Efficient and Scalable Enantioselective Synthesis of a Key Intermediate for Rimegepant: An Oral CGRP Receptor Antagonist

Abstract: Rimegepant is a calcitonin gene-related peptide antagonist used for acute treatment and prevention of migraine. We herein attempt to explore an efficient and practiced method for scale-up, regio- and enantioselective synthesis of (R)-9-hydroxy-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-5-one (1), a key intermediate of rimegepant. In this work, a Ru-catalyzed asymmetric transfer hydrogenation (ATH) reaction was a key step. The optimization of the reaction conditions involved exploring the reaction parameters including catalysts, bases, and solvents. The results suggested that the Ru-catalyzed ATH process using formic acid as the hydrogen donor could be operated under mild conditions at a low catalyst loading (0.5 mol%), affording a high yield (92.1% yield with 99.8% purity) and gratifying enantioselectivity (99.9% ee) of the target product (1). This work first reported the Ru-catalyzed ATH process in the synthesis of key intermediates of rimegepant. The optimized ATH process was easy to implement and cost-effective, making it particularly suitable for manufacturing scale production.

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch

References and Relationships

• Bibliographic citation: Efficient and Scalable Enantioselective Synthesis of a Key Intermediate for Rimegepant: An Oral CGRP Receptor Antagonist ; volume:06 ; number:01 ; year:2024 ; pages:e62-e68 ; Pharmaceutical fronts ; 06, Heft 01 (2024), e62-e68

Contributors, Places and Time

• Contributor: Luo, Zhonghua ; Sun, Guodong ; Wang, Guowei ; Zhang, Xin ; Zhang, Yang ; Zhang, Ji

Further information

• DOI: 10.1055/s-0044-1780495
• URN: urn:nbn:de:101:1-2405021145297.901379353697
• Rights: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 14.08.2025, 11:02 AM CEST