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5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸的合成与工艺研究

Study on Synthesis of 2,4-Dimethyl-5-formyl-1H-pyrrole-3-carboxylic Acid
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摘要 5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸是抗癌药苹果酸舒尼替尼的重要中间体。以乙酰乙酸叔丁酯为起始原料,依次经过Knorr缩合反应、脱羧反应、Vilsmeier反应、水解反应4步反应合成了目标化合物5-甲酰基-2,4-二甲基-1H-吡咯-3-羧酸,总收率55.4%。并对合成工艺进行了优化,适合于工业化生产。 2,4-Dimethyl-5-formyl- 1H-pyrrole-3-carboxylic acid is an important intermediate of sunitinib malate （Sutent）. It was synthesized from t-butyl acetoacetate via the reactions of Knorr condensation, decarboxylation, Vilsmeier reaction and hydrolyzation. The overall yield was 55.4%. The factors influencing on the synthetic process were investigated and the optimum conditions were obtained. This was a promising industrial synthetic route.
作者 刘翔宇 杜焕达 王琳 王玉玲 刘雅茹 孟繁浩
机构地区 中国医科大学药学院 浙江普洛康裕制药有限公司 杭州海达医药化工有限公司
出处 《精细化工中间体》 CAS 2009年第3期40-42,共3页 Fine Chemical Intermediates
基金 辽宁省药物源头创新研究课题资助(2006226031-221)
关键词 医药中间体 5-甲酰基-2 4-二甲基-1H-吡咯-3-羧酸 苹果酸舒尼替尼 合成 intermediate 2,4-dimethyl-5-formyl-1H-pyrrole-3-carboxylic acid Sunitinib malate synthesis
分类号 R914 [医药卫生—药物化学]
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精细化工中间体
2009年 第3期

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