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【结 构 式】 
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【药物名称】Pemedolac, AY-30715 【化学名称】(±)-cis-4-Benzyl-1-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indole-1-acetic acid 【CA登记号】114716-16-4, 114030-45-4 ((-)-cis-isomer), 114030-44-3 ((+)-cis-isomer), 113975-74-9 ((±)-trans-isomer), 103024-44-8 (undefined 【 分 子 式 】C22H23NO3 【 分 子 量 】349.43351 |
【开发单位】Wyeth Pharmaceuticals (Originator) 【药理作用】ANALGESIC AND ANESTHETIC DRUGS, Analgesic Drugs, Non-Opioid Analgesics, Non-Steroidal Antiinflammatory Drugs |
合成路线1
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.
| 【1】 Gavin, G.; Katz, A.H.; Conway, K.M.; Asselin, A.A.; Demerson, C.A.; Guinoso, C.; Shah, V.; Mobilio, D.; Noureldin, R.; Humber, L.G.; Chau, T.T.; Jensen, N.P.; Schimid, J.; Shaw, C.-C.; Weichman, B.M.; Van Engen, D.; Synthesis and analgesic activity of pemedolac (cis. J Med Chem 1988, 31, 6, 1244. |
| 【2】 Katz, A.H.; Demerson, C.A.; Humber, L.G. (American Home Products Corp.); Substd. 1,3,4,9-tetrahydropyrano[3,4-b]indole-1-ac. EP 0238226; JP 1987221688; US 4670462; US 4775690 . |
| 【3】 Castaner, J.; Prous, J.; Pemedolac. Drugs Fut 1988, 13, 9, 834. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 14098 | 2,3-Indolinedione; 1H-Indole-2,3-dione; Isatin | 91-56-5 | C8H5NO2 | 详情 | 详情 |
| (II) | 23523 | methyl 3-phenylpropanoate | 103-25-3 | C10H12O2 | 详情 | 详情 |
| (III) | 23524 | methyl 2-(3-hydroxy-2-oxo-2,3-dihydro-1H-indol-3-yl)-3-phenylpropanoate | C18H17NO4 | 详情 | 详情 | |
| (IV) | 23525 | 2-(1H-indol-3-yl)-3-phenyl-1-propanol | C17H17NO | 详情 | 详情 | |
| (V) | 15536 | methyl 3-oxopentanoate | 30414-53-0 | C6H10O3 | 详情 | 详情 |
| (VI) | 23527 | methyl 2-(4-benzyl-1-ethyl-1,3,4,9-tetrahydropyrano[3,4-b]indol-1-yl)acetate | C23H25NO3 | 详情 | 详情 | |
| (VII) | 23528 | 2-(1H-Indol-3-yl)acetic acid methyl ester | 1912-33-0 | C11H11NO2 | 详情 | 详情 |
| (VIII) | 19171 | 1-(Chloromethyl)benzene; Benzyl chloride | 100-44-7 | C7H7Cl | 详情 | 详情 |
| (IX) | 23529 | methyl 2-(1H-indol-3-yl)-3-phenylpropanoate | C18H17NO2 | 详情 | 详情 |