新产品编号:1663191
Chemical Name: 12-Amino-9-ethyl-3-methyl-6,7,10,11-tetrahydro-7(S),11(S)-methanocycloocta[b]quinoline
项目整合开发状态: Biological Testing
项目研究机构: Medichem (Originator)
合成路线:Condensation of diketone (I) with the organocerium reagent derived from ethylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-methylbenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-fluorobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-aminobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
📌 参考资料/链接：
参考文献标题:Polycyclic aminopyridine cpds.which are acetylcholinesterase inhibitors,process for preparing them and their use
文献作者:Contreras Lascorz,J.; El Achab,R.; Camps Garcia,P.; Ba駉s Diez,J.E.; Mu駉z-Torrero Lopez-Ibarra,D.; Badia Sancho,A.; Morral Cardoner,J.; Simon Fornell,M.; G鰎big Romeu,M.; Vivas,N.M.(Medichem SA)
参考来源:EP 0796849; ES 2100129; US 5965569; WO 9713754
📄 详细内容
合成路线:Condensation of diketone (I) with the organocerium reagent derived from ethylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-methylbenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-fluorobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-aminobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
参考文献标题:Synthesis,in vitro pharmacology,and molecular modeling of very potent tacrine - Huperzine A hybrids as acetylcholinesterase inhibitors of potential interest for the treatment of Alzheimer's disease
文献作者:Camps,P.; El Achad,R.; G鰎big,D.M.; Morral,J.; Munoz-Torrero,D.; Badia,A.; Eladi Banos,J.; Vivas,N.M.; Barril,X.; Orozco,M.; Luque,F.J.
参考来源:J Med Chem 1999,42(17),3227
合成路线:Condensation of diketone (I) with the organocerium reagent derived from ethylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-methylbenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-amino-4-fluorobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
合成路线:Condensation of diketone (I) with the organocerium reagent derived from methylmagnesium bromide and CeCl3 afforded the oxaadamantanol (II),which was further converted to mesylate (III) upon reaction with methanesulfonyl chloride and Et3N.Subsequent fragmentation of (III) by treatment with silica gel in CH2Cl2 produced bicyclic enone (IV).This was condensed with 2-aminobenzonitrile (V) in the presence of AlCl3 in refluxing 1,2-dichloroethane to furnish the target tetracyclic derivative.Resolution was then achieved by chiral MPLC.
参考文献标题:
文献作者:
参考来源:Tetrahedron 1996,51(16),5867-80