Development of an Efficient Pd-Catalyzed Coupling Process for Axitinib
Development of an Efficient Pd-Catalyzed Coupling Process for Axitinib
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DOI：
10.1021/op400088k
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发表时间：
2014-01-01
影响因子：
3.4
通讯作者：
Withbroe, Gregory J.
中科院分区：
文献类型：
--
作者：
Chekal, Brian P.;Guinness, Steven M.;Withbroe, Gregory J.
阿西替尼（1）的生产工艺涉及两个Pd催化的偶联反应，Migita偶联反应和Heck反应。这两个关键键形成步骤的优化进行了讨论，以及控制阿西替尼中杂质的方法。控制策略的关键是优化Heck反应，以最大限度地减少杂质的形成，以及开发有效分离粗阿昔替尼以清除杂质。
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.