Clopimozide, R-29764
氯哌莫齐Chemical Name: 1-[1-[4,4-Bis(4-fluorophenyl)butyl]piperidin-4-yl]-5-chloro-2,3-dihydro-1H-benzimidazol-2-one
CAS No. 53179-12-7
项目整合开发状态: Not Determined
项目研究机构:
合成路线:The reaction of ethyl 4-piperidone-1-carboxylate (I) with hydroxylamine gives the corresponding oxime (II),which by catalytic hydrogenation over Raney-Ni yields ethyl 4-aminopiperidine-1-carboxylate (III).The condensation of (III) with 2,5-dichloronitrobenzene (IV) by means of K2CO3 and KI in cyclohexanol at 160 C affords ethyl 4-(4-chloro-2-nitroanilino)-1-piperidinecarboxylate (V),which is reduced with H2 over Raney-Ni to the corresponding amino compound (VI).The cyclization of (VI) with urea (VII) at 170-80 C gives ethyl 4-(1,3-dihydro-2-oxo-5-chloro-2H-benzimidazol-1-yl)-1-piperidinecarboxylate (VIII),which is hydrolyzed and decarboxylated by treatment with KOH in refluxing propanol - water giving 1,3-dihydro-1-(4-piperidinyl)-5-chloro-2H-benzimidazol-2-one (IX).Finally this compound is condensed with 4,4-bis(p-fluorophenyl)butyl chloride (X) by means of NaHCO3 in refluxing ethanol.
📌 参考资料/链接：
参考文献标题:
文献作者:Janssen,P.A.J.; et al.
参考来源:BE 830403; DE 2527261; FR 2275210; JP 7613780; NL 7507368; US 3989707
📄 详细内容
合成路线:The reaction of ethyl 4-piperidone-1-carboxylate (I) with hydroxylamine gives the corresponding oxime (II),which by catalytic hydrogenation over Raney-Ni yields ethyl 4-aminopiperidine-1-carboxylate (III).The condensation of (III) with 2,5-dichloronitrobenzene (IV) by means of K2CO3 and KI in cyclohexanol at 160 C affords ethyl 4-(4-chloro-2-nitroanilino)-1-piperidinecarboxylate (V),which is reduced with H2 over Raney-Ni to the corresponding amino compound (VI).The cyclization of (VI) with urea (VII) at 170-80 C gives ethyl 4-(1,3-dihydro-2-oxo-5-chloro-2H-benzimidazol-1-yl)-1-piperidinecarboxylate (VIII),which is hydrolyzed and decarboxylated by treatment with KOH in refluxing propanol - water giving 1,3-dihydro-1-(4-piperidinyl)-5-chloro-2H-benzimidazol-2-one (IX).Finally this compound is condensed with 4,4-bis(p-fluorophenyl)butyl chloride (X) by means of NaHCO3 in refluxing ethanol.
参考文献标题:Clopimozide
文献作者:Castar,J.; Owen,R.T.
参考来源:Drugs Fut 1978,3(8),578
产品链接: CAS No. 53179-12-7››