反应详情

温度

100 °C

To a solution of 6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-thiol (50 g, 268 mmol) in DMF (750 mL) is added 5-iodo-2-methyl-2H-indazole (55.5 g, 215.1 mmol), 2-Pyridinecarboxylic Acid (5.5 g, 44.7 mmoles), Copper (I) Iodide (4 g, 21.0 mmoles), and Cesium Carbonate (212.5 g, 652.2 moles). The mixture is under N2 and stirred at 100° C. for 10 hours. The reaction mixture is then cooled to room temperature and poured into water (2000 mL). After stirring at room temperature for 30 min, the mixture is extracted with a mixed solvent (2 L×2, CHCl3/IPA=3/1). The combined organic layer is then washed four times with mixed solution (25% NH4OH(aq)/brine=¼; 800 mL), sat. LiCl(aq) (1 L), sat. brine (1.5 L×2), and dry over Na2SO4. The organic solution is concentrated under reduced pressure to give a brown crude solid product. The crude product is triturated with ethyl acetate (800 mL) at room temperature for 3 hours and the pure product is collected by filtration to afford the title compound (68 g, 87.2%) as a white solid. MS (m/z): 363.0 (M+H).

1. temperatureThe reaction mixture is then cooled to room temperature
2. stirringAfter stirring at room temperature for 30 min
3. extractionthe mixture is extracted with a mixed solvent (2 L×2, CHCl3/IPA=3/1)
4. washThe combined organic layer is then washed four times with mixed solution (25% NH4OH(aq)/brine=¼; 800 mL), sat. LiCl(aq) (1 L), sat. brine (1.5 L×2)
5. dry with materialdry over Na2SO4
6. concentrationThe organic solution is concentrated under reduced pressure
7. customto give a brown crude solid product
8. customThe crude product is triturated with ethyl acetate (800 mL) at room temperature for 3 hours
9. filtrationthe pure product is collected by filtration