盐酸阿比朵尔的合成

Synthesis of Arbidol Hydrochloride

以4-硝基苯酚为原料,经乙酰化、硝基还原得4-乙酰氧基苯胺,与乙酰乙酸乙酯在溴化铟作用下反应,再在碳酸钾、乙酸钯及乙酸铜作用下闭环得5-乙酰氧基-2-甲基-1H-吲哚-3-羧酸乙酯,再经甲基化、溴代、苯硫酚取代和脱保护制得6-溴-5-羟基-1-甲基-2-苯硫甲基-1H-吲哚-3-羧酸乙酯,然后以氨基磺酸为酸试剂、水为溶剂,经Mannich反应得盐酸阿比朵尔,总收率45.4%(以4-硝基苯酚计)。

4-Acetoxylaniline was prepared by acetylation of 4-nitrophenol and reduction, then it reacted with ethyl acetoacetate with indium bromide as the catalyst, followed by cyclization in the presence of potassium carbonate, palladium acetate and cupric acetate to give ethyl 5-acetoxy-2-methyl-1H-indole-3-carboxylate, the latter was subjected to methylation followed by bromination, substitution with thiophenol and deprotection to afford ethyl 6-bromo-5-hydroxy- 1-methyl-2-（phenylthio） methyl-lH-indole-3-carboxylate, then it was subjected to a Mannich reaction in the presence of sulfamic acid in water to give arbidol hydrochloride with an overall yield of 45.4 % （based on 4-nitrophenol）.