硫代乙内酰脲衍生物Ru59063合成工艺

A New Method for Synthetic Methods of Thiohydantoin Derivative Ru59063

摘要:

Ru59063在临床上用来治疗前列腺癌,具有较好的疗效,研究以 4-氨基-2-(三氟甲基)苯甲腈为原料,通过硫光气制备硫代异氰酸酯,然后与2-氨基异丁酸甲酯盐酸盐进行[3+2]环加成反应构建硫代乙内酰脲环、然后与卤代醚发生乌尔曼C-N偶联反应,最后进行羟基脱保护共4 步反应得到Ru59063,总收率为 61.5%。相比于传统方法,该法收率提高了40%以上,并且未用到氰化物,可以更方便、更安全的制备 Ru59063。

Abstract:

Ru59063 is clinically used to treat prostate cancer and has a good effect. In this study, 4-amino-2- ( trifluoromethyl ) benzonitrile was used as raw material to prepare thioisocyanate by thiophosgene, and then [3+2] cycloaddition reaction with 2-aminoisobutyrate methyl ester hydrochloride was carried out to construct thiohydantoin ring, and then Ullmann C-N coupling reaction with halogenated ether was carried out. Finally, a total of 4 steps of hydroxyl deprotection were carried out to obtain Ru59063, with an overall yield of 61.5 %. Compared with the traditional method, the yield of this method is increased by more than 40 %, and no cyanide is used, It is more convenient and safer to prepare Ru59063.