|
【结 构 式】 
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【分子编号】28203 【品名】2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane 【CA登记号】3308-94-9 |
【 分 子 式 】C12H14ClFO2 【 分 子 量 】244.6930632 【元素组成】C 58.9% H 5.77% Cl 14.49% F 7.76% O 13.08% |
合成路线1
该中间体在本合成路线中的序号：(XVI)The condensation of 4-methoxybenzylmagnesium chloride (I) with 3,4-dimethylpyridine methiodide (II) gives N,3,4-trimethyl-2-(p-methoxybenzyl)-1,2-dihydropyridine (III), which by partial reduction with NaBH4 in methanol is converted into the corresponding 1,2,5,6-tetrahydro derivative (IV). The cyclization of (IV) by refluxing with AlBr3 in CS2 yields 2,5,9-trimethyl-2'-hydroxy-7-benzomorphane (V), which is acetylated with acetic anhydride to the acetoxy compound (VI) and treated with BrCN in refluxing CHCl3 to afford the N-cyano compound (VII). This compound is refluxed with 6% HCl yielding 5,9-dimethyl-2'-hydroxy-6,7-benzomorphane (VIII) , which is condensed with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) by means of NaHCO3 in DMF at 140 C to afford the corresponding N-alkyl derivative (IX). Finally, this compound is hydrolyzed by refluxing with diluted aqueous HCl.
| 【1】 Atsumi, T.; et al.; JP 7319314 . |
| 【2】 Atsumi, T.; et al.; JP 7343352 . |
| 【3】 Yamamoto, H.; et al.; The synthesis and pharmacology of a new analgesic, ID-1229. Arzneim-Forsch Drug Res 1975, 25, 5, 795-801. |
| 【4】 Atsumi, T.; et al. (Sumitomo Chemical Co., Ltd.); Novel benzomorphan and their salts as analgesics. US 3873706 . |
| 【5】 Castaner, J.; Paton, D.M.; ID-1229. Drugs Fut 1978, 3, 4, 298. |
| 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) | 39855 | chloro(4-methoxybenzyl)magnesium | C8H9ClMgO | 详情 | 详情 | |
| (II) | 39856 | 1,3,4-trimethylpyridinium iodide | C8H12IN | 详情 | 详情 | |
| (III) | 39857 | methyl 4-[(1,3,4-trimethyl-1,2-dihydro-2-pyridinyl)methyl]phenyl ether; 2-(4-methoxybenzyl)-1,3,4-trimethyl-1,2-dihydropyridine | C16H21NO | 详情 | 详情 | |
| (IV) | 39858 | 6-(4-methoxybenzyl)-1,4,5-trimethyl-1,2,3,6-tetrahydropyridine; methyl 4-[(1,3,4-trimethyl-1,2,5,6-tetrahydro-2-pyridinyl)methyl]phenyl ether | C16H23NO | 详情 | 详情 | |
| (V) | 39859 | (1R,9R,13R)-1,10,13-trimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-ol | C15H21NO | 详情 | 详情 | |
| (VI) | 39860 | (1R,9R,13R)-1,10,13-trimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-yl acetate | C17H23NO2 | 详情 | 详情 | |
| (VII) | 39861 | (1R,9R,13R)-10-cyano-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-yl acetate | C17H20N2O2 | 详情 | 详情 | |
| (VIII) | 36016 | (1R,9R,13R)-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-ol | C14H19NO | 详情 | 详情 | |
| (IX) | 39862 | (1R,9R,13R)-10-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-methoxy-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-triene; (1R,9R,13R)-10-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-1,13-dimethyl-10-azatricyclo[7.3.1.0(2,7)]trideca-2,4,6-trien-4-yl methyl ether | C27H34FNO3 | 详情 | 详情 | |
| (XVI) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XVI)The condensation of 3,4-dimethylpyridine (XV) with 4-(p-fluorophenyl)-4,4-ethylenedioxy-1-chlorobutane (XVI) gives the corresponding pyridinium salt (XVII), which by reaction with p-methoxybenzylmagnesium chloride (I) in ether yields the dihydropyridine (XVIII). The reduction of (XVIII) with NaBH4 in methanol affords the tetrahydropyridine (XIX), which is finally cyclized by refluxing with AlBr3 in CS2; this reaction can also be performed by heating (XIX) with 48% aqueous HBr at 130 C.
