Tonazocine mesylate, Win-421562
托那佐辛 Chemical Name: (?-(2alpha,6alpha,11S*)-1-(1,2,3,4,5,6-Hexahydro-8-hydroxy-3,6,11-trimethyl-2,6-methano-3-benzazocin-11-yl)-3-octanone methanesulfonate (salt); (?-1-[(2R*,6S*,11S*)]-1,2,3,4,5,6-Hexahydro-8-hydroxy-3,6,11-trimethyl-2,6-methano-3-benzazocin-11-yl)-3-octanone methanesulfonate (salt); (?-(2R*,6S*,11S*)-1,2,3,4,5,6-Hexahydro-8-hydroxy-3,6,11-trimethyl-11-(3-oxo-1-octyl)-2,6-methano-3-benzazocine methanesulfonate (salt)
CAS No. 73789-00-1, 71461-18-2 (free base)
项目整合开发状态: Phase II
项目研究机构: Sanofi-Aventis (Originator)
合成路线:The reaction of 4-methoxybenzylmagnesium bromide (I) with 1,3,4-trimethylpyridinium bromide (II) in ether,followed by a Diels-Alder condensation with ethyl acrylate (III) gives ethyl 3-(4-methoxybenzyl)-2,4,8-trimethyl-2-azabicyclo[2.2.2]oct-7-ene-6-carboxylate (IV),which is cyclized by means of HF yielding ethyl 1,2,3,4,4a,5,10,10a-octahydro-7-methoxy-1,4a,5-trimethyl-2,5-methanobenzo[g]quinoline-3-carboxylate (V).Acylation of (V) with hexanoyl chloride (VI) and butyllithium-diisopropylamine in THF affords the corresponding acyl derivative (VII),which is submitted to a reductive ring opening with formic acid in refluxing mesytilene giving 1,2,3,4,5,6-hexahydro-8-methoxy-3,6,11-trimethyl-11-(3-oxo-1-octyl)-2,6-methano-3-benzazocine (VIII).Finally,this compound is demethylated with 48% HBr and treated with methanesulfonic acid.
📌 参考资料/链接：
参考文献标题:Tonazocine mesylate
文献作者:Castar,J.; Serradell,M.N.
参考来源:Drugs Fut 1984,9(11),844
📄 详细内容
合成路线:The reaction of 4-methoxybenzylmagnesium bromide (I) with 1,3,4-trimethylpyridinium bromide (II) in ether,followed by a Diels-Alder condensation with ethyl acrylate (III) gives ethyl 3-(4-methoxybenzyl)-2,4,8-trimethyl-2-azabicyclo[2.2.2]oct-7-ene-6-carboxylate (IV),which is cyclized by means of HF yielding ethyl 1,2,3,4,4a,5,10,10a-octahydro-7-methoxy-1,4a,5-trimethyl-2,5-methanobenzo[g]quinoline-3-carboxylate (V).Acylation of (V) with hexanoyl chloride (VI) and butyllithium-diisopropylamine in THF affords the corresponding acyl derivative (VII),which is submitted to a reductive ring opening with formic acid in refluxing mesytilene giving 1,2,3,4,5,6-hexahydro-8-methoxy-3,6,11-trimethyl-11-(3-oxo-1-octyl)-2,6-methano-3-benzazocine (VIII).Finally,this compound is demethylated with 48% HBr and treated with methanesulfonic acid.
参考文献标题:2,6-Methano-3-benzazocin-11beta-yl)alkalones.1.Alkylalkalones: A new series of N-methyl derivatives with novel opiate activity profiles
文献作者:Michne,W.F.; Lewis,T.R.; Michalec,S.J.; Pierson,A.K.; Rosenberg,F.J.
参考来源:J Med Chem 1979,22(10),1158-63
合成路线:The reaction of 4-methoxybenzylmagnesium bromide (I) with 1,3,4-trimethylpyridinium bromide (II) in ether,followed by a Diels-Alder condensation with ethyl acrylate (III) gives ethyl 3-(4-methoxybenzyl)-2,4,8-trimethyl-2-azabicyclo[2.2.2]oct-7-ene-6-carboxylate (IV),which is cyclized by means of HF yielding ethyl 1,2,3,4,4a,5,10,10a-octahydro-7-methoxy-1,4a,5-trimethyl-2,5-methanobenzo[g]quinoline-3-carboxylate (V).Acylation of (V) with hexanoyl chloride (VI) and butyllithium-diisopropylamine in THF affords the corresponding acyl derivative (VII),which is submitted to a reductive ring opening with formic acid in refluxing mesytilene giving 1,2,3,4,5,6-hexahydro-8-methoxy-3,6,11-trimethyl-11-(3-oxo-1-octyl)-2,6-methano-3-benzazocine (VIII).Finally,this compound is demethylated with 48% HBr and treated with methanesulfonic acid.
参考文献标题:11-Substituted hexahydro-2,6-methano-3-benzazocines
文献作者:Michne,W.F.
参考来源:US 4255579
产品链接: CAS No. 73789-00-1›› 产品链接: CAS No.71461-18-2››