抗肿瘤药物苹果酸舒尼替尼的合成

目的 合成抗肿瘤药物苹果酸舒尼替尼。方法 以乙酰乙酸叔丁酯为起始原料，通过Knorr吡咯合成法、脱叔丁氧羰基、Vilsmeier甲酰化、酯水解反应得中间体5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸（6），6与碳酰二咪唑反应生成酰基咪唑，不经分离直接用“一锅煮”方法与5-氟吲哚啉-2-酮和2-(二乙氨基)乙二胺缩合，最后成盐得到苹果酸舒尼替尼。 结果与结论 合成的苹果酸舒尼替尼经核磁共振、质谱和元素分析确证结构，总收率达28%。

Synthesis of antitumor agent sunitinib malate

Aim To synthesize the antitumor agent sunitinib malate.Methods Starting from tert-butyl acetoacetate,2-tert-butyl-4-ethyl-3,5-dimethyl-1H-pyrrole-2,4-dicarboxylate was obtained via classic Knorr pyrrole reaction.After facile decarboxylation,Vilsmeier formylation,and hydrolysis of the ethyl ester,5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid was formed.Sunitinib was obtained by one-pot reaction of this intermediate with N,N-diethylethylenediamine and 5-fluoro-1,3-dihydro-indol-2-one,then salt formation.Results and conclusion The target compound was synthesized and its structure was identified by 1H-NMR,MS,elemental analysis,and the overall yield was 28%.