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Updated: Nov 29, 2025

Scaled-Up Preparation of an Intermediate of Upatinib, ACT051-3
Published on: April 7, 2023
Investigation into the Formation of Impurities during the Optimization of Brigatinib
Aofeng Guo1, Qiankun Zhang1, Junming Zhang1
1Key Laboratory of Structure-Based Drug Design& Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, P. R. China.
Abstract:
During the process development of brigatinib, we have made an unusual observation about some impurities. Detailed investigation has led to the conclusion that impurity A is formed via the raw material 2 oxidation, impurity B is formed via the pyrolysis of DMF, impurity C is formed via raw material 4, and impurity D is formed via HCl-catalyzed decomposition of intermediate 3. The present work details a report of the journey toward the development of an efficient process for the commercial production of brigatinib substantially free from all the impurities.
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