American Chemical Society
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New Efficient Asymmetric Synthesis of Taranabant, a CB1R Inverse Agonist for the Treatment of Obesity

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journal contribution
posted on 2009-01-16, 00:00 authored by 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
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.