Indian Patents
Title of Invention

PYRIDOPYRIMIDINE DERIVATIVES, PROCESS FOR THEIR PREPARATION, COMPOSITION COMPRISING THE SAME AND INTERMEDIATES
Abstract Fungicidal compositions having the general formula (1): formula (1) wherein W and Y are both N and X and Z are both CR<SUP>8</SUP> or X and Z are both N and W and Y are both CR<SUP>8</SUP> , R<SUP>8</SUP> is H, halo, C<SUB>1-4</SUB> alkyl, C<SUB>1-4</SUB> alkoxy or halo(C1-4)alkyl; R and R<SUP>2</SUP> are independently H, halo, C<SUB>1-8</SUB> alkyl, C<SUB>1-8</SUB> alkoxy, C<SUB>1-8</SUB> alkylthio, C<SUB>2-8</SUB> alkenyl, C<SUB>2-8</SUB> alkynyl, cyano or NR<SUP>3</SUP>R<SUP>4</SUP>, provided that at least one of R and R<SUP>2</SUP> is NR<SUP>3</SUP> R<SUP>4</SUP> ; R<SUP>1</SUP> is halo, C<SUB>1-8</SUB> alkyl, C<SUB>2-8</SUB> alkenyl, C<SUB>2-8</SUB> alkynyl, C<SUB>3-8</SUB> cycloalkyl, C<SUB>3-8</SUB> cycloalkyl(C<SUB>1-6</SUB>)-alkyl, C<SUB>1-8</SUB> alkoxy, C<SUB>1-8</SUB> alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C<SUB>1-4</SUB>)alkyl, aryl(C<SUB>1-4</SUB>)alkoxy, heteroaryl(C<SUB>1-4</SUB>)alkyl, heteroaryl(C<SUB>1-4</SUB>)alkoxy, aryl(C<SUB>1-4</SUB>)alkylthio, heteroaryl(C<SUB>1-4</SUB>)alkylthio, morpholino, piperidino or pyrrolidino.
Full Text

FUNGICIDES
This invention relates to novel derivatives of pyridopyrimidines, to processes for preparing them, to certain intermediate chemicals used in their manufacture, to compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.
Derivatives of the nitrogen-containing 5,6 ring system s-l,2.4-triazoIo[l,5-a]pyri-midine are known from the patent literature as being useful for controlling phytopathogenic fungi. Examples of recent patent publications include EP-A-1249452. WO 02/051845, WO 02/083676, WO 02/0S3677, WO 02/088125, WO 02/0S8126, WO 02/0S8127. Certain derivatives of pyridopyrimidines are described, for example, in US 5597776 and WO 01/17972 as herbicide antagonists. Others are known for pharmaceutical applications (see, for example, J. Med. Chem. (1983), 26(3), 403).
The present invention is concerned with the provision of novel pyridopyriTnidines for combating phytopathogenic diseases on plants and harvested food crops. Thus, according to the present invention, there is provided a compound of the general formula (1):
wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both
CR8;
R8 is H, halo, C1-4 alky], C1-4 alkoxy or halo(C1-4)alkyI;
R and R2 are independently H, halo,C1-8 alkyl,C1-8 alkoxy,C1-8 alkylthio, C2-8 alkenyl, C2-8
alkynyl, cyano or NR3R4, provided that at least one of R and R2 is NR3R4;
Rl is halo, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-g cycloalkyl, C3-8cycloalkyl(C1-6)alkyl,
C1-8 alkoxy,C1-8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,
aryl(C1-4)alkyl, aryl(C1-6)alkoxy, heteroaryl(C1-4)alkyl, heteroary!(C1-4)alkoxy, aryl(C1-6)alkyl-
thio, heteroaryl(C].4)alkylthio, morpholino, piperidino or pyrrolidino;

not both R3 and R4 are H or NR5R6, or
R and R together fonn a C3-7 alkylene or C3.7 alkenylene chain optionally substituted with
one or more C1-4 alkyl or C1-4 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R3 and R4 foR"" a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazineiV-(C1-4)alkyl (especially TV-methyl) ring; and
R5 and R6 are independently H, C1-4 alkyl, C2-8 alkenyl, C2-8 alkynyl aryl, aryl(C1-8)alkyl, C3-8
cycloalkyl, C3-8 cycloalkyl(C1-4)alkyl, heteroaryl orheteroaryl(C1-8)alkyI;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
R ) being optionally substituted with halogen, cyano, C1-4 alkoxy, C1-6alkylcarbonyl, C1-4
alkoxycarbonyl, C1-4 haloalkoxy, C1-4 alkylthio, tri(C1-4)alkylsilyl, C1-4 alkylamino or C1-4
dialkylamino,
any of the foregoing moipholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings
being optionally substituted with C1-4 alkyl (especially methyl), and
any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with
one or more substituents selected'from halo, hydroxy, mercapto, C1-6 alkyl, C2-6 alkenyl, C2-6
alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, halo(C1-6)alkyl, halo(C1-6)alkoxy, C1-6
alkylthio, halo(C1-6)alkylthio, hydroxy(C1-6)alkyl, C1-4 alkoxy(C|.6)alkyl, C3-6 cycloalkyl, C3-6
cycloalkyl(C1-6)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, iso-
thiocyanato, nitro, -NR""R"", -NHCOR'", -NHCONR,"R"", -CONR""R"", -S02R"", -OS02R",
-COR"", -CR""=NR"" or -N=CR""R"", in which R"" and R"" are independently hydrogen, C1-4
alky], halo(C1-4)alkyl, C1-4 alkoxy, halo(C1-6)aIkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6
cycloalkyl(C1-4)a!kyl, phenyl or benzyl, the phenyl and benzyl groups being optionally
substituted with halogen, C1-4 alkyl or C1-4 alkoxy;
provided that Y is not CCH3 when W is CH, X and Z are N, R is NHCH3, R1 is 2,6-
dichlorophenyl and R2 is H.
The invention includes a compound of the general foR""ula (1) as defined immediately above except that: alkoxy and C1-4 alkylthio are excluded as values of R and R2; C7 alkylene and C3-7 alkenylene are excluded as chains foR""ed by R and R ; the C3-6 chain that
1 A
R and R may foR"" may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may-foR""; tri(C1-4)alkylsilyl is excluded as a subst:::..;;.

any alkyl, alkeny], alkynyl or cycloalkyl group or moiety and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
The invention also includes a compound of the general foR""ula (1) as defined above where R" is other than H and also a compound of the general foR""ula (1) as defined above where Rs is H.
The compounds of the invention may contain one or more asymmetric carbon atoms and may exist as enantiomers (or as pairs of diastereoisomers) or as mixtures of such. They may also exist as diastereoisomers by virtue of restricted rotation about a bond. However, mixtures of enantiomers or diastereoisomers may be separated into individual isomers or isomer pairs, and this invention embraces such isomers and mixtures thereof in all proportions. It is to be expected that for any given compound, one isomer may be more fungicidally active than another.
Except where otherwise stated, alkyl groups and alkyl moieties of alkoxy, alkylthio, etc., contain from 1 to 8, suitably from 1 to 6 and typically from 1 to 4, carbon atoms in the foR"" of straight or branched chains. Examples are methyl, ethyl, n- and iso- and terf-butyl, n-pentyl and n-hexyl. Cycloalkyl groups contain from 3 to 8, typically from 3 to 6, carbon atams and include bicycloalkyl groups such as the bicyclo[2.2.1]heptyl group. Haloalkyl groups or moieties are typically trichloromethyl or trifluoromethyl or contain a trichloromethyl or trifluoromethyl teR""inal group.
Except where otherwise stated, alkenyl and alkynyl moieties also contain from 2 to 8, suitably from 2 to 6 and typically from 2 to 4, carbon atoms in the foR"" of straight or branched chains. Examples are allyl, 2-methylallyl and propargyl. Optional substituents include halo, typically fluoro. An example of halo-substituted alkenyl is 3,4,4-trifluoro-/z-butenyl.
Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro, chloro or bromo and usually fluoro or chloro.
Aryl is usually phenyl but also includes naphthyl, anthryl and phenanthryl.
Heteroaryl is typically a 5- or"6-membered aromatic ring containing one or more O, N or S heteroatoms, which may be fused to one or more other aromatic or heteroaromatic rings, such as a benzene ring. Examples are thienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl,

benzothiazolyl, benzoxazolyl, benzimidazolyl, indolyl, quinolinyl and quinoxalinyl groups and, where appropriate, N-oxides thereof.
The 6,6-ring systems embraced by the general foR""ula (1) are pyrido[2,3-d]pyri-midines (where W and Y are both CRS and X and Z are both N) and pyrido[3,2-d]pyri-midines (where X and Z are both CR8 and W and Y are both N).
R, which may be the same or different for the two CR values of W, X, Y and Z, is H, halo (for example bromo), C1-4 alkyl (for example methyl), C1-4 alkoxy (for example methoxy) or halo(C1-4)alkyl (for example trifluoromethyl). Usually R8 will be H.
One of R and R , preferably R , is NR R . The other is typically halo, especially chloro or fluoro. in the case of pyrido[3,2-d]pyrimidine ring systems, the more active compounds are those where R is NR R . R is typicallyC1-8 alkyl (for example ethyl, n-propyl, n-butyl, sec-butyl (the S- or R-isomer or the racemate) and /erf-butyl), halo(C1-8)alkyl (for example 2,2,2-trifluoroethyl, 2,2,2-trifluoro-l-methylethyl (the S- or R-isomer or the racemate), 3,3,3-trifluoropropyl and 4,4,4-trifluorobutyl), hydroxy(C1-8)alkyl (for example hydroxyethyl), C1-4 alkoxy(C1-8)alkyl (for example methoxymethyl and methoxy-zso-butyl), C1-4 alkoxyhalo(C1-8)alkyl (for example 2-methoxy-2-trifluoromethylethyl), tri(C1-4)-alkylsilyl(Ct.6)alkyI (for example trimethylsilylmethyl), C1-4 alkylcarbonyl(C1-8)alkyl (for example 1-acetylethyl and l-Terf-butylcarbonylethyl), C1-4 alkylcarbonyIhalo(C1-8)alkyl (for example l-acetyl-2,2,2-trifluoroethyl), phenyl(M)alkyl (for example benzyl), C2-8 alkenyl (for example allyl and methylallyl), halo(C2-g)alkenyl (for example 3-methyl-4,4-difluorobut-3-enyl), C2.3 alkynyl (for example propargyl), C3-6cycloalkyl (for example cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl) optionally substituted with chloro, fluoro or methyl, C3-8 cycloalkyl(C1-4)alkyl (for example cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl), phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo (typically fluoro, chloro or bromo), C1-4 alkyl (typically methyl), halo(C1-6)alkyl (typically trifluoromethyl), C1-4 alkoxy (typically methoxy) and halo(C1-4)alkoxy (typically trifluoromethoxy)/R4 is typically H, C1-4alkyl (for example ethyl and N-propyI), halo(C1-4)alkyl (for example 2,2,2-trifluoroethyl) or amino. Alternatively R3 and R4 together foR"" a C4-6 alkylene chain optionally substituted with methyl, for example 3-methylpentylene, or, together with the nitrogen atom to which they are attached, R and R4 foR"" a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide

ring or a piperazine or piperazine N-(C1-4)alkyl (especially TV-methyl) ring, in which the morpholine or piperazine rings are optionally substituted with methyl.
Typically R1 is phenyl optionally substituted with from one to five halogen atoms, particularly fluorine and chlorine atoms and especially fluorine atoms or with from one to three substituents selected from halo (for example fluoro and chloro), C1-4 alkyl (for example methyl), haIo(C1-4)alkyI (for example trifluoromethyl), C1-4 alkoxy (for example methoxy) or halo(C1-6)alkoxy (for example trifluoromethoxy). Examples are 2,6-difluoropheny], 2-fluoro-6-chlorophenyl, 2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl, pentafluorophenyl, 2-fluorophenyl, 2,3,5,6-tetrafluorophenyl, 2-chloro-4,6-difluorophenyl, 2-chlorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl, 2,4,6-trichlorophenyl, 2,3,6-trichloro-phenyl, pentachlorophenyl, 2-fluoro-4,6-dichlorophenyl, 4-fluoro-2,6-dichlorophenyl, 2-bromophenyl, 2-fluoro-6-bromophenyl, 2-bromo-4,6-difluorophenyl, 2-fluoro-6-methyl-phenyl, 2-chloro-6-methylphenyl, 2-methoxyphenyl, 2,6-dimethoxyphenyl, 2-fluoro-6-methoxyphenyl, 2-trifluoromethylphenyl, 2-fluoro-6-trifluoromethylphenyl, 2,6-di-(trifluoro-methyl)phenyl, 2-chloro-6-trifluoromethylphenyl, 2,4-difluoro-6-trifluoromethyIphenyl, 2,4-difluoro-6-methoxyphenyl and 2,4-difluoro-6-methylphenyl.
Also of particular interest are compounds where R is pyridyl optionally substituted
with from one to four halogen atoms or with from one to three substituents selected from
halo (for example fluoro and chloro), C1-4 alkyl (for example methyl), halo(C1-4)alkyl (for
example trifluoromethyl), C1-4 alkoxy (for example methoxy) or halo(C1-6)alkoxy (for
example trifluoromethoxy). Examples are2,4-difluoropyrid-3-yl, 3,5-difluoropyrid-4-yl,
tetrafluoropyrid-4-yl, 3-fluoropyrid-2-yl? 4-fluoropyrid-3-yl, 3-fluoropyrid-4-yl, 2-fluoro-
pyrid-3-yl, 2,4,6-trifluoropyrid-3-yl, 3,5-difluoropyrid-2-yl, 2,6-difluoropyrid-3-yl, 2,4-
difluoro-6-methoxypyrid-3-yl, 2-fluoro-4-chloropyrid-3-yi, 3-fluoro-5-chloropyrid-4-yl, 2-
chloro-4-fluoropyrid-3-yl, 2,4-dichloropyrid-3-yl, 3-chloropyrid-2-yl I, 4-chloropyrid-3-yl, 3-
chloropyrid-4-yl, 2-chIoropyrid-3-yl, 3-trifluoromethylpyrid-2-yl, 4-trifluoromethylpyrid-3-
yl, 3,5-dichloropyrid-2-yl, 4,6-dichloropyrid-3-yl, 3-trifluoromethylpyrid-4-yl, 2-trifluoro-
» methylpyrid-3-yl, 2-fluoro-4-trifluoromethylpyrid-3-yl, 3-fluoro-54rifluoromethylpyrid-4-yl,
4-fluoro-2-trifluoromethylpyrid-3-yl, 2,6-dichloropyrid-3-yl, 3,5-dichloropyrid-4-yl, 3-
chloro-6-trifluoromethylpyrid-2-yl, 3-fluoro-6-trifluoromethylpyrid-2-yl, pyrid-2-yl, pyrid-3-

