Lesopitron dihydrochloride, E-4424
来索吡琼 Chemical Name: 2-[4-[4-(4-Chloropyrazol-1-yl)butyl]piperazin-1-yl]pyrimidine dihydrochloride
CAS No. 132449-89-9, 132449-46-8 (free base), 132449-88-8 (monoHCl)
项目整合开发状态: Phase II
项目研究机构: Esteve (Originator)
合成路线:Lesopitron dihydrochloride was obtained following two related procedures.1) Reaction of 4-chloropyrazole (I) with 1,4-dibromobutane (II) gives 1-(4-bromobutyl)-4-chloropyrazole (III).Compound (III) is refluxed with 2-(1-piperazinyl)pyrimidine (IV) and potassium carbonate in DMF to give lesopitron (V),which is treated with isopropyl alcohol saturated with hydrochloric acid to pH 4.5-5 .2) 2-(1-Piperazinyl)pyrimidine (IV) reacts with 1,4-dibromobutane (II) to yield 8-(2-pyrimidinyl)-8-aza-5-azoniaspiro[4.5]decane bromide (VI).The quaternary salt (VI) undergoes reaction with 4-chloropyrazole (I) in DMF in the presence of potassium carbonate to afford the free base.
📌 参考资料/链接：
参考文献标题:Process for the preparation of aryl (or heteroaryl) piperazinylbutylazole derivs
文献作者:Merce-Vidal,R.; Frigola-Constansa,J.; Pares-Corominas,J.(Laboratorios del Dr.Esteve,SA)
参考来源:AU 9211429; CA 2062468; EP 0502786; ES 2036145; FR 2673628; JP 1993078313; NO 9200888; US 5227486; ZA 9201682
📄 详细内容
合成路线:Lesopitron dihydrochloride was obtained following two related procedures.1) Reaction of 4-chloropyrazole (I) with 1,4-dibromobutane (II) gives 1-(4-bromobutyl)-4-chloropyrazole (III).Compound (III) is refluxed with 2-(1-piperazinyl)pyrimidine (IV) and potassium carbonate in DMF to give lesopitron (V),which is treated with isopropyl alcohol saturated with hydrochloric acid to pH 4.5-5 .2) 2-(1-Piperazinyl)pyrimidine (IV) reacts with 1,4-dibromobutane (II) to yield 8-(2-pyrimidinyl)-8-aza-5-azoniaspiro[4.5]decane bromide (VI).The quaternary salt (VI) undergoes reaction with 4-chloropyrazole (I) in DMF in the presence of potassium carbonate to afford the free base.
参考文献标题:Lesopitron Dihydrochloride
文献作者:Frigola,J.; Farr? A.
参考来源:Drugs Fut 1994,19(7),651