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【结 构 式】 
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【分子编号】53881 【品名】5-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxylic acid 【CA登记号】n/a |
【 分 子 式 】C15H11NO4 【 分 子 量 】269.25668 【元素组成】C 66.91% H 4.12% N 5.2% O 23.77% |
合成路线1
该中间体在本合成路线中的序号：(V)The condensation of 2-(4-nitrophenyl)ethyl bromide (I) with 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline (II) by means of K2CO3 and KI in DMF at 100 C gives 6,7-dimethoxy-2-[2-(4-nitrophenyl)ethyl]-1,2,3,4-tetrahydroisoquinoline (III), which is reduced with H2 over Pd/C in ethanol to yield the corresponding amine (IV). Finally, this compound is condensed with 5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxylic acid (V) by means of DCC and HOBt in DMF to afford the target carboxamide. The intermediate 5-methoxy-9-oxo-9,10-dihydroacridine-4-carboxylic acid (V) has been obtained as follows: The condensation of 2-amino-3-methoxybenzoic acid (VI) with 2-bromobenzoic acid (VII) by means of K2CO3 and copper dust give the diphenylamine (VIII), which is cyclized to the target acridine (V) by means of POCl3 in refluxing acetonitrile.
| 【1】 Dodic, N.; et al.; Synthesis and activity against multidrug resistance in Chinese hamster ovary cells of new acridone-4-carboxamides. J Med Chem 1995, 38, 13, 2418. |
| 【2】 Dumaitre, B.A.; Dodic, N. (GlaxoSmithKline plc); Acridine derivs.. EP 0494623; EP 0569380; JP 1994506440; US 5604237; WO 9212132 . |
| 【3】 Sharp, M.J.; Mader, C.J.; Strachan, C. (GlaxoSmithKline plc); Synthesis of acridine deriv. multidrug-resistant inhibitors. WO 9852923 . |
| 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) | 19191 | 1-(2-bromoethyl)-4-nitrobenzene | 5339-26-4 | C8H8BrNO2 | 详情 | 详情 |
| (II) | 25859 | 6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline; 6-methoxy-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether | C11H15NO2 | 详情 | 详情 | |
| (III) | 19193 | 6,7-dimethoxy-2-(4-nitrophenethyl)-1,2,3,4-tetrahydroisoquinoline; 6-methoxy-2-(4-nitrophenethyl)-1,2,3,4-tetrahydro-7-isoquinolinyl methyl ether | C19H22N2O4 | 详情 | 详情 | |
| (IV) | 19194 | 4-[2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl]aniline; 4-[2-[6,7-dimethoxy-3,4-dihydro-2(1H)-isoquinolinyl]ethyl]phenylamine | C19H24N2O2 | 详情 | 详情 | |
| (V) | 53881 | 5-methoxy-9-oxo-9,10-dihydro-4-acridinecarboxylic acid | n/a | C15H11NO4 | 详情 | 详情 |
| (VI) | 53879 | 2-Amino-3-methoxybenzoic acid; 2-Amino-m-anisic acid; 3-Methoxyanthranilic acid | 3177-80-8 | C8H9NO3 | 详情 | 详情 |
| (VII) | 15546 | 2-bromobenzoic acid; o-bromobenzoic acid | 88-65-3 | C7H5BrO2 | 详情 | 详情 |
| (VIII) | 53880 | 2-(2-carboxyanilino)-3-methoxybenzoic acid | n/a | C15H13NO5 | 详情 | 详情 |