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

Molecules

Isabelle Aillaud¹  Caroline Haurena¹  Erwan Le Gall¹  Thierry Martens¹ 

[1] ¹Électrochimie et Synthèse Organique, Institut de Chimie et des Matériaux Paris Est, ICMPE, UMR 7182 CNRS - Université Paris-Est Créteil Val-de-Marne, 2-8 rue Henri Dunant, 94320 Thiais, France ²Sanofi-Aventis, Process Development, 45 Chemin de Mételine, BP 15, 04201 Sisteron cedex, France

关键词: multicomponent reactions;    organozinc reagents;    amino acids;    cobalt;    zinc;   

DOI  :  10.3390/molecules15118144

来源: mdpi

【 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).

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.