Also of particular interest are compounds where R1 is 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo (for example fluoro and chloro), C1-4 alkyl (for example methyl), halo-(C].4)aikyl (for example trifluoromethyl), C1-4 alkoxy (for example methoxy) or halo(C1-6)-alkoxy (for example trifluoromethoxy). Examples are 3-fluorothien-2-yl, 3-ehlorothien-2-yl, 2,4-difluorothien-3-yl, 2,4-dichlorothien-3-yl and 2,4,5-trichIorothien-3-yl.
Examples of other values of R1 of especial interest are unsubstituted piperidino and morpholino, 2-methylpiperidino? 2,6-dimethyIpiperidino and 2,6-dimethylmorpholino
In one aspect the invention provides a compound of the general foR""ula (1) wherein W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both CR8;
R8 is H, halo, C1-4 alkyl, C1-4 alkoxy or ha!o(C1-4)alkyl; one of R and R2 (preferably R2) is NR3R4 and the other is halo;
R1 is halo,C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6cycloalkyl, C3-8cycloalkyl(Ci_6)aIkyI, alkoxy,C1-8alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C1-6)alkyl, aryl(C1-6)alkoxy, heteroaryl(C1-6)aIkyl, heteroaryl(C1-6)alkoxy, aryl(C1-4alkylthio, heteroaryl(C1-6)alkylthio, morpholino, piperidino or pyrrolidine;
R3 and R4 are independently H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl, aryI(C1-8)alkyl, C3-8 cycloalkyl, C3-8cycloalkyl(Ci,6)alkyI, heteroaryl, heteroaryl(C1-8)alkyl, NR5R6, provided that not both R3 and R4 are H or NR5R6, or
R3 and R4 together foR"" a C3.7 alkylene chain or C3.7 alkenylene chain optionally substituted with one or more C1-4 alkyl or C1-4 alkoxy groups, or,
1 A
together with the nitrogen atom to which they are attached, R~ and R foR"" a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(C1-4)alkyl (especially Af-methyl) ring; and
R5 and R6 are independently}!,C1-8 alkyl, C2-8alkenyl, C2-8 alkynyl, aryl, aryI(C1-8)alkyl, C3-8
cycloalkyl, C3-8 cycloalkyl(Cj-6)alkyl, heteroaryl or heteroaryl(C1-8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
R8) being optionally substituted with halogen, cyano, C1-6 alkoxy, C1-6 alkylcarbonyl, C1-6
alkoxycarbonyl, C1-6 haloalkoxy, C1-6 alkylthio, tri(C1-4)alkylsilyl, C1-4 aikylamino or C1-6
dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings

being optionally substituted with C1-4 alkyl (especially methyl), and any of the foregoing aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto,C1-8alkyl, C2-6 alkenyl, C2.6 alkynyl, C1-4alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, halo(C1-6)alkyl, halo(C1-6)alkoxy, C1-6 alkylthio, halo(C1-6)alkylthio, hydroxy(C1-6)alkyl, C1-4aIkoxy(C1-6)-alkyl, C3.0 cycloalkyl, C3-6 cycIoalkyl(C1-6)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR""R"", -NHCOR"', -NHCONR"'R"M, -CONR,nR"", -S02R", -OS02R", -COR"", -CR'^NR"" or -N=CR",R"", in which R"" and R"" are independently hydrogen, C1-4 alkyl, halo(C1-6)alkyl, C1-4 alkoxy, halo(C1-4)alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(Q_4)alkyI, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alky] or C1-4 alkoxy. Of particular interest are compounds where R is H.
The invention includes a compound of the general foR""ula (1) as defined immediately above except that: C7 alkylene and C3.7 alkenylene are excluded as chains foR""ed by R and R4; the C3-6 chain that R3 and R4 may foR"" may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may foR""; tri(C1-4)alkylsilyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
In another aspect the invention provides a compound of the general foR""ula (1) wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both CR8;
R8 is H, halo, C1-4 alkyl, C1-4 alkoxy or halo(C1-6)alkyl; one of R and R2 (preferably R2) is NR3R4 and the other is halo;
R1 is halo, C1-8 alkyl, C2-8alkenyl C2-8 alkynyl, C3-8 cycloalkyl, C3-8 cycloalkyl(C1-6)alkyl, C1-8 alkoxy,C1-8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(Cj.4)alkyl, aryl(C1-4)alkoxy, heteroaryl(C1-4)alkyl, heteroaryl(C1-4)alkoxy, aryl(C1-4)alkyI-thio, heteroaryl(C1-4)alkylthio, morpholino, piperidino orpyrrolidino; R3 is C1-4 alkyl, halo(C1-4)alkyL C2-4 alkenyl, C3-6 cycloalkyl, C3-6 cycIoalkyl(C1-4)alkyl or

R is H, C1-4 alky] or amino, or
R and R together foR"" a C4-6 alkylene chain optionally substituted with C1-4 alkyl or C1-4 alkoxy, or,
together with the nitrogen atom to which they are attached, R3 and R4 foR"" a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine JV-(C1-4)alkyI (especially W-methyl) ring; any of the foregoing alkyl, alkenyl, alkynyl or cycloalk}'l groups or moieties (other than for
Q
R ) being optionally substituted with halogen, cyano, C1-4alkoxy, C1-6alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 haloalkoxy, C1-6 alkylthio, tri(C1-6)alkylsilyl, C1-6 alkylamino or C1-6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally substituted with C1-4 alkyl (especially methyl), and any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1-6alkyl C2-6 alkenyl, C2-6 alkynyl, C1-6 alkoxy, C2-6 alkenyloxy, C2-6 alkynyloxy, haIo(C1-6)alkyl, halo(C1-6)alkoxy, C1-4 alkylthio, halo(C1-6alkylthio, hydroxy(C1-6)alkylfC1-6 alkoxy(C1-6)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyI(C1-6)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, iso-thiocyanato, nitro, -NR'"R"", -NHCOR"', -NHCONR'-R"", -CONR-R"", -S02R"", -OS02R"", -COR'", -CRW=NR"" or -N=CR'"R"", in which R"" and R'm are independently hydrogen, C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy, halo(C1-4)aIkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally substituted with halogen, C1-4 alkyl or C1-4 alkoxy. Of particular interest are compounds where R is H.
The invention includes a compound of the general foR""ula (1) as defined immediately above except that: the C4_6 chain that R3 and R4 may foR"" may only be optionally substituted with methyl; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may foR""; tri(C1-4)alkylsiIyl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine or pyrrolidine ring is unsubstituted.
In yet another aspect the invention provides a compound of the general foR""ula (1) wherein W-and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both

CR8;
R8 is H, halo, C1-4 alkyl, C1-4 alkoxy or halo(C1-4)aIkyl;
R and R2 are independently H, halo, C1-8 alkyl,C1-8 alkoxy. C].s alkylthio, C2-8 alkenyl, C2-6
alkyny], cyano or NR3R4, provided that at least one of R and R2 (preferably R2) is NR3R4;
R1 is optionally substituted phenyl;
R3 and R4 are independently H, C).8 alkyl,C2-8alkenyl, C2-8 alkynyl, aryl, aryl(C1-8)alkyl, C3-8
cycloalkyl, C3-Scycloalkyl(C1-6)alkyl, heteroaryl, heteroaryl(Ci.8)alkyl, NR5R6, provided that
not both R3 and R4 are H or NR5R6, or
R and R together foR"" a C3.7 alkylene or C3.7 alkenylene chain optionally substituted with
one or more C1-4 alkyl or C1-4 alkoxy groups, or,
together with the nitrogen atom to which they are attached, R~ and R foR"" a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(Ci_4)alkyl (especiallNmethyl) ring; and
R' and R° are independently H,C1-8 alkyl, C2-8 alkenyl C2-8 alkynyl, aryl, aryl(C1-8)alkyl, C3-8
cycloalkyl, C3.S cycloalkyl(C1-6)alkyi, heteroaryl or heteroaryI(Q-8)alkyl;
any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for
R ) being optionally substituted with halogen, cyano, Ci_e alkoxy, C1-6alkylcarbonyl, Cj-6
alkoxycarbonyl, d.6 haloalkoxy, C1-4 alkylthio, tri(C1-4)alkylsilyl, C1-6 alkylamino or C1-4
dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings
being optionally substituted with C1-4 alkyl (especially methyl), and
any of the foregoing aryl or heteroaryl groups or moieties, including the phenyl group of R1,
being optionally substituted with one or more substituents selected from halo, hydroxy,
mercapto, C1-4 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 alkoxy, C2.6 alkenyloxy, C2-6 alkynyloxy,
halo(C1-6)alkyl, halo(C1-6)alkoxy, C1-4 alkylthio, halo(Ci-d)alkyIthio, hydroxy(C1-6)alkyl, C1-4
alkoxy(C1-6)alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenoxy, benzyloxy, benzoyl-
oxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR"'R"", -NHCOR"',
-NHCONR""R"", -CONR"",R"", -S02R", -OS02R"",,-COR"", -CR""=NR"" or -N=CR""R"", in
which Rr" and R"" are independently hydrogen, C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy, halo-
(C1-4)alkoxy, C1-4 alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyI(C1-4)alkyl, phenyl or benzyl, the

provided that Y is not CCH3 when W is CH, X and Z are N, R is NHCH3, R1 is 2,6-
dichlorophenyl and R2 is H.
Of particular interest are compounds where R8 is H.
The invention includes a compound of the general foR""ula (1) as defined immediately above except that:C1-8alkoxy and C|_8 alkylthio are excluded as values of R and R"; C7 alkylene and C3.7 alkenylene are excluded as chains foR""ed by R3 and R4; the C3-6 chain that R and R may foR"" may only be optionally substituted with one or more methyl groups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine are excluded as rings that R3 and R4 may foR""; tri(C1-4)alkylsi]yl is excluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkyl group or moiety, and the morpholine ring that R3 and R may foR"" is unsubstituted.
In still yet another aspect the invention provides a compound of the general foR""ula (1) wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both CR8;
R8 is H, halo (e.g. fluoro, chloro or bromo), C1-4 alkyl (e.g. methyl), C1-4 alkoxy (e.g. methoxy)orhalo(C1-4)alkyl (e.g. trifluorometfryl);
R is H, halo (e.g. fluoro, chloro or bromo). C1-4 alkyl (e.g. methyl), C1-4 alkoxy (e.g. methoxy)orcyano;
R1 is phenyl optionally substituted with from one to five halogen atoms or with from one to three substituents selected from halo, C1-4 alkyl, halo(C1-6)alkyl, C1-4 alkoxy or halo(C1-4)-alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo. C1-4 alkyl, halo(C1-4)alkyl, C1-4 alkoxy or halo(Cj-4)-alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C1-4 alkyl, halo(C1-6)alkyl, C1-4 alkoxy or halo(C1-4)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups; R2 is NR3R4;
R3 is C1-8 alkyl, halo(C1-8)alkyl, hydroxy(C1-8)aIkyl, C1-4 alkoxy(C1-8)aIkyl, C1-4 alkoxyhalo-(C1-8)alkyl, tri(C1-4)alkylsilyl(C1-6)alkyl, C1-4 alkylcarbonyl(C].8)alkyl, C1-4 alkylcarbonyl-halo(Ci.g)alkyl, phenyl(]_4)alkyl, C2-8 alkenyl, halo(C2-8)alkenyl, C2-8 alkynyl, C3-8 cycloalkyl optionally substituted with chloro, fluoro or methyl, C3-8 cycloalkyl(C1-6)alkyl, phenylamino,

piperidino or morpholino, the phenyl ring of phenylalkyi or phenylamino being optionally
substituted with one, two or three substituents selected from halo, C1-4 alkyl, halo(C].4)alkyl,
C1-4 alkoxy and halo(C1-4)alkoxy; and
R is H, C1-4 alkyl, halo(C1-4)alkyl or amino, or
R" and R together foR"" a C3-7 alkylene or C3-7 alkenylene chain optionally substituted with
methyl, or,
together with the nitrogen atom to which they are attached, R3 and R4 foR"" a morpholine,
thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or
piperazine N-(C,.4)a.,ky] (especially /V-methyl) ring, in which the morpholine or piperazine
rings are optionally substituted with methyl;
provided that Y is not CCH3 when W is CH, X and Z are N, R is NHCH3, R1 is 2,6-
dichlorophenyl and R2 is H.
Of particular interest are compounds where R is H.
In still yet another aspect the invention provides a compound of the general foR""ula (1)
wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y are both
CR8;
R8 is H, halo, C1-4 alkyl. C1-4 alkoxy or halo(C].4)alkyl;
R is halo;
R1 is phenyl optionally substituted with from one to five halogen atoms or with from one to
three substituents selected from halo, C1-4 alkyl, halo(C1-6)alkyli C1-4 alkoxy or halo(C1-4)-
alkoxy;
R2isNR3R4;
R3 is C1-4 alkyl, halo(C1-4)alkyl, C2-4 alkenyl, C3-6 cycloalkyl, C3-6 cycloalkyI(C1-4)alkyl or
phenylamino in which the phenyl ring is optionally substituted with one, two or three
substituents selected from halo. C1-4 alkyl, halo(d-4)alkyl, C1-4 alkoxy and halo(C1-4)alkoxy;
and
R4 is H,C1-4 alkyl or amino, or R3 and R4 together foR"" a C4-6 alkylene chain optionally
substituted with methyl, or, together with the nitrogen atom to which they are attached, R3
and R foR"" a morpholine ring.