| 【1】 Atsumi, T.; et al. (Sumitomo Chemical Co., Ltd.); Preparation of 2-benzoylalkylbenzomorphan. DE 2128525; FR 2100743; GB 1329504; US 3953441 . |
| 【2】 Castaner, J.; Paton, D.M.; ID-1229. Drugs Fut 1978, 3, 4, 298. |
| 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) | 39855 | chloro(4-methoxybenzyl)magnesium | C8H9ClMgO | 详情 | 详情 | |
| (XV) | 39869 | 3,4-dimethylpyridine | 583-58-4 | C7H9N | 详情 | 详情 |
| (XVI) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (XVII) | 39870 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-3,4-dimethylpyridinium chloride | C19H23ClFNO2 | 详情 | 详情 | |
| (XVIII) | 39871 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-2-(4-methoxybenzyl)-3,4-dimethyl-1,2-dihydropyridine; 4-[(1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-3,4-dimethyl-1,2-dihydro-2-pyridinyl)methyl]phenyl methyl ether | C27H32FNO3 | 详情 | 详情 | |
| (XIX) | 39872 | 1-(4-fluorophenyl)-4-[6-(4-methoxybenzyl)-4,5-dimethyl-3,6-dihydro-1(2H)-pyridinyl]-1-butanone | C25H30FNO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(II)The reaction of 4-chloro-1-(4-fluorophenyl)-1-butanone (I) with ethylene glycol and p-toluenesulfonic acid in refluxing benzene gives the corresponding ethyleneketal (II), which is condensed with 4-hydroxypiperidine (III) by means of K2CO3 in hot DMF yielding 1-(4-fluorophenyl)-4-(4-hydroxypiperidin-1-yl)-1-butanone ethyleneketal (IV). The Oppenauer oxidation of (IV) with 9-fluorenone and potassium tert-butoxide in hot benzene affords the piperidinone (V), which is condensed with 4-bromo-N-(trimethylsilyl)aniline (VI) by means of BuLi in hot hexane to give 4-[4-(4-aminophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-1-butanone (VII). Finally, this compound is treated with CuBr2 and NO in THF.
| 【1】 Vincent, S.H.; et al.; Synthesis of [82Br]bromperidol and preliminary tissue distribution studies in the rat. J Med Chem 1980, 23, 1, 75. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 | |
| (I) | 35864 | 4-chloro-1-(4-fluorophenyl)-1-butanone | 3874-54-2 | C10H10ClFO | 详情 | 详情 |
| (II) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (III) | 12076 | 4-Piperidinol; 4-Hydroxypiperidine | 5382-16-1 | C5H11NO | 详情 | 详情 |
| (IV) | 35865 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinol | C17H24FNO3 | 详情 | 详情 | |
| (V) | 35866 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinone | C17H22FNO3 | 详情 | 详情 | |
| (VI) | 35867 | N-(4-bromophenyl)(trimethyl)silanamine; N-(4-bromophenyl)-N-(trimethylsilyl)amine | C9H14BrNSi | 详情 | 详情 | |
| (VII) | 35868 | 4-[4-(4-aminophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone | C21H25FN2O2 | 详情 | 详情 | |
| (VIII) | 22531 | 4-Bromoaniline; 4-Bromophenylamine | 106-40-1 | C6H6BrN | 详情 | 详情 |
| (IX) | 35869 | C6H5Br2MgN | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(II)The reaction of 4-chloro-1-(4-fluorophenyl)-1-butanone (I) with ethylene glycol and p-toluenesulfonic acid in refluxing benzene gives the corresponding ethyleneketal (II), which is condensed with 4-(chlorophenyl)-4-hydroxypiperidine (VIII) by means of K2CO3 in hot DMF yielding 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-1-butanone ethyleneketal (IX). The reaction of (IX) with HCl in methanol yields the corresponding free butanone (X), which is treated with trimethylstannyl sodium in glyme to afford the expected stannyl derivative (XI). Finally, this compound is treated with Br2 in chloroform.
| 【1】 Moerlein, S.M.; Stocklin, G.L.; Synthesis of high specific activity [75Br]- and [77Br]-bromperidol and tissue distribution studies in the rat. J Med Chem 1985, 28, 9, 1319. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 | |
| (I) | 35864 | 4-chloro-1-(4-fluorophenyl)-1-butanone | 3874-54-2 | C10H10ClFO | 详情 | 详情 |
| (II) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (III) | 35870 | 4-(4-chlorophenyl)-4-piperidinol; 4-(4-Chlorophenyl)-4-hydroxypiperidine | 39512-49-7 | C11H14ClNO | 详情 | 详情 |
| (IX) | 35871 | 4-(4-chlorophenyl)-1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinol | C23H27ClFNO3 | 详情 | 详情 | |
| (X) | 35872 | 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone | 52-86-8 | C21H23ClFNO2 | 详情 | 详情 |
| (XI) | 35873 | 1-(4-fluorophenyl)-4-[4-hydroxy-4-[4-(trimethylstannyl)phenyl]-1-piperidinyl]-1-butanone | C24H32FNO2Sn | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(II)The reaction of 4-chloro-1-(4-fluorophenyl)-1-butanone (I) with ethylene glycol and p-toluenesulfonic acid in refluxing benzene gives the corresponding ethylene-ketal (II), which is condensed with 4-hydroxypiperidine (III) by means of K2CO3 in hot DMF yielding 1-(4-fluorophenyl)-4-(4-hydroxypiperidin-1-yl)-1-butanone ethyle-neketal (IV). The Oppenauer oxidation of (IV) with 9-fluorenone and potassium tert-butoxide in hot benzene affords the piperidinone (V), which is condensed with 4-bromo-N-(trimethylsilyl)aniline (VI) by means of BuLi in hot hexane to give 4-[4-(4-aminophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-1-butanone (VII). Finally, this compound is treated with Cu82Br2 and NO in THF.
| 【1】 Vincent, S.H.; et al.; Synthesis of [82Br]bromperidol and preliminary tissue distribution studies in the rat. J Med Chem 1980, 23, 1, 75. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 | |
| (I) | 35864 | 4-chloro-1-(4-fluorophenyl)-1-butanone | 3874-54-2 | C10H10ClFO | 详情 | 详情 |
| (II) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (III) | 12076 | 4-Piperidinol; 4-Hydroxypiperidine | 5382-16-1 | C5H11NO | 详情 | 详情 |
| (IV) | 35865 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinol | C17H24FNO3 | 详情 | 详情 | |
| (V) | 35866 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinone | C17H22FNO3 | 详情 | 详情 | |
| (VI) | 35867 | N-(4-bromophenyl)(trimethyl)silanamine; N-(4-bromophenyl)-N-(trimethylsilyl)amine | C9H14BrNSi | 详情 | 详情 | |
| (VII) | 35868 | 4-[4-(4-aminophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone | C21H25FN2O2 | 详情 | 详情 | |
| (VIII) | 22531 | 4-Bromoaniline; 4-Bromophenylamine | 106-40-1 | C6H6BrN | 详情 | 详情 |
| (IX) | 35869 | C6H5Br2MgN | 详情 | 详情 |
合成路线6
该中间体在本合成路线中的序号：(II)The reaction of 4-chloro-1-(4-fluorophenyl)-1-butanone (I) with ethylene glycol and p-toluenesulfonic acid in refluxing benzene gives the corresponding ethylene-ketal (II), which is condensed with 4-(chlorophenyl)-4-hydroxypiperidine (III) by means of K2CO3 in hot DMF yielding 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)-1-butanone ethyleneketal (IV). The reaction of (IV) with HCl in methanol yields the corresponding free butanone (V), which is treated with trimethylstannyl sodium in glyme to afford the expected stannyl derivative (VI). Finally, this compound is treated with 75Br2 or 77Br2 and dichloramin T in methanol or H2O2 in acetic acid.
