【结 构 式】 |
【分子编号】62385 【品名】(2S)-2-(3,4-dichlorophenyl)-N-methyl-4-penten-1-amine; N-[(2S)-2-(3,4-dichlorophenyl)-4-pentenyl]-N-methylamine 【CA登记号】 |
【 分 子 式 】C12H15Cl2N 【 分 子 量 】244.16324 【元素组成】C 59.03% H 6.19% Cl 29.04% N 5.74% |
合成路线1
该中间体在本合成路线中的序号:(XXIII)In a different procedure, 3,4-dichlorophenylacetic acid (XIV) was condensed with the lithiated chiral oxazolidinone (XV), via activation as the mixed anhydride with pivaloyl chloride, to afford the N-acyl oxazolidinone (XVI). Diastereoselective alkylation of the sodium enolate of (XVI) with allyl iodide (XVII) afforded the (S)-pentenyl oxazolidinone (XVIII), which was further hydrolyzed to the chiral acid (XIX) by means of lithium peroxide. Alternatively, acid (XIX) was obtained by alkylation of the lithium dianion of 3,4-dichlorophenylacetic acid (XIV) with allyl bromide (XX), followed by resolution of the resultant racemic acid (XXI) with (S)-1-phenylethylamine. Acid (XIX) was converted to the amide (XXII) via the corresponding acid chloride. Reduction of amide (XXII) with DIBAL gave the secondary amine (XXIII), which was subsequently acylated with benzoyl chloride, yielding benzamide (XXIV). Dihydroxylation of the olefin double bond with N-methylmorpholine-N-oxide in the presence of OsO4, followed by oxidative cleavage of the resultant diol (XXV) with sodium periodate furnished aldehyde (XXVI). Finally, reductive amination of aldehyde (XXVI) with piperidine (III) in the presence of NaBH3CN provided the title compound
【1】 Hale, J.J.; Finke, P.E.; MacCross, M.; A facile synthesis of the novel neurokinin A antagonist SR 48968. Bioorg Med Chem Lett 1993, 3, 2, 319. |
【2】 Finke, P.E.; Mills, S.G.; Hale, J.J.; MacCoss, M. (Merck & Co., Inc.); Process of making chiral 2-aryl-1,4-butanediamine derivs.. WO 9407839 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(III) | 59283 | N-(4-phenyl-4-piperidinyl)acetamide | C13H18N2O | 详情 | 详情 | |
(XIV) | 30414 | 2-(3,4-dichlorophenyl)acetic acid;2-(3,4-Dichlorophenyl)acetic acid | 5807-30-7 | C8H6Cl2O2 | 详情 | 详情 |
(XV) | 58942 | C10H10LiNO2 | 详情 | 详情 | ||
(XVI) | 62381 | (4S)-4-benzyl-3-[2-(3,4-dichlorophenyl)acetyl]-1,3-oxazolidin-2-one | C18H15Cl2NO3 | 详情 | 详情 | |
(XVII) | 32112 | 3-iodo-1-propene;3-iodo-propen;allyl iodide | 556-56-9 | C3H5I | 详情 | 详情 |
(XVIII) | 62382 | (4S)-4-benzyl-3-[(2S)-2-(3,4-dichlorophenyl)-4-pentenoyl]-1,3-oxazolidin-2-one | C21H19Cl2NO3 | 详情 | 详情 | |
(XIX) | 62383 | (2S)-2-(3,4-dichlorophenyl)-4-pentenoic acid | C11H10Cl2O2 | 详情 | 详情 | |
(XX) | 11463 | 3-Bromo-1-propene; 3-Bromopropene;allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
(XXI) | 50421 | 2-(3,4-dichlorophenyl)-4-pentenoic acid | C11H10Cl2O2 | 详情 | 详情 | |
(XXII) | 62384 | (2S)-2-(3,4-dichlorophenyl)-N-methyl-4-pentenamide | C12H13Cl2NO | 详情 | 详情 | |
(XXIII) | 62385 | (2S)-2-(3,4-dichlorophenyl)-N-methyl-4-penten-1-amine; N-[(2S)-2-(3,4-dichlorophenyl)-4-pentenyl]-N-methylamine | C12H15Cl2N | 详情 | 详情 | |
(XXIV) | 62386 | N-[(2S)-2-(3,4-dichlorophenyl)-4-pentenyl]-N-methylbenzamide | C19H19Cl2NO | 详情 | 详情 | |
(XXV) | 62387 | N-[(2S)-2-(3,4-dichlorophenyl)-4,5-dihydroxypentyl]-N-methylbenzamide | C19H21Cl2NO3 | 详情 | 详情 | |
(XXVI) | 26943 | N-[(2S)-2-(3,4-dichlorophenyl)-4-oxobutyl]-N-methylbenzamide | C18H17Cl2NO2 | 详情 | 详情 |