苹果酸舒尼替尼的合成方法改进

Improved synthesis of sunitinib malate

目的合成抗肿瘤药苹果酸舒尼替尼。方法以二乙烯酮和乙酰乙酸叔丁基酯为起始原料,经酰胺化、Knorr环合、脱羧、Vilsmeier甲酰化4步反应制得中间体N-[2-(二乙胺基)乙基]-2,4-二甲基-5-甲酰基-1H-吡咯-3-甲酰胺,该中间体与5-氟-吲哚-2-酮经羟醛缩合、成盐2步反应制得目标物苹果酸舒尼替尼。结果与结论目标化合物的结构经1H-NMR、HR-EI-MS谱确证,总收率为37.9%。

Aim To synthesize the antitumor agent sunitinib malate. Methods N- （2-diethylaminoethyl）-2,4-dimethyl-5-formyl-lH-pyrrole-3-carboxamide was synthesized from the diketene and ten-butyl acetoacetate via four steps, including amidation, Knorr reaction, decarboxylation, Vilsmeier formylation. The sunitnib malate was prepared from N-（2-diethylaminoethyl）-2,4-dimethyl-5-formyl-lH-pyrrole-3-carboxamide and 5- fluoroindolin-2-one via two steps, aldol condensation and salt formation in ethyl ether. Results and conclusion The target compound was synthesized and its structure was identified by ^1H-NMR,HR-EI-MS, and the total yield was 37.9%.