Late-Stage Kinetic Hydrolysis to Prepare an Advanced Intermediate for Ibuzatrelvir
Abstract Ibuzatrelvir is a second-generation, orally administered protease inhibitor of the SARS-CoV-2 MPro virus that is currently being evaluated for the treatment of Covid-19. The molecule contains a substituted trans-trifluoromethylproline fragment that, although it had been the focus of previous synthetic efforts, was still identified as a target for improvement. Herein, we describe a route featuring the late-stage introduction of a stereocenter via a mechanistically distinct diastereoselective kinetic hydrolysis. This bold strategy has resulted in significant efficiency, environmental, and process dividends, underscoring the impact of a continuous-improvement approach to chemical development.
Authors
- Dylan Pedro (ORCID: https://orcid.org/0009-0001-1660-2546)
- Johnny W. Lee (ORCID: https://orcid.org/0000-0002-0950-7815)
- Christophe Allais (ORCID: https://orcid.org/0000-0002-3443-9391)
- Shu Yu (ORCID: https://orcid.org/0009-0008-3328-1028)
- Emily Lennert (ORCID: https://orcid.org/0000-0003-0647-5253)
- Chintelle James
- Aaron F. Baldwin (ORCID: https://orcid.org/0000-0002-5621-0555)
- Gabrielle E. Cabrera
- María González‐Esguevillas (ORCID: https://orcid.org/0000-0003-3779-5516)
- D.W. Place (ORCID: https://orcid.org/0000-0001-6174-0721)
- Melissa Lee (ORCID: https://orcid.org/0000-0002-0216-0193)
- Michael Herr (ORCID: https://orcid.org/0000-0001-5614-1820)
- R. Matthew Weekly
- Philipp C. Roosen
- Gerald A. Weisenburger
- Russell F. Algera (ORCID: https://orcid.org/0000-0001-8973-5684)
- Jeffrey M. Massicott
- Robert J. Pearson
- Lesly Mejia
Institutions
- Pfizer (United States) (US)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2026-09-11
- DOI
- https://doi.org/10.1021/acs.oprd.6c00096
- Primary Topic
- Chemical Synthesis and Analysis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Pfizer