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【结 构 式】 
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【分子编号】68183 【品名】4-amino-6-fluoro-2-benzofuran-1(3H)-one 【CA登记号】 |
【 分 子 式 】C8H6FNO2 【 分 子 量 】167.13958 【元素组成】C 57.49% H 3.62% F 11.37% N 8.38% O 19.14% |
合成路线1
该中间体在本合成路线中的序号：(XI)Intermediate (X) can also be prepared by coupling of 4-amino-6-fluoro-2-benzofuran-1(3H)-one (XI) with 4-fluorobenzaldehyde (V) in the presence of MgSO4 in refluxing CH2Cl2 to afford the benzylidene derivative (XII), which by cyclocondensation with 1-methyl-1H-1,2,4-triazole-5-carbaldehyde (II) in the presence of NaOEt in ethyl propionate at 40 °C yields the tetrahydroquinolone (XIII). Finally, ethyl ester (XIII) is condensed with NH2NH2·H2O in MeOH .
Alternatively, the reaction of alkene (III) with NH2NH2·H2O in THF gives the 1,2-dihydrophthalazine derivative (XIV), which is then condensed with 4-fluorobenzaldehyde (V) in refluxing acetonitrile to yield imine (XV). Finally, intermediate (XV) is submitted to intramolecular cyclizacyclization by means of Cs2CO3 in THF at 55 °C and provides the racemate (X) .
| 【2】 Wang, B., Chu, D. (LEAD Therapeutics, Inc.). Dihydropyridophthalazinone inhibitors of poly(ADP-ribose)polymerase (PARP). CN 102171214, EP 2326650, GB 2462361, JP 2011530513, KR 2011040973, US 2010035883, US 8012976, US 2011237581, US 8420650, US 2013190306, WO 2010017055. |
| 【1】 Wang, B., Chu, D., Liu, Y., Jiang, Q., Lu, L. (BioMarin Pharmaceutical, Inc.). Processes of synthesizing dihydropyridophthalazinone derivatives. EP 2533640, JP 2013518910, KR 2012125630, US 2011196153, WO 2011097602. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (II) | 68175 | 1-methyl-1H-1,2,4-triazole-5-carbaldehyde | C4H5N3O | 详情 | 详情 | |
| (III) | 68176 | (Z)-6-fluoro-3-((1-methyl-1H-1,2,4-triazol-5-yl)methylene)-4-nitroisobenzofuran-1(3H)-one | C12H7FN4O4 | 详情 | 详情 | |
| (V) | 12337 | 4-fluorobenzaldehyde | 459-57-4 | C7H5FO | 详情 | 详情 |
| (X) | 68182 | 5-fluoro-8-(4-fluorophenyl)-9-(1-methyl-1H-1,2,4-triazol-5-yl)-8,9-dihydro-2H-pyrido[4,3,2-de]phthalazin-3(7H)-one | C19H14F2N6O | 详情 | 详情 | |
| (XI) | 68183 | 4-amino-6-fluoro-2-benzofuran-1(3H)-one | C8H6FNO2 | 详情 | 详情 | |
| (XII) | 68184 | (E)-6-fluoro-4-((4-fluorobenzylidene)amino)isobenzofuran-1(3H)-one | C15H9F2NO2 | 详情 | 详情 | |
| (XIII) | 68185 | ethyl 7-fluoro-2-(4-fluorophenyl)-3-(1-methyl-1H-1,2,4-triazol-5-yl)-4-oxo-1,2,3,4-tetrahydroquinoline-5-carboxylate | C21H18F2N4O3 | 详情 | 详情 | |
| (XIV) | 68186 | 5-amino-7-fluoro-4-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)phthalazin-1(2H)-one | C12H11FN6O | 详情 | 详情 | |
| (XV) | 68187 | (E)-7-fluoro-5-((4-fluorobenzylidene)amino)-4-((1-methyl-1H-1,2,4-triazol-5-yl)methyl)phthalazin-1(2H)-one | C19H14F2N6O | 详情 | 详情 |