抗高血压药马西替坦的合成工艺优化

Process Optimization for Synthesis of Antihypertensive Agent Macitentan

以4-溴苯乙酸甲酯为起始原料,经碳负离子亲核取代、关环、氯代、氮负离子亲核取代、氧负离子亲核取代等6步反应制得抗高血压药马西替坦,并对合成工艺进行了优化。优化后的工艺使中间体的纯度得到了提高,操作更加简便,更有利于工业化生产。中间体和产物的结构均经~1H-NMR和ESI-MS确证。

Using methyl 4-bromophenylacetate as the starting material,Macitentan was synthesized by a 6-step reaction of nucleophilic substitution of carbon anion,ring-closing reaction,chlorination,nucleophilic substitution of nitrogen anion, nucleophilic substitution of oxygen anion, and the synthetic process was also optimized. The structures of the intermediates and products were confirmed by ~1 H-NMR and ESI-MS. The optimized process improves the purity of the intermediate,the operation is more simple and more conducive to industrial production.