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

作者：Wang, Li-Mei; Du, Bao-Quan; Zuo, Da-Zhuang; Cheng, Ming-Ke; Zhao, Meng; Zhao, Si-Jia; Zhai, Xin^*; Gong, Ping^*

来源：Research on Chemical Intermediates, 2016, 42(4): 3209-3218.

DOI：10.1007/s11164-015-2206-z

• Regorafenib
• 4-(4-amino-3-fluorophenoxy)-N-methylpicolinamide
• O-alkylation
• Nitration
• Reduction

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 %.

• 出版日期2016-4
• 单位沈阳药科大学