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.