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【结 构 式】 
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【分子编号】52479 【品名】1,1-dimethylethyl 4-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-2-[2-(methyloxy)-2-oxoethyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylate 【CA登记号】 |
【 分 子 式 】C25H37N3O7 【 分 子 量 】491.5848 【元素组成】C 61.08% H 7.59% N 8.55% O 22.78% |
合成路线1
该中间体在本合成路线中的序号：(VII)Condensation of tert-butyl 4-fluoro-3-(bromomethyl)benzoate (I) with N-Boc-1,3-propanediamine (II) afforded the aminomethyl benzoate derivative (III). This was coupled with N-Cbz-L-aspartic acid beta-methyl ester (IV), yielding amide (V). After hydrogenolysis of the carbobenzoxy protecting group of (V), the resultant fluoro amine (VI) was cyclized to the benzodiazepinone (VII) upon treatment with 2,6-di-tert-butylpyridine in hot NMP. Acidic cleavage of both the tert-butyl ester and the N-Boc groups of (VII), followed by reprotection of the amine with Boc2O, furnished the N-Boc acid (VIII). This was then coupled to 2-(methylaminomethyl)benzimidazole (IX) to afford, after acidic Boc group cleavage, the amino amide (X).
| 【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeled with Tc99m for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 77. |
| 【2】 Sworin, M.; Cheesman, E.H.; Rajopadhyem, M. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. EP 1140864; WO 0035887 . |
| 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) | 52473 | 1,1-dimethylethyl 3-(bromomethyl)-4-fluorobenzoate | C12H14BrFO2 | 详情 | 详情 | |
| (II) | 52474 | 1,1-dimethylethyl 3-aminopropylcarbamate | C8H18N2O2 | 详情 | 详情 | |
| (III) | 52475 | 1,1-dimethylethyl 3-({[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]amino}methyl)-4-fluorobenzoate | C20H31FN2O4 | 详情 | 详情 | |
| (IV) | 52476 | O-methyl-4-oxo-N-{[(phenylmethyl)oxy]carbonyl}homoserine | C13H15NO6 | 详情 | 详情 | |
| (V) | 52477 | 1,1-dimethylethyl 3-({[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl][4-(methyloxy)-4-oxo-2-({[(phenylmethyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-4-fluorobenzoate | C33H44FN3O9 | 详情 | 详情 | |
| (VI) | 52478 | 1,1-dimethylethyl 3-({[2-amino-4-(methyloxy)-4-oxobutanoyl][3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]amino}methyl)-4-fluorobenzoate | C25H38FN3O7 | 详情 | 详情 | |
| (VII) | 52479 | 1,1-dimethylethyl 4-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-2-[2-(methyloxy)-2-oxoethyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylate | C25H37N3O7 | 详情 | 详情 | |
| (VIII) | 52480 | 4-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-2-[2-(methyloxy)-2-oxoethyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid | C21H29N3O7 | 详情 | 详情 | |
| (IX) | 52481 | 1H-benzimidazol-2-yl-N-methylmethanamine; N-(1H-benzimidazol-2-ylmethyl)-N-methylamine | C9H11N3 | 详情 | 详情 | |
| (X) | 52482 | methyl 2-(4-(3-aminopropyl)-7-{[(1H-benzimidazol-2-ylmethyl)(methyl)amino]carbonyl}-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-yl)acetate | C25H30N6O4 | 详情 | 详情 |