solid, mp 234 'C decMS (ISP) 373.2 [(M+H)'].} (0.71 g, 1.9 mmol), l,3-dichloro-2-propanone (0,36 g, 2.85 mmol) and sodium bicarbonate (0.24 g, 2.85 mmol) in 1,4-dioxane (15 mL) was heated to 60 °C for 48 h. The clear solution was evaporated in vacuvun. The a solution of the residue in 1,4-dioxane (5 mL) was acided 2N KOH (3.8 mL) and the mixture was stirred at 20 °C for 1 h. Water (100 mL) was acided and the mixture was stirred for 0,5 h. The precipitate formed was collected by filtration and crystallized from dichloromethane to give the title compound (0.69 g) as pale-yellow solid. MS (ISP) 427.2 [ (M+H)-]; mp 134 X dec. Example 20 8-Chloro-7-dimethylamino-4-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyll -L3-dihvdrO'benzo fbl \ 1,41 diazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M19) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (34 mg). MS (ISP) 438 [(M+H)--] and 440 [(M+2+H)-']; mp 145-160 °C Example 21 8-Chloro-7-dimethylamino-4-f3-(3-methoxvmethyl-isoxazol-5-yl)-phenyl1L3-dihydro-benzoFbl [1.41 diazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butjrl ester (Example M20) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (157 mg). MS (ISP) 425 [(M+H)+] and 427 [(M+2+H)']; mp 191 °C. Example 22 4-(8-Dimethylamino-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo Fbl \ 1.41 diazepin'2-yl)-pyridine-2-carbonitrile The title compoxmd was prepared from {2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylarnino]-5-dimethylamino-4-trifluoromethyl-phenyi}-carbainic acid tert.-butyl ester (Example M21) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (158 mg). MS (ISP) 374 [(M+H)--]; mp 248 X. Example 23 8-(2-Fluoro-phenyl)-4'(3-imida2ol-l-vI-phenyl-7-(2.2,2-trifluoro-ethoxv)-L3-dihydro-benzofb] [ L41 diazepin-2-one The title compound was prepared from [2'-fluoro-5-[3-(3-nmdazol-l-yl-phenyl)-3-oxo-propionylamino] -2- (2,2,2-trifluoro-ethoxy)-biphenyl-4-yi] -carbamic acid tert,-butyl ester (Example M22) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (50 mg). MS (EI) 494 (M^); mp 208-210 °C Example 24 8-(2-Fluoro-phenyl)-4-f3-f3-methyl-isoxazQl-5-vIVphenyl]-7-(2,2.2-trifluoro-ethoxy)-1,3-dihydro-benzo f b] \ 1,41 diazepin-2-one The title compound was prepared from [2'-fluoro-5{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyi]-3-oxo-propionylamino}-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example M23) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (21 mg). MS (EI) 509 (M^); mp 218-220 -'C. Example 25 8'(2-FIuoro-phenyl)-4'(3-ri.23kriazol-l-yl-phenyl)-7-r2.2,2-trifluoro-ethoxv)-13-dihydro-benzofb] f 1,4ldiazepin'2-one The title compound was prepared from [2-fluoro-5-[3-oxo-3-(3-[l,2,3]triazoM-yI-phenyl)-propionylamino]-2-(2^,2-trifluoro-ethoxy)-biphen)d-4-yl]-carbamicacid tert.butyl ester (Example M24) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (45 mg)- MS (EI) 495 (M^). Example 26 8-(2-Fluoro-phenyl)-4-f3-(5-hvdroxvmethyl4l.2.3ltriazoI-l-yl]-phenyl)-7-(2,2,2-trifluoro-ethoxy)-13'dihvdro-ben2ofblfL4ldiazepin-2-one The title compound was prepared from (RS)-[2'-fluoro-5-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-^oxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid terL-butyl ester (Example Iyl25) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (10 mg). MS (ISP) 526 [(M+H)1; mp 232-234 °C Example 27 8-Chloro-7-dimethylamino-4-f3-f4-hydroxvmethy]-oxazol-2-yl)-phenyl1-13-dihydro-benzofb] ri,4]diazepin-2-one The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (170 mg) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxa2ol-2-yl] -phenyl}-propionic acid tert-butyi ester (Example Kll) (270 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (110 mg). MS (ISP) 41L2 [(M+H)--]; mp 193-195 °C Example 28 8-Chloro-7'(ethyl-methyl-amino)-4-f3-(5-hvdroxymetfayl-fL23ltriazoM'yl)-phenyl]-L3-dihvdrO'benzofb1fl,4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(ethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M26) (0.5 g, 0.8 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white soKd (60 mg). MS (ISP) 425.4 [(M+H)-]; mp 206 °C (dec). Example 29 8-Chloro-7-fmethyl-propyl-amino)-4-r3-(5-hydroxvmethyl-fL2.3ltriazol-l-yl')-phenyl] -1,3-dihydrO'benzo fbl [ 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M27) (0.41 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (110 mg). MS (ISP) 439.3 [(M+H)1; mp 178 °C (dec). Jbxample 30 8-Chloro-7-fdiethyl-amino)-4-f3-(5-hvdroxvmethyl-rL23ltriazoUl-yl)-phenvI1-L3-dihydro-benzofb][L4]diazepin-2-one The title compoimd was prepared from (RS)-(4-chloro-5-(diethyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tm-butyl ester (Example M28) (0.53 g, 0.827 mmol) by treatment with TFA in CH;Q: according to the general procedure N. Obtained as an off-white solid (210 mg). MS (ISP) 439.3 [(M+H)--]; mp 208 °C (dec). Example 3 i 8-Chloro-7-dimethylamino-4y3-(3-hvdroxvmeth>^-isoxazol-5-yl)-phenyl]-1.3-dihydro-benzofblfL4]diazepin-2-onc The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5->d]-phen)d}-propionyiamino)-phenylj-carbamic acid terL-butyi ester (Example M29) (81 mg, 0.13 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (38 mg). MS (ISP) 411 [(M+H)+] and 413 [(M+2+H)']; mp 132 °C. Example 32 8-CHoro-4-r3-(5-hvdroxymethyl-rL23]triazol-l-vI)'phenyl17-pvrrolidin-l-yl-L dihydro-benzorb1fL4]diazepin-2-one The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionylamino)-5-pyrrolidin-1-}d-phenyl]-carbaniic acid tert.-butyl ester (Example M30) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (58 mg). MS (ISP) 437 l(M+H)+] and 439 [(M+2+H)'-]; mp 193-197 X. Example 33 7-Dimethylamino-4-f3-(2-methyl-2H-pvrazol-3-yl)-phenvIl-8-trifluoromethyl-L3-dihydro-benzofbl [ L4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)'phenyl]-3-oxo-propionylari3ino}-4-trifluoromethyl-phenyl)-carbaniic acid terL-butyl ester (Example M31) (78 mg, 0.14 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid(48 mg). MS (ISP) 428 [(M+H)1; mp 225 °Q Example 34 4-f7-Chloro-8-('cvclopropyl-methyl-aminoV4-oxo-4,5-dihydrQ-3H-benzo Fbl f 1.41 diazepin-2-yl] -pvridine-2-carbonitrile The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyi-amino)-phenyl]-carbamic acid terL-butyl ester (Example Jll) (150 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (150 mg, 0.61 mmol) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg), MS (ISN) 364.1 [(M-H)-] and 366 [(M+2-H)-]; mp 199-201 °C. Example 35 8-Chloro-7-dimethylamino-4-[3-(4-hvd^oxvTnethyl-3-meth^d-isoxa^ol^5-yD-phenyl1-1.3-dihydro-benzo[bUL4ldiazepin-2-one The titie compoxmd was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tert,-butyl ester (Example M32) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (60 mg). MS (ISP) 425 [(M-hH)--] and 427 [(M+2-hH)-']; mp 232-233 'C. Example 36 8-CHoro-7-fcvclopropyl-methyl'amino)-4-f3-(3-melhyl-isoxazol-5-yl)-phenyll-13-dihvdro-benzofb1[L4ldiazepin-2-one The title compound was prepared from [2-aminO-4-chloro-5-(cyclopropyl-methyl-ammo)-phenyl]-carbamic acid tert.-butyl ester (Example Jll) (156 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (170 mg, 0.56 mmol) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (49 mg). MS (ISP) 42L3 [(M+H)--] and 423 [(M+2+H)^; mp 195-197 X. Example 37 8-Chloro-7-fcvclopropyl-methyl-amino)-4-f3-(5-hvdroxvmethyl-fL23ltria2ol--l-yl)-phenyl] -1.3-dihvdro-benzof b1 f 1.4] diazepin-2-one The title compound was prepared from (RS)-[4-chioro-5-(cyclopropyl-methyl-amino)-2-(3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M33) (200 mg, 0.313 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (54 mg). MS (ISP) 437.3 [(M+H)+] and 439 [(M+2+H)+]. Example 38 7-Dimethylamino-4- [3-f 5-dimethylaminomethyl- [ 1.2,31 triazoM-vD-phenyll -8-trifluoromethyl-13-dihydro-benzo[bUl,4ldiazepin'2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl- (1,2,3] triazol-1 -yl)-phenyl] -3-oxo-propionylamino}-4-trifluoromethyl phenyl)-carbamic acid tert.-butyl ester (Example M34) (126 mg, 0.214 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (23 mg). MS (ISP) 472 [(M+H)--]; mp 200 °C. Example 39 8-ChlorO'7-dimethylamino-4-f3-f5hvdroxymethyl-2-methyl-2H-pvra2ol-3-yl)' phenyll-13-dihydro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-{3-[2-methyl-5-(tetrahydro-pyran-2-ylox)Tncth)1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tat.-butyl ester (Example M35) (278 mg, 0.44 mmol) by treatment with TFA in CHjQ: according to the general procedure N. Obtained as a Hght yellow solid (129 mg), MS (ISP) 424 [(M+H)--] and 426 ((M+2+H)-]; mp 184 X. Example 40 4-(4-Oxo-8-pvrrolidin-l-yl-7-trifluoromethyl-4.5-dihvdrO'3H-benzo[bUL4ldiazepin-2-yl)-pyridine-2'Carbonitrile The title compound was prepared from {2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M36) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg). MS (ISP) 400.4 [(M+H)--]; mp 188 -C (dec). Example 41 443-(5-Hvdroxvmethyl-rL23ltriazol-l-vI)-phenyll-7-pvrrolidin-l-yl-8-trifluoromethyl-13dihvdro-ben2ofb1fL4ldiazepin2-one The title compound was prepared from (RS)-[2-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M37) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid(33 mg). MS (ISP) 471.2 [(M+H)+]; mp 134 °C. Example 42 7-Dimetfaylamino-8-fluoro-4- [3- f 5-hvdroxvmethyl- f 1.2.31 triazol-1 -yl)-phenvil -1.3-dihvdro-benzofbl rh4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-)4]-phenyi}-propionyi-amino)-phenyl]-carbamic acid tert.-butyl ester (Example M38) (375 mg, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg). MS (ISP) 395 [(M+H)1; mp 75 °C. Example 43 7-Dimethylamino-4-[3'(5-dimethylaminomethyl-fL2,3ltria2oI-l-yl)-phenyl1-8-fluoro-13-dihydro-benzo[bUL4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionylanaino}-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example M39) (170 mg, 0.32 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (34 mg). MS (ISP) 422 [(M+H)+]; mp 181 °C. Example 44 7-Dimethylamino-8-fluoro-4-F3-f3-hydroxymethyl-isoxazol-5-yD-phenvI1-l,3-dihydro-benzofbUl,4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M40) (314 mg, 0,53 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (95 mg). MS (ISP) 395 [(M+H)--]; mp 187 °C. Example 45 8-Chloro-7-dimethylamino-4-[3-(5-pvrrolidin-l-ylmethyl-ri,23ltriazol-l-vD-phenyl1-13-dihydro-benzo[b1fL4ldiazepin-2'One The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxy-methyl- [ 1,2,3] triazol-1 -yl)-phenyl] -1,3-dihydro-ben2o [b] [1,4] diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (0.044 mL, 0.6 mmol) in CH2Cl2 (2 mL) from 23 °C to reflux for 15 min, followed by evaporation to dryness. The crude chloride was dissolved in DMF (2 mL) and stirred with cat amount of Nal and pyrrolidine (0.248 mL, 3.0 mmol) at 23 °C until tic indicated complete conversion of the chloride. The reaction mixture was taken up in EtOAc, washed with water and brine, dried over Na2S04. Removal of the solvent in vacuum left a yellow semisolid. which was purified by silica gel colxxmn chromatography. Obtained as a yellow solid (101 mg). MS (ISP) 464 [(M+H)1 and 466 [(M+2+H)-']; mp 180-182 --C. Example 46 7-Dimethylamino-4-f3-f3'hvdroxvmetfayl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzofb1fL4]diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenylj-carbamic acid tert.-butyl ester (Example M41) (680 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (294 mg). MS (ISP) 455 [(M+H)--]; mp 219 °C. Example 47 7-Dimethylamino-8-fluorO'4--[3-(3-methyl-isoxazol-5-yl)-phenyl-l,3-dihvdro-benzo [bl [ 1.41 diazepin-2-one The title compound was prepared from (5-dimethylamino-4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M42) (233 mg, 0.47 nunol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow-brown solid (59 mg). MS (ISP) 379 [(M+H)--]; mp 124 X. Example 48 4-[3-(5-Azetidin-l-ylmethyl-fl.23ltriazol-l-yl)-phenyl-8-chloro-7-dimethylaminOr 13-dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and trimethylen imine (10 eq.) as described in Example 45. Obtained as a yellow solid (17 mg). MS (ISP) 450 [(M+H)-']; mp 153 °C Example 49 8'Chloro-7-dimethylamino-4- f 3- f 5-hvdroxvmethyl'isoxazol-3-vD-phenyn -1.3-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M43) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (113 mg). MS (ISP) 411.3 [(M+H)1 and 413 [(M+2+H)']; mp 211 °C (dec). Example 50 8--Chloro-4-[3--(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-7-piperidin-l-yl-13-dihvdro-benzo f b U1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl]-carbamic acid tert.-butyl ester (Example M44) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (99 mg). MS (ISP) 451.3 [(M+H)+] and 453 [(M+2+H)-']; mp 246 X (dec). Example 51 7-Dimethylamino-'4-f3-(5-hydroxvmethyl-isoxazoI'3-yl)-phenyll-8-trifluoromethyl- L3-dihvdrQ-benzofb1fL4]diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert--butyl ester (Example M45) by treatment with TFA in CH3CI2 according to the general procedure N. Obtained as a light yeUow solid (103 mg), MS (ISP) 445.3 [(M+H)+]; mp 211 °C (dec). Example 52 8-Chloro-7-dimeAylamino-4-f3-pvrazol-l-yl-phenylyl3-dihydro-benzofbl ri.4ldiazepin-2-one The title compound was prepared from {4-chloro-5-dimethylamino-2-[3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propion7lamino]-phenyl}-carbamic acid terL-butyl ester (Example M46) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (75 mg). MS (ISP) 380 [(M+H)1 and 382 [(M+2+H)+]; mp 231-234°C Example 53 7-DimethyIamino-4-f3-f3-pvrrolidin-l'ylmethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo fb] f L4l diazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl] -8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 46) (111 mg, 0.25 mmol) by treatment with SOCI2 (3 eq.) and pyrrolidine (10 eq.) as described in Example 45. Obtained as a yellow solid (28 mg). MS (ISP) 498 [(M+H)+]; mp 160 °C. Example 54 7-Dimethylamino-4-[3-(3-morpholin-4-ylmethyl-isoxa2ol-5-yl)-phenyl-8-trifluoromethyl-l,3-dihvdrO'benzofbl f l,4ldiazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and morpholine (10 eq.) as described in Example 45. Obtained as a yellow solid (33 mg). MS (ISP) 514 [(M+H)+]; mp 165 °C Example 55 7-Dimethylamino-4-f3-(3-dimethylaminomethyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-L3-dihvdrQ-benz6fbUl,4ldiazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and 40 % aqueous Me2NH-sol (10 eq.) as described in Example 45. Obtained as a light yellow solid (21 mg). MS (ISP) 472 [(M+H)--]; mp 160 °C Example 56 4-f7-Fluoro-4-oxo-8-pvrrolidin-l-yl-45-dihvdro-3H-benzo[bUl.4ldiazepin-2-vD-pyridine-2-carbQnitrile The title compoimd was prepared from {2-[3-(2-Cyano-pyridin-4-yI)-3-oxo-propionylamino]-4-fluoro-5-pyrrolidin-l-yl-phenyl}-carbamic acid tert.-butyl ester (Example M47) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (54 mg). MS (ISP) 350 [(M+H)--]; mp 278-279 °C Example 57 8-FluorQ-4-f3-(3-methyl-isoxazol-5-vD-phenyl]-7-pvrrolidin-l-yl-13-dihvdro-benzo[bUl,4ldiazepin-2-one The title compoimd was prepared from (4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example M48) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (86 mg). MS (ISP) 405 [(M+H)--]; mp 236 -C Example 58 8-Fluoro-443-(5-hvdroxvmethyl-[L2.3ltriazol-l-vD-phenyl1-7-pvTrolidin-l-yl-L3-dihvdrO'benzofbl f l,4ldiazepin-2-one The title compound was prepared from (RS)-[4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-ylox)nnieth.yl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl] -carbamic acid tert-butyl ester (Example M49) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (72 mg). MS (ISP) 421 [(M+H)--]; mp 184-185 °C. Example 59 4-f8-Azetidin-l-yl-7-chloro-4-oxo-45-dihvdro-3H-benzofb1[l,4ldiazepin-2-yl)-pyridine-2-carbonitrile The title compound was prepared from {5-a2etidin-l-yl-4-chloro-2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-phenyl}-carbainic acid terL-butyl ester (Example M50) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (66 mg). MS (ISP) 352 [(M+H)'] and 354 [(M+2+H)1; mp 276 °C. Example 60 4- f 3- f 5-Hvdroxymethyl-isoxa2ol-3-yl)'phenyl1 -7-pvrrolidin- 1 -yl-8-trifluoromethyl-L3-dihydro-benzo fb] f L4l diazepin-2-one The title compound was prepared from (RS)-[2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M51) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (224 mg). MS (ISP) 47L2 [(M+H)--]; mp 206-208 X. Example 61 4-f 8-Azetidin- l-yl-4-oxo-7-trifluoromethyl-4.5-dihydrO'3H-benzo [bl \ 1.41 diazepin-2-yl)'pyridine-2-carbonitrile The title compound was prepared from {5-azetidin-l-yl-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid terL-butyl ester (Example M52) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (51 mg), MS (ISN) 384.2 [(M-H)']; mp 241 °C. Example 62 7-A2etidin-l-yl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8'trifluoromethyl-l,3-dihydro-benzofbUL4ldiazepin'2-one The title compoimd was prepared from (5-azetidin-l-yl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M53) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg). MS (ISP) 441.3 [(M+H)--]; mp 239 °C (dec). Example 63 7-A2etidin-l-yl-443-(5-hvdroxvmethyl-rL23ltriazoM-yl)-phenyl1-8-trifluoromethyl-13-dihydro-benzofblfl.4ldiazepin'2-one The title compound was prepared from (RS)-[5-azetidin-l-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiamino)-4-trifluoromethyl-phenylj-carbamic acid terL-butyi ester (Example M54) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (182 mg). MS (ISP) 457,4 [(M+H)+]; mp 202 X (dec). Example 64 7-Dimethylamino-4-13-pyra2ol-l -yl-phenyl)-8-trifluoromethyl-1,3-dihvdro-benzo^b] f l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M55) (438 mg, 0.82 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (238 mg). MS (ISP) 414 [(M+H)--]; mp 176 °C Example 65 7-Dimethylamino4-f3-fL2.4ltriazol-4-yl-phenyl)'8-trifluoromet3iyl-l,3-dihydro-benzolb] [l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-4-yl-phenyl)-propionylamino]-4-trifluoroinethyl-phenyl}-carbamic acid tert.-butyl ester (Example M56) (280 mg, 0.526 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (121 mg). MS (ISP) 415.3 [(M+H)--]; mp 247-250 °C. Example 66 7-Dimethylamino-4-(3-imidazol-l-yl-phenyl)-8-trifluoromethyl-l>3-dihvdro-benzolbl [ l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-(3-imidazol-l-yl-phenyl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbainic acid tert.-butyl ester (Example M57) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (132 mg), MS (ISP) 414 [(M+H)--]; mp 203-205 °C. Example 67 8-Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-pvra2ol-l-yl)-phenyl1-L3-dihvdro-benzo fb] F1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chIoro-5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M58) (642 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (365 mg). MS (ISP) 410 [(M+H)--]; mp 211 °C. Example 68 7-DimethylaminO'4-f3-(4-hydroxvmethyl-pyrazol-l-yl')-phenyl1-8-trifluoromethyl-13-dihvdro-ben2orb1[l,4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (°Cample M58) (590 mg, 0.91 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (299 mg). MS (ISP) 444 [(M+H)--]; mp 175 °C Example 69 7-Dimethylamino-4-f3-(4-hydroxvmethyl-3-methyl-isoxazol-5-yl)-phenvI1-8-trifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[3-methyI-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylarnino)-4-trifluoromethyi-phenyi]-carbamic acid tert--butyl ester (Example M60) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (64 mg). MS (ISP) 459 [(M-hH)--]; mp 207-208 °C. Example 70 7-Dimethylamino-4-f3'(4-hvdroxvmethyi-isoxazol-3-yl)-phenyl8-trifluoromethyl-L3-dihvdro-benzofb1fL4ldiazepin-2'one The title compound was prepared from (RS)-l5-dimethylamino-2-(3-oxo-3-{3-l4-(tetrahydrO-pyran-2-yloxymcthyl)-isoxa2ol-3-yl)-phenyl}-propionylamino)-4-trifluoromethyl-phenyi)-carbamic acid tert.-butyl ester (Example M61) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (50 mg), MS (ISP) 445 [(M+H)+]; mp 217-219 M EMmpk7l 7-Dimethylamino-4-f3-(2-methylsulfanyl-imida2ol-l-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2orb1fL4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyisulfanyl-imidazol-l-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M62) (450 mg. 0.78 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (253 mg). MS (ISP) 460 [(M+H)--]; mp 192 X. Example 72 7-Dimethylamino-4'f3-(4'hvdroxvmethyl-2-methyl-2H-pyrazol3-yl)-phenyll-8' trifluoromethyl-13-dihvdro-benzofb1 f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yi]-phenyl}-3-oxo-propionyl-amino)-4-trifiuoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M63) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (272 mg), MS (ISP) 458 [(M+H)+]; mp 243-244 °C. Example 73 8-Chloro-7-dimethylamino-4-f3-fL2,4ltriazoM-yl-phenyl)-13-dihvdro-benzprb] f l,4ldiazepin-2-one The title compound was prepared from {4-Chloro-5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-l-yl-phenyl)-propionyiamino]-phenyi}-carbamic acid tert-butyl ester (Example M64) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (316 mg). MS (ISP) 381 [(M+H)1 and 383 [(M+2+Hr]; mp 239-241 °C Example 74 7-Dimetfaylamino-4- (5-\l .2,41 triazol-1 -yl-phenyl) - 8-trifluoromethyl-13-dihydro-benzoFb] [L4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,4]triazoH-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M65) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(269 mg). MS (ISP) 415 [(M+H)--]; mp 228-230 X. Example 75 3-f8-Dimethylamino-4-oxo-7-trifluoromethyl-4,5-dihvdro-3H-benzorbirL4ldiazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-trifluoromethyl-phenyl}-carbanaic acid tert.-butyl ester (Example M66) (180 mg, LO mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg). MS (ISN) 371 [(M-H)-]; mp 224-227 X. Example 76 7-Dimethylamino-4-(3-l5-f('2,2.2-trifluoro-ethylaminoVmethyl]-rL23ltriazol-l-vU-phenyl)-8-trifluoromethyl-l>3-dihydro-benzorb1fL4ldiazepin-2-one The title compoxmd was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l>2,3]triazol-l-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 17) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and 2>2,2-trifluoroethylamine (10 eq.) as described in Example 45. Obtained as a light yellow solid(19mg). MS (ISP) 526 [(M+H)'];mp 168-170 °C. Example 77 7-(Cyclopropylmethyl-methyl-aminoV4-[3-(5-hvdroxvmethyl-fL23ltriazoM-vI)-phenyl1-8-trifluorQmethyl-13-dihvdro-benzofbiri.4]diazepin-2one The title compound was prepared from (RS)-[5-(cyclopropylmethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M67) (939 mg> 1.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (544 mg). MS (ISN) 483 [(M-H)-]; mp 212 °C. Example 78 4-f8-fCvclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin-2-vn 'pyridine-2-carbonitrile The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M68) (173 mg, 0.33 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (81 mg), MS (ISN) 412 [(M-H)]; mp 155 °C Example 79 4- [ 3- (4-Cyclopropylaminomethyl'pyrazol-1 -yl) -phenvH -7'dimethylamino-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(4-hydroxymethyl-pyrazoH-)d)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 68) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (45 mg). MS (ISP) 483 [(M+H)--]; mp 135 °C. Example 80 4-[3-(5-Cyclopropylaminomethyl-ri.2,3ltriazol-l-yl)-phenyl1-7-fcyclopropylmethyl-methylaminoV8-trifluoromethyl-13-dihvdrO-benzorblfl,4ldiazepin-2-one The title compound was prepared from 7-(cyclopropylmethyi-methyl-amino)-4-[3-(5-hydroxymethyl-[1^3]triazol-l-yl)-phenyl]-8-trifluoromethyl-13- SOCh (3 eq.) and cyclopropji amine (10 eq.) as described in Example 45. Obtained as a yellow solid (97 mg). MS (ISP) 524 [(M+H)--]; mp 35-46 °C Examples! 7-Dimethylamino-4-B-r2-(2-hvdrorv-ethyl)-2H-pvrazol-3-yl]-phenvD-8-trifluoromethyl-l.S-dihvdro-benzQfbl f 1.4ldia7epin-2-one The title compound was prepared from (RS)-l5-dimetliylainino-2-[3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyi]-2H-p>Tazol-3-yi}-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tcrL-butyl ester (Example M69) (237 mg, 0.36 mmol) by treatment with TFA in CH:Q: according to the general procedure N. Obtained as an off-white solid (48 mg). MS (ISP) 458 [(M+H)--]; mp 138 °C Example 82 4-[3'(5-Cvclopropylaminomethyl-fL2.3]tria2ol-l-yl)-phenyl1-7-dimethylamino-8-trifluorometfayl-1.3-dihvdro-benzorbUL4ldiazeptn-2-one The title compound was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-trifluoromethyi-13-dihydro-benzo[b][l,4)diazepin-2-one (Example 17) (444 mg, 1.0 mmol) by treatment with SOQ2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (248 mg), Mp 145-148 °C, Example 83 4-f8-(Cyclopropyl-methyl-amino)-4-oxo-7-trifluoromethyM.5-dihvdro-3H-benzo fb] [ 1,41 diazepin-2-yll -pvridine-2-carbonitrile The title compoxmd was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester (Example M70) (215 mg, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (87 mg). MS (ISP) 400.4 [(M+H)--]; mp 200-205 °C. Example 84 7-Diinethylamino-8-(2-fluoro-phenyl)-4-f3-fh23ltria2ol-l-yl-phenyl)-L3-dihvdro-benzofbl f 1.4ldiazepin-2-one The title compound was prepared from {2-dimethylamino-2-fiuoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert.-butyl ester (Example M70) (810 mg, L45 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (61 mg). MS (ISP) 400.4 [(M+H)+]; mp 225-230 °C. Example 85 7-Dimethylamino-4-B-(5-(2-hvdroxv-ethyl)-fL23ltria2oM-yl)-phenvU-8-trifluoromethyl-13-dihvdro-benzo \b] [ 1.41 diazepin-2-one The title compound was prepared from (RS)-{5-dimethylamino-2-[3-oxO-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,2,3] triazol- 1-yl}-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M72) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (179 mg). MS (ISP) 459 [(M+H)+]; mp 172-175 °C. Example 86 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-pvrazol-l-vD-phenyl1-8-trifluoromethyl- 1.3-dihvdro-benzQrb1fL4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M73) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow soHd(109mg). MS (ISP) 444 [(M+H)1; mp 228-229 °C Example 87 7-Dimethylammo-4-(3-[h2.3ltriazol-l-yl-phenyl)-8-trifluoromethyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[1^3]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic add tert.-butyl ester (Example M74) (905 mg, 1.7 mmol) by treatment with TFA in CH2Cl2 according to tihie general procedure N. Obtained as a yellow solid (566 mg). MS (ISN) 413.2 [(M-H)-]; mp 210-212 'C. Example 88 4-r4-Oxo-842.2.2-trifluoro-ethoxv)-7-trifluoromethyl-4.5-dihvdro-3H-benzofbl f 1,41 diazepin-2-yl1 -pyridine-2-carbonitrile The tide compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl] -carbamic acid tert.-butyl ester (Example M75) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (100 mg). MS (H) 428.2 (M^); mp 252-255 °C. Example 89 3-(8-Dimethylamino-7-methyl-4-oxo-43-dihydro-3H-benzorblfl.4ldiazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-Cyano-phenyl)-3-oxo-propionyi-amino]-4-dimethylamino-5-methyl-phenyl}-carbamic acid tert-butyl ester (Example M76) (0.24 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (114 mg, 59%). MS (ISP) 319.3 [(M+H)1; mp 257 °C. Example 90 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-8-methyl-L3-dihydro-benzofbl rL4ldiazepin-2-one The tide compound was prepared from (RS)-[5-dimethylamino-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M77) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). ' MS (ISP) 391.3 [(M+H)--]; mp 190 X. Example 91 2-f3-Cyano-phenyl)-8-dimetfaylamino-4-oxo-4.5-dihydrO'3H-benzo[bl[L4ldiazepine-7-carbonitriIe The title compound was prepared from {5-cyano-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-4-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example M78) (0.28 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (36 mg, 59%). MS (ISP) 328.3 [(M-H)-]; mp 251 °C Example 92 3-f7-methyl-8-(methyl-propyl-amino)-4-oxo-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin2-yl1 -benzonitrile The title compound was prepared from [2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-methyl-4-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M79) (0.17 g, 0.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg> 58%). MS (ISP) 347.4 [(M+H)1; mp 195 X. Example 93 4-[3-(5-HvdroxvTnethyl-[1.2.3ltriazol-l-yl)-phenyl1'8-methyl-7-(methyl-propvI-amino)-L3-dihvdro-benzo [bl [1,41 diazepin-2-one The title compound was prepared from (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M80) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). MS (ISP) 419.4 [(M+H)1; mp 186 °C. Example 94 7-fEthyl-methyl-amino)-4-f3-(5-hvdroxvmethyl[l,23ltriazol-l-yl)-phenyl1-8-methyl-13-dihvdro-benzo[b1fl.4ldiazepin-2-one The title compound was prepared from (RS)-[5-(ethyi-methyl-amino)-4-meth)i-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionyiamino)-phenyl]-carbamic acid tert-butyl ester (Example M81) (0.39 g, 0.64 mmol) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a off-white solid (159 mg, 61%). MS (ISP) 405.5 [(M+H)+]; mp 207 °C Example 95 8-Dimethylamino-2-f3-(5-hydroxymethyl-fl,2,3ltriazol-l-yD-phenyn-4-oxo-4.5-dihvdro-3H-benzo fb] f 1.41 diazepine-7-carbonitrile The tide compound was prepared from (RS)-[4-cyano-5-dimethylainino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoM-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl.ester (Example M82) (0.35 g, 0.58 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(149 mg> 64%). MS (ISP) 402.5 [(M+H)--]; mp 234 °C. Example 96 8-Chloro-4- f 3- f 5-hvdroxymethyl- [ 1.231 triazol- l-vD-phenyll -7-f isopropyl-methyl-amino)-L3-dihydro-benzorb1\|'l,4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M83) (0.53 g, 0.83 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a off-white solid (120 mg, 33%). MS (ISP) 439.5 [(M+H)--]; mp 207 X. Example 97 8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyll-7-(methyl-propyl-aminoyl.3-dihydro-benzofblfl.4ldiazepin-2-one The title compound was prepared from [4-methyl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M84) (0.33 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as alight yellow solid (163 mg, 64%). MS (ISP) 403.4 [(M+H)--]; mp 194 '°C. Example 98 8-Dimethylamino-2-[3-(3-methyl-isoxa2ol-5-yl)-phenyll-4-oxO'43-dihydro-3H-benzo fbl f 1.41 diazepine-7carbonitrile The title compound was prepared from (4-cyano-5-dimethyiamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-Carbaniic acid tert-butyl ester (Example M85) (0.31 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (171 mg, 72%). MS (ISP) 386.3 [(M+H)--]; mp 248 °C. Example 99 7-fEthyl-methyl-amino)-8-methyl-4-F3-(3-methyl-isoxazol-5-yl)-phenyl]L3-dihvdro-benzo fbl [ 1.41 diazepin-2-one The title compound was prepared from (5-(ethyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M86) (0.38 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow solid (160 mg, 55%). MS (ISP) 389.5 [(M+H)--]; mp 198 °C Example 100 7-DimethylaminO-8-methyl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-l3-dihydro-benzoFbl [l,4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M87) (0.32 g, 0.65 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (140 mg, 57%). MS (ISP) 375.4 [(M+H)--]; mp 204 °C. Example 101 8-Chloro-4- r3- f 5-hvdrQYvmethyl- \ 1.23ltriazol-l-yl)-phenyl1 -7-f isobutyl-methyl-amino)-13-dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isobutyl-methyl-ainino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazoM-yi]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M88) (0.32 g, 0.49 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtzdned as an ofF-white solid (107 mg, 48%)- MS (ISP) 453.4 [(M+H)--]; mp 201 °C. Example 102 8-Cbloro-7-(isobutyl-methylamino)-4-f3-f3-methyl-isoxazol-5-yD-phenyn-L3-dihvdro-benzofbirL4ldiazepin-2-one The title compound was prepared from (4-chloro-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M89) (0.35 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (114 mg, 41%), MS (ISP) 437.4 [(M+H)+]; mp 194 °C. Example 103 2-f3-(5-Hvdroxvmethyl-fl.23ltriazol-l-yl)-phenyl]-4-oxo-8-pyrrolidin-l-yl-4.5-dihvdrO-3H-benzo[b1fL4]diazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example M90) (0.37 g, 0.59 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (140 mg, 56%). MS (ISP) 428.5 [(M+H)1; mp 241 °C. Example 104 2-f3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-8-pvrrolidin-l-yM,5-dihydro-3H-benzofbl f L4l diazepine-7-carbonitrile Prepared from (4cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M91) (0.41 g, 0.77 mmol) by treatment with TFA m CH2Cl2 according to the general procedure N. Obtained as a yellow solid (90 mg, 28%). MS (ISP) 412.3 [(M+H)--]; mp 267 °C. Example 105 2-f3-(5-Hvdroxvmethyl-fl.2,3ltriazol-l-yl)-phenyl1-8-fmethyl-propvi-aminol-4-oxo-45-dihvdro-3H-benzo f b1 \ 1.41 diazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiannino)-phenyl]-carbamic acid tert-butyl ester (Example M92) (0.43 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedmre N. Obtained as a yellow solid (100 mg, 34%). MS (ISP) 430.5 [(M+H)--]; mp 221 °C. Example 106 2-f3-f3-Methyl-isoxa2ol-5-vD-phenyl-8-(methyl-propyl-amino)-4-oxo-4,5-dihvdro-3H-benzofb1 [ l,4ldiazepine-7-carbonitrile The title compound was prepared from [4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M93) (0.36 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg, 34%). MS (ISP) 414.4 [(M+H)--]; mp 133 °C Example 107 8-Diethylamino-2-[3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-4>5-dihydro-3H-benzofbl f 1.4] diazepine-7-carbonitrile The title compound was prepared from (4-cyanO-5-diethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxO-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M94) (0.35 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(209 mg, 77%). MS (ISP) 414.4 [(M+H)+]; mp 191 °C. Example 108 8-fIsopropyl-methyl-amino)-2-f3f3-methyl-isoxa2ol-5-yl)-phenyn-4-0X0-4.5-dihvdro-3H-benzofb11 L4ldiazepine-7-carbonitrile The title compound was prepared from (4-cyano-5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M95) (0.37 g, 0.70 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (219 mg, 76%). MS (ISP) 414.4 KM+H)--]; mp 197 °C. Example 109 2- r3-(5-HvdrQxvmethyl- f 1,2.3 Itriazol- l-yl)-phenyl1 -8-f isopropyi-metfayl-amino)-4-oxo-4.5-dihvdro-3H-benzo Fbl f 1,41 diazepme-7-carbonitrile The title compoimd was prepared from (RS)-[4-cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-)d]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M96) (0.45 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (236 mg, 77%). MS (ISP) 430.5 [(M+H)+]; mp 206 °C. Example 110 8-(Isobutyl-methyl-aminoV2-f3-f3-methyl-isoxazol-5-yl)-phenyn-4-0X0-4,5-dihvdro-3H-ben2ofbl [ l,4]diazepine-7-carbonitrile The title compoimd was prepared from (4-cyano-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M97) (0.39 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (230 mg, 75%). MS (ISP) 428.5 [(M+H)+]; mp 170 °C. Example 111 2-f3-(5-Hvdroxvmethyl-fL23ltriazol-l-vD-phenyl-8-(isobutyl-methyl-aminoV4-oxo-4.5-dihvdro-3H-benzofb]Fl,4ldiazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M98) (0.46 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (180 mg, 57%). MS (ISP) 444.4 [(M+H)+]; mp 199 X. Example 112 2-f3-(3-methyl-isoxazol-5-yl)-phenYll-4-oxo-8-piperidin-l-yl-43-dihydro-3H-benzofbUL4ldiazepine-7-carbonitrile The title compoimd was prepared from (4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M99) (0.41 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (226 mg, 70%). MS (ISP) 426.4 [(M+H)--]; mp 246 °C. Example 113 8-Chloro-7-isobutylamino-4-r3-(3-methyl-isoxazol-5'yl)-phenyl-13-dihvdro-benzofbl ri,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-isobutylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example MlOO) (0.34 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (216 mg, 81%). MS (ISP) 423.3 [(M+H)--]; mp 249 X. Example 114 8--Chloro-4-[3-(5-hvdroxymethyl-[L23]triazol-l'yl)-phenv]]-7-isobutylaminO'l,3-dihydrO'benzorb1fl,4ldiazepin-2-one The tide compoimd was prepared from (RS)-[4-chloro-5-isobutylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example MlOl) (0.17 g, 0.27 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg, 35%). MS (ISP) 439.4 [(M+H)--]; mp 214 X. Example 115 4-f3-(5-Hydroxvmethyl-fL2.3ltriazol-l-yl)-phenyl]-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzofb1[L4ldiazepin-2-one The title compound was prepared from (RS)-[5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M102) (0.15 g, 0-22 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (31 mg, 30%). MS (ISP) 473.2 [(M+H)--]; mp 230 °C Example 116 4-f3-(3-MethyMsoxazol-5-yiVphenyl]-7-fmethyl-propyl-aminoV8-trifluoromethyl-1.3-dihvdro-ben2orb1fL4ldiazepin-2-one The title compound was prepared from [2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M103) (0.26 g, 0.45 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (127 mg, 61%). MS (ISP) 457.4 [(M+H)+]; mp 193 °C Example 117 4'f3-(5-Hvdroxvmethyl-fl.23ltria2ol-l-\dVphenyll-7-fisobutyl-metfayl-amino)-8-trifluoromethyl-L3-dihydro-benzorbl[L4ldiazepin-2-one The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M104) (0.51 g, 0.74 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (169 mg, 47%). MS (ISP) 487.3 [(M+H)-]; mp 230 °C. Example 118 7-fIsobutyl-methyi-aminoV4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8-trifluoromethyl-13-dihvdro-benzofbUL4ldiazepin-2-one The title compound was prepared from (5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M105) (0.42 g, 0.71 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (161 mg, 48%). MS (ISP) 471.2 [(M+H)--]; mp 195 X. Example 119 4-r3-(5-Hvdroxvmethyl-ri.23ltriazol-l-yl)-phenyll-7-fisopropyl-methyl-aminoV8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-(5-(tetrahydro-pyran-2-yloxymeth)4)-[l^,3]triazol-l-yl]-phenyl}-propionyl- amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example M106) (0.50 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofif-white solid (156 mg, 45%). MS (ISP) 473.3 [(M+H)--]; mp 234 X. Example 120 7-fIsopropyl-methyl-aminoV4-f3-(3-methyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2o fbl [ 1.41 diazepin-2-one The tide compound was prepared from (5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M107) (0.37 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg, 25%). MS (ISP) 457,4 [(M+H)+]; mp 199 °C. Example 121 8-Chloro-7-fmethyl-propyl-amino)-4-f3-(5-pvrrolidin-l-ylmethyl-[1.2.3ltria2ol-l-yl)-phenyll -13'dihydro-benzo Fbl [ 1,4] diazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-ainino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepm-2-one (Example 29) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a yellow foam (63 mg, 26%). MS (ISP) 492.3 [(M+H)+]. Example 122 4-f3-(5-A2etidin-l-ylmethyl4L2.3ltriazol-l-yl)-phenyn-8-chloro-7-fmethyl-propyl-amino)-L3-dihydro-benzo fbl [l,4]diazepin-2-one The title compoimd was prepared from 8-chIoro-7-(methyl-propyi-amino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 29) (118 mg, 0.27 namol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine in DMF according to the method described in Example 45. Obtained as a light yellow solid(65 mg, 50%), MS (ISP) 478.3 [(M+HD; mp 169 °C Example 123 8-CMoro-4-f3-(5-diethylaminomcthyi-fL2J)triazol-l-yl)-phenyl]-7-fmethyl-propyl-aminoyl,3-dihvdro-benzorblfL4]dia7q?in-2-one The tide compound was prepared from 8-chloro-7-(meth-5d-propyl-amino)-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol-1 ->i)-phen\1 j -13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction wth thionylchloride in dichloro-methane and subsequent treatment of the corresponding chloride with diethylamine in DMF according to the method described in Example 45. Obtained as a Ught yellow solid (123 mg, 50%). MS (ISP) 494.3 [(M+H)--]; mp 151 °C Sample 124 8-Chloro-4-C3-l5-rfisopropvI-methyl-amino)-methyll-fL23ltriazoM-ylt-phenyD-7-(methyl-propyl-amino)-13-dihvdro-benzofbUL4]diazepin-2-one The tide compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymediyl-[l,2,3]triazol-l-yl)-phenyl]-13-dihydro-ben2o[b][l,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (129 mg, 52%), MS (ISP) 494.3 [(M+H)--]; mp 148 °C. Example 125 8-Chloro-7-fisopropyl-methyl-amino)-4-f3-f5pvrrolidin-l-ylmethyl-fL23ltria2ol-l'yI)-phenyl]-13-dihvdro-benzo[b1fL4ldiazepin-2-one The tide compound was prepared from 8-chloro-4-l3-(5-hydroxymethyi- [lA3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrroUdine in DMF according to the method described in Example 45. Obtained as a light yellow solid (157 mg, 64%). MS (ISP) 492.3 [(M+H)--]; mp 172 °C. Example 126 8-Chloro-7-fisobutyl-methyl-aminoV4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1 -13-dihvdro-benzo[b1 ri.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [ 1,2,3] triazol- l-yl)-phenyl]-7-(isobutyl-methyl-amino)- 1,3-dihydro- ben2o[b] [l,4]diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Erample 45. Obtained as a light yellow solid (163 mg, 64%), MS (ISP) 506.3 [(M+H)+]; mp 190 X. Example 127 8-Chloro-4-f3-(5-dimethylaminomethyl-fL2,3ltriazoM-yD-phenyl-7-(isopropyl-methyl-aminoyl3-dihydro-benzofb1[1.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro- benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (143 mg, 61%). MS (ISP) 566.3 [(M+H)+]; mp 225 X. Example 128 8-Chloro-4-f3-(5-dimethylaminomethyl-rL2.3ltriazoM-vD-phenyl]-7-risobutvI-methyl-aminoyl,3-dihvdro-benzofbUL4]diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro- benzo[b] [1,4] diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (134 mg, 56%). MS (ISP) 480.5 [(M+H)--]; mp 199 X. Example 129 4-[3-(5-Azetidin-l-ylmethyl-[1.2,3]triazol-l-yl)-phenyl1-8-chlorO'7-fisopropvI-methyl-amino V13-dihydro-ben2o [b] F1.41 diazepin-2one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyI-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg> 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine m DMF according to the method described in Example 45. Obtained as a light brown solid (102 mg, 43%). MS (ISP) 478.3 [(M+H)--]; mp 177 °C. Example 130 4-f3-(5-Azetidin-l-ylmethyl'fh2J]triazol-l-vD-phenyl>8-chloro-7-risobutyl-methyl-amino)-1.3-dihvdro-benzo[bl[l,4ldiazepin-2'One The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3'dihydro-benzo[b][l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimelhylene-imine in DMF according to the method described in Example 45. Obtained as a light brown solid (125 mg, 52%). MS (ISP) 492.3 [(M+H)+]; mp 191 °C. Example 131 8-Chloro-4-f3-(5'methylaminomethyl-rL2.3ltriazol-l-vD-phenyl-7-fmethyl-propyl-amino)-L3-dihvdro-benzoFb1fl.4ldiazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyi]-l,3-dihydrO-benzoIb][l,4]diazepin-2-one (Example 29) (230 mg, 0.52 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with methylamine in DMF according to method described in Example 45. Obtained as a Kght yellow solid(122 mg, 52%). MS (ISP) 452.4 [(M+H)--]; mp 185 °C. Example 132 4-f3-(5-Hvdroxvmethyl-fl,23]triazol-l-yl)-phenyl1-7-fisobulTl-methyl-amino) methyl- L3-dihvdro-ben20 Fbl [ L4l diazepin-2-one The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M108) (0.33 g, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a pale brown solid (188 mg, 79%). MS (ISP) 43L4 [(M-H)-]; mp 198 -C. Example 133 443-(5-Hvdroxvmethyl-ri23ltriazol-l-yl)-phenyl1-8-methyl-7-pvrrolidin-l-yl-13-dihydrO'benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-methyl-2-(3-oxo-3-{3-[5-(tetrahydxo-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylainino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example MHO) (0,41 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (239 mg, 86%). MS (ISP) 417-3 [(M+H)--]; mp 202 °C. Example 134 7-(Isobutyl-methyl'amino)-8-methyl-4-f3-f3-methyl-isQxazol-5-yl)-phenylyl3-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from (5-(isobutyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyI)-carbamicacid tert-butyl ester (Example M109) (0.33 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (136 mg, 53%). MS (ISP) 417.3 [(M+H)--]; mp 187C. Example 135 8-methyl-4-r3-f3-methyl-isoxazol-5-yl)-phenyl1-7-pvrrolidin-l-yl-13-dihvdro-benzofbl f L4ldiazepin-2-one The title compoimd was prepared from (4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionyiainino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyi ester ^iixample M111; (U.33 g, 0.64 mmolj by tr . nent with TFA in CH2Cl2 according to the general procedure N. Obtained a^ an off-white solid (223 mg, 87%). MS (ISP) 401.5 [(M+H)--]; mp 211 '°C. Example 136 4-F3-(5-Dimethylaminomethyl-fL2.3ltriazol-l-yl)-phenyl-7-(isobutyl-methyl-amino)-8-trifluoromethyl-13-dihydro-benzofbiri.4ldiazepin-2-one The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7-(isobutyl-methyl-amino)-8-trifluoromethyl- 1,3-dihydro-ben2o[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 35%). MS (ISP) 514.3 [(M+H)-]; mp 182 °C. Example 137 8-(Isobutyl-methyl-aminoV4-oxo-2-[3-(5-pvrrolidin-l-ylmethyl-rL23ltriazol-l-yl)-phenyn-4.5-dihydro-3H-benzorb1fl,4ldiazepine-7-carbonitrile The title compoxmd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-benzo[b][l,4]diazepine-7-carbonitrile (Example 111) (200 mg, 0.45 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (140 mg, 63%). MS (ISP) 497.3 [(M+H)--]; mp 174 °C, Example 138 7-(Isobutyl-methyl-aminoV4-f3-(5-pyrrolidin-l-ylmethyl-fl.23ltriazol-l-vIV phenyl]'8-trifluoromethyl13-dihydro-benzofb1[h4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yi)- phenyl]-7-(isobutyl-methyl-ainino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a Ught orange foam (80 mg, 24%). MS (ISP) 540.5 [(M+H)+).. Example 139 7-('Isobutyl-methyl-amino)-8-methyl-4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1-1.3-dihydro-benzorbirL4Tdiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yI)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 132) (200 mg, 0.46 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (50 mg, 22%). MS (ISP) 486.4 [(M+H)--]; mp 177 °C. Example 140 8-(Isobutyl-methyl-amino)-2-(3-{5-f(isobutyl-methyl-amino)'methyl]-rL23ltriazol-l-yll-phenyl)-4-oxo-4.5-dihvdro-3H-ben2o[b1[l,4ldiazepine'7-carbonitrile The title compoimd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepine-7-carbonitrile (Example HI) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutyl-methylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (100 mg, 39%). MS (ISP) 513.4 [(M+H)+]; mp 169 °C. Example 141 7-fIsobutyl-methyl-amino)-4-f3-l5-[(isopropyl-methyl-amino)-methyl]-[L2,3ltria2ol-l-vU-phenyl)-8-trifluoromethyl-L3-dihvdro-benzofb1[1.4ldiazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2oM-yl)- phenyl]-7-(isobutyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 117) (260 mg, 0,53 nrnnol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (70 mg, 24%), MS (ISP) 542.3 [(M+H)--]; mp 157 °C Example 142 8'Chloro-4-F3-(5-cyclopentylaminomethyl-[L23ltriazol-l-vIVphenyll-7-(isopropyl-methyl-aminoyl3-dihvdro-ben2o[b1Fl.4]diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopentylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (170 mg, 67%). MS (ISP) 506.3 [(M+H)--]; mp 174 °C. Example 143 4-f3-l5-[(Cvclopropylmethyl'amino)'methyl1-rL2.3ltriazoll-yU-phenvD-7-(isobutyl-methyl-amino)-8-methyl-L3-dihydro-benzofblfl,4]diazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyM,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 132) (250 mg, 0.58 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylmethylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (50 mg, 18%). MS (ISP) 486.4 [(M+H)+]; mp 184 °C, Example 144 8-Cbloro-7-fisobutvI-methyl-aminoV4-[3-(5-piperidin-l-ylmethyl-[1.23ltriazol-l' yl)-phenyl1-13-dihvdro-ben2ofb1fL4ldiazepin-2-one The title compoimd was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol- l-yl)-phenyl]-7- (isobutyl-methyl-amino)- 1,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with piperidine in DMF according to the method described in Example 45. Obtained as a light brown solid (250 mg, 99%). MS (ISP) 520,3 [(M+H)--]; mp 169 «C. Example 145 8-Chloro-4-B-(5-(isopropylaminO-methyl)-fL2,3ltriazol-l'yl]-phenvU-7-(isopropyl-methyl-aminoyl.3-dihvdro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenylj-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 67%), MS (ISP) 480.3 [(M+H)+]; mp 208 °C. Example 146 8-Chloro-7-fisopropyl'methyl-aminoV4-[3-(5-{f(2-methoxy-ethyl)methyl-amino1- methvU-fL2,3ltriazol-l-yl)-phenyl1-l3-dihydro-benzo[b1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-(2-methoxyethyl)methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 47%). MS (ISP) 510.4 [(M+H)+]; mp 119 °C. Example 147 8-Chloro-4-(3-{5-[(cvclopropylmethyl-aminoVmethyl]-fL23ltria2ol-l-yll-phenyl)-7-(isopropyl-methyl-amino)'13-dihvdro-benzorbl[1.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, D.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with aminomethyl-cyclopropane in DMF according to the method described in Example 45. Obtained as a light brown solid (150 mg, 61%). MS (ISP) 592,2 KM+H)--]; mp 151 °C Example 148 8-ChlorO-7-(isopropyl-methyI-aminoV4-f3-l5-f('isopropyl-metfayl-amino)-methyl]-fL23ltriazoM-yll-phenylyl3-dihvdro-benzorbUL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazoH-yl)-phenyi]-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropylmethylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 49%). MS (ISP) 494.3 [(M+H)--]; mp 180 °C. Example 149 8-Chloro-4-f3-{5-rfisobutyl-methyl-aminoVm€thyl)-rL23ltriazoM-yl]-phenyl)-7-(isopropyl-methyl-amino)-13-dihvdro-benzo[b1 [1.41 diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro- ben2o[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutylmethylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (190 mg, 75%). MS (ISP) 508.4 [(M+H)--]; mp 182 °C Example 150 4-f3'(5'DimethylaminomethyI-fL2,3]triazoI-l-yl)-phenyl]-7-risopropyl'metfayl-aminoV8-trifluoromethyl--13-dihvdro-benzofb][1.4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l>4]diazepin-2-one (Example 119) (200 mg, 0,42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as an off-white solid (80 mg, 38%). MS (ISP) 500.4 [(M+H)--]; mp 197 »C. Example 151 7-fIsopropyl-methyl-amino)-4-r3-(5-pvrrolidin-l-ylmethyl-fL23ltriazoI-l-yl)-phenyll -8'trifluoromethyl-13-dihvdro-ben20 f hi f 1,41 diazepin'2-one The title compound was prepared from 4- [3-(5-hydroxymethyl- [l,2,3]triazol- 1-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (200 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light brown solid (140 mg, 63%). MS (ISP) 526.2 [(M+H)--]; mp 175 X. Example 152 7-Qsopropyl-methyl-aminoV4-(3-l5-f(isopropyl-methyl-amino)-methyl1- fl.2.3ltriazol-l'yl}-phenyl)-8-trifluoromethyI-L3-dihvdro-benzofbUl.4]diazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (220 mg, 0.47 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropylmethylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (110 mg, 45%). MS (ISP) 528.4 [(M+H)1; mp 182 °C, Example 153 4,f3-\|5-r(CvclopropylmethylaminoVmethyl1-rL23Uria2ol-l-yll-phenyl)-7-fisopropyI-methyl-aminoV8-trifluoromethyl-L3-dihvdro-benzorb1fl,4ldiazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (210 mg, 0.44 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with aminomethyl-cyclopropane in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 47%). MS (ISP) 526.2 [(M+H)--]; mp 152 °C Example 154 8-Chloro-4- TS-f 5-cyclopropylaminomethyl- [ h2.3ltriazol-l-yl)-phenyll-7-f isopropyl-methyl-amino V13'dihvdro-b enzo f b1 f 1.41 diazepin-2- one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[ 1,2,3 ] triazol-1 -yl)-phenyl] -7- (isopropyi-methyl-amino) -13-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0,50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (40 mg, 17%). MS (ISP) 478.4 [(M+H)--];mp 144 °C Example 155 4-l3-(5-fIsopropylamino-methyl)-rL23ltriazol-l-yl]-phenyll-7-(isopropyl-methyl-amino)-8-trifluoromethyl-L3-dihvdrO'benzorbirL4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (100 mg, 39%). MS (ISP) 514.4 [(M+H)+]; mp 191 °C. Example 156 8-Chloro-4-(3-r5-fisobutylamino-methvD-fL23ltriazol-l-yl1-phenyll-7-(isopropyl-methyl-aminoyl3'dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isobutylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 65%). MS (ISP) 494.4 [(M+H)--]; mp 182 X. Example 157 4-f3-(5-Cvclopropylaminomethyl-fl.2.3ltriazoM-yl)-phenyl1-7-fisopropyl-methyl-aminoV8-trifluoromethyl1.3-dihvdro-benzofblfL4ldia2epm-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-tri6uoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethanc and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (70 mg, 27%). MS (ISP) 512.4 [(M+H)--]; mp 178 '°C Example 158 7-fIsobutyl-methyl-amino)-8-methyl-4'f3-(5-pvrrolidin-l-ylmethylfL2,4ltria2ol-l-vD-phenvI1-13-dihvdro-benzoib1fL4ldiazepin-2-one The title compound was prepared from 4-(3-(5-hydroxymethyl-[l,23]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as an ofif-white solid (106 mg, 52%). MS (ISP) 486,5 [(M+H)']; mp 164 °C. Example 159 4-[3-(5-Cyclopropylaminomethyl-fL2,4ltriazol-l-yl]-phenyl1-7-(isobutyl'methyl* amino)-8-methyl-1.3-dihydro-benzofb][L4ldiazepin-2-one The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7- (isobutyl-methyl-amino)-8-methyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (108 mg, 55%). MS (ISP) 472.4 [(M+H)--]; mp 114 °C. Example 160 8-Chloro-7-isopropylamino-4-f3-f3-methyl-isoxazol-5-vD-phenyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one The title compound was prepared from (4-chloro-5-isopropylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example Ml 12) (0.16 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (120 mg, 93%). MS (ISP) 409.4 [(M+H)--]; mp 225 °C. Example 161 8-Chloro-4-f3-(5-hvdroxvmethyl-\|-l,2,3ltriazol-l-vD-phenyll-7-isopropylamino-13-dihvdro-benzofbl [ L4l diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-isopropylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M113) (0.37 g, 0.60 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (209 mg, 82%). MS (ISP) 425.4 [(M+H)--]; mp 250 °C. Example 162 8-Chloro-7-(methyl-propyl-amino)-4-f3-(5-hvdroxvmethyl-[L2,4ltriazol-l-yl)-phenyl! -1,3-dihydro-benzo f b1 f 1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 14) (1.47 g, 2.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid(1.0 g, 99%). MS (ISP) 439.5 [(M+H)--]; mp 192 °C, Example 163 8-Chloro-4-r3-(5-hvdroxvmethyl-rL2.4ltriazol-l-yl)-phenyll-7-risobutyl-methyl-aminoyl3-dihvdro-benzofbirL4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isobutyi-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 15) (0.61 g, 0.93 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Hght brown solid (290 mg, 69%). MS (ISP) 453.5 [(M+H)--]; mp 195 °C Example 164 8-ChlorO-7-(methyl-propyl-amino)-4-f3-(5-pyrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yIVphenyll-l,3-dihvdro-benzo[b1fl,4]diazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (114 mg, 46%). MS (ISP) 492.3 [(M+H)1; mp 183^0. Example 165 8-Chloro-7'fisobutyl-methyl-aminoV4-r3-(5-pvrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yl)-phenyl] 13-dihvdro-benzo f bl [ 1.41 diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,4]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-One (Example 163) (200 mg, 0,44 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45, Obtained as a light yellow solid (99 mg, 44%). MS (ISP) 506.4 [(M+H)+]; mp 164 °C. Example 166 8-Chloro-4-f3-(5-dimethylaminomethyl-[L2.4ltriazol'l-yl)-phenyl1-7-fmethyl-propyl-amino)-1.3-dihydro-benzorblfl,4ldiazepin-2-one The title compound was prepared-from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4ltriazol-l-yl)-phenyl]-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethyiamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (93 mg, 540%). MS (ISP) 466.4 [(M+H)--]; mp 170 X, Example 167 8-Chloro-4-r3-(5-cvclopropylaminomethyl-fL2,4]tria2ol-l-yl)-phenyl1-7-fmethyl' propyl-aminoyl,3-dihvdro-benzofbUL4ldiazepin-2-one The title compound was prepared from 8-chIoro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymiethyl-[l,2,4]tria2ol-l-yl)-phcnyi)-13-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (95 mg, 40%). MS (ISP) 478.4 [(M+H)--]; mp 123 ^'C Example 168 4-f3-(5-Hvdroxymethyl-fL2,4]triazol-l-\i)-phenyll-7-fisobutyl-methyl-aminoV8-methyl'l,3-dihydro-benzofb1 (h4]diazepin-2-one Prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyi-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazoM-yl]-phenyl}-propion)iamino)-phenyi]-carbamic acid tert-butyl ester (Example Ml 16) (0.96 g, 1.51 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (480 mg, 73%). MS (ISP) 433.6 [(M+H)+]; mp 191X. Example 169 7-(methyl-propyl-aminoV4'f3-fL2,4ltriazol-l-yl-phenyl)-8-trifluoromethyM3-dihvdro-benzorbUl.4ldiazepin-2-one The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M117) (0.31 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light ydlow solid (192 mg,78%). MS (ISP) 443.4 [(M+H)--]; mp 185 C. Example 170 7-(methyl-propyl-aminoV4-(3-[l,23ltriazol-l-yl-phenvD-8-tiifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 18) (0.33 g, 0.59 mmol) by treatment -with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (115 mg, 44%). MS (ISP) 443.4 [(M+H)+]; mp 147 X. Example 171 7-(I$obutyl-methyl-aminoV4-(3-pyrazoI-l-yl-phenyl)-8-trifluoromethyl-13-dihydro-benzo fbl \ 1,41 diazepin-2-one The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 19) (0.49 g, 0.85 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (324 mg, 83%). MS (ISP) 454.4 [(M-H)-]; mp 182 X. Example 172 4-f8-(Isopropyl-methyl-amino)-4-oxQ-7-trifluoromethyl-4,5-dihvdro-3H-benzofb1[L4ldiazepin-2-yl1-pyridine-2-carbonitrile The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(isopropyI-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M120) (0.67 g, 1.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (210 mg, 41%). MS (ISP) 400.3 [(M-H)-l; mp 189 °C. Example 173 8'Chloro-7-fisobutyl-methyl-aminoV4-f3-fl.2.4ltriazol-l-yl-phenvD-13-dihvdro-benzofbl rL4ldiazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-phenyl}-carbamicacidtert-butyl ester (Example M121) (0.76 g, 1.41 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a li^t orange solid (530 mg, 89%), MS (ISP) 423.4 [(M+H)-]; mp 213 °C. Example 174 7-fIsobutyl-methylaminoV4-(3-fl,2.4ltriazol-l-yl-phenvD-8-trifluoromethyl-l,3-dihvdro-benzofbiri,4ldiazepin-2-one Prepared from {5-(isobutyl-methyl-amino)-2-[3oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M122) (0.50 g, 0,87 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (350 mg, 88%). MS (ISP) 457.5 [(M+H)-]; mp 198 X, Example 175 8-Chloro-7-(isobutvI-methyl-aminoV4-(3-[L23ltriazol-l-yl-phenylyl3-dihvdro-benzoFbl f L4]diazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M123) (0.17 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a hght yellow solid (100 mg, 75%), MS (ISP) 423.5 [(M+H)--]; mp 85 °C. Example 176 7-fIsobutyl-methyl-aminoV4-f3-fl.23ltriazol-l-'vi-phenyl)-8-trifluoromethvM3-dihvdro-benzorblfL4]diazepin-2one The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[ 1,2,3 ] triazol- l-yl-phenyl)-propionyiamino] -4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M124) (0.44 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (170 mg, 49%), MS (ISP) 457.5 [(M+H)--]; mp 202 °C Example 177 4-f3-Imida2ol-l-yl-phenvD-7-isobutylamino-8-trifluoromethyI-13-dihvdro-benzofbl ri,4ldiazepin-2-one The title compound was prepared from {2-[3-(3-imida2ol-l-yl-phenyl)-3-oxo- . propionylamino] -5-isobutylamino-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M125) (0.43 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (260 mg, 76%). MS (ISP) 442.4 [(M+H)1; mp 221 °C. Example 178 8-ChlorO'4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-L3-dihvdro-benzofb] f h4]diazepin-2-one The title compound was prepared from {4-chlorO-2-[3-(3-imidazoM-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-phenyl}-carbamic acid tert-butyl ester (Example M126) (0.33 g> 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (240 mg, 94%). MS (ISP) 408,4 [(M+H)+]; mp 212 °C. Example 179 8-Chloro-7-(isobutyl-aminoV4-f3-ri,2.3ltriazol-l-yl-phenylyl3-dihvdro-benzofbl [l,4ldiazepin'2-one The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazoH-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M127) (0.22 g, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (90 mg, 53%). MS (ISP) 407.3 [(M-H)']; mp 249 °C. Example 180 7-(Isobutyl-amino)-4-r34L23ltriazol-l-vI-phenyl)-8-trifluoromethyl-13-dihvdro-benzofbl f l,4ldiazepin-2-one The title compovmd was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionyiamino]-4-trifluoromethyl-phenyl}-carbamic add tert-butyl ester (Example M128) (0.34 g, 0.61 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (150 mg> 56%). MS (ISP) 443.4 [(M+H)+]; mp 212 °C. Example 181 8-Chloro-7-(isobutyl-aminoV4-f3-[L2,4ltriazol-l-yl-phenvD-L3-dihvdro-benzofbl [L4ldiazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carban:iic acid tert-butyl ester (Example M129) (0.39 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light orange solid (270 mg, 89%). MS (ISP) 407.3 [(M-H)-]; mp 222 X. Example 182 7-fIsobutyl-aminoV4-f3-[L2.4ltriazol-l-yl-phenyl)-8-trifluoromethyl-L3-dihvdrO' benzo[bl f 1.4]diazepin-2-one The title compound was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M130) (0.43 g, 077 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (270 mg, 61%). MS (ISP) 441.3 [(M-H)-]; mp 191X. Example 183 8-Chloro-7-fethyl-methyl-amino)-4-f3-f4-hvdroxymethyl-thiazol-2-yl)-phenyl-l,3-dihydro-benzoTbl f l,4]diazepin-'2-one The title compound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.14 g). MS (ISN) 439.2 [(M-H)]; mp 136-137 °C. Example 184 8-Chloro-4-f3-f4-hvdroxymethyl-thiazol-2-yD-phenyll-7-fmetfayl-propyl-amino)-1,3-dihydro-ben20 [b] [ 1.4] diazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-t±iiazol-2-yl]-phenyl] -propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0-10 g). MS (ISN) 453.2 [(M-H)-]; mp 211-213 °C Example 185 8-Chloro-4-[3-(4-hvdroxymethyl-thiazol-2-yl)-phenyll-7-(isopropyl-methyl-amino)-L3dihydro-benzo[b1fL4ldiazepin-2-one The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light-brown solid (0.05 g). MS (ISP) 455.2 [(M+H)1; mp 193-195 °C Example 186 8-Chloro-4-f3-(4-hydroxymethyl-thiazol-2-yl)-phenyn-7-(isobutyI-methyl-amino)-L3-dihydrO'benzofb1fl,4ldiazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyi -amino)-phenyI]-carbamic acid tert-butyl ester (0.23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.32 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g). MS (ISP) 469.1 [(M+H)--]; mp 135-136 °C Example 187 8-Chloro-7-fetfayl-methyl-aminoV4-r3-f4-hydroxvmethyl-oxa2ol-2-yl)-phenyn-l,3-dihvdro-benzofbl f l,4ldiazepin-2-one The title compound was prepared from [2-amino-4-Chloro-5-(ethyl-methyl-amino)-phenylj-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxyxnethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedxire N. Obtained as a yellow solid (0.10 g). MS (ISN) 423.1 [(M-H)-]; mp 165-166 °C. Example 188 8-Chloro-4-[3-f4-hvdroxvmethyl-oxazol-2-yD-phenyll-7-fmethyl-propyl-aminoV L3-dihvdro-benzofb1fl.4]diazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g). MS (ISP) 437.2 [(M-H)-]; mp 166-167 °C Example 189 8-Chloro-4-f3-(4-hvdroxymethyl-oxazol-2-yl)-phenyl1-7-fisopropyl-methyl-amino)-L3-dihydro-ben2ofb1 [1.41 diazepin-2-one The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyI]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-l4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a ydlow solid (0.05 g). MS (ISP) 439.3 [(M+H)-]; mp 143-145 X. Example 190 8-ChlorO-4-r3-f4hvdroxvmethyl-oxazol-2-yl)-phenyll-7-fisobutyl-methyl-amino)-13-dihvdro-benzo\|-b][1.4]diazepin-2-one The title compound was prepared from [2-aminO-4-chloro-5-(isobutyl-methyI -amino)-phenyl]-carbamic acid tert-butyl ester (0,23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (0.31 g) (Example Kll) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0,18 g), MS (ISP) 453,3 [(M+H)-]; mp 166-167 °C. Example 191 8-Chloro-7-dimethylamino-4-f3-(4-methylaminomethyl-thiazol-2-yl)-phenyll-1.3-dihydro-benzofb]fL4ldiazepin-2-one al 8-ChIoro-4-f3-(4-chloromethyl-thia2oI-2-yl)-phenyll-7-dimethylamino-13' dihydro-benzo[b][1.4]diazepin-2-one A mixture of 8-chIoro-7-dimethylamino-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.38g) (Example 19) andthionyl chloride (0,1 mL) in CH2Cl2 was heated to 40 -°C for 2 h. The heterogeneous mixture was evaporated in vacuum and the residue was triturated with AcOEt to give the title compound (0,44 g) as a light-brown soHd, MS (ISP) 445.1 [(M+H)+], b) 8-Chloro-7-dimethyiamino-4-f3-(4-methylaminomethyl-thiazol-2-vD-phenyl-l,3-dihydro-ben2orb][l,4]diazepin-2-one A mixture of 8-chloro-4-[3-(4-chloromethyl-thia2ol-2-yl)-phenyl] -7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (89 mg) and KI (3 mg) in a 8M solution of methylamine in EtOH (1 mL) was stirred at 20 °C for 20 h. H2O (25 mL) was acided and the pH of the mixture was set to 11 by acidition of 2N NaOH. The precipitate was collected by filtration and purified by chromatography on silica gel using MeOH as eluent. The product was stirred with 20% aqueous MeOH (10 mL) and the solid was isolated by filtration to give the title compound (49 mg) as a yellow powder, MS (ISP) 440.2 [(M+H)--]; mp 129-130 °C. Example 192 8-Chloro-7-dimethylamino-4-f3-f4-morpholin-4-ylmethyl-thia2ol-2-yD-phenyl1-1.3-dihvdro-benzofbl ri,4ldiazepin-2-one A mixture of 8-chlo^o-4-[3-(4-chloromethyl-thiazol-2-yl)-phenyl]-7-dimethyla^mlo-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one (89 mg) (Example 191a), morpholine (0.17 mL) and KI (3 mg) in EtOH (0.5 mL) was stirred at 60° C for 3 h. H2O (25 mL) was acided to the cooled solution and the precipitate was collected by filtration and purified by chromatography on silica gel using AcOEt/acetone (1:1) as eluent The product was stirred with 20% acjueous MeOH (20 mL) The pH of the mixture was set to 11 by acidition of IN NaOH and the solid was subsequently isolated by filtration to give the title compound (55 mg) as yellow powder. MS (ISP) 496.2 [(M+H)--]; mp 138-143 °C Example 193 8-Chloro-7-dimethylaminO-4-[3-(2-hydroxvmethyl-thiazol-4-vD-phenylyl3-dihydrO'benzorb][L4ldiazepin-2-one a)4-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylaminO'13-dihvdro-benzofb] [L4Tdiazepin-2-one A solution of 3-Oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (2.34 g) (Example K28) and (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example J2) (L57 g) in toluene (16 mL) was heated to 100 C for 5 h. The solvent was evaporated in vacuimi and the crude product was purified by chromatography on silica gel using CH2Cl2/AcOEt (1:20) as eluent. A solution of the purified material (2.4 g) in CH2Cl2/TFA (1:1,30 mL) was stirred at 20 °C for 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated. The residue was crystallized firom AcOEt/EtaO to give 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b] [l,4]diazepin-2-one as light-brown solid. b^8-Chloro-7-dimethylamino-4-f3-(2-hvdroxvmethyl-thiazol-4-yl)-phenyl1-L3-dihvdro-benzofbl f L4ldiazepin-2-one A mixture of 4-(3-bromoacetyi-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-beiizo[b][l,4]diazepin-2-one (0.22 g) and 2-(tert-butylcarbonyl-oxy)thioacetamide (0.11 g) in EtOH (3 mL) was heated at 80 C for 0.5 h. The solution was diluted with AcOEt, washed with saL NaHCOa solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (8 mL) and L5N KOH (8 mL) at 20 °C for 20 min. H2O (30 ml) was acided and the precipitated product collected by filtration to give the title compound (0.9 g) as yellow powder. MS (ISP) 427.3 [(M+H)']; mp 176-178 °C Example 194 4-r3-(2-Amino-thiazol-4-yl)-phenNi1-8-chloro-7-dimethylamino-l.3-dihvdro-benzo [bl f 1.41 diazepin-2-one A mixture of 4-(3-bromoacetyi-phcn>1)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.73 g) (Example 193a) and thiourea (0,13 g) inTHF (10 mL) was heated to 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and vsith brine. The organic layer was dried and evaporated and the residue was stirred \%-ith CH:Q: to give the title compound (0.14 g) as yellow solid, MS (ISN) 410.2 [(M^H)-]; mp 247-248 °C Example 195 8-Chloro-7-dimethylamino-4-f3-(2-ethylamino-thiazol-4-yl)-phenyl1-13-dihvdro-benzofbl [L4ldiazepin-2-one A mixture of 4-(3-bromoacetyl-phenyi)-8-chloro-7-dimethylamino-13-dihydro-benzo[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THE (3mL) was heated at 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et20 to give the title compound (24 mg) as yellow solid. MS (ISP) 440.3 [(M+H)--]; mp 122-123 °C. Example 196 N-{4-f3-(7-ChlorO'8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb1fL4ldiazepin-2-vD-phenyl1-thiazol-2-yl}-guanidine A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-amidino-thiourea (35 mg) in THE (3mL) was heated at 60 'C for 1 h- The mixture was diluted with AcOEt and washed with sat NaHCOa solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/MeOH (20:1) as eluent. The purified product was crystallyzed from acetone to give the title compound (22 mg) as yellow solid. MS (ISP) 454.2 [(M+H)--]; mp 221 X dec. Example 197 8-Chloro-7'dimethylamino-4-(3-[2-(pyridin-4'ylamino)-thiazol-4-yl]'phenvU-13-dihvdro-benzo[b1[1.4ldiazepin-2-one A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and l-(4-pyridyl)-2-thiourea (46 mg) in THE (3mL) was heated at 60 X for 45 min. The mixture was dfluted with AcOEt and washed with sat NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was triturated with Et20 to give the title compound (55 mg) as yellow solid. MS (ISP) 489.2 [(M+H)']; mp 231-234 °C. Example 198 8-ChlorO-4-f3-(2-metfayl-Oxazol-4-yl)-phenyl1-7-(methyl-propyl-amino)-l,3-dihydro-benzorb1fl>4'idiazepin-2-one The title compoimd was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (0.17 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.07 g). MS (ISP) 423.2 [(M+H)-]; mp 163-164 X. Example 199 4-f3-(4-HydrGxymethyl-thiazol-2-yl)-phenyl-8-methyl-7-rmethyl-propyl-aminoV L3-dihvdro-benzofb1 f l.>41diazepin-2-one The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.09 g). MS (ISP) 435.3 [(M+Hr];mp 222-224^0. Example 200 4-f3-f4-Hvdroxymethyl-oxazol-2-yl)-phenyl1-8-methyl-7-fmethyl-propyi'aminoV L3-dihydro-benzo[b1fl.4]diazepin-2-one The title compound was prepared from [2-amino-4-methyl-5-(meth)i-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4- (tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example Kll) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.16 g). MS (ISP) 419.3 [(M+H)+]; mp 200-202 °C. Example 201 7-Dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-8-trifluoromethyl-1,3 - dihvdro-benzo f b1 [ 1 A] diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.12 g). MS (ISP) 461.2 [(M+H)1; mp 198-199 °C, Example 202 7-Dimethylamino-4-[3-(4-hvdroxvmethyl-oxazol-2-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofblfL4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phen)d]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.11 g). MS (ISP) 445.0 [(M+H)]; mp 197-198 °C Example 203 4-f3-f4-Hvdroxymethyl-thiazol-2-y!VphenvI1-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2one The title compound was prepared from [2-amino-5-(methyl-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tcrt-butyl ester (0.17 g) (Example J35) and 3-0X0-3- [3- [4-(tetrahydro-pyran-2->'iox>TOCthyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cydizcd by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g). MS (ISP) 489.2 [(M+Hr];mp 177-180^ ^3B^mple 204 7-Dimethylamino-4-f3-(5-hvdroxymeth\i-fL3.4]thiadiazol-2-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzofb]fl.4ldia7epin-2-one The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyi ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadia2ol-2-yl]-phenyi}-propionicacid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as ofif-white solid (0.06 g). MS (ISP) 462.1[(M+H)'-]; mp 242-246 X. Example 205 7-Dimethylamino-4-{3-r5-(2-hvdroxv-ethvD-fL3,4lthiadiazol-2-yl1-phenylt-8-trifluoromethyl-13-dihydro-ben2o Fb ] f L4l diazepin-2-one The title compoxmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,3,4]thiadiazoI-2-yl}-phenyi)-propionic acid tert-butyl ester (0.24 g) (Example K3I) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a oflF-white solid (0.06 g). MS (ISN) 474.2 [(M-H)-]; mp 234-237 X, Example 206 7-Dimetfaylamino-4-f3-(5-hvdroxvmethyI-fl3.4loxadiazol-2-yl)-phenyn-8-trifluoromethyl-13-dihvdro-benzo f b] [ 1,41 diazepin-2-one The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (1.44 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3>4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (2.17 g) (Example K32) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g). MS (ISP) 463.2 [(M+NH4)+]. Example 207 7-Dimethylamino-4-(3-r5-(2-hvdroxv-ethyl)-[13.4loxadia2ol-2-yl1-phenvU-8-trifluoromethyl-13-dihydro-benzo f b] f 1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [1,3,4] oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (0.23 g) (Example K33) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g). MS (ISP) 460.2 [(M+H)--]; mp 237 °C dec. Example 208 7-Dimethylamino-4-(3-oxazol-4-yl-phenyl)-ig-trifluoromethyl-L3-dihvdro-benzofbl f h4ldiazepin-2-one The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K34) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (50 mg). MS (ISP) 415.2 [(M+H)--]; mp 218-219 °C. Example 209 7'Dimethylamino-4-f3-tfaia2ol-4-yl-phenyl)-8-trifluoromethyl-L3-dihydro-benzofbl f l,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (109 mg) (Example K35) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (61 mg). MS (ISP) 431.2 [(M+H)--]; mp 200 °C dec. Example 210 7-Dimethylamino-4-[3-(2-methyl-oxazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofb] f L4ldiazepin-2'One The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(2-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.18 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.04 g). MS (ISP) 429.3[(M-hH)-']; mp 192-193 °C. Example 211 7-DimethyIamino-4-f3-(5-methyl-oxazoI-4-yn-phenyn-8-trifluoromethyl-L3-dihvdro-benzofb1fl,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyi)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,18 g) (Example K36) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.13 g). MS (ISP) 429.3 [(M+H)--]; mp 238-239 °C. Example 212 7-Dimethylamino-4-[3-(2-methyl-5-propyI-oxa2ol-4-yi)-phenyl-8-trifluoromethyl-1.3-dihydro-benzo[b]fl.4]diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (80 mg) (Example J6) and 3-[3-(2-methyl-5-propyl-oxazoI-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K37) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as pale-yellow solid (20 mg). MS (ISP) 471,2 [(M+H)'];mp 211-212 °C. Example 213 7-Dimethylamino-4-[3-(5-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzofb] [ L4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-[3-(5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,19 g) (Example K38) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0,06 g). MS (ISP) 445.2 [(M+H)1; mp 214-215 °C Example 214 7-Dimethylamino-4-[3-(2,5-dimethyl-thiazol-4-yl)-phenyn-8-trifluoromethyM,3-dihydro-benzofbl f L4]diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (48 mg) (Example J6) and 3-[3-(2>5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (50 mg) (Example K39) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (38 mg). MS (ISP) 459.2 [(M+H)--]; mp 208-209 X. Example 215 7-Dimethylamino-4-f3-(2-hvdroxymethyIthiazol-4-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one a)4(3-Bromoacetyl-phenyl)-7-dimethylamino-'8-trifluoromethyl1.3-dihydro-benzofbl f l,4ldiazepin-2-one A solution of (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (0.32 g) and 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyi ester (0.43 g) (Example K28) in toluene (3 mL) was heated to 100 °C for 2 L The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using AcOEt /Hexan(l:3) as eluent A solution of the purified material (0.57 g) in CH2Cl2/TFA (1:1,7 mL) was stirred at 20 ®Cfor 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated to give crude 4-(3-bromoacetyl-phenyl)-7-dimethylainino-8-trifluoromethyM,3-dihydro-benzo[b][l,4]diazepin-2-one (0.22 g) as light-brown solid. b) 7-Dimethylamino-4-f3-(2-hvdroxymethyl-thiazol-4-yl)-phenyl1 -8-trifluoro-methyl-1.3-dihydro-benzo fbl F1,41 diazepin-2-one A mixture of 4-(3-bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-l>3-dihydro-benzo[b][l,4]diazepin-2-one (0.40 g) and 2-(tert.-butylcarbonyloxy)thio-acetamide (0.21 g) in EtOH (5 mL) was heated at 80 'C for 0.5 h. The solution was diluted with AcOEt, washed with sat NaHCOs solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (5 mL) and L5N KOH (5 mL) at 20 ^'C for 20 min. H2O was acided and the predpitated product coDected by filtration and purified by chromatography on silica gel using AcOEt as eluent to give the title compound (0.01 g) as yellow solid. MS (ISP) 461.1 [(M+H)--]. Example 216 7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-methyl-thia2ol-4-yl)-phenyil-8-trifluoromethyl-1,3-dihydro-benzofb1 \ 1.41 diazepin-2-one The title compound was prepared firom (2-an:iinO-5-dimethylamino-4-trifluoro-methyi-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-mediyl-2-(tetrahydro-pyran-2-yloxymedi)d)-thiazol-4-yl]-phen)i}-propionicadd tert-butyl ester (0.26 g) (Example K40) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as light-yellow solid (0.11 g). MS (ISP) 475.2 [(MH-H)I; mp 190-193 °C Example 217 7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-propyl'thiazol-4-vD-phenyl1-8-trifluoromethyl-h3-dihydro-benzofb1 [1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (79 mg) (Example J6) and 3-oxo-3-{3-[5-propyl-2-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (138 mg) (Example K41) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (45 mg). MS (ISP) 503.2 [(M+H)1; mp 112-114 °C Example 218 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-2-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzorbUl,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionicacid tert-butyl ester (0.26 g) (Example K42) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid(0.11 g). MS (ISN) 473.0 [(M-H)']; mp 226-227 '°C. Example 219 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-thiazol-4-yl)-phenyll-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{[5-(tetrahydro-pyran-2-yioxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (0,25 g) (Example K43) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0-08 g). MS (ISN) 459.3 [(M-H)-]. Example 220 4-(3-f5'f(CvcIopropylmethyl-amino)-methyll-thiazol-4-yn-phenyl)-7-dimethylamino-8-trifluoromethyl-L3-dihvdro-benzorb1fL4ldiazepin-2-one A mixture of 7-dimethylamino-4-[3-(5-hydroxymethyl-thiazol-4-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 219) (65 mg) and thionyl chloride (0.015 mL) in CH2Cl2 (0.3 mL) was stirred at 20 °C for 1 h. The heterogeneous mixture was evaporated in vacuum and the residue was suspended in EtOH (0.5 mL). Aminomethyl-cyclopropane (0.12 mL) and KI (3 mg) were acided and the mixture was stirred at 80 ^'C for 5 h. The mixture was evaporated in vacuum ant the residue was purified by chromatography on silica gel using AcOEt/MeOH (50:1) as eluent The resulting product was stirred with 20% aqueous MeOH (10 mL)) the pH of the mixture being set to 11 by the acidition of IN NaOH, and the solid was isolated by filtration to give the title compound (44 mg) as off-white solid. MS (ISP) 514.3 [(M+H)--]; 157-158° C. Example 221 7-Dimethylamino-4-f3-(2-isopropyl-lH-imidazol-4-yl)-phenyl1-8-trifluoromethyl-L3-dihydro-benzo[birL4ldiazepin-2-one The title compotmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbanuc acid tert-butyl ester (0.13 g) (Example J6) and 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.20 g) (Example K44) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.10 g). MS (ISP) 456.4 [(M+H)--]; mp 150 Xdec. Example 222 4-f3-(5-Hvdroxymethyl-[13.4lthiadiazol-2-yl)-phenyl-7-(methyl-propyl-aminoV8-trifluoromethyl-13-dihvdro-benzo[b1fL4ldiazepin-2-one The title compound was prepared from [2-amino-5-(methyi-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (0.17 g) (Example J35) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[13>4]thiadiazol-2-yi]-phenyl}-propionic acid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.02 g). MS (ISP) 490.2 [(M+H)--]; mp 193-194 --C. Example 223 8-Chloro-7-dimethylamino-4-l3-r5-(2-hvdroxv-ethyl)-ri,3,4lthiadiazol-2-yl]-phenyl)-13-dihvdro-ben2ofb1fl.4]diazepin-2-one The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (0.15) and crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phenyl)-propionicacid tert-butyl ester (0.24 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g). MS (ISN) 440.2 [(M-H)-]; mp 198-200 °C. The active ingredient having a suitable particle size, the crystalline lactose and the microcrystaUine cellulose are homogeneously mixed with one another, sieved and thereafter talc and magnesium stcarate are admixed. The final mixture is filled into hard gelatine capsules of suitable size. Example I Tablets of the following composition are produced in a conventional maimer mg/Tablet Active ingredient 100 Powdered, lactose 95 White com starch 35 Polyvinylpyrrolidone 8 Na carboxymethylstarch 10 Magnesium stearate _2 Tablet weight 250 Example II Tablets of the following composition are produced in a conventional manner: mg/Tablet Active ingredient 200 Powdered, lactose 100 White corn starch 64 Polyvinylpyrrolidone 12 Na carboxymethylstarch 20 Magnesium stearate ^ Tablet weight 400 Example III Capsules of the following composition are produced: mg/Capsule Active ingredient 50 Crystalline, lactose 60 Microcrystalline cellulose 34 Talc 5 Magnesium stearate 1 Capsule fill weight 150 Case 20871 Dihydro-benzo[b] [l,4]diazepin-2-one derivatives as mGluR2 antagonists II The present invention relates to compounds of general formula I selected from the group consisting of halogen, lower alkyl, fluoro-lower alkyl, C3-C6-cycloalkyl, lower alkoxy and fluoro-lower alkoxy; R2 is -NR'R-, fluoro4ower alkoxy or S-oxo-piperazin-l-yl, pyrrolidin-l-yl or piperidm-l-}d, which rings are optionally substituted by R-; R' is hydrogen, lower alkyl, C3-C6-cycloalkyl, fluoro-lower alkyl or 2-lower alkoxy lower alkyl; R- is hydrogen, lower alkyl, and to their pharmaceutically acceptable addition salts. It has surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists. Compounds of formula I are distinguished by valuable therapeutic properties. In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, which is sent out by a neuron, with a neuroreceptor. . L-glutamic acid, the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms hgand-controUed ion channels. The metabotropic glutamate receptors (mGluR) form the second main group and, furthermore, belong to the family of G-protein-coupled receptors. At present, eight different members of these mGluR are known and of these some even have sub-types. On the basis of structural parameters, the different influences on the synthesis of secondary metabolites and the different affinity to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGluRl and mGluRS belong to group I, mGluR2 and mGluR3 belong to group II and mGluR4, mGluR6, mGluR7 and mGluRS belong to group III. Ligands of metabotropic glutamate receptors belonging to the group II can be used for the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications in this connection are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are chronic and acute pain, Himtington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutarnate-defidency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, opiate addiction, anxiety, vomiting, dyskinesia and depressions. Objects of the present invention are compounds of formula I and their pharmaceutically acceptable salts per se and as pharmaceutically active substances, their manufacture, medicaments based on a compound in accordance with the invention and their production, as well as the use of the compounds in accordance with the invention in the control or prevention of illnesses of the aforementioned kind, and, respectively, for the production of corresponding medicaments. The compounds of formula I can also be used in form of their prodrugs. Examples are esters, N-oxides, phosphate esters, glycoamide esters, glyceride conjugates and the like. The prodrugs may add to the value of the present compounds advantages in absorption, pharmacokinetics in distribution and transport to the brain. All tautomeric forms of the compounds of the invention are also embraced herewith. Preferred are compounds of formula I, wherein X is a single bond. Exemplarly preferred are compovmds, wherein R^ is trifluoromethyl, and especially those wherein R is cyano, for example the following compounds: 4-(4-oxo-8-pyTrolidin-l-yl-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-pyridine-2-carbonitrile, 4-[8-(cyclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ l,4]diazepin-2-yl] -pyridine-2-carbonitrile, 4-[8-(cyclopropylmethyl-amino)-4-oxo-7-trifiuoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl]-pyridine-2-carbonitrile, 4-[4-oxo-8-(2,2,2-trifluoro-ethoxy)-7-trifluoromethyI-4,5-dihydro-3H-ben2o[b] [l,4]diazepin-2-yl]-pyridine-2-carbonitrile, and 4-[8-(isopropyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ 1,4] diazepin-2-yl] -pyridine-2-carbonitrile. Further preferred are compounds, wherein X is a single bond, R^ is trifluoromethyl and R is an optionally substituted five-membered aromatic heterocyde, which may be substituted by halogen, fluoro-lower alkyl, fluoro-lower alkoxy, cyano, -(CH2)n-NR'R-, -(CH2)n-C(O)-0R-, -(CH2)n-C(O).NR'R-, .(CH2)n-S02-NR'R-, -(CH2)„-C(NH2)=NR-, hydroxy, lower alkoxy, lower alkyithio, or by lower alkyl, which is optionally substituted by fluoro, hydroxy, lower alkoxy, cyano or carbamoyloxy. Examples of such compounds are the following: 7-dimethylamino-4-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimethylaimnO-4-[3-(2-metiiyl-2H-pyra2ol-3-yl)-phenyi]-8-tri dihydro-benzo [b] [ 1,4] diazepin-2-one, 7-dimethylamino-4-(3-imidazol-1 -yl-p}ienyl)-8-trifluoromethyl- 1,3-dihydro- benzo[b] [l,4]diazepin-2-one, 4-[3-(3-methyHsoxa2ol-5-yl)-phenyl]-7-(methyl-propyl-ainino)-8-trifluoromethyl-1,3-dLhydro-benzo [b] [ 1,4] diazepin-2-one, 7-(isobutyl-methyl-amino)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-8-trifluorom l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-(isopropyl-inethyl-ainmo)-4- [3-(3-methyl-isoxa2ol-5-yl)-phenyl] -8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-(isobu1yl-methyl-amino)-4-(3-{5-[(isopropyl-methyI-ainino)-inethyl]- [ 1,2,3] triazol-1-yl}-phenyl)-8-trifluoromethyl-l,3-dihydro-ben2o [b] [ 1,4] diazepin-2- one, 7-(isopropyl-methyl-amino}-4-[3-(5-pyrroKdin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl] -8-txifluorometliyl-l,3-dihydro-benzo [b] [1,4] diazepin-2-one, 7-(methyl-propyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-8-trifluoromethyl-l,3 dihydro-benzo[b][l,4]diazepin-2-one, 7-(isobutyl-methyl-amino)-4-(3-[l,2,3]tria2ol-l-yl-phenyl)-8-trifluoromethyl-1,3 dihydro-benzo [b] [ l,4]diazepin-2-one, 4-(3-imidazol-l-yl-phenyl)-7-isobutylaniino-8-trifluoroinethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimeliiylaiiuno-4-[3-(4-hydroxymethyl-liiiazol-2-yl)-phenyl]-8-trifluoronieA^ l,3-dihydro-benzo[b][l,4]diazepin-2-one, 7-dimethylamino-4-[3-(4-hydroxyniethyl-Oxazol-2-yl)-phenyl]-8-1xifluoronieli^ l,3-dihydxo-ben2o[b] [1,4] diazepin-2-one, 4-[3-(4-hydroxynxethyl-thiazol-2-yl)-phenyl]-7-(niethyl-propyl-anriino)-8-trifluoroniethyl-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one, and 4-[3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-phenyl]-7-(niethyl-propyI-aniino) trifluoromethyl-1,3-dihydro-ben2o [b] [ 1,4] diazepin-2-one. Also preferred are compounds, wherein X is a single bond, and R is chloro, tor example the following compounds: 8-diloro-7-isobutyla,in-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro- ben2o[b] [l,4]diazepin-2-one, 8-cUoro-7-(methyl-propyl-amino)-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydrO-benzo[b] [l,4]diazepin-2-one, 8-chloro-7-(isopropyl-methyl-amino)-4-[3-(5-pyrrolidin«l-ylmethyI-[l,2,3]triazoI-l-yl)-phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one, 8-cHoro-7-(isobutyl-methyl-amino)-4-[3-(5-pyrroHdin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one, 8-chloro-4-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-8-chloro-7-(isopropyl-methyl-amino)-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one, 4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazl-yl)-phenyl]-8-chloro-7-(isobutyl-methyi-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one, 8-chloro-7-(isobutyl-methyI-amino)-4-[3-(5-piperidin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one, 8-chlorO-7-(isopropyl-methyl-amino)-4-(3-{5-[(isopropyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-13-dihydro-benzo[b][l,4]diazepin-2-one, 8-chloro-4-(3-{5-[(isobutyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-7-(isopropyl-methyl-amino)- 1,3-dihydro-benzo [b] [1,4] diazepin-2-one, 8-chloro-7-isopropylamino-4-[3-(3-methyl-isoxazol-5-yl)-phenyi]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 8-chloro-7-(isobutyl-methyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 8-chIoro-4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-1,3-dihydro-benzo [b] 11,4] diazepin-2-one, 8-chloro-7-(ethyl-methyl-amino)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one 8-chloro-4-[3-(4-hydroxymethyi-thiazol-2-yl)-phenyl]-7-(methyl-propyl-amino)-13-dihydro-benzo[b]l [l,4ldiazepin-2-one 7-(ethyl-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-dimethylamino-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, 7-(isobutyi-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one> 7-(isobutyl-methyl-amino)-8-methyi-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, and 4-(3-{5-[(cyclopropylmethyl-amino)-methyI]-[l,2,3]triazol-l-yl}-phenyl)-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one. Preferred are further compounds, wherein R is -N(CH3)2 or pyrrolidine. Also preferred are compounds, wherein R2 is isopropyl-amino, isopropyl-methyl-amino, isobutyl-amino or isobutyl-methyl-amino. Preferred compounds of formula I in the scope of the present invention are further those, wherein R is cyano or an optionally substituted five-membered aromatic heterocycle, which may be substituted by -CH2OH or -CH2N(CH3)2. The term -lower alkyl- used in the present description denotes straight-chain or branched saturated hydrocarbon residues with 1-7 carbon atoms, preferably with 1-4 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl and the like. The term 'lower alkoxy- denotes a lower alkyl residue in the sense of the foregoing definition bound via an oxygen atom. Examples of'lower alkoxy- residues include methoxy, ethoxy, isopropoxy and the like. The term -halogen- embraces fluorine, chlorine, bromine and iodine. The term -fluoro-lower alkyl- means a lower alkyl residue, wherein one or more hydrogen-atoms may be replaced by fluoro. The term -fluoro-lower alkoxy- denotes a lower alkoxy residue in the sense of the definition herein before, wherein one or more hydrogen-atoms may be replaced by fluoro. The term -C3-C6-cycloalkyl- means a cycloalkyl group containing 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The term -lower alkylthio- denotes a lower alkyi residue in the sense of the foregoing definition bound via an sulfur atom, for example methylsulfanyl. The expression -five-membered aromatic heteroqrde' embraces fiirane, thiophene, thiazole, pyrrole, imidazole, pyrazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole and tetrazole. Preferred heterocycles are 1,2,3-triazole, 1,2,4-triazole, isoxazole, l,3-oxa2ole, 1,3-thiazole, 1,3,4-oxadiazole or imidazole, -Optionally substituted- means that a group may or may not be substituted with one or more, preferably one or two substituents independently selected from the specified group. The term -pharmaceutically acceptable addition salt- refers to any salt derived from an inorganic or organic acid or base. The compounds of general formula I and their pharmaceutically acceptable salts can be manufactured according to methods, which process comprises a) reacting a compound of formula II which subsequently undergoes deprotection of the amino group and cyclization, to obtain a compound of formula 1 According to scheme A, compounds of general formula I, in which X, Y, R1 R2 and R3 are as described above, can be prepared from compounds of general formula II via an acyiation-deprotection-cyclization sequence; For example reacting compounds of general formula II with a dioxinone IV, in which Y and R3 are as described above> in an inert solvent such as toluene or xylene at elevated temperatures, preferably between 80 °C and 160 °C gives rise to compounds of general formula III. Alternatively, compounds of general formula III can also be prepared by for example reaction of a compound of general formula II with a p-ketoester (general formula rVa), in which Y and R^ are as described above using the same conditions as described for the reaction with the dioxinones. Afterwards, deaving the BOC protecting group in compounds of general formula III and concomitant cydization of the deprotected compound yidds the desired compounds of general formula I. Any other suitable amino protecting group, such as e.g- Fmoc or benzyloxycarbonyl (Z), can be altemativdy used instead of the BOC group. The deprotection-cyclization step can be carried out by treating the compounds of general formula III with for example a Bronsted add such as trifluoroacetic add in an inert solvent such as dichloromethane (DCM). The reaction is preferably carried out at temperatures between 0°C and 50 °C- It may be advantageous to use also anisole or 1,3-dimethoxybenzene as a carbocation scavenger in the reaction mixture. According to scheme B, compounds of general formula 11 in which R^ is phenyl optionally substituted as described above for compounds where X is a single bond and R is as described above, can be prepared by different routes depending on the nature of R3 from the iodo-compounds of general formula V, in which R3 is as described above. As shown in scheme B, the key step is a coupling reaction of Suzuki-type to produce compounds of the general formula Via. Compounds of general formula II, in which R1, R3 and X are as described above can be prepared according to scheme B, by reducing the nitro group in compounds of general formula Via to the amino group. The reduction can for example be carried out using hydrogen gas in presence of a suitable catalyst like for example Raney-Nickel or Palladium on carbon. Another possible reduction method is using stannous (II) chloride (SnCl2-2H2O) in ethanol at temperatures between 70 --C and 80 °C (as described in Tetrahedron Lett, 1984,25,839), or alternatively in polar aprotic solvents, like DMF, DMA or NMP and the like, optionally in the presence of bases, like for example pyridine or triethylamine and the like, at temperatures between 0°C and 80 °C. Another suitable method is using zinc-powder in the presence of ammonium chloride in protic solvents like for example water or ethanol at temperatures between 20 °C and 80 °C. The exact conditions for the respective compounds of general formula II can be found in the experimental part. Compounds of general formula V, in which R1 is as described above, can be prepared by different routes depending on the individual residue R2: As shown in scheme C, compound Bl can be prepared from the commercially available 5-chloro-2-nitroaniline by iodination to give the synthetic intermediate Al, which in turn can be protected to yield the compound BL The iodination step can be carried out by for example using iodine monochloride in acetic acid in the presence of sodium acetate. The reaction can be for example carried out at temperatures between 20°C and 80 °C. The protection of the amino function can be applied to a number of commercially available starting materials or compounds synthesized by anyone skilled in the art to produce the corresponding 2-nitroanilines with the general formula VII, in which X is a single bond and R1 is as described above. This transformation leads to the key intermediates of the general formula VIb, and the exact conditions for the respective compounds used in this invention can be foimd in the experimental part. ) One possibility for the protection of the amino function is for example reacting compounds of general formula VII with di-tert-butyl-carbonate in the presence of a base such as cesium carbonate. The reaction can be carried out in polar solvents such as acetone or butanone and the like at temperatures between 20 °C and 60 °C. Alternatively, the protection of the amino group can be achieved by preparing the intermediate isocyanate by treatment of compoimds of the general formula VII with diphosgene, preferably in aprotic solvents such as ethyl acetate or 1,4-dioxane at temperatures from 0 °C to 100 °C, and subsequent treatment of the isocyanate with tert. butanol in solvents such as dichloromethane or 1,2-dichloroethane and the like at temperatures between 20 °C and 85 °C to give the desired compoimds of general formula Vlb. Another suitable method to achieve this protection step is the intermediate formation of a di-BOC compound by treatment of compounds of the general formula VII with di-tert.-butyl-carbonate in the presence of DMAP in an aprotic solvent such as tetrahydrofuran and the like, followed by selective removal of a single BOC-group by treatment with a Bronsted-acid, like e.g. TFA, in aprotic solvents such as dichloromethane, chloroform or 1,2-dichloroethane at temperatures between 0 °C and 20 °C to give the desired compounds of general formula VIb. According to scheme D, compounds of general formula VII in which R1 is pyrrol- 1-yl optionally substituted as described above, X is a single bond and R is chloride, can be prepared from known 5-chloro-2-nitro-l,4-phenylenediamine [CAS-No. 26196-45-2] by selective condensation of the 4-amino-group with a suitable substituted 2,5-dimethoxytetrahydrofuran with the general formula VIII, as described in/. Heterocycl Chem, 1988,25,1003. The reaction is preferably carried out in acidic media, like for example acetic acid or propionic add and the like, at temperatures between 40 °C to 100 °C. The exact conditions for the respective compounds can be found in the experimental part The corresponding substituted 2,5-dimethoxytetrahydrofurans -with the general formula VIII, in which Ra, Rb and Rc are as described above in the general claim for the pyrrol-1-yl compounds, are either commercially available, or synthesized from the suitable substituted furan, as shown in scheme E. The corresponding substituents can optionally be protected with suitable protecting groups, known to someone skilled in the art, or alternatively can be introduced after the pyrrol ring synthesis. The two-step sequence consists of reacting the furan with bromine in MeOH at low temperature, like for example -35 '°C, followed by treatment with base, like for example triethylamine and the like or potassium carbonate or sodium hydrogen carbonate and the like. The resulting 2,5-dimethoxydihydrofuran with the general formula VIII, in which Ra, Rb and Rc are as described above, can be reduced by catalytic hydrogenation, preferably in MeOH with catalysts like for example Palladium on carbon or Raney-Nickel and the like, to produce the desired 2,5-dimethoxytetrahydrofurans with the general formula VIII. An example for this sequence can be found in Tetrahedron 1971,27, 1973-1996. The exact conditions for the individual compounds to be synthesized can be found in the experimental part. As shown in scheme F, compounds of general formula VIc, in which R2 is attached via a nitrogen-atom and is as described above, can be prepared from the intermediate compounds with the general formula VIb - which individual synthesis can be found in the experimental part - by a nucleophilic substitution reaction with the respective amines in the presence of a suitable base. The reaction is preferably carried out in a polar, aprotic solvent such as dimethyl formamide, N-methyl-pyrrolidone or dimethyl sulfoxide and the like. The base can be selected from the sterically hindered amines such as triethylamine or Hiinig's base, alkoxides such as sodium methoxide and tert.-butoxide, or hydrides such as sodium hydride. The reaction can be performed at temperatures between 20 C and 110 ^C, depending on the individual compounds to be synthesized. According to scheme G> compounds of general formula II in which R^ is as described above for compounds where X is an ethynediyl group can be prepared by different routes from the iodo-compounds V, depending on the nature of R and R As shown in scheme G, the transformation can for example be carried out a) by directly attaching the R1-alkynediyl-substituent to a compound of general formula V via a Sonogashira-type coupling to produce compounds of the general formula VId followed by the reduction of the nitro group or b) by two stepwise Sonogashira-type couplings, in which first trimethylsilyi-acetylene is coupled to a compound of general formula V to yield, after desilylation with sodium hydroxide in methanol, the intermediate X which then can be transformed via a second Sonogashira-type coupling with the appropriate reactant R1-I, R1-Br or R1-OSO2CF3 into compounds of the general formula VId and reduction of the nitro group leads to the desired compounds of general formula IL The exact conditions for the respective compounds can be found in the experimental part. According to Scheme H, the dioxinones and 6-keto esters building blocks with the general formula TV and IVa can be prepared by methods known to someone skilled in the art from the corresponding carboxylic acid derivatives R -COR, i.e. free acids, methyl or ethyl esters and acid chlorides. The exact conditions for the corresponding compounds can be found in the experimental part. The pharmaceutically acceptable salts can be manufactured readily according to methods known per se and taking into consideration the nature of the compound to be converted into a salt. Inorganic or organic adds such as, for example, hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid or citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric add, methanesulphonic add, p-toluenesulphonic add and the like are suitable for the formation of pharmaceutically acceptable salts of basic compounds of formula I. The compounds of formula I and their pharmaceutically acceptable salts are metabotropic glutamate receptor antagonists and can be used for the treatment or prevention of acute and/or chronic neurological disorders, such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are acute and chronic pain, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate-deficient functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, dyskinesia and depression. The compounds of formula I and pharmaceutically acceptable salts thereof can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, the administration can also be effected rectally, e.g. in the form of suppositories, or parenterally, e.g. in the form of injection solutions. The compounds of formula I and pharmaceutically acceptable salts thereof can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical preparations. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like; depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules- Suitable carriers for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose and the like. Adjuvants, such as alcohols, polyols, glycerol, vegetable oils and the like, can be used for aqueous injection solutions of water-soluble salts of compounds of formula I, but as a rule are not necessary. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like. In addition, the pharmaceutical preparations can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances. As mentioned earlier, medicaments containing a compound of formula I or a pharmaceutically acceptable salt thereof and a therapeutically inert excipient are also an object of the present invention, as is a process for the production of such medicaments which comprises bringing one or more compounds of formda I or pharmaceutically acceptable salts thereof and, if desired, one or more other therapeutically valuable substances into a galenical dosage form together with one or more therapeutically inert carriers. The dosage can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, the effective dosage for oral or parenteral administration is between 0.01-20 mg/kg/day, with a dosage of 0.1-10 mg/ kg/day being preferred for all of the indications described. The daily dosage for an adult human being weighing 70 kg accordingly lies between 0.7-1400 mg per day, preferably between 7 and 700 mg per day. The present invention relates also to the use of compounds of formula I and of pharmaceutically acceptable salts thereof for the production of medicaments, especially for the control or prevention of acute and/or chronic neurological disorders of the aforementioned kind. The compounds of the present invention are group II mGlu receptor antagonists. The compounds show activities, as measured in the assay described below, of 10μM or less, typically 1μM or less, and ideally of 0.3μM or less. In the table below are described some specific Ki values of preferred compounds. Transfection and cell culture cDNA encoding the rat mGlu2 receptor protein in pBluescript II was obtained from Prof. S. Nakanishi (Kyoto, Japan), and subcloned into the eukaryotic expression vector pcDNA I-amp from Invitrogen (NV Leek, The Netherlands). This vector construct (pcDlmGR2) was co-transfected with a psvNeo plasmid encoding the gene for neomycin resistance, into CHO cells by a modified calcium phosphate method described by Chen & Okayama (1988), The cells were maintained in Dulbecco's Modified Eagle medium with reduced L-glutamine (2 -mM final concentration) and 10 % dialysed foetal calf serum from Gibco BRL (Basel, Switzerland). Selection was made in the presence of G-418 (1000 ug/ml final). Clones were identified by reverse transcription of 5 μg total RNA, followed by PCR using mGlu2 receptor specific primers 5'-atcactgcttgggtttctggcactg-3' and 5'-agcatcactgtgggtggcataggagc-3' in 60 mM Tris HCl (pH 10), 15 mM (NH4)2SO4,2 mM MgCl2, 25 units/nil Taq Polymerase with 30 cycles annealing at 60 oC for 1 min., extention at 72 °C for 30 s, and 1 min. 95 °C denaturation. Membrane preparation Cells, cultured as above, were harvested and washed three times with cold PBS and frozen at -80 °C. The pellet was resuspended in cold 20 mM HEPES-NaOH buffer containing 10 mM EDTA (pH 7.4), and homogenised with a polytron (Kinematica, AG, Littau, Switzerland) for 10 s at 10 000 rpm. After centrifugation for 30 min. at 4 °C, the pellet was washed once with the same buffer, and once with cold 20 mM HEPES-NaOH buffer containing 0.1 mM EDTA, (pH 7.4). Protein content was measured using the Pierce method (Socochim, Lausanne, Switzerland) using bovine serum albumin as standard. [3H]'LY354740 binding After thawing, the membranes were resuspended in cold 50mM Tris-HCl buffer containing 2 mM MgClo and 2 mM CaCl2, (pH 7) (binding buffer). The final concentration of the membranes in the assays was 25°Cg protein/ml. Inhibition experiments were performed with membranes incubated with 10 nM [3H]-LY354740 at room temperature, for 1 hour, in presence of various concentrations of the compound to be tested. Following the incubations, membranes were filtered onto Whatmann GF/C glass fiber filters and washed 5 times with cold binding buffer. Non specific binding was measured in the presence of 10°CM DCG IV. After transfer of the filters into plastic vials containing 10 ml of Ultima-gold scintillation fluid (Packard, Zurich, Switzerland), the radioactivity was measured by liquid scintillation in a Tri-Carb 2500 TR counter (Packard, Zurich, Switzerland), Data analysis. The inhibition curves were fitted with a four parameter logistic equation giving K1 values, and Hill coefficients. EXAMPLES General procedure A Preparation of 4-iodo-2-nitroanilines by iodination of 2-nitroanilines [according to Wilson, J. Gerald; Hunt, Frederick C Aust /, Chem. 1983,36^ 2317-25] To a stirred solution of the Z-nitroanilinc (LO mol) in HOAc (500 mL) containing anhydrous NaOAc (93-103 g, 1.125-1.25 mol), iodine monochloride (59-66 mL, 1.125-1.25 mol) in HOAc (300 mL) was added over 60 min. The reaction mixture was heated to the given temperature until thin layer chromatography (tic) indicated complete conversion of the starting material, stirred for another 30 min at 23 oC, then diluted slowly with H2O (1000 mL) which caused the separation of the crystalline product. Stirring was continued for 1 h and the product was filtered off, washed free of HOAc and dried in vacuum at 60 oC. Example A1 5-Chloro-4-iodo-2-nitro-phenylamine The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80oC). Obtained as an orange solid. MS (EI) 298 (M^) and 300 [(M-f2)^]; mp 202-203 C (dec). General procedure B: Preparation of ('2-nitro-phenvl)-carbamic acid tert.-butyl esters from 2-nitroanilines Method a (from 2-nitroanilines): To a solution of diphosgene (4.1 mL, 34,1 mmol) in EtOAc (40 mL) at 0 °C was added a solution of the 2-nitroaniline (45.5 mmol) in EtOAc (200-500 mL), and the mixture was heated to reflux for 18 h. The solvent was removed in vacuum to leave a brown solid, which was triturated with hot hexane (200 mL). The solid material was filtered off and the filtrate was concentrated xmder reduced pressure to leave the pure 2-nitrophenylisocyanate as a yellow soild This material was refluxed in a mixture of excess terL-BuOH in CH2CI2 for 2.5 h. Removal of the solvent left an orange solid which was pmified by silica gel colunm chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbainic acid tert-butyl ester as a yellow solid Method b (from 2-nitroanilines): To a mixture of the 2-nitroaniline (142 mmol) and cesium carbonate (55.5 g, 170 mmol) in 2-butanone (740 mL) was dropwise added a solution of BOC2O (37.8 g, 173 mmol) in 2-butanone (170 mL) and the resulting mixture was stirred at 50 ^C to 80 C until tic indicated complete conversion. The solvent was removed in vacuxun, the residue was treated with a mixture of H2O (240 mL) and MeOH (240 mL) and extracted with hexane (3 x 500 mL). The combined hexane layer was washed with brine (200 mL) and all aqueous layers were reextracted with hexane (300 mL). All combined hexane layers were dried over MgSO4, filtered and the solvent was removed in vacuum to give an orange solid, which was purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid. Method c (fi-om 2'nitroanilines): To a solution of the 2-nitroaniline (550 mmol) and DMAP (1.22 g, 10 mmol) in THF (1000 mL) at 23 °C was dropwise added within 70 min a solution of Boc2O (246 g, 1128 mmol) in THF (500 mL) and stirring was continued at 23 °C for 75 min. The entire mixture was evaporated to dryness and dried at HV to leave a dark brown solid. This material was dissolved in DCM (1100 mL), cooled to 0 --C and TFA (84 mL, 1100 mmol) was added dropwise. The mixture was stirred at 0 °C for 2 h2 poured into icecold sat. NaHCO3-sol, extracted with DCM, washed with brine and dried over MgSO4. Removal of the solvent in vacuum left a dark brown solid which was coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid. Method d (firom 2'nitroacetanilides): To a solution of the 2-nitroacetanilide (100 mmol) and DMAP (122 mg, 1mmaol) in THF (100 mL) at 23 X was dropwise added within 15 min a solution of B0C2O (22.92 g, 105 mmol) in THF (100 mL) and stirring was continued at 23 oC until tic indicated completed conversion. The entire mixture was evaporated to dryness and dried at HV to leave a yellow to dark brown solid. This material was dissolved in THF (200 mL) and 25 % NH4OH (77 mL, 500 mmol) was added dropwise. The mixture was stirred at 23 oC until tic indicated complete conversion, poured into IN HCl-sol, extracted with EtOAc, washed the organic layer with sat. NaHC03-soL and brine, dried over MgSO4. Removal of the solvent in vacuum left an yellow to brown solid which was generally pure enough for fiirther transformation or - if necessary - coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert-butyl ester as a yellow solid. Example Bl f 5-Chloro-4-iodo-2-nitrO'phenvlVcarbamic acid tert.