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【结 构 式】 
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【分子编号】26100 【品名】3-Carbethoxy-5-hydroxy-2-methylindole; 5-Hydroxy-2-methylindole-3-carboxylic acid ethyl ester; 5-Hydroxy-2-methyl-1H-indole-3-carboxylic acid ethyl ester 【CA登记号】7598-91-6 |
【 分 子 式 】C12H13NO3 【 分 子 量 】219.24016 【元素组成】C 65.74% H 5.98% N 6.39% O 21.89% |
合成路线1
该中间体在本合成路线中的序号：(I)Ethyl 5-hydroxy-2-methylindole (I) was dimethylated with iodomethane in the presence of KH to give (II). Nitration of (II) in AcOH afforded the 4-nitroindole (III) together with some 6-nitro isomer (IV), which were separated by column chromatography. Reduction of (III) with Sn and HCl yielded the 4-aminoindole (V). This was then oxidized with Fremy's salt to afford the corresponding indolequinone (VI) (1). Quinone (VI) was reduced to the hydroquinone (VII) with sodium dithionite, and this was further reduced with DIBAL-H to give, after oxidative work-up with FeCl3 to regenerate the quinone, the 3-(hydroxymethyl) indolequinone (VIII). Finally, substitution of the methoxy group of (VIII) with aziridine (IX) in DMF yielded the target compound (2).
| 【1】 Beall, H.D.; Winski, S.; Swann, E.; Hudnott, A.R.; Cotterill, A.S.; O'Sullivan, N.; Green, S.J.; Bien, R.; Siegel, D.; Ross, D.; Moody, C.J.; Indolequinone antitumor agents: Correlation between quinone structure, rate of metabolism by recombinant human NAD(P)H:quinone oxidoreductase, and in vitro cytotoxicity. J Med Chem 1998, 41, 24, 4755. |
| 【2】 Naylor, M.A.; et al.; Indolequinone antitumor agents: Reductive activation and elimination from (5-methoxy-1-methyl-4,7-dioxoindol-3-yl)methyl derivatives and hypoxia-selective cytotoxicity in vitro. J Med Chem 1998, 41, 15, 2720. |
| 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) | 26100 | 3-Carbethoxy-5-hydroxy-2-methylindole; 5-Hydroxy-2-methylindole-3-carboxylic acid ethyl ester; 5-Hydroxy-2-methyl-1H-indole-3-carboxylic acid ethyl ester | 7598-91-6 | C12H13NO3 | 详情 | 详情 |
| (II) | 26101 | ethyl 5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate | C14H17NO3 | 详情 | 详情 | |
| (III) | 26102 | ethyl 5-methoxy-1,2-dimethyl-4-nitro-1H-indole-3-carboxylate | C14H16N2O5 | 详情 | 详情 | |
| (IV) | 26103 | ethyl 5-methoxy-1,2-dimethyl-6-nitro-1H-indole-3-carboxylate | C14H16N2O5 | 详情 | 详情 | |
| (V) | 26104 | ethyl 4-amino-5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate | C14H18N2O3 | 详情 | 详情 | |
| (VI) | 26105 | ethyl 5-methoxy-1,2-dimethyl-4,7-dioxo-4,7-dihydro-1H-indole-3-carboxylate | C14H15NO5 | 详情 | 详情 | |
| (VII) | 26106 | ethyl 4,7-dihydroxy-5-methoxy-1,2-dimethyl-1H-indole-3-carboxylate | C14H17NO5 | 详情 | 详情 | |
| (VIII) | 26107 | 3-(hydroxymethyl)-5-methoxy-1,2-dimethyl-1H-indole-4,7-dione | C12H13NO4 | 详情 | 详情 | |
| (IX) | 10151 | Ethyleneimine; Aziridine; Azirane | 151-56-4 | C2H5N | 详情 | 详情 |