Synthesis of the (3R,6S)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache
详细信息 查看全文
- 作者：Christopher S. Burgey ; Daniel V. Paone ; Anthony W. Shaw ; James Z. Deng ; Diem N. Nguyen ; Craig M. Potteiger ; Samuel L. Graham ; Joseph P. Vacca ; Theresa M. Williams
- 刊名：Organic Letters
- 出版年：2008
- 出版时间：August 7, 2008
- 年：2008
- 卷：10
- 期：15
- 页码：3235-3238
- 全文大小：151K
- 年卷期：v.10,no.15(August 7, 2008)
- ISSN：1523-7052
文摘
Two novel routes have been developed to the (3R,6S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one 2 of the CGRP receptor antagonist clinical candidate telcagepant (MK-0974, 1). The first employs a ring-closing metathesis of the styrene 7 as the key reaction, while the second makes use of a highly diastereoselective Hayashi−Miyaura Rh-catalyzed arylboronic acid addition to nitroalkene 16. The latter route has been implemented to produce multigram quantities of telcagepant for extensive preclinical evaluation.