反应详情

A mixture of 4′-[(4-butyl-2-methyl-6-oxo-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (0.50 g), (2,2-dimethyl-3,4-dihydro-2H-chromen-6-yl)boronic acid (0.30 g), copper(II) acetate (0.27 g), pyridine (0.59 mL), triethylamine (1.0 mL), molecular sieves 4 A (1.0 g) and dichloromethane (5 mL) was stirred for 3 days. The reaction mixture was diluted with ethyl acetate, and the insoluble material was filtered off. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography. The resulting crudely purified product was added to a mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (7 mL), and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, washed with water and then with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in tetrahydrofuran (7 mL), N,N′-carbonyldiimidazole (0.34 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 mL) were added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogen sulfate 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 (0.64 g, 80%) as a colorless solid.

1. filtrationthe insoluble material was filtered off
2. concentrationThe filtrate was concentrated under reduced pressure
3. customthe residue was purified by silica gel column chromatography
4. additionThe resulting crudely purified product was added to a mixture of hydroxylammonium chloride (0.97 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (7 mL)
5. stirringthe mixture was stirred at 90° C. for 16 hr
6. additionThe reaction mixture was diluted with ethyl acetate
7. washwashed 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 (7 mL)
11. additionN,N′-carbonyldiimidazole (0.34 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.31 mL) were added
12. stirringthe mixture was stirred at room temperature for 1 hr
13. additionThe reaction mixture was diluted with ethyl acetate
14. washwashed with saturated aqueous potassium hydrogen sulfate 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