FORM 2
THE PATENT ACT 1970
(39 of 1970)
&
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rulel3)
1. TITLE OF THE INVENTION:
A PROCESS FOR PREPARATION OF FORM A OF (E)-N,N-DIETHYL-2-CYANO-3-(3,4-DIHYDROXY-5-NITROPHENYL)ACRYLAMIDE
2. APPLICANT (S)
(a) NAME: WOCKHARDT LTD.
(b) NATIONALITY: INDIAN
(c) ADDRESS: Wockhardt Limited, D-4, MIDC, Chikalthana,
Aurangabad (M.S.) INDIA.
3. PREAMBLE TO THE DESCRIPTION
The present invention provides a process for preparation of form A of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention provides a process for preparation of form A of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.
Entacapone of formula I, chemically known as (E)-N, N-Diethyl-2- cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide. It is indicated for the treatment of Parkinson's disease.


C—C„ CH *C H*

Formula I
British patent No. 8,727,854 describes entacapone as a potent inhibitor of catechol-O-methyl- transferase (COMT) enzyme.
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 has found process of preparation of form A entacapone by suspending any polymorphic form of entacapone in an organic solvent or the mixture of organic solvent with an organic acid.

In the aspect of invention there is provided a process of preparation of form A entacapone. The process induces steps of,
a) contacting entacapone with an organic solvent or organic solvent mixture,
b) isolating entacapone form A from the reaction mass thereof.
The process of present invention involves suspending any polymorphic form or mixture of polymorphic forms of entacapone in an organic solvent or mixture of organic solvent with an organic acid which include acetic acid and formic acid. The reaction mixture is stirred for two hours and entacapone is isolated in polymorphic form A from the reaction mass thereof.
The term "organic solvent" include one or more from the group of straight chain and branched chain C1-C6 alcohols, ketone solvent, ester and ether solvent such as methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, tetrahydrofuran, ethyl acetate and acetone or mixture water and organic solvent.
The present invention is further illustrated by the following example which are provided merely to be exemplary of the invention and do not limit the scope of the invention. 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.
Conversion of other polymorphic of (E)-N, N-Diethyl-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl) acrylamide to Form-A (Entacapone) Example :1
The entacapone (100 gm) was charged with methanol (250 ml).The reaction mass was heated at 60°C for 1 hours and the cooled to 25°C. The reaction mass was further stirred for 2hours. The solid was filtered and washed with methanol

(100ml). The product was dried to get the (E)-N, N-Diethyl-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl) acrylamide of Form A.
Yield: 85 gm.
Example :2
The entacapone (25 gm) was charged with methanol (50 ml) and water (50 ml).The reaction mass was heated at 60CC for 1 hours and the cooled to 25°C. The reaction mass was further stirred for 2hours. The solid was filtered and washed with methanol (100ml). The product was dried to get the (E)-N, N-Diethyl-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl) acrylamide of Form A.
Yield: 20 gm.
Example :3
The entacapone (25 gm) was charged with acetic acid (50 ml) and water (50 ml).The reaction mass was heated at 50°C for 1 hours and the cooled to 25°C. The reaction mass was further stirred for 2hours. The solid was filtered and washed with water (50ml). The product was dried to get the (E)-N, N-Diethyl-2-cyano-3-(3, 4-dihydroxy-5-nitrophenyl) acrylamide of Form A.
Yield: 22 gm.

WE CLAIM:
1. A process of preparation of form A entacapone wherein the process comprises of,
a) contacting entacapone with an organic solvent or organic solvent mixture,
b) isolating entacapone form A from the reaction mass thereof.

2. The process of claim 1, wherein organic solvent is selected from the group of C1-C6 alcohols, ketone, ester and ether solvents or mixtures thereof.
3. The process of claim 2 wherein solvent is selected from the group of methyl alcohol, ethyl alcohol, n-propyl alcohol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, tetrahydrofuran, ethyl acetate and acetone or mixture thereof.
4. The process of claim 2 wherein organic solvent is optionally used in a mixture of organic solvent and water.
5. The process of claim 1, wherein organic solvent mixture is mixture of organic acid and organic solvent.
6. The process of claim 5, wherein organic acid is selected from acetic acid or formic acid.

Abstract
The present invention provides a process for preparation of form A of (E)-N,N-diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide.