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【结 构 式】 
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【分子编号】60775 【品名】8-fluoro-5-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole 【CA登记号】 |
【 分 子 式 】C17H14F2N2 【 分 子 量 】284.3084464 【元素组成】C 71.82% H 4.96% F 13.36% N 9.85% |
合成路线1
该中间体在本合成路线中的序号：(VI)The chlorination of N,N-bis(4-fluorophenyl)urea (I) gives N,N-bis(4-fluorophenyl)-N'-chlorourea (II), which by reaction with sodium methoxide is converted into N,N-bis(4-fluorophenyl)-N-(methoxycarbony)hydrazine (III). Hydrolytic decarboxylation of (III) affords N,N-bis(4-fluorophenyl)hydrazine (IV), which is cyclocondensed with N-benzoyl-4-piperidone (V) yielding 8-fluoro-5-(4-fluorophenyl)-1,2,3,4-tetrahydro-gamma-carboline (VI). Finally this compound is condensed with 5-(4-fluorophenyl)-2-hydroxytetrahydrofuran (VII).
| 【1】 EP 900197 . |
| 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) | 60770 | N,N-bis(4-fluorophenyl)urea | C13H10F2N2O | 详情 | 详情 | |
| (II) | 60771 | N'-chloro-N,N-bis(4-fluorophenyl)urea | C13H9ClF2N2O | 详情 | 详情 | |
| (III) | 60772 | methyl 2,2-bis(4-fluorophenyl)-1-hydrazinecarboxylate | C14H12F2N2O2 | 详情 | 详情 | |
| (IV) | 60773 | 1,1-bis(4-fluorophenyl)hydrazine | C12H10F2N2 | 详情 | 详情 | |
| (V) | 60774 | 1-benzoyl-4-piperidinone | C12H13NO2 | 详情 | 详情 | |
| (VI) | 60775 | 8-fluoro-5-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | C17H14F2N2 | 详情 | 详情 | |
| (VII) | 60776 | 5-(4-fluorophenyl)tetrahydro-2-furanol | C10H11FO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)The cyclization of p-fluorophenylhydrazine (I) with 1-carbethoxy-4-piperidinone (II) in refluxing ethanol gives 2-carbethoxy-8-fluoro-1,2,3,4-tetrahydro-gamma-carboline (III), which is arylated with p-fluorobromobenzene (IV), by means of Na2CO3 - Cu2Br2 in N-methyl-2-pyrrolidinone heated at 200 C to yield 2-carbethoxy-8-fluoro-5-(p-fluorophenyl)-1,2,3,4-tetrahydro-gamma-carboline (V). The hydrolytic decarboxylation of (V) with KOH in refluxing ethanol affords 8-fluoro-5-(p-fluorophenyl)-1,2,3,4-tetrahydro-gamma-carboline (VI), which is alkylated with p-fluoro-gamma-bromobutyrophenone (VII) by means of Na2CO3 in hot DMF to give 8-fluoro-5-(p-fluorophenyl)-2-[4-(p-fluorophenyl)-4-oxobutyl]-1,2,3,4-tetrahydro-gamma-carboline (VIII). Finally this compound is reduced with NaBH4 in ethanol - THF
| 【1】 Harbert, C.A.; et al.; Neuroleptic activity in 5-aryl-tetrahydro-gamma-carbolines. J Med Chem 1980, 23, Suppl. 3, 635. |
| 【2】 Plattner, J.J.; et al. (Pfizer Inc.); US 4001263 . |
| 【3】 Blancafort, P.; Serradell, M.N.; Castaner, J.; Leeson, P.A.; Mealy, N.E.; Flutroline. Drugs Fut 1981, 6, 2, 84. |
| 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) | 22135 | 1-(4-fluorophenyl)hydrazine | 371-14-2 | C6H7FN2 | 详情 | 详情 |
| (II) | 13486 | Ethyl 4-oxo-1-piperidinecarboxylate; N-Carbethoxy-4-piperidone | 29976-53-2 | C8H13NO3 | 详情 | 详情 |
| (III) | 22137 | ethyl 8-fluoro-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate | C14H15FN2O2 | 详情 | 详情 | |
| (IV) | 29012 | 1-bromo-4-fluorobenzene | 460-00-4 | C6H4BrF | 详情 | 详情 |
| (V) | 60777 | ethyl 8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indole-2-carboxylate | C20H18F2N2O2 | 详情 | 详情 | |
| (VI) | 60775 | 8-fluoro-5-(4-fluorophenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole | C17H14F2N2 | 详情 | 详情 | |
| (VII) | 60778 | 4-bromo-1-(4-fluorophenyl)-1-butanone | C10H10BrFO | 详情 | 详情 | |
| (VIII) | 60779 | 4-[8-fluoro-5-(4-fluorophenyl)-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl]-1-(4-fluorophenyl)-1-butanone | C27H23F3N2O | 详情 | 详情 |