-butyl ester The title compound was prepared via the isocyanate from 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (7.0 g> 23.45 mmol) with diphosgene (2.12 mL, 17.6 mmol) in EtOAc (30 mL), followed by treatment with tert.-BuOH (100 mL) in CH3CI2 (100 mL) according to the general procedure B (method a). Obtained as a yellow solid (7.1 g, 76%). MS (EI) 398 (M^) and 400 [(M-f2)^]; mp 82-84 °C Example B2 f4,5-Dichloro-2-nitro-phenvlVcarbamic acid tert.-butyl ester The title compound was prepared via the di-Boc-compound from commercially available 4,5-dichlorO-2-nitroaniline (15 g, 72.5 mmol) and BOC2O (32.4 g, 148.5 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained as abrown solid (21.63 g, 97 %). MS (ISN) 305 [(M-H)-]; mp 68-73 °C. Example B3 (5-Fluoro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared via the di-Boc-compound from 5-fluoro-2-nitro-4-trifluoromethyl-phenylamine; prepared from commercially available 4-amino-2-fluorobenzotrifluoride by acetylation with Ac2O in toluene at 23 °C, nitration with 100 % nitric acid from 10-23 °C and deacetylation with 2N NaOH in THE at 50 °C] (5.21 g, 23.2 mmol) and Boc2O (10.63 g, 48.7 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a light yellow solid(6.33 g, 84 %). MS (ISN) 323 [(M-H)-]; mp 104 °C Example B4 [4-Iodo-2-nitrO'5-f2,2.2-trifluoro-ethoxy)-phenvll-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenyiamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (8.95 g, 30 mmol), 2,2,2-trifluoroethanol (30 mL) and KOH (4.36 g, 66 mmol) in DMSO (60 mL) at 23 °C for 35 days.] (10.41 g, 29 mmol) and BOC2O (12,87 g, 59 mmol), followed by treatment with 2 eq. TFA in CR2CL2 according to the general procedure B (method c). Obtained as a yellow solid (13.34 g, 100 %), MS(ISN)461[(M-H)-]. Example B5 (5-Chloro-2-nitro-4-trifIuoromethvl-phenvl)-carbamic acid tert,-butyl ester The title compound was prepared via the di-Boc-compound from commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (22.61 g, 94 mmol) and BOC2O (42.06 g, 193 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (31,82 g, 99%). MS (ISN) 339.1 [(M-H)-]and 341 [(M+2-H)-];mp 113-115 °C. Example B6 (5-Chloro-4-fluoro-2-nitro-phenvl')-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from commercially available 3'-chloro-4'-fluoro-6'-nitroacetanmde [CAS-No. 81962-58-5] (59 g, 254 mmol), and BOC2O (58.13 g, 266 mmol), followed by treatment with NH4OH (25%, 77.5 mL, 507 mmol) according to the general procedure B (method d). Obtained as a yellow solid(73,53 g, 100 %). MS (ISN) 289 [(M-H)-] and 291 [(M+2-H)-]; mp 73-74 °C Example B7 [2-Nitro-5-(2,2,2-trifluoro-ethoxv)-4-trifluoromethyl-phenvn-carbamic acid tert.-butylester The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenylamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al), 2,2,2-trifluoroethanol and KOH in DMSO at 23 °C for 32.5 days.] and BOC2O, followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (18.955 g). MS (ISN) 403 [(M-H)-]. Example B8 (5-Chloro-4-methyl-2-nitro-phenyl)-carbamic add tert-butyl ester The title compound was prepared via the di-Boc compound from commercially available 5-chloro-4-methyl-2-nitroaniline (10.0 g, 53.6 mmol) and BOC2O (23.9 g, 109 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (toluene/ethylacetate 19:1) as a yellow solid (14.6 g, 95%). MS (ISN) 285.1 [(M-H)'l. Example B9 (4-Cyano-5-fluoro-2-nitro-'phenyl)-Carbamic acid tert-butyl ester The tide compound was prepared via the di-Boc compound from 4-cyano-5-fluoro-2-nitroaniline (24.9 g, 137 mmol) [Ohmori et al. J, Med. Chem. 1994,37,467 - 475] and BOC2O (61,5 g, 282 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (hexane/ethylacetate 4:1) as a light yellow solid (14.5 g, 39%). MS (ISN) 280.1 [(M-H)']. General procedure C: Preparation of 5-N-substituted-(2-nitro-phenyl)-carbamic acid tert.-butylesters: (5-Chloro or -fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester was stirred with the desired amine optionally with DMSO, DMF, DMA, NMP or THF and/or DIPEA or Et3N at temperatures from 23 °C to 130 °C until tic indicated complete disappearance of the chloride or fluoride. The reaction was cooled to 23 °C poured into ice-water, the precipitate was filtered off, washed with water and dried in vacuum. In cases were the product did not precipitate, the mixture was extracted with EtOAc, washed with water and brine, dried over Na2SO4. Filtration and removal of the solvent in vacuum left a crude product, which was - if necessary - purified by silica gel column chromatography with hexane/EtOAc to give the pure title compound. Example CI (4-Chloro-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butylester The tide compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and dimethylamine (5.6 N in EtOH, 8.7 mL, 48.8 mmol) in DMSO (35 mL) at 23 o'C according to the general procedure C. Obtained as a yellow solid (2.81 g). MS (ISP) 316 [(M+H)--] and 318 [(M-h2+H)']; mp 136-138 °C Example C2 (5-DimethylaminO-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic acid tert,-butyl ester (Example Bl) (399 mg, 1 mmol) and dimethylamine (5.6 N in EtOH, 0.36 mL, 2 mmol) in THE (3 mL) at 65 °C for 18 h in a sealed tube according to the general procedure C. Obtained as a yellow solid (386 mg). MS (EI) 407 (M+); mp 120-122 °C. Example C3 (4-Chloro-5- rr2-methoxv-ethyl)-methyl-amino1-2-nitro-phenyl}-carbamic add tert,-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol), N-(2-methoxyethyl)methylamine (2.43 mL, 23 mmol) and Et3N (4.2 mL, 30 mmol) in DMSO (20 mL) at 23 °C according to the general procedure C. Obtained as a brown oil (3,57 g), MS (ISP) 360 [(M+H)+_] and 362 [(M+2-i-H)^]. Example C4 (5-Dimethylamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (5-fluoro-2-mtro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B3) (1.62 g, 5.0 mmol) and dimethylamine (5.6 N in EtOH, 4.47 mL, 25.0 mmol) in DMSO (10 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(1,48 g). MS (ISN) 348 [(M-H)-]; mp 110 X. Example C5 r \|4-Chloro-5-(ethvI-methyI-aminoV2-nitro-phenvi]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-ethyl-methylamine (2.89 g, 48.8 mmol) in DMSO (35 mL) at RT according to the general procedure C. Obtained as a pale brown solid(3.21 g). MS(ISP)330.3 [(M+H)1;mp94oC. Example C6 f4-Chloro-5-(methyl-propyl-aminoV2-nitro-phenyl-carbamic acid tert-butylester The title compound was prepared from (4,5-dichlorO-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-methyl-propyl-amine (2,50 g, 34.2 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a pale brown solid (3.58 g), MS (ISP) 344.3 [(M+H)+]; mp 68 °C, Example C7 f4--Chloro-5'(dietfavl-amino)-2-nitro-phenyn-carbamic acid tert-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and diethyl-amine (3.57 g, 48.8 mmol) in DMSO (35 mL) at 60°C according to the general procedure C. Obtained as a yellow solid (2.63 g). MS (ISP) 344.3 [(M+H)--]; mp 95 °C. Example C8 (4-Chloro-2-nitro-5-pyrrolidin-l'yl'phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and pyrrolidine inDMSO at 23 -€ according to the general procedure C. Obtained as a yellow solid (6.65 g). MS (ISP) 342 [(M+H)--] and 344 [(M+2+H)']; mp 157-158 °C. Example C9 [4-Chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and EtsN (6.97 mL, 50 nunol) in DMSO (30 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.25 g). MS (ISP) 342.2 [(M+H)+ and 344 [(M+2+H)-']; mp 104-106 °C. Example CIO (2-Nitro-5-pyrrolidin-l-yl-4-trifluoromethyl'-phenyl)_-carbamic acid tert-butyl ester The tide compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5) (6,81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) inDMSO (70 mL) at 23 --C according to the general procedure C. Obtained as a yellow solid (7.35 g). MS (ISN) 374 [(M-H)-]; mp 138-141 °C . Example CI 1 f 5-DimethylaminO-4'fluoro-2-nitro-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (5-chloTO-4-fluoro-2'nitro-phenyl)~carbamic acid tert-butyl ester (Example B6) (4.94 g, 17 mmol) and MeaNH (40% in H2O, 7.9M, 10.9 mL, 86 mmol) inDMSO (35 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.93 g), MS (ISP) 303 [(M+H)+]; mp 144-148 X. Example C12 ('4-Chloro-2-nitro-5-piperidin-l-yl-phenylVcarbamic acid tert,-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and piperidine inDMSO at 23 oC according to the general procedure C. Obtained as a yellow solid (1.173 g). MS (ISP) 356 [(M+H)+] and 358 [(M+2+H)']; mp 132-133 °C. Example CI 3 (4-Fluoro-2-nitro-5-pvrrolidin-l-yl-phenylVcarbamic acid tert.-butylester The title compound was prepared from (5-chloro-4-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B6) (5.81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (6.42 g). MS (ISP) 326 [(M+H)--]; mp 188-193 °C. Example C14 (5-A2etidin'l-yi-4-chloro-2-nitro-phenyl')-carbamic acid tert.-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyi ester (Example B2) (6.14 g, 20 mmol), azetidine (2.33 mL, 34 mmol) and Et3N (8.4 mL, 60 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as an orange solid (5.85 g). MS (H) 327 (M+) and 329 [(M+2)+]. Example CI 5 (5-Azetidin-l-yl-2-nitro-4-trifluoromethyl-phenylVcarbaniic acid tert.-butyl ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5), azetidine and Et3N in DMSO at 23 °C according to the general procedure C. Obtained as a yellow solic (6.925 g). MS (ISN) 360 [(M-H)-]. Example C16 (5-(CvclopropylmethyI-methyl-amino)-2-nitro-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B5) (5.11 g 15 mmol), cyclopropylmethyl-methyl-amine hydrochloride (5.47 g, 45 mmol) and Et3N (10.5 mL, 75 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(5.73 g). MS (ISN) 388 l(M-H)']; mp 5 1°C . Example C17 (5-(CycIopropvI-methyI-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamicacid tert.-but\4 ester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl) carbamic acid tert-butyl ester (Example B5) (3.40 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and Et3N (6.97 mL, 50 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.74 g). MS (ISP) 374.2 [(M+H)1, Example C18 (2-Dimethylamino-2'-fluoro-5'nitro-biphenyl-4-yl)-carbamic acid tert.-butylester The title compound was prepared from (2-chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example D3) (9,568 g, ca. 26 mmol) and Me2NH (60% in H20,12 mL) inDMSO (87 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.54 g). MS (ISP) 376.3 [(M+Hrj. Example C19 (5-Dimethylamino-4-methyl-2-nitro-phenylVcarbamic acid tert-butyl ester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and dimethylamine (11 ml, 33% in EtOH, 61.0 mmol) in DMSO (35 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid (3.50 g, 97%). MS (ISP) 296.3 [(M+H)-]. Example C20 f4-Cvano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7.11 mmol) and dimethylamine (6.3 ml, 33% in EtOH, 35.0 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.87 g, 86%). MS (ISP) 307.3 [(M+H)'], Example C21 [4-methyl-5-(methyl-propyl-aminol-2'mtro-phenyn-Carbamic acid tert-butylester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-methylpropylamine (6.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (3.89 g, 98%). MS (ISP) 324.4 [(M+H)--]. Example C22 (5-fEthyl-metfayl-amino)-4-methyl-2-nitro-phenyl-carbamic add tert-butyl ester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-ethylmethylamine (5.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.58 g, 95%). MS (ISP) 310.3 [(M+H)--]. Example C23 f4-Chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isopropyl-methyiamine (5.95 g, 81.4 mmol) in DMSO (50 mL) at 75 °C according to the general procedure C. Obtained as a yellow solid (4.07 g, 73%). MS (ISP) 344.3 [(M+H)+]. Example C24 [4-Chloro-5-(isobutyl-methyl-amino)-2-nitro--phenyl]-carbamic acid tert-butylester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isobutyl-methylamine (7.09 g, 81,4 mmol) in DMSO (50 mL) at RT according to the general procedure C. Obtained as a brown oil (5.79 g, 99%). MS (ISP) 358.2 [(M+H)--]. Example C25 f4-Cvano-2-nitro-5-pyrrolidin-l'yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7,11 mmol) and pyrrolidine (2.94 ml, 35.6 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.97 g, 83%). MS (ISP) 331.2 [(M-H)-]. Example C26 f4-Cvano-5-fmethyl-propyl-amino)-2-nitro-phenyl-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-methyl-propylamine (3.72 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.75 g, 75%). MS (ISP) 333.3 [(M-H)']. (4-Cyano-5-diethylamino-2-nitro-phcn>i>-carbamic add tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and NJSI-diethyiamine (3.60 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.78 g, 77%). MS (ISP) 333.2 [(M-H)-]. Example C28 [4-Cvano-5-(isopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butyl ester The title compound was prepcured from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isopropyl-N-methylamine (3.60 ml, 34.7 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.84 g, 79%). MS (ISP) 333.3 [(M-H)']. Example C29 f4-Cvano-5-(isobutyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isobutyl-N-methylamine (3.02 g, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C Obtained as a yellow solid (1.87 g, 77%). MS (ISP) 347,4 [(M-H)-]. Example C30 f4-Cyano-2-nitro-5-piperidin-l--'yi-phenyl)-carbamic acid tert-butylester The title compoimd was prepared from (4-cyano-5-£luoro-2-nitro-phenyi)-carbamic acid tert-butyl ester (Example B9) (2.0 g> 7.11 mmol) and piperidine (3.51 ml, 35.6 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.94 g, 79%). MS (ISP) 345.3 [(M-H)-]. Example C31 (4-Chloro-5-isobutylamino-2-nitro-phenyl--carbamic acid tert-butyl ester The title compound was prepared from (4>5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and isobutylamine (3.57 g, 48.8 mmol) in DMSO (20 mL) at 55°C according to the general procedure C. Obtained as a brown solid (2.26 g, 67%). MS (ISP) 344.2 [(M+H)--]. Example C32 [5-fMethyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-methyl-propyl-amine (1.89 ml, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.04 g, 91%). MS (ISP) 378.3 [(M+H)-]. Example C33 f 5-(Isobutyl-methyl-amino V2-nitro-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol),N-isobutyl-methyl-amine (L54 g, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.18 g, 91%). MS (ISP) 390.3 [(M-H)-]. Example C34 f 5-f Isopropyl-methyl-aminoV2-nitro-4-trifluoromethyl-phenyn -carbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-isopropyl-methyl-amine (3.67 ml, 35.2 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid(3.27 g, 74%). MS (ISP) 376.3 [(M-H)']. Example C35 (5-(IsobutvI-methyl-aminoV4-methyl-2-nitro-phenyl-carbamic acid tert-butylester The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and N-isobutyl-methylamine (4.56 g, 52.3 nunol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (1.84 g, 52%). MS (ISP) 336.3 [(M-H)']. Example C36 (4-MethyI-2-nitro-5-pvTrolidin-l-yl-phenyl Vcarbamic acid tert-butylester The title compound was prepared from (5-chlorO-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and pyrrolidine (4.33 ml, 52.3 mmol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.27 g, 97%). MS (ISP) 320.3 [(M-H)-]; mp 145 °C Example C37 (4-Chloro-5-isopropylamino-2-nitro-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert.-butyl ester (Example B2) (5,0 g, 16,3 mmol) and isopropylamine (7,0 ml, 81.4 mmol) in DMSO (35 mL) at 55 o'C according to the general procedure C. Obtained as a brown solid (3.95 g, 73%). MS (ISP) 330.2 [(M+H)--]. ' Example C38 (5-Isobmylamino-2-mtro-4-trifluoromethyl-phenylVcarbamic acid tert-butylester The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (5.00 g, 14.7 mmol), isobutyl-amine (7.36 mL, 73.4 mmol) in DMSO (35 mL) at RT according to the general procedure C Obtained as a yellow solid (5.39 g, 97%). MS (ISP) 376.3 [(M-H)-], General procedure D: Preparation of (4-arvI-2-nitro-phenyl)-carbamic acid tert.-butyl esters by direct Suzuki-coupling of ('4-iodo-2-nitro-phenyl)carbamic acid tert.-butylesters with arylboronic acids A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (3.0 mmol), the arylboronic acid (4.5 mmol) and PdCl2(PPh3)2 (2 mol%) was refluxed in 1,4-dioxane (25 mL) and 2M NaaCO2-sol. (7.5 mL) [or alternatively with IM NaHCOa-sol. (7.5 mL), LiCl (6.0 mmol) and (Ph3P)4Pd (3 mol%) in DME (30 mL); also possible with EtaN (9,0 mmol), Pd(0Ac)2 (3 mol%), PPhs (6 mol%) in DMF (10 mL) at 100 °C] until tic indicated complete conversion of the iodide. The mixture was transferred into a separating funnel, H2O (25 mL) was added and the product was extracted with ether or EtOAc (3 x 30 mL). The combined organic layers were washed with brine (50 mL) and dried over Na2S04. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound Example Dl (2-Dimethylamino-2\3'-difluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester The tide compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C2) and 2,3-difluorophenylboronic acid according to the general procedure D. Obtained as a yellow solid (3,096 g). MS(ISN)392[(M-H)-]. Example D2 f2'-Fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yll-carbamic acid tert,-butylester The title compound was prepared from [4-iodO-2-nitro-5-(2,2,2-trifluoro-ethox7)-phenyl]-carbamic add tert-butyl ester (Example B4) and 2-fluorophenylboronic add according to the general procedure D. Obtained as a yeDow solid (1.39 g). MS (ISP) 491 [(M+H)--]; mp 73-75 °C. Example D3 (2-Chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic add tert-butyl ester (Example Bl) (30 g, 75.3 mmol) and 2-fIuorophenylboronic acid (13.82 g, 98.8 nrniol) according to the general procedure D. Obtained as a yellow gum (1.39 g). MS (ISN) 365.0 [(M-H)-]. General procedure E: Preparation of (4-aryl-2-nitro-phenyl)-carbamic acid tert.-butyl esters by Suzuki-coupling of (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butylesters with bisfpinacolato)diboron and subsequent reaction with aryl halides A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (2,0 mmol), bis(pmacolato)diboron (2,2 mmol), KOAc (6.0 mmol) and PdCl2(PPh3)2 (3 mol%) in 1,4-dioxane (25 mL) was stirred at 100 °C until tic indicated complete conversion of the iodide [cf. Tetr. Lett. 1997,38,3841-3844]. After addition of the aryl halide (4.0 mmol), PdCl2(PPh3)2 (3 mol%) and 2M Na2CO3-soL (7.5 mL) the mixture was stirred at 100 oC until tic indicated complete conversion of the intermediate boronic ester. The mixture was transferred into a separating furnnel, H2O (30 mL) was added and the product was extracted with ether or EtOAc (3 x 50 mL). The combined organic layers were washed with brine (100 mL) and dried over Na2SO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound. General procedure F: Preparation of 5-chIoro-2'-nitro-4-pyrroI-l-yl-phenylamines by condensation of 5-chlorO-2-nitro-l,4-phenylenediamine with 2,5-dimethoxvtetrahydrofurans [cf. /. Heterocycl Chem 1988,25y 1003-1005]: A mixture of the 5-chloro-2-nitro-l,4-phenylenediamine (4.69 g, 25 mmol), the 2,5-dimethoxytetrahydrofuran (26 - 32,5 mmol) in HOAc (150 mL) was stirred at 60-120 °C until tic indicated complete conversion of the phenylenediamine. After cooling to 23 °C, the mixture was poured into brine (500 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (300 xriL) and dried over MgSO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/EtOAc to give the title compound. General procedure G: Preparation of 23-dimethoxvdihvdrofurans by bromination of furans in MeOH [cf. Tetrahedron 1971,27,1973-1996]: To a solution of the furan (177.5 mmol) in a mixture of anhydrous ether (54 mL) and abs. MeOH (79 mL) kept at -35 °C bromine (10.0 mL, 195 mmol) in MeOH (105 mL) was added gradually with stirring. The reaction mixture was stirred for 30 min, saturated with gaseous NH3 to pH 8, and allowed to warm up to 23 °C. Poured into ice-water, extracted with ether (3 x 400 mL), washed with brine, dried over Na2So4. Evaporation of the solvent left a yellow liquid, which was purified by vacuum distillation to give the title compound. General procedure H: Preparation of (4-alkynyl-2-nitro-phenyll-carbamic acid tert,-butylesters by Sonogashira-coupling of f4-iodo-2-nitro-phenyI)-carbamic acid tert.-butylesters with acetylenic compounds; also Sonogashira-coupling of (4-ethynyl-2-nitro-phenyl)-carbamic acid tert-butyl esters with aryl halides: A mixture of the halide (3.0-4.5 mmol), acetylenic compound (3.0-4.5 mmol), Et3N (13.5 mmol), PdCl2(PPh3)2 (5 mol%) and PPh3 (2.5 mol%) in THF (12 mL) [with very insoluble material DMF (up to 12 mL) could be added] was stirred for 20 min at 23 °C while being purged with Argon. Cul (1.2 mol %) was added and stirring was continued at 60 °C under Argon atmosphere until tic indicated complete conversion of the minor component [cf. /. Org. Chenu 1998,63,8551]. The mixture was transferred into a separating funnel, 5% citric add (50 mL) was added and the product was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with sat. NaHCOs-sol. (50 mL) and brine (50 mL), followed by drying over MgSO4. Removal of the solvent left a yellow residue, which was purified by silica gel colunm chromatography with hexane/EtOAc and/or triturated with hexane or aqueous EtOH to give the title compound. Example Hi (5-Hydroxymethyl-2-nitro-4-phenylethvnyl-phenyl)'Carbamic acid tert.-butylester The title compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C2) (386 mg, 0.97mmol) and phenylacetylene (149 mg, 1.46 mmol) according to the general procedure H. Obtained as an orange solid (370 mg). MS (EI) 381 (M+); mp 141-149 °C. General procedure T: Preparation of the (2-amino-phenyl)-carbamic acid tert.-butylesters bv reduction of (2-nitro-phenyl)-carbamic acid tert.-butylesters: Method a: Catalytic hydrogenation A mixture of the nitro compound (1.0 mmol) in MeOH or EtOH and THF (1:1 ca. 20 mL) [or solely EtOAc for aromatic chlorides] and 10% Palladium on carbon (20 mg), Raney-Ni (20 mg) or 5% Platinum on carbon was stirred vigorously at 23 °C under hydrogen atmosphere until tic indicated complete conversion. The catalyst was filtered off, washed thoroughly with MeOH or EtOH and THF (1:1) [or EtOAc], the solvent was removed in vacuum to give the title compound, which was generally pure enough for further transformations, but could be crystallized firom hot hexane if necessary. Method b: Reduction with SnCl2'2H2O A mixture of the nitro compound (1.0 mmol) and SnCl2'2H2O (5.0 mmol) was either stirred in EtOH (30 mL) at 70-80 °C or alternatively in pyridine (3 mL) and DMF (12 mL) at 23 °C under Argon atmosphere until tic indicated complete conversion [cf. Tetr. Lett. 1984,25, 839]. The reaction mixture was brought to pH 8 by addition of sat NaHC03-sol. and extracted with EtOAc (2 X 100 mL). The combined organic layer were washed with brine and dried over Na2SO4. Removal of the solvent left a yellow solid, which - if necessary - can be purified by silica gel column chromatography. Method c: Reduction with Zn and NH°Cl To a mixture of the nitro compound (1.0 mmol) in EtOH/THF/sat NH4CI-S0I. (1:1:1> 30 mL) was added Zinc dust (3.0 mmol) and the mixture was stirred at 70 °C imder Argon atmosphere until tic indicated complete conversion. Aqueous workup as described in method b. Example Tl (2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-chlorO-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example CI) (2,76 g, 8.74 nunol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid(2.3 g). MS (ISP) 286 [(M+H)--] and 288 [(M+2+H)+]; mp 96-101 °C. Example T2 f2-Amino-5-dimethylamino-4-phenylethynyl-phenvD-carbamic acid tert.-butyl esr T The title compound was prepared from (5-dimethylaminO-2-nitro-4-phenylethynyl-phenyl)-carbamic acid tert.-butyl ester (Example Hi) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a brown solid (1.927 g). MS(ISP)352[(M+H)+]. Example T3 (5-Amino-2-dimethylamino--2,3'-difluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-dimethylamino-2',3'-di£luoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example Dl) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (2,206 g), MS(ISP)364[(M+H)-'], Example T4 {2-AminQ-4-chloro-5- f f 2-methoxv-ethyl-methyl-amino1 -phenyll-carbamic acid tert.-butyl ester The title compound was prepared from {4-chloro-5-[(2-methoxy-ethyl)-methyi-amino]-2-nitro-phenyl}-carbamic acid te t-butyl ester (Example C3) (3.46 g, 9,62 mmol) by reduction with SnCl22H2O according to the general procedure J.(method b). Obtained as a yellow solid (2.25 g). MS (ISP) 330 [(M+H)1 and 332 [(M+2+H)']; mp 112 X. Example T5 [5-Amino-2-fluoro-2-(2.2.2-trifluoro-ethoxyVbiphenyl-4-yl1 -carbamic acid tert.-butyl ester The title compound was prepared from [2'-fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert,-butyl ester (Example D2) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (U7g). MS(ISP)401[(M+H)1. Example T6 (2-Amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert^-butylester The title compound was prepared from (5-dimethyiamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C4) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as an amorphous yellow substance (1.34 g), MS (ISP) 320 [(M+H)1. Example T7 [2-Amino-4-chloro-5-(ethyl-methvI-aminoVphenyl]-carbamic acid tert-butylester The title compoimd was prepared from [4-chloro-5-(ethyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C5) (3.0 g, 9.09 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.64 g). MS (ISP) 300.3 [(M+H)']; mp 81 X. Example T8 f2-Amino-4-chloro-5-(methyl-propyl-aminQVphenyl-carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C6) (3.15 g, 9.16 mmol) by reduction with SnClf 2H2O accordmg to the general procedure J (method b). Obtained as a pale brown solid (2.58 g). MS (ISP) 314.3 [(M+H)-']; mp 92 X. Example T9 f2'Amino-4'-chIoro-5-fdiethyl-amino)-phenyn'Carbamic add tert-butyl ester The title compound was prepared from [4-chloro-5-(diethyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example G7) (2.25 g, 6.54 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (1.55 g). MS (ISP) 314.3 [(M+H)+]; mp 110 °C. Example TIP (2-Amino-4-chloro-5-pyrrolidin-l-yl-phenylVcarbamic acid tert.-butyl ester The tide compound was prepared from (4-chloro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (&cample C8) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a red solid (4.80 g). MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']; mp 136-138 °C Example Til f 2-Amino-4-chloro-5-(cyclopropyl-methvI-amino')-phenyl1 -carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert.-butyl ester (Example C9) (3.2 g, 9.36 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as brown solid (2.00 g), MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']. Example T12 (2-Amino-5-pvrrolidin-l-yl-4-trifluoromethyl-phenylVcarbamic acid tert.-butylester The title compound was prepared from (2-nitro-5-pyrroHdin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example CIO) (7.35 g, 19.75 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light orange solid (6.75 g). MS (ISP) 346 [(M+H)--]; mp 101-103 °C Example T13 (2-Amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester The title compoiond was prepared from (5-dimethylamino-4-fluoro-2-nitro-phenyI)-carbamic acid tert.-butyl ester (Example C11) (4.88 g, 16 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a green solid(4.55 g). MS (ISP) 270 [(M+H)+]; mp 120-123 °C. Example T14 (2-Amino-4-chlorO-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-chloro-2-nitro-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C12) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as light brown solid (747 mg). MS (ISP) 326 [(M+H)+] and 328 [(M+2+H)1;mp 149-151 °C Example Tl 5 (2-Amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (4-fluoro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example C13) (6,37 g, 20 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (5.92 g). MS (ISP) 296 [(M+H)--]; mp 75-76 °C Example 116 (2-Amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (5-azetidin-l-yl-4-chloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C14) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (3.664 g). MS (ISP) 298 [(M+H)--] and 300 [(M+2+H)-']; mp 176-179 -C Example T17 (2-Amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic add tert.-butylester The title compound was prepared from (5-a2etidin-l-yl-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C15) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (5.173 g). MS (ISP) 332 [(M+H)+]; mp 166-167 °C Example Tl 8 f2-Amino-5-(cyclopropylmethyl-methyl-aminoV4-trifluoromethyl-phen\d1-carbamic acid tert.'butyl ester The title compoimd was prepared from [5-(cyclopropylmethyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C16) (5.66 g, 14.5 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as yellow solid (4.7 g). MS (ISP) 360 [(M+H)+]; mp 56 X. Example T19 [2-Amino-5--rcvclopropvI-methyl-amino)-4-trifluoromethyl-phenyn-carbamicacid tert,-butyl ester The title compound was prepared from [5-(cyclopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C17) (3.74 g, 9.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange semisolid (2.00 g). MS (ISP) 346.4 [(M+H)--]. Example 120 (5-Amino-2-dimethylamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butylester The title compound was prepared from (2-dimethylamino-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert-butyl ester (Example CIS) (4.54 g, 12.1 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light brown solid (3.324 g). MS (ISP) 346.4 [(M+H)+]. Example T21 [2-Amino-5-f2.2.2-trifluoro-ethoxyV4-trifluoromethyl-phenvIl-carbamic acid tert-butyl ester The title compound was prepared from l2-nitro-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tcrt-butyl ester (Example B7) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a yellow solid (17.374 g). MS(ISP)375[(M+Hr]. Example 22 (2-Amino-5-dimethylamino-4-methyl-phenyl)-Carbamic acid tert-butylester The title compound was prepared from (5-dimeth>1amino-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C19) (3.22 g, 10.9 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a gray solid (2.05 g, 58%). MS (ISP) 266.3 I(M+H)+]; mp 78 X. Example 123 (2-Amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C20) (3.9 g, 12.7 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.05 g, 58%). MS (ISP) 277.2 [(M+H)+]; mp 120 -C Example T24 (2-Amino-4-methyl-5-(methyl-propyI-amino)-phenyl1-carbamic acid tert-butylester The title compound was prepared from [4-methyl-5-(methyi-propyi-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C21) (3.59 g, 11.1 namol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (3.23 g, 99%). MS (ISP) 294.4 [(M+H)--]. Example T25 (2-Amino-5-(ethyl-methyl-amino)=4-methyl-phenvIl-carbamic acid tert-butyl ester The title compound was prepared from [5-(ethyl-methyI-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C22) (3.28 g, 10.6 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (2.94 g, 99%). MS (ISP) 280.3 [(M+H)1. Example T26 [2-Amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl1 -carbamic add tert-butylester The title compoimd was prepared from [4-chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C23) (4.07 g, 11.8 mmol) by reduction with SnClf 2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.08 g, 83%). MS (ISP) 314.3 [(M+H)1; mp 116 °C. Example T27 [2-Amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl1-carbamic acid tert-butylester The title compound was prepared from [4-chloro-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C24) (5.55 g, 15.5 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.98 g, 78%). MS (ISP) 328.3 [(M+H)1. Example T28 (2-Amino-4-cyano-5-pvrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester The tide compound was prepared from (4-cyano-2-mtro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C25) (1.82 g, 5.48 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a pale brown solid (1.27 g, 77%). MS (ISP) 303.2 [(M+H)--]. Example T29 (2-Amino-4-cyano-5-fmethyl-propyl-aminoVphenyl1-carbamic acid tert-butylester The title compound was prepared from [4-cyano-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C26) (1.64 g, 4.90 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a dark red oil (1.24 g, 83%), MS (ISP) 305.3 [(M+Hf], Example T30 (2-Amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butylester The title compound was prepared from (4-cyano-5-diethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C27) (1.66 g, 4.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.38 g, 91%). MS (ISP) 305.3 [(M+H)+]; mp 151 °C Example T31 (2-Amino-4-cyano-5-(isopropyl-methyl-aminoVphenyl1 -carbamic acid tert-butylester The title compound was prepared from [4-cyano-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C28) (1.73 g, 5.17 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.56 g, 99%). MS (ISP) 305.3 [(M+H)--]; mp 77 °C. Example T32 [2-Amino-4-cyano-5-(isobutyl-methyl-amino)-phenyn-carbamic acid tert-butyl ester The title compound was prepared from [4-cyano-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C29) (1.76 g> 5.05 mmol) by reduction with SnCV2H2O according to the general procedure J (method b). Obtained as a light brown solid (1.55 g, 96%). MS (ISP) 319.5 [(M+H)--]; mp 88 oC. Example T33 (2-Amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-cyano-2-nitro-5-piperidin-l-yi-phenyl)-carbamic acid tert-butyl ester (Example C30) (2.08 g, 5.71 mmol) by reduction with SnCl2'2H2O according to the general procedure I (method b). Obtained as an off-white solid (L67 g, 99%). MS (ISP) 317.2 l(M+H)+]; mp 86 oC Example 134 (2-Amino-4-chloro-5-isobutylamino-phen\1)-carbamic acid tert-butylester The title compound was prepared from (4-chloro-5-isobutylainino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C31) (1.93 g, 5.61 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a brown solid (1.30 g, 74%). MS (ISP) 314.3 [(M+H)^. Example 135 (2-Amino-5-(methyl-propyl-aminoV4-trifluoromethyl-phenyl1 -carbamic acid tert-butyl ester The title compound was prepared from [5-(methyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C32) (3.78 g, 10.0 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a red oil (3.40 g, 98%). MS (ISP) 248.4 [(M+H)+]. Example T36 [2-Amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C33) (3.88 g, 9,91 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.70 g, 75%). MS (ISP) 362.3 [(M+H)--]. Example T37 (2-Amino-5-(isopropyl-methyl-aminoV4-trifluoromethyl-phenyn-carbamic acid tert-butyl ester The title compound was prepared from [5-(isopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C34) (2.98 g, 7.90 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.42 g, 88%). MS (ISP) 348.5 [(M-hH)--]. Example T38 (2-Amino-5-fisobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-methyl-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C35) (1.48 g, 4.39 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a white solid (1.08 g, 80%). MS (ISP) 308.3 [(M+H)']; mp 71 °C Example T39 (2-Amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester The tide compound was prepared from (4-methyl-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C36) (3.27 g, 10.2 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale brown solid (2.48 g, 83%). MS (ISP) 292.3 [(M+H)--]; mp 115 °C Example T40 j (2-Amino-4'Chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (4-chloro-5-i$opropylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C37) (3.75 g> 11.3 mmol) by reduction with SnCl3 2H2O according to the general procedure J (method b). Obtained as a brown solid (2.90 g, 86%). MS (ISP) 303.3 [(M+H)--]. Example T41 f 2-Amino-5-f isobutyl-amino V4-trifluoroir.ethyl-phenyl -carbamic acid tert-butylester The title compound was prepared from [5-(isobutyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic.acid tert-butyl ester (°Cample C38) (5.28 g, 13.99 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale yellow solid (3.69 g, 76%). MS (ISP) 348.5 [(M+H)--]; mp 141 °C. The following examples relate to the preparation of the ethyl or tert.-butyl 3-aryl-3-oxo-propionates (general formula IVa), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H): General procedure K Method a) Preparation of ethyl or tert.-butyl3-aryl-3-oxo-propionates The ethyl or tert.-butyl 3-aryl-3-oxo-propionates were prepared from the aryl acid chlorides and ethyl or tert.-butyl malonate potassium salt [CAS-no. 6148-64-7 and 75486-33-8] with Et3N and MgCla in CH3CN at 0 °C to 23 °C according to Synthesis 1993,290. If the free aryl carboxylic acid was employed in this reaction, it was activated by treatment with ethyl chloroformate and Et3N in THF/CH3CN at 0 °C prior to reaction with the malonate salt. Method b) Preparation of tert.-butyl3-aryI-3-oxo-propionates The tert.-butyl 3-aryl-3-oxo-propionates were alternatively prepared from the methyl or ethyl aryl esters by treatment with lithium tert.-butyl acetate [prepared by treatment of tert.-butyl acetate with lithium diisopropylamide in THF at -78 °C] in the prese- :e of lithium tert.-butoxide according to Synthesis 1985,45. If the product contained residual starting material after workup, thus could be removed by selective saponification with LiOH in THF/MeOH/H2O at 23 °C. Method c) Preparation of 3-aryl-3--oxo-propionic acids The 3-aryl-3-oxo-propiomc acids were prepared from the aryl acid chlorides and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 °C according to Synth Commun. 1985,15,1039 (method cl) or with n-BuLi in ether at -60°C o 0 °C according to Synthesis 1979,787 (method c2). Example Kl 3-Oxo-3'(3-f L23ltria2ol-l-yl-phenyl)-propionic acid ethyl ester The title compound was prepared from 3-[l,2,3]tria2ol-l-yl-ben2oic acid, prepared by refluxing of methyl 3-azidobenzoate [CAS-No. 93066-93-4] in trimethylsUyl-acetylene, followed by saponification with aqueous NaOH in refluxing EtOH] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with EtaN and MgCl2 in CH3CN according to general procedure K (method a). Obtained as a light yellow solid(2.22 g). MS (EI) 259 (W); mp 72-74°C, Example K2 3-(3-cyano-phenyl)-3-oxo-propiQnic acid tert.-butyl ester The title compound was prepared from methyl 3-cyanobenzoate [CAS-No, 13531-48-1] by treatment with lithium tert--butyl acetate according to general procedure K (method b). Obtained as a light brown oily semisolid. MS (EI) 245 (M+). Example K3 3-(2-Cyano-pvridin-4-yl)-3-oxo-propiomc acid tert.-butyl ester The title compound was prepared from 2-cyano-isonicotinic acid ethyl ester [CAS-No. 58481-14-4] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light brown solid (7.70 g). MS(ISN)245[(M-H)1. Example K4 3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionic acid tert.-butylester The title compound was prepared from ethyl 3-(3-methyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, acetaldoxime, Et3N and cat amount of pyridine in CHCI3 at 50 'C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (2.54 g). MS (ISP) 302 [(M+H)1; mp 50-56 -C. Example K5 fRSV3-Oxo-3-B45-ftetrahvdro-pvran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phneyl}- propionic acid tert.-butylester The title compound was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-l-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) methyl 3-azidobenzoate [CAS-No. 93066-93-4] (15.55 g, 88 mmol) and (RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-l-ynyl]-silane [CAS-No. 135294-85-8] (33.50 g, 132 mmol) were heated to 60 --C for 10 days; ii.) The obtained material (48.2 g, ca. 88 mmol) was stirred in TBAF (300 mL, IM in THF) at 70°C for 6 days and subsequently refluxed in IN HCl (400 mL) for 2 h; iii.) The obtained material (16.15 g, 74 mmol) was stirred in MeOH (400 mL) and cone. H2S04 (30 mL) at 23 °C for 11 days, iv.) Part of the obtained material (4.60 g, 19.7 mmol) was reacted with 3,4-dihydro-2H-pyran (2.67 mL, 29.5 mmol) and cat. amount p-TsOH.H2O in DCM (38 mL) at 23 -°C for 20 h.] (6.20 g, 19.5 mmol) by treatment with lithium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (8.47 MS(ISP)402[(M+H)-']. Example K6 3-[2-(3-methyl-isoxazol-5-yl)-pvridin-4-yn-3-oxo-propionic acid tert.-butylester The title compound was prepared from 2-(3-methyl-isoxazol-5-yl)-isonicotinic acid methyl ester [prepared by i.) reaction of 2-iodo-isonicotinic acid methyl ester [CAS-No. 134579-47-8] with trimethylsilylacetylene according to general procedure H; ii.) desilylation by reaction with cat. K2CO3 in MeOH at 0 -°C for 4 h; iii.) cycloadditon with a mixture of NCS, acetaldoxime, Et3N and cat. amount of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a brown solid (5.17 g). MS (EI) 302 (M^); mp 59-67 °C Example K7 3-[3-(2-methyl-2H-pyTazol-3-yl)-phenyl1-3-oxo-propionic acid tert.-butylester The title compound was prepared from 3-(2-methyi-2H-pyrazol-3-yl)-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyi)-3-dimethylamino-propenone [CAS-No. 163852-04-81 with methylhydrazine in EtOH at 23 °C for 2.5 days; ii.) chromatographic separation of the obtained isomers; iii.) treatment of the dean isomer -with n-BuLi in THF at -78 °C for 1 h, followed by quenching with a stream of CO2 and subsequent esterification with MeOH and cone, H2SO4 at 23 °C for 48 h.] by treatment with Uthium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.96 g), MS (EI) 300 (M+), Example K8 3- [3-f 5-Dimethylaminomethyl- [ 12,31 triazol- l-yl)-phenyll -3-oxo-propionic acid tert.-butylester The title compound was prepared firom 3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-benzoic acid methyl ester [prepared from methyl 3-azidobenzoate following the synthetic steps i.) to iii.) as described in the preparation of Example K5 and reacting the obtained product with SOCI2 in THF at 0 to 23 °C for 1 h, followed by acidition of dimethylamine (7.9 M in H2O) and stirring at 23 to 70 'C fori h.] (2.14 g, 8.22 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (2.90 g). MS(ISP)345[(M+H)-']. Example K9 3-[3-f3-Methoxvmethyl-isoxazol-5-yl)-phenyl1-3-oxo-propionic acid tert.-butylester The title compound was prepared from methyl 3-(3-methoxymethyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, 2-methoxyacetaldoxime [CAS-No. 71494-93-4], Et3N and cat, amoimt of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40^ 2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow liquid (1.548 g). MS (EI) 331 (M+), Example KlO (RSV3-Oxo-3-{3-f4-(tetrahvdro-pvran-2-yloxvmethyl)-thiazol-2-yl1-phenyll-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yioxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 13-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 °C for 24 h. The reaction mixture was cooled to 20°C and acided to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL), Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii,) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g). MS (ISP) 418.2 [(M+H)1. Example K11 (RS)-3-Oxo-3-{3-F4-ftetrahvdro-pvran-2-yloxvmethyl)-oxazol-2-\yl]-phenyl]-propionic acid tert-butylester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-carbamoyl-benzoic acid methyl ester [CAS-No. 106748-24-7] (17.9 g) and l,3-dichloro-2-propanone (14.0 g) was heated to 140 °C for 1.5 h. The mixture was cooled to 20 °C and cone, sulfuric acid (12 mL) was carefully acided. The mixture was stirred for 10 min. and then poured into ice-water. The product was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as duent to give 3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methyl ester (11.8 g) as a pale-yellow oil. MS (ISP) 252.2 [(M+H)--]. ii.) I A solution of this material (7.6 g) and lithium hydroxide monohydrate (5.0 g) in DMSO (30 mL) was heated to 60 -°C for 7 h. The cooled reaction mixture was poured into ice-water and the mixture was extracted with diethyl ether. The aqueous layer was acidified to pH 1 by the acidition of 6N HCl and the precipitate formed was collected by filtration and crystallized from dichloromethane/hexane. The pale-yellow crystals 5 (5.5 g) were dissolved in DMSO (25 mL), and after the acidition of N,N,N'N'- tetramethyl-guanidine (4.4 mL) and methyl iodide (2.2 mL), the mixture was stirred at 20 ^°C for 1 h. Ethyl acetate was acided and the mixture was washed successively with water, IN HCl and brine. The organic layer was dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as eluent and the purified product was crystallized firom diethyl ether/hexane to give 3-(4-hydroxymethyl-oxazol-2-yl)-benzoic acid methyl ester (2.1 g) as white crystals, mp 118-119 °C. iii.) A mixture of this material (2,1 g), dihydropyrane (1.2 mL) and p-toluenesulfonic acid hydrate (0.1 g) in ethyl acetate (15 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester (3,5 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g). MS (ISP) 402.5 [(M+H)1. Example K12 (RS')-3-Oxo-3-(3-r3-rtetrahvdro-pvran-2-yloxvmethyl)-isoxazol-5-vn-phenyl-propionic acid tert,-butylester The title compound was prepared from (RS)-3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (7.55 g, 23 mmol) and hydroxylamme hydrochloride (4.74 g, 68 mmol) were refluxed in EtOH for 1 h; ii.) The obtained ester (5.94 g, 20 nrniol) was reduced with LiAlH4 (761 mg, 20 mmol) in THF at -10 °C for 1 h; iii.) The obtained alcohol (4.90 g, 19 mmol) was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH.HaO in DCM at 23 °C for 20 h. iv.) The obtained THP-ether (5.24 g, 15 mmol) was treated with n-BuLi at -78 'C for 45 min, followed by a stream of CO2- v.) The obtained crude acid was stirred in MeOH (90 mL) and cone, H2SO4 (6.5 mL) at 50 X for 12 h. vi.) The obtained material (2.01 g, 8.62 mmol) was reacted with 3,4-dihydro-2H-pyran (1.17 mL, 12.9 mmol) and cat, amount p-TsOH.H2O in DCM (17 mL) at 23 °C for 5 h.] (2.44 g, 7.7 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.06 g). MS(ISP)402((M+H)-']. Example K13 (RS)3-(3-f3-Methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phneyl}-3-oxo-propionic acid tert,-butyl ester The title compound was prepared from (RS)-3-[3-methyi-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yi]-benzoic acid methyl ester [prepared by the following sequence: i.) (3-bromO-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 21575-91-7], pyrrolidine and TMSOTf in benzene were refluxed for 16 h {Org. Synth, 53y 59); ii.) The obtained 3-(3-bromo-phenyl)-3-pyrrolidin-l-yl-acrylic acid ethyl ester was reacted with nitroethane, POCI3 and Et3N at 23 °C; iii,) The obtained 5-(3-bromo-phenyI)-3-methyl-isoxazole-4-carboxylic acid ethyl ester was reduced with LiAlHH4 in THF at -10 -°C for 1 h iv.) The obtained [5-(3-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol was reacted with 3,4-dihydrO'2H-pyran and cat amount p-TsOH-HiO in DCM at 23 -C for 20 h. iv.) The obtained THP-ether was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vi.) The obtained 3-(4-hydroxymethyI-3-methyl-isoxazol-5-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (972 mg). MS(EI)416[(M+H)1. Example K14 (RSV3-[3'-[2-methyl-5-(tetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl]-phenylt-3-oxo-propionic acid tert.-butylester The title compound was prepared from (RS)-3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (6.135 g, 21 mmol), MeNHNH2 (1.296 mL, 25 mmol) and HCl (4M in dioxane, 6.25 mL, 25 mol) in EtOH (35 mL) were refluxed for 1.5 h; ii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyrazole-3-carboxylic acid ethyl ester (7.02 g, 22.7 mmol) was reduced with LiAlH4 (862 mg, 22.7 mmol) in THF (60 mL) at -10 °C for 1 h; iii.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-3-yi]-methanol (6.34 g, 24 mmol) was reacted with 3,4-dihydro-2H-pyran (3.25 mL, 36 mmol) and cat amount p-TsOH.H2O in DCM (50 mL) at 23 X for 23 h. iv.) The obtained (RS)-[5-(3-bromo-phenyl)-l-methyl-3-(tetrahydro-pyran-2-yloxymethyl)-lH-pyrazole(8.64 g, 25 mmol) was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. V.) The obtained crude acid was stirred in MeOH (90 mL) and cone. H2SO4 (6.5 mL) at 50 °C for 5 h. vi.) The obtained 3-(5-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (3.41 g, 13.85 mmol) was reacted with 3,4-dihydro-2H-pyran (1.75 mL, 20.77 mmol) and cat amount p-TsOH.H2O in DCM (28 mL) at 23 --C for 18 L] (3.93 g, 11.9 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (4.90 g). MS(ISP)415[(M+H)']. Example K15 propionic acid tert.-butylester The title compound was prepared from (RS)-3-(5-(tctrahydro-pyran-2-yloxymethyI)-isoxazol-3-yl]-benzoic acid methyl ester [prepared from (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] by treatment with NCS, cat amount pyridine in CHCI3 followed by acidition of (RS)-tetrahydro-2-(2-propynyloxy)-2H-pyran and slow acidition of Et3N in CHQ3 at 23 oC-] by treatment with hthium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g). MS (ISN) 400.5 [(M-H)-], Example Kl 6 3-Oxo-3-(3-pyrazol-l-yl-phenyl)-propiQnic acid tert-butvi ester The title compound was prepared from 3-pyrazol-l-yl-benzoic acid methyl ester [CAS-No. 168618-35-7] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.00 g). MS (EI) 286 (M+), Example K17 fRS)-3-Oxo-3-{3-[4-ftetrahvdro-pyran-2-yloxymethyl)-pvrazol-l-yl1-phenyl-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-1-yl]-benzoic acid methyl ester [prepared by the following sequence: L) A mixture of 3-hydrazino-benzoic acid methyl ester hydrochloride [CAS-No. 167626-26-8] (15.14 g, 75 mmol), 2-cyano-3-ethoxy-acryiic acid benzyl ester [CAS-No. 32016-27-6] (17.36 g, 75 mmol) and Et3N (10.5 mL, 75 mmol) in isopropanol (115 mL) was refluxed for 1.5 h. ii.) The obtained 5-amino-l-(3-methoxycarbonyl- phenyl)-lH-pyra2ole-4-carboxylic acid benzyl ester (26.0 g, 74 mmol) was refluxed with isopentyl nitrite (30 mL, 225 mmol; 10 mL) in THF (200 mL) for 22 h. iii.) The obtained l-(3-methoxycarbonyl-phenyl)-lH-pyrazole-4-carboxylic acid benzyl ester (18.98 g, 56 mmol) was hydrogenated in the presence of Pd/C (10% Pd/C, 600 mg, 1 mol%) in EtOAc (350 mL) and THF (250 mL) at 23 oC for 16 h. iv.) The obtained 1-(3-methox7carbonyl-phenyl)-lH-pyrazole-4-carboxylic acid (13.70 g, 55.6 mmol) was reduced with BH3.SMea (28.46 mL, 278.2 mmol) m THF (364 mL) at 5 to 23 °C for 16 h. V.) The obtained 3-(4-hydroxymethyl-pyrazol-l-yl)-benzoic acid methyl ester (10.66 g, 45.9 mmol) was reacted with 3,4-dihydro-2H-pyran (6.24 mL, 68.9 mmol) and cat. amount p-TsOH-HaO in DCM (91 mL) at 23 °C for 22 h.] (14.18 g, 44.8 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (15.87 g), MS(ISN)399[(M.H)-]. Example K18 (RS)-3-Oxo-3-{3-[4'(tetrahvdro-pyran-2yloxvmethyl)-isoxazol-3-yn-phenyll-propionic acid tert.'butyl ester The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] was treated with NCS, cat amount pyridine in CHCI3 followed by acidition of (E)-3-pyrrolidin-l-yl-acryhc acid tert.-butyl ester [CAS-No. 340257-76-3] and slow acidition of Et3N in CHCI3 at 23 -°C. ii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid tert-butyl ester was stirred in formic acid at 50 °C for 18 h. iii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid was reduced with BH3SMe2 in THF at 5 to 23 'C for 16 h. iv.) The obtained 3-(4-hydroxymethyl-isoxazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH-HzO in DCM at 23 °C for 1L] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (1.817 g). MS(ISN)400[(M-H)-]. Example Kl 9 fRS)-3-l3-(2-methyl-4-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl 3'OXo-propionic acid tert--butyl ester The title compound was prepared from (RS)-3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyra2ol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 3-bromobenzoyl chloride and 3-isopropylamino-acrylic acid methyl ester [CAS-No. 89895-40-9] were reacted in toluene and Et3N according to Synthesis 1982, 318. ii.) The obtained 2-(3-bromo-benzoyl)-3-isopropylamino-acrylic acid methyl ester was reacted with methylhydrazine in ether at 23 °C according to Synthesis 1982, 318. iii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyra2ole-4-carboxylic acid methyl ester was reduced with LiAlH4 in THF at -10 °C for 1 h. iv.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-4-yl]-methanol was reacted with 3,4-dihydro-2H-pyran and cat. amoimt p-TsOH-HaO in DCM at 23°C for 20 h. v.) The obtained (RS)-5-(3-bromo-phenyl)-l-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-iH-pyrazole was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. vi.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vii.) The obtained 3-(4-methoxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with IM BBrs-sol. in DCM at -78 to 23 -°C for 1 h. viii.) The obtained crude bromide was reacted with KOAc in DMF at 60 °C for 30 min. ix.) The obtained crude acetate was reacted with NaOMe-sol. In MeOH at 23 °C for 20 min. X-) The obtained 3-(4-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (11.106 g). MS(ISN)413[(M-H)-]. Example K20 (RS)-3-Oxo-3-(3-{2-(2-ftetrahvdrQ-pyran-2-yloxvVethyl1-2H-pvrazol-3-yl}-phenyl)-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyl)-3-dimethylamino-propenone [CAS-No. 163852-04-8] with 2-hydroxy-ethylhydrazine in EtOH at 23 °C for 2.5 days, ii.) The obtained mixture of pyrazoles (12.36 g, 35.19 mmol) was reacted with 3,4-dihydro-2H-pyran (4.79 mL, 52.8 mmol) and cat amount p-TsOH-H2O in DCM (70 mL) at 23 °C for 20 h iii.) chromatographic separation of the obtained isomers, iv.) treatment of the clean isomer (7.35 g, 73.7 mmol) was treated with n-BuLi (13.08 mL, 20,9 mmol) in THF (42 mL) at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid was reacted (4.56 g, 14.1 mmol) was reacted with KHCO3 (2.89 g, 28.8 mmol) and Mel (0.99 mL, 15.9 mmol) in DMF (29 mL) at 23 °C for 2 h,] (2.96 g, 8.96 mmol) by treatment with Uthium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g). MS(ISP)415[(M+H)+]. Example k21 (RSV3-Oxo-3-f3-{5-r2-ftetrahvdro-p\Tan-2-\dox\'Vethyll-rL23ltriazol-l--vil-phenyl-propionic acid tert.-butyl ester The title compound was prepared from (RS)-3-{5-[2-(tetrahydro-pyran-2-yioxy)-ethyl]-[l,2,3]triazol-l-yl}-benzoic acid methyl ester (prepared by the following sequence: L) methyl 3-azidobenzoate [CAS-No. 93066-93-4] and (RS)-tert-butyl-dimethyl-[4-(tetrahydro-pyran-2-yioxy)-but-l-ynyi]-silane [CAS-No. 198411-20-0] were heated to 60 °C for 10 days; ii.) The obtained material was stirred in TBAF (IM m THF) at 70 °C for 6 days and subsequently refluxed in IN HCl for 2 h; iii.) The obtained 3-[5-(2-hydroxy-ethyl)-[l,2,3]triazol-l-yl]-benzoic acid was stirred in MeOH and cone. H2SO4 at 23 °C for 11 days, iv.) The obtained 3-[5-(2-hydroxy-ethyl)-[ 1,2,3]triazol-l-yl]-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH'H2O in DCM at 23 °C for 20 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (6.748 g). MS(ISP)416[(M+H)-']. Example K22 (RS)-3-Oxo-3-l3-(5-rtetrahvdro-pyran-2-yloyvmethyl)-pvrazol-l-yll-phenyll-propionic acid ethyl ester The title compoxmd was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yioxymethyl)-pyrazol-l-yl]-benzoic acid [prepared by the following sequence: i.) A mixture of 3-hydrazino-benzoic acid [CAS-No. 38235-71-1], 4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester [CAS-No. 67751-14-8] in acetic acid was refluxed for 15.5 h. ii.) The obtained 2-(3-carboxy-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was stirred DMF-di-tert-butyl acetal in toluene at 80 X for 45 h. iii.) The obtained 2-(3-terL-butoxycarbonyl-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was saponified 150°C Cristallisation from water and ethyl acetate/hexane (1:1) yielded a light brown solid (24.3 g, 54%) mp 164°C; ii,) The obtained material (24-3 g, 104 mmol) was reacted with 3,4-dihydro-2H-pyran (29.3 mL, 320 mmol) and cat amount p-TsOH-H2O in dichloromethane (360 mL)/ THF (300 ml) at 23 °C for 20 L Purification by column chromatography on silica gd (toluene/ethyl acetate 1:1) gave a light brown oil.] (16.6 g, 52.3 mmol) by treatment with hthiimi tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (14.3 g, 68%). MS (ISP) 400.4 [(M-H)-]. Example K25 3-Oxo-3-(3-[1.2.4]triazol-yl-phenyl)-pTopionic acid tert-butylester The title compound was prepared from methyl 3-[l,2,4]triazol-1-yl-benzoate [CAS-No. 167626-27-9] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange liquid (2.41 g), MS (EI) 287 (M^). Example K26 3-(3-Imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butylester The title compound was prepared from methyl 3-(lH-imida2ol-l-yl)benzoate [prepared from 3-(lH-imidazol-l-yl)benzoic acid (/. Med, Chetn. 1987,30,1342; CAS-No. [108035-47-8] by reflioxing in cone. H2SO4/MeOH] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange-brown oil. MS (ISP) 287 [(M+H)+]. Example K27 3-0X0-3-f3-f4-ftetrahydro-pyran-2-yloxvmethyl')-thia2ol-2-yl]-phenyl]-propionic acid tert-butylester al 3-f4-Hvdroxymethyl-thiazol-2-yl)-benzoic acid methyl ester A mixture of 3-thiocarbamoyl-benzoic acid methyl ester (7,8 g), l,3-dichloro-2-propanone (8.4 g) and NaHCOs (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 -°Cfor 24 h. The reaction mixture was cooled to 20 °C and acided to a stirred solution of NaOMe (5.4 g) in MeOH (200 mL). Stirring was continued for 0,5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ACOEL The organic layer was washed with brine, dried and evaporated in vacuum- The residue was crystallized from CH2Cl2/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-ben2oic acid methyl ester (7.5 g) as light-brown crystals, mp 115-117 °C. b) 3-f4-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-2-yn-benzoic acid methyl ester A mixture of the material prepared in a) (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in AcOEt (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried over Na2SO4 and evaporated in vacuo. The residual oil was purified by chromatography on silica gel using AcOEt /hexane (1:2) as eluent to give 3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil. c) 3-Oxo-3-f3-r4-ftetrahvdro-pyran-2-yloxvmethyD-thiazoI-2-yI1-phenyl]-propionic acid tert-butylester A sample of the material prepared in b) (3.3 g) was treated with lithium tert,-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (3.25 g) as a pale-yeUow oil, MS (ISP) 418.2 [(M-fH)--]. Example K28 3-Oxo-3-f3-(2-bromo-lJ-dimethoxy-ethyl')-phenyll-propionic acid tert-butylester a) 3-(2-Bromo-Ll-dimethoxy-ethyl')-ben2oic acid methyl ester A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-No 62423-73-8] (2.43 g), 4-toluenesulfonic acid hydrate (0.38 g) and trimethyl orthoformiate (5.5 ml) in MeOH (40 mL) was heated at reflux for 20 h. The cooled solution was diluted with AcOEt (0.15 L), washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum to give 3-(2-bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.0 g) as a pale-yellow oil. b) 3-Oxo-3-[3-(2-bromo-l,1-dimethoxv-ethyl)-phenyl1-propionic acid tert-butylester 3-(2-Bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.9 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyi]-propionic acid tert-butyl ester (2.8 g) as a yellow oil. Example K29 3-Oxo-3-r3-(2-methyl-oxazol-4-yl)-phenyn-propionic acid tert-butyl ester a) 3-(2-methyl-oxazol-4-yl)-benzoic acid A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g) and acetamide (1.77 g) was heated with stirring to 130 'C for 40 min. The mixture was cooled and diluted with H2O (30 mL) and the precipitate formed was collected by filtration to give 3-(2-methyl-oxa2ol-4-yl)-ben2oic acid (1.51 g) as brown solid. b) 3-(2-methyl-oxazol-4'yl')-benzoic acid methyl ester A solution of 3-(2^methyl-oxazol-4-)d)-benzoic acid (1.42 g) in a mixture of MeOH (30 mL) and 4NHC1/Et20 (6 mL) was heated to 40 -°C for 4 h. The solution was evaporated in vacuum and the residual oil was stirred with H2O (30 mL), the pH of the mixture being set to about 6 by the acidition of sat NaHCOa solution. The precipitate was isolated by filtration to give 3-(2-methyl-oxa2ol-4-yl)-benzoic acid methyl ester (1.18 g) as light-brown solid, MS (ISP) 218.2 [(M+H)-^]. c) 3-Oxo-3-f3-('2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester 3-(2-Methyl-oxazol-4-yl)-benzoic acid methyl ester (1.02 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (1.50 g) as a pale-yellow oil. Example K30 3-Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3.4lthiadiazol-2'yl1-phenyll-propionic acid tert-butyl ester a) 3-rN'-tert-butoxvcarbonyl-hvdra2inocarbothioyl)-benzoic acid methyl ester A mixture of 3-(N'-tert-butoxycarbonyl-hydrazinocarbonyl)-benzoic acid methyl ester (1.47 g) and Lawesson reagent (1.62 g) in toluene (30 mL) was heated to 70 °C for L5 h. The mixture was concentrated in vacuum and then subjected to chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-(N'-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (1.31 g) as a yellow solid, MS (ISP) 328.3 [(M+NH4)1. b) 3-Hvdra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate A solution of 3-(N1-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (0.93 g) in TFA (9 mL)/anisole (2 mL) was stirred at 0 X for 1 h. The solvents were evaporated in vacuum to give crude 3-hydrazinothiocarbonyl-ben2oic acid methyl ester trifluoroacetate (0.98 g) as a crystallizing oil. c) 3-(5-Hydroxymethyl-[L3,4lthiadiazoI-2-yl)-benzoic acid methyl ester A mixture of 3-hydrazinothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.49 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.47 g) in EtOH (6 mL) was heated to 80 °C for 2.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated. The residual oil (0.8 g) was dissolved in MeOH (5 mL), MeONa (0,08 g) was acided and the solution was heated to 65 °Cfor 0.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (0.15 g) as a white soHd, MS (ISP) 25L2 [(M+H)+]. d) 3'(5-fTetrahvdro-pyran2-yloxvmethyl)-fL3,4lthiadiazol-2-ylUbenzoicacid methyl ester A mixture of 3-(5-hydxoxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (7.8 g), dihydropyrane (5.6 mL) and p-toluenesulfonic acid hydrate (0.59 g) in AcOEt (80 mL) was stirred at 20 °Cfor 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on sihca gel using AcOEt/hexane (1:2) as eluent to give 3-[5-{tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5,85 g) as a pale-yellow oil. e)3'Oxo-3-B-r5-ftetrahvdrO'pyran-2-vIoxvmethyl)-fl3.4lthiadiazQl-2-yl]-phenyl-propionic acid tert-butylester 3-[5-(Tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5.85 g) was treated with lithium tert,-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (8.9 g) as a pale-yellow oil. Example K31 3-Oxo-3-(3-(5-r2-ftetrahvdro-pyran-2-vIoxy)-ethyl14L3.4lthiadia2ol-2-yl}-phenyl)-propionic acid tert-butylester a) 3-[5-(2-Hydroxy-ethyl)-ri3,4lthiadiazol-2-yl1-benzoic acid methyl ester A mixture of 3-hydra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.45 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (0.35 g) in pyridine (5 mL) was heated to 100 °C for 1.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was chromatography on siUca gel using AcOEt/hexane (1:1) as eluent to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]thiadiazol-2-yl]-ben2oic acid methyl ester (0.37 g) as a white solid, MS (ISP) 265.3 [(M+H)+]. b) 3-15- [2-fTetrahydro-pyran-2-yloxy)-ethyl1 - [ 1,3>4]thiadiazol-2-yn-benzoic acid methyl ester A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3>4]thiadia2ol-2-yl]-ben2oic acid methyl ester (1.86 g), dihydropyrane (0.95 mL) and p-toluenesulfonic acid hydrate (0.13 g) in AcOEt (25 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyI]-[l,3,4]thiadia2ol-2-yl}-benzoic acid methyl ester (1.60 g) as a pale-yellow oil. c)3-Oxo-3-r3-l5-r2-ftetrahvdro-pyran-2-vIoxv)-ethyl]-rL3.4lthiadiazoI-2-yl?-phenyD-propionic acid tert-butylester 3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadia2ol-2-yl}-benzoicacid methyl ester (1.60 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phen}i)-propionic acid tert-butyl ester (2.1 g) as a pale-yellow oil. Example K32 3-Oxo-3-(3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3,4loxadiazol-2-yl]-phenyll-propionic acid tert-butyl ester z) 3-(5-HvdrQXvmethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester A mixture of 3-hydrazinocarbonyl-benzoic acid methyl (0.97 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.95 g) in EtOH (20 mL) was heated to 80 -°C for 1 h. The mixture was diluted with AcOEt and washed with IN HCI and with brine. The organic layer was dried and evaporated and the residual oil (1.1 g) was dissolved in DMF (4 mL). Upon acidition of AcOK (0.59 g) and KI (0.07 g), the mixture was stirred at 100 Xfor 0.5 h. After cooling to 20 °C, MeOH (10 mL) and NaOMe (0.14 g) were acided and stirring was continued for 0.5 h at 65 °C. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester (0.72 g) as a white solid, MS (ISP) 235.3 [(M+H)--]. b) 3-(5-(Tetrahvdro-pyran-2-yloxvmethyl)-[ 1.3.4lthiadiazol-2-vn -benzoic acid methyl ester A mixture of 3-(5-hydroxymethyl-[l,3>4]oxadiazol-2-yl)-benzoic acid methyl ester (9.8 g), dihydropyrane (7.7 mL) and p-toluenesulfonic acid hydrate (0.80 g) in AcOEt (100 mL) was stirred at 20 € for 1 h. The solution was diluted with AcOEt, washed with 5% NaHC03 solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-[5-(tetrahydrO-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (12.6 g) as a pale-yellow oil. c)3-Oxo-3-{3-[5-(tetrahydro-pyran-2-yloxvmethvD-fl3,4loxadiazol-2-yn-phenyll-propionic acid tert-butylester 3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,3,4]thiadiazol-2-yl] -benzoic acid methyl ester (12,6 g) was treated with Uthium tert.-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (17.0 g) as a pale-yellow oil. Example K33 3-Oxo-3-f3-{5-[2-ftetrahvdro-pyran-2-yloxvVethyl]-[L3.4loxadiazol-2-yll-phenyl)-propionic acid tert-butylester 2L) 3-[5-(2-Hvdroxv-ethyl)-ri3,4l6xadiazol-2-yl1-benzoic acid methyl ester A mixture of crude 3-hydrazinocarbonyl-ben2oic acid methyl (2,90 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (2.76 g) in pyridine (10 mL) was heated to 100 °Cfor 2 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was crystallized from Et20 to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yI]-benzoic acid methyl ester (2.5 g) as a white solid, MS (ISP) 249.1 [(M+H)--], b)3-l5-(2-fTetrahydro-pyran-2-yloxvVethyl]-fL3,4lthiadiazol-2-vU-benzoicacid methyl ester A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yl]-benzoic acid methyl ester (7.45 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0,57 g) in AcOEt (80 mL) was stirred at 20 'Cfor 2 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoic acid methyl ester (8.2 g) as a pale-yellow oil. cl3-Oxo-3-(3-(5-(2-(tetrahvdro-pyran-2-yloxv)-ethyl]-rL3.4loxadiazol-2-vU-phenyl)-propionic acid tert-butylester 3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoicacid methyl ester (8.2 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (11.6 g) as a pale-yellow oil. Example K34 3-(3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester a) 3-Oxazol-4-yl-benzoic acid methyl ester A mbcture of 3-(2-bromo-acetyl)-benzoic acid (1.94 g) and formamide (1.08 g) was heated with stirring to 130 ^'Cfor 3 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was dissolved in a mixture of MeOH (30 mL) and 4NHC1/Et20 (8 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOs solution and brine, dried and evaporated. The residue was chromatographed on sihca gel using AcOEt/hexane (1:3) as eluentto give 3-oxazol-4-yl-benzoic acid methyl ester (0.85 g) as off-white solid, MS (ISP) 204.1 [(M+H)--]. b) 3-r3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester 3-Oxazol-4-yl-benzoic acid methyl ester (0.85 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (1.46 g) as a pale-yellow oil. Example K35 3-Oxo-3-f3-thiazoI-4-vI-phenyl)-propionic acid tert-butylester a) 3-Thiazol-4-yl-benzoic acid methyl ester A solution of 3-(2-bromo-acetyi)-benzoic acid (L22 g) and thioformamide (0.46 g) in EtOH (5 mL) was heated to 80 •C for 1 L The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was dissolved in a mixture of MeOH (20 mL) and 4NHCl/Et20 (5 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOj solution and brine, dried and evaporated. The residue was chromatographed on siUca gel using AcOEt/hcxanc (1:3) as eluent to give 3-thiazol-4-yl-benzoic acid methyl ester (0,98 g) as off-white solid, MS (ISP) 220.2 [(M+H)--]. b) 3-Oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butylester 3-Thiazol-4-yl-benzoic acid methyd ester (0.91 g) was treated with lithitun terL-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (1.54 g) as a pale-yellow oil. Example K36 3-f3-(5-Methyl-oxazol-4-yI)-phen)d]-3-oxo-propionic acid tert-butylester a) 3-tert-Butoxvcarbonylacetyl-benzoic acid methyl ester Dimethyl isophthaiate (67.9 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give crude 3-tert-butoxycarbonyiacetyi-benzoic acid methyl ester (74.5 g) as a pale-yellow oil. b) 3-Propionyl-benzoic acid methyl ester To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (ILl g) and Mel (2.2 mL) m DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil> 1.4 g). Stirring was continued at 0 ®C for 15 min and at 20 °C for 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated The residue was stirred in a mixture of CH2Cl2 (30 mL) and TEA (30 mL) for 40 min at 20 °C. After the evaporation of the solvents, the solution of the residue in AcOEt was extracted with ice-cold sat NaaCOs solution and the aqueous extracts were immediately acidified with 3N HQ and extracted with AcOEt The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HCl (3 mL) to 100 °C for 1 h. The cooled mixture was diluted with AcOEt, washed with sat. NaHCOs and brine, dried and evaporated to give 3-propionyi-benzoic acid methyl ester (3.87 g) as white solid, MS (ISP) 193.2 [(M+H)--]. c) rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester A mixture of 3-propionyl-benzoic acid methyl ester (3.6 g) and CuBri (7.45 g) in AcOEt (45 mL) was heated at reflux for 2 h. Unsoluble material was filtered oflFfrom the cooled mixture and the clear solution was washed with brine, dried and evaporated to give crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (5.0 g) as pale-yeUow oO. d) 3-r5'methyl-oxazol-4-yl)-benzoic acid methyl ester rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester (5.42 g) and formamide (3.6 ml) were heated together to 130 °C for 5 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as eluent to give 3-(5-methyI-oxazol-4-yl)-benzoic acid methyl ester (2.52 g) as white solid. e) 3-[3-(5-Methyl-oxazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester 3-(5-methyl-oxazol-4-yl)-beruoic acid methyl ester (0.87 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (L46 g) as a pale-yellow oil. Example K37 3-[3-(2-methyl'5-propyl-oxazol-4-yl)-phenyl-3-oxo-propionic acid tert-butyl ester al 3-Pent-4-enoyl-benzoic acid methyl ester To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (11.1 g) and allyl bromide (3.0 mL) in DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil, 1.44 g). Stirring was continued at 0 °C for 20 min and at 20 °Cfor 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated. The residual oil was stirred in a mixture of CH2Cl2 (30 mL) and TFA (30 mL) for 40 min at 20 'C. The solvents were evaporated. The solution of the residue in AcOEt was extracted with ice-cold saL NaaCOa solution and the aqueous extracts were immediately acidified with 3N HCl and extracted with ACOEL The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HQ (2 mL) to 100 ^'C for 1 h. The cooled mbcture was diluted with AcOEt, washed with saL NaHCOs and brine, dried and evaporated to give 3-pent-4-enoyi-ben2oic acid methyl ester (5.11 g) as a pale-yellow oil, MS (ISP) 236.2 [(M+NH4)']. b) rac-3-(2-Bromo-pentanoyl)-benzoic acid methyl ester A sample of 3-pent-4-enoyl-benzoic acid methyl ester (3.93 g) was hydrogenated in AcOEt (50 mL) in the presence of 5% Pd-C (190 mg) for 30 min at 20 ^'C. The catalyst was filtered off, CuBr2 (4.44 g) was acided to the solution and the mixture was heated at reflux for 1 h. Unsoluble material was filtered off from the cooled mixture and the clear solution was washed with IN HCl and brine, dried and evaporated to give crude rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (3.6 g) as pale-yellow oil. c) 3-(2-methyl-5-propvI-oxazol-4-yl)-benzoic acid methyl ester A sample of rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (1.50 g) and acetamide (0.89 g) were heated together to 130 C for 15 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oE was chromatographed on silica gel using AcOEt/hexane (1:3) as duent to give 3-(2-methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0.47 g) as a light-yellow oil. d) 3-f3-(2-methyl-5-propyl-oxazol-4-yl')-phenyl1-3-oxO'propionic acid tert-butylester 3-(2-Methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0,47 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(2-methyl-5-propyl-oxazol-4-yl)-phenyl]-3-oxo-propiomc acid tert-butyl ester (0.58 g) as a light-brown oil. Example K38 3-[3-(5-methyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butylester z) 3-(5-methyl-thia2Ql-4-yl)-benzoic acid methyl ester A solution of crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (2,71 g) and thioformamide (1.83 g) in EtOH (20 ml) was heated at reflux for 1 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as duent to give 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (2.41 g) as white solid. h) 3-[3-(5-methyl-Aiazol-4-yl)-phenyll-3-oxo-propiQnic acid tert-butylester A sample of 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g) was treated with Uthium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-thia2ol-4-yi)-phcnyl]-3-oxo-propiomc acid tert-butyl ester (L9 g) as a pale-yellow oil Example K39 3-f3-(23-Dimethyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester z) 3-(2,5-Diinethyl-thiazol-4-yl)-ben2oic acid methyl ester A mixture of rac-3-(2-bromo-propionyl)-bcn2oic acid methyl ester (6.78 g) and thioacetamide (5.63 g) was heated to 130 ^'Cfor 20 min. The mixture was partitioned between AcOEt and H2O, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gd using AcOEt/hcxane (1:4) as duent to give 3-(2,5-dimethyl-thia2;ol-4-yl)-benzoic acid meth>1 ester (4.97 g) as yellow oil. b) 3-r3-(2>5-Dimethyl-thiazol-4-y!)-phen\i]-3-oxo-propionic acid tert-butyl ester A sample of 3-(2,5-dimethyl-thia2ol-4-yl)-ben2oic acid methyl ester (0.99 g) was treated with lithiimi tert-butyl acetate according to the general procedure K (method b) to give 3-[3-(2,5-dimethyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (1.12 g) as a pale-yellow oil. Example K40 3-Oxo-3-[3-(5-methyl-4-(tetrahvdro-pyran-2-yloxvmethyl)-thia2ol-4-yl]-phenyi1-propionic acid tert-butyl ester a) 3-(2-HydroxymethyI-5-methyl-thia2ol-4-yl)-ben2oic acid methyl ester A solution of rac-3-(2-bromo-propionyI)-ben2oic acid methyl ester (2 Jl g) and 2-(tert.-butylcarbonyloxy)thioacetanude (2.1 g) in EtOH (20 mL) was heated at reflux for 6 h. The mixture was partitioned between AcOEt and brine, and the organic layer was dried and evaporated. A solution of the residual oil and NaOMe (0.54 g) in MeOH (20 mL) was stirred at 60 °C for 1 h. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (1.17 g) as white crystals, MS (ISP) 264.1 [(M+H)^. h) 3-(5-methyl-4-ftetrahvdro-pyran-2-yloxymethyl')-thiazQl-4-yl1-benzoic acid methyl ester A mixture of 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g), dihydropyrane (0.73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 -°C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCO3 solution and with brine, dried and evaporated The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-l5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1,45 g) as a pale-yellow oil. c) 3-0x0-3- [3 r5-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-4-yll -phenyl] -propionic acid tert-butyl ester 3-[5-Methyl-4-(tetrahydro-pyran-2--yloxymethyl)-thiazol-4-yl]-ben2oic acid methyl ester (1.45 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl]-propionic acid tert-butyl ester (2.13 g) as a pale-yellow oil. Example K41 3-Oxo-3-[3[5-propyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-2-yl]-phenyl-propionic acid tert-butyl ester a) 3-(2-Hydroxvmethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester A sample of rac- 3-(2-bromo-pentanoyl)-benzoic acid methyl ester (0.60 g) and and 2-(tert.-butylcarbonyloxy)thioacetamide (0.36 g) in EtOH (4 mL) was heated at reflux for 5 h. The mixture was partitioned between AcOEt and 5% NaHCOs solution, the organic layer was washed with brine, dried and evaporated. A solution of the residual oil and of NaOMe (0.13 g) in MeOH (10 mL) was stirred at 60 °C for 30 min. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.44 g) as an oil. b) 3-f 5-Propyl-4-(tetrahydro-pyran-2-yloxymethyl)-tfaiazol-2-yl1-benzoic acid methyl gster 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (0,73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 ^'C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as duent to give 3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (0.36 g) as a pale-yellow oil. c)3'Oxo-3-f3-(5-propyl-4-(tetrahvdro-pyran-2-yloxyme&yl)-tfaiazol-2-yl]-pheny^ propionic acid tert-butyl ester 3-l5-Propyl-4-(tetrahydro-pyran-2-yloxymeth)d)-thia2ol-2-yl]-benzoic acid methyl ester (0-34 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.42 g) as a pale-yellow oil. Example K42 3-Oxo-3-f3-r2-methyl-5-ftetrahydro-pyran-2-yloxvmetfayl)-thiazQl-4'yl]-phenyl-propionic acid tert-butyl ester al 3-(5-Bromomethyl-2-methyl-thia2oI-4-yl)-benzoic acid methyl ester A mixture of 3-(2,5-dimethyl-thiazol-4-yl)-benzoic acid methyl ester (3.96 g), N-bromosuccinimid (3.13 g) and (X,a'-bis(isobutyronitrile) (0.02 g) in CCI4 (60 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-ben2oic acid methyl ester (6,2 g) as an oil. h) 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-ben2oic acid methyl ester 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-benzoic acid methyl ester was stirred in DMF (16 mL) together with KOAc (2.35 g) at 20 °C for 20 min. MeOH (32 mL) and naOMe (0.86 g) were acided and stirring was continued at 50 '°C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:1) as eluentto give 3-(5-hydroxytnethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (2,93 g) as a white solid. c) 3-[2-methyl-5-ftetrahydro-pyran-2-yloxymethyl)-thiazol-4-yll-benzoic acid methyl ester 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (2.01 mL) and p-toluenesulfonic acid hydrate (0.21 g) in AcOEt (25 mL) was stirred at 20 °Cfor 1 h. The solution was diluted AcOEt, washed with 5% NaHCOa solution and with brine, dried and evaporated. The residual oil was purified by chromatography on siUca gd using AcOEt/hexane (1:3) as eluent to give 3- [2-methyl-5-(tetrahydro-pyran-2-)doxymethyl)-tiuazol-4-yl]-benzoic acid methyl ester (3.8 g) as a pale-ydlow oiL d) 3-0x0-3-r3-r2-methyI-5'rtetrahydro-pyran-2-vIoxvmethyI)-tHazol-4-yl^ propionic acid tert-butyl ester 3-[2-Methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-ben2oic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (methodb) to give crude 3-oxo-3-[3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)' thiazol-4-yl]-phenyl]-propionic acid tert-butyl ester (5.45 g) as a pale-yellow oil. Example K43 3--OXO-3-I [5-(tetrahydro-pyTan'2-yloxymethyl)-thiazol-4-vn -phenyl!-propionic acid tert-butyl ester a) 3-f 5-Bromomethyl-thiazol-4-yl')-benzoic acid methyl ester A mixture of 3-(5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (2.40 g), N-bromosuccinimid (2.01 g) and oc,a'-bis(isobutyronitrile) (0.02 g) in CCU (40 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-thia2ol-4-yl)-benzoic acid methyl ester (3.36 g) as an oil. b^ 3-f 5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester 3-(5-Bromomethyl-thiazol-4-yl)-benzoic acid methyl ester was stirred in DMF (10 mL) together with KOAc (1.52 g) at 20 ^'C for 30 min, MeOH (20 mL) and NaOMe (0.84 g) were acided and stirring was continued at 50 °C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:2) as eluent to give 3-(5-hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (1.43 g) as a white solid. c) 3-[5-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-4-yl]-benzoic acid methyl ester 3-(5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (L25 g), dihydropyrane (0,84 mL) and p-toluenesulfonic acid hydrate (0.10 g) in AcOEt (12 mL) was stirred at 20 °Cfor 3 h. The solution was diluted AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-[5-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1.60 g) as a pale-yellow oil. d) 3-Oxo-3-( (5-(tetrahvdro-pyran-2-yloxyTnethyl)-thia2ol-4-yl]-phenyll-propionic acid tert-butyl ester 3-[5-(Tetrahydro-pyran-2-yioxymethyl)-thiazol--4-yi]-beiizoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-{[5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionic acid tert-butyl ester (2.3 g) as a pale-yellow oil. Example K44 3-[3-(2-Isopropyi-3H'imida2ol-4-yl')-phenyll-3-oxo-propionic acid tert-butyl ester 3) 3-Dihydroxyacetyl-benzoic acid methyl ester A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g), DMSO (17 mL) and 48% HBr (3.4 mL) was heated to 55 °C for 30 min. The mixture was partitioned between AcOEt and H2O and the organic layer was washed with brine, dried and evaporated to give 3-dihydroxyacetyl-benzoic acid methyl ester (1.06 g) as a white solid. h) 3'(2-I$opropyl-3H-imidazol-4-yl)-benzoic acid methyl ester A solution of 3-dihydroxyacetyl-benzoic acid methyl ester (0.36 g) and 2-methyl-propionaldehyde (0.24 ml) in 5% aqueous NH3 (6 mL) was heated to 100 °C for Ih, The mixture was evaporated in vacuum and the solution of the residue in a mixture of MeOH (10 mL) and 4NHC1/Et20 (2 mL) was heated to 40 °C for 18 h. The solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaaCOa solution and brine, dried and evaporated. The residue was chromatographed on silica gel using AcOEt as eluent to give 3-(2-isopropyl-3H-imidazol-4-yl)'ben2oic acid methyl ester (0.37 g) as a pale-yellow oil. c) 3'f3-(2-Isopropyl-3H-imidazol-4-yl)-phenyll-3-oxo-propionic acid tert-butylester 3-(2-Isopropyl-3H-imidazol-4-yl)-benzoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give cmde 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (0.25 g) as a pale-yellow oil. The following examples relate to the preparation of the 6-aryl-2,2-diniethyl-[l,3]dioxin-4-ones (general formula IV), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H): General procedure L Preparation of 6-aryl-2,2-dimethyl-fL3]dioxin-4-ones Method a) The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from 3-aryl-3-oxo-propionic acids and catalytic amount of cone. H2SO4 or trifluoroacetic acid (TFA) in isopropenyl acetate at 23 -€ according to Chem, Pharm, Bull 1983,3J, 1896. The final products were purified by silica gel coliunn chromatography with hexane/EtOAc. Method b) The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from the tert.-butyl 3-aryl-3-oxo-propionates by treatment with trifluoroacetic anhydride (TFAA) in a mixture of TFA and acetone at 23 -°C according to Tetrahedron Lett. 1998,39,2253. The final products were if necessary purified by silica gel column chromatography with hexane/EtOAc. Example LI 3-(2,2-Dimethyl-6-oxo-6H-ri.3ldioxin-4'vD-benzonitrile The 3-(3-cyano-phenyl)-3-oxo-propionic acid was prepared from 3-cyanobenzoyl chloride (828 mg, 5 mmol) and bis(trimethylsilyl)malonate (2.56 mL, 10 mmol) with n-BuLi (1,6M in hexane, 6.25 mL) in ether at-60 °C to 0 °C according to general procedure M (method c2). The crude material (1.04 g) was transformed into the title compound by stirring in isopropenyl acetate and TFA according to general procedure L (method a). Obtained as a light yellow solid (0.8 g). MS (EI) 229 (M^); mp 138 °C (dec). Example L2 4-(2.2-Dimethyl-6-oxo-6H-fL3ldioxin-4-yl1-pvridine-2-carbonitrile The title compound was prepared from 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example MlO) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a brown solid (3.30 g). MS (H) 230 (M^); mp 132 X (dec). Example L3 6'f3'Imidazol-l-yl-phenyi)-2.2-dimethyl-fh3ldioxin-4-one The 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid was prepared from 3-(lH-imidazol-l-yl)ben2oyl chloride hydrochloride [prepared by treatment of 3-(lH-imidazoM-yl)-benzoic acid (/. Med. Chem. 1987,30,1342; CAS-No. [108035-47-8] with SOCI2) and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 ^'C according to general procedure K (method cl). The crude material was transformed into the title compound by stirring in isopropenyl acetate and cone. H2SO4 according to general procedure L (method a). Obtained as an orange semisolid (617 mg). MS (EI) 270 (M^). Example L4 2.2-Dimethyl-6-f3-fL23ltriazol-l-vI-phenyl)-rL3ldioxin-4-one The tide compound was prepared from 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K23) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a beige solid (7.80 g). MS (EI) 271 (M--); mp 144-147 °C (dec). General procedure M: Preparation of {2-[3-aryI-3-oxo-propionylamino]-phenyl}-carbamic acid tert.-butyl ester by reaction of (2-amino-phenyl)-carbamic acid tert-butyl esters with ethyl or tert.-butyi 3-aryl-3-oxo-propionates or 6-aryl-2^-dimethyl-[l,3]dioxin-4-ones: A mixture of the (2-amino-phenyl)-carbamic acid tert.-butyl ester or (1.0-1-2 mmol) and (1.0-1-5 mmol) of the ethyl or tert.-butyl 3-aryl-3-oxo-propionate or 6-aryl-2,2-dimethyl-[l,3]dioxin-4-one was heated in toluene (4-8 mL) to 80 *€ to 120 'C until tic indicated complete consumption of the minor component. The solution was allowed to cool to 23 °C, whereupon the product generally crystallized (in cases where crystallization failed to appear it was induced by acidition of hexane or ether, alternatively the reaction mixture was directly subjected to silica gel column chromatography). The solid was filtered off, washed with ether or mixtures of ether/hexane and dried in vacuum to give the {2-[3-aryl-3-oxo-propionylamino]' phenyil-carbamic acid terL-butyl esters, which was used direcdy in the following step or - if necessary - was purified by recrystallization or by silica gd column chromatography. Example Ml {4-Chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimethylamino-phenyll-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (0.5 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 62088-13-5; prepared from 3-cyanobenzoyl chloride according to general procedure K, method a] (0.55 mmol) according to the general procedure M. Obtained as a white solid (160 mg). MS (ISP) 457 [(M+H)--]; mp 159-163 °C. Example M2 l4-Chloro-5-dimethylamino-2-r3-oxo-3-r3-rh23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) (150 mg> 0.58 mmol) according to the general procedure M. Obtained as a beige solid (160 mg). MS (ISP) 499 [(M+H)--] and 501 [(M+2+H)1; mp 136-137 °C. Example M3 fRS)-r4-Chloro-5-dimethylamino-2-f3-oxo-3-^3-[5-ftetrahvdro-pyran-2- yloxvmethyl)-fL2.3ltria2ol-l-yll-phenyl}-prQpionylaminoVphenyl-carbamicacid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow oil (257 mg). MS (ISP) 613 [(M+H)'] and 615 [(M+2+H)']. Example M4 (243-f3-cyano-phenvD-3-oxo-propiQnylamino1-5-dime1hylamino-4-phenvIethvnyl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carbamic acid tert.-but7l ester (Example J2) and 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-ben2onitrile (Example LI) according to the general procedure M. Obtained as an orange solid (108 mg). MS(ISP)523[(M+H)1. Example M5 /5-Dimethylamino-2-r3'Oxo-3-r3-fL2.3ltriazol-l-yI-phenyD-propionylamino1-4' phenylethvnyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylaminO-phenyl)-carbamic acid tert.-butyl ester (Example J2) and 3-oxo-3-(3-[l,2,3]tria2oM-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as an orange solid (148 mg). MS(ISP)565[(M+H)']. Example M6 f4-Chloro-5-dimetfaylamino-2-l3-[3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylamino I-phenyl) - carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(3-methyi-isoxa2ol-5-yI)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (450 mg, 075 mmol) according to the general procedure M. Obtained as a white solid (136 mg). MS (ISP) 513 [(M-hH)--] and 515 [(M+2+H)']; mp 109-114 °C Example M7 fRS)-r2-Dimethylamino-2'3'-diflu6ro-5-r3-oxo-3-l^-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23]triazoM-yl1-phenvU-propionylamino)-biphenyl-4-yll-carbamic add tert.-butylester The title compound was prepared from (5-amino-2-dimethyiamino-2,3'-difluoro-biphenyl-4-yl)-carbamic acid terL-butyl ester (Example J3) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2^]tria2ol-l-yl]-phenyi}-propionic acid tert- butyl ester (Example K5) according to the general procedure M. Obtained as a yellow solid (253 mg). MS (ISP) 691 [(M+H)--]. Example M8 (2-Dimethylamino-2\3'-difluoro-5-r3-oxo-3-f3-rL23ltria2ol-l-yl-phenyl)-propionylamino1-biphenyl-4'yll-carbamic acid tert.-butylester The title compoimd was prepared from (5-amino-2-dimethylamino-2',3-difIuoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J3) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as a yellow solid (253 mg), MS (ISP) 577 [(M+H)--], Example M9 {5-f3-(3-cyano-phenyl')-3-oxo-propionylaminol-2-dimethylamino-2\3'-difluorO' biphenyl-4-yll-Carbamic acid tert.-butylester The title compound was prepared from (5-amino-2-dimethylantiino-2',3'-difluoro-biphenyl-4-yl)-Carbamic acid tert.-butyl ester (Example J3) 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-benzonitrile (Example LI) according to the general procedure M. Obtained as a yellow solid (145 mg). MS(ISP)535[(M+H)1. Example MlO (4-Chloro-5-dimethylamino-2'{3-(2-f3-methyl-isoxazol-5-vIVpvridin-4-yn-3-oxo-propionylaminol-phenyD-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-Carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yl]-3-oxo-propionic acid tert.-butyl ester (Example K6) (170 mg, 0.56 mmol) according to the general procedure M. Obtained as a brown solid (206 mg). MS (ISP) 514 [(M+H)+] and 516 [(M+2+H)+]; mp 181-183 °C. Example Mil (4-CMoro-5-r(2-metfaoxy-ethyl)-methyl-aminol-2-l3-f3-(3-methyl-isoxa2ol-5-yD-phenyl]-3-oxO'propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (165 mg, 0.55 nrniol) according to the general procedure M. Obtained as an amorphous yellow substance (207 mg), MS (ISP) 557 [(M+H)1 and 559 [(M+2+H)-']. Example M12 (4-Chloro-5-f(2-methoxy-etfavi)>methyl-aminol-2-l3-(2-f3-methvMsoxazoI-5-yl)-pvridin-4-yI1-3-oxo-propionylaminol-phenyIVcarbamic acid tert.-butylester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert,-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yI]-3-oxo-propionic acid tert.-butyl ester (Example K6) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (190 mg). MS (ISP) 558 [(M+H)1 and 560 [(M+2+H)']; mp 148 °C Example M13 (RS)-f4-Chloro-5-f(2-methoxv-ethyl)-methyl-amino1-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-vIoxvmethyl)- f 1,2,31 triazol-1 -yl] -phenyl-propionylamino)-phenyl -carbamic acid tert.-butvi ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyi)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyi ester (Example K5) (200 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg). MS (ISP) 657 [(M+H)+] and 659 [(M+2+H)1. Example M14 U-Chloro-5-[(2-methoxv-ethyl)-methyl-amino1-243-oxo-3-f3Jl,23ltriazol-l-v^ phenyl)-propionylamino]'phenvH-carbamic acid tert--butyl ester The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-eth7l)-methyl-amino]-phenyl}-carbamic acid tcrt-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-oxo-3-(3-[l,23]tria2oM->1-phenyl)-propionicacid ethyl ester (Example Kl) (165 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (167 mg). MS (ISP) 543 [(M-hH)--] and 545 [(M+2^H)1. tompl^Ml? {4-Chloro-2-f3-(2-cyano-p)Tidin-4-\i)-3-oxo-propionylaminoV5-dimethylamino-phenylj-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethyiamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (155 mg). MS (ISP) 458 [(M+H)--] and 460 [(M+2+H)+];mp llO°C Example M16 (4-Chloro-5-dimet3aylamino-2-{3-f3-(2-methyl-2H-pvrazol-3-vD-phenvi1'3oxO-propionyiaminol-phenyl)-carbamic acid tert.-butylester The title compoimd was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K7) (180 mg, 0,6 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg). MS (ISP) 512 [(M+H)--] and 514 [(M+2+H)+]. - Example M17 (RS)-(5-Dimethylamino-2-(3-oxo-3-(3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23ltriazol-l'yl]-phenvU-propionylamino)-4-trifluoromethyl-phen'vdl-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (160 mg, 03 mmol) and (RS)-3 -oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (201 mg, 0-5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (247 mg). MS (ISP) 647 [(M+H)--]. Example Ml8 (5-Dimethylamino-2-J3-f3-f3-methyl-isoxazol'5-vD-phenyl1-3-oxo-propionylaminoU4'trifluoromethyl-phenyl')-Carbamic acid tert,-butylester The title compoimd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid terL-butyl ester (Example K4) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (94 mg). MS (ISP) 547 [(M+H)+]. Example M19 f4-ChlorO'5-dimethylamino-2-{3-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0,5 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionicacidtert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (176 mg). MS (ISP) 556 [(M+H)--] and 558 [(M+2+H)+]. Example M20 f4-Chloro--5'dimethylamino--2-B-f3-f3-methoxvmethyl-isoxazol-5-yl)-phenyl)-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester The title compotmd was prepared from (2-ainino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (Example K9) according to the general procedure M. Obtained as a yellow solid (205 mg). MS (ISP) 543 [(M+H)T and 545 [(M+2-fH)--]. Example M21 (2-r3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino]-5-dimethylamino-4-trifluoromethyl-phenyll-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromet]iyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, LO mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example K3) (246 mg, 1.0 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (297 mg). MS(ISP)492[(M+H)+]. Example M22 (2'-Fluoro-5-[3-(3-imidazol-l-yl-phenyD-3-oxo-propionylamino1-2-(2,2.2-trifluoro-ethoxv)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 6-(3-imidazoH-yl-phenyl)-2,2-dimethyl-[l,3]dioxin-4-one (Example L3) (160 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous brown substance (167 mg). MS(ISP)492[(M+H)-']. Example M23 (2'-Fluoro-5-(3-r3-(3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-2-f 2.2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (160 mg, 0.53 mmol) according to the general procedure M. Obtained as a white solid (40 mg). MS (ISN) 626 [(M-H)-]; mp 121-123 °C. Example M24 (2'-FIuoro-5-f3-oxo-3-(34h23ltriazol-l-yl-phenyl)-propiQnylamino1-2-(2,2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester The title compoxmd was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifiuoro-ethoxy)-biphen)d-4-yl]-carbamic acid tert-butyl ester (Example J5) (200 mg, 0-5 mmol) and 3-oxo3-(3-[l^,3]triazol-l-yl-phenyl)-propionicacid ethyl ester (Example Kl) (150 mg, 0.57 mmol) according to the general procedure M. Obtained as a light yeUow solid (110 mg). MS (ISP) 614 [(M+H)--]; mp 54-56 °C Example M25 (RS)-[2^-Fluoro-5-(3-oxo-3-{345-ftetrahvdro-pwan-2-ylox\nmethyl)-fL23ltria2o^ yl1-phenyl}-propionvIamino)-2-('2.2.2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester The title compound was prepared from [5-amino-2'-fluorO-2-(2,2>2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (220 mg, 0.55 mmol) according to the general procedure M. Obtained as a yellow oil(100 mg). Example M26 (RS)-[4-Chloro-5-fethyl-methyl-aminoV2-(3-oxo-3-(3-r5-ftetrahydro-pyran-2-yloxymethyl)-rL23ltriazol-l-yll-phenyll-propionylamino)-phenyl1-carbamicadd tert-butylester The titlt ipound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)' phenyl]-curbamic acid tert-butyl ester (Example J7) (300 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl\|-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (500 mg), MS (ISP) 627.1 [(M+H)--]. Example M27 (RSVf4-Chloro-5-(methyl-propyl-amino)-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-yIoxvTnethyl]-fl,23ltriazol-l-yl1-phenyIt-propionylamino)-phenyl-carbamicadd tert'butylester The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (402mg, I.O mmol) according to the general procedure M. Obtained as a yellow foam (410 mg). MS (ISP) 641.3 [(M+H)1. Example M28 (RS)-r4-Chloro-5-fdiethyl-ammQV2-f3-oxo-3-(3-r5-ftetrahvdro-pyran-2-yloxymethvD- \ 1.231 triazol-1 -yll -phenyl-propionylamino Vphenyll -carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(diethyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J9) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yI]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg). MS (ISP) 64L3 [(M+H)+]. Example M29 fRSVI'4-Chloro-5-dimethylamino-2-(3-oxo-3-i3-f3-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol'5-yll-phenyU-propionylamino)-phenyl1-carbamicacidtert.-butyl ester The title compotind was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3- [3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl] -phenyl}-propionic acid tert.-butyl ester (Example K12) (201 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg). MS (ISP) 613.1 [(M+H)--] and 615 [(M+2H-H)+]. Example M30 (RS)-r4-CHoro-2-f3-oxo-3-l345-ftetrahvdro-pyran-2-yloxvmetfayl)-[L2,3ltriazol'l-yll -phenyll-propionylaminoV5-pvrrolidin-l'yl-phenyl1 -carbamic acid tert.-butylester The tide compoimd was prepared from (2-amino-4-chloro-5-pyrrolidin-l-yl-phenyl)-carbaniic acid tert.-butyl ester (Example JIO) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.' butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (228 mg), MS (ISP) 639 [(M+H)--] and 641 [(M+2+H)+]. Example M31 (5-Dimethylamino-2-^3-r3-(2-metfayl'2H-pvrazol-3-yl)-phenyll-3-oxo-propionylaminQl-4-trifluoromethyI-phenyD-carbainic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K7) (150 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (90 mg). MS (ISP) 546.2 [(M+H)--], Example M32 fRS)-r4-Chloro-5-dimethylamino-2-f3-B-F3-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol-5-yl] -phenAd}-3-oxo-propionylamino)-phenyl1 -carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethyIamino-phenyO-carbamic acid terL-butyl ester (Example Jl) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]'phenyl}-3-oxo-propionic acid tert-butyl ester (Example K13) according to the general procedure M, Obtained as a light yellow solid (187 mg). MS (ISN) 626 [(M-H)-] and 628 [(M+2-H)']. Example M33 fRS)-r4-Chloro-5-fcvclopropvI-methyl-amino)-2-f3-oxo-3-l3-r5-rtetrahvdro-pyran-2-yloxvmethyl)-fl.2.3ltriazol-l-yl]-phenvU-propionylaminoVphenyl]-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example JU) (156 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2oH-yl]-phenyll-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow solid (215 mg). MS (ISN) 637.1 [(M-H)'] and 639 [(M+2-H)-]; mp 47-49 °C. Example M34 (5-Dimethylamino-2-l3-f3-(5-dimethylaminomethyl-ri.23ltriazoM-yl)-phenyl-3-oxo-propionvIaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (160 mg, 0.5 rQmol)and3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (195 mg). MS (ISN) 588 [(M-H)-]. Example M35 (RS)-[4-Chloro-5-dimethylamino-2-f3-l3-(2-methyl'5-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pyrazol-3-yn-phenvU-3-oxo-propionylaminoVphenyn-carbamic acid tert.-butylester The title compound was prepared from (2-amino-4-chIoro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (200 mg, 0.7 mmol) and (RS)-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K14) (290 mg, 07 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (329 mg). MS (ISN) 624.0 [(M-H)-] and 626 [(M+2-H)']. Example M36 {2-[3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino1-5-pvrrolidin-l-yl-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-pyTrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J12) (173 mg, 0.5 nrniol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (150 mg, 0,61 mmol) according to the general procedure M. Obtained as a yellow solid (140 mg). MS(ISP)518[(M+H)1- Example M37 fRS)42-r3-Oxo-3-i3-(5-(tetrahvdro-pyran-2-yloxvmethvD4L23ltriazol-l-yl1-phenvU-propionylamino)-5--pvrrolidin-l-yl'4-trifluorometfayl-phenyl]-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifIuoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J12) (173 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-I-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as an orange foam (168 mg). MS(ISP)673[(M-hH)+]. Example M38 f RS)- (5-Dimethylamino-4'fluoro-2-(3-0X0-3-13- f 5-f tetrahydro-pyran-2-yloxvmethyl)-fL23ltriazol-l-yn-phenyll-propionylamino)-phenyn-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-fiuoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1,0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid terL-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (417 mg). MS(ISN)595[(M-H)-]. Example M39 (5-Dimethylammo-2-l3-[3-(5-dimethylaminomethyl'[L2.3ltria2ol-l-vD-phenyl-3-oxo-propionylamino}-4-fluoro-phenyl)-carbamic acid tert.-butyl ester The title compound was prepared from (2-anfiino-5-dimethylamino-4-£luoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (344 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (211 mg). MS(ISN)538[(M-H)-]. Example M40 fRSVr5-Dimetfaylamino-4-fluoro-2-(3-oxo-3-B-r3-(tetrahvdro-pyran-2-yloxymetfavD-isoxazol'5-yl]-phenyl}-propionylamino)-phenyncarbamic acid tert.-butyl ester The tide compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example KI2) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (360 mg). MS(ISN)595[(M-H)-]. Example M41 (RS)-(5-DimethylaminO'2-f3-oxo-3-{3-f3-ftetrahvdro-pyran-2-yloxvmethyl)-isoxazol-5-yll -phenyl}-propionylamino)-4-trifluoromethyl-phenyl1 -carbamic acid tert.-butyl ester The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (565 mg, L77 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example K12) (710 mg, 1,77 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (721 mg), MS(ISN)645[(M-H)']. Example M42 (RSV(5-Dimethylamino-4-fluoro-2-r3>oxQ-3-{3-f3-ftetrahvdro-pyran-2-yloxymethyl)-isoxa2ol-5-yn-phenyl}-propionylamino)-phenyiVcarbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M- Obtained as a yellow amorphous substance (273 mg). MS(ISP)497l(M-f-H)-']. Example M43 fRSVf4-ChloTu-5-dimethylamino-2-f3-oxo-3-B45-rtetrahvdro-pyran-2-yloxvmethyl)-isoxazol-3-vn -phenyll-propionylamino)-phenyll -carbamic acid tert.* butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionic acid tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (232 mg). MS (ISN) 611.1 [(M-H)-] and 613 [{M+2-Hr]. Example M44 (RSVf4-ChIoro-2-(3-oxo-3-l3-r5-ftetrahvdro-pyran-2-yIoxvmethyl)-[L23ltriazol-l-yIl-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl1-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-4-chloro-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example J14) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (257 mg). MS (ISP) 653.2 [(M+H)+] and 655 [(M+2+H)1. Example M45 (RS)-f5'Dimethylamino-2-(3-oxQ-3-l3-r5-(tetrahydro-pyran-2-yloxymethyD-isoxazol-3-yl1 -phenyll-propionylamino)-4-trifluoromethyl-phenyn -carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl] -phenyl}-propionic acid tert.-butyl ester (Example K15) according to the general procedure M. Obtained as a light yellow foam (224 mg). MS (ISP) 647.2 KM+H)--]. Example M46 {4-ChIoro-5-dimethylamino-2-f3-OXo-3-(3-pyrazol-lyl-phenyl)-propionyIamino]-phenyl}-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K16) according to the general procedure M. Obtained as a light yellow solid (135 mg). MS (ISP) 498 [(M-hH)--] and 500 [(M+2+Hr]; mp 148-149 °C. Example M47 {2-r3-(2-Cyano-pyridin-4-yI)-3-oxo-propionyIaminol-4-fluoro-5'pyrrolidin-l-yl-phenyU-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert,-butyl ester (Example 115) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (196 mg). MS (ISP) 468 [(M+H)']; mp 231 °C (dec). Example M48 (4-Fluoro-2-l3-[3-(3-methyl-isoxa2oI-5-yl')-phenvI1-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-fiuoro-5-pyrrolidin-l-yl-phenyl)-carbamic acidtert,-butyl ester (Example Jl5) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propiomc acid tert.-butyl ester (Example K4) according to the general procedure M. Obtained as a light yellow solid (126 mg). MS (ISP) 468 [(M+H)+]; mp 186 °C Example M49 fRS)-[4-Fluoro-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-rL23ltria2ol-l-yl1-phenvU-propionylamino)-5-pyrroIidin-l-yl-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidiQ-l-yl-phenyl) carbamic acid tert-butyl ester (Example Jl5) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>23]triazol-l-yi]-phenyl}-propionic acid terL-but)i ester (Example K5) according to the general procedure M. Obtained as an orange viscous oU (268 mg). MS(ISP)623[(M+Hr]. Example M50 l5-Azetidin-l-yl-4-chloro-2-[3-r2-cyano-pyridin-4-vI)-3-oxo-propionylamino]-phenvU-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butyl ester (Example J16) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (142 mg). MS (ISP) 470 [(M+H)--] and 472 [(M+2+H)']; mp 168 °C (dec). Example M51 fRSV(2-f3-Oxo-3-l3-[5-(tetrahydro-pyran'2-ylQxymethyD-isoxazol-3-yll'phenyll-propionylaminoVS-pyrrolidin- l-yl'4-trifluoromethylphenyl -carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI2) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yIoxymethyI)-isoxa2oI-3-yl]-phenyl}-propionicadd tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (522 mg). MS (ISN) 671.2 [(M-H)-], Example M52 l5'Azetidin-l-yl-2-(-3-(2-cyano-pvridin-4-yl)-3-oxo-propionylamino1'4-trifluoromethyl-phenylt-carbamic acid tert.-but\^ ester The title compound was prepared from (2-aminO-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J17) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light yellow solid(131 mg). MS (ISP) 470 [(M+H)--]; mp 166-167 °C. Example M53 (5-Azetidin-l-yl-2-B-r3-f3-m€thyl-isoxa2ol'5-yl>>phenyll-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.'butylester The tide compound was prepared from (2-amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Lxamplc J17) and 3-[3-(3-methyHsoxazol-5-yl)-phenyl]-3-oxo-propionic acid tcrL-but)1 ester (Example K4) according to the general procedure M. Obtained as a light ycUow foam (218 mg). MS (ISN) 557.2 [(M-H)']; mp 83-84 C fRSV[5-Azetidin-l-yl-2-(3-oxo>3- fh23ltria2ol-l-yl1-phenyll-propionylamino)-4-trifluoromethyl-phenyll'Carbamic acid tert.-butylester ——.^1 ,11-1. , The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI7) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoI-l-yi]-phen)d}-propionic acid tert-butyl ester (Example K5) according to the general procedure M, Obtained as a yellow foam (450 mg). MS (ISN) 657.1 [(M-H)']; mp 76-77 X. Example M55 {5-Dimethylamino-2-[3-OXO'3-(3-pyra2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl'phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (485 mg), MS (ISN) 530 [(M-H)+]. Example M56 t5-Dimethylamino-2-f3-QXo-3-f3-fl.2.4ltriazol-4-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoromethyl-phenyi)-carbamic acid tert-butyl ester (Example J6) (383 mg, 1.2 mmol) and 3-oxO-3-(3-[l,2,4]triazol-4-yl-phenyl)-propionic acid ethyl ester [CAS-No. 335255-97-5] (259 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow solid (290 mg). MS (ISP) 533.3 [(M-i-H)l; mp 58-62 °C. Example M57 (5-Dimethylamino-2-f3-r3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)--Carbamic acid tert-butyl ester (Example J6) and 6-(3-imidazol-l-yl-phenyl)-2>2-dimethyl-[l,3]dioxin-4-one (Example L3) according to the general procedure M. Obtained as an orange oil (238 mg). MS(ISP)432[(M+H)']. Example M58 (RS)-f4-Chloro-5-dimethylamino-2-f3-oxo-3-(3--f4-(tetrahydrQ-pyran-2-ylQxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyI]-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (429 mg, L5 mmol) and (RS)-3-oxo-3- {3- [4- (tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl} -propionic acid tert.-butyl ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (710 mg). MS (ISN) 610 [(M-H)-] and 612 [(M+2-H)'l. Example M59 fRSV(5-Dimethylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-yloxvmethvD-pyrazol-l-yl'\|-phenvU-propionylamino)-4-trifluoromethyl-phenyIl-carbamicacid tert.-butyl ester The title compoimd was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (479 mg, 1.5 mmol) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yioxymethyi)-pyrazol-l-yl]-phenyl}-propionic acid tert-butyi ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M. Obtained as a piiik amorphous substance (641 mg). MS (ISN) 644 [(M'H)-]. Example M60 fRS)'[5-Dimethylamino-2-(3-B-[3-methyl-4-('tetrahvdrO'pyran-2-vIoxymethyl)-isoxa2ol-5'yI]-phenyn3-oxo-propionylamino)-4-trifluoromethyl-phenyI1-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K13) according to the general procedure M. Obtained as a red oil (424 mg). MS (ISN) 626 [(M-H)-]. Example M61 fRSV(5-Dimetfaylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-vioxvmetfayl)-isoxazol-S-yll -phenyl KpropionylaminoV4-trifluoromethyl-phenyn -carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionicadd terL-butyl ester (Example K18) according to the general procedure M. Obtained as a light yellow solid(145 mg). MS(ISP)647[(M+Hn. Example M62 (RSV(5-DimethyIamino-2-(3'[3-(2-methylsuIfanvI-imidazoI-l-yl)-phenyl-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-tri£luoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (319 mg, 1-0 mmol) and 3-[3-(2-methylsulfanyI-imida2oI-l-yl)-phenyI]-3-oxo-propiomcadd tert-butyl ester [CAS-No. 335256-01-4] (432 mg, 1.3 mmol) according to the general procedure M. Obtained as a light brown amorphous substance (493 mg). MS (ISP) 333.2 [(M+H)--]. Example M63 fRSVr5-Dimethylamino-2-(3-(3-(2-methyl-4-(tetrahvdro-pyran-2-ylQXvmethyl)-2H-pyra2o]-3-yl1-phenyil-3'OXopropionylaminoV4'trifluorometfayl-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-{3-[2-methyl-4-(tetrahydro-pyran-2-ylox)Tneth>1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert-butyl ester (Example K19) according to the general procedure M. Obtained as a light red solid (576 mg). MS (ISN) 658 [(M-H)-]. Example M64 l4-Chloro-5-dimethylamino-2-f3-oxo-3-f 3-\| 1 >2,4]tria2ol-l-yl-phenyl) propionylamino1-phenyllcarbamic acid tert.-butyl ester The title compo d was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carban. dcid terL-but)d ester (Example Jl) and 3-oxo-3-(3-[l>2,4]tria2ol-l-yl-phenyl)-propionic acid tert-but)d ester [G\S-No, 335255-88-4] according to the general procedure M. Obtained as a light yellow solid (427 mg). MS (ISN) 497 [(M-H)-] and 499 [(M+2-H)-]. Example M65 {5-Dimethylamino-2-f3-oxo-3-(3-[l,2,4]triazoM-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-anuno-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and 3-oxo-3-(3' [l>2,4]triazol-l-yl-phenyi)-propionic acid tert-butyl ester [CAS-No. 335255-88-4] according to the general procedure M. Obtained as a light red solid (502 mg). MS(ISN)531[(M-H)-]. . Example M66 {2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimeth^amino-4-trifluorometh^^-phenyll-carbamic acid tert.-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (320 mg, 1-0 mmol) and 3-(2,2-dimethyi-6-oxo-6H-[13]dioxin-4-yl)-benzonitrile (Example LI) (275 mg, 1.2 mmol) according to the general procedure M. Obtained as a reid viscous oil (196 mg). MS (ISN) 489.1 [(M-H)-]. Example M67 fRS)-r5-fCvcIopropvImethyl-methyl-amino)-2-f3-oxo-3-{3-(5-ftetrahvdrO'pyran-2-yloxvinethyD - [ 1,231 triazol- l-yl1 -phenyl! -propionylamino V4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-anmio-5-(cyclopropylmethyl-methyl-amino)-4-trxfluoromethyI-phenyl]-carbamicacid tert,-butyl ester (Example JIS) (719 mg, 2.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (803 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (985 mg). MS (ISP) 687 [(M+H)+]. Example M68 [2-f3-(2-Cyano-pyridin-4-yl)-3-oxo-propiQnvIamino]-5-fcyclopropylmethyI-metfayl' amino)-4-trifluorometfayl-phenyl-carbamic acid tert.