Indian Patents. 256374:IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE

Title of Invention	IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE
Abstract	The Present invention relates to an improved process for preparing (±)-N-2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxy phenoxy)propyl]-1-piperazineacetamide and its pharmaceutically acceptable salts, which is known as Ranolazine of Formula (I) and its useful intermediates thereof.

Full Text	FORM 2 THE PATENTS ACT, 1970 (39 of 1970) & The Patent Rules, 2003 PROVISIONAL SPECIFICATION (See section 10 and rule 13) TITLE OF THE INVENTION "IMPROVED PROCESS FOR THE PREPARATION OF RANOLAZINE" We, CADILA HEALTHCARE LIMITED, a company incorporated under the Companies Act, 1956, of Zydus Tower, Satellite Cross Roads, Ahmedabad-380015, Gujarat, India. The following specification describes the invention: 1 FIELD OF THE INVENTION: The present invention relates to an improved process for preparing (±)-N-(2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-l-piperazineacetamide and its pharmaceutically acceptable salts , which is known as Ranolazine of formula (I) or its pharmaceutically acceptable salt as shown below Formula I BACKGROUND OF THE INVENTION: Ranolazine dihydrochloride is a novel anti-anginal agent which has been reported to protect against biochemical electrophysiological and mermodynamic consequences of transient myocardial ischmia in the pentobarbitone-anesthetized dog, without inducing overt hemodynamic effects. US Patent 4567264 describes the preparation of Ranolazine base and pharmaceutically acceptable salts thereof by two reaction schemes as shown below : Scheme-1 o OMe OMe OH r^^NH I ' > CI-^Y-HN O Me Scheme-2 o o- OH According to the described process, Ranolazine base was purified by column chromatography and isolated as oil. Thus reported process discloses the purification of Ranolazine by column chromatography. It is always preferable to use the process, which is feasible at commercial production and avoids such cumbersome and time-consuming purification process. EP 0483932 describes the preparation of Ranolazine by condensation of a-[ N,N -bis (2-choroetiiyl)-amino]-2,6-dimetliylacetanilide hydrochloride with l-[3-(2-methoxy phenoxy)-2-hydroxy]-propylamine, which was converted to its hydrochloride salt by treating with methanolic hydrochloric acid and crystallized by addition of diethyl ether as co-solvent to obtain a product with melting point 229- 230°C. Scheme-3 NT > 0 ,OMe There is a long-standing need to avoid laborious and expensive column chromatographic methods and achieving the higher yields of Ranolazine. The processes for preparing Ranolazine involves higher mole equivalents of piperazine for the formation of Ranolazine. Moreover, the prior art process for preparing Ranolazine is also result in dimeric impurity. 3 WO2006008753A1 discloses the process for the preparation of crystalline Ranolazine base and its dihydrochloride salt by reaction of l-(2-methoxyphenoxy)-2,3-epoxypropane with excess piperazine preferably in 4 to 20 molar proportion in the presence of water or alcoholic solvent to obtain l-[3-(2 methoxyphenoxy)-2-hydroxypropyl] piperazine, which is purified by weak acid addition salt such as acetates, fumarate, succinaate, lactate for maleate and subsequent conversion to base. The purified l-[3-(2-methoxyphenoxy)-2-hydroxypropyljpiperazine is reacted with [(2,6-dimethylphenyl) aminocarbonyl methyl)chloride in dimethlylformamide as a solvent in presence of anhydrous alkali carbonate as base and alkali halide as a catalyst. Ranolazine base is isolated by formation of hydrochloride salt and neutralization with base. To overcome the drawbacks of the prior art process the present invention relates to provide a simple, cost effective, non-hazardous and easily scaleable at large commercial production process for preparation of Ranolazine. OBJECTS OF INVENTION: It is an object of the present invention is to provide an improved process for preparation of Ranolazine. Another, object of the present invention is to provide Ranolazine with higher yield and purity. Yet another object of the present invention is to overcome the problems associated with the prior art process Further object of the present invention is prepare pure Ranolazine by simple, cost effective, non-hazardous, easily scaleable and industrially viable process. DETAILED DESCRIPTION OF INVENTION: Formula I 4 The present invention relates to an improved process for preparing (±)-N-(2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-l-piperazineacetamide i.e. Ranolazine compound of formula I or its pharmaceutically acceptable salt, which comprises condensation of l-methoxy-2-(oxiranylmethoxy)benzene of formula (A) and N-(2,6-dimethyl phenyl)-1-piperazineacetamide of formula (B) in organic solvent selected from alcohols. In the preferred embodiment, condensation reaction is carried out in organic solvent selected from alcohols selected from methanol, ethanol, isopropaol, n-propanol, n-butanol, tert-butanol or mixtures thereof. In the one of the embodiment of the present invention, reaction of l-methoxy-2-(oxiranylmethoxy)benzene of formula (A) and N-(2,6-dimethyl phenyl)-1-piperazineacetamide of formula (B) can be also carried out in presence of alcohol and polar solvent selected from DMF, DMSO, THF and the like. O O NH OH The inventors of the present invention has surprisingly found that when alcohol is used as solvent for condensation reaction for preparing Ranolazine, the process does not required column chromatography. The advantageous process for preparing Ranolazine does not involve laborious and expensive column chromatographic methods. Rather, the process involves the crystallization technique