| 【1】 Moerlein, S.M.; Stocklin, G.L.; Synthesis of high specific activity [75Br]- and [77Br]-bromperidol and tissue distribution studies in the rat. J Med Chem 1985, 28, 9, 1319. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 11295 | Polyethylene glycol;1,2-Ethanediol;Monoethylene glycol; Ethylene glycol | 107-21-1 | C2H6O2 | 详情 | 详情 | |
| (I) | 35864 | 4-chloro-1-(4-fluorophenyl)-1-butanone | 3874-54-2 | C10H10ClFO | 详情 | 详情 |
| (II) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (III) | 35870 | 4-(4-chlorophenyl)-4-piperidinol; 4-(4-Chlorophenyl)-4-hydroxypiperidine | 39512-49-7 | C11H14ClNO | 详情 | 详情 |
| (IV) | 35871 | 4-(4-chlorophenyl)-1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-4-piperidinol | C23H27ClFNO3 | 详情 | 详情 | |
| (V) | 35872 | 4-[4-(4-chlorophenyl)-4-hydroxy-1-piperidinyl]-1-(4-fluorophenyl)-1-butanone | 52-86-8 | C21H23ClFNO2 | 详情 | 详情 |
| (VI) | 35873 | 1-(4-fluorophenyl)-4-[4-hydroxy-4-[4-(trimethylstannyl)phenyl]-1-piperidinyl]-1-butanone | C24H32FNO2Sn | 详情 | 详情 |
合成路线7
该中间体在本合成路线中的序号：(VI)The reaction of 2-chloro-5-fluoro-4-(methylsulfanyl)pyrimidine (I) with N-carbethoxypiperazine (II) yields (III), which upon treatment with Raney Nickel affords ethyl 4-(5-fluoro-2-pyrimidinyl)-1-piperazinecarboxylate (IV). Hydrolysis and decarboxylation of (IV) generates 5-fluoro-2-(1-piperazinyl)pyrimidine (V). The reaction of (V) with the alpha-chloroketal (VI) generates the butyrophenone derivative (VII). Sodium borohydride reduction of (VII) and treatment with ethanolic hydrochloric acid yields BMY-14802-1.
| 【1】 Lobeck, W.G. Jr.; Yevich, J.P. (Bristol-Myers Squibb Co.); Antipsychotic 1-fluorophenylbutyl-4-(2-pyrimidinyl)piperazine derivatives. AU 8539449; BE 0901880; CH 663022; DE 3507983; ES 8607254; FR 2560878; GB 2155925; JP 1986000075; US 4605655 . |
| 【2】 Yocca, F.D.; Yevich, J.P.; New, J.S.; BMY-14802-1. Drugs Fut 1987, 12, 8, 752. |
| 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) | 28200 | 2-chloro-5-fluoro-4-(methylsulfanyl)pyrimidine | C5H4ClFN2S | 详情 | 详情 | |
| (II) | 24694 | N-ethoxycarbonylpiperidine; Ethyl 1-piperazinecarboxylate; N-Ethoxycarbonyl piperazine; N-Carbethoxy piperazine | 120-43-4 | C7H14N2O2 | 详情 | 详情 |
| (III) | 28201 | ethyl 4-[5-fluoro-4-(methylsulfanyl)-2-pyrimidinyl]-1-piperazinecarboxylate | C12H17FN4O2S | 详情 | 详情 | |
| (IV) | 28202 | ethyl 4-(5-fluoro-2-pyrimidinyl)-1-piperazinecarboxylate | C11H15FN4O2 | 详情 | 详情 | |
| (V) | 11426 | 5-Fluoro-2-piperazinopyrimidine | C8H11FN4 | 详情 | 详情 | |
| (VI) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (VII) | 28204 | 1-(4-fluorophenyl)-4-[4-(5-fluoro-2-pyrimidinyl)-1-piperazinyl]-1-butanone | C18H20F2N4O | 详情 | 详情 |
合成路线8
该中间体在本合成路线中的序号：(A)FG5803 is obtained in a three-step synthesis: In the first step 4-(4-fluorophenyl)-4,4-ethylenedioxybutylchloride (A) reacts with piperazine (B) to give 1-[4-(4-fluorophenyl)-4,4-ethylenedioxybutyl]piperazine (I), which is reacted with cyclohexylisocyanate (C) to form 4-[4-(4-fluorophenyl)-4,4-ethylenedioxybutyl]-N-cyclohexyl-1-piperazinecarboxamide (II). The protecting group is removed by HCl in ethanol and the final product is isolated, 4-[4-(4-fluorophenyl)-4-oxobutyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (III).
