马西替坦的合成

Synthesis of Macitentan

5-(4-溴苯基)-4,6-二氯嘧啶与N-丙胺基磺酰胺钾盐发生胺化反应制得N-[5-(4-溴苯基)-6-氯-4-嘧啶基]-N'-丙胺基磺酰胺,在叔丁醇钾作用下与乙二醇发生醇解反应制得N-[5-(4-溴苯基)-6-(2-羟乙氧基)-4-嘧啶基]-N'-丙胺基磺酰胺,与5-溴-2-氯嘧啶发生缩合反应并经过甲醇精制得到马西替坦,总收率为66%。

5-（4-Bromophenyl）-4,6-dichloropyrimidine was aminated by potassium N-propylsulfamide to give N-E5-（4-bromophenyl）-6-chloro-4-pyrimidinyll-N＇propylsulfamide, which reacted with ethylene glycol in the presence of potassium tert-butoxide to provide N- E5- （4-bromophenyl） -6- （2-hydroxyethoxy） -4-pyrimidinyl] -N＇-propylsulfamide, then the latter was condensed with 5-bromo-2-chloropyrimidine, macitentan was prepared with an overall yield of 66 % after recrystallization from methanol.