抗呕吐药昂丹司琼相关杂质的合成

Related Impurities Synthesis of Ondansetron Hydrochloride

首次合成了欧洲药典9.0中规定的昂丹司琼相关杂质A、D、G和H。分别以1,2,3,9-四氢-9-甲基-4H-咔唑-4-酮和1,2,3,9-四氢-4H-咔唑-4-酮为原料,先与多聚甲醛、二甲胺盐酸盐发生曼尼希反应,最后与咪唑或2-甲基咪唑发生反应得到相关杂质。方法易于操作,所得杂质收率高。

In this work,the related impurities A,D,G and H of ondansetron in EP 9.0 were synthesized for the first time.2,3-Dihydro-1 H-carbazol-4（9H）-one and 9-methyl-2,3-dihydro-1 H-carbazol-4（9H）-one were used as starting material respectively.At first,the starting material reacted with paraformaldehyde and dimethylamine hydrochloride.Impurities A and D were obtained via this Mannich reaction.Then the products in the first step reacted with imidazole or 2-methylimidazole and gave impurities G and H.This synthetic method is easy to operate and afforded these impurities with high yields.