Vanoxerine hydrochloride, I-893, GBR-12909, -Drug Synthesis Database

【结构式】

【药物名称】Vanoxerine hydrochloride, I-893, GBR-12909

【化学名称】1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine dihydrochloride

【CA登记号】67469-69-6 (free base)

【分子式】C₂₈H₃₄Cl₂F₂N₂O

【分子量】523.49878

【开发单位】Yamanouchi (Originator), National Institutes of Health (Licensee)

【药理作用】Treatment of Cocaine Dependency, TREATMENT OF POISONING, DRUG ABUSE & DEPENDENCY, Treatment of Substance Dependency, Dopamine Reuptake Inhibitors

合成路线1 合成路线2

合成路线1

Condensation of bis(4-fluorophenyl)methyl 2-chloroethyl ether (I) with piperazine (II) in refluxing toluene afforded the monosubstituted piperazine (III). This was then alkylated with (3-bromopropyl)benzene (IV) in boiling EtOH to furnish the title compound.

参考文献中间体

【1】 Gootjes, J. (Gist-Brocades NV); Piperazine derivs., process for their preparation and their use. DE 2755752; US 4202896 .
【2】 Van der Zee, P.; et al.; Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 1980, 15, 4, 363.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	54931	1-[(2-chloroethoxy)(4-fluorophenyl)methyl]-4-fluorobenzene; bis(4-fluorophenyl)methyl 2-chloroethyl ether		C₁₅H₁₃ClF₂O	详情	详情
(II)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(III)	54932	1-{2-[bis(4-fluorophenyl)methoxy]ethyl}piperazine; bis(4-fluorophenyl)methyl 2-(1-piperazinyl)ethyl ether		C₁₉H₂₂F₂N₂O	详情	详情
(IV)	20884	1-(3-bromopropyl)benzene	637-59-2	C₉H₁₁Br	详情	详情

合成路线2

1-(3-Phenylpropyl)piperazine (III) has been obtained by condensation of 3-phenylpropyl bromide (I) with piperazine (II) in refluxing acetonitrile. The condensation of bis(4-fluorophenyl)methanol (IV) with 2-chloroethanol (V) by means of sulfuric acid gives the 2-chloroethyl bis(4-fluorophenyl)methyl ether (VI), which si treated with NaI to yield the corresponding iodo derivative (VII). Finally this compound is condensed with the intermediate piperazine (III) by means of aq. Na2CO3 to afford the target disubstituted piperazine.

参考文献中间体

【1】 Zhang, J.; Ironside, M.D.; Sugathapala, P.M.; Robertson, J.; Darey, M.C.P.; Scale-up synthesis of the dopamine uptake inhibitor GBR-12909. Org Process Res Dev 2002, 6, 5, 621.

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(I)	20884	1-(3-bromopropyl)benzene	637-59-2	C₉H₁₁Br	详情	详情
(II)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(III)	38636	1-(3-phenylpropyl)piperazine		C₁₃H₂₀N₂	详情	详情
(IV)	41974	4,4'-Difluorobenzhydrol; bis(4-Fluorophenyl)methanol; alpha-(4-fluorophenyl)benzenemethanol; 4-fluoro-alpha-(4-fluorophenyl)benzenemethanol	365-24-2	C₁₃H₁₀F₂O	详情	详情
(V)	10384	2-Chloro-1-ethanol; Ethylene chlorohydrin	107-07-3	C₂H₅ClO	详情	详情
(VI)	54931	1-[(2-chloroethoxy)(4-fluorophenyl)methyl]-4-fluorobenzene; bis(4-fluorophenyl)methyl 2-chloroethyl ether		C₁₅H₁₃ClF₂O	详情	详情
(VII)	56868	bis(4-fluorophenyl)methyl 2-iodoethyl ether; 1-fluoro-4-[(4-fluorophenyl)(2-iodoethoxy)methyl]benzene		C₁₅H₁₃F₂IO	详情	详情

Extended Information