阿立哌唑和布瑞哌唑中间体的合成工艺

Synthesis of Aripiprazole and Brexpiprazole Intermediates

以3-硝基苯酚为原料,经过醚化反应,与1-(2,3-二氯苯基)哌嗪盐酸盐或1-(苯并[b]噻吩基)哌嗪盐酸盐进行N-烷基化反应,分别制得1-(2,3-二氯苯基)-4-[4-(3-硝基苯氧基)丁基]哌嗪(5a)或1-(苯并[b]噻吩基)-4-[4-(3-硝基苯氧基)丁基]哌嗪(5b)。5a或5b分别经电还原反应,制得抗精神病药物阿立哌唑中间体1-(2,3-二氯苯基)-4-[4-(3-氨基苯氧基)丁基]哌嗪(3a)和布瑞哌唑中间体1-(苯并[b]噻吩基)-4-[4-(3-氨基苯氧基)丁基]哌嗪(3b),还原反应收率分别为93%和97%。

1-(2,3-Dichlorophenyl)-4-[4-(3-nitrophenoxy)butyl]piperazine(5a)or 1-(benzo[b]thiophenyl)-4-[4-(3-nitrophenoxy)butyl]piperazine(5b)were prepared from 3-nitrophenol by etherification,and then N-alkylation reaction with 1-(2,3-dichlorophenyl)piperazine hydrochloride or 1-(benzo[b]thiophenyl)piperazine hydrochloride.The intermediate of aripiprazole or brexpiprazole,1-(2,3-dichlorophenyl)-4-[4-(3-aminophenoxy)butyl]piperazine(3a)or 1-(benzo[b]thiophenyl)-4-[4-(3-aminophenoxy)butyl]piperazine(3b)were prepared by electroreduction reactions of 5a or 5b with yields of 93%and 97%,respectively.