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【结 构 式】 
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【分子编号】12999 【品名】5-Methoxy-3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indole; Methyl 3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indol-5-yl ether 【CA登记号】 |
【 分 子 式 】C24H28N2O 【 分 子 量 】360.4992 【元素组成】C 79.96% H 7.83% N 7.77% O 4.44% |
合成路线1
该中间体在本合成路线中的序号：(I)By demethylation of 5-methoxy-3-[4-(4-phenyl-1,2,3,6-tetrahydropyridin-1-yl)butyl]-1H-indole (I) with diisobutylaluminum hydride (DBH) in hot toluene. The methylated compound (I) can be obtained by two similar ways: a) By condensation of 3-(4-chlorobutyl)-5-methoxy-1H-indole (II), or 3-(4-bromobutyl)-5-methoxy-1H-indole (III) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) in acetonitrile at room temperature. b) By condensation of 4-(3-indolyl)butyric acid (V) with 4-phenyl-1,2,3,6-tetrahydropyridine (IV) by means of carbonyldiimdazole (CDI) in THF yielding 1-[4-(3-indolyl)butyryl]-4-phenyl-1,2,3,6-tetrahydropyridine (VI), followed by reduction of the carbonyl group of (VI) with LiAlH4 in THF.
| 【1】 Robinson, C.; Castaner, J.; Roxindole Mesylate. Drugs Fut 1995, 20, 12, 1228. |
| 【2】 Hausberg, H.-H.; Bottcher, H.; Seyfried, C.; Bergmann, R. (Merck Patent GmbH); Use of hydroxyindole derivs. for the preparation of an antihypertensive agent. DE 3419935; EP 0166183; JP 1985258117; US 4711893 . |
| 【3】 Hausberg, H.-H.; Koppe, V.; Poetsch, E.; Saiko, O.; Seyfried, C. (Merck Patent GmbH); Indolalkylamines, pharmaceutical compsns. containing them and process for their preparation. EP 0007399 . |
| 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) | 12999 | 5-Methoxy-3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indole; Methyl 3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indol-5-yl ether | C24H28N2O | 详情 | 详情 | |
| (II) | 13000 | 3-(4-Chlorobutyl)-1H-indol-5-yl methyl ether; 3-(4-Chlorobutyl)-5-methoxy-1H-indole | C13H16ClNO | 详情 | 详情 | |
| (III) | 13001 | 3-(4-Bromobutyl)-1H-indol-5-yl methyl ether; 3-(4-Bromobutyl)-5-methoxy-1H-indole | C13H16BrNO | 详情 | 详情 | |
| (IV) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
| (V) | 13003 | 4-(5-Methoxy-1H-indol-3-yl)butyric acid | C13H15NO3 | 详情 | 详情 | |
| (VI) | 13004 | 4-(5-Methoxy-1H-indol-3-yl)-1-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]-1-butanone | C24H26N2O2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)A new synthesis of roxindole has been described: The condensation of 5-methoxyindole (I) with succinic anhydride (II) by means of methylmagnesium bromide in hot anisole gives the 4-oxobutyric acid derivative (III), which is condensed with the 4-phenyltetrahydropyridine (IV) by means of EDC and DIPEA in DMF yielding the butanedione (V). The reduction of (V) with LiAlH4 in refluxing THF affords intermediate (VI), which is finally demethylated with DIBAH in refluxing toluene.
| 【1】 Lange, J.H.M.; et al.; A straightforward synthetic approach for roxindole. Bioorg Med Chem Lett 1999, 9, 7, 1055. |
| 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) | 25902 | 1H-Indol-5-yl methyl ether; 5-Methoxy-1H-indole; 5-Methoxyindole | 1006-94-6 | C9H9NO | 详情 | 详情 |
| (II) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |
| (III) | 30614 | 4-(5-methoxy-1H-indol-3-yl)-4-oxobutyric acid | C13H13NO4 | 详情 | 详情 | |
| (IV) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
| (V) | 30615 | 1-(5-methoxy-1H-indol-3-yl)-4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]-1,4-butanedione | C24H24N2O3 | 详情 | 详情 | |
| (VI) | 12999 | 5-Methoxy-3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indole; Methyl 3-[4-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]butyl]-1H-indol-5-yl ether | C24H28N2O | 详情 | 详情 |