Pyridine → 5-{[3-chloro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-3-(2,2-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-2-methyl-6-propylpyrimidin-4(3H)-one

To a suspension of 3′-chloro-4′-[(2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl)methyl]biphenyl-2-carbonitrile (0.65 g), (2,2-dimethyl-2,3-dihydro-1-benzofuran-5-yl)boronic acid (0.66 g), triethylamine (0.8 mL), pyridine (1.6 mL) and molecular sieves 4 A (1.60 g) in dichloromethane (20 mL) was added copper(II) acetate (0.65 g) and the mixture was stirred at room temperature for 2 days. The reaction mixture was diluted with ethyl acetate, the insoluble material was filtered off through celite, and the filtrate was concentrated. The residue was purified by silica gel column chromatography. The crudely purified product was added to a mixture of hydroxylammonium chloride (1.38 g), sodium hydrogen carbonate (2.22 g) and dimethyl sulfoxide (20 mL), which had been stirred at 40° C. for 30 min, and the mixture was stirred at 90° C. for 18 hr. The reaction mixture was allowed to cool to room temperature, ethyl acetate and water were added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (20 mL). N,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.30 mL) were added, and the mixture was stirred at room temperature for 3 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid 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 (0.68 g, 62%).

1. filtrationthe insoluble material was filtered off through celite
2. concentrationthe filtrate was concentrated
3. customThe residue was purified by silica gel column chromatography
4. additionThe crudely purified product was added to a mixture of hydroxylammonium chloride (1.38 g), sodium hydrogen carbonate (2.22 g) and dimethyl sulfoxide (20 mL), which
5. stirringhad been stirred at 40° C. for 30 min
6. stirringthe mixture was stirred at 90° C. for 18 hr
7. temperatureto cool to room temperature
8. additionethyl acetate and water were added
9. extractionthe mixture was extracted with ethyl acetate
10. washThe organic layer was washed with saturated brine
11. dry with materialdried over anhydrous magnesium sulfate
12. customThe solvent was evaporated
13. dissolutionthe residue was dissolved in tetrahydrofuran (20 mL)
14. additionN,N′-carbonyldiimidazole (0.33 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.30 mL) were added
15. stirringthe mixture was stirred at room temperature for 3 hr
16. additionThe reaction mixture was diluted with ethyl acetate
17. washwashed with 1 M hydrochloric acid
18. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
19. customThe solvent was evaporated under reduced pressure
20. customthe residue was purified by silica gel column chromatography

ORD record

ord-8ff03e3e916f412ebc1a713978d3f5cd

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2