title: Stereoselective synthesis of new conformationally restricted analogues of a potent CGRP receptor antagonist.
abstract: [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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 5100, Wallingford, Connecticut 06492, USA. dmitry.zuev@bms.com
authors.forename: Dmitry
authors.initials: D
authors.lastname: Zuev
authors.forename: Jodi A
authors.initials: JA
authors.lastname: Michne
authors.forename: Hong
authors.initials: H
authors.lastname: Huang
authors.forename: Brett R
authors.initials: BR
authors.lastname: Beno
authors.forename: Dedong
authors.initials: D
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Gao
authors.forename: John R
authors.initials: JR
authors.lastname: Torrente
authors.forename: Cen
authors.initials: C
authors.lastname: Xu
authors.forename: Charles M
authors.initials: CM
authors.lastname: Conway
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: 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
chemical_list: 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