Compounds that foR"" part of the invention are illustrated in Tables I to 126 below. Characterising data are given later in the Examples and in Table 132.
In Table 1 the compounds have the general foR""ula (1 A), where W and Y are N, X and Z are CH, R is CI, R1 is 2,4,6-trifluorophenyl and R3 and R4 are as shown in the table.




















Table 2
Table 2 consists of 662 compounds of the general foR""ula (1 A), where W and Y are
N, X and Z are CH, R is CI, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 2 is the same as compound 1 of Table 1 except
that in compound 1 of Table 2, R1 is 2,5,6-trifluorophenyl. Similarly, compounds 2 to 662 of
Table 2 are the same as compounds 2 to 662 of Table 1 except that in the compounds of
Table 2, R1 is 2,5,6-trifluorophenyl.
Table 3
Table 3 consists of 662 compounds of the general foR""ula (1 A), where W and Y are
N, X and Z are CH, R is CI, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 3 is the same as compound 1 of Table 1
except that in compound 1 of Table 3, R1 is 2,3,4,5,6-pentafluorophenyl. Similarly,
compounds 2 to 662 of Table 3 are the same as compounds 2 to 662 of Table 1 except that in
the compounds of Table 3, R1 is 2,3,4,5,6-pentafluorophenyl.
Table 4
Table 4 consists of 662 compounds of the general foR""ula (1 A), where W and Y are
N, X and Z are CH, R is CI, R! is 2,6-difluoro-4-methoxyphenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 4 is the same as compound 1 of Table 1
except that in compound 1 of Table 4, R1 is 2,6-difluoro-4-methoxyphenyl. Similarly,
compounds 2 to 662 of Table 4 are the same as compounds 2 to 662 of Table 1 except that in
the compounds of Table 4, R1 is 2,6-difluoro-4-methoxyphenyl.
Table 5
Table 5 consists of 662 compounds of the general foR""ula (1A), where W and Y are
N, X and Z are CH, R is CI, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 5 is the same as compound 1 of Table 1 except
that in compound 1 of Table 5, R1 is 2-fluoro-6-chlorophenyl. Similarly, compounds 2 to 662
of Table 5 are the same as compounds 2 to 662 of Table 1 except that in the compounds of
Table 5, R1 is 2-fluoro-6-chlorophenyl.

Table 6
Table 6 consists of 662 compounds of the general foR""ula (IB), where W and Y are
N, X and Z are CH, R is CI, R1 is 2,4,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 6 is the same as compound 1 of Table 1 except
that in compound 1 of Table 6, the compound has the general foR""ula (IB). Similarly,
compounds 2 to 662 of Table 6 are the same as compounds 2 to 662 of Table 1 except that in
the compounds of Table 6, the compounds have the general foR""ula (IB).
Table 7
Table 7 consists of 662 compounds of the general foR""ula (IB), where W and Y are
N, X and Z are CH, R is CI, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 7 is the same as compound 1 of Table 2 except
that in compound 1 of Table 7, the compound has the general foR""ula (IB).-Similarly,
compounds 2 to 662 of Table 7 are the same as compounds 2 to 662 of Table 2 except that in
the compounds of Table 7, the compounds have the general foR""ula (IB).
Table 8
Table S consists of 662 compounds of the general foR""ula (IB), where W and Y are
N, X and Z are CH, R is CI, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and R4
are as listed in Table 3. Thus, compound 1 of Table S is the same as compound 1 of Table 3
except that in compound 1 of Table 8, the compound has the general foR""ula (IB). Similarly,
compounds 2 to 662 of Table 8 are the same as compounds 2 to 662 of Table 3 except that in
the compounds of Table 8, the compounds have the general foR""ula (IB).
Table 9
Table 9 consists of 662 compounds of the general foR""ula (IB), where W and Y are
N, X and Z are CH, R is CI, R1 is 2?6-difluoro-4-methoxyphenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 9 is the same as compound 1 of Table 4
except that in compound 1 of Table 9, the compound has the general foR""ula (IB). Similarly,

Table 10
Table 10 consists of 662 compounds of the general foR""ula (IB), where W and Y are
N, X and Z are CH, R is CI, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 10 is the same as compound 1 of Table 5
except that in compound 1 of Table 10, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 10 are the same as compounds 2 to 662 of Table 5
except that in the compounds of Table 10, the compounds have the general foR""ula (IB).
Table 11
Table 11 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH, X and Z are N, R is CI, R! is 2,4,6-trifluorophenyI, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 11 is the same as compound 1 of Table 1 except that in compound 1 of Table 11, the compound has the general foR""ula (1 A) where W and Y are CH, X and Z are N. Similarly, compounds 2 to 662 of Table 11 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 11, the compounds have the general foR""ula (1 A) where W and Y are CH, X and Z are N. Table 12
Table 12 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH, X and Z are N, R is CI, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 12 is the same as compound 1 of Table 2 except that in compound 1 of Table 12, the compound has the general foR""ula (1A) where W and Y are CH, X and Z are N. Similarly, compounds 2 to 662 of Table 12 are the same as compounds 2 to 662 of Table 2 except that in the compounds of Table 12, the compounds have the general foR""ula (1 A) where W and Y are CH, X and Z are N. Table 13
Table 13 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH, X and Z are N, R is CI, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 13 is the same as compound 1 of Table 3 except that in compound 1 of Table 13, the compound has the general foR""ula (1A) where W and Y are CH, X and Z are N. Similarly, compounds 2 to 662 of Table 13 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 13, the compounds

Table 14
Table 14 consists of 662 compounds of the general foR""ula (1 A), where W and Y are CH, X and Z are N, R is CI, R1 is 2,6-difiuoro-4-methoxyphenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 14 is the same as compound 1 of Table 4 except that in compound 1 of Table 14, the compound has the general foR""ula (1A) where W and Y are CH, X and Z are N. Similarly, compounds 2 to 662 of Table 14 are the same as compounds 2 to 662 of Table 4 except that in the compounds of Table 14, the compounds have the general foR""ula (1A) where W and Y are CH, X and Z are N. Table 15
Table 15 consists of 662 compounds of the general foR""ula (1 A), where W and Y are CH, X and Z are N, R is CI, R1 is 2-fluoro-6-chIorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 15 is the same as compound 1 of Table 5 except that in compound 1 of Table 15, the compound has the general foR""ula (1A) where W and Y are CH,X and Z are N. Similarly, compounds 2 to 662 of Table 15 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 15, the compounds have the general foR""ula (1A) where W and Y are CH, X and Z are N. Table 16
Table 16 consists of 662 compounds of the general foR""ula (IB), where W and Y are
CH, X and Z are N, R is CI, R1 is 2,4,6-trifluorophenyI, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 16 is the same as compound 1 of Table 11
except that in compound 1 of Table 16, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 16 are the same as compounds 2 to 662 of Table 11
except that in the compounds of Table 16, the compounds have the general foR""ula (IB).
Table 17
Table 17 consists of 662 compounds of the general foR""ula (IB), where W and Y are
CH, X and Z are N, R is CI, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 17 is the same as compound 1 of Table 12
except that in compound 1 of Table-17, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 17 are the same as compounds 2 to 662 of Table 12
except that in the compounds of Table 17, the compounds have the general foR""ula (IB).
Table 1S

are as listed in Table 1. Thus, compound 1 of Table IS is the same as compound 1 of Table
13 except that in compound 1 of Table 18, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 18 are the same as compounds 2 to 662 of Table 13
except that in the compounds of Table 18, the compounds have the general foR""ula (IB).
Table 19
Table 19 consists of 662 compounds of the general foR""ula (IB), where W and Y are
CH, X and Z are N, R is CI, R1 is 2,6-difIuoro-4-methoxyphenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 19 is the same as compound 1 of Table
14 except that in compound 1 of Table 19, the compound lias the genera] foR""ula (IB).
Similarly, compounds 2 to 662 of Table 19 are the same as compounds 2 to 662 of Table 14
except that in the compounds of Table 19, the compounds have the general foR""ula (IB).
Table 20
Table 20 consists of 662 compounds of the general foR""ula (IB), where W and Y are
CH, X and Z are N, R is CI, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 20 is the same as compound 1 of Table 15
except that in compound 1 of Table 20, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 20 are the same as compounds 2 to 662 of Table 15
except that in the compounds of Table 20,the compounds have the general foR""ula (IB).
Table 21
Table 21 consists of 662 compounds of the general foR""ula (1A), where W and Y are N and X and Z are CH, R is F, R1 is 2,4,6-trifluorophenyI, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 21 is the same as compound 1 of Table 1 except that in compound 1 of Table 21, R is F instead of CI. Similarly, compounds 2 to 662 of Table 21 are the same as compounds 2 to 662 of Table 1 except that in the compounds of Table 21, R is F instead of CI. Table 22
Table 22 consists of 662 compounds of the general foR""ula (1A), where W and Y are N and X and Z are CH, R is F, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 22 is the same as compound 1 of Table 2 except that in compound 1 of Table 22, R is F instead of CI. Similarly, compounds 2 to 662

Table 23
Table 23 consists of 662 compounds of the general foR""ula (1 A), where W and Y are N and X and Z are CH, R is F, R1 is 2,3,4,5,6-pentafluorophenyI, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 23 is the same as compound 1 of Table 3 except that in compound 1 of Table 23, R is F instead of CI. Similarly, compounds 2 to 662 of Table 23 are the same as compounds 2 to 662 of Table 3 except that in the compounds of Table 23, R is F instead of CI. Table 24
Table 24 consists of 662 compounds of the general foR""ula (1 A), where W and Y are N and X and Z are CH, R is F, R is 2,6-difIuoro-4-methoxyphenyl, and the values of RJ and R are as listed in Table 1. Thus,, compound 1 of Table 24 is the same as compound 1 of Table 4 except that in compound 1 of Table 24, R is F instead of CI. Similarly, compounds 2 to 662 of Table 24 are the same as compounds 2 to 662 of Table 4 except that in the - compounds of Table 24, R is F instead of CI. Table 25
Table 25 consists of 662 compounds of the general foR""ula (1 A), where W and Y are N and X and Z are CH, R is F, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 25 is the same as compound 1 of Table 5 except that in compound 1 of Table 25, R is F instead of CI. Similarly, compounds 2 to 662 of Table 25 are the same as compounds 2 to 662 of Table 5 except that in the compounds of Table 25, R is F instead of CI. Table 26
Table 26 consists of 662 compounds of the general foR""ula (1 A), where W and Y are CH and X and Z are N, R is F, R1 is 2,4,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 26 is the same as compound 1 of Table 11 except that in compound 1 of Table 26, R is F instead of CI. Similarly, compounds 2 to 662 of Table 26 are the same as compounds 2 to 662 of Table 11 except that in the compounds of Table 26, R is F instead of CI. Table 27
Table 27 consists of 662 compounds of the general foR""ula (1 A), where W and Y are

except that in compound 1 of Table 27, R is F instead of CI. Similarly, compounds 2 to 662 of Table 27 are the same as compounds 2 to 662 of Table 12 except that in the compounds of Table 27, R is F instead of CI. Table 28
Table 28 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH and X and Z are N, R is F, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 2S is the same as compound 1 of Table 13 except that in compound 1 of Table 28, R is F instead of CI. Similarly, compounds 2 to 662 of Table 28 are the same as compounds 2 to 662 of Table 13 except that in the compounds of Table 28, R is F instead of CI. Table 29
Table 29 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH and X and Z are N, R is F, R1 is 2,6-difluoro-4-methoxyphenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 29 is the same as compound 1 of Table 14 except that in compound 1 of Table 29, R is F instead of CI. Similarly, compounds 2 to 662 of Table 29 are the same as compounds 2 to 662 of Table 14 except that in the compounds of Table 29, R is F instead of CI. Table 30
Table 30 consists of 662 compounds of the general foR""ula (1A), where W and Y are CH and X and Z are N, R is F, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 30 is the same as compound 1 of Table 15 except that in compound 1 of Table 30, R is F instead of CI. Similarly, compounds 2 to 662 of Table 30 are the same as compounds 2 to 662 of Table 15 except that in the compounds of Table 30, R is F instead of CI. Table 31 Table 31 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly

exactly the same a,compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 31 R1 is 2,6-difluorophenyl instead of 2-fluoro-6-chIorophenyI. Table 32
Table 32 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 32 R1 is 2-fluorophenyi- instead of 2-fluoro-6-chlorophenyl. Table 33
Table 33 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 33 R1 is 2,3,5,6-tetrafluorophenyl instead of 2-fluoro-6-chlorophenyl. Table 34
Table 34 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 34 R1 is 2-chloro~4,6-difluorophenyl instead of 2-fluoro-6-chloro-phenyl.