-butylester The title compound was prepared from [2-amino-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example JIB) (180 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (206 mg). MS (ISP) 532 [(M+H)+]. Example M69 (RS)-l5-Dimethylamino-2-r3-oxo-3-f3-{2-r2-(tetrahvdro-pyran-2-yloxvVethyl1-2H-pvrazoI-3-yll-phenyl)-propionylaminol-4-trifluoromethyl-phenyn-carbamicacid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifiuoro-methyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (639 mg, 2.0 mmol) and (RS)-3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-phenyl)-propionic acid tert-butyl ester (Example K20) (829 mg, 2.0 mmol) according to the general procedure M. Obtained as a pink amorphous substance (272 mg). MS (ISN) 658 [(M-H)-]. Example M70 (2-r3-(2-cyano-pvridin-4-yl)-3-OXo-propionylaminoV5-fcvclopropyl-methyl-aminoV4-trifluoromethyl-phenyl-carbamic acid tert.-butyl ester The title compound was prepared from [2-amino-5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example J19) (259 mg, 0.75 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert,-butyl ester (Example K3) (192 mg, 0.78 mmol) according to the general procedure M. Obtained as a yellow solid (228 mg). MS (ISN) 516.2 [(M-H)-]; mp 114-116 °C. Example M71 {2-Dimethylamino-2'-fluoro-5-f3-oxo-3-f3-fL23ltriazQl-l-yl-phenyl)-propionylamino1-biphenyl-4-yU-carbamic acid tert-butyi ester The title compound was prepared from (5-amino-2-dimethyIamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J20) (691 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazoM-yl-phenyl)-[l,3]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow solid (820 mg). Mp 125-135 °C. Example M72 (RSyl5-Dimethylamino-2-[3-oxo-3-(3-l5-(2-ftetrahvdro-pyran-2-yloxvVethyll-fl.23ltria2ol-l-yll-phenyl)-propionvIamino1-4-trifluoromethyl-phenvU-carbamic acid tert,-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,2,3]triazol-l-yl}-phenyl)-propionicacid tert-butyl ester (Example K21) according to the general procedure M. Obtained as a light red oil (527 mg). MS (ISP) 577 [(M+H)--]. Example M73 fRS)-[5-Dimethylamino-2-(3-oxo-3-f3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-pyrazol-l-yl]-phenyll-propionylamino)-4-trifluoromethyl-phenyl1-carbamicacid tert.-butylester The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionic acid ethyl ester (Example K22) according to the general procedure M. Obtained as a brown oil (179 mg). MS (ISP) 646 [(M+H)-]. Example M74 (5-Dimetfaylamino-2-f3-oxo-3-('3-[L23ltriazoM-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (639 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazol-l-yl-phenyl)-[13]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a red solid (915 mg). MS (ISP) 533,3 [(M+H)+]; mp 79-81 °C. Example M75 [2-f3-(2-cyano-pyridin-4-yl)'3-oxo-propionylamino1-5-(2,2.2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J21) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light brown s.olid (262 mg). MS (ISN) 545.0 [(M-H)']; mp 158 °C (dec). Example M76 l2-[3-(3-cyano-phenyl)-3-oxQ-propionyIamino1-4-dimethylaminO'5-methyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (300 mg, 1.0 mmol) and 3-(3-cyano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (250 mg> 57%). MS (ISP) 437.4 [(M+H)--]. Example M77 (RSV[5-DimethylaminO'4-methyl'2-(3-oxo-3-{3'[5-(tetrahydro-pyran-2-yloxvmethyl)-fl.2.3ltria2ol-l-yl1-phenyU-propionylaminoVphenyl]-carbamicadd tert-butylester The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic add tert-butyl ester (Example K5) (402 mg, 1-0 mmol) according to the general procedure M. Obtained as a yellow foam (420 mg, 71%). MS (ISP) 593.5 [(M+H)--]. Example M78 {5-Cyano-2-f3-(3-cyano-phenyl)-3-oxo-propionylamino1-4-dimethylamino-phenyl}-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butyi ester (Example J23) (276 mg, 1.0 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a brown foam (290 mg, 65%). MS (ISP) 448.3 [(M+H)--]. Example M79 [2-f3-f3-cyano-phenvD-3-oxo-propionylamino]-5-methyI-4fmethyl-propyl-amino)phenv]]-carbamic acid tert-butylester The title compound was prepared from [2-aminO-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (293 mg, 1.0 mmol) and 3-(3-qrano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (170 mg, 37%). MS (ISP) 463.3 [(M-H)-], Example M80 (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-l3-(5-(tetrahvdropyran-2-yloxymethvD-[l,2,3ltriazoI-l-vI]-phenvU-propionylamino)-phenyl'Carbamicacid tert-butylester The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-pheiiyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (350 mg, 56%). MS (ISP) 621.2 [(M+H)1. Example M81 fRSV[5-fEthyl-methyl-aminoV4'methyl-2-(3-QXo-3-(3-(5-(tetrahvdro-pyran-2-yloxymethvD-fL2.3ltriazol-l-yl]-phenyI}-propionylamino)-phenyl-carbamicacid tert-butylester The title compound was prepared from [2-amino-5-(ethyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J25) (279 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (400 mg, 66%). MS (ISP) 607.1 [(M+H)1. Example M82 (RSVf4-cyano-5-dimethylamino-2-(3-oxo-3-(3-(5-ftetrahvdro>pyran-2-yloxvmethyl)-fl.23ltriazol-l-yl1-phenyU-propionylamino)-phenyll-carbamicadd tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-dimethylaminO-phenyl)-carbamic acid tert-butyl ester (Example J23) (276 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyi}-propionicadd tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to tiie general procedure M. Obtained as a light brovm foam (360 mg, 59%). MS (ISP) 602.1 [(M-H)1. Example M83 fRS)-[4-Chloro-5-fisopropyl-methyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyl)-Fl,2,3ltriazol-l-yll-phenyl}-propionylamino)-phenyl)-carbamicadd tert-butyl ester The title compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J26) (300 mg, 0.96 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (383 mg, 0.96 mmol) according to the general procedxire M. Obtained as a light yellow oil (530 mg, 86%). MS (ISP) 639.2 [(M-H)-]. Example M84 [4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionylaminol-5-(methyl-propyl-amino)-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyi]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 65%)! MS (ISP) 519.3 [(M-H)'], &tapiple M?5 (4-Cyano-5-dimethylamino-2- The tide compound was prepared from (2-amino-4-q^ano-5-dimethylaxnino-phenyl)-carbamic acid tert-butyl ester (Example ]23) (276 mg, 1.0 mmol) and 3-[3-(3methyl-isoxazol-5-yl)-phenyI]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (320 mg, 64%). MS (ISP) 504.3 [(M+H)+]. (5-(£thyl-methyl-amino)-4-methv'i-2-(3'[3-(3-methyi-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester The title compoiund was prepared from {2-amino-5-(cthyl-methyi-amino)-4-methyl-phenyl]-carbamic acid tert-but)d ester (Example J25) (279 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M, Obtained as a brown foam (390mg,77%). MS (ISP) 505.3 [(M-H)']. Example M87 (5-Dimethylamino-4-methyI-2-l3-[3-f3-methyl-isQxazol-5-yl)-phenyll-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-5-dimethyiamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phen)d]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M. Obtained as a brown foam (330 mg, 67%). MS(ISP)49L3[(M.H)']. Example M88 fRS)-f4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxymethyl)-fh23ltria2ol-l-yl]-phenyn-propionylamino)-phenyl]-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-cliloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,3]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 50%). MS (ISP) 655.1 [(M+H)--]. Example M89 (4-Chloro-5-fisobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl')-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carban[iic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (360 mg, 65%). MS (ISP) 555.1 [(M+H)1. Example M9Q fRS)-[4-cyano-2-(3-oxo-3-B-(5-ftetrahvdro-pyran-2-yloxvmethyl)-ri.23ltriazol-l-ylj-phenvD-propionylaminoVS-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-)doxymethyi)-[l,2,3]tria2ol-l-yl]-phenyl}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light orange foam (380 mg, 60%). MS (ISP) 630.1 [(M+H)--]. Example M91 (4-cyano-2-(3-f3-f3-methyl-isoxazol-5-vD-phenvI1-3-oxo-propionylamino}-5-pvrrolidin-1-yl-phenyl)-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-ph€nyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 79%). MS (ISP) 530.2 [(M+H)+]. Example M92 (RSV[4-cyano-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvTnethyl)-fL2.3ltriazol-l-yn-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (440 mg, 70%). MS (ISP) 630-1 [(M+H)+]. Example M93 f4-cyano-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-5-(methyl-propyl-aminoVphenyll-carbamic acid tert-butylester The title compoimd was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 namol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (370 mg, 70%). MS (ISP) 532.3 [(M+H)+]. Example M94 (4-cyano-5-diethylamino-2-{3-[3-f3-methyl-isoxazol-5-yl)-phenyl-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butyl ester (Example J30) (304 mg, LO mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butj^l ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (360 mg, 68%). MS (ISP) 530.2 [(M+H)--]. Example M95 (4-Cyano-5-(isopropyl-methyl-aminoV2-l3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 71%). MS (ISP) 530.2 [(M-H)']. Example M96 (RS)-f4-Cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-r5-(tetrahvdro-pyran-2-yIoxvTnethyl]-[L2.3ltriazol-l-yl]-phenyl}-propion)damino)-phenyl]-carbamicadd tert-butylester The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (460 mg, 73%). MS(ISP)630.1[(M-H)-]. Example M97 (4-cyano-5-fisobutyl-methyl-amino)-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M, Obtained as a light brown foam (400 mg, 73%). MS (ISP) 544.3 [(M-H)']. Example M98 (RSVT4-cyano-5-(isobutyI-methyl-aminoV2-(3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fl,2.3ltriazol-l-yll-phenvU-propionylamino)-phenyll-carbamicacid tert-butyl ester —■'■■> - The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (470 mg, 73%). MS (ISP) 644.2 [(M-H)-]. Example M99 (4-cyano-2-(3-f3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-5-piperidin-l-yl-phenvD-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J33) (316 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 77%). MS (ISP) 544.2 [(M+H)+]. Example MlOO (4-Chloro-5-isobutylamino-2-l3-f3-f3-methyl-isoxazol-5-vD-phenyl-3-oxo-propionylaminol-phenvD-carbamic acid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-isobut7lamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M, Obtained as an off-white foam (340 mg, 63%). MS (ISP) 542.2 [(M+H)--]. Example MlOl fRSVf4-Chloro-5-isobutylamino-2-f3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxymethyl)-FL2.3ltriazol-l-yl'\|-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyI}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a red oU (180 mg, 28%). MS (ISP) 640.2 [(M-H)-]. Example Ml02 (RS)-[5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxvmethyl) - [ 1,231 triazol-1 -yll -phenyll -propionylamino) -4-trifluoromethyl-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (380 mg, L09 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (439 mg, 1.09 mmol) according to the general procedure M. Obtained as a red foam (150 mg, 20%). MS (ISP) 675.4 [(M-H)']. Example M103 (2-{3-f3-f3-methyl-isoxazol-5-vI)-phenyl1-3-Qxo-propionylaminol-5-fmethyl-propyl-aminQV4-trifluoromethyl-phenyl'\|-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]'Carbamic acid tert-butyl ester (Example J35) (360 mg, L04 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (312 mg, 1.04 mmol) according to the general procedure M-Obtained as a light red foam (270 mg, 45%), MS (ISP) 573.2 [(M-H)-]. Example M104 (RSV[5-(I$obutyl-methyl-aminoV2-(3'Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxymethyl')'[L2^3ltriazol-l-yll-phenvU-prQpionylamino)-4-trifluorometh\d-phenyl]-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutjd-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J36) (370 mg, 1.02 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (411 mg, 1.02 mmol) according to the general procedure M. Obtained as a light brown foam (520 mg, 74%). MS (ISP) 687.2 [(M-H)']. Example M105 (5-fIsobutyl-methyl-aminQV2-{3'f3-(3-methyl-isoxa2ol'5-yl)-phenyl)-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)--carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(i$obutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J36) (360 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (302 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (430 mg, 73%). MS (ISP) 587.3 [(M-H)-]. Example M106 fRSV(5-fIsopropyl-methyl-amino)-2-f3-oxQ-3-{3-(5-ftetrahvdrO'pyran-2-yloxvmethyl)-fL23ltria2oM-yl]-phenyll-propionylaminoV4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isopropyl-methyl-ancuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (340 mg, 0.98 mmol) and (RS)-3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)- [ l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (393 mg, 0.98 mmol) according to the general procedure M. Obtained as alight yellow foam (510 mg, 77%). MS (ISP) 673,3 [(M-H)-]. Example M107 ('5-(Isopropyl-metfayl-aminoV2-(3-f3-(3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isopropyl-methyl-anuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (350 mg, 1.01 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (304 mg, 1.01 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 66%). MS (ISP) 573.2 [(M-H)-]. Example M108 (RSV(5-(Isobutyl-methyl-aminoV4-methyl-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxvmethyl)-[L2.3ltriazol-l-yl1-phenyll-propionylamino)-phenyl]-carbamicacid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenylj-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and (RS)-3-oxo-3-(3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 52%). MS (ISP) 635.2 [(M+H)--]. Example M109 (5-fIsobutyl-methyl-aminoV4-methyl-2-{3-[3-f3-methyl'isoxazol-5-yl)-phenyl1-3-oxo-propionylamino}'phenyl)-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 62%). MS (ISP) 535.4 [(M+H)1. Example Ml 10 (RS)-[4-methyl-2-(3-oxo-3-f3-(5-(tetrahvdro-pyran-2-yloxvmethvD-rL2,3ltriazol-l-yI]-phenyl}-propionylaminoV5-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester The title compoimd was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester acid tert-butyl ester (Example J39) (292 mg, 1.0 imnol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (410 mg, 66%). MS (ISP) 619,3 [(M+H)1. Example Mill (4-Methyl-2-{3-f3-(3-methyl-isoxazol-5-yiVphenyl]-3-oxo-propionylaminol-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J39) (291 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 64%). MS (ISP) 517.3 [(M-H)1. Example Ml 12 (4'-Chloro-5-isQprQpylamino-2-{3-[3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester The title compoimd was prepared from (2-amino-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brovm foam (169 mg, 32%). MS (ISP) 525.2 [(M-H)-]. Example Ml 13 fRS)-f4-Chloro-5-isopropylamino-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyD-ri,23]triazol-l'-yl1-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester The title compoxmd was prepared from (2-andno-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, LO nunol) according to the general procedure M. Obtained as a light yellow foam (375 mg, 60%). MS (ISP) 625.1 [(M-H)-]. Example Ml 14 (RS)-r4-Chloro-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyD-[l,2,4ltriazol-l-yl]-phenyll-propionylamino)-phenyll-carbamicacid tert-butylester The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (LOg, 3,19 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (L28 g, 3.19 mmol) according to the general procedure M. Obtained as a yellow foam (L48 g). MS (ISP) 641.3 [(M+H)--]. Example Ml 15 fRSVr4-Chloro-5-fisobutyl-methyl-aminoV2-(3-oxo-3-l3-(5-ftetrahydro-pyran-2-yloxymethyl)-[L2,4ltriazol-l-yl]-phenyl}-propionviamino)-phenyl1-carbamicacid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (1.0 mg, 3.05 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.22 g, 3.05 mmol) according to the general procedure M. Obtained as a light brown foam (620 mg, 31%). MS (ISP) 655.1 [(M+H)1. Example Ml 16 fRS)-l'5-(Isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-J3-(5-(tetrahvdro-pyran-2- yIoxvmethyl)-fl.2,4ltriazol-l-yl1-phenyU-propionylamino')-phenyl1-carbamicacid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (1.0 g, 3.25 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.31 g> 3.25 mmol) according to the general procedure M. Obtained as a light yellow foam (970 mg> 47%). MS (ISP) 635.2 [(M+H)1. Example Ml 17 {5-(methyl-propyl-aminoV2-F3-oxo-3-f3-fL2.4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvD-carbamic acid tert-butylester The title compound was prepared from [2-ainino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (320 mg, 57%). MS (ISP) 561.4 [(M+H)1. Example M118 i5-(Methyl-propyl-aminQV2-f3-oxo-3-(3-fl,23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvU-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxO-3-(3-[l>2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (340 mg, 61%). MS (ISP) 561.3 [(M+H)1. Example Ml 19 l5-fIsobutyl-methyl-amino)-2-[3-oxo-3-r3-pvra2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J40) (361 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, LO mmol) according to the general procedure M. Obtained as a light brown foam (500 mg, 87%). MS (ISP) 574.2 [(M+H)1. Example M120 r2-f3-('2-cyano-pyridin-4-yl)-3-oxo-propionylamino1-5-fisopropyl-methyl-amino)-4-trifluoromethyl-phenyl1-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isoproyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J37) (500 mg, 1,44 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (355 mg, 1.44 mmol) according to the general procedure M. Obtained as a light orange oil (670 mg, 90%). MS (ISP) 518.1 [(M-H)-]. Example M121 U-Chloro-5-fisobutyl-methyl-aminoV2-[3-oxo-3-f3-fL2,4ltriazol-l-yl-phenvi)-propionylaminol-phenvU-carbamic acid tert-hutyl ester The title compound was prepared from [2-amino-4-chloro-5-(isobutyi-methyi-amino)-phen)i]-carbamic acid tert-butyl ester (Example J27) (500 mg, 1.53 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yi-phenyl)-propionic acid tert-butyl ester (Example K25) (438 mg, L53 mmol) according to the general procedure M. Obtained as a light orange foam (700 mg, 85%). MS (ISP) 539.2 [(M-H)-]. {5-(Isobutyl-methyI-amino)-2-f30!(o-3'f3-fl.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluorometh>i-phen\il'Carbamic acid tert-butyl ester The title compound was prepared from l2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example J36) (361 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2oM->1-phcn>'l)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (490 mg, 85%). MS (ISP) 575.2 [(M+H)-]. Example Ml23 l4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-f3-fh2.3]triazol-I-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-4-chioro-5-(isobutyl-methyI-amino)-phenyl]-Carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as an orange oil (250 mg, 46%). MS (ISP) 539.2 [(M-H)-]. Example Ml24 {5-fIsobutyl-methyl-aminoV2-f3-QXo-3-f3-[L2.3ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvmcarbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (460 mg, 1.27 mmol) and 3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionic acid tert-butjd ester (Example K23) (364 mg, 1.27 mmol) according to the general procedxire M. Obtained as ahght brown oil (480 mg, 69%). MS (ISP) 573.1 [(M-H)-]. Example M125 (2-f3-r3-Imidazol-l-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg> 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 iiunol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 77%). MS (ISP) 558.2 [(M-H)-]. Example M126 {4-Chloro-2-[3-f3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-5-isobutylamino-phenyll-carbamic acid tert-butyl ester The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 63%). MS (ISP) 524.1 [(M-H)']. Example M127 {4-Chloro-5-fisobutyl-aminoV2-r3-oxo-3-f3-[1.23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-ainino)-phenyl]-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a pale brown foam (220 mg, 42%). M^:iSP) 525.1 [(M-H)1. Example M128 (5-fIsobutyl-aminQV2-f3-oxO'3-(3-fL23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyU-carbamic acid tert-butyl ester The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoro-methyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg, LO mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 60%). MS (ISP) 559.2 [(M-H)-]. Example Ml29 H-Chloro-5-('isobutyl-aminoV2-f3-oxo-3-f3-fL2,4ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M, Obtained as a light ydlow foam (390 mg, 74%). MS (ISP) 525.1 [(M-H)-]. Example Ml30 {5-('Isobutyl-aminoV2-f3-oxo-3-f3-[1.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butylester The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 11%). MS (ISP) 559.2 [(M+H)--], General procedure N: Preparation of 4-aryl-13-dihvdro-benzofb1 f L4ldiazepin-2-ones: A solution or suspension of the {2-[3-arj4-3-oxo-propionylamino]-phenyl}-carbamic acid tert-butyl ester or {2-[3-aryi-3-oxo-propionyIamino]-phenyl}-carbamic acid tert-butjd ester (1.0 mmol) in CH2Cl2 (5 mL) (anisolc or l^-dimethoxybenzene (5-15 mmol) can be acided if necessary] was treated with TFA (0.5-5.0 mL) at 0 '°C and stirring was continued at 23 °C until tic indicated complete consumption of the starting material. Worlcup procedure a: The solvent was removed in vacuum, the residue treated with little ether, whereupon it crystallized. The solid vas stirred with sat. NaHCOs-sol. or IM NaaCOs-sol., filtered, washed with H2O and ether or mixtures of ether/THF/MeOH and was dried to give the tide compound, which if necessary can be purified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cyclohexane/EtOAc or EtOAc/EtOH. Workup procedure b: The reaction mixture was diluted with DCM or EtOAc, washed with sat. NaHCOs-sol. or IM Na2C03-soL, brine and dried over MgSO4 or Na2S04. Removal of the solvent in vacuum left a material, which could be triturated with ether or mixtures of ether/THF/MeOH to give the title compound, or which if necessary can be pmified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cycIohexane/EtOAc or EtOAc/EtOH. Example 1 3-f7-Chloro-8-dimethylamino-4-oxo-4,5-dihvdro-3H-benzo[blfl.4]diazepin-2-yl)-benzonitrile The tide compoimd was prepared firom {4-chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example Ml) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (85 mg). MS (ISP) 339 [(M+H)--] and 341 [(M+2+H)']; mp >250 »C. Example 2 8-Chloro-7-dimethylamino-4-f3-fl,2,3ltriazol-l-yl-phenyl)-l,3-dihydro-benzofbl f L4ldiazepin-2-one The title compoxmd was prepared from {4-chloro-5-dimethylamino-2-[3-OXo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert.-butyl ester (Example M2) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (87 mg). MS (ISP) 381 [(M+H)--] and 383 [(M+2+H)-']; mp 222-225 °C. Example 3 8-Chloro-7-dimethylamino-4- r3-(5-hvdroxvmethyl-1- 1.2,3ltriazol- 1-yD-phenyll -1,3-dihydro-benzo f b1 \ 1,4] diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl] -carbamic acid tert.-butyl ester (Example M3) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (60 mg). MS (ISP) 411 [(M+H)--] and 413 [(M+2+H)']; mp 210-214 X, Example 4 3-(8-Dimethylamino-4-oxo-7-phenylethynyl-4,5-dihydro-3H-benzofbl \ 1,41 diazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-phenylethynyl-phenyl}-carbamic acid tert.-butyl ester (Example M4) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg). MS (ISP) 405 [(M+H)--]; mp 215-216 °C. Example 5 7-Dimethylamino-8-phenylethvnyl-4-f3-rL23ltriazol-l-yl-phenvi)-K3-dihvdro-benzofbl f 1.41 diazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyi)-propionylamino]-4-phenylethynyl-phenyi}-carbantiicadd tert-butyi ester (Example M5) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (76 mg). MS (ISP) 447 [(M+H)--]; mp 185-186 °C. Example 6 8-Chloro-7-dimethylamino-4-r3-f3-methyl-isoxazol-5-yl')-phenyl1-L3-dihvdro-benzoFb1fl,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacidtert.-butyl ester (Example M6) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (68 mg). MS (EI) 394 (M^) and 396 [(M+2r]; mp 212-215 °C Example 7 8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-('5-hvdroxymethyl-[1.23ltria2ol-l-yl)-phenyl-1.3-dihvdro-benzofb]fL4ldiazepin-2-one The title compound was prepared from (RS)-[2-dimethylamino-2',3'-difluoro-5-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-biphenyl-4-yl]-carbamic acid tert-butyl ester (Example M7) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (26 mg). MS(ISP)489[(M+H)']. Example 8 8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-fL23ltriazQl-l-yl-phenylyl3-dihvdrO'benzo l-b] [ 1.41 diazepin'2-one The title compound was prepared from {2-dimethylamino-2\3-difluoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert-butyl ester (Example M8) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (47 mg). MS (ISP) 459 [(M+H)--]; mp 197-199 °C. Example 9 3-r7-(23-Difluoro-phenyl)-8-dimethylamino-4-QXO-4.5-dihydro-3H-benzofbl \ 1,41 diazepin-2-vn -benzonitrile The title compound was prepared from {5-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-2-dimethylamino-2\3-difluoro-biphenyi-4-yl}-carbamic acid terL-butyl ester (Example M9) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a light yellow solid (75 mg). MS (ISP) 417 [(M+H)--]; mp 228-229 ^'C Example 10 8-CMoro-7-dimethylamino-4-(2-(3-metfayl-isoxazol-5-yl)-pvridin-4-yl1-1.3-dihvdrO-benzofbl f 1.4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimetiiylanuno-2-{3- [2-(3-methyl-isoxazol-5-yI)-pyridin-4-yl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example MIO) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (111 mg). MS (ISP) 396 [(M+H)+] and 398 [(M+H-f 2)--]; mp >250 X. Example 11 8-Chloro-7-[(2-methoxy-ethyl)-methyl-amino1-4'f3-(3-methyl-isoxazol-5-yI')-phenyll -13-dihvdro-benzo [bl f 1 A] diazepin-2-one The title compound was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-2-{3-[3-(3-methyi-isoxazol-5-yl)-phenyl]-3-OXO-propionylamino}-phenyl)-carbanciic acid tert.-butyl ester (Example Ml 1) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg). MS (EI) 438 (M*-) and 440 [(M+2)+]; mp 182 °C. Example 12 8-Chloro-7-f(2-methQxy-ethyl)-methyl'amino1-4-[2-f3-methyl-isoxazoI-5-yl)-pyridin-4-ylyl3-dihydro-benzofb]fl.4ldiazepin'2-one The title compoimd was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-ainino]-2-{3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4~yl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M12) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (106 mg). MS (ISP) 440 [(M+H)'] and 442 [(M+H+2)1; mp 213 °C Example 13 8-ChlorQ-4-r3-(5-hvdroxvmethyl-rL23ltriazol-l-yl]-phenyl-7-r(2-methoxv-ethyl)-methyl-amino1-l3-dihvdro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-[(2-methoxy-ethyl)-methyL amino]-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M13) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (50 mg). MS (ISP) 4.55 [(M+H)'] and 457 [(M+H+2)']; mp 185 X. Example 14 8-Chloro-7-r(2-methoxv-etfayl)-methyl-amino1-4-f3-fl.23]triazol-l-yl-phenylyl.3-dihydro-benzofb] rL4ldiazepin-2-one The title compotmd was prepared from {4-chIoro-5-[(2-methoxy-ethyl)-methyl-amino] -2- [3-oxo-3-(3- [ l,2,3]triazoM-yl-phenyl)-propionylamino] -phenyl}-carbamic acid tert.-butyl ester (Example M14) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg). MS (ISP) 425 [(M+H)--] and427 [(M+H+2)+]; mp 156 °C. Example 15 4-f7-Ch]orO-8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb]fl,4ldiazepin-2-vI)-pyridine-2-carbonitrile The title compoimd was prepared from {4-chlorO-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert.-butyl ester (Example M15) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (50 mg). MS (ISP) 340 [(M+H)--] and 342 [(M+2+H)-^]; mp 216 X. Example 16 8-ChlorO-7-dimethylamino-4-f3-(2-methyI-2H-pvrazol-3-yl)-phenyl]-1.3-dihvdro- benzofbl f l,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert.-butyl ester (Example M16) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofiF-white solid (67 mg). MS (ISP) 394 [(M+H)--] and 396'{(M+2+H)']; mp 225 X. Example 17 7-Dimethylamino-4-f3-(5-hydrox\TOethyl4l,2,3ltria2ol>l'yl)-phenyll'8-trifluoromethy[-L3-dihydro-benzofblfL4ldiazepin-2one The title compound was prepared torn (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester (Example M17) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (62 mg). MS (ISP) 445 [(M+H)+]; mp 210 '°C. Example 18 7-Dimethylamino-4-f3-(3-methyl-isoxa2oI-5-yl)-phenyI]-8-trifluoromethyM.3-dihydro-benzofb] [1,41 diazepin-2'One The title compound was prepared from (5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-OXo-propionylamino}-4-trifiuoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example Ml8) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (28 mg). MS (ISP) 429 [(M+H)+]; mp 223 °C, Example 19 8'Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-l,3-dihvdro-benzo f b] f 1,41 diazepin-2-one The title compound was prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-thiobenzamide (prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [1,4] diazepin-2-yl)-benzonitrile (Example 1) as follows: To a solution of hexamethyldisUthiane (0.55 mL, 2.6 mmol) in l,3dimethyl-2-inaida2olidinone (2.6 mL) was acided at 20 X sodium methoxide (0.13 g, 2.5 mmol). The mixture was stirred for 15 min. and the blue solution formed was then acided to a solution of 3-(7-chloro-8-dimethyIamino-4-oxo-4,5-dihydro-3H-benzo[b][l,4ldiazepin-2-yi)-ben2omtrile (Example 1) (0.34 g, 1.0 mmol) in 1,3-dimethyl-2-imida2olidinone (2 mL). The mixture was stirred for 3 h at 20 °C and then poured into water. The precipitate was isolated by filtration and triturated with acetone to give 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [l,4]diazepin-2-yi)-thiobenzamide (035 g) as yellow solid, mp 234 'C decMS (ISP) 373.2 [(M+H)'].} (0.71 g, 1.9 mmol), l,3-dichloro-2-propanone (0,36 g, 2.85 mmol) and sodium bicarbonate (0.24 g, 2.85 mmol) in 1,4-dioxane (15 mL) was heated to 60 °C for 48 h. The clear solution was evaporated in vacuvun. The a solution of the residue in 1,4-dioxane (5 mL) was acided 2N KOH (3.8 mL) and the mixture was stirred at 20 °C for 1 h. Water (100 mL) was acided and the mixture was stirred for 0,5 h. The precipitate formed was collected by filtration and crystallized from dichloromethane to give the title compound (0.69 g) as pale-yellow solid. MS (ISP) 427.2 [ (M+H)-]; mp 134 X dec. Example 20 8-Chloro-7-dimethylamino-4-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyll -L3-dihvdrO'benzo fbl \ 1,41 diazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M19) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (34 mg). MS (ISP) 438 [(M+H)--] and 440 [(M+2+H)-']; mp 145-160 °C Example 21 8-Chloro-7-dimethylamino-4-f3-(3-methoxvmethyl-isoxazol-5-yl)-phenyl1L3-dihydro-benzoFbl [1.41 diazepin-2-one The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butjrl ester (Example M20) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (157 mg). MS (ISP) 425 [(M+H)+] and 427 [(M+2+H)']; mp 191 °C. Example 22 4-(8-Dimethylamino-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo Fbl \ 1.41 diazepin'2-yl)-pyridine-2-carbonitrile The title compoxmd was prepared from {2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylarnino]-5-dimethylamino-4-trifluoromethyl-phenyi}-carbainic acid tert.-butyl ester (Example M21) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (158 mg). MS (ISP) 374 [(M+H)--]; mp 248 X. Example 23 8-(2-Fluoro-phenyl)-4'(3-imida2ol-l-vI-phenyl-7-(2.2,2-trifluoro-ethoxv)-L3-dihydro-benzofb] [ L41 diazepin-2-one The title compound was prepared from [2'-fluoro-5-[3-(3-nmdazol-l-yl-phenyl)-3-oxo-propionylamino] -2- (2,2,2-trifluoro-ethoxy)-biphenyl-4-yi] -carbamic acid tert,-butyl ester (Example M22) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (50 mg). MS (EI) 494 (M^); mp 208-210 °C Example 24 8-(2-Fluoro-phenyl)-4-f3-f3-methyl-isoxazQl-5-vIVphenyl]-7-(2,2.2-trifluoro-ethoxy)-1,3-dihydro-benzo f b] \ 1,41 diazepin-2-one The title compound was prepared from [2'-fluoro-5{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyi]-3-oxo-propionylamino}-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example M23) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (21 mg). MS (EI) 509 (M^); mp 218-220 -'C. Example 25 8'(2-FIuoro-phenyl)-4'(3-ri.23kriazol-l-yl-phenyl)-7-r2.2,2-trifluoro-ethoxv)-13-dihydro-benzofb] f 1,4ldiazepin'2-one The title compound was prepared from [2-fluoro-5-[3-oxo-3-(3-[l,2,3]triazoM-yI-phenyl)-propionylamino]-2-(2^,2-trifluoro-ethoxy)-biphen)d-4-yl]-carbamicacid tert.butyl ester (Example M24) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (45 mg)- MS (EI) 495 (M^). Example 26 8-(2-Fluoro-phenyl)-4-f3-(5-hvdroxvmethyl4l.2.3ltriazoI-l-yl]-phenyl)-7-(2,2,2-trifluoro-ethoxy)-13'dihvdro-ben2ofblfL4ldiazepin-2-one The title compound was prepared from (RS)-[2'-fluoro-5-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-^oxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid terL-butyl ester (Example Iyl25) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (10 mg). MS (ISP) 526 [(M+H)1; mp 232-234 °C Example 27 8-Chloro-7-dimethylamino-4-f3-f4-hydroxvmethy]-oxazol-2-yl)-phenyl1-13-dihydro-benzofb] ri,4]diazepin-2-one The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (170 mg) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxa2ol-2-yl] -phenyl}-propionic acid tert-butyi ester (Example Kll) (270 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (110 mg). MS (ISP) 41L2 [(M+H)--]; mp 193-195 °C Example 28 8-Chloro-7'(ethyl-methyl-amino)-4-f3-(5-hvdroxymetfayl-fL23ltriazoM'yl)-phenyl]-L3-dihvdrO'benzofb1fl,4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(ethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M26) (0.5 g, 0.8 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white soKd (60 mg). MS (ISP) 425.4 [(M+H)-]; mp 206 °C (dec). Example 29 8-Chloro-7-fmethyl-propyl-amino)-4-r3-(5-hydroxvmethyl-fL2.3ltriazol-l-yl')-phenyl] -1,3-dihydrO'benzo fbl [ 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M27) (0.41 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (110 mg). MS (ISP) 439.3 [(M+H)1; mp 178 °C (dec). Jbxample 30 8-Chloro-7-fdiethyl-amino)-4-f3-(5-hvdroxvmethyl-rL23ltriazoUl-yl)-phenvI1-L3-dihydro-benzofb][L4]diazepin-2-one The title compoimd was prepared from (RS)-(4-chloro-5-(diethyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tm-butyl ester (Example M28) (0.53 g, 0.827 mmol) by treatment with TFA in CH;Q: according to the general procedure N. Obtained as an off-white solid (210 mg). MS (ISP) 439.3 [(M+H)--]; mp 208 °C (dec). Example 3 i 8-Chloro-7-dimethylamino-4y3-(3-hvdroxvmeth>^-isoxazol-5-yl)-phenyl]-1.3-dihydro-benzofblfL4]diazepin-2-onc The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5->d]-phen)d}-propionyiamino)-phenylj-carbamic acid terL-butyi ester (Example M29) (81 mg, 0.13 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (38 mg). MS (ISP) 411 [(M+H)+] and 413 [(M+2+H)']; mp 132 °C. Example 32 8-CHoro-4-r3-(5-hvdroxymethyl-rL23]triazol-l-vI)'phenyl17-pvrrolidin-l-yl-L dihydro-benzorb1fL4]diazepin-2-one The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionylamino)-5-pyrrolidin-1-}d-phenyl]-carbaniic acid tert.-butyl ester (Example M30) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (58 mg). MS (ISP) 437 l(M+H)+] and 439 [(M+2+H)'-]; mp 193-197 X. Example 33 7-Dimethylamino-4-f3-(2-methyl-2H-pvrazol-3-yl)-phenvIl-8-trifluoromethyl-L3-dihydro-benzofbl [ L4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)'phenyl]-3-oxo-propionylari3ino}-4-trifluoromethyl-phenyl)-carbaniic acid terL-butyl ester (Example M31) (78 mg, 0.14 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid(48 mg). MS (ISP) 428 [(M+H)1; mp 225 °Q Example 34 4-f7-Chloro-8-('cvclopropyl-methyl-aminoV4-oxo-4,5-dihydrQ-3H-benzo Fbl f 1.41 diazepin-2-yl] -pvridine-2-carbonitrile The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyi-amino)-phenyl]-carbamic acid terL-butyl ester (Example Jll) (150 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (150 mg, 0.61 mmol) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg), MS (ISN) 364.1 [(M-H)-] and 366 [(M+2-H)-]; mp 199-201 °C. Example 35 8-Chloro-7-dimethylamino-4-[3-(4-hvd^oxvTnethyl-3-meth^d-isoxa^ol^5-yD-phenyl1-1.3-dihydro-benzo[bUL4ldiazepin-2-one The titie compoxmd was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tert,-butyl ester (Example M32) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (60 mg). MS (ISP) 425 [(M-hH)--] and 427 [(M+2-hH)-']; mp 232-233 'C. Example 36 8-CHoro-7-fcvclopropyl-methyl'amino)-4-f3-(3-melhyl-isoxazol-5-yl)-phenyll-13-dihvdro-benzofb1[L4ldiazepin-2-one The title compound was prepared from [2-aminO-4-chloro-5-(cyclopropyl-methyl-ammo)-phenyl]-carbamic acid tert.-butyl ester (Example Jll) (156 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (170 mg, 0.56 mmol) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (49 mg). MS (ISP) 42L3 [(M+H)--] and 423 [(M+2+H)^; mp 195-197 X. Example 37 8-Chloro-7-fcvclopropyl-methyl-amino)-4-f3-(5-hvdroxvmethyl-fL23ltria2ol--l-yl)-phenyl] -1.3-dihvdro-benzof b1 f 1.4] diazepin-2-one The title compound was prepared from (RS)-[4-chioro-5-(cyclopropyl-methyl-amino)-2-(3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M33) (200 mg, 0.313 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (54 mg). MS (ISP) 437.3 [(M+H)+] and 439 [(M+2+H)+]. Example 38 7-Dimethylamino-4- [3-f 5-dimethylaminomethyl- [ 1.2,31 triazoM-vD-phenyll -8-trifluoromethyl-13-dihydro-benzo[bUl,4ldiazepin'2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl- (1,2,3] triazol-1 -yl)-phenyl] -3-oxo-propionylamino}-4-trifluoromethyl phenyl)-carbamic acid tert.-butyl ester (Example M34) (126 mg, 0.214 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (23 mg). MS (ISP) 472 [(M+H)--]; mp 200 °C. Example 39 8-ChlorO'7-dimethylamino-4-f3-f5hvdroxymethyl-2-methyl-2H-pvra2ol-3-yl)' phenyll-13-dihydro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-{3-[2-methyl-5-(tetrahydro-pyran-2-ylox)Tncth)1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tat.-butyl ester (Example M35) (278 mg, 0.44 mmol) by treatment with TFA in CHjQ: according to the general procedure N. Obtained as a Hght yellow solid (129 mg), MS (ISP) 424 [(M+H)--] and 426 ((M+2+H)-]; mp 184 X. Example 40 4-(4-Oxo-8-pvrrolidin-l-yl-7-trifluoromethyl-4.5-dihvdrO'3H-benzo[bUL4ldiazepin-2-yl)-pyridine-2'Carbonitrile The title compound was prepared from {2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M36) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg). MS (ISP) 400.4 [(M+H)--]; mp 188 -C (dec). Example 41 443-(5-Hvdroxvmethyl-rL23ltriazol-l-vI)-phenyll-7-pvrrolidin-l-yl-8-trifluoromethyl-13dihvdro-ben2ofb1fL4ldiazepin2-one The title compound was prepared from (RS)-[2-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M37) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid(33 mg). MS (ISP) 471.2 [(M+H)+]; mp 134 °C. Example 42 7-Dimetfaylamino-8-fluoro-4- [3- f 5-hvdroxvmethyl- f 1.2.31 triazol-1 -yl)-phenvil -1.3-dihvdro-benzofbl rh4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-)4]-phenyi}-propionyi-amino)-phenyl]-carbamic acid tert.-butyl ester (Example M38) (375 mg, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg). MS (ISP) 395 [(M+H)1; mp 75 °C. Example 43 7-Dimethylamino-4-[3'(5-dimethylaminomethyl-fL2,3ltria2oI-l-yl)-phenyl1-8-fluoro-13-dihydro-benzo[bUL4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionylanaino}-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example M39) (170 mg, 0.32 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (34 mg). MS (ISP) 422 [(M+H)+]; mp 181 °C. Example 44 7-Dimethylamino-8-fluoro-4-F3-f3-hydroxymethyl-isoxazol-5-yD-phenvI1-l,3-dihydro-benzofbUl,4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M40) (314 mg, 0,53 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (95 mg). MS (ISP) 395 [(M+H)--]; mp 187 °C. Example 45 8-Chloro-7-dimethylamino-4-[3-(5-pvrrolidin-l-ylmethyl-ri,23ltriazol-l-vD-phenyl1-13-dihydro-benzo[b1fL4ldiazepin-2'One The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxy-methyl- [ 1,2,3] triazol-1 -yl)-phenyl] -1,3-dihydro-ben2o [b] [1,4] diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (0.044 mL, 0.6 mmol) in CH2Cl2 (2 mL) from 23 °C to reflux for 15 min, followed by evaporation to dryness. The crude chloride was dissolved in DMF (2 mL) and stirred with cat amount of Nal and pyrrolidine (0.248 mL, 3.0 mmol) at 23 °C until tic indicated complete conversion of the chloride. The reaction mixture was taken up in EtOAc, washed with water and brine, dried over Na2S04. Removal of the solvent in vacuum left a yellow semisolid. which was purified by silica gel colxxmn chromatography. Obtained as a yellow solid (101 mg). MS (ISP) 464 [(M+H)1 and 466 [(M+2+H)-']; mp 180-182 --C. Example 46 7-Dimethylamino-4-f3-f3'hvdroxvmetfayl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzofb1fL4]diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenylj-carbamic acid tert.-butyl ester (Example M41) (680 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (294 mg). MS (ISP) 455 [(M+H)--]; mp 219 °C. Example 47 7-Dimethylamino-8-fluorO'4--[3-(3-methyl-isoxazol-5-yl)-phenyl-l,3-dihvdro-benzo [bl [ 1.41 diazepin-2-one The title compound was prepared from (5-dimethylamino-4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M42) (233 mg, 0.47 nunol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow-brown solid (59 mg). MS (ISP) 379 [(M+H)--]; mp 124 X. Example 48 4-[3-(5-Azetidin-l-ylmethyl-fl.23ltriazol-l-yl)-phenyl-8-chloro-7-dimethylaminOr 13-dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and trimethylen imine (10 eq.) as described in Example 45. Obtained as a yellow solid (17 mg). MS (ISP) 450 [(M+H)-']; mp 153 °C Example 49 8'Chloro-7-dimethylamino-4- f 3- f 5-hvdroxvmethyl'isoxazol-3-vD-phenyn -1.3-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M43) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (113 mg). MS (ISP) 411.3 [(M+H)1 and 413 [(M+2+H)']; mp 211 °C (dec). Example 50 8--Chloro-4-[3--(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-7-piperidin-l-yl-13-dihvdro-benzo f b U1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl]-carbamic acid tert.-butyl ester (Example M44) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (99 mg). MS (ISP) 451.3 [(M+H)+] and 453 [(M+2+H)-']; mp 246 X (dec). Example 51 7-Dimethylamino-'4-f3-(5-hydroxvmethyl-isoxazoI'3-yl)-phenyll-8-trifluoromethyl- L3-dihvdrQ-benzofb1fL4]diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert--butyl ester (Example M45) by treatment with TFA in CH3CI2 according to the general procedure N. Obtained as a light yeUow solid (103 mg), MS (ISP) 445.3 [(M+H)+]; mp 211 °C (dec). Example 52 8-Chloro-7-dimeAylamino-4-f3-pvrazol-l-yl-phenylyl3-dihydro-benzofbl ri.4ldiazepin-2-one The title compound was prepared from {4-chloro-5-dimethylamino-2-[3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propion7lamino]-phenyl}-carbamic acid terL-butyl ester (Example M46) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (75 mg). MS (ISP) 380 [(M+H)1 and 382 [(M+2+H)+]; mp 231-234°C Example 53 7-DimethyIamino-4-f3-f3-pvrrolidin-l'ylmethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo fb] f L4l diazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl] -8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 46) (111 mg, 0.25 mmol) by treatment with SOCI2 (3 eq.) and pyrrolidine (10 eq.) as described in Example 45. Obtained as a yellow solid (28 mg). MS (ISP) 498 [(M+H)+]; mp 160 °C. Example 54 7-Dimethylamino-4-[3-(3-morpholin-4-ylmethyl-isoxa2ol-5-yl)-phenyl-8-trifluoromethyl-l,3-dihvdrO'benzofbl f l,4ldiazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and morpholine (10 eq.) as described in Example 45. Obtained as a yellow solid (33 mg). MS (ISP) 514 [(M+H)+]; mp 165 °C Example 55 7-Dimethylamino-4-f3-(3-dimethylaminomethyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-L3-dihvdrQ-benz6fbUl,4ldiazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and 40 % aqueous Me2NH-sol (10 eq.) as described in Example 45. Obtained as a light yellow solid (21 mg). MS (ISP) 472 [(M+H)--]; mp 160 °C Example 56 4-f7-Fluoro-4-oxo-8-pvrrolidin-l-yl-45-dihvdro-3H-benzo[bUl.4ldiazepin-2-vD-pyridine-2-carbQnitrile The title compoimd was prepared from {2-[3-(2-Cyano-pyridin-4-yI)-3-oxo-propionylamino]-4-fluoro-5-pyrrolidin-l-yl-phenyl}-carbamic acid tert.-butyl ester (Example M47) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (54 mg). MS (ISP) 350 [(M+H)--]; mp 278-279 °C Example 57 8-FluorQ-4-f3-(3-methyl-isoxazol-5-vD-phenyl]-7-pvrrolidin-l-yl-13-dihvdro-benzo[bUl,4ldiazepin-2-one The title compoimd was prepared from (4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example M48) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (86 mg). MS (ISP) 405 [(M+H)--]; mp 236 -C Example 58 8-Fluoro-443-(5-hvdroxvmethyl-[L2.3ltriazol-l-vD-phenyl1-7-pvTrolidin-l-yl-L3-dihvdrO'benzofbl f l,4ldiazepin-2-one The title compound was prepared from (RS)-[4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-ylox)nnieth.yl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl] -carbamic acid tert-butyl ester (Example M49) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (72 mg). MS (ISP) 421 [(M+H)--]; mp 184-185 °C. Example 59 4-f8-Azetidin-l-yl-7-chloro-4-oxo-45-dihvdro-3H-benzofb1[l,4ldiazepin-2-yl)-pyridine-2-carbonitrile The title compound was prepared from {5-a2etidin-l-yl-4-chloro-2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-phenyl}-carbainic acid terL-butyl ester (Example M50) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (66 mg). MS (ISP) 352 [(M+H)'] and 354 [(M+2+H)1; mp 276 °C. Example 60 4- f 3- f 5-Hvdroxymethyl-isoxa2ol-3-yl)'phenyl1 -7-pvrrolidin- 1 -yl-8-trifluoromethyl-L3-dihydro-benzo fb] f L4l diazepin-2-one The title compound was prepared from (RS)-[2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M51) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (224 mg). MS (ISP) 47L2 [(M+H)--]; mp 206-208 X. Example 61 4-f 8-Azetidin- l-yl-4-oxo-7-trifluoromethyl-4.5-dihydrO'3H-benzo [bl \ 1.41 diazepin-2-yl)'pyridine-2-carbonitrile The title compound was prepared from {5-azetidin-l-yl-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid terL-butyl ester (Example M52) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (51 mg), MS (ISN) 384.2 [(M-H)']; mp 241 °C. Example 62 7-A2etidin-l-yl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8'trifluoromethyl-l,3-dihydro-benzofbUL4ldiazepin'2-one The title compoimd was prepared from (5-azetidin-l-yl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M53) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg). MS (ISP) 441.3 [(M+H)--]; mp 239 °C (dec). Example 63 7-A2etidin-l-yl-443-(5-hvdroxvmethyl-rL23ltriazoM-yl)-phenyl1-8-trifluoromethyl-13-dihydro-benzofblfl.4ldiazepin'2-one The title compound was prepared from (RS)-[5-azetidin-l-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiamino)-4-trifluoromethyl-phenylj-carbamic acid terL-butyi ester (Example M54) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (182 mg). MS (ISP) 457,4 [(M+H)+]; mp 202 X (dec). Example 64 7-Dimethylamino-4-13-pyra2ol-l -yl-phenyl)-8-trifluoromethyl-1,3-dihvdro-benzo^b] f l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M55) (438 mg, 0.82 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (238 mg). MS (ISP) 414 [(M+H)--]; mp 176 °C Example 65 7-Dimethylamino4-f3-fL2.4ltriazol-4-yl-phenyl)'8-trifluoromet3iyl-l,3-dihydro-benzolb] [l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-4-yl-phenyl)-propionylamino]-4-trifluoroinethyl-phenyl}-carbamic acid tert.-butyl ester (Example M56) (280 mg, 0.526 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (121 mg). MS (ISP) 415.3 [(M+H)--]; mp 247-250 °C. Example 66 7-Dimethylamino-4-(3-imidazol-l-yl-phenyl)-8-trifluoromethyl-l>3-dihvdro-benzolbl [ l,4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-(3-imidazol-l-yl-phenyl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbainic acid tert.-butyl ester (Example M57) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (132 mg), MS (ISP) 414 [(M+H)--]; mp 203-205 °C. Example 67 8-Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-pvra2ol-l-yl)-phenyl1-L3-dihvdro-benzo fb] F1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chIoro-5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M58) (642 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (365 mg). MS (ISP) 410 [(M+H)--]; mp 211 °C. Example 68 7-DimethylaminO'4-f3-(4-hydroxvmethyl-pyrazol-l-yl')-phenyl1-8-trifluoromethyl-13-dihvdro-ben2orb1[l,4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (°Cample M58) (590 mg, 0.91 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (299 mg). MS (ISP) 444 [(M+H)--]; mp 175 °C Example 69 7-Dimethylamino-4-f3-(4-hydroxvmethyl-3-methyl-isoxazol-5-yl)-phenvI1-8-trifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[3-methyI-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylarnino)-4-trifluoromethyi-phenyi]-carbamic acid tert--butyl ester (Example M60) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (64 mg). MS (ISP) 459 [(M-hH)--]; mp 207-208 °C. Example 70 7-Dimethylamino-4-f3'(4-hvdroxvmethyi-isoxazol-3-yl)-phenyl8-trifluoromethyl-L3-dihvdro-benzofb1fL4ldiazepin-2'one The title compound was prepared from (RS)-l5-dimethylamino-2-(3-oxo-3-{3-l4-(tetrahydrO-pyran-2-yloxymcthyl)-isoxa2ol-3-yl)-phenyl}-propionylamino)-4-trifluoromethyl-phenyi)-carbamic acid tert.-butyl ester (Example M61) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (50 mg), MS (ISP) 445 [(M+H)+]; mp 217-219 M EMmpk7l 7-Dimethylamino-4-f3-(2-methylsulfanyl-imida2ol-l-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2orb1fL4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyisulfanyl-imidazol-l-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M62) (450 mg. 0.78 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (253 mg). MS (ISP) 460 [(M+H)--]; mp 192 X. Example 72 7-Dimethylamino-4'f3-(4'hvdroxvmethyl-2-methyl-2H-pyrazol3-yl)-phenyll-8' trifluoromethyl-13-dihvdro-benzofb1 f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yi]-phenyl}-3-oxo-propionyl-amino)-4-trifiuoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M63) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (272 mg), MS (ISP) 458 [(M+H)+]; mp 243-244 °C. Example 73 8-Chloro-7-dimethylamino-4-f3-fL2,4ltriazoM-yl-phenyl)-13-dihvdro-benzprb] f l,4ldiazepin-2-one The title compound was prepared from {4-Chloro-5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-l-yl-phenyl)-propionyiamino]-phenyi}-carbamic acid tert-butyl ester (Example M64) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (316 mg). MS (ISP) 381 [(M+H)1 and 383 [(M+2+Hr]; mp 239-241 °C Example 74 7-Dimetfaylamino-4- (5-\l .2,41 triazol-1 -yl-phenyl) - 8-trifluoromethyl-13-dihydro-benzoFb] [L4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,4]triazoH-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M65) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(269 mg). MS (ISP) 415 [(M+H)--]; mp 228-230 X. Example 75 3-f8-Dimethylamino-4-oxo-7-trifluoromethyl-4,5-dihvdro-3H-benzorbirL4ldiazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-trifluoromethyl-phenyl}-carbanaic acid tert.-butyl ester (Example M66) (180 mg, LO mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg). MS (ISN) 371 [(M-H)-]; mp 224-227 X. Example 76 7-Dimethylamino-4-(3-l5-f('2,2.2-trifluoro-ethylaminoVmethyl]-rL23ltriazol-l-vU-phenyl)-8-trifluoromethyl-l>3-dihydro-benzorb1fL4ldiazepin-2-one The title compoxmd was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l>2,3]triazol-l-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 17) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and 2>2,2-trifluoroethylamine (10 eq.) as described in Example 45. Obtained as a light yellow solid(19mg). MS (ISP) 526 [(M+H)'];mp 168-170 °C. Example 77 7-(Cyclopropylmethyl-methyl-aminoV4-[3-(5-hvdroxvmethyl-fL23ltriazoM-vI)-phenyl1-8-trifluorQmethyl-13-dihvdro-benzofbiri.4]diazepin-2one The title compound was prepared from (RS)-[5-(cyclopropylmethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M67) (939 mg> 1.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (544 mg). MS (ISN) 483 [(M-H)-]; mp 212 °C. Example 78 4-f8-fCvclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin-2-vn 'pyridine-2-carbonitrile The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M68) (173 mg, 0.33 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (81 mg), MS (ISN) 412 [(M-H)]; mp 155 °C Example 79 4- [ 3- (4-Cyclopropylaminomethyl'pyrazol-1 -yl) -phenvH -7'dimethylamino-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one The title compound was prepared from 7-dimethylamino-4-[3-(4-hydroxymethyl-pyrazoH-)d)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 68) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (45 mg). MS (ISP) 483 [(M+H)--]; mp 135 °C. Example 80 4-[3-(5-Cyclopropylaminomethyl-ri.2,3ltriazol-l-yl)-phenyl1-7-fcyclopropylmethyl-methylaminoV8-trifluoromethyl-13-dihvdrO-benzorblfl,4ldiazepin-2-one The title compound was prepared from 7-(cyclopropylmethyi-methyl-amino)-4-[3-(5-hydroxymethyl-[1^3]triazol-l-yl)-phenyl]-8-trifluoromethyl-13- SOCh (3 eq.) and cyclopropji amine (10 eq.) as described in Example 45. Obtained as a yellow solid (97 mg). MS (ISP) 524 [(M+H)--]; mp 35-46 °C Examples! 7-Dimethylamino-4-B-r2-(2-hvdrorv-ethyl)-2H-pvrazol-3-yl]-phenvD-8-trifluoromethyl-l.S-dihvdro-benzQfbl f 1.4ldia7epin-2-one The title compound was prepared from (RS)-l5-dimetliylainino-2-[3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyi]-2H-p>Tazol-3-yi}-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tcrL-butyl ester (Example M69) (237 mg, 0.36 mmol) by treatment with TFA in CH:Q: according to the general procedure N. Obtained as an off-white solid (48 mg). MS (ISP) 458 [(M+H)--]; mp 138 °C Example 82 4-[3'(5-Cvclopropylaminomethyl-fL2.3]tria2ol-l-yl)-phenyl1-7-dimethylamino-8-trifluorometfayl-1.3-dihvdro-benzorbUL4ldiazeptn-2-one The title compound was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-trifluoromethyi-13-dihydro-benzo[b][l,4)diazepin-2-one (Example 17) (444 mg, 1.0 mmol) by treatment with SOQ2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (248 mg), Mp 145-148 °C, Example 83 4-f8-(Cyclopropyl-methyl-amino)-4-oxo-7-trifluoromethyM.5-dihvdro-3H-benzo fb] [ 1,41 diazepin-2-yll -pvridine-2-carbonitrile The title compoxmd was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester (Example M70) (215 mg, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (87 mg). MS (ISP) 400.4 [(M+H)--]; mp 200-205 °C. Example 84 7-Diinethylamino-8-(2-fluoro-phenyl)-4-f3-fh23ltria2ol-l-yl-phenyl)-L3-dihvdro-benzofbl f 1.4ldiazepin-2-one The title compound was prepared from {2-dimethylamino-2-fiuoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert.-butyl ester (Example M70) (810 mg, L45 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (61 mg). MS (ISP) 400.4 [(M+H)+]; mp 225-230 °C. Example 85 7-Dimethylamino-4-B-(5-(2-hvdroxv-ethyl)-fL23ltria2oM-yl)-phenvU-8-trifluoromethyl-13-dihvdro-benzo \b] [ 1.41 diazepin-2-one The title compound was prepared from (RS)-{5-dimethylamino-2-[3-oxO-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,2,3] triazol- 1-yl}-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M72) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (179 mg). MS (ISP) 459 [(M+H)+]; mp 172-175 °C. Example 86 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-pvrazol-l-vD-phenyl1-8-trifluoromethyl- 1.3-dihvdro-benzQrb1fL4ldiazepin-2-one The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M73) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow soHd(109mg). MS (ISP) 444 [(M+H)1; mp 228-229 °C Example 87 7-Dimethylammo-4-(3-[h2.3ltriazol-l-yl-phenyl)-8-trifluoromethyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[1^3]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic add tert.-butyl ester (Example M74) (905 mg, 1.7 mmol) by treatment with TFA in CH2Cl2 according to tihie general procedure N. Obtained as a yellow solid (566 mg). MS (ISN) 413.2 [(M-H)-]; mp 210-212 'C. Example 88 4-r4-Oxo-842.2.2-trifluoro-ethoxv)-7-trifluoromethyl-4.5-dihvdro-3H-benzofbl f 1,41 diazepin-2-yl1 -pyridine-2-carbonitrile The tide compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl] -carbamic acid tert.-butyl ester (Example M75) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (100 mg). MS (H) 428.2 (M^); mp 252-255 °C. Example 89 3-(8-Dimethylamino-7-methyl-4-oxo-43-dihydro-3H-benzorblfl.4ldiazepin-2-yl)-benzonitrile The title compound was prepared from {2-[3-(3-Cyano-phenyl)-3-oxo-propionyi-amino]-4-dimethylamino-5-methyl-phenyl}-carbamic acid tert-butyl ester (Example M76) (0.24 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (114 mg, 59%). MS (ISP) 319.3 [(M+H)1; mp 257 °C. Example 90 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-8-methyl-L3-dihydro-benzofbl rL4ldiazepin-2-one The tide compound was prepared from (RS)-[5-dimethylamino-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M77) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). ' MS (ISP) 391.3 [(M+H)--]; mp 190 X. Example 91 2-f3-Cyano-phenyl)-8-dimetfaylamino-4-oxo-4.5-dihydrO'3H-benzo[bl[L4ldiazepine-7-carbonitriIe The title compound was prepared from {5-cyano-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-4-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example M78) (0.28 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (36 mg, 59%). MS (ISP) 328.3 [(M-H)-]; mp 251 °C Example 92 3-f7-methyl-8-(methyl-propyl-amino)-4-oxo-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin2-yl1 -benzonitrile The title compound was prepared from [2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-methyl-4-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M79) (0.17 g, 0.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg> 58%). MS (ISP) 347.4 [(M+H)1; mp 195 X. Example 93 4-[3-(5-HvdroxvTnethyl-[1.2.3ltriazol-l-yl)-phenyl1'8-methyl-7-(methyl-propvI-amino)-L3-dihvdro-benzo [bl [1,41 diazepin-2-one The title compound was prepared from (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M80) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). MS (ISP) 419.4 [(M+H)1; mp 186 °C. Example 94 7-fEthyl-methyl-amino)-4-f3-(5-hvdroxvmethyl[l,23ltriazol-l-yl)-phenyl1-8-methyl-13-dihvdro-benzo[b1fl.4ldiazepin-2-one The title compound was prepared from (RS)-[5-(ethyi-methyl-amino)-4-meth)i-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionyiamino)-phenyl]-carbamic acid tert-butyl ester (Example M81) (0.39 g, 0.64 mmol) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a off-white solid (159 mg, 61%). MS (ISP) 405.5 [(M+H)+]; mp 207 °C Example 95 8-Dimethylamino-2-f3-(5-hydroxymethyl-fl,2,3ltriazol-l-yD-phenyn-4-oxo-4.5-dihvdro-3H-benzo fb] f 1.41 diazepine-7-carbonitrile The tide compound was prepared from (RS)-[4-cyano-5-dimethylainino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoM-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl.ester (Example M82) (0.35 g, 0.58 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(149 mg> 64%). MS (ISP) 402.5 [(M+H)--]; mp 234 °C. Example 96 8-Chloro-4- f 3- f 5-hvdroxymethyl- [ 1.231 triazol- l-vD-phenyll -7-f isopropyl-methyl-amino)-L3-dihydro-benzorb1\|'l,4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M83) (0.53 g, 0.83 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a off-white solid (120 mg, 33%). MS (ISP) 439.5 [(M+H)--]; mp 207 X. Example 97 8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyll-7-(methyl-propyl-aminoyl.3-dihydro-benzofblfl.4ldiazepin-2-one The title compound was prepared from [4-methyl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M84) (0.33 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as alight yellow solid (163 mg, 64%). MS (ISP) 403.4 [(M+H)--]; mp 194 '°C. Example 98 8-Dimethylamino-2-[3-(3-methyl-isoxa2ol-5-yl)-phenyll-4-oxO'43-dihydro-3H-benzo fbl f 1.41 diazepine-7carbonitrile The title compound was prepared from (4-cyano-5-dimethyiamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-Carbaniic acid tert-butyl ester (Example M85) (0.31 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (171 mg, 72%). MS (ISP) 386.3 [(M+H)--]; mp 248 °C. Example 99 7-fEthyl-methyl-amino)-8-methyl-4-F3-(3-methyl-isoxazol-5-yl)-phenyl]L3-dihvdro-benzo fbl [ 1.41 diazepin-2-one The title compound was prepared from (5-(ethyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M86) (0.38 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow solid (160 mg, 55%). MS (ISP) 389.5 [(M+H)--]; mp 198 °C Example 100 7-DimethylaminO-8-methyl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-l3-dihydro-benzoFbl [l,4ldiazepin-2-one The title compound was prepared from (5-dimethylamino-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M87) (0.32 g, 0.65 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (140 mg, 57%). MS (ISP) 375.4 [(M+H)--]; mp 204 °C. Example 101 8-Chloro-4- r3- f 5-hvdrQYvmethyl- \ 1.23ltriazol-l-yl)-phenyl1 -7-f isobutyl-methyl-amino)-13-dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isobutyl-methyl-ainino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazoM-yi]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M88) (0.32 g, 0.49 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtzdned as an ofF-white solid (107 mg, 48%)- MS (ISP) 453.4 [(M+H)--]; mp 201 °C. Example 102 8-Cbloro-7-(isobutyl-methylamino)-4-f3-f3-methyl-isoxazol-5-yD-phenyn-L3-dihvdro-benzofbirL4ldiazepin-2-one The title compound was prepared from (4-chloro-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M89) (0.35 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (114 mg, 41%), MS (ISP) 437.4 [(M+H)+]; mp 194 °C. Example 103 2-f3-(5-Hvdroxvmethyl-fl.23ltriazol-l-yl)-phenyl]-4-oxo-8-pyrrolidin-l-yl-4.5-dihvdrO-3H-benzo[b1fL4]diazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example M90) (0.37 g, 0.59 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (140 mg, 56%). MS (ISP) 428.5 [(M+H)1; mp 241 °C. Example 104 2-f3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-8-pvrrolidin-l-yM,5-dihydro-3H-benzofbl f L4l diazepine-7-carbonitrile Prepared from (4cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M91) (0.41 g, 0.77 mmol) by treatment with TFA m CH2Cl2 according to the general procedure N. Obtained as a yellow solid (90 mg, 28%). MS (ISP) 412.3 [(M+H)--]; mp 267 °C. Example 105 2-f3-(5-Hvdroxvmethyl-fl.2,3ltriazol-l-yl)-phenyl1-8-fmethyl-propvi-aminol-4-oxo-45-dihvdro-3H-benzo f b1 \ 1.41 diazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiannino)-phenyl]-carbamic acid tert-butyl ester (Example M92) (0.43 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedmre N. Obtained as a yellow solid (100 mg, 34%). MS (ISP) 430.5 [(M+H)--]; mp 221 °C. Example 106 2-f3-f3-Methyl-isoxa2ol-5-vD-phenyl-8-(methyl-propyl-amino)-4-oxo-4,5-dihvdro-3H-benzofb1 [ l,4ldiazepine-7-carbonitrile The title compound was prepared from [4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M93) (0.36 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg, 34%). MS (ISP) 414.4 [(M+H)--]; mp 133 °C Example 107 8-Diethylamino-2-[3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-4>5-dihydro-3H-benzofbl f 1.4] diazepine-7-carbonitrile The title compound was prepared from (4-cyanO-5-diethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxO-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M94) (0.35 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(209 mg, 77%). MS (ISP) 414.4 [(M+H)+]; mp 191 °C. Example 108 8-fIsopropyl-methyl-amino)-2-f3f3-methyl-isoxa2ol-5-yl)-phenyn-4-0X0-4.5-dihvdro-3H-benzofb11 L4ldiazepine-7-carbonitrile The title compound was prepared from (4-cyano-5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M95) (0.37 g, 0.70 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (219 mg, 76%). MS (ISP) 414.4 KM+H)--]; mp 197 °C. Example 109 2- r3-(5-HvdrQxvmethyl- f 1,2.3 Itriazol- l-yl)-phenyl1 -8-f isopropyi-metfayl-amino)-4-oxo-4.5-dihvdro-3H-benzo Fbl f 1,41 diazepme-7-carbonitrile The title compoimd was prepared from (RS)-[4-cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-)d]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M96) (0.45 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (236 mg, 77%). MS (ISP) 430.5 [(M+H)+]; mp 206 °C. Example 110 8-(Isobutyl-methyl-aminoV2-f3-f3-methyl-isoxazol-5-yl)-phenyn-4-0X0-4,5-dihvdro-3H-ben2ofbl [ l,4]diazepine-7-carbonitrile The title compoimd was prepared from (4-cyano-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M97) (0.39 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (230 mg, 75%). MS (ISP) 428.5 [(M+H)+]; mp 170 °C. Example 111 2-f3-(5-Hvdroxvmethyl-fL23ltriazol-l-vD-phenyl-8-(isobutyl-methyl-aminoV4-oxo-4.5-dihvdro-3H-benzofb]Fl,4ldiazepine-7-carbonitrile The title compound was prepared from (RS)-[4-cyano-5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M98) (0.46 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (180 mg, 57%). MS (ISP) 444.4 [(M+H)+]; mp 199 X. Example 112 2-f3-(3-methyl-isoxazol-5-yl)-phenYll-4-oxo-8-piperidin-l-yl-43-dihydro-3H-benzofbUL4ldiazepine-7-carbonitrile The title compoimd was prepared from (4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M99) (0.41 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (226 mg, 70%). MS (ISP) 426.4 [(M+H)--]; mp 246 °C. Example 113 8-Chloro-7-isobutylamino-4-r3-(3-methyl-isoxazol-5'yl)-phenyl-13-dihvdro-benzofbl ri,4ldiazepin-2-one The title compound was prepared from (4-chloro-5-isobutylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example MlOO) (0.34 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (216 mg, 81%). MS (ISP) 423.3 [(M+H)--]; mp 249 X. Example 114 8--Chloro-4-[3-(5-hvdroxymethyl-[L23]triazol-l'yl)-phenv]]-7-isobutylaminO'l,3-dihydrO'benzorb1fl,4ldiazepin-2-one The tide compoimd was prepared from (RS)-[4-chloro-5-isobutylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example MlOl) (0.17 g, 0.27 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg, 35%). MS (ISP) 439.4 [(M+H)--]; mp 214 X. Example 115 4-f3-(5-Hydroxvmethyl-fL2.3ltriazol-l-yl)-phenyl]-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzofb1[L4ldiazepin-2-one The title compound was prepared from (RS)-[5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M102) (0.15 g, 0-22 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (31 mg, 30%). MS (ISP) 473.2 [(M+H)--]; mp 230 °C Example 116 4-f3-(3-MethyMsoxazol-5-yiVphenyl]-7-fmethyl-propyl-aminoV8-trifluoromethyl-1.3-dihvdro-ben2orb1fL4ldiazepin-2-one The title compound was prepared from [2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M103) (0.26 g, 0.45 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (127 mg, 61%). MS (ISP) 457.4 [(M+H)+]; mp 193 °C Example 117 4'f3-(5-Hvdroxvmethyl-fl.23ltria2ol-l-\dVphenyll-7-fisobutyl-metfayl-amino)-8-trifluoromethyl-L3-dihydro-benzorbl[L4ldiazepin-2-one The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M104) (0.51 g, 0.74 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (169 mg, 47%). MS (ISP) 487.3 [(M+H)-]; mp 230 °C. Example 118 7-fIsobutyl-methyi-aminoV4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8-trifluoromethyl-13-dihvdro-benzofbUL4ldiazepin-2-one The title compound was prepared from (5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M105) (0.42 g, 0.71 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (161 mg, 48%). MS (ISP) 471.2 [(M+H)--]; mp 195 X. Example 119 4-r3-(5-Hvdroxvmethyl-ri.23ltriazol-l-yl)-phenyll-7-fisopropyl-methyl-aminoV8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-(5-(tetrahydro-pyran-2-yloxymeth)4)-[l^,3]triazol-l-yl]-phenyl}-propionyl- amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example M106) (0.50 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofif-white solid (156 mg, 45%). MS (ISP) 473.3 [(M+H)--]; mp 234 X. Example 120 7-fIsopropyl-methyl-aminoV4-f3-(3-methyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2o fbl [ 1.41 diazepin-2-one The tide compound was prepared from (5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M107) (0.37 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg, 25%). MS (ISP) 457,4 [(M+H)+]; mp 199 °C. Example 121 8-Chloro-7-fmethyl-propyl-amino)-4-f3-(5-pvrrolidin-l-ylmethyl-[1.2.3ltria2ol-l-yl)-phenyll -13'dihydro-benzo Fbl [ 1,4] diazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-ainino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepm-2-one (Example 29) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a yellow foam (63 mg, 26%). MS (ISP) 492.3 [(M+H)+]. Example 122 4-f3-(5-A2etidin-l-ylmethyl4L2.3ltriazol-l-yl)-phenyn-8-chloro-7-fmethyl-propyl-amino)-L3-dihydro-benzo fbl [l,4]diazepin-2-one The title compoimd was prepared from 8-chIoro-7-(methyl-propyi-amino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 29) (118 mg, 0.27 namol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine in DMF according to the method described in Example 45. Obtained as a light yellow solid(65 mg, 50%), MS (ISP) 478.3 [(M+HD; mp 169 °C Example 123 8-CMoro-4-f3-(5-diethylaminomcthyi-fL2J)triazol-l-yl)-phenyl]-7-fmethyl-propyl-aminoyl,3-dihvdro-benzorblfL4]dia7q?in-2-one The tide compound was prepared from 8-chloro-7-(meth-5d-propyl-amino)-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol-1 ->i)-phen\1 j -13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction wth thionylchloride in dichloro-methane and subsequent treatment of the corresponding chloride with diethylamine in DMF according to the method described in Example 45. Obtained as a Ught yellow solid (123 mg, 50%). MS (ISP) 494.3 [(M+H)--]; mp 151 °C Sample 124 8-Chloro-4-C3-l5-rfisopropvI-methyl-amino)-methyll-fL23ltriazoM-ylt-phenyD-7-(methyl-propyl-amino)-13-dihvdro-benzofbUL4]diazepin-2-one The tide compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymediyl-[l,2,3]triazol-l-yl)-phenyl]-13-dihydro-ben2o[b][l,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (129 mg, 52%), MS (ISP) 494.3 [(M+H)--]; mp 148 °C. Example 125 8-Chloro-7-fisopropyl-methyl-amino)-4-f3-f5pvrrolidin-l-ylmethyl-fL23ltria2ol-l'yI)-phenyl]-13-dihvdro-benzo[b1fL4ldiazepin-2-one The tide compound was prepared from 8-chloro-4-l3-(5-hydroxymethyi- [lA3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrroUdine in DMF according to the method described in Example 45. Obtained as a light yellow solid (157 mg, 64%). MS (ISP) 492.3 [(M+H)--]; mp 172 °C. Example 126 8-Chloro-7-fisobutyl-methyl-aminoV4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1 -13-dihvdro-benzo[b1 ri.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [ 1,2,3] triazol- l-yl)-phenyl]-7-(isobutyl-methyl-amino)- 1,3-dihydro- ben2o[b] [l,4]diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Erample 45. Obtained as a light yellow solid (163 mg, 64%), MS (ISP) 506.3 [(M+H)+]; mp 190 X. Example 127 8-Chloro-4-f3-(5-dimethylaminomethyl-fL2,3ltriazoM-yD-phenyl-7-(isopropyl-methyl-aminoyl3-dihydro-benzofb1[1.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro- benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (143 mg, 61%). MS (ISP) 566.3 [(M+H)+]; mp 225 X. Example 128 8-Chloro-4-f3-(5-dimethylaminomethyl-rL2.3ltriazoM-vD-phenyl]-7-risobutvI-methyl-aminoyl,3-dihvdro-benzofbUL4]diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro- benzo[b] [1,4] diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (134 mg, 56%). MS (ISP) 480.5 [(M+H)--]; mp 199 X. Example 129 4-[3-(5-Azetidin-l-ylmethyl-[1.2,3]triazol-l-yl)-phenyl1-8-chlorO'7-fisopropvI-methyl-amino V13-dihydro-ben2o [b] F1.41 diazepin-2one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyI-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg> 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine m DMF according to the method described in Example 45. Obtained as a light brown solid (102 mg, 43%). MS (ISP) 478.3 [(M+H)--]; mp 177 °C. Example 130 4-f3-(5-Azetidin-l-ylmethyl'fh2J]triazol-l-vD-phenyl>8-chloro-7-risobutyl-methyl-amino)-1.3-dihvdro-benzo[bl[l,4ldiazepin-2'One The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3'dihydro-benzo[b][l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimelhylene-imine in DMF according to the method described in Example 45. Obtained as a light brown solid (125 mg, 52%). MS (ISP) 492.3 [(M+H)+]; mp 191 °C. Example 131 8-Chloro-4-f3-(5'methylaminomethyl-rL2.3ltriazol-l-vD-phenyl-7-fmethyl-propyl-amino)-L3-dihvdro-benzoFb1fl.4ldiazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyi]-l,3-dihydrO-benzoIb][l,4]diazepin-2-one (Example 29) (230 mg, 0.52 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with methylamine in DMF according to method described in Example 45. Obtained as a Kght yellow solid(122 mg, 52%). MS (ISP) 452.4 [(M+H)--]; mp 185 °C. Example 132 4-f3-(5-Hvdroxvmethyl-fl,23]triazol-l-yl)-phenyl1-7-fisobulTl-methyl-amino) methyl- L3-dihvdro-ben20 Fbl [ L4l diazepin-2-one The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M108) (0.33 g, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a pale brown solid (188 mg, 79%). MS (ISP) 43L4 [(M-H)-]; mp 198 -C. Example 133 443-(5-Hvdroxvmethyl-ri23ltriazol-l-yl)-phenyl1-8-methyl-7-pvrrolidin-l-yl-13-dihydrO'benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (RS)-[4-methyl-2-(3-oxo-3-{3-[5-(tetrahydxo-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylainino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example MHO) (0,41 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (239 mg, 86%). MS (ISP) 417-3 [(M+H)--]; mp 202 °C. Example 134 7-(Isobutyl-methyl'amino)-8-methyl-4-f3-f3-methyl-isQxazol-5-yl)-phenylyl3-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from (5-(isobutyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyI)-carbamicacid tert-butyl ester (Example M109) (0.33 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (136 mg, 53%). MS (ISP) 417.3 [(M+H)--]; mp 187C. Example 135 8-methyl-4-r3-f3-methyl-isoxazol-5-yl)-phenyl1-7-pvrrolidin-l-yl-13-dihvdro-benzofbl f L4ldiazepin-2-one The title compoimd was prepared from (4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionyiainino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyi ester ^iixample M111; (U.33 g, 0.64 mmolj by tr . nent with TFA in CH2Cl2 according to the general procedure N. Obtained a^ an off-white solid (223 mg, 87%). MS (ISP) 401.5 [(M+H)--]; mp 211 '°C. Example 136 4-F3-(5-Dimethylaminomethyl-fL2.3ltriazol-l-yl)-phenyl-7-(isobutyl-methyl-amino)-8-trifluoromethyl-13-dihydro-benzofbiri.4ldiazepin-2-one The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7-(isobutyl-methyl-amino)-8-trifluoromethyl- 1,3-dihydro-ben2o[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 35%). MS (ISP) 514.3 [(M+H)-]; mp 182 °C. Example 137 8-(Isobutyl-methyl-aminoV4-oxo-2-[3-(5-pvrrolidin-l-ylmethyl-rL23ltriazol-l-yl)-phenyn-4.5-dihydro-3H-benzorb1fl,4ldiazepine-7-carbonitrile The title compoxmd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-benzo[b][l,4]diazepine-7-carbonitrile (Example 111) (200 mg, 0.45 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (140 mg, 63%). MS (ISP) 497.3 [(M+H)--]; mp 174 °C, Example 138 7-(Isobutyl-methyl-aminoV4-f3-(5-pyrrolidin-l-ylmethyl-fl.23ltriazol-l-vIV phenyl]'8-trifluoromethyl13-dihydro-benzofb1[h4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yi)- phenyl]-7-(isobutyl-methyl-ainino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a Ught orange foam (80 mg, 24%). MS (ISP) 540.5 [(M+H)+).. Example 139 7-('Isobutyl-methyl-amino)-8-methyl-4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1-1.3-dihydro-benzorbirL4Tdiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yI)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 132) (200 mg, 0.46 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (50 mg, 22%). MS (ISP) 486.4 [(M+H)--]; mp 177 °C. Example 140 8-(Isobutyl-methyl-amino)-2-(3-{5-f(isobutyl-methyl-amino)'methyl]-rL23ltriazol-l-yll-phenyl)-4-oxo-4.5-dihvdro-3H-ben2o[b1[l,4ldiazepine'7-carbonitrile The title compoimd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepine-7-carbonitrile (Example HI) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutyl-methylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (100 mg, 39%). MS (ISP) 513.4 [(M+H)+]; mp 169 °C. Example 141 7-fIsobutyl-methyl-amino)-4-f3-l5-[(isopropyl-methyl-amino)-methyl]-[L2,3ltria2ol-l-vU-phenyl)-8-trifluoromethyl-L3-dihvdro-benzofb1[1.4ldiazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2oM-yl)- phenyl]-7-(isobutyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 117) (260 mg, 0,53 nrnnol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (70 mg, 24%), MS (ISP) 542.3 [(M+H)--]; mp 157 °C Example 142 8'Chloro-4-F3-(5-cyclopentylaminomethyl-[L23ltriazol-l-vIVphenyll-7-(isopropyl-methyl-aminoyl3-dihvdro-ben2o[b1Fl.4]diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopentylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (170 mg, 67%). MS (ISP) 506.3 [(M+H)--]; mp 174 °C. Example 143 4-f3-l5-[(Cvclopropylmethyl'amino)'methyl1-rL2.3ltriazoll-yU-phenvD-7-(isobutyl-methyl-amino)-8-methyl-L3-dihydro-benzofblfl,4]diazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyM,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 132) (250 mg, 0.58 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylmethylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (50 mg, 18%). MS (ISP) 486.4 [(M+H)+]; mp 184 °C, Example 144 8-Cbloro-7-fisobutvI-methyl-aminoV4-[3-(5-piperidin-l-ylmethyl-[1.23ltriazol-l' yl)-phenyl1-13-dihvdro-ben2ofb1fL4ldiazepin-2-one The title compoimd was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol- l-yl)-phenyl]-7- (isobutyl-methyl-amino)- 1,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with piperidine in DMF according to the method described in Example 45. Obtained as a light brown solid (250 mg, 99%). MS (ISP) 520,3 [(M+H)--]; mp 169 «C. Example 145 8-Chloro-4-B-(5-(isopropylaminO-methyl)-fL2,3ltriazol-l'yl]-phenvU-7-(isopropyl-methyl-aminoyl.3-dihvdro-benzofb1fl.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazol-l-yl)-phenylj-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 67%), MS (ISP) 480.3 [(M+H)+]; mp 208 °C. Example 146 8-Chloro-7-fisopropyl'methyl-aminoV4-[3-(5-{f(2-methoxy-ethyl)methyl-amino1- methvU-fL2,3ltriazol-l-yl)-phenyl1-l3-dihydro-benzo[b1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-(2-methoxyethyl)methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 47%). MS (ISP) 510.4 [(M+H)+]; mp 119 °C. Example 147 8-Chloro-4-(3-{5-[(cvclopropylmethyl-aminoVmethyl]-fL23ltria2ol-l-yll-phenyl)-7-(isopropyl-methyl-amino)'13-dihvdro-benzorbl[1.4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, D.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with aminomethyl-cyclopropane in DMF according to the method described in Example 45. Obtained as a light brown solid (150 mg, 61%). MS (ISP) 592,2 KM+H)--]; mp 151 °C Example 148 8-ChlorO-7-(isopropyl-methyI-aminoV4-f3-l5-f('isopropyl-metfayl-amino)-methyl]-fL23ltriazoM-yll-phenylyl3-dihvdro-benzorbUL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]triazoH-yl)-phenyi]-7-(isopropyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropylmethylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 49%). MS (ISP) 494.3 [(M+H)--]; mp 180 °C. Example 149 8-Chloro-4-f3-{5-rfisobutyl-methyl-aminoVm€thyl)-rL23ltriazoM-yl]-phenyl)-7-(isopropyl-methyl-amino)-13-dihvdro-benzo[b1 [1.41 diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro- ben2o[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutylmethylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (190 mg, 75%). MS (ISP) 508.4 [(M+H)--]; mp 182 °C Example 150 4-f3'(5'DimethylaminomethyI-fL2,3]triazoI-l-yl)-phenyl]-7-risopropyl'metfayl-aminoV8-trifluoromethyl--13-dihvdro-benzofb][1.4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l>4]diazepin-2-one (Example 119) (200 mg, 0,42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as an off-white solid (80 mg, 38%). MS (ISP) 500.4 [(M+H)--]; mp 197 »C. Example 151 7-fIsopropyl-methyl-amino)-4-r3-(5-pvrrolidin-l-ylmethyl-fL23ltriazoI-l-yl)-phenyll -8'trifluoromethyl-13-dihvdro-ben20 f hi f 1,41 diazepin'2-one The title compound was prepared from 4- [3-(5-hydroxymethyl- [l,2,3]triazol- 1-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (200 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light brown solid (140 mg, 63%). MS (ISP) 526.2 [(M+H)--]; mp 175 X. Example 152 7-Qsopropyl-methyl-aminoV4-(3-l5-f(isopropyl-methyl-amino)-methyl1- fl.2.3ltriazol-l'yl}-phenyl)-8-trifluoromethyI-L3-dihvdro-benzofbUl.4]diazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (220 mg, 0.47 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropylmethylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (110 mg, 45%). MS (ISP) 528.4 [(M+H)1; mp 182 °C, Example 153 4,f3-\|5-r(CvclopropylmethylaminoVmethyl1-rL23Uria2ol-l-yll-phenyl)-7-fisopropyI-methyl-aminoV8-trifluoromethyl-L3-dihvdro-benzorb1fl,4ldiazepin-2- one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (210 mg, 0.44 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with aminomethyl-cyclopropane in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 47%). MS (ISP) 526.2 [(M+H)--]; mp 152 °C Example 154 8-Chloro-4- TS-f 5-cyclopropylaminomethyl- [ h2.3ltriazol-l-yl)-phenyll-7-f isopropyl-methyl-amino V13'dihvdro-b enzo f b1 f 1.41 diazepin-2- one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[ 1,2,3 ] triazol-1 -yl)-phenyl] -7- (isopropyi-methyl-amino) -13-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0,50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (40 mg, 17%). MS (ISP) 478.4 [(M+H)--];mp 144 °C Example 155 4-l3-(5-fIsopropylamino-methyl)-rL23ltriazol-l-yl]-phenyll-7-(isopropyl-methyl-amino)-8-trifluoromethyl-L3-dihvdrO'benzorbirL4ldiazepin-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (100 mg, 39%). MS (ISP) 514.4 [(M+H)+]; mp 191 °C. Example 156 8-Chloro-4-(3-r5-fisobutylamino-methvD-fL23ltriazol-l-yl1-phenyll-7-(isopropyl-methyl-aminoyl3'dihvdro-benzofb1fL4ldiazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isobutylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 65%). MS (ISP) 494.4 [(M+H)--]; mp 182 X. Example 157 4-f3-(5-Cvclopropylaminomethyl-fl.2.3ltriazoM-yl)-phenyl1-7-fisopropyl-methyl-aminoV8-trifluoromethyl1.3-dihvdro-benzofblfL4ldia2epm-2-one The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)- phenyl]-7-(isopropyl-methyl-amino)-8-tri6uoromethyl-l,3-dihydro- benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethanc and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (70 mg, 27%). MS (ISP) 512.4 [(M+H)--]; mp 178 '°C Example 158 7-fIsobutyl-methyl-amino)-8-methyl-4'f3-(5-pvrrolidin-l-ylmethylfL2,4ltria2ol-l-vD-phenvI1-13-dihvdro-benzoib1fL4ldiazepin-2-one The title compound was prepared from 4-(3-(5-hydroxymethyl-[l,23]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as an ofif-white solid (106 mg, 52%). MS (ISP) 486,5 [(M+H)']; mp 164 °C. Example 159 4-[3-(5-Cyclopropylaminomethyl-fL2,4ltriazol-l-yl]-phenyl1-7-(isobutyl'methyl* amino)-8-methyl-1.3-dihydro-benzofb][L4ldiazepin-2-one The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7- (isobutyl-methyl-amino)-8-methyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (108 mg, 55%). MS (ISP) 472.4 [(M+H)--]; mp 114 °C. Example 160 8-Chloro-7-isopropylamino-4-f3-f3-methyl-isoxazol-5-vD-phenyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one The title compound was prepared from (4-chloro-5-isopropylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example Ml 12) (0.16 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (120 mg, 93%). MS (ISP) 409.4 [(M+H)--]; mp 225 °C. Example 161 8-Chloro-4-f3-(5-hvdroxvmethyl-\|-l,2,3ltriazol-l-vD-phenyll-7-isopropylamino-13-dihvdro-benzofbl [ L4l diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-isopropylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M113) (0.37 g, 0.60 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (209 mg, 82%). MS (ISP) 425.4 [(M+H)--]; mp 250 °C. Example 162 8-Chloro-7-(methyl-propyl-amino)-4-f3-(5-hvdroxvmethyl-[L2,4ltriazol-l-yl)-phenyl! -1,3-dihydro-benzo f b1 f 1.41 diazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 14) (1.47 g, 2.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid(1.0 g, 99%). MS (ISP) 439.5 [(M+H)--]; mp 192 °C, Example 163 8-Chloro-4-r3-(5-hvdroxvmethyl-rL2.4ltriazol-l-yl)-phenyll-7-risobutyl-methyl-aminoyl3-dihvdro-benzofbirL4ldiazepin-2-one The title compound was prepared from (RS)-[4-chloro-5-(isobutyi-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 15) (0.61 g, 0.93 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Hght brown solid (290 mg, 69%). MS (ISP) 453.5 [(M+H)--]; mp 195 °C Example 164 8-ChlorO-7-(methyl-propyl-amino)-4-f3-(5-pyrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yIVphenyll-l,3-dihvdro-benzo[b1fl,4]diazepin-2-one The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (114 mg, 46%). MS (ISP) 492.3 [(M+H)1; mp 183^0. Example 165 8-Chloro-7'fisobutyl-methyl-aminoV4-r3-(5-pvrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yl)-phenyl] 13-dihvdro-benzo f bl [ 1.41 diazepin-2-one The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl- [l,2,4]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro- benzo[b] [l,4]diazepin-2-One (Example 163) (200 mg, 0,44 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45, Obtained as a light yellow solid (99 mg, 44%). MS (ISP) 506.4 [(M+H)+]; mp 164 °C. Example 166 8-Chloro-4-f3-(5-dimethylaminomethyl-[L2.4ltriazol'l-yl)-phenyl1-7-fmethyl-propyl-amino)-1.3-dihydro-benzorblfl,4ldiazepin-2-one The title compound was prepared-from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4ltriazol-l-yl)-phenyl]-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethyiamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (93 mg, 540%). MS (ISP) 466.4 [(M+H)--]; mp 170 X, Example 167 8-Chloro-4-r3-(5-cvclopropylaminomethyl-fL2,4]tria2ol-l-yl)-phenyl1-7-fmethyl' propyl-aminoyl,3-dihvdro-benzofbUL4ldiazepin-2-one The title compound was prepared from 8-chIoro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymiethyl-[l,2,4]tria2ol-l-yl)-phcnyi)-13-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (95 mg, 40%). MS (ISP) 478.4 [(M+H)--]; mp 123 ^'C Example 168 4-f3-(5-Hvdroxymethyl-fL2,4]triazol-l-\i)-phenyll-7-fisobutyl-methyl-aminoV8-methyl'l,3-dihydro-benzofb1 (h4]diazepin-2-one Prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyi-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazoM-yl]-phenyl}-propion)iamino)-phenyi]-carbamic acid tert-butyl ester (Example Ml 16) (0.96 g, 1.51 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (480 mg, 73%). MS (ISP) 433.6 [(M+H)+]; mp 191X. Example 169 7-(methyl-propyl-aminoV4'f3-fL2,4ltriazol-l-yl-phenyl)-8-trifluoromethyM3-dihvdro-benzorbUl.4ldiazepin-2-one The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M117) (0.31 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light ydlow solid (192 mg,78%). MS (ISP) 443.4 [(M+H)--]; mp 185 C. Example 170 7-(methyl-propyl-aminoV4-(3-[l,23ltriazol-l-yl-phenvD-8-tiifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 18) (0.33 g, 0.59 mmol) by treatment -with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (115 mg, 44%). MS (ISP) 443.4 [(M+H)+]; mp 147 X. Example 171 7-(I$obutyl-methyl-aminoV4-(3-pyrazoI-l-yl-phenyl)-8-trifluoromethyl-13-dihydro-benzo fbl \ 1,41 diazepin-2-one The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 19) (0.49 g, 0.85 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (324 mg, 83%). MS (ISP) 454.4 [(M-H)-]; mp 182 X. Example 172 4-f8-(Isopropyl-methyl-amino)-4-oxQ-7-trifluoromethyl-4,5-dihvdro-3H-benzofb1[L4ldiazepin-2-yl1-pyridine-2-carbonitrile The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(isopropyI-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M120) (0.67 g, 1.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (210 mg, 41%). MS (ISP) 400.3 [(M-H)-l; mp 189 °C. Example 173 8'Chloro-7-fisobutyl-methyl-aminoV4-f3-fl.2.4ltriazol-l-yl-phenvD-13-dihvdro-benzofbl rL4ldiazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-phenyl}-carbamicacidtert-butyl ester (Example M121) (0.76 g, 1.41 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a li^t orange solid (530 mg, 89%), MS (ISP) 423.4 [(M+H)-]; mp 213 °C. Example 174 7-fIsobutyl-methylaminoV4-(3-fl,2.4ltriazol-l-yl-phenvD-8-trifluoromethyl-l,3-dihvdro-benzofbiri,4ldiazepin-2-one Prepared from {5-(isobutyl-methyl-amino)-2-[3oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M122) (0.50 g, 0,87 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (350 mg, 88%). MS (ISP) 457.5 [(M+H)-]; mp 198 X, Example 175 8-Chloro-7-(isobutvI-methyl-aminoV4-(3-[L23ltriazol-l-yl-phenylyl3-dihvdro-benzoFbl f L4]diazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M123) (0.17 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a hght yellow solid (100 mg, 75%), MS (ISP) 423.5 [(M+H)--]; mp 85 °C. Example 176 7-fIsobutyl-methyl-aminoV4-f3-fl.23ltriazol-l-'vi-phenyl)-8-trifluoromethvM3-dihvdro-benzorblfL4]diazepin-2one The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[ 1,2,3 ] triazol- l-yl-phenyl)-propionyiamino] -4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M124) (0.44 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (170 mg, 49%), MS (ISP) 457.5 [(M+H)--]; mp 202 °C Example 177 4-f3-Imida2ol-l-yl-phenvD-7-isobutylamino-8-trifluoromethyI-13-dihvdro-benzofbl ri,4ldiazepin-2-one The title compound was prepared from {2-[3-(3-imida2ol-l-yl-phenyl)-3-oxo- . propionylamino] -5-isobutylamino-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M125) (0.43 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (260 mg, 76%). MS (ISP) 442.4 [(M+H)1; mp 221 °C. Example 178 8-ChlorO'4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-L3-dihvdro-benzofb] f h4]diazepin-2-one The title compound was prepared from {4-chlorO-2-[3-(3-imidazoM-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-phenyl}-carbamic acid tert-butyl ester (Example M126) (0.33 g> 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (240 mg, 94%). MS (ISP) 408,4 [(M+H)+]; mp 212 °C. Example 179 8-Chloro-7-(isobutyl-aminoV4-f3-ri,2.3ltriazol-l-yl-phenylyl3-dihvdro-benzofbl [l,4ldiazepin'2-one The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazoH-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M127) (0.22 g, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (90 mg, 53%). MS (ISP) 407.3 [(M-H)']; mp 249 °C. Example 180 7-(Isobutyl-amino)-4-r34L23ltriazol-l-vI-phenyl)-8-trifluoromethyl-13-dihvdro-benzofbl f l,4ldiazepin-2-one The title compovmd was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionyiamino]-4-trifluoromethyl-phenyl}-carbamic add tert-butyl ester (Example M128) (0.34 g, 0.61 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (150 mg> 56%). MS (ISP) 443.4 [(M+H)+]; mp 212 °C. Example 181 8-Chloro-7-(isobutyl-aminoV4-f3-[L2,4ltriazol-l-yl-phenvD-L3-dihvdro-benzofbl [L4ldiazepin-2-one The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carban:iic acid tert-butyl ester (Example M129) (0.39 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light orange solid (270 mg, 89%). MS (ISP) 407.3 [(M-H)-]; mp 222 X. Example 182 7-fIsobutyl-aminoV4-f3-[L2.4ltriazol-l-yl-phenyl)-8-trifluoromethyl-L3-dihvdrO' benzo[bl f 1.4]diazepin-2-one The title compound was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M130) (0.43 g, 077 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (270 mg, 61%). MS (ISP) 441.3 [(M-H)-]; mp 191X. Example 183 8-Chloro-7-fethyl-methyl-amino)-4-f3-f4-hvdroxymethyl-thiazol-2-yl)-phenyl-l,3-dihydro-benzoTbl f l,4]diazepin-'2-one The title compound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.14 g). MS (ISN) 439.2 [(M-H)]; mp 136-137 °C. Example 184 8-Chloro-4-f3-f4-hvdroxymethyl-thiazol-2-yD-phenyll-7-fmetfayl-propyl-amino)-1,3-dihydro-ben20 [b] [ 1.4] diazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-t±iiazol-2-yl]-phenyl] -propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0-10 g). MS (ISN) 453.2 [(M-H)-]; mp 211-213 °C Example 185 8-Chloro-4-[3-(4-hvdroxymethyl-thiazol-2-yl)-phenyll-7-(isopropyl-methyl-amino)-L3dihydro-benzo[b1fL4ldiazepin-2-one The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light-brown solid (0.05 g). MS (ISP) 455.2 [(M+H)1; mp 193-195 °C Example 186 8-Chloro-4-f3-(4-hydroxymethyl-thiazol-2-yl)-phenyn-7-(isobutyI-methyl-amino)-L3-dihydrO'benzofb1fl,4ldiazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyi -amino)-phenyI]-carbamic acid tert-butyl ester (0.23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.32 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g). MS (ISP) 469.1 [(M+H)--]; mp 135-136 °C Example 187 8-Chloro-7-fetfayl-methyl-aminoV4-r3-f4-hydroxvmethyl-oxa2ol-2-yl)-phenyn-l,3-dihvdro-benzofbl f l,4ldiazepin-2-one The title compound was prepared from [2-amino-4-Chloro-5-(ethyl-methyl-amino)-phenylj-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxyxnethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedxire N. Obtained as a yellow solid (0.10 g). MS (ISN) 423.1 [(M-H)-]; mp 165-166 °C. Example 188 8-Chloro-4-[3-f4-hvdroxvmethyl-oxazol-2-yD-phenyll-7-fmethyl-propyl-aminoV L3-dihvdro-benzofb1fl.4]diazepin-2-one The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g). MS (ISP) 437.2 [(M-H)-]; mp 166-167 °C Example 189 8-Chloro-4-f3-(4-hvdroxymethyl-oxazol-2-yl)-phenyl1-7-fisopropyl-methyl-amino)-L3-dihydro-ben2ofb1 [1.41 diazepin-2-one The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyI]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-l4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a ydlow solid (0.05 g). MS (ISP) 439.3 [(M+H)-]; mp 143-145 X. Example 190 8-ChlorO-4-r3-f4hvdroxvmethyl-oxazol-2-yl)-phenyll-7-fisobutyl-methyl-amino)-13-dihvdro-benzo\|-b][1.4]diazepin-2-one The title compound was prepared from [2-aminO-4-chloro-5-(isobutyl-methyI -amino)-phenyl]-carbamic acid tert-butyl ester (0,23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (0.31 g) (Example Kll) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0,18 g), MS (ISP) 453,3 [(M+H)-]; mp 166-167 °C. Example 191 8-Chloro-7-dimethylamino-4-f3-(4-methylaminomethyl-thiazol-2-yl)-phenyll-1.3-dihydro-benzofb]fL4ldiazepin-2-one al 8-ChIoro-4-f3-(4-chloromethyl-thia2oI-2-yl)-phenyll-7-dimethylamino-13' dihydro-benzo[b][1.4]diazepin-2-one A mixture of 8-chIoro-7-dimethylamino-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.38g) (Example 19) andthionyl chloride (0,1 mL) in CH2Cl2 was heated to 40 -°C for 2 h. The heterogeneous mixture was evaporated in vacuum and the residue was triturated with AcOEt to give the title compound (0,44 g) as a light-brown soHd, MS (ISP) 445.1 [(M+H)+], b) 8-Chloro-7-dimethyiamino-4-f3-(4-methylaminomethyl-thiazol-2-vD-phenyl-l,3-dihydro-ben2orb][l,4]diazepin-2-one A mixture of 8-chloro-4-[3-(4-chloromethyl-thia2ol-2-yl)-phenyl] -7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (89 mg) and KI (3 mg) in a 8M solution of methylamine in EtOH (1 mL) was stirred at 20 °C for 20 h. H2O (25 mL) was acided and the pH of the mixture was set to 11 by acidition of 2N NaOH. The precipitate was collected by filtration and purified by chromatography on silica gel using MeOH as eluent. The product was stirred with 20% aqueous MeOH (10 mL) and the solid was isolated by filtration to give the title compound (49 mg) as a yellow powder, MS (ISP) 440.2 [(M+H)--]; mp 129-130 °C. Example 192 8-Chloro-7-dimethylamino-4-f3-f4-morpholin-4-ylmethyl-thia2ol-2-yD-phenyl1-1.3-dihvdro-benzofbl ri,4ldiazepin-2-one A mixture of 8-chlo^o-4-[3-(4-chloromethyl-thiazol-2-yl)-phenyl]-7-dimethyla^mlo-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one (89 mg) (Example 191a), morpholine (0.17 mL) and KI (3 mg) in EtOH (0.5 mL) was stirred at 60° C for 3 h. H2O (25 mL) was acided to the cooled solution and the precipitate was collected by filtration and purified by chromatography on silica gel using AcOEt/acetone (1:1) as eluent The product was stirred with 20% acjueous MeOH (20 mL) The pH of the mixture was set to 11 by acidition of IN NaOH and the solid was subsequently isolated by filtration to give the title compound (55 mg) as yellow powder. MS (ISP) 496.2 [(M+H)--]; mp 138-143 °C Example 193 8-Chloro-7-dimethylaminO-4-[3-(2-hydroxvmethyl-thiazol-4-vD-phenylyl3-dihydrO'benzorb][L4ldiazepin-2-one a)4-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylaminO'13-dihvdro-benzofb] [L4Tdiazepin-2-one A solution of 3-Oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (2.34 g) (Example K28) and (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example J2) (L57 g) in toluene (16 mL) was heated to 100 C for 5 h. The solvent was evaporated in vacuimi and the crude product was purified by chromatography on silica gel using CH2Cl2/AcOEt (1:20) as eluent. A solution of the purified material (2.4 g) in CH2Cl2/TFA (1:1,30 mL) was stirred at 20 °C for 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated. The residue was crystallized firom AcOEt/EtaO to give 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b] [l,4]diazepin-2-one as light-brown solid. b^8-Chloro-7-dimethylamino-4-f3-(2-hvdroxvmethyl-thiazol-4-yl)-phenyl1-L3-dihvdro-benzofbl f L4ldiazepin-2-one A mixture of 4-(3-bromoacetyi-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-beiizo[b][l,4]diazepin-2-one (0.22 g) and 2-(tert-butylcarbonyl-oxy)thioacetamide (0.11 g) in EtOH (3 mL) was heated at 80 C for 0.5 h. The solution was diluted with AcOEt, washed with saL NaHCOa solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (8 mL) and L5N KOH (8 mL) at 20 °C for 20 min. H2O (30 ml) was acided and the precipitated product collected by filtration to give the title compound (0.9 g) as yellow powder. MS (ISP) 427.3 [(M+H)']; mp 176-178 °C Example 194 4-r3-(2-Amino-thiazol-4-yl)-phenNi1-8-chloro-7-dimethylamino-l.3-dihvdro-benzo [bl f 1.41 diazepin-2-one A mixture of 4-(3-bromoacetyi-phcn>1)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.73 g) (Example 193a) and thiourea (0,13 g) inTHF (10 mL) was heated to 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and vsith brine. The organic layer was dried and evaporated and the residue was stirred \%-ith CH:Q: to give the title compound (0.14 g) as yellow solid, MS (ISN) 410.2 [(M^H)-]; mp 247-248 °C Example 195 8-Chloro-7-dimethylamino-4-f3-(2-ethylamino-thiazol-4-yl)-phenyl1-13-dihvdro-benzofbl [L4ldiazepin-2-one A mixture of 4-(3-bromoacetyl-phenyi)-8-chloro-7-dimethylamino-13-dihydro-benzo[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THE (3mL) was heated at 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et20 to give the title compound (24 mg) as yellow solid. MS (ISP) 440.3 [(M+H)--]; mp 122-123 °C. Example 196 N-{4-f3-(7-ChlorO'8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb1fL4ldiazepin-2-vD-phenyl1-thiazol-2-yl}-guanidine A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-amidino-thiourea (35 mg) in THE (3mL) was heated at 60 'C for 1 h- The mixture was diluted with AcOEt and washed with sat NaHCOa solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/MeOH (20:1) as eluent. The purified product was crystallyzed from acetone to give the title compound (22 mg) as yellow solid. MS (ISP) 454.2 [(M+H)--]; mp 221 X dec. Example 197 8-Chloro-7'dimethylamino-4-(3-[2-(pyridin-4'ylamino)-thiazol-4-yl]'phenvU-13-dihvdro-benzo[b1[1.4ldiazepin-2-one A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and l-(4-pyridyl)-2-thiourea (46 mg) in THE (3mL) was heated at 60 X for 45 min. The mixture was dfluted with AcOEt and washed with sat NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was triturated with Et20 to give the title compound (55 mg) as yellow solid. MS (ISP) 489.2 [(M+H)']; mp 231-234 °C. Example 198 8-ChlorO-4-f3-(2-metfayl-Oxazol-4-yl)-phenyl1-7-(methyl-propyl-amino)-l,3-dihydro-benzorb1fl>4'idiazepin-2-one The title compoimd was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (0.17 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.07 g). MS (ISP) 423.2 [(M+H)-]; mp 163-164 X. Example 199 4-f3-(4-HydrGxymethyl-thiazol-2-yl)-phenyl-8-methyl-7-rmethyl-propyl-aminoV L3-dihvdro-benzofb1 f l.>41diazepin-2-one The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.09 g). MS (ISP) 435.3 [(M+Hr];mp 222-224^0. Example 200 4-f3-f4-Hvdroxymethyl-oxazol-2-yl)-phenyl1-8-methyl-7-fmethyl-propyi'aminoV L3-dihydro-benzo[b1fl.4]diazepin-2-one The title compound was prepared from [2-amino-4-methyl-5-(meth)i-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4- (tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example Kll) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.16 g). MS (ISP) 419.3 [(M+H)+]; mp 200-202 °C. Example 201 7-Dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-8-trifluoromethyl-1,3 - dihvdro-benzo f b1 [ 1 A] diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.12 g). MS (ISP) 461.2 [(M+H)1; mp 198-199 °C, Example 202 7-Dimethylamino-4-[3-(4-hvdroxvmethyl-oxazol-2-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofblfL4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phen)d]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.11 g). MS (ISP) 445.0 [(M+H)]; mp 197-198 °C Example 203 4-f3-f4-Hvdroxymethyl-thiazol-2-y!VphenvI1-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2one The title compound was prepared from [2-amino-5-(methyl-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tcrt-butyl ester (0.17 g) (Example J35) and 3-0X0-3- [3- [4-(tetrahydro-pyran-2->'iox>TOCthyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cydizcd by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g). MS (ISP) 489.2 [(M+Hr];mp 177-180^ ^3B^mple 204 7-Dimethylamino-4-f3-(5-hvdroxymeth\i-fL3.4]thiadiazol-2-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzofb]fl.4ldia7epin-2-one The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyi ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadia2ol-2-yl]-phenyi}-propionicacid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as ofif-white solid (0.06 g). MS (ISP) 462.1[(M+H)'-]; mp 242-246 X. Example 205 7-Dimethylamino-4-{3-r5-(2-hvdroxv-ethvD-fL3,4lthiadiazol-2-yl1-phenylt-8-trifluoromethyl-13-dihydro-ben2o Fb ] f L4l diazepin-2-one The title compoxmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,3,4]thiadiazoI-2-yl}-phenyi)-propionic acid tert-butyl ester (0.24 g) (Example K3I) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a oflF-white solid (0.06 g). MS (ISN) 474.2 [(M-H)-]; mp 234-237 X, Example 206 7-Dimetfaylamino-4-f3-(5-hvdroxvmethyI-fl3.4loxadiazol-2-yl)-phenyn-8-trifluoromethyl-13-dihvdro-benzo f b] [ 1,41 diazepin-2-one The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (1.44 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3>4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (2.17 g) (Example K32) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g). MS (ISP) 463.2 [(M+NH4)+]. Example 207 7-Dimethylamino-4-(3-r5-(2-hvdroxv-ethyl)-[13.4loxadia2ol-2-yl1-phenvU-8-trifluoromethyl-13-dihydro-benzo f b] f 1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [1,3,4] oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (0.23 g) (Example K33) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g). MS (ISP) 460.2 [(M+H)--]; mp 237 °C dec. Example 208 7-Dimethylamino-4-(3-oxazol-4-yl-phenyl)-ig-trifluoromethyl-L3-dihvdro-benzofbl f h4ldiazepin-2-one The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K34) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (50 mg). MS (ISP) 415.2 [(M+H)--]; mp 218-219 °C. Example 209 7'Dimethylamino-4-f3-tfaia2ol-4-yl-phenyl)-8-trifluoromethyl-L3-dihydro-benzofbl f l,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (109 mg) (Example K35) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (61 mg). MS (ISP) 431.2 [(M+H)--]; mp 200 °C dec. Example 210 7-Dimethylamino-4-[3-(2-methyl-oxazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofb] f L4ldiazepin-2'One The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(2-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.18 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.04 g). MS (ISP) 429.3[(M-hH)-']; mp 192-193 °C. Example 211 7-DimethyIamino-4-f3-(5-methyl-oxazoI-4-yn-phenyn-8-trifluoromethyl-L3-dihvdro-benzofb1fl,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyi)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,18 g) (Example K36) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.13 g). MS (ISP) 429.3 [(M+H)--]; mp 238-239 °C. Example 212 7-Dimethylamino-4-[3-(2-methyl-5-propyI-oxa2ol-4-yi)-phenyl-8-trifluoromethyl-1.3-dihydro-benzo[b]fl.4]diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (80 mg) (Example J6) and 3-[3-(2-methyl-5-propyl-oxazoI-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K37) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as pale-yellow solid (20 mg). MS (ISP) 471,2 [(M+H)'];mp 211-212 °C. Example 213 7-Dimethylamino-4-[3-(5-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzofb] [ L4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-[3-(5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,19 g) (Example K38) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0,06 g). MS (ISP) 445.2 [(M+H)1; mp 214-215 °C Example 214 7-Dimethylamino-4-[3-(2,5-dimethyl-thiazol-4-yl)-phenyn-8-trifluoromethyM,3-dihydro-benzofbl f L4]diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (48 mg) (Example J6) and 3-[3-(2>5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (50 mg) (Example K39) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (38 mg). MS (ISP) 459.2 [(M+H)--]; mp 208-209 X. Example 215 7-Dimethylamino-4-f3-(2-hvdroxymethyIthiazol-4-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one a)4(3-Bromoacetyl-phenyl)-7-dimethylamino-'8-trifluoromethyl*1.3-dihydro-benzofbl f l,4ldiazepin-2-one A solution of (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (0.32 g) and 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyi ester (0.43 g) (Example K28) in toluene (3 mL) was heated to 100 °C for 2 L The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using AcOEt /Hexan(l:3) as eluent A solution of the purified material (0.57 g) in CH2Cl2/TFA (1:1,7 mL) was stirred at 20 ®Cfor 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated to give crude 4-(3-bromoacetyl-phenyl)-7-dimethylainino-8-trifluoromethyM,3-dihydro-benzo[b][l,4]diazepin-2-one (0.22 g) as light-brown solid. b) 7-Dimethylamino-4-f3-(2-hvdroxymethyl-thiazol-4-yl)-phenyl1 -8-trifluoro-methyl-1.3-dihydro-benzo fbl F1,41 diazepin-2-one A mixture of 4-(3-bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-l>3-dihydro-benzo[b][l,4]diazepin-2-one (0.40 g) and 2-(tert.-butylcarbonyloxy)thio-acetamide (0.21 g) in EtOH (5 mL) was heated at 80 'C for 0.5 h. The solution was diluted with AcOEt, washed with sat NaHCOs solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (5 mL) and L5N KOH (5 mL) at 20 ^'C for 20 min. H2O was acided and the predpitated product coDected by filtration and purified by chromatography on silica gel using AcOEt as eluent to give the title compound (0.01 g) as yellow solid. MS (ISP) 461.1 [(M+H)--]. Example 216 7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-methyl-thia2ol-4-yl)-phenyil-8-trifluoromethyl-1,3-dihydro-benzofb1 \ 1.41 diazepin-2-one The title compound was prepared firom (2-an:iinO-5-dimethylamino-4-trifluoro-methyi-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-mediyl-2-(tetrahydro-pyran-2-yloxymedi)d)-thiazol-4-yl]-phen)i}-propionicadd tert-butyl ester (0.26 g) (Example K40) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as light-yellow solid (0.11 g). MS (ISP) 475.2 [(MH-H)I; mp 190-193 °C Example 217 7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-propyl'thiazol-4-vD-phenyl1-8-trifluoromethyl-h3-dihydro-benzofb1 [1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (79 mg) (Example J6) and 3-oxo-3-{3-[5-propyl-2-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (138 mg) (Example K41) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (45 mg). MS (ISP) 503.2 [(M+H)1; mp 112-114 °C Example 218 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-2-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzorbUl,4ldiazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionicacid tert-butyl ester (0.26 g) (Example K42) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid(0.11 g). MS (ISN) 473.0 [(M-H)']; mp 226-227 '°C. Example 219 7-Dimethylamino-4-f3-(5-hvdroxvmethyl-thiazol-4-yl)-phenyll-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{[5-(tetrahydro-pyran-2-yioxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (0,25 g) (Example K43) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0-08 g). MS (ISN) 459.3 [(M-H)-]. Example 220 4-(3-f5'f(CvcIopropylmethyl-amino)-methyll-thiazol-4-yn-phenyl)-7-dimethylamino-8-trifluoromethyl-L3-dihvdro-benzorb1fL4ldiazepin-2-one A mixture of 7-dimethylamino-4-[3-(5-hydroxymethyl-thiazol-4-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 219) (65 mg) and thionyl chloride (0.015 mL) in CH2Cl2 (0.3 mL) was stirred at 20 °C for 1 h. The heterogeneous mixture was evaporated in vacuum and the residue was suspended in EtOH (0.5 mL). Aminomethyl-cyclopropane (0.12 mL) and KI (3 mg) were acided and the mixture was stirred at 80 ^'C for 5 h. The mixture was evaporated in vacuum ant the residue was purified by chromatography on silica gel using AcOEt/MeOH (50:1) as eluent The resulting product was stirred with 20% aqueous MeOH (10 mL)) the pH of the mixture being set to 11 by the acidition of IN NaOH, and the solid was isolated by filtration to give the title compound (44 mg) as off-white solid. MS (ISP) 514.3 [(M+H)--]; 157-158° C. Example 221 7-Dimethylamino-4-f3-(2-isopropyl-lH-imidazol-4-yl)-phenyl1-8-trifluoromethyl-L3-dihydro-benzo[birL4ldiazepin-2-one The title compotmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbanuc acid tert-butyl ester (0.13 g) (Example J6) and 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.20 g) (Example K44) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.10 g). MS (ISP) 456.4 [(M+H)--]; mp 150 Xdec. Example 222 4-f3-(5-Hvdroxymethyl-[13.4lthiadiazol-2-yl)-phenyl-7-(methyl-propyl-aminoV8-trifluoromethyl-13-dihvdro-benzo[b1fL4ldiazepin-2-one The title compound was prepared from [2-amino-5-(methyi-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (0.17 g) (Example J35) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[13>4]thiadiazol-2-yi]-phenyl}-propionic acid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.02 g). MS (ISP) 490.2 [(M+H)--]; mp 193-194 --C. Example 223 8-Chloro-7-dimethylamino-4-l3-r5-(2-hvdroxv-ethyl)-ri,3,4lthiadiazol-2-yl]-phenyl)-13-dihvdro-ben2ofb1fl.4]diazepin-2-one The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (0.15) and crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phenyl)-propionicacid tert-butyl ester (0.24 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g). MS (ISN) 440.2 [(M-H)-]; mp 198-200 °C. The active ingredient having a suitable particle size, the crystalline lactose and the microcrystaUine cellulose are homogeneously mixed with one another, sieved and thereafter talc and magnesium stcarate are admixed. The final mixture is filled into hard gelatine capsules of suitable size. Example I Tablets of the following composition are produced in a conventional maimer mg/Tablet Active ingredient 100 Powdered, lactose 95 White com starch 35 Polyvinylpyrrolidone 8 Na carboxymethylstarch 10 Magnesium stearate _2 Tablet weight 250 Example II Tablets of the following composition are produced in a conventional manner: mg/Tablet Active ingredient 200 Powdered, lactose 100 White corn starch 64 Polyvinylpyrrolidone 12 Na carboxymethylstarch 20 Magnesium stearate ^ Tablet weight 400 Example III Capsules of the following composition are produced: mg/Capsule Active ingredient 50 Crystalline, lactose 60 Microcrystalline cellulose 34 Talc 5 Magnesium stearate 1 Capsule fill weight 150

