Pemedolac, AY-30715
右培美酸Chemical Name: (?-cis-4-Benzyl-1-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid
CAS No. 114716-16-4, 114030-45-4 ((-)-cis-isomer), 114030-44-3 ((+)-cis-isomer), 113975-74-9 ((?-trans-isomer), 103024-44-8 (undefined stereoch.)
项目整合开发状态: Phase II
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:This compound can be prepared by two related ways:1) The condensation of isatin (I) with methyl 3-phenylpropionate (II) by means of lithium diisopropylamide (LDA) in THF gives methyl alpha-benzyl-3 hydroxy-2-oxo-2,3-dihydro-1H-indole-3-acetate (III),which is reduced with LiAlH4 in THF to afford beta-benzylindole-3-ethanol (IV).The cyclization of (IV) with methyl propionylacetate (V) by means of boron trifluoride ethearate to toluene yields methyl 4-benzyl-1-ethyl 1,3,4,9 tetrahydropyrano[3,4-b]indole-1-acetate (VI),which is finally hydrolyzed with NaOH in refluxing ethanol.2) The alkylation of methyl indole-3-acetate (VII) with benzyl chloride (VIII) by means of LDA o THF gives methyl alpha-benzylindole-3-acetate (IX),which is reduced with LiAlH4 in THF to the alcohol (IV),already obtained.
📌 参考资料/链接：
参考文献标题:Substd.1,3,4,9-tetrahydropyrano[3,4-b]indole-1-ac
文献作者:Katz,A.H.; Demerson,C.A.; Humber,L.G.(American Home Products Corp.)
参考来源:EP 0238226; JP 1987221688; US 4670462; US 4775690
📄 详细内容
合成路线:This compound can be prepared by two related ways:1) The condensation of isatin (I) with methyl 3-phenylpropionate (II) by means of lithium diisopropylamide (LDA) in THF gives methyl alpha-benzyl-3 hydroxy-2-oxo-2,3-dihydro-1H-indole-3-acetate (III),which is reduced with LiAlH4 in THF to afford beta-benzylindole-3-ethanol (IV).The cyclization of (IV) with methyl propionylacetate (V) by means of boron trifluoride ethearate to toluene yields methyl 4-benzyl-1-ethyl 1,3,4,9 tetrahydropyrano[3,4-b]indole-1-acetate (VI),which is finally hydrolyzed with NaOH in refluxing ethanol.2) The alkylation of methyl indole-3-acetate (VII) with benzyl chloride (VIII) by means of LDA o THF gives methyl alpha-benzylindole-3-acetate (IX),which is reduced with LiAlH4 in THF to the alcohol (IV),already obtained.
参考文献标题:Pemedolac
文献作者:Castar,J.; Prous,J.
参考来源:Drugs Fut 1988,13(9),834
合成路线:This compound can be prepared by two related ways:1) The condensation of isatin (I) with methyl 3-phenylpropionate (II) by means of lithium diisopropylamide (LDA) in THF gives methyl alpha-benzyl-3 hydroxy-2-oxo-2,3-dihydro-1H-indole-3-acetate (III),which is reduced with LiAlH4 in THF to afford beta-benzylindole-3-ethanol (IV).The cyclization of (IV) with methyl propionylacetate (V) by means of boron trifluoride ethearate to toluene yields methyl 4-benzyl-1-ethyl 1,3,4,9 tetrahydropyrano[3,4-b]indole-1-acetate (VI),which is finally hydrolyzed with NaOH in refluxing ethanol.2) The alkylation of methyl indole-3-acetate (VII) with benzyl chloride (VIII) by means of LDA o THF gives methyl alpha-benzylindole-3-acetate (IX),which is reduced with LiAlH4 in THF to the alcohol (IV),already obtained.
参考文献标题:Synthesis and analgesic activity of pemedolac (cis-1-ethyl-1,3,4,9-tetrahydro-4-(phenylmethyl)pyrano[3,4-b]ind ole-1- acetic acid).
文献作者:Katz,A.H.; Demerson,C.A.; Shaw,C.C.; Asselin,A.A.; Humber,L.G.; Conway,K.M.; Gavin,G.; Guinosso,C.; Jensen,N.P.; Mobilio,D.; et al.
参考来源:J Med Chem 1988,31(6),1244
产品链接: CAS No. 114716-16-4›› 产品链接: CAS No.114030-44-3››