Indian Patents. 268555:IMPROVED SYNTHESIS OF(2S-CIS)-2-(BROMOMETHYL)-2-(4-CHLOROPHENYL)-1,3 DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER).

Title of Invention	IMPROVED SYNTHESIS OF(2S-CIS)-2-(BROMOMETHYL)-2-(4-CHLOROPHENYL)-1,3 DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER).
Abstract	The present invention relates to an improved process for the preparation of (2S-cis)-2-(bromomethyl)-2- (4-chlorophenyl)-1,3-dioxolane-4-methanol methanesulfonate(ester). a key intermediate for the preparation of the apoB secretion/MTP inhibitor mitratapide.

Full Text	FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & THE PATENTS RULES, 2003 COMPLETE SPECIFICATION [See section 10 and rule 13] Title: IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL>2-(4-CHLOROPHENYL)-l,3 DIOXOLANE-4-METHANOL METHANESULFONATE (ESTER) Applicant: JANSSEN PHARMACEUTICA NV having its principal place of business at Turnhoutseweg 30,2340 Beerse, Belgium The following specification particularly describes the nature of the invention and the manner in which it is tobe performed:- IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL>-2-(4-CHLOROPHENYL)- 1 ,3-DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER) 5 The present invention relates to an improved process for the preparation of (2S-cis)-2- (bromomethy l)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methanesulftmate(ester), a key intermediate for the preparation of the apoB secretion/MTP inhibitor mitratapide. wherein the substituents on the 1,3-dioxolane ring have the (2S,4S) stereochemistry 30 according to the Cahn-lngold-Prelog nomenclature. Mitratapide is the INN (International Non Proprietary Name) for the compound (-)-[2S- 10 [2a,4a(S)]]-4-[4-[4-[4-[[2-(4-chlorophenyl)-2-[[(4-methyI-4//-l ,2,4-triazol-3- yl)thio]methyi]-l ,3-dioxolan-4-yl]methoxyl-phenyl]-1 -piperazinyl]phenyl]-2,4- dihydro-2-( 1 -methylpropyl)-3//-1,2,4-triazoI-3-one having the following structure. Mitratapide has been described in WO-96/13499 as compound (40) having apolipoprotein B secretion and microsomal triglyceride transfer protein inhibiting properties therefore useful as a lipid lowering agent in the treatment of obesity. 20 WO-00/37463 discloses S-oxide derivatives of mitratapide and a procedure to prepare (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- sulfonate(ester) as intermediate (18) in working example A.7 on page 20. (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- 25 sulfonate(ester) (hereinafter referred to as "compound A") has the following structure Since two of the three chiral carbon atoms of mitratapide are located on the 1,3-dioxolane ring an efficient synthesis of compound A is therefore highly desirable. The preparation of compound A has been described in WO-OO/37463 in Examples A.6 5 and A.7 as follows : Compound A was obtained with a yield of 23,7% according to the procedure of 10 Example A.7 in WO-OO/37463, i.e. reaction of (2S)-2,2-dimethyl-1,3-dioxoIane-4- methanol methane,sulfonate(ester) with 2-bromo-1 -(4-chloro-phenyl)-ethanone in dichloromethane as solvent. Unexpectedly, it has now been found that the yield of said reaction can be markedly 15 improved by performing the same reaction in the absence of a solvent while bubbling nitrogen through the reaction mixture or applying underpressure to remove the acetone formed during the said reaction. Chromatographic analysis by GC (HP5-column, length : 25.m, ID 320 ^m; film thickness 0.52 ^m; on column; initial temperature : 50°C; heating at 10°C/mm to 300°C) showed said (2S-cis)-2~(bromomethyl)-2-(4-chloropheny!)-1,3-dioxolane-4- methanol methane-sulfonate(ester) had a purity of more than 95% of the cis- 5 stereoisomer and less than 5% of the trans-stereoisomer. Claims 1. A process for preparing (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-l,3- dioxolane-4-methanol methanc-sulfonate(ester) by reacting (2S)-2,2-dimethyl~l,3- 5 dioxolane-4-methanol methanesulfonate(ester) with 2-bromo-l -(4-chloro-phenyl)- ethanone in the presence of a catalyst characterized in that the reaction is performed in the absence of a solvent while nitrogen is bubbled through the reaction mixture or an underpressure is applied. 10 2. A process according to claim 1 wherein the catalyst is selected from methanesulfonic acid, p-tohienesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoroacetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid solution. J5 3. A process according to claim 2 wherein the catalyst is methanesulfonic acid. 4. A process whereby the product obtained by the process according to any of claims 1 to 3 is purified by crystallisation from an organic solvent selected from ethanol, 20 2-propanol, methyl terf-butyl ether, or ethyl acetate, 5. A process whereby the product obtained by the process of claim 4 is purified by dissolving it in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the 25 precipitate. Dated this 24th day of December 2009 IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL)-2-(4-CHLOROPHENYL)- 1 ,3-DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER) 5 The present invention relates to an improved process for the preparation of (2S-cis)-2- (bromomethy l)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methanesulfon.ate(ester), a key intermediate for the preparation of the apoB secretion/MTP inhibitor mitratapide. wherein the substituents on the 1,3-dioxolane ring have the (2S,4S) stereochemistry 30 according to the Cahn-lngold-Prelog nomenclature. Mitratapide is the INN (International Non Proprietary Name) for the compound (-)-[2S- 10 [2a,4a(S)]]-4-[4-[4-[4-[[2-(4-chlorophenyl)-2-[[(4-methyI-4//-l ,2,4-triazol-3- yl)thio]methyl]-l ,3-dioxolan-4-yl]methoxyl-phenyl]-1 -piperazinyl]phenyl]-2,4- dihydro-2-( 1 -methylpropyl)-3//-1,2,4-triazoI-3-one having the following structure. 