using an organic solvent to isolate highly pure Ranolazine. The preferred organic solvent for the crystallization technique is selected from the group of alcoholic solvents like methanol, ethanol, isopropanol etc. The preferred organic solvent for the crystallization technique is isopropanol. According to the embodiment of the present invention, the present invention provides a process for the preparation of compound of formula A and compound of formula B. O B The process for preparing compound of formula A involves reaction of reaction of 2-methoxyphenol of formula (II) with epichlorohydrin (III) in a single organic solvent seleced from polar aprotic solvent in the presence of a base. 5 o (III) (III) The preferred single organic solvent is toluene and the preferred base is sodium hydroxide for the formation of compound of formula A. According to one of the embodiment of the present invention, the present invention provides a process for preparing compound of formula B, which involves the reaction of 2,6-dimethylbenzeamine with chloroacetyl chloride with a single organic solvent in the presence of a base to provide 2-chloro-N-(2,6-dimethylphenyl)acetamide, which is reacted with anhydrous piperazine an organic solvent selected from the group of alcoholic solvents like methanol, ethanol, isopropanol n-propanol or mixtures thereof in the presence of base selected from sodium hydroxide or potassium hydroxide to provide compound of formula (B). The process for preparing compound of formula (B) can be shown by following scheme: NH* ci-coc. (^YNHY^ci HNQ" n The preferred single organic solvent is acetone and the preferred base is sodium bicarbonate for the formation of intermediate compound for the preparation of compound formula B. According to the present invention by using preferred solvent system for reaction of 2-chloro-N-(2,6-dimethylphenyl)acetamide with piperazine provides advantage as it requires only two mole equivalents of piprazine unlike the prior art methods discloses use of four mole equivalents of pieprazine. Yet another, embodiment of the present invention is the isolation of dimeric impurity formed during the condensation of compound of formula A and formula B. The dimeric impurity of following formula has been characterized, which can be used as reference marker for the analysis of Ranolazine. 6 Further, the invention provides Ranolazine having purity greater than 99% and dimeric impurity less than 0.15%. Having thus described the invention with reference to particular preferred embodiments and illustrative examples, those in the art would appreciate modifications to the invention as described and illustrated that do not depart from the spirit and scope of the invention as disclosed in the specification. The examples are set forth to aid in understanding the invention but are not intended to, and should not be construed to, limit its scope in any way. The examples do not include detailed descriptions of conventional methods. Such methods are well known to those of ordinary skill in the art and are described in numerous publications. Working Examples: Example 1 Preparation of 2-chloro-N-(2,6-dimethylphenyl)acetamide 2,6-xylidine (100 g, 0.826 mole) was added to a four-neck 2 litre round bottom flask. Acetone (1000 mL) and sodium bicarbonate (111.08 g, 1.322 mole) were added to the RB flask at 25 to 35°C. The reaction mass was cooled to 0 to 5°C and chloro acetylchloride (107.40 g, 0.950 mole) was added within 1 Hr. The reaction mass was stirred for 1 hour. After completion of the reaction, acetone was distilled under vacuum at 50 C. The reaction was cooled to 10°C and water was added to the solid residue and stirred for 25 to 35 C for 1 hour. The reaction mass was filtered and washed with water and dried at 60 to 65 C for 8 Hrs to afford the title compound as 2-chloro-N-(2,6-dimethylphenyl)acetamide. Example 1 Preparation of N-(2,6-dimethylphenyl)-piperazineacetamide 2-chloro-N-(2,6-dimethylphenyl)acetamide (100 g, 0.506 mole) was added to a four-neck 2 litre round bottom flask. Methanol (1000 mL) and piperazine (87.20, 1.012 mole) were added at 25 to 35°C and retluxed till completion of reaction. The reaction mass was filtered and. The read ion mass was treated with cone. HC1 and stirred for 30 min at 25 to 35°C. Aqueous layer was treated with MDC and sodium hydroxide and reaction mass was stirred for 30 min at 25 to 35°C. The solvent were distilled off to obtain N-(2,6-dimethylphenyl)-piperazineacetamide. 7 Example 3 Preparation of l-methoxy-2-(oxiranylmethoxy)benzene 2-methoxy phenol (100 g, 0.806 mole) was added to a four-neck 2 litre round bottom flask. To this, aqueous sodium hydroxide (41.93 g, 1.0483 mole) was added at 25 to 35°C. Toluene (400 mL) and epichlorohydrine (111.15 g, 1.206 mole) were added and heated up to 50 to 55°C till the completion of the reaction. The reaction mass was cooled to 25 to 35°C and layers were settled and separated. Organic layer was distilled off to to afford the title compound as 1 -methoxy-2-(oxiranylmethoxy)benzene. Example 4 Preparation of N-(2,6-dimethylphenyl)4-[2-hydroxy-3-(2-methoxy phenoxy)propyI-l-piperazineacetamide l-methoxy-2-(oxiranylmethoxy)benzene (100 g, 0.555 mole) and N-(2,6- dimethylphenyl)-piperazineacetamide (137.41 g, 0.555 mole) were added with methanol (1000 mL) to a four-neck 2 litre round bottom flask. The reaction mass was refluxed for 5-7 Hrs. Upon completion of the reaction, reaction mass was cooled to 25 to 35°C. about 50% of Methanol was distilled out and reaction mass filtered and washed with methanol (2 x 50 mL). The residue was dried at 50 to 55°C to afford the title compound as N-(2,6-dimethyl phenyl)4-[2-hydroxy-3-(2-methoxy phenoxy)propyl-l-piperazineacetamide [Ranolazine]. 8

