左西孟旦合成工艺的改进

目的:探讨合成左西孟旦的新方法。方法:通过对加料顺序、拆分方法、重结晶溶剂的改进,以N-4-(2-氯丙酰)苯基]乙酰胺为起始原料,经缩合、脱羧、环合、拆分、重氮化后再缩合得到左西孟旦,并考察收率和纯度。结果:关键中间体6-(4-氨基苯基)-4,5-二氢哒嗪-5-甲基-3(2H)-哒嗪酮的收率达93%以上,经拆分后的纯度达99.5%以上;左西孟旦单一杂质含量小于0.1%,收率为82.6%。结论:改进后的工艺简单、条件温和,产品纯度高,适合大规模生产。

Improvement of Synthesis Technology of Levosimendan

OBJECTIVE： To explore a new method for the synthesis of levosimendan. METHODS： N-4-（2-chloropropanoyl） phenyl]acetamide as raw materials were condensated, decarboxylated and cyclizated after improving charging sequence, separation method, recrystallization agent. Levosimendan could be prepared by diazotization and condensation. The yield and purity of levosi- mendan were determined. RESULTS ： Yield of key intermediate 6- （4-aminophenyl）-4,5-dihydro pyridazine-5-methyl-3 （2H）-pyrid- azinone reached above 93%, while optical purity reached over 99.5%. The content of single impurity in levosimendan was less than 0.1%, with yield of 82.6%. CONCLUSIONS： The improved technology is simple and mild in reaction with high purity of products, and can be used for large scale production of levosimendan.