抗高血压药阿齐沙坦的合成工艺改进

Improved synthesis of antihypertensive drug azilsartan

目的对阿齐沙坦的合成工艺进行优化。方法以2-乙氧基-1-(2'-氰基联苯-4-甲基)苯并咪唑-7-羧酸甲酯为起始原料,依次经偕胺肟化、噁二唑环化、水解反应制得目标产物阿齐沙坦。结果与结论目标化合物的结构经HRMS、1H-NM R和13C-NM R谱确证。总收率为64. 8%(以2-乙氧基-1-(2'-氰基联苯-4-甲基)苯并咪唑-7-羧酸甲酯计),纯度为99. 9%(HPLC法)。优化后的工艺各步反应条件温和,操作简便,收率和纯度均较高,杂质较少,对环境污染少,适合工业化生产。

Azilsartan is a new antihypertensive drug developed by Takeda.Based on the literatures and patents,a synthetic route to azilsartan was established and optimized thoroughly.Starting from methyl 1-[(2'-cyanobiphenyl-4-yl) methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate,azilsartan was synthesized by ammoximation,cyclization and hydrolysis.The total yield of azilsartan was 64.8% (calculated from methyl 1-[(2'-cyanobiphenyl-4-yl) methyl]-2-ethoxy-1H-benzimidazole-7-carboxylate) which was 19.9% higher than that reported in literature and its purity was 99.9% determined by HPLC.The improved process is more suitable for industrial production owing to the mild conditions,simple operation,high yield and purity,less impurities,less environmental pollution.The structure of azilsartan was confirmed by HRMS,1H-NMR and 13C-NMR.