反应详情

1,8-Diazabicyclo[5.4.0]-7-undecene (0.750 mL, 5.02 mmol) was added to a suspension of 3-(piperidin-4-yl)-1H-pyrazol-5-amine hydrochloride (0.400 g, 1.67 mmol) produced in Reference Example 33 in dimethyl sulfoxide (4 mL), and the mixture was stirred at room temperature for 10 minutes. Then, 3,6-dichloropyridazine (0.249 g, 1.67 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour and at 60° C. for 4 hours. After cooling to room temperature, water was added to the reaction solution, followed by extraction with ethyl acetate. The obtained organic layer was washed with brine and dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography [elute: ethyl acetate/methanol=95/5-90/10 (gradient)] to obtain the title compound (0.330 g, yield: 71%).

1. stirringthe mixture was stirred at room temperature for 1 hour and at 60° C. for 4 hours
2. temperatureAfter cooling to room temperature
3. extractionfollowed by extraction with ethyl acetate
4. washThe obtained organic layer was washed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. distillationthe solvent was distilled off under reduced pressure
7. customThe obtained residue was purified by silica gel column chromatography [elute: ethyl acetate/methanol=95/5-90/10 (gradient)]