15 Mitratapide has been described in WO-96/13499 as compound (40) having apolipoprotein B secretion and microsomal triglyceride transfer protein inhibiting properties therefore useful as a lipid lowering agent in the treatment of obesity. 20 WO-00/37463 discloses S-oxide derivatives of mitratapide and a procedure to prepare (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- sulfonate(ester) as intermediate (18) in working example A.7 on page 20. (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- 15 sulfonate(ester) (hereinafter referred to as "compound A") has the following structure Since two of the three chiral carbon atoms of mitratapide are located on the 1,3-dioxolane ring an efficient synthesis of compound A is therefore highly desirable. The preparation of compound A has been described in WO-OO/37463 in Examples A.6 5 and A.7 as follows : Compound A was obtained with a yield of 23,7% according to the procedure of 10 Example A.7 in WO-OO/37463, i.e. reaction of (2S)-2,2-dimethyl-1,3-dioxoIane-4- methanol methanesulfonate(ester) with 2-bromo-l-(4-chloro-phenyl)-ethanone in dichloromethane as solvent. Unexpectedly, it has now been found that the yield of said reaction can be markedly 15 improved by performing the same reaction in the absence of a solvent while bubbling nitrogen through the reaction mixture or applying underpressure to remove the acetone formed during the said reaction. As demonstrated further in Example 1 of the Experimental Part, the improved procedure for preparing "compound A" has a yield of 64.8% which is an almost threefold increase over the prior art method yield of 23.7%. 5 Methanesulfonic acid is used in the reaction as a catalyst. Other suitable catalysts are p-toluenesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoro acetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid 10 solution. The reaction product obtained from this reaction can be purified by crystallisation from a suitable organic solvent such as ethanol, 2-propanol, methyl tert-butyl ether, or ethyl acetate. 15 Further purification can be done by dissolving the product obtained after crystallisation in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the precipitate. 20 Experimental part- Example 1 A mixture of (2S)-2,2-dimethyl-1,3-dioxolane-4-methanol methanesulfonate(ester) (1 mol), 2-bromo-l-(4-chloro-phenyl)-ethanone (0.8 mol) was stirred in a flask. Methanesulfonic acid (0.24 mol) was added and the reaction mixture was stirred while 25 nitrogen was bubbled through the reaction mixture (alternatively the reaction mixture may also be stirred under vacuum). After six hours, stirring of the reaction mixture was stopped and the reaction mixture was left overnight. Ethyl acetate (1500 ml) was added and the mixture was stirred until it became homogeneous. The reaction mixture was then washed successively with water (200 ml), an aqueous Na2C03 solution (150 ml), 30 and water. (150 ml). The organic layer was evaporated till dryness and the residue was crystallised from ethanol (1 liter), yielding a solid residue. This residue was dissolved in diisopropylether (DIPE) and stirred for one week. Then methanol was added and after stirring for two hours, the precipitate was filtered off and dried, yielding 250.1 g (64.8%) of (2S-cis)-2 Chromatographic analysis by GC (HP5-column, length : 25.m, ID 320 ^m; film thickness 0.52 µm; on column; initial temperature : 50°C; heating at 10°C/mm to 300°C) showed said (2S-cis)-2~(bromomethyl)-2-(4-chloropheny 1)-1,3-dioxolane-4- methanol methane-sulfonate(ester) had a purity of more than 95% of the cis- 5 stereoisomer and less than 5% of the trans-stereoisomer. Claims 1. A process for preparing (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-l,3- dioxolane-4-methanol methanc-sulfonate(ester) by reacting (2S)-2,2- dimethyi~l ,3- 5 dioxolane-4-methanol methanesulfonate(ester) with 2-bromo-l -(4-chloro-phenyl)- ethanone in the presence of a catalyst characterized in that the reaction is performed in the absence of a solvent while nitrogen is bubbled through the reaction mixture or an underpressure is applied. 10 2. A process according to claim 1 wherein the catalyst is selected from methanesulfonic acid, p-tohienesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoroacetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid solution. J5 3. A process according to claim 2 wherein the catalyst is methanesulfonic acid. 4. A process whereby the product obtained by the process according to any of claims 1 to 3 is purified by crystallisation from an organic solvent selected from ethanol, 20 2-propanol, methyl terf-butyl ether, or ethyl acetate, 5. A process whereby the product obtained by the process of claim 4 is purified by dissolving it in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the 25 precipitate.

