Process for preparing dipeptidyl iv inhibitors and...

C - Chemistry – Metallurgy – 07 – D

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C07D 209/04 (2006.01) C12N 1/20 (2006.01) C12N 9/06 (2006.01)

Patent

CA 2563903

A process for production of cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV is provided which employs a BOC-protected amine of the structure (3) prepared by subjecting an acid of the structure (1) to reduce amination by treating the acid with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase/formate dehydrogenase enzyme concentrate (PDH/FDH) and without isolating treating the resulting amine of the structure (2) with di-tert-butyl dicarbonate to form the BOC-protected amine.

L'invention concerne un procédé de production d'inhibiteurs à base de pyrrolidine fusionnée à du cyclopropyle de dipeptidyl peptidase IV. Ce procédé fait appel à une amine de structure (3) protégée par BOC préparée par la soumission d'un acide de structure (1) pour réduire une amination par le traitement de l'acide avec du méthanoate d'ammonium, du dinucléotide de l'adénine nicotinamide, du dithiothréitol et du concentrat d'enzymes de déshydrogénase/méthanoate déshydrogénase de phénylalamine partiellement purifiée (PDH/FDH), et sans isolement, par le traitement de l'amine obtenue de structure (2) avec du bicarbonate de di-tert-butyle pour former l'amine protégée par BOC.

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