New Efficient Asymmetric Synthesis of Taranabant, a CB1R Inverse Agonist for the Treatment of Obesity
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- 作者：Debra J. Wallace ; Kevin R. Campos ; C. Scott Shultz ; Artis Klapars ; Daniel Zewge ; Brian R. Crump ; Brian D. Phenix ; J. Christopher McWilliams ; Shane Krska ; Yongkui Sun ; Cheng-yi Chen ; Felix Spindler
- 刊名：Organic Process Research & Development
- 出版年：2009
- 出版时间：January 16, 2009
- 年：2009
- 卷：13
- 期：1
- 页码：84-90
- 全文大小：193K
- 年卷期：v.13,no.1(January 16, 2009)
- ISSN：1520-586X
文摘
Taranabant (1) is a cannabinoid-1 receptor (CB1R) inverse agonist that was recently in late-stage clinical development for the treatment of obesity. The previously employed synthesis exhibited a number of shortcomings for continuing development, and in this paper we report an improved synthesis of the target molecule that is suitable for large-scale implementation. Palladium-catalyzed amidation of an enol tosylate afforded a stereodefined tetrasubstituted enamide, and asymmetric hydrogenation thereof provided the target molecule.