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Synfacts 2019; 15(01): 0003
DOI: 10.1055/s-0037-1611441
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Beclabuvir

Contributor(s):
Philip Kocienski
DelMonte AJ. * et al. Bristol-Meyers Squibb Company, New Brunswick, USA
The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor.

Org. Process Res. Dev. 2018;
22: 1393-1408
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Further Information

Publication History

Publication Date:
14 December 2018 (online)

 
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Key words

beclabuvir - asymmetric cyclopropanation - arylation - Heck reaction - rhodium - palladium

Significance

Beclabuvir (Ximency®, BMS-791325) is a non-nucleoside, nonstructural protein 5B (NS5B) RNA polymerase inhibitor that was approved in Japan for use in combination with Asunaprevir and Daclatasvir for the treatment of hepatitis C virus infection.


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Comment

Key steps in the large-scale synthesis depicted include (1) the rhodium-catalyzed asymmetric cyclopropanation of styrene C (94% yield, 83% ee) and (2) the construction of the seven-membered ring by an intramolecular Heck reaction. Beclabuvir was prepared in twelve linear steps with five isolations in 8% overall yield.


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