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【结 构 式】 
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【分子编号】49769 【品名】(3R)-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one 【CA登记号】 |
【 分 子 式 】C15H21N3O 【 分 子 量 】259.35136 【元素组成】C 69.47% H 8.16% N 16.2% O 6.17% |
合成路线1
该中间体在本合成路线中的序号：(IX)The condensation of the mono-protected 2,3-diaminopropionic acid (I) with 2-fluoronitrobenzene (II) produced the nitro acid (III). After catalytic hydrogenation of the nitro group of (III), the resulting amino acid (IV) was cyclized to the benzodiazepinone (V) upon refluxing in toluene. Alkylation of (V) with cyclohexenyl bromide (VI) afforded the 5-cyclohexenyl benzodiazepinone (VII), which was further hydrogenated to the cyclohexyl derivative (VIII). Acid cleavage of the Boc protecting group of (VIII) furnished the aminobenzodiazepinone (IX).
| 【1】 Murata, M.; Shinozaki, K.; Yoneta, T.; Miura, N.; Maeda, K. (Zeria Pharmaceutical Co., Ltd.); 1,5-Benzodiazepine derivs.. EP 0945445; US 6239131; WO 9825911 . |
| 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) | 49763 | Boc-D-diaminopropionic acid | C8H16N2O4 | 详情 | 详情 | |
| (II) | 13463 | o-Fluoronitrobenzene; 1-fluoro-2-nitrobenzene | 1493-27-2 | C6H4FNO2 | 详情 | 详情 |
| (III) | 49764 | (2R)-2-[(tert-butoxycarbonyl)amino]-3-(2-nitroanilino)propionic acid | C14H19N3O6 | 详情 | 详情 | |
| (IV) | 49765 | (2R)-3-(2-aminoanilino)-2-[(tert-butoxycarbonyl)amino]propionic acid | C14H21N3O4 | 详情 | 详情 | |
| (V) | 49766 | tert-butyl (3R)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-ylcarbamate | C14H19N3O3 | 详情 | 详情 | |
| (VI) | 30800 | 3-bromo-1-cyclohexene | 1521-51-3 | C6H9Br | 详情 | 详情 |
| (VII) | 49767 | tert-butyl (3R)-1-(2-cyclohexen-1-yl)-4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-ylcarbamate | C20H27N3O3 | 详情 | 详情 | |
| (VIII) | 49768 | tert-butyl (3R)-1-cyclohexyl-4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-ylcarbamate | C20H29N3O3 | 详情 | 详情 | |
| (IX) | 49769 | (3R)-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one | C15H21N3O | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)Isocyanate (XI) was prepared by treatment of tert-butyl 3-aminobenzoate (X) with triphosgene and triethylamine. Coupling of isocyanate (XI) with amine (IX) gave rise to the urea (XII). The lactam N of (XII) was then alkylated with bromomethyl tert-butyl ketone (XIII) in the presence of K2CO3 and tetrabutylammonium bromide to give (XIV). Cleavage of the tert-butyl ester group of (XIV) with trifluoroacetic acid yielded the carboxylic acid (XV), which was finally isolated as the corresponding calcium salt.
| 【1】 Murata, M.; Shinozaki, K.; Yoneta, T.; Miura, N.; Maeda, K. (Zeria Pharmaceutical Co., Ltd.); 1,5-Benzodiazepine derivs.. EP 0945445; US 6239131; WO 9825911 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IX) | 49769 | (3R)-3-amino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one | C15H21N3O | 详情 | 详情 | |
| (X) | 49770 | tert-butyl 3-aminobenzoate | C11H15NO2 | 详情 | 详情 | |
| (XI) | 49771 | tert-butyl 3-isocyanatobenzoate | C12H13NO3 | 详情 | 详情 | |
| (XII) | 49772 | tert-butyl 3-[([[(3R)-1-cyclohexyl-4-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]amino]carbonyl)amino]benzoate | C27H34N4O4 | 详情 | 详情 | |
| (XIII) | 30809 | 1-bromo-3,3-dimethyl-2-butanone | 5469-26-1 | C6H11BrO | 详情 | 详情 |
| (XIV) | 49773 | tert-butyl 3-[([[(3R)-5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]amino]carbonyl)amino]benzoate | C33H44N4O5 | 详情 | 详情 | |
| (XV) | 49774 | 3-[([[(3R)-5-cyclohexyl-1-(3,3-dimethyl-2-oxobutyl)-2-oxo-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]amino]carbonyl)amino]benzoic acid | C29H36N4O5 | 详情 | 详情 |