Full Text

Case 20871
Dihydro-benzo[b] [l,4]diazepin-2-one derivatives as mGluR2 antagonists II
The present invention relates to compounds of general formula I

selected from the group consisting of halogen, lower alkyl, fluoro-lower alkyl, C3-C6-cycloalkyl, lower alkoxy and fluoro-lower alkoxy;

R2 is -NR'R-, fluoro4ower alkoxy or
S-oxo-piperazin-l-yl, pyrrolidin-l-yl or piperidm-l-}d, which rings are optionally substituted by R-;
R' is hydrogen, lower alkyl, C3-C6-cycloalkyl, fluoro-lower alkyl or 2-lower alkoxy lower alkyl;
R- is hydrogen, lower alkyl,

and to their pharmaceutically acceptable addition salts.

It has surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists. Compounds of formula I are distinguished by valuable therapeutic properties.
In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, which is sent out by a neuron, with a neuroreceptor.
. L-glutamic acid, the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms hgand-controUed ion channels. The metabotropic glutamate receptors (mGluR) form the second main group and, furthermore, belong to the family of G-protein-coupled receptors.
At present, eight different members of these mGluR are known and of these some even have sub-types. On the basis of structural parameters, the different influences on the synthesis of secondary metabolites and the different affinity to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGluRl and mGluRS belong to group I, mGluR2 and mGluR3 belong to group II and mGluR4, mGluR6, mGluR7 and mGluRS belong to group III.
Ligands of metabotropic glutamate receptors belonging to the group II can be used for the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits.
Other treatable indications in this connection are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are chronic and acute pain, Himtington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutarnate-defidency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, opiate addiction, anxiety, vomiting, dyskinesia and depressions.

Objects of the present invention are compounds of formula I and their pharmaceutically acceptable salts per se and as pharmaceutically active substances, their manufacture, medicaments based on a compound in accordance with the invention and their production, as well as the use of the compounds in accordance with the invention in the control or prevention of illnesses of the aforementioned kind, and, respectively, for the production of corresponding medicaments.
The compounds of formula I can also be used in form of their prodrugs. Examples are esters, N-oxides, phosphate esters, glycoamide esters, glyceride conjugates and the like. The prodrugs may add to the value of the present compounds advantages in absorption, pharmacokinetics in distribution and transport to the brain.
All tautomeric forms of the compounds of the invention are also embraced herewith.
Preferred are compounds of formula I, wherein X is a single bond. Exemplarly preferred are compovmds, wherein R^ is trifluoromethyl, and especially those wherein R is cyano, for example the following compounds:
4-(4-oxo-8-pyTrolidin-l-yl-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-pyridine-2-carbonitrile,
4-[8-(cyclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ l,4]diazepin-2-yl] -pyridine-2-carbonitrile,
4-[8-(cyclopropylmethyl-amino)-4-oxo-7-trifiuoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl]-pyridine-2-carbonitrile,
4-[4-oxo-8-(2,2,2-trifluoro-ethoxy)-7-trifluoromethyI-4,5-dihydro-3H-ben2o[b] [l,4]diazepin-2-yl]-pyridine-2-carbonitrile, and
4-[8-(isopropyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ 1,4] diazepin-2-yl] -pyridine-2-carbonitrile.
Further preferred are compounds, wherein X is a single bond, R^ is trifluoromethyl and R is an optionally substituted five-membered aromatic heterocyde, which may be substituted by halogen, fluoro-lower alkyl, fluoro-lower alkoxy, cyano, -(CH2)n-NR'R-, -(CH2)n-C(O)-0R-, -(CH2)n-C(O).NR'R-, .(CH2)n-S02-NR'R-, -(CH2)„-C(NH2)=NR-, hydroxy, lower alkoxy, lower alkyithio, or by lower alkyl, which is optionally substituted by fluoro, hydroxy, lower alkoxy, cyano or carbamoyloxy. Examples of such compounds are the following:

7-dimethylamino-4-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimethylaimnO-4-[3-(2-metiiyl-2H-pyra2ol-3-yl)-phenyi]-8-tri dihydro-benzo [b] [ 1,4] diazepin-2-one,
7-dimethylamino-4-(3-imidazol-1 -yl-p}ienyl)-8-trifluoromethyl- 1,3-dihydro-
benzo[b] [l,4]diazepin-2-one,
4-[3-(3-methyHsoxa2ol-5-yl)-phenyl]-7-(methyl-propyl-ainino)-8-trifluoromethyl-1,3-dLhydro-benzo [b] [ 1,4] diazepin-2-one,
7-(isobutyl-methyl-amino)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-8-trifluorom l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-(isopropyl-inethyl-ainmo)-4- [3-(3-methyl-isoxa2ol-5-yl)-phenyl] -8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-(isobu1yl-methyl-amino)-4-(3-{5-[(isopropyl-methyI-ainino)-inethyl]-
[ 1,2,3] triazol-1-yl}-phenyl)-8-trifluoromethyl-l,3-dihydro-ben2o [b] [ 1,4] diazepin-2-
one,
7-(isopropyl-methyl-amino}-4-[3-(5-pyrroKdin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl] -8-txifluorometliyl-l,3-dihydro-benzo [b] [1,4] diazepin-2-one,
7-(methyl-propyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-8-trifluoromethyl-l,3 dihydro-benzo[b][l,4]diazepin-2-one,
7-(isobutyl-methyl-amino)-4-(3-[l,2,3]tria2ol-l-yl-phenyl)-8-trifluoromethyl-1,3 dihydro-benzo [b] [ l,4]diazepin-2-one,
4-(3-imidazol-l-yl-phenyl)-7-isobutylaniino-8-trifluoroinethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimeliiylaiiuno-4-[3-(4-hydroxymethyl-liiiazol-2-yl)-phenyl]-8-trifluoronieA^ l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-dimethylamino-4-[3-(4-hydroxyniethyl-Oxazol-2-yl)-phenyl]-8-1xifluoronieli^ l,3-dihydxo-ben2o[b] [1,4] diazepin-2-one,
4-[3-(4-hydroxynxethyl-thiazol-2-yl)-phenyl]-7-(niethyl-propyl-anriino)-8-trifluoroniethyl-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one, and
4-[3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-phenyl]-7-(niethyl-propyI-aniino) trifluoromethyl-1,3-dihydro-ben2o [b] [ 1,4] diazepin-2-one.

Also preferred are compounds, wherein X is a single bond, and R is chloro, tor example the following compounds:
8-diloro-7-isobutyla,in-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-
ben2o[b] [l,4]diazepin-2-one,
8-cUoro-7-(methyl-propyl-amino)-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydrO-benzo[b] [l,4]diazepin-2-one,
8-chloro-7-(isopropyl-methyl-amino)-4-[3-(5-pyrrolidin«l-ylmethyI-[l,2,3]triazoI-l-yl)-phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one,
8-cHoro-7-(isobutyl-methyl-amino)-4-[3-(5-pyrroHdin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one,
8-chloro-4-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-8-chloro-7-(isopropyl-methyl-amino)-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one,
4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazl-yl)-phenyl]-8-chloro-7-(isobutyl-methyi-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
8-chloro-7-(isobutyl-methyI-amino)-4-[3-(5-piperidin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one,
8-chlorO-7-(isopropyl-methyl-amino)-4-(3-{5-[(isopropyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-13-dihydro-benzo[b][l,4]diazepin-2-one,
8-chloro-4-(3-{5-[(isobutyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-7-(isopropyl-methyl-amino)- 1,3-dihydro-benzo [b] [1,4] diazepin-2-one,
8-chloro-7-isopropylamino-4-[3-(3-methyl-isoxazol-5-yl)-phenyi]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
8-chloro-7-(isobutyl-methyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
8-chIoro-4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-1,3-dihydro-benzo [b] 11,4] diazepin-2-one,
8-chloro-7-(ethyl-methyl-amino)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one
8-chloro-4-[3-(4-hydroxymethyi-thiazol-2-yl)-phenyl]-7-(methyl-propyl-amino)-13-dihydro-benzo[b]l [l,4ldiazepin-2-one

7-(ethyl-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimethylamino-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-(isobutyi-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one>
7-(isobutyl-methyl-amino)-8-methyi-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, and
4-(3-{5-[(cyclopropylmethyl-amino)-methyI]-[l,2,3]triazol-l-yl}-phenyl)-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one.
Preferred are further compounds, wherein R is -N(CH3)2 or pyrrolidine. Also preferred are compounds, wherein R2 is isopropyl-amino, isopropyl-methyl-amino, isobutyl-amino or isobutyl-methyl-amino.
Preferred compounds of formula I in the scope of the present invention are further those, wherein R is cyano or an optionally substituted five-membered aromatic heterocycle, which may be substituted by -CH2OH or -CH2N(CH3)2.
The term -lower alkyl- used in the present description denotes straight-chain or branched saturated hydrocarbon residues with 1-7 carbon atoms, preferably with 1-4 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl and the like.
The term 'lower alkoxy- denotes a lower alkyl residue in the sense of the foregoing definition bound via an oxygen atom. Examples of'lower alkoxy- residues include methoxy, ethoxy, isopropoxy and the like.
The term -halogen- embraces fluorine, chlorine, bromine and iodine.
The term -fluoro-lower alkyl- means a lower alkyl residue, wherein one or more hydrogen-atoms may be replaced by fluoro.
The term -fluoro-lower alkoxy- denotes a lower alkoxy residue in the sense of the definition herein before, wherein one or more hydrogen-atoms may be replaced by fluoro.
The term -C3-C6-cycloalkyl- means a cycloalkyl group containing 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The term -lower alkylthio- denotes a lower alkyi residue in the sense of the foregoing definition bound via an sulfur atom, for example methylsulfanyl.

The expression -five-membered aromatic heteroqrde' embraces fiirane, thiophene, thiazole, pyrrole, imidazole, pyrazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole and tetrazole. Preferred heterocycles are 1,2,3-triazole, 1,2,4-triazole, isoxazole, l,3-oxa2ole, 1,3-thiazole, 1,3,4-oxadiazole or imidazole,
-Optionally substituted- means that a group may or may not be substituted with one or more, preferably one or two substituents independently selected from the specified group.
The term -pharmaceutically acceptable addition salt- refers to any salt derived from an inorganic or organic acid or base.
The compounds of general formula I and their pharmaceutically acceptable salts can be manufactured according to methods, which process comprises
a) reacting a compound of formula II

which subsequently undergoes deprotection of the amino group and cyclization, to obtain a compound of formula

1
According to scheme A, compounds of general formula I, in which X, Y, R1 R2 and R3 are as described above, can be prepared from compounds of general formula II via an acyiation-deprotection-cyclization sequence;
For example reacting compounds of general formula II with a dioxinone IV, in which Y and R3 are as described above> in an inert solvent such as toluene or xylene at elevated temperatures, preferably between 80 °C and 160 °C gives rise to compounds of general formula III.
Alternatively, compounds of general formula III can also be prepared by for example reaction of a compound of general formula II with a p-ketoester (general formula rVa), in which Y and R^ are as described above using the same conditions as described for the reaction with the dioxinones.
Afterwards, deaving the BOC protecting group in compounds of general formula III and concomitant cydization of the deprotected compound yidds the desired compounds of general formula I. Any other suitable amino protecting group, such as e.g- Fmoc or benzyloxycarbonyl (Z), can be altemativdy used instead of the BOC group.

The deprotection-cyclization step can be carried out by treating the compounds of general formula III with for example a Bronsted add such as trifluoroacetic add in an inert solvent such as dichloromethane (DCM). The reaction is preferably carried out at temperatures between 0°C and 50 °C- It may be advantageous to use also anisole or 1,3-dimethoxybenzene as a carbocation scavenger in the reaction mixture.

According to scheme B, compounds of general formula 11 in which R^ is phenyl optionally substituted as described above for compounds where X is a single bond and R is as described above, can be prepared by different routes depending on the nature of R3 from the iodo-compounds of general formula V, in which R3 is as described above. As shown in scheme B, the key step is a coupling reaction of Suzuki-type to produce compounds of the general formula Via.
Compounds of general formula II, in which R1, R3 and X are as described above can be prepared according to scheme B, by reducing the nitro group in compounds of general formula Via to the amino group. The reduction can for example be carried out using hydrogen gas in presence of a suitable catalyst like for example Raney-Nickel or Palladium on carbon. Another possible reduction method is using stannous (II) chloride (SnCl2-2H2O) in ethanol at temperatures between 70 --C and 80 °C (as described in Tetrahedron Lett, 1984,25,839), or alternatively in polar aprotic solvents, like DMF, DMA or NMP and the like, optionally in the presence of bases, like for example pyridine or triethylamine and the like, at temperatures between 0°C and 80 °C. Another suitable method is using zinc-powder in the presence of ammonium

chloride in protic solvents like for example water or ethanol at temperatures between 20 °C and 80 °C. The exact conditions for the respective compounds of general formula II can be found in the experimental part.
Compounds of general formula V, in which R1 is as described above, can be prepared by different routes depending on the individual residue R2:

As shown in scheme C, compound Bl can be prepared from the commercially available 5-chloro-2-nitroaniline by iodination to give the synthetic intermediate Al, which in turn can be protected to yield the compound BL
The iodination step can be carried out by for example using iodine monochloride in acetic acid in the presence of sodium acetate. The reaction can be for example carried out at temperatures between 20°C and 80 °C.
The protection of the amino function can be applied to a number of commercially available starting materials or compounds synthesized by anyone skilled in the art to produce the corresponding 2-nitroanilines with the general formula VII, in which X is a single bond and R1 is as described above. This transformation leads to the key intermediates of the general formula VIb, and the exact conditions for the respective compounds used in this invention can be foimd in the experimental part.
) One possibility for the protection of the amino function is for example reacting compounds of general formula VII with di-tert-butyl-carbonate in the presence of a base such as cesium carbonate. The reaction can be carried out in polar solvents such as acetone or butanone and the like at temperatures between 20 °C and 60 °C.

Alternatively, the protection of the amino group can be achieved by preparing the intermediate isocyanate by treatment of compoimds of the general formula VII with diphosgene, preferably in aprotic solvents such as ethyl acetate or 1,4-dioxane at temperatures from 0 °C to 100 °C, and subsequent treatment of the isocyanate with tert. butanol in solvents such as dichloromethane or 1,2-dichloroethane and the like at temperatures between 20 °C and 85 °C to give the desired compoimds of general formula Vlb.
Another suitable method to achieve this protection step is the intermediate formation of a di-BOC compound by treatment of compounds of the general formula VII with di-tert.-butyl-carbonate in the presence of DMAP in an aprotic solvent such as tetrahydrofuran and the like, followed by selective removal of a single BOC-group by treatment with a Bronsted-acid, like e.g. TFA, in aprotic solvents such as dichloromethane, chloroform or 1,2-dichloroethane at temperatures between 0 °C and 20 °C to give the desired compounds of general formula VIb.
According to scheme D, compounds of general formula VII in which R1 is pyrrol- 1-yl optionally substituted as described above, X is a single bond and R is chloride, can be prepared from known 5-chloro-2-nitro-l,4-phenylenediamine [CAS-No. 26196-45-2] by selective condensation of the 4-amino-group with a suitable substituted 2,5-dimethoxytetrahydrofuran with the general formula VIII, as described in/. Heterocycl Chem, 1988,25,1003.

The reaction is preferably carried out in acidic media, like for example acetic acid or propionic add and the like, at temperatures between 40 °C to 100 °C. The exact conditions for the respective compounds can be found in the experimental part

The corresponding substituted 2,5-dimethoxytetrahydrofurans -with the general formula VIII, in which Ra, Rb and Rc are as described above in the general claim for the pyrrol-1-yl compounds, are either commercially available, or synthesized from the suitable substituted furan, as shown in scheme E. The corresponding substituents can optionally be protected with suitable protecting groups, known to someone skilled in the art, or alternatively can be introduced after the pyrrol ring synthesis. The two-step sequence consists of reacting the furan with bromine in MeOH at low temperature, like for example -35 '°C, followed by treatment with base, like for example triethylamine and the like or potassium carbonate or sodium hydrogen carbonate and the like. The resulting 2,5-dimethoxydihydrofuran with the general formula VIII, in which Ra, Rb and Rc are as described above, can be reduced by catalytic hydrogenation, preferably in MeOH with catalysts like for example Palladium on carbon or Raney-Nickel and the like, to produce the desired 2,5-dimethoxytetrahydrofurans with the general formula VIII. An example for this sequence can be found in Tetrahedron 1971,27, 1973-1996.

The exact conditions for the individual compounds to be synthesized can be found in the experimental part.
As shown in scheme F, compounds of general formula VIc, in which R2 is attached via a nitrogen-atom and is as described above, can be prepared from the intermediate compounds with the general formula VIb - which individual synthesis can be found in the experimental part - by a nucleophilic substitution reaction with the respective amines in the presence of a suitable base.

The reaction is preferably carried out in a polar, aprotic solvent such as dimethyl formamide, N-methyl-pyrrolidone or dimethyl sulfoxide and the like. The base can be selected from the sterically hindered amines such as triethylamine or Hiinig's base, alkoxides such as sodium methoxide and tert.-butoxide, or hydrides such as sodium hydride. The reaction can be performed at temperatures between 20 **C and 110 ^C, depending on the individual compounds to be synthesized.

According to scheme G> compounds of general formula II in which R^ is as described above for compounds where X is an ethynediyl group can be prepared by different routes from the iodo-compounds V, depending on the nature of R and R As shown in scheme G, the transformation can for example be carried out
a) by directly attaching the R1-alkynediyl-substituent to a compound of general
formula V via a Sonogashira-type coupling to produce compounds of the general
formula VId followed by the reduction of the nitro group or
b) by two stepwise Sonogashira-type couplings, in which first trimethylsilyi-acetylene
is coupled to a compound of general formula V to yield, after desilylation with sodium
hydroxide in methanol, the intermediate X which then can be transformed via a

second Sonogashira-type coupling with the appropriate reactant R1-I, R1-Br or R1-OSO2CF3 into compounds of the general formula VId and reduction of the nitro group leads to the desired compounds of general formula IL
The exact conditions for the respective compounds can be found in the experimental part.

According to Scheme H, the dioxinones and 6-keto esters building blocks with the general formula TV and IVa can be prepared by methods known to someone skilled in the art from the corresponding carboxylic acid derivatives R -COR, i.e. free acids, methyl or ethyl esters and acid chlorides. The exact conditions for the corresponding compounds can be found in the experimental part.
The pharmaceutically acceptable salts can be manufactured readily according to methods known per se and taking into consideration the nature of the compound to be converted into a salt. Inorganic or organic adds such as, for example, hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid or citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric add, methanesulphonic add, p-toluenesulphonic add and the like are suitable for the formation of pharmaceutically acceptable salts of basic compounds of formula I.

The compounds of formula I and their pharmaceutically acceptable salts are metabotropic glutamate receptor antagonists and can be used for the treatment or prevention of acute and/or chronic neurological disorders, such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are acute and chronic pain, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate-deficient functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, dyskinesia and depression.
The compounds of formula I and pharmaceutically acceptable salts thereof can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, the administration can also be effected rectally, e.g. in the form of suppositories, or parenterally, e.g. in the form of injection solutions.
The compounds of formula I and pharmaceutically acceptable salts thereof can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical preparations. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like; depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules- Suitable carriers for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose and the like. Adjuvants, such as alcohols, polyols, glycerol, vegetable oils and the like, can be used for aqueous injection solutions of water-soluble salts of compounds of formula I, but as a rule are not necessary. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like.
In addition, the pharmaceutical preparations can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances.

As mentioned earlier, medicaments containing a compound of formula I or a pharmaceutically acceptable salt thereof and a therapeutically inert excipient are also an object of the present invention, as is a process for the production of such medicaments which comprises bringing one or more compounds of formda I or pharmaceutically acceptable salts thereof and, if desired, one or more other therapeutically valuable substances into a galenical dosage form together with one or more therapeutically inert carriers.
The dosage can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, the effective dosage for oral or parenteral administration is between 0.01-20 mg/kg/day, with a dosage of 0.1-10 mg/ kg/day being preferred for all of the indications described. The daily dosage for an adult human being weighing 70 kg accordingly lies between 0.7-1400 mg per day, preferably between 7 and 700 mg per day.
The present invention relates also to the use of compounds of formula I and of pharmaceutically acceptable salts thereof for the production of medicaments, especially for the control or prevention of acute and/or chronic neurological disorders of the aforementioned kind.
The compounds of the present invention are group II mGlu receptor antagonists. The compounds show activities, as measured in the assay described
below, of 10μM or less, typically 1μM or less, and ideally of 0.3μM or less.
In the table below are described some specific Ki values of preferred compounds.

Transfection and cell culture
cDNA encoding the rat mGlu2 receptor protein in pBluescript II was obtained from Prof. S. Nakanishi (Kyoto, Japan), and subcloned into the eukaryotic expression vector pcDNA I-amp from Invitrogen (NV Leek, The Netherlands). This vector construct (pcDlmGR2) was co-transfected with a psvNeo plasmid encoding the gene for neomycin resistance, into CHO cells by a modified calcium phosphate method described by Chen & Okayama (1988), The cells were maintained in Dulbecco's Modified Eagle medium with reduced L-glutamine (2 -mM final concentration) and 10 % dialysed foetal calf serum from Gibco BRL (Basel, Switzerland). Selection was made in the presence of G-418 (1000 ug/ml final). Clones were identified by reverse transcription of 5 μg total RNA, followed by PCR using mGlu2 receptor specific primers 5'-atcactgcttgggtttctggcactg-3' and 5'-agcatcactgtgggtggcataggagc-3' in 60 mM Tris HCl (pH 10), 15 mM (NH4)2SO4,2 mM MgCl2, 25 units/nil Taq Polymerase with 30 cycles annealing at 60 oC for 1 min., extention at 72 °C for 30 s, and 1 min. 95 °C denaturation.

Membrane preparation
Cells, cultured as above, were harvested and washed three times with cold PBS and frozen at -80 °C. The pellet was resuspended in cold 20 mM HEPES-NaOH buffer containing 10 mM EDTA (pH 7.4), and homogenised with a polytron (Kinematica, AG, Littau, Switzerland) for 10 s at 10 000 rpm. After centrifugation for 30 min. at 4 °C, the pellet was washed once with the same buffer, and once with cold 20 mM HEPES-NaOH buffer containing 0.1 mM EDTA, (pH 7.4). Protein content was measured using the Pierce method (Socochim, Lausanne, Switzerland) using bovine serum albumin as standard.
[3H]'LY354740 binding
After thawing, the membranes were resuspended in cold 50mM Tris-HCl buffer containing 2 mM MgClo and 2 mM CaCl2, (pH 7) (binding buffer). The final concentration of the membranes in the assays was 25°Cg protein/ml. Inhibition experiments were performed with membranes incubated with 10 nM [3H]-LY354740 at room temperature, for 1 hour, in presence of various concentrations of the compound to be tested. Following the incubations, membranes were filtered onto Whatmann GF/C glass fiber filters and washed 5 times with cold binding buffer. Non specific binding was measured in the presence of 10°CM DCG IV. After transfer of the filters into plastic vials containing 10 ml of Ultima-gold scintillation fluid (Packard, Zurich, Switzerland), the radioactivity was measured by liquid scintillation in a Tri-Carb 2500 TR counter (Packard, Zurich, Switzerland),
Data analysis.
The inhibition curves were fitted with a four parameter logistic equation giving K1
values, and Hill coefficients.

EXAMPLES
General procedure A
Preparation of 4-iodo-2-nitroanilines by iodination of 2-nitroanilines [according to Wilson, J. Gerald; Hunt, Frederick C Aust /, Chem. 1983,36^ 2317-25]
To a stirred solution of the Z-nitroanilinc (LO mol) in HOAc (500 mL) containing anhydrous NaOAc (93-103 g, 1.125-1.25 mol), iodine monochloride (59-66 mL, 1.125-1.25 mol) in HOAc (300 mL) was added over 60 min. The reaction mixture was heated to the given temperature until thin layer chromatography (tic) indicated complete conversion of the starting material, stirred for another 30 min at 23 oC, then diluted slowly with H2O (1000 mL) which caused the separation of the crystalline product. Stirring was continued for 1 h and the product was filtered off, washed free of HOAc and dried in vacuum at 60 oC.
Example A1
5-Chloro-4-iodo-2-nitro-phenylamine
The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80oC). Obtained as an orange solid.
MS (EI) 298 (M^) and 300 [(M-f2)^]; mp 202-203 **C (dec).
General procedure B:
Preparation of ('2-nitro-phenvl)-carbamic acid tert.-butyl esters from 2-nitroanilines
Method a (from 2-nitroanilines): To a solution of diphosgene (4.1 mL, 34,1 mmol) in EtOAc (40 mL) at 0 °C was added a solution of the 2-nitroaniline (45.5 mmol) in EtOAc (200-500 mL), and the mixture was heated to reflux for 18 h. The solvent was removed in vacuum to leave a brown solid, which was triturated with hot hexane (200 mL). The solid material was filtered off and the filtrate was concentrated xmder reduced pressure to leave the pure 2-nitrophenylisocyanate as a yellow soild This material was refluxed in a mixture of excess terL-BuOH in CH2CI2 for 2.5 h. Removal of the solvent left an orange solid which was pmified by silica gel colunm chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbainic acid tert-butyl ester as a yellow solid

Method b (from 2-nitroanilines): To a mixture of the 2-nitroaniline (142 mmol) and cesium carbonate (55.5 g, 170 mmol) in 2-butanone (740 mL) was dropwise added a solution of BOC2O (37.8 g, 173 mmol) in 2-butanone (170 mL) and the resulting mixture was stirred at 50 ^C to 80 **C until tic indicated complete conversion. The solvent was removed in vacuxun, the residue was treated with a mixture of H2O (240 mL) and MeOH (240 mL) and extracted with hexane (3 x 500 mL). The combined hexane layer was washed with brine (200 mL) and all aqueous layers were reextracted with hexane (300 mL). All combined hexane layers were dried over MgSO4, filtered and the solvent was removed in vacuum to give an orange solid, which was purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid.
Method c (fi-om 2'nitroanilines): To a solution of the 2-nitroaniline (550 mmol) and DMAP (1.22 g, 10 mmol) in THF (1000 mL) at 23 °C was dropwise added within 70 min a solution of Boc2O (246 g, 1128 mmol) in THF (500 mL) and stirring was continued at 23 °C for 75 min. The entire mixture was evaporated to dryness and dried at HV to leave a dark brown solid. This material was dissolved in DCM (1100 mL), cooled to 0 --C and TFA (84 mL, 1100 mmol) was added dropwise. The mixture was stirred at 0 °C for 2 h2 poured into icecold sat. NaHCO3-sol, extracted with DCM, washed with brine and dried over MgSO4. Removal of the solvent in vacuum left a dark brown solid which was coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid.
Method d (firom 2'nitroacetanilides): To a solution of the 2-nitroacetanilide (100 mmol) and DMAP (122 mg, 1mmaol) in THF (100 mL) at 23 X was dropwise added within 15 min a solution of B0C2O (22.92 g, 105 mmol) in THF (100 mL) and stirring was continued at 23 oC until tic indicated completed conversion. The entire mixture was evaporated to dryness and dried at HV to leave a yellow to dark brown solid. This material was dissolved in THF (200 mL) and 25 % NH4OH (77 mL, 500 mmol) was added dropwise. The mixture was stirred at 23 oC until tic indicated complete conversion, poured into IN HCl-sol, extracted with EtOAc, washed the organic layer with sat. NaHC03-soL and brine, dried over MgSO4. Removal of the solvent in vacuum left an yellow to brown solid which was generally pure enough for fiirther transformation or - if necessary - coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert-butyl ester as a yellow solid.

Example Bl
f 5-Chloro-4-iodo-2-nitrO'phenvlVcarbamic acid tert.-butyl ester
The title compound was prepared via the isocyanate from 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (7.0 g> 23.45 mmol) with diphosgene (2.12 mL, 17.6 mmol) in EtOAc (30 mL), followed by treatment with tert.-BuOH (100 mL) in CH3CI2 (100 mL) according to the general procedure B (method a). Obtained as a yellow solid (7.1 g, 76%).
MS (EI) 398 (M^) and 400 [(M-f2)^]; mp 82-84 °C
Example B2
f4,5-Dichloro-2-nitro-phenvlVcarbamic acid tert.-butyl ester
The title compound was prepared via the di-Boc-compound from commercially available 4,5-dichlorO-2-nitroaniline (15 g, 72.5 mmol) and BOC2O (32.4 g, 148.5 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained as abrown solid (21.63 g, 97 %).
MS (ISN) 305 [(M-H)-]; mp 68-73 °C.
Example B3
(5-Fluoro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared via the di-Boc-compound from 5-fluoro-2-nitro-4-trifluoromethyl-phenylamine; prepared from commercially available 4-amino-2-fluorobenzotrifluoride by acetylation with Ac2O in toluene at 23 °C, nitration with 100 % nitric acid from 10-23 °C and deacetylation with 2N NaOH in THE at 50 °C] (5.21 g, 23.2 mmol) and Boc2O (10.63 g, 48.7 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a light yellow solid(6.33 g, 84 %).
MS (ISN) 323 [(M-H)-]; mp 104 °C
Example B4
[4-Iodo-2-nitrO'5-f2,2.2-trifluoro-ethoxy)-phenvll-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenyiamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (8.95 g, 30 mmol), 2,2,2-trifluoroethanol (30 mL) and KOH (4.36 g, 66 mmol) in DMSO (60 mL) at 23 °C for 35 days.] (10.41 g, 29 mmol) and BOC2O (12,87 g, 59 mmol), followed by treatment with 2 eq. TFA in CR2CL2

according to the general procedure B (method c). Obtained as a yellow solid (13.34 g, 100 %),
MS(ISN)461[(M-H)-].
Example B5
(5-Chloro-2-nitro-4-trifIuoromethvl-phenvl)-carbamic acid tert,-butyl ester
The title compound was prepared via the di-Boc-compound from commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (22.61 g, 94 mmol) and BOC2O (42.06 g, 193 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (31,82 g, 99%).
MS (ISN) 339.1 [(M-H)-]and 341 [(M+2-H)-];mp 113-115 °C.
Example B6
(5-Chloro-4-fluoro-2-nitro-phenvl')-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from commercially available 3'-chloro-4'-fluoro-6'-nitroacetanmde [CAS-No. 81962-58-5] (59 g, 254 mmol), and BOC2O (58.13 g, 266 mmol), followed by treatment with NH4OH (25%, 77.5 mL, 507 mmol) according to the general procedure B (method d). Obtained as a yellow solid(73,53 g, 100 %).
MS (ISN) 289 [(M-H)-] and 291 [(M+2-H)-]; mp 73-74 °C
Example B7
[2-Nitro-5-(2,2,2-trifluoro-ethoxv)-4-trifluoromethyl-phenvn-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenylamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al), 2,2,2-trifluoroethanol and KOH in DMSO at 23 °C for 32.5 days.] and BOC2O, followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (18.955 g).
MS (ISN) 403 [(M-H)-].

Example B8
(5-Chloro-4-methyl-2-nitro-phenyl)-carbamic add tert-butyl ester
The title compound was prepared via the di-Boc compound from commercially available 5-chloro-4-methyl-2-nitroaniline (10.0 g, 53.6 mmol) and BOC2O (23.9 g, 109 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (toluene/ethylacetate 19:1) as a yellow solid (14.6 g, 95%).
MS (ISN) 285.1 [(M-H)'l.
Example B9
(4-Cyano-5-fluoro-2-nitro-'phenyl)-Carbamic acid tert-butyl ester
The tide compound was prepared via the di-Boc compound from 4-cyano-5-fluoro-2-nitroaniline (24.9 g, 137 mmol) [Ohmori et al. J, Med. Chem. 1994,37,467 - 475] and BOC2O (61,5 g, 282 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (hexane/ethylacetate 4:1) as a light yellow solid (14.5 g, 39%).
MS (ISN) 280.1 [(M-H)'].
General procedure C:
Preparation of 5-N-substituted-(2-nitro-phenyl)-carbamic acid tert.-butylesters:
(5-Chloro or -fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester was stirred with the desired amine optionally with DMSO, DMF, DMA, NMP or THF and/or DIPEA or Et3N at temperatures from 23 °C to 130 °C until tic indicated complete disappearance of the chloride or fluoride. The reaction was cooled to 23 °C poured into ice-water, the precipitate was filtered off, washed with water and dried in vacuum. In cases were the product did not precipitate, the mixture was extracted with EtOAc, washed with water and brine, dried over Na2SO4. Filtration and removal of the solvent in vacuum left a crude product, which was - if necessary - purified by silica gel column chromatography with hexane/EtOAc to give the pure title compound.
Example CI
(4-Chloro-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butylester
The tide compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and dimethylamine (5.6 N in EtOH,

8.7 mL, 48.8 mmol) in DMSO (35 mL) at 23 o'C according to the general procedure C. Obtained as a yellow solid (2.81 g).
MS (ISP) 316 [(M+H)--] and 318 [(M-h2+H)']; mp 136-138 °C
Example C2
(5-DimethylaminO-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic acid tert,-butyl ester (Example Bl) (399 mg, 1 mmol) and dimethylamine (5.6 N in EtOH, 0.36 mL, 2 mmol) in THE (3 mL) at 65 °C for 18 h in a sealed tube according to the general procedure C. Obtained as a yellow solid (386 mg).
MS (EI) 407 (M+); mp 120-122 °C.
Example C3
(4-Chloro-5- rr2-methoxv-ethyl)-methyl-amino1-2-nitro-phenyl}-carbamic add tert,-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol), N-(2-methoxyethyl)methylamine (2.43 mL, 23 mmol) and Et3N (4.2 mL, 30 mmol) in DMSO (20 mL) at 23 °C according to the general procedure C. Obtained as a brown oil (3,57 g),
MS (ISP) 360 [(M+H)+_] and 362 [(M+2-i-H)^].
Example C4
(5-Dimethylamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (5-fluoro-2-mtro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B3) (1.62 g, 5.0 mmol) and dimethylamine (5.6 N in EtOH, 4.47 mL, 25.0 mmol) in DMSO (10 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(1,48 g).
MS (ISN) 348 [(M-H)-]; mp 110 X.
Example C5
r
|4-Chloro-5-(ethvI-methyI-aminoV2-nitro-phenvi]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-ethyl-methylamine (2.89 g, 48.8 mmol) in DMSO (35 mL) at RT according to the general procedure C. Obtained as a pale brown solid(3.21 g).

MS(ISP)330.3 [(M+H)1;mp94oC.
Example C6
f4-Chloro-5-(methyl-propyl-aminoV2-nitro-phenyl-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichlorO-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-methyl-propyl-amine (2,50 g, 34.2 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a pale brown solid (3.58 g),
MS (ISP) 344.3 [(M+H)+]; mp 68 °C,
Example C7
f4--Chloro-5'(dietfavl-amino)-2-nitro-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and diethyl-amine (3.57 g, 48.8 mmol) in DMSO (35 mL) at 60°C according to the general procedure C. Obtained as a yellow solid (2.63 g).
MS (ISP) 344.3 [(M+H)--]; mp 95 °C.
Example C8
(4-Chloro-2-nitro-5-pyrrolidin-l'yl'phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and pyrrolidine inDMSO at 23 -*€ according to the general procedure C. Obtained as a yellow solid (6.65 g).
MS (ISP) 342 [(M+H)--] and 344 [(M+2+H)']; mp 157-158 °C.
Example C9
[4-Chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and EtsN (6.97 mL, 50 nunol) in DMSO (30 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.25 g).
MS (ISP) 342.2 [(M+H)+ and 344 [(M+2+H)-']; mp 104-106 °C.

Example CIO
(2-Nitro-5-pyrrolidin-l-yl-4-trifluoromethyl'-phenyl)_-carbamic acid tert-butyl ester
The tide compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5) (6,81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) inDMSO (70 mL) at 23 --C according to the general procedure C. Obtained as a yellow solid (7.35 g).
MS (ISN) 374 [(M-H)-]; mp 138-141 °C
. Example CI 1
f 5-DimethylaminO-4'fluoro-2-nitro-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (5-chloTO-4-fluoro-2'nitro-phenyl)~carbamic acid tert-butyl ester (Example B6) (4.94 g, 17 mmol) and MeaNH (40% in H2O, 7.9M, 10.9 mL, 86 mmol) inDMSO (35 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.93 g),
MS (ISP) 303 [(M+H)+]; mp 144-148 X.
Example C12
('4-Chloro-2-nitro-5-piperidin-l-yl-phenylVcarbamic acid tert,-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and piperidine inDMSO at 23 oC according to the general procedure C. Obtained as a yellow solid (1.173 g).
MS (ISP) 356 [(M+H)+] and 358 [(M+2+H)*']; mp 132-133 °C.
Example CI 3
(4-Fluoro-2-nitro-5-pvrrolidin-l-yl-phenylVcarbamic acid tert.-butylester
The title compound was prepared from (5-chloro-4-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B6) (5.81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (6.42 g).
MS (ISP) 326 [(M+H)--]; mp 188-193 °C.
Example C14
(5-A2etidin'l-yi-4-chloro-2-nitro-phenyl')-carbamic acid tert.-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyi ester (Example B2) (6.14 g, 20 mmol), azetidine (2.33 mL, 34 mmol) and

Et3N (8.4 mL, 60 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as an orange solid (5.85 g).
MS (H) 327 (M+) and 329 [(M+2)+].
Example CI 5
(5-Azetidin-l-yl-2-nitro-4-trifluoromethyl-phenylVcarbaniic acid tert.-butyl ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5), azetidine and Et3N in DMSO at 23 °C according to the general procedure C. Obtained as a yellow solic (6.925 g).
MS (ISN) 360 [(M-H)-].
Example C16
(5-(CvclopropylmethyI-methyl-amino)-2-nitro-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B5) (5.11 g 15 mmol), cyclopropylmethyl-methyl-amine hydrochloride (5.47 g, 45 mmol) and Et3N (10.5 mL, 75 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(5.73 g).
MS (ISN) 388 l(M-H)']; mp 5 1°C .
Example C17
(5-(CycIopropvI-methyI-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamicacid tert.-but\4 ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl) carbamic acid tert-butyl ester (Example B5) (3.40 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and Et3N (6.97 mL, 50 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.74 g).
MS (ISP) 374.2 [(M+H)1,

Example C18
(2-Dimethylamino-2'-fluoro-5'nitro-biphenyl-4-yl)-carbamic acid tert.-butylester
The title compound was prepared from (2-chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example D3) (9,568 g, ca. 26 mmol) and Me2NH (60% in H20,12 mL) inDMSO (87 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.54 g).
MS (ISP) 376.3 [(M+Hrj.
Example C19
(5-Dimethylamino-4-methyl-2-nitro-phenylVcarbamic acid tert-butyl ester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and dimethylamine (11 ml, 33% in EtOH, 61.0 mmol) in DMSO (35 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid (3.50 g, 97%).
MS (ISP) 296.3 [(M+H)*-].
Example C20
f4-Cvano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7.11 mmol) and dimethylamine (6.3 ml, 33% in EtOH, 35.0 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.87 g, 86%).
MS (ISP) 307.3 [(M+H)'],
Example C21
[4-methyl-5-(methyl-propyl-aminol-2'mtro-phenyn-Carbamic acid tert-butylester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-methylpropylamine (6.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (3.89 g, 98%).
MS (ISP) 324.4 [(M+H)--].

Example C22
(5-fEthyl-metfayl-amino)-4-methyl-2-nitro-phenyl-carbamic add tert-butyl ester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-ethylmethylamine (5.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.58 g, 95%).
MS (ISP) 310.3 [(M+H)--].
Example C23
f4-Chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isopropyl-methyiamine (5.95 g, 81.4 mmol) in DMSO (50 mL) at 75 °C according to the general procedure C. Obtained as a yellow solid (4.07 g, 73%).
MS (ISP) 344.3 [(M+H)+].
Example C24
[4-Chloro-5-(isobutyl-methyl-amino)-2-nitro--phenyl]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isobutyl-methylamine (7.09 g, 81,4 mmol) in DMSO (50 mL) at RT according to the general procedure C. Obtained as a brown oil (5.79 g, 99%).
MS (ISP) 358.2 [(M+H)--].
Example C25
f4-Cvano-2-nitro-5-pyrrolidin-l'yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7,11 mmol) and pyrrolidine (2.94 ml, 35.6 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.97 g, 83%).
MS (ISP) 331.2 [(M-H)-].

Example C26
f4-Cvano-5-fmethyl-propyl-amino)-2-nitro-phenyl-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-methyl-propylamine (3.72 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.75 g, 75%).
MS (ISP) 333.3 [(M-H)'].
(4-Cyano-5-diethylamino-2-nitro-phcn>i>-carbamic add tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and NJSI-diethyiamine (3.60 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.78 g, 77%).
MS (ISP) 333.2 [(M-H)-].
Example C28
[4-Cvano-5-(isopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butyl ester
The title compound was prepcured from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isopropyl-N-methylamine (3.60 ml, 34.7 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.84 g, 79%).
MS (ISP) 333.3 [(M-H)'].
Example C29
f4-Cvano-5-(isobutyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isobutyl-N-methylamine (3.02 g, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C Obtained as a yellow solid (1.87 g, 77%).
MS (ISP) 347,4 [(M-H)-].

Example C30
f4-Cyano-2-nitro-5-piperidin-l--'yi-phenyl)-carbamic acid tert-butylester
The title compoimd was prepared from (4-cyano-5-£luoro-2-nitro-phenyi)-carbamic acid tert-butyl ester (Example B9) (2.0 g> 7.11 mmol) and piperidine (3.51 ml, 35.6 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.94 g, 79%).
MS (ISP) 345.3 [(M-H)-].
Example C31
(4-Chloro-5-isobutylamino-2-nitro-phenyl--carbamic acid tert-butyl ester
The title compound was prepared from (4>5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and isobutylamine (3.57 g, 48.8 mmol) in DMSO (20 mL) at 55°C according to the general procedure C. Obtained as a brown solid (2.26 g, 67%).
MS (ISP) 344.2 [(M+H)--].
Example C32
[5-fMethyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-methyl-propyl-amine (1.89 ml, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.04 g, 91%).
MS (ISP) 378.3 [(M+H)*-].
Example C33
f 5-(Isobutyl-methyl-amino V2-nitro-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol),N-isobutyl-methyl-amine (L54 g, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.18 g, 91%).
MS (ISP) 390.3 [(M-H)-].

Example C34
f 5-f Isopropyl-methyl-aminoV2-nitro-4-trifluoromethyl-phenyn -carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-isopropyl-methyl-amine (3.67 ml, 35.2 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid(3.27 g, 74%).
MS (ISP) 376.3 [(M-H)'].
Example C35
(5-(IsobutvI-methyl-aminoV4-methyl-2-nitro-phenyl-carbamic acid tert-butylester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and N-isobutyl-methylamine (4.56 g, 52.3 nunol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (1.84 g, 52%).
MS (ISP) 336.3 [(M-H)'].
Example C36
(4-MethyI-2-nitro-5-pvTrolidin-l-yl-phenyl Vcarbamic acid tert-butylester
The title compound was prepared from (5-chlorO-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and pyrrolidine (4.33 ml, 52.3 mmol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.27 g, 97%).
MS (ISP) 320.3 [(M-H)-]; mp 145 °C
Example C37
(4-Chloro-5-isopropylamino-2-nitro-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert.-butyl ester (Example B2) (5,0 g, 16,3 mmol) and isopropylamine (7,0 ml, 81.4 mmol) in DMSO (35 mL) at 55 o'C according to the general procedure C. Obtained as a brown solid (3.95 g, 73%).
MS (ISP) 330.2 [(M+H)--]. '

Example C38
(5-Isobmylamino-2-mtro-4-trifluoromethyl-phenylVcarbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (5.00 g, 14.7 mmol), isobutyl-amine (7.36 mL, 73.4 mmol) in DMSO (35 mL) at RT according to the general procedure C Obtained as a yellow solid (5.39 g, 97%).
MS (ISP) 376.3 [(M-H)-],
General procedure D:
Preparation of (4-arvI-2-nitro-phenyl)-carbamic acid tert.-butyl esters by direct Suzuki-coupling of ('4-iodo-2-nitro-phenyl)*carbamic acid tert.-butylesters with arylboronic acids
A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (3.0 mmol), the arylboronic acid (4.5 mmol) and PdCl2(PPh3)2 (2 mol%) was refluxed in 1,4-dioxane (25 mL) and 2M NaaCO2-sol. (7.5 mL) [or alternatively with IM NaHCOa-sol. (7.5 mL), LiCl (6.0 mmol) and (Ph3P)4Pd (3 mol%) in DME (30 mL); also possible with EtaN (9,0 mmol), Pd(0Ac)2 (3 mol%), PPhs (6 mol%) in DMF (10 mL) at 100 °C] until tic indicated complete conversion of the iodide. The mixture was transferred into a separating funnel, H2O (25 mL) was added and the product was extracted with ether or EtOAc (3 x 30 mL). The combined organic layers were washed with brine (50 mL) and dried over Na2S04. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound
Example Dl
(2-Dimethylamino-2\3'-difluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester
The tide compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C2) and 2,3-difluorophenylboronic acid according to the general procedure D. Obtained as a yellow solid (3,096 g).
MS(ISN)392[(M-H)-].

Example D2
f2'-Fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yll-carbamic acid tert,-butylester
The title compound was prepared from [4-iodO-2-nitro-5-(2,2,2-trifluoro-ethox7)-phenyl]-carbamic add tert-butyl ester (Example B4) and 2-fluorophenylboronic add according to the general procedure D. Obtained as a yeDow solid (1.39 g).
MS (ISP) 491 [(M+H)--]; mp 73-75 °C.
Example D3
(2-Chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester
The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic add tert-butyl ester (Example Bl) (30 g, 75.3 mmol) and 2-fIuorophenylboronic acid (13.82 g, 98.8 nrniol) according to the general procedure D. Obtained as a yellow gum (1.39 g).
MS (ISN) 365.0 [(M-H)-].
General procedure E:
Preparation of (4-aryl-2-nitro-phenyl)-carbamic acid tert.-butyl esters by Suzuki-coupling of (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butylesters with bisfpinacolato)diboron and subsequent reaction with aryl halides
A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (2,0 mmol), bis(pmacolato)diboron (2,2 mmol), KOAc (6.0 mmol) and PdCl2(PPh3)2 (3 mol%) in 1,4-dioxane (25 mL) was stirred at 100 °C until tic indicated complete conversion of the iodide [cf. Tetr. Lett. 1997,38,3841-3844]. After addition of the aryl halide (4.0 mmol), PdCl2(PPh3)2 (3 mol%) and 2M Na2CO3-soL (7.5 mL) the mixture was stirred at 100 oC until tic indicated complete conversion of the intermediate boronic ester. The mixture was transferred into a separating furnnel, H2O (30 mL) was added and the product was extracted with ether or EtOAc (3 x 50 mL). The combined organic layers were washed with brine (100 mL) and dried over Na2SO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound.

General procedure F:
Preparation of 5-chIoro-2'-nitro-4-pyrroI-l-yl-phenylamines by condensation of 5-chlorO-2-nitro-l,4-phenylenediamine with 2,5-dimethoxvtetrahydrofurans [cf. /. Heterocycl Chem 1988,25y 1003-1005]:
A mixture of the 5-chloro-2-nitro-l,4-phenylenediamine (4.69 g, 25 mmol), the 2,5-dimethoxytetrahydrofuran (26 - 32,5 mmol) in HOAc (150 mL) was stirred at 60-120 °C until tic indicated complete conversion of the phenylenediamine. After cooling to 23 °C, the mixture was poured into brine (500 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (300 xriL) and dried over MgSO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/EtOAc to give the title compound.
General procedure G:
Preparation of 23-dimethoxvdihvdrofurans by bromination of furans in MeOH [cf. Tetrahedron 1971,27,1973-1996]:
To a solution of the furan (177.5 mmol) in a mixture of anhydrous ether (54 mL) and abs. MeOH (79 mL) kept at -35 °C bromine (10.0 mL, 195 mmol) in MeOH (105 mL) was added gradually with stirring. The reaction mixture was stirred for 30 min, saturated with gaseous NH3 to pH 8, and allowed to warm up to 23 °C. Poured into ice-water, extracted with ether (3 x 400 mL), washed with brine, dried over Na2So4. Evaporation of the solvent left a yellow liquid, which was purified by vacuum distillation to give the title compound.
General procedure H:
Preparation of (4-alkynyl-2-nitro-phenyll-carbamic acid tert,-butylesters by Sonogashira-coupling of f4-iodo-2-nitro-phenyI)-carbamic acid tert.-butylesters with acetylenic compounds;
also Sonogashira-coupling of (4-ethynyl-2-nitro-phenyl)-carbamic acid tert-butyl esters with aryl halides:
A mixture of the halide (3.0-4.5 mmol), acetylenic compound (3.0-4.5 mmol), Et3N (13.5 mmol), PdCl2(PPh3)2 (5 mol%) and PPh3 (2.5 mol%) in THF (12 mL) [with very insoluble material DMF (up to 12 mL) could be added] was stirred for 20 min at 23 °C while being purged with Argon. Cul (1.2 mol %) was added and stirring was continued at 60 °C under Argon atmosphere until tic indicated complete conversion of the minor component [cf. /. Org. Chenu 1998,63,8551]. The mixture was

transferred into a separating funnel, 5% citric add (50 mL) was added and the product was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with sat. NaHCOs-sol. (50 mL) and brine (50 mL), followed by drying over MgSO4. Removal of the solvent left a yellow residue, which was purified by silica gel colunm chromatography with hexane/EtOAc and/or triturated with hexane or aqueous EtOH to give the title compound.
Example Hi
(5-Hydroxymethyl-2-nitro-4-phenylethvnyl-phenyl)'Carbamic acid tert.-butylester
The title compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C2) (386 mg, 0.97mmol) and phenylacetylene (149 mg, 1.46 mmol) according to the general procedure H. Obtained as an orange solid (370 mg).
MS (EI) 381 (M+); mp 141-149 °C.
General procedure T:
Preparation of the (2-amino-phenyl)-carbamic acid tert.-butylesters bv reduction of (2-nitro-phenyl)-carbamic acid tert.-butylesters:
Method a: Catalytic hydrogenation
A mixture of the nitro compound (1.0 mmol) in MeOH or EtOH and THF (1:1 ca. 20 mL) [or solely EtOAc for aromatic chlorides] and 10% Palladium on carbon (20 mg), Raney-Ni (20 mg) or 5% Platinum on carbon was stirred vigorously at 23 *°C under hydrogen atmosphere until tic indicated complete conversion. The catalyst was filtered off, washed thoroughly with MeOH or EtOH and THF (1:1) [or EtOAc], the solvent was removed in vacuum to give the title compound, which was generally pure enough for further transformations, but could be crystallized firom hot hexane if necessary. Method b: Reduction with SnCl2'2H2O
A mixture of the nitro compound (1.0 mmol) and SnCl2'2H2O (5.0 mmol) was either stirred in EtOH (30 mL) at 70-80 °C or alternatively in pyridine (3 mL) and DMF (12 mL) at 23 °C under Argon atmosphere until tic indicated complete conversion [cf. Tetr. Lett. 1984,25, 839]. The reaction mixture was brought to pH 8 by addition of sat NaHC03-sol. and extracted with EtOAc (2 X 100 mL). The combined organic layer were washed with brine and dried over Na2SO4. Removal of the solvent left a yellow solid, which - if necessary - can be purified by silica gel column chromatography.

Method c: Reduction with Zn and NH°Cl
To a mixture of the nitro compound (1.0 mmol) in EtOH/THF/sat NH4CI-S0I. (1:1:1> 30 mL) was added Zinc dust (3.0 mmol) and the mixture was stirred at 70 °C imder Argon atmosphere until tic indicated complete conversion. Aqueous workup as described in method b.
Example Tl
(2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-chlorO-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example CI) (2,76 g, 8.74 nunol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid(2.3 g).
MS (ISP) 286 [(M+H)--] and 288 [(M+2+H)+]; mp 96-101 °C.
Example T2
f2-Amino-5-dimethylamino-4-phenylethynyl-phenvD-carbamic acid tert.-butyl esr T
The title compound was prepared from (5-dimethylaminO-2-nitro-4-phenylethynyl-phenyl)-carbamic acid tert.-butyl ester (Example Hi) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a brown solid (1.927 g).
MS(ISP)352[(M+H)+].
Example T3
(5-Amino-2-dimethylamino--2,3'-difluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-dimethylamino-2',3'-di£luoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example Dl) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (2,206 g),
MS(ISP)364[(M+H)-'],
Example T4
{2-AminQ-4-chloro-5- f f 2-methoxv-ethyl-methyl-amino1 -phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from {4-chloro-5-[(2-methoxy-ethyl)-methyi-amino]-2-nitro-phenyl}-carbamic acid te t-butyl ester (Example C3) (3.46 g, 9,62

mmol) by reduction with SnCl22H2O according to the general procedure J.(method b). Obtained as a yellow solid (2.25 g).
MS (ISP) 330 [(M+H)1 and 332 [(M+2+H)']; mp 112 X.
Example T5
[5-Amino-2*-fluoro-2-(2.2.2-trifluoro-ethoxyVbiphenyl-4-yl1 -carbamic acid tert.-butyl ester
The title compound was prepared from [2'-fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert,-butyl ester (Example D2) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (U7g).
MS(ISP)401[(M+H)1.
Example T6
(2-Amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert^-butylester
The title compound was prepared from (5-dimethyiamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C4) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as an amorphous yellow substance (1.34 g),
MS (ISP) 320 [(M+H)1.
Example T7
[2-Amino-4-chloro-5-(ethyl-methvI-aminoVphenyl]-carbamic acid tert-butylester
The title compoimd was prepared from [4-chloro-5-(ethyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C5) (3.0 g, 9.09 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.64 g).
MS (ISP) 300.3 [(M+H)']; mp 81 X.
Example T8
f2-Amino-4-chloro-5-(methyl-propyl-aminQVphenyl-carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C6) (3.15 g, 9.16 mmol) by reduction with SnClf 2H2O accordmg to the general procedure J (method b). Obtained as a pale brown solid (2.58 g).

MS (ISP) 314.3 [(M+H)-']; mp 92 X.
Example T9
f2'Amino-4'-chIoro-5-fdiethyl-amino)-phenyn'Carbamic add tert-butyl ester
The title compound was prepared from [4-chloro-5-(diethyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example G7) (2.25 g, 6.54 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (1.55 g).
MS (ISP) 314.3 [(M+H)+]; mp 110 °C.
Example TIP
(2-Amino-4-chloro-5-pyrrolidin-l-yl-phenylVcarbamic acid tert.-butyl ester
The tide compound was prepared from (4-chloro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (&cample C8) by reduction with SnCl2*2H2O according to the general procedure J (method b). Obtained as a red solid (4.80 g).
MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']; mp 136-138 °C
Example Til
f 2-Amino-4-chloro-5-(cyclopropyl-methvI-amino')-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert.-butyl ester (Example C9) (3.2 g, 9.36 mmol) by reduction with SnCl2*2H2O according to the general procedure J (method b). Obtained as brown solid (2.00 g),
MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)'].
Example T12
(2-Amino-5-pvrrolidin-l-yl-4-trifluoromethyl-phenylVcarbamic acid tert.-butylester
The title compound was prepared from (2-nitro-5-pyrroHdin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example CIO) (7.35 g, 19.75 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light orange solid (6.75 g).
MS (ISP) 346 [(M+H)--]; mp 101-103 °C

Example T13
(2-Amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester
The title compoiond was prepared from (5-dimethylamino-4-fluoro-2-nitro-phenyI)-carbamic acid tert.-butyl ester (Example C11) (4.88 g, 16 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a green solid(4.55 g).
MS (ISP) 270 [(M+H)+]; mp 120-123 °C.
Example T14
(2-Amino-4-chlorO-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-chloro-2-nitro-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C12) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as light brown solid (747 mg).
MS (ISP) 326 [(M+H)+] and 328 [(M+2+H)1;mp 149-151 °C
Example Tl 5
(2-Amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-fluoro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example C13) (6,37 g, 20 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (5.92 g).
MS (ISP) 296 [(M+H)--]; mp 75-76 °C
Example 116
(2-Amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (5-azetidin-l-yl-4-chloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C14) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (3.664 g).
MS (ISP) 298 [(M+H)--] and 300 [(M+2+H)-']; mp 176-179 -C

Example T17
(2-Amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic add tert.-butylester
The title compound was prepared from (5-a2etidin-l-yl-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C15) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid
(5.173 g).
MS (ISP) 332 [(M+H)+]; mp 166-167 °C
Example Tl 8
f2-Amino-5-(cyclopropylmethyl-methyl-aminoV4-trifluoromethyl-phen\d1-carbamic acid tert.'butyl ester
The title compoimd was prepared from [5-(cyclopropylmethyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C16) (5.66 g, 14.5 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as yellow solid (4.7 g).
MS (ISP) 360 [(M+H)+]; mp 56 X.
Example T19
[2-Amino-5--rcvclopropvI-methyl-amino)-4-trifluoromethyl-phenyn-carbamicacid tert,-butyl ester
The title compound was prepared from [5-(cyclopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C17) (3.74 g, 9.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange semisolid (2.00 g).
MS (ISP) 346.4 [(M+H)--].
Example 120
(5-Amino-2-dimethylamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butylester
The title compound was prepared from (2-dimethylamino-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert-butyl ester (Example CIS) (4.54 g, 12.1 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light brown solid (3.324 g).
MS (ISP) 346.4 [(M+H)+].

Example T21
[2-Amino-5-f2.2.2-trifluoro-ethoxyV4-trifluoromethyl-phenvIl-carbamic acid tert-butyl ester
The title compound was prepared from l2-nitro-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tcrt-butyl ester (Example B7) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a yellow solid (17.374 g).
MS(ISP)375[(M+Hr].
Example 22
(2-Amino-5-dimethylamino-4-methyl-phenyl)-Carbamic acid tert-butylester
The title compound was prepared from (5-dimeth>1amino-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C19) (3.22 g, 10.9 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a gray solid (2.05 g, 58%).
MS (ISP) 266.3 I(M+H)+]; mp 78 X.
Example 123
(2-Amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C20) (3.9 g, 12.7 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.05 g, 58%).
MS (ISP) 277.2 [(M+H)+]; mp 120 -C
Example T24
(2-Amino-4-methyl-5-(methyl-propyI-amino)-phenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-methyl-5-(methyi-propyi-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C21) (3.59 g, 11.1 namol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (3.23 g, 99%).
MS (ISP) 294.4 [(M+H)--].

Example T25
(2-Amino-5-(ethyl-methyl-amino)=4-methyl-phenvIl-carbamic acid tert-butyl ester
The title compound was prepared from [5-(ethyl-methyI-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C22) (3.28 g, 10.6 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (2.94 g, 99%).
MS (ISP) 280.3 [(M+H)1.
Example T26
[2-Amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl1 -carbamic add tert-butylester
The title compoimd was prepared from [4-chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C23) (4.07 g, 11.8 mmol) by reduction with SnClf 2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.08 g, 83%).
MS (ISP) 314.3 [(M+H)1; mp 116 °C.
Example T27
[2-Amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C24) (5.55 g, 15.5 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.98 g, 78%).
MS (ISP) 328.3 [(M+H)1.
Example T28
(2-Amino-4-cyano-5-pvrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The tide compound was prepared from (4-cyano-2-mtro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C25) (1.82 g, 5.48 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a pale brown solid (1.27 g, 77%).
MS (ISP) 303.2 [(M+H)--].

Example T29
(2-Amino-4-cyano-5-fmethyl-propyl-aminoVphenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-cyano-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C26) (1.64 g, 4.90 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a dark red oil (1.24 g, 83%),
MS (ISP) 305.3 [(M+Hf],
Example T30
(2-Amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-diethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C27) (1.66 g, 4.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.38 g, 91%).
MS (ISP) 305.3 [(M+H)+]; mp 151 °C
Example T31
(2-Amino-4-cyano-5-(isopropyl-methyl-aminoVphenyl1 -carbamic acid tert-butylester
The title compound was prepared from [4-cyano-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C28) (1.73 g, 5.17 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.56 g, 99%).
MS (ISP) 305.3 [(M+H)--]; mp 77 °C.
Example T32
[2-Amino-4-cyano-5-(isobutyl-methyl-amino)-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from [4-cyano-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C29) (1.76 g> 5.05 mmol) by reduction with SnCV2H2O according to the general procedure J (method b). Obtained as a light brown solid (1.55 g, 96%).
MS (ISP) 319.5 [(M+H)--]; mp 88 oC.

Example T33
(2-Amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-2-nitro-5-piperidin-l-yi-phenyl)-carbamic acid tert-butyl ester (Example C30) (2.08 g, 5.71 mmol) by reduction with SnCl2'2H2O according to the general procedure I (method b). Obtained as an off-white solid (L67 g, 99%).
MS (ISP) 317.2 l(M+H)+]; mp 86 oC
Example 134
(2-Amino-4-chloro-5-isobutylamino-phen\1)-carbamic acid tert-butylester
The title compound was prepared from (4-chloro-5-isobutylainino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C31) (1.93 g, 5.61 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a brown solid (1.30 g, 74%).
MS (ISP) 314.3 [(M+H)^.
Example 135
(2-Amino-5-(methyl-propyl-aminoV4-trifluoromethyl-phenyl1 -carbamic acid tert-butyl ester
The title compound was prepared from [5-(methyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C32) (3.78 g, 10.0 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a red oil (3.40 g, 98%).
MS (ISP) 248.4 [(M+H)+].
Example T36
[2-Amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C33) (3.88 g, 9,91 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.70 g, 75%).
MS (ISP) 362.3 [(M+H)--].

Example T37
(2-Amino-5-(isopropyl-methyl-aminoV4-trifluoromethyl-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from [5-(isopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C34) (2.98 g, 7.90 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.42 g, 88%).
MS (ISP) 348.5 [(M-hH)--].
Example T38
(2-Amino-5-fisobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-methyl-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C35) (1.48 g, 4.39 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a white solid (1.08 g, 80%).
MS (ISP) 308.3 [(M+H)']; mp 71 °C
Example T39
(2-Amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester
The tide compound was prepared from (4-methyl-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C36) (3.27 g, 10.2 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale brown solid (2.48 g, 83%).
MS (ISP) 292.3 [(M+H)--]; mp 115 °C
Example T40
j (2-Amino-4'Chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-chloro-5-i$opropylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C37) (3.75 g> 11.3 mmol) by reduction with SnCl3 2H2O according to the general procedure J (method b). Obtained as a brown solid (2.90 g, 86%).
MS (ISP) 303.3 [(M+H)--].

Example T41
f 2-Amino-5-f isobutyl-amino V4-trifluoroir.ethyl-phenyl -carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic.acid tert-butyl ester (°Cample C38) (5.28 g, 13.99 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale yellow solid (3.69 g, 76%).
MS (ISP) 348.5 [(M+H)--]; mp 141 °C.
The following examples relate to the preparation of the ethyl or tert.-butyl 3-aryl-3-oxo-propionates (general formula IVa), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H):
General procedure K
Method a) Preparation of ethyl or tert.-butyl3-aryl-3-oxo-propionates
The ethyl or tert.-butyl 3-aryl-3-oxo-propionates were prepared from the aryl acid chlorides and ethyl or tert.-butyl malonate potassium salt [CAS-no. 6148-64-7 and 75486-33-8] with Et3N and MgCla in CH3CN at 0 °C to 23 °C according to Synthesis 1993,290. If the free aryl carboxylic acid was employed in this reaction, it was activated by treatment with ethyl chloroformate and Et3N in THF/CH3CN at 0 °C prior to reaction with the malonate salt.
Method b) Preparation of tert.-butyl3-aryI-3-oxo-propionates
The tert.-butyl 3-aryl-3-oxo-propionates were alternatively prepared from the methyl or ethyl aryl esters by treatment with lithium tert.-butyl acetate [prepared by treatment of tert.-butyl acetate with lithium diisopropylamide in THF at -78 °C] in the prese- :e of lithium tert.-butoxide according to Synthesis 1985,45. If the product contained residual starting material after workup, thus could be removed by selective saponification with LiOH in THF/MeOH/H2O at 23 °C.
Method c) Preparation of 3-aryl-3--oxo-propionic acids
The 3-aryl-3-oxo-propiomc acids were prepared from the aryl acid chlorides and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 °C according to Synth Commun. 1985,15,1039 (method cl) or with n-BuLi in ether at -60°C o 0 °C according to Synthesis 1979,787 (method c2).

Example Kl
3-Oxo-3'(3-f L23ltria2ol-l-yl-phenyl)-propionic acid ethyl ester
The title compound was prepared from 3-[l,2,3]tria2ol-l-yl-ben2oic acid, prepared by refluxing of methyl 3-azidobenzoate [CAS-No. 93066-93-4] in trimethylsUyl-acetylene, followed by saponification with aqueous NaOH in refluxing EtOH] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with EtaN and MgCl2 in CH3CN according to general procedure K (method a). Obtained as a light yellow solid(2.22 g).
MS (EI) 259 (W); mp 72-74°C,
Example K2
3-(3-cyano-phenyl)-3-oxo-propiQnic acid tert.-butyl ester
The title compound was prepared from methyl 3-cyanobenzoate [CAS-No, 13531-48-1] by treatment with lithium tert--butyl acetate according to general procedure K (method b). Obtained as a light brown oily semisolid.
MS (EI) 245 (M+).
Example K3
3-(2-Cyano-pvridin-4-yl)-3-oxo-propiomc acid tert.-butyl ester
The title compound was prepared from 2-cyano-isonicotinic acid ethyl ester [CAS-No. 58481-14-4] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light brown solid (7.70 g).
MS(ISN)245[(M-H)1.
Example K4
3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionic acid tert.-butylester
The title compound was prepared from ethyl 3-(3-methyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, acetaldoxime, Et3N and cat amount of pyridine in CHCI3 at 50 'C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (2.54
g).
MS (ISP) 302 [(M+H)1; mp 50-56 -C.

Example K5
fRSV3-Oxo-3-B45-ftetrahvdro-pvran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phneyl}-
propionic acid tert.-butylester
The title compound was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-l-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) methyl 3-azidobenzoate [CAS-No. 93066-93-4] (15.55 g, 88 mmol) and (RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-l-ynyl]-silane [CAS-No. 135294-85-8] (33.50 g, 132 mmol) were heated to 60 --C for 10 days; ii.) The obtained material (48.2 g, ca. 88 mmol) was stirred in TBAF (300 mL, IM in THF) at 70°C for 6 days and subsequently refluxed in IN HCl (400 mL) for 2 h; iii.) The obtained material (16.15 g, 74 mmol) was stirred in MeOH (400 mL) and cone. H2S04 (30 mL) at 23 °C for 11 days, iv.) Part of the obtained material (4.60 g, 19.7 mmol) was reacted with 3,4-dihydro-2H-pyran (2.67 mL, 29.5 mmol) and cat. amount p-TsOH.H2O in DCM (38 mL) at 23 -°C for 20 h.] (6.20 g, 19.5 mmol) by treatment with lithium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (8.47 MS(ISP)402[(M+H)-'].
Example K6
3-[2-(3-methyl-isoxazol-5-yl)-pvridin-4-yn-3-oxo-propionic acid tert.-butylester
The title compound was prepared from 2-(3-methyl-isoxazol-5-yl)-isonicotinic acid methyl ester [prepared by i.) reaction of 2-iodo-isonicotinic acid methyl ester [CAS-No. 134579-47-8] with trimethylsilylacetylene according to general procedure H; ii.) desilylation by reaction with cat. K2CO3 in MeOH at 0 -°C for 4 h; iii.) cycloadditon with a mixture of NCS, acetaldoxime, Et3N and cat. amount of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a brown solid (5.17 g).
MS (EI) 302 (M^); mp 59-67 °C
Example K7
3-[3-(2-methyl-2H-pyTazol-3-yl)-phenyl1-3-oxo-propionic acid tert.-butylester
The title compound was prepared from 3-(2-methyi-2H-pyrazol-3-yl)-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyi)-3-dimethylamino-propenone [CAS-No. 163852-04-81 with methylhydrazine in EtOH at 23 °C for 2.5

days; ii.) chromatographic separation of the obtained isomers; iii.) treatment of the dean isomer -with n-BuLi in THF at -78 °C for 1 h, followed by quenching with a stream of CO2 and subsequent esterification with MeOH and cone, H2SO4 at 23 °C for 48 h.] by treatment with Uthium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.96 g),
MS (EI) 300 (M+),
Example K8
3- [3-f 5-Dimethylaminomethyl- [ 12,31 triazol- l-yl)-phenyll -3-oxo-propionic acid tert.-butylester
The title compound was prepared firom 3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-benzoic acid methyl ester [prepared from methyl 3-azidobenzoate following the synthetic steps i.) to iii.) as described in the preparation of Example K5 and reacting the obtained product with SOCI2 in THF at 0 to 23 °C for 1 h, followed by acidition of dimethylamine (7.9 M in H2O) and stirring at 23 to 70 'C fori h.] (2.14 g, 8.22 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (2.90 g).
MS(ISP)345[(M+H)-'].
Example K9
3-[3-f3-Methoxvmethyl-isoxazol-5-yl)-phenyl1-3-oxo-propionic acid tert.-butylester
The title compound was prepared from methyl 3-(3-methoxymethyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, 2-methoxyacetaldoxime [CAS-No. 71494-93-4], Et3N and cat, amoimt of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40^ 2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow liquid (1.548 g).
MS (EI) 331 (M+),
Example KlO
(RSV3-Oxo-3-{3-f4-(tetrahvdro-pvran-2-yloxvmethyl)-thiazol-2-yl1-phenyll-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yioxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 13-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180

mL) was heated to 60 °C for 24 h. The reaction mixture was cooled to 20°C and acided to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL), Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii,) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).
MS (ISP) 418.2 [(M+H)1.
Example K11
(RS)-3-Oxo-3-{3-F4-ftetrahvdro-pvran-2-yloxvmethyl)-oxazol-2-\yl]-phenyl]-propionic acid tert-butylester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-carbamoyl-benzoic acid methyl ester [CAS-No. 106748-24-7] (17.9 g) and l,3-dichloro-2-propanone (14.0 g) was heated to 140 °C for 1.5 h. The mixture was cooled to 20 °C and cone, sulfuric acid (12 mL) was carefully acided. The mixture was stirred for 10 min. and then poured into ice-water. The product was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as duent to give 3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methyl ester (11.8 g) as a pale-yellow oil. MS (ISP) 252.2 [(M+H)--]. ii.)
I A solution of this material (7.6 g) and lithium hydroxide monohydrate (5.0 g) in DMSO (30 mL) was heated to 60 -°C for 7 h. The cooled reaction mixture was poured into ice-water and the mixture was extracted with diethyl ether. The aqueous layer was acidified to pH 1 by the acidition of 6N HCl and the precipitate formed was collected by filtration and crystallized from dichloromethane/hexane. The pale-yellow crystals
5 (5.5 g) were dissolved in DMSO (25 mL), and after the acidition of N,N,N'N'-

tetramethyl-guanidine (4.4 mL) and methyl iodide (2.2 mL), the mixture was stirred at 20 ^°C for 1 h. Ethyl acetate was acided and the mixture was washed successively with water, IN HCl and brine. The organic layer was dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as eluent and the purified product was crystallized firom diethyl ether/hexane to give 3-(4-hydroxymethyl-oxazol-2-yl)-benzoic acid methyl ester (2.1 g) as white crystals, mp 118-119 °C. iii.) A mixture of this material (2,1 g), dihydropyrane (1.2 mL) and p-toluenesulfonic acid hydrate (0.1 g) in ethyl acetate (15 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester (3,5 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).
MS (ISP) 402.5 [(M+H)1.
Example K12
(RS')-3-Oxo-3-(3-r3-rtetrahvdro-pvran-2-yloxvmethyl)-isoxazol-5-vn-phenyl-propionic acid tert,-butylester
The title compound was prepared from (RS)-3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (7.55 g, 23 mmol) and hydroxylamme hydrochloride (4.74 g, 68 mmol) were refluxed in EtOH for 1 h; ii.) The obtained ester (5.94 g, 20 nrniol) was reduced with LiAlH4 (761 mg, 20 mmol) in THF at -10 °C for 1 h; iii.) The obtained alcohol (4.90 g, 19 mmol) was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH.HaO in DCM at 23 °C for 20 h. iv.) The obtained THP-ether (5.24 g, 15 mmol) was treated with n-BuLi at -78 'C for 45 min, followed by a stream of CO2- v.) The obtained crude acid was stirred in MeOH (90 mL) and cone, H2SO4 (6.5 mL) at 50 X for 12 h. vi.) The obtained material (2.01 g, 8.62 mmol) was reacted with 3,4-dihydro-2H-pyran (1.17 mL, 12.9 mmol) and cat, amount p-TsOH.H2O in DCM (17 mL) at 23 °C for 5 h.] (2.44 g, 7.7 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.06 g).
MS(ISP)402((M+H)-'].

Example K13
(RS)3-(3-f3-Methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phneyl}-3-oxo-propionic acid tert,-butyl ester
The title compound was prepared from (RS)-3-[3-methyi-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yi]-benzoic acid methyl ester [prepared by the following sequence: i.) (3-bromO-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 21575-91-7], pyrrolidine and TMSOTf in benzene were refluxed for 16 h {Org. Synth, 53y 59); ii.) The obtained 3-(3-bromo-phenyl)-3-pyrrolidin-l-yl-acrylic acid ethyl ester was reacted with nitroethane, POCI3 and Et3N at 23 °C; iii,) The obtained 5-(3-bromo-phenyI)-3-methyl-isoxazole-4-carboxylic acid ethyl ester was reduced with LiAlHH4 in THF at -10 -°C for 1 h iv.) The obtained [5-(3-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol was reacted with 3,4-dihydrO'2H-pyran and cat amount p-TsOH-HiO in DCM at 23 -C for 20 h. iv.) The obtained THP-ether was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vi.) The obtained 3-(4-hydroxymethyI-3-methyl-isoxazol-5-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (972 mg).
MS(EI)416[(M+H)1.
Example K14
(RSV3-[3'-[2-methyl-5-(tetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl]-phenylt-3-oxo-propionic acid tert.-butylester
The title compound was prepared from (RS)-3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (6.135 g, 21 mmol), MeNHNH2 (1.296 mL, 25 mmol) and HCl (4M in dioxane, 6.25 mL, 25 mol) in EtOH (35 mL) were refluxed for 1.5 h; ii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyrazole-3-carboxylic acid ethyl ester (7.02 g, 22.7 mmol) was reduced with LiAlH4 (862 mg, 22.7 mmol) in THF (60 mL) at -10 °C for 1 h; iii.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-3-yi]-methanol (6.34 g, 24 mmol) was reacted with 3,4-dihydro-2H-pyran (3.25 mL, 36 mmol) and cat amount p-TsOH.H2O in DCM (50 mL) at 23 X for 23 h. iv.) The obtained (RS)-[5-(3-bromo-phenyl)-l-methyl-3-(tetrahydro-pyran-2-yloxymethyl)-lH-pyrazole(8.64
g, 25 mmol) was treated with n-BuLi at -78 °C for 45 min, followed by a stream of

CO2. V.) The obtained crude acid was stirred in MeOH (90 mL) and cone. H2SO4 (6.5 mL) at 50 °C for 5 h. vi.) The obtained 3-(5-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (3.41 g, 13.85 mmol) was reacted with 3,4-dihydro-2H-pyran (1.75 mL, 20.77 mmol) and cat amount p-TsOH.H2O in DCM (28 mL) at 23 --C for 18 L] (3.93 g, 11.9 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (4.90 g).
MS(ISP)415[(M+H)'].
Example K15
propionic acid tert.-butylester
The title compound was prepared from (RS)-3-(5-(tctrahydro-pyran-2-yloxymethyI)-isoxazol-3-yl]-benzoic acid methyl ester [prepared from (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] by treatment with NCS, cat amount pyridine in CHCI3 followed by acidition of (RS)-tetrahydro-2-(2-propynyloxy)-2H-pyran and slow acidition of Et3N in CHQ3 at 23 oC-] by treatment with hthium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g).
MS (ISN) 400.5 [(M-H)-],
Example Kl 6
3-Oxo-3-(3-pyrazol-l-yl-phenyl)-propiQnic acid tert-butvi ester
The title compound was prepared from 3-pyrazol-l-yl-benzoic acid methyl ester [CAS-No. 168618-35-7] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.00 g).
MS (EI) 286 (M+),
Example K17
fRS)-3-Oxo-3-{3-[4-ftetrahvdro-pyran-2-yloxymethyl)-pvrazol-l-yl1-phenyl-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-1-yl]-benzoic acid methyl ester [prepared by the following sequence: L) A mixture of 3-hydrazino-benzoic acid methyl ester hydrochloride [CAS-No. 167626-26-8] (15.14 g, 75 mmol), 2-cyano-3-ethoxy-acryiic acid benzyl ester [CAS-No. 32016-27-6] (17.36 g, 75 mmol) and Et3N (10.5 mL, 75 mmol) in isopropanol (115 mL) was refluxed for 1.5 h. ii.) The obtained 5-amino-l-(3-methoxycarbonyl-

phenyl)-lH-pyra2ole-4-carboxylic acid benzyl ester (26.0 g, 74 mmol) was refluxed with isopentyl nitrite (30 mL, 225 mmol; 10 mL) in THF (200 mL) for 22 h. iii.) The obtained l-(3-methoxycarbonyl-phenyl)-lH-pyrazole-4-carboxylic acid benzyl ester (18.98 g, 56 mmol) was hydrogenated in the presence of Pd/C (10% Pd/C, 600 mg, 1 mol%) in EtOAc (350 mL) and THF (250 mL) at 23 oC for 16 h. iv.) The obtained 1-(3-methox7carbonyl-phenyl)-lH-pyrazole-4-carboxylic acid (13.70 g, 55.6 mmol) was reduced with BH3.SMea (28.46 mL, 278.2 mmol) m THF (364 mL) at 5 to 23 °C for 16 h. V.) The obtained 3-(4-hydroxymethyl-pyrazol-l-yl)-benzoic acid methyl ester (10.66 g, 45.9 mmol) was reacted with 3,4-dihydro-2H-pyran (6.24 mL, 68.9 mmol) and cat. amount p-TsOH-HaO in DCM (91 mL) at 23 °C for 22 h.] (14.18 g, 44.8 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (15.87 g),
MS(ISN)399[(M.H)-].
Example K18
(RS)-3-Oxo-3-{3-[4'(tetrahvdro-pyran-2*yloxvmethyl)-isoxazol-3-yn-phenyll-propionic acid tert.'butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] was treated with NCS, cat amount pyridine in CHCI3 followed by acidition of (E)-3-pyrrolidin-l-yl-acryhc acid tert.-butyl ester [CAS-No. 340257-76-3] and slow acidition of Et3N in CHCI3 at 23 -°C. ii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid tert-butyl ester was stirred in formic acid at 50 °C for 18 h. iii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid was reduced with BH3*SMe2 in THF at 5 to 23 'C for 16 h. iv.) The obtained 3-(4-hydroxymethyl-isoxazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH-HzO in DCM at 23 °C for 1L] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (1.817 g).
MS(ISN)400[(M-H)-].

Example Kl 9
fRS)-3-l3-(2-methyl-4-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl 3'OXo-propionic acid tert--butyl ester
The title compound was prepared from (RS)-3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyra2ol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 3-bromobenzoyl chloride and 3-isopropylamino-acrylic acid methyl ester [CAS-No. 89895-40-9] were reacted in toluene and Et3N according to Synthesis 1982, 318. ii.) The obtained 2-(3-bromo-benzoyl)-3-isopropylamino-acrylic acid methyl ester was reacted with methylhydrazine in ether at 23 °C according to Synthesis 1982, 318. iii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyra2ole-4-carboxylic acid methyl ester was reduced with LiAlH4 in THF at -10 °C for 1 h. iv.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-4-yl]-methanol was reacted with 3,4-dihydro-2H-pyran and cat. amoimt p-TsOH-HaO in DCM at 23°C for 20 h. v.) The obtained (RS)-5-(3-bromo-phenyl)-l-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-iH-pyrazole was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. vi.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vii.) The obtained 3-(4-methoxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with IM BBrs-sol. in DCM at -78 to 23 -°C for 1 h. viii.) The obtained crude bromide was reacted with KOAc in DMF at 60 °C for 30 min. ix.) The obtained crude acetate was reacted with NaOMe-sol. In MeOH at 23 °C for 20 min. X-) The obtained 3-(4-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (11.106 g).
MS(ISN)413[(M-H)-].
Example K20
(RS)-3-Oxo-3-(3-{2-(2-ftetrahvdrQ-pyran-2-yloxvVethyl1-2H-pvrazol-3-yl}-phenyl)-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyl)-3-dimethylamino-propenone [CAS-No. 163852-04-8] with 2-hydroxy-ethylhydrazine in EtOH at 23 °C for 2.5 days, ii.) The obtained mixture of pyrazoles (12.36 g, 35.19 mmol) was reacted with 3,4-dihydro-2H-pyran (4.79 mL, 52.8 mmol) and cat amount p-TsOH-H2O in DCM (70 mL) at 23 °C for 20 h iii.) chromatographic separation of the obtained isomers, iv.) treatment of the clean

isomer (7.35 g, 73.7 mmol) was treated with n-BuLi (13.08 mL, 20,9 mmol) in THF (42 mL) at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid was reacted (4.56 g, 14.1 mmol) was reacted with KHCO3 (2.89 g, 28.8 mmol) and Mel (0.99 mL, 15.9 mmol) in DMF (29 mL) at 23 °C for 2 h,] (2.96 g, 8.96 mmol) by treatment with Uthium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g).
MS(ISP)415[(M+H)+].
Example k21
(RSV3-Oxo-3-f3-{5-r2-ftetrahvdro-p\Tan-2-\dox\'Vethyll-rL23ltriazol-l--vil-phenyl-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-{5-[2-(tetrahydro-pyran-2-yioxy)-ethyl]-[l,2,3]triazol-l-yl}-benzoic acid methyl ester (prepared by the following sequence: L) methyl 3-azidobenzoate [CAS-No. 93066-93-4] and (RS)-tert-butyl-dimethyl-[4-(tetrahydro-pyran-2-yioxy)-but-l-ynyi]-silane [CAS-No. 198411-20-0] were heated to 60 °C for 10 days; ii.) The obtained material was stirred in TBAF (IM m THF) at 70 °C for 6 days and subsequently refluxed in IN HCl for 2 h; iii.) The obtained 3-[5-(2-hydroxy-ethyl)-[l,2,3]triazol-l-yl]-benzoic acid was stirred in MeOH and cone. H2SO4 at 23 °C for 11 days, iv.) The obtained 3-[5-(2-hydroxy-ethyl)-[ 1,2,3]triazol-l-yl]-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH'H2O in DCM at 23 °C for 20 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (6.748 g).
MS(ISP)416[(M+H)-'].
Example K22
(RS)-3-Oxo-3-l3-(5-rtetrahvdro-pyran-2-yloyvmethyl)-pvrazol-l-yll-phenyll-propionic acid ethyl ester
The title compoxmd was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yioxymethyl)-pyrazol-l-yl]-benzoic acid [prepared by the following sequence: i.) A mixture of 3-hydrazino-benzoic acid [CAS-No. 38235-71-1], 4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester [CAS-No. 67751-14-8] in acetic acid was refluxed for 15.5 h. ii.) The obtained 2-(3-carboxy-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was stirred DMF-di-tert-butyl acetal in toluene at 80 X for 45 h. iii.) The obtained 2-(3-terL-butoxycarbonyl-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was saponified

150°C Cristallisation from water and ethyl acetate/hexane (1:1) yielded a light brown solid (24.3 g, 54%) mp 164°C; ii,) The obtained material (24-3 g, 104 mmol) was

reacted with 3,4-dihydro-2H-pyran (29.3 mL, 320 mmol) and cat amount p-TsOH-H2O in dichloromethane (360 mL)/ THF (300 ml) at 23 °C for 20 L Purification by column chromatography on silica gd (toluene/ethyl acetate 1:1) gave a light brown oil.] (16.6 g, 52.3 mmol) by treatment with hthiimi tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (14.3 g, 68%).
MS (ISP) 400.4 [(M-H)-].
Example K25
3-Oxo-3-(3-[1.2.4]triazol-yl-phenyl)-pTopionic acid tert-butylester
The title compound was prepared from methyl 3-[l,2,4]triazol-1-yl-benzoate [CAS-No. 167626-27-9] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange liquid (2.41 g),
MS (EI) 287 (M^).
Example K26
3-(3-Imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butylester
The title compound was prepared from methyl 3-(lH-imida2ol-l-yl)benzoate [prepared from 3-(lH-imidazol-l-yl)benzoic acid (/. Med, Chetn. 1987,30,1342; CAS-No. [108035-47-8] by reflioxing in cone. H2SO4/MeOH] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange-brown oil.
MS (ISP) 287 [(M+H)+].
Example K27
3-0X0-3-f3-f4-ftetrahydro-pyran-2-yloxvmethyl')-thia2ol-2-yl]-phenyl]-propionic acid tert-butylester
al 3-f4-Hvdroxymethyl-thiazol-2-yl)-benzoic acid methyl ester
A mixture of 3-thiocarbamoyl-benzoic acid methyl ester (7,8 g), l,3-dichloro-2-propanone (8.4 g) and NaHCOs (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 -°Cfor 24 h. The reaction mixture was cooled to 20 °C and acided to a stirred solution of NaOMe (5.4 g) in MeOH (200 mL). Stirring was continued for 0,5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ACOEL The organic layer was washed with brine, dried and evaporated in vacuum-

The residue was crystallized from CH2Cl2/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-ben2oic acid methyl ester (7.5 g) as light-brown crystals, mp 115-117 °C.
b) 3-f4-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-2-yn-benzoic acid methyl ester
A mixture of the material prepared in a) (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in AcOEt (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried over Na2SO4 and evaporated in vacuo. The residual oil was purified by chromatography on silica gel using AcOEt /hexane (1:2) as eluent to give 3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.
c) 3-Oxo-3-f3-r4-ftetrahvdro-pyran-2-yloxvmethyD-thiazoI-2-yI1-phenyl]-propionic acid tert-butylester
A sample of the material prepared in b) (3.3 g) was treated with lithium tert,-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (3.25 g) as a pale-yeUow oil, MS (ISP) 418.2 [(M-fH)--].
Example K28
3-Oxo-3-f3-(2-bromo-lJ-dimethoxy-ethyl')-phenyll-propionic acid tert-butylester
a) 3-(2-Bromo-Ll-dimethoxy-ethyl')-ben2oic acid methyl ester
A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-No 62423-73-8] (2.43 g), 4-toluenesulfonic acid hydrate (0.38 g) and trimethyl orthoformiate (5.5 ml) in MeOH (40 mL) was heated at reflux for 20 h. The cooled solution was diluted with AcOEt (0.15 L), washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum to give 3-(2-bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.0 g) as a pale-yellow oil.
b) 3-Oxo-3-[3-(2-bromo-l,1-dimethoxv-ethyl)-phenyl1-propionic acid tert-butylester
3-(2-Bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.9 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyi]-propionic acid tert-butyl ester (2.8 g) as a yellow oil.

Example K29 3-Oxo-3-r3-(2-methyl-oxazol-4-yl)-phenyn-propionic acid tert-butyl ester
a) 3-(2-methyl-oxazol-4-yl)-benzoic acid
A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g) and acetamide (1.77 g) was heated with stirring to 130 'C for 40 min. The mixture was cooled and diluted with H2O (30 mL) and the precipitate formed was collected by filtration to give 3-(2-methyl-oxa2ol-4-yl)-ben2oic acid (1.51 g) as brown solid.
b) 3-(2-methyl-oxazol-4'yl')-benzoic acid methyl ester
A solution of 3-(2^methyl-oxazol-4-)d)-benzoic acid (1.42 g) in a mixture of MeOH (30 mL) and 4NHC1/Et20 (6 mL) was heated to 40 -°C for 4 h. The solution was evaporated in vacuum and the residual oil was stirred with H2O (30 mL), the pH of the mixture being set to about 6 by the acidition of sat NaHCOa solution. The precipitate was isolated by filtration to give 3-(2-methyl-oxa2ol-4-yl)-benzoic acid methyl ester (1.18 g) as light-brown solid, MS (ISP) 218.2 [(M+H)-^].
c) 3-Oxo-3-f3-('2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester
3-(2-Methyl-oxazol-4-yl)-benzoic acid methyl ester (1.02 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (1.50 g) as a pale-yellow oil.
Example K30
3-Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3.4lthiadiazol-2'yl1-phenyll-propionic acid tert-butyl ester
a) 3-rN'-tert-butoxvcarbonyl-hvdra2inocarbothioyl)-benzoic acid methyl ester
A mixture of 3-(N'-tert-butoxycarbonyl-hydrazinocarbonyl)-benzoic acid methyl ester (1.47 g) and Lawesson reagent (1.62 g) in toluene (30 mL) was heated to 70 °C for L5 h. The mixture was concentrated in vacuum and then subjected to chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-(N'-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (1.31 g) as a yellow solid, MS (ISP) 328.3 [(M+NH4)1.

b) 3-Hvdra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate
A solution of 3-(N1-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (0.93 g) in TFA (9 mL)/anisole (2 mL) was stirred at 0 X for 1 h. The solvents were evaporated in vacuum to give crude 3-hydrazinothiocarbonyl-ben2oic acid methyl ester trifluoroacetate (0.98 g) as a crystallizing oil.
c) 3-(5-Hydroxymethyl-[L3,4lthiadiazoI-2-yl)-benzoic acid methyl ester
A mixture of 3-hydrazinothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.49 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.47 g) in EtOH (6 mL) was heated to 80 °C for 2.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated. The residual oil (0.8 g) was dissolved in MeOH (5 mL), MeONa (0,08 g) was acided and the solution was heated to 65 °Cfor 0.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (0.15 g) as a white soHd, MS (ISP) 25L2 [(M+H)+].
d) 3'(5-fTetrahvdro-pyran*2-yloxvmethyl)-fL3,4lthiadiazol-2-ylUbenzoicacid
methyl ester
A mixture of 3-(5-hydxoxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (7.8 g), dihydropyrane (5.6 mL) and p-toluenesulfonic acid hydrate (0.59 g) in AcOEt (80 mL) was stirred at 20 °Cfor 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on sihca gel using AcOEt/hexane (1:2) as eluent to give 3-[5-{tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5,85 g) as a pale-yellow oil.
e)3'Oxo-3-B-r5-ftetrahvdrO'pyran-2-vIoxvmethyl)-fl3.4lthiadiazQl-2-yl]-phenyl-propionic acid tert-butylester
3-[5-(Tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5.85 g) was treated with lithium tert,-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (8.9 g) as a pale-yellow oil.

Example K31
3-Oxo-3-(3-(5-r2-ftetrahvdro-pyran-2-vIoxy)-ethyl14L3.4lthiadia2ol-2-yl}-phenyl)-propionic acid tert-butylester
a) 3-[5-(2-Hydroxy-ethyl)-ri3,4lthiadiazol-2-yl1-benzoic acid methyl ester
A mixture of 3-hydra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.45 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (0.35 g) in pyridine (5 mL) was heated to 100 °C for 1.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was chromatography on siUca gel using AcOEt/hexane (1:1) as eluent to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]thiadiazol-2-yl]-ben2oic acid methyl ester (0.37 g) as a white solid, MS (ISP) 265.3 [(M+H)+].
b) 3-15- [2-fTetrahydro-pyran-2-yloxy)-ethyl1 - [ 1,3>4]thiadiazol-2-yn-benzoic acid
methyl ester
A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3>4]thiadia2ol-2-yl]-ben2oic acid methyl ester (1.86 g), dihydropyrane (0.95 mL) and p-toluenesulfonic acid hydrate (0.13 g) in AcOEt (25 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyI]-[l,3,4]thiadia2ol-2-yl}-benzoic acid methyl ester (1.60 g) as a pale-yellow oil.
c)3-Oxo-3-r3-l5-r2-ftetrahvdro-pyran-2-vIoxv)-ethyl]-rL3.4lthiadiazoI-2-yl?-phenyD-propionic acid tert-butylester
3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadia2ol-2-yl}-benzoicacid methyl ester (1.60 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phen}i)-propionic acid tert-butyl ester (2.1 g) as a pale-yellow oil.
Example K32
3-Oxo-3-(3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3,4loxadiazol-2-yl]-phenyll-propionic acid tert-butyl ester
z) 3-(5-HvdrQXvmethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester
A mixture of 3-hydrazinocarbonyl-benzoic acid methyl (0.97 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.95 g) in EtOH (20 mL) was heated to 80

-°C for 1 h. The mixture was diluted with AcOEt and washed with IN HCI and with brine. The organic layer was dried and evaporated and the residual oil (1.1 g) was dissolved in DMF (4 mL). Upon acidition of AcOK (0.59 g) and KI (0.07 g), the mixture was stirred at 100 Xfor 0.5 h. After cooling to 20 °C, MeOH (10 mL) and NaOMe (0.14 g) were acided and stirring was continued for 0.5 h at 65 °C. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester (0.72 g) as a white solid, MS (ISP) 235.3 [(M+H)--].
b) 3-(5-(Tetrahvdro-pyran-2-yloxvmethyl)-[ 1.3.4lthiadiazol-2-vn -benzoic acid methyl ester
A mixture of 3-(5-hydroxymethyl-[l,3>4]oxadiazol-2-yl)-benzoic acid methyl ester (9.8 g), dihydropyrane (7.7 mL) and p-toluenesulfonic acid hydrate (0.80 g) in AcOEt (100 mL) was stirred at 20 **€ for 1 h. The solution was diluted with AcOEt, washed with 5% NaHC03 solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-[5-(tetrahydrO-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (12.6 g) as a pale-yellow oil.
c)3-Oxo-3-{3-[5-(tetrahydro-pyran-2-yloxvmethvD-fl3,4loxadiazol-2-yn-phenyll-propionic acid tert-butylester
3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,3,4]thiadiazol-2-yl] -benzoic acid methyl ester (12,6 g) was treated with Uthium tert.-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (17.0 g) as a pale-yellow oil.
Example K33
3-Oxo-3-f3-{5-[2-ftetrahvdro-pyran-2-yloxvVethyl]-[L3.4loxadiazol-2-yll-phenyl)-propionic acid tert-butylester
2L) 3-[5-(2-Hvdroxv-ethyl)-ri3,4l6xadiazol-2-yl1-benzoic acid methyl ester
A mixture of crude 3-hydrazinocarbonyl-ben2oic acid methyl (2,90 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (2.76 g) in pyridine (10 mL) was heated to 100 °Cfor 2 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was

crystallized from Et20 to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yI]-benzoic acid methyl ester (2.5 g) as a white solid, MS (ISP) 249.1 [(M+H)--],
b)3-l5-(2-fTetrahydro-pyran-2-yloxvVethyl]-fL3,4lthiadiazol-2-vU-benzoicacid methyl ester
A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yl]-benzoic acid methyl ester (7.45 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0,57 g) in AcOEt (80 mL) was stirred at 20 'Cfor 2 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoic acid methyl ester (8.2 g) as a pale-yellow oil.
cl3-Oxo-3-(3-(5-(2-(tetrahvdro-pyran-2-yloxv)-ethyl]-rL3.4loxadiazol-2-vU-phenyl)-propionic acid tert-butylester
3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoicacid methyl ester (8.2 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (11.6 g) as a pale-yellow oil.
Example K34
3-(3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester
a) 3-Oxazol-4-yl-benzoic acid methyl ester
A mbcture of 3-(2-bromo-acetyl)-benzoic acid (1.94 g) and formamide (1.08 g) was heated with stirring to 130 ^'Cfor 3 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was dissolved in a mixture of MeOH (30 mL) and 4NHC1/Et20 (8 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOs solution and brine, dried and evaporated. The residue was chromatographed on sihca gel using AcOEt/hexane (1:3) as eluentto give 3-oxazol-4-yl-benzoic acid methyl ester (0.85 g) as off-white solid, MS (ISP) 204.1 [(M+H)-*-].
b) 3-r3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester
3-Oxazol-4-yl-benzoic acid methyl ester (0.85 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (1.46 g) as a pale-yellow oil.

Example K35 3-Oxo-3-f3-thiazoI-4-vI-phenyl)-propionic acid tert-butylester
a) 3-Thiazol-4-yl-benzoic acid methyl ester
A solution of 3-(2-bromo-acetyi)-benzoic acid (L22 g) and thioformamide (0.46 g) in EtOH (5 mL) was heated to 80 •C for 1 L The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was dissolved in a mixture of MeOH (20 mL) and 4NHCl/Et20 (5 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOj solution and brine, dried and evaporated. The residue was chromatographed on siUca gel using AcOEt/hcxanc (1:3) as eluent to give 3-thiazol-4-yl-benzoic acid methyl ester (0,98 g) as off-white solid, MS (ISP) 220.2 [(M+H)--].
b) 3-Oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butylester
3-Thiazol-4-yl-benzoic acid methyd ester (0.91 g) was treated with lithitun terL-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (1.54 g) as a pale-yellow oil.
Example K36
3-f3-(5-Methyl-oxazol-4-yI)-phen)d]-3-oxo-propionic acid tert-butylester
a) 3-tert-Butoxvcarbonylacetyl-benzoic acid methyl ester
Dimethyl isophthaiate (67.9 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give crude 3-tert-butoxycarbonyiacetyi-benzoic acid methyl ester (74.5 g) as a pale-yellow oil.
b) 3-Propionyl-benzoic acid methyl ester
To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (ILl g) and Mel (2.2 mL) m DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil> 1.4 g). Stirring was continued at 0 ®C for 15 min and at 20 °C for 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated The residue was stirred in a mixture of CH2Cl2 (30 mL) and TEA (30 mL) for 40 min at 20 °C. After the evaporation of the solvents, the solution of the residue in AcOEt was extracted with ice-cold sat NaaCOs solution and the aqueous extracts were immediately acidified with 3N HQ and extracted with AcOEt The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HCl (3 mL) to 100 °C for 1 h. The cooled mixture was diluted with AcOEt, washed

with sat. NaHCOs and brine, dried and evaporated to give 3-propionyi-benzoic acid methyl ester (3.87 g) as white solid, MS (ISP) 193.2 [(M+H)--].
c) rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester
A mixture of 3-propionyl-benzoic acid methyl ester (3.6 g) and CuBri (7.45 g) in AcOEt (45 mL) was heated at reflux for 2 h. Unsoluble material was filtered oflFfrom the cooled mixture and the clear solution was washed with brine, dried and evaporated to give crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (5.0 g) as pale-yeUow oO.
d) 3-r5'methyl-oxazol-4-yl)-benzoic acid methyl ester
rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester (5.42 g) and formamide (3.6 ml) were heated together to 130 °C for 5 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as eluent to give 3-(5-methyI-oxazol-4-yl)-benzoic acid methyl ester (2.52 g) as white solid.
e) 3-[3-(5-Methyl-oxazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester
3-(5-methyl-oxazol-4-yl)-beruoic acid methyl ester (0.87 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (L46 g) as a pale-yellow oil.
Example K37
3-[3-(2-methyl'5-propyl-oxazol-4-yl)-phenyl-3-oxo-propionic acid tert-butyl ester
al 3-Pent-4-enoyl-benzoic acid methyl ester
To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (11.1 g) and allyl bromide (3.0 mL) in DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil, 1.44 g). Stirring was continued at 0 °C for 20 min and at 20 °Cfor 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated. The residual oil was stirred in a mixture of CH2Cl2 (30 mL) and TFA (30 mL) for 40 min at 20 'C. The solvents were evaporated. The solution of the residue in AcOEt was extracted with ice-cold saL NaaCOa solution and the aqueous extracts were immediately acidified with 3N HCl and extracted with ACOEL The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HQ (2 mL) to 100 ^'C for 1 h. The cooled mbcture was diluted with AcOEt, washed

with saL NaHCOs and brine, dried and evaporated to give 3-pent-4-enoyi-ben2oic acid methyl ester (5.11 g) as a pale-yellow oil, MS (ISP) 236.2 [(M+NH4)'].
b) rac-3-(2-Bromo-pentanoyl)-benzoic acid methyl ester
A sample of 3-pent-4-enoyl-benzoic acid methyl ester (3.93 g) was hydrogenated in AcOEt (50 mL) in the presence of 5% Pd-C (190 mg) for 30 min at 20 ^'C. The catalyst was filtered off, CuBr2 (4.44 g) was acided to the solution and the mixture was heated at reflux for 1 h. Unsoluble material was filtered off from the cooled mixture and the clear solution was washed with IN HCl and brine, dried and evaporated to give crude rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (3.6 g) as pale-yellow oil.
c) 3-(2-methyl-5-propvI-oxazol-4-yl)-benzoic acid methyl ester
A sample of rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (1.50 g) and acetamide (0.89 g) were heated together to 130 *C for 15 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oE was chromatographed on silica gel using AcOEt/hexane (1:3) as duent to give 3-(2-methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0.47 g) as a light-yellow oil.
d) 3-f3-(2-methyl-5-propyl-oxazol-4-yl')-phenyl1-3-oxO'propionic acid tert-butylester
3-(2-Methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0,47 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(2-methyl-5-propyl-oxazol-4-yl)-phenyl]-3-oxo-propiomc acid tert-butyl ester (0.58 g) as a light-brown oil.
Example K38
3-[3-(5-methyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butylester
z) 3-(5-methyl-thia2Ql-4-yl)-benzoic acid methyl ester
A solution of crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (2,71 g) and thioformamide (1.83 g) in EtOH (20 ml) was heated at reflux for 1 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as duent to give 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (2.41 g) as white solid.
h) 3-[3-(5-methyl-Aiazol-4-yl)-phenyll-3-oxo-propiQnic acid tert-butylester
A sample of 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g) was treated with Uthium tert-butyl acetate according to the general procedure K (method b) to

give crude 3-[3-(5-methyl-thia2ol-4-yi)-phcnyl]-3-oxo-propiomc acid tert-butyl ester (L9 g) as a pale-yellow oil
Example K39
3-f3-(23-Dimethyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester z) 3-(2,5-Diinethyl-thiazol-4-yl)-ben2oic acid methyl ester
A mixture of rac-3-(2-bromo-propionyl)-bcn2oic acid methyl ester (6.78 g) and thioacetamide (5.63 g) was heated to 130 ^'Cfor 20 min. The mixture was partitioned between AcOEt and H2O, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gd using AcOEt/hcxane (1:4) as duent to give 3-(2,5-dimethyl-thia2;ol-4-yl)-benzoic acid meth>1 ester (4.97 g) as yellow oil.
b) 3-r3-(2>5-Dimethyl-thiazol-4-y!)-phen\i]-3-oxo-propionic acid tert-butyl ester
A sample of 3-(2,5-dimethyl-thia2ol-4-yl)-ben2oic acid methyl ester (0.99 g) was treated with lithiimi tert-butyl acetate according to the general procedure K (method b) to give 3-[3-(2,5-dimethyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (1.12 g) as a pale-yellow oil.
Example K40
3-Oxo-3-[3-(5-methyl-4-(tetrahvdro-pyran-2-yloxvmethyl)-thia2ol-4-yl]-phenyi1-propionic acid tert-butyl ester
a) 3-(2-HydroxymethyI-5-methyl-thia2ol-4-yl)-ben2oic acid methyl ester
A solution of rac-3-(2-bromo-propionyI)-ben2oic acid methyl ester (2 Jl g) and 2-(tert.-butylcarbonyloxy)thioacetanude (2.1 g) in EtOH (20 mL) was heated at reflux for 6 h. The mixture was partitioned between AcOEt and brine, and the organic layer was dried and evaporated. A solution of the residual oil and NaOMe (0.54 g) in MeOH (20 mL) was stirred at 60 °C for 1 h. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (1.17 g) as white crystals, MS (ISP) 264.1 [(M+H)^.
h) 3-(5-methyl-4-ftetrahvdro-pyran-2-yloxymethyl')-thiazQl-4-yl1-benzoic acid methyl ester
A mixture of 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g), dihydropyrane (0.73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 -°C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCO3 solution and with brine, dried and evaporated The residual

oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-l5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1,45 g) as a pale-yellow oil.
c) 3-0x0-3- [3* r5-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-4-yll -phenyl] -propionic acid tert-butyl ester
3-[5-Methyl-4-(tetrahydro-pyran-2--yloxymethyl)-thiazol-4-yl]-ben2oic acid methyl ester (1.45 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl]-propionic acid tert-butyl ester (2.13 g) as a pale-yellow oil.
Example K41
3-Oxo-3-[3*[5-propyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-2-yl]-phenyl-propionic acid tert-butyl ester
a) 3-(2-Hydroxvmethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester
A sample of rac- 3-(2-bromo-pentanoyl)-benzoic acid methyl ester (0.60 g) and and 2-(tert.-butylcarbonyloxy)thioacetamide (0.36 g) in EtOH (4 mL) was heated at reflux for 5 h. The mixture was partitioned between AcOEt and 5% NaHCOs solution, the organic layer was washed with brine, dried and evaporated. A solution of the residual oil and of NaOMe (0.13 g) in MeOH (10 mL) was stirred at 60 °C for 30 min. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.44 g) as an oil.
b) 3-f 5-Propyl-4-(tetrahydro-pyran-2-yloxymethyl)-tfaiazol-2-yl1-benzoic acid methyl
gster
3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (0,73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 ^'C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as duent to give 3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (0.36 g) as a pale-yellow oil.

c)3'Oxo-3-f3-(5-propyl-4-(tetrahvdro-pyran-2-yloxyme&yl)-tfaiazol-2-yl]-pheny^ propionic acid tert-butyl ester
3-l5-Propyl-4-(tetrahydro-pyran-2-yloxymeth)d)-thia2ol-2-yl]-benzoic acid methyl ester (0-34 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.42 g) as a pale-yellow oil.
Example K42
3-Oxo-3-f3-r2-methyl-5-ftetrahydro-pyran-2-yloxvmetfayl)-thiazQl-4'yl]-phenyl-propionic acid tert-butyl ester
al 3-(5-Bromomethyl-2-methyl-thia2oI-4-yl)-benzoic acid methyl ester
A mixture of 3-(2,5-dimethyl-thiazol-4-yl)-benzoic acid methyl ester (3.96 g), N-bromosuccinimid (3.13 g) and (X,a'-bis(isobutyronitrile) (0.02 g) in CCI4 (60 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-ben2oic acid methyl ester (6,2 g) as an oil.
h) 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-ben2oic acid methyl ester
3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-benzoic acid methyl ester was stirred in DMF (16 mL) together with KOAc (2.35 g) at 20 °C for 20 min. MeOH (32 mL) and naOMe (0.86 g) were acided and stirring was continued at 50 '°C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:1) as eluentto give 3-(5-hydroxytnethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (2,93 g) as a white solid.
c) 3-[2-methyl-5-ftetrahydro-pyran-2-yloxymethyl)-thiazol-4-yll-benzoic acid methyl ester
3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (2.01 mL) and p-toluenesulfonic acid hydrate (0.21 g) in AcOEt (25 mL) was stirred at 20 °Cfor 1 h. The solution was diluted AcOEt, washed with 5% NaHCOa solution and with brine, dried and evaporated. The residual oil was purified by chromatography on siUca gd using AcOEt/hexane (1:3) as eluent to give 3- [2-methyl-5-(tetrahydro-pyran-2-)doxymethyl)-tiuazol-4-yl]-benzoic acid methyl ester (3.8 g) as a pale-ydlow oiL

d) 3-0x0-3-r3-r2-methyI-5'rtetrahydro-pyran-2-vIoxvmethyI)-tHazol-4-yl^ propionic acid tert-butyl ester
3-[2-Methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-ben2oic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (methodb) to give crude 3-oxo-3-[3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)' thiazol-4-yl]-phenyl]-propionic acid tert-butyl ester (5.45 g) as a pale-yellow oil.
Example K43
3--OXO-3-I [5-(tetrahydro-pyTan'2-yloxymethyl)-thiazol-4-vn -phenyl!-propionic acid tert-butyl ester
a) 3-f 5-Bromomethyl-thiazol-4-yl')-benzoic acid methyl ester
A mixture of 3-(5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (2.40 g), N-bromosuccinimid (2.01 g) and oc,a'-bis(isobutyronitrile) (0.02 g) in CCU (40 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-thia2ol-4-yl)-benzoic acid methyl ester (3.36 g) as an oil.
b^ 3-f 5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester
3-(5-Bromomethyl-thiazol-4-yl)-benzoic acid methyl ester was stirred in DMF (10 mL) together with KOAc (1.52 g) at 20 ^'C for 30 min, MeOH (20 mL) and NaOMe (0.84 g) were acided and stirring was continued at 50 °C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:2) as eluent to give 3-(5-hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (1.43 g) as a white solid.
c) 3-[5-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-4-yl]-benzoic acid methyl ester
3-(5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (L25 g), dihydropyrane (0,84 mL) and p-toluenesulfonic acid hydrate (0.10 g) in AcOEt (12 mL) was stirred at 20 °Cfor 3 h. The solution was diluted AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-[5-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1.60 g) as a pale-yellow oil.

d) 3-Oxo-3-( (5-(tetrahvdro-pyran-2-yloxyTnethyl)-thia2ol-4-yl]-phenyll-propionic acid tert-butyl ester
3-[5-(Tetrahydro-pyran-2-yioxymethyl)-thiazol--4-yi]-beiizoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-{[5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionic acid tert-butyl ester (2.3 g) as a pale-yellow oil.
Example K44
3-[3-(2-Isopropyi-3H'imida2ol-4-yl')-phenyll-3-oxo-propionic acid tert-butyl ester
3) 3-Dihydroxyacetyl-benzoic acid methyl ester
A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g), DMSO (17 mL) and 48% HBr (3.4 mL) was heated to 55 °C for 30 min. The mixture was partitioned between AcOEt and H2O and the organic layer was washed with brine, dried and evaporated to give 3-dihydroxyacetyl-benzoic acid methyl ester (1.06 g) as a white solid.
h) 3'(2-I$opropyl-3H-imidazol-4-yl)-benzoic acid methyl ester
A solution of 3-dihydroxyacetyl-benzoic acid methyl ester (0.36 g) and 2-methyl-propionaldehyde (0.24 ml) in 5% aqueous NH3 (6 mL) was heated to 100 °C for Ih, The mixture was evaporated in vacuum and the solution of the residue in a mixture of MeOH (10 mL) and 4NHC1/Et20 (2 mL) was heated to 40 °C for 18 h. The solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaaCOa solution and brine, dried and evaporated. The residue was chromatographed on silica gel using AcOEt as eluent to give 3-(2-isopropyl-3H-imidazol-4-yl)'ben2oic acid methyl ester (0.37 g) as a pale-yellow oil.
c) 3'f3-(2-Isopropyl-3H-imidazol-4-yl)-phenyll-3-oxo-propionic acid tert-butylester
3-(2-Isopropyl-3H-imidazol-4-yl)-benzoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give cmde 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (0.25 g) as a pale-yellow oil.

