(S)-苹果酸卡赞替尼的合成

Synthesis of Cabozantinib(S)-Malate

3,4-二甲氧基苯胺(2)与5-(甲氧基亚甲基)-2,2-二甲基-1,3-二噁烷-4,6-二酮发生取代反应,再经环合、氯代,与对硝基苯酚反应制得6,7-二甲氧基-4-(4-硝基苯氧基)喹啉,再经过Pd/C-H2还原、酰化、成盐反应得到抗肿瘤药(S)-苹果酸卡赞替尼,总收率约44%(以2计)。

Cabozantinib （S） -malate, an antineoplastic agent, was synthesized from 3,4-dimethoxyaniline （2） by substitution with 5-（methoxymethylene）-2,2-dimethyl-l,3-dioxane-4,6-dione, cyclization, chlorination and nucleophilic substitution with p-nitrophenol to give 6,7-dimethoxy-4-（4-nitrophenoxy）quinoline, which was subjected to Pd/C-H2 reduction, acylation and salt forming reaction with an overall yield of about 44 % （based on 2）.