Full Text

FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
[See section 10 and rule 13]
Title: IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL>2-(4-CHLOROPHENYL)-l,3 DIOXOLANE-4-METHANOL METHANESULFONATE (ESTER)
Applicant: JANSSEN PHARMACEUTICA NV having its principal place of business at Turnhoutseweg 30,2340 Beerse, Belgium

The following specification particularly describes the nature of the invention and the manner in which it is tobe performed:-

IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL>-2-(4-CHLOROPHENYL)- 1 ,3-DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER)
5 The present invention relates to an improved process for the preparation of (2S-cis)-2- (bromomethy l)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methanesulftmate(ester), a key intermediate for the preparation of the apoB secretion/MTP inhibitor mitratapide.
wherein the substituents on the 1,3-dioxolane ring have the (2S,4S) stereochemistry 30 according to the Cahn-lngold-Prelog nomenclature.
Mitratapide is the INN (International Non Proprietary Name) for the compound (-)-[2S- 10 [2a,4a(S*)]]-4-[4-[4-[4-[[2-(4-chlorophenyl)-2-[[(4-methyI-4//-l ,2,4-triazol-3- yl)thio]methyi]-l ,3-dioxolan-4-yl]methoxyl-phenyl]-1 -piperazinyl]phenyl]-2,4- dihydro-2-( 1 -methylpropyl)-3//-1,2,4-triazoI-3-one having the following structure.

Mitratapide has been described in WO-96/13499 as compound (40) having apolipoprotein B secretion and microsomal triglyceride transfer protein inhibiting properties therefore useful as a lipid lowering agent in the treatment of obesity.
20 WO-00/37463 discloses S-oxide derivatives of mitratapide and a procedure to prepare (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- sulfonate(ester) as intermediate (18) in working example A.7 on page 20.
(2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- 25 sulfonate(ester) (hereinafter referred to as "compound A") has the following structure

Since two of the three chiral carbon atoms of mitratapide are located on the 1,3-dioxolane ring an efficient synthesis of compound A is therefore highly desirable.
The preparation of compound A has been described in WO-OO/37463 in Examples A.6 5 and A.7 as follows :

Compound A was obtained with a yield of 23,7% according to the procedure of 10 Example A.7 in WO-OO/37463, i.e. reaction of (2S)-2,2-dimethyl-1,3-dioxoIane-4- methanol methane,sulfonate(ester) with 2-bromo-1 -(4-chloro-phenyl)-ethanone in dichloromethane as solvent.
Unexpectedly, it has now been found that the yield of said reaction can be markedly 15 improved by performing the same reaction in the absence of a solvent while bubbling nitrogen through the reaction mixture or applying underpressure to remove the acetone formed during the said reaction.