Table 35
Table 35 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 3 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3,10 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 35 R1 is 2-chlorophenyl instead of 2-fluoro-6-chlorophenyl. Table 36
Table 36 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 36 R1 is 2,6-dichlorophenyl instead of 2-fluoro-6-chlorophenyl. Table 37
Table 37 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 37 R1 is 2,4-dichloropjienyl instead of 2-fluoro-6-chlorophenyl, Table .38
Table 38 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds i 10 ooz of Table 10 respectively, compounds exactly me same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are

same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table. 38 R1 is 2,4,6-trichIorophenyl instead of 2~fluoro-6-chlorophenyl. Table 39
Table 39 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 39 R1 is 2,3,6-trichlorophenyl instead of 2-fluoro-6-chlorophenyl. Table 40
Table 40 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 40 R1 is pentachlorophenyl instead of 2-fluoro-6-chlorophenyl. Table 41
Table 41 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds Tto662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the

Table 42
Table 42 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 42 R1 is 4-fluoro-2,6-dichlorophenyl instead of 2-fluoro-6-chloro-phenyl. Table 43
Table 43 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same "as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 43 R1 is 2-bromophenyl instead of 2-fluoro-6-chlorophenyl. Table 44
Table 44 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 44 R1 is 2-fluoro-6-bromophenyl instead of 2-fluoro-6-chlorophenyl.


as compounds 1 to 662 of Table 15 respectively, compounds 19S7 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 45 R1 is 2-bromo-4,6-difluorophenyl instead of 2-fluoro-6-chloro-phenyl. Table 46
Table 46 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly ttie same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 46 Rl is 2-fluoro-6-methylphenyl instead of 2-fluoro-6-chIorophenyl. Table 47 ~~
Table 47 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 47 R1 is 2-chloro-6-methylphenyl instead of 2~fluoro-6-chlorophenyl. Table 48
Table 48 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 19S7 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly

exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 4S R1 is 2-methoxyphenyl instead of 2-fluoro-6~chlorophenyl. Table 49
Table 49 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 49 R1 is 2,6-dimethoxyphenyl instead of 2-fluoro-6-chlorophenyl. Table 50
Table 50 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 50 R1 is 2-fluoro-6-methoxyphenyl instead of 2-fluoro-6-chlorophenyl. Table 51
Table 51 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 51 R1 is 2-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl.

compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 52 R1 is 2-fiuoro-6-trifluoromethyIphenyl instead of 2-fluoro-6-chloro-phenyl. Table 53
Table 53 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 1.0 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 53 R1 is 2,6-di-(triiluoromethyI)phenyl instead of 2-fluoro-6-chIoro-phenyl. Table 54
Table 54 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 54 Rl is 2-chloro-6-trifluoromethylphenyl instead of 2-fluoro-6-chlorophenyl. Table 55
Table 55 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as

same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 55 R1 is 2,4-difluoro-6-trifIuoromethylphenyl instead of 2-fluoro-6-chlorophenyl. Table 56
Table 56 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as
compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same
as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the
same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly
the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are
exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the
compounds of Table 56 R1 is 2,4-difluoro-6-methoxyphenyl instead of 2-fluoro-6-chloro-
phenyl.
Table 57 ;
Table "57 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 57 R1 is 2,4-difluoro-6-methylphenyl instead of 2-fluoro-6-chloro-phenyl. Table 58
Table 5S consists of 3972 compounds. Compounds , to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds

exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 58 R1 is 2,4-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 59
Table 59 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to-662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as "compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 59 R1 is 3,5-difluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 60
Table 60 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 60 R1 is tetrafluoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 61
Table 61 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 61 R1 is 3-fluoropyrid-2-yl instead of 2-fluoro-6-chlorophenyl. Table 62

compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the same as compounds 1 to. 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 62 R1 is 4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyI. Table 63
Table 63 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 63 R1 is 3-fIuoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 64
Table 64 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 64 R1 is 2-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 65
Table 65 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 resoectively. and compound,

exactly the same as compounds 1 to 662 of Table 30 respectively, except that in ail of the compounds of Table 65 R1 is 2,4,6-trifluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 66
Table 66 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 66 R1 is 3,5-difluoropyrid-2~yl instead of 2-fluoro-6-chlorophenyL Table 67
Table 67 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 67 R1 is 2,6-difluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 68
Table 68 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 68 R1 is 2,4-difluoro-6-methoxypyrid-3-yl instead of 2-fluoro-6-chloro-phenyl.

Table 69
Table 69 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 69 R! is 2-fluoro-4~chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 70
Table 70 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same . as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 70 R1 is 3-fluoro-5-chloropyrid-4~yl instead of 2-fluoro-6-chlorophenyl. Table 71
Table 71 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 71 R1 is 2-chloro-4-fluoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 72
Table 72 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are

same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 72 R1 is 2,4-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 73
Table 73 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 73 R1 is 3-chloropyrid-2-yl instead of 2-fluoro-6-chlorophenyl. ' Table 74
Table 74 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 74 R1 is 4-chloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 75
Table 75 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the

Table 76
Table 76 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 76 R1 is 2-chloropyrid-3-yl instead of 2-fluoro~6-chlorophenyl. Table 77
Tqjble 77 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are " exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 77 R1 is 3-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl. Table 78
Table 78 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 19S7 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 78 R1 is 4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-ohlorophenyl. Table 79
Table 79 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exact

same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 79 R1 is 3,5-dichIoropyrid-2-yl instead of 2-fluoro-6-chIorophenyl. Table SO
Table 80 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 80 R1 is 4,6-dichIoropyrid-3-yl instead of 2-fluoro-6-chlorophenyl.
Table 81 ~ I -
. i —. -i. ., _ - i
Table 81 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 81 R1 is 3-trifluoromethylpyrid-4-yl instead of 2-fluoro-6-chIorophenyl. Table S2
Table 82 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the

Table 83
Table 83 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 83 R1 is 2-fluoro-4-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 84
Table 84 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310. are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 84 R1 is 3-fluoro-5-trifluoromethylpyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 85
Table 85 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 85 R1 is 4-fluoro-2-trifluoromethylpyrid-3-yl instead of 2-fluoro-6-chlorophenyl.

Table 86
Table 86 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 19S7 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 86 R] is 2,6-dichloropyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 87
Table 87 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 87 R1 is 3,5-dichIoropyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 88
Table 88 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 88 R1 is 3-chIoro-6-trifluoromethylpyrid-2-yI instead of 2-fluoro-6-chlorophenyl. Table 89
Table 89 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as
compounds 1 to 662

as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 89 R1 is 3-fluoro-6-trifluoromethylpyrid-2-yl instead of 2-fluoro-6-chlorophenyl. Table 90
Table 90 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 90 R1 is pyrid-2-yl instead of 2-fluoro-6-chlorophenyl. Table 91
Table 91 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 91 R1 is pyrid-3-yl instead of 2-fluoro-6-chlorophenyl. Table 92
Table 92 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 resr>ectively, and compounds 3311 to 3972 are

exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the compounds of Table 92 R1 is pyrid-4-yl instead of 2-fluoro-6-chlorophenyl. Table 93
Table 93 consists of 3972 compounds. Compounds 1 tc 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 93 R! is 3-fIuorothien-2-yl instead of 2-fluoro-6-chlorophenyl. Table 94
Table 94 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 94 Rl is 3-chlorothien-2-yl instead of 2-fluoro-6-chlorophenyl. Table 95
Table 95 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as ,. compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 95 R1 is 2,4-difluorothien-3-yl instead of 2-fluoro-6-chlorophenyl. Table 96

'compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 264S are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 96 Rl is 2,4-dichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl. Table 97
Table 97 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 19S6 are exactly the same as compounds 1 to 662 ofTable 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 ofTable 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 ofTable 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 ofTable 30 respectively, except that in all of the compounds ofTable 97 R1 is 2,4,5-trichlorothien-3-yl instead of 2-fluoro-6-chlorophenyl. Table 98
Table 98 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 ofTable 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 ofTable 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 ofTable 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 ofTable 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 ofTable 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 ofTable 30 respectively, except that in all of the compounds ofTable 98 R1 is piperidino instead of 2-fluoro-6-chlorophenyl. Table 99
Table 99 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 ofTable 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 ofTable 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 ofTable 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 ofTable 20 respectively, compounds 2649 to 3310 are exactly

exactly the same as compounds I to 662 of Table 30 respectively, except that in all of the compounds of Table 99 R1 is 2-methylpiperidino instead of 2-fluoro-6-chlorophenyl. Table 100
Table 100 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 100 R1 is 2,6-dimethylpiperidjno instead of 2-fluoro-6-chlorophenyl. Table 101
Table 101 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all of the compounds of Table 101 R1 is morpholino instead of 2-fluoro-6-chlorophenyl. Table 102
Table 102 consists of 3972 compounds. Compounds 1 to 662 are exactly the same as compounds 1 to 662 of Table 5 respectively, compounds 663 to 1324 are exactly the same as compounds 1 to 662 of Table 10 respectively, compounds 1325 to 1986 are exactly the same as compounds 1 to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly the same as compounds 1 to 662 of Table 20 respectively, compounds 2649 to 3310 are exactly the same as compounds 1 to 662 of Table 25 respectively, and compounds 3311 to 3972 are exactly the same as compounds 1 to 662 of Table 30 respectively, except that in all oT the compounds of Table 102 R1 is 2,6-dimethylmorpholino instead of 2-fluoro-6-chlorophenyI.

Table 103 is the same as compound i of Table 1, compound 663 of Table 103 is the same as compound 1 of Table 2, compound 19,861 of Table 103 is the same as compound 1 of Table 31, compound 305,844 of Table 103 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 103 R is ethyl instead of CI or F. Table 104
Table 104 consists of 305,844 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 104 is the same as compound 1 of Table 1, compound 663 of Table 104 is the same as compound 1 of Table 2, compound 19,861 of Table 104 is the same as compound 1 of Table 31, compound 305,844 of Table 104 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 104 R is Br instead of CI or F. Table 105
Table 105 consists of 305,844 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 105 is the same as compound 1 of Table 1, compound 663 of Table 105 is the same as compound 1 of Table 2, compound 19,861 of Table 105 is the same as compouad 1 of Table-31, compound 305,844 of Table 105 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 105 R is methyl instead of CI or F. Table 106
Table 106 consists of 305,844 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 106 is the same as compound 1 of Table 1, compound 663 of Table 106 is the same as compound 1 of Table 2, compound 19,861 of Table 106 is the same as compound 1 of Table 31, compound 305,844 of Table 106 is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 106 R is H instead of CI or F. Table 107
Table 107 consists of 305,844 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 107 is the same as compound 1 of Table 1, compound 663 of Table 107 is the same as compound 1 of Table 2, compound 19,861 of Table 107 is the same as compound 1 of Table

Table IPS
Table 108 consists of 305,844 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 102 (thus, for example, compound 1 of Table 108 is the same as compound 1 of Table 1, compound 663 of Table 108 is the same as compound 1 of Table 2, compound 19,861 of Table 108 is the same as compound 1 of Table 31, compound 305,844 of Table 10S is the same as compound 3,972 of Table 102) except that in all of the compounds of Table 108 R is methoxy instead of CI or F. Table 109
Table 109 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 10 (thus, for example, compound 1 of Table
109 is the same as compound 1 of Table 1, compound 663 of Table 109 is the same as
compound 1 of Table 2, etc.) except that in all of the compounds of Table 109 X is CF
instead of CH.
Table 110
Table 110 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 10 (thus, for example, compound 1 of Table
110 is the same as compound 1 of Table 1, compound 663 of Table 110 is the same as
compound 1 of Table 2, etc.) except that in all of the compounds of Table 110 X is CC1
instead of CH.
Table 111
Table 111 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 10 (thus, for example, compound 1 of Table
111 is the same as compound 1 of Table 1, compound 663 of Table 111 is the same as
compound 1 of Table 2, etc.) except that in all of the compounds of Table 111 X is CBr
instead of CH.
Table 112
Table 112 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 1 to 10 (thus, for example, compound 1 of Table
112 is the same as compound 1 of Table 1, compound 663 of Table 112 is the same as
compound 1 of Table 2, etc.) except that in all of the compounds of Table 112 X is CCH3

Table 113 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 11 to 20 (thus, for example, compound 1 of Table
113 is the same as compound 1 of Table 11, compound 663 of Table 113 is the same as
compound 1 of Table 12, etc) except that in all of the compounds of Table 113 Y is CF
instead of CH.
Table 114
Table 114 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 11 to 20 (thus, for example, compound 1 of Table
114 is the same as compound 1 of Table 11, compound 663 of Table 114 is the same as
compound 1 of Table 12, etc.) except that in all of the compounds of Table 114 Y is CC1
instead of CH.
Table 115
Table 115 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 11 to 20 (thus, for example, compound 1 of Table
115 is the same as compound 1 of Table 11, compound 663 of Table 115 is the same as
compound 1 of Table 12, etc.) except that in all of the compounds of Table 115 Y is CBr.
instead ofCH.
Table 116
Table 116 consists of 6620 compounds. Each of these compounds is exactly the same as the corresponding compound in Tables 11 to 20 (thus, for example, compound 1 of Table
116 is the same as compound 1 of Table 11, compound 663 of Table 116 is the same as
compound 1 of Table 12, etc.) except that in all of the compounds of Table 116 Y is CCH3
instead of CH.
Table 117
Table 117 consists of 662 compounds of the general foR""ula (IB), where W and Y are N and X and Z are CH, R is F, R1 is 2,4,6-trifluorophenyl, and the values of R3 and R4 are as listed in Table 1. Thus, compound 1 of Table 117.isAhe same as compound 1 of Table 21 except that in compound 1 of Table 117, the compound has the general foR""ula (IB). Similarly, compounds 2 to 662 of Table 117 are the same as compounds 2 to 662 of Table 21 except that in the compounds of Table 117, the compounds have the general foR""ula (IB).

