咪唑斯汀的生产工艺改进

Improvement on the Production Process of Mizolastine

首先以4-氟苄基氯和2-氯-1H-苯并咪唑为起始原料合成1-[(4-氟苯基)甲基]-2-氯-1H-苯并咪唑中间体;所得中间体进一步与甲胺哌啶反应得1-[1-(4-氟苄基)甲基-1H-苯并咪唑-2-基]-N-甲基-4-哌啶胺;最后,第二步产物进一步与2-甲硫基-4-嘧啶酮反应制得(2-[[1-[1-(4-氟苄基)-1H-苯并咪唑-2-基]-4-哌啶基]甲胺基]-4(1H)-嘧啶酮)(咪唑斯汀),总生产收率达54%。

Firstly, 1-（4-Fluorobenzyl）-2-chloro-1H-benzoimidazole was synthesized from 4-fluorobenzyl chloride and 2-chloro-1H-benzimidazole. Secondly, the obtained 1-（4-Fluorobenzyl）-2-chloro-1H-benzoimidazole ammonolysis reacted with methylamine piperidine to give 1-[1-（4-fluoro-benzyl）methyl-1H-benzimidazol-2-yl]-N-methyl-4– piperidinamine. Finally, mizolastine was synthesized from 1-[1-（4-fluoro-benzyl）methyl-1H-benzimidazol-2-yl]-N-methyl-4-piperidinamine and 2-methylthio-4-pyrimidone.The overall yield was about 54%.