2-Chlorophenyl Zinc Bromide: A Convenient Nucleophile for the Mannich-Related Multicomponent Synthesis of Clopidogrel and Ticlopidine

摘要

A methodological study devoted to the Mannich-like multicomponent synthesis of the antiplatelet agent (±)-clopidogrel (>7) and the ethyl ester analogue >6 is described. The process involves the formation of 2-chlorophenyl zinc bromide (>2) and its subsequent reaction with an alkyl glyoxylate and 4,5,6,7-tetrahydrothieno[3,2-c]pyridine (>3). We demonstrate that the organozinc reagent >2 also constitutes a very convenient nucleophile for the multicomponent synthesis of the benzylamine core of ticlopidine (>9).