An efficient and high-yielding protocol for the production of Regorafenib via a new synthetic strategy

An improved, high-yielding, and efficient protocol for the production of Regorafenib ( 1 ), a novel diaryl urea inhibitor of multiple protein kinases, is described. The highlight of the process chemistry design and development is an optimization of the route for preparing key intermediate 4-(4-amino...

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Bibliographic Details
Published in:Research on chemical intermediates 2016-04, Vol.42 (4), p.3209-3218
Main Authors: Wang, Li-Mei, Du, Bao-Quan, Zuo, Da-Zhuang, Cheng, Ming-Ke, Zhao, Meng, Zhao, Si-Jia, Zhai, Xin, Gong, Ping
Format: Article
Language:English
Subjects:
Catalysis
Chemistry
Chemistry and Materials Science
Inorganic Chemistry
Physical Chemistry
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Summary:An improved, high-yielding, and efficient protocol for the production of Regorafenib ( 1 ), a novel diaryl urea inhibitor of multiple protein kinases, is described. The highlight of the process chemistry design and development is an optimization of the route for preparing key intermediate 4-(4-amino-3-fluorophenoxy)- N -methylpicolinamide ( 7 ) by O -alkylation, nitration and reduction reactions. The developed process avoids using column chromatography to isolate 7 , reduces the reaction requirements and is cost-saving, resulting in an increased overall yield from 35.0 to 57.0 % and purity from 97.0 to 99.8 %.
ISSN:0922-6168
1568-5675
DOI:10.1007/s11164-015-2206-z