【药物名称】Pemedolac, AY-30715
化学结构式(Chemical Structure):
参考文献No.6956
标题:Substd. 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-ac
作者:Katz, A.H.; Demerson, C.A.; Humber, L.G. (American Home Products Corp.)
来源:EP 0238226; JP 1987221688; US 4670462; US 4775690
合成路线图解说明:

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No.63038
标题:Pemedolac
作者:Casta馿r, J.; Prous, J.
来源:Drugs Fut 1988,13(9),834
合成路线图解说明:

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No.547117
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).
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.
来源:J Med Chem 1988,31(6),1244
合成路线图解说明:

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.

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