| 【1】 Bjork, A.; Fex, T.; Olsson, K.; Abramo, A.; Gustafsson, B.; Christensson, E. (Ferrosan AB); Novel 1-piperazinecarboxamide derivs.. EP 0136274; ES 8704917; ES 8705411; ES 8802039; JP 1985501956; US 4935419; WO 8500811 . |
| 【2】 Lundstedt, T.; Bjork, A.; Pettersson, G.; Svartengren, J.; Christensson, E.; Gustavsson, B.; FG5803. Drugs Fut 1990, 15, 12, 1176. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (B) | 10355 | Diethylenediamine; Piperazine | 110-85-0 | C4H10N2 | 详情 | 详情 |
| (A) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (I) | 31226 | 1-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]piperazine | C16H23FN2O2 | 详情 | 详情 | |
| (II) | 31227 | N-cyclohexyl-4-[3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl]-1-piperazinecarboxamide | C23H34FN3O3 | 详情 | 详情 | |
| (C) | 18108 | 1-isocyanatocyclohexane; cyclohexyl isocyanate | 3173-53-3 | C7H11NO | 详情 | 详情 |
合成路线9
该中间体在本合成路线中的序号：(I)The reaction of 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane (I) with 4-aminopyridine (II) gives the corresponding pyridinium salt (III), which is reduced with NaBH4 to 2-[3-(4-aminopiperidyl)propyl]-2-(4-fluorophenyl)-1,3-dioxolane (IV). The condensation of (IV) with 2-chloronitrobenzene (V) yields 2-[3-[4-(2-nitroanilino)piperidyl]propyl]-2-(4-fluorophenyl)-1,3-dioxolane (VI), which is hydrogenated with H2 over Raney-Ni affording the corresponding amino compound (VII). Finally this compound is cyclized with carbon disulfide and KOH
| 【1】 JP 76095096 . |
| 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) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (II) | 25661 | 4-pyridinamine; 4-aminopyridine | 5044-74-5 | C5H6N2 | 详情 | 详情 |
| (III) | 60701 | 4-amino-1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}pyridinium chloride | C17H20ClFN2O2 | 详情 | 详情 | |
| (IV) | 60702 | 1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinamine; 1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinylamine | C17H25FN2O2 | 详情 | 详情 | |
| (V) | 15248 | 1-chloro-2-nitrobenzene | 88-73-3 | C6H4ClNO2 | 详情 | 详情 |
| (VI) | 60703 | 1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-N-(2-nitrophenyl)-4-piperidinamine; N-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)-N-(2-nitrophenyl)amine | C23H28FN3O4 | 详情 | 详情 | |
| (VII) | 60704 | N-(2-aminophenyl)-N-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)amine; N~1~-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)-1,2-benzenediamine | C23H30FN3O2 | 详情 | 详情 |
合成路线10
该中间体在本合成路线中的序号：(I)The reaction of o-phenylenediamine (IX) with 4-chloropyridine (VIII) gives 2-(4-pyridylamino)aniline (X), which is condensed with 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane (I) to give the corresponding pyridinium salt (XI). The reduction of (XI) with NaBH4 yields amino compound (VII). Finally this compound is cyclized with carbon disulfide and KOH