The following examples relate to the preparation of the 6-aryl-2,2-diniethyl-[l,3]dioxin-4-ones (general formula IV), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H):
General procedure L
Preparation of 6-aryl-2,2-dimethyl-fL3]dioxin-4-ones Method a)
The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from 3-aryl-3-oxo-propionic acids and catalytic amount of cone. H2SO4 or trifluoroacetic acid (TFA) in isopropenyl acetate at 23 *-€ according to Chem, Pharm, Bull 1983,3J, 1896. The final products were purified by silica gel coliunn chromatography with hexane/EtOAc.
Method b)
The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from the tert.-butyl 3-aryl-3-oxo-propionates by treatment with trifluoroacetic anhydride (TFAA) in a mixture of TFA and acetone at 23 -°C according to Tetrahedron Lett. 1998,39,2253. The final products were if necessary purified by silica gel column chromatography with hexane/EtOAc.
Example LI
3-(2,2-Dimethyl-6-oxo-6H-ri.3ldioxin-4'vD-benzonitrile
The 3-(3-cyano-phenyl)-3-oxo-propionic acid was prepared from 3-cyanobenzoyl chloride (828 mg, 5 mmol) and bis(trimethylsilyl)malonate (2.56 mL, 10 mmol) with n-BuLi (1,6M in hexane, 6.25 mL) in ether at-60 °C to 0 °C according to general procedure M (method c2). The crude material (1.04 g) was transformed into the title compound by stirring in isopropenyl acetate and TFA according to general procedure L (method a). Obtained as a light yellow solid (0.8 g).
MS (EI) 229 (M^); mp 138 °C (dec).
Example L2
4-(2.2-Dimethyl-6-oxo-6H-fL3ldioxin-4-yl1-pvridine-2-carbonitrile
The title compound was prepared from 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example MlO) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a brown solid (3.30 g).
MS (H) 230 (M^); mp 132 X (dec).

Example L3
6'f3'Imidazol-l-yl-phenyi)-2.2-dimethyl-fh3ldioxin-4-one
The 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid was prepared from 3-(lH-imidazol-l-yl)ben2oyl chloride hydrochloride [prepared by treatment of 3-(lH-imidazoM-yl)-benzoic acid (/. Med. Chem. 1987,30,1342; CAS-No. [108035-47-8] with SOCI2) and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 ^'C according to general procedure K (method cl). The crude material was transformed into the title compound by stirring in isopropenyl acetate and cone. H2SO4 according to general procedure L (method a). Obtained as an orange semisolid (617 mg).
MS (EI) 270 (M^).
Example L4
2.2-Dimethyl-6-f3-fL23ltriazol-l-vI-phenyl)-rL3ldioxin-4-one
The tide compound was prepared from 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K23) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a beige solid (7.80 g).
MS (EI) 271 (M--); mp 144-147 °C (dec).
General procedure M:
Preparation of {2-[3-aryI-3-oxo-propionylamino]-phenyl}-carbamic acid tert.-butyl ester by reaction of (2-amino-phenyl)-carbamic acid tert-butyl esters with ethyl or tert.-butyi 3-aryl-3-oxo-propionates or 6-aryl-2^-dimethyl-[l,3]dioxin-4-ones:
A mixture of the (2-amino-phenyl)-carbamic acid tert.-butyl ester or (1.0-1-2 mmol) and (1.0-1-5 mmol) of the ethyl or tert.-butyl 3-aryl-3-oxo-propionate or 6-aryl-2,2-dimethyl-[l,3]dioxin-4-one was heated in toluene (4-8 mL) to 80 **€ to 120 'C until tic indicated complete consumption of the minor component. The solution was allowed to cool to 23 °C, whereupon the product generally crystallized (in cases where crystallization failed to appear it was induced by acidition of hexane or ether, alternatively the reaction mixture was directly subjected to silica gel column chromatography). The solid was filtered off, washed with ether or mixtures of ether/hexane and dried in vacuum to give the {2-[3-aryl-3-oxo-propionylamino]' phenyil-carbamic acid terL-butyl esters, which was used direcdy in the following step or - if necessary - was purified by recrystallization or by silica gd column chromatography.

Example Ml
{4-Chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimethylamino-phenyll-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (0.5 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 62088-13-5; prepared from 3-cyanobenzoyl chloride according to general procedure K, method a] (0.55 mmol) according to the general procedure M. Obtained as a white solid (160 mg).
MS (ISP) 457 [(M+H)--]; mp 159-163 *°C.
Example M2
l4-Chloro-5-dimethylamino-2-r3-oxo-3-r3-rh23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) (150 mg> 0.58 mmol) according to the general procedure M. Obtained as a beige solid (160 mg).
MS (ISP) 499 [(M+H)--] and 501 [(M+2+H)1; mp 136-137 °C.
Example M3
fRS)-r4-Chloro-5-dimethylamino-2-f3-oxo-3-^3-[5-ftetrahvdro-pyran-2-
yloxvmethyl)-fL2.3ltria2ol-l-yll-phenyl}-prQpionylaminoVphenyl-carbamicacid
tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
acid tert-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow oil (257 mg).
MS (ISP) 613 [(M+H)'] and 615 [(M+2+H)'].

Example M4
(243-f3-cyano-phenvD-3-oxo-propiQnylamino1-5-dime1hylamino-4-phenvIethvnyl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carbamic acid tert.-but7l ester (Example J2) and 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-ben2onitrile (Example LI) according to the general procedure M. Obtained as an orange solid (108 mg).
MS(ISP)523[(M+H)1.
Example M5
/5-Dimethylamino-2-r3'Oxo-3-r3-fL2.3ltriazol-l-yI-phenyD-propionylamino1-4' phenylethvnyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylaminO-phenyl)-carbamic acid tert.-butyl ester (Example J2) and 3-oxo-3-(3-[l,2,3]tria2oM-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as an orange solid (148 mg).
MS(ISP)565[(M+H)'].
Example M6
f4-Chloro-5-dimetfaylamino-2-l3-[3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylamino I-phenyl) - carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(3-methyi-isoxa2ol-5-yI)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (450 mg, 075 mmol) according to the general procedure M. Obtained as a white solid (136 mg).
MS (ISP) 513 [(M-hH)--] and 515 [(M+2+H)']; mp 109-114 °C
Example M7
fRS)-r2-Dimethylamino-2'3'-diflu6ro-5-r3-oxo-3-l^-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23]triazoM-yl1-phenvU-propionylamino)-biphenyl-4-yll-carbamic
add tert.-butylester
The title compound was prepared from (5-amino-2-dimethyiamino-2*,3'-difluoro-biphenyl-4-yl)-carbamic acid terL-butyl ester (Example J3) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2^]tria2ol-l-yl]-phenyi}-propionic acid tert-

butyl ester (Example K5) according to the general procedure M. Obtained as a yellow solid (253 mg).
MS (ISP) 691 [(M+H)--].
Example M8
(2-Dimethylamino-2\3'-difluoro-5-r3-oxo-3-f3-rL23ltria2ol-l-yl-phenyl)-propionylamino1-biphenyl-4'yll-carbamic acid tert.-butylester
The title compoimd was prepared from (5-amino-2-dimethylamino-2',3*-difIuoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J3) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as a yellow solid (253 mg),
MS (ISP) 577 [(M+H)--],
Example M9
{5-f3-(3-cyano-phenyl')-3-oxo-propionylaminol-2-dimethylamino-2\3'-difluorO' biphenyl-4-yll-Carbamic acid tert.-butylester
The title compound was prepared from (5-amino-2-dimethylantiino-2',3'-difluoro-biphenyl-4-yl)-Carbamic acid tert.-butyl ester (Example J3) 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-benzonitrile (Example LI) according to the general procedure M. Obtained as a yellow solid (145 mg).
MS(ISP)535[(M+H)1.
Example MlO
(4-Chloro-5-dimethylamino-2'{3-(2-f3-methyl-isoxazol-5-vIVpvridin-4-yn-3-oxo-propionylaminol-phenyD-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-Carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yl]-3-oxo-propionic acid tert.-butyl ester (Example K6) (170 mg, 0.56 mmol) according to the general procedure M. Obtained as a brown solid (206 mg).
MS (ISP) 514 [(M+H)+] and 516 [(M+2+H)+]; mp 181-183 °C.

Example Mil
(4-CMoro-5-r(2-metfaoxy-ethyl)-methyl-aminol-2-l3-f3-(3-methyl-isoxa2ol-5-yD-phenyl]-3-oxO'propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (165 mg, 0.55 nrniol) according to the general procedure M. Obtained as an amorphous yellow substance (207 mg),
MS (ISP) 557 [(M+H)1 and 559 [(M+2+H)-'].
Example M12
(4-Chloro-5-f(2-methoxy-etfavi)>methyl-aminol-2-l3-(2-f3-methvMsoxazoI-5-yl)-pvridin-4-yI1-3-oxo-propionylaminol-phenyIVcarbamic acid tert.-butylester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert,-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yI]-3-oxo-propionic acid tert.-butyl ester (Example K6) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (190 mg).
MS (ISP) 558 [(M+H)1 and 560 [(M+2+H)']; mp 148 °C
Example M13
(RS)-f4-Chloro-5-f(2-methoxv-ethyl)-methyl-amino1-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-vIoxvmethyl)- f 1,2,31 triazol-1 -yl] -phenyl-propionylamino)-phenyl -carbamic acid tert.-butvi ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyi)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyi ester (Example K5) (200 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg).
MS (ISP) 657 [(M+H)+] and 659 [(M+2+H)1.

Example M14
U-Chloro-5-[(2-methoxv-ethyl)-methyl-amino1-243-oxo-3-f3Jl,23ltriazol-l-v^ phenyl)-propionylamino]'phenvH-carbamic acid tert--butyl ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-eth7l)-methyl-amino]-phenyl}-carbamic acid tcrt-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-oxo-3-(3-[l,23]tria2oM->1-phenyl)-propionicacid ethyl ester (Example Kl) (165 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (167 mg).
MS (ISP) 543 [(M-hH)--] and 545 [(M+2^H)1.
tompl^Ml?
{4-Chloro-2-f3-(2-cyano-p)Tidin-4-\i)-3-oxo-propionylaminoV5-dimethylamino-phenylj-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethyiamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (155 mg).
MS (ISP) 458 [(M+H)--] and 460 [(M+2+H)+];mp llO°C
Example M16
(4-Chloro-5-dimet3aylamino-2-{3-f3-(2-methyl-2H-pvrazol-3-vD-phenvi1'3*oxO-propionyiaminol-phenyl)-carbamic acid tert.-butylester
The title compoimd was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K7) (180 mg, 0,6 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg).
MS (ISP) 512 [(M+H)--] and 514 [(M+2+H)+].
- Example M17
(RS)-(5-Dimethylamino-2-(3-oxo-3-(3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23ltriazol-l'yl]-phenvU-propionylamino)-4-trifluoromethyl-phen'vdl-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (160 mg, 03

mmol) and (RS)-3 -oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (201 mg, 0-5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (247 mg).
MS (ISP) 647 [(M+H)--].
Example Ml8
(5-Dimethylamino-2-J3-f3-f3-methyl-isoxazol'5-vD-phenyl1-3-oxo-propionylaminoU4'trifluoromethyl-phenyl')-Carbamic acid tert,-butylester
The title compoimd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid terL-butyl ester (Example K4) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (94 mg).
MS (ISP) 547 [(M+H)+].
Example M19
f4-ChlorO'5-dimethylamino-2-{3-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0,5 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionicacidtert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (176 mg).
MS (ISP) 556 [(M+H)--] and 558 [(M+2+H)+].
Example M20
f4-Chloro--5'dimethylamino--2-B-f3-f3-methoxvmethyl-isoxazol-5-yl)-phenyl)-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compotmd was prepared from (2-ainino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (Example K9) according to the general procedure M. Obtained as a yellow solid (205 mg).
MS (ISP) 543 [(M+H)T and 545 [(M+2-fH)-*-].

Example M21
(2-r3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino]-5-dimethylamino-4-trifluoromethyl-phenyll-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromet]iyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, LO mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example K3) (246 mg, 1.0 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (297 mg).
MS(ISP)492[(M+H)+].
Example M22
(2'-Fluoro-5-[3-(3-imidazol-l-yl-phenyD-3-oxo-propionylamino1-2-(2,2.2-trifluoro-ethoxv)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 6-(3-imidazoH-yl-phenyl)-2,2-dimethyl-[l,3]dioxin-4-one (Example L3) (160 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous brown substance (167 mg).
MS(ISP)492[(M+H)-'].
Example M23
(2'-Fluoro-5-(3-r3-(3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-2-f 2.2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (160 mg, 0.53 mmol) according to the general procedure M. Obtained as a white solid (40 mg).
MS (ISN) 626 [(M-H)-]; mp 121-123 °C.
Example M24
(2'-FIuoro-5-f3-oxo-3-(34h23ltriazol-l-yl-phenyl)-propiQnylamino1-2-(2,2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The title compoxmd was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifiuoro-ethoxy)-biphen)d-4-yl]-carbamic acid tert-butyl ester (Example J5) (200 mg, 0-5

mmol) and 3-oxo*3-(3-[l^,3]triazol-l-yl-phenyl)-propionicacid ethyl ester (Example Kl) (150 mg, 0.57 mmol) according to the general procedure M. Obtained as a light yeUow solid (110 mg).
MS (ISP) 614 [(M+H)--]; mp 54-56 °C
Example M25
(RS)-[2^-Fluoro-5-(3-oxo-3-{345-ftetrahvdro-pwan-2-ylox\nmethyl)-fL23ltria2o^ yl1-phenyl}-propionvIamino)-2-('2.2.2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester
The title compound was prepared from [5-amino-2'-fluorO-2-(2,2>2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (220 mg, 0.55 mmol) according to the general procedure M. Obtained as a yellow oil(100 mg).
Example M26
(RS)-[4-Chloro-5-fethyl-methyl-aminoV2-(3-oxo-3-(3-r5-ftetrahydro-pyran-2-yloxymethyl)-rL23ltriazol-l-yll-phenyll-propionylamino)-phenyl1-carbamicadd tert-butylester
The titlt ipound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)' phenyl]-curbamic acid tert-butyl ester (Example J7) (300 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl|-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (500 mg),
MS (ISP) 627.1 [(M+H)--].
Example M27
(RSVf4-Chloro-5-(methyl-propyl-amino)-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-yIoxvTnethyl]-fl,23ltriazol-l-yl1-phenyIt-propionylamino)-phenyl-carbamicadd tert'butylester
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (402mg, I.O mmol) according to the general procedure M. Obtained as a yellow foam (410 mg).
MS (ISP) 641.3 [(M+H)1.

Example M28
(RS)-r4-Chloro-5-fdiethyl-ammQV2-f3-oxo-3-(3-r5-ftetrahvdro-pyran-2-yloxymethvD- \ 1.231 triazol-1 -yll -phenyl-propionylamino Vphenyll -carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(diethyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J9) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yI]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg).
MS (ISP) 64L3 [(M+H)+].
Example M29
fRSVI'4-Chloro-5-dimethylamino-2-(3-oxo-3-i3-f3-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol'5-yll-phenyU-propionylamino)-phenyl1-carbamicacidtert.-butyl ester
The title compotind was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3- [3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl] -phenyl}-propionic acid tert.-butyl ester (Example K12) (201 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg).
MS (ISP) 613.1 [(M+H)--] and 615 [(M+2H-H)+].
Example M30
(RS)-r4-CHoro-2-f3-oxo-3-l345-ftetrahvdro-pyran-2-yloxvmetfayl)-[L2,3ltriazol'l-yll -phenyll-propionylaminoV5-pvrrolidin-l'yl-phenyl1 -carbamic acid tert.-butylester
The tide compoimd was prepared from (2-amino-4-chloro-5-pyrrolidin-l-yl-phenyl)-carbaniic acid tert.-butyl ester (Example JIO) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.' butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (228 mg),
MS (ISP) 639 [(M+H)--] and 641 [(M+2+H)+].

Example M31
(5-Dimethylamino-2-^3-r3-(2-metfayl'2H-pvrazol-3-yl)-phenyll-3-oxo-propionylaminQl-4-trifluoromethyI-phenyD-carbainic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K7) (150 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (90 mg).
MS (ISP) 546.2 [(M+H)--],
Example M32
fRS)-r4-Chloro-5-dimethylamino-2-f3-B-F3-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol-5-yl] -phenAd}-3-oxo-propionylamino)-phenyl1 -carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethyIamino-phenyO-carbamic acid terL-butyl ester (Example Jl) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]'phenyl}-3-oxo-propionic acid tert-butyl ester (Example K13) according to the general procedure M, Obtained as a light yellow solid (187 mg).
MS (ISN) 626 [(M-H)-] and 628 [(M+2-H)'].
Example M33
fRS)-r4-Chloro-5-fcvclopropvI-methyl-amino)-2-f3-oxo-3-l3-r5-rtetrahvdro-pyran-2-yloxvmethyl)-fl.2.3ltriazol-l-yl]-phenvU-propionylaminoVphenyl]-carbamicacid
tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example JU) (156 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2oH-yl]-phenyll-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow solid (215 mg).
MS (ISN) 637.1 [(M-H)'] and 639 [(M+2-H)-]; mp 47-49 °C.

Example M34
(5-Dimethylamino-2-l3-f3-(5-dimethylaminomethyl-ri.23ltriazoM-yl)-phenyl-3-oxo-propionvIaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (160 mg, 0.5 rQmol)and3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (195 mg).
MS (ISN) 588 [(M-H)-].
Example M35
(RS)-[4-Chloro-5-dimethylamino-2-f3-l3-(2-methyl'5-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pyrazol-3-yn-phenvU-3-oxo-propionylaminoVphenyn-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chIoro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (200 mg, 0.7 mmol) and (RS)-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K14) (290 mg, 07 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (329 mg).
MS (ISN) 624.0 [(M-H)-] and 626 [(M+2-H)'].
Example M36
{2-[3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino1-5-pvrrolidin-l-yl-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-pyTrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J12) (173 mg, 0.5 nrniol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (150 mg, 0,61 mmol) according to the general procedure M. Obtained as a yellow solid (140 mg).
MS(ISP)518[(M+H)1-

Example M37
fRS)42-r3-Oxo-3-i3-(5-(tetrahvdro-pyran-2-yloxvmethvD4L23ltriazol-l-yl1-phenvU-propionylamino)-5--pvrrolidin-l-yl'4-trifluorometfayl-phenyl]-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifIuoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J12) (173 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-I-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as an orange foam (168 mg).
MS(ISP)673[(M-hH)+].
Example M38
f RS)- (5-Dimethylamino-4'fluoro-2-(3-0X0-3-13- f 5-f tetrahydro-pyran-2-yloxvmethyl)-fL23ltriazol-l-yn-phenyll-propionylamino)-phenyn-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-fiuoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1,0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid terL-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (417 mg).
MS(ISN)595[(M-H)-].
Example M39
(5-Dimethylammo-2-l3-[3-(5-dimethylaminomethyl'[L2.3ltria2ol-l-vD-phenyl-3-oxo-propionylamino}-4-fluoro-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-anfiino-5-dimethylamino-4-£luoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (344 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (211 mg).
MS(ISN)538[(M-H)-].

Example M40
fRSVr5-Dimetfaylamino-4-fluoro-2-(3-oxo-3-B-r3-(tetrahvdro-pyran-2-yloxymetfavD-isoxazol'5-yl]-phenyl}-propionylamino)-phenyn*carbamic acid tert.-butyl ester
The tide compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example KI2) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (360 mg).
MS(ISN)595[(M-H)-].
Example M41
(RS)-(5-DimethylaminO'2-f3-oxo-3-{3-f3-ftetrahvdro-pyran-2-yloxvmethyl)-isoxazol-5-yll -phenyl}-propionylamino)-4-trifluoromethyl-phenyl1 -carbamic acid tert.-butyl ester
The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (565 mg, L77 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example K12) (710 mg, 1,77 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (721 mg),
MS(ISN)645[(M-H)'].
Example M42
(RSV(5-Dimethylamino-4-fluoro-2-r3>oxQ-3-{3-f3-ftetrahvdro-pyran-2-yloxymethyl)-isoxa2ol-5-yn-phenyl}-propionylamino)-phenyiVcarbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M- Obtained as a yellow amorphous substance (273 mg).
MS(ISP)497l(M-f-H)-'].

Example M43
fRSVf4-ChloTu-5-dimethylamino-2-f3-oxo-3-B45-rtetrahvdro-pyran-2-yloxvmethyl)-isoxazol-3-vn -phenyll-propionylamino)-phenyll -carbamic acid tert.* butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionic acid tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam
(232 mg).
MS (ISN) 611.1 [(M-H)-] and 613 [{M+2-Hr].
Example M44
(RSVf4-ChIoro-2-(3-oxo-3-l3-r5-ftetrahvdro-pyran-2-yIoxvmethyl)-[L23ltriazol-l-yIl-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl1-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example J14) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (257 mg).
MS (ISP) 653.2 [(M+H)+] and 655 [(M+2+H)1.
Example M45
(RS)-f5'Dimethylamino-2-(3-oxQ-3-l3-r5-(tetrahydro-pyran-2-yloxymethyD-isoxazol-3-yl1 -phenyll-propionylamino)-4-trifluoromethyl-phenyn -carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl] -phenyl}-propionic acid tert.-butyl ester (Example K15) according to the general procedure M. Obtained as a light yellow foam (224 mg).
MS (ISP) 647.2 KM+H)--].

Example M46
{4-ChIoro-5-dimethylamino-2-f3-OXo-3-(3-pyrazol-l*yl-phenyl)-propionyIamino]-phenyl}-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K16) according to the general procedure M. Obtained as a light yellow solid (135 mg).
MS (ISP) 498 [(M-hH)--] and 500 [(M+2+Hr]; mp 148-149 °C.
Example M47
{2-r3-(2-Cyano-pyridin-4-yI)-3-oxo-propionyIaminol-4-fluoro-5'pyrrolidin-l-yl-phenyU-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert,-butyl ester (Example 115) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (196 mg).
MS (ISP) 468 [(M+H)']; mp 231 °C (dec).
Example M48
(4-Fluoro-2-l3-[3-(3-methyl-isoxa2oI-5-yl')-phenvI1-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-fiuoro-5-pyrrolidin-l-yl-phenyl)-carbamic acidtert,-butyl ester (Example Jl5) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propiomc acid tert.-butyl ester (Example K4) according to the general procedure M. Obtained as a light yellow solid (126 mg).
MS (ISP) 468 [(M+H)+]; mp 186 °C
Example M49
fRS)-[4-Fluoro-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-rL23ltria2ol-l-yl1-phenvU-propionylamino)-5-pyrroIidin-l-yl-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidiQ-l-yl-phenyl) carbamic acid tert-butyl ester (Example Jl5) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>23]triazol-l-yi]-phenyl}-propionic acid terL-but)i ester

(Example K5) according to the general procedure M. Obtained as an orange viscous oU (268 mg).
MS(ISP)623[(M+Hr].
Example M50
l5-Azetidin-l-yl-4-chloro-2-[3-r2-cyano-pyridin-4-vI)-3-oxo-propionylamino]-phenvU-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butyl ester (Example J16) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (142 mg).
MS (ISP) 470 [(M+H)--] and 472 [(M+2+H)']; mp 168 °C (dec).
Example M51
fRSV(2-f3-Oxo-3-l3-[5-(tetrahydro-pyran'2-ylQxymethyD-isoxazol-3-yll'phenyll-propionylaminoVS-pyrrolidin- l-yl'4-trifluoromethyl*phenyl -carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI2) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yIoxymethyI)-isoxa2oI-3-yl]-phenyl}-propionicadd tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (522 mg).
MS (ISN) 671.2 [(M-H)-],
Example M52
l5'Azetidin-l-yl-2-(-3-(2-cyano-pvridin-4-yl)-3-oxo-propionylamino1'4-trifluoromethyl-phenylt-carbamic acid tert.-but\^ ester
The title compound was prepared from (2-aminO-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J17) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light yellow solid(131 mg).
MS (ISP) 470 [(M+H)--]; mp 166-167 °C.

Example M53
(5-Azetidin-l-yl-2-B-r3-f3-m€thyl-isoxa2ol'5-yl>>phenyll-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.'butylester
The tide compound was prepared from (2-amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Lxamplc J17) and 3-[3-(3-methyHsoxazol-5-yl)-phenyl]-3-oxo-propionic acid tcrL-but)1 ester (Example K4) according to the general procedure M. Obtained as a light ycUow foam (218 mg).
MS (ISN) 557.2 [(M-H)']; mp 83-84 *C
fRSV[5-Azetidin-l-yl-2-(3-oxo>3- fh23ltria2ol-l-yl1-phenyll-propionylamino)-4-trifluoromethyl-phenyll'Carbamic
acid tert.-butylester ——.^1 ,11-1. ,
The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI7) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoI-l-yi]-phen)d}-propionic acid tert-butyl ester (Example K5) according to the general procedure M, Obtained as a yellow foam (450 mg).
MS (ISN) 657.1 [(M-H)']; mp 76-77 X.
Example M55
{5-Dimethylamino-2-[3-OXO'3-(3-pyra2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl'phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (485 mg),
MS (ISN) 530 [(M-H)+].
Example M56
t5-Dimethylamino-2-f3-QXo-3-f3-fl.2.4ltriazol-4-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoromethyl-phenyi)-carbamic acid tert-butyl ester (Example J6) (383 mg, 1.2

mmol) and 3-oxO-3-(3-[l,2,4]triazol-4-yl-phenyl)-propionic acid ethyl ester [CAS-No. 335255-97-5] (259 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow solid (290 mg).
MS (ISP) 533.3 [(M-i-H)l; mp 58-62 °C.
Example M57
(5-Dimethylamino-2-f3-r3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)--Carbamic acid tert-butyl ester (Example J6) and 6-(3-imidazol-l-yl-phenyl)-2>2-dimethyl-[l,3]dioxin-4-one (Example L3) according to the general procedure M. Obtained as an orange oil (238 mg).
MS(ISP)432[(M+H)'].
Example M58
(RS)-f4-Chloro-5-dimethylamino-2-f3-oxo-3-(3--f4-(tetrahydrQ-pyran-2-ylQxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyI]-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (429 mg, L5 mmol) and (RS)-3-oxo-3- {3- [4- (tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl} -propionic acid tert.-butyl ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (710 mg).
MS (ISN) 610 [(M-H)-] and 612 [(M+2-H)'l.
Example M59
fRSV(5-Dimethylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-yloxvmethvD-pyrazol-l-yl'|-phenvU-propionylamino)-4-trifluoromethyl-phenyIl-carbamicacid tert.-butyl ester
The title compoimd was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (479 mg, 1.5 mmol) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yioxymethyi)-pyrazol-l-yl]-phenyl}-propionic acid tert-butyi ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M. Obtained as a piiik amorphous substance (641 mg).
MS (ISN) 644 [(M'H)-].

Example M60
fRS)'[5-Dimethylamino-2-(3-B-[3-methyl-4-('tetrahvdrO'pyran-2-vIoxymethyl)-isoxa2ol-5'yI]-phenyn*3-oxo-propionylamino)-4-trifluoromethyl-phenyI1-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K13) according to the general procedure M. Obtained as a red oil (424 mg).
MS (ISN) 626 [(M-H)-].
Example M61
fRSV(5-Dimetfaylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-vioxvmetfayl)-isoxazol-S-yll -phenyl KpropionylaminoV4-trifluoromethyl-phenyn -carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionicadd terL-butyl ester (Example K18) according to the general procedure M. Obtained as a light yellow solid(145 mg).
MS(ISP)647[(M+Hn.
Example M62
(RSV(5-DimethyIamino-2-(3'[3-(2-methylsuIfanvI-imidazoI-l-yl)-phenyl-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-tri£luoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (319 mg, 1-0 mmol) and 3-[3-(2-methylsulfanyI-imida2oI-l-yl)-phenyI]-3-oxo-propiomcadd tert-butyl ester [CAS-No. 335256-01-4] (432 mg, 1.3 mmol) according to the general procedure M. Obtained as a light brown amorphous substance (493 mg).
MS (ISP) 333.2 [(M+H)--].

Example M63
fRSVr5-Dimethylamino-2-(3-(3-(2-methyl-4-(tetrahvdro-pyran-2-ylQXvmethyl)-2H-pyra2o]-3-yl1-phenyil-3'OXo*propionylaminoV4'trifluorometfayl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-{3-[2-methyl-4-(tetrahydro-pyran-2-ylox)Tneth>1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert-butyl ester (Example K19) according to the general procedure M. Obtained as a light red solid (576 mg).
MS (ISN) 658 [(M-H)-].
Example M64
l4-Chloro-5-dimethylamino-2-f3-oxo-3-f 3-| 1 >2,4]tria2ol-l-yl-phenyl)* propionylamino1-phenyll*carbamic acid tert.-butyl ester
The title compo d was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carban. dcid terL-but)d ester (Example Jl) and 3-oxo-3-(3-[l>2,4]tria2ol-l-yl-phenyl)-propionic acid tert-but)d ester [G\S-No, 335255-88-4] according to the general procedure M. Obtained as a light yellow solid (427 mg).
MS (ISN) 497 [(M-H)-] and 499 [(M+2-H)-].
Example M65
{5-Dimethylamino-2-f3-oxo-3-(3-[l,2,4]triazoM-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-anuno-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and 3-oxo-3-(3' [l>2,4]triazol-l-yl-phenyi)-propionic acid tert-butyl ester [CAS-No. 335255-88-4] according to the general procedure M. Obtained as a light red solid (502 mg).
MS(ISN)531[(M-H)-].
. Example M66
{2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimeth^amino-4-trifluorometh^^-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (320 mg, 1-0 mmol) and 3-(2,2-dimethyi-6-oxo-6H-[13]dioxin-4-yl)-benzonitrile (Example LI)

(275 mg, 1.2 mmol) according to the general procedure M. Obtained as a reid viscous oil (196 mg).
MS (ISN) 489.1 [(M-H)-].
Example M67
fRS)-r5-fCvcIopropvImethyl-methyl-amino)-2-f3-oxo-3-{3-(5-ftetrahvdrO'pyran-2-yloxvinethyD - [ 1,231 triazol- l-yl1 -phenyl! -propionylamino V4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-anmio-5-(cyclopropylmethyl-methyl-amino)-4-trxfluoromethyI-phenyl]-carbamicacid tert,-butyl ester (Example JIS) (719 mg, 2.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (803 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (985 mg).
MS (ISP) 687 [(M+H)+].
Example M68
[2-f3-(2-Cyano-pyridin-4-yl)-3-oxo-propiQnvIamino]-5-fcyclopropylmethyI-metfayl' amino)-4-trifluorometfayl-phenyl-carbamic acid tert.-butylester
The title compound was prepared from [2-amino-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example JIB) (180 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (206 mg).
MS (ISP) 532 [(M+H)+].
Example M69
(RS)-l5-Dimethylamino-2-r3-oxo-3-f3-{2-r2-(tetrahvdro-pyran-2-yloxvVethyl1-2H-pvrazoI-3-yll-phenyl)-propionylaminol-4-trifluoromethyl-phenyn-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifiuoro-methyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (639 mg, 2.0 mmol) and (RS)-3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-phenyl)-propionic acid tert-butyl ester (Example K20) (829 mg, 2.0 mmol) according to the general procedure M. Obtained as a pink amorphous substance (272 mg).

MS (ISN) 658 [(M-H)-].
Example M70
(2-r3-(2-cyano-pvridin-4-yl)-3-OXo-propionylaminoV5-fcvclopropyl-methyl-aminoV4-trifluoromethyl-phenyl-carbamic acid tert.-butyl ester
The title compound was prepared from [2-amino-5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example J19) (259 mg, 0.75 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert,-butyl ester (Example K3) (192 mg, 0.78 mmol) according to the general procedure M. Obtained as a yellow solid (228 mg).
MS (ISN) 516.2 [(M-H)-]; mp 114-116 °C.
Example M71
{2-Dimethylamino-2'-fluoro-5-f3-oxo-3-f3-fL23ltriazQl-l-yl-phenyl)-propionylamino1-biphenyl-4-yU-carbamic acid tert-butyi ester
The title compound was prepared from (5-amino-2-dimethyIamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J20) (691 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazoM-yl-phenyl)-[l,3]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow solid (820 mg).
Mp 125-135 °C.
Example M72
(RSyl5-Dimethylamino-2-[3-oxo-3-(3-l5-(2-ftetrahvdro-pyran-2-yloxvVethyll-fl.23ltria2ol-l-yll-phenyl)-propionvIamino1-4-trifluoromethyl-phenvU-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,2,3]triazol-l-yl}-phenyl)-propionicacid tert-butyl ester (Example K21) according to the general procedure M. Obtained as a light red oil (527 mg).
MS (ISP) 577 [(M+H)--].

Example M73
fRS)-[5-Dimethylamino-2-(3-oxo-3-f3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-pyrazol-l-yl]-phenyll-propionylamino)-4-trifluoromethyl-phenyl1-carbamicacid tert.-butylester
The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionic acid ethyl ester (Example K22) according to the general procedure M. Obtained as a brown oil (179 mg).
MS (ISP) 646 [(M+H)-*].
Example M74
(5-Dimetfaylamino-2-f3-oxo-3-('3-[L23ltriazoM-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (639 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazol-l-yl-phenyl)-[13]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a red solid (915 mg).
MS (ISP) 533,3 [(M+H)+]; mp 79-81 °C.
Example M75
[2-f3-(2-cyano-pyridin-4-yl)'3-oxo-propionylamino1-5-(2,2.2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J21) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light brown s.olid (262 mg).
MS (ISN) 545.0 [(M-H)']; mp 158 *°C (dec).

Example M76
l2-[3-(3-cyano-phenyl)-3-oxQ-propionyIamino1-4-dimethylaminO'5-methyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (300 mg, 1.0 mmol) and 3-(3-cyano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (250 mg> 57%).
MS (ISP) 437.4 [(M+H)--].
Example M77
(RSV[5-DimethylaminO'4-methyl'2-(3-oxo-3-{3'[5-(tetrahydro-pyran-2-yloxvmethyl)-fl.2.3ltria2ol-l-yl1-phenyU-propionylaminoVphenyl]-carbamicadd tert-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
add tert-butyl ester (Example K5) (402 mg, 1-0 mmol) according to the general procedure M. Obtained as a yellow foam (420 mg, 71%).
MS (ISP) 593.5 [(M+H)--].
Example M78
{5-Cyano-2-f3-(3-cyano-phenyl)-3-oxo-propionylamino1-4-dimethylamino-phenyl}-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butyi ester (Example J23) (276 mg, 1.0 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a brown foam (290 mg, 65%).
MS (ISP) 448.3 [(M+H)--].

Example M79
[2-f3-f3-cyano-phenvD-3-oxo-propionylamino]-5-methyI-4*fmethyl-propyl-amino)*phenv]]-carbamic acid tert-butylester
The title compound was prepared from [2-aminO-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (293 mg, 1.0 mmol) and 3-(3-qrano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (170 mg, 37%).
MS (ISP) 463.3 [(M-H)-],
Example M80
(RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-l3-(5-(tetrahvdro*pyran-2-yloxymethvD-[l,2,3ltriazoI-l-vI]-phenvU-propionylamino)-phenyl'Carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-pheiiyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (350 mg, 56%).
MS (ISP) 621.2 [(M+H)1.
Example M81
fRSV[5-fEthyl-methyl-aminoV4'methyl-2-(3-QXo-3-(3-(5-(tetrahvdro-pyran-2-yloxymethvD-fL2.3ltriazol-l-yl]-phenyI}-propionylamino)-phenyl-carbamicacid
tert-butylester
The title compound was prepared from [2-amino-5-(ethyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J25) (279 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (400 mg, 66%).
MS (ISP) 607.1 [(M+H)1.

Example M82
(RSVf4-cyano-5-dimethylamino-2-(3-oxo-3-(3-(5-ftetrahvdro>pyran-2-yloxvmethyl)-fl.23ltriazol-l-yl1-phenyU-propionylamino)-phenyll-carbamicadd tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-dimethylaminO-phenyl)-carbamic acid tert-butyl ester (Example J23) (276 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyi}-propionicadd tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to tiie general procedure M. Obtained as a light brovm foam (360 mg, 59%).
MS (ISP) 602.1 [(M-H)1.
Example M83
fRS)-[4-Chloro-5-fisopropyl-methyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyl)-Fl,2,3ltriazol-l-yll-phenyl}-propionylamino)-phenyl)-carbamicadd tert-butyl ester
The title compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J26) (300 mg, 0.96 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (383 mg, 0.96 mmol) according to the general procedxire M. Obtained as a light yellow oil (530 mg, 86%).
MS (ISP) 639.2 [(M-H)-].
Example M84
[4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionylaminol-5-(methyl-propyl-amino)-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyi]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 65%)!
MS (ISP) 519.3 [(M-H)'],

&tapiple M?5
(4-Cyano-5-dimethylamino-2- The tide compound was prepared from (2-amino-4-q^ano-5-dimethylaxnino-phenyl)-carbamic acid tert-butyl ester (Example ]23) (276 mg, 1.0 mmol) and 3-[3-(3*methyl-isoxazol-5-yl)-phenyI]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (320 mg, 64%).
MS (ISP) 504.3 [(M+H)+].
(5-(£thyl-methyl-amino)-4-methv'i-2-(3'[3-(3-methyi-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester
The title compoiund was prepared from {2-amino-5-(cthyl-methyi-amino)-4-methyl-phenyl]-carbamic acid tert-but)d ester (Example J25) (279 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M, Obtained as a brown foam (390mg,77%).
MS (ISP) 505.3 [(M-H)'].
Example M87
(5-Dimethylamino-4-methyI-2-l3-[3-f3-methyl-isQxazol-5-yl)-phenyll-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-5-dimethyiamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phen)d]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M. Obtained as a brown foam (330 mg, 67%).
MS(ISP)49L3[(M.H)'].

Example M88
fRS)-f4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxymethyl)-fh23ltria2ol-l-yl]-phenyn-propionylamino)-phenyl]-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-cliloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,3]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 50%).
MS (ISP) 655.1 [(M+H)--].
Example M89
(4-Chloro-5-fisobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl')-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carban[iic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (360 mg, 65%).
MS (ISP) 555.1 [(M+H)1.
Example M9Q
fRS)-[4-cyano-2-(3-oxo-3-B-(5-ftetrahvdro-pyran-2-yloxvmethyl)-ri.23ltriazol-l-ylj-phenvD-propionylaminoVS-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-)doxymethyi)-[l,2,3]tria2ol-l-yl]-phenyl}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light orange foam (380 mg, 60%).
MS (ISP) 630.1 [(M+H)--].

Example M91
(4-cyano-2-(3-f3-f3-methyl-isoxazol-5-vD-phenvI1-3-oxo-propionylamino}-5-pvrrolidin-1-yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-ph€nyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 79%).
MS (ISP) 530.2 [(M+H)+].
Example M92
(RSV[4-cyano-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvTnethyl)-fL2.3ltriazol-l-yn-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (440 mg, 70%).
MS (ISP) 630-1 [(M+H)+].
Example M93
f4-cyano-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-5-(methyl-propyl-aminoVphenyll-carbamic acid tert-butylester
The title compoimd was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 namol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (370 mg, 70%).
MS (ISP) 532.3 [(M+H)+].

Example M94
(4-cyano-5-diethylamino-2-{3-[3-f3-methyl-isoxazol-5-yl)-phenyl-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butyl ester (Example J30) (304 mg, LO mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butj^l ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (360 mg, 68%).
MS (ISP) 530.2 [(M+H)--].
Example M95
(4-Cyano-5-(isopropyl-methyl-aminoV2-l3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 71%).
MS (ISP) 530.2 [(M-H)'].
Example M96
(RS)-f4-Cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-r5-(tetrahvdro-pyran-2-yIoxvTnethyl]-[L2.3ltriazol-l-yl]-phenyl}-propion)damino)-phenyl]-carbamicadd tert-butylester
The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (460 mg, 73%).
MS(ISP)630.1[(M-H)-].

Example M97
(4-cyano-5-fisobutyl-methyl-amino)-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M, Obtained as a light brown foam (400 mg, 73%).
MS (ISP) 544.3 [(M-H)'].
Example M98
(RSVT4-cyano-5-(isobutyI-methyl-aminoV2-(3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fl,2.3ltriazol-l-yll-phenvU-propionylamino)-phenyll-carbamicacid
tert-butyl ester
—■'■■> -
The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (470 mg, 73%).
MS (ISP) 644.2 [(M-H)-].
Example M99
(4-cyano-2-(3-f3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-5-piperidin-l-yl-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J33) (316 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 77%).
MS (ISP) 544.2 [(M+H)+].

Example MlOO
(4-Chloro-5-isobutylamino-2-l3-f3-f3-methyl-isoxazol-5-vD-phenyl-3-oxo-propionylaminol-phenvD-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-isobut7lamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M, Obtained as an off-white foam (340 mg, 63%).
MS (ISP) 542.2 [(M+H)--].
Example MlOl
fRSVf4-Chloro-5-isobutylamino-2-f3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxymethyl)-FL2.3ltriazol-l-yl'|-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyI}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a red oU (180 mg, 28%).
MS (ISP) 640.2 [(M-H)-].
Example Ml02
(RS)-[5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxvmethyl) - [ 1,231 triazol-1 -yll -phenyll -propionylamino) -4-trifluoromethyl-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (380 mg, L09 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (439 mg, 1.09 mmol) according to the general procedure M. Obtained as a red foam (150 mg, 20%).
MS (ISP) 675.4 [(M-H)'].

Example M103
(2-{3-f3-f3-methyl-isoxazol-5-vI)-phenyl1-3-Qxo-propionylaminol-5-fmethyl-propyl-aminQV4-trifluoromethyl-phenyl'|-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]'Carbamic acid tert-butyl ester (Example J35) (360 mg, L04 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (312 mg, 1.04 mmol) according to the general procedure M-Obtained as a light red foam (270 mg, 45%),
MS (ISP) 573.2 [(M-H)-].
Example M104
(RSV[5-(I$obutyl-methyl-aminoV2-(3'Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxymethyl')'[L2^3ltriazol-l-yll-phenvU-prQpionylamino)-4-trifluorometh\d-phenyl]-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutjd-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J36) (370 mg, 1.02 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (411 mg, 1.02 mmol) according to the general procedure M. Obtained as a light brown foam (520 mg, 74%).
MS (ISP) 687.2 [(M-H)'].
Example M105
(5-fIsobutyl-methyl-aminQV2-{3'f3-(3-methyl-isoxa2ol'5-yl)-phenyl)-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)--carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(i$obutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J36) (360 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (302 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (430 mg, 73%).
MS (ISP) 587.3 [(M-H)-].

Example M106
fRSV(5-fIsopropyl-methyl-amino)-2-f3-oxQ-3-{3-(5-ftetrahvdrO'pyran-2-yloxvmethyl)-fL23ltria2oM-yl]-phenyll-propionylaminoV4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isopropyl-methyl-ancuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (340 mg, 0.98 mmol) and (RS)-3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)- [ l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (393 mg, 0.98 mmol) according to the general procedure M. Obtained as alight yellow foam (510 mg, 77%).
MS (ISP) 673,3 [(M-H)-].
Example M107
('5-(Isopropyl-metfayl-aminoV2-(3-f3-(3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isopropyl-methyl-anuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (350 mg, 1.01 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (304 mg, 1.01 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 66%).
MS (ISP) 573.2 [(M-H)-].
Example M108
(RSV(5-(Isobutyl-methyl-aminoV4-methyl-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxvmethyl)-[L2.3ltriazol-l-yl1-phenyll-propionylamino)-phenyl]-carbamicacid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenylj-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and (RS)-3-oxo-3-(3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 52%).
MS (ISP) 635.2 [(M+H)--].

Example M109
(5-fIsobutyl-methyl-aminoV4-methyl-2-{3-[3-f3-methyl'isoxazol-5-yl)-phenyl1-3-oxo-propionylamino}'phenyl)-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 62%).
MS (ISP) 535.4 [(M+H)1.
Example Ml 10
(RS)-[4-methyl-2-(3-oxo-3-f3-(5-(tetrahvdro-pyran-2-yloxvmethvD-rL2,3ltriazol-l-yI]-phenyl}-propionylaminoV5-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester
The title compoimd was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester acid tert-butyl ester (Example J39) (292 mg, 1.0 imnol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (410 mg, 66%).
MS (ISP) 619,3 [(M+H)1.
Example Mill
(4-Methyl-2-{3-f3-(3-methyl-isoxazol-5-yiVphenyl]-3-oxo-propionylaminol-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J39) (291 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 64%).
MS (ISP) 517.3 [(M-H)1.

Example Ml 12
(4'-Chloro-5-isQprQpylamino-2-{3-[3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester
The title compoimd was prepared from (2-amino-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brovm foam (169 mg, 32%).
MS (ISP) 525.2 [(M-H)-].
Example Ml 13
fRS)-f4-Chloro-5-isopropylamino-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyD-ri,23]triazol-l'-yl1-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compoxmd was prepared from (2-andno-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, LO nunol) according to the general procedure M. Obtained as a light yellow foam (375 mg, 60%).
MS (ISP) 625.1 [(M-H)-].
Example Ml 14
(RS)-r4-Chloro-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyD-[l,2,4ltriazol-l-yl]-phenyll-propionylamino)-phenyll-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (LOg, 3,19 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (L28 g, 3.19 mmol) according to the general procedure M. Obtained as a yellow foam (L48 g).
MS (ISP) 641.3 [(M+H)--].

Example Ml 15
fRSVr4-Chloro-5-fisobutyl-methyl-aminoV2-(3-oxo-3-l3-(5-ftetrahydro-pyran-2-yloxymethyl)-[L2,4ltriazol-l-yl]-phenyl}-propionviamino)-phenyl1-carbamicacid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (1.0 mg, 3.05 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.22 g, 3.05 mmol) according to the general procedure M. Obtained as a light brown foam (620 mg, 31%).
MS (ISP) 655.1 [(M+H)1.
Example Ml 16
fRS)-l'5-(Isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-J3-(5-(tetrahvdro-pyran-2-
yIoxvmethyl)-fl.2,4ltriazol-l-yl1-phenyU-propionylamino')-phenyl1-carbamicacid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (1.0 g, 3.25 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.31 g> 3.25 mmol) according to the general procedure M. Obtained as a light yellow foam (970 mg> 47%).
MS (ISP) 635.2 [(M+H)1.
Example Ml 17
{5-(methyl-propyl-aminoV2-F3-oxo-3-f3-fL2.4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvD-carbamic acid tert-butylester
The title compound was prepared from [2-ainino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (320 mg, 57%).
MS (ISP) 561.4 [(M+H)1.

Example M118
i5-(Methyl-propyl-aminQV2-f3-oxo-3-(3-fl,23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvU-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxO-3-(3-[l>2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (340 mg, 61%).
MS (ISP) 561.3 [(M+H)1.
Example Ml 19
l5-fIsobutyl-methyl-amino)-2-[3-oxo-3-r3-pvra2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J40) (361 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, LO mmol) according to the general procedure M. Obtained as a light brown foam (500 mg, 87%).
MS (ISP) 574.2 [(M+H)1.
Example M120
r2-f3-('2-cyano-pyridin-4-yl)-3-oxo-propionylamino1-5-fisopropyl-methyl-amino)-4-trifluoromethyl-phenyl1-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isoproyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J37) (500 mg, 1,44 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (355 mg, 1.44 mmol) according to the general procedure M. Obtained as a light orange oil (670 mg, 90%).
MS (ISP) 518.1 [(M-H)-].
Example M121
U-Chloro-5-fisobutyl-methyl-aminoV2-[3-oxo-3-f3-fL2,4ltriazol-l-yl-phenvi)-propionylaminol-phenvU-carbamic acid tert-hutyl ester
The title compound was prepared from [2-amino-4-chloro-5-(isobutyi-methyi-amino)-phen)i]-carbamic acid tert-butyl ester (Example J27) (500 mg, 1.53 mmol)

and 3-oxo-3-(3-[l,2,4]tria2ol-l-yi-phenyl)-propionic acid tert-butyl ester (Example K25) (438 mg, L53 mmol) according to the general procedure M. Obtained as a light orange foam (700 mg, 85%).
MS (ISP) 539.2 [(M-H)-].
{5-(Isobutyl-methyI-amino)-2-f3*0!(o-3'f3-fl.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluorometh>i-phen\il'Carbamic acid tert-butyl ester
The title compound was prepared from l2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example J36) (361 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2oM->1-phcn>'l)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (490 mg, 85%).
MS (ISP) 575.2 [(M+H)*-].
Example Ml23
l4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-f3-fh2.3]triazol-I-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chioro-5-(isobutyl-methyI-amino)-phenyl]-Carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as an orange oil (250 mg, 46%).
MS (ISP) 539.2 [(M-H)-].
Example Ml24
{5-fIsobutyl-methyl-aminoV2-f3-QXo-3-f3-[L2.3ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvmcarbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (460 mg, 1.27 mmol) and 3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionic acid tert-butjd ester (Example K23) (364 mg, 1.27 mmol) according to the general procedxire M. Obtained as ahght brown oil (480 mg, 69%).
MS (ISP) 573.1 [(M-H)-].

Example M125
(2-f3-r3-Imidazol-l-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg> 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 iiunol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 77%).
MS (ISP) 558.2 [(M-H)-].
Example M126
{4-Chloro-2-[3-f3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-5-isobutylamino-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 63%).
MS (ISP) 524.1 [(M-H)'].
Example M127
{4-Chloro-5-fisobutyl-aminoV2-r3-oxo-3-f3-[1.23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-ainino)-phenyl]-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a pale brown foam (220 mg, 42%).
M^:iSP) 525.1 [(M-H)1.

Example M128
(5-fIsobutyl-aminQV2-f3-oxO'3-(3-fL23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyU-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoro-methyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg, LO mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 60%).
MS (ISP) 559.2 [(M-H)-].
Example Ml29
H-Chloro-5-('isobutyl-aminoV2-f3-oxo-3-f3-fL2,4ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M, Obtained as a light ydlow foam (390 mg, 74%).
MS (ISP) 525.1 [(M-H)-].
Example Ml30
{5-('Isobutyl-aminoV2-f3-oxo-3-f3-[1.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 11%).
MS (ISP) 559.2 [(M+H)--],

General procedure N:
Preparation of 4-aryl-13-dihvdro-benzofb1 f L4ldiazepin-2-ones:
A solution or suspension of the {2-[3-arj4-3-oxo-propionylamino]-phenyl}-carbamic acid tert-butyl ester or {2-[3-aryi-3-oxo-propionyIamino]-phenyl}-carbamic acid tert-butjd ester (1.0 mmol) in CH2Cl2 (5 mL) (anisolc or l^-dimethoxybenzene (5-15 mmol) can be acided if necessary] was treated with TFA (0.5-5.0 mL) at 0 '°C and stirring was continued at 23 °C until tic indicated complete consumption of the starting material.
Worlcup procedure a: The solvent was removed in vacuum, the residue treated with little ether, whereupon it crystallized. The solid vas stirred with sat. NaHCOs-sol. or IM NaaCOs-sol., filtered, washed with H2O and ether or mixtures of ether/THF/MeOH and was dried to give the tide compound, which if necessary can be purified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cyclohexane/EtOAc or EtOAc/EtOH.
Workup procedure b: The reaction mixture was diluted with DCM or EtOAc, washed with sat. NaHCOs-sol. or IM Na2C03-soL, brine and dried over MgSO4 or Na2S04. Removal of the solvent in vacuum left a material, which could be triturated with ether or mixtures of ether/THF/MeOH to give the title compound, or which if necessary can be pmified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cycIohexane/EtOAc or EtOAc/EtOH.
Example 1
3-f7-Chloro-8-dimethylamino-4-oxo-4,5-dihvdro-3H-benzo[blfl.4]diazepin-2-yl)-benzonitrile
The tide compoimd was prepared firom {4-chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example Ml) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (85 mg).
MS (ISP) 339 [(M+H)--] and 341 [(M+2+H)']; mp >250 *»C.

Example 2
8-Chloro-7-dimethylamino-4-f3-fl,2,3ltriazol-l-yl-phenyl)-l,3-dihydro-benzofbl f L4ldiazepin-2-one
The title compoxmd was prepared from {4-chloro-5-dimethylamino-2-[3-OXo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert.-butyl ester (Example M2) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (87 mg).
MS (ISP) 381 [(M+H)--] and 383 [(M+2+H)-']; mp 222-225 °C.
Example 3
8-Chloro-7-dimethylamino-4- r3-(5-hvdroxvmethyl-1- 1.2,3ltriazol- 1-yD-phenyll -1,3-dihydro-benzo f b1 \ 1,4] diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl] -carbamic acid tert.-butyl ester (Example M3) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (60 mg).
MS (ISP) 411 [(M+H)--] and 413 [(M+2+H)']; mp 210-214 X,
Example 4
3-(8-Dimethylamino-4-oxo-7-phenylethynyl-4,5-dihydro-3H-benzofbl \ 1,41 diazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-phenylethynyl-phenyl}-carbamic acid tert.-butyl ester (Example M4) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg).
MS (ISP) 405 [(M+H)--]; mp 215-216 °C.
Example 5
7-Dimethylamino-8-phenylethvnyl-4-f3-rL23ltriazol-l-yl-phenvi)-K3-dihvdro-benzofbl f 1.41 diazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyi)-propionylamino]-4-phenylethynyl-phenyi}-carbantiicadd tert-butyi ester (Example M5) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (76 mg).
MS (ISP) 447 [(M+H)--]; mp 185-186 °C.

Example 6
8-Chloro-7-dimethylamino-4-r3-f3-methyl-isoxazol-5-yl')-phenyl1-L3-dihvdro-benzoFb1fl,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacidtert.-butyl ester (Example M6) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (68 mg).
MS (EI) 394 (M^) and 396 [(M+2r]; mp 212-215 °C
Example 7
8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-('5-hvdroxymethyl-[1.23ltria2ol-l-yl)-phenyl-1.3-dihvdro-benzofb]fL4ldiazepin-2-one
The title compound was prepared from (RS)-[2-dimethylamino-2',3'-difluoro-5-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-biphenyl-4-yl]-carbamic acid tert-butyl ester (Example M7) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (26 mg).
MS(ISP)489[(M+H)'].
Example 8
8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-fL23ltriazQl-l-yl-phenylyl3-dihvdrO'benzo l-b] [ 1.41 diazepin'2-one
The title compound was prepared from {2-dimethylamino-2\3*-difluoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert-butyl ester (Example M8) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (47 mg).
MS (ISP) 459 [(M+H)--]; mp 197-199 °C.
Example 9
3-r7-(23-Difluoro-phenyl)-8-dimethylamino-4-QXO-4.5-dihydro-3H-benzofbl \ 1,41 diazepin-2-vn -benzonitrile
The title compound was prepared from {5-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-2-dimethylamino-2\3*-difluoro-biphenyi-4-yl}-carbamic acid terL-butyl ester (Example M9) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a light yellow solid (75 mg).

MS (ISP) 417 [(M+H)--]; mp 228-229 ^'C
Example 10
8-CMoro-7-dimethylamino-4-(2-(3-metfayl-isoxazol-5-yl)-pvridin-4-yl1-1.3-dihvdrO-benzofbl f 1.4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimetiiylanuno-2-{3- [2-(3-methyl-isoxazol-5-yI)-pyridin-4-yl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example MIO) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (111 mg).
MS (ISP) 396 [(M+H)+] and 398 [(M+H-f 2)--]; mp >250 X.
Example 11
8-Chloro-7-[(2-methoxy-ethyl)-methyl-amino1-4'f3-(3-methyl-isoxazol-5-yI')-phenyll -13-dihvdro-benzo [bl f 1 A] diazepin-2-one
The title compound was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-2-{3-[3-(3-methyi-isoxazol-5-yl)-phenyl]-3-OXO-propionylamino}-phenyl)-carbanciic acid tert.-butyl ester (Example Ml 1) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg).
MS (EI) 438 (M**-) and 440 [(M+2)+]; mp 182 °C.
Example 12
8-Chloro-7-f(2-methQxy-ethyl)-methyl'amino1-4-[2-f3-methyl-isoxazoI-5-yl)-pyridin-4-ylyl3-dihydro-benzofb]fl.4ldiazepin'2-one
The title compoimd was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-ainino]-2-{3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4~yl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M12) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (106 mg).
MS (ISP) 440 [(M+H)'] and 442 [(M+H+2)1; mp 213 °C
Example 13
8-ChlorQ-4-r3-(5-hvdroxvmethyl-rL23ltriazol-l-yl]-phenyl-7-r(2-methoxv-ethyl)-methyl-amino1-l3-dihvdro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-[(2-methoxy-ethyl)-methyL amino]-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M13) by

treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (50 mg).
MS (ISP) 4.55 [(M+H)'] and 457 [(M+H+2)']; mp 185 X.
Example 14
8-Chloro-7-r(2-methoxv-etfayl)-methyl-amino1-4-f3-fl.23]triazol-l-yl-phenylyl.3-dihydro-benzofb] rL4ldiazepin-2-one
The title compotmd was prepared from {4-chIoro-5-[(2-methoxy-ethyl)-methyl-amino] -2- [3-oxo-3-(3- [ l,2,3]triazoM-yl-phenyl)-propionylamino] -phenyl}-carbamic acid tert.-butyl ester (Example M14) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg).
MS (ISP) 425 [(M+H)--] and427 [(M+H+2)+]; mp 156 °C.
Example 15
4-f7-Ch]orO-8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb]fl,4ldiazepin-2-vI)-pyridine-2-carbonitrile
The title compoimd was prepared from {4-chlorO-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert.-butyl ester (Example M15) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (50 mg).
MS (ISP) 340 [(M+H)--] and 342 [(M+2+H)-^]; mp 216 X.
Example 16
8-ChlorO-7-dimethylamino-4-f3-(2-methyI-2H-pvrazol-3-yl)-phenyl]-1.3-dihvdro-
benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert.-butyl ester (Example M16) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofiF-white solid (67 mg).
MS (ISP) 394 [(M+H)--] and 396'{(M+2+H)']; mp 225 X.

Example 17
7-Dimethylamino-4-f3-(5-hydrox\TOethyl4l,2,3ltria2ol>l'yl)-phenyll'8-trifluoromethy[-L3-dihydro-benzofblfL4ldiazepin-2*one
The title compound was prepared torn (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester (Example M17) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (62 mg).
MS (ISP) 445 [(M+H)+]; mp 210 '°C.
Example 18
7-Dimethylamino-4-f3-(3-methyl-isoxa2oI-5-yl)-phenyI]-8-trifluoromethyM.3-dihydro-benzofb] [1,41 diazepin-2'One
The title compound was prepared from (5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-OXo-propionylamino}-4-trifiuoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example Ml8) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (28 mg).
MS (ISP) 429 [(M+H)+]; mp 223 °C,
Example 19
8'Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-l,3-dihvdro-benzo f b] f 1,41 diazepin-2-one
The title compound was prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-thiobenzamide (prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [1,4] diazepin-2-yl)-benzonitrile (Example 1) as follows: To a solution of hexamethyldisUthiane (0.55 mL, 2.6 mmol) in l,3*dimethyl-2-inaida2olidinone (2.6 mL) was acided at 20 X sodium methoxide (0.13 g, 2.5 mmol). The mixture was stirred for 15 min. and the blue solution formed was then acided to a solution of 3-(7-chloro-8-dimethyIamino-4-oxo-4,5-dihydro-3H-benzo[b][l,4ldiazepin-2-yi)-ben2omtrile (Example 1) (0.34 g, 1.0 mmol) in 1,3-dimethyl-2-imida2olidinone (2 mL). The mixture was stirred for 3 h at 20 °C and then poured into water. The precipitate was isolated by filtration and triturated with acetone to give 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [l,4]diazepin-2-yi)-thiobenzamide (035 g) as yellow solid, mp 234 'C decMS (ISP) 373.2 [(M+H)'].} (0.71 g, 1.9 mmol), l,3-dichloro-2-propanone (0,36

g, 2.85 mmol) and sodium bicarbonate (0.24 g, 2.85 mmol) in 1,4-dioxane (15 mL) was heated to 60 °C for 48 h. The clear solution was evaporated in vacuvun. The a solution of the residue in 1,4-dioxane (5 mL) was acided 2N KOH (3.8 mL) and the mixture was stirred at 20 °C for 1 h. Water (100 mL) was acided and the mixture was stirred for 0,5 h. The precipitate formed was collected by filtration and crystallized from dichloromethane to give the title compound (0.69 g) as pale-yellow solid.
MS (ISP) 427.2 [ (M+H)**-]; mp 134 X dec.
Example 20
8-Chloro-7-dimethylamino-4-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyll -L3-dihvdrO'benzo fbl \ 1,41 diazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M19) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (34 mg).
MS (ISP) 438 [(M+H)--] and 440 [(M+2+H)-']; mp 145-160 °C
Example 21
8-Chloro-7-dimethylamino-4-f3-(3-methoxvmethyl-isoxazol-5-yl)-phenyl1*L3-dihydro-benzoFbl [1.41 diazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butjrl ester (Example M20) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (157 mg).
MS (ISP) 425 [(M+H)+] and 427 [(M+2+H)']; mp 191 °C.
Example 22
4-(8-Dimethylamino-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo Fbl \ 1.41 diazepin'2-yl)-pyridine-2-carbonitrile
The title compoxmd was prepared from {2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylarnino]-5-dimethylamino-4-trifluoromethyl-phenyi}-carbainic acid tert.-butyl ester (Example M21) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (158 mg).
MS (ISP) 374 [(M+H)--]; mp 248 X.

Example 23
8-(2-Fluoro-phenyl)-4'(3-imida2ol-l-vI-phenyl-7-(2.2,2-trifluoro-ethoxv)-L3-dihydro-benzofb] [ L41 diazepin-2-one
The title compound was prepared from [2'-fluoro-5-[3-(3-nmdazol-l-yl-phenyl)-3-oxo-propionylamino] -2- (2,2,2-trifluoro-ethoxy)-biphenyl-4-yi] -carbamic acid tert,-butyl ester (Example M22) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (50 mg).
MS (EI) 494 (M^); mp 208-210 °C
Example 24
8-(2-Fluoro-phenyl)-4-f3-f3-methyl-isoxazQl-5-vIVphenyl]-7-(2,2.2-trifluoro-ethoxy)-1,3-dihydro-benzo f b] \ 1,41 diazepin-2-one
The title compound was prepared from [2'-fluoro-5*{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyi]-3-oxo-propionylamino}-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example M23) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (21 mg).
MS (EI) 509 (M^); mp 218-220 -'C.
Example 25
8'(2-FIuoro-phenyl)-4'(3-ri.23kriazol-l-yl-phenyl)-7-r2.2,2-trifluoro-ethoxv)-13-dihydro-benzofb] f 1,4ldiazepin'2-one
The title compound was prepared from [2*-fluoro-5-[3-oxo-3-(3-[l,2,3]triazoM-yI-phenyl)-propionylamino]-2-(2^,2-trifluoro-ethoxy)-biphen)d-4-yl]-carbamicacid tert.*butyl ester (Example M24) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (45 mg)-
MS (EI) 495 (M^).
Example 26
8-(2-Fluoro-phenyl)-4-f3-(5-hvdroxvmethyl4l.2.3ltriazoI-l-yl]-phenyl)-7-(2,2,2-trifluoro-ethoxy)-13'dihvdro-ben2ofblfL4ldiazepin-2-one
The title compound was prepared from (RS)-[2'-fluoro-5-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-^oxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid terL-butyl ester (Example Iyl25) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (10 mg).

MS (ISP) 526 [(M+H)1; mp 232-234 °C
Example 27
8-Chloro-7-dimethylamino-4-f3-f4-hydroxvmethy]-oxazol-2-yl)-phenyl1-13-dihydro-benzofb] ri,4]diazepin-2-one
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (170 mg) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxa2ol-2-yl] -phenyl}-propionic acid tert-butyi ester (Example Kll) (270 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (110 mg).
MS (ISP) 41L2 [(M+H)--]; mp 193-195 °C
Example 28
8-Chloro-7'(ethyl-methyl-amino)-4-f3-(5-hvdroxymetfayl-fL23ltriazoM'yl)-phenyl]-L3-dihvdrO'benzofb1fl,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(ethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M26) (0.5 g, 0.8 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white soKd (60 mg).
MS (ISP) 425.4 [(M+H)-*]; mp 206 °C (dec).
Example 29
8-Chloro-7-fmethyl-propyl-amino)-4-r3-(5-hydroxvmethyl-fL2.3ltriazol-l-yl')-phenyl] -1,3-dihydrO'benzo fbl [ 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M27) (0.41 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (110 mg).
MS (ISP) 439.3 [(M+H)1; mp 178 °C (dec).

Jbxample 30
8-Chloro-7-fdiethyl-amino)-4-f3-(5-hvdroxvmethyl-rL23ltriazoUl-yl)-phenvI1-L3-dihydro-benzofb][L4]diazepin-2-one
The title compoimd was prepared from (RS)-(4-chloro-5-(diethyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tm-butyl ester (Example M28) (0.53 g, 0.827 mmol) by treatment with TFA in CH;Q: according to the general procedure N. Obtained as an off-white solid (210 mg).
MS (ISP) 439.3 [(M+H)--]; mp 208 *°C (dec).
Example 3 i
8-Chloro-7-dimethylamino-4*y3-(3-hvdroxvmeth>^-isoxazol-5-yl)-phenyl]-1.3-dihydro-benzofblfL4]diazepin-2-onc
The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5->d]-phen)d}-propionyiamino)-phenylj-carbamic acid terL-butyi ester (Example M29) (81 mg, 0.13 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (38 mg).
MS (ISP) 411 [(M+H)+] and 413 [(M+2+H)*']; mp 132 °C.
Example 32
8-CHoro-4-r3-(5-hvdroxymethyl-rL23]triazol-l-vI)'phenyl1*7-pvrrolidin-l-yl-L dihydro-benzorb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionylamino)-5-pyrrolidin-1-}d-phenyl]-carbaniic acid tert.-butyl ester (Example M30) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (58 mg).
MS (ISP) 437 l(M+H)+] and 439 [(M+2+H)'-]; mp 193-197 X.

Example 33
7-Dimethylamino-4-f3-(2-methyl-2H-pvrazol-3-yl)-phenvIl-8-trifluoromethyl-L3-dihydro-benzofbl [ L4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)'phenyl]-3-oxo-propionylari3ino}-4-trifluoromethyl-phenyl)-carbaniic acid terL-butyl ester (Example M31) (78 mg, 0.14 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid(48 mg).
MS (ISP) 428 [(M+H)1; mp 225 °Q
Example 34
4-f7-Chloro-8-('cvclopropyl-methyl-aminoV4-oxo-4,5-dihydrQ-3H-benzo Fbl f 1.41 diazepin-2-yl] -pvridine-2-carbonitrile
The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyi-amino)-phenyl]-carbamic acid terL-butyl ester (Example Jll) (150 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (150 mg, 0.61 mmol) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg),
MS (ISN) 364.1 [(M-H)-] and 366 [(M+2-H)-]; mp 199-201 °C.
Example 35
8-Chloro-7-dimethylamino-4-[3-(4-hvd^oxvTnethyl-3-meth^d-isoxa^ol^5-yD-phenyl1-1.3-dihydro-benzo[bUL4ldiazepin-2-one
The titie compoxmd was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tert,-butyl ester (Example M32) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (60 mg).
MS (ISP) 425 [(M-hH)--] and 427 [(M+2-hH)-']; mp 232-233 'C.

Example 36
8-CHoro-7-fcvclopropyl-methyl'amino)-4-f3-(3-melhyl-isoxazol-5-yl)-phenyll-13-dihvdro-benzofb1[L4ldiazepin-2-one
The title compound was prepared from [2-aminO-4-chloro-5-(cyclopropyl-methyl-ammo)-phenyl]-carbamic acid tert.-butyl ester (Example Jll) (156 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (170 mg, 0.56 mmol) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (49 mg).
MS (ISP) 42L3 [(M+H)--] and 423 [(M+2+H)^; mp 195-197 X.
Example 37
8-Chloro-7-fcvclopropyl-methyl-amino)-4-f3-(5-hvdroxvmethyl-fL23ltria2ol--l-yl)-phenyl] -1.3-dihvdro-benzof b1 f 1.4] diazepin-2-one
The title compound was prepared from (RS)-[4-chioro-5-(cyclopropyl-methyl-amino)-2-(3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M33) (200 mg, 0.313 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (54 mg).
MS (ISP) 437.3 [(M+H)+] and 439 [(M+2+H)+].
Example 38
7-Dimethylamino-4- [3-f 5-dimethylaminomethyl- [ 1.2,31 triazoM-vD-phenyll -8-trifluoromethyl-13-dihydro-benzo[bUl,4ldiazepin'2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl- (1,2,3] triazol-1 -yl)-phenyl] -3-oxo-propionylamino}-4-trifluoromethyl phenyl)-carbamic acid tert.-butyl ester (Example M34) (126 mg, 0.214 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (23 mg).
MS (ISP) 472 [(M+H)--]; mp 200 °C.

Example 39
8-ChlorO'7-dimethylamino-4-f3-f5*hvdroxymethyl-2-methyl-2H-pvra2ol-3-yl)' phenyll-13-dihydro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-{3-[2-methyl-5-(tetrahydro-pyran-2-ylox)Tncth)1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tat.-butyl ester (Example M35) (278 mg, 0.44 mmol) by treatment with TFA in CHjQ: according to the general procedure N. Obtained as a Hght yellow solid (129 mg),
MS (ISP) 424 [(M+H)--] and 426 ((M+2+H)-]; mp 184 X.
Example 40
4-(4-Oxo-8-pvrrolidin-l-yl-7-trifluoromethyl-4.5-dihvdrO'3H-benzo[bUL4ldiazepin-2-yl)-pyridine-2'Carbonitrile
The title compound was prepared from {2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M36) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg).
MS (ISP) 400.4 [(M+H)--]; mp 188 -C (dec).
Example 41
443-(5-Hvdroxvmethyl-rL23ltriazol-l-vI)-phenyll-7-pvrrolidin-l-yl-8-trifluoromethyl-13*dihvdro-ben2ofb1fL4ldiazepin*2-one
The title compound was prepared from (RS)-[2-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M37) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid(33 mg).
MS (ISP) 471.2 [(M+H)+]; mp 134 °C.
Example 42
7-Dimetfaylamino-8-fluoro-4- [3- f 5-hvdroxvmethyl- f 1.2.31 triazol-1 -yl)-phenvil -1.3-dihvdro-benzofbl rh4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-)4]-phenyi}-propionyi-amino)-phenyl]-carbamic acid tert.-butyl ester (Example M38) (375 mg, 0.63 mmol)

by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg).
MS (ISP) 395 [(M+H)1; mp 75 °C.
Example 43
7-Dimethylamino-4-[3'(5-dimethylaminomethyl-fL2,3ltria2oI-l-yl)-phenyl1-8-fluoro-13-dihydro-benzo[bUL4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionylanaino}-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example M39) (170 mg, 0.32 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (34 mg).
MS (ISP) 422 [(M+H)+]; mp 181 °C.
Example 44
7-Dimethylamino-8-fluoro-4-F3-f3-hydroxymethyl-isoxazol-5-yD-phenvI1-l,3-dihydro-benzofbUl,4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M40) (314 mg, 0,53 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (95 mg).
MS (ISP) 395 [(M+H)--]; mp 187 °C.
Example 45
8-Chloro-7-dimethylamino-4-[3-(5-pvrrolidin-l-ylmethyl-ri,23ltriazol-l-vD-phenyl1-13-dihydro-benzo[b1fL4ldiazepin-2'One
The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxy-methyl- [ 1,2,3] triazol-1 -yl)-phenyl] -1,3-dihydro-ben2o [b] [1,4] diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (0.044 mL, 0.6 mmol) in CH2Cl2 (2 mL) from 23 °C to reflux for 15 min, followed by evaporation to dryness. The crude chloride was dissolved in DMF (2 mL) and stirred with cat amount of Nal and pyrrolidine (0.248 mL, 3.0 mmol) at 23 °C until tic indicated complete conversion of the chloride. The reaction mixture was taken up in EtOAc, washed with water and brine, dried over Na2S04. Removal of the solvent in vacuum left a yellow semisolid.

which was purified by silica gel colxxmn chromatography. Obtained as a yellow solid (101 mg).
MS (ISP) 464 [(M+H)1 and 466 [(M+2+H)-']; mp 180-182 --C.
Example 46
7-Dimethylamino-4-f3-f3'hvdroxvmetfayl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzofb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenylj-carbamic acid tert.-butyl ester (Example M41) (680 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (294 mg).
MS (ISP) 455 [(M+H)--]; mp 219 °C.
Example 47
7-Dimethylamino-8-fluorO'4--[3-(3-methyl-isoxazol-5-yl)-phenyl-l,3-dihvdro-benzo [bl [ 1.41 diazepin-2-one
The title compound was prepared from (5-dimethylamino-4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M42) (233 mg, 0.47 nunol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow-brown solid (59 mg).
MS (ISP) 379 [(M+H)-*-]; mp 124 X.
Example 48
4-[3-(5-Azetidin-l-ylmethyl-fl.23ltriazol-l-yl)-phenyl-8-chloro-7-dimethylaminOr 13-dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and trimethylen imine (10 eq.) as described in Example 45. Obtained as a yellow solid (17 mg).
MS (ISP) 450 [(M+H)-']; mp 153 °C

Example 49
8'Chloro-7-dimethylamino-4- f 3- f 5-hvdroxvmethyl'isoxazol-3-vD-phenyn -1.3-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M43) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (113 mg).
MS (ISP) 411.3 [(M+H)1 and 413 [(M+2+H)']; mp 211 °C (dec).
Example 50
8--Chloro-4-[3--(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-7-piperidin-l-yl-13-dihvdro-benzo f b U1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl]-carbamic acid tert.-butyl ester (Example M44) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (99 mg).
MS (ISP) 451.3 [(M+H)+] and 453 [(M+2+H)-']; mp 246 X (dec).
Example 51
7-Dimethylamino-'4-f3-(5-hydroxvmethyl-isoxazoI'3-yl)-phenyll-8-trifluoromethyl-
L3-dihvdrQ-benzofb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert--butyl ester (Example M45) by treatment with TFA in CH3CI2 according to the general procedure N. Obtained as a light yeUow solid (103 mg),
MS (ISP) 445.3 [(M+H)+]; mp 211 °C (dec).

Example 52
8-Chloro-7-dimeAylamino-4-f3-pvrazol-l-yl-phenylyl3-dihydro-benzofbl ri.4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-dimethylamino-2-[3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propion7lamino]-phenyl}-carbamic acid terL-butyl ester (Example M46) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (75 mg).
MS (ISP) 380 [(M+H)1 and 382 [(M+2+H)+]; mp 231-234°C
Example 53
7-DimethyIamino-4-f3-f3-pvrrolidin-l'ylmethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo fb] f L4l diazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl] -8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 46) (111 mg, 0.25 mmol) by treatment with SOCI2 (3 eq.) and pyrrolidine (10 eq.) as described in Example 45. Obtained as a yellow solid (28 mg).
MS (ISP) 498 [(M+H)+]; mp 160 °C.
Example 54
7-Dimethylamino-4-[3-(3-morpholin-4-ylmethyl-isoxa2ol-5-yl)-phenyl-8-trifluoromethyl-l,3-dihvdrO'benzofbl f l,4ldiazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and morpholine (10 eq.) as described in Example 45. Obtained as a yellow solid (33 mg).
MS (ISP) 514 [(M+H)+]; mp 165 °C
Example 55
7-Dimethylamino-4-f3-(3-dimethylaminomethyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-L3-dihvdrQ-benz6fbUl,4ldiazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and 40 % aqueous Me2NH-sol (10 eq.) as described in Example 45. Obtained as a light yellow solid (21 mg).

MS (ISP) 472 [(M+H)--]; mp 160 °C
Example 56
4-f7-Fluoro-4-oxo-8-pvrrolidin-l-yl-45-dihvdro-3H-benzo[bUl.4ldiazepin-2-vD-pyridine-2-carbQnitrile
The title compoimd was prepared from {2-[3-(2-Cyano-pyridin-4-yI)-3-oxo-propionylamino]-4-fluoro-5-pyrrolidin-l-yl-phenyl}-carbamic acid tert.-butyl ester (Example M47) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (54 mg).
MS (ISP) 350 [(M+H)--]; mp 278-279 °C
Example 57
8-FluorQ-4-f3-(3-methyl-isoxazol-5-vD-phenyl]-7-pvrrolidin-l-yl-13-dihvdro-benzo[bUl,4ldiazepin-2-one
The title compoimd was prepared from (4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example M48) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (86 mg).
MS (ISP) 405 [(M+H)--]; mp 236 -C
Example 58
8-Fluoro-443-(5-hvdroxvmethyl-[L2.3ltriazol-l-vD-phenyl1-7-pvTrolidin-l-yl-L3-dihvdrO'benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-ylox)nnieth.yl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl] -carbamic acid tert-butyl ester (Example M49) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (72 mg).
MS (ISP) 421 [(M+H)--]; mp 184-185 °C.
Example 59
4-f8-Azetidin-l-yl-7-chloro-4-oxo-45-dihvdro-3H-benzofb1[l,4ldiazepin-2-yl)-pyridine-2-carbonitrile
The title compound was prepared from {5-a2etidin-l-yl-4-chloro-2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-phenyl}-carbainic acid terL-butyl ester (Example M50) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (66 mg).

MS (ISP) 352 [(M+H)'] and 354 [(M+2+H)1; mp 276 °C.
Example 60
4- f 3- f 5-Hvdroxymethyl-isoxa2ol-3-yl)'phenyl1 -7-pvrrolidin- 1 -yl-8-trifluoromethyl-L3-dihydro-benzo fb] f L4l diazepin-2-one
The title compound was prepared from (RS)-[2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M51) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (224 mg).
MS (ISP) 47L2 [(M+H)--]; mp 206-208 X.
Example 61
4-f 8-Azetidin- l-yl-4-oxo-7-trifluoromethyl-4.5-dihydrO'3H-benzo [bl \ 1.41 diazepin-2-yl)'pyridine-2-carbonitrile
The title compound was prepared from {5-azetidin-l-yl-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid terL-butyl ester (Example M52) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (51 mg),
MS (ISN) 384.2 [(M-H)']; mp 241 °C.
Example 62
7-A2etidin-l-yl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8'trifluoromethyl-l,3-dihydro-benzofbUL4ldiazepin'2-one
The title compoimd was prepared from (5-azetidin-l-yl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M53) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg).
MS (ISP) 441.3 [(M+H)--]; mp 239 °C (dec).
Example 63
7-A2etidin-l-yl-443-(5-hvdroxvmethyl-rL23ltriazoM-yl)-phenyl1-8-trifluoromethyl-13-dihydro-benzofblfl.4ldiazepin'2-one
The title compound was prepared from (RS)-[5-azetidin-l-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiamino)-4-trifluoromethyl-phenylj-carbamic acid terL-butyi ester (Example M54) by treatment

with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (182 mg).
MS (ISP) 457,4 [(M+H)+]; mp 202 X (dec).
Example 64
7-Dimethylamino-4-13-pyra2ol-l -yl-phenyl)-8-trifluoromethyl-1,3-dihvdro-benzo^b] f l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M55) (438 mg, 0.82 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (238 mg).
MS (ISP) 414 [(M+H)--]; mp 176 °C
Example 65
7-Dimethylamino*4-f3-fL2.4ltriazol-4-yl-phenyl)'8-trifluoromet3iyl-l,3-dihydro-benzolb] [l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-4-yl-phenyl)-propionylamino]-4-trifluoroinethyl-phenyl}-carbamic acid tert.-butyl ester (Example M56) (280 mg, 0.526 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (121 mg).
MS (ISP) 415.3 [(M+H)--]; mp 247-250 °C.
Example 66
7-Dimethylamino-4-(3-imidazol-l-yl-phenyl)-8-trifluoromethyl-l>3-dihvdro-benzolbl [ l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-(3-imidazol-l-yl-phenyl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbainic acid tert.-butyl ester (Example M57) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (132 mg),
MS (ISP) 414 [(M+H)--]; mp 203-205 °C.

Example 67
8-Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-pvra2ol-l-yl)-phenyl1-L3-dihvdro-benzo fb] F1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chIoro-5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M58) (642 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (365 mg).
MS (ISP) 410 [(M+H)--]; mp 211 *°C.
Example 68
7-DimethylaminO'4-f3-(4-hydroxvmethyl-pyrazol-l-yl')-phenyl1-8-trifluoromethyl-13-dihvdro-ben2orb1[l,4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (°Cample M58) (590 mg, 0.91 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (299 mg).
MS (ISP) 444 [(M+H)--]; mp 175 °C
Example 69
7-Dimethylamino-4-f3-(4-hydroxvmethyl-3-methyl-isoxazol-5-yl)-phenvI1-8-trifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[3-methyI-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylarnino)-4-trifluoromethyi-phenyi]-carbamic acid tert--butyl ester (Example M60) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (64 mg).
MS (ISP) 459 [(M-hH)--]; mp 207-208 °C.

Example 70
7-Dimethylamino-4-f3'(4-hvdroxvmethyi-isoxazol-3-yl)-phenyl*8-trifluoromethyl-L3-dihvdro-benzofb1fL4ldiazepin-2'one
The title compound was prepared from (RS)-l5-dimethylamino-2-(3-oxo-3-{3-l4-(tetrahydrO-pyran-2-yloxymcthyl)-isoxa2ol-3-yl)-phenyl}-propionylamino)-4-trifluoromethyl-phenyi)-carbamic acid tert.-butyl ester (Example M61) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (50 mg),
MS (ISP) 445 [(M+H)+]; mp 217-219 M
EMmpk7l
7-Dimethylamino-4-f3-(2-methylsulfanyl-imida2ol-l-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2orb1fL4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyisulfanyl-imidazol-l-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M62) (450 mg. 0.78 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (253 mg).
MS (ISP) 460 [(M+H)--]; mp 192 X.
Example 72
7-Dimethylamino-4'f3-(4'hvdroxvmethyl-2-methyl-2H-pyrazol*3-yl)-phenyll-8' trifluoromethyl-13-dihvdro-benzofb1 f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yi]-phenyl}-3-oxo-propionyl-amino)-4-trifiuoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M63) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (272 mg),
MS (ISP) 458 [(M+H)+]; mp 243-244 °C.
Example 73
8-Chloro-7-dimethylamino-4-f3-fL2,4ltriazoM-yl-phenyl)-13-dihvdro-benzprb] f l,4ldiazepin-2-one
The title compound was prepared from {4-Chloro-5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-l-yl-phenyl)-propionyiamino]-phenyi}-carbamic acid tert-butyl ester

(Example M64) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (316 mg).
MS (ISP) 381 [(M+H)1 and 383 [(M+2+Hr]; mp 239-241 °C
Example 74
7-Dimetfaylamino-4- (5-\l .2,41 triazol-1 -yl-phenyl) - 8-trifluoromethyl-13-dihydro-benzoFb] [L4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,4]triazoH-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M65) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(269 mg).
MS (ISP) 415 [(M+H)--]; mp 228-230 X.
Example 75
3-f8-Dimethylamino-4-oxo-7-trifluoromethyl-4,5-dihvdro-3H-benzorbirL4ldiazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-trifluoromethyl-phenyl}-carbanaic acid tert.-butyl ester (Example M66) (180 mg, LO mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg).
MS (ISN) 371 [(M-H)-]; mp 224-227 X.
Example 76
7-Dimethylamino-4-(3-l5-f('2,2.2-trifluoro-ethylaminoVmethyl]-rL23ltriazol-l-vU-phenyl)-8-trifluoromethyl-l>3-dihydro-benzorb1fL4ldiazepin-2-one
The title compoxmd was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l>2,3]triazol-l-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 17) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and 2>2,2-trifluoroethylamine (10 eq.) as described in Example 45. Obtained as a light yellow solid(19mg).
MS (ISP) 526 [(M+H)'];mp 168-170 °C.

Example 77
7-(Cyclopropylmethyl-methyl-aminoV4-[3-(5-hvdroxvmethyl-fL23ltriazoM-vI)-phenyl1-8-trifluorQmethyl-13-dihvdro-benzofbiri.4]diazepin-2*one
The title compound was prepared from (RS)-[5-(cyclopropylmethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M67) (939 mg> 1.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (544 mg).
MS (ISN) 483 [(M-H)-]; mp 212 °C.
Example 78
4-f8-fCvclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin-2-vn 'pyridine-2-carbonitrile
The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M68) (173 mg, 0.33 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (81 mg),
MS (ISN) 412 [(M-H)*]; mp 155 °C
Example 79
4- [ 3- (4-Cyclopropylaminomethyl'pyrazol-1 -yl) -phenvH -7'dimethylamino-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(4-hydroxymethyl-pyrazoH-)d)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 68) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (45 mg).
MS (ISP) 483 [(M+H)--]; mp 135 °C.
Example 80
4-[3-(5-Cyclopropylaminomethyl-ri.2,3ltriazol-l-yl)-phenyl1-7-fcyclopropylmethyl-methyl*aminoV8-trifluoromethyl-13-dihvdrO-benzorblfl,4ldiazepin-2-one
The title compound was prepared from 7-(cyclopropylmethyi-methyl-amino)-4-[3-(5-hydroxymethyl-[1^3]triazol-l-yl)-phenyl]-8-trifluoromethyl-13-
SOCh (3 eq.) and cyclopropji amine (10 eq.) as described in Example 45. Obtained as a yellow solid (97 mg).
MS (ISP) 524 [(M+H)--]; mp 35-46 °C
Examples!
7-Dimethylamino-4-B-r2-(2-hvdrorv-ethyl)-2H-pvrazol-3-yl]-phenvD-8-trifluoromethyl-l.S-dihvdro-benzQfbl f 1.4ldia7epin-2-one
The title compound was prepared from (RS)-l5-dimetliylainino-2-[3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyi]-2H-p>Tazol-3-yi}-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tcrL-butyl ester (Example M69) (237 mg, 0.36 mmol) by treatment with TFA in CH:Q: according to the general procedure N. Obtained as an off-white solid (48 mg).
MS (ISP) 458 [(M+H)--]; mp 138 °C
Example 82
4-[3'(5-Cvclopropylaminomethyl-fL2.3]tria2ol-l-yl)-phenyl1-7-dimethylamino-8-trifluorometfayl-1.3-dihvdro-benzorbUL4ldiazeptn-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-trifluoromethyi-13-dihydro-benzo[b][l,4)diazepin-2-one (Example 17) (444 mg, 1.0 mmol) by treatment with SOQ2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (248 mg),
Mp 145-148 °C,
Example 83
4-f8-(Cyclopropyl-methyl-amino)-4-oxo-7-trifluoromethyM.5-dihvdro-3H-benzo fb] [ 1,41 diazepin-2-yll -pvridine-2-carbonitrile
The title compoxmd was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester (Example M70) (215 mg, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (87 mg).
MS (ISP) 400.4 [(M+H)--]; mp 200-205 °C.

Example 84
7-Diinethylamino-8-(2-fluoro-phenyl)-4-f3-fh23ltria2ol-l-yl-phenyl)-L3-dihvdro-benzofbl f 1.4ldiazepin-2-one
The title compound was prepared from {2-dimethylamino-2*-fiuoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert.-butyl ester (Example M70) (810 mg, L45 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (61 mg).
MS (ISP) 400.4 [(M+H)+]; mp 225-230 °C.
Example 85
7-Dimethylamino-4-B-(5-(2-hvdroxv-ethyl)-fL23ltria2oM-yl)-phenvU-8-trifluoromethyl-13-dihvdro-benzo \b] [ 1.41 diazepin-2-one
The title compound was prepared from (RS)-{5-dimethylamino-2-[3-oxO-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,2,3] triazol- 1-yl}-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M72) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (179 mg).
MS (ISP) 459 [(M+H)+]; mp 172-175 °C.
Example 86
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-pvrazol-l-vD-phenyl1-8-trifluoromethyl-
1.3-dihvdro-benzQrb1fL4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M73) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow soHd(109mg).
MS (ISP) 444 [(M+H)1; mp 228-229 °C
Example 87
7-Dimethylammo-4-(3-[h2.3ltriazol-l-yl-phenyl)-8-trifluoromethyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[1^3]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic

add tert.-butyl ester (Example M74) (905 mg, 1.7 mmol) by treatment with TFA in CH2Cl2 according to tihie general procedure N. Obtained as a yellow solid (566 mg).
MS (ISN) 413.2 [(M-H)-]; mp 210-212 'C.
Example 88
4-r4-Oxo-842.2.2-trifluoro-ethoxv)-7-trifluoromethyl-4.5-dihvdro-3H-benzofbl f 1,41 diazepin-2-yl1 -pyridine-2-carbonitrile
The tide compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl] -carbamic acid tert.-butyl ester (Example M75) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (100 mg).
MS (H) 428.2 (M^); mp 252-255 °C.
Example 89
3-(8-Dimethylamino-7-methyl-4-oxo-43-dihydro-3H-benzorblfl.4ldiazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-Cyano-phenyl)-3-oxo-propionyi-amino]-4-dimethylamino-5-methyl-phenyl}-carbamic acid tert-butyl ester (Example M76) (0.24 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (114 mg, 59%).
MS (ISP) 319.3 [(M+H)1; mp 257 °C.
Example 90
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-8-methyl-L3-dihydro-benzofbl rL4ldiazepin-2-one
The tide compound was prepared from (RS)-[5-dimethylamino-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M77) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). '
MS (ISP) 391.3 [(M+H)--]; mp 190 X.

Example 91
2-f3-Cyano-phenyl)-8-dimetfaylamino-4-oxo-4.5-dihydrO'3H-benzo[bl[L4ldiazepine-7-carbonitriIe
The title compound was prepared from {5-cyano-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-4-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example M78) (0.28 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (36 mg, 59%).
MS (ISP) 328.3 [(M-H)-]; mp 251 °C
Example 92
3-f7-methyl-8-(methyl-propyl-amino)-4-oxo-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin*2-yl1 -benzonitrile
The title compound was prepared from [2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-methyl-4-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M79) (0.17 g, 0.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg> 58%).
MS (ISP) 347.4 [(M+H)1; mp 195 X.
Example 93
4-[3-(5-HvdroxvTnethyl-[1.2.3ltriazol-l-yl)-phenyl1'8-methyl-7-(methyl-propvI-amino)-L3-dihvdro-benzo [bl [1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M80) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%).
MS (ISP) 419.4 [(M+H)1; mp 186 °C.
Example 94
7-fEthyl-methyl-amino)-4-f3-(5-hvdroxvmethyl*[l,23ltriazol-l-yl)-phenyl1-8-methyl-13-dihvdro-benzo[b1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(ethyi-methyl-amino)-4-meth)i-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionyiamino)-phenyl]-carbamic acid tert-butyl ester (Example M81) (0.39 g, 0.64 mmol) by treatment with TFA in CH2a2 according to the general procedure N.

Obtained as a off-white solid (159 mg, 61%). MS (ISP) 405.5 [(M+H)+]; mp 207 °C
Example 95
8-Dimethylamino-2-f3-(5-hydroxymethyl-fl,2,3ltriazol-l-yD-phenyn-4-oxo-4.5-dihvdro-3H-benzo fb] f 1.41 diazepine-7-carbonitrile
The tide compound was prepared from (RS)-[4-cyano-5-dimethylainino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoM-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl.ester (Example M82) (0.35 g, 0.58 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(149 mg> 64%).
MS (ISP) 402.5 [(M+H)--]; mp 234 °C.
Example 96
8-Chloro-4- f 3- f 5-hvdroxymethyl- [ 1.231 triazol- l-vD-phenyll -7-f isopropyl-methyl-amino)-L3-dihydro-benzorb1|'l,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M83) (0.53 g, 0.83 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a off-white solid (120 mg, 33%).
MS (ISP) 439.5 [(M+H)--]; mp 207 X.
Example 97
8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyll-7-(methyl-propyl-aminoyl.3-dihydro-benzofblfl.4ldiazepin-2-one
The title compound was prepared from [4-methyl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M84) (0.33 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as alight yellow solid (163 mg, 64%).
MS (ISP) 403.4 [(M+H)--]; mp 194 '°C.

Example 98
8-Dimethylamino-2-[3-(3-methyl-isoxa2ol-5-yl)-phenyll-4-oxO'43-dihydro-3H-benzo fbl f 1.41 diazepine-7*carbonitrile
The title compound was prepared from (4-cyano-5-dimethyiamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-Carbaniic acid tert-butyl ester (Example M85) (0.31 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (171 mg, 72%).
MS (ISP) 386.3 [(M+H)--]; mp 248 °C.
Example 99
7-fEthyl-methyl-amino)-8-methyl-4-F3-(3-methyl-isoxazol-5-yl)-phenyl]*L3-dihvdro-benzo fbl [ 1.41 diazepin-2-one
The title compound was prepared from (5-(ethyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M86) (0.38 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow solid (160 mg, 55%).
MS (ISP) 389.5 [(M+H)--]; mp 198 °C
Example 100
7-DimethylaminO-8-methyl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-l3-dihydro-benzoFbl [l,4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M87) (0.32 g, 0.65 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (140 mg, 57%).
MS (ISP) 375.4 [(M+H)--]; mp 204 °C.
Example 101
8-Chloro-4- r3- f 5-hvdrQYvmethyl- \ 1.23ltriazol-l-yl)-phenyl1 -7-f isobutyl-methyl-amino)-13-dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isobutyl-methyl-ainino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazoM-yi]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M88) (0.32 g, 0.49 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtzdned as an ofF-white solid (107 mg, 48%)-

MS (ISP) 453.4 [(M+H)--]; mp 201 °C.
Example 102
8-Cbloro-7-(isobutyl-methyl*amino)-4-f3-f3-methyl-isoxazol-5-yD-phenyn-L3-dihvdro-benzofbirL4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M89) (0.35 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (114 mg, 41%),
MS (ISP) 437.4 [(M+H)+]; mp 194 °C.
Example 103
2-f3-(5-Hvdroxvmethyl-fl.23ltriazol-l-yl)-phenyl]-4-oxo-8-pyrrolidin-l-yl-4.5-dihvdrO-3H-benzo[b1fL4]diazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example M90) (0.37 g, 0.59 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (140 mg, 56%).
MS (ISP) 428.5 [(M+H)1; mp 241 °C.
Example 104
2-f3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-8-pvrrolidin-l-yM,5-dihydro-3H-benzofbl f L4l diazepine-7-carbonitrile
Prepared from (4*cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M91) (0.41 g, 0.77 mmol) by treatment with TFA m CH2Cl2 according to the general procedure N. Obtained as a yellow solid (90 mg, 28%).
MS (ISP) 412.3 [(M+H)--]; mp 267 °C.
Example 105
2-f3-(5-Hvdroxvmethyl-fl.2,3ltriazol-l-yl)-phenyl1-8-fmethyl-propvi-aminol-4-oxo-45-dihvdro-3H-benzo f b1 \ 1.41 diazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiannino)-phenyl]-carbamic acid tert-butyl ester (Example M92) (0.43 g, 0.68

mmol) by treatment with TFA in CH2Cl2 according to the general procedmre N. Obtained as a yellow solid (100 mg, 34%).
MS (ISP) 430.5 [(M+H)--]; mp 221 °C.
Example 106
2-f3-f3-Methyl-isoxa2ol-5-vD-phenyl-8-(methyl-propyl-amino)-4-oxo-4,5-dihvdro-3H-benzofb1 [ l,4ldiazepine-7-carbonitrile
The title compound was prepared from [4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M93) (0.36 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg, 34%).
MS (ISP) 414.4 [(M+H)--]; mp 133 °C
Example 107
8-Diethylamino-2-[3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-4>5-dihydro-3H-benzofbl f 1.4] diazepine-7-carbonitrile
The title compound was prepared from (4-cyanO-5-diethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxO-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M94) (0.35 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(209 mg, 77%).
MS (ISP) 414.4 [(M+H)+]; mp 191 °C.
Example 108
8-fIsopropyl-methyl-amino)-2-f3*f3-methyl-isoxa2ol-5-yl)-phenyn-4-0X0-4.5-dihvdro-3H-benzofb11 L4ldiazepine-7-carbonitrile
The title compound was prepared from (4-cyano-5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M95) (0.37 g, 0.70 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (219 mg, 76%).
MS (ISP) 414.4 KM+H)--]; mp 197 °C.

Example 109
2- r3-(5-HvdrQxvmethyl- f 1,2.3 Itriazol- l-yl)-phenyl1 -8-f isopropyi-metfayl-amino)-4-oxo-4.5-dihvdro-3H-benzo Fbl f 1,41 diazepme-7-carbonitrile
The title compoimd was prepared from (RS)-[4-cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-)d]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M96) (0.45 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (236 mg, 77%).
MS (ISP) 430.5 [(M+H)+]; mp 206 °C.
Example 110
8-(Isobutyl-methyl-aminoV2-f3-f3-methyl-isoxazol-5-yl)-phenyn-4-0X0-4,5-dihvdro-3H-ben2ofbl [ l,4]diazepine-7-carbonitrile
The title compoimd was prepared from (4-cyano-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M97) (0.39 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (230 mg, 75%).
MS (ISP) 428.5 [(M+H)+]; mp 170 °C.
Example 111
2-f3-(5-Hvdroxvmethyl-fL23ltriazol-l-vD-phenyl-8-(isobutyl-methyl-aminoV4-oxo-4.5-dihvdro-3H-benzofb]Fl,4ldiazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M98) (0.46 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (180 mg, 57%).
MS (ISP) 444.4 [(M+H)+]; mp 199 X.
Example 112
2-f3-(3-methyl-isoxazol-5-yl)-phenYll-4-oxo-8-piperidin-l-yl-43-dihydro-3H-benzofbUL4ldiazepine-7-carbonitrile
The title compoimd was prepared from (4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl

ester (Example M99) (0.41 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (226 mg, 70%).
MS (ISP) 426.4 [(M+H)--]; mp 246 °C.
Example 113
8-Chloro-7-isobutylamino-4-r3-(3-methyl-isoxazol-5'yl)-phenyl-13-dihvdro-benzofbl ri,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-isobutylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example MlOO) (0.34 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (216 mg, 81%).
MS (ISP) 423.3 [(M+H)--]; mp 249 X.
Example 114
8--Chloro-4-[3-(5-hvdroxymethyl-[L23]triazol-l'yl)-phenv]]-7-isobutylaminO'l,3-dihydrO'benzorb1fl,4ldiazepin-2-one
The tide compoimd was prepared from (RS)-[4-chloro-5-isobutylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example MlOl) (0.17 g, 0.27 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg, 35%).
MS (ISP) 439.4 [(M+H)--]; mp 214 X.
Example 115
4-f3-(5-Hydroxvmethyl-fL2.3ltriazol-l-yl)-phenyl]-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzofb1[L4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M102) (0.15 g, 0-22 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (31 mg, 30%).
MS (ISP) 473.2 [(M+H)--]; mp 230 °C

Example 116
4-f3-(3-MethyMsoxazol-5-yiVphenyl]-7-fmethyl-propyl-aminoV8-trifluoromethyl-1.3-dihvdro-ben2orb1fL4ldiazepin-2-one
The title compound was prepared from [2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M103) (0.26 g, 0.45 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (127 mg, 61%).
MS (ISP) 457.4 [(M+H)+]; mp 193 °C
Example 117
4'f3-(5-Hvdroxvmethyl-fl.23ltria2ol-l-\dVphenyll-7-fisobutyl-metfayl-amino)-8-trifluoromethyl-L3-dihydro-benzorbl[L4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M104) (0.51 g, 0.74 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (169 mg, 47%).
MS (ISP) 487.3 [(M+H)*-]; mp 230 °C.
Example 118
7-fIsobutyl-methyi-aminoV4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8-trifluoromethyl-13-dihvdro-benzofbUL4ldiazepin-2-one
The title compound was prepared from (5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M105) (0.42 g, 0.71 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (161 mg, 48%).
MS (ISP) 471.2 [(M+H)--]; mp 195 X.
Example 119
4-r3-(5-Hvdroxvmethyl-ri.23ltriazol-l-yl)-phenyll-7-fisopropyl-methyl-aminoV8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-(5-(tetrahydro-pyran-2-yloxymeth)4)-[l^,3]triazol-l-yl]-phenyl}-propionyl-

amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example M106) (0.50 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofif-white solid (156 mg, 45%).
MS (ISP) 473.3 [(M+H)--]; mp 234 X.
Example 120
7-fIsopropyl-methyl-aminoV4-f3-(3-methyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2o fbl [ 1.41 diazepin-2-one
The tide compound was prepared from (5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M107) (0.37 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg, 25%).
MS (ISP) 457,4 [(M+H)+]; mp 199 °C.
Example 121
8-Chloro-7-fmethyl-propyl-amino)-4-f3-(5-pvrrolidin-l-ylmethyl-[1.2.3ltria2ol-l-yl)-phenyll -13'dihydro-benzo Fbl [ 1,4] diazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-ainino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepm-2-one (Example 29) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a yellow foam (63 mg, 26%).
MS (ISP) 492.3 [(M+H)+].
Example 122
4-f3-(5-A2etidin-l-ylmethyl4L2.3ltriazol-l-yl)-phenyn-8-chloro-7-fmethyl-propyl-amino)-L3-dihydro-benzo fbl [l,4]diazepin-2-one
The title compoimd was prepared from 8-chIoro-7-(methyl-propyi-amino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 29) (118 mg, 0.27 namol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine in DMF according to the method described in Example 45. Obtained as a light yellow solid(65 mg, 50%),

MS (ISP) 478.3 [(M+HD; mp 169 *°C
Example 123
8-CMoro-4-f3-(5-diethylaminomcthyi-fL2J)triazol-l-yl)-phenyl]-7-fmethyl-propyl-aminoyl,3-dihvdro-benzorblfL4]dia7q?in-2-one
The tide compound was prepared from 8-chloro-7-(meth-5d-propyl-amino)-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol-1 ->i)-phen\1 j -13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction wth thionylchloride in dichloro-methane and subsequent treatment of the corresponding chloride with diethylamine in DMF according to the method described in Example 45. Obtained as a Ught yellow solid (123 mg, 50%).
MS (ISP) 494.3 [(M+H)--]; mp 151 °C
Sample 124
8-Chloro-4-C3-l5-rfisopropvI-methyl-amino)-methyll-fL23ltriazoM-ylt-phenyD-7-(methyl-propyl-amino)-13-dihvdro-benzofbUL4]diazepin-2-one
The tide compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymediyl-[l,2,3]triazol-l-yl)-phenyl]-13-dihydro-ben2o[b][l,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (129 mg, 52%),
MS (ISP) 494.3 [(M+H)-*-]; mp 148 °C.
Example 125
8-Chloro-7-fisopropyl-methyl-amino)-4-f3-f5*pvrrolidin-l-ylmethyl-fL23ltria2ol-l'yI)-phenyl]-13-dihvdro-benzo[b1fL4ldiazepin-2-one
The tide compound was prepared from 8-chloro-4-l3-(5-hydroxymethyi-
[lA3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (219 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrroUdine in DMF according to the method described in Example 45.
Obtained as a light yellow solid (157 mg, 64%).
MS (ISP) 492.3 [(M+H)--]; mp 172 °C.

Example 126
8-Chloro-7-fisobutyl-methyl-aminoV4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1 -13-dihvdro-benzo[b1 ri.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[ 1,2,3] triazol- l-yl)-phenyl]-7-(isobutyl-methyl-amino)- 1,3-dihydro-
ben2o[b] [l,4]diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Erample 45.
Obtained as a light yellow solid (163 mg, 64%),
MS (ISP) 506.3 [(M+H)+]; mp 190 X.
Example 127
8-Chloro-4-f3-(5-dimethylaminomethyl-fL2,3ltriazoM-yD-phenyl-7-(isopropyl-methyl-aminoyl3-dihydro-benzofb1[1.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as a light brown solid (143 mg, 61%).
MS (ISP) 566.3 [(M+H)+]; mp 225 X.
Example 128
8-Chloro-4-f3-(5-dimethylaminomethyl-rL2.3ltriazoM-vD-phenyl]-7-risobutvI-methyl-aminoyl,3-dihvdro-benzofbUL4]diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-
benzo[b] [1,4] diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as a light brown solid (134 mg, 56%).
MS (ISP) 480.5 [(M+H)--]; mp 199 X.

Example 129
4-[3-(5-Azetidin-l-ylmethyl-[1.2,3]triazol-l-yl)-phenyl1-8-chlorO'7-fisopropvI-methyl-amino V13-dihydro-ben2o [b] F1.41 diazepin-2*one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyI-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg> 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine m DMF according to the method described in Example 45. Obtained as a light brown solid (102 mg, 43%).
MS (ISP) 478.3 [(M+H)--]; mp 177 °C.
Example 130
4-f3-(5-Azetidin-l-ylmethyl'fh2J]triazol-l-vD-phenyl>8-chloro-7-risobutyl-methyl-amino)-1.3-dihvdro-benzo[bl[l,4ldiazepin-2'One
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3'dihydro-benzo[b][l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimelhylene-imine in DMF according to the method described in Example 45. Obtained as a light brown solid (125 mg, 52%).
MS (ISP) 492.3 [(M+H)+]; mp 191 °C.
Example 131
8-Chloro-4-f3-(5'methylaminomethyl-rL2.3ltriazol-l-vD-phenyl-7-fmethyl-propyl-amino)-L3-dihvdro-benzoFb1fl.4ldiazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyi]-l,3-dihydrO-benzoIb][l,4]diazepin-2-one
(Example 29) (230 mg, 0.52 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with methylamine in DMF according to method described in Example 45. Obtained as a Kght yellow solid(122 mg, 52%).
MS (ISP) 452.4 [(M+H)--]; mp 185 °C.

Example 132
4-f3-(5-Hvdroxvmethyl-fl,23]triazol-l-yl)-phenyl1-7-fisobulTl-methyl-amino) methyl- L3-dihvdro-ben20 Fbl [ L4l diazepin-2-one
The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M108) (0.33 g, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a pale brown solid (188 mg, 79%).
MS (ISP) 43L4 [(M-H)-]; mp 198 -C.
Example 133
443-(5-Hvdroxvmethyl-ri23ltriazol-l-yl)-phenyl1-8-methyl-7-pvrrolidin-l-yl-13-dihydrO'benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-methyl-2-(3-oxo-3-{3-[5-(tetrahydxo-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylainino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example MHO) (0,41 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (239 mg, 86%).
MS (ISP) 417-3 [(M+H)--]; mp 202 °C.
Example 134
7-(Isobutyl-methyl'amino)-8-methyl-4-f3-f3-methyl-isQxazol-5-yl)-phenylyl3-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from (5-(isobutyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyI)-carbamicacid tert-butyl ester (Example M109) (0.33 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (136 mg, 53%).
MS (ISP) 417.3 [(M+H)--]; mp 187C.
Example 135
8-methyl-4-r3-f3-methyl-isoxazol-5-yl)-phenyl1-7-pvrrolidin-l-yl-13-dihvdro-benzofbl f L4ldiazepin-2-one
The title compoimd was prepared from (4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionyiainino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyi

ester ^iixample M111; (U.33 g, 0.64 mmolj by tr . nent with TFA in CH2Cl2 according to the general procedure N. Obtained a^ an off-white solid (223 mg, 87%).
MS (ISP) 401.5 [(M+H)--]; mp 211 '°C.
Example 136
4-F3-(5-Dimethylaminomethyl-fL2.3ltriazol-l-yl)-phenyl-7-(isobutyl-methyl-amino)-8-trifluoromethyl-13-dihydro-benzofbiri.4ldiazepin-2-one
The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7-(isobutyl-methyl-amino)-8-trifluoromethyl- 1,3-dihydro-ben2o[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 35%).
MS (ISP) 514.3 [(M+H)*-]; mp 182 °C.
Example 137
8-(Isobutyl-methyl-aminoV4-oxo-2-[3-(5-pvrrolidin-l-ylmethyl-rL23ltriazol-l-yl)-phenyn-4.5-dihydro-3H-benzorb1fl,4ldiazepine-7-carbonitrile
The title compoxmd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-benzo[b][l,4]diazepine-7-carbonitrile (Example 111) (200 mg, 0.45 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (140 mg, 63%).
MS (ISP) 497.3 [(M+H)--]; mp 174 °C,
Example 138
7-(Isobutyl-methyl-aminoV4-f3-(5-pyrrolidin-l-ylmethyl-fl.23ltriazol-l-vIV phenyl]'8-trifluoromethyl*13-dihydro-benzofb1[h4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yi)-
phenyl]-7-(isobutyl-methyl-ainino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45.
Obtained as a Ught orange foam (80 mg, 24%).

MS (ISP) 540.5 [(M+H)+)..
Example 139
7-('Isobutyl-methyl-amino)-8-methyl-4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1-1.3-dihydro-benzorbirL4Tdiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yI)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 132) (200 mg, 0.46 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (50 mg, 22%).
MS (ISP) 486.4 [(M+H)--]; mp 177 °C.
Example 140
8-(Isobutyl-methyl-amino)-2-(3-{5-f(isobutyl-methyl-amino)'methyl]-rL23ltriazol-l-yll-phenyl)-4-oxo-4.5-dihvdro-3H-ben2o[b1[l,4ldiazepine'7-carbonitrile
The title compoimd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepine-7-carbonitrile (Example HI) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutyl-methylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (100 mg, 39%).
MS (ISP) 513.4 [(M+H)+]; mp 169 °C.
Example 141
7-fIsobutyl-methyl-amino)-4-f3-l5-[(isopropyl-methyl-amino)-methyl]-[L2,3ltria2ol-l-vU-phenyl)-8-trifluoromethyl-L3-dihvdro-benzofb1[1.4ldiazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2oM-yl)-
phenyl]-7-(isobutyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 117) (260 mg, 0,53 nrnnol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropyl-methylamine in DMF according to the method described
in Example 45. Obtained as a light brown solid (70 mg, 24%),
MS (ISP) 542.3 [(M+H)--]; mp 157 °C

Example 142
8'Chloro-4-F3-(5-cyclopentylaminomethyl-[L23ltriazol-l-vIVphenyll-7-(isopropyl-methyl-aminoyl3-dihvdro-ben2o[b1Fl.4]diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopentylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (170 mg, 67%).
MS (ISP) 506.3 [(M+H)--]; mp 174 *°C.
Example 143
4-f3-l5-[(Cvclopropylmethyl'amino)'methyl1-rL2.3ltriazol*l-yU-phenvD-7-(isobutyl-methyl-amino)-8-methyl-L3-dihydro-benzofblfl,4]diazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyM,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 132) (250 mg, 0.58 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylmethylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (50 mg, 18%).
MS (ISP) 486.4 [(M+H)+]; mp 184 °C,
Example 144
8-Cbloro-7-fisobutvI-methyl-aminoV4-[3-(5-piperidin-l-ylmethyl-[1.23ltriazol-l' yl)-phenyl1-13-dihvdro-ben2ofb1fL4ldiazepin-2-one
The title compoimd was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[ l,2,3]tria2ol- l-yl)-phenyl]-7- (isobutyl-methyl-amino)- 1,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with piperidine in DMF according to the method described in Example 45.
Obtained as a light brown solid (250 mg, 99%).
MS (ISP) 520,3 [(M+H)--]; mp 169 «C.