Table 118
Table 118 consists of 662 compounds of the general foR""ula (IB where W and Y are
N and X and Z are CH, R is F, R1 is 2,5,6-trifluorophenyl, and the values of R3 and R4 are as
listed in Table 1. Thus, compound 1 of Table 118 is the same as compound 1 of Table 22
except that in compound 1 of Table 118, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 1 IS are the same as compounds 2 to 662 of Table 22
except that in the compounds of Table 118, the compounds have the general foR""ula (IB).
Table 119
Table 119 consists of 662 compounds of the general foR""ula (IB), where W and Y
are N and X and Z are CH, R is F, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R"
and R are as listed in Table 1. Thus, compound 1 of Table 119 is the same as compound 1 of
Table 23 except that in compound 1 of Table 119, the compound has the general foR""ula
(IB). Similarly, compounds 2 to 662 of Table 119 are the same as compounds 2 to 662 of
Table 23 except that in the compounds of Table 119, the compounds havejthe general
foR""ula (IB).
Table 120 ^
Table 120 consists of 662 compounds of the general foR""ula (IB), where W and Y
are N and X and Z are CH, R is F, Rl is 2,6-difluoro-4-methoxyphenyl, and the values of R3
and R are as listed in Table 1. Thus, compound 1 of Table 120 is the same as compound 1 of
Table 24 except that in compound 1 of Table 120, the compound has the general foR""ula
(IB). Similarly, compounds 2 to 662 of Table 120 are the same as compounds 2 to 662 of
Table 24 except that in the compounds of Table 120, the compounds have the general
foR""ula (IB).
Table 121
Table 121 consists of 662 compounds of the general foR""ula (IB), where W and Y
are N and X and Z are CH, R is F, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 121 is the same as compound 1 of Table
25 except that in compound 1 of Table 121, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 121 are the same as compounds 2 to 662 of Table 25
except that in the compounds of Table 121, the compounds have the general foR""ula (IB).
Table 122

as listed in Table 1. Thus, compound 1 of Table 122 is the same as compound 1 of Table 26
except that in compound 1 of Table 122, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 122 are the same as compounds 2 to 662 of Table 26
except that in the compounds of Table 122, the compounds have the general foR""ula (IB).
Table 123
Table 123 consists of 662 compounds of the general foR""ula (IB), where W and Y
are CH and X and Z are N, R is F, R1 is 2,4,5-trifluorophenyl, and the values of R3 and R4 are
as listed in Table 1. Thus, compound 1 of Table 123 is the same as compound 1 of Table 27
except that in compound 1 of Table 123, the compound has the general foR""ula (IB).
Similarly, compounds 2 to 662 of Table 123 are the same as compounds 2 to 662 of Table 27
except that in the compounds of Table 123wthe compounds have the general foR""ula (IB).
Table 124
Table 124 consists of 662 compounds of the general foR""ula (IB), where W and Y
are CH and X and Z are N, R is F, R1 is 2,3,4,5,6-pentafluorophenyl, and the values of R3
and R are as listed in Table 1. Thus, compound 1 of Table 124 is the same as compound 1 of
Table 28 except that in compound 1 of Table 124, the compound has the general foR""ula
(IB). Similarly, compounds 2 to 662 of Table 124 are the same-as compounds 2 to 662 of
Table 28 except that in the compounds of Table 124, the compounds have the general
foR""ula (IB).
Table 125
Table 125 consists of 662 compounds of the general foR""ula (IB), where W and Y
are CH and X and Z are N, R is F, R1 is 2,6-difluoro-4-methoxyphenyl, and the values of R3
andR4 are as listed in Table 1. Thus, compound 1 of Table 125 is the same as compound 1 of
Table 29 except that in compound 1 of Table 125, the compound has the general foR""ula
(IB). Similarly, compounds 2 to 662 of Table 125 are the same as compounds 2 to 662 of
Table 29 except that in the compounds of Table 125, the compounds have the general
foR""ula (IB).
Table 126
Table 126 consists of 662 compounds of the general foR""ula (IB), where W and Y
are CH and X and Z are N, R is F, R1 is 2-fluoro-6-chlorophenyl, and the values of R3 and R4
are as listed in Table 1. Thus, compound 1 of Table 126 is the same as compound 1 of

Similarly, compounds 2 to 662 of Table 126 are the same as compounds 2 to 662 of Table 30 except that in the compounds of Table 126, the compounds have the general foR""ula (IB).
Compounds of foR""ula (7) or (8), which are examples of compounds of general foR""ula (1) where one of R and R is NR R ,can be made as shown in Scheme 1, in which W, X, Y, Z, R , R" and R have the meanings given above and R is Cj.4 alkyl.

Compounds of general foR""ula (4) can be prepared from compounds of general foR""ula (2), which are either commercially available or made by methods known in the literature, by reaction with acids of general foR""ula (3), using standard coupling methods, for example by conversion to the acid chloride using a chlorinating agent such as thionyl chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene. Compounds of general foR""ula (5) can be prepared by treating compounds of general . foR""ula (4) with a base such as sodium hydride, optionally in the presence of a Lewis acid

general foR""ula (6) can be prepared by reaction of compounds of general foR""ula (5) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene, at between 50 and 150°C, but preferably between SO and 110°C, or in a microwave reactor at between 150 and 300°C, but preferably between 200 and 250°C. Compounds of foR""ula (7) and (S) can be prepared by reaction of compounds of general foR""ula (6) with an amine R3R4NH, either neat, or in a suitable solvent such as DMF, between room temperature and 150°C, but preferably between 50 and S0°C. If compounds
(7) and (8) are produced as a mixture they can be separated by suitable means such as
crystallisation or chromatography under noR""al or reverse phase conditions.
Compounds of the general foR""ulae (5), (6), (7) and (8) may be derivatised, via the chloro or hydroxy substituents, using routine chemical techniques to foR"" other compounds of the general foR""ula (1). Alternatively, other compounds of the general foR""ula (1) maybe prepared using a similar methodology to that described for preparing the compounds (5) to
(8) and employing preparative techniques known from the chemical literature.
Compounds of foR""ula (7) can also be made as shown in Scheme 2.

Compounds of general foR""ula (10) can be prepared from compounds of general

example by conversion to the acid chloride using a chlorinating agent such as thionyl chloride, followed by reaction of the resultant acid chloride optionally in the presence of a base such as triethylamine, in a suitable solvent such as dichloromethane or toluene. Compounds of general foR""ula (11) can be prepared by treating compounds of general foR""ula (10) with a base such as sodium hydride, optionally in the presence of a Lewis acid such as magnesium oxide, in a suitable solvent such as NNdimethylfoR""amide (DMF) or toluene, at between room temperature and 150°C, but preferably at 60-90°C. Compounds of general foR""ula (12) can be prepared by reaction of compounds of general foR""ula (11) with a chlorination reagent such as phosphorus oxychloride, either neat or in a suitable solvent such as toluene, at between 50 and 150°C, but preferably between 80 and 110°C, or in a microwave reactor at between 150 and 300°C, but preferably between 200 and 250°C. Compounds of foR""ula (7) can be prepared from compounds of foR""ula (12) by reductive amination, for example by reaction with a ketone or aldehyde in a suitable solvent such as ethanol or toluene, at between room temperature and reflux, optionally in the presence of an acid catalyst such as para-toluenesulphonic acid or a drying agent such as molecular sieves, followed by treatment with a suitable reducing agent such as sodium borohydride, at between -20°C and 40°C, but preferably at room temperature. The aldehyde or ketone is chosen so that the desired groups R3 and R4 are foR""ed after reduction of the product of reaction with the amine (12). For example if compounds of foR""ula (12) are reacted with one equivalent of propionaldehyde and then sodium borohydride, compounds of foR""ula (7) where R3 is n~ propyl, and R4 is hydrogen are foR""ed. If required, the reaction can be repeated with a different aldehyde or ketone. For example, if acetone is used for the second reaction, then compounds of foR""ula (7) where R3 is N-propyl and R is iso-propyl, are foR""ed. Alternatively compounds of foR""ula (7) can be foR""ed from compounds of foR""ula (12) by alkylation with a group R3LG, where LG is a leaving group, by treatment with a suitable base such as sodium hydride in a solvent such as DMF, or a base such as potassium carbonate in a solvent such as acetone or DMF, at between -7S°C and 100°C, but preferably between room temperatureand 60°C, followed by treatment with R4TG in a second step under the same conditions if required.


Compounds of foR""ula (13) can be prepared as shown in Scheme 3 from compounds of foR""ula (6) by reaction with a source of fluoride ion, such as potassium fluoride, in a suitable solvent such as sulpholane, at a temperature between 50°C and 200°C, but preferably at 80-150°C. Compounds of foR""ula (14) and/or compounds of foR""ula (15) can be prepared from difluoro compounds of foR""ula (13) by reaction with an amine of foR""ula RJRNH in a suitable solvent such as DMF or CH2CI2, at a temperature of 0°C-100°C, but preferably at room temperature.

Compounds of general foR""ula (16), where Hal is chlorine or fluorine, can be converted into compounds of foR""ula (17), (18), (19), (20), (21), (22) or (23) as shown in Scheme 4. Compounds of general foR""ula (17) where Hal2 is bromine or iodine can be foR""ed by reacting compounds of general foR""ula (16) with a metal halide, for example cuprous bromide, in a suitable solvent, for example DMF, at between room temperature and 155°C, but preferably between 70°C and 155°C. Compounds of general foR""ula (18) where V is oxygen or sulphur and R9 is Cj-s alkyl, can be foR""ed by reacting compounds of general foR""ula (16) with a metal alkoxide or thioalkoxide MVR9 in a suitable solvent, for example sodium methoxide in methanol, at room temperature to 65°C. Compounds of general foR""ula

155°C but preferably between 50°C and 155°C, Compounds of general foR""ula (20) where R is C i-s alky], can be foR""ed by reacting compounds of general foR""ula (16) with an alkyl metal derivative in a suitable solvent, for example methyl magnesium bromide in THF, optionally in the presence of catalyst such as cuprous bromide or Pd(Ph)4, between -40°C and 50°C. Compounds of general foR""ula (21) can be foR""ed by reduction of compounds of general foR""ula (16), where Hal1 is chlorine, for example by hydrogenolysis with hydrogen gas and a metal catalyst such as palladium on carbon in a suitable solvent such as ethanol, at room temperature. Compounds of general foR""ula (22) where Rn is hydrogen or Cj.^ alkyl, can be foR""ed by reaction of compounds of general foR""ula (16) with an alkyl acetylene under the Sonogashira conditions, for example with 1-propyne in triethylamine in the presence of a cuprous salt such as cuprous iodide and a palladium catalyst such as Pd(Ph)4, between room temperature and 70°C. Compounds of general foR""ula (23) where R/2 is hydrogen or C1-6 alkyl, can be foR""ed by reaction of compounds of general foR""ula (16) with an alkenyl metal derivative in a suitable solvent, such as ethenylboronic acid in THF, in the presence of a palladium catalyst such as Pd(Ph)4 and a base such as caesium carbonate, between room temperature and 65°C.