Full Text

FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
The Patent Rules, 2003
PROVISIONAL SPECIFICATION
(See section 10 and rule 13)
TITLE OF THE INVENTION
"IMPROVED PROCESS FOR THE PREPARATION OF
RANOLAZINE"
We, CADILA HEALTHCARE LIMITED, a company incorporated under the Companies Act, 1956, of Zydus Tower, Satellite Cross Roads, Ahmedabad-380015, Gujarat, India.
The following specification describes the invention:
1

FIELD OF THE INVENTION:
The present invention relates to an improved process for preparing (±)-N-(2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-l-piperazineacetamide and its pharmaceutically acceptable salts , which is known as Ranolazine of formula (I) or its pharmaceutically acceptable salt as shown below

Formula I
BACKGROUND OF THE INVENTION:
Ranolazine dihydrochloride is a novel anti-anginal agent which has been reported to protect against biochemical electrophysiological and mermodynamic consequences of transient myocardial ischmia in the pentobarbitone-anesthetized dog, without inducing overt hemodynamic effects.
US Patent 4567264 describes the preparation of Ranolazine base and pharmaceutically acceptable salts thereof by two reaction schemes as shown below :
Scheme-1

o
OMe

OMe

OH r^^NH
I ' >

CI-^Y-HN
O
Me

Scheme-2

o o-

OH

According to the described process, Ranolazine base was purified by column chromatography and isolated as oil. Thus reported process discloses the purification of Ranolazine by column chromatography. It is always preferable to use the process, which is feasible at commercial production and avoids such cumbersome and time-consuming purification process.
EP 0483932 describes the preparation of Ranolazine by condensation of a-[ N,N -bis (2-choroetiiyl)-amino]-2,6-dimetliylacetanilide hydrochloride with l-[3-(2-methoxy phenoxy)-2-hydroxy]-propylamine, which was converted to its hydrochloride salt by treating with methanolic hydrochloric acid and crystallized by addition of diethyl ether as co-solvent to obtain a product with melting point 229- 230°C.
Scheme-3

