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【结 构 式】 
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【分子编号】33030 【品名】2-[2-(4-oxocyclohexyl)ethyl]-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile 【CA登记号】 |
【 分 子 式 】C18H22N2O 【 分 子 量 】282.38556 【元素组成】C 76.56% H 7.85% N 9.92% O 5.67% |
合成路线1
该中间体在本合成路线中的序号：(VIII)Swern oxidation of hydroxy ketal (V) led to aldehyde (VI), which was reductively condensed with tetrahydroquinoline (IV) in the presence of sodium triacetoxyborohydride to produce the N-alkylated quinoline (VII). Acid hydrolysis of the ethylene ketal of (VII) afforded the corresponding ketone (VIII). Subsequent reductive amination of (VIII) with ammonium acetate in the presence of sodium borohydride furnished the primary amine (IXa-b) as a mixture of cis and trans isomers. Coupling of (IXa-b) with indole-2-carboxylic acid (X) employing EDC and HOBt yielded the corresponding amide as a mixture of geometric isomers. The target trans isomer was finally isolated by chromatography on silica gel.
| 【1】 Branch, C.L.; Stemp, G.; Johnson, C.N. (SmithKline Beecham plc); Tetrahydroisoquinoline derivs. as modulators of dopamine D3 receptors. EP 0983244; WO 9850364 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IXa) | 33031 | 2-[2-(4-aminocyclohexyl)ethyl]-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile | C18H25N3 | 详情 | 详情 | |
| (IXb) | 33032 | 2-[2-(4-aminocyclohexyl)ethyl]-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile | C18H25N3 | 详情 | 详情 | |
| (IV) | 33026 | 1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile | C10H10N2 | 详情 | 详情 | |
| (V) | 33027 | 2-(1,4-dioxaspiro[4.5]dec-8-yl)-1-ethanol | C10H18O3 | 详情 | 详情 | |
| (VI) | 33028 | 2-(1,4-dioxaspiro[4.5]dec-8-yl)acetaldehyde | C10H16O3 | 详情 | 详情 | |
| (VII) | 33029 | 2-[2-(1,4-dioxaspiro[4.5]dec-8-yl)ethyl]-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile | C20H26N2O2 | 详情 | 详情 | |
| (VIII) | 33030 | 2-[2-(4-oxocyclohexyl)ethyl]-1,2,3,4-tetrahydro-7-isoquinolinecarbonitrile | C18H22N2O | 详情 | 详情 | |
| (X) | 25226 | 1H-Indole-2-carboxylic acid; Indole-2-carboxylic acid | 1477-50-5 | C9H7NO2 | 详情 | 详情 |