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

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...

Full description

Saved in:
Bibliographic Details
Published in:Organic process research & development 2016-07, Vol.20 (7), p.1217-1226
Main Authors: Chekal, Brian P, Ewers, Jason, Guinness, Steven M, Ide, Nathan D, Leeman, Kyle R, Post, Ronald J, Rane, Anil M, Sutherland, Karen, Wang, Ke, Webster, Mark, Withbroe, Gregory J, Draper, John, Lynch, Denis, McAuliffe, Marie, Keane, Joseph
Format: Article
Language:English
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1083-6160
1520-586X
DOI:10.1021/acs.oprd.6b00071