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 (73 mg, 0.16 mmol) produced in Example 31-B(i), (2-iodoethyl)benzoate (88 mg, 0.32 mmol), potassium carbonate (44 mg, 0.32 mmol) and N,N-dimethylformamide (3 mL) was stirred at 60° C. for 4 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0). The obtained solution was concentrated under reduced pressure. 1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue, and the mixture was stirred at 60° C. for 1 hr. To the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL), and the mixture was stirred at 60° C. for 2 hr. To the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL), and the mixture was stirred at room temperature for 1 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The collected organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the obtained residue was washed with diisopropyl ether to give the title compound (54 mg, 81%) as a colorless solid.

1. extractionthe mixture was extracted with ethyl acetate
2. washThe collected organic layer was washed with saturated brine
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationthe insoluble material was filtered off
5. concentrationThe filtrate was concentrated under reduced pressure
6. customthe obtained residue was purified by basic silica gel column chromatography (ethyl acetate/hexane=30/70→100/0)
7. concentrationThe obtained solution was concentrated under reduced pressure
8. addition1N Hydrochloric acid (2 mL), methanol (2 mL) and tetrahydrofuran (2 mL) were added to the obtained residue
9. stirringthe mixture was stirred at 60° C. for 1 hr
10. additionTo the reaction mixture were added methanol (1 mL) and tetrahydrofuran (1 mL)
11. stirringthe mixture was stirred at 60° C. for 2 hr
12. additionTo the reaction mixture was added 2N aqueous sodium hydroxide solution (2 mL)
13. stirringthe mixture was stirred at room temperature for 1 hr
14. additionTo the reaction mixture was added water
15. extractionthe mixture was extracted with ethyl acetate
16. washThe collected organic layer was washed with saturated brine
17. dry with materialdried over anhydrous magnesium sulfate
18. filtrationthe insoluble material was filtered off
19. concentrationThe filtrate was concentrated under reduced pressure
20. washthe obtained residue was washed with diisopropyl ether