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【结 构 式】 
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【分子编号】50432 【品名】1-ethyl-2-(hydroxymethyl)-1H-indole-6-carbonitrile 【CA登记号】 |
【 分 子 式 】C12H12N2O 【 分 子 量 】200.24016 【元素组成】C 71.98% H 6.04% N 13.99% O 7.99% |
合成路线1
该中间体在本合成路线中的序号：(VI)Electrophilic nitration of p-tolunitrile (I) afforded the 3-nitro derivative (II), which was condensed with diethyl oxalate in the presence of sodium ethoxide to produce the sodium enolate of the alpha-keto ester (III). Compound (III) was then subjected to Reissert indole synthesis by means of Zn and HOAc to furnish ethyl 6-cyanoindole-2-carboxylate (IV). N-alkylation of indole (IV) with iodoethane and NaH in DMF gave (V), whose carboxylate group was reduced to alcohol (VI) employing in situ-generated calcium borohydride (obtained from NaBH4 and CaI2 in THF in the presence of NaHCO3). Treatment of alcohol (VI) with PBr3 in methylene chloride yielded the corresponding bromide (VII), which was then converted into the phosphonium salt (VIII) by means of triphenylphosphine in refluxing toluene.
| 【1】 Koo, B.A.; Min, J.K.; Hong, W.S.; Ryu, E.J.; Nam, W.H.; Kim, J.M. (C & C Research Laboratories); Aromatic amidine derivs. useful as selective thrombin inhibitors. EP 0918768; JP 2000504030; US 6201006; WO 9745424 . |
| 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) | 15458 | 4-methylbenzonitrile; p-tolunitrile | 104-85-8 | C8H7N | 详情 | 详情 |
| (II) | 50428 | 4-methyl-3-nitrobenzonitrile | C8H6N2O2 | 详情 | 详情 | |
| (III) | 50429 | sodium (Z)-1-(4-cyano-2-nitrophenyl)-3-ethoxy-3-oxo-1-propen-2-olate | C12H9N2NaO5 | 详情 | 详情 | |
| (IV) | 50430 | ethyl 6-cyano-1H-indole-2-carboxylate | C12H10N2O2 | 详情 | 详情 | |
| (V) | 50431 | ethyl 6-cyano-1-ethyl-1H-indole-2-carboxylate | C14H14N2O2 | 详情 | 详情 | |
| (VI) | 50432 | 1-ethyl-2-(hydroxymethyl)-1H-indole-6-carbonitrile | C12H12N2O | 详情 | 详情 | |
| (VII) | 50433 | 2-(bromomethyl)-1-ethyl-1H-indole-6-carbonitrile | C12H11BrN2 | 详情 | 详情 | |
| (VIII) | 50434 | [(6-cyano-1-ethyl-1H-indol-2-yl)methyl](triphenyl)phosphonium bromide | C30H26BrN2P | 详情 | 详情 |