Indian Patents. 259827:A METHOD OF DRYING AND PROCESS FOR THE PREPARATION OF STABLE POLYMORPHIC FORM-D OF ENTACAPONE

Title of Invention	A METHOD OF DRYING AND PROCESS FOR THE PREPARATION OF STABLE POLYMORPHIC FORM-D OF ENTACAPONE
Abstract	The present invention provides a process for the preparation of stable polymorphic form-D of entacapone, wherein the said process comprising a) adding entacapone to dimethyl acetamide, b) isolating and drying the polymorphic form-D of Entacapone from reaction mass thereof.

Full Text	FORM 2THE PATENT ACT 1970(39 Of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rule 13) 1. TITLE OF THE INVENTIONA METHOD OF DRYING AND PROCESS FOR THE PREPARATION OF STABLE POLYMORPHIC FORM-D OF ENTACAPONE 2. APPLICANT (S)(a) NAME: WOCKHARDT LTD.(b) NATIONALITY: INDIAN(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra (East), Mumbai - 400 051. 3. PREAMBLE TO THE DESCRIPTIONThe present invention provides a method of drying and process for the preparation of stable polymorphic form-D of entacapone. The following specification particularly describes the invention and the manner in which it is to be performed. 1 4. DESCRIPTION The present invention provides a method of drying and process for the preparation of stable polymorphic form-D of entacapone. Entacapone of formula I is chemically known as (E)-N, N-Diethyl-2- cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide. British patent No. 8,727,854 describes entacapone as a potent inhibitor of catechol-O-methyl- transferase (COMT) enzyme. The product is indicated for the treatment of Parkinson's disease. US Patent 4,963,590 discloses a process for the preparation of entacapone (Formula I) by the condensation of 3,4-Dihydroxy-5- nitrobenzaldehyde and N,N-diethylcyanoacetamide in anhydrous ethanol. US Patent 5,135,950 discloses crystallographically essentially pure and stable polymorphic form A of entacapone. The processes of preparation of entacapone and different polymorphic forms are also disclosed in PCT patent application WO 2005063693; WO 2005063695; WO 2005063696; WO 2005066117 and WO 200507088. The inventors have surprisingly found that the stable polymorphic form-D of entacapone is obtained in pure form when dried in fluidized bed dryer as compared to tray drying technique. This is an industrially advantagious process for the preparation of stable and pure polymorphic form-D of entacapone. 2 In the aspect of present invention there is provided a process for the preparation of stable polymorphic form-D of entacapone, wherein the said process includes step of, a) adding entacapone to dimethyl acetamide, b) isolating and drying the polymorphic form-D of Entacapone from reaction mass thereof. The process involves adding entacapone to dimethylacetamide and reaction mixture was then stirred and diluted with alcohol. To the mixture water and sulphuric acid was added and stirred. The polymorph form-D of entacapone was isolated from the reaction mass thereof and dried in fluidized bed dryer. The XRD of D-form of entacapone dried in fluidized bed dryer and tray dryer are as shown in figure 1 and 2 respectively. The non-limiting examples of alcohol include straight chain and branched chain C1-C6 alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol and the like. While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention. EXAMPLE-1 Preparation of stable polymorph form-D of entacapone: Charged dimethylacetamide (400 ml) and entacapone (200 gm). The reaction mixture was stirred for 20-30 minutes and diluted with methanol (400 ml). Then the reaction mixture was added with water (4.0 litre) and sulphuric acid (6 ml) mixture. The reaction mass was further stirred for 20-30 minutes and the polymorph form-D of entacapone was isolated and dried in fluidized bed dryer. Yield: 194 gm. Purity (by HPLC): 99.9%. 3 EXAMPLE-2 Preparation of mix polymorph of entacapone: Charged dimethylacetamide (400 ml) and entacapone (200 gm). The reaction mixture was stirred for 20-30 minutes and diluted with methanol (400 ml). Then the reaction mixture was added with the mixture of water (4.0 Litre) and sulphuric acid (6 ml). The mass was further stirred for 20-30 minutes and the polymorph form-D of entacapone was isolated and dried in tray dryer. Yield: 194.4 gm. Purity (by HPLC): 99.9%. Mixture of polymorph D and A. 4 WE CLAIM: 1. A process for the preparation of stable polymorphic form-D of entacapone, wherein the said process comprising a) adding entacapone to dimethyl acetamide, b) isolating and drying the polymorphic form-D of Entacapone from reaction mass thereof. 2. A process of claim 2 wherein the alcohol is added to isolate the product. 3. The alcohol is selected from the group of straight chain and branched chain C1-C6 alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol and the like. 4. A process of claim 2 wherein the alcohol is added after stirring the mixture of entacapone with dimethyl acetamide. 5. A process of claim 1 wherein the drying is carried out in Fluidized bed dryer. Dated this 19TH day of Jan, 2007 For Wockhardt Limited (Mandar Kodgule) Authorized Signatory 5

Full Text

FORM 2THE PATENT ACT 1970(39 Of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rule 13)
1. TITLE OF THE INVENTIONA METHOD OF DRYING AND PROCESS FOR THE PREPARATION OF STABLE POLYMORPHIC FORM-D OF ENTACAPONE
2. APPLICANT (S)(a) NAME: WOCKHARDT LTD.(b) NATIONALITY: INDIAN(c) ADDRESS: Wockhardt Towers, Bandra-Kurla Complex, Bandra (East), Mumbai - 400 051.
3. PREAMBLE TO THE DESCRIPTIONThe present invention provides a method of drying and process for the preparation of stable polymorphic form-D of entacapone.
The following specification particularly describes the invention and the manner in which it is to be performed.
1

4. DESCRIPTION
The present invention provides a method of drying and process for the preparation of stable polymorphic form-D of entacapone.
Entacapone of formula I is chemically known as (E)-N, N-Diethyl-2- cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.

