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【结 构 式】 
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【分子编号】26532 【品名】Indole-3-butyric acid; 4-(3-Indolyl)butyric acid; 4-(1H-Indol-3-yl)butyric acid 【CA登记号】133-32-4 |
【 分 子 式 】C12H13NO2 【 分 子 量 】203.24076 【元素组成】C 70.92% H 6.45% N 6.89% O 15.74% |
合成路线1
该中间体在本合成路线中的序号：(I)The reaction of 4-(3-indolyl)butyric acid (I) with 4-phenyl-3,4-dehydropiperidine (II) by means of carbonyldiimidazole (A) in THF gives 3-[4-oxo-4-(4-phenyl-3,4-dehydro-1-piperidyl)butyl]indole (III), which is reduced with LiAlH4 in THF.
| 【1】 Hausberg, H.H.; Koppe, V.; Poetsch, E.; Saiko, O.; Seyfried, C.; US 4251538 . |
| 【2】 Blancafort, P.; Hillier, K.; Serradell, M.N.; Castaner, J.; EMD-23,448. Drugs Fut 1983, 8, 5, 400. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 11353 | 1,1'-Carbonyldiimidazole; Di(1H-imidazol-1-yl)methanone; N,N-Carbonyldiimidazole; 1,1'-Carbonylbis(1H-imidazole) | 530-62-1 | C7H6N4O | 详情 | 详情 |
| (I) | 26532 | Indole-3-butyric acid; 4-(3-Indolyl)butyric acid; 4-(1H-Indol-3-yl)butyric acid | 133-32-4 | C12H13NO2 | 详情 | 详情 |
| (II) | 13002 | 4-Phenyl-1,2,3,6-tetrahydropyridine; 1,2,3,6-Tetrahydro-4-phenyl-pyridine | 10338-69-9 | C11H13N | 详情 | 详情 |
| (III) | 36089 | 4-(1H-indol-3-yl)-1-[4-phenyl-3,6-dihydro-1(2H)-pyridinyl]-1-butanone | C23H24N2O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Cyclization of m-cresol (I) with ethyl 2-oxocyclohexanecarboxylate (II) in H2SO4 afforded tricyclic benzopyranone (III). This was treated with MeMgBr in boiling anisole to provide the tricyclic dimethylbenzopyran (IV). Dehydrogenation of (IV) using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone gave dibenzopyran (V), which by further bromination with N-bromosuccinimide and 2,2'-azobis(4-methoxy-2,4-dimethylvaleronitrile) produced bromide (VI). Finally, N-alkylation of 4-(3-indolyl)butyric acid (VII) with bromide (VI) in the presence of two equivalents of NaH yielded the title compound.
| 【1】 Sawada, K.; Hirai, H.; Golden, P.; Okada, S.; Sawada, Y.; Hashimoto, M.; Tanaka, H.; (1-Benzylindole-3-yl)-alkanoic acids; novel nonsteroidal inhibitors of steroid 5alpha-reductase (I). Chem Pharm Bull 1998, 46, 11, 1683. |
| 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) | 17793 | m-cresol; m-Methylphenol | 108-39-4 | C7H8O | 详情 | 详情 |
| (II) | 11889 | ethyl 2-oxocyclohexanecarboxylate; Ethyl 2-cyclohexanonecarboxylate | 1655-07-8 | C9H14O3 | 详情 | 详情 |
| (III) | 26528 | 3-methyl-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one | C14H14O2 | 详情 | 详情 | |
| (IV) | 26529 | 3,6,6-trimethyl-7,8,9,10-tetrahydro-6H-benzo[c]chromene | C16H20O | 详情 | 详情 | |
| (V) | 26530 | 3,6,6-trimethyl-6H-benzo[c]chromene | C16H16O | 详情 | 详情 | |
| (VI) | 26531 | 3-(bromomethyl)-6,6-dimethyl-6H-benzo[c]chromene | C16H15BrO | 详情 | 详情 | |
| (VII) | 26532 | Indole-3-butyric acid; 4-(3-Indolyl)butyric acid; 4-(1H-Indol-3-yl)butyric acid | 133-32-4 | C12H13NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(I)3-Indolebutyric acid (I) was activated as the hydroxamate (II) by coupling with N,O-dimethylhydroxylamine in the presence of EDC and DMAP. Addition of cyclopentenylmagnesium bromide (III) to hydroxamate (II) furnished the unsaturated ketone (IV). Then, Michael addition of coenzyme A (V) to the unsaturated ketone (IV) in the presence of triethylammonium bicarbonate buffer provided the desired adduct.
| 【1】 Cole, P.A.; Kim, C.M.; Bisubstrate ketone analogues as serotonin N-acetyltransferase inhibitors. J Med Chem 2001, 44, 15, 2479. |
| 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) | 26532 | Indole-3-butyric acid; 4-(3-Indolyl)butyric acid; 4-(1H-Indol-3-yl)butyric acid | 133-32-4 | C12H13NO2 | 详情 | 详情 |
| (II) | 50653 | 4-(1H-indol-3-yl)-N-methoxy-N-methylbutanamide | C14H18N2O2 | 详情 | 详情 | |
| (III) | 50654 | bromo(1-cyclopenten-1-yl)magnesium | C5H7BrMg | 详情 | 详情 | |
| (IV) | 50655 | 1-(1-cyclopenten-1-yl)-4-(1H-indol-3-yl)-1-butanone | C17H19NO | 详情 | 详情 | |
| (V) | 50656 | C21H34N7O16P3S | 详情 | 详情 |