Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonist.
[structures: see text] A stereocontrolled racemic synthesis of conformationally restricted analogues 2a and 2b of a potent CGRP receptor antagonist 1 by novel functionalization of 2-substituted octahydropyrido[1,2-a]pyrazin-6-ones is described. The new diastereoselective LDA-promoted alpha-nitration of intermediate lactams established the required trans-configuration in the desired products.
Zuev
Dmitry
D
Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5100, Wallingford, Connecticut 06492, USA. dmitry.zuev@bms.com
Michne
Jodi A
JA
Huang
Hong
H
Beno
Brett R
BR
Wu
Dedong
D
Gao
Qi
Q
Torrente
John R
JR
Xu
Cen
C
Conway
Charles M
CM
Macor
John E
JE
Dubowchik
Gene M
GM
D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018360:Crystallography, X-Ray; D007769:Lactams / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry; D011719:Pyrazines / Q000737:chemistry*; D013237:Stereoisomerism
C425984:4-(2-oxo-2,3-dihydrobenzimidazol-1-yl)piperidine-1-carboxylic acid (1-(3,5-dibromo-4-hydroxybenzyl)-2-oxo-2-(4-phenylpiperazin-1-yl)ethyl)amide; D001562:Benzimidazoles; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D007769:Lactams; D010879:Piperazines; D010880:Piperidines; D011719:Pyrazines