British patent No. 8,727,854 describes entacapone as a potent inhibitor of catechol-O-methyl- transferase (COMT) enzyme. The product is indicated for the treatment of Parkinson's disease.
US Patent 4,963,590 discloses a process for the preparation of entacapone (Formula I) by the condensation of 3,4-Dihydroxy-5- nitrobenzaldehyde and N,N-diethylcyanoacetamide in anhydrous ethanol.
US Patent 5,135,950 discloses crystallographically essentially pure and stable polymorphic form A of entacapone.
The processes of preparation of entacapone and different polymorphic forms are also disclosed in PCT patent application WO 2005063693; WO 2005063695; WO 2005063696; WO 2005066117 and WO 200507088.
The inventors have surprisingly found that the stable polymorphic form-D of entacapone is obtained in pure form when dried in fluidized bed dryer as compared to tray drying technique. This is an industrially advantagious process for the preparation of stable and pure polymorphic form-D of entacapone.
2

In the aspect of present invention there is provided a process for the preparation of stable polymorphic form-D of entacapone, wherein the said process includes step of,
a) adding entacapone to dimethyl acetamide,
b) isolating and drying the polymorphic form-D of Entacapone from reaction mass thereof.
The process involves adding entacapone to dimethylacetamide and reaction mixture was then stirred and diluted with alcohol. To the mixture water and sulphuric acid was added and stirred. The polymorph form-D of entacapone was isolated from the reaction mass thereof and dried in fluidized bed dryer. The XRD of D-form of entacapone dried in fluidized bed dryer and tray dryer are as shown in figure 1 and 2 respectively.
The non-limiting examples of alcohol include straight chain and branched chain C1-C6 alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol and the like.
While the present invention has been described in terms of its specific embodiments, certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.
EXAMPLE-1
Preparation of stable polymorph form-D of entacapone:
Charged dimethylacetamide (400 ml) and entacapone (200 gm). The reaction mixture was stirred for 20-30 minutes and diluted with methanol (400 ml). Then the reaction mixture was added with water (4.0 litre) and sulphuric acid (6 ml) mixture. The reaction mass was further stirred for 20-30 minutes and the polymorph form-D of entacapone was isolated and dried in fluidized bed dryer. Yield: 194 gm.
Purity (by HPLC): 99.9%.
3

EXAMPLE-2 Preparation of mix polymorph of entacapone:
Charged dimethylacetamide (400 ml) and entacapone (200 gm). The reaction mixture was stirred for 20-30 minutes and diluted with methanol (400 ml). Then the reaction mixture was added with the mixture of water (4.0 Litre) and sulphuric acid (6 ml). The mass was further stirred for 20-30 minutes and the polymorph form-D of entacapone was isolated and dried in tray dryer.
Yield: 194.4 gm.
Purity (by HPLC): 99.9%.
Mixture of polymorph D and A.
4

WE CLAIM:
1. A process for the preparation of stable polymorphic form-D of entacapone,
wherein the said process comprising
a) adding entacapone to dimethyl acetamide,
b) isolating and drying the polymorphic form-D of Entacapone from reaction mass thereof.

2. A process of claim 2 wherein the alcohol is added to isolate the product.
3. The alcohol is selected from the group of straight chain and branched chain C1-C6 alcohols such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol and the like.
4. A process of claim 2 wherein the alcohol is added after stirring the mixture of entacapone with dimethyl acetamide.
5. A process of claim 1 wherein the drying is carried out in Fluidized bed dryer.
Dated this 19TH day of Jan, 2007 For Wockhardt Limited

(Mandar Kodgule) Authorized Signatory

5

Documents:

119-MUM-2007-CLAIMS(AMENDED)-(13-6-2013).pdf

119-MUM-2007-CLAIMS(AMENDED)-(28-2-2014).pdf

119-MUM-2007-CLAIMS(MARKED COPY)-(13-6-2013).pdf

119-mum-2007-claims.doc

119-mum-2007-claims.pdf

119-mum-2007-correspondance-received.pdf

119-mum-2007-description (complete).pdf

119-mum-2007-drawings.pdf

119-MUM-2007-FORM 18(19-10-2010).pdf

119-MUM-2007-FORM 2(TITLE PAGE)-(19-1-2007).pdf

119-mum-2007-form-1.pdf

119-mum-2007-form-2.doc

119-mum-2007-form-2.pdf

119-MUM-2007-REPLY TO EXAMINATION REPORT(13-6-2013).pdf

119-MUM-2007-REPLY TO HEARING(28-2-2014).pdf

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Patent Number

259827

Indian Patent Application Number

119/MUM/2007

PG Journal Number

13/2014

Publication Date

28-Mar-2014

Grant Date

28-Mar-2014

Date of Filing

19-Jan-2007

Name of Patentee

WOCKHARDT LIMITED

Applicant Address

WOCKHARDT TOWERS, BANDRA-KURLA COMPLEX, BANDRA (EAST), MUMBAI

Inventors:

#	Inventor's Name	Inventor's Address
1	YADAV RAM PRASAD	VILLAGE: LAKHANPUR, POST: MAWAIYA, DIST.MIRZAPUR-231001,
2	SHAIKH ZAKIR GAFOOR	VILLAGE & POST - WARIGAON, TEHSIL-KOPARGAON, DIST. AHMEDNAGAR-413708
3	SIDDIQUI MOHAMMED JAWEED MUKARRAM	H.NO. 4-8-65,NAWABPURA, NEAR NAGINA MASJID, AURANGABAD 431001

PCT International Classification Number

C07C253/30

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA