Process for the preparation of cgrp antagonist

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 471/04 (2006.01)

Patent

CA 2649159

An efficient synthesis for the preparation of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine -1-carboxamide, by coupling (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one and 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochloride with 1,1'-carbonyldiimidazole (~CDI~) as carbonyl source; and an efficient preparation of the potassium salt of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine -1-carboxamide.

L'invention concerne une synthèse efficace de préparation de N-[(3R,6S)-6-(2,3-difluorophényl)-2-oxo-1-(2,2,2-trifluoroéthyl)azépane-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)pipéridine -1-carboxamide par couplage de (3R,6S)-3-amino-6-(2,3-difluorophényl)-1-(2,2,2-trifluoroéthyl)azépane-2-one et 2-oxo-1-(4-piperidinyl)-2,3-dihydro-1H-imidazo[4,5-b]pyridine dihydrochlorure avec 1,1'-carbonyldiimidazole (~CDI~) comme source carbonyle; et une préparation efficace du sel de potassium de N-[(3R,6S)-6-(2,3-difluorophényl)-2-oxo-1-(2,2,2-trifluoroéthyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)pipéridine -1-carboxamide.

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