Example 145
8-Chloro-4-B-(5-(isopropylaminO-methyl)-fL2,3ltriazol-l'yl]-phenvU-7-(isopropyl-methyl-aminoyl.3-dihvdro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenylj-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with isopropylamine in DMF according to the method described in Example
45. Obtained as a light yellow solid (160 mg, 67%),
MS (ISP) 480.3 [(M+H)+]; mp 208 °C.
Example 146
8-Chloro-7-fisopropyl'methyl-aminoV4-[3-(5-{f(2-methoxy-ethyl)*methyl-amino1-
methvU-fL2,3ltriazol-l-yl)-phenyl1-l3-dihydro-benzo[b1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-(2-methoxyethyl)methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 47%).
MS (ISP) 510.4 [(M+H)+]; mp 119 °C.
Example 147
8-Chloro-4-(3-{5-[(cvclopropylmethyl-aminoVmethyl]-fL23ltria2ol-l-yll-phenyl)-7-(isopropyl-methyl-amino)'13-dihvdro-benzorbl[1.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, D.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with aminomethyl-cyclopropane in DMF according to the method described
in Example 45. Obtained as a light brown solid (150 mg, 61%).
MS (ISP) 592,2 KM+H)--]; mp 151 °C

Example 148
8-ChlorO-7-(isopropyl-methyI-aminoV4-f3-l5-f('isopropyl-metfayl-amino)-methyl]-fL23ltriazoM-yll-phenylyl3-dihvdro-benzorbUL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazoH-yl)-phenyi]-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropylmethylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (120 mg, 49%).
MS (ISP) 494.3 [(M+H)--]; mp 180 °C.
Example 149
8-Chloro-4-f3-{5-rfisobutyl-methyl-aminoVm€thyl)-rL23ltriazoM-yl]-phenyl)-7-(isopropyl-methyl-amino)-13-dihvdro-benzo[b1 [1.41 diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-
ben2o[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isobutylmethylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (190 mg, 75%).
MS (ISP) 508.4 [(M+H)--]; mp 182 °C
Example 150
4-f3'(5'DimethylaminomethyI-fL2,3]triazoI-l-yl)-phenyl]-7-risopropyl'metfayl-aminoV8-trifluoromethyl--13-dihvdro-benzofb][1.4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l>4]diazepin-2-one (Example 119) (200 mg, 0,42 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as an off-white solid (80 mg, 38%).
MS (ISP) 500.4 [(M+H)--]; mp 197 »C.

Example 151
7-fIsopropyl-methyl-amino)-4-r3-(5-pvrrolidin-l-ylmethyl-fL23ltriazoI-l-yl)-phenyll -8'trifluoromethyl-13-dihvdro-ben20 f hi f 1,41 diazepin'2-one
The title compound was prepared from 4- [3-(5-hydroxymethyl- [l,2,3]triazol- 1-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (200 mg, 0.42 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45.
Obtained as a light brown solid (140 mg, 63%).
MS (ISP) 526.2 [(M+H)--]; mp 175 X.
Example 152
7-Qsopropyl-methyl-aminoV4-(3-l5-f(isopropyl-methyl-amino)-methyl1-
fl.2.3ltriazol-l'yl}-phenyl)-8-trifluoromethyI-L3-dihvdro-benzofbUl.4]diazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (220 mg, 0.47 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropylmethylamine in DMF according to the method described in
Example 45, Obtained as a light yellow solid (110 mg, 45%).
MS (ISP) 528.4 [(M+H)1; mp 182 °C,
Example 153
4,f3-|5-r(Cvclopropylmethyl*aminoVmethyl1-rL23Uria2ol-l-yll-phenyl)-7-fisopropyI-methyl-aminoV8-trifluoromethyl-L3-dihvdro-benzorb1fl,4ldiazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (210 mg, 0.44 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with aminomethyl-cyclopropane in DMF according to the method described
in Example 45. Obtained as a light brown solid (110 mg, 47%).
MS (ISP) 526.2 [(M+H)--]; mp 152 °C

Example 154
8-Chloro-4- TS-f 5-cyclopropylaminomethyl- [ h2.3ltriazol-l-yl)-phenyll-7-f isopropyl-methyl-amino V13'dihvdro-b enzo f b1 f 1.41 diazepin-2- one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[ 1,2,3 ] triazol-1 -yl)-phenyl] -7- (isopropyi-methyl-amino) -13-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0,50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (40 mg, 17%).
MS (ISP) 478.4 [(M+H)--];mp 144 °C
Example 155
4-l3-(5-fIsopropylamino-methyl)-rL23ltriazol-l-yl]-phenyll-7-(isopropyl-methyl-amino)-8-trifluoromethyl-L3-dihvdrO'benzorbirL4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with isopropylamine in DMF according to the method described in Example
45. Obtained as a light yellow solid (100 mg, 39%).
MS (ISP) 514.4 [(M+H)+]; mp 191 °C.
Example 156
8-Chloro-4-(3-r5-fisobutylamino-methvD-fL23ltriazol-l-yl1-phenyll-7-(isopropyl-methyl-aminoyl3'dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isobutylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 65%).
MS (ISP) 494.4 [(M+H)--]; mp 182 X.

Example 157
4-f3-(5-Cvclopropylaminomethyl-fl.2.3ltriazoM-yl)-phenyl1-7-fisopropyl-methyl-aminoV8-trifluoromethyl*1.3-dihvdro-benzofblfL4ldia2epm-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-tri6uoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethanc and subsequent treatment of the corresponding
chloride with cyclopropylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (70 mg, 27%).
MS (ISP) 512.4 [(M+H)--]; mp 178 '°C
Example 158
7-fIsobutyl-methyl-amino)-8-methyl-4'f3-(5-pvrrolidin-l-ylmethyl*fL2,4ltria2ol-l-vD-phenvI1-13-dihvdro-benzoib1fL4ldiazepin-2-one
The title compound was prepared from 4-(3-(5-hydroxymethyl-[l,23]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as an ofif-white solid (106 mg, 52%).
MS (ISP) 486,5 [(M+H)']; mp 164 °C.
Example 159
4-[3-(5-Cyclopropylaminomethyl-fL2,4ltriazol-l-yl]-phenyl1-7-(isobutyl'methyl* amino)-8-methyl-1.3-dihydro-benzofb][L4ldiazepin-2-one
The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7- (isobutyl-methyl-amino)-8-methyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (108 mg, 55%).
MS (ISP) 472.4 [(M+H)--]; mp 114 °C.

Example 160
8-Chloro-7-isopropylamino-4-f3-f3-methyl-isoxazol-5-vD-phenyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-isopropylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example Ml 12) (0.16 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (120 mg, 93%).
MS (ISP) 409.4 [(M+H)--]; mp 225 *°C.
Example 161
8-Chloro-4-f3-(5-hvdroxvmethyl-|-l,2,3ltriazol-l-vD-phenyll-7-isopropylamino-13-dihvdro-benzofbl [ L4l diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-isopropylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M113) (0.37 g, 0.60 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (209 mg, 82%).
MS (ISP) 425.4 [(M+H)--]; mp 250 °C.
Example 162
8-Chloro-7-(methyl-propyl-amino)-4-f3-(5-hvdroxvmethyl-[L2,4ltriazol-l-yl)-phenyl! -1,3-dihydro-benzo f b1 f 1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 14) (1.47 g, 2.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid(1.0 g, 99%).
MS (ISP) 439.5 [(M+H)--]; mp 192 °C,
Example 163
8-Chloro-4-r3-(5-hvdroxvmethyl-rL2.4ltriazol-l-yl)-phenyll-7-risobutyl-methyl-aminoyl3-dihvdro-benzofbirL4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isobutyi-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 15) (0.61 g, 0.93

mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Hght brown solid (290 mg, 69%).
MS (ISP) 453.5 [(M+H)--]; mp 195 °C
Example 164
8-ChlorO-7-(methyl-propyl-amino)-4-f3-(5-pyrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yIVphenyll-l,3-dihvdro-benzo[b1fl,4]diazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (114 mg, 46%).
MS (ISP) 492.3 [(M+H)1; mp 183^0.
Example 165
8-Chloro-7'fisobutyl-methyl-aminoV4-r3-(5-pvrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yl)-phenyl] * 13-dihvdro-benzo f bl [ 1.41 diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,4]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-One (Example 163) (200 mg, 0,44 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45,
Obtained as a light yellow solid (99 mg, 44%).
MS (ISP) 506.4 [(M+H)+]; mp 164 °C.
Example 166
8-Chloro-4-f3-(5-dimethylaminomethyl-[L2.4ltriazol'l-yl)-phenyl1-7-fmethyl-propyl-amino)-1.3-dihydro-benzorblfl,4ldiazepin-2-one
The title compound was prepared-from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4ltriazol-l-yl)-phenyl]-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethyiamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (93 mg, 540%).

MS (ISP) 466.4 [(M+H)--]; mp 170 X,
Example 167
8-Chloro-4-r3-(5-cvclopropylaminomethyl-fL2,4]tria2ol-l-yl)-phenyl1-7-fmethyl' propyl-aminoyl,3-dihvdro-benzofbUL4ldiazepin-2-one
The title compound was prepared from 8-chIoro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymiethyl-[l,2,4]tria2ol-l-yl)-phcnyi)-13-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (95 mg, 40%).
MS (ISP) 478.4 [(M+H)--]; mp 123 ^'C
Example 168
4-f3-(5-Hvdroxymethyl-fL2,4]triazol-l-\i)-phenyll-7-fisobutyl-methyl-aminoV8-methyl'l,3-dihydro-benzofb1 (h4]diazepin-2-one
Prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyi-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazoM-yl]-phenyl}-propion)iamino)-phenyi]-carbamic acid tert-butyl ester (Example Ml 16) (0.96 g, 1.51 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (480 mg, 73%).
MS (ISP) 433.6 [(M+H)+]; mp 191X.
Example 169
7-(methyl-propyl-aminoV4'f3-fL2,4ltriazol-l-yl-phenyl)-8-trifluoromethyM3-dihvdro-benzorbUl.4ldiazepin-2-one
The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M117) (0.31 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light ydlow solid (192 mg,78%).
MS (ISP) 443.4 [(M+H)--]; mp 185 *C.

Example 170
7-(methyl-propyl-aminoV4-(3-[l,23ltriazol-l-yl-phenvD-8-tiifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 18) (0.33 g, 0.59 mmol) by treatment -with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (115 mg, 44%).
MS (ISP) 443.4 [(M+H)+]; mp 147 X.
Example 171
7-(I$obutyl-methyl-aminoV4-(3-pyrazoI-l-yl-phenyl)-8-trifluoromethyl-13-dihydro-benzo fbl \ 1,41 diazepin-2-one
The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 19) (0.49 g, 0.85 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (324 mg, 83%).
MS (ISP) 454.4 [(M-H)-]; mp 182 X.
Example 172
4-f8-(Isopropyl-methyl-amino)-4-oxQ-7-trifluoromethyl-4,5-dihvdro-3H-benzofb1[L4ldiazepin-2-yl1-pyridine-2-carbonitrile
The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(isopropyI-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M120) (0.67 g, 1.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (210 mg, 41%).
MS (ISP) 400.3 [(M-H)-l; mp 189 *°C.

Example 173
8'Chloro-7-fisobutyl-methyl-aminoV4-f3-fl.2.4ltriazol-l-yl-phenvD-13-dihvdro-benzofbl rL4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-phenyl}-carbamicacidtert-butyl ester (Example M121) (0.76 g, 1.41 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a li^t orange solid (530 mg, 89%),
MS (ISP) 423.4 [(M+H)-*]; mp 213 °C.
Example 174
7-fIsobutyl-methyl*aminoV4-(3-fl,2.4ltriazol-l-yl-phenvD-8-trifluoromethyl-l,3-dihvdro-benzofbiri,4ldiazepin-2-one
Prepared from {5-(isobutyl-methyl-amino)-2-[3*oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M122) (0.50 g, 0,87 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (350 mg, 88%).
MS (ISP) 457.5 [(M+H)*-]; mp 198 X,
Example 175
8-Chloro-7-(isobutvI-methyl-aminoV4-(3-[L23ltriazol-l-yl-phenylyl3-dihvdro-benzoFbl f L4]diazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M123) (0.17 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a hght yellow solid (100 mg, 75%),
MS (ISP) 423.5 [(M+H)--]; mp 85 °C.
Example 176
7-fIsobutyl-methyl-aminoV4-f3-fl.23ltriazol-l-'vi-phenyl)-8-trifluoromethvM3-dihvdro-benzorblfL4]diazepin-2*one
The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[ 1,2,3 ] triazol- l-yl-phenyl)-propionyiamino] -4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M124) (0.44 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (170 mg, 49%),

MS (ISP) 457.5 [(M+H)--]; mp 202 °C
Example 177
4-f3-Imida2ol-l-yl-phenvD-7-isobutylamino-8-trifluoromethyI-13-dihvdro-benzofbl ri,4ldiazepin-2-one
The title compound was prepared from {2-[3-(3-imida2ol-l-yl-phenyl)-3-oxo- . propionylamino] -5-isobutylamino-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M125) (0.43 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (260 mg, 76%).
MS (ISP) 442.4 [(M+H)1; mp 221 °C.
Example 178
8-ChlorO'4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-L3-dihvdro-benzofb] f h4]diazepin-2-one
The title compound was prepared from {4-chlorO-2-[3-(3-imidazoM-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-phenyl}-carbamic acid tert-butyl ester (Example M126) (0.33 g> 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (240 mg, 94%).
MS (ISP) 408,4 [(M+H)+]; mp 212 °C.
Example 179
8-Chloro-7-(isobutyl-aminoV4-f3-ri,2.3ltriazol-l-yl-phenylyl3-dihvdro-benzofbl [l,4ldiazepin'2-one
The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazoH-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M127) (0.22 g, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (90 mg, 53%).
MS (ISP) 407.3 [(M-H)']; mp 249 °C.
Example 180
7-(Isobutyl-amino)-4-r34L23ltriazol-l-vI-phenyl)-8-trifluoromethyl-13-dihvdro-benzofbl f l,4ldiazepin-2-one
The title compovmd was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionyiamino]-4-trifluoromethyl-phenyl}-carbamic
add tert-butyl ester (Example M128) (0.34 g, 0.61 mmol) by treatment with TFA in

CH2Cl2 according to the general procedure N. Obtained as a light brown solid (150 mg> 56%).
MS (ISP) 443.4 [(M+H)+]; mp 212 °C.
Example 181
8-Chloro-7-(isobutyl-aminoV4-f3-[L2,4ltriazol-l-yl-phenvD-L3-dihvdro-benzofbl [L4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carban:iic acid tert-butyl ester (Example M129) (0.39 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light orange solid (270 mg, 89%).
MS (ISP) 407.3 [(M-H)-]; mp 222 X.
Example 182
7-fIsobutyl-aminoV4-f3-[L2.4ltriazol-l-yl-phenyl)-8-trifluoromethyl-L3-dihvdrO' benzo[bl f 1.4]diazepin-2-one
The title compound was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M130) (0.43 g, 077 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (270 mg, 61%).
MS (ISP) 441.3 [(M-H)-]; mp 191X.
Example 183
8-Chloro-7-fethyl-methyl-amino)-4-f3-f4-hvdroxymethyl-thiazol-2-yl)-phenyl-l,3-dihydro-benzoTbl f l,4]diazepin-'2-one
The title compound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.14 g).
MS (ISN) 439.2 [(M-H)*]; mp 136-137 °C.

Example 184
8-Chloro-4-f3-f4-hvdroxymethyl-thiazol-2-yD-phenyll-7-fmetfayl-propyl-amino)-1,3-dihydro-ben20 [b] [ 1.4] diazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-t±iiazol-2-yl]-phenyl] -propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0-10 g).
MS (ISN) 453.2 [(M-H)-]; mp 211-213 °C
Example 185
8-Chloro-4-[3-(4-hvdroxymethyl-thiazol-2-yl)-phenyll-7-(isopropyl-methyl-amino)-L3*dihydro-benzo[b1fL4ldiazepin-2-one
The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light-brown solid (0.05 g).
MS (ISP) 455.2 [(M+H)1; mp 193-195 °C
Example 186
8-Chloro-4-f3-(4-hydroxymethyl-thiazol-2-yl)-phenyn-7-(isobutyI-methyl-amino)-L3-dihydrO'benzofb1fl,4ldiazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyi -amino)-phenyI]-carbamic acid tert-butyl ester (0.23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl
ester (0.32 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g).
MS (ISP) 469.1 [(M+H)--]; mp 135-136 °C

Example 187
8-Chloro-7-fetfayl-methyl-aminoV4-r3-f4-hydroxvmethyl-oxa2ol-2-yl)-phenyn-l,3-dihvdro-benzofbl f l,4ldiazepin-2-one
The title compound was prepared from [2-amino-4-Chloro-5-(ethyl-methyl-amino)-phenylj-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxyxnethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedxire N. Obtained as a yellow solid (0.10 g).
MS (ISN) 423.1 [(M-H)-]; mp 165-166 °C.
Example 188
8-Chloro-4-[3-f4-hvdroxvmethyl-oxazol-2-yD-phenyll-7-fmethyl-propyl-aminoV L3-dihvdro-benzofb1fl.4]diazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g).
MS (ISP) 437.2 [(M-H)-]; mp 166-167 °C
Example 189
8-Chloro-4-f3-(4-hvdroxymethyl-oxazol-2-yl)-phenyl1-7-fisopropyl-methyl-amino)-L3-dihydro-ben2ofb1 [1.41 diazepin-2-one
The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyI]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-l4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a ydlow solid (0.05 g).
MS (ISP) 439.3 [(M+H)*-]; mp 143-145 X.

Example 190
8-ChlorO-4-r3-f4*hvdroxvmethyl-oxazol-2-yl)-phenyll-7-fisobutyl-methyl-amino)-13-dihvdro-benzo|-b][1.4]diazepin-2-one
The title compound was prepared from [2-aminO-4-chloro-5-(isobutyl-methyI -amino)-phenyl]-carbamic acid tert-butyl ester (0,23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (0.31 g) (Example Kll) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0,18 g),
MS (ISP) 453,3 [(M+H)*-]; mp 166-167 °C.
Example 191
8-Chloro-7-dimethylamino-4-f3-(4-methylaminomethyl-thiazol-2-yl)-phenyll-1.3-dihydro-benzofb]fL4ldiazepin-2-one
al 8-ChIoro-4-f3-(4-chloromethyl-thia2oI-2-yl)-phenyll-7-dimethylamino-13' dihydro-benzo[b][1.4]diazepin-2-one
A mixture of 8-chIoro-7-dimethylamino-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.38g) (Example 19) andthionyl chloride (0,1 mL) in CH2Cl2 was heated to 40 -°C for 2 h. The heterogeneous mixture was evaporated in vacuum and the residue was triturated with AcOEt to give the title compound (0,44 g) as a light-brown soHd, MS (ISP) 445.1 [(M+H)+],
b) 8-Chloro-7-dimethyiamino-4-f3-(4-methylaminomethyl-thiazol-2-vD-phenyl-l,3-dihydro-ben2orb][l,4]diazepin-2-one
A mixture of 8-chloro-4-[3-(4-chloromethyl-thia2ol-2-yl)-phenyl] -7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (89 mg) and KI (3 mg) in a 8M solution of methylamine in EtOH (1 mL) was stirred at 20 °C for 20 h. H2O (25 mL) was acided and the pH of the mixture was set to 11 by acidition of 2N NaOH. The precipitate was collected by filtration and purified by chromatography on silica gel using MeOH as eluent. The product was stirred with 20% aqueous MeOH (10 mL) and the solid was isolated by filtration to give the title compound (49 mg) as a yellow powder,
MS (ISP) 440.2 [(M+H)--]; mp 129-130 °C.

Example 192
8-Chloro-7-dimethylamino-4-f3-f4-morpholin-4-ylmethyl-thia2ol-2-yD-phenyl1-1.3-dihvdro-benzofbl ri,4ldiazepin-2-one
A mixture of 8-chlo^o-4-[3-(4-chloromethyl-thiazol-2-yl)-phenyl]-7-dimethyla^mlo-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one (89 mg) (Example 191a), morpholine (0.17 mL) and KI (3 mg) in EtOH (0.5 mL) was stirred at 60° C for 3 h. H2O (25 mL) was acided to the cooled solution and the precipitate was collected by filtration and purified by chromatography on silica gel using AcOEt/acetone (1:1) as eluent The product was stirred with 20% acjueous MeOH (20 mL) The pH of the mixture was set to 11 by acidition of IN NaOH and the solid was subsequently isolated by filtration to give the title compound (55 mg) as yellow powder.
MS (ISP) 496.2 [(M+H)--]; mp 138-143 °C
Example 193
8-Chloro-7-dimethylaminO-4-[3-(2-hydroxvmethyl-thiazol-4-vD-phenylyl3-dihydrO'benzorb][L4ldiazepin-2-one
a)4-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylaminO'13-dihvdro-benzofb] [L4Tdiazepin-2-one
A solution of 3-Oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (2.34 g) (Example K28) and (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example J2) (L57 g) in toluene (16 mL) was heated to 100 *C for 5 h. The solvent was evaporated in vacuimi and the crude product was purified by chromatography on silica gel using CH2Cl2/AcOEt (1:20) as eluent. A solution of the purified material (2.4 g) in CH2Cl2/TFA (1:1,30 mL) was stirred at 20 °C for 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated. The residue was crystallized firom AcOEt/EtaO to give 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b] [l,4]diazepin-2-one as light-brown solid.
b^8-Chloro-7-dimethylamino-4-f3-(2-hvdroxvmethyl-thiazol-4-yl)-phenyl1-L3-dihvdro-benzofbl f L4ldiazepin-2-one
A mixture of 4-(3-bromoacetyi-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-beiizo[b][l,4]diazepin-2-one (0.22 g) and 2-(tert-butylcarbonyl-oxy)thioacetamide (0.11 g) in EtOH (3 mL) was heated at 80 *C for 0.5 h. The solution was diluted with AcOEt, washed with saL NaHCOa solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (8 mL) and L5N KOH (8 mL) at 20 °C for

20 min. H2O (30 ml) was acided and the precipitated product collected by filtration to give the title compound (0.9 g) as yellow powder.
MS (ISP) 427.3 [(M+H)']; mp 176-178 °C
Example 194
4-r3-(2-Amino-thiazol-4-yl)-phenNi1-8-chloro-7-dimethylamino-l.3-dihvdro-benzo [bl f 1.41 diazepin-2-one
A mixture of 4-(3-bromoacetyi-phcn>1)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.73 g) (Example 193a) and thiourea (0,13 g) inTHF (10 mL) was heated to 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and vsith brine. The organic layer was dried and evaporated and the residue was stirred \%-ith CH:Q: to give the title compound (0.14 g) as yellow solid,
MS (ISN) 410.2 [(M^H)-]; mp 247-248 °C
Example 195
8-Chloro-7-dimethylamino-4-f3-(2-ethylamino-thiazol-4-yl)-phenyl1-13-dihvdro-benzofbl [L4ldiazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyi)-8-chloro-7-dimethylamino-13-dihydro-benzo[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THE (3mL) was heated at 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et20 to give the title compound (24 mg) as yellow solid.
MS (ISP) 440.3 [(M+H)--]; mp 122-123 °C.
Example 196
N-{4-f3-(7-ChlorO'8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb1fL4ldiazepin-2-vD-phenyl1-thiazol-2-yl}-guanidine
A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-amidino-thiourea (35 mg) in THE (3mL) was heated at 60 'C for 1 h- The mixture was diluted with AcOEt and washed with sat NaHCOa solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using

AcOEt/MeOH (20:1) as eluent. The purified product was crystallyzed from acetone to give the title compound (22 mg) as yellow solid.
MS (ISP) 454.2 [(M+H)--]; mp 221 X dec.
Example 197
8-Chloro-7'dimethylamino-4-(3-[2-(pyridin-4'ylamino)-thiazol-4-yl]'phenvU-13-dihvdro-benzo[b1[1.4ldiazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and l-(4-pyridyl)-2-thiourea (46 mg) in THE (3mL) was heated at 60 X for 45 min. The mixture was dfluted with AcOEt and washed with sat NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was triturated with Et20 to give the title compound (55 mg) as yellow solid.
MS (ISP) 489.2 [(M+H)*']; mp 231-234 °C.
Example 198
8-ChlorO-4-f3-(2-metfayl-Oxazol-4-yl)-phenyl1-7-(methyl-propyl-amino)-l,3-dihydro-benzorb1fl>4'idiazepin-2-one
The title compoimd was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (0.17 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.07 g).
MS (ISP) 423.2 [(M+H)-*]; mp 163-164 X.
Example 199
4-f3-(4-HydrGxymethyl-thiazol-2-yl)-phenyl-8-methyl-7-rmethyl-propyl-aminoV L3-dihvdro-benzofb1 f l.>41diazepin-2-one
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.09 g).

MS (ISP) 435.3 [(M+Hr];mp 222-224^0.
Example 200
4-f3-f4-Hvdroxymethyl-oxazol-2-yl)-phenyl1-8-methyl-7-fmethyl-propyi'aminoV L3-dihydro-benzo[b1fl.4]diazepin-2-one
The title compound was prepared from [2-amino-4-methyl-5-(meth)i-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4- (tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example Kll) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.16 g).
MS (ISP) 419.3 [(M+H)+]; mp 200-202 °C.
Example 201
7-Dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-8-trifluoromethyl-1,3 - dihvdro-benzo f b1 [ 1 A] diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.12 g).
MS (ISP) 461.2 [(M+H)1; mp 198-199 °C,
Example 202
7-Dimethylamino-4-[3-(4-hvdroxvmethyl-oxazol-2-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofblfL4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phen)d]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.11 g).
MS (ISP) 445.0 [(M+H)*]; mp 197-198 °C

Example 203
4-f3-f4-Hvdroxymethyl-thiazol-2-y!VphenvI1-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2*one
The title compound was prepared from [2-amino-5-(methyl-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tcrt-butyl ester (0.17 g) (Example J35) and 3-0X0-3- [3- [4-(tetrahydro-pyran-2->'iox>TOCthyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cydizcd by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g).
MS (ISP) 489.2 [(M+Hr];mp 177-180^
^3B^mple 204
7-Dimethylamino-4-f3-(5-hvdroxymeth\i-fL3.4]thiadiazol-2-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzofb]fl.4ldia7epin-2-one
The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyi ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadia2ol-2-yl]-phenyi}-propionicacid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as ofif-white solid (0.06 g).
MS (ISP) 462.1[(M+H)'-]; mp 242-246 X.
Example 205
7-Dimethylamino-4-{3-r5-(2-hvdroxv-ethvD-fL3,4lthiadiazol-2-yl1-phenylt-8-trifluoromethyl-13-dihydro-ben2o Fb ] f L4l diazepin-2-one
The title compoxmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,3,4]thiadiazoI-2-yl}-phenyi)-propionic acid tert-butyl ester (0.24 g) (Example K3I) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a oflF-white solid (0.06 g).
MS (ISN) 474.2 [(M-H)-]; mp 234-237 X,

Example 206
7-Dimetfaylamino-4-f3-(5-hvdroxvmethyI-fl3.4loxadiazol-2-yl)-phenyn-8-trifluoromethyl-13-dihvdro-benzo f b] [ 1,41 diazepin-2-one
The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (1.44 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3>4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (2.17 g) (Example K32) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g).
MS (ISP) 463.2 [(M+NH4)+].
Example 207
7-Dimethylamino-4-(3-r5-(2-hvdroxv-ethyl)-[13.4loxadia2ol-2-yl1-phenvU-8-trifluoromethyl-13-dihydro-benzo f b] f 1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [1,3,4] oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (0.23 g) (Example K33) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g).
MS (ISP) 460.2 [(M+H)--]; mp 237 *°C dec.
Example 208
7-Dimethylamino-4-(3-oxazol-4-yl-phenyl)-ig-trifluoromethyl-L3-dihvdro-benzofbl f h4ldiazepin-2-one
The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K34) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (50 mg).
MS (ISP) 415.2 [(M+H)--]; mp 218-219 °C.

Example 209
7'Dimethylamino-4-f3-tfaia2ol-4-yl-phenyl)-8-trifluoromethyl-L3-dihydro-benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (109 mg) (Example K35) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (61 mg).
MS (ISP) 431.2 [(M+H)--]; mp 200 °C dec.
Example 210
7-Dimethylamino-4-[3-(2-methyl-oxazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofb] f L4ldiazepin-2'One
The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(2-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.18 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.04 g).
MS (ISP) 429.3[(M-hH)-']; mp 192-193 °C.
Example 211
7-DimethyIamino-4-f3-(5-methyl-oxazoI-4-yn-phenyn-8-trifluoromethyl-L3-dihvdro-benzofb1fl,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyi)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,18 g) (Example K36) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.13 g).
MS (ISP) 429.3 [(M+H)--]; mp 238-239 °C.

Example 212
7-Dimethylamino-4-[3-(2-methyl-5-propyI-oxa2ol-4-yi)-phenyl-8-trifluoromethyl-1.3-dihydro-benzo[b]fl.4]diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (80 mg) (Example J6) and 3-[3-(2-methyl-5-propyl-oxazoI-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K37) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as pale-yellow solid (20 mg).
MS (ISP) 471,2 [(M+H)'*];mp 211-212 °C.
Example 213
7-Dimethylamino-4-[3-(5-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzofb] [ L4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-[3-(5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,19 g) (Example K38) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0,06 g).
MS (ISP) 445.2 [(M+H)1; mp 214-215 °C
Example 214
7-Dimethylamino-4-[3-(2,5-dimethyl-thiazol-4-yl)-phenyn-8-trifluoromethyM,3-dihydro-benzofbl f L4]diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (48 mg) (Example J6) and 3-[3-(2>5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (50 mg) (Example K39) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (38 mg).
MS (ISP) 459.2 [(M+H)--]; mp 208-209 X.

Example 215
7-Dimethylamino-4-f3-(2-hvdroxymethyI*thiazol-4-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one
a)4*(3-Bromoacetyl-phenyl)-7-dimethylamino-'8-trifluoromethyl*1.3-dihydro-benzofbl f l,4ldiazepin-2-one
A solution of (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (0.32 g) and 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyi ester (0.43 g) (Example K28) in toluene (3 mL) was heated to 100 °C for 2 L The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using AcOEt /Hexan(l:3) as eluent A solution of the purified material (0.57 g) in CH2Cl2/TFA (1:1,7 mL) was stirred at 20 ®Cfor 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated to give crude 4-(3-bromoacetyl-phenyl)-7-dimethylainino-8-trifluoromethyM,3-dihydro-benzo[b][l,4]diazepin-2-one (0.22 g) as light-brown solid.
b) 7-Dimethylamino-4-f3-(2-hvdroxymethyl-thiazol-4-yl)-phenyl1 -8-trifluoro-methyl-1.3-dihydro-benzo fbl F1,41 diazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-l>3-dihydro-benzo[b][l,4]diazepin-2-one (0.40 g) and 2-(tert.-butylcarbonyloxy)thio-acetamide (0.21 g) in EtOH (5 mL) was heated at 80 'C for 0.5 h. The solution was diluted with AcOEt, washed with sat NaHCOs solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (5 mL) and L5N KOH (5 mL) at 20 ^'C for 20 min. H2O was acided and the predpitated product coDected by filtration and purified by chromatography on silica gel using AcOEt as eluent to give the title compound (0.01 g) as yellow solid.
MS (ISP) 461.1 [(M+H)--].
Example 216
7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-methyl-thia2ol-4-yl)-phenyil-8-trifluoromethyl-1,3-dihydro-benzofb1 \ 1.41 diazepin-2-one
The title compound was prepared firom (2-an:iinO-5-dimethylamino-4-trifluoro-methyi-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-mediyl-2-(tetrahydro-pyran-2-yloxymedi)d)-thiazol-4-yl]-phen)i}-propionicadd
tert-butyl ester (0.26 g) (Example K40) according to the general procedure M. The

obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as light-yellow solid (0.11 g).
MS (ISP) 475.2 [(MH-H)I; mp 190-193 °C
Example 217
7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-propyl'thiazol-4-vD-phenyl1-8-trifluoromethyl-h3-dihydro-benzofb1 [1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (79 mg) (Example J6) and 3-oxo-3-{3-[5-propyl-2-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (138 mg) (Example K41) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (45 mg).
MS (ISP) 503.2 [(M+H)1; mp 112-114 °C
Example 218
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-2-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzorbUl,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionicacid tert-butyl ester (0.26 g) (Example K42) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid(0.11 g).
MS (ISN) 473.0 [(M-H)']; mp 226-227 '°C.
Example 219
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-thiazol-4-yl)-phenyll-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{[5-(tetrahydro-pyran-2-yioxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (0,25 g) (Example K43) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0-08 g).

MS (ISN) 459.3 [(M-H)-].
Example 220
4-(3-f5'f(CvcIopropylmethyl-amino)-methyll-thiazol-4-yn-phenyl)-7-dimethylamino-8-trifluoromethyl-L3-dihvdro-benzorb1fL4ldiazepin-2-one
A mixture of 7-dimethylamino-4-[3-(5-hydroxymethyl-thiazol-4-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 219) (65 mg) and thionyl chloride (0.015 mL) in CH2Cl2 (0.3 mL) was stirred at 20 °C for 1 h. The heterogeneous mixture was evaporated in vacuum and the residue was suspended in EtOH (0.5 mL). Aminomethyl-cyclopropane (0.12 mL) and KI (3 mg) were acided and the mixture was stirred at 80 ^'C for 5 h. The mixture was evaporated in vacuum ant the residue was purified by chromatography on silica gel using AcOEt/MeOH (50:1) as eluent The resulting product was stirred with 20% aqueous MeOH (10 mL)) the pH of the mixture being set to 11 by the acidition of IN NaOH, and the solid was isolated by filtration to give the title compound (44 mg) as off-white solid.
MS (ISP) 514.3 [(M+H)--]; 157-158° C.
Example 221
7-Dimethylamino-4-f3-(2-isopropyl-lH-imidazol-4-yl)-phenyl1-8-trifluoromethyl-L3-dihydro-benzo[birL4ldiazepin-2-one
The title compotmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbanuc acid tert-butyl ester (0.13 g) (Example J6) and 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.20 g) (Example K44) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.10 g).
MS (ISP) 456.4 [(M+H)--]; mp 150 Xdec.
Example 222
4-f3-(5-Hvdroxymethyl-[13.4lthiadiazol-2-yl)-phenyl-7-(methyl-propyl-aminoV8-trifluoromethyl-13-dihvdro-benzo[b1fL4ldiazepin-2-one
The title compound was prepared from [2-amino-5-(methyi-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (0.17 g) (Example J35) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[13>4]thiadiazol-2-yi]-phenyl}-propionic acid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cydized by treatment with

TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.02
g).
MS (ISP) 490.2 [(M+H)--]; mp 193-194 --C.
Example 223
8-Chloro-7-dimethylamino-4-l3-r5-(2-hvdroxv-ethyl)-ri,3,4lthiadiazol-2-yl]-phenyl)-13-dihvdro-ben2ofb1fl.4]diazepin-2-one
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (0.15) and crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phenyl)-propionicacid tert-butyl ester (0.24 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g).
MS (ISN) 440.2 [(M-H)-]; mp 198-200 °C.

The active ingredient having a suitable particle size, the crystalline lactose and the microcrystaUine cellulose are homogeneously mixed with one another, sieved and thereafter talc and magnesium stcarate are admixed. The final mixture is filled into hard gelatine capsules of suitable size.

Example I Tablets of the following composition are produced in a conventional maimer
mg/Tablet
Active ingredient 100
Powdered, lactose 95
White com starch 35
Polyvinylpyrrolidone 8
Na carboxymethylstarch 10
Magnesium stearate _2
Tablet weight 250
Example II
Tablets of the following composition are produced in a conventional manner:
mg/Tablet
Active ingredient 200
Powdered, lactose 100
White corn starch 64
Polyvinylpyrrolidone 12
Na carboxymethylstarch 20
Magnesium stearate ^
Tablet weight 400
Example III
Capsules of the following composition are produced:
mg/Capsule
Active ingredient 50
Crystalline, lactose 60
Microcrystalline cellulose 34
Talc 5
Magnesium stearate 1
Capsule fill weight 150

Case 20871
Dihydro-benzo[b] [l,4]diazepin-2-one derivatives as mGluR2 antagonists II
The present invention relates to compounds of general formula I

selected from the group consisting of halogen, lower alkyl, fluoro-lower alkyl, C3-C6-cycloalkyl, lower alkoxy and fluoro-lower alkoxy;

R2 is -NR'R-, fluoro4ower alkoxy or
S-oxo-piperazin-l-yl, pyrrolidin-l-yl or piperidm-l-}d, which rings are optionally substituted by R-;
R' is hydrogen, lower alkyl, C3-C6-cycloalkyl, fluoro-lower alkyl or 2-lower alkoxy lower alkyl;
R- is hydrogen, lower alkyl,

and to their pharmaceutically acceptable addition salts.

It has surprisingly been found that the compounds of general formula I are metabotropic glutamate receptor antagonists. Compounds of formula I are distinguished by valuable therapeutic properties.
In the central nervous system (CNS) the transmission of stimuli takes place by the interaction of a neurotransmitter, which is sent out by a neuron, with a neuroreceptor.
. L-glutamic acid, the most commonly occurring neurotransmitter in the CNS, plays a critical role in a large number of physiological processes. The glutamate-dependent stimulus receptors are divided into two main groups. The first main group forms hgand-controUed ion channels. The metabotropic glutamate receptors (mGluR) form the second main group and, furthermore, belong to the family of G-protein-coupled receptors.
At present, eight different members of these mGluR are known and of these some even have sub-types. On the basis of structural parameters, the different influences on the synthesis of secondary metabolites and the different affinity to low-molecular weight chemical compounds, these eight receptors can be sub-divided into three sub-groups: mGluRl and mGluRS belong to group I, mGluR2 and mGluR3 belong to group II and mGluR4, mGluR6, mGluR7 and mGluRS belong to group III.
Ligands of metabotropic glutamate receptors belonging to the group II can be used for the treatment or prevention of acute and/or chronic neurological disorders such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits.
Other treatable indications in this connection are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are chronic and acute pain, Himtington's chorea, amyotrophic lateral sclerosis (ALS), dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutarnate-defidency functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, opiate addiction, anxiety, vomiting, dyskinesia and depressions.

Objects of the present invention are compounds of formula I and their pharmaceutically acceptable salts per se and as pharmaceutically active substances, their manufacture, medicaments based on a compound in accordance with the invention and their production, as well as the use of the compounds in accordance with the invention in the control or prevention of illnesses of the aforementioned kind, and, respectively, for the production of corresponding medicaments.
The compounds of formula I can also be used in form of their prodrugs. Examples are esters, N-oxides, phosphate esters, glycoamide esters, glyceride conjugates and the like. The prodrugs may add to the value of the present compounds advantages in absorption, pharmacokinetics in distribution and transport to the brain.
All tautomeric forms of the compounds of the invention are also embraced herewith.
Preferred are compounds of formula I, wherein X is a single bond. Exemplarly preferred are compovmds, wherein R^ is trifluoromethyl, and especially those wherein R is cyano, for example the following compounds:
4-(4-oxo-8-pyTrolidin-l-yl-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-pyridine-2-carbonitrile,
4-[8-(cyclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ l,4]diazepin-2-yl] -pyridine-2-carbonitrile,
4-[8-(cyclopropylmethyl-amino)-4-oxo-7-trifiuoromethyl-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl]-pyridine-2-carbonitrile,
4-[4-oxo-8-(2,2,2-trifluoro-ethoxy)-7-trifluoromethyI-4,5-dihydro-3H-ben2o[b] [l,4]diazepin-2-yl]-pyridine-2-carbonitrile, and
4-[8-(isopropyl-methyl-amino)-4-oxo-7-trifluoromethyl-4,5-dihydro-3H-ben2o[b] [ 1,4] diazepin-2-yl] -pyridine-2-carbonitrile.
Further preferred are compounds, wherein X is a single bond, R^ is trifluoromethyl and R is an optionally substituted five-membered aromatic heterocyde, which may be substituted by halogen, fluoro-lower alkyl, fluoro-lower alkoxy, cyano, -(CH2)n-NR'R-, -(CH2)n-C(O)-0R-, -(CH2)n-C(O).NR'R-, .(CH2)n-S02-NR'R-, -(CH2)„-C(NH2)=NR-, hydroxy, lower alkoxy, lower alkyithio, or by lower alkyl, which is optionally substituted by fluoro, hydroxy, lower alkoxy, cyano or carbamoyloxy. Examples of such compounds are the following:

7-dimethylamino-4-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimethylaimnO-4-[3-(2-metiiyl-2H-pyra2ol-3-yl)-phenyi]-8-tri dihydro-benzo [b] [ 1,4] diazepin-2-one,
7-dimethylamino-4-(3-imidazol-1 -yl-p}ienyl)-8-trifluoromethyl- 1,3-dihydro-
benzo[b] [l,4]diazepin-2-one,
4-[3-(3-methyHsoxa2ol-5-yl)-phenyl]-7-(methyl-propyl-ainino)-8-trifluoromethyl-1,3-dLhydro-benzo [b] [ 1,4] diazepin-2-one,
7-(isobutyl-methyl-amino)-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-8-trifluorom l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-(isopropyl-inethyl-ainmo)-4- [3-(3-methyl-isoxa2ol-5-yl)-phenyl] -8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-(isobu1yl-methyl-amino)-4-(3-{5-[(isopropyl-methyI-ainino)-inethyl]-
[ 1,2,3] triazol-1-yl}-phenyl)-8-trifluoromethyl-l,3-dihydro-ben2o [b] [ 1,4] diazepin-2-
one,
7-(isopropyl-methyl-amino}-4-[3-(5-pyrroKdin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl] -8-txifluorometliyl-l,3-dihydro-benzo [b] [1,4] diazepin-2-one,
7-(methyl-propyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-8-trifluoromethyl-l,3 dihydro-benzo[b][l,4]diazepin-2-one,
7-(isobutyl-methyl-amino)-4-(3-[l,2,3]tria2ol-l-yl-phenyl)-8-trifluoromethyl-1,3 dihydro-benzo [b] [ l,4]diazepin-2-one,
4-(3-imidazol-l-yl-phenyl)-7-isobutylaniino-8-trifluoroinethyl-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimeliiylaiiuno-4-[3-(4-hydroxymethyl-liiiazol-2-yl)-phenyl]-8-trifluoronieA^ l,3-dihydro-benzo[b][l,4]diazepin-2-one,
7-dimethylamino-4-[3-(4-hydroxyniethyl-Oxazol-2-yl)-phenyl]-8-1xifluoronieli^ l,3-dihydxo-ben2o[b] [1,4] diazepin-2-one,
4-[3-(4-hydroxynxethyl-thiazol-2-yl)-phenyl]-7-(niethyl-propyl-anriino)-8-trifluoroniethyl-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one, and
4-[3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-phenyl]-7-(niethyl-propyI-aniino) trifluoromethyl-1,3-dihydro-ben2o [b] [ 1,4] diazepin-2-one.

Also preferred are compounds, wherein X is a single bond, and R is chloro, tor example the following compounds:
8-diloro-7-isobutyla,in-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-
ben2o[b] [l,4]diazepin-2-one,
8-cUoro-7-(methyl-propyl-amino)-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydrO-benzo[b] [l,4]diazepin-2-one,
8-chloro-7-(isopropyl-methyl-amino)-4-[3-(5-pyrrolidin«l-ylmethyI-[l,2,3]triazoI-l-yl)-phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one,
8-cHoro-7-(isobutyl-methyl-amino)-4-[3-(5-pyrroHdin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-ben20 [b] [ 1,4] diazepin-2-one,
8-chloro-4-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazol-l-yl)-phenyl]-8-chloro-7-(isopropyl-methyl-amino)-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one,
4-[3-(5-azetidin-l-ylmethyl-[l,2,3]triazl-yl)-phenyl]-8-chloro-7-(isobutyl-methyi-amino)-l,3-dihydro-benzo[b][l,4]diazepin-2-one,
8-chloro-7-(isobutyl-methyI-amino)-4-[3-(5-piperidin-l-ylmethyl-[l,2,3]triazol-l-yl) -phenyl] -1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one,
8-chlorO-7-(isopropyl-methyl-amino)-4-(3-{5-[(isopropyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-13-dihydro-benzo[b][l,4]diazepin-2-one,
8-chloro-4-(3-{5-[(isobutyl-methyl-amino)-methyl]-[l,2,3]triazol-l-yl}-phenyl)-7-(isopropyl-methyl-amino)- 1,3-dihydro-benzo [b] [1,4] diazepin-2-one,
8-chloro-7-isopropylamino-4-[3-(3-methyl-isoxazol-5-yl)-phenyi]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
8-chloro-7-(isobutyl-methyl-amino)-4-(3-[l,2,3]triazol-l-yl-phenyl)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
8-chIoro-4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-1,3-dihydro-benzo [b] 11,4] diazepin-2-one,
8-chloro-7-(ethyl-methyl-amino)-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one
8-chloro-4-[3-(4-hydroxymethyi-thiazol-2-yl)-phenyl]-7-(methyl-propyl-amino)-13-dihydro-benzo[b]l [l,4ldiazepin-2-one

7-(ethyl-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-dimethylamino-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one,
7-(isobutyi-methyl-amino)-8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyl]-l,3-dihydro-benzo [b] [ 1,4] diazepin-2-one>
7-(isobutyl-methyl-amino)-8-methyi-4-[3-(5-pyrrolidin-l-ylmethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b] [l,4]diazepin-2-one, and
4-(3-{5-[(cyclopropylmethyl-amino)-methyI]-[l,2,3]triazol-l-yl}-phenyl)-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one.
Preferred are further compounds, wherein R is -N(CH3)2 or pyrrolidine. Also preferred are compounds, wherein R2 is isopropyl-amino, isopropyl-methyl-amino, isobutyl-amino or isobutyl-methyl-amino.
Preferred compounds of formula I in the scope of the present invention are further those, wherein R is cyano or an optionally substituted five-membered aromatic heterocycle, which may be substituted by -CH2OH or -CH2N(CH3)2.
The term -lower alkyl- used in the present description denotes straight-chain or branched saturated hydrocarbon residues with 1-7 carbon atoms, preferably with 1-4 carbon atoms, such as methyl, ethyl, n-propyl, i-propyl and the like.
The term 'lower alkoxy- denotes a lower alkyl residue in the sense of the foregoing definition bound via an oxygen atom. Examples of'lower alkoxy- residues include methoxy, ethoxy, isopropoxy and the like.
The term -halogen- embraces fluorine, chlorine, bromine and iodine.
The term -fluoro-lower alkyl- means a lower alkyl residue, wherein one or more hydrogen-atoms may be replaced by fluoro.
The term -fluoro-lower alkoxy- denotes a lower alkoxy residue in the sense of the definition herein before, wherein one or more hydrogen-atoms may be replaced by fluoro.
The term -C3-C6-cycloalkyl- means a cycloalkyl group containing 3 to 6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.
The term -lower alkylthio- denotes a lower alkyi residue in the sense of the foregoing definition bound via an sulfur atom, for example methylsulfanyl.

The expression -five-membered aromatic heteroqrde' embraces fiirane, thiophene, thiazole, pyrrole, imidazole, pyrazole, oxazole, isoxazole, triazole, oxadiazole, thiadiazole and tetrazole. Preferred heterocycles are 1,2,3-triazole, 1,2,4-triazole, isoxazole, l,3-oxa2ole, 1,3-thiazole, 1,3,4-oxadiazole or imidazole,
-Optionally substituted- means that a group may or may not be substituted with one or more, preferably one or two substituents independently selected from the specified group.
The term -pharmaceutically acceptable addition salt- refers to any salt derived from an inorganic or organic acid or base.
The compounds of general formula I and their pharmaceutically acceptable salts can be manufactured according to methods, which process comprises
a) reacting a compound of formula II

which subsequently undergoes deprotection of the amino group and cyclization, to obtain a compound of formula

1
According to scheme A, compounds of general formula I, in which X, Y, R1 R2 and R3 are as described above, can be prepared from compounds of general formula II via an acyiation-deprotection-cyclization sequence;
For example reacting compounds of general formula II with a dioxinone IV, in which Y and R3 are as described above> in an inert solvent such as toluene or xylene at elevated temperatures, preferably between 80 °C and 160 °C gives rise to compounds of general formula III.
Alternatively, compounds of general formula III can also be prepared by for example reaction of a compound of general formula II with a p-ketoester (general formula rVa), in which Y and R^ are as described above using the same conditions as described for the reaction with the dioxinones.
Afterwards, deaving the BOC protecting group in compounds of general formula III and concomitant cydization of the deprotected compound yidds the desired compounds of general formula I. Any other suitable amino protecting group, such as e.g- Fmoc or benzyloxycarbonyl (Z), can be altemativdy used instead of the BOC group.

The deprotection-cyclization step can be carried out by treating the compounds of general formula III with for example a Bronsted add such as trifluoroacetic add in an inert solvent such as dichloromethane (DCM). The reaction is preferably carried out at temperatures between 0°C and 50 °C- It may be advantageous to use also anisole or 1,3-dimethoxybenzene as a carbocation scavenger in the reaction mixture.

According to scheme B, compounds of general formula 11 in which R^ is phenyl optionally substituted as described above for compounds where X is a single bond and R is as described above, can be prepared by different routes depending on the nature of R3 from the iodo-compounds of general formula V, in which R3 is as described above. As shown in scheme B, the key step is a coupling reaction of Suzuki-type to produce compounds of the general formula Via.
Compounds of general formula II, in which R1, R3 and X are as described above can be prepared according to scheme B, by reducing the nitro group in compounds of general formula Via to the amino group. The reduction can for example be carried out using hydrogen gas in presence of a suitable catalyst like for example Raney-Nickel or Palladium on carbon. Another possible reduction method is using stannous (II) chloride (SnCl2-2H2O) in ethanol at temperatures between 70 --C and 80 °C (as described in Tetrahedron Lett, 1984,25,839), or alternatively in polar aprotic solvents, like DMF, DMA or NMP and the like, optionally in the presence of bases, like for example pyridine or triethylamine and the like, at temperatures between 0°C and 80 °C. Another suitable method is using zinc-powder in the presence of ammonium

chloride in protic solvents like for example water or ethanol at temperatures between 20 °C and 80 °C. The exact conditions for the respective compounds of general formula II can be found in the experimental part.
Compounds of general formula V, in which R1 is as described above, can be prepared by different routes depending on the individual residue R2:

As shown in scheme C, compound Bl can be prepared from the commercially available 5-chloro-2-nitroaniline by iodination to give the synthetic intermediate Al, which in turn can be protected to yield the compound BL
The iodination step can be carried out by for example using iodine monochloride in acetic acid in the presence of sodium acetate. The reaction can be for example carried out at temperatures between 20°C and 80 °C.
The protection of the amino function can be applied to a number of commercially available starting materials or compounds synthesized by anyone skilled in the art to produce the corresponding 2-nitroanilines with the general formula VII, in which X is a single bond and R1 is as described above. This transformation leads to the key intermediates of the general formula VIb, and the exact conditions for the respective compounds used in this invention can be foimd in the experimental part.
) One possibility for the protection of the amino function is for example reacting compounds of general formula VII with di-tert-butyl-carbonate in the presence of a base such as cesium carbonate. The reaction can be carried out in polar solvents such as acetone or butanone and the like at temperatures between 20 °C and 60 °C.

Alternatively, the protection of the amino group can be achieved by preparing the intermediate isocyanate by treatment of compoimds of the general formula VII with diphosgene, preferably in aprotic solvents such as ethyl acetate or 1,4-dioxane at temperatures from 0 °C to 100 °C, and subsequent treatment of the isocyanate with tert. butanol in solvents such as dichloromethane or 1,2-dichloroethane and the like at temperatures between 20 °C and 85 °C to give the desired compoimds of general formula Vlb.
Another suitable method to achieve this protection step is the intermediate formation of a di-BOC compound by treatment of compounds of the general formula VII with di-tert.-butyl-carbonate in the presence of DMAP in an aprotic solvent such as tetrahydrofuran and the like, followed by selective removal of a single BOC-group by treatment with a Bronsted-acid, like e.g. TFA, in aprotic solvents such as dichloromethane, chloroform or 1,2-dichloroethane at temperatures between 0 °C and 20 °C to give the desired compounds of general formula VIb.
According to scheme D, compounds of general formula VII in which R1 is pyrrol- 1-yl optionally substituted as described above, X is a single bond and R is chloride, can be prepared from known 5-chloro-2-nitro-l,4-phenylenediamine [CAS-No. 26196-45-2] by selective condensation of the 4-amino-group with a suitable substituted 2,5-dimethoxytetrahydrofuran with the general formula VIII, as described in/. Heterocycl Chem, 1988,25,1003.

The reaction is preferably carried out in acidic media, like for example acetic acid or propionic add and the like, at temperatures between 40 °C to 100 °C. The exact conditions for the respective compounds can be found in the experimental part

The corresponding substituted 2,5-dimethoxytetrahydrofurans -with the general formula VIII, in which Ra, Rb and Rc are as described above in the general claim for the pyrrol-1-yl compounds, are either commercially available, or synthesized from the suitable substituted furan, as shown in scheme E. The corresponding substituents can optionally be protected with suitable protecting groups, known to someone skilled in the art, or alternatively can be introduced after the pyrrol ring synthesis. The two-step sequence consists of reacting the furan with bromine in MeOH at low temperature, like for example -35 '°C, followed by treatment with base, like for example triethylamine and the like or potassium carbonate or sodium hydrogen carbonate and the like. The resulting 2,5-dimethoxydihydrofuran with the general formula VIII, in which Ra, Rb and Rc are as described above, can be reduced by catalytic hydrogenation, preferably in MeOH with catalysts like for example Palladium on carbon or Raney-Nickel and the like, to produce the desired 2,5-dimethoxytetrahydrofurans with the general formula VIII. An example for this sequence can be found in Tetrahedron 1971,27, 1973-1996.

The exact conditions for the individual compounds to be synthesized can be found in the experimental part.
As shown in scheme F, compounds of general formula VIc, in which R2 is attached via a nitrogen-atom and is as described above, can be prepared from the intermediate compounds with the general formula VIb - which individual synthesis can be found in the experimental part - by a nucleophilic substitution reaction with the respective amines in the presence of a suitable base.

The reaction is preferably carried out in a polar, aprotic solvent such as dimethyl formamide, N-methyl-pyrrolidone or dimethyl sulfoxide and the like. The base can be selected from the sterically hindered amines such as triethylamine or Hiinig's base, alkoxides such as sodium methoxide and tert.-butoxide, or hydrides such as sodium hydride. The reaction can be performed at temperatures between 20 **C and 110 ^C, depending on the individual compounds to be synthesized.

According to scheme G> compounds of general formula II in which R^ is as described above for compounds where X is an ethynediyl group can be prepared by different routes from the iodo-compounds V, depending on the nature of R and R As shown in scheme G, the transformation can for example be carried out
a) by directly attaching the R1-alkynediyl-substituent to a compound of general
formula V via a Sonogashira-type coupling to produce compounds of the general
formula VId followed by the reduction of the nitro group or
b) by two stepwise Sonogashira-type couplings, in which first trimethylsilyi-acetylene
is coupled to a compound of general formula V to yield, after desilylation with sodium
hydroxide in methanol, the intermediate X which then can be transformed via a

second Sonogashira-type coupling with the appropriate reactant R1-I, R1-Br or R1-OSO2CF3 into compounds of the general formula VId and reduction of the nitro group leads to the desired compounds of general formula IL
The exact conditions for the respective compounds can be found in the experimental part.

According to Scheme H, the dioxinones and 6-keto esters building blocks with the general formula TV and IVa can be prepared by methods known to someone skilled in the art from the corresponding carboxylic acid derivatives R -COR, i.e. free acids, methyl or ethyl esters and acid chlorides. The exact conditions for the corresponding compounds can be found in the experimental part.
The pharmaceutically acceptable salts can be manufactured readily according to methods known per se and taking into consideration the nature of the compound to be converted into a salt. Inorganic or organic adds such as, for example, hydrochloric acid, hydrobromic acid, sulphuric acid, nitric acid, phosphoric acid or citric acid, formic acid, fumaric acid, maleic acid, acetic acid, succinic acid, tartaric add, methanesulphonic add, p-toluenesulphonic add and the like are suitable for the formation of pharmaceutically acceptable salts of basic compounds of formula I.

The compounds of formula I and their pharmaceutically acceptable salts are metabotropic glutamate receptor antagonists and can be used for the treatment or prevention of acute and/or chronic neurological disorders, such as psychosis, schizophrenia, Alzheimer's disease, cognitive disorders and memory deficits. Other treatable indications are restricted brain function caused by bypass operations or transplants, poor blood supply to the brain, spinal cord injuries, head injuries, hypoxia caused by pregnancy, cardiac arrest and hypoglycaemia. Further treatable indications are acute and chronic pain, Huntington's chorea, ALS, dementia caused by AIDS, eye injuries, retinopathy, idiopathic parkinsonism or parkinsonism caused by medicaments as well as conditions which lead to glutamate-deficient functions, such as e.g. muscle spasms, convulsions, migraine, urinary incontinence, nicotine addiction, psychoses, opiate addiction, anxiety, vomiting, dyskinesia and depression.
The compounds of formula I and pharmaceutically acceptable salts thereof can be used as medicaments, e.g. in the form of pharmaceutical preparations. The pharmaceutical preparations can be administered orally, e.g. in the form of tablets, coated tablets, dragees, hard and soft gelatine capsules, solutions, emulsions or suspensions. However, the administration can also be effected rectally, e.g. in the form of suppositories, or parenterally, e.g. in the form of injection solutions.
The compounds of formula I and pharmaceutically acceptable salts thereof can be processed with pharmaceutically inert, inorganic or organic carriers for the production of pharmaceutical preparations. Lactose, corn starch or derivatives thereof, talc, stearic acid or its salts and the like can be used, for example, as such carriers for tablets, coated tablets, dragees and hard gelatine capsules. Suitable carriers for soft gelatine capsules are, for example, vegetable oils, waxes, fats, semi-solid and liquid polyols and the like; depending on the nature of the active substance no carriers are, however, usually required in the case of soft gelatine capsules- Suitable carriers for the production of solutions and syrups are, for example, water, polyols, sucrose, invert sugar, glucose and the like. Adjuvants, such as alcohols, polyols, glycerol, vegetable oils and the like, can be used for aqueous injection solutions of water-soluble salts of compounds of formula I, but as a rule are not necessary. Suitable carriers for suppositories are, for example, natural or hardened oils, waxes, fats, semi-liquid or liquid polyols and the like.
In addition, the pharmaceutical preparations can contain preservatives, solubilizers, stabilizers, wetting agents, emulsifiers, sweeteners, colorants, flavorants, salts for varying the osmotic pressure, buffers, masking agents or antioxidants. They can also contain still other therapeutically valuable substances.

As mentioned earlier, medicaments containing a compound of formula I or a pharmaceutically acceptable salt thereof and a therapeutically inert excipient are also an object of the present invention, as is a process for the production of such medicaments which comprises bringing one or more compounds of formda I or pharmaceutically acceptable salts thereof and, if desired, one or more other therapeutically valuable substances into a galenical dosage form together with one or more therapeutically inert carriers.
The dosage can vary within wide limits and will, of course, be fitted to the individual requirements in each particular case. In general, the effective dosage for oral or parenteral administration is between 0.01-20 mg/kg/day, with a dosage of 0.1-10 mg/ kg/day being preferred for all of the indications described. The daily dosage for an adult human being weighing 70 kg accordingly lies between 0.7-1400 mg per day, preferably between 7 and 700 mg per day.
The present invention relates also to the use of compounds of formula I and of pharmaceutically acceptable salts thereof for the production of medicaments, especially for the control or prevention of acute and/or chronic neurological disorders of the aforementioned kind.
The compounds of the present invention are group II mGlu receptor antagonists. The compounds show activities, as measured in the assay described
below, of 10μM or less, typically 1μM or less, and ideally of 0.3μM or less.
In the table below are described some specific Ki values of preferred compounds.

Transfection and cell culture
cDNA encoding the rat mGlu2 receptor protein in pBluescript II was obtained from Prof. S. Nakanishi (Kyoto, Japan), and subcloned into the eukaryotic expression vector pcDNA I-amp from Invitrogen (NV Leek, The Netherlands). This vector construct (pcDlmGR2) was co-transfected with a psvNeo plasmid encoding the gene for neomycin resistance, into CHO cells by a modified calcium phosphate method described by Chen & Okayama (1988), The cells were maintained in Dulbecco's Modified Eagle medium with reduced L-glutamine (2 -mM final concentration) and 10 % dialysed foetal calf serum from Gibco BRL (Basel, Switzerland). Selection was made in the presence of G-418 (1000 ug/ml final). Clones were identified by reverse transcription of 5 μg total RNA, followed by PCR using mGlu2 receptor specific primers 5'-atcactgcttgggtttctggcactg-3' and 5'-agcatcactgtgggtggcataggagc-3' in 60 mM Tris HCl (pH 10), 15 mM (NH4)2SO4,2 mM MgCl2, 25 units/nil Taq Polymerase with 30 cycles annealing at 60 oC for 1 min., extention at 72 °C for 30 s, and 1 min. 95 °C denaturation.

Membrane preparation
Cells, cultured as above, were harvested and washed three times with cold PBS and frozen at -80 °C. The pellet was resuspended in cold 20 mM HEPES-NaOH buffer containing 10 mM EDTA (pH 7.4), and homogenised with a polytron (Kinematica, AG, Littau, Switzerland) for 10 s at 10 000 rpm. After centrifugation for 30 min. at 4 °C, the pellet was washed once with the same buffer, and once with cold 20 mM HEPES-NaOH buffer containing 0.1 mM EDTA, (pH 7.4). Protein content was measured using the Pierce method (Socochim, Lausanne, Switzerland) using bovine serum albumin as standard.
[3H]'LY354740 binding
After thawing, the membranes were resuspended in cold 50mM Tris-HCl buffer containing 2 mM MgClo and 2 mM CaCl2, (pH 7) (binding buffer). The final concentration of the membranes in the assays was 25°Cg protein/ml. Inhibition experiments were performed with membranes incubated with 10 nM [3H]-LY354740 at room temperature, for 1 hour, in presence of various concentrations of the compound to be tested. Following the incubations, membranes were filtered onto Whatmann GF/C glass fiber filters and washed 5 times with cold binding buffer. Non specific binding was measured in the presence of 10°CM DCG IV. After transfer of the filters into plastic vials containing 10 ml of Ultima-gold scintillation fluid (Packard, Zurich, Switzerland), the radioactivity was measured by liquid scintillation in a Tri-Carb 2500 TR counter (Packard, Zurich, Switzerland),
Data analysis.
The inhibition curves were fitted with a four parameter logistic equation giving K1
values, and Hill coefficients.

EXAMPLES
General procedure A
Preparation of 4-iodo-2-nitroanilines by iodination of 2-nitroanilines [according to Wilson, J. Gerald; Hunt, Frederick C Aust /, Chem. 1983,36^ 2317-25]
To a stirred solution of the Z-nitroanilinc (LO mol) in HOAc (500 mL) containing anhydrous NaOAc (93-103 g, 1.125-1.25 mol), iodine monochloride (59-66 mL, 1.125-1.25 mol) in HOAc (300 mL) was added over 60 min. The reaction mixture was heated to the given temperature until thin layer chromatography (tic) indicated complete conversion of the starting material, stirred for another 30 min at 23 oC, then diluted slowly with H2O (1000 mL) which caused the separation of the crystalline product. Stirring was continued for 1 h and the product was filtered off, washed free of HOAc and dried in vacuum at 60 oC.
Example A1
5-Chloro-4-iodo-2-nitro-phenylamine
The title compound was prepared from 5-chloro-2-nitroaniline by iodination with iodine monochloride in HOAc/NaOAc according to the general procedure A (80oC). Obtained as an orange solid.
MS (EI) 298 (M^) and 300 [(M-f2)^]; mp 202-203 **C (dec).
General procedure B:
Preparation of ('2-nitro-phenvl)-carbamic acid tert.-butyl esters from 2-nitroanilines
Method a (from 2-nitroanilines): To a solution of diphosgene (4.1 mL, 34,1 mmol) in EtOAc (40 mL) at 0 °C was added a solution of the 2-nitroaniline (45.5 mmol) in EtOAc (200-500 mL), and the mixture was heated to reflux for 18 h. The solvent was removed in vacuum to leave a brown solid, which was triturated with hot hexane (200 mL). The solid material was filtered off and the filtrate was concentrated xmder reduced pressure to leave the pure 2-nitrophenylisocyanate as a yellow soild This material was refluxed in a mixture of excess terL-BuOH in CH2CI2 for 2.5 h. Removal of the solvent left an orange solid which was pmified by silica gel colunm chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbainic acid tert-butyl ester as a yellow solid

Method b (from 2-nitroanilines): To a mixture of the 2-nitroaniline (142 mmol) and cesium carbonate (55.5 g, 170 mmol) in 2-butanone (740 mL) was dropwise added a solution of BOC2O (37.8 g, 173 mmol) in 2-butanone (170 mL) and the resulting mixture was stirred at 50 ^C to 80 **C until tic indicated complete conversion. The solvent was removed in vacuxun, the residue was treated with a mixture of H2O (240 mL) and MeOH (240 mL) and extracted with hexane (3 x 500 mL). The combined hexane layer was washed with brine (200 mL) and all aqueous layers were reextracted with hexane (300 mL). All combined hexane layers were dried over MgSO4, filtered and the solvent was removed in vacuum to give an orange solid, which was purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid.
Method c (fi-om 2'nitroanilines): To a solution of the 2-nitroaniline (550 mmol) and DMAP (1.22 g, 10 mmol) in THF (1000 mL) at 23 °C was dropwise added within 70 min a solution of Boc2O (246 g, 1128 mmol) in THF (500 mL) and stirring was continued at 23 °C for 75 min. The entire mixture was evaporated to dryness and dried at HV to leave a dark brown solid. This material was dissolved in DCM (1100 mL), cooled to 0 --C and TFA (84 mL, 1100 mmol) was added dropwise. The mixture was stirred at 0 °C for 2 h2 poured into icecold sat. NaHCO3-sol, extracted with DCM, washed with brine and dried over MgSO4. Removal of the solvent in vacuum left a dark brown solid which was coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert.-butyl ester as a yellow solid.
Method d (firom 2'nitroacetanilides): To a solution of the 2-nitroacetanilide (100 mmol) and DMAP (122 mg, 1mmaol) in THF (100 mL) at 23 X was dropwise added within 15 min a solution of B0C2O (22.92 g, 105 mmol) in THF (100 mL) and stirring was continued at 23 oC until tic indicated completed conversion. The entire mixture was evaporated to dryness and dried at HV to leave a yellow to dark brown solid. This material was dissolved in THF (200 mL) and 25 % NH4OH (77 mL, 500 mmol) was added dropwise. The mixture was stirred at 23 oC until tic indicated complete conversion, poured into IN HCl-sol, extracted with EtOAc, washed the organic layer with sat. NaHC03-soL and brine, dried over MgSO4. Removal of the solvent in vacuum left an yellow to brown solid which was generally pure enough for fiirther transformation or - if necessary - coated on silica gel and purified by silica gel column chromatography with hexane/EtOAc to give the (2-nitro-phenyl)-carbamic acid tert-butyl ester as a yellow solid.

Example Bl
f 5-Chloro-4-iodo-2-nitrO'phenvlVcarbamic acid tert.-butyl ester
The title compound was prepared via the isocyanate from 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (7.0 g> 23.45 mmol) with diphosgene (2.12 mL, 17.6 mmol) in EtOAc (30 mL), followed by treatment with tert.-BuOH (100 mL) in CH3CI2 (100 mL) according to the general procedure B (method a). Obtained as a yellow solid (7.1 g, 76%).
MS (EI) 398 (M^) and 400 [(M-f2)^]; mp 82-84 °C
Example B2
f4,5-Dichloro-2-nitro-phenvlVcarbamic acid tert.-butyl ester
The title compound was prepared via the di-Boc-compound from commercially available 4,5-dichlorO-2-nitroaniline (15 g, 72.5 mmol) and BOC2O (32.4 g, 148.5 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained as abrown solid (21.63 g, 97 %).
MS (ISN) 305 [(M-H)-]; mp 68-73 °C.
Example B3
(5-Fluoro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared via the di-Boc-compound from 5-fluoro-2-nitro-4-trifluoromethyl-phenylamine; prepared from commercially available 4-amino-2-fluorobenzotrifluoride by acetylation with Ac2O in toluene at 23 °C, nitration with 100 % nitric acid from 10-23 °C and deacetylation with 2N NaOH in THE at 50 °C] (5.21 g, 23.2 mmol) and Boc2O (10.63 g, 48.7 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a light yellow solid(6.33 g, 84 %).
MS (ISN) 323 [(M-H)-]; mp 104 °C
Example B4
[4-Iodo-2-nitrO'5-f2,2.2-trifluoro-ethoxy)-phenvll-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenyiamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al) (8.95 g, 30 mmol), 2,2,2-trifluoroethanol (30 mL) and KOH (4.36 g, 66 mmol) in DMSO (60 mL) at 23 °C for 35 days.] (10.41 g, 29 mmol) and BOC2O (12,87 g, 59 mmol), followed by treatment with 2 eq. TFA in CR2CL2

according to the general procedure B (method c). Obtained as a yellow solid (13.34 g, 100 %),
MS(ISN)461[(M-H)-].
Example B5
(5-Chloro-2-nitro-4-trifIuoromethvl-phenvl)-carbamic acid tert,-butyl ester
The title compound was prepared via the di-Boc-compound from commercially available 5-chloro-2-nitro-4-trifluoromethyl-phenylamine [CAS-No. 35375-74-7] (22.61 g, 94 mmol) and BOC2O (42.06 g, 193 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (31,82 g, 99%).
MS (ISN) 339.1 [(M-H)-]and 341 [(M+2-H)-];mp 113-115 °C.
Example B6
(5-Chloro-4-fluoro-2-nitro-phenvl')-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from commercially available 3'-chloro-4'-fluoro-6'-nitroacetanmde [CAS-No. 81962-58-5] (59 g, 254 mmol), and BOC2O (58.13 g, 266 mmol), followed by treatment with NH4OH (25%, 77.5 mL, 507 mmol) according to the general procedure B (method d). Obtained as a yellow solid(73,53 g, 100 %).
MS (ISN) 289 [(M-H)-] and 291 [(M+2-H)-]; mp 73-74 °C
Example B7
[2-Nitro-5-(2,2,2-trifluoro-ethoxv)-4-trifluoromethyl-phenvn-carbamic acid tert.-butylester
The title compound was prepared via the di-Boc-compound from 4-iodo-2-nitro-5-(2,2,2-trifluoro-ethoxy)-phenylamine [prepared by stirring 5-chloro-4-iodo-2-nitro-phenylamine (Example Al), 2,2,2-trifluoroethanol and KOH in DMSO at 23 °C for 32.5 days.] and BOC2O, followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained as a yellow solid (18.955 g).
MS (ISN) 403 [(M-H)-].

Example B8
(5-Chloro-4-methyl-2-nitro-phenyl)-carbamic add tert-butyl ester
The title compound was prepared via the di-Boc compound from commercially available 5-chloro-4-methyl-2-nitroaniline (10.0 g, 53.6 mmol) and BOC2O (23.9 g, 109 mmol), followed by treatment with 2 eq, TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (toluene/ethylacetate 19:1) as a yellow solid (14.6 g, 95%).
MS (ISN) 285.1 [(M-H)'l.
Example B9
(4-Cyano-5-fluoro-2-nitro-'phenyl)-Carbamic acid tert-butyl ester
The tide compound was prepared via the di-Boc compound from 4-cyano-5-fluoro-2-nitroaniline (24.9 g, 137 mmol) [Ohmori et al. J, Med. Chem. 1994,37,467 - 475] and BOC2O (61,5 g, 282 mmol), followed by treatment with 2 eq. TFA in CH2Cl2 according to the general procedure B (method c). Obtained by column chromatography (hexane/ethylacetate 4:1) as a light yellow solid (14.5 g, 39%).
MS (ISN) 280.1 [(M-H)'].
General procedure C:
Preparation of 5-N-substituted-(2-nitro-phenyl)-carbamic acid tert.-butylesters:
(5-Chloro or -fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester was stirred with the desired amine optionally with DMSO, DMF, DMA, NMP or THF and/or DIPEA or Et3N at temperatures from 23 °C to 130 °C until tic indicated complete disappearance of the chloride or fluoride. The reaction was cooled to 23 °C poured into ice-water, the precipitate was filtered off, washed with water and dried in vacuum. In cases were the product did not precipitate, the mixture was extracted with EtOAc, washed with water and brine, dried over Na2SO4. Filtration and removal of the solvent in vacuum left a crude product, which was - if necessary - purified by silica gel column chromatography with hexane/EtOAc to give the pure title compound.
Example CI
(4-Chloro-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butylester
The tide compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and dimethylamine (5.6 N in EtOH,

8.7 mL, 48.8 mmol) in DMSO (35 mL) at 23 o'C according to the general procedure C. Obtained as a yellow solid (2.81 g).
MS (ISP) 316 [(M+H)--] and 318 [(M-h2+H)']; mp 136-138 °C
Example C2
(5-DimethylaminO-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic acid tert,-butyl ester (Example Bl) (399 mg, 1 mmol) and dimethylamine (5.6 N in EtOH, 0.36 mL, 2 mmol) in THE (3 mL) at 65 °C for 18 h in a sealed tube according to the general procedure C. Obtained as a yellow solid (386 mg).
MS (EI) 407 (M+); mp 120-122 °C.
Example C3
(4-Chloro-5- rr2-methoxv-ethyl)-methyl-amino1-2-nitro-phenyl}-carbamic add tert,-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol), N-(2-methoxyethyl)methylamine (2.43 mL, 23 mmol) and Et3N (4.2 mL, 30 mmol) in DMSO (20 mL) at 23 °C according to the general procedure C. Obtained as a brown oil (3,57 g),
MS (ISP) 360 [(M+H)+_] and 362 [(M+2-i-H)^].
Example C4
(5-Dimethylamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (5-fluoro-2-mtro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B3) (1.62 g, 5.0 mmol) and dimethylamine (5.6 N in EtOH, 4.47 mL, 25.0 mmol) in DMSO (10 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(1,48 g).
MS (ISN) 348 [(M-H)-]; mp 110 X.
Example C5
r
|4-Chloro-5-(ethvI-methyI-aminoV2-nitro-phenvi]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-ethyl-methylamine (2.89 g, 48.8 mmol) in DMSO (35 mL) at RT according to the general procedure C. Obtained as a pale brown solid(3.21 g).

MS(ISP)330.3 [(M+H)1;mp94oC.
Example C6
f4-Chloro-5-(methyl-propyl-aminoV2-nitro-phenyl-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichlorO-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and N-methyl-propyl-amine (2,50 g, 34.2 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a pale brown solid (3.58 g),
MS (ISP) 344.3 [(M+H)+]; mp 68 °C,
Example C7
f4--Chloro-5'(dietfavl-amino)-2-nitro-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.0 g, 9.77 mmol) and diethyl-amine (3.57 g, 48.8 mmol) in DMSO (35 mL) at 60°C according to the general procedure C. Obtained as a yellow solid (2.63 g).
MS (ISP) 344.3 [(M+H)--]; mp 95 °C.
Example C8
(4-Chloro-2-nitro-5-pyrrolidin-l'yl'phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and pyrrolidine inDMSO at 23 -*€ according to the general procedure C. Obtained as a yellow solid (6.65 g).
MS (ISP) 342 [(M+H)--] and 344 [(M+2+H)']; mp 157-158 °C.
Example C9
[4-Chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (3.07 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and EtsN (6.97 mL, 50 nunol) in DMSO (30 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.25 g).
MS (ISP) 342.2 [(M+H)+ and 344 [(M+2+H)-']; mp 104-106 °C.

Example CIO
(2-Nitro-5-pyrrolidin-l-yl-4-trifluoromethyl'-phenyl)_-carbamic acid tert-butyl ester
The tide compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5) (6,81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) inDMSO (70 mL) at 23 --C according to the general procedure C. Obtained as a yellow solid (7.35 g).
MS (ISN) 374 [(M-H)-]; mp 138-141 °C
. Example CI 1
f 5-DimethylaminO-4'fluoro-2-nitro-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (5-chloTO-4-fluoro-2'nitro-phenyl)~carbamic acid tert-butyl ester (Example B6) (4.94 g, 17 mmol) and MeaNH (40% in H2O, 7.9M, 10.9 mL, 86 mmol) inDMSO (35 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.93 g),
MS (ISP) 303 [(M+H)+]; mp 144-148 X.
Example C12
('4-Chloro-2-nitro-5-piperidin-l-yl-phenylVcarbamic acid tert,-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) and piperidine inDMSO at 23 oC according to the general procedure C. Obtained as a yellow solid (1.173 g).
MS (ISP) 356 [(M+H)+] and 358 [(M+2+H)*']; mp 132-133 °C.
Example CI 3
(4-Fluoro-2-nitro-5-pvrrolidin-l-yl-phenylVcarbamic acid tert.-butylester
The title compound was prepared from (5-chloro-4-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B6) (5.81 g, 20 mmol) and pyrrolidine (8.27 mL, 100 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (6.42 g).
MS (ISP) 326 [(M+H)--]; mp 188-193 °C.
Example C14
(5-A2etidin'l-yi-4-chloro-2-nitro-phenyl')-carbamic acid tert.-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyi ester (Example B2) (6.14 g, 20 mmol), azetidine (2.33 mL, 34 mmol) and

Et3N (8.4 mL, 60 mmol) in DMSO (40 mL) at 23 °C according to the general procedure C. Obtained as an orange solid (5.85 g).
MS (H) 327 (M+) and 329 [(M+2)+].
Example CI 5
(5-Azetidin-l-yl-2-nitro-4-trifluoromethyl-phenylVcarbaniic acid tert.-butyl ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example B5), azetidine and Et3N in DMSO at 23 °C according to the general procedure C. Obtained as a yellow solic (6.925 g).
MS (ISN) 360 [(M-H)-].
Example C16
(5-(CvclopropylmethyI-methyl-amino)-2-nitro-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example B5) (5.11 g 15 mmol), cyclopropylmethyl-methyl-amine hydrochloride (5.47 g, 45 mmol) and Et3N (10.5 mL, 75 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid(5.73 g).
MS (ISN) 388 l(M-H)']; mp 5 1°C .
Example C17
(5-(CycIopropvI-methyI-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamicacid tert.-but\4 ester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl) carbamic acid tert-butyl ester (Example B5) (3.40 g, 10 mmol) and cyclopropyl-methyl-amine hydrochloride (3.22g, 30 mmol) and Et3N (6.97 mL, 50 mmol) in DMSO (50 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (3.74 g).
MS (ISP) 374.2 [(M+H)1,

Example C18
(2-Dimethylamino-2'-fluoro-5'nitro-biphenyl-4-yl)-carbamic acid tert.-butylester
The title compound was prepared from (2-chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example D3) (9,568 g, ca. 26 mmol) and Me2NH (60% in H20,12 mL) inDMSO (87 mL) at 23 °C according to the general procedure C. Obtained as a yellow solid (4.54 g).
MS (ISP) 376.3 [(M+Hrj.
Example C19
(5-Dimethylamino-4-methyl-2-nitro-phenylVcarbamic acid tert-butyl ester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and dimethylamine (11 ml, 33% in EtOH, 61.0 mmol) in DMSO (35 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid (3.50 g, 97%).
MS (ISP) 296.3 [(M+H)*-].
Example C20
f4-Cvano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7.11 mmol) and dimethylamine (6.3 ml, 33% in EtOH, 35.0 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.87 g, 86%).
MS (ISP) 307.3 [(M+H)'],
Example C21
[4-methyl-5-(methyl-propyl-aminol-2'mtro-phenyn-Carbamic acid tert-butylester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-methylpropylamine (6.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (3.89 g, 98%).
MS (ISP) 324.4 [(M+H)--].

Example C22
(5-fEthyl-metfayl-amino)-4-methyl-2-nitro-phenyl-carbamic add tert-butyl ester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.5 g, 12.2 mmol) and N-ethylmethylamine (5.5 ml, 61.0 mmol) in DMSO (35 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.58 g, 95%).
MS (ISP) 310.3 [(M+H)--].
Example C23
f4-Chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isopropyl-methyiamine (5.95 g, 81.4 mmol) in DMSO (50 mL) at 75 °C according to the general procedure C. Obtained as a yellow solid (4.07 g, 73%).
MS (ISP) 344.3 [(M+H)+].
Example C24
[4-Chloro-5-(isobutyl-methyl-amino)-2-nitro--phenyl]-carbamic acid tert-butylester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example B2) (5.0 g, 16.3 mmol) and N-isobutyl-methylamine (7.09 g, 81,4 mmol) in DMSO (50 mL) at RT according to the general procedure C. Obtained as a brown oil (5.79 g, 99%).
MS (ISP) 358.2 [(M+H)--].
Example C25
f4-Cvano-2-nitro-5-pyrrolidin-l'yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (2.0 g, 7,11 mmol) and pyrrolidine (2.94 ml, 35.6 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.97 g, 83%).
MS (ISP) 331.2 [(M-H)-].

Example C26
f4-Cvano-5-fmethyl-propyl-amino)-2-nitro-phenyl-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-methyl-propylamine (3.72 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.75 g, 75%).
MS (ISP) 333.3 [(M-H)'].
(4-Cyano-5-diethylamino-2-nitro-phcn>i>-carbamic add tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbainic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and NJSI-diethyiamine (3.60 ml, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.78 g, 77%).
MS (ISP) 333.2 [(M-H)-].
Example C28
[4-Cvano-5-(isopropyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butyl ester
The title compound was prepcured from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isopropyl-N-methylamine (3.60 ml, 34.7 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.84 g, 79%).
MS (ISP) 333.3 [(M-H)'].
Example C29
f4-Cvano-5-(isobutyl-methyl-amino)-2-nitro-phenyll-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-fluoro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B9) (1.95 g, 6.93 mmol) and N-isobutyl-N-methylamine (3.02 g, 34.7 mmol) in DMSO (20 mL) at RT according to the general procedure C Obtained as a yellow solid (1.87 g, 77%).
MS (ISP) 347,4 [(M-H)-].

Example C30
f4-Cyano-2-nitro-5-piperidin-l--'yi-phenyl)-carbamic acid tert-butylester
The title compoimd was prepared from (4-cyano-5-£luoro-2-nitro-phenyi)-carbamic acid tert-butyl ester (Example B9) (2.0 g> 7.11 mmol) and piperidine (3.51 ml, 35.6 mmol) in DMSO (20 mL) at RT according to the general procedure C. Obtained as a yellow solid (1.94 g, 79%).
MS (ISP) 345.3 [(M-H)-].
Example C31
(4-Chloro-5-isobutylamino-2-nitro-phenyl--carbamic acid tert-butyl ester
The title compound was prepared from (4>5-dichloro-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B2) (3.0 g, 9.77 mmol) and isobutylamine (3.57 g, 48.8 mmol) in DMSO (20 mL) at 55°C according to the general procedure C. Obtained as a brown solid (2.26 g, 67%).
MS (ISP) 344.2 [(M+H)--].
Example C32
[5-fMethyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl-carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-methyl-propyl-amine (1.89 ml, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.04 g, 91%).
MS (ISP) 378.3 [(M+H)*-].
Example C33
f 5-(Isobutyl-methyl-amino V2-nitro-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol),N-isobutyl-methyl-amine (L54 g, 17.6 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at RT according to the general procedure C. Obtained as a yellow solid (4.18 g, 91%).
MS (ISP) 390.3 [(M-H)-].

Example C34
f 5-f Isopropyl-methyl-aminoV2-nitro-4-trifluoromethyl-phenyn -carbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (4.00 g, 11.7 mmol), N-isopropyl-methyl-amine (3.67 ml, 35.2 mmol) and triethylamine (5.73 ml, 41.1 mmol) in DMSO (30 mL) at 50 °C according to the general procedure C. Obtained as a yellow solid(3.27 g, 74%).
MS (ISP) 376.3 [(M-H)'].
Example C35
(5-(IsobutvI-methyl-aminoV4-methyl-2-nitro-phenyl-carbamic acid tert-butylester
The title compound was prepared from (5-chloro-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and N-isobutyl-methylamine (4.56 g, 52.3 nunol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow oil (1.84 g, 52%).
MS (ISP) 336.3 [(M-H)'].
Example C36
(4-MethyI-2-nitro-5-pvTrolidin-l-yl-phenyl Vcarbamic acid tert-butylester
The title compound was prepared from (5-chlorO-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example B8) (3.01 g, 10.5 mmol) and pyrrolidine (4.33 ml, 52.3 mmol) in DMSO (30 mL) at 55 °C according to the general procedure C. Obtained as a yellow solid (3.27 g, 97%).
MS (ISP) 320.3 [(M-H)-]; mp 145 °C
Example C37
(4-Chloro-5-isopropylamino-2-nitro-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (4,5-dichloro-2-nitro-phenyl)-carbamic add tert.-butyl ester (Example B2) (5,0 g, 16,3 mmol) and isopropylamine (7,0 ml, 81.4 mmol) in DMSO (35 mL) at 55 o'C according to the general procedure C. Obtained as a brown solid (3.95 g, 73%).
MS (ISP) 330.2 [(M+H)--]. '

Example C38
(5-Isobmylamino-2-mtro-4-trifluoromethyl-phenylVcarbamic acid tert-butylester
The title compound was prepared from (5-chloro-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example B5) (5.00 g, 14.7 mmol), isobutyl-amine (7.36 mL, 73.4 mmol) in DMSO (35 mL) at RT according to the general procedure C Obtained as a yellow solid (5.39 g, 97%).
MS (ISP) 376.3 [(M-H)-],
General procedure D:
Preparation of (4-arvI-2-nitro-phenyl)-carbamic acid tert.-butyl esters by direct Suzuki-coupling of ('4-iodo-2-nitro-phenyl)*carbamic acid tert.-butylesters with arylboronic acids
A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (3.0 mmol), the arylboronic acid (4.5 mmol) and PdCl2(PPh3)2 (2 mol%) was refluxed in 1,4-dioxane (25 mL) and 2M NaaCO2-sol. (7.5 mL) [or alternatively with IM NaHCOa-sol. (7.5 mL), LiCl (6.0 mmol) and (Ph3P)4Pd (3 mol%) in DME (30 mL); also possible with EtaN (9,0 mmol), Pd(0Ac)2 (3 mol%), PPhs (6 mol%) in DMF (10 mL) at 100 °C] until tic indicated complete conversion of the iodide. The mixture was transferred into a separating funnel, H2O (25 mL) was added and the product was extracted with ether or EtOAc (3 x 30 mL). The combined organic layers were washed with brine (50 mL) and dried over Na2S04. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound
Example Dl
(2-Dimethylamino-2\3'-difluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester
The tide compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C2) and 2,3-difluorophenylboronic acid according to the general procedure D. Obtained as a yellow solid (3,096 g).
MS(ISN)392[(M-H)-].

Example D2
f2'-Fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yll-carbamic acid tert,-butylester
The title compound was prepared from [4-iodO-2-nitro-5-(2,2,2-trifluoro-ethox7)-phenyl]-carbamic add tert-butyl ester (Example B4) and 2-fluorophenylboronic add according to the general procedure D. Obtained as a yeDow solid (1.39 g).
MS (ISP) 491 [(M+H)--]; mp 73-75 °C.
Example D3
(2-Chloro-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic add tert.-butylester
The title compound was prepared from (5-chloro-4-iodo-2-nitro-phenyl)-carbamic add tert-butyl ester (Example Bl) (30 g, 75.3 mmol) and 2-fIuorophenylboronic acid (13.82 g, 98.8 nrniol) according to the general procedure D. Obtained as a yellow gum (1.39 g).
MS (ISN) 365.0 [(M-H)-].
General procedure E:
Preparation of (4-aryl-2-nitro-phenyl)-carbamic acid tert.-butyl esters by Suzuki-coupling of (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butylesters with bisfpinacolato)diboron and subsequent reaction with aryl halides
A mixture of the (4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (2,0 mmol), bis(pmacolato)diboron (2,2 mmol), KOAc (6.0 mmol) and PdCl2(PPh3)2 (3 mol%) in 1,4-dioxane (25 mL) was stirred at 100 °C until tic indicated complete conversion of the iodide [cf. Tetr. Lett. 1997,38,3841-3844]. After addition of the aryl halide (4.0 mmol), PdCl2(PPh3)2 (3 mol%) and 2M Na2CO3-soL (7.5 mL) the mixture was stirred at 100 oC until tic indicated complete conversion of the intermediate boronic ester. The mixture was transferred into a separating furnnel, H2O (30 mL) was added and the product was extracted with ether or EtOAc (3 x 50 mL). The combined organic layers were washed with brine (100 mL) and dried over Na2SO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/ether or cyclohexane/EtOAc to give the title compound.

General procedure F:
Preparation of 5-chIoro-2'-nitro-4-pyrroI-l-yl-phenylamines by condensation of 5-chlorO-2-nitro-l,4-phenylenediamine with 2,5-dimethoxvtetrahydrofurans [cf. /. Heterocycl Chem 1988,25y 1003-1005]:
A mixture of the 5-chloro-2-nitro-l,4-phenylenediamine (4.69 g, 25 mmol), the 2,5-dimethoxytetrahydrofuran (26 - 32,5 mmol) in HOAc (150 mL) was stirred at 60-120 °C until tic indicated complete conversion of the phenylenediamine. After cooling to 23 °C, the mixture was poured into brine (500 mL) and extracted with EtOAc (3 x 200 mL). The combined organic layers were washed with brine (300 xriL) and dried over MgSO4. Removal of the solvent left a brown residue, which was purified by silica gel column chromatography with cyclohexane/EtOAc to give the title compound.
General procedure G:
Preparation of 23-dimethoxvdihvdrofurans by bromination of furans in MeOH [cf. Tetrahedron 1971,27,1973-1996]:
To a solution of the furan (177.5 mmol) in a mixture of anhydrous ether (54 mL) and abs. MeOH (79 mL) kept at -35 °C bromine (10.0 mL, 195 mmol) in MeOH (105 mL) was added gradually with stirring. The reaction mixture was stirred for 30 min, saturated with gaseous NH3 to pH 8, and allowed to warm up to 23 °C. Poured into ice-water, extracted with ether (3 x 400 mL), washed with brine, dried over Na2So4. Evaporation of the solvent left a yellow liquid, which was purified by vacuum distillation to give the title compound.
General procedure H:
Preparation of (4-alkynyl-2-nitro-phenyll-carbamic acid tert,-butylesters by Sonogashira-coupling of f4-iodo-2-nitro-phenyI)-carbamic acid tert.-butylesters with acetylenic compounds;
also Sonogashira-coupling of (4-ethynyl-2-nitro-phenyl)-carbamic acid tert-butyl esters with aryl halides:
A mixture of the halide (3.0-4.5 mmol), acetylenic compound (3.0-4.5 mmol), Et3N (13.5 mmol), PdCl2(PPh3)2 (5 mol%) and PPh3 (2.5 mol%) in THF (12 mL) [with very insoluble material DMF (up to 12 mL) could be added] was stirred for 20 min at 23 °C while being purged with Argon. Cul (1.2 mol %) was added and stirring was continued at 60 °C under Argon atmosphere until tic indicated complete conversion of the minor component [cf. /. Org. Chenu 1998,63,8551]. The mixture was

transferred into a separating funnel, 5% citric add (50 mL) was added and the product was extracted with EtOAc (2 x 100 mL). The combined organic layers were washed with sat. NaHCOs-sol. (50 mL) and brine (50 mL), followed by drying over MgSO4. Removal of the solvent left a yellow residue, which was purified by silica gel colunm chromatography with hexane/EtOAc and/or triturated with hexane or aqueous EtOH to give the title compound.
Example Hi
(5-Hydroxymethyl-2-nitro-4-phenylethvnyl-phenyl)'Carbamic acid tert.-butylester
The title compound was prepared from (5-dimethylamino-4-iodo-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C2) (386 mg, 0.97mmol) and phenylacetylene (149 mg, 1.46 mmol) according to the general procedure H. Obtained as an orange solid (370 mg).
MS (EI) 381 (M+); mp 141-149 °C.
General procedure T:
Preparation of the (2-amino-phenyl)-carbamic acid tert.-butylesters bv reduction of (2-nitro-phenyl)-carbamic acid tert.-butylesters:
Method a: Catalytic hydrogenation
A mixture of the nitro compound (1.0 mmol) in MeOH or EtOH and THF (1:1 ca. 20 mL) [or solely EtOAc for aromatic chlorides] and 10% Palladium on carbon (20 mg), Raney-Ni (20 mg) or 5% Platinum on carbon was stirred vigorously at 23 *°C under hydrogen atmosphere until tic indicated complete conversion. The catalyst was filtered off, washed thoroughly with MeOH or EtOH and THF (1:1) [or EtOAc], the solvent was removed in vacuum to give the title compound, which was generally pure enough for further transformations, but could be crystallized firom hot hexane if necessary. Method b: Reduction with SnCl2'2H2O
A mixture of the nitro compound (1.0 mmol) and SnCl2'2H2O (5.0 mmol) was either stirred in EtOH (30 mL) at 70-80 °C or alternatively in pyridine (3 mL) and DMF (12 mL) at 23 °C under Argon atmosphere until tic indicated complete conversion [cf. Tetr. Lett. 1984,25, 839]. The reaction mixture was brought to pH 8 by addition of sat NaHC03-sol. and extracted with EtOAc (2 X 100 mL). The combined organic layer were washed with brine and dried over Na2SO4. Removal of the solvent left a yellow solid, which - if necessary - can be purified by silica gel column chromatography.

Method c: Reduction with Zn and NH°Cl
To a mixture of the nitro compound (1.0 mmol) in EtOH/THF/sat NH4CI-S0I. (1:1:1> 30 mL) was added Zinc dust (3.0 mmol) and the mixture was stirred at 70 °C imder Argon atmosphere until tic indicated complete conversion. Aqueous workup as described in method b.
Example Tl
(2-Amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-chlorO-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example CI) (2,76 g, 8.74 nunol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid(2.3 g).
MS (ISP) 286 [(M+H)--] and 288 [(M+2+H)+]; mp 96-101 °C.
Example T2
f2-Amino-5-dimethylamino-4-phenylethynyl-phenvD-carbamic acid tert.-butyl esr T
The title compound was prepared from (5-dimethylaminO-2-nitro-4-phenylethynyl-phenyl)-carbamic acid tert.-butyl ester (Example Hi) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a brown solid (1.927 g).
MS(ISP)352[(M+H)+].
Example T3
(5-Amino-2-dimethylamino--2,3'-difluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-dimethylamino-2',3'-di£luoro-5-nitro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example Dl) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (2,206 g),
MS(ISP)364[(M+H)-'],
Example T4
{2-AminQ-4-chloro-5- f f 2-methoxv-ethyl-methyl-amino1 -phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from {4-chloro-5-[(2-methoxy-ethyl)-methyi-amino]-2-nitro-phenyl}-carbamic acid te t-butyl ester (Example C3) (3.46 g, 9,62

mmol) by reduction with SnCl22H2O according to the general procedure J.(method b). Obtained as a yellow solid (2.25 g).
MS (ISP) 330 [(M+H)1 and 332 [(M+2+H)']; mp 112 X.
Example T5
[5-Amino-2*-fluoro-2-(2.2.2-trifluoro-ethoxyVbiphenyl-4-yl1 -carbamic acid tert.-butyl ester
The title compound was prepared from [2'-fluoro-5-nitro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert,-butyl ester (Example D2) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (U7g).
MS(ISP)401[(M+H)1.
Example T6
(2-Amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert^-butylester
The title compound was prepared from (5-dimethyiamino-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C4) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as an amorphous yellow substance (1.34 g),
MS (ISP) 320 [(M+H)1.
Example T7
[2-Amino-4-chloro-5-(ethyl-methvI-aminoVphenyl]-carbamic acid tert-butylester
The title compoimd was prepared from [4-chloro-5-(ethyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C5) (3.0 g, 9.09 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.64 g).
MS (ISP) 300.3 [(M+H)']; mp 81 X.
Example T8
f2-Amino-4-chloro-5-(methyl-propyl-aminQVphenyl-carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C6) (3.15 g, 9.16 mmol) by reduction with SnClf 2H2O accordmg to the general procedure J (method b). Obtained as a pale brown solid (2.58 g).

MS (ISP) 314.3 [(M+H)-']; mp 92 X.
Example T9
f2'Amino-4'-chIoro-5-fdiethyl-amino)-phenyn'Carbamic add tert-butyl ester
The title compound was prepared from [4-chloro-5-(diethyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example G7) (2.25 g, 6.54 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange solid (1.55 g).
MS (ISP) 314.3 [(M+H)+]; mp 110 °C.
Example TIP
(2-Amino-4-chloro-5-pyrrolidin-l-yl-phenylVcarbamic acid tert.-butyl ester
The tide compound was prepared from (4-chloro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (&cample C8) by reduction with SnCl2*2H2O according to the general procedure J (method b). Obtained as a red solid (4.80 g).
MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)']; mp 136-138 °C
Example Til
f 2-Amino-4-chloro-5-(cyclopropyl-methvI-amino')-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(cyclopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert.-butyl ester (Example C9) (3.2 g, 9.36 mmol) by reduction with SnCl2*2H2O according to the general procedure J (method b). Obtained as brown solid (2.00 g),
MS (ISP) 312 [(M+H)+] and 314 [(M+2+H)'].
Example T12
(2-Amino-5-pvrrolidin-l-yl-4-trifluoromethyl-phenylVcarbamic acid tert.-butylester
The title compound was prepared from (2-nitro-5-pyrroHdin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example CIO) (7.35 g, 19.75 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light orange solid (6.75 g).
MS (ISP) 346 [(M+H)--]; mp 101-103 °C

Example T13
(2-Amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester
The title compoiond was prepared from (5-dimethylamino-4-fluoro-2-nitro-phenyI)-carbamic acid tert.-butyl ester (Example C11) (4.88 g, 16 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a green solid(4.55 g).
MS (ISP) 270 [(M+H)+]; mp 120-123 °C.
Example T14
(2-Amino-4-chlorO-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-chloro-2-nitro-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C12) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as light brown solid (747 mg).
MS (ISP) 326 [(M+H)+] and 328 [(M+2+H)1;mp 149-151 °C
Example Tl 5
(2-Amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (4-fluoro-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example C13) (6,37 g, 20 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a grey solid (5.92 g).
MS (ISP) 296 [(M+H)--]; mp 75-76 °C
Example 116
(2-Amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (5-azetidin-l-yl-4-chloro-2-nitro-phenyl)-carbamic acid tert.-butyl ester (Example C14) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid (3.664 g).
MS (ISP) 298 [(M+H)--] and 300 [(M+2+H)-']; mp 176-179 -C

Example T17
(2-Amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic add tert.-butylester
The title compound was prepared from (5-a2etidin-l-yl-2-nitro-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example C15) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a white solid
(5.173 g).
MS (ISP) 332 [(M+H)+]; mp 166-167 °C
Example Tl 8
f2-Amino-5-(cyclopropylmethyl-methyl-aminoV4-trifluoromethyl-phen\d1-carbamic acid tert.'butyl ester
The title compoimd was prepared from [5-(cyclopropylmethyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C16) (5.66 g, 14.5 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as yellow solid (4.7 g).
MS (ISP) 360 [(M+H)+]; mp 56 X.
Example T19
[2-Amino-5--rcvclopropvI-methyl-amino)-4-trifluoromethyl-phenyn-carbamicacid tert,-butyl ester
The title compound was prepared from [5-(cyclopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example C17) (3.74 g, 9.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an orange semisolid (2.00 g).
MS (ISP) 346.4 [(M+H)--].
Example 120
(5-Amino-2-dimethylamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butylester
The title compound was prepared from (2-dimethylamino-2'-fluoro-5-nitro-biphenyl-4-yl)-carbamic acid tert-butyl ester (Example CIS) (4.54 g, 12.1 mmol) by hydrogenation with 10 % Pd/C according to the general procedure J (method a). Obtained as a light brown solid (3.324 g).
MS (ISP) 346.4 [(M+H)+].

Example T21
[2-Amino-5-f2.2.2-trifluoro-ethoxyV4-trifluoromethyl-phenvIl-carbamic acid tert-butyl ester
The title compound was prepared from l2-nitro-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tcrt-butyl ester (Example B7) by hydrogenation with 5 % Pt/C according to the general procedure J (method a). Obtained as a yellow solid (17.374 g).
MS(ISP)375[(M+Hr].
Example 22
(2-Amino-5-dimethylamino-4-methyl-phenyl)-Carbamic acid tert-butylester
The title compound was prepared from (5-dimeth>1amino-4-methyl-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C19) (3.22 g, 10.9 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a gray solid (2.05 g, 58%).
MS (ISP) 266.3 I(M+H)+]; mp 78 X.
Example 123
(2-Amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-dimethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C20) (3.9 g, 12.7 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a pale brown solid (2.05 g, 58%).
MS (ISP) 277.2 [(M+H)+]; mp 120 -C
Example T24
(2-Amino-4-methyl-5-(methyl-propyI-amino)-phenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-methyl-5-(methyi-propyi-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C21) (3.59 g, 11.1 namol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (3.23 g, 99%).
MS (ISP) 294.4 [(M+H)--].

Example T25
(2-Amino-5-(ethyl-methyl-amino)=4-methyl-phenvIl-carbamic acid tert-butyl ester
The title compound was prepared from [5-(ethyl-methyI-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C22) (3.28 g, 10.6 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a purple solid (2.94 g, 99%).
MS (ISP) 280.3 [(M+H)1.
Example T26
[2-Amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl1 -carbamic add tert-butylester
The title compoimd was prepared from [4-chloro-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C23) (4.07 g, 11.8 mmol) by reduction with SnClf 2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.08 g, 83%).
MS (ISP) 314.3 [(M+H)1; mp 116 °C.
Example T27
[2-Amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-chloro-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C24) (5.55 g, 15.5 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a pale brown solid (3.98 g, 78%).
MS (ISP) 328.3 [(M+H)1.
Example T28
(2-Amino-4-cyano-5-pvrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The tide compound was prepared from (4-cyano-2-mtro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C25) (1.82 g, 5.48 mmol) by reduction with SnCl22H2O according to the general procedure J (method b). Obtained as a pale brown solid (1.27 g, 77%).
MS (ISP) 303.2 [(M+H)--].

Example T29
(2-Amino-4-cyano-5-fmethyl-propyl-aminoVphenyl1-carbamic acid tert-butylester
The title compound was prepared from [4-cyano-5-(methyl-propyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C26) (1.64 g, 4.90 mmol) by reduction with SnCl2.2H2O according to the general procedure J (method b). Obtained as a dark red oil (1.24 g, 83%),
MS (ISP) 305.3 [(M+Hf],
Example T30
(2-Amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (4-cyano-5-diethylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C27) (1.66 g, 4.96 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.38 g, 91%).
MS (ISP) 305.3 [(M+H)+]; mp 151 °C
Example T31
(2-Amino-4-cyano-5-(isopropyl-methyl-aminoVphenyl1 -carbamic acid tert-butylester
The title compound was prepared from [4-cyano-5-(isopropyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C28) (1.73 g, 5.17 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as an off-white solid (1.56 g, 99%).
MS (ISP) 305.3 [(M+H)--]; mp 77 °C.
Example T32
[2-Amino-4-cyano-5-(isobutyl-methyl-amino)-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from [4-cyano-5-(isobutyl-methyl-amino)-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C29) (1.76 g> 5.05 mmol) by reduction with SnCV2H2O according to the general procedure J (method b). Obtained as a light brown solid (1.55 g, 96%).
MS (ISP) 319.5 [(M+H)--]; mp 88 oC.

Example T33
(2-Amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-cyano-2-nitro-5-piperidin-l-yi-phenyl)-carbamic acid tert-butyl ester (Example C30) (2.08 g, 5.71 mmol) by reduction with SnCl2'2H2O according to the general procedure I (method b). Obtained as an off-white solid (L67 g, 99%).
MS (ISP) 317.2 l(M+H)+]; mp 86 oC
Example 134
(2-Amino-4-chloro-5-isobutylamino-phen\1)-carbamic acid tert-butylester
The title compound was prepared from (4-chloro-5-isobutylainino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C31) (1.93 g, 5.61 mmol) by reduction with SnCl2'2H2O according to the general procedure J (method b). Obtained as a brown solid (1.30 g, 74%).
MS (ISP) 314.3 [(M+H)^.
Example 135
(2-Amino-5-(methyl-propyl-aminoV4-trifluoromethyl-phenyl1 -carbamic acid tert-butyl ester
The title compound was prepared from [5-(methyl-propyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C32) (3.78 g, 10.0 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a red oil (3.40 g, 98%).
MS (ISP) 248.4 [(M+H)+].
Example T36
[2-Amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl1 -carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C33) (3.88 g, 9,91 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.70 g, 75%).
MS (ISP) 362.3 [(M+H)--].

Example T37
(2-Amino-5-(isopropyl-methyl-aminoV4-trifluoromethyl-phenyn-carbamic acid tert-butyl ester
The title compound was prepared from [5-(isopropyl-methyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example C34) (2.98 g, 7.90 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a orange oil (2.42 g, 88%).
MS (ISP) 348.5 [(M-hH)--].
Example T38
(2-Amino-5-fisobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-methyl-amino)-4-methyl-2-nitro-phenyl]-carbamic acid tert-butyl ester (Example C35) (1.48 g, 4.39 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a white solid (1.08 g, 80%).
MS (ISP) 308.3 [(M+H)']; mp 71 °C
Example T39
(2-Amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester
The tide compound was prepared from (4-methyl-2-nitro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example C36) (3.27 g, 10.2 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale brown solid (2.48 g, 83%).
MS (ISP) 292.3 [(M+H)--]; mp 115 °C
Example T40
j (2-Amino-4'Chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (4-chloro-5-i$opropylamino-2-nitro-phenyl)-carbamic acid tert-butyl ester (Example C37) (3.75 g> 11.3 mmol) by reduction with SnCl3 2H2O according to the general procedure J (method b). Obtained as a brown solid (2.90 g, 86%).
MS (ISP) 303.3 [(M+H)--].

Example T41
f 2-Amino-5-f isobutyl-amino V4-trifluoroir.ethyl-phenyl -carbamic acid tert-butylester
The title compound was prepared from [5-(isobutyl-amino)-2-nitro-4-trifluoromethyl-phenyl]-carbamic.acid tert-butyl ester (°Cample C38) (5.28 g, 13.99 mmol) by hydrogenation with 10% Pd/C according to the general procedure J (method a). Obtained as a pale yellow solid (3.69 g, 76%).
MS (ISP) 348.5 [(M+H)--]; mp 141 °C.
The following examples relate to the preparation of the ethyl or tert.-butyl 3-aryl-3-oxo-propionates (general formula IVa), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H):
General procedure K
Method a) Preparation of ethyl or tert.-butyl3-aryl-3-oxo-propionates
The ethyl or tert.-butyl 3-aryl-3-oxo-propionates were prepared from the aryl acid chlorides and ethyl or tert.-butyl malonate potassium salt [CAS-no. 6148-64-7 and 75486-33-8] with Et3N and MgCla in CH3CN at 0 °C to 23 °C according to Synthesis 1993,290. If the free aryl carboxylic acid was employed in this reaction, it was activated by treatment with ethyl chloroformate and Et3N in THF/CH3CN at 0 °C prior to reaction with the malonate salt.
Method b) Preparation of tert.-butyl3-aryI-3-oxo-propionates
The tert.-butyl 3-aryl-3-oxo-propionates were alternatively prepared from the methyl or ethyl aryl esters by treatment with lithium tert.-butyl acetate [prepared by treatment of tert.-butyl acetate with lithium diisopropylamide in THF at -78 °C] in the prese- :e of lithium tert.-butoxide according to Synthesis 1985,45. If the product contained residual starting material after workup, thus could be removed by selective saponification with LiOH in THF/MeOH/H2O at 23 °C.
Method c) Preparation of 3-aryl-3--oxo-propionic acids
The 3-aryl-3-oxo-propiomc acids were prepared from the aryl acid chlorides and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 °C according to Synth Commun. 1985,15,1039 (method cl) or with n-BuLi in ether at -60°C o 0 °C according to Synthesis 1979,787 (method c2).

Example Kl
3-Oxo-3'(3-f L23ltria2ol-l-yl-phenyl)-propionic acid ethyl ester
The title compound was prepared from 3-[l,2,3]tria2ol-l-yl-ben2oic acid, prepared by refluxing of methyl 3-azidobenzoate [CAS-No. 93066-93-4] in trimethylsUyl-acetylene, followed by saponification with aqueous NaOH in refluxing EtOH] by activation with ethyl chloroformate/Et3N and reaction with ethyl malonate potassium salt with EtaN and MgCl2 in CH3CN according to general procedure K (method a). Obtained as a light yellow solid(2.22 g).
MS (EI) 259 (W); mp 72-74°C,
Example K2
3-(3-cyano-phenyl)-3-oxo-propiQnic acid tert.-butyl ester
The title compound was prepared from methyl 3-cyanobenzoate [CAS-No, 13531-48-1] by treatment with lithium tert--butyl acetate according to general procedure K (method b). Obtained as a light brown oily semisolid.
MS (EI) 245 (M+).
Example K3
3-(2-Cyano-pvridin-4-yl)-3-oxo-propiomc acid tert.-butyl ester
The title compound was prepared from 2-cyano-isonicotinic acid ethyl ester [CAS-No. 58481-14-4] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a light brown solid (7.70 g).
MS(ISN)245[(M-H)1.
Example K4
3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionic acid tert.-butylester
The title compound was prepared from ethyl 3-(3-methyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, acetaldoxime, Et3N and cat amount of pyridine in CHCI3 at 50 'C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (2.54
g).
MS (ISP) 302 [(M+H)1; mp 50-56 -C.

