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【结 构 式】 
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【分子编号】51636 【品名】4-Chloro-2-methoxy-1-nitrobenzene; 4-Chloro-2-methoxynitrobenzene; 5-Chloro-2-nitroanisole 【CA登记号】6627-53-8 |
【 分 子 式 】C7H6ClNO3 【 分 子 量 】187.58228 【元素组成】C 44.82% H 3.22% Cl 18.9% N 7.47% O 25.59% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 5-chloro-2-nitroanisole (V) with diethyl malonate (VI) by means of NaH in hot DMF gives 2-(3-methoxy-4-nitrophenyl)malonic acid diethyl ester (VII), which is reduced with H2 over Pd/C in ethyl acetate, yielding the corresponding amino derivative (VIII). The condensation of (VIII) with 2-methylphenyl isocyanate (IX) by means of TEA in dichloromethane affords the expected urea (X), which is submitted to a decarboxylative hydrolysis with NaOH in refluxing tert-butanol to provide the phenylacetic acid (XI). The condensation of acetic acid (XI) with the amino group of the isoxazole intermediate (IV) by means of HOBt, DIEA and EDC in DMF gives the amide (XII), which is treated with NaOH in tert-butanol to afford the target propionic acid.
| 【1】 Duplantier, A.J.; et al.; Isoxazolyl, oxazolyl, and thiazolylpropionic acid derivatives as potent alpha4beta1 integrin antagonists. Bioorg Med Chem Lett 2001, 11, 19, 2593. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 51635 | methyl 3-[3-[(1S)-1-amino-3-methylbutyl]-5-isoxazolyl]propanoate | C12H20N2O3 | 详情 | 详情 | |
| (V) | 51636 | 4-Chloro-2-methoxy-1-nitrobenzene; 4-Chloro-2-methoxynitrobenzene; 5-Chloro-2-nitroanisole | 6627-53-8 | C7H6ClNO3 | 详情 | 详情 |
| (VI) | 16829 | Diethyl malonate | 105-53-3 | C7H12O4 | 详情 | 详情 |
| (VII) | 51637 | diethyl 2-(3-methoxy-4-nitrophenyl)malonate | C14H17NO7 | 详情 | 详情 | |
| (VIII) | 51638 | diethyl 2-(4-amino-3-methoxyphenyl)malonate | C14H19NO5 | 详情 | 详情 | |
| (IX) | 27106 | 1-isocyanato-2-methylbenzene | 614-68-6 | C8H7NO | 详情 | 详情 |
| (X) | 51639 | diethyl 2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]malonate | C22H26N2O6 | 详情 | 详情 | |
| (XI) | 39718 | 2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetic acid | C17H18N2O4 | 详情 | 详情 | |
| (XII) | 51640 | methyl 3-(3-[(1S)-1-[(2-[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl]acetyl)amino]-3-methylbutyl]-5-isoxazolyl)propanoate | C29H36N4O6 | 详情 | 详情 |