摘要
改进抗癌新药瑞戈非尼的合成工艺,以2-吡啶甲酸为原料通过卤化,酰胺化,得到4-氯-N-甲基吡啶-2-甲酰胺,成盐酸盐得到4-氯-N-甲基吡啶-2-甲酰胺盐酸盐,与3-氟-4-氨基苯酚亲核取代反应得到4-(4-氨基-3-氟苯氧基)-N-甲基吡啶-2-甲酰胺,然后和4-氯-3-三氟甲基苯异氰酸酯缩合反应得到瑞戈非尼,总收率为47%。
This study is to synthesize the new anticancer drug regorafenib and improve the process. The 4-chloro-N-methylpyridine-2-carboxamide hydrochloride was synthesized from pyridine-2-carboxylic acid by chlorination, amidation and then it was reacted with 3-fluoro-4-aminophenol, through nucleophileic substitution to give 4-(4-amino-3-fluorophenoxy)-N-methylpyridine-2-carboxamide, and then it was con-densed with 4-chloro-3-(trifluoromethyl) phenyl isocyanate to form regorafenib with an overall yield of 47%.
出处
《药学与临床研究》
2015年第4期368-369,共2页
Pharmaceutical and Clinical Research
关键词
瑞戈非尼
抗癌新药
合成
Regorafenib
New anticancer drug
Synthesis
