Research On Preparation Of Clopidogrel Related Compound A And C And Clopidogrel Crystal Form And Diastereoisomeric Salt

This thesis focused on the preparation of antiplatelet drug Clopidogrel related compound A and C that is reported by USP, research on the Clopidogrel crystal form especially the crystal form IV, prediction of higher melt point diastereoisomeric salt precipitates during an optical resolution through analysis on the thermodynamics property of five pairs of diastereoisomeric salt successfully obtained from chemical resolution include Clopidogrel intermediate.2-chlorophenyl glycine ester (4) which was esterified from 2-(2-chlorophenyl)-glycine(2) in various kinds of alcohols. Resolved by L-(+)-tartaric acid to give (S)-(+)-2-chlorophenyl glycine ester L-tartrate(5).Directly condensation reaction of (5) and (6) to give (S)-(+)-2-(2-thienylethamino)-(2-chlorophenyl)acetate (7). Then cyclization reaction with formaldehyde, and salt-forming reaction with concentrated sulfuric acid to get a series of Clopidogrel derivant,hydrolyzed under alkaline condition, Clopidogrel related compound A was obtained by yield 31.1%.Preparation Clopidogrel from II, III, IV, V, VI by using Clopidogrel form I obtained previously, especially culture single crystal of Clopidogrel form IV.