Chromatographic analysis by GC (HP5-column, length : 25.m, ID 320 ^m; film thickness 0.52 ^m; on column; initial temperature : 50°C; heating at 10°C/mm to 300°C) showed said (2S-cis)-2~(bromomethyl)-2-(4-chloropheny!)-1,3-dioxolane-4- methanol methane-sulfonate(ester) had a purity of more than 95% of the cis-
5 stereoisomer and less than 5% of the trans-stereoisomer.
Claims
1. A process for preparing (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-l,3-
dioxolane-4-methanol methanc-sulfonate(ester) by reacting (2S)-2,2-dimethyl~l,3- 5 dioxolane-4-methanol methanesulfonate(ester) with 2-bromo-l -(4-chloro-phenyl)-
ethanone in the presence of a catalyst characterized in that the reaction is performed in the absence of a solvent while nitrogen is bubbled through the reaction mixture or an underpressure is applied.
10 2. A process according to claim 1 wherein the catalyst is selected from
methanesulfonic acid, p-tohienesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoroacetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid solution.
J5
3. A process according to claim 2 wherein the catalyst is methanesulfonic acid.
4. A process whereby the product obtained by the process according to any of claims 1 to 3 is purified by crystallisation from an organic solvent selected from ethanol,
20 2-propanol, methyl terf-butyl ether, or ethyl acetate,
5. A process whereby the product obtained by the process of claim 4 is purified by dissolving it in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the
25 precipitate.
Dated this 24th day of December 2009

IMPROVED SYNTHESIS OF (2S-CIS)-2-(BROMOMETHYL)-2-(4-CHLOROPHENYL)- 1 ,3-DIOXOLANE-4-METHANOL METHANESULFONATE(ESTER)
5 The present invention relates to an improved process for the preparation of (2S-cis)-2- (bromomethy l)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methanesulfon.ate(ester), a key intermediate for the preparation of the apoB secretion/MTP inhibitor mitratapide.
wherein the substituents on the 1,3-dioxolane ring have the (2S,4S) stereochemistry 30 according to the Cahn-lngold-Prelog nomenclature.
Mitratapide is the INN (International Non Proprietary Name) for the compound (-)-[2S- 10 [2a,4a(S*)]]-4-[4-[4-[4-[[2-(4-chlorophenyl)-2-[[(4-methyI-4//-l ,2,4-triazol-3- yl)thio]methyl]-l ,3-dioxolan-4-yl]methoxyl-phenyl]-1 -piperazinyl]phenyl]-2,4- dihydro-2-( 1 -methylpropyl)-3//-1,2,4-triazoI-3-one having the following structure.

15
Mitratapide has been described in WO-96/13499 as compound (40) having apolipoprotein B secretion and microsomal triglyceride transfer protein inhibiting properties therefore useful as a lipid lowering agent in the treatment of obesity.
20 WO-00/37463 discloses S-oxide derivatives of mitratapide and a procedure to prepare (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- sulfonate(ester) as intermediate (18) in working example A.7 on page 20.
(2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-1,3-dioxolane-4-methanol methane- 15 sulfonate(ester) (hereinafter referred to as "compound A") has the following structure

Since two of the three chiral carbon atoms of mitratapide are located on the 1,3-dioxolane ring an efficient synthesis of compound A is therefore highly desirable.
The preparation of compound A has been described in WO-OO/37463 in Examples A.6 5 and A.7 as follows :

Compound A was obtained with a yield of 23,7% according to the procedure of 10 Example A.7 in WO-OO/37463, i.e. reaction of (2S)-2,2-dimethyl-1,3-dioxoIane-4- methanol methanesulfonate(ester) with 2-bromo-l-(4-chloro-phenyl)-ethanone in dichloromethane as solvent.
Unexpectedly, it has now been found that the yield of said reaction can be markedly 15 improved by performing the same reaction in the absence of a solvent while bubbling nitrogen through the reaction mixture or applying underpressure to remove the acetone formed during the said reaction.

As demonstrated further in Example 1 of the Experimental Part, the improved procedure for preparing "compound A" has a yield of 64.8% which is an almost threefold increase over the prior art method yield of 23.7%.
5
Methanesulfonic acid is used in the reaction as a catalyst. Other suitable catalysts are p-toluenesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoro acetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid 10 solution.
The reaction product obtained from this reaction can be purified by crystallisation from a suitable organic solvent such as ethanol, 2-propanol, methyl tert-butyl ether, or ethyl acetate.
15
Further purification can be done by dissolving the product obtained after crystallisation in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the precipitate.

