2,4-二甲基-5-甲酰基-1H-吡咯-3-甲酸的合成

Synthesis of 2,4-Dimethyl-5-formyl-1H-pyrrole-3-carboxylic Acid

乙酰乙酸叔丁酯经系列反应得到的氨基酮与乙酰乙酸乙酯经Knorr反应得2,4-二甲基-3-乙氧羰基-1H-吡咯-5-羧酸叔丁酯,再经甲酰化、水解得抗肿瘤药舒尼替尼的重要中间体2,4-二甲基-5-甲酰基-1H-吡咯-3-甲酸,总收率约为44%。

2,4-Dimethyl-5-formyl-1H-pyrrole-3-carboxylic acid, the key intermediate of antitumor agent sunitinib, was synthesized from ethyl acetoacetate via Knorr reaction with keto-amino which prepared from tert-butyl acetoacetate to give tert-butyl 2,4-dimethyl-1H-pyrrole-3-carbethoxy-5-carboxylate, which was subjected to reaction with trifluoroacetic acid and triethyl orthoformate, followed by hydrolysis with an overall yield of about 44 %.