左西孟旦中间体6-(4-氨基苯基)-5-甲基-4,5-二氢-3(2H)-哒嗪酮的合成新方法

摘要

目的:设计经济、安全、实用的制备6-(4-氨基苯基)-5-甲基-4,5-二氢-3 (2H)-哒嗪酮的路线.方法:以乙酰苯胺和2-氯丙酰氯为起始原料,经傅克酞化,缩合,水解脱羧及环合得到目标产物.结果:酰化、缩合、水解脱羧和环合收率分别为85%,90%,88%和96%,总收率64.6%.各步产物结构经HPLC和核磁共振氢谱确证,终产物纯度99%以上.结论:新合成路线以2-氯丙酰氯与乙酰苯胺的傅克酰化一步反应代替文献中的两步反应,具有原料价廉易得、操作简便、安全性好等优点,适合工业化生产.%Objective: To develop an economical, safe and practical method to produce levosimendan intermediate 6-(4-aminophenyl ) -5-methyl-4,5-dihydro-3 ( 2H)-pyridazinone.Methods: Acetanilide was acylated with 2-chloropropionyl chloride, condensed with diethyl malonate, hydrolysed and decarboxylated, and cyclized to obtain the targeted compound.Results: Yields of acylation, condensation, hydrolysis and decarboxylation, and eyclization were 85％, 90％, 88％ and 96％ , respectively.The overall yield was 64.6％ and all compounds were characterized by HPLC and 1H-NMR spectroscopy.Conclusion: The new method includes two-step literature processes of Friedel-Crafts acylation of acetanilide with propionyl chloride, and bromination replaced by direct Friedel-Crafts acylation of acetanilide with 2-chloropropionyl chloride.The novel process combines the advantages of lower materials cost, simpler process, and safer operation, and can be scaled up readily.