CHIRAL 1-(4-METHYLPHENYLMETHYL)-5-OXO-{N-[(3-T-BUTOXYCARBONYL- AMINOMETHYL)]-PIPERIDIN-1-YL}-PYRROLIDINE-2-CARBOXAMIDES AS INHIBITORS OF COLLAGEN INDUCED PLATELET ACTIVATION AND ADHESION

摘要

Chiral l-(4-methylphenylmethyl)-5-oxo-{N-[(3-t-butoxycarbonyl-aminomethyl)]- piperidin-l-yl}-pyrrolidine-2-carboxamides as inhibitors of collagen induced platelet activation and adhesion The present invention provides chiral (2S)-l-(4-methylphenylmethyl)-5-oxo-(3S)-{N-[(3-t- butoxycarbonyl aminomethyl)]-piperidin-l-yl}-pyrrolidine-2-carboxamide, and (2S)-1-(4- methylphenylmethyl)-5-oxo-(3R)-{N-[(3-t-butoxycarbonyl amino methyl)]-piperidin-l-yl}- pyrrolidine-2-carboxamide of formula 6 and 7 respectively. The present invention also relates to use of these moieties as inhibitors of collagen induced platelet adhesion and aggregation mediated through collagen receptors. The present invention provides a process for preparation of chiral carboxamides of formula 6 and 7 using the process which has advantage to avoid any racemization at the a-carboxylic center, during N-alkylation. The reagent LiHMDS is used at low temperatures to furnish methyl N-(p- methylphenylmethyl)lpyroglutamate in good chiral purity.