Industrial process for preparation of Clopidogrel hydrogen sulphate

US7629465B2 · kind B2 · utility

Assignee

• IPCA LABORATORIES LIMITED · IN

Inventors

• Ashok Kumar · Jamkhed, IN
• Ketan Dhansukhlal Vyas · Mumbai, IN
• Sanjay Govind Barve · Jamkhed, IN
• Priti Jayesh Bhayani · Jamkhed, IN
• Sanjay Nandavadekar · Jamkhed, IN
• Chirag Hasmukh Shah · Jamkhed, IN
• Sandeep Madhavrao Burudkar · Jamkhed, IN
• Lavkesh Dayashankar Kushwaha · Jamkhed, IN

Key dates

• Filing date: Mar 4, 2005
• Grant date: Dec 8, 2009
• Expiry date: Aug 19, 2025

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D495/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

An improved process for the manufacture of Clopidogrel starting from 2-(2-thienyl) ethylamine, which eliminates the isolation of an unstable intermediate like 2-(2-thienyl) ethyl formimine by subjecting it to a one pot cyclization to get 4, 5, 6, 7-tetrahydrothieno (3,2-c) pyridine of Formula II and further reacting with halo-compound of Formula III (where X is Cl or Br) at 20 to 90° C. temperature characterized in a solvent like water and/or dichloroethane in presence of organic or inorganic bases is disclosed herein. This invention further discloses a process for resolution of racemic Clopidogrel into its optical antipodes and converting the dextroclopidogrel base into its known polymorphs namely ‘Form I’ or ‘Form II’ in solvents selected from methyl propyl ketone, methyl isopropyl ketone, diethyl ketone or their mixture thereof, mixture of ethyl acetate and methyl propyl ketone, mixture of ethyl acetate and methyl isopropyl ketone, or mixture of ethyl acetate and diethyl ketone or ethyl acetate.