Example K5
fRSV3-Oxo-3-B45-ftetrahvdro-pvran-2-yloxymethyl)-[1,2,3]triazol-1-yl]-phneyl}-
propionic acid tert.-butylester
The title compound was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-l-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) methyl 3-azidobenzoate [CAS-No. 93066-93-4] (15.55 g, 88 mmol) and (RS)-tert.-butyl-dimethyl-[3-(tetrahydro-pyran-2-yloxy)-prop-l-ynyl]-silane [CAS-No. 135294-85-8] (33.50 g, 132 mmol) were heated to 60 --C for 10 days; ii.) The obtained material (48.2 g, ca. 88 mmol) was stirred in TBAF (300 mL, IM in THF) at 70°C for 6 days and subsequently refluxed in IN HCl (400 mL) for 2 h; iii.) The obtained material (16.15 g, 74 mmol) was stirred in MeOH (400 mL) and cone. H2S04 (30 mL) at 23 °C for 11 days, iv.) Part of the obtained material (4.60 g, 19.7 mmol) was reacted with 3,4-dihydro-2H-pyran (2.67 mL, 29.5 mmol) and cat. amount p-TsOH.H2O in DCM (38 mL) at 23 -°C for 20 h.] (6.20 g, 19.5 mmol) by treatment with lithium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (8.47 MS(ISP)402[(M+H)-'].
Example K6
3-[2-(3-methyl-isoxazol-5-yl)-pvridin-4-yn-3-oxo-propionic acid tert.-butylester
The title compound was prepared from 2-(3-methyl-isoxazol-5-yl)-isonicotinic acid methyl ester [prepared by i.) reaction of 2-iodo-isonicotinic acid methyl ester [CAS-No. 134579-47-8] with trimethylsilylacetylene according to general procedure H; ii.) desilylation by reaction with cat. K2CO3 in MeOH at 0 -°C for 4 h; iii.) cycloadditon with a mixture of NCS, acetaldoxime, Et3N and cat. amount of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40,2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a brown solid (5.17 g).
MS (EI) 302 (M^); mp 59-67 °C
Example K7
3-[3-(2-methyl-2H-pyTazol-3-yl)-phenyl1-3-oxo-propionic acid tert.-butylester
The title compound was prepared from 3-(2-methyi-2H-pyrazol-3-yl)-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyi)-3-dimethylamino-propenone [CAS-No. 163852-04-81 with methylhydrazine in EtOH at 23 °C for 2.5

days; ii.) chromatographic separation of the obtained isomers; iii.) treatment of the dean isomer -with n-BuLi in THF at -78 °C for 1 h, followed by quenching with a stream of CO2 and subsequent esterification with MeOH and cone, H2SO4 at 23 °C for 48 h.] by treatment with Uthium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.96 g),
MS (EI) 300 (M+),
Example K8
3- [3-f 5-Dimethylaminomethyl- [ 12,31 triazol- l-yl)-phenyll -3-oxo-propionic acid tert.-butylester
The title compound was prepared firom 3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-benzoic acid methyl ester [prepared from methyl 3-azidobenzoate following the synthetic steps i.) to iii.) as described in the preparation of Example K5 and reacting the obtained product with SOCI2 in THF at 0 to 23 °C for 1 h, followed by acidition of dimethylamine (7.9 M in H2O) and stirring at 23 to 70 'C fori h.] (2.14 g, 8.22 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (2.90 g).
MS(ISP)345[(M+H)-'].
Example K9
3-[3-f3-Methoxvmethyl-isoxazol-5-yl)-phenyl1-3-oxo-propionic acid tert.-butylester
The title compound was prepared from methyl 3-(3-methoxymethyl-isoxazol-5-yl)-benzoate [prepared by reaction of ethyl 3-ethynylbenzoate [CAS-No. 178742-95-5] with a mixture of NCS, 2-methoxyacetaldoxime [CAS-No. 71494-93-4], Et3N and cat, amoimt of pyridine in CHCI3 at 50 -°C according to Tetrahedron 1984,40^ 2985-2988] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow liquid (1.548 g).
MS (EI) 331 (M+),
Example KlO
(RSV3-Oxo-3-{3-f4-(tetrahvdro-pvran-2-yloxvmethyl)-thiazol-2-yl1-phenyll-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yioxymethyl)-thiazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-thiocarbamoyl-benzoic acid methyl ester [CAS-No. 106748-27-0] (7.8 g), 13-dichloro-2-propanone (8.4 g) and sodium bicarbonate (8.4 g) in 1,4-dioxane (180

mL) was heated to 60 °C for 24 h. The reaction mixture was cooled to 20°C and acided to a stirred solution of sodium methoxide (5.4 g) in methanol (200 mL), Stirring was continued for 0.5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was crystallized from dichloromethane/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-benzoic acid methyl ester (7.5 g) as light-brown crystals, 115-117 °C. ii,) A mixture of this material (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in ethyl acetate (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).
MS (ISP) 418.2 [(M+H)1.
Example K11
(RS)-3-Oxo-3-{3-F4-ftetrahvdro-pvran-2-yloxvmethyl)-oxazol-2-\yl]-phenyl]-propionic acid tert-butylester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) A mixture of 3-carbamoyl-benzoic acid methyl ester [CAS-No. 106748-24-7] (17.9 g) and l,3-dichloro-2-propanone (14.0 g) was heated to 140 °C for 1.5 h. The mixture was cooled to 20 °C and cone, sulfuric acid (12 mL) was carefully acided. The mixture was stirred for 10 min. and then poured into ice-water. The product was extracted with ethyl acetate and the organic layer was washed with brine, dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as duent to give 3-(4-chloromethyl-oxazol-2-yl)-benzoic acid methyl ester (11.8 g) as a pale-yellow oil. MS (ISP) 252.2 [(M+H)--]. ii.)
I A solution of this material (7.6 g) and lithium hydroxide monohydrate (5.0 g) in DMSO (30 mL) was heated to 60 -°C for 7 h. The cooled reaction mixture was poured into ice-water and the mixture was extracted with diethyl ether. The aqueous layer was acidified to pH 1 by the acidition of 6N HCl and the precipitate formed was collected by filtration and crystallized from dichloromethane/hexane. The pale-yellow crystals
5 (5.5 g) were dissolved in DMSO (25 mL), and after the acidition of N,N,N'N'-

tetramethyl-guanidine (4.4 mL) and methyl iodide (2.2 mL), the mixture was stirred at 20 ^°C for 1 h. Ethyl acetate was acided and the mixture was washed successively with water, IN HCl and brine. The organic layer was dried over sodium sulfate and evaporated in vacuum. The residue was chromatographed on silica gel using ethyl acetate/hexane (1:1) as eluent and the purified product was crystallized firom diethyl ether/hexane to give 3-(4-hydroxymethyl-oxazol-2-yl)-benzoic acid methyl ester (2.1 g) as white crystals, mp 118-119 °C. iii.) A mixture of this material (2,1 g), dihydropyrane (1.2 mL) and p-toluenesulfonic acid hydrate (0.1 g) in ethyl acetate (15 mL) was stirred at 20 °C for 1 h. The solution was diluted with ethyl acetate, washed with 5% sodium bicarbonate solution and with brine, dried over sodium sulfate and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using ethyl acetate/hexane (1:2) as eluent to give (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-benzoic acid methyl ester (3,5 g) as a pale-yellow oil.] (3.5 g, 11 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a pale yellow oil (3.8 g).
MS (ISP) 402.5 [(M+H)1.
Example K12
(RS')-3-Oxo-3-(3-r3-rtetrahvdro-pvran-2-yloxvmethyl)-isoxazol-5-vn-phenyl-propionic acid tert,-butylester
The title compound was prepared from (RS)-3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (7.55 g, 23 mmol) and hydroxylamme hydrochloride (4.74 g, 68 mmol) were refluxed in EtOH for 1 h; ii.) The obtained ester (5.94 g, 20 nrniol) was reduced with LiAlH4 (761 mg, 20 mmol) in THF at -10 °C for 1 h; iii.) The obtained alcohol (4.90 g, 19 mmol) was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH.HaO in DCM at 23 °C for 20 h. iv.) The obtained THP-ether (5.24 g, 15 mmol) was treated with n-BuLi at -78 'C for 45 min, followed by a stream of CO2- v.) The obtained crude acid was stirred in MeOH (90 mL) and cone, H2SO4 (6.5 mL) at 50 X for 12 h. vi.) The obtained material (2.01 g, 8.62 mmol) was reacted with 3,4-dihydro-2H-pyran (1.17 mL, 12.9 mmol) and cat, amount p-TsOH.H2O in DCM (17 mL) at 23 °C for 5 h.] (2.44 g, 7.7 mmol) by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.06 g).
MS(ISP)402((M+H)-'].

Example K13
(RS)3-(3-f3-Methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phneyl}-3-oxo-propionic acid tert,-butyl ester
The title compound was prepared from (RS)-3-[3-methyi-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yi]-benzoic acid methyl ester [prepared by the following sequence: i.) (3-bromO-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 21575-91-7], pyrrolidine and TMSOTf in benzene were refluxed for 16 h {Org. Synth, 53y 59); ii.) The obtained 3-(3-bromo-phenyl)-3-pyrrolidin-l-yl-acrylic acid ethyl ester was reacted with nitroethane, POCI3 and Et3N at 23 °C; iii,) The obtained 5-(3-bromo-phenyI)-3-methyl-isoxazole-4-carboxylic acid ethyl ester was reduced with LiAlHH4 in THF at -10 -°C for 1 h iv.) The obtained [5-(3-bromo-phenyl)-3-methyl-isoxazol-4-yl]-methanol was reacted with 3,4-dihydrO'2H-pyran and cat amount p-TsOH-HiO in DCM at 23 -C for 20 h. iv.) The obtained THP-ether was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vi.) The obtained 3-(4-hydroxymethyI-3-methyl-isoxazol-5-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (972 mg).
MS(EI)416[(M+H)1.
Example K14
(RSV3-[3'-[2-methyl-5-(tetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl]-phenylt-3-oxo-propionic acid tert.-butylester
The title compound was prepared from (RS)-3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 4-(3-bromo-phenyl)-2,4-dioxo-butyric acid ethyl ester [CAS-No. 151646-31-0] (6.135 g, 21 mmol), MeNHNH2 (1.296 mL, 25 mmol) and HCl (4M in dioxane, 6.25 mL, 25 mol) in EtOH (35 mL) were refluxed for 1.5 h; ii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyrazole-3-carboxylic acid ethyl ester (7.02 g, 22.7 mmol) was reduced with LiAlH4 (862 mg, 22.7 mmol) in THF (60 mL) at -10 °C for 1 h; iii.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-3-yi]-methanol (6.34 g, 24 mmol) was reacted with 3,4-dihydro-2H-pyran (3.25 mL, 36 mmol) and cat amount p-TsOH.H2O in DCM (50 mL) at 23 X for 23 h. iv.) The obtained (RS)-[5-(3-bromo-phenyl)-l-methyl-3-(tetrahydro-pyran-2-yloxymethyl)-lH-pyrazole(8.64
g, 25 mmol) was treated with n-BuLi at -78 °C for 45 min, followed by a stream of

CO2. V.) The obtained crude acid was stirred in MeOH (90 mL) and cone. H2SO4 (6.5 mL) at 50 °C for 5 h. vi.) The obtained 3-(5-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester (3.41 g, 13.85 mmol) was reacted with 3,4-dihydro-2H-pyran (1.75 mL, 20.77 mmol) and cat amount p-TsOH.H2O in DCM (28 mL) at 23 --C for 18 L] (3.93 g, 11.9 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (4.90 g).
MS(ISP)415[(M+H)'].
Example K15
propionic acid tert.-butylester
The title compound was prepared from (RS)-3-(5-(tctrahydro-pyran-2-yloxymethyI)-isoxazol-3-yl]-benzoic acid methyl ester [prepared from (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] by treatment with NCS, cat amount pyridine in CHCI3 followed by acidition of (RS)-tetrahydro-2-(2-propynyloxy)-2H-pyran and slow acidition of Et3N in CHQ3 at 23 oC-] by treatment with hthium tert,-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g).
MS (ISN) 400.5 [(M-H)-],
Example Kl 6
3-Oxo-3-(3-pyrazol-l-yl-phenyl)-propiQnic acid tert-butvi ester
The title compound was prepared from 3-pyrazol-l-yl-benzoic acid methyl ester [CAS-No. 168618-35-7] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (5.00 g).
MS (EI) 286 (M+),
Example K17
fRS)-3-Oxo-3-{3-[4-ftetrahvdro-pyran-2-yloxymethyl)-pvrazol-l-yl1-phenyl-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-1-yl]-benzoic acid methyl ester [prepared by the following sequence: L) A mixture of 3-hydrazino-benzoic acid methyl ester hydrochloride [CAS-No. 167626-26-8] (15.14 g, 75 mmol), 2-cyano-3-ethoxy-acryiic acid benzyl ester [CAS-No. 32016-27-6] (17.36 g, 75 mmol) and Et3N (10.5 mL, 75 mmol) in isopropanol (115 mL) was refluxed for 1.5 h. ii.) The obtained 5-amino-l-(3-methoxycarbonyl-

phenyl)-lH-pyra2ole-4-carboxylic acid benzyl ester (26.0 g, 74 mmol) was refluxed with isopentyl nitrite (30 mL, 225 mmol; 10 mL) in THF (200 mL) for 22 h. iii.) The obtained l-(3-methoxycarbonyl-phenyl)-lH-pyrazole-4-carboxylic acid benzyl ester (18.98 g, 56 mmol) was hydrogenated in the presence of Pd/C (10% Pd/C, 600 mg, 1 mol%) in EtOAc (350 mL) and THF (250 mL) at 23 oC for 16 h. iv.) The obtained 1-(3-methox7carbonyl-phenyl)-lH-pyrazole-4-carboxylic acid (13.70 g, 55.6 mmol) was reduced with BH3.SMea (28.46 mL, 278.2 mmol) m THF (364 mL) at 5 to 23 °C for 16 h. V.) The obtained 3-(4-hydroxymethyl-pyrazol-l-yl)-benzoic acid methyl ester (10.66 g, 45.9 mmol) was reacted with 3,4-dihydro-2H-pyran (6.24 mL, 68.9 mmol) and cat. amount p-TsOH-HaO in DCM (91 mL) at 23 °C for 22 h.] (14.18 g, 44.8 mmol) by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (15.87 g),
MS(ISN)399[(M.H)-].
Example K18
(RS)-3-Oxo-3-{3-[4'(tetrahvdro-pyran-2*yloxvmethyl)-isoxazol-3-yn-phenyll-propionic acid tert.'butyl ester
The title compound was prepared from (RS)-3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) (Z)-3-(hydroxyimino-methyl)-benzoic acid methyl ester [CAS-No. 91186-80-0] was treated with NCS, cat amount pyridine in CHCI3 followed by acidition of (E)-3-pyrrolidin-l-yl-acryhc acid tert.-butyl ester [CAS-No. 340257-76-3] and slow acidition of Et3N in CHCI3 at 23 -°C. ii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid tert-butyl ester was stirred in formic acid at 50 °C for 18 h. iii.) The obtained 3-(3-methoxycarbonyl-phenyl)-isoxazole-4-carboxylic acid was reduced with BH3*SMe2 in THF at 5 to 23 'C for 16 h. iv.) The obtained 3-(4-hydroxymethyl-isoxazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat amount p-TsOH-HzO in DCM at 23 °C for 1L] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (1.817 g).
MS(ISN)400[(M-H)-].

Example Kl 9
fRS)-3-l3-(2-methyl-4-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pvrazol-3-yl 3'OXo-propionic acid tert--butyl ester
The title compound was prepared from (RS)-3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyra2ol-3-yl]-benzoic acid methyl ester [prepared by the following sequence: i.) 3-bromobenzoyl chloride and 3-isopropylamino-acrylic acid methyl ester [CAS-No. 89895-40-9] were reacted in toluene and Et3N according to Synthesis 1982, 318. ii.) The obtained 2-(3-bromo-benzoyl)-3-isopropylamino-acrylic acid methyl ester was reacted with methylhydrazine in ether at 23 °C according to Synthesis 1982, 318. iii.) The obtained 5-(3-bromo-phenyl)-l-methyl-lH-pyra2ole-4-carboxylic acid methyl ester was reduced with LiAlH4 in THF at -10 °C for 1 h. iv.) The obtained [5-(3-bromo-phenyl)-l-methyl-lH-pyrazol-4-yl]-methanol was reacted with 3,4-dihydro-2H-pyran and cat. amoimt p-TsOH-HaO in DCM at 23°C for 20 h. v.) The obtained (RS)-5-(3-bromo-phenyl)-l-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-iH-pyrazole was treated with n-BuLi at -78 °C for 45 min, followed by a stream of CO2. vi.) The obtained crude acid was stirred in MeOH and cone. H2SO4 at 50 °C for 18 h. vii.) The obtained 3-(4-methoxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with IM BBrs-sol. in DCM at -78 to 23 -°C for 1 h. viii.) The obtained crude bromide was reacted with KOAc in DMF at 60 °C for 30 min. ix.) The obtained crude acetate was reacted with NaOMe-sol. In MeOH at 23 °C for 20 min. X-) The obtained 3-(4-hydroxymethyl-2-methyl-2H-pyrazol-3-yl)-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH.H2O in DCM at 23 °C for 1 h.] by treatment with lithium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow solid (11.106 g).
MS(ISN)413[(M-H)-].
Example K20
(RS)-3-Oxo-3-(3-{2-(2-ftetrahvdrQ-pyran-2-yloxvVethyl1-2H-pvrazol-3-yl}-phenyl)-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid methyl ester [prepared by i.) reaction of l-(3-bromo-phenyl)-3-dimethylamino-propenone [CAS-No. 163852-04-8] with 2-hydroxy-ethylhydrazine in EtOH at 23 °C for 2.5 days, ii.) The obtained mixture of pyrazoles (12.36 g, 35.19 mmol) was reacted with 3,4-dihydro-2H-pyran (4.79 mL, 52.8 mmol) and cat amount p-TsOH-H2O in DCM (70 mL) at 23 °C for 20 h iii.) chromatographic separation of the obtained isomers, iv.) treatment of the clean

isomer (7.35 g, 73.7 mmol) was treated with n-BuLi (13.08 mL, 20,9 mmol) in THF (42 mL) at -78 °C for 45 min, followed by a stream of CO2. v.) The obtained (RS)-3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-benzoic acid was reacted (4.56 g, 14.1 mmol) was reacted with KHCO3 (2.89 g, 28.8 mmol) and Mel (0.99 mL, 15.9 mmol) in DMF (29 mL) at 23 °C for 2 h,] (2.96 g, 8.96 mmol) by treatment with Uthium tert-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (3.00 g).
MS(ISP)415[(M+H)+].
Example k21
(RSV3-Oxo-3-f3-{5-r2-ftetrahvdro-p\Tan-2-\dox\'Vethyll-rL23ltriazol-l--vil-phenyl-propionic acid tert.-butyl ester
The title compound was prepared from (RS)-3-{5-[2-(tetrahydro-pyran-2-yioxy)-ethyl]-[l,2,3]triazol-l-yl}-benzoic acid methyl ester (prepared by the following sequence: L) methyl 3-azidobenzoate [CAS-No. 93066-93-4] and (RS)-tert-butyl-dimethyl-[4-(tetrahydro-pyran-2-yioxy)-but-l-ynyi]-silane [CAS-No. 198411-20-0] were heated to 60 °C for 10 days; ii.) The obtained material was stirred in TBAF (IM m THF) at 70 °C for 6 days and subsequently refluxed in IN HCl for 2 h; iii.) The obtained 3-[5-(2-hydroxy-ethyl)-[l,2,3]triazol-l-yl]-benzoic acid was stirred in MeOH and cone. H2SO4 at 23 °C for 11 days, iv.) The obtained 3-[5-(2-hydroxy-ethyl)-[ 1,2,3]triazol-l-yl]-benzoic acid methyl ester was reacted with 3,4-dihydro-2H-pyran and cat. amount p-TsOH'H2O in DCM at 23 °C for 20 h.] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as a yellow oil (6.748 g).
MS(ISP)416[(M+H)-'].
Example K22
(RS)-3-Oxo-3-l3-(5-rtetrahvdro-pyran-2-yloyvmethyl)-pvrazol-l-yll-phenyll-propionic acid ethyl ester
The title compoxmd was prepared from (RS)-3-[5-(tetrahydro-pyran-2-yioxymethyl)-pyrazol-l-yl]-benzoic acid [prepared by the following sequence: i.) A mixture of 3-hydrazino-benzoic acid [CAS-No. 38235-71-1], 4-dimethylamino-2-oxo-but-3-enoic acid ethyl ester [CAS-No. 67751-14-8] in acetic acid was refluxed for 15.5 h. ii.) The obtained 2-(3-carboxy-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was stirred DMF-di-tert-butyl acetal in toluene at 80 X for 45 h. iii.) The obtained 2-(3-terL-butoxycarbonyl-phenyl)-2H-pyrazole-3-carboxyiic acid ethyl ester was saponified

150°C Cristallisation from water and ethyl acetate/hexane (1:1) yielded a light brown solid (24.3 g, 54%) mp 164°C; ii,) The obtained material (24-3 g, 104 mmol) was

reacted with 3,4-dihydro-2H-pyran (29.3 mL, 320 mmol) and cat amount p-TsOH-H2O in dichloromethane (360 mL)/ THF (300 ml) at 23 °C for 20 L Purification by column chromatography on silica gd (toluene/ethyl acetate 1:1) gave a light brown oil.] (16.6 g, 52.3 mmol) by treatment with hthiimi tert.-butyl acetate according to general procedure K (method b). Obtained as a light yellow oil (14.3 g, 68%).
MS (ISP) 400.4 [(M-H)-].
Example K25
3-Oxo-3-(3-[1.2.4]triazol-yl-phenyl)-pTopionic acid tert-butylester
The title compound was prepared from methyl 3-[l,2,4]triazol-1-yl-benzoate [CAS-No. 167626-27-9] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange liquid (2.41 g),
MS (EI) 287 (M^).
Example K26
3-(3-Imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butylester
The title compound was prepared from methyl 3-(lH-imida2ol-l-yl)benzoate [prepared from 3-(lH-imidazol-l-yl)benzoic acid (/. Med, Chetn. 1987,30,1342; CAS-No. [108035-47-8] by reflioxing in cone. H2SO4/MeOH] by treatment with lithium tert.-butyl acetate according to general procedure K (method b). Obtained as an orange-brown oil.
MS (ISP) 287 [(M+H)+].
Example K27
3-0X0-3-f3-f4-ftetrahydro-pyran-2-yloxvmethyl')-thia2ol-2-yl]-phenyl]-propionic acid tert-butylester
al 3-f4-Hvdroxymethyl-thiazol-2-yl)-benzoic acid methyl ester
A mixture of 3-thiocarbamoyl-benzoic acid methyl ester (7,8 g), l,3-dichloro-2-propanone (8.4 g) and NaHCOs (8.4 g) in 1,4-dioxane (180 mL) was heated to 60 -°Cfor 24 h. The reaction mixture was cooled to 20 °C and acided to a stirred solution of NaOMe (5.4 g) in MeOH (200 mL). Stirring was continued for 0,5 h. The mixture was poured into ice-cold 2N HCl (200 mL) and the product was extracted with ACOEL The organic layer was washed with brine, dried and evaporated in vacuum-

The residue was crystallized from CH2Cl2/hexane to give 3-(4-hydroxymethyl-thiazol-2-yl)-ben2oic acid methyl ester (7.5 g) as light-brown crystals, mp 115-117 °C.
b) 3-f4-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-2-yn-benzoic acid methyl ester
A mixture of the material prepared in a) (7.5 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0.19 g) in AcOEt (50 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried over Na2SO4 and evaporated in vacuo. The residual oil was purified by chromatography on silica gel using AcOEt /hexane (1:2) as eluent to give 3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (9.6 g) as a pale-yellow oil.
c) 3-Oxo-3-f3-r4-ftetrahvdro-pyran-2-yloxvmethyD-thiazoI-2-yI1-phenyl]-propionic acid tert-butylester
A sample of the material prepared in b) (3.3 g) was treated with lithium tert,-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (3.25 g) as a pale-yeUow oil, MS (ISP) 418.2 [(M-fH)--].
Example K28
3-Oxo-3-f3-(2-bromo-lJ-dimethoxy-ethyl')-phenyll-propionic acid tert-butylester
a) 3-(2-Bromo-Ll-dimethoxy-ethyl')-ben2oic acid methyl ester
A mixture of 3-(2-bromo-acetyl)-benzoic acid [CAS-No 62423-73-8] (2.43 g), 4-toluenesulfonic acid hydrate (0.38 g) and trimethyl orthoformiate (5.5 ml) in MeOH (40 mL) was heated at reflux for 20 h. The cooled solution was diluted with AcOEt (0.15 L), washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum to give 3-(2-bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.0 g) as a pale-yellow oil.
b) 3-Oxo-3-[3-(2-bromo-l,1-dimethoxv-ethyl)-phenyl1-propionic acid tert-butylester
3-(2-Bromo-l,l-dimethoxy-ethyl)-benzoic acid methyl ester (3.9 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyi]-propionic acid tert-butyl ester (2.8 g) as a yellow oil.

Example K29 3-Oxo-3-r3-(2-methyl-oxazol-4-yl)-phenyn-propionic acid tert-butyl ester
a) 3-(2-methyl-oxazol-4-yl)-benzoic acid
A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g) and acetamide (1.77 g) was heated with stirring to 130 'C for 40 min. The mixture was cooled and diluted with H2O (30 mL) and the precipitate formed was collected by filtration to give 3-(2-methyl-oxa2ol-4-yl)-ben2oic acid (1.51 g) as brown solid.
b) 3-(2-methyl-oxazol-4'yl')-benzoic acid methyl ester
A solution of 3-(2^methyl-oxazol-4-)d)-benzoic acid (1.42 g) in a mixture of MeOH (30 mL) and 4NHC1/Et20 (6 mL) was heated to 40 -°C for 4 h. The solution was evaporated in vacuum and the residual oil was stirred with H2O (30 mL), the pH of the mixture being set to about 6 by the acidition of sat NaHCOa solution. The precipitate was isolated by filtration to give 3-(2-methyl-oxa2ol-4-yl)-benzoic acid methyl ester (1.18 g) as light-brown solid, MS (ISP) 218.2 [(M+H)-^].
c) 3-Oxo-3-f3-('2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester
3-(2-Methyl-oxazol-4-yl)-benzoic acid methyl ester (1.02 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (1.50 g) as a pale-yellow oil.
Example K30
3-Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3.4lthiadiazol-2'yl1-phenyll-propionic acid tert-butyl ester
a) 3-rN'-tert-butoxvcarbonyl-hvdra2inocarbothioyl)-benzoic acid methyl ester
A mixture of 3-(N'-tert-butoxycarbonyl-hydrazinocarbonyl)-benzoic acid methyl ester (1.47 g) and Lawesson reagent (1.62 g) in toluene (30 mL) was heated to 70 °C for L5 h. The mixture was concentrated in vacuum and then subjected to chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-(N'-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (1.31 g) as a yellow solid, MS (ISP) 328.3 [(M+NH4)1.

b) 3-Hvdra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate
A solution of 3-(N1-tert-butoxy-carbonyl-hydrazinocarbothioyl)-benzoic acid methyl ester (0.93 g) in TFA (9 mL)/anisole (2 mL) was stirred at 0 X for 1 h. The solvents were evaporated in vacuum to give crude 3-hydrazinothiocarbonyl-ben2oic acid methyl ester trifluoroacetate (0.98 g) as a crystallizing oil.
c) 3-(5-Hydroxymethyl-[L3,4lthiadiazoI-2-yl)-benzoic acid methyl ester
A mixture of 3-hydrazinothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.49 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.47 g) in EtOH (6 mL) was heated to 80 °C for 2.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated. The residual oil (0.8 g) was dissolved in MeOH (5 mL), MeONa (0,08 g) was acided and the solution was heated to 65 °Cfor 0.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (0.15 g) as a white soHd, MS (ISP) 25L2 [(M+H)+].
d) 3'(5-fTetrahvdro-pyran*2-yloxvmethyl)-fL3,4lthiadiazol-2-ylUbenzoicacid
methyl ester
A mixture of 3-(5-hydxoxymethyl-[l,3,4]thiadiazol-2-yl)-benzoic acid methyl ester (7.8 g), dihydropyrane (5.6 mL) and p-toluenesulfonic acid hydrate (0.59 g) in AcOEt (80 mL) was stirred at 20 °Cfor 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on sihca gel using AcOEt/hexane (1:2) as eluent to give 3-[5-{tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5,85 g) as a pale-yellow oil.
e)3'Oxo-3-B-r5-ftetrahvdrO'pyran-2-vIoxvmethyl)-fl3.4lthiadiazQl-2-yl]-phenyl-propionic acid tert-butylester
3-[5-(Tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (5.85 g) was treated with lithium tert,-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (8.9 g) as a pale-yellow oil.

Example K31
3-Oxo-3-(3-(5-r2-ftetrahvdro-pyran-2-vIoxy)-ethyl14L3.4lthiadia2ol-2-yl}-phenyl)-propionic acid tert-butylester
a) 3-[5-(2-Hydroxy-ethyl)-ri3,4lthiadiazol-2-yl1-benzoic acid methyl ester
A mixture of 3-hydra2inothiocarbonyl-benzoic acid methyl ester trifluoroacetate (0.45 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (0.35 g) in pyridine (5 mL) was heated to 100 °C for 1.5 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was chromatography on siUca gel using AcOEt/hexane (1:1) as eluent to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]thiadiazol-2-yl]-ben2oic acid methyl ester (0.37 g) as a white solid, MS (ISP) 265.3 [(M+H)+].
b) 3-15- [2-fTetrahydro-pyran-2-yloxy)-ethyl1 - [ 1,3>4]thiadiazol-2-yn-benzoic acid
methyl ester
A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3>4]thiadia2ol-2-yl]-ben2oic acid methyl ester (1.86 g), dihydropyrane (0.95 mL) and p-toluenesulfonic acid hydrate (0.13 g) in AcOEt (25 mL) was stirred at 20 °C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyI]-[l,3,4]thiadia2ol-2-yl}-benzoic acid methyl ester (1.60 g) as a pale-yellow oil.
c)3-Oxo-3-r3-l5-r2-ftetrahvdro-pyran-2-vIoxv)-ethyl]-rL3.4lthiadiazoI-2-yl?-phenyD-propionic acid tert-butylester
3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadia2ol-2-yl}-benzoicacid methyl ester (1.60 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phen}i)-propionic acid tert-butyl ester (2.1 g) as a pale-yellow oil.
Example K32
3-Oxo-3-(3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-fL3,4loxadiazol-2-yl]-phenyll-propionic acid tert-butyl ester
z) 3-(5-HvdrQXvmethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester
A mixture of 3-hydrazinocarbonyl-benzoic acid methyl (0.97 g) and 2-chloro-acetimidic acid ethyl ester hydrochloride (0.95 g) in EtOH (20 mL) was heated to 80

-°C for 1 h. The mixture was diluted with AcOEt and washed with IN HCI and with brine. The organic layer was dried and evaporated and the residual oil (1.1 g) was dissolved in DMF (4 mL). Upon acidition of AcOK (0.59 g) and KI (0.07 g), the mixture was stirred at 100 Xfor 0.5 h. After cooling to 20 °C, MeOH (10 mL) and NaOMe (0.14 g) were acided and stirring was continued for 0.5 h at 65 °C. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residue was crystallized from AcOEt/hexane to give 3-(5-hydroxymethyl-[13,4]oxadiazol-2-yl)-benzoic acid methyl ester (0.72 g) as a white solid, MS (ISP) 235.3 [(M+H)--].
b) 3-(5-(Tetrahvdro-pyran-2-yloxvmethyl)-[ 1.3.4lthiadiazol-2-vn -benzoic acid methyl ester
A mixture of 3-(5-hydroxymethyl-[l,3>4]oxadiazol-2-yl)-benzoic acid methyl ester (9.8 g), dihydropyrane (7.7 mL) and p-toluenesulfonic acid hydrate (0.80 g) in AcOEt (100 mL) was stirred at 20 **€ for 1 h. The solution was diluted with AcOEt, washed with 5% NaHC03 solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as eluent to give 3-[5-(tetrahydrO-pyran-2-yloxymethyl)-[l,3,4]thiadiazol-2-yl]-benzoic acid methyl ester (12.6 g) as a pale-yellow oil.
c)3-Oxo-3-{3-[5-(tetrahydro-pyran-2-yloxvmethvD-fl3,4loxadiazol-2-yn-phenyll-propionic acid tert-butylester
3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,3,4]thiadiazol-2-yl] -benzoic acid methyl ester (12,6 g) was treated with Uthium tert.-butyl acetate according to general procedure K (method b) to give crude 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (17.0 g) as a pale-yellow oil.
Example K33
3-Oxo-3-f3-{5-[2-ftetrahvdro-pyran-2-yloxvVethyl]-[L3.4loxadiazol-2-yll-phenyl)-propionic acid tert-butylester
2L) 3-[5-(2-Hvdroxv-ethyl)-ri3,4l6xadiazol-2-yl1-benzoic acid methyl ester
A mixture of crude 3-hydrazinocarbonyl-ben2oic acid methyl (2,90 g) and 3-hydroxy-propionimidic acid ethyl ester hydrochloride (2.76 g) in pyridine (10 mL) was heated to 100 °Cfor 2 h. The mixture was diluted with AcOEt and washed with IN HCl and with brine. The organic layer was dried and evaporated and the residual oil was

crystallized from Et20 to give 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yI]-benzoic acid methyl ester (2.5 g) as a white solid, MS (ISP) 249.1 [(M+H)--],
b)3-l5-(2-fTetrahydro-pyran-2-yloxvVethyl]-fL3,4lthiadiazol-2-vU-benzoicacid methyl ester
A mixture of 3-[5-(2-hydroxy-ethyl)-[l,3,4]oxadiazol-2-yl]-benzoic acid methyl ester (7.45 g), dihydropyrane (4.1 mL) and p-toluenesulfonic acid hydrate (0,57 g) in AcOEt (80 mL) was stirred at 20 'Cfor 2 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated in vacuum. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:2) as duent to give 3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoic acid methyl ester (8.2 g) as a pale-yellow oil.
cl3-Oxo-3-(3-(5-(2-(tetrahvdro-pyran-2-yloxv)-ethyl]-rL3.4loxadiazol-2-vU-phenyl)-propionic acid tert-butylester
3-{5-[2-(Tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-benzoicacid methyl ester (8.2 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (11.6 g) as a pale-yellow oil.
Example K34
3-(3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester
a) 3-Oxazol-4-yl-benzoic acid methyl ester
A mbcture of 3-(2-bromo-acetyl)-benzoic acid (1.94 g) and formamide (1.08 g) was heated with stirring to 130 ^'Cfor 3 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was dissolved in a mixture of MeOH (30 mL) and 4NHC1/Et20 (8 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOs solution and brine, dried and evaporated. The residue was chromatographed on sihca gel using AcOEt/hexane (1:3) as eluentto give 3-oxazol-4-yl-benzoic acid methyl ester (0.85 g) as off-white solid, MS (ISP) 204.1 [(M+H)-*-].
b) 3-r3-Oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester
3-Oxazol-4-yl-benzoic acid methyl ester (0.85 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (1.46 g) as a pale-yellow oil.

Example K35 3-Oxo-3-f3-thiazoI-4-vI-phenyl)-propionic acid tert-butylester
a) 3-Thiazol-4-yl-benzoic acid methyl ester
A solution of 3-(2-bromo-acetyi)-benzoic acid (L22 g) and thioformamide (0.46 g) in EtOH (5 mL) was heated to 80 •C for 1 L The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was dissolved in a mixture of MeOH (20 mL) and 4NHCl/Et20 (5 mL). After being kept at 20 °Cfor 18 h, the solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaHCOj solution and brine, dried and evaporated. The residue was chromatographed on siUca gel using AcOEt/hcxanc (1:3) as eluent to give 3-thiazol-4-yl-benzoic acid methyl ester (0,98 g) as off-white solid, MS (ISP) 220.2 [(M+H)--].
b) 3-Oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butylester
3-Thiazol-4-yl-benzoic acid methyd ester (0.91 g) was treated with lithitun terL-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (1.54 g) as a pale-yellow oil.
Example K36
3-f3-(5-Methyl-oxazol-4-yI)-phen)d]-3-oxo-propionic acid tert-butylester
a) 3-tert-Butoxvcarbonylacetyl-benzoic acid methyl ester
Dimethyl isophthaiate (67.9 g) was treated with lithium tert.-butyl acetate according to general procedure K (method b) to give crude 3-tert-butoxycarbonyiacetyi-benzoic acid methyl ester (74.5 g) as a pale-yellow oil.
b) 3-Propionyl-benzoic acid methyl ester
To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (ILl g) and Mel (2.2 mL) m DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil> 1.4 g). Stirring was continued at 0 ®C for 15 min and at 20 °C for 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated The residue was stirred in a mixture of CH2Cl2 (30 mL) and TEA (30 mL) for 40 min at 20 °C. After the evaporation of the solvents, the solution of the residue in AcOEt was extracted with ice-cold sat NaaCOs solution and the aqueous extracts were immediately acidified with 3N HQ and extracted with AcOEt The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HCl (3 mL) to 100 °C for 1 h. The cooled mixture was diluted with AcOEt, washed

with sat. NaHCOs and brine, dried and evaporated to give 3-propionyi-benzoic acid methyl ester (3.87 g) as white solid, MS (ISP) 193.2 [(M+H)--].
c) rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester
A mixture of 3-propionyl-benzoic acid methyl ester (3.6 g) and CuBri (7.45 g) in AcOEt (45 mL) was heated at reflux for 2 h. Unsoluble material was filtered oflFfrom the cooled mixture and the clear solution was washed with brine, dried and evaporated to give crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (5.0 g) as pale-yeUow oO.
d) 3-r5'methyl-oxazol-4-yl)-benzoic acid methyl ester
rac-3-(2-Bromo-propionyl)-benzoic acid methyl ester (5.42 g) and formamide (3.6 ml) were heated together to 130 °C for 5 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as eluent to give 3-(5-methyI-oxazol-4-yl)-benzoic acid methyl ester (2.52 g) as white solid.
e) 3-[3-(5-Methyl-oxazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester
3-(5-methyl-oxazol-4-yl)-beruoic acid methyl ester (0.87 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (L46 g) as a pale-yellow oil.
Example K37
3-[3-(2-methyl'5-propyl-oxazol-4-yl)-phenyl-3-oxo-propionic acid tert-butyl ester
al 3-Pent-4-enoyl-benzoic acid methyl ester
To a stirred solution of 3-tert-butoxycarbonylacetyl-benzoic acid methyl ester (11.1 g) and allyl bromide (3.0 mL) in DMF (40 mL) was acided portionwise at 0 °C NaH (55% dispersion in mineral oil, 1.44 g). Stirring was continued at 0 °C for 20 min and at 20 °Cfor 30 min. The mixture was partitioned between AcOEt and brine, the pH being set to 7 by the acidition of 3N HCl. The organic layer was dried and evaporated. The residual oil was stirred in a mixture of CH2Cl2 (30 mL) and TFA (30 mL) for 40 min at 20 'C. The solvents were evaporated. The solution of the residue in AcOEt was extracted with ice-cold saL NaaCOa solution and the aqueous extracts were immediately acidified with 3N HCl and extracted with ACOEL The solvent of this extract was evaporated and the residue heated in a mixture of toluene (40 mL) and 3N HQ (2 mL) to 100 ^'C for 1 h. The cooled mbcture was diluted with AcOEt, washed

with saL NaHCOs and brine, dried and evaporated to give 3-pent-4-enoyi-ben2oic acid methyl ester (5.11 g) as a pale-yellow oil, MS (ISP) 236.2 [(M+NH4)'].
b) rac-3-(2-Bromo-pentanoyl)-benzoic acid methyl ester
A sample of 3-pent-4-enoyl-benzoic acid methyl ester (3.93 g) was hydrogenated in AcOEt (50 mL) in the presence of 5% Pd-C (190 mg) for 30 min at 20 ^'C. The catalyst was filtered off, CuBr2 (4.44 g) was acided to the solution and the mixture was heated at reflux for 1 h. Unsoluble material was filtered off from the cooled mixture and the clear solution was washed with IN HCl and brine, dried and evaporated to give crude rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (3.6 g) as pale-yellow oil.
c) 3-(2-methyl-5-propvI-oxazol-4-yl)-benzoic acid methyl ester
A sample of rac-3-(2-bromo-pentanoyl)-benzoic acid methyl ester (1.50 g) and acetamide (0.89 g) were heated together to 130 *C for 15 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oE was chromatographed on silica gel using AcOEt/hexane (1:3) as duent to give 3-(2-methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0.47 g) as a light-yellow oil.
d) 3-f3-(2-methyl-5-propyl-oxazol-4-yl')-phenyl1-3-oxO'propionic acid tert-butylester
3-(2-Methyl-5-propyl-oxazol-4-yl)-benzoic acid methyl ester (0,47 g) was treated with lithium tert-butyl acetate according to the general procedure K (method b) to give crude 3-[3-(2-methyl-5-propyl-oxazol-4-yl)-phenyl]-3-oxo-propiomc acid tert-butyl ester (0.58 g) as a light-brown oil.
Example K38
3-[3-(5-methyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butylester
z) 3-(5-methyl-thia2Ql-4-yl)-benzoic acid methyl ester
A solution of crude rac-3-(2-bromo-propionyl)-benzoic acid methyl ester (2,71 g) and thioformamide (1.83 g) in EtOH (20 ml) was heated at reflux for 1 h. The mixture was partitioned between AcOEt and brine, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gel using AcOEt/hexane (1:4) as duent to give 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (2.41 g) as white solid.
h) 3-[3-(5-methyl-Aiazol-4-yl)-phenyll-3-oxo-propiQnic acid tert-butylester
A sample of 3-(5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g) was treated with Uthium tert-butyl acetate according to the general procedure K (method b) to

give crude 3-[3-(5-methyl-thia2ol-4-yi)-phcnyl]-3-oxo-propiomc acid tert-butyl ester (L9 g) as a pale-yellow oil
Example K39
3-f3-(23-Dimethyl-thiazol-4-yl)-phenyl1-3-oxo-propionic acid tert-butyl ester z) 3-(2,5-Diinethyl-thiazol-4-yl)-ben2oic acid methyl ester
A mixture of rac-3-(2-bromo-propionyl)-bcn2oic acid methyl ester (6.78 g) and thioacetamide (5.63 g) was heated to 130 ^'Cfor 20 min. The mixture was partitioned between AcOEt and H2O, the organic layer was dried and evaporated and the residual oil was chromatographed on silica gd using AcOEt/hcxane (1:4) as duent to give 3-(2,5-dimethyl-thia2;ol-4-yl)-benzoic acid meth>1 ester (4.97 g) as yellow oil.
b) 3-r3-(2>5-Dimethyl-thiazol-4-y!)-phen\i]-3-oxo-propionic acid tert-butyl ester
A sample of 3-(2,5-dimethyl-thia2ol-4-yl)-ben2oic acid methyl ester (0.99 g) was treated with lithiimi tert-butyl acetate according to the general procedure K (method b) to give 3-[3-(2,5-dimethyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (1.12 g) as a pale-yellow oil.
Example K40
3-Oxo-3-[3-(5-methyl-4-(tetrahvdro-pyran-2-yloxvmethyl)-thia2ol-4-yl]-phenyi1-propionic acid tert-butyl ester
a) 3-(2-HydroxymethyI-5-methyl-thia2ol-4-yl)-ben2oic acid methyl ester
A solution of rac-3-(2-bromo-propionyI)-ben2oic acid methyl ester (2 Jl g) and 2-(tert.-butylcarbonyloxy)thioacetanude (2.1 g) in EtOH (20 mL) was heated at reflux for 6 h. The mixture was partitioned between AcOEt and brine, and the organic layer was dried and evaporated. A solution of the residual oil and NaOMe (0.54 g) in MeOH (20 mL) was stirred at 60 °C for 1 h. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (1.17 g) as white crystals, MS (ISP) 264.1 [(M+H)^.
h) 3-(5-methyl-4-ftetrahvdro-pyran-2-yloxymethyl')-thiazQl-4-yl1-benzoic acid methyl ester
A mixture of 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (1.05 g), dihydropyrane (0.73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 -°C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCO3 solution and with brine, dried and evaporated The residual

oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-l5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1,45 g) as a pale-yellow oil.
c) 3-0x0-3- [3* r5-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-4-yll -phenyl] -propionic acid tert-butyl ester
3-[5-Methyl-4-(tetrahydro-pyran-2--yloxymethyl)-thiazol-4-yl]-ben2oic acid methyl ester (1.45 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl]-propionic acid tert-butyl ester (2.13 g) as a pale-yellow oil.
Example K41
3-Oxo-3-[3*[5-propyl-4-(tetrahydro-pyran-2-yloxvmethyl)-thiazol-2-yl]-phenyl-propionic acid tert-butyl ester
a) 3-(2-Hydroxvmethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester
A sample of rac- 3-(2-bromo-pentanoyl)-benzoic acid methyl ester (0.60 g) and and 2-(tert.-butylcarbonyloxy)thioacetamide (0.36 g) in EtOH (4 mL) was heated at reflux for 5 h. The mixture was partitioned between AcOEt and 5% NaHCOs solution, the organic layer was washed with brine, dried and evaporated. A solution of the residual oil and of NaOMe (0.13 g) in MeOH (10 mL) was stirred at 60 °C for 30 min. The solution was diluted with AcOEt, washed with IN HCl and brine, dried and evaporated to give 3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.44 g) as an oil.
b) 3-f 5-Propyl-4-(tetrahydro-pyran-2-yloxymethyl)-tfaiazol-2-yl1-benzoic acid methyl
gster
3-(2-hydroxymethyl-5-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (0,73 mL) and p-toluenesulfonic acid hydrate (0.07 g) in AcOEt (10 mL) was stirred at 20 ^'C for 1 h. The solution was diluted with AcOEt, washed with 5% NaHCOs solution and brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as duent to give 3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-benzoic acid methyl ester (0.36 g) as a pale-yellow oil.

c)3'Oxo-3-f3-(5-propyl-4-(tetrahvdro-pyran-2-yloxyme&yl)-tfaiazol-2-yl]-pheny^ propionic acid tert-butyl ester
3-l5-Propyl-4-(tetrahydro-pyran-2-yloxymeth)d)-thia2ol-2-yl]-benzoic acid methyl ester (0-34 g) was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-[3-[5-propyl-4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.42 g) as a pale-yellow oil.
Example K42
3-Oxo-3-f3-r2-methyl-5-ftetrahydro-pyran-2-yloxvmetfayl)-thiazQl-4'yl]-phenyl-propionic acid tert-butyl ester
al 3-(5-Bromomethyl-2-methyl-thia2oI-4-yl)-benzoic acid methyl ester
A mixture of 3-(2,5-dimethyl-thiazol-4-yl)-benzoic acid methyl ester (3.96 g), N-bromosuccinimid (3.13 g) and (X,a'-bis(isobutyronitrile) (0.02 g) in CCI4 (60 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-ben2oic acid methyl ester (6,2 g) as an oil.
h) 3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-ben2oic acid methyl ester
3-(5-bromomethyl-2-methyl-thia2ol-4-yl)-benzoic acid methyl ester was stirred in DMF (16 mL) together with KOAc (2.35 g) at 20 °C for 20 min. MeOH (32 mL) and naOMe (0.86 g) were acided and stirring was continued at 50 '°C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:1) as eluentto give 3-(5-hydroxytnethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (2,93 g) as a white solid.
c) 3-[2-methyl-5-ftetrahydro-pyran-2-yloxymethyl)-thiazol-4-yll-benzoic acid methyl ester
3-(5-Hydroxymethyl-2-methyl-thiazol-4-yl)-benzoic acid methyl ester (0.38 g), dihydropyrane (2.01 mL) and p-toluenesulfonic acid hydrate (0.21 g) in AcOEt (25 mL) was stirred at 20 °Cfor 1 h. The solution was diluted AcOEt, washed with 5% NaHCOa solution and with brine, dried and evaporated. The residual oil was purified by chromatography on siUca gd using AcOEt/hexane (1:3) as eluent to give 3- [2-methyl-5-(tetrahydro-pyran-2-)doxymethyl)-tiuazol-4-yl]-benzoic acid methyl ester (3.8 g) as a pale-ydlow oiL

d) 3-0x0-3-r3-r2-methyI-5'rtetrahydro-pyran-2-vIoxvmethyI)-tHazol-4-yl^ propionic acid tert-butyl ester
3-[2-Methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-ben2oic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (methodb) to give crude 3-oxo-3-[3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)' thiazol-4-yl]-phenyl]-propionic acid tert-butyl ester (5.45 g) as a pale-yellow oil.
Example K43
3--OXO-3-I [5-(tetrahydro-pyTan'2-yloxymethyl)-thiazol-4-vn -phenyl!-propionic acid tert-butyl ester
a) 3-f 5-Bromomethyl-thiazol-4-yl')-benzoic acid methyl ester
A mixture of 3-(5-methyl-thia2ol-4-yl)-benzoic acid methyl ester (2.40 g), N-bromosuccinimid (2.01 g) and oc,a'-bis(isobutyronitrile) (0.02 g) in CCU (40 mL) was heated at reflux for 30 min. The cooled mixture was filtered and the solvent was evaporated to give crude 3-(5-bromomethyl-thia2ol-4-yl)-benzoic acid methyl ester (3.36 g) as an oil.
b^ 3-f 5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester
3-(5-Bromomethyl-thiazol-4-yl)-benzoic acid methyl ester was stirred in DMF (10 mL) together with KOAc (1.52 g) at 20 ^'C for 30 min, MeOH (20 mL) and NaOMe (0.84 g) were acided and stirring was continued at 50 °C for 30 min. The mixture was partitioned between AcOEt and brine and the organic layer was dried and evaporated. The residual oil was chromatographed on silica gel using AcOEt/hexane (1:2) as eluent to give 3-(5-hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (1.43 g) as a white solid.
c) 3-[5-fTetrahvdro-pyran-2-yloxvmethyl)-thiazol-4-yl]-benzoic acid methyl ester
3-(5-Hydroxymethyl-thiazol-4-yl)-benzoic acid methyl ester (L25 g), dihydropyrane (0,84 mL) and p-toluenesulfonic acid hydrate (0.10 g) in AcOEt (12 mL) was stirred at 20 °Cfor 3 h. The solution was diluted AcOEt, washed with 5% NaHCOs solution and with brine, dried and evaporated. The residual oil was purified by chromatography on silica gel using AcOEt/hexane (1:3) as eluent to give 3-[5-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-benzoic acid methyl ester (1.60 g) as a pale-yellow oil.

d) 3-Oxo-3-( (5-(tetrahvdro-pyran-2-yloxyTnethyl)-thia2ol-4-yl]-phenyll-propionic acid tert-butyl ester
3-[5-(Tetrahydro-pyran-2-yioxymethyl)-thiazol--4-yi]-beiizoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give crude 3-oxo-3-{[5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionic acid tert-butyl ester (2.3 g) as a pale-yellow oil.
Example K44
3-[3-(2-Isopropyi-3H'imida2ol-4-yl')-phenyll-3-oxo-propionic acid tert-butyl ester
3) 3-Dihydroxyacetyl-benzoic acid methyl ester
A mixture of 3-(2-bromo-acetyl)-benzoic acid (2.43 g), DMSO (17 mL) and 48% HBr (3.4 mL) was heated to 55 °C for 30 min. The mixture was partitioned between AcOEt and H2O and the organic layer was washed with brine, dried and evaporated to give 3-dihydroxyacetyl-benzoic acid methyl ester (1.06 g) as a white solid.
h) 3'(2-I$opropyl-3H-imidazol-4-yl)-benzoic acid methyl ester
A solution of 3-dihydroxyacetyl-benzoic acid methyl ester (0.36 g) and 2-methyl-propionaldehyde (0.24 ml) in 5% aqueous NH3 (6 mL) was heated to 100 °C for Ih, The mixture was evaporated in vacuum and the solution of the residue in a mixture of MeOH (10 mL) and 4NHC1/Et20 (2 mL) was heated to 40 °C for 18 h. The solution was concentrated in vacuum, diluted with AcOEt, washed with sat. NaaCOa solution and brine, dried and evaporated. The residue was chromatographed on silica gel using AcOEt as eluent to give 3-(2-isopropyl-3H-imidazol-4-yl)'ben2oic acid methyl ester (0.37 g) as a pale-yellow oil.
c) 3'f3-(2-Isopropyl-3H-imidazol-4-yl)-phenyll-3-oxo-propionic acid tert-butylester
3-(2-Isopropyl-3H-imidazol-4-yl)-benzoic acid methyl ester was treated with lithium tert.-butyl acetate according to the general procedure K (method b) to give cmde 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (0.25 g) as a pale-yellow oil.

The following examples relate to the preparation of the 6-aryl-2,2-diniethyl-[l,3]dioxin-4-ones (general formula IV), which serve as building blocks in the synthesis of the target compounds (Synthetic Scheme H):
General procedure L
Preparation of 6-aryl-2,2-dimethyl-fL3]dioxin-4-ones Method a)
The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from 3-aryl-3-oxo-propionic acids and catalytic amount of cone. H2SO4 or trifluoroacetic acid (TFA) in isopropenyl acetate at 23 *-€ according to Chem, Pharm, Bull 1983,3J, 1896. The final products were purified by silica gel coliunn chromatography with hexane/EtOAc.
Method b)
The 6-aryl-2,2-dimethyl-[l,3]dioxin-4-ones were prepared from the tert.-butyl 3-aryl-3-oxo-propionates by treatment with trifluoroacetic anhydride (TFAA) in a mixture of TFA and acetone at 23 -°C according to Tetrahedron Lett. 1998,39,2253. The final products were if necessary purified by silica gel column chromatography with hexane/EtOAc.
Example LI
3-(2,2-Dimethyl-6-oxo-6H-ri.3ldioxin-4'vD-benzonitrile
The 3-(3-cyano-phenyl)-3-oxo-propionic acid was prepared from 3-cyanobenzoyl chloride (828 mg, 5 mmol) and bis(trimethylsilyl)malonate (2.56 mL, 10 mmol) with n-BuLi (1,6M in hexane, 6.25 mL) in ether at-60 °C to 0 °C according to general procedure M (method c2). The crude material (1.04 g) was transformed into the title compound by stirring in isopropenyl acetate and TFA according to general procedure L (method a). Obtained as a light yellow solid (0.8 g).
MS (EI) 229 (M^); mp 138 °C (dec).
Example L2
4-(2.2-Dimethyl-6-oxo-6H-fL3ldioxin-4-yl1-pvridine-2-carbonitrile
The title compound was prepared from 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example MlO) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a brown solid (3.30 g).
MS (H) 230 (M^); mp 132 X (dec).

Example L3
6'f3'Imidazol-l-yl-phenyi)-2.2-dimethyl-fh3ldioxin-4-one
The 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid was prepared from 3-(lH-imidazol-l-yl)ben2oyl chloride hydrochloride [prepared by treatment of 3-(lH-imidazoM-yl)-benzoic acid (/. Med. Chem. 1987,30,1342; CAS-No. [108035-47-8] with SOCI2) and bis(trimethylsilyl)malonate with Et3N and LiBr in CH3CN at 0 ^'C according to general procedure K (method cl). The crude material was transformed into the title compound by stirring in isopropenyl acetate and cone. H2SO4 according to general procedure L (method a). Obtained as an orange semisolid (617 mg).
MS (EI) 270 (M^).
Example L4
2.2-Dimethyl-6-f3-fL23ltriazol-l-vI-phenyl)-rL3ldioxin-4-one
The tide compound was prepared from 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K23) by stirring in TFA/acetone with TFAA according to general procedure L (method b). Obtained as a beige solid (7.80 g).
MS (EI) 271 (M--); mp 144-147 °C (dec).
General procedure M:
Preparation of {2-[3-aryI-3-oxo-propionylamino]-phenyl}-carbamic acid tert.-butyl ester by reaction of (2-amino-phenyl)-carbamic acid tert-butyl esters with ethyl or tert.-butyi 3-aryl-3-oxo-propionates or 6-aryl-2^-dimethyl-[l,3]dioxin-4-ones:
A mixture of the (2-amino-phenyl)-carbamic acid tert.-butyl ester or (1.0-1-2 mmol) and (1.0-1-5 mmol) of the ethyl or tert.-butyl 3-aryl-3-oxo-propionate or 6-aryl-2,2-dimethyl-[l,3]dioxin-4-one was heated in toluene (4-8 mL) to 80 **€ to 120 'C until tic indicated complete consumption of the minor component. The solution was allowed to cool to 23 °C, whereupon the product generally crystallized (in cases where crystallization failed to appear it was induced by acidition of hexane or ether, alternatively the reaction mixture was directly subjected to silica gel column chromatography). The solid was filtered off, washed with ether or mixtures of ether/hexane and dried in vacuum to give the {2-[3-aryl-3-oxo-propionylamino]' phenyil-carbamic acid terL-butyl esters, which was used direcdy in the following step or - if necessary - was purified by recrystallization or by silica gd column chromatography.

Example Ml
{4-Chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimethylamino-phenyll-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (0.5 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid ethyl ester [CAS-No. 62088-13-5; prepared from 3-cyanobenzoyl chloride according to general procedure K, method a] (0.55 mmol) according to the general procedure M. Obtained as a white solid (160 mg).
MS (ISP) 457 [(M+H)--]; mp 159-163 *°C.
Example M2
l4-Chloro-5-dimethylamino-2-r3-oxo-3-r3-rh23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) (150 mg> 0.58 mmol) according to the general procedure M. Obtained as a beige solid (160 mg).
MS (ISP) 499 [(M+H)--] and 501 [(M+2+H)1; mp 136-137 °C.
Example M3
fRS)-r4-Chloro-5-dimethylamino-2-f3-oxo-3-^3-[5-ftetrahvdro-pyran-2-
yloxvmethyl)-fL2.3ltria2ol-l-yll-phenyl}-prQpionylaminoVphenyl-carbamicacid
tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
acid tert-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow oil (257 mg).
MS (ISP) 613 [(M+H)'] and 615 [(M+2+H)'].

Example M4
(243-f3-cyano-phenvD-3-oxo-propiQnylamino1-5-dime1hylamino-4-phenvIethvnyl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carbamic acid tert.-but7l ester (Example J2) and 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-ben2onitrile (Example LI) according to the general procedure M. Obtained as an orange solid (108 mg).
MS(ISP)523[(M+H)1.
Example M5
/5-Dimethylamino-2-r3'Oxo-3-r3-fL2.3ltriazol-l-yI-phenyD-propionylamino1-4' phenylethvnyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylaminO-phenyl)-carbamic acid tert.-butyl ester (Example J2) and 3-oxo-3-(3-[l,2,3]tria2oM-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as an orange solid (148 mg).
MS(ISP)565[(M+H)'].
Example M6
f4-Chloro-5-dimetfaylamino-2-l3-[3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylamino I-phenyl) - carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(3-methyi-isoxa2ol-5-yI)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (450 mg, 075 mmol) according to the general procedure M. Obtained as a white solid (136 mg).
MS (ISP) 513 [(M-hH)--] and 515 [(M+2+H)']; mp 109-114 °C
Example M7
fRS)-r2-Dimethylamino-2'3'-diflu6ro-5-r3-oxo-3-l^-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23]triazoM-yl1-phenvU-propionylamino)-biphenyl-4-yll-carbamic
add tert.-butylester
The title compound was prepared from (5-amino-2-dimethyiamino-2*,3'-difluoro-biphenyl-4-yl)-carbamic acid terL-butyl ester (Example J3) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2^]tria2ol-l-yl]-phenyi}-propionic acid tert-

butyl ester (Example K5) according to the general procedure M. Obtained as a yellow solid (253 mg).
MS (ISP) 691 [(M+H)--].
Example M8
(2-Dimethylamino-2\3'-difluoro-5-r3-oxo-3-f3-rL23ltria2ol-l-yl-phenyl)-propionylamino1-biphenyl-4'yll-carbamic acid tert.-butylester
The title compoimd was prepared from (5-amino-2-dimethylamino-2',3*-difIuoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J3) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid ethyl ester (Example Kl) according to the general procedure M. Obtained as a yellow solid (253 mg),
MS (ISP) 577 [(M+H)--],
Example M9
{5-f3-(3-cyano-phenyl')-3-oxo-propionylaminol-2-dimethylamino-2\3'-difluorO' biphenyl-4-yll-Carbamic acid tert.-butylester
The title compound was prepared from (5-amino-2-dimethylantiino-2',3'-difluoro-biphenyl-4-yl)-Carbamic acid tert.-butyl ester (Example J3) 3-(2,2-dimethyl-6-oxo-6H-[l,3]dioxin-4-yl)-benzonitrile (Example LI) according to the general procedure M. Obtained as a yellow solid (145 mg).
MS(ISP)535[(M+H)1.
Example MlO
(4-Chloro-5-dimethylamino-2'{3-(2-f3-methyl-isoxazol-5-vIVpvridin-4-yn-3-oxo-propionylaminol-phenyD-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-Carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yl]-3-oxo-propionic acid tert.-butyl ester (Example K6) (170 mg, 0.56 mmol) according to the general procedure M. Obtained as a brown solid (206 mg).
MS (ISP) 514 [(M+H)+] and 516 [(M+2+H)+]; mp 181-183 °C.

Example Mil
(4-CMoro-5-r(2-metfaoxy-ethyl)-methyl-aminol-2-l3-f3-(3-methyl-isoxa2ol-5-yD-phenyl]-3-oxO'propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (165 mg, 0.55 nrniol) according to the general procedure M. Obtained as an amorphous yellow substance (207 mg),
MS (ISP) 557 [(M+H)1 and 559 [(M+2+H)-'].
Example M12
(4-Chloro-5-f(2-methoxy-etfavi)>methyl-aminol-2-l3-(2-f3-methvMsoxazoI-5-yl)-pvridin-4-yI1-3-oxo-propionylaminol-phenyIVcarbamic acid tert.-butylester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-phenyl}-carbamic acid tert,-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4-yI]-3-oxo-propionic acid tert.-butyl ester (Example K6) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (190 mg).
MS (ISP) 558 [(M+H)1 and 560 [(M+2+H)']; mp 148 °C
Example M13
(RS)-f4-Chloro-5-f(2-methoxv-ethyl)-methyl-amino1-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-vIoxvmethyl)- f 1,2,31 triazol-1 -yl] -phenyl-propionylamino)-phenyl -carbamic acid tert.-butvi ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-ethyi)-methyl-amino]-phenyl}-carbamic acid tert.-butyl ester (Example J4) (165 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyi ester (Example K5) (200 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg).
MS (ISP) 657 [(M+H)+] and 659 [(M+2+H)1.

Example M14
U-Chloro-5-[(2-methoxv-ethyl)-methyl-amino1-243-oxo-3-f3Jl,23ltriazol-l-v^ phenyl)-propionylamino]'phenvH-carbamic acid tert--butyl ester
The title compound was prepared from {2-amino-4-chloro-5-[(2-methoxy-eth7l)-methyl-amino]-phenyl}-carbamic acid tcrt-butyl ester (Example J4) (165 mg, 0.5 mmol) and 3-oxo-3-(3-[l,23]tria2oM->1-phenyl)-propionicacid ethyl ester (Example Kl) (165 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (167 mg).
MS (ISP) 543 [(M-hH)--] and 545 [(M+2^H)1.
tompl^Ml?
{4-Chloro-2-f3-(2-cyano-p)Tidin-4-\i)-3-oxo-propionylaminoV5-dimethylamino-phenylj-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethyiamino-phenyl)-carbamic acid tert,-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow solid (155 mg).
MS (ISP) 458 [(M+H)--] and 460 [(M+2+H)+];mp llO°C
Example M16
(4-Chloro-5-dimet3aylamino-2-{3-f3-(2-methyl-2H-pvrazol-3-vD-phenvi1'3*oxO-propionyiaminol-phenyl)-carbamic acid tert.-butylester
The title compoimd was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K7) (180 mg, 0,6 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (160 mg).
MS (ISP) 512 [(M+H)--] and 514 [(M+2+H)+].
- Example M17
(RS)-(5-Dimethylamino-2-(3-oxo-3-(3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fL23ltriazol-l'yl]-phenvU-propionylamino)-4-trifluoromethyl-phen'vdl-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (160 mg, 03

mmol) and (RS)-3 -oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (201 mg, 0-5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (247 mg).
MS (ISP) 647 [(M+H)--].
Example Ml8
(5-Dimethylamino-2-J3-f3-f3-methyl-isoxazol'5-vD-phenyl1-3-oxo-propionylaminoU4'trifluoromethyl-phenyl')-Carbamic acid tert,-butylester
The title compoimd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid terL-butyl ester (Example K4) (151 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (94 mg).
MS (ISP) 547 [(M+H)+].
Example M19
f4-ChlorO'5-dimethylamino-2-{3-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (143 mg, 0,5 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionicacidtert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (176 mg).
MS (ISP) 556 [(M+H)--] and 558 [(M+2+H)+].
Example M20
f4-Chloro--5'dimethylamino--2-B-f3-f3-methoxvmethyl-isoxazol-5-yl)-phenyl)-3-oxo-propionylaminol-phenyl)-carbamic acid tert.-butyl ester
The title compotmd was prepared from (2-ainino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyi ester (Example K9) according to the general procedure M. Obtained as a yellow solid (205 mg).
MS (ISP) 543 [(M+H)T and 545 [(M+2-fH)-*-].

Example M21
(2-r3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino]-5-dimethylamino-4-trifluoromethyl-phenyll-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromet]iyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, LO mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid terL-butyl ester (Example K3) (246 mg, 1.0 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (297 mg).
MS(ISP)492[(M+H)+].
Example M22
(2'-Fluoro-5-[3-(3-imidazol-l-yl-phenyD-3-oxo-propionylamino1-2-(2,2.2-trifluoro-ethoxv)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 6-(3-imidazoH-yl-phenyl)-2,2-dimethyl-[l,3]dioxin-4-one (Example L3) (160 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous brown substance (167 mg).
MS(ISP)492[(M+H)-'].
Example M23
(2'-Fluoro-5-(3-r3-(3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-2-f 2.2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The tide compound was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (160 mg, 0.53 mmol) according to the general procedure M. Obtained as a white solid (40 mg).
MS (ISN) 626 [(M-H)-]; mp 121-123 °C.
Example M24
(2'-FIuoro-5-f3-oxo-3-(34h23ltriazol-l-yl-phenyl)-propiQnylamino1-2-(2,2.2-trifluoro-ethoxy)-biphenyl-4-yl1-carbamic acid tert.-butyl ester
The title compoxmd was prepared from [5-amino-2'-fluoro-2-(2,2,2-trifiuoro-ethoxy)-biphen)d-4-yl]-carbamic acid tert-butyl ester (Example J5) (200 mg, 0-5

mmol) and 3-oxo*3-(3-[l^,3]triazol-l-yl-phenyl)-propionicacid ethyl ester (Example Kl) (150 mg, 0.57 mmol) according to the general procedure M. Obtained as a light yeUow solid (110 mg).
MS (ISP) 614 [(M+H)--]; mp 54-56 °C
Example M25
(RS)-[2^-Fluoro-5-(3-oxo-3-{345-ftetrahvdro-pwan-2-ylox\nmethyl)-fL23ltria2o^ yl1-phenyl}-propionvIamino)-2-('2.2.2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester
The title compound was prepared from [5-amino-2'-fluorO-2-(2,2>2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example J5) (200 mg, 0.5 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (220 mg, 0.55 mmol) according to the general procedure M. Obtained as a yellow oil(100 mg).
Example M26
(RS)-[4-Chloro-5-fethyl-methyl-aminoV2-(3-oxo-3-(3-r5-ftetrahydro-pyran-2-yloxymethyl)-rL23ltriazol-l-yll-phenyll-propionylamino)-phenyl1-carbamicadd tert-butylester
The titlt ipound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)' phenyl]-curbamic acid tert-butyl ester (Example J7) (300 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl|-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (500 mg),
MS (ISP) 627.1 [(M+H)--].
Example M27
(RSVf4-Chloro-5-(methyl-propyl-amino)-2-f3-oxo-3-l3-(5-ftetrahvdro-pyran-2-yIoxvTnethyl]-fl,23ltriazol-l-yl1-phenyIt-propionylamino)-phenyl-carbamicadd tert'butylester
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (402mg, I.O mmol) according to the general procedure M. Obtained as a yellow foam (410 mg).
MS (ISP) 641.3 [(M+H)1.

Example M28
(RS)-r4-Chloro-5-fdiethyl-ammQV2-f3-oxo-3-(3-r5-ftetrahvdro-pyran-2-yloxymethvD- \ 1.231 triazol-1 -yll -phenyl-propionylamino Vphenyll -carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(diethyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J9) (310 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yI]-phenyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg).
MS (ISP) 64L3 [(M+H)+].
Example M29
fRSVI'4-Chloro-5-dimethylamino-2-(3-oxo-3-i3-f3-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol'5-yll-phenyU-propionylamino)-phenyl1-carbamicacidtert.-butyl ester
The title compotind was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert-butyl ester (Example Jl) (143 mg, 0.5 mmol) and (RS)-3-oxo-3-{3- [3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl] -phenyl}-propionic acid tert.-butyl ester (Example K12) (201 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (530 mg).
MS (ISP) 613.1 [(M+H)--] and 615 [(M+2H-H)+].
Example M30
(RS)-r4-CHoro-2-f3-oxo-3-l345-ftetrahvdro-pyran-2-yloxvmetfayl)-[L2,3ltriazol'l-yll -phenyll-propionylaminoV5-pvrrolidin-l'yl-phenyl1 -carbamic acid tert.-butylester
The tide compoimd was prepared from (2-amino-4-chloro-5-pyrrolidin-l-yl-phenyl)-carbaniic acid tert.-butyl ester (Example JIO) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.' butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (228 mg),
MS (ISP) 639 [(M+H)--] and 641 [(M+2+H)+].

Example M31
(5-Dimethylamino-2-^3-r3-(2-metfayl'2H-pvrazol-3-yl)-phenyll-3-oxo-propionylaminQl-4-trifluoromethyI-phenyD-carbainic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (160 mg, 0.5 mmol) and 3-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K7) (150 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow foam (90 mg).
MS (ISP) 546.2 [(M+H)--],
Example M32
fRS)-r4-Chloro-5-dimethylamino-2-f3-B-F3-methyl-4-(tetrahydro-pyran-2-yloxvmethyl)-isoxazol-5-yl] -phenAd}-3-oxo-propionylamino)-phenyl1 -carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethyIamino-phenyO-carbamic acid terL-butyl ester (Example Jl) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]'phenyl}-3-oxo-propionic acid tert-butyl ester (Example K13) according to the general procedure M, Obtained as a light yellow solid (187 mg).
MS (ISN) 626 [(M-H)-] and 628 [(M+2-H)'].
Example M33
fRS)-r4-Chloro-5-fcvclopropvI-methyl-amino)-2-f3-oxo-3-l3-r5-rtetrahvdro-pyran-2-yloxvmethyl)-fl.2.3ltriazol-l-yl]-phenvU-propionylaminoVphenyl]-carbamicacid
tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example JU) (156 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2oH-yl]-phenyll-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as a yellow solid (215 mg).
MS (ISN) 637.1 [(M-H)'] and 639 [(M+2-H)-]; mp 47-49 °C.

Example M34
(5-Dimethylamino-2-l3-f3-(5-dimethylaminomethyl-ri.23ltriazoM-yl)-phenyl-3-oxo-propionvIaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (160 mg, 0.5 rQmol)and3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (172 mg, 0.5 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (195 mg).
MS (ISN) 588 [(M-H)-].
Example M35
(RS)-[4-Chloro-5-dimethylamino-2-f3-l3-(2-methyl'5-ftetrahvdro-pyran-2-yloxvmethyl)-2H-pyrazol-3-yn-phenvU-3-oxo-propionylaminoVphenyn-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-4-chIoro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (200 mg, 0.7 mmol) and (RS)-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K14) (290 mg, 07 mmol) according to the general procedure M. Obtained as an amorphous yellow substance (329 mg).
MS (ISN) 624.0 [(M-H)-] and 626 [(M+2-H)'].
Example M36
{2-[3-(2-cyano-pvridin-4-yl)-3-oxO'propionylamino1-5-pvrrolidin-l-yl-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-pyTrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J12) (173 mg, 0.5 nrniol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (150 mg, 0,61 mmol) according to the general procedure M. Obtained as a yellow solid (140 mg).
MS(ISP)518[(M+H)1-

Example M37
fRS)42-r3-Oxo-3-i3-(5-(tetrahvdro-pyran-2-yloxvmethvD4L23ltriazol-l-yl1-phenvU-propionylamino)-5--pvrrolidin-l-yl'4-trifluorometfayl-phenyl]-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifIuoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J12) (173 mg, 0.5 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-I-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (250 mg, 0.62 mmol) according to the general procedure M. Obtained as an orange foam (168 mg).
MS(ISP)673[(M-hH)+].
Example M38
f RS)- (5-Dimethylamino-4'fluoro-2-(3-0X0-3-13- f 5-f tetrahydro-pyran-2-yloxvmethyl)-fL23ltriazol-l-yn-phenyll-propionylamino)-phenyn-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-fiuoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1,0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid terL-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (417 mg).
MS(ISN)595[(M-H)-].
Example M39
(5-Dimethylammo-2-l3-[3-(5-dimethylaminomethyl'[L2.3ltria2ol-l-vD-phenyl-3-oxo-propionylamino}-4-fluoro-phenyl)-carbamic acid tert.-butyl ester
The title compound was prepared from (2-anfiino-5-dimethylamino-4-£luoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(5-dimethylaminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K8) (344 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (211 mg).
MS(ISN)538[(M-H)-].

Example M40
fRSVr5-Dimetfaylamino-4-fluoro-2-(3-oxo-3-B-r3-(tetrahvdro-pyran-2-yloxymetfavD-isoxazol'5-yl]-phenyl}-propionylamino)-phenyn*carbamic acid tert.-butyl ester
The tide compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid tert-butyl ester (Example J13) (269 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example KI2) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (360 mg).
MS(ISN)595[(M-H)-].
Example M41
(RS)-(5-DimethylaminO'2-f3-oxo-3-{3-f3-ftetrahvdro-pyran-2-yloxvmethyl)-isoxazol-5-yll -phenyl}-propionylamino)-4-trifluoromethyl-phenyl1 -carbamic acid tert.-butyl ester
The title compound was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (565 mg, L77 mmol) and (RS)-3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5-yl]-phenyl}-propionic acid tert.-butyl ester (Example K12) (710 mg, 1,77 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (721 mg),
MS(ISN)645[(M-H)'].
Example M42
(RSV(5-Dimethylamino-4-fluoro-2-r3>oxQ-3-{3-f3-ftetrahvdro-pyran-2-yloxymethyl)-isoxa2ol-5-yn-phenyl}-propionylamino)-phenyiVcarbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example J13) (269 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M- Obtained as a yellow amorphous substance (273 mg).
MS(ISP)497l(M-f-H)-'].

Example M43
fRSVf4-ChloTu-5-dimethylamino-2-f3-oxo-3-B45-rtetrahvdro-pyran-2-yloxvmethyl)-isoxazol-3-vn -phenyll-propionylamino)-phenyll -carbamic acid tert.* butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionic acid tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam
(232 mg).
MS (ISN) 611.1 [(M-H)-] and 613 [{M+2-Hr].
Example M44
(RSVf4-ChIoro-2-(3-oxo-3-l3-r5-ftetrahvdro-pyran-2-yIoxvmethyl)-[L23ltriazol-l-yIl-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl1-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-piperidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example J14) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) according to the general procedure M. Obtained as a yellow foam (257 mg).
MS (ISP) 653.2 [(M+H)+] and 655 [(M+2+H)1.
Example M45
(RS)-f5'Dimethylamino-2-(3-oxQ-3-l3-r5-(tetrahydro-pyran-2-yloxymethyD-isoxazol-3-yl1 -phenyll-propionylamino)-4-trifluoromethyl-phenyn -carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl] -phenyl}-propionic acid tert.-butyl ester (Example K15) according to the general procedure M. Obtained as a light yellow foam (224 mg).
MS (ISP) 647.2 KM+H)--].

Example M46
{4-ChIoro-5-dimethylamino-2-f3-OXo-3-(3-pyrazol-l*yl-phenyl)-propionyIamino]-phenyl}-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) and 3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propionic acid tert.-butyl ester (Example K16) according to the general procedure M. Obtained as a light yellow solid (135 mg).
MS (ISP) 498 [(M-hH)--] and 500 [(M+2+Hr]; mp 148-149 °C.
Example M47
{2-r3-(2-Cyano-pyridin-4-yI)-3-oxo-propionyIaminol-4-fluoro-5'pyrrolidin-l-yl-phenyU-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert,-butyl ester (Example 115) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (196 mg).
MS (ISP) 468 [(M+H)']; mp 231 °C (dec).
Example M48
(4-Fluoro-2-l3-[3-(3-methyl-isoxa2oI-5-yl')-phenvI1-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-fiuoro-5-pyrrolidin-l-yl-phenyl)-carbamic acidtert,-butyl ester (Example Jl5) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propiomc acid tert.-butyl ester (Example K4) according to the general procedure M. Obtained as a light yellow solid (126 mg).
MS (ISP) 468 [(M+H)+]; mp 186 °C
Example M49
fRS)-[4-Fluoro-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-rL23ltria2ol-l-yl1-phenvU-propionylamino)-5-pyrroIidin-l-yl-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-fluoro-5-pyrrolidiQ-l-yl-phenyl) carbamic acid tert-butyl ester (Example Jl5) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>23]triazol-l-yi]-phenyl}-propionic acid terL-but)i ester

(Example K5) according to the general procedure M. Obtained as an orange viscous oU (268 mg).
MS(ISP)623[(M+Hr].
Example M50
l5-Azetidin-l-yl-4-chloro-2-[3-r2-cyano-pyridin-4-vI)-3-oxo-propionylamino]-phenvU-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-chloro-phenyl)-carbamic acid tert.-butyl ester (Example J16) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a yellow solid (142 mg).
MS (ISP) 470 [(M+H)--] and 472 [(M+2+H)']; mp 168 °C (dec).
Example M51
fRSV(2-f3-Oxo-3-l3-[5-(tetrahydro-pyran'2-ylQxymethyD-isoxazol-3-yll'phenyll-propionylaminoVS-pyrrolidin- l-yl'4-trifluoromethyl*phenyl -carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI2) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yIoxymethyI)-isoxa2oI-3-yl]-phenyl}-propionicadd tert-butyl ester (Example K15) according to the general procedure M. Obtained as a yellow foam (522 mg).
MS (ISN) 671.2 [(M-H)-],
Example M52
l5'Azetidin-l-yl-2-(-3-(2-cyano-pvridin-4-yl)-3-oxo-propionylamino1'4-trifluoromethyl-phenylt-carbamic acid tert.-but\^ ester
The title compound was prepared from (2-aminO-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J17) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light yellow solid(131 mg).
MS (ISP) 470 [(M+H)--]; mp 166-167 °C.

Example M53
(5-Azetidin-l-yl-2-B-r3-f3-m€thyl-isoxa2ol'5-yl>>phenyll-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert.'butylester
The tide compound was prepared from (2-amino-5-azetidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Lxamplc J17) and 3-[3-(3-methyHsoxazol-5-yl)-phenyl]-3-oxo-propionic acid tcrL-but)1 ester (Example K4) according to the general procedure M. Obtained as a light ycUow foam (218 mg).
MS (ISN) 557.2 [(M-H)']; mp 83-84 *C
fRSV[5-Azetidin-l-yl-2-(3-oxo>3- fh23ltria2ol-l-yl1-phenyll-propionylamino)-4-trifluoromethyl-phenyll'Carbamic
acid tert.-butylester ——.^1 ,11-1. ,
The title compound was prepared from (2-amino-5-a2etidin-l-yl-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example JI7) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoI-l-yi]-phen)d}-propionic acid tert-butyl ester (Example K5) according to the general procedure M, Obtained as a yellow foam (450 mg).
MS (ISN) 657.1 [(M-H)']; mp 76-77 X.
Example M55
{5-Dimethylamino-2-[3-OXO'3-(3-pyra2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl'phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (319 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (485 mg),
MS (ISN) 530 [(M-H)+].
Example M56
t5-Dimethylamino-2-f3-QXo-3-f3-fl.2.4ltriazol-4-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoromethyl-phenyi)-carbamic acid tert-butyl ester (Example J6) (383 mg, 1.2

mmol) and 3-oxO-3-(3-[l,2,4]triazol-4-yl-phenyl)-propionic acid ethyl ester [CAS-No. 335255-97-5] (259 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow solid (290 mg).
MS (ISP) 533.3 [(M-i-H)l; mp 58-62 °C.
Example M57
(5-Dimethylamino-2-f3-r3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)--Carbamic acid tert-butyl ester (Example J6) and 6-(3-imidazol-l-yl-phenyl)-2>2-dimethyl-[l,3]dioxin-4-one (Example L3) according to the general procedure M. Obtained as an orange oil (238 mg).
MS(ISP)432[(M+H)'].
Example M58
(RS)-f4-Chloro-5-dimethylamino-2-f3-oxo-3-(3--f4-(tetrahydrQ-pyran-2-ylQxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyI]-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (429 mg, L5 mmol) and (RS)-3-oxo-3- {3- [4- (tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl} -propionic acid tert.-butyl ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M, Obtained as a yellow amorphous substance (710 mg).
MS (ISN) 610 [(M-H)-] and 612 [(M+2-H)'l.
Example M59
fRSV(5-Dimethylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-yloxvmethvD-pyrazol-l-yl'|-phenvU-propionylamino)-4-trifluoromethyl-phenyIl-carbamicacid tert.-butyl ester
The title compoimd was prepared from (2-aminO-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) (479 mg, 1.5 mmol) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yioxymethyi)-pyrazol-l-yl]-phenyl}-propionic acid tert-butyi ester (Example K17) (601 mg, 1.5 mmol) according to the general procedure M. Obtained as a piiik amorphous substance (641 mg).
MS (ISN) 644 [(M'H)-].

Example M60
fRS)'[5-Dimethylamino-2-(3-B-[3-methyl-4-('tetrahvdrO'pyran-2-vIoxymethyl)-isoxa2ol-5'yI]-phenyn*3-oxo-propionylamino)-4-trifluoromethyl-phenyI1-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-{3-[3-methyl-4-(tetrahydro-pyran-2-yIoxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionic acid tert.-butyl ester (Example K13) according to the general procedure M. Obtained as a red oil (424 mg).
MS (ISN) 626 [(M-H)-].
Example M61
fRSV(5-Dimetfaylamino-2-(3-oxo-3-l3-f4-ftetrahvdro-pyran-2-vioxvmetfayl)-isoxazol-S-yll -phenyl KpropionylaminoV4-trifluoromethyl-phenyn -carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionicadd terL-butyl ester (Example K18) according to the general procedure M. Obtained as a light yellow solid(145 mg).
MS(ISP)647[(M+Hn.
Example M62
(RSV(5-DimethyIamino-2-(3'[3-(2-methylsuIfanvI-imidazoI-l-yl)-phenyl-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-tri£luoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) (319 mg, 1-0 mmol) and 3-[3-(2-methylsulfanyI-imida2oI-l-yl)-phenyI]-3-oxo-propiomcadd tert-butyl ester [CAS-No. 335256-01-4] (432 mg, 1.3 mmol) according to the general procedure M. Obtained as a light brown amorphous substance (493 mg).
MS (ISP) 333.2 [(M+H)--].

Example M63
fRSVr5-Dimethylamino-2-(3-(3-(2-methyl-4-(tetrahvdro-pyran-2-ylQXvmethyl)-2H-pyra2o]-3-yl1-phenyil-3'OXo*propionylaminoV4'trifluorometfayl-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and (RS)-3-{3-[2-methyl-4-(tetrahydro-pyran-2-ylox)Tneth>1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionic acid tert-butyl ester (Example K19) according to the general procedure M. Obtained as a light red solid (576 mg).
MS (ISN) 658 [(M-H)-].
Example M64
l4-Chloro-5-dimethylamino-2-f3-oxo-3-f 3-| 1 >2,4]tria2ol-l-yl-phenyl)* propionylamino1-phenyll*carbamic acid tert.-butyl ester
The title compo d was prepared from (2-amino-4-chloro-5-dimethylamino-phenyi)-carban. dcid terL-but)d ester (Example Jl) and 3-oxo-3-(3-[l>2,4]tria2ol-l-yl-phenyl)-propionic acid tert-but)d ester [G\S-No, 335255-88-4] according to the general procedure M. Obtained as a light yellow solid (427 mg).
MS (ISN) 497 [(M-H)-] and 499 [(M+2-H)-].
Example M65
{5-Dimethylamino-2-f3-oxo-3-(3-[l,2,4]triazoM-yl-phenyl)-propionylaminol-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-anuno-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid terL-butyl ester (Example J6) and 3-oxo-3-(3' [l>2,4]triazol-l-yl-phenyi)-propionic acid tert-butyl ester [CAS-No. 335255-88-4] according to the general procedure M. Obtained as a light red solid (502 mg).
MS(ISN)531[(M-H)-].
. Example M66
{2-[3-(3-cyano-phenyl)-3-oxo-propionylamino1-5-dimeth^amino-4-trifluorometh^^-phenyll-carbamic acid tert.-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (320 mg, 1-0 mmol) and 3-(2,2-dimethyi-6-oxo-6H-[13]dioxin-4-yl)-benzonitrile (Example LI)

(275 mg, 1.2 mmol) according to the general procedure M. Obtained as a reid viscous oil (196 mg).
MS (ISN) 489.1 [(M-H)-].
Example M67
fRS)-r5-fCvcIopropvImethyl-methyl-amino)-2-f3-oxo-3-{3-(5-ftetrahvdrO'pyran-2-yloxvinethyD - [ 1,231 triazol- l-yl1 -phenyl! -propionylamino V4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-anmio-5-(cyclopropylmethyl-methyl-amino)-4-trxfluoromethyI-phenyl]-carbamicacid tert,-butyl ester (Example JIS) (719 mg, 2.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert.-butyl ester (Example K5) (803 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (985 mg).
MS (ISP) 687 [(M+H)+].
Example M68
[2-f3-(2-Cyano-pyridin-4-yl)-3-oxo-propiQnvIamino]-5-fcyclopropylmethyI-metfayl' amino)-4-trifluorometfayl-phenyl-carbamic acid tert.-butylester
The title compound was prepared from [2-amino-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example JIB) (180 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) (123 mg, 0.5 mmol) according to the general procedure M. Obtained as a yellow amorphous substance (206 mg).
MS (ISP) 532 [(M+H)+].
Example M69
(RS)-l5-Dimethylamino-2-r3-oxo-3-f3-{2-r2-(tetrahvdro-pyran-2-yloxvVethyl1-2H-pvrazoI-3-yll-phenyl)-propionylaminol-4-trifluoromethyl-phenyn-carbamicacid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifiuoro-methyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (639 mg, 2.0 mmol) and (RS)-3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-2H-pyrazol-3-yl}-phenyl)-propionic acid tert-butyl ester (Example K20) (829 mg, 2.0 mmol) according to the general procedure M. Obtained as a pink amorphous substance (272 mg).

MS (ISN) 658 [(M-H)-].
Example M70
(2-r3-(2-cyano-pvridin-4-yl)-3-OXo-propionylaminoV5-fcvclopropyl-methyl-aminoV4-trifluoromethyl-phenyl-carbamic acid tert.-butyl ester
The title compound was prepared from [2-amino-5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example J19) (259 mg, 0.75 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert,-butyl ester (Example K3) (192 mg, 0.78 mmol) according to the general procedure M. Obtained as a yellow solid (228 mg).
MS (ISN) 516.2 [(M-H)-]; mp 114-116 °C.
Example M71
{2-Dimethylamino-2'-fluoro-5-f3-oxo-3-f3-fL23ltriazQl-l-yl-phenyl)-propionylamino1-biphenyl-4-yU-carbamic acid tert-butyi ester
The title compound was prepared from (5-amino-2-dimethyIamino-2'-fluoro-biphenyl-4-yl)-carbamic acid tert.-butyl ester (Example J20) (691 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazoM-yl-phenyl)-[l,3]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a yellow solid (820 mg).
Mp 125-135 °C.
Example M72
(RSyl5-Dimethylamino-2-[3-oxo-3-(3-l5-(2-ftetrahvdro-pyran-2-yloxvVethyll-fl.23ltria2ol-l-yll-phenyl)-propionvIamino1-4-trifluoromethyl-phenvU-carbamic acid tert,-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,2,3]triazol-l-yl}-phenyl)-propionicacid tert-butyl ester (Example K21) according to the general procedure M. Obtained as a light red oil (527 mg).
MS (ISP) 577 [(M+H)--].

Example M73
fRS)-[5-Dimethylamino-2-(3-oxo-3-f3-(5-ftetrahvdro-pyran-2-yloxvmethyl)-pyrazol-l-yl]-phenyll-propionylamino)-4-trifluoromethyl-phenyl1-carbamicacid tert.-butylester
The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert.-butyl ester (Example J6) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionic acid ethyl ester (Example K22) according to the general procedure M. Obtained as a brown oil (179 mg).
MS (ISP) 646 [(M+H)-*].
Example M74
(5-Dimetfaylamino-2-f3-oxo-3-('3-[L23ltriazoM-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert.-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert,-butyl ester (Example J6) (639 mg, 2.0 mmol) and 2,2-dimethyl-6-(3-[l,2,3]triazol-l-yl-phenyl)-[13]dioxin-4-one (Example L4) (543 mg, 2.0 mmol) according to the general procedure M. Obtained as a red solid (915 mg).
MS (ISP) 533,3 [(M+H)+]; mp 79-81 °C.
Example M75
[2-f3-(2-cyano-pyridin-4-yl)'3-oxo-propionylamino1-5-(2,2.2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester
The title compound was prepared from [2-amino-5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J21) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert.-butyl ester (Example K3) according to the general procedure M. Obtained as a light brown s.olid (262 mg).
MS (ISN) 545.0 [(M-H)']; mp 158 *°C (dec).

Example M76
l2-[3-(3-cyano-phenyl)-3-oxQ-propionyIamino1-4-dimethylaminO'5-methyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (300 mg, 1.0 mmol) and 3-(3-cyano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (250 mg> 57%).
MS (ISP) 437.4 [(M+H)--].
Example M77
(RSV[5-DimethylaminO'4-methyl'2-(3-oxo-3-{3'[5-(tetrahydro-pyran-2-yloxvmethyl)-fl.2.3ltria2ol-l-yl1-phenyU-propionylaminoVphenyl]-carbamicadd tert-butylester
The title compound was prepared from (2-amino-5-dimethylamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
add tert-butyl ester (Example K5) (402 mg, 1-0 mmol) according to the general procedure M. Obtained as a yellow foam (420 mg, 71%).
MS (ISP) 593.5 [(M+H)--].
Example M78
{5-Cyano-2-f3-(3-cyano-phenyl)-3-oxo-propionylamino1-4-dimethylamino-phenyl}-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-dimethylamino-phenyl)-carbamic acid tert-butyi ester (Example J23) (276 mg, 1.0 mmol) and 3-(3-cyano-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a brown foam (290 mg, 65%).
MS (ISP) 448.3 [(M+H)--].

Example M79
[2-f3-f3-cyano-phenvD-3-oxo-propionylamino]-5-methyI-4*fmethyl-propyl-amino)*phenv]]-carbamic acid tert-butylester
The title compound was prepared from [2-aminO-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (293 mg, 1.0 mmol) and 3-(3-qrano-plienyl)-3-oxo-propionic acid tert-butyl ester (Example K2) (245 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (170 mg, 37%).
MS (ISP) 463.3 [(M-H)-],
Example M80
(RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-l3-(5-(tetrahvdro*pyran-2-yloxymethvD-[l,2,3ltriazoI-l-vI]-phenvU-propionylamino)-phenyl'Carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-pheiiyl}-propionic acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (350 mg, 56%).
MS (ISP) 621.2 [(M+H)1.
Example M81
fRSV[5-fEthyl-methyl-aminoV4'methyl-2-(3-QXo-3-(3-(5-(tetrahvdro-pyran-2-yloxymethvD-fL2.3ltriazol-l-yl]-phenyI}-propionylamino)-phenyl-carbamicacid
tert-butylester
The title compound was prepared from [2-amino-5-(ethyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J25) (279 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic
acid tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (400 mg, 66%).
MS (ISP) 607.1 [(M+H)1.

Example M82
(RSVf4-cyano-5-dimethylamino-2-(3-oxo-3-(3-(5-ftetrahvdro>pyran-2-yloxvmethyl)-fl.23ltriazol-l-yl1-phenyU-propionylamino)-phenyll-carbamicadd tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-dimethylaminO-phenyl)-carbamic acid tert-butyl ester (Example J23) (276 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyi}-propionicadd tert-butyl ester (Example K5) (402 mg, 1.0 mmol) according to tiie general procedure M. Obtained as a light brovm foam (360 mg, 59%).
MS (ISP) 602.1 [(M-H)1.
Example M83
fRS)-[4-Chloro-5-fisopropyl-methyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyl)-Fl,2,3ltriazol-l-yll-phenyl}-propionylamino)-phenyl)-carbamicadd tert-butyl ester
The title compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J26) (300 mg, 0.96 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (383 mg, 0.96 mmol) according to the general procedxire M. Obtained as a light yellow oil (530 mg, 86%).
MS (ISP) 639.2 [(M-H)-].
Example M84
[4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyn-3-oxo-propionylaminol-5-(methyl-propyl-amino)-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyi]-carbamic acid tert-butyl ester(Example J24) (293 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 65%)!
MS (ISP) 519.3 [(M-H)'],

&tapiple M?5
(4-Cyano-5-dimethylamino-2- The tide compound was prepared from (2-amino-4-q^ano-5-dimethylaxnino-phenyl)-carbamic acid tert-butyl ester (Example ]23) (276 mg, 1.0 mmol) and 3-[3-(3*methyl-isoxazol-5-yl)-phenyI]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (320 mg, 64%).
MS (ISP) 504.3 [(M+H)+].
(5-(£thyl-methyl-amino)-4-methv'i-2-(3'[3-(3-methyi-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester
The title compoiund was prepared from {2-amino-5-(cthyl-methyi-amino)-4-methyl-phenyl]-carbamic acid tert-but)d ester (Example J25) (279 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M, Obtained as a brown foam (390mg,77%).
MS (ISP) 505.3 [(M-H)'].
Example M87
(5-Dimethylamino-4-methyI-2-l3-[3-f3-methyl-isQxazol-5-yl)-phenyll-3-oxo-propionylaminol-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-5-dimethyiamino-4-methyl-phenyl)-carbamic acid tert-butyl ester (Example J22) (265 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yi)-phen)d]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, LO mmol) according to the general procedure M. Obtained as a brown foam (330 mg, 67%).
MS(ISP)49L3[(M.H)'].

Example M88
fRS)-f4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxymethyl)-fh23ltria2ol-l-yl]-phenyn-propionylamino)-phenyl]-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-cliloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,3]triazol-l-yi]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 50%).
MS (ISP) 655.1 [(M+H)--].
Example M89
(4-Chloro-5-fisobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl')-phenyl-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carban[iic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (360 mg, 65%).
MS (ISP) 555.1 [(M+H)1.
Example M9Q
fRS)-[4-cyano-2-(3-oxo-3-B-(5-ftetrahvdro-pyran-2-yloxvmethyl)-ri.23ltriazol-l-ylj-phenvD-propionylaminoVS-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-)doxymethyi)-[l,2,3]tria2ol-l-yl]-phenyl}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light orange foam (380 mg, 60%).
MS (ISP) 630.1 [(M+H)--].

Example M91
(4-cyano-2-(3-f3-f3-methyl-isoxazol-5-vD-phenvI1-3-oxo-propionylamino}-5-pvrrolidin-1-yl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-cyano-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J28) (302 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-ph€nyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 79%).
MS (ISP) 530.2 [(M+H)+].
Example M92
(RSV[4-cyano-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvTnethyl)-fL2.3ltriazol-l-yn-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (440 mg, 70%).
MS (ISP) 630-1 [(M+H)+].
Example M93
f4-cyano-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-5-(methyl-propyl-aminoVphenyll-carbamic acid tert-butylester
The title compoimd was prepared from [2-amino-4-cyano-5-(methyl-propyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J29) (304 mg, 1.0 namol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (370 mg, 70%).
MS (ISP) 532.3 [(M+H)+].

Example M94
(4-cyano-5-diethylamino-2-{3-[3-f3-methyl-isoxazol-5-yl)-phenyl-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-diethylamino-phenyl)-carbamic acid tert-butyl ester (Example J30) (304 mg, LO mmol) and 3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo- propionic acid tert-butj^l ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (360 mg, 68%).
MS (ISP) 530.2 [(M+H)--].
Example M95
(4-Cyano-5-(isopropyl-methyl-aminoV2-l3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 71%).
MS (ISP) 530.2 [(M-H)'].
Example M96
(RS)-f4-Cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-r5-(tetrahvdro-pyran-2-yIoxvTnethyl]-[L2.3ltriazol-l-yl]-phenyl}-propion)damino)-phenyl]-carbamicadd tert-butylester
The title compound was prepared from [2-amino-4-cyano-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J31) (304 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (460 mg, 73%).
MS(ISP)630.1[(M-H)-].

Example M97
(4-cyano-5-fisobutyl-methyl-amino)-2-l3-f3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyD-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M, Obtained as a light brown foam (400 mg, 73%).
MS (ISP) 544.3 [(M-H)'].
Example M98
(RSVT4-cyano-5-(isobutyI-methyl-aminoV2-(3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxvmethyl)-fl,2.3ltriazol-l-yll-phenvU-propionylamino)-phenyll-carbamicacid
tert-butyl ester
—■'■■> -
The title compound was prepared from [2-amino-4-cyano-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J32) (318 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a yellow foam (470 mg, 73%).
MS (ISP) 644.2 [(M-H)-].
Example M99
(4-cyano-2-(3-f3-f3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-5-piperidin-l-yl-phenvD-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-cyano-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J33) (316 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M. Obtained as a light brown foam (420 mg, 77%).
MS (ISP) 544.2 [(M+H)+].

Example MlOO
(4-Chloro-5-isobutylamino-2-l3-f3-f3-methyl-isoxazol-5-vD-phenyl-3-oxo-propionylaminol-phenvD-carbamic acid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-isobut7lamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1-0 mmol) according to the general procedure M, Obtained as an off-white foam (340 mg, 63%).
MS (ISP) 542.2 [(M+H)--].
Example MlOl
fRSVf4-Chloro-5-isobutylamino-2-f3-oxo-3-l3-(5-(tetrahvdro-pyran-2-yloxymethyl)-FL2.3ltriazol-l-yl'|-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (314 mg, 1.0 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyI}-propionicadd tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a red oU (180 mg, 28%).
MS (ISP) 640.2 [(M-H)-].
Example Ml02
(RS)-[5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxvmethyl) - [ 1,231 triazol-1 -yll -phenyll -propionylamino) -4-trifluoromethyl-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (380 mg, L09 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (439 mg, 1.09 mmol) according to the general procedure M. Obtained as a red foam (150 mg, 20%).
MS (ISP) 675.4 [(M-H)'].

Example M103
(2-{3-f3-f3-methyl-isoxazol-5-vI)-phenyl1-3-Qxo-propionylaminol-5-fmethyl-propyl-aminQV4-trifluoromethyl-phenyl'|-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]'Carbamic acid tert-butyl ester (Example J35) (360 mg, L04 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (312 mg, 1.04 mmol) according to the general procedure M-Obtained as a light red foam (270 mg, 45%),
MS (ISP) 573.2 [(M-H)-].
Example M104
(RSV[5-(I$obutyl-methyl-aminoV2-(3'Oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxymethyl')'[L2^3ltriazol-l-yll-phenvU-prQpionylamino)-4-trifluorometh\d-phenyl]-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutjd-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J36) (370 mg, 1.02 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (411 mg, 1.02 mmol) according to the general procedure M. Obtained as a light brown foam (520 mg, 74%).
MS (ISP) 687.2 [(M-H)'].
Example M105
(5-fIsobutyl-methyl-aminQV2-{3'f3-(3-methyl-isoxa2ol'5-yl)-phenyl)-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)--carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(i$obutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J36) (360 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (302 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (430 mg, 73%).
MS (ISP) 587.3 [(M-H)-].

Example M106
fRSV(5-fIsopropyl-methyl-amino)-2-f3-oxQ-3-{3-(5-ftetrahvdrO'pyran-2-yloxvmethyl)-fL23ltria2oM-yl]-phenyll-propionylaminoV4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isopropyl-methyl-ancuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (340 mg, 0.98 mmol) and (RS)-3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)- [ l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (393 mg, 0.98 mmol) according to the general procedure M. Obtained as alight yellow foam (510 mg, 77%).
MS (ISP) 673,3 [(M-H)-].
Example M107
('5-(Isopropyl-metfayl-aminoV2-(3-f3-(3-methyl-isoxazol-5-yl)-phenyl1-3-oxo-propionylaminol-4-trifluoromethyl-phenyl)-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isopropyl-methyl-anuno)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J37) (350 mg, 1.01 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (304 mg, 1.01 mmol) according to the general procedure M. Obtained as a light brown foam (380 mg, 66%).
MS (ISP) 573.2 [(M-H)-].
Example M108
(RSV(5-(Isobutyl-methyl-aminoV4-methyl-2-f3-oxo-3-{3-r5-ftetrahvdro-pyran-2-yloxvmethyl)-[L2.3ltriazol-l-yl1-phenyll-propionylamino)-phenyl]-carbamicacid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenylj-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and (RS)-3-oxo-3-(3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 52%).
MS (ISP) 635.2 [(M+H)--].

Example M109
(5-fIsobutyl-methyl-aminoV4-methyl-2-{3-[3-f3-methyl'isoxazol-5-yl)-phenyl1-3-oxo-propionylamino}'phenyl)-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (307 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 62%).
MS (ISP) 535.4 [(M+H)1.
Example Ml 10
(RS)-[4-methyl-2-(3-oxo-3-f3-(5-(tetrahvdro-pyran-2-yloxvmethvD-rL2,3ltriazol-l-yI]-phenyl}-propionylaminoV5-pyrrolidin-l-yl-phenyn-carbamic acid tert-butylester
The title compoimd was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester acid tert-butyl ester (Example J39) (292 mg, 1.0 imnol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (410 mg, 66%).
MS (ISP) 619,3 [(M+H)1.
Example Mill
(4-Methyl-2-{3-f3-(3-methyl-isoxazol-5-yiVphenyl]-3-oxo-propionylaminol-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-methyl-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example J39) (291 mg, 1.0 mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown foam (330 mg, 64%).
MS (ISP) 517.3 [(M-H)1.

Example Ml 12
(4'-Chloro-5-isQprQpylamino-2-{3-[3-f3-methyl-isoxa2ol-5-yl)-phenyl1-3-oxo-propionylaminol-phenyl)-carbamic acid tert-butylester
The title compoimd was prepared from (2-amino-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and 3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-0X0- propionic acid tert-butyl ester (Example K4) (301 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brovm foam (169 mg, 32%).
MS (ISP) 525.2 [(M-H)-].
Example Ml 13
fRS)-f4-Chloro-5-isopropylamino-2-(3-oxo-3-{3-(5-ftetrahvdro-pyran-2-yloxvmethyD-ri,23]triazol-l'-yl1-phenyll-propionylamino)-phenyl1-carbamicacid tert-butylester
The title compoxmd was prepared from (2-andno-4-chloro-5-isopropylamino-phenyl)-carbamic acid tert-butyl ester (Example J40) (300 mg, LO mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K5) (401 mg, LO nunol) according to the general procedure M. Obtained as a light yellow foam (375 mg, 60%).
MS (ISP) 625.1 [(M-H)-].
Example Ml 14
(RS)-r4-Chloro-5-(methyl-propyl-aminoV2-(3-oxo-3-{3-[5-ftetrahvdro-pyran-2-yloxymethyD-[l,2,4ltriazol-l-yl]-phenyll-propionylamino)-phenyll-carbamicacid tert-butylester
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J8) (LOg, 3,19 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yIoxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (L28 g, 3.19 mmol) according to the general procedure M. Obtained as a yellow foam (L48 g).
MS (ISP) 641.3 [(M+H)--].

Example Ml 15
fRSVr4-Chloro-5-fisobutyl-methyl-aminoV2-(3-oxo-3-l3-(5-ftetrahydro-pyran-2-yloxymethyl)-[L2,4ltriazol-l-yl]-phenyl}-propionviamino)-phenyl1-carbamicacid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example J24) (1.0 mg, 3.05 mmol) and(RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.22 g, 3.05 mmol) according to the general procedure M. Obtained as a light brown foam (620 mg, 31%).
MS (ISP) 655.1 [(M+H)1.
Example Ml 16
fRS)-l'5-(Isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-J3-(5-(tetrahvdro-pyran-2-
yIoxvmethyl)-fl.2,4ltriazol-l-yl1-phenyU-propionylamino')-phenyl1-carbamicacid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-methyl-phenyl]-carbamic acid tert-butyl ester (Example J38) (1.0 g, 3.25 mmol) and (RS)-3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,4]tria2ol-l-yl]-phenyl}-propionic acid tert-butyl ester (Example K24) (1.31 g> 3.25 mmol) according to the general procedure M. Obtained as a light yellow foam (970 mg> 47%).
MS (ISP) 635.2 [(M+H)1.
Example Ml 17
{5-(methyl-propyl-aminoV2-F3-oxo-3-f3-fL2.4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvD-carbamic acid tert-butylester
The title compound was prepared from [2-ainino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (320 mg, 57%).
MS (ISP) 561.4 [(M+H)1.

Example M118
i5-(Methyl-propyl-aminQV2-f3-oxo-3-(3-fl,23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvU-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J35) (347 mg, 1.0 mmol) and 3-oxO-3-(3-[l>2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light brown oil (340 mg, 61%).
MS (ISP) 561.3 [(M+H)1.
Example Ml 19
l5-fIsobutyl-methyl-amino)-2-[3-oxo-3-r3-pvra2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J40) (361 mg, 1.0 mmol) and 3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K16) (286 mg, LO mmol) according to the general procedure M. Obtained as a light brown foam (500 mg, 87%).
MS (ISP) 574.2 [(M+H)1.
Example M120
r2-f3-('2-cyano-pyridin-4-yl)-3-oxo-propionylamino1-5-fisopropyl-methyl-amino)-4-trifluoromethyl-phenyl1-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isoproyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J37) (500 mg, 1,44 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (355 mg, 1.44 mmol) according to the general procedure M. Obtained as a light orange oil (670 mg, 90%).
MS (ISP) 518.1 [(M-H)-].
Example M121
U-Chloro-5-fisobutyl-methyl-aminoV2-[3-oxo-3-f3-fL2,4ltriazol-l-yl-phenvi)-propionylaminol-phenvU-carbamic acid tert-hutyl ester
The title compound was prepared from [2-amino-4-chloro-5-(isobutyi-methyi-amino)-phen)i]-carbamic acid tert-butyl ester (Example J27) (500 mg, 1.53 mmol)

and 3-oxo-3-(3-[l,2,4]tria2ol-l-yi-phenyl)-propionic acid tert-butyl ester (Example K25) (438 mg, L53 mmol) according to the general procedure M. Obtained as a light orange foam (700 mg, 85%).
MS (ISP) 539.2 [(M-H)-].
{5-(Isobutyl-methyI-amino)-2-f3*0!(o-3'f3-fl.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluorometh>i-phen\il'Carbamic acid tert-butyl ester
The title compound was prepared from l2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example J36) (361 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2oM->1-phcn>'l)-propionic acid tert-butyl ester (Example K25) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light red foam (490 mg, 85%).
MS (ISP) 575.2 [(M+H)*-].
Example Ml23
l4-Chloro-5-(isobutyl-methyl-amino)-2-f3-oxo-3-f3-fh2.3]triazol-I-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-4-chioro-5-(isobutyl-methyI-amino)-phenyl]-Carbamic acid tert-butyl ester (Example J27) (328 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as an orange oil (250 mg, 46%).
MS (ISP) 539.2 [(M-H)-].
Example Ml24
{5-fIsobutyl-methyl-aminoV2-f3-QXo-3-f3-[L2.3ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenvmcarbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isobutyl-methyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (460 mg, 1.27 mmol) and 3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionic acid tert-butjd ester (Example K23) (364 mg, 1.27 mmol) according to the general procedxire M. Obtained as ahght brown oil (480 mg, 69%).
MS (ISP) 573.1 [(M-H)-].

Example M125
(2-f3-r3-Imidazol-l-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-4-trifluoromethyl-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg> 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 iiunol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 77%).
MS (ISP) 558.2 [(M-H)-].
Example M126
{4-Chloro-2-[3-f3-imidazol-l-yl-phenyl)-3-oxo-propionylamino1-5-isobutylamino-phenyll-carbamic acid tert-butyl ester
The title compound was prepared from (2-amino-4-chloro-5-isobutylamino-phenyl)-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-(3-imidazol-l-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (Example K26) (286 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (330 mg, 63%).
MS (ISP) 524.1 [(M-H)'].
Example M127
{4-Chloro-5-fisobutyl-aminoV2-r3-oxo-3-f3-[1.23ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-ainino)-phenyl]-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a pale brown foam (220 mg, 42%).
M^:iSP) 525.1 [(M-H)1.

Example M128
(5-fIsobutyl-aminQV2-f3-oxO'3-(3-fL23ltria2ol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyU-carbamic acid tert-butyl ester
The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoro-methyl-phenyl]-carbamic acid tert-butyl ester (Example J41) (347 mg, LO mmol) and 3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K23) (287 mg, 1.0 mmol) according to the general procedure M. Obtained as a light yellow foam (340 mg, 60%).
MS (ISP) 559.2 [(M-H)-].
Example Ml29
H-Chloro-5-('isobutyl-aminoV2-f3-oxo-3-f3-fL2,4ltriazol-l-yl-phenyl)-propionylaminol-phenyll-carbamic acid tert-butyl ester
The title compoimd was prepared from [2-amino-4-chloro-5-(isobutyl-amino)-phenylj-carbamic acid tert-butyl ester (Example J34) (313 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M, Obtained as a light ydlow foam (390 mg, 74%).
MS (ISP) 525.1 [(M-H)-].
Example Ml30
{5-('Isobutyl-aminoV2-f3-oxo-3-f3-[1.2,4ltriazol-l-yl-phenyl)-propionylamino1-4-trifluoromethyl-phenyll-carbamic acid tert-butylester
The title compound was prepared from [2-amino-5-(isobutyl-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (Example J41) (347 mg, 1.0 mmol) and 3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionic acid tert-butyl ester (Example K25) (287 mg, 1,0 mmol) according to the general procedure M. Obtained as a light yellow foam (430 mg, 11%).
MS (ISP) 559.2 [(M+H)--],

General procedure N:
Preparation of 4-aryl-13-dihvdro-benzofb1 f L4ldiazepin-2-ones:
A solution or suspension of the {2-[3-arj4-3-oxo-propionylamino]-phenyl}-carbamic acid tert-butyl ester or {2-[3-aryi-3-oxo-propionyIamino]-phenyl}-carbamic acid tert-butjd ester (1.0 mmol) in CH2Cl2 (5 mL) (anisolc or l^-dimethoxybenzene (5-15 mmol) can be acided if necessary] was treated with TFA (0.5-5.0 mL) at 0 '°C and stirring was continued at 23 °C until tic indicated complete consumption of the starting material.
Worlcup procedure a: The solvent was removed in vacuum, the residue treated with little ether, whereupon it crystallized. The solid vas stirred with sat. NaHCOs-sol. or IM NaaCOs-sol., filtered, washed with H2O and ether or mixtures of ether/THF/MeOH and was dried to give the tide compound, which if necessary can be purified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cyclohexane/EtOAc or EtOAc/EtOH.
Workup procedure b: The reaction mixture was diluted with DCM or EtOAc, washed with sat. NaHCOs-sol. or IM Na2C03-soL, brine and dried over MgSO4 or Na2S04. Removal of the solvent in vacuum left a material, which could be triturated with ether or mixtures of ether/THF/MeOH to give the title compound, or which if necessary can be pmified by crystallization firom 1,4-dioxane or by silica gel column chromatography with cycIohexane/EtOAc or EtOAc/EtOH.
Example 1
3-f7-Chloro-8-dimethylamino-4-oxo-4,5-dihvdro-3H-benzo[blfl.4]diazepin-2-yl)-benzonitrile
The tide compoimd was prepared firom {4-chloro-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example Ml) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (85 mg).
MS (ISP) 339 [(M+H)--] and 341 [(M+2+H)']; mp >250 *»C.

Example 2
8-Chloro-7-dimethylamino-4-f3-fl,2,3ltriazol-l-yl-phenyl)-l,3-dihydro-benzofbl f L4ldiazepin-2-one
The title compoxmd was prepared from {4-chloro-5-dimethylamino-2-[3-OXo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert.-butyl ester (Example M2) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (87 mg).
MS (ISP) 381 [(M+H)--] and 383 [(M+2+H)-']; mp 222-225 °C.
Example 3
8-Chloro-7-dimethylamino-4- r3-(5-hvdroxvmethyl-1- 1.2,3ltriazol- 1-yD-phenyll -1,3-dihydro-benzo f b1 \ 1,4] diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyTan-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl] -carbamic acid tert.-butyl ester (Example M3) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (60 mg).
MS (ISP) 411 [(M+H)--] and 413 [(M+2+H)']; mp 210-214 X,
Example 4
3-(8-Dimethylamino-4-oxo-7-phenylethynyl-4,5-dihydro-3H-benzofbl \ 1,41 diazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-phenylethynyl-phenyl}-carbamic acid tert.-butyl ester (Example M4) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg).
MS (ISP) 405 [(M+H)--]; mp 215-216 °C.
Example 5
7-Dimethylamino-8-phenylethvnyl-4-f3-rL23ltriazol-l-yl-phenvi)-K3-dihvdro-benzofbl f 1.41 diazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyi)-propionylamino]-4-phenylethynyl-phenyi}-carbantiicadd tert-butyi ester (Example M5) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (76 mg).
MS (ISP) 447 [(M+H)--]; mp 185-186 °C.

