反应详情

温度

110 °C

In an oven dried round-bottom flask, [4-(6-chloropyridazin-3-yl)piperazin-1-yl]-(2-trifluoromethylphenyl)methanone (1.80 g, 4.85 mmol), Pd2(dba)3 (0.130 g, 0.14 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.161 g, 0.29 mmol), Zn powder (0.317 g, 4.85 mmol) and Zn(CN)2 (0.569 g, 4.85 mmol) were placed under nitrogen atmosphere. Dimethylacetamide (10 mL) was added and the suspension was purged with nitrogen. The mixture was then heated at 110° C. overnight, then cooled to room temperature and then concentrated in vacuo. The brown residue was dissolved in ethyl acetate (15 mL) and washed with water (2×10 mL), dried over anhydrous Na2SO4 and then concentrated. The crude product was purified using column chromatography to afford 6-[4-(2-trifluoromethylbenzoyl)piperazin-1-yl]pyridazine-3-carbonitrile as a pale yellow syrup in 59% yield (1.03 g). 1H NMR (300 MHz, CDCl3) δ 7.71 (d, J=7.8 Hz, 1H), 7.63-7.50 (m, 2H), 7.48 (d, J=9.6 Hz, 1H), 7.32 (d, J=7.3 Hz, 1H), 6.89 (d, J=9.6 Hz, 1H), 4.12-3.98 (m, 1H), 3.92-3.70 (m, 5H), 3.31 (t, J=5.3 Hz, 2H), 13C NMR (75 MHz, CDCl3) δ 167.7, 158.4, 132.4, 130.8, 130.0, 129.6, 127.1, 126.9, 126.8, 116.5, 110.2, 46.2, 44.2, 43.9, 41.1. MS (ES+) m/z 362.3 (M+H).

1. customthe suspension was purged with nitrogen
2. temperaturecooled to room temperature
3. concentrationconcentrated in vacuo
4. dissolutionThe brown residue was dissolved in ethyl acetate (15 mL)
5. washwashed with water (2×10 mL)
6. dry with materialdried over anhydrous Na2SO4
7. concentrationconcentrated
8. customThe crude product was purified