抗肿瘤药物苹果酸舒尼替尼的合成  

Synthesis of antitumor agent sunitinib malate

作　　者：董肖椿[1] 周福生[1] 闻韧[1] 

机构地区：[1]复旦大学药学院药物化学教研室,上海200032

出　　处：《中国药物化学杂志》2008年第1期28-31,共4页Chinese Journal of Medicinal Chemistry

摘　　要：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%。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-1 H-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 %.

关 键 词：化学合成 苹果酸舒尼替尼 抗肿瘤药物 乙酰乙酸叔丁酯 

分 类 号：R914[医药卫生—药物化学]