In Scheme 5 compounds of general foR""ula (24), where the two R3R4N groups are identical, can be made from compounds of general foR""ula (13) by reaction with a large excess of amine R3R4NH in a suitable solvent such as DMF, at a temperature between 0°C and 150°C, but preferably between room temperature and 100°C
Further assistance in the preparation of the compounds of foR""ula (1) may be derived from the following publications: Emilio, Toja, et, ai, J. Heterocyclic Chem., 23, 1955 (1986), H. Schafer, et. al„ J.f.prakt. Chemie, 321(4), 695 (1970) and H. Bredereck et. af.f


wherein W, X, Y, Z, R! and R7 are as define above, are believed to be novel compounds (other than the three compounds of foR""ula (5) in which W and Y are both CH, X and Z are both N and R1 is CH3, C2H5 or C6H5, disclosed in H. Bredereck el al.t Chem. Ber. 96, 1868-1872 (1993)) and foR"" a further part of this invention.
It should be noted that the inteR""ediate of general foR""ula (5) may exist in the tautomeric foR""s (a), (b) and (c) as well as in the foR"" shown in foR""ula (5):

The invention as defined by the general foR""ula (5) embraces all such tautomers. Of particular interest are the inteR""ediates listed in Tables 127 to 134 below. In Table
7 1
127 the compounds have the general foR""ula (4) where R is methyl and W, X, Y, Z and R have the values shown in the table.



Table 12S
Table 128 consists of 24 compounds of the general foR""ula (5), where W, X, Y, Z and R1 have the values given in Table 127. Thus, compound 1 of Table 128 has the same W, X, Y, Z and R1 values as compound 1 of Table 127, etc. Table 129
Table 129 consists of 24 compounds of the general foR""ula (6), where W, X, Y, Z and Rl have the values given in Table 127. Thus, compound 1 of Table 129 has the same W, X, Y, Z and R1 values as compound 1 of Table 127, etc. Table 130
Table 130 consists of 24 compounds of the general foR""ula (13), where W, X, Y, Z and R1 have the values given in Table 127. Thus, compound 1 of Table 130 has the same W, X, Y, Z and R1 values as compound 1 of Table 127, etc.

instead of methyl. Similarly, compounds 2 to 24 of Table 131 are the same as compounds 2 to 24 of Table 127 except that in the compounds of Table 131, R7 is ethyl.
The compounds of formula (1) are active fungicides and may be used to control one or more of the following pathogens: Pyhcularia oiyzae (Magnaporthe grisea) on rice and wheat and other Pyricularia spp. on other hosts; Puccinia triticina (or reconduct), Puccinia striiformis and other rusts on wheat, Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts (for example turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants); Erysiphe cichoracearum on cucurbits (for example melon); Blumeria (or Eiysiphe) graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts, such as Sphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerotheca fuliginea) on cucurbits (for example cucumber), Leveillula taurica on tomatoes, aubergine and green pepper, Podosphaera leucotricha on apples and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp; [Pyrenophora spp.), Rhynchosporium spp., Mycosphaerella graminicola (Septoria tritici) and Phaeosphaeria nodorwn (Stagonospora nodorum or Septoria nodorum), Pseadocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (for example wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora spp. on other hosts, for example sugar beet, bananas, soya beans and rice; Botjytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botjytis spp. on other hosts; Alternaria spp. on vegetables (for example carrots), oil-seed rape, apples, tomatoes, potatoes, cereals (for example wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (for example wheat) and tomatoes; Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Stemphylium spp. (Pleospora spp.) on apples, pears, onions and other hosts; summer diseases (for example bitter rot (Glomerella cingidata), black rot or frogeye leaf spot (Botiyosphaeria obtusa), Brooks fruit spot (Mycosphaerella pomi), Cedar apple rust

Plasmopara viticola on vines; other downy mildews, such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora hamuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium idtimum) on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper ornamentals, tobacco, cocoa and other hosts; Thanatephonis cucumeris on rice and turf and other Rhizoctonia spp. on various hosts such as wheat and barley, peanuts, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, potatoes, oil-seed rape and other hosts; Sclerotiwn spp. on turf, peanuts and other hosts; Gibberella fujikuroi on rice; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. on bananas, peanuts;ckrus, pecans, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Verticillium spp. on a range of hosts including hops, potatoes and tomatoes; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa . causing vascular streak dieback; Fusarium spp., Typhula spp., Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp. and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize; Ramularia spp. on sugar beet, barley and other hosts; post-harvest diseases particularly of fruit (for example Penicillium digitaturn, Penicillium italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musanim on bananas and Botiytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniams, Phomopsis viticola, Pseudopeziza tracheiphila and Steream hirsutum; other pathogens on trees (for example Lophodermium seditiosum) or lumber, notably Cephaloascns fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and iiingal vectors of viral diseases (for example Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV) and Polymyxa betae on sugar beet as the vector of rhizomania).
A compound of formula (1) may move acropetally, basipetally or locally in plant tissue to be active against one or more fungi. Moreover, a compound of formula (1) maybe

The invention therefore provides a method of combating or controlling phytopatho-genie fungi which comprises applying a fungicidally effective amount of a compound of formula (1), or a composition containing a compound of formula (1), to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or any other plant growth medium, e.g. nutrient solution.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes protectant, curative, systemic, eradicant and antisporulant treatments.
The compounds of formula (1) are preferably used for agricultural, horticultural and turfgrass purposes in the form of a composition.
In order to apply a compound of formula (1) to a plant; to a seed of a plant, to the locus of the plant or seed or to soil or any other growth medium, a compound of formula (1) is usually formulated into a composition which includes, in addition to the compound of formula (1), a suitable inert diluent or carrier and, optionally, a surface active agent (SFA). SFAs are chemicals that are able to modify the properties of an interface (for example, liquid/solid, liquid/air or liquid/liquid interfaces) by lowering the interfacial tension and thereby leading to changes in other properties (for example dispersion, emulsification and wetting). It is preferred that all compositions (both solid and liquid formulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to S5%, for example 5 to 60%, of a compound of formula (1). The composition is generally used for the control of fungi such that a compound of formula (1) is applied at a rate of from 0. lg tol 0kg per hectare, preferably from lg to 6kg per hectare, more preferably from lg to 1kg per hectare.
When used in a seed dressing, a compound of formula (1) is used at a rate of 0.000lg to lOg (for example 0.001 g or 0.05g), preferably 0.005g to 10g, more preferably 0.005 g to 4g, per kilogram of seed.
In another aspect the present invention provides a fungicidal composition comprising a fungicidally effective amount of a compound of formula (1) and a suitable carrier or diluent therefor.
In a still further aspect the invention provides a method of combating and controlling fungi at a locus, which comprises treating the fungi, or the locus of the fungi with a

The compositions can be chosen from a number of formulation types, including dustable powders (DP), soluble powders (SP), water soluble granules (SG), water dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil miscible liquids (OL), ultra low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil in water (EW) and water in oil (EO)), micro-emulsions (ME), suspension concentrates (SC), aerosols, fogging/smoke formulations, capsule suspensions (CS) and seed treatment formulations. The formulation type chosen in any instance will depend upon the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (1).
Dustable powders (DP) maybe prepared by mixing a compound of formula (1) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium carbonates, sulphur, lime, flours, talc and other organic and inorganic solid carriers) and mechanically grinding the mixture to a fine powder.
Soluble powders (SP) may be prepared by mixing a compound of formula (1) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve water dispersibility/solubility. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water soluble granules (SG).
Wettable powders (WP) may be prepared by mixing a compound of formula (1) with one or more solid diluents or carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, one or more suspending agents to facilitate the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).
Granules (GR) may be formed either by granulating a mixture of a compound of formula (1) and one or more powdered solid diluents or carriers? or from pre-formed blank granules by absorbing a compound of formula (1) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr,

commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).
Dispersible Concentrates (DC) may be prepared by dissolving a compound of formula (1) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surface active agent (for example to improve water dilution or prevent crystallisation in a spray tank).
Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of formula (1) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), ketones (such as cyclohexanone or methylcyclo-hexanone), alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), Af-alkylpyr-rolidones (such as TV-methylpyrrolidone or 7V-octylpyrrolidone), dimethyl amides of fatty acids (such as Cs-Cio fatty acid diethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment. Preparation of an EW involves obtaining a compound of formula (1) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SFAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents that have a low solubility in water.
Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SFAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of formula (1) is present initially in either the

system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming a conventional oil-in-v.ater emulsion.
Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (1). SCs may be prepared by ball or bead milling the solid compound of formula (3) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle- Alternatively, a compound of formula (1) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.
Aerosol formulations comprise a compound of formula (1) and a suitable propellant (for example /z-butane). A compound of formula (1) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as /2-propanoI) to provide compositions for use in non-pressurised, hand-actuated spray pumps.
A compound of formula (1) maybe mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating, in an enclosed space, a smoke containing the compound.
Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of formula (1) and, optionally, a carrier or diluent therefor. The polymeric shell maybe produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of formula (1) and they may be used for seed treatment. A compound of formula (1) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of formula (1)).
A compound of formula (1) may also be formulated for use as a seed treatment, for example as a powder composition, including a powder for dry seed treatment (DS), a water soluble powder (SS) or a water dispersible powder for slurry treatment (WS), or as a liquid composition, including a flowable concentrate (FS), a solution (LS) or a capsule suspension (CS). The preparations of DS, SS, WS, FS and LS compositions are very similar to those of, respectively, DP, SP? WP, SC and DC compositions described above. Compositions for treating seed may include an agent for assisting the adhesion of the composition to the seed (for example a mineral oil or a film-forming barrier).
Wetting agents, dispersing agents and emulsifying agents may be SFAs of the -cationic, anionic, amphoteric or non-ionic type.
Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.
Suitable anionic SFAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecyl-benzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di~isopropyl- and tri-/5^propyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium Iaureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates and lignosulphonates.
Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.
Suitable SFAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol,

(comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example Iauryl dimethyl amine oxide); and lecithins.
Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carbox#methylceliulose)-and swelling clays (such as bentonite or attapulgite).
A compound of formula (1) may be applied by any of the known means of applying fungicidal compounds. For example, it may be applied, formulated or unformulated, to any part of the plant, including the foliage, stems, branches or roots, to the seed before it is planted or to other media in which plants are growing or are to be planted (such as soil surrounding the roots, the soil generally, paddy water or hydroponic culture systems), directly or it may be sprayed on, dusted on, applied by dipping, applied as a cream or paste formulation, applied as a vapour or applied through distribution or incorporation of a composition (such as a granular composition or a composition packed in a water-soluble bag) in soil or an aqueous environment.
A compound of formula (1) may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
Compositions for use as aqueous preparations (aqueous solutions or dispersions) are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being added to water before use. These concentrates, which may include DCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often required to withstand storage for prolonged periods and, after such storage, to be capable of addition to water to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. Such aqueous preparations may contain varying amounts of a compound of formula (1) (for example 0.0001 to 10%, by weight) depending upon the purpose for which they are to be used.
A compound of formula (1) may be used in mixtures with fertilisers (for example nitrogen-, potassium- or phosphorus-containing fertilisers). Suitable formulation types

The invention therefore also provides s fertiliser composition comprising a fertiliser and a compound of formula (1).
The compositions of this invention may contain other compounds having biological activity, for example micronutrients or compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidai, insecticidal, nematicidal or acaricidal activity.
By including another fungicide, the resulting composition may have a broader spectrum of activity or a greater level of intrinsic activity than the compound of formula (1) alone. Further the other fungicide may have a synergistic effect on the fungicidal activity of the compound of formula (1).
The compound of formula (1) may be-the sole active ingredient of the composition or it may be admixed with one or more additional active ingredients such as a pesticide, fungicide, synergist, herbicide or plant growth regulator where appropriate. An additional active ingredient may: provide a composition having a broader spectrum of activity or increased persistence at a locus; synergise the activity or complement the activity (for example by increasing the speed of effect or overcoming repellency) of the compound of formula (1); or help to overcome or prevent the development of resistance to individual components. The particular additional active ingredient will depend upon the intended utility of the composition.
Examples of fungicidal compounds which may be included in the composition of the invention are AC 3S2042 (7^-(l-cyano-l,2-dimethylpropyl)-2-(2,4-dichlorophenoxy) pro-pionamide), acibenzolar-S-methyl, alanycarb, aldimorph, anilazine, azaconazole, azafenidin, azoxystrobin, benalaxyl, benomyl, benthiavalicarb, biloxazol, bitertanol, blasticidin S, boscalid (new name for nicobifen), bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, carpropamid, carvone, CGA 41396, CGA 41397, chinomethionate, chlorbenzthiazone, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cyamidazosulfamid, cyazofamid (BCF-916), cyflufenamid, cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide l,l'-dioxide, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb,

dinocap, dithianon. dodecyl dimethyl ammonium chloride, dodemorph, dodine, doguadine, cdifenphos, epoxiccnazole, ethaboxam, ethirimol, ethyl (Z)-iY-benzyl-M[methyl(methyl-thioethylideneaminooxycarbonyl)amino]thio)-p-alaninate, etridiazole, famoxadone, fenamidone, fenarinioi, fenbuconazole, fenfuram, fenhexarnid, fenoxanil (AC 3S2042), fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, flumetover, flumorph, fluoroimide, fluoxastrohin, fluquinconazole, flusilazole, flusulfamide, flutolanil, flutriafol, folpet, fosetyl-aluminium, fuberidazole, furalaxyl, furametpyr. guazatine, hexaconazole. hydroxyisoxazole, hymexazole, imazalil. imibenconazole, iminoctadine, iminoctadine triacetate, ipconazole, iprobenfos. iprodione, iprovalicarb, isopropanyl butyl carbamate, isoprothioiane, kasugamycin, kresoxim-methyl, LY186054, LY211795, LY 248908, mancozeb, maneb, mefenoxam, mepanip\Tim, mepronil, metalaxyl, metalaxyl M, metconazole, metiram, metiram-zinc, metominostrohin, metra-fenone, MON65500 f.V
-aIlyI-4,5-dimethyl-2-trimethylsiIylthiophene-3-carboxamide), myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothale-isopropyl, nuarirnol, ofurace, organomercury compounds, orysastrobin, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosphorus acids, phthalide, picoxystrobin, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, proquinazid, prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinomethionate, quinoxyfen, quintozene, silthiofam (MON 65500), S-imazalil, simeconazole, sipconazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole. tecloftalam, tecnazene, tetraconazole, thiabendazole, thifluzamide, 2-(thiocyanomethy]thio/benzothiazole, thiophanate-methyl, thiram, tiadinil, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon, triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph, trifloxystrobin, triflumizole, triforine, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb, ziram, zoxamide and compounds of the formulae:

The compounds of formula (1) may be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases.
Some mixtures may comprise active ingredients, which have significantly different physical, chemical or biological properties such that they do not easily lend themselves to the same conventional formulation type. In these circumstances other formulation types may be prepared. For example, where one active ingredient is a water insoluble solid and the other a water insoluble liquid, it may nevertheless be possible to disperse each active ingredient in the same continuous aqueous phase by dispersing the solid active ingredient as a suspension (using a preparation analogous to that of an SC) but dispersing the liquid active ingredient as an emulsion (using a preparation analogous to that of an EW). The resultant composition is a suspoemulsion (SE) formulation.


