Vonafexor(EYP001)的合成

Synthesis of Vonafexor(EYP001)

以5-溴水杨醛为起始原料,与溴乙酸乙酯通过2步反应环合生成5-溴苯并呋喃-2-甲酸乙酯,再与1-Boc哌嗪反应生成5-(4-叔丁氧羰基哌嗪)苯并呋喃-2-甲酸乙酯;接着经N-氯代丁二酰亚胺(NCS)氯代得到4-氯-5-(4-叔丁氧羰基哌嗪)苯并呋喃-2-甲酸乙酯;最后脱去Boc保护基,与2,6-二氯苯磺酰氯反应得到4-氯-5-[4-(2,6-二氯苯磺酰基)-1-哌嗪基]苯并呋喃-2-甲酸乙酯,水解后得到目标化合物EYP001,总收率为58.3%.

In this paper,5-bromosalicylic aldehyde was used as the starting material and cyclized with ethyl bromoacetate through a two-step reaction.The ethyl 5-bromobenzofuran-2-carboxylate was achieved,which was then reacted with 1-Boc piperazine to yield tert-butyl 4-(2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylate.A chlorination reaction with N-chlorosuccinimide(NCS)was followed to give tertbutyl 4-(4-chloro-2-(ethoxycarbonyl)benzofuran-5-yl)piperazine-1-carboxylate whose Boc protecting group was removed afterwards.Finally EYP001 was obtained by a sulfonation reaction with 2,6-dichlorobenzenesulfonyl chloride and then hydrolyzed with a total yield of 58.3%.