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...

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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
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cited_by cdi_FETCH-LOGICAL-a280t-34f504bc633e7410bd155aac7278476a9b10e5ebfc735ea3151f723497aa2d4c3
cites cdi_FETCH-LOGICAL-a280t-34f504bc633e7410bd155aac7278476a9b10e5ebfc735ea3151f723497aa2d4c3
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container_issue 7
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container_title Organic process research & development
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creator 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
description 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.
doi_str_mv 10.1021/acs.oprd.6b00071
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title Palbociclib Commercial Manufacturing Process Development. Part III. Deprotection Followed by Crystallization for API Particle Property Control
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