Stepl
Potassium 5-nitro-2,6-dioxo-l,2,3,6-tetrahydro-pyrimidine-4-carboxylate (40.0 g) was rcfluxcd in ethanol (400 ml) containing concentrated sulphuric acid (60 ml) for 8 hours. The mixture was cooled and filtered and the solid washed with ethanol to give 5-nitro-2,6-dioxo-l,2,3,6-tetrahydro-pyrimidine-4-carboxyIic acid ethyl ester as a white powder (49.54 g), m.p. 259°C
'H NMR (d6-DMSO) 5 ppm: 1.28 (UH), 4.35 (q,2H), 5.10 (bs,lH), 12.0 (s,l H) Step 2
Phosphorus oxychloride (156 ml) was added to a mixture of the product from Step 1 (15.4 g) and yV,/V-diethylani!ine (20 ml) and stirred for 30 minutes at room temperature. The reaction was then refluxed for 1.5 hour and the phosphorus oxychloride was evaporated, and the residue was put on ice and extracted with diethyl ether. The ether fraction was washed with 2 M hydrochloric acid, saturated sodium bicarbonate and water, and then the ether was evaporated. The residue was purified by column chromatography on silica gel (40-60) eluting with hexane:ethyl acetate (4:1) to give 2,4-dichloro-6-nitro-pyrimidine-5-carboxylic acid methyl ester as a light brown oil (15.5 g). 1H NMR (d6-DMSO) 5 ppm: 1.4 (t,3H), 4.5 (q,2H) Step 3
The product from step 2 (2.64 g) was hydrogenated at room temperature at a pressure of 3.75 bar hydrogen gas for 5 hours, in dioxane (180 ml) and in the presence of magnesium oxide (1.96 g) and 5% palladium on carbon (2.44 g). The reaction mixture was filtered through celite, washed with dioxane, ethyl acetate, and methanol. The solvents were combined and evaporated and the reaction mixture was purified by column chromatography on silica gel (40-60) eluting with ethyl acetate to give 5-amino-2-chloro-pyrimidine-4-carboxylic acid ethyl ester as a yellow solid (1.38 g).
1H NMR (CDC13) 5 ppm: 1.45 (t,3H), 4.5 (q,2H), 5.75 (bs,2H), 8.3 (s,lH).
Step 4
The product from Step 3 (0.64 g) in methanol (60 ml) and triethylamine (0.66 ml) was hydrogenated at a pressure of 3.50 bar hydrogen gas in the presence of 5% palladium on carbon (0.64 g) for 3 hours. The reaction mixture was filtered through celite and washed with

chromatography on silica gel (40-60) eluting with hexane:ethyl acetate (1:2) to give 5-amino-
pyrimidine-4-carboxylic acid ethyl ester as a yellow solid (0.150 g).
1H NMR (CDC13) 8 ppm: 1.48 (t,3H), 4.4S (q,2H), 5.71 (bs, 2 H), 8.41 (s,lH), 8.68 (s,lH)
Step 5
To the product from Step 4 (0.755 g) in dry DCM (50 ml) in an ice bath was added pyridine (0.73 ml), followed after 5 minutes by a slow addition of 2,4,6-trifluorophenylacetyl chloride (1.41 g) in dry DCM (10 ml). The reaction mixture was stirred for 3 hours and allowed to warm to room temperature. A further portion of 2,4,6-trifluorophenylacetyl chloride (0.3 g) was added and the reaction was stirred at room temperature for 1 hour. The DCM was evaporated, and the residue was purified by column chromatography on silica gel (40-60) eluting with hexane:ethyl acetate (1:1), to give 5-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyrimidine-4-carboxylic acid ethyl ester as a white-solid (1.1 g). 1HNMR (CDCI3) 5 ppm: 1.48 (t,3H), 3.88 (s,2H), 4.5 (q,2H), 6.78 (m,2H), 9.06 (s,lH), 10.2 (s,lH), 10.8(s,lH). Step 6
The product from Step 5 (0.55 g) was heated with potassium carbonate (0.056 g) in dry DMF (25 ml) at 125°C for 1 hour. The DMF was evaporated, and the residue treated with water and acidified with dilute aqueous hydrochloric acid, and then extracted with ethyl acetate. The ethyl acetate was dried over magnesium sulphate, filtered and evaporated. The residue was purified by column chromatography on silica gel (40-60) eluting with ethyl acetate:methanol (1:1), and then triturated with diethyl ether to give 6-hydroxy-7-(2,4,6-trifluorophenyl)-5//-pyrido[3,2-d]pyrimidin-8-one as a brown solid (0.083 g). lH NMR (d6-DMSO) 5 ppm: 7.12 (m,2H), 8.71 (s,lH), 8.87 (bs,lH), 10.82 (bs,lH). Step 7
The product of Step 6 (0.015 g) was heated with phenyl phosphonic dichloride (1.5 ml) at 165°C overnight, then cooled and poured onto ice, and extracted with ethyl acetate. The organic fraction was dried over magnesium sulphate, and evaporated. The residue was purified by column chromatography on silica gel (40-60) eluting with hexane:ethyl acetate (1:1), to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-d]pyrimidine (0.007 g).
!H NMR (CDCI3) 8 ppm: 6.9 (m,2H), 9.5S (s,lH), 9.68 (s,lH).

Step 8
The product from Step 7 (0.007 g) was stirred in isopropylamine (2 ml) at room temperature overnight in sealed tube. The reaction mixture was evaporated and the residue was purified by column chromatography on silica gel (40-60) eluting with hexane:ethyl acetate (2:1) to give the title compound [6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-d]pvTimidin-8-yI]-isopropylamine (0.004 g).
'H NMR (CDCI3) 8 opm: 1.12 (d,6H), 3.32 (m,lH), 6.S2 (t,2H), 6.92 (m,lH). 9.2 (s,lH), 9.38 (s,lH).
EXAMPLE 2 This Example illustrates the preparation of 5£c-butyI-[7-chloro-6-(2,4.6-trifluorophenyI)-pyrido[2,3-d]pyrimidin-5-yl]-amine (Compound No: 23 from Table 11) and 5^c-butyl-[5-chIoro-6-(2,4,6-trifluorophenyI)-pyrido[2,3-d]pyrimidin-7-yl]-amine (Compound No. 23 from Table 16)
Step 1
4-Amino-pyrimidine-5-carboxylic acid hydrochloride (10.4 g) was suspended in ethanol (300 ml) at room temperature. DMAP (14.6 g) was added in one portion and the reaction stirred to give a clear yellow solution. EDC (11.5 g) was then added, and the reaction was stirred at room temperature for 17 hours. The solvent was removed to leave a solid, which was dissolved in water and extracted with DCM (2x 200ml). The DCM fraction was dried over magnesium sulphate, and then evaporated to give 4-amino-pyrimidine-5-carboxylic acid methyl ester as a buff solid (16.2 g), as a 1:1 mixture with DMAP, which was used without further purification. 'H NMR (CDCh) S ppm: 1.35 (t,3H), 4.35 (q,2H), 6.7 (bs,lH\ 7.8 fbsJH). 8.5 (s.lH). 8.9

Step 2
The crude product from Step 1 (13.5 g) was dissolved in dry DCM (100ml) and then
pyridine (10ml) was added giving a dark brown solution. The stirred solution was cooled in
an ice bath, and the 2,4,6-trifluorophenyIacetyl chloride (9.0 g) in dry DCM (100ml) was
added dropwise. The mixture was stirred for 6 hours and stood overnight. A further portion
of acid chloride (3.0 g) was added and the reaction was stirred for another 10 hours. The
solvent was evaporated to give an orange sludge. Water was added and the solid was
dissolved in ethyl acetate and then washed with sodium bicarbonate solution and a small
amount of 1M hydrochloric acid (10 ml) solution. The water and the ethyl acetate fraction
was dried over magnesium sulphate. The solvent was evaporated to yield a solid, which was
triturated with ether to give 4-f2-(2,4,6-trifluorophenyl)-acetylamino]-pyrimidine-5-
carboxylic acid ethyl ester as a buff coloured solid (10.3 g).
JH NMR (CDC13) 5 ppm: 1.45 (t,3H), 4.2 (s,2H), 4.45 (q,2H) 6.75 (t,2H), 9.05 (bs,lH), 9.2
(s,lH), 11.0(s,lH).
Step 3
The product from Step 2 (0.90 g) was dissolved in DMF (10 ml) and was added
dropwise to a stirred suspension of sodium hydridc(0.32 g of a 60% dispersion in oil) in
DMF (20 ml). The reaction was stirred at room temperature for 2 hours and then heated to
80°C for 8 hours. The reaction mixture was cooled and the DMF was evaporated to give a
yellow solid, which was then acidified with dilute aqueous hydrochloric acid. The white
suspension was filtered and collected, washed with diethyl ether and dried to give 6-(2,4,6-
trifluorophenyl)-8H-pyrido[2,3-d]pyrimidine-5,7-dione (0.30 g).
]U NMR (CD3OD) 5 ppm: 7.0 (t,2H), 9.0 (s,lH), 9.25 (s,lH). Step 4
The product from Step 3 (0.12 g) was suspended in phosphorus oxychloride (5.0 ml)
and stirred at room temperature. Phosphorus pentachloride (0.10 g) was added and the
reaction was brought to reflux for 17 hours. The reaction was cooled and solvents were
evaporated to give a brown oil, which was poured onto ice and stirred for 10 minutes. The
crude mixture was extracted with ethyl acetate, and the organic fraction was washed with
saturated sodium bicarbonate and then dried over magnesium sulphate. The solvent was

Step 5
The product from Step 4 (0.1 g) was dissolved in DMF (2 ml). Sec-butylamine (0.05 ml) and DMAP (0.01 g) were added and the mixture was stirred in a sealed tube at 40°C for
14 hours. The yellow coloured reaction mixture was diluted with diethyl ether, washed with brine and dried over sodium sulphate. After evaporation of the solvent the resulting yellow-gum, which w as a mixture of two isomers, was purified by flash column chromatography on silica gel (40-60) in toluenerdiethyl ether 1:1 to give two isomers: 5ec-butyl-[7-chloro-6-(2,4,6-trifluorophenyl)-pyrido[23-d]pyrimidin-5-yl]-arnine, as a yellow solid (0.04g), m.p. 193 °C:
lH NMR (CDC13) 5 ppm: 0.79 (td,3H), 1.11 (d,3H), 1.49 (m,2H), 4.49 (m,lH), 4.61 (m,lH), 6.74 (t,2H), 9.15 (s,lH), 9.30 (s,lH);
5ec-butyl-[5-chloro-6-(2,4,64rifluorophenyl)-pyrido[2,3"d]pyTimidin-7-yl]-amine as a white solid (0.035g), m.p. 179°C:
!H NMR (CDC13) 5 ppm: 0.79 (t,3H), 1.15 (d,3H), 1.51 (m,2H), 3.68 (m,lH), 4.49 (m,lH), 6.68 (t,2H), 9.32 (s,lH), 9.48 (s,lH).

Step 1
5?7-Dichloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyrimidine (0.3 g) was dissolved in dry sulpholane (2 ml). Spray dried potassium fluoride (0.16 g) was added and the mixture was heated in a sealed tube at 100°C for 14 hours. The honey coloured reaction mixture was cooled to ambient "temperature, diluted with diethvl ether, and then washed with water to give a yellow oil, which was purified by flash column chromatography on silica gel (40-60) eluting with toluene:diethyl ether, 1:1, to give 5?7-difluoro-6-(2,4,6-trifluorophenyl)-

Step 2
The product from Step 1 (0.13g) was dissolved in DMF (4 ml). Seobutylamine (0.2
ml) and DMAP (0.01 g) were added and the mixture was stirred in a sealed tube at 40°C for
14 hours. The light yellow coloured reaction mixture was diluted with diethyl ether, washed
with brine and dried over sodium sulphate. After evaporation of the solvent the resulting
colourless gum was purified by flash column chromatography on silica gel (40-60) in
toluene:diethyl ether 1:1 togive5ec-butyl-[7-fluoro-6-(2,4,6-trifluorophenyl)-pyrido[2:,3-d]pyrimidin-5-yl]-amine as a white solid (O.OSg), m.p.l99°C:
1H NMR (CDC13) 5 ppm: 0.78 (m,3H), 1.21 (t,3H), 1.51 (m,2H), 4.02 (m,2H), 6.71 (t,2H),
9.09 (s,lH), 9.21 (s,lH).



