反应详情

温度

60 °C

A mixture of 2-methyl-3-{4-phenyl-5-[1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazol-2-yl}pyrazolo[1,5-a]pyridin-5-ol (100 mg, 0.22 mmol) obtained in Example 31-B(i), 5-(chloromethyl)-2-(trifluoromethyl)pyridine (64 mg, 0.33 mmol), potassium carbonate (60 mg, 0.44 mmol) and DMF (4 mL) was stirred at 60° C. for 2 h. Water (100 mL) and EtOAc (100 mL) were added to the reaction mixture, and the mixture was stirred for 30 min. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. Insoluble materials were removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was dissolved in MeOH (5 mL) and THF (30 mL), 6 N hydrochloric acid (3 mL) was added, and the mixture was stirred at 70° C. for 3 h. The reaction mixture was allowed to cool to rt, and the mixture was concentrated under reduced pressure. To the residue were added EtOAc (50 mL), THF (50 mL), 8 N aqueous sodium hydroxide solution (3 mL) and water (30 mL), and the mixture was stirred for 30 min. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and insoluble materials were removed by filtration. The filtrate was concentrated under reduced pressure. The residue was crystallized from EtOAc to give the title compound (107 mg, 92%) as a white solid.

1. stirringthe mixture was stirred for 30 min
2. washThe organic layer was washed with brine
3. dry with materialdried over anhydrous magnesium sulfate
4. customInsoluble materials were removed by filtration
5. concentrationthe filtrate was concentrated under reduced pressure
6. dissolutionThe residue was dissolved in MeOH (5 mL)
7. additionTHF (30 mL), 6 N hydrochloric acid (3 mL) was added
8. stirringthe mixture was stirred at 70° C. for 3 h
9. temperatureto cool to rt
10. concentrationthe mixture was concentrated under reduced pressure
11. additionTo the residue were added EtOAc (50 mL), THF (50 mL), 8 N aqueous sodium hydroxide solution (3 mL) and water (30 mL)
12. stirringthe mixture was stirred for 30 min
13. washThe organic layer was washed with brine
14. dry with materialdried over anhydrous magnesium sulfate, and insoluble materials
15. customwere removed by filtration
16. concentrationThe filtrate was concentrated under reduced pressure
17. customThe residue was crystallized from EtOAc