Process for making CGRP receptor antagonists
The invention encompasses a novel process for making piperidinone carboxamide indane and azainane derivatives, which are CGRP receptor antagonists useful for the treatment of migraine.
1. Crystalline (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3 -b]pyridine]-3 -carboxamide monohydrate.
2. Crystalline (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxamide monohydrate according to claim 1 having a DSC extrapolated onset melting temperature of about 144° C. and a DSC peak melting temperature of about 175° C.
3. Crystalline (S)-N-((3S,5S,6R)-6-methyl-2-oxo-1-(2,2,2-trifluoroethyl)-5-(2,3,6-trifluorophenyl)piperidin-3-yl)-2′-oxo-1′,2′,5,7-tetrahydrospiro[cyclopenta[b]pyridine-6,3′-pyrrolo[2,3-b]pyridine]-3-carboxamide monohydrate according to claim 1 having d-spacings determined by x-ray powder diffraction, Cu K alpha, of about 12.7, 8.9, 8.1, 7.4, 6.4, 5.2, 4.9, 4.8 and 4.0 angstroms.