| 【1】 JP 76095096 . |
| 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) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (VII) | 60704 | N-(2-aminophenyl)-N-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)amine; N~1~-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)-1,2-benzenediamine | C23H30FN3O2 | 详情 | 详情 | |
| (VIII) | 32889 | 4-chloropyridine | 7379-35-3 | C5H4ClN | 详情 | 详情 |
| (IX) | 12824 | 2-Aminophenylamine; o-Phenylenediamine; 1,2-Benzenediamine | 95-54-5 | C6H8N2 | 详情 | 详情 |
| (X) | 60705 | N-(2-aminophenyl)-N-(4-pyridinyl)amine; N~1~-(4-pyridinyl)-1,2-benzenediamine | C11H11N3 | 详情 | 详情 | |
| (XI) | 60706 | 4-(2-aminoanilino)-1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}pyridinium chloride | C23H25ClFN3O2 | 详情 | 详情 |
合成路线11
该中间体在本合成路线中的序号：(I)By condesation of 4-chloro-1-(4-fluorophenyl)-1-butanone ethylene ketal (I) with 1-(4-piperidyl)-2-mercaptobenzimidazole (II) by means of KI in refluxing butanol
| 【1】 Katsujiro, U.; et al. (Daiichi Seiyaku Co., Ltd.); DE 2526393; GB 1467097; US 3963727 . |
| 【2】 Sato, A. (Daiichi Seiyaku Co., Ltd.); JP 7584578 . |
| 【3】 Castaner, J.; Blancafort, P.; DD-3480. Drugs Fut 1978, 3, 6, 451. |
合成路线12
该中间体在本合成路线中的序号：(I)The condensation of 4-chloro-1-(4-fluorophenyl)-1-butanone ethylene ketal (I) with 4-(2-nitroanilino)piperidine (III) by means of KI in refluxing butanol gives 1-[3-(4-fluorobenzoyl)propyl]-4-(2-nitroanilino)piperidine ethylene ketal (IV), which is reduced with H2 over Raney-Ni in methanol yielding the corresponding amino compound (V). Finally this compound is cyclized with CS2 by means of KOH in refluxing ethanol
| 【1】 Katsujiro, U.; et al. (Daiichi Seiyaku Co., Ltd.); DE 2526393; GB 1467097; US 3963727 . |
| 【2】 Katsujiro, U.; et al. (Daiichi Seiyaku Co., Ltd.); JP 7584579 . |
| 【3】 Katsujiro, U.; et al. (Daiichi Seiyaku Co.; Ltd.); BE 830171; ZA 7593577 . |
| 【4】 Castaner, J.; Blancafort, P.; DD-3480. Drugs Fut 1978, 3, 6, 451. |
| 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) | 28203 | 2-(3-chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolane | 3308-94-9 | C12H14ClFO2 | 详情 | 详情 |
| (III) | 60708 | N-(2-nitrophenyl)-4-piperidinamine; N-(2-nitrophenyl)-N-(4-piperidinyl)amine | C11H15N3O2 | 详情 | 详情 | |
| (IV) | 60703 | 1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-N-(2-nitrophenyl)-4-piperidinamine; N-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)-N-(2-nitrophenyl)amine | C23H28FN3O4 | 详情 | 详情 | |
| (V) | 60704 | N-(2-aminophenyl)-N-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)amine; N~1~-(1-{3-[2-(4-fluorophenyl)-1,3-dioxolan-2-yl]propyl}-4-piperidinyl)-1,2-benzenediamine | C23H30FN3O2 | 详情 | 详情 |