Example 6
8-Chloro-7-dimethylamino-4-r3-f3-methyl-isoxazol-5-yl')-phenyl1-L3-dihvdro-benzoFb1fl,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacidtert.-butyl ester (Example M6) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (68 mg).
MS (EI) 394 (M^) and 396 [(M+2r]; mp 212-215 °C
Example 7
8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-('5-hvdroxymethyl-[1.23ltria2ol-l-yl)-phenyl-1.3-dihvdro-benzofb]fL4ldiazepin-2-one
The title compound was prepared from (RS)-[2-dimethylamino-2',3'-difluoro-5-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-biphenyl-4-yl]-carbamic acid tert-butyl ester (Example M7) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (26 mg).
MS(ISP)489[(M+H)'].
Example 8
8-(23-Difluoro-phenyl)-7-dimethylamino-4-f3-fL23ltriazQl-l-yl-phenylyl3-dihvdrO'benzo l-b] [ 1.41 diazepin'2-one
The title compound was prepared from {2-dimethylamino-2\3*-difluoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert-butyl ester (Example M8) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (47 mg).
MS (ISP) 459 [(M+H)--]; mp 197-199 °C.
Example 9
3-r7-(23-Difluoro-phenyl)-8-dimethylamino-4-QXO-4.5-dihydro-3H-benzofbl \ 1,41 diazepin-2-vn -benzonitrile
The title compound was prepared from {5-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-2-dimethylamino-2\3*-difluoro-biphenyi-4-yl}-carbamic acid terL-butyl ester (Example M9) by treatment with TFA in CH2a2 according to the general procedure N. Obtained as a light yellow solid (75 mg).

MS (ISP) 417 [(M+H)--]; mp 228-229 ^'C
Example 10
8-CMoro-7-dimethylamino-4-(2-(3-metfayl-isoxazol-5-yl)-pvridin-4-yl1-1.3-dihvdrO-benzofbl f 1.4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimetiiylanuno-2-{3- [2-(3-methyl-isoxazol-5-yI)-pyridin-4-yl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example MIO) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (111 mg).
MS (ISP) 396 [(M+H)+] and 398 [(M+H-f 2)--]; mp >250 X.
Example 11
8-Chloro-7-[(2-methoxy-ethyl)-methyl-amino1-4'f3-(3-methyl-isoxazol-5-yI')-phenyll -13-dihvdro-benzo [bl f 1 A] diazepin-2-one
The title compound was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-amino]-2-{3-[3-(3-methyi-isoxazol-5-yl)-phenyl]-3-OXO-propionylamino}-phenyl)-carbanciic acid tert.-butyl ester (Example Ml 1) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg).
MS (EI) 438 (M**-) and 440 [(M+2)+]; mp 182 °C.
Example 12
8-Chloro-7-f(2-methQxy-ethyl)-methyl'amino1-4-[2-f3-methyl-isoxazoI-5-yl)-pyridin-4-ylyl3-dihydro-benzofb]fl.4ldiazepin'2-one
The title compoimd was prepared from (4-chloro-5-[(2-methoxy-ethyl)-methyl-ainino]-2-{3-[2-(3-methyl-isoxazol-5-yl)-pyridin-4~yl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M12) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (106 mg).
MS (ISP) 440 [(M+H)'] and 442 [(M+H+2)1; mp 213 °C
Example 13
8-ChlorQ-4-r3-(5-hvdroxvmethyl-rL23ltriazol-l-yl]-phenyl-7-r(2-methoxv-ethyl)-methyl-amino1-l3-dihvdro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-[(2-methoxy-ethyl)-methyL amino]-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M13) by

treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (50 mg).
MS (ISP) 4.55 [(M+H)'] and 457 [(M+H+2)']; mp 185 X.
Example 14
8-Chloro-7-r(2-methoxv-etfayl)-methyl-amino1-4-f3-fl.23]triazol-l-yl-phenylyl.3-dihydro-benzofb] rL4ldiazepin-2-one
The title compotmd was prepared from {4-chIoro-5-[(2-methoxy-ethyl)-methyl-amino] -2- [3-oxo-3-(3- [ l,2,3]triazoM-yl-phenyl)-propionylamino] -phenyl}-carbamic acid tert.-butyl ester (Example M14) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg).
MS (ISP) 425 [(M+H)--] and427 [(M+H+2)+]; mp 156 °C.
Example 15
4-f7-Ch]orO-8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb]fl,4ldiazepin-2-vI)-pyridine-2-carbonitrile
The title compoimd was prepared from {4-chlorO-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-dimethylamino-phenyl}-carbamic acid tert.-butyl ester (Example M15) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (50 mg).
MS (ISP) 340 [(M+H)--] and 342 [(M+2+H)-^]; mp 216 X.
Example 16
8-ChlorO-7-dimethylamino-4-f3-(2-methyI-2H-pvrazol-3-yl)-phenyl]-1.3-dihvdro-
benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert.-butyl ester (Example M16) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofiF-white solid (67 mg).
MS (ISP) 394 [(M+H)--] and 396'{(M+2+H)']; mp 225 X.

Example 17
7-Dimethylamino-4-f3-(5-hydrox\TOethyl4l,2,3ltria2ol>l'yl)-phenyll'8-trifluoromethy[-L3-dihydro-benzofblfL4ldiazepin-2*one
The title compound was prepared torn (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyI-phenyl]-carbamic acid tert.-butyl ester (Example M17) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (62 mg).
MS (ISP) 445 [(M+H)+]; mp 210 '°C.
Example 18
7-Dimethylamino-4-f3-(3-methyl-isoxa2oI-5-yl)-phenyI]-8-trifluoromethyM.3-dihydro-benzofb] [1,41 diazepin-2'One
The title compound was prepared from (5-dimethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-OXo-propionylamino}-4-trifiuoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example Ml8) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (28 mg).
MS (ISP) 429 [(M+H)+]; mp 223 °C,
Example 19
8'Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-l,3-dihvdro-benzo f b] f 1,41 diazepin-2-one
The title compound was prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepin-2-yl)-thiobenzamide (prepared from 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [1,4] diazepin-2-yl)-benzonitrile (Example 1) as follows: To a solution of hexamethyldisUthiane (0.55 mL, 2.6 mmol) in l,3*dimethyl-2-inaida2olidinone (2.6 mL) was acided at 20 X sodium methoxide (0.13 g, 2.5 mmol). The mixture was stirred for 15 min. and the blue solution formed was then acided to a solution of 3-(7-chloro-8-dimethyIamino-4-oxo-4,5-dihydro-3H-benzo[b][l,4ldiazepin-2-yi)-ben2omtrile (Example 1) (0.34 g, 1.0 mmol) in 1,3-dimethyl-2-imida2olidinone (2 mL). The mixture was stirred for 3 h at 20 °C and then poured into water. The precipitate was isolated by filtration and triturated with acetone to give 3-(7-chloro-8-dimethylamino-4-oxo-4,5-dihydro-3H-benzo[b] [l,4]diazepin-2-yi)-thiobenzamide (035 g) as yellow solid, mp 234 'C decMS (ISP) 373.2 [(M+H)'].} (0.71 g, 1.9 mmol), l,3-dichloro-2-propanone (0,36

g, 2.85 mmol) and sodium bicarbonate (0.24 g, 2.85 mmol) in 1,4-dioxane (15 mL) was heated to 60 °C for 48 h. The clear solution was evaporated in vacuvun. The a solution of the residue in 1,4-dioxane (5 mL) was acided 2N KOH (3.8 mL) and the mixture was stirred at 20 °C for 1 h. Water (100 mL) was acided and the mixture was stirred for 0,5 h. The precipitate formed was collected by filtration and crystallized from dichloromethane to give the title compound (0.69 g) as pale-yellow solid.
MS (ISP) 427.2 [ (M+H)**-]; mp 134 X dec.
Example 20
8-Chloro-7-dimethylamino-4-f3-(5-dimethylaminomethyl-fl.23ltriazol-l-yl)-phenyll -L3-dihvdrO'benzo fbl \ 1,41 diazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(5-dimethylaminomethyl-[l,2,3]triazol-l-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M19) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a beige solid (34 mg).
MS (ISP) 438 [(M+H)--] and 440 [(M+2+H)-']; mp 145-160 °C
Example 21
8-Chloro-7-dimethylamino-4-f3-(3-methoxvmethyl-isoxazol-5-yl)-phenyl1*L3-dihydro-benzoFbl [1.41 diazepin-2-one
The title compound was prepared from (4-chloro-5-dimethylamino-2-{3-[3-(3-methoxymethyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butjrl ester (Example M20) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (157 mg).
MS (ISP) 425 [(M+H)+] and 427 [(M+2+H)']; mp 191 °C.
Example 22
4-(8-Dimethylamino-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo Fbl \ 1.41 diazepin'2-yl)-pyridine-2-carbonitrile
The title compoxmd was prepared from {2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylarnino]-5-dimethylamino-4-trifluoromethyl-phenyi}-carbainic acid tert.-butyl ester (Example M21) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (158 mg).
MS (ISP) 374 [(M+H)--]; mp 248 X.

Example 23
8-(2-Fluoro-phenyl)-4'(3-imida2ol-l-vI-phenyl-7-(2.2,2-trifluoro-ethoxv)-L3-dihydro-benzofb] [ L41 diazepin-2-one
The title compound was prepared from [2'-fluoro-5-[3-(3-nmdazol-l-yl-phenyl)-3-oxo-propionylamino] -2- (2,2,2-trifluoro-ethoxy)-biphenyl-4-yi] -carbamic acid tert,-butyl ester (Example M22) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (50 mg).
MS (EI) 494 (M^); mp 208-210 °C
Example 24
8-(2-Fluoro-phenyl)-4-f3-f3-methyl-isoxazQl-5-vIVphenyl]-7-(2,2.2-trifluoro-ethoxy)-1,3-dihydro-benzo f b] \ 1,41 diazepin-2-one
The title compound was prepared from [2'-fluoro-5*{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyi]-3-oxo-propionylamino}-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid tert.-butyl ester (Example M23) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (21 mg).
MS (EI) 509 (M^); mp 218-220 -'C.
Example 25
8'(2-FIuoro-phenyl)-4'(3-ri.23kriazol-l-yl-phenyl)-7-r2.2,2-trifluoro-ethoxv)-13-dihydro-benzofb] f 1,4ldiazepin'2-one
The title compound was prepared from [2*-fluoro-5-[3-oxo-3-(3-[l,2,3]triazoM-yI-phenyl)-propionylamino]-2-(2^,2-trifluoro-ethoxy)-biphen)d-4-yl]-carbamicacid tert.*butyl ester (Example M24) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (45 mg)-
MS (EI) 495 (M^).
Example 26
8-(2-Fluoro-phenyl)-4-f3-(5-hvdroxvmethyl4l.2.3ltriazoI-l-yl]-phenyl)-7-(2,2,2-trifluoro-ethoxy)-13'dihvdro-ben2ofblfL4ldiazepin-2-one
The title compound was prepared from (RS)-[2'-fluoro-5-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-^oxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-2-(2,2,2-trifluoro-ethoxy)-biphenyl-4-yl]-carbamic acid terL-butyl ester (Example Iyl25) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (10 mg).

MS (ISP) 526 [(M+H)1; mp 232-234 °C
Example 27
8-Chloro-7-dimethylamino-4-f3-f4-hydroxvmethy]-oxazol-2-yl)-phenyl1-13-dihydro-benzofb] ri,4]diazepin-2-one
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example J2) (170 mg) and (RS)-3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxa2ol-2-yl] -phenyl}-propionic acid tert-butyi ester (Example Kll) (270 mg) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (110 mg).
MS (ISP) 41L2 [(M+H)--]; mp 193-195 °C
Example 28
8-Chloro-7'(ethyl-methyl-amino)-4-f3-(5-hvdroxymetfayl-fL23ltriazoM'yl)-phenyl]-L3-dihvdrO'benzofb1fl,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(ethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M26) (0.5 g, 0.8 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white soKd (60 mg).
MS (ISP) 425.4 [(M+H)-*]; mp 206 °C (dec).
Example 29
8-Chloro-7-fmethyl-propyl-amino)-4-r3-(5-hydroxvmethyl-fL2.3ltriazol-l-yl')-phenyl] -1,3-dihydrO'benzo fbl [ 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M27) (0.41 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (110 mg).
MS (ISP) 439.3 [(M+H)1; mp 178 °C (dec).

Jbxample 30
8-Chloro-7-fdiethyl-amino)-4-f3-(5-hvdroxvmethyl-rL23ltriazoUl-yl)-phenvI1-L3-dihydro-benzofb][L4]diazepin-2-one
The title compoimd was prepared from (RS)-(4-chloro-5-(diethyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tm-butyl ester (Example M28) (0.53 g, 0.827 mmol) by treatment with TFA in CH;Q: according to the general procedure N. Obtained as an off-white solid (210 mg).
MS (ISP) 439.3 [(M+H)--]; mp 208 *°C (dec).
Example 3 i
8-Chloro-7-dimethylamino-4*y3-(3-hvdroxvmeth>^-isoxazol-5-yl)-phenyl]-1.3-dihydro-benzofblfL4]diazepin-2-onc
The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-5->d]-phen)d}-propionyiamino)-phenylj-carbamic acid terL-butyi ester (Example M29) (81 mg, 0.13 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (38 mg).
MS (ISP) 411 [(M+H)+] and 413 [(M+2+H)*']; mp 132 °C.
Example 32
8-CHoro-4-r3-(5-hvdroxymethyl-rL23]triazol-l-vI)'phenyl1*7-pvrrolidin-l-yl-L dihydro-benzorb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[ 1,2,3] triazol-1-yl]-phenyl}-propionylamino)-5-pyrrolidin-1-}d-phenyl]-carbaniic acid tert.-butyl ester (Example M30) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (58 mg).
MS (ISP) 437 l(M+H)+] and 439 [(M+2+H)'-]; mp 193-197 X.

Example 33
7-Dimethylamino-4-f3-(2-methyl-2H-pvrazol-3-yl)-phenvIl-8-trifluoromethyl-L3-dihydro-benzofbl [ L4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyl-2H-pyra2ol-3-yl)'phenyl]-3-oxo-propionylari3ino}-4-trifluoromethyl-phenyl)-carbaniic acid terL-butyl ester (Example M31) (78 mg, 0.14 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid(48 mg).
MS (ISP) 428 [(M+H)1; mp 225 °Q
Example 34
4-f7-Chloro-8-('cvclopropyl-methyl-aminoV4-oxo-4,5-dihydrQ-3H-benzo Fbl f 1.41 diazepin-2-yl] -pvridine-2-carbonitrile
The title compound was prepared from [2-amino-4-chloro-5-(cyclopropyl-methyi-amino)-phenyl]-carbamic acid terL-butyl ester (Example Jll) (150 mg, 0.5 mmol) and 3-(2-cyano-pyridin-4-yl)-3-oxo-propionic acid tert-butyl ester (Example K3) (150 mg, 0.61 mmol) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (69 mg),
MS (ISN) 364.1 [(M-H)-] and 366 [(M+2-H)-]; mp 199-201 °C.
Example 35
8-Chloro-7-dimethylamino-4-[3-(4-hvd^oxvTnethyl-3-meth^d-isoxa^ol^5-yD-phenyl1-1.3-dihydro-benzo[bUL4ldiazepin-2-one
The titie compoxmd was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-{3-[3-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tert,-butyl ester (Example M32) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (60 mg).
MS (ISP) 425 [(M-hH)--] and 427 [(M+2-hH)-']; mp 232-233 'C.

Example 36
8-CHoro-7-fcvclopropyl-methyl'amino)-4-f3-(3-melhyl-isoxazol-5-yl)-phenyll-13-dihvdro-benzofb1[L4ldiazepin-2-one
The title compound was prepared from [2-aminO-4-chloro-5-(cyclopropyl-methyl-ammo)-phenyl]-carbamic acid tert.-butyl ester (Example Jll) (156 mg, 0.5 mmol) and 3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionic acid tert.-butyl ester (Example K4) (170 mg, 0.56 mmol) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (49 mg).
MS (ISP) 42L3 [(M+H)--] and 423 [(M+2+H)^; mp 195-197 X.
Example 37
8-Chloro-7-fcvclopropyl-methyl-amino)-4-f3-(5-hvdroxvmethyl-fL23ltria2ol--l-yl)-phenyl] -1.3-dihvdro-benzof b1 f 1.4] diazepin-2-one
The title compound was prepared from (RS)-[4-chioro-5-(cyclopropyl-methyl-amino)-2-(3-oxO-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M33) (200 mg, 0.313 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (54 mg).
MS (ISP) 437.3 [(M+H)+] and 439 [(M+2+H)+].
Example 38
7-Dimethylamino-4- [3-f 5-dimethylaminomethyl- [ 1.2,31 triazoM-vD-phenyll -8-trifluoromethyl-13-dihydro-benzo[bUl,4ldiazepin'2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl- (1,2,3] triazol-1 -yl)-phenyl] -3-oxo-propionylamino}-4-trifluoromethyl phenyl)-carbamic acid tert.-butyl ester (Example M34) (126 mg, 0.214 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (23 mg).
MS (ISP) 472 [(M+H)--]; mp 200 °C.

Example 39
8-ChlorO'7-dimethylamino-4-f3-f5*hvdroxymethyl-2-methyl-2H-pvra2ol-3-yl)' phenyll-13-dihydro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-(4-chloro-5-dimethylamino-2-(3-{3-[2-methyl-5-(tetrahydro-pyran-2-ylox)Tncth)1)-2H-pyrazol-3-yl]-phenyl}-3-oxo-propionylamino)-phenyl]-carbamic acid tat.-butyl ester (Example M35) (278 mg, 0.44 mmol) by treatment with TFA in CHjQ: according to the general procedure N. Obtained as a Hght yellow solid (129 mg),
MS (ISP) 424 [(M+H)--] and 426 ((M+2+H)-]; mp 184 X.
Example 40
4-(4-Oxo-8-pvrrolidin-l-yl-7-trifluoromethyl-4.5-dihvdrO'3H-benzo[bUL4ldiazepin-2-yl)-pyridine-2'Carbonitrile
The title compound was prepared from {2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M36) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (65 mg).
MS (ISP) 400.4 [(M+H)--]; mp 188 -C (dec).
Example 41
443-(5-Hvdroxvmethyl-rL23ltriazol-l-vI)-phenyll-7-pvrrolidin-l-yl-8-trifluoromethyl-13*dihvdro-ben2ofb1fL4ldiazepin*2-one
The title compound was prepared from (RS)-[2-(3-oxo-3-{3-l5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M37) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid(33 mg).
MS (ISP) 471.2 [(M+H)+]; mp 134 °C.
Example 42
7-Dimetfaylamino-8-fluoro-4- [3- f 5-hvdroxvmethyl- f 1.2.31 triazol-1 -yl)-phenvil -1.3-dihvdro-benzofbl rh4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,23]tria2ol-l-)4]-phenyi}-propionyi-amino)-phenyl]-carbamic acid tert.-butyl ester (Example M38) (375 mg, 0.63 mmol)

by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (115 mg).
MS (ISP) 395 [(M+H)1; mp 75 °C.
Example 43
7-Dimethylamino-4-[3'(5-dimethylaminomethyl-fL2,3ltria2oI-l-yl)-phenyl1-8-fluoro-13-dihydro-benzo[bUL4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(5-dimethyl-aminomethyl-[l,2,3]tria2ol-l-yl)-phenyl]-3-oxo-propionylanaino}-4-fluoro-phenyl)-carbamic acid terL-butyl ester (Example M39) (170 mg, 0.32 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (34 mg).
MS (ISP) 422 [(M+H)+]; mp 181 °C.
Example 44
7-Dimethylamino-8-fluoro-4-F3-f3-hydroxymethyl-isoxazol-5-yD-phenvI1-l,3-dihydro-benzofbUl,4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-4-fluoro-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M40) (314 mg, 0,53 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (95 mg).
MS (ISP) 395 [(M+H)--]; mp 187 °C.
Example 45
8-Chloro-7-dimethylamino-4-[3-(5-pvrrolidin-l-ylmethyl-ri,23ltriazol-l-vD-phenyl1-13-dihydro-benzo[b1fL4ldiazepin-2'One
The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxy-methyl- [ 1,2,3] triazol-1 -yl)-phenyl] -1,3-dihydro-ben2o [b] [1,4] diazepin-2-one (Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (0.044 mL, 0.6 mmol) in CH2Cl2 (2 mL) from 23 °C to reflux for 15 min, followed by evaporation to dryness. The crude chloride was dissolved in DMF (2 mL) and stirred with cat amount of Nal and pyrrolidine (0.248 mL, 3.0 mmol) at 23 °C until tic indicated complete conversion of the chloride. The reaction mixture was taken up in EtOAc, washed with water and brine, dried over Na2S04. Removal of the solvent in vacuum left a yellow semisolid.

which was purified by silica gel colxxmn chromatography. Obtained as a yellow solid (101 mg).
MS (ISP) 464 [(M+H)1 and 466 [(M+2+H)-']; mp 180-182 --C.
Example 46
7-Dimethylamino-4-f3-f3'hvdroxvmetfayl-isoxa2ol-5-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzofb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[3-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenylj-carbamic acid tert.-butyl ester (Example M41) (680 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (294 mg).
MS (ISP) 455 [(M+H)--]; mp 219 °C.
Example 47
7-Dimethylamino-8-fluorO'4--[3-(3-methyl-isoxazol-5-yl)-phenyl-l,3-dihvdro-benzo [bl [ 1.41 diazepin-2-one
The title compound was prepared from (5-dimethylamino-4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert.-butyl ester (Example M42) (233 mg, 0.47 nunol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow-brown solid (59 mg).
MS (ISP) 379 [(M+H)-*-]; mp 124 X.
Example 48
4-[3-(5-Azetidin-l-ylmethyl-fl.23ltriazol-l-yl)-phenyl-8-chloro-7-dimethylaminOr 13-dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 3) (123 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and trimethylen imine (10 eq.) as described in Example 45. Obtained as a yellow solid (17 mg).
MS (ISP) 450 [(M+H)-']; mp 153 °C

Example 49
8'Chloro-7-dimethylamino-4- f 3- f 5-hvdroxvmethyl'isoxazol-3-vD-phenyn -1.3-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxa2ol-3-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M43) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (113 mg).
MS (ISP) 411.3 [(M+H)1 and 413 [(M+2+H)']; mp 211 °C (dec).
Example 50
8--Chloro-4-[3--(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-7-piperidin-l-yl-13-dihvdro-benzo f b U1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-piperidin-l-yl-phenyl]-carbamic acid tert.-butyl ester (Example M44) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (99 mg).
MS (ISP) 451.3 [(M+H)+] and 453 [(M+2+H)-']; mp 246 X (dec).
Example 51
7-Dimethylamino-'4-f3-(5-hydroxvmethyl-isoxazoI'3-yl)-phenyll-8-trifluoromethyl-
L3-dihvdrQ-benzofb1fL4]diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert--butyl ester (Example M45) by treatment with TFA in CH3CI2 according to the general procedure N. Obtained as a light yeUow solid (103 mg),
MS (ISP) 445.3 [(M+H)+]; mp 211 °C (dec).

Example 52
8-Chloro-7-dimeAylamino-4-f3-pvrazol-l-yl-phenylyl3-dihydro-benzofbl ri.4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-dimethylamino-2-[3-oxo-3-(3-pyra2ol-l-yl-phenyl)-propion7lamino]-phenyl}-carbamic acid terL-butyl ester (Example M46) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (75 mg).
MS (ISP) 380 [(M+H)1 and 382 [(M+2+H)+]; mp 231-234°C
Example 53
7-DimethyIamino-4-f3-f3-pvrrolidin-l'ylmethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo fb] f L4l diazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl] -8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 46) (111 mg, 0.25 mmol) by treatment with SOCI2 (3 eq.) and pyrrolidine (10 eq.) as described in Example 45. Obtained as a yellow solid (28 mg).
MS (ISP) 498 [(M+H)+]; mp 160 °C.
Example 54
7-Dimethylamino-4-[3-(3-morpholin-4-ylmethyl-isoxa2ol-5-yl)-phenyl-8-trifluoromethyl-l,3-dihvdrO'benzofbl f l,4ldiazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and morpholine (10 eq.) as described in Example 45. Obtained as a yellow solid (33 mg).
MS (ISP) 514 [(M+H)+]; mp 165 °C
Example 55
7-Dimethylamino-4-f3-(3-dimethylaminomethyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-L3-dihvdrQ-benz6fbUl,4ldiazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(3-hydroxymethyl-isoxazol-5-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 46) (53 mg, 0.12 mmol) by treatment with SOCI2 (3 eq.) and 40 % aqueous Me2NH-sol (10 eq.) as described in Example 45. Obtained as a light yellow solid (21 mg).

MS (ISP) 472 [(M+H)--]; mp 160 °C
Example 56
4-f7-Fluoro-4-oxo-8-pvrrolidin-l-yl-45-dihvdro-3H-benzo[bUl.4ldiazepin-2-vD-pyridine-2-carbQnitrile
The title compoimd was prepared from {2-[3-(2-Cyano-pyridin-4-yI)-3-oxo-propionylamino]-4-fluoro-5-pyrrolidin-l-yl-phenyl}-carbamic acid tert.-butyl ester (Example M47) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (54 mg).
MS (ISP) 350 [(M+H)--]; mp 278-279 °C
Example 57
8-FluorQ-4-f3-(3-methyl-isoxazol-5-vD-phenyl]-7-pvrrolidin-l-yl-13-dihvdro-benzo[bUl,4ldiazepin-2-one
The title compoimd was prepared from (4-fluoro-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert.-butyl ester (Example M48) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a brown solid (86 mg).
MS (ISP) 405 [(M+H)--]; mp 236 -C
Example 58
8-Fluoro-443-(5-hvdroxvmethyl-[L2.3ltriazol-l-vD-phenyl1-7-pvTrolidin-l-yl-L3-dihvdrO'benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-fluoro-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-ylox)nnieth.yl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl] -carbamic acid tert-butyl ester (Example M49) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (72 mg).
MS (ISP) 421 [(M+H)--]; mp 184-185 °C.
Example 59
4-f8-Azetidin-l-yl-7-chloro-4-oxo-45-dihvdro-3H-benzofb1[l,4ldiazepin-2-yl)-pyridine-2-carbonitrile
The title compound was prepared from {5-a2etidin-l-yl-4-chloro-2-[3-(2-cyano-pyridin-4-yi)-3-oxo-propionylamino]-phenyl}-carbainic acid terL-butyl ester (Example M50) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (66 mg).

MS (ISP) 352 [(M+H)'] and 354 [(M+2+H)1; mp 276 °C.
Example 60
4- f 3- f 5-Hvdroxymethyl-isoxa2ol-3-yl)'phenyl1 -7-pvrrolidin- 1 -yl-8-trifluoromethyl-L3-dihydro-benzo fb] f L4l diazepin-2-one
The title compound was prepared from (RS)-[2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yioxymethyl)-isoxazol-3-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M51) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (224 mg).
MS (ISP) 47L2 [(M+H)--]; mp 206-208 X.
Example 61
4-f 8-Azetidin- l-yl-4-oxo-7-trifluoromethyl-4.5-dihydrO'3H-benzo [bl \ 1.41 diazepin-2-yl)'pyridine-2-carbonitrile
The title compound was prepared from {5-azetidin-l-yl-2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid terL-butyl ester (Example M52) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an orange solid (51 mg),
MS (ISN) 384.2 [(M-H)']; mp 241 °C.
Example 62
7-A2etidin-l-yl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8'trifluoromethyl-l,3-dihydro-benzofbUL4ldiazepin'2-one
The title compoimd was prepared from (5-azetidin-l-yl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M53) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg).
MS (ISP) 441.3 [(M+H)--]; mp 239 °C (dec).
Example 63
7-A2etidin-l-yl-443-(5-hvdroxvmethyl-rL23ltriazoM-yl)-phenyl1-8-trifluoromethyl-13-dihydro-benzofblfl.4ldiazepin'2-one
The title compound was prepared from (RS)-[5-azetidin-l-yl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiamino)-4-trifluoromethyl-phenylj-carbamic acid terL-butyi ester (Example M54) by treatment

with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (182 mg).
MS (ISP) 457,4 [(M+H)+]; mp 202 X (dec).
Example 64
7-Dimethylamino-4-13-pyra2ol-l -yl-phenyl)-8-trifluoromethyl-1,3-dihvdro-benzo^b] f l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M55) (438 mg, 0.82 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (238 mg).
MS (ISP) 414 [(M+H)--]; mp 176 °C
Example 65
7-Dimethylamino*4-f3-fL2.4ltriazol-4-yl-phenyl)'8-trifluoromet3iyl-l,3-dihydro-benzolb] [l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-4-yl-phenyl)-propionylamino]-4-trifluoroinethyl-phenyl}-carbamic acid tert.-butyl ester (Example M56) (280 mg, 0.526 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (121 mg).
MS (ISP) 415.3 [(M+H)--]; mp 247-250 °C.
Example 66
7-Dimethylamino-4-(3-imidazol-l-yl-phenyl)-8-trifluoromethyl-l>3-dihvdro-benzolbl [ l,4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-(3-imidazol-l-yl-phenyl)-3-oxo-propionylamino]-4-trifluoromethyl-phenyl}-carbainic acid tert.-butyl ester (Example M57) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (132 mg),
MS (ISP) 414 [(M+H)--]; mp 203-205 °C.

Example 67
8-Chloro-7-dimethylamino-4-f3-(4-hvdroxymethyl-pvra2ol-l-yl)-phenyl1-L3-dihvdro-benzo fb] F1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chIoro-5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert.-butyl ester (Example M58) (642 mg, 1.05 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (365 mg).
MS (ISP) 410 [(M+H)--]; mp 211 *°C.
Example 68
7-DimethylaminO'4-f3-(4-hydroxvmethyl-pyrazol-l-yl')-phenyl1-8-trifluoromethyl-13-dihvdro-ben2orb1[l,4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[4-(tetrahydro-pyran-2-yloxymethyl)-pyra2ol- 1-yl] -phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (°Cample M58) (590 mg, 0.91 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (299 mg).
MS (ISP) 444 [(M+H)--]; mp 175 °C
Example 69
7-Dimethylamino-4-f3-(4-hydroxvmethyl-3-methyl-isoxazol-5-yl)-phenvI1-8-trifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[3-methyI-4-(tetrahydro-pyran-2-yloxymethyl)-isoxazol-5-yl]-phenyl}-3-oxo-propionylarnino)-4-trifluoromethyi-phenyi]-carbamic acid tert--butyl ester (Example M60) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (64 mg).
MS (ISP) 459 [(M-hH)--]; mp 207-208 °C.

Example 70
7-Dimethylamino-4-f3'(4-hvdroxvmethyi-isoxazol-3-yl)-phenyl*8-trifluoromethyl-L3-dihvdro-benzofb1fL4ldiazepin-2'one
The title compound was prepared from (RS)-l5-dimethylamino-2-(3-oxo-3-{3-l4-(tetrahydrO-pyran-2-yloxymcthyl)-isoxa2ol-3-yl)-phenyl}-propionylamino)-4-trifluoromethyl-phenyi)-carbamic acid tert.-butyl ester (Example M61) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (50 mg),
MS (ISP) 445 [(M+H)+]; mp 217-219 M
EMmpk7l
7-Dimethylamino-4-f3-(2-methylsulfanyl-imida2ol-l-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2orb1fL4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-2-{3-[3-(2-methyisulfanyl-imidazol-l-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert.-butyl ester (Example M62) (450 mg. 0.78 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (253 mg).
MS (ISP) 460 [(M+H)--]; mp 192 X.
Example 72
7-Dimethylamino-4'f3-(4'hvdroxvmethyl-2-methyl-2H-pyrazol*3-yl)-phenyll-8' trifluoromethyl-13-dihvdro-benzofb1 f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-{3-[2-methyl-4-(tetrahydro-pyran-2-yloxymethyl)-2H-pyrazol-3-yi]-phenyl}-3-oxo-propionyl-amino)-4-trifiuoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M63) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (272 mg),
MS (ISP) 458 [(M+H)+]; mp 243-244 °C.
Example 73
8-Chloro-7-dimethylamino-4-f3-fL2,4ltriazoM-yl-phenyl)-13-dihvdro-benzprb] f l,4ldiazepin-2-one
The title compound was prepared from {4-Chloro-5-dimethylamino-2-[3-oxo-3-(3-[l^,4]triazol-l-yl-phenyl)-propionyiamino]-phenyi}-carbamic acid tert-butyl ester

(Example M64) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (316 mg).
MS (ISP) 381 [(M+H)1 and 383 [(M+2+Hr]; mp 239-241 °C
Example 74
7-Dimetfaylamino-4- (5-\l .2,41 triazol-1 -yl-phenyl) - 8-trifluoromethyl-13-dihydro-benzoFb] [L4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[l,2,4]triazoH-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M65) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(269 mg).
MS (ISP) 415 [(M+H)--]; mp 228-230 X.
Example 75
3-f8-Dimethylamino-4-oxo-7-trifluoromethyl-4,5-dihvdro-3H-benzorbirL4ldiazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-cyano-phenyl)-3-oxo-propionyl-amino]-5-dimethylamino-4-trifluoromethyl-phenyl}-carbanaic acid tert.-butyl ester (Example M66) (180 mg, LO mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg).
MS (ISN) 371 [(M-H)-]; mp 224-227 X.
Example 76
7-Dimethylamino-4-(3-l5-f('2,2.2-trifluoro-ethylaminoVmethyl]-rL23ltriazol-l-vU-phenyl)-8-trifluoromethyl-l>3-dihydro-benzorb1fL4ldiazepin-2-one
The title compoxmd was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l>2,3]triazol-l-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 17) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and 2>2,2-trifluoroethylamine (10 eq.) as described in Example 45. Obtained as a light yellow solid(19mg).
MS (ISP) 526 [(M+H)'];mp 168-170 °C.

Example 77
7-(Cyclopropylmethyl-methyl-aminoV4-[3-(5-hvdroxvmethyl-fL23ltriazoM-vI)-phenyl1-8-trifluorQmethyl-13-dihvdro-benzofbiri.4]diazepin-2*one
The title compound was prepared from (RS)-[5-(cyclopropylmethyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M67) (939 mg> 1.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (544 mg).
MS (ISN) 483 [(M-H)-]; mp 212 °C.
Example 78
4-f8-fCvclopropylmethyl-methyl-amino)-4-oxo-7-trifluoromethyl-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin-2-vn 'pyridine-2-carbonitrile
The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(cyclopropylmethyl-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert.-butyl ester (Example M68) (173 mg, 0.33 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (81 mg),
MS (ISN) 412 [(M-H)*]; mp 155 °C
Example 79
4- [ 3- (4-Cyclopropylaminomethyl'pyrazol-1 -yl) -phenvH -7'dimethylamino-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(4-hydroxymethyl-pyrazoH-)d)-phenyl]-8-trifluoromethyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 68) (133 mg, 0.3 mmol) by treatment with SOCI2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (45 mg).
MS (ISP) 483 [(M+H)--]; mp 135 °C.
Example 80
4-[3-(5-Cyclopropylaminomethyl-ri.2,3ltriazol-l-yl)-phenyl1-7-fcyclopropylmethyl-methyl*aminoV8-trifluoromethyl-13-dihvdrO-benzorblfl,4ldiazepin-2-one
The title compound was prepared from 7-(cyclopropylmethyi-methyl-amino)-4-[3-(5-hydroxymethyl-[1^3]triazol-l-yl)-phenyl]-8-trifluoromethyl-13-
SOCh (3 eq.) and cyclopropji amine (10 eq.) as described in Example 45. Obtained as a yellow solid (97 mg).
MS (ISP) 524 [(M+H)--]; mp 35-46 °C
Examples!
7-Dimethylamino-4-B-r2-(2-hvdrorv-ethyl)-2H-pvrazol-3-yl]-phenvD-8-trifluoromethyl-l.S-dihvdro-benzQfbl f 1.4ldia7epin-2-one
The title compound was prepared from (RS)-l5-dimetliylainino-2-[3-oxo-3-(3-{2-[2-(tetrahydro-pyran-2-yloxy)-ethyi]-2H-p>Tazol-3-yi}-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tcrL-butyl ester (Example M69) (237 mg, 0.36 mmol) by treatment with TFA in CH:Q: according to the general procedure N. Obtained as an off-white solid (48 mg).
MS (ISP) 458 [(M+H)--]; mp 138 °C
Example 82
4-[3'(5-Cvclopropylaminomethyl-fL2.3]tria2ol-l-yl)-phenyl1-7-dimethylamino-8-trifluorometfayl-1.3-dihvdro-benzorbUL4ldiazeptn-2-one
The title compound was prepared from 7-dimethylamino-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-trifluoromethyi-13-dihydro-benzo[b][l,4)diazepin-2-one (Example 17) (444 mg, 1.0 mmol) by treatment with SOQ2 (3 eq.) and cyclopropyl amine (10 eq.) as described in Example 45. Obtained as a yellow solid (248 mg),
Mp 145-148 °C,
Example 83
4-f8-(Cyclopropyl-methyl-amino)-4-oxo-7-trifluoromethyM.5-dihvdro-3H-benzo fb] [ 1,41 diazepin-2-yll -pvridine-2-carbonitrile
The title compoxmd was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(cyclopropyl-methyl-amino)-4-trifluoromethyl-phenyl] -carbamic acid tert-butyl ester (Example M70) (215 mg, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (87 mg).
MS (ISP) 400.4 [(M+H)--]; mp 200-205 °C.

Example 84
7-Diinethylamino-8-(2-fluoro-phenyl)-4-f3-fh23ltria2ol-l-yl-phenyl)-L3-dihvdro-benzofbl f 1.4ldiazepin-2-one
The title compound was prepared from {2-dimethylamino-2*-fiuoro-5-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-biphenyl-4-yl}-carbamicacidtert.-butyl ester (Example M70) (810 mg, L45 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (61 mg).
MS (ISP) 400.4 [(M+H)+]; mp 225-230 °C.
Example 85
7-Dimethylamino-4-B-(5-(2-hvdroxv-ethyl)-fL23ltria2oM-yl)-phenvU-8-trifluoromethyl-13-dihvdro-benzo \b] [ 1.41 diazepin-2-one
The title compound was prepared from (RS)-{5-dimethylamino-2-[3-oxO-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,2,3] triazol- 1-yl}-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert.-butyl ester (Example M72) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (179 mg).
MS (ISP) 459 [(M+H)+]; mp 172-175 °C.
Example 86
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-pvrazol-l-vD-phenyl1-8-trifluoromethyl-
1.3-dihvdro-benzQrb1fL4ldiazepin-2-one
The title compound was prepared from (RS)-[5-dimethylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-pyrazol-l-yl]-phenyl}-propionylamino)-4-trifluoromethyl-phenyl]-carbamic acid terL-butyl ester (Example M73) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow soHd(109mg).
MS (ISP) 444 [(M+H)1; mp 228-229 °C
Example 87
7-Dimethylammo-4-(3-[h2.3ltriazol-l-yl-phenyl)-8-trifluoromethyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one
The title compound was prepared from {5-dimethylamino-2-[3-oxo-3-(3-[1^3]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic

add tert.-butyl ester (Example M74) (905 mg, 1.7 mmol) by treatment with TFA in CH2Cl2 according to tihie general procedure N. Obtained as a yellow solid (566 mg).
MS (ISN) 413.2 [(M-H)-]; mp 210-212 'C.
Example 88
4-r4-Oxo-842.2.2-trifluoro-ethoxv)-7-trifluoromethyl-4.5-dihvdro-3H-benzofbl f 1,41 diazepin-2-yl1 -pyridine-2-carbonitrile
The tide compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino] -5-(2,2,2-trifluoro-ethoxy)-4-trifluoromethyl-phenyl] -carbamic acid tert.-butyl ester (Example M75) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (100 mg).
MS (H) 428.2 (M^); mp 252-255 °C.
Example 89
3-(8-Dimethylamino-7-methyl-4-oxo-43-dihydro-3H-benzorblfl.4ldiazepin-2-yl)-benzonitrile
The title compound was prepared from {2-[3-(3-Cyano-phenyl)-3-oxo-propionyi-amino]-4-dimethylamino-5-methyl-phenyl}-carbamic acid tert-butyl ester (Example M76) (0.24 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (114 mg, 59%).
MS (ISP) 319.3 [(M+H)1; mp 257 °C.
Example 90
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-rL23ltriazol-l-vD-phenyll-8-methyl-L3-dihydro-benzofbl rL4ldiazepin-2-one
The tide compound was prepared from (RS)-[5-dimethylamino-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M77) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%). '
MS (ISP) 391.3 [(M+H)--]; mp 190 X.

Example 91
2-f3-Cyano-phenyl)-8-dimetfaylamino-4-oxo-4.5-dihydrO'3H-benzo[bl[L4ldiazepine-7-carbonitriIe
The title compound was prepared from {5-cyano-2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-4-dimethylamino-phenyl}-carbamic acid tert-butyl ester (Example M78) (0.28 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (36 mg, 59%).
MS (ISP) 328.3 [(M-H)-]; mp 251 °C
Example 92
3-f7-methyl-8-(methyl-propyl-amino)-4-oxo-4.5-dihvdro-3H-benzo fbl [ 1,41 diazepin*2-yl1 -benzonitrile
The title compound was prepared from [2-[3-(3-cyano-phenyl)-3-oxo-propionylamino]-5-methyl-4-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example M79) (0.17 g, 0.37 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg> 58%).
MS (ISP) 347.4 [(M+H)1; mp 195 X.
Example 93
4-[3-(5-HvdroxvTnethyl-[1.2.3ltriazol-l-yl)-phenyl1'8-methyl-7-(methyl-propvI-amino)-L3-dihvdro-benzo [bl [1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-methyl-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M80) (0.42 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid (200 mg, 72%).
MS (ISP) 419.4 [(M+H)1; mp 186 °C.
Example 94
7-fEthyl-methyl-amino)-4-f3-(5-hvdroxvmethyl*[l,23ltriazol-l-yl)-phenyl1-8-methyl-13-dihvdro-benzo[b1fl.4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(ethyi-methyl-amino)-4-meth)i-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l>2,3]triazol-l-yl]-phenyl}-propionyiamino)-phenyl]-carbamic acid tert-butyl ester (Example M81) (0.39 g, 0.64 mmol) by treatment with TFA in CH2a2 according to the general procedure N.

Obtained as a off-white solid (159 mg, 61%). MS (ISP) 405.5 [(M+H)+]; mp 207 °C
Example 95
8-Dimethylamino-2-f3-(5-hydroxymethyl-fl,2,3ltriazol-l-yD-phenyn-4-oxo-4.5-dihvdro-3H-benzo fb] f 1.41 diazepine-7-carbonitrile
The tide compound was prepared from (RS)-[4-cyano-5-dimethylainino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazoM-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl.ester (Example M82) (0.35 g, 0.58 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(149 mg> 64%).
MS (ISP) 402.5 [(M+H)--]; mp 234 °C.
Example 96
8-Chloro-4- f 3- f 5-hvdroxymethyl- [ 1.231 triazol- l-vD-phenyll -7-f isopropyl-methyl-amino)-L3-dihydro-benzorb1|'l,4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M83) (0.53 g, 0.83 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a off-white solid (120 mg, 33%).
MS (ISP) 439.5 [(M+H)--]; mp 207 X.
Example 97
8-methyl-4-[3-(3-methyl-isoxazol-5-yl)-phenyll-7-(methyl-propyl-aminoyl.3-dihydro-benzofblfl.4ldiazepin-2-one
The title compound was prepared from [4-methyl-2-{3-[3-(3-methyl-isoxazoI-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M84) (0.33 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as alight yellow solid (163 mg, 64%).
MS (ISP) 403.4 [(M+H)--]; mp 194 '°C.

Example 98
8-Dimethylamino-2-[3-(3-methyl-isoxa2ol-5-yl)-phenyll-4-oxO'43-dihydro-3H-benzo fbl f 1.41 diazepine-7*carbonitrile
The title compound was prepared from (4-cyano-5-dimethyiamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-Carbaniic acid tert-butyl ester (Example M85) (0.31 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (171 mg, 72%).
MS (ISP) 386.3 [(M+H)--]; mp 248 °C.
Example 99
7-fEthyl-methyl-amino)-8-methyl-4-F3-(3-methyl-isoxazol-5-yl)-phenyl]*L3-dihvdro-benzo fbl [ 1.41 diazepin-2-one
The title compound was prepared from (5-(ethyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M86) (0.38 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Ught yellow solid (160 mg, 55%).
MS (ISP) 389.5 [(M+H)--]; mp 198 °C
Example 100
7-DimethylaminO-8-methyl-4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-l3-dihydro-benzoFbl [l,4ldiazepin-2-one
The title compound was prepared from (5-dimethylamino-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M87) (0.32 g, 0.65 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (140 mg, 57%).
MS (ISP) 375.4 [(M+H)--]; mp 204 °C.
Example 101
8-Chloro-4- r3- f 5-hvdrQYvmethyl- \ 1.23ltriazol-l-yl)-phenyl1 -7-f isobutyl-methyl-amino)-13-dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isobutyl-methyl-ainino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyi)-[l,2,3]triazoM-yi]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M88) (0.32 g, 0.49 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtzdned as an ofF-white solid (107 mg, 48%)-

MS (ISP) 453.4 [(M+H)--]; mp 201 °C.
Example 102
8-Cbloro-7-(isobutyl-methyl*amino)-4-f3-f3-methyl-isoxazol-5-yD-phenyn-L3-dihvdro-benzofbirL4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M89) (0.35 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (114 mg, 41%),
MS (ISP) 437.4 [(M+H)+]; mp 194 °C.
Example 103
2-f3-(5-Hvdroxvmethyl-fl.23ltriazol-l-yl)-phenyl]-4-oxo-8-pyrrolidin-l-yl-4.5-dihvdrO-3H-benzo[b1fL4]diazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example M90) (0.37 g, 0.59 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (140 mg, 56%).
MS (ISP) 428.5 [(M+H)1; mp 241 °C.
Example 104
2-f3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-8-pvrrolidin-l-yM,5-dihydro-3H-benzofbl f L4l diazepine-7-carbonitrile
Prepared from (4*cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyl ester (Example M91) (0.41 g, 0.77 mmol) by treatment with TFA m CH2Cl2 according to the general procedure N. Obtained as a yellow solid (90 mg, 28%).
MS (ISP) 412.3 [(M+H)--]; mp 267 °C.
Example 105
2-f3-(5-Hvdroxvmethyl-fl.2,3ltriazol-l-yl)-phenyl1-8-fmethyl-propvi-aminol-4-oxo-45-dihvdro-3H-benzo f b1 \ 1.41 diazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyiannino)-phenyl]-carbamic acid tert-butyl ester (Example M92) (0.43 g, 0.68

mmol) by treatment with TFA in CH2Cl2 according to the general procedmre N. Obtained as a yellow solid (100 mg, 34%).
MS (ISP) 430.5 [(M+H)--]; mp 221 °C.
Example 106
2-f3-f3-Methyl-isoxa2ol-5-vD-phenyl-8-(methyl-propyl-amino)-4-oxo-4,5-dihvdro-3H-benzofb1 [ l,4ldiazepine-7-carbonitrile
The title compound was prepared from [4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-phenyl]-carbamicacid tert-butyl ester (Example M93) (0.36 g, 0.68 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (94 mg, 34%).
MS (ISP) 414.4 [(M+H)--]; mp 133 °C
Example 107
8-Diethylamino-2-[3-(3-methyl-isoxazol-5-yl)-phenyl-4-oxo-4>5-dihydro-3H-benzofbl f 1.4] diazepine-7-carbonitrile
The title compound was prepared from (4-cyanO-5-diethylamino-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxO-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example M94) (0.35 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid(209 mg, 77%).
MS (ISP) 414.4 [(M+H)+]; mp 191 °C.
Example 108
8-fIsopropyl-methyl-amino)-2-f3*f3-methyl-isoxa2ol-5-yl)-phenyn-4-0X0-4.5-dihvdro-3H-benzofb11 L4ldiazepine-7-carbonitrile
The title compound was prepared from (4-cyano-5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M95) (0.37 g, 0.70 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (219 mg, 76%).
MS (ISP) 414.4 KM+H)--]; mp 197 °C.

Example 109
2- r3-(5-HvdrQxvmethyl- f 1,2.3 Itriazol- l-yl)-phenyl1 -8-f isopropyi-metfayl-amino)-4-oxo-4.5-dihvdro-3H-benzo Fbl f 1,41 diazepme-7-carbonitrile
The title compoimd was prepared from (RS)-[4-cyano-5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-)d]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M96) (0.45 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (236 mg, 77%).
MS (ISP) 430.5 [(M+H)+]; mp 206 °C.
Example 110
8-(Isobutyl-methyl-aminoV2-f3-f3-methyl-isoxazol-5-yl)-phenyn-4-0X0-4,5-dihvdro-3H-ben2ofbl [ l,4]diazepine-7-carbonitrile
The title compoimd was prepared from (4-cyano-5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamicacid tert-butyl ester (Example M97) (0.39 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (230 mg, 75%).
MS (ISP) 428.5 [(M+H)+]; mp 170 °C.
Example 111
2-f3-(5-Hvdroxvmethyl-fL23ltriazol-l-vD-phenyl-8-(isobutyl-methyl-aminoV4-oxo-4.5-dihvdro-3H-benzofb]Fl,4ldiazepine-7-carbonitrile
The title compound was prepared from (RS)-[4-cyano-5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M98) (0.46 g, 0.71 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (180 mg, 57%).
MS (ISP) 444.4 [(M+H)+]; mp 199 X.
Example 112
2-f3-(3-methyl-isoxazol-5-yl)-phenYll-4-oxo-8-piperidin-l-yl-43-dihydro-3H-benzofbUL4ldiazepine-7-carbonitrile
The title compoimd was prepared from (4-cyano-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-5-piperidin-l-yl-phenyl)-carbamic acid tert-butyl

ester (Example M99) (0.41 g, 0.75 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (226 mg, 70%).
MS (ISP) 426.4 [(M+H)--]; mp 246 °C.
Example 113
8-Chloro-7-isobutylamino-4-r3-(3-methyl-isoxazol-5'yl)-phenyl-13-dihvdro-benzofbl ri,4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-isobutylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl] -3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example MlOO) (0.34 g, 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (216 mg, 81%).
MS (ISP) 423.3 [(M+H)--]; mp 249 X.
Example 114
8--Chloro-4-[3-(5-hvdroxymethyl-[L23]triazol-l'yl)-phenv]]-7-isobutylaminO'l,3-dihydrO'benzorb1fl,4ldiazepin-2-one
The tide compoimd was prepared from (RS)-[4-chloro-5-isobutylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2>3]triazol-l-yl]-phenyl}-propionyl-amino)-phenyl]-carbamic acid tert-butyl ester (Example MlOl) (0.17 g, 0.27 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (41 mg, 35%).
MS (ISP) 439.4 [(M+H)--]; mp 214 X.
Example 115
4-f3-(5-Hydroxvmethyl-fL2.3ltriazol-l-yl)-phenyl]-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzofb1[L4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M102) (0.15 g, 0-22 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an off-white solid (31 mg, 30%).
MS (ISP) 473.2 [(M+H)--]; mp 230 °C

Example 116
4-f3-(3-MethyMsoxazol-5-yiVphenyl]-7-fmethyl-propyl-aminoV8-trifluoromethyl-1.3-dihvdro-ben2orb1fL4ldiazepin-2-one
The title compound was prepared from [2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-5-(methyl-propyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M103) (0.26 g, 0.45 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (127 mg, 61%).
MS (ISP) 457.4 [(M+H)+]; mp 193 °C
Example 117
4'f3-(5-Hvdroxvmethyl-fl.23ltria2ol-l-\dVphenyll-7-fisobutyl-metfayl-amino)-8-trifluoromethyl-L3-dihydro-benzorbl[L4ldiazepin-2-one
The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]tria2ol-l-yl]-phenyl}-propionyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M104) (0.51 g, 0.74 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N, Obtained as an off-white solid (169 mg, 47%).
MS (ISP) 487.3 [(M+H)*-]; mp 230 °C.
Example 118
7-fIsobutyl-methyi-aminoV4-f3-f3-methyl-isoxazol-5-yl)-phenyl1-8-trifluoromethyl-13-dihvdro-benzofbUL4ldiazepin-2-one
The title compound was prepared from (5-(isobutyl-methyl-amino)-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M105) (0.42 g, 0.71 mmol) by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (161 mg, 48%).
MS (ISP) 471.2 [(M+H)--]; mp 195 X.
Example 119
4-r3-(5-Hvdroxvmethyl-ri.23ltriazol-l-yl)-phenyll-7-fisopropyl-methyl-aminoV8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[5-(isopropyl-methyl-amino)-2-(3-oxo-3-{3-(5-(tetrahydro-pyran-2-yloxymeth)4)-[l^,3]triazol-l-yl]-phenyl}-propionyl-

amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyi ester (Example M106) (0.50 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as an ofif-white solid (156 mg, 45%).
MS (ISP) 473.3 [(M+H)--]; mp 234 X.
Example 120
7-fIsopropyl-methyl-aminoV4-f3-(3-methyl-isoxazol-5-yl)-phenyl-8-trifluoromethyl-13-dihvdro-ben2o fbl [ 1.41 diazepin-2-one
The tide compound was prepared from (5-(isopropyl-methyl-amino)-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example M107) (0.37 g, 0.64 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (74 mg, 25%).
MS (ISP) 457,4 [(M+H)+]; mp 199 °C.
Example 121
8-Chloro-7-fmethyl-propyl-amino)-4-f3-(5-pvrrolidin-l-ylmethyl-[1.2.3ltria2ol-l-yl)-phenyll -13'dihydro-benzo Fbl [ 1,4] diazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-ainino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepm-2-one (Example 29) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a yellow foam (63 mg, 26%).
MS (ISP) 492.3 [(M+H)+].
Example 122
4-f3-(5-A2etidin-l-ylmethyl4L2.3ltriazol-l-yl)-phenyn-8-chloro-7-fmethyl-propyl-amino)-L3-dihydro-benzo fbl [l,4]diazepin-2-one
The title compoimd was prepared from 8-chIoro-7-(methyl-propyi-amino)-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one
(Example 29) (118 mg, 0.27 namol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine in DMF according to the method described in Example 45. Obtained as a light yellow solid(65 mg, 50%),

MS (ISP) 478.3 [(M+HD; mp 169 *°C
Example 123
8-CMoro-4-f3-(5-diethylaminomcthyi-fL2J)triazol-l-yl)-phenyl]-7-fmethyl-propyl-aminoyl,3-dihvdro-benzorblfL4]dia7q?in-2-one
The tide compound was prepared from 8-chloro-7-(meth-5d-propyl-amino)-4-[3-(5-hydroxymethyl- [ l,2,3]tria2ol-1 ->i)-phen\1 j -13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction wth thionylchloride in dichloro-methane and subsequent treatment of the corresponding chloride with diethylamine in DMF according to the method described in Example 45. Obtained as a Ught yellow solid (123 mg, 50%).
MS (ISP) 494.3 [(M+H)--]; mp 151 °C
Sample 124
8-Chloro-4-C3-l5-rfisopropvI-methyl-amino)-methyll-fL23ltriazoM-ylt-phenyD-7-(methyl-propyl-amino)-13-dihvdro-benzofbUL4]diazepin-2-one
The tide compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymediyl-[l,2,3]triazol-l-yl)-phenyl]-13-dihydro-ben2o[b][l,4]diazepin-2-one (Example 29) (219 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isopropyl-methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (129 mg, 52%),
MS (ISP) 494.3 [(M+H)-*-]; mp 148 °C.
Example 125
8-Chloro-7-fisopropyl-methyl-amino)-4-f3-f5*pvrrolidin-l-ylmethyl-fL23ltria2ol-l'yI)-phenyl]-13-dihvdro-benzo[b1fL4ldiazepin-2-one
The tide compound was prepared from 8-chloro-4-l3-(5-hydroxymethyi-
[lA3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (219 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrroUdine in DMF according to the method described in Example 45.
Obtained as a light yellow solid (157 mg, 64%).
MS (ISP) 492.3 [(M+H)--]; mp 172 °C.

Example 126
8-Chloro-7-fisobutyl-methyl-aminoV4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1 -13-dihvdro-benzo[b1 ri.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[ 1,2,3] triazol- l-yl)-phenyl]-7-(isobutyl-methyl-amino)- 1,3-dihydro-
ben2o[b] [l,4]diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Erample 45.
Obtained as a light yellow solid (163 mg, 64%),
MS (ISP) 506.3 [(M+H)+]; mp 190 X.
Example 127
8-Chloro-4-f3-(5-dimethylaminomethyl-fL2,3ltriazoM-yD-phenyl-7-(isopropyl-methyl-aminoyl3-dihydro-benzofb1[1.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as a light brown solid (143 mg, 61%).
MS (ISP) 566.3 [(M+H)+]; mp 225 X.
Example 128
8-Chloro-4-f3-(5-dimethylaminomethyl-rL2.3ltriazoM-vD-phenyl]-7-risobutvI-methyl-aminoyl,3-dihvdro-benzofbUL4]diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-
benzo[b] [1,4] diazepin-2-one (Example 101) (226 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as a light brown solid (134 mg, 56%).
MS (ISP) 480.5 [(M+H)--]; mp 199 X.

Example 129
4-[3-(5-Azetidin-l-ylmethyl-[1.2,3]triazol-l-yl)-phenyl1-8-chlorO'7-fisopropvI-methyl-amino V13-dihydro-ben2o [b] F1.41 diazepin-2*one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyI-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 99) (219 mg> 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimethylene-imine m DMF according to the method described in Example 45. Obtained as a light brown solid (102 mg, 43%).
MS (ISP) 478.3 [(M+H)--]; mp 177 °C.
Example 130
4-f3-(5-Azetidin-l-ylmethyl'fh2J]triazol-l-vD-phenyl>8-chloro-7-risobutyl-methyl-amino)-1.3-dihvdro-benzo[bl[l,4ldiazepin-2'One
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3'dihydro-benzo[b][l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with trimelhylene-imine in DMF according to the method described in Example 45. Obtained as a light brown solid (125 mg, 52%).
MS (ISP) 492.3 [(M+H)+]; mp 191 °C.
Example 131
8-Chloro-4-f3-(5'methylaminomethyl-rL2.3ltriazol-l-vD-phenyl-7-fmethyl-propyl-amino)-L3-dihvdro-benzoFb1fl.4ldiazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyi]-l,3-dihydrO-benzoIb][l,4]diazepin-2-one
(Example 29) (230 mg, 0.52 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with methylamine in DMF according to method described in Example 45. Obtained as a Kght yellow solid(122 mg, 52%).
MS (ISP) 452.4 [(M+H)--]; mp 185 °C.

Example 132
4-f3-(5-Hvdroxvmethyl-fl,23]triazol-l-yl)-phenyl1-7-fisobulTl-methyl-amino) methyl- L3-dihvdro-ben20 Fbl [ L4l diazepin-2-one
The title compound was prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyl-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M108) (0.33 g, 0.52 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a pale brown solid (188 mg, 79%).
MS (ISP) 43L4 [(M-H)-]; mp 198 -C.
Example 133
443-(5-Hvdroxvmethyl-ri23ltriazol-l-yl)-phenyl1-8-methyl-7-pvrrolidin-l-yl-13-dihydrO'benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (RS)-[4-methyl-2-(3-oxo-3-{3-[5-(tetrahydxo-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylainino)-5-pyrrolidin-l-yl-phenyl]-carbamic acid tert-butyl ester (Example MHO) (0,41 g, 0.66 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as a light yellow solid (239 mg, 86%).
MS (ISP) 417-3 [(M+H)--]; mp 202 °C.
Example 134
7-(Isobutyl-methyl'amino)-8-methyl-4-f3-f3-methyl-isQxazol-5-yl)-phenylyl3-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from (5-(isobutyl-methyl-amino)-4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyI)-carbamicacid tert-butyl ester (Example M109) (0.33 g, 0.62 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (136 mg, 53%).
MS (ISP) 417.3 [(M+H)--]; mp 187C.
Example 135
8-methyl-4-r3-f3-methyl-isoxazol-5-yl)-phenyl1-7-pvrrolidin-l-yl-13-dihvdro-benzofbl f L4ldiazepin-2-one
The title compoimd was prepared from (4-methyl-2-{3-[3-(3-methyl-isoxazol-5-yl)-phenyl]-3-oxo-propionyiainino}-5-pyrrolidin-l-yl-phenyl)-carbamic acid tert-butyi

ester ^iixample M111; (U.33 g, 0.64 mmolj by tr . nent with TFA in CH2Cl2 according to the general procedure N. Obtained a^ an off-white solid (223 mg, 87%).
MS (ISP) 401.5 [(M+H)--]; mp 211 '°C.
Example 136
4-F3-(5-Dimethylaminomethyl-fL2.3ltriazol-l-yl)-phenyl-7-(isobutyl-methyl-amino)-8-trifluoromethyl-13-dihydro-benzofbiri.4ldiazepin-2-one
The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7-(isobutyl-methyl-amino)-8-trifluoromethyl- 1,3-dihydro-ben2o[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethylamine in DMF according to the method described in Example 45. Obtained as a light brown solid (110 mg, 35%).
MS (ISP) 514.3 [(M+H)*-]; mp 182 °C.
Example 137
8-(Isobutyl-methyl-aminoV4-oxo-2-[3-(5-pvrrolidin-l-ylmethyl-rL23ltriazol-l-yl)-phenyn-4.5-dihydro-3H-benzorb1fl,4ldiazepine-7-carbonitrile
The title compoxmd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-benzo[b][l,4]diazepine-7-carbonitrile (Example 111) (200 mg, 0.45 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (140 mg, 63%).
MS (ISP) 497.3 [(M+H)--]; mp 174 °C,
Example 138
7-(Isobutyl-methyl-aminoV4-f3-(5-pyrrolidin-l-ylmethyl-fl.23ltriazol-l-vIV phenyl]'8-trifluoromethyl*13-dihydro-benzofb1[h4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yi)-
phenyl]-7-(isobutyl-methyl-ainino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 117) (300 mg, 0.62 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45.
Obtained as a Ught orange foam (80 mg, 24%).

MS (ISP) 540.5 [(M+H)+)..
Example 139
7-('Isobutyl-methyl-amino)-8-methyl-4-f3-(5-pvrrolidin-l-ylmethyl-[L23ltriazol-l-yl)-phenyl1-1.3-dihydro-benzorbirL4Tdiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yI)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 132) (200 mg, 0.46 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (50 mg, 22%).
MS (ISP) 486.4 [(M+H)--]; mp 177 °C.
Example 140
8-(Isobutyl-methyl-amino)-2-(3-{5-f(isobutyl-methyl-amino)'methyl]-rL23ltriazol-l-yll-phenyl)-4-oxo-4.5-dihvdro-3H-ben2o[b1[l,4ldiazepine'7-carbonitrile
The title compoimd was prepared from 2-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-8-(isobutyl-methyl-amino)-4-oxo-4,5-dihydro-3H-ben2o[b][l,4]diazepine-7-carbonitrile (Example HI) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-isobutyl-methylamine in DMF according to the method described in Example 45, Obtained as a light yellow solid (100 mg, 39%).
MS (ISP) 513.4 [(M+H)+]; mp 169 °C.
Example 141
7-fIsobutyl-methyl-amino)-4-f3-l5-[(isopropyl-methyl-amino)-methyl]-[L2,3ltria2ol-l-vU-phenyl)-8-trifluoromethyl-L3-dihvdro-benzofb1[1.4ldiazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2oM-yl)-
phenyl]-7-(isobutyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 117) (260 mg, 0,53 nrnnol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropyl-methylamine in DMF according to the method described
in Example 45. Obtained as a light brown solid (70 mg, 24%),
MS (ISP) 542.3 [(M+H)--]; mp 157 °C

Example 142
8'Chloro-4-F3-(5-cyclopentylaminomethyl-[L23ltriazol-l-vIVphenyll-7-(isopropyl-methyl-aminoyl3-dihvdro-ben2o[b1Fl.4]diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopentylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (170 mg, 67%).
MS (ISP) 506.3 [(M+H)--]; mp 174 *°C.
Example 143
4-f3-l5-[(Cvclopropylmethyl'amino)'methyl1-rL2.3ltriazol*l-yU-phenvD-7-(isobutyl-methyl-amino)-8-methyl-L3-dihydro-benzofblfl,4]diazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyM,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 132) (250 mg, 0.58 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylmethylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (50 mg, 18%).
MS (ISP) 486.4 [(M+H)+]; mp 184 °C,
Example 144
8-Cbloro-7-fisobutvI-methyl-aminoV4-[3-(5-piperidin-l-ylmethyl-[1.23ltriazol-l' yl)-phenyl1-13-dihvdro-ben2ofb1fL4ldiazepin-2-one
The title compoimd was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[ l,2,3]tria2ol- l-yl)-phenyl]-7- (isobutyl-methyl-amino)- 1,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 101) (220 mg, 0.49 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with piperidine in DMF according to the method described in Example 45.
Obtained as a light brown solid (250 mg, 99%).
MS (ISP) 520,3 [(M+H)--]; mp 169 «C.

Example 145
8-Chloro-4-B-(5-(isopropylaminO-methyl)-fL2,3ltriazol-l'yl]-phenvU-7-(isopropyl-methyl-aminoyl.3-dihvdro-benzofb1fl.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazol-l-yl)-phenylj-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with isopropylamine in DMF according to the method described in Example
45. Obtained as a light yellow solid (160 mg, 67%),
MS (ISP) 480.3 [(M+H)+]; mp 208 °C.
Example 146
8-Chloro-7-fisopropyl'methyl-aminoV4-[3-(5-{f(2-methoxy-ethyl)*methyl-amino1-
methvU-fL2,3ltriazol-l-yl)-phenyl1-l3-dihydro-benzo[b1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with N-(2-methoxyethyl)methylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (120 mg, 47%).
MS (ISP) 510.4 [(M+H)+]; mp 119 °C.
Example 147
8-Chloro-4-(3-{5-[(cvclopropylmethyl-aminoVmethyl]-fL23ltria2ol-l-yll-phenyl)-7-(isopropyl-methyl-amino)'13-dihvdro-benzorbl[1.4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-13-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, D.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with aminomethyl-cyclopropane in DMF according to the method described
in Example 45. Obtained as a light brown solid (150 mg, 61%).
MS (ISP) 592,2 KM+H)--]; mp 151 °C

Example 148
8-ChlorO-7-(isopropyl-methyI-aminoV4-f3-l5-f('isopropyl-metfayl-amino)-methyl]-fL23ltriazoM-yll-phenylyl3-dihvdro-benzorbUL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]triazoH-yl)-phenyi]-7-(isopropyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropylmethylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (120 mg, 49%).
MS (ISP) 494.3 [(M+H)--]; mp 180 °C.
Example 149
8-Chloro-4-f3-{5-rfisobutyl-methyl-aminoVm€thyl)-rL23ltriazoM-yl]-phenyl)-7-(isopropyl-methyl-amino)-13-dihvdro-benzo[b1 [1.41 diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,3]tria2ol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-
ben2o[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isobutylmethylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (190 mg, 75%).
MS (ISP) 508.4 [(M+H)--]; mp 182 °C
Example 150
4-f3'(5'DimethylaminomethyI-fL2,3]triazoI-l-yl)-phenyl]-7-risopropyl'metfayl-aminoV8-trifluoromethyl--13-dihvdro-benzofb][1.4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l>4]diazepin-2-one (Example 119) (200 mg, 0,42 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with dimethylamine in DMF according to the method described in Example
45. Obtained as an off-white solid (80 mg, 38%).
MS (ISP) 500.4 [(M+H)--]; mp 197 »C.

Example 151
7-fIsopropyl-methyl-amino)-4-r3-(5-pvrrolidin-l-ylmethyl-fL23ltriazoI-l-yl)-phenyll -8'trifluoromethyl-13-dihvdro-ben20 f hi f 1,41 diazepin'2-one
The title compound was prepared from 4- [3-(5-hydroxymethyl- [l,2,3]triazol- 1-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (200 mg, 0.42 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45.
Obtained as a light brown solid (140 mg, 63%).
MS (ISP) 526.2 [(M+H)--]; mp 175 X.
Example 152
7-Qsopropyl-methyl-aminoV4-(3-l5-f(isopropyl-methyl-amino)-methyl1-
fl.2.3ltriazol-l'yl}-phenyl)-8-trifluoromethyI-L3-dihvdro-benzofbUl.4]diazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (220 mg, 0.47 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with N-isopropylmethylamine in DMF according to the method described in
Example 45, Obtained as a light yellow solid (110 mg, 45%).
MS (ISP) 528.4 [(M+H)1; mp 182 °C,
Example 153
4,f3-|5-r(Cvclopropylmethyl*aminoVmethyl1-rL23Uria2ol-l-yll-phenyl)-7-fisopropyI-methyl-aminoV8-trifluoromethyl-L3-dihvdro-benzorb1fl,4ldiazepin-2-
one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (210 mg, 0.44 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with aminomethyl-cyclopropane in DMF according to the method described
in Example 45. Obtained as a light brown solid (110 mg, 47%).
MS (ISP) 526.2 [(M+H)--]; mp 152 °C

Example 154
8-Chloro-4- TS-f 5-cyclopropylaminomethyl- [ h2.3ltriazol-l-yl)-phenyll-7-f isopropyl-methyl-amino V13'dihvdro-b enzo f b1 f 1.41 diazepin-2- one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[ 1,2,3 ] triazol-1 -yl)-phenyl] -7- (isopropyi-methyl-amino) -13-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0,50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (40 mg, 17%).
MS (ISP) 478.4 [(M+H)--];mp 144 °C
Example 155
4-l3-(5-fIsopropylamino-methyl)-rL23ltriazol-l-yl]-phenyll-7-(isopropyl-methyl-amino)-8-trifluoromethyl-L3-dihvdrO'benzorbirL4ldiazepin-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-trifluoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with isopropylamine in DMF according to the method described in Example
45. Obtained as a light yellow solid (100 mg, 39%).
MS (ISP) 514.4 [(M+H)+]; mp 191 °C.
Example 156
8-Chloro-4-(3-r5-fisobutylamino-methvD-fL23ltriazol-l-yl1-phenyll-7-(isopropyl-methyl-aminoyl3'dihvdro-benzofb1fL4ldiazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl]-7-(isopropyl-methyl-amino)-l,3-dihydro-benzo[b] [l,4]diazepin-2-one (Example 96) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with isobutylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (160 mg, 65%).
MS (ISP) 494.4 [(M+H)--]; mp 182 X.

Example 157
4-f3-(5-Cvclopropylaminomethyl-fl.2.3ltriazoM-yl)-phenyl1-7-fisopropyl-methyl-aminoV8-trifluoromethyl*1.3-dihvdro-benzofblfL4ldia2epm-2-one
The title compound was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]tria2ol-l-yl)-
phenyl]-7-(isopropyl-methyl-amino)-8-tri6uoromethyl-l,3-dihydro-
benzo[b] [l,4]diazepin-2-one (Example 119) (236 mg, 0.50 mmol) by reaction with
thionylchloride in dichloromethanc and subsequent treatment of the corresponding
chloride with cyclopropylamine in DMF according to the method described in
Example 45. Obtained as a light yellow solid (70 mg, 27%).
MS (ISP) 512.4 [(M+H)--]; mp 178 '°C
Example 158
7-fIsobutyl-methyl-amino)-8-methyl-4'f3-(5-pvrrolidin-l-ylmethyl*fL2,4ltria2ol-l-vD-phenvI1-13-dihvdro-benzoib1fL4ldiazepin-2-one
The title compound was prepared from 4-(3-(5-hydroxymethyl-[l,23]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-8-methyl-13-dihydro-benzo[b] [ 1,4]diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as an ofif-white solid (106 mg, 52%).
MS (ISP) 486,5 [(M+H)']; mp 164 °C.
Example 159
4-[3-(5-Cyclopropylaminomethyl-fL2,4ltriazol-l-yl]-phenyl1-7-(isobutyl'methyl* amino)-8-methyl-1.3-dihydro-benzofb][L4ldiazepin-2-one
The title compoimd was prepared from 4-[3-(5-hydroxymethyl-[l,2,3]triazol-l-yl)-phenyl] -7- (isobutyl-methyl-amino)-8-methyl-1,3-dihydro-benzo [b] [ 1,4] diazepin-2-one (Example 132) (180 mg, 0.42 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (108 mg, 55%).
MS (ISP) 472.4 [(M+H)--]; mp 114 °C.

Example 160
8-Chloro-7-isopropylamino-4-f3-f3-methyl-isoxazol-5-vD-phenyl-1.3-dihydro-benzofbl f L4ldiazepin-2-one
The title compound was prepared from (4-chloro-5-isopropylamino-2-{3-[3-(3-methyl-isoxa2ol-5-yl)-phenyl]-3-oxo-propionylamino}-phenyl)-carbamic acid tert-butyl ester (Example Ml 12) (0.16 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (120 mg, 93%).
MS (ISP) 409.4 [(M+H)--]; mp 225 *°C.
Example 161
8-Chloro-4-f3-(5-hvdroxvmethyl-|-l,2,3ltriazol-l-vD-phenyll-7-isopropylamino-13-dihvdro-benzofbl [ L4l diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-isopropylamino-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,3]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example M113) (0.37 g, 0.60 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (209 mg, 82%).
MS (ISP) 425.4 [(M+H)--]; mp 250 °C.
Example 162
8-Chloro-7-(methyl-propyl-amino)-4-f3-(5-hvdroxvmethyl-[L2,4ltriazol-l-yl)-phenyl! -1,3-dihydro-benzo f b1 f 1.41 diazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(methyl-propyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 14) (1.47 g, 2.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale yellow solid(1.0 g, 99%).
MS (ISP) 439.5 [(M+H)--]; mp 192 °C,
Example 163
8-Chloro-4-r3-(5-hvdroxvmethyl-rL2.4ltriazol-l-yl)-phenyll-7-risobutyl-methyl-aminoyl3-dihvdro-benzofbirL4ldiazepin-2-one
The title compound was prepared from (RS)-[4-chloro-5-(isobutyi-methyl-amino)-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]tria2ol-l-yl]-phenyl}-propionylamino)-phenyl]-carbamic acid tert-butyl ester (Example Ml 15) (0.61 g, 0.93

mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a Hght brown solid (290 mg, 69%).
MS (ISP) 453.5 [(M+H)--]; mp 195 °C
Example 164
8-ChlorO-7-(methyl-propyl-amino)-4-f3-(5-pyrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yIVphenyll-l,3-dihvdro-benzo[b1fl,4]diazepin-2-one
The title compound was prepared from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4]triazol-l-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with pyrrolidine in DMF according to the method described in Example 45. Obtained as a light yellow solid (114 mg, 46%).
MS (ISP) 492.3 [(M+H)1; mp 183^0.
Example 165
8-Chloro-7'fisobutyl-methyl-aminoV4-r3-(5-pvrrolidin-l-ylmethyl-ri.2,4ltriazol-l-yl)-phenyl] * 13-dihvdro-benzo f bl [ 1.41 diazepin-2-one
The title compound was prepared from 8-chloro-4-[3-(5-hydroxymethyl-
[l,2,4]triazol-l-yl)-phenyl]-7-(isobutyl-methyl-amino)-l,3-dihydro-
benzo[b] [l,4]diazepin-2-One (Example 163) (200 mg, 0,44 mmol) by reaction with
thionylchloride in dichloromethane and subsequent treatment of the corresponding
chloride with pyrrolidine in DMF according to the method described in Example 45,
Obtained as a light yellow solid (99 mg, 44%).
MS (ISP) 506.4 [(M+H)+]; mp 164 °C.
Example 166
8-Chloro-4-f3-(5-dimethylaminomethyl-[L2.4ltriazol'l-yl)-phenyl1-7-fmethyl-propyl-amino)-1.3-dihydro-benzorblfl,4ldiazepin-2-one
The title compound was prepared-from 8-chloro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymethyl-[l,2,4ltriazol-l-yl)-phenyl]-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with dimethyiamine in DMF according to the method described in Example 45. Obtained as a light yellow solid (93 mg, 540%).

MS (ISP) 466.4 [(M+H)--]; mp 170 X,
Example 167
8-Chloro-4-r3-(5-cvclopropylaminomethyl-fL2,4]tria2ol-l-yl)-phenyl1-7-fmethyl' propyl-aminoyl,3-dihvdro-benzofbUL4ldiazepin-2-one
The title compound was prepared from 8-chIoro-7-(methyl-propyl-amino)-4-[3-(5-hydroxymiethyl-[l,2,4]tria2ol-l-yl)-phcnyi)-13-dihydro-benzo[b][l,4]diazepin-2-one (Example 162) (220 mg, 0.50 mmol) by reaction with thionylchloride in dichloromethane and subsequent treatment of the corresponding chloride with cyclopropylamine in DMF according to the method described in Example 45. Obtained as a Hght yellow solid (95 mg, 40%).
MS (ISP) 478.4 [(M+H)--]; mp 123 ^'C
Example 168
4-f3-(5-Hvdroxymethyl-fL2,4]triazol-l-\i)-phenyll-7-fisobutyl-methyl-aminoV8-methyl'l,3-dihydro-benzofb1 (h4]diazepin-2-one
Prepared from (RS)-[5-(isobutyl-methyl-amino)-4-methyi-2-(3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,2,4]triazoM-yl]-phenyl}-propion)iamino)-phenyi]-carbamic acid tert-butyl ester (Example Ml 16) (0.96 g, 1.51 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a pale brown solid (480 mg, 73%).
MS (ISP) 433.6 [(M+H)+]; mp 191X.
Example 169
7-(methyl-propyl-aminoV4'f3-fL2,4ltriazol-l-yl-phenyl)-8-trifluoromethyM3-dihvdro-benzorbUl.4ldiazepin-2-one
The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M117) (0.31 g, 0.55 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light ydlow solid (192 mg,78%).
MS (ISP) 443.4 [(M+H)--]; mp 185 *C.

Example 170
7-(methyl-propyl-aminoV4-(3-[l,23ltriazol-l-yl-phenvD-8-tiifluoromethyl-13-dihvdro-benzo [b1 f 1,41 diazepin-2-one
The title compound was prepared from {5-(methyl-propyl-amino)-2-[3-oxo-3-(3-[l,2,3]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 18) (0.33 g, 0.59 mmol) by treatment -with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (115 mg, 44%).
MS (ISP) 443.4 [(M+H)+]; mp 147 X.
Example 171
7-(I$obutyl-methyl-aminoV4-(3-pyrazoI-l-yl-phenyl)-8-trifluoromethyl-13-dihydro-benzo fbl \ 1,41 diazepin-2-one
The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-pyrazol-l-yl-phenyl)-propionylamino] -4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example Ml 19) (0.49 g, 0.85 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yeUow solid (324 mg, 83%).
MS (ISP) 454.4 [(M-H)-]; mp 182 X.
Example 172
4-f8-(Isopropyl-methyl-amino)-4-oxQ-7-trifluoromethyl-4,5-dihvdro-3H-benzofb1[L4ldiazepin-2-yl1-pyridine-2-carbonitrile
The title compound was prepared from [2-[3-(2-cyano-pyridin-4-yl)-3-oxo-propionylamino]-5-(isopropyI-methyl-amino)-4-trifluoromethyl-phenyl]-carbamic acid tert-butyl ester (Example M120) (0.67 g, 1.29 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (210 mg, 41%).
MS (ISP) 400.3 [(M-H)-l; mp 189 *°C.

Example 173
8'Chloro-7-fisobutyl-methyl-aminoV4-f3-fl.2.4ltriazol-l-yl-phenvD-13-dihvdro-benzofbl rL4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-phenyl}-carbamicacidtert-butyl ester (Example M121) (0.76 g, 1.41 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a li^t orange solid (530 mg, 89%),
MS (ISP) 423.4 [(M+H)-*]; mp 213 °C.
Example 174
7-fIsobutyl-methyl*aminoV4-(3-fl,2.4ltriazol-l-yl-phenvD-8-trifluoromethyl-l,3-dihvdro-benzofbiri,4ldiazepin-2-one
Prepared from {5-(isobutyl-methyl-amino)-2-[3*oxo-3-(3-[l,2,4]tria2ol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M122) (0.50 g, 0,87 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (350 mg, 88%).
MS (ISP) 457.5 [(M+H)*-]; mp 198 X,
Example 175
8-Chloro-7-(isobutvI-methyl-aminoV4-(3-[L23ltriazol-l-yl-phenylyl3-dihvdro-benzoFbl f L4]diazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M123) (0.17 g, 0.31 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a hght yellow solid (100 mg, 75%),
MS (ISP) 423.5 [(M+H)--]; mp 85 °C.
Example 176
7-fIsobutyl-methyl-aminoV4-f3-fl.23ltriazol-l-'vi-phenyl)-8-trifluoromethvM3-dihvdro-benzorblfL4]diazepin-2*one
The title compound was prepared from {5-(isobutyl-methyl-amino)-2-[3-oxo-3-(3-[ 1,2,3 ] triazol- l-yl-phenyl)-propionyiamino] -4-trifluoromethyl-phenyi}-carbamic acid tert-butyl ester (Example M124) (0.44 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (170 mg, 49%),

MS (ISP) 457.5 [(M+H)--]; mp 202 °C
Example 177
4-f3-Imida2ol-l-yl-phenvD-7-isobutylamino-8-trifluoromethyI-13-dihvdro-benzofbl ri,4ldiazepin-2-one
The title compound was prepared from {2-[3-(3-imida2ol-l-yl-phenyl)-3-oxo- . propionylamino] -5-isobutylamino-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M125) (0.43 g, 0.77 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (260 mg, 76%).
MS (ISP) 442.4 [(M+H)1; mp 221 °C.
Example 178
8-ChlorO'4-(3-imidazol-l-yl-phenyl)-7-isobutylamino-L3-dihvdro-benzofb] f h4]diazepin-2-one
The title compound was prepared from {4-chlorO-2-[3-(3-imidazoM-yl-phenyl)-3-oxo-propionylamino]-5-isobutylamino-phenyl}-carbamic acid tert-butyl ester (Example M126) (0.33 g> 0.63 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (240 mg, 94%).
MS (ISP) 408,4 [(M+H)+]; mp 212 °C.
Example 179
8-Chloro-7-(isobutyl-aminoV4-f3-ri,2.3ltriazol-l-yl-phenylyl3-dihvdro-benzofbl [l,4ldiazepin'2-one
The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazoH-yl-phenyl)-propionylamino]-phenyl}-carbamic acid tert-butyl ester (Example M127) (0.22 g, 0.42 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light yellow solid (90 mg, 53%).
MS (ISP) 407.3 [(M-H)']; mp 249 °C.
Example 180
7-(Isobutyl-amino)-4-r34L23ltriazol-l-vI-phenyl)-8-trifluoromethyl-13-dihvdro-benzofbl f l,4ldiazepin-2-one
The title compovmd was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,3]triazol-l-yl-phenyl)-propionyiamino]-4-trifluoromethyl-phenyl}-carbamic
add tert-butyl ester (Example M128) (0.34 g, 0.61 mmol) by treatment with TFA in

CH2Cl2 according to the general procedure N. Obtained as a light brown solid (150 mg> 56%).
MS (ISP) 443.4 [(M+H)+]; mp 212 °C.
Example 181
8-Chloro-7-(isobutyl-aminoV4-f3-[L2,4ltriazol-l-yl-phenvD-L3-dihvdro-benzofbl [L4ldiazepin-2-one
The title compound was prepared from {4-chloro-5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-phenyl}-carban:iic acid tert-butyl ester (Example M129) (0.39 g, 0.74 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light orange solid (270 mg, 89%).
MS (ISP) 407.3 [(M-H)-]; mp 222 X.
Example 182
7-fIsobutyl-aminoV4-f3-[L2.4ltriazol-l-yl-phenyl)-8-trifluoromethyl-L3-dihvdrO' benzo[bl f 1.4]diazepin-2-one
The title compound was prepared from {5-(isobutyl-amino)-2-[3-oxo-3-(3-[l,2,4]triazol-l-yl-phenyl)-propionylamino]-4-trifluoromethyl-phenyl}-carbamic acid tert-butyl ester (Example M130) (0.43 g, 077 mmol) by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a light brown solid (270 mg, 61%).
MS (ISP) 441.3 [(M-H)-]; mp 191X.
Example 183
8-Chloro-7-fethyl-methyl-amino)-4-f3-f4-hvdroxymethyl-thiazol-2-yl)-phenyl-l,3-dihydro-benzoTbl f l,4]diazepin-'2-one
The title compound was prepared from [2-amino-4-chloro-5-(ethyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.14 g).
MS (ISN) 439.2 [(M-H)*]; mp 136-137 °C.

Example 184
8-Chloro-4-f3-f4-hvdroxymethyl-thiazol-2-yD-phenyll-7-fmetfayl-propyl-amino)-1,3-dihydro-ben20 [b] [ 1.4] diazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-t±iiazol-2-yl]-phenyl] -propionic acid tert-butyl ester (0.23 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cycUzed by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0-10 g).
MS (ISN) 453.2 [(M-H)-]; mp 211-213 °C
Example 185
8-Chloro-4-[3-(4-hvdroxymethyl-thiazol-2-yl)-phenyll-7-(isopropyl-methyl-amino)-L3*dihydro-benzo[b1fL4ldiazepin-2-one
The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a light-brown solid (0.05 g).
MS (ISP) 455.2 [(M+H)1; mp 193-195 °C
Example 186
8-Chloro-4-f3-(4-hydroxymethyl-thiazol-2-yl)-phenyn-7-(isobutyI-methyl-amino)-L3-dihydrO'benzofb1fl,4ldiazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(isobutyl-methyi -amino)-phenyI]-carbamic acid tert-butyl ester (0.23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl
ester (0.32 g) (Example K27) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g).
MS (ISP) 469.1 [(M+H)--]; mp 135-136 °C

Example 187
8-Chloro-7-fetfayl-methyl-aminoV4-r3-f4-hydroxvmethyl-oxa2ol-2-yl)-phenyn-l,3-dihvdro-benzofbl f l,4ldiazepin-2-one
The title compound was prepared from [2-amino-4-Chloro-5-(ethyl-methyl-amino)-phenylj-carbamic acid tert-butyl ester (0.15 g) (Example J7) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxyxnethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedxire N. Obtained as a yellow solid (0.10 g).
MS (ISN) 423.1 [(M-H)-]; mp 165-166 °C.
Example 188
8-Chloro-4-[3-f4-hvdroxvmethyl-oxazol-2-yD-phenyll-7-fmethyl-propyl-aminoV L3-dihvdro-benzofb1fl.4]diazepin-2-one
The title compound was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g).
MS (ISP) 437.2 [(M-H)-]; mp 166-167 °C
Example 189
8-Chloro-4-f3-(4-hvdroxymethyl-oxazol-2-yl)-phenyl1-7-fisopropyl-methyl-amino)-L3-dihydro-ben2ofb1 [1.41 diazepin-2-one
The tide compound was prepared from [2-amino-4-chloro-5-(isopropyl-methyl-amino)-phenyI]-carbamic acid tert-butyl ester (0.17 g) (Example J26) and 3-oxo-3-[3-l4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phenyl]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a ydlow solid (0.05 g).
MS (ISP) 439.3 [(M+H)*-]; mp 143-145 X.

Example 190
8-ChlorO-4-r3-f4*hvdroxvmethyl-oxazol-2-yl)-phenyll-7-fisobutyl-methyl-amino)-13-dihvdro-benzo|-b][1.4]diazepin-2-one
The title compound was prepared from [2-aminO-4-chloro-5-(isobutyl-methyI -amino)-phenyl]-carbamic acid tert-butyl ester (0,23 g) (Example J27) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (0.31 g) (Example Kll) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0,18 g),
MS (ISP) 453,3 [(M+H)*-]; mp 166-167 °C.
Example 191
8-Chloro-7-dimethylamino-4-f3-(4-methylaminomethyl-thiazol-2-yl)-phenyll-1.3-dihydro-benzofb]fL4ldiazepin-2-one
al 8-ChIoro-4-f3-(4-chloromethyl-thia2oI-2-yl)-phenyll-7-dimethylamino-13' dihydro-benzo[b][1.4]diazepin-2-one
A mixture of 8-chIoro-7-dimethylamino-4-[3-(4-hydroxymethyl-thiazol-2-yl)-phenyl]-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.38g) (Example 19) andthionyl chloride (0,1 mL) in CH2Cl2 was heated to 40 -°C for 2 h. The heterogeneous mixture was evaporated in vacuum and the residue was triturated with AcOEt to give the title compound (0,44 g) as a light-brown soHd, MS (ISP) 445.1 [(M+H)+],
b) 8-Chloro-7-dimethyiamino-4-f3-(4-methylaminomethyl-thiazol-2-vD-phenyl-l,3-dihydro-ben2orb][l,4]diazepin-2-one
A mixture of 8-chloro-4-[3-(4-chloromethyl-thia2ol-2-yl)-phenyl] -7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (89 mg) and KI (3 mg) in a 8M solution of methylamine in EtOH (1 mL) was stirred at 20 °C for 20 h. H2O (25 mL) was acided and the pH of the mixture was set to 11 by acidition of 2N NaOH. The precipitate was collected by filtration and purified by chromatography on silica gel using MeOH as eluent. The product was stirred with 20% aqueous MeOH (10 mL) and the solid was isolated by filtration to give the title compound (49 mg) as a yellow powder,
MS (ISP) 440.2 [(M+H)--]; mp 129-130 °C.

Example 192
8-Chloro-7-dimethylamino-4-f3-f4-morpholin-4-ylmethyl-thia2ol-2-yD-phenyl1-1.3-dihvdro-benzofbl ri,4ldiazepin-2-one
A mixture of 8-chlo^o-4-[3-(4-chloromethyl-thiazol-2-yl)-phenyl]-7-dimethyla^mlo-l,3-dihydro-ben2o[b] [l,4]diazepin-2-one (89 mg) (Example 191a), morpholine (0.17 mL) and KI (3 mg) in EtOH (0.5 mL) was stirred at 60° C for 3 h. H2O (25 mL) was acided to the cooled solution and the precipitate was collected by filtration and purified by chromatography on silica gel using AcOEt/acetone (1:1) as eluent The product was stirred with 20% acjueous MeOH (20 mL) The pH of the mixture was set to 11 by acidition of IN NaOH and the solid was subsequently isolated by filtration to give the title compound (55 mg) as yellow powder.
MS (ISP) 496.2 [(M+H)--]; mp 138-143 °C
Example 193
8-Chloro-7-dimethylaminO-4-[3-(2-hydroxvmethyl-thiazol-4-vD-phenylyl3-dihydrO'benzorb][L4ldiazepin-2-one
a)4-(3-Bromoacetyl-phenyl)-8-chloro-7-dimethylaminO'13-dihvdro-benzofb] [L4Tdiazepin-2-one
A solution of 3-Oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyl ester (2.34 g) (Example K28) and (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert,-butyl ester (Example J2) (L57 g) in toluene (16 mL) was heated to 100 *C for 5 h. The solvent was evaporated in vacuimi and the crude product was purified by chromatography on silica gel using CH2Cl2/AcOEt (1:20) as eluent. A solution of the purified material (2.4 g) in CH2Cl2/TFA (1:1,30 mL) was stirred at 20 °C for 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated. The residue was crystallized firom AcOEt/EtaO to give 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b] [l,4]diazepin-2-one as light-brown solid.
b^8-Chloro-7-dimethylamino-4-f3-(2-hvdroxvmethyl-thiazol-4-yl)-phenyl1-L3-dihvdro-benzofbl f L4ldiazepin-2-one
A mixture of 4-(3-bromoacetyi-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-beiizo[b][l,4]diazepin-2-one (0.22 g) and 2-(tert-butylcarbonyl-oxy)thioacetamide (0.11 g) in EtOH (3 mL) was heated at 80 *C for 0.5 h. The solution was diluted with AcOEt, washed with saL NaHCOa solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (8 mL) and L5N KOH (8 mL) at 20 °C for

20 min. H2O (30 ml) was acided and the precipitated product collected by filtration to give the title compound (0.9 g) as yellow powder.
MS (ISP) 427.3 [(M+H)']; mp 176-178 °C
Example 194
4-r3-(2-Amino-thiazol-4-yl)-phenNi1-8-chloro-7-dimethylamino-l.3-dihvdro-benzo [bl f 1.41 diazepin-2-one
A mixture of 4-(3-bromoacetyi-phcn>1)-8-chloro-7-dimethylamino-l,3-dihydro-benzo[b][l,4]diazepin-2-one (0.73 g) (Example 193a) and thiourea (0,13 g) inTHF (10 mL) was heated to 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and vsith brine. The organic layer was dried and evaporated and the residue was stirred \%-ith CH:Q: to give the title compound (0.14 g) as yellow solid,
MS (ISN) 410.2 [(M^H)-]; mp 247-248 °C
Example 195
8-Chloro-7-dimethylamino-4-f3-(2-ethylamino-thiazol-4-yl)-phenyl1-13-dihvdro-benzofbl [L4ldiazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyi)-8-chloro-7-dimethylamino-13-dihydro-benzo[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-ethyl-thiourea (31 mg) in THE (3mL) was heated at 60 °C for 15 min. The mixture was diluted with AcOEt and washed with sat. NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using AcOEt/hexane (1:1) as eluent. The purified product was triturated with Et20 to give the title compound (24 mg) as yellow solid.
MS (ISP) 440.3 [(M+H)--]; mp 122-123 °C.
Example 196
N-{4-f3-(7-ChlorO'8-dimethylamino-4-oxo-4.5-dihvdro-3H-benzofb1fL4ldiazepin-2-vD-phenyl1-thiazol-2-yl}-guanidine
A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and N-amidino-thiourea (35 mg) in THE (3mL) was heated at 60 'C for 1 h- The mixture was diluted with AcOEt and washed with sat NaHCOa solution and with brine. The organic layer was dried and evaporated and the residue was purified by chromatography on silica gel using

AcOEt/MeOH (20:1) as eluent. The purified product was crystallyzed from acetone to give the title compound (22 mg) as yellow solid.
MS (ISP) 454.2 [(M+H)--]; mp 221 X dec.
Example 197
8-Chloro-7'dimethylamino-4-(3-[2-(pyridin-4'ylamino)-thiazol-4-yl]'phenvU-13-dihvdro-benzo[b1[1.4ldiazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyl)-8-chloro-7-dimethylamino-l,3-dihydro-ben2o[b][l,4]diazepin-2-one (130 mg) (Example 193a) and l-(4-pyridyl)-2-thiourea (46 mg) in THE (3mL) was heated at 60 X for 45 min. The mixture was dfluted with AcOEt and washed with sat NaHCOs solution and with brine. The organic layer was dried and evaporated and the residue was triturated with Et20 to give the title compound (55 mg) as yellow solid.
MS (ISP) 489.2 [(M+H)*']; mp 231-234 °C.
Example 198
8-ChlorO-4-f3-(2-metfayl-Oxazol-4-yl)-phenyl1-7-(methyl-propyl-amino)-l,3-dihydro-benzorb1fl>4'idiazepin-2-one
The title compoimd was prepared from [2-amino-4-chloro-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.16 g) (Example J8) and 3-oxo-3-[3-(2-methyl-oxazol-4-yl)-phenyl]-propionic acid tert-butyl ester (0.17 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.07 g).
MS (ISP) 423.2 [(M+H)-*]; mp 163-164 X.
Example 199
4-f3-(4-HydrGxymethyl-thiazol-2-yl)-phenyl-8-methyl-7-rmethyl-propyl-aminoV L3-dihvdro-benzofb1 f l.>41diazepin-2-one
The title compound was prepared from [2-amino-4-methyl-5-(methyl-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.09 g).

MS (ISP) 435.3 [(M+Hr];mp 222-224^0.
Example 200
4-f3-f4-Hvdroxymethyl-oxazol-2-yl)-phenyl1-8-methyl-7-fmethyl-propyi'aminoV L3-dihydro-benzo[b1fl.4]diazepin-2-one
The title compound was prepared from [2-amino-4-methyl-5-(meth)i-propyl-amino)-phenyl]-carbamic acid tert-butyl ester (0.21 g) (Example J24) and 3-oxo-3-[3-[4- (tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example Kll) (0.31 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.16 g).
MS (ISP) 419.3 [(M+H)+]; mp 200-202 °C.
Example 201
7-Dimethylamino-4-f3-(4-hvdroxymethyl-thiazol-2-yl)-phenyl1-8-trifluoromethyl-1,3 - dihvdro-benzo f b1 [ 1 A] diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-thiazol-2-yl]-phenyl]-propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.12 g).
MS (ISP) 461.2 [(M+H)1; mp 198-199 °C,
Example 202
7-Dimethylamino-4-[3-(4-hvdroxvmethyl-oxazol-2-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofblfL4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-oxo-3-[3-[4-(tetrahydro-pyran-2-yloxymethyl)-oxazol-2-yl]-phen)d]-propionic acid tert-butyl ester (0.22 g) (Example Kll) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.11 g).
MS (ISP) 445.0 [(M+H)*]; mp 197-198 °C

Example 203
4-f3-f4-Hvdroxymethyl-thiazol-2-y!VphenvI1-7-fmethyl-propyl-amino)-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2*one
The title compound was prepared from [2-amino-5-(methyl-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tcrt-butyl ester (0.17 g) (Example J35) and 3-0X0-3- [3- [4-(tetrahydro-pyran-2->'iox>TOCthyl)-thiazol-2-yl] -phenyl] -propionic acid tert-butyl ester (Example K27) (0.23 g) according to the general procedure M. The obtained material was deprotected and cydizcd by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.06 g).
MS (ISP) 489.2 [(M+Hr];mp 177-180^
^3B^mple 204
7-Dimethylamino-4-f3-(5-hvdroxymeth\i-fL3.4]thiadiazol-2-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzofb]fl.4ldia7epin-2-one
The title compound was prepared from (2-amino-5-dimethyiamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyi ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3,4]thiadia2ol-2-yl]-phenyi}-propionicacid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as ofif-white solid (0.06 g).
MS (ISP) 462.1[(M+H)'-]; mp 242-246 X.
Example 205
7-Dimethylamino-4-{3-r5-(2-hvdroxv-ethvD-fL3,4lthiadiazol-2-yl1-phenylt-8-trifluoromethyl-13-dihydro-ben2o Fb ] f L4l diazepin-2-one
The title compoxmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [ 1,3,4]thiadiazoI-2-yl}-phenyi)-propionic acid tert-butyl ester (0.24 g) (Example K3I) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a oflF-white solid (0.06 g).
MS (ISN) 474.2 [(M-H)-]; mp 234-237 X,

Example 206
7-Dimetfaylamino-4-f3-(5-hvdroxvmethyI-fl3.4loxadiazol-2-yl)-phenyn-8-trifluoromethyl-13-dihvdro-benzo f b] [ 1,41 diazepin-2-one
The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoromethyI-phenyl)-carbamic acid tert-butyl ester (1.44 g) (Example J6) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[l,3>4]oxadiazol-2-yl]-phenyl}-propionic acid tert-butyl ester (2.17 g) (Example K32) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g).
MS (ISP) 463.2 [(M+NH4)+].
Example 207
7-Dimethylamino-4-(3-r5-(2-hvdroxv-ethyl)-[13.4loxadia2ol-2-yl1-phenvU-8-trifluoromethyl-13-dihydro-benzo f b] f 1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-(3-{5- [2-(tetrahydro-pyran-2-yloxy)-ethyl] - [1,3,4] oxadiazol-2-yl}-phenyl)-propionic acid tert-butyl ester (0.23 g) (Example K33) according to the general procedure M, The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.88 g).
MS (ISP) 460.2 [(M+H)--]; mp 237 *°C dec.
Example 208
7-Dimethylamino-4-(3-oxazol-4-yl-phenyl)-ig-trifluoromethyl-L3-dihvdro-benzofbl f h4ldiazepin-2-one
The tide compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-(3-oxazol-4-yl-phenyl)-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K34) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (50 mg).
MS (ISP) 415.2 [(M+H)--]; mp 218-219 °C.

Example 209
7'Dimethylamino-4-f3-tfaia2ol-4-yl-phenyl)-8-trifluoromethyl-L3-dihydro-benzofbl f l,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (96 mg) (Example J6) and 3-oxo-3-(3-thiazol-4-yl-phenyl)-propionic acid tert-butyl ester (109 mg) (Example K35) according to the general procedure M. The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (61 mg).
MS (ISP) 431.2 [(M+H)--]; mp 200 °C dec.
Example 210
7-Dimethylamino-4-[3-(2-methyl-oxazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihvdro-benzofb] f L4ldiazepin-2'One
The title compovmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(2-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.18 g) (Example K29) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.04 g).
MS (ISP) 429.3[(M-hH)-']; mp 192-193 °C.
Example 211
7-DimethyIamino-4-f3-(5-methyl-oxazoI-4-yn-phenyn-8-trifluoromethyl-L3-dihvdro-benzofb1fl,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyi)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-[3-(5-methyl-oxazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,18 g) (Example K36) according to the general procedure M, The obtained material was deprotected and cydized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0.13 g).
MS (ISP) 429.3 [(M+H)--]; mp 238-239 °C.

Example 212
7-Dimethylamino-4-[3-(2-methyl-5-propyI-oxa2ol-4-yi)-phenyl-8-trifluoromethyl-1.3-dihydro-benzo[b]fl.4]diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (80 mg) (Example J6) and 3-[3-(2-methyl-5-propyl-oxazoI-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (103 mg) (Example K37) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as pale-yellow solid (20 mg).
MS (ISP) 471,2 [(M+H)'*];mp 211-212 °C.
Example 213
7-Dimethylamino-4-[3-(5-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzofb] [ L4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0,16 g) (Example J6) and 3-[3-(5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0,19 g) (Example K38) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (0,06 g).
MS (ISP) 445.2 [(M+H)1; mp 214-215 °C
Example 214
7-Dimethylamino-4-[3-(2,5-dimethyl-thiazol-4-yl)-phenyn-8-trifluoromethyM,3-dihydro-benzofbl f L4]diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (48 mg) (Example J6) and 3-[3-(2>5-methyl-thiazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (50 mg) (Example K39) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (38 mg).
MS (ISP) 459.2 [(M+H)--]; mp 208-209 X.

Example 215
7-Dimethylamino-4-f3-(2-hvdroxymethyI*thiazol-4-yl)-phenyl]-8-trifluoromethyl-13-dihvdro-benzo fbl f 1,41 diazepin-2-one
a)4*(3-Bromoacetyl-phenyl)-7-dimethylamino-'8-trifluoromethyl*1.3-dihydro-benzofbl f l,4ldiazepin-2-one
A solution of (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (Example J6) (0.32 g) and 3-oxo-3-[3-(2-bromo-l,l-dimethoxy-ethyl)-phenyl]-propionic acid tert-butyi ester (0.43 g) (Example K28) in toluene (3 mL) was heated to 100 °C for 2 L The solvent was evaporated in vacuum and the crude product was purified by chromatography on silica gel using AcOEt /Hexan(l:3) as eluent A solution of the purified material (0.57 g) in CH2Cl2/TFA (1:1,7 mL) was stirred at 20 ®Cfor 15 min and then evaporated. The residual oil was dissolved in AcOEt and the solution was washed with IN HCl and with brine, dried and evaporated to give crude 4-(3-bromoacetyl-phenyl)-7-dimethylainino-8-trifluoromethyM,3-dihydro-benzo[b][l,4]diazepin-2-one (0.22 g) as light-brown solid.
b) 7-Dimethylamino-4-f3-(2-hvdroxymethyl-thiazol-4-yl)-phenyl1 -8-trifluoro-methyl-1.3-dihydro-benzo fbl F1,41 diazepin-2-one
A mixture of 4-(3-bromoacetyl-phenyl)-7-dimethylamino-8-trifluoromethyl-l>3-dihydro-benzo[b][l,4]diazepin-2-one (0.40 g) and 2-(tert.-butylcarbonyloxy)thio-acetamide (0.21 g) in EtOH (5 mL) was heated at 80 'C for 0.5 h. The solution was diluted with AcOEt, washed with sat NaHCOs solution and with brine, dried and evaporated. The residue was stirred in a mixture of MeOH (5 mL) and L5N KOH (5 mL) at 20 ^'C for 20 min. H2O was acided and the predpitated product coDected by filtration and purified by chromatography on silica gel using AcOEt as eluent to give the title compound (0.01 g) as yellow solid.
MS (ISP) 461.1 [(M+H)--].
Example 216
7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-methyl-thia2ol-4-yl)-phenyil-8-trifluoromethyl-1,3-dihydro-benzofb1 \ 1.41 diazepin-2-one
The title compound was prepared firom (2-an:iinO-5-dimethylamino-4-trifluoro-methyi-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[5-mediyl-2-(tetrahydro-pyran-2-yloxymedi)d)-thiazol-4-yl]-phen)i}-propionicadd
tert-butyl ester (0.26 g) (Example K40) according to the general procedure M. The

obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N, Obtained as light-yellow solid (0.11 g).
MS (ISP) 475.2 [(MH-H)I; mp 190-193 °C
Example 217
7-Dimethylamino-4-f3-(2-hvdroxvmethyl-5-propyl'thiazol-4-vD-phenyl1-8-trifluoromethyl-h3-dihydro-benzofb1 [1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoromethyl-phenyl)-carbamic acid tert-butyl ester (79 mg) (Example J6) and 3-oxo-3-{3-[5-propyl-2-(tetrahydro-pyran-2-yloxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (138 mg) (Example K41) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid (45 mg).
MS (ISP) 503.2 [(M+H)1; mp 112-114 °C
Example 218
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-2-methyl-thiazol-4-yl)-phenyl1-8-trifluoromethyl-l,3-dihydro-benzorbUl,4ldiazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{3-[2-methyl-5-(tetrahydro-pyran-2-yloxymethyl)-thia2ol-4-yl]-phenyl}-propionicacid tert-butyl ester (0.26 g) (Example K42) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as yellow solid(0.11 g).
MS (ISN) 473.0 [(M-H)']; mp 226-227 '°C.
Example 219
7-Dimethylamino-4-f3-(5-hvdroxvmethyl-thiazol-4-yl)-phenyll-8-trifluoromethyl-13-dihvdro-benzo Fbl f 1,41 diazepin-2-one
The title compound was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbamic acid tert-butyl ester (0.16 g) (Example J6) and 3-oxo-3-{[5-(tetrahydro-pyran-2-yioxymethyl)-thiazol-4-yl]-phenyl}-propionic acid tert-butyl ester (0,25 g) (Example K43) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0-08 g).

MS (ISN) 459.3 [(M-H)-].
Example 220
4-(3-f5'f(CvcIopropylmethyl-amino)-methyll-thiazol-4-yn-phenyl)-7-dimethylamino-8-trifluoromethyl-L3-dihvdro-benzorb1fL4ldiazepin-2-one
A mixture of 7-dimethylamino-4-[3-(5-hydroxymethyl-thiazol-4-yl)-phenyl]-8-trifluoromethyl-l,3-dihydro-benzo[b][l,4]diazepin-2-one (Example 219) (65 mg) and thionyl chloride (0.015 mL) in CH2Cl2 (0.3 mL) was stirred at 20 °C for 1 h. The heterogeneous mixture was evaporated in vacuum and the residue was suspended in EtOH (0.5 mL). Aminomethyl-cyclopropane (0.12 mL) and KI (3 mg) were acided and the mixture was stirred at 80 ^'C for 5 h. The mixture was evaporated in vacuum ant the residue was purified by chromatography on silica gel using AcOEt/MeOH (50:1) as eluent The resulting product was stirred with 20% aqueous MeOH (10 mL)) the pH of the mixture being set to 11 by the acidition of IN NaOH, and the solid was isolated by filtration to give the title compound (44 mg) as off-white solid.
MS (ISP) 514.3 [(M+H)--]; 157-158° C.
Example 221
7-Dimethylamino-4-f3-(2-isopropyl-lH-imidazol-4-yl)-phenyl1-8-trifluoromethyl-L3-dihydro-benzo[birL4ldiazepin-2-one
The title compotmd was prepared from (2-amino-5-dimethylamino-4-trifluoro-methyl-phenyl)-carbanuc acid tert-butyl ester (0.13 g) (Example J6) and 3-[3-(2-isopropyl-3H-imidazol-4-yl)-phenyl]-3-oxo-propionic acid tert-butyl ester (0.20 g) (Example K44) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TEA in CH2Cl2 according to the general procedure N. Obtained as off-white solid (0.10 g).
MS (ISP) 456.4 [(M+H)--]; mp 150 Xdec.
Example 222
4-f3-(5-Hvdroxymethyl-[13.4lthiadiazol-2-yl)-phenyl-7-(methyl-propyl-aminoV8-trifluoromethyl-13-dihvdro-benzo[b1fL4ldiazepin-2-one
The title compound was prepared from [2-amino-5-(methyi-propyi-amino)-4-trifluoromethyl-phenylj-carbamic acid tert-butyl ester (0.17 g) (Example J35) and 3-oxo-3-{3-[5-(tetrahydro-pyran-2-yloxymethyl)-[13>4]thiadiazol-2-yi]-phenyl}-propionic acid tert-butyl ester (0.23 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cydized by treatment with

TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.02
g).
MS (ISP) 490.2 [(M+H)--]; mp 193-194 --C.
Example 223
8-Chloro-7-dimethylamino-4-l3-r5-(2-hvdroxv-ethyl)-ri,3,4lthiadiazol-2-yl]-phenyl)-13-dihvdro-ben2ofb1fl.4]diazepin-2-one
The title compound was prepared from (2-amino-4-chloro-5-dimethylamino-phenyl)-carbamic acid tert.-butyl ester (Example Jl) (0.15) and crude 3-oxo-3-(3-{5-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-[l,3,4]thiadiazol-2-yl}-phenyl)-propionicacid tert-butyl ester (0.24 g) (Example K30) according to the general procedure M. The obtained material was deprotected and cyclized by treatment with TFA in CH2Cl2 according to the general procedure N. Obtained as a yellow solid (0.10 g).
MS (ISN) 440.2 [(M-H)-]; mp 198-200 °C.

The active ingredient having a suitable particle size, the crystalline lactose and the microcrystaUine cellulose are homogeneously mixed with one another, sieved and thereafter talc and magnesium stcarate are admixed. The final mixture is filled into hard gelatine capsules of suitable size.

Example I Tablets of the following composition are produced in a conventional maimer
mg/Tablet
Active ingredient 100
Powdered, lactose 95
White com starch 35
Polyvinylpyrrolidone 8
Na carboxymethylstarch 10
Magnesium stearate _2
Tablet weight 250
Example II
Tablets of the following composition are produced in a conventional manner:
mg/Tablet
Active ingredient 200
Powdered, lactose 100
White corn starch 64
Polyvinylpyrrolidone 12
Na carboxymethylstarch 20
Magnesium stearate ^
Tablet weight 400
Example III
Capsules of the following composition are produced:
mg/Capsule
Active ingredient 50
Crystalline, lactose 60
Microcrystalline cellulose 34
Talc 5
Magnesium stearate 1
Capsule fill weight 150

Documents:

1610-chenp-2003-abstract.pdf

1610-chenp-2003-claims duplicate.pdf

1610-chenp-2003-claims original.pdf

1610-chenp-2003-correspondnece-others.pdf

1610-chenp-2003-correspondnece-po.pdf

1610-chenp-2003-description(complete)duplicate.pdf

1610-chenp-2003-description(complete)original.pdf

1610-chenp-2003-form 1.pdf

1610-chenp-2003-form 18.pdf

1610-chenp-2003-form 26.pdf

1610-chenp-2003-form 3.pdf

1610-chenp-2003-form 5.pdf

1610-chenp-2003-pct.pdf

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Patent Number

203568

Indian Patent Application Number

1610/CHENP/2003

PG Journal Number

13/2007

Publication Date

30-Mar-2007

Grant Date

19-Dec-2006

Date of Filing

10-Oct-2003

Name of Patentee

M/S. F. HOFFMANN-LA ROCHE AG

Applicant Address

Grenzacherstrasse 124 CH-4070 Basle

Inventors:

#	Inventor's Name	Inventor's Address
1	ADAM, Geo	8 Untere Staltenstrasse 79650 Schopfheim
2	GOETSCHI, Erwin	23 Landhofweg CH-4153 Reinach
3	MUTEL, Vincent	6, Rue des Grands Champs F-68350 Brunstatt
4	WICHMANN, Juergen	32 Im Wolfischbuehl 79585 Steinen
5	WOLTERING, Thomas, Johannes	13 Riedlistrasse 79576 Weil am Rhein

PCT International Classification Number

C07D401/04

PCT International Application Number

PCT/EP2002/003644

PCT International Filing date

2002-04-02

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	01109125.3	2001-04-12	EUROPEAN UNION