Development of an Efficient Pd-Catalyzed Coupling Process for Axitinib

被引：53

作者：

Chekal, Brian P. ^{[1
]}

Guinness, Steven M. ^{[1
]}

Lillie, Brett M. ^{[1
]}

McLaughlin, Robert W. ^{[1
]}

Palmer, Charles W. ^{[2
]}

Post, Ronald J. ^{[1
]}

Sieser, Janice E. ^{[1
]}

Singer, Robert A. ^{[1
]}

Sluggett, Gregory W. ^{[2
]}

Vaidyanathan, Rajappa ^{[1
]}

Withbroe, Gregory J. ^{[1
]}

机构：

[1] Pfizer Worldwide Res & Dev, Groton Labs, Chem Res & Dev, Groton, CT 06340 USA

[2] Pfizer Worldwide Res & Dev, Groton Labs, Analyt Res & Dev, Groton, CT 06340 USA

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2014年 / 18卷 / 01期

关键词：

ENDOTHELIAL GROWTH-FACTOR; ARYL HALIDES; OXIDATIVE-ADDITION; PALLADIUM REMOVAL; HECK REACTION; SULFUR BOND; S-S; SUBSTITUTION; DISULFIDES; CHEMISTRY;

D O I：

10.1021/op400088k

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The manufacturing process of axitinib (1) involves two Pd-catalyzed coupling reactions, a Migita coupling and a Heck reaction. Optimization of both of these pivotal bond-formation steps is discussed as well as the approach to control impurities in axitinib. Essential to the control strategy was the optimization of the Heck reaction to minimize formation of impurities, in addition to the development of an efficient isolation of crude axitinib to purge impurities.

引用

页码：266 / 274

页数：9

共 36 条

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