20 Experimental part- Example 1
A mixture of (2S)-2,2-dimethyl-1,3-dioxolane-4-methanol methanesulfonate(ester) (1 mol), 2-bromo-l-(4-chloro-phenyl)-ethanone (0.8 mol) was stirred in a flask. Methanesulfonic acid (0.24 mol) was added and the reaction mixture was stirred while 25 nitrogen was bubbled through the reaction mixture (alternatively the reaction mixture may also be stirred under vacuum). After six hours, stirring of the reaction mixture was stopped and the reaction mixture was left overnight. Ethyl acetate (1500 ml) was added and the mixture was stirred until it became homogeneous. The reaction mixture was then washed successively with water (200 ml), an aqueous Na2C03 solution (150 ml), 30 and water. (150 ml). The organic layer was evaporated till dryness and the residue was crystallised from ethanol (1 liter), yielding a solid residue. This residue was dissolved in diisopropylether (DIPE) and stirred for one week. Then methanol was added and after stirring for two hours, the precipitate was filtered off and dried, yielding 250.1 g (64.8%) of (2S-cis)-2

Chromatographic analysis by GC (HP5-column, length : 25.m, ID 320 ^m; film thickness 0.52 µm; on column; initial temperature : 50°C; heating at 10°C/mm to 300°C) showed said (2S-cis)-2~(bromomethyl)-2-(4-chloropheny 1)-1,3-dioxolane-4- methanol methane-sulfonate(ester) had a purity of more than 95% of the cis- 5 stereoisomer and less than 5% of the trans-stereoisomer.
Claims
1. A process for preparing (2S-cis)-2-(bromomethyl)-2-(4-chlorophenyl)-l,3-
dioxolane-4-methanol methanc-sulfonate(ester) by reacting (2S)-2,2- dimethyi~l ,3- 5 dioxolane-4-methanol methanesulfonate(ester) with 2-bromo-l -(4-chloro-phenyl)-
ethanone in the presence of a catalyst characterized in that the reaction is performed in the absence of a solvent while nitrogen is bubbled through the reaction mixture or an underpressure is applied.
10 2. A process according to claim 1 wherein the catalyst is selected from
methanesulfonic acid, p-tohienesulfonic acid monohydrate, hydrogen chloride, sulfuric acid, phosphoric acid, nitric acid, formic acid, trifluoroacetic acid, camphorsulfonic acid, hydrogen chloride in 2-propanol solution, and hydrogen bromide in acetic acid solution or propionic acid solution.
J5
3. A process according to claim 2 wherein the catalyst is methanesulfonic acid.
4. A process whereby the product obtained by the process according to any of claims 1 to 3 is purified by crystallisation from an organic solvent selected from ethanol,
20 2-propanol, methyl terf-butyl ether, or ethyl acetate,
5. A process whereby the product obtained by the process of claim 4 is purified by dissolving it in diisopropylether until a homogeneous solution is obtained, stirring said solution for 7 days and adding methanol to said solution and filtering off the
25 precipitate.

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Patent Number

268555

Indian Patent Application Number

2394/MUMNP/2009

PG Journal Number

36/2015

Publication Date

04-Sep-2015

Grant Date

03-Sep-2015

Date of Filing

24-Dec-2009

Name of Patentee

JANSSEN PHARMACEUTICA NV

Applicant Address

TURNHOUTSEWEG 30, 2340 BEERSE BELGIUM.

Inventors:

#	Inventor's Name	Inventor's Address
1	FILLIERS, WALTER FERDINAND MARIA.	C/O:JANSSEN PHARMACEUTICA NV, TUMHOUTSEWEG 30, 2340 BEERSE, BELGIUM.
2	VERSTAPPEN, WALTER LOUIS ANTOINE.	C/O:JANSSEN PHARMACEUTICA NV, TUMHOUTSEWEG 30, 2340 BEERSE, BELGIUM.
3	BELLINKX, RONNY.	C/O:JANSSEN PHARMACEUTICA NV, TUMHOUTSEWEG 30, 2340 BEERSE, BELGIUM.

PCT International Classification Number

C07D405/14

PCT International Application Number

PCT/EP2008/056355

PCT International Filing date

2008-05-23

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1	07108944.5	2007-05-25	EPO