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【结 构 式】 
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【分子编号】23017 【品名】2-phenyloxirane 【CA登记号】96-09-3 |
【 分 子 式 】C8H8O 【 分 子 量 】120.15092 【元素组成】C 79.97% H 6.71% O 13.32% |
合成路线1
该中间体在本合成路线中的序号：(I)By condensation of styrene oxide (I) with 3,4-dimethoxyphenylethylamine (II) at 100 C to give N-(beta-hydroxy-beta-phenyl)ethyl-2-(3',4'-dimethoxyphenyl)ehtylamine (III), which is cyclized with H2SO4 to 1-phenyl-7,8-dimethoxy-2,3,4,5-tetrahydro-3,1-benzazepine (IV). This product is finally methylated with a refluxing mixture of formaldehyde and formic acid.
| 【1】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645. |
| 【2】 Walter, L.A.; Chang, W.K. (Schering Corp.); Novel benzazepines. US 3393192 . |
| 【3】 Castaner, J.; Thorpe, P.; Trimopam. Drugs Fut 1976, 1, 4, 194. |
| 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) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 详情 | 详情 |
| (II) | 10098 | 2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine | 120-20-7 | C10H15NO2 | 详情 | 详情 |
| (III) | 39206 | 2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol | C18H23NO3 | 详情 | 详情 | |
| (IV) | 39207 | 7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C18H21NO2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The condensation of 3,4-dimethoxyphenethylamine (I) with styrene oxide (II) by heating at 100 C gives N-[2-(3,4-dimethoxyphenyl)ethyl]-2-phenyl-2-hydroxyethylamine (III), which can be cyclized with H2SO4 in refluxing trifluoroacetic acid yielding 2,3,4,5-tetrahydro-7,8-dimethoxy-1-phenyl-1H-3-benzazepine (IV). Finally, intermediate (IV) is demethylated with refluxing 48% HBr (III) can also by cyclized and demethylated simultaneously by refluxing with 48% HBr.
| 【1】 Kaiser, C.; et al.; DE 2629887 . |
| 【2】 Hieble, J.P.; Wilson III, J.W.; Weinstock, J.; The chemistry and pharmacology of 3-benzazepines derivatives. Drugs Fut 1985, 10, 8, 645. |
| 【3】 Castaner, J.; Hillier, K.; SKF-38393. Drugs Fut 1980, 5, 10, 507. |
| 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) | 10098 | 2-(3,4-Dimethoxyphenyl)-1-ethanamine; 3,4-Dimethoxyphenethylamine; 2-(3,4-Dimethoxyphenyl)ethylamine | 120-20-7 | C10H15NO2 | 详情 | 详情 |
| (II) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 详情 | 详情 |
| (III) | 39206 | 2-[(3,4-dimethoxyphenethyl)amino]-1-phenyl-1-ethanol | C18H23NO3 | 详情 | 详情 | |
| (IV) | 39207 | 7,8-dimethoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 8-methoxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl methyl ether | C18H21NO2 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(XV)In a different method, reaction of styrene oxide (XV) with methylamine provided amino alcohol (XVI), which was further condensed with ethylene oxide (XVII) to afford amino diol (XVIII). Alternatively, diol (XVIII) was prepared by a more direct procedure by condensation of epoxide (XV) with 2-(methylamino)ethanol (XIX). Chlorination of (XVIII) employing SOCl2 yielded the dichloro derivative (XX), which was subsequently condensed with 2-aminobenzyl alcohol (X) leading to piperazine (XXI). Cyclization of (XXI) to the title compound was accomplished by treatment with hot polyphosphoric acid. Optionally, alcohol (XXI) was converted to chloride (XXII), which was then cyclized in the presence of AlCl3. In a related method, alcohol (XXI) was esterified with AcOH, and the resultant acetate ester (XXIII) was then cyclized in the presence of polyphosphoric acid
| 【1】 Olivié, J.; Synthesis for the preparation of tetracyclic cpds.. US 4217452 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 18619 | (2-aminophenyl)methanol; 2-Amino-benzenemethanol；2-Hydroxymethyl aniline;2-aminobenzyl alcohol;o-Aminobenzyl 2-aminobenzylalcohol;alcohol; 2-aminobenzenemethanol; 2-aminobenzyl alcohol | 5344-90-1 | C7H9NO | 详情 | 详情 |
| (XV) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 详情 | 详情 |
| (XVI) | 62404 | 2-(methylamino)-1-phenyl-1-ethanol | C9H13NO | 详情 | 详情 | |
| (XVII) | 10393 | Oxirane; Ethylene oxide | 75-21-8 | C2H4O | 详情 | 详情 |
| (XVIII) | 62405 | 2-[(2-hydroxyethyl)(methyl)amino]-1-phenyl-1-ethanol | C11H17NO2 | 详情 | 详情 | |
| (XIX) | 13324 | 2-Methylaminoethanol; 2-(Methylamino)-1-ethanol | 109-83-1 | C3H9NO | 详情 | 详情 |
| (XX) | 62406 | 2-chloro-N-(2-chloroethyl)-N-methyl-2-phenyl-1-ethanamine; N-(2-chloroethyl)-N-(2-chloro-2-phenylethyl)-N-methylamine | C11H15Cl2N | 详情 | 详情 | |
