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【结 构 式】 
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【药物名称】 【化学名称】2-[4-[8-Hydroxy-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-3-yl]butyl]-2-[3-(trifluoromethyl)benzyl]malonic acid triethylamine salt hydrate 【CA登记号】273224-16-1 (anhydrous), 273224-15-0 (anhydrous free acid) 【 分 子 式 】C27H40F3N5O6 【 分 子 量 】587.64495 |
【开发单位】Metabasis (Originator) 【药理作用】Angina pectoris, Treatment of, CARDIOVASCULAR DRUGS, Cerebrovascular Diseases, Treatment of, NEUROLOGIC DRUGS, Stroke, Treatment of, Treatment of Disorders of the Coronary Arteries and Atherosclerosis, AMP Deaminase Inhibitors |
合成路线1
Dibenzyl malonate (I) was alkylated with 3-(trifluoromethyl)benzyl bromide (II) in the presence of Na in DMF to yield the 3-(trifluoromethyl)benzylmalonate (III). Further alkylation of (III) with 1,4-dibromobutane (IV) provided the bromobutyl derivative (V). Condensation of the known 6,7-dihydroimidazo[4,5-d][1,3]diazepin-8-one (VI) with bromide (V) in the presence of NaH and NaI furnished adduct (VII). The keto group of (VII) was then reduced to alcohol (VIII) employing NaBH4 in MeOH-CH2Cl2. Finally, hydrogenolysis of the benzyl ester groups of (VIII) in the presence of Pd/C and Et3N afforded the title dicarboxylate triethylammonium salt.
| 【1】 Bookser, B.C.; Kasibhatla, S.R.; Erion, M.D.; AMP deaminase inhibitors. 4. Further N3-substituted coformycin aglycon analogues: N3-alkylmalonates as ribose 5'-monophosphate mimetics. J Med Chem 2000, 43, 8, 1519. |
| 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) | 16013 | dibenzyl malonate | 15014-25-2 | C17H16O4 | 详情 | 详情 |
| (II) | 40803 | 1-(bromomethyl)-3-(trifluoromethyl)benzene | 402-23-3 | C8H6BrF3 | 详情 | 详情 |
| (III) | 40804 | dibenzyl 2-[3-(trifluoromethyl)benzyl]malonate | C25H21F3O4 | 详情 | 详情 | |
| (IV) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
| (V) | 40805 | dibenzyl 2-(4-bromobutyl)-2-[3-(trifluoromethyl)benzyl]malonate | C29H28BrF3O4 | 详情 | 详情 | |
| (VI) | 40806 | 6,7-dihydroimidazo[4,5-d][1,3]diazepin-8(3H)-one | C6H6N4O | 详情 | 详情 | |
| (VII) | 40807 | dibenzyl 2-[4-[8-oxo-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl]butyl]-2-[3-(trifluoromethyl)benzyl]malonate | C35H33F3N4O5 | 详情 | 详情 | |
| (VIII) | 40808 | dibenzyl 2-[4-[8-hydroxy-7,8-dihydroimidazo[4,5-d][1,3]diazepin-3(6H)-yl]butyl]-2-[3-(trifluoromethyl)benzyl]malonate | C35H35F3N4O5 | 详情 | 详情 |