反应详情

A mixture of 3′-fluoro-4′-[(5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl)methyl]biphenyl-2-carbonitrile (1 g), iodoethane (0.25 mL), potassium carbonate (0.71 g) and N,N-dimethylformamide (10 mL) was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 5% aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue obtained by silica gel column chromatography was dissolved in dimethyl sulfoxide (5 mL), and the mixture was added to a mixture of hydroxylammonium chloride (0.4 g), sodium hydrogen carbonate (0.65 g) and dimethyl sulfoxide (5 mL), which had been stirred in advance at 40° C. for 30 min. The reaction mixture was stirred at 90° C. for 16 hr, and diluted with ethyl acetate, and the mixture was washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.063 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.1 g, 8%).

1. washwashed with 5% aqueous potassium hydrogensulfate solution
2. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
3. customThe solvent was evaporated under reduced pressure
4. customThe residue obtained by silica gel column chromatography
5. stirringhad been stirred in advance at 40° C. for 30 min
6. stirringThe reaction mixture was stirred at 90° C. for 16 hr
7. washthe mixture was washed with water
8. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
9. customThe solvent was evaporated under reduced pressure
10. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
11. additionN,N′-Carbonyldiimidazole (0.075 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.063 mL) were added
12. stirringthe mixture was stirred at room temperature for 2 hr
13. additionThe reaction mixture was diluted with ethyl acetate
14. washwashed with saturated aqueous potassium hydrogensulfate solution
15. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
16. customThe solvent was evaporated under reduced pressure
17. customthe residue was purified by silica gel column chromatography