NT > 0
,OMe

There is a long-standing need to avoid laborious and expensive column chromatographic methods and achieving the higher yields of Ranolazine. The processes for preparing Ranolazine involves higher mole equivalents of piperazine for the formation of Ranolazine. Moreover, the prior art process for preparing Ranolazine is also result in dimeric impurity.
3

WO2006008753A1 discloses the process for the preparation of crystalline Ranolazine base and its dihydrochloride salt by reaction of l-(2-methoxyphenoxy)-2,3-epoxypropane with excess piperazine preferably in 4 to 20 molar proportion in the presence of water or alcoholic solvent to obtain l-[3-(2 methoxyphenoxy)-2-hydroxypropyl] piperazine, which is purified by weak acid addition salt such as acetates, fumarate, succinaate, lactate for maleate and subsequent conversion to base. The purified l-[3-(2-methoxyphenoxy)-2-hydroxypropyljpiperazine is reacted with [(2,6-dimethylphenyl) aminocarbonyl methyl)chloride in dimethlylformamide as a solvent in presence of anhydrous alkali carbonate as base and alkali halide as a catalyst. Ranolazine base is isolated by formation of hydrochloride salt and neutralization with base.
To overcome the drawbacks of the prior art process the present invention relates to provide a simple, cost effective, non-hazardous and easily scaleable at large commercial production process for preparation of Ranolazine.
OBJECTS OF INVENTION:
It is an object of the present invention is to provide an improved process for preparation of Ranolazine.
Another, object of the present invention is to provide Ranolazine with higher yield and purity.
Yet another object of the present invention is to overcome the problems associated with the prior art process
Further object of the present invention is prepare pure Ranolazine by simple, cost effective, non-hazardous, easily scaleable and industrially viable process.
DETAILED DESCRIPTION OF INVENTION:

Formula I
4
The present invention relates to an improved process for preparing (±)-N-(2,6-dimethyl phenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-l-piperazineacetamide i.e. Ranolazine compound of formula I or its pharmaceutically acceptable salt, which comprises condensation of l-methoxy-2-(oxiranylmethoxy)benzene of formula (A) and N-(2,6-dimethyl phenyl)-1-piperazineacetamide of formula (B) in organic solvent selected from alcohols.

In the preferred embodiment, condensation reaction is carried out in organic solvent selected from alcohols selected from methanol, ethanol, isopropaol, n-propanol, n-butanol, tert-butanol or mixtures thereof.
In the one of the embodiment of the present invention, reaction of l-methoxy-2-(oxiranylmethoxy)benzene of formula (A) and N-(2,6-dimethyl phenyl)-1-piperazineacetamide of formula (B) can be also carried out in presence of alcohol and polar solvent selected from DMF, DMSO, THF and the like.

O
O

NH

OH

The inventors of the present invention has surprisingly found that when alcohol is used as solvent for condensation reaction for preparing Ranolazine, the process does not required column chromatography.
The advantageous process for preparing Ranolazine does not involve laborious and expensive column chromatographic methods. Rather, the process involves the crystallization technique using an organic solvent to isolate highly pure Ranolazine.
The preferred organic solvent for the crystallization technique is selected from the group of alcoholic solvents like methanol, ethanol, isopropanol etc. The preferred organic solvent for the crystallization technique is isopropanol.
According to the embodiment of the present invention, the present invention provides a process for the preparation of compound of formula A and compound of formula B.
O B
The process for preparing compound of formula A involves reaction of reaction of 2-methoxyphenol of formula (II) with epichlorohydrin (III) in a single organic solvent seleced from polar aprotic solvent in the presence of a base.
5

o
(III) (III)

