title: Asymmetric Synthesis of Heterocyclic Analogues of a CGRP Receptor Antagonist for Treating Migraine.
abstract: An asymmetric synthesis of novel heterocyclic analogue of the CGRP receptor antagonist rimegepant (BMS-927711, 3) is reported. The cycloheptane ring was constructed by an intramolecular Heck reaction. The application of Hayashi-Miyaura and Ellman reactions furnished the aryl and the amine chiral centers, while the separable diastereomeric third chiral center alcohols led to both carbamate and urea analogues. This synthetic approach was applicable to both 6- and 5-membered heterocycles as exemplified by pyrazine and thiazole derivatives.
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Luo
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Conway
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Walter
authors.initials: W
authors.lastname: Kostich
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
authors.affiliation: Bristol-Myers Squibb Research & Development, 5 Research Parkway, Wallingford, Connecticut 06492, United States.
authors.forename: Gene M
authors.initials: GM
authors.lastname: Dubowchik
mesh_terms: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003508:Cycloheptanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008881:Migraine Disorders / Q000188:drug therapy*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003508:Cycloheptanes; D010880:Piperidines; D011725:Pyridines; C578443:rimegepant sulfate