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【结 构 式】 
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【分子编号】64509 【品名】ethyl 2-{[(E)-(dimethylamino)methylidene]amino}-2-(7-fluoro-4-methyl-5-oxo-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ylidene)acetate 【CA登记号】 |
【 分 子 式 】C17H21FN4O3 【 分 子 量 】348.3773032 【元素组成】C 58.61% H 6.08% F 5.45% N 16.08% O 13.78% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 7-fluoro-4-methyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-2,5-dione (I) with POCl3 and N,N-dimethyl-p-toluidine in hot toluene gives 2-chloro-7-fluoro-4-methyl-4,5-dihydro-3H-1,4-benzodiazepin-5 one (II), which is condensed with N-(dimethylaminomethylene)glycine ethyl ester (III) (obtained by condensation of glycine ethyl ester (IV) with dimethylformamide (V) and TEA in dichloromethane) to yield a mixture of intermediates (VI) and (VII). Finally, these compounds are cyclized in refluxing AcOH to provide the target flumazenil.
| 【1】 Rogers-Evans, M.; Spurr, P.; Hennig, M.; The isolation and use of a benzodiazepine iminochloride for the efficient construction of flumazenil. Tetrahedron Lett 2003, 44, 11, 2425. |
| 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) | 31965 | 7-Fluoro-4-methyl-3,4-dihydro-1H-1,4-benzodiazepine-2,5-dione; 7-Fluoro-4-methyl-3,4-dihydro-2H-1,4-benzodiazepin-2,5(1H)-dione | C10H9FN2O2 | 详情 | 详情 | |
| (II) | 64506 | 2-chloro-7-fluoro-4-methyl-3,4-dihydro-5H-1,4-benzodiazepin-5-one | C10H8ClFN2O | 详情 | 详情 | |
| (III) | 64507 | ethyl 2-{[(E)-(dimethylamino)methylidene]amino}acetate | C7H14N2O2 | 详情 | 详情 | |
| (IV) | 10309 | ethyl 2-aminoacetate; Glycine ethyl ester | 459-73-4 | C4H9NO2 | 详情 | 详情 |
| (V) | 33491 | Dimethylformamide | 68-12-2 | C3H7NO | 详情 | 详情 |
| (VI) | 64508 | ethyl 2-{[(E)-(dimethylamino)methylidene]amino}-2-(7-fluoro-4-methyl-5-oxo-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ylidene)acetate | C17H21FN4O3 | 详情 | 详情 | |
| (VII) | 64509 | ethyl 2-{[(E)-(dimethylamino)methylidene]amino}-2-(7-fluoro-4-methyl-5-oxo-1,3,4,5-tetrahydro-2H-1,4-benzodiazepin-2-ylidene)acetate | C17H21FN4O3 | 详情 | 详情 |