Compounds were tested in a leaf disk assay, with methods described below. Test compounds were dissolved in DMSO, and diluted into water to 200 ppm. Erysiphe graminisf.sp, hordei (barley powdery mildew): barley leaf segments were placed on agar in a 24-well plate and sprayed with a solution of the test compound. After allowing to dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After appropriate incubation the activity of a compound was assessed four days after inoculation as preventive fungicidal activity.

dry completely, for between 12 and 24 hours, the leaf disks were inoculated with a spore
suspension of the fungus. After appropriate incubation the activity of a compound was
assessed four days after inoculation as preventive fungicidal activity.
Pyricidaria oiyzae (rice blast): rice leaf segments were placed on agar in a 24-well plate and
sprayed with a solution of the test compound. After allowing to dry completely, for between
12 and 24 hours, the leaf disks were inoculated with a spore suspension of the fungus. After
appropriate incubation the activity of a compound was assessed four days after inoculation as
preventive fungicidal activity.
The following compounds gave greater than 60% control of disease (number of compound
first, followed by table number in brackets):
Eiysiphe graminis fsp. hordei, Compound 3 (1);
Eiysiphe graminis f.sp. tritici, Compound 3 (1);
Pyricularia otyzae, Compound 3 (1).


CLAIMS
1. The compound of the general formula (1): .
wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y
are both CR8;
RL is H, halo, C1-4alkyl, C1-4 alkoxy or halo(C1-4)a!kyI;
R and R2 are independently H, halo, C1-8 alkyl, C1-8alkoxy, C1-8 alkylthio, C1-8
alkenyl, C2-8 alkynyl, cyano or NR R , provided that at least one of R and R" is
NR3R4;
R1 is halo, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C3-8cycloalkyl(C1-6)-
aikyl, C1-8 alkoxy, C1-8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy,
heteroarylthio, aryl(Ci.4)alkyl, aryl(C1-4)alkoxy, heteroaryl(C1-4)alkyl, heteroaryl(C1-
4)alkoxy, aryl(C1-4)alkylthio, heteroaryl(C1-4)alkylthio, morpholino, piperidino or
pyrrolidino;


any of the foregoing morpholine, thiomorphcline, piperidine, piperazine and pyrrolidine rings being optionally substituted with C1-4alkyl (especially methyl), and any of the foregoing aryl or heteroaryl groups or moieties being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1-6alkyl, C2-6

provided that Y is not CCH3 when W is CH, X and Z are N, R is NHCH3, R1 is 2,6-dichlorophenyl and R2 is H.
A compound according to claim 1 wherein W and Y are both N and X and Z are both CH or X and Z are both N and W and Y are both CH.
A compound according to claim 1 or 2 wherein R2 is NR3R4.
A compound according to claim 3 wherein R is halo.

alkynyl, C3-8 cycloalkyl optionally substituted with chloro, fluoro or methyl, C3-8 cycloalkyl(C1-4)aIkyL phenylamino, piperidino or morpholino, the phenyl ring of phenylalkyl or phenylamino being optionally substituted with one, two or three substituents selected from halo, C1-4alkyl, halo(C1-4)alkyl, C1-4alkoxy and halo-(C1-4)alkoxy; and

R is H, C1-4alkyl. halo(C1-4)alkyl or amino, or
R and R together form a C3-C7 alkylene or alkenylcne chain optionally substituted
with methyl, or,
together with the nitrogen atom to which they are attached, R" and R7 form a
morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide
ring or a piperazine or piperazine N-(C1-4)aIkyl (especially iV-methyl) ring, in which
the morpholine or piperazine rings are optionally substituted with methyl.
A compound according to any one of the preceding claims wherein R is phenyl optionally substituted with from one to five halogen atoms or with from • one to three substituents selected from halo, C1-4 alkyl, halo(C1-4)alkyL C1-4alkoxy or ha!o(C1-4)alkoxy, pyridyl optionally substituted with from one to four halogen atoms or with from one to three substituents selected from halo, C1-4alkyl, halo(C1-4)alkyl, C1-4 alkoxy ofhalo(C1-4)alkoxy, 2- or 3-thienyl optionally substituted with from one to three halogen atoms or with from one to three substituents selected from halo, C1-4alkyl, halo(C]-:)alkyl, C1-4alkoxy or halo(C1-4)alkoxy, or piperidino or morpholino both optionally substituted with one or two methyl groups.

A compound according to claim 1 wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y
are both CRS;
Rs is H, halo, C1-4alkyl, C1-4alkoxy or halo(Ci^)alkyl;
one of R and R2 (preferably R2) is NR3R4 and the other is halo;
R1 is halo,. C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8 cycloalkyl, C3-s cycloaIkyl(C1-6)-
alkyl, C\.% alkoxy, C1-8alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy,
heteroarylthio, aryKC1-4-alkyl. aryl(C1-4)alkoxy, heteroaryl(C1-4)alkyl, heteroaryl-


R3 and R4 are independently H, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl, ary](C1-8)-alkyl, C3-8 cycloalkyl, C3-8cycIoalkyl(C1-6)alkyl, heteroaryl, heteroaryl(C1-8)alkyl, NR5R6, provided that not both R3 and R4 are H or NR5R6, or
R and R4 together form a C3-7 alkylene or a C3-7 alkylene chain optionally substituted with one or more C1-4alkyl or C 1.4 alkoxy groups, or, together with the nitrogen atom to which they are attached, R3 and R4 form a morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazine or piperazine N-(C1-4)alkyl (especiallyNV-methyl) ring; and R3 and R6 are independently H, C1-8alkyl, C2-8 alkenyl, C2-8 alkynyl, aryl, aryl(C1-8)-alkyi, C3-8cycloalkyl, C3-8cycloalkyl(C1-6)alkyl, heteroaryl orheteroaryl(C1-8)alkyl; any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R ) being optionally substituted with halogen, cyano, C1-4alkoxy, C1-6 alkylcarbonyl, C1-6alkoxycarbonyl, C1-6 haloalkoxy, C1-6 alkylthio, tri(C1-4)alkylsilyl, C1-6 alkylamino or C1-4dialkylammo,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and pyrrolidine rings being optionally;substituted with C1-4alkyl (especially methyl), and any of the aryl, heteroaryl, aryloxy or heteroaryl groups being optionally substituted with one or more substituents selected from halo, hydroxy, mercapto, C1-4alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4alkoxy. C2-6 alkenyloxy, C2-6 alkynyloxy, halo(C2-6)alkyl, halo(C2-6)alkoxy,C1-4alkylthio, halo(C2-6)alkylthio, hydroxy(C1-6)alkyl, C1-4alkoxy-(C1-6)alkyl, C3.6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyI, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato, nitro, -NR",R"", -NHCOR'", -NHCONR"'R"", -CONR"R", -S02R"', -OS02R", -COR"', -CR"=NR"" or -N=CR"R"", in which R" and R"m are independently hydrogen, C1-4alkyl, haio-(C1-4)alkyl, C1-4alkoxy, halo(C1-6alkoxy, C1-4alkylthio, C3-6 cycloalkyl, C3-6 cycloalkyl(C1-4)alkyl, phenyl or benzyl, the phenyl and benzyl groups being optionally
substituted with halogen, C1-4alkyl or C1-4alkoxy.
»
A compound according to claim 1 wherein
W and Y are both N and X and Z are both CR8 or X and Z are both N and W and Y
arc bom CR ;
R8 is H, halo, C1-4alkyl, C1-4alkoxy or halo(C1-4)alkyl;

one of R and R2 (preferably R2) is NR3R4 and the other is halo;
Rl is halo, C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-8cycloalkyl, C3-8cycloalkyl(C2-6)-
alkyL, C1-8 alkoxy, C1-8 alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy,
heteroarylthio, aryl(C1-4)aIkyl, aryl(C1-4)alkoxy, heteroaryI(C1-4)alkyl, heteroaryl-
(C1-4)alkoxy, aryl(C1-4)alkylthio,heteroaryl(C1-4)alkylthio, morpholino. piperidino or
pyrrolidine;
R1 is C1-4 alkyl, halo(C1-4)alkyI, C2-4 alkenyl, C3-6 cycloalkyl C3-6 cycloalkyI(C1-4)-
alkyl or phenylamino in which the phenyl ring is optionally substituted with one, two
or three substituents selected from halo, C1-4 alkyl, halo(C1-4)alkyl, C1-4alkoxy and
halo(C1-4)alkoxy: and R is H, C1-4 alkyl or amino, or
R and R together form a C4-6 alkylene chain optionally substituted with C1-4alkyl or
C1-4 alkoxy, or,
together with the nitrogen atom to which they are attached, R3 and R4 form a
morpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholine S-dioxide
ring or a piperazine or piperazine N-(C1-4)alkyl (especially N-methyl) ring;
any of the alkyl, alkenyl, alkynyl or cycloalkyl groups or moieties (other than for R )
being optionally substituted with halogen, cyano, C1-6 alkoxy, C2-6 alkylcarbonyl, alkoxycarbonyl, C\.$ haloalkoxy, C1-4alkylthio, tri(C1-4)alkylsilyl, C1-4alkylamino or
C1-6 dialkylamino,
any of the foregoing morpholine, thiomorpholine, piperidine, piperazine and
pyrrolidine rings being optionally substituted with C1-4alkyl (especially methyl), and
any of the aryl or heteroaryl groups or moieties being optionally substituted with one
or more substituents selected from halo, hydroxy, mercapto, C1-4alkyl, C2-6 alkenyl,


A process for preparing a compound of the general formula (1) according to claim 1 wherein one of R and R2 is chloro or fluoro and the other is NR3R4 and W, X, Y, Z, R,R3andR4 are as defined in claim 1, which comprises reacting an amine of the general formula NR3R4 with a compound of the general formula (6) or (13):

wherein W, X, Y, Z and R1 are as defined in claim 1 and R7 is C1-4alkyl, other than those compounds of the general formula (5) wherein W and Y are both CH and X and Z are both N and R! is methyl, ethyl or phenyl, and other than those compounds of the general formula (5) wherein W is CH, Y is CH3-C and X and Z are both N and R1 is methyl, ethyl or phenyl, and other than the compound of the general formula (4) wherein W and Y are both CH3-C and X and Z are both N and R1 is methyl and R7 is ethyl
A plant fungicidal composition comprising a fungicidally effective amount of a compound as defined in claim 1 and a suitable carrier or diluent therefor.
A method of combating or controlling phytopathogenic fungi which comprises applying to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or to any other plant growth medium, a fungicidally effective amount of a compound according to claim 1 or a composition according to claim 12.

AMENDED CLAIMS
[Received by the International Bureau on 10 May 2004 (10.05.2004); original claim 14 replaced by amended claim 14, other claims unchanged
(1 page)]

those compounds of the general formula (5) wherein W and Y are both CH and X and Z are both N and R1 is methyl, ethyl; or phenyl, and other than those compounds of the general formula (5) wherein W is CH, Y is CHa-C and X and Z are both N and R1 is methyl, ethyl or phenyl, and other than the compound of the general formula (4V wherein W and Y are both CHa-C and X and Z are both N and R1 is methyl and R7 is ethyl
15. A plant fungicidal composition comprising a fungicidally effective amount of a
compound as defined in claim 1 and a suitable carrier or diluent therefor.
16. A method of combating or controlling phytopathogenic fungi which comprises
applying to a plant, to a seed of a plant, to the locus of the plant or seed or to soil or to
any other plant growth medium, a fungicidally effective amount of a compound

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Patent Number 222666
Indian Patent Application Number 1370/CHENP/2005
PG Journal Number 47/2008
Publication Date 21-Nov-2008
Grant Date 20-Aug-2008
Date of Filing 22-Jun-2005
Name of Patentee SYNGENTA LIMITED
Applicant Address REGIONAL CENTRE, PRIESTLEY ROAD, SURREY RESEARCH PARK GUILDFORD, SURREY GU2 7YH,
Inventors:
# Inventor's Name Inventor's Address
1 CROWLEY, PATRICK, JELF SYNGENTA LIMITED, JEALOTT'S HILL INTERNATIONAL RESEARCH CENTRE, BRACKNELL, BERKS RG42 6EY,
2 DOBLER, MARKUS NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH INC., 250 MASSACHUSETTS AVENUE, CAMBRIDGE, MA 02139,
3 MUELLER, URS SYNGENTA CROP PROTECTION AG, SCHWARZWALDALLEE 215, CH-4058 BASEL,
4 WILLIAMS, JOHN SYNGENTA LIMITED, JEALOTT'S HILL INTERNATIONAL RESEARCH CENTRE, BRACKNELL, BERKS RG42 6EY,
PCT International Classification Number C07D471/04
PCT International Application Number PCT/GB03/05273
PCT International Filing date 2003-12-04
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 0230019.2 2002-12-23 U.K.