The preferred single organic solvent is toluene and the preferred base is sodium hydroxide for the formation of compound of formula A.
According to one of the embodiment of the present invention, the present invention provides a process for preparing compound of formula B, which involves the reaction of 2,6-dimethylbenzeamine with chloroacetyl chloride with a single organic solvent in the presence of a base to provide 2-chloro-N-(2,6-dimethylphenyl)acetamide, which is reacted with anhydrous piperazine an organic solvent selected from the group of alcoholic solvents like methanol, ethanol, isopropanol n-propanol or mixtures thereof in the presence of base selected from sodium hydroxide or potassium hydroxide to provide compound of formula (B).
The process for preparing compound of formula (B) can be shown by following scheme:

NH* ci-coc. (^YNHY^ci HNQ" n

The preferred single organic solvent is acetone and the preferred base is sodium bicarbonate for the formation of intermediate compound for the preparation of compound formula B.
According to the present invention by using preferred solvent system for reaction of 2-chloro-N-(2,6-dimethylphenyl)acetamide with piperazine provides advantage as it requires only two mole equivalents of piprazine unlike the prior art methods discloses use of four mole equivalents of pieprazine.
Yet another, embodiment of the present invention is the isolation of dimeric impurity formed during the condensation of compound of formula A and formula B. The dimeric impurity of following formula has been characterized, which can be used as reference marker for the analysis of Ranolazine.
6

Further, the invention provides Ranolazine having purity greater than 99% and dimeric impurity less than 0.15%.
Having thus described the invention with reference to particular preferred embodiments and illustrative examples, those in the art would appreciate modifications to the invention as described and illustrated that do not depart from the spirit and scope of the invention as disclosed in the specification. The examples are set forth to aid in understanding the invention but are not intended to, and should not be construed to, limit its scope in any way. The examples do not include detailed descriptions of conventional methods. Such methods are well known to those of ordinary skill in the art and are described in numerous publications. Working Examples: Example 1 Preparation of 2-chloro-N-(2,6-dimethylphenyl)acetamide
2,6-xylidine (100 g, 0.826 mole) was added to a four-neck 2 litre round bottom flask. Acetone (1000 mL) and sodium bicarbonate (111.08 g, 1.322 mole) were added to the RB flask at 25 to 35°C. The reaction mass was cooled to 0 to 5°C and chloro acetylchloride (107.40 g, 0.950 mole) was added within 1 Hr. The reaction mass was stirred for 1 hour. After completion of the reaction, acetone was distilled under vacuum at 50 C. The reaction was cooled to 10°C and water was added to the solid residue and stirred for 25 to 35 C for 1 hour. The reaction mass was filtered and washed with water and dried at 60 to 65 C for 8 Hrs to afford the title compound as 2-chloro-N-(2,6-dimethylphenyl)acetamide.
Example 1
Preparation of N-(2,6-dimethylphenyl)-piperazineacetamide
2-chloro-N-(2,6-dimethylphenyl)acetamide (100 g, 0.506 mole) was added to a four-neck 2 litre round bottom flask. Methanol (1000 mL) and piperazine (87.20, 1.012 mole) were added at 25 to 35°C and retluxed till completion of reaction. The reaction mass was filtered and. The read ion mass was treated with cone. HC1 and stirred for 30 min at 25 to 35°C. Aqueous layer was treated with MDC and sodium hydroxide and reaction mass was stirred for 30 min at 25 to 35°C. The solvent were distilled off to obtain N-(2,6-dimethylphenyl)-piperazineacetamide.
7
Example 3
Preparation of l-methoxy-2-(oxiranylmethoxy)benzene
2-methoxy phenol (100 g, 0.806 mole) was added to a four-neck 2 litre round bottom flask. To this, aqueous sodium hydroxide (41.93 g, 1.0483 mole) was added at 25 to 35°C. Toluene (400 mL) and epichlorohydrine (111.15 g, 1.206 mole) were added and heated up to 50 to 55°C till the completion of the reaction. The reaction mass was cooled to 25 to 35°C and layers were settled and separated. Organic layer was distilled off to to afford the title compound as 1 -methoxy-2-(oxiranylmethoxy)benzene. Example 4
Preparation of N-(2,6-dimethylphenyl)4-[2-hydroxy-3-(2-methoxy phenoxy)propyI-l-piperazineacetamide
l-methoxy-2-(oxiranylmethoxy)benzene (100 g, 0.555 mole) and N-(2,6-
dimethylphenyl)-piperazineacetamide (137.41 g, 0.555 mole) were added with methanol
(1000 mL) to a four-neck 2 litre round bottom flask. The reaction mass was refluxed for 5-7
Hrs. Upon completion of the reaction, reaction mass was cooled to 25 to 35°C. about 50% of
Methanol was distilled out and reaction mass filtered and washed with methanol (2 x 50 mL).
The residue was dried at 50 to 55°C to afford the title compound as N-(2,6-dimethyl
phenyl)4-[2-hydroxy-3-(2-methoxy phenoxy)propyl-l-piperazineacetamide [Ranolazine].