| (XXI) | 62407 | [2-(4-methyl-2-phenyl-1-piperazinyl)phenyl]methanol | C18H22N2O | 详情 | 详情 | |
| (XXII) | 62408 | 1-[2-(chloromethyl)phenyl]-4-methyl-2-phenylpiperazine | C18H21ClN2 | 详情 | 详情 | |
| (XXIII) | 62409 | 2-(4-methyl-2-phenyl-1-piperazinyl)benzyl acetate | C20H24N2O2 | 详情 | 详情 |
合成路线4
该中间体在本合成路线中的序号：(XV)In a further procedure, styrene oxide (XV) was condensed with 2-(benzylamino)ethanol (XXVIII) to give amino diol (XXIX). After chlorination of (XXIX) using SOCl2 and DMAP, dichloro derivative (XXX) was condensed with 2-aminobenzyl alcohol (X) yielding piperazine (XXXI). Cyclization of (XXXI) in hot sulfuric acid afforded the tetracyclic compound (XXXII). The N-benzyl group of (XXXII) was then removed by treatment with butyl chloroformate producing carbamate (XXXIII), which was further hydrolyzed and decarboxylated to (XXXIV) under basic conditions. Finally, methylation of the secondary amine (XXXIV) was performed by reductive alkylation with formaldehyde either in the presence of formic acid under Leuckart-Wallach conditions or by catalytic hydrogenation
| 【1】 Grafe, I.; Ahrens, K.-H.; Morsdorf, J.P.; Kisielowski-Ruppert, L. (Heumann Pharma GmbH); Process for the preparation of 1,2,3,4,10,14b-hexahydro-2-methyldibenzo[c,f]pyrazino[1,2-a]azepin and their salts. DE 4305659; EP 0612745 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 18619 | (2-aminophenyl)methanol; 2-Amino-benzenemethanol；2-Hydroxymethyl aniline;2-aminobenzyl alcohol;o-Aminobenzyl 2-aminobenzylalcohol;alcohol; 2-aminobenzenemethanol; 2-aminobenzyl alcohol | 5344-90-1 | C7H9NO | 详情 | 详情 |
| (XV) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 详情 | 详情 |
| (XXVIII) | 25630 | 2-(benzylamino)-1-ethanol | 104-63-2 | C9H13NO | 详情 | 详情 |
| (XXIX) | 62414 | 2-[benzyl(2-hydroxyethyl)amino]-1-phenyl-1-ethanol | C17H21NO2 | 详情 | 详情 | |
| (XXX) | 62415 | N-benzyl-2-chloro-N-(2-chloroethyl)-2-phenyl-1-ethanamine; N-benzyl-N-(2-chloroethyl)-N-(2-chloro-2-phenylethyl)amine | C17H19Cl2N | 详情 | 详情 | |
| (XXXI) | 62416 | [2-(4-benzyl-2-phenyl-1-piperazinyl)phenyl]methanol | C24H26N2O | 详情 | 详情 | |
| (XXXII) | 62417 | 2-benzyl-1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine | C24H24N2 | 详情 | 详情 | |
| (XXXIII) | 62418 | butyl 3,4,10,14b-tetrahydrodibenzo[c,f]pyrazino[1,2-a]azepine-2(1H)-carboxylate | C22H26N2O2 | 详情 | 详情 | |
| (XXXIV) | 62419 | 1,2,3,4,10,14b-hexahydrodibenzo[c,f]pyrazino[1,2-a]azepine | C17H18N2 | 详情 | 详情 |
合成路线5
该中间体在本合成路线中的序号：(VI)The reaction of 4-(3-hydroxy-3-methylbutyl)benzoic acid (I) with HCN in acetic acid-H2SO4 gives 4-[3-(formylamino)-3-methyibutylbenzoic acid (II), which is hydrolyzed to the corresponding amine (III) with aqueous HCl at 100 C. The reaction of benzoic acid (III) with SOCl2 gives the corresponding acyl chloride (IV), which by reaction with NH3 is converted to the benzamide (V). Finally, this compound is condensed with styrene oxide (VI) by means of hexamethyldisylazane in DMSO and hydrolyzed with NaOH in butanone water.
| 【1】 Weigel, L.O. (Eli Lilly and Company); Process for preparing 2-hydroxy-2-phenethylamines. EP 0104888 . |
| 【2】 Mills, J.; Schmiegel, K.K.; Toomey, R.E. (Eli Lilly and Company); Phenethanolamines, their formulations, preparation. EP 0007206 . |
| 【3】 Castaner, J.; Prous, J.; LY-195448. Drugs Fut 1988, 13, 12, 1045. |
| 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) | 23012 | 4-(3-hydroxy-3-methylbutyl)benzoic acid | C12H16O3 | 详情 | 详情 | |
| (II) | 23013 | 4-[3-(formylamino)-3-methylbutyl]benzoic acid | C13H17NO3 | 详情 | 详情 | |
| (III) | 23014 | 4-(3-amino-3-methylbutyl)benzoic acid | C12H17NO2 | 详情 | 详情 | |
| (IV) | 23015 | 4-(3-amino-3-methylbutyl)benzoyl chloride | C12H16ClNO | 详情 | 详情 | |
| (V) | 23016 | 4-(3-amino-3-methylbutyl)benzamide | C12H18N2O | 详情 | 详情 | |
| (VI) | 23017 | 2-phenyloxirane | 96-09-3 | C8H8O | 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 title compound has been synthesized by two different methods. Condensation of 2-amino-2-methyl-1-propanol (I) with styrene oxide (II) provided the target amino diol.
| 【1】 Montoro, F.; Calatayud, J.; Vila-Coro, A.; De la Fuente, R. (Byk Elmu SA); Process for the preparation of ethyl-1-hydroxy-1-phenyl-2-(2-methyl-1-propanol)-amine, a new drug with antiinflammatory activity. ES 453351 . |
| 【2】 Staibano, G.; Fanelli, O. (Istituto Gentili SpA); Diethanolamine derivs.. GB 1336732 . |