Trefentanil hydrochloride, ANQ-3665, A-3665
曲芬太尼 丙酰胺,N-[1-[2-(4-乙基-4,5-二氢-5-氧-1H-四唑-1-基)乙基]-4-苯基-4-哌啶基]-N-(2-氟苯基)-盐酸盐(1:1) Chemical Name: 1-[2-(4-Ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-[N-(2-fluorophenyl)propionamido]-4-phenylpiperidine hydrochloride; N-[1-[2-(4-Ethyl-5-oxo-4,5-dihydro-1H-tetrazol-1-yl)ethyl]-4-phenylpiperidin-4-yl]-N-(2-fluorophenyl)propionamide hydrochloride
CAS No. 120656-74-8 (free base), 120656-93-1 (monoHCl), 122823-06-7 (oxalate salt)
项目整合开发状态: Phase II
项目研究机构: Baxter (Originator), BOC (Originator)
合成路线:Condensation of 1-benzyl-4-piperidone (I) with 2-fluoroaniline (II) affords imine (III).Addition of phenyllithium (IV) to imine (III) gives amine (V),which is acylated with propionyl chloride and the resultant amide (VI) is debenzylated via 1-chloroethyl chloroformate in refluxing 1,2-dichloroethane followed by methanolysis to give (VII).Amine (VII)) is alkylated with 1-(2-bromoethyl)-4-ethyl-4,5-dihydro-1H-tetrazol-5-one(VIII) to yield A-3665.A-3665 hydrochloride is precipitated with dry HCl gas in ethyl ether.
📌 参考资料/链接：
参考文献标题:4-Phenyl-4-[N-(phenyl)amido]piperidine derivs.and pharmaceuticalcompsns.and methods employing such cpds
文献作者:Kudzma,L.V.; Spencer,H.K.; Severnak,S.A.(BOC Health Care,Inc.)
参考来源:AU 8824558; EP 0315405; JP 1990015061; JP 1990152963; US 4791121; US 4921864
📄 详细内容
合成路线:Condensation of 1-benzyl-4-piperidone (I) with 2-fluoroaniline (II) affords imine (III).Addition of phenyllithium (IV) to imine (III) gives amine (V),which is acylated with propionyl chloride and the resultant amide (VI) is debenzylated via 1-chloroethyl chloroformate in refluxing 1,2-dichloroethane followed by methanolysis to give (VII).Amine (VII)) is alkylated with 1-(2-bromoethyl)-4-ethyl-4,5-dihydro-1H-tetrazol-5-one(VIII) to yield A-3665.A-3665 hydrochloride is precipitated with dry HCl gas in ethyl ether.
参考文献标题:A-3665
文献作者:Kudzma,L.V.; Ossipov,M.H.; Benvenga,M.J.; Spaulding,T.C.; Rudo,F.G.
参考来源:Drugs Fut 1990,15(6),559
产品链接: CAS No. 120656-74-8›› 产品链接: CAS No.120656-93-1››