FORM 2THE PATENT ACT 1970(39 of 1970)&The Patents Rules, 2003COMPLETE SPECIFICATION(See section 10 and rulel3)
1. TITLE OF THE INVENTION:PROCESS FOR RANOLAZINE AND SALTS THEREOF.
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 relates to a process for ranolazine and salts thereof.
The following specification particularly describes the invention and the manner in which it is to be performed.

4. DESCRIPTION
The present invention relates to a process for ranolazine and salts thereof.
Ranolazine of Formula I, is chemically 1-piperazineacetamide, N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl]-,(±) and it is indicated for the treatment of chronic angina.

U.S. Patent No. 4,567,264 discloses racemic (±)-N-(2,6-dimethylphenyl)-4-[2-hydroxy-3-(2-methoxyphenoxy)propyl The '264 patent further discloses the use of methanol and toluene for coupling of 1-(2-methoxyphenoxy)2,3-epoxypropane with 4-[(2,6-dimethylphenyl)aminocarbonylmethyl]piperazine. Ranolazine is recovered from methanol/ether.
European application EP483932 A1 discloses the use of 1-(2-methoxyphenoxy)-3-aminopropan-2-ol, as an intermediate for ranolazine preparation.
PCT application WO2006008753 disclosed polymorphic Form A of Ranolazine, and process for the same.
While working on the process for ranolazine, it was found by the present inventors that coupling of 1-(2-methoxyphenoxy) 2,3-epoxypropane with 4-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine could be done using a single solvent.
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The process of the present invention is economical, simple and costeffective.
In one aspect of the present invention there is provided a process for preparation of ranolazine or salts thereof. The process includes step of,
a) coupling 1-(2-methoxyphenoxy) 2,3-epoxypropane compound of Formula II, with 4-[(2,6-dimethylphenyl) aminocarbonyl methyl] piperazine
compound of Formula III, in presence of a single organic solvent.

Formula II Formula III
b) isolating ranolazine or salts thereof from the reaction mass.
The ranolazine free base if obtained, can be converted to its acid addition salts thereof by the process known to the skilled artisan. The non-limiting examples of salts include hydrochloric, sulfuric, maleic, succinic, citric, methanesulfonic, benzene sulphonic acid toluenesulfonic acids, and the like.
The non-limiting examples of the single organic solvent include n-butanol, isopropanol (IPA), n-propanol, ethanol, methanol, hexane, benzene, toluene, diethyl ether, chloroform, ethyl acetate, dichloromethane (DCM), methylethylketone, acetone, acetophenone, water 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.
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Example 1: Ranolazine dimesylate.
To a solution of 1-(2-methoxyphenoxy) 2,3-epoxypropane (4.1 g) in isopropyl alcohol, 4-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine (5.0 g) was added. The content was stirred for 4 hours at about 70-85 °C. After completion of the reaction, the reaction mass was cooled to about 20-30 °C then methanesulfonic acid was added. The resultant material was stirred for 2 hours at 20-30 °C, filtered and dried to recover ranolazine dimesylate. Purity by HPLC 98.4 %
Example 2: Ranolazine dihvdrochloride.
To a solution of 1-(2-methoxyphenoxy) 2,3-epoxypropane (41 g) in methylethylketone, 4-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine (50 g) was added. The content was stirred for 4 hours at about 70-85 °C. After completion of the reaction, the reaction mass was cooled to about 20-30 °C then IPA.HCI was added. The resultant material was stirred for 2 hours at 20-30 °C, filtered and dried to recover ranolazine dihydrochloride. Purity by HPLC 98.2 %
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WE CLAIM:
1. A process for preparation of ranolazine or salt thereof comprising,
a) coupling 1-(2-methoxyphenoxy) 2,3-epoxypropane compound of Formula II, with 4-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine compound of Formula III, in presence of a single organic solvent;

Formula II Formula III
b) isolating ranolazine or salt thereof from the reaction mass.
2. A process for preparation of ranolazine or salts thereof as per claim 1, wherein the solvent is selected from n-butanol, isopropanol (IPA), n-propanol, ethanol, methanol, hexane, benzene, toluene, diethyl ether, chloroform, ethyl acetate, dichloromethane (DCM), methylethylketone, acetone, acetophenone, water and the like.
3. A process for preparation of ranolazine as per claim 1, wherein the solvent is isopropanol.
4. A process for preparation of ranolazine or salts thereof as per claim 1, wherein the acid addition salt include hydrochloric, sulfuric, maleic, succinic, citric, methanesulfonic, benzene sulphonic acid toluenesulfonic acids, and the like.
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5. A process for preparation of ranolazine or salt thereof as per claim 1, wherein

Abstract
The present invention relates to a process for Ranolazine and salts thereof. More particularly it relates to a process of coupling of 1-(2-methoxyphenoxy) 2,3-epoxypropane with 4-[(2,6-dimethylphenyl) aminocarbonylmethyl] piperazine using a single organic solvent.
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