A new pathway via intermediate 4-amino-3-fluorophenol for the synthesis of regorafenib |
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Authors: | Fangyu Du Qifan Zhou Yajie Shi Miao Yu Wenjiao Sun |
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Affiliation: | Key Laboratory of Structure-Based Drugs Design and Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang, P. R. China |
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Abstract: | A practical synthetic route to regorafenib, in which the target compound was obtained via a 10-step synthesis starting from 2-picolinic acid, 4-chloro-3-(trifluoromethyl)aniline, and 3-fluorophenol, is reported. Crucial to the strategy is the preparation of 4-amino-3-fluorophenol via Fries and Beckman rearrangements using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and an acceptable overall yield. A scale-up experiment was carried out to provide regorafenib with 99.96% purity in 46.5% total yield. |
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Keywords: | Regorafenib Fries rearrangement Beckman rearrangement Optimization |
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