Asymmetric Synthesis of Heterocyclic Analogues of a CGRP Receptor Antagonist for Treating Migraine

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• 作者：Guanglin Luo ; Ling Chen ; Charles M. Conway ; Walter Kostich ; John E. Macor ; Gene M. Dubowchik
• 刊名：Organic Letters
• 出版年：2015
• 出版时间：December 18, 2015
• 年：2015
• 卷：17
• 期：24
• 页码：5982-5985
• 全文大小：385K
• ISSN：1523-7052

文摘

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鈥揗iyaura 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.