【结 构 式】 |
【分子编号】28643 【品名】benzyl (2R)-2-(benzylamino)-4-methylpentanoate 【CA登记号】 |
【 分 子 式 】C20H25NO2 【 分 子 量 】311.42404 【元素组成】C 77.14% H 8.09% N 4.5% O 10.27% |
合成路线1
该中间体在本合成路线中的序号:(III)The esterification of D-leucine (I) with benzyl alcohol and HCl gives the corresponding ester (II), which is N-benzylated by reductocondensation with benzaldehyde and sodium cyanoborohydride yielding N-benzyl-D-leucine benzyl ester (III). The condensation of (III) with methyl phenyl phosphinyl chloride (IV) by means of N-methylmorpholine in dichloromethane affords the phosphinylamino derivative (V), which is treated with H2 over Pd/C in methanol to give N-benzyl-N-[methyl(phenyl)phosphinyl]-D-leucine (VI). The condensation of (VI) with O-benzylhydroxylamine (VII) by means of 1-[3-(dimethylamino) propyl]-3-ethylcarbodiimide (DEC) and HOBT in DMF yields the N-benzyl hydroxamic acid (VIII) as a diastereomeric mixture that is separated by flash chromatography providing the diastereomer (IX). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C in methanol.
【1】 Elst, L.V.; et al.; A multinuclear MR study of Gd-EOB-DTPA: Comprehensive preclinical characterization of an organ specific MRI contrast agent. Magn Reson Med 1997, 38, 4, 604. |
【2】 Taiwo, Y.O.; Pikul, S.; De, B.; McDow-Dunham, K.L. (The Procter & Gamble Co.); Phosphinic acid amides as matrix metalloprotease inhibitors. US 5830915; WO 9808853 . |
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) | 16010 | D-leucine | 328-38-1 | C6H13NO2 | 详情 | 详情 |
(II) | 28648 | benzyl (2R)-2-amino-4-methylpentanoate | C13H19NO2 | 详情 | 详情 | |
(III) | 28643 | benzyl (2R)-2-(benzylamino)-4-methylpentanoate | C20H25NO2 | 详情 | 详情 | |
(IV) | 28644 | methyl(phenyl)phosphinic chloride | 5761-97-7 | C7H8ClOP | 详情 | 详情 |
(V) | 28645 | benzyl (2R)-2-[benzyl[methyl(phenyl)phosphoryl]amino]-4-methylpentanoate | C27H32NO3P | 详情 | 详情 | |
(VI) | 28646 | (2R)-2-[benzyl[methyl(phenyl)phosphoryl]amino]-4-methylpentanoic acid | C20H26NO3P | 详情 | 详情 | |
(VII) | 14640 | O-benzylhydroxylamine; 1-[(aminooxy)methyl]benzene | 622-33-3 | C7H9NO | 详情 | 详情 |
(VIII) | 28647 | (2R)-2-[benzyl[methyl(phenyl)phosphoryl]amino]-N-(benzyloxy)-4-methylpentanamide | C27H33N2O3P | 详情 | 详情 | |
(IX) | 28649 | (2R)-2-[benzyl[methyl(phenyl)phosphoryl]amino]-N-(benzyloxy)-4-methylpentanamide | C27H33N2O3P | 详情 | 详情 |