阿法替尼的合成

Synthesis of Afatinib

对阿法替尼合成工艺进行研究。以4-氟-2-氨基苯甲酸为起始原料,经环合、硝化、氯化、取代反应得到中间体6;中间体6与(S)-3-羟基四氢呋喃经醚化、还原、酰化和取代后得到化合物10(即阿法替尼游离碱);最后化合物10与马来酸成盐得到目标化合物阿法替尼,总收率约5.4%。

The synthesis process of afatinib. With 2 -amino -4 -fluorobenzoic acid as the starting material, intermediate 6 was got through cyclization, nitrition, chlorination and substitution. Then the intermediate 6 was reacted with (S) -3 -hydroxytetrahydrofuran through the following steps: etherification,reduction, acylation and substitution, getting compound 10 (free base of afatinib). At last, compound 10 was reacted with maleic acid and got the target compound afatinib. The total yield of the process was 5.4%.