乐伐替尼的合成

Synthesis of Lenvatinib

本研究以N,N'-羰基二咪唑代替文献中常用的高毒的氯甲酸苯酯,先与环丙胺反应生成N-环丙基-1H-咪唑-1-甲酰胺,不经纯化,直接与4-(4-氨基-3-氯苯氧基)-7-甲氧基喹啉-6-甲酰胺反应制得乐伐替尼,总收率73%,纯度99.2%。本工艺操作简便、收率高,适合工业化生产。

N-Cyclopropyl-1 H-imidazole-1-carboxamide（4） was prepared by the reaction of cyclopropylamine with N,N＇-carbonyldiimidazole instead of the highly toxic phenyl chloroformate. Then compound 4 was subjected to a substitution with 4-（4-amino-3-chlorophenoxy）-7-methoxyquinoline-6-formamide to afford lenvatinib with a total yield of 73%, and a purity of 99.2%. This process has some advantages such as high yield, simple operation, and it is suitable for industrial production.