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【结 构 式】 
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【药物名称】RO-28-2653 【化学名称】5-(4-Biphenylyl)-5-[4-(4-nitrophenyl)piperazin-1-yl]barbituric acid 【CA登记号】261956-22-3 【 分 子 式 】C26H23N5O5 【 分 子 量 】485.50371 |
【开发单位】Roche (Originator) 【药理作用】Oncolytic Drugs, Angiogenesis Inhibitors, Matrix Metalloproteinase Inhibitors |
合成路线1
Esterification of (4'-biphenyl)acetic acid (I) with ethanol and p-toluenesulfonic acid provides the corresponding ethyl ester (II). Subsequent carbethoxylation of (II) with diethyl carbonate (III) under Claisen's condensation conditions furnishes the biphenylmalonate (IV). Cyclization of malonate (IV) with urea (V) in the presence of NaOEt leads to 5-(4'-biphenyl)barbituric acid (VI), which is further brominated to (VII) employing Br2 in aqueous HBr. The title compound is finally obtained by displacement of the 5-bromo barbituric acid (VII) with N-(4-nitrophenyl)piperazine (VIII) in refluxing MeOH.
| 【1】 Bosies, E.; Esswein, A.; Grams, F.; Krell, H.-W.; Menta, E. (Roche Diagnostics GmbH); New barbituric acid derivs., processes for their production and pharmaceutical agents containing these cpds.. DE 19548624; EP 0869947; JP 2000505069; US 6110924; US 6472396; WO 9723465 . |
| 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) | 58170 | 2-[1,1'-biphenyl]-4-ylacetic acid | C14H12O2 | 详情 | 详情 | |
| (II) | 58171 | ethyl 2-[1,1'-biphenyl]-4-ylacetate | C16H16O2 | 详情 | 详情 | |
| (III) | 17470 | diethyl carbonate; diethylcarbonate | 105-58-8 | C5H10O3 | 详情 | 详情 |
| (IV) | 58172 | diethyl 2-[1,1'-biphenyl]-4-ylmalonate | C19H20O4 | 详情 | 详情 | |
| (V) | 19310 | urea | 57-13-6 | CH4N2O | 详情 | 详情 |
| (VI) | 58173 | 5-[1,1'-biphenyl]-4-yl-2,4,6(1H,3H,5H)-pyrimidinetrione | C16H12N2O3 | 详情 | 详情 | |
| (VII) | 58174 | 5-[1,1'-biphenyl]-4-yl-5-bromo-2,4,6(1H,3H,5H)-pyrimidinetrione | C16H11BrN2O3 | 详情 | 详情 | |
| (VIII) | 20299 | 1-(4-nitrophenyl)piperazine | 6269-89-2 | C10H13N3O2 | 详情 | 详情 |