8

Documents:

1494-MUM-2007--CLAIMS(AMENDED)-(10-2-2012).pdf

1494-MUM-2007--CLAIMS(MARKED COPY)-(10-2-2012).pdf

1494-MUM-2007-ABSTRACT 4-8-2008.pdf

1494-MUM-2007-CLAIMS 4-8-2008.pdf

1494-MUM-2007-CLAIMS(AMENDED)-(10-2-2012).pdf

1494-MUM-2007-CLAIMS(AMENDED)-(11-6-2012).pdf

1494-MUM-2007-CLAIMS(AMENDED)-(17-1-2013).pdf

1494-MUM-2007-CLAIMS(MARKED COPY)-(10-2-2012).pdf

1494-MUM-2007-CORRESPONDENCE 4-8-2008.pdf

1494-MUM-2007-CORRESPONDENCE(10-2-2012).pdf

1494-MUM-2007-CORRESPONDENCE(11-6-2012).pdf

1494-MUM-2007-CORRESPONDENCE(17-1-2013).pdf

1494-MUM-2007-CORRESPONDENCE(2-1-2013).pdf

1494-MUM-2007-CORRESPONDENCE(21-2-2012).pdf

1494-MUM-2007-CORRESPONDENCE(24-5-2012).pdf

1494-MUM-2007-CORRESPONDENCE(26-4-2010).pdf

1494-MUM-2007-CORRESPONDENCE(27-10-2008).pdf

1494-mum-2007-correspondence(4-8-2008).pdf

1494-MUM-2007-CORRESPONDENCE(8-3-2011).pdf

1494-MUM-2007-CORRESPONDENCE(8-5-2013).pdf

1494-mum-2007-correspondence-received.pdf

1494-mum-2007-description (provisional).pdf

1494-MUM-2007-DESCRIPTION(COMPLETE) 4-8-2008.pdf

1494-mum-2007-form 1(5-9-2007).pdf

1494-MUM-2007-FORM 13(10-2-2012).pdf

1494-MUM-2007-FORM 18(27-10-2008).pdf

1494-mum-2007-form 2 4-8-2008.pdf

1494-MUM-2007-FORM 2(TITLE PAGE) 4-8-2008.pdf

1494-MUM-2007-FORM 5 4-8-2008.pdf

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1494-mum-2007-form-2(digram).doc

1494-mum-2007-form-2.doc

1494-mum-2007-form-2.pdf

1494-mum-2007-form-26.pdf

1494-mum-2007-form-3.pdf

1494-MUM-2007-REPLY TO EXAMINATION REPORT(10-2-2012).pdf

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Patent Number

256374

Indian Patent Application Number

1494/MUM/2007

PG Journal Number

24/2013

Publication Date

14-Jun-2013

Grant Date

07-Jun-2013

Date of Filing

02-Aug-2007

Name of Patentee

CADILA HEALTHCARE LIMITED

Applicant Address

ZYDUS TOWER, SATELLITE CROSS ROADS, AHMEDABAD.

Inventors:

#	Inventor's Name	Inventor's Address
1	JAIN, KULDEEP NATWARLAL	ZYDUS TOWER, SATELLITE CROSS ROADS, AHMEDABAD 380 015.
2	HOLKAR, ANIL GANPAT	ZYDUS TOWER, SATELLITE CROSS ROADS, AHMEDABAD 380 015.
3	DWIVEDI, SHRIPRAKASH DHAR	ZYDUS TOWER, SATELLITE CROSS ROADS, AHMEDABAD 380 015.

PCT International Classification Number

C07D233/02

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA