Palbociclib Commercial Manufacturing Process Development. Part III. Deprotection Followed by Crystallization for API Particle Property Control

Abstract

A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, reversible inhibitor of CDK 4/6. The third step of the palbociclib process is composed of an acid-catalyzed deprotection reaction telescoped through extractive workup and distillation operations into a controlled crystallization process. The selection of n-butanol and anisole as the cosolvents for this step allowed for the development of a robust process for each unit operation and for tight control of the API particle size.