Development and Optimization of a Scalable Palladium-Catalyzed C–N Coupling and Acid-Catalyzed Protecting Group Removal Telescope Process for the Synthesis of CDK2-Selective Candidate Tegtociclib (PF-07104091)
PF-07104091 is a cyclin-dependent kinase 2 (CDK2)-selective inhibitor under investigation as an oncology treatment with breast cancer as the leading indication. In this report, we detail the process development and optimization of a telescoped palladium-catalyzed C–N coupling and acid-catalyzed protecting group removal. This optimized process was demonstrated on pilot plant scale production of >700 kg of intermediate 6.
Authors
- Yiqing Feng (ORCID: https://orcid.org/0000-0002-6090-3370)
- Sarah J. Karasik
- Dylan Pedro (ORCID: https://orcid.org/0009-0001-1660-2546)
- Angela L. A. Puchlopek-Dermenci
- Asaad Nematalla
- Thomas A. Brandt (ORCID: https://orcid.org/0000-0003-1998-5789)
- Tyler J. Potter
- Melissa Lee (ORCID: https://orcid.org/0000-0002-0216-0193)
- Michael Herr (ORCID: https://orcid.org/0000-0001-5614-1820)
- Sergei Tcyrulnikov
- Sébastien Monfette (ORCID: https://orcid.org/0000-0002-8394-4423)
- Robert D. Bright
- Mark A. Olivier
- Robert C. North
- Gary R. Jolin
Institutions
- Pfizer (United States) (US)
- Pfizer (United Kingdom) (GB)
Publication Details
- Journal
- Organic Process Research & Development
- Published
- 2025-10-09
- DOI
- https://doi.org/10.1021/acs.oprd.5c00269
- Citations
- 2
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 3.04