2-chlorophenyl zinc bromide: a convenient nucleophile for the mannich-related multicomponent synthesis of clopidogrel and ticlopidine.
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).
Institut de Chimie et des Matériaux Paris Est, ICMPE, UMR CNRS, Université Paris-Est Créteil Val-de-Marne, Thiais, France. iaillaud@cpe.fr
Isabelle
I
Aillaud
Caroline
C
Haurena
Erwan Le
EL
Gall
Thierry
T
Martens
Gino
G
Ricci
D001965:Bromides / Q000737:chemistry*; D000077144:Clopidogrel; D003035:Cobalt / Q000737:chemistry; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry; D017967:Zinc Compounds / Q000737:chemistry*
D001965:Bromides; D010975:Platelet Aggregation Inhibitors; D017967:Zinc Compounds; D003035:Cobalt; D000077144:Clopidogrel; D015032:Zinc; D013988:Ticlopidine; C093802:zinc bromide