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

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• 作者：Brian P. Chekal ; Jason Ewers ; Steven M. Guinness ; Nathan D. Ide ; Kyle R. Leeman ; Ronald J. Post ; Anil M. Rane ; Karen Sutherland ; Ke Wang ; Mark Webster ; Gregory J. Withbroe ; John Draper ; Denis Lynch ; Marie McAuliffe ; Joseph Keane
• 刊名：Organic Process Research & Development
• 出版年：2016
• 出版时间：July 15, 2016
• 年：2016
• 卷：20
• 期：7
• 页码：1217-1226
• 全文大小：453K
• 年卷期：0
• ISSN：1520-586X

文摘

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.