Investigation into the Formation of Impurities during the Optimization of Brigatinib

[Image: see text] 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...

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Autores principales: Guo, Aofeng, Zhang, Qiankun, Zhang, Junming, Chen, Jiale, Chen, Jiaqi, Sha, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2020
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676304/
https://www.ncbi.nlm.nih.gov/pubmed/33225157
http://dx.doi.org/10.1021/acsomega.0c03816
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author Guo, Aofeng
Zhang, Qiankun
Zhang, Junming
Chen, Jiale
Chen, Jiaqi
Sha, Yu
author_facet Guo, Aofeng
Zhang, Qiankun
Zhang, Junming
Chen, Jiale
Chen, Jiaqi
Sha, Yu
author_sort Guo, Aofeng
collection PubMed
description [Image: see text] 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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spelling pubmed-76763042020-11-20 Investigation into the Formation of Impurities during the Optimization of Brigatinib Guo, Aofeng Zhang, Qiankun Zhang, Junming Chen, Jiale Chen, Jiaqi Sha, Yu ACS Omega [Image: see text] 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. American Chemical Society 2020-11-03 /pmc/articles/PMC7676304/ /pubmed/33225157 http://dx.doi.org/10.1021/acsomega.0c03816 Text en © 2020 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Guo, Aofeng
Zhang, Qiankun
Zhang, Junming
Chen, Jiale
Chen, Jiaqi
Sha, Yu
Investigation into the Formation of Impurities during the Optimization of Brigatinib
title Investigation into the Formation of Impurities during the Optimization of Brigatinib
title_full Investigation into the Formation of Impurities during the Optimization of Brigatinib
title_fullStr Investigation into the Formation of Impurities during the Optimization of Brigatinib
title_full_unstemmed Investigation into the Formation of Impurities during the Optimization of Brigatinib
title_short Investigation into the Formation of Impurities during the Optimization of Brigatinib
title_sort investigation into the formation of impurities during the optimization of brigatinib
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676304/
https://www.ncbi.nlm.nih.gov/pubmed/33225157
http://dx.doi.org/10.1021/acsomega.0c03816
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