Dimethyl Sulfoxide → 3-[4-(2-hydroxy-1,1-dimethylethoxy)phenyl]-2-methyl-5-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-6-propylpyrimidin-4(3H)-one

Temperatur

40 °C

A mixture of hydroxylammonium chloride (0.68 g), sodium hydrogen carbonate (0.98 g) and dimethyl sulfoxide (5 mL) was stirred at 40° C. for 30 min, 4′-({1-[4-(2-hydroxy-1,1-dimethylethoxy)phenyl]-2-methyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl}methyl)biphenyl-2-carbonitrile (0.49 g) was added, 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 (5 mL). N,N′-carbonyldiimidazole (0.19 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.17 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 a colorless solid (0.14 g, 26%).

1. stirringthe mixture was stirred at 90° C. for 18 hr
2. temperatureto cool to room temperature
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. customThe solvent was evaporated
7. dissolutionthe residue was dissolved in tetrahydrofuran (5 mL)
8. additionN,N′-carbonyldiimidazole (0.19 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.17 mL) were added
9. stirringthe mixture was stirred at room temperature for 3 hr
10. additionThe reaction mixture was diluted with ethyl acetate
11. washwashed with 1 M hydrochloric acid
12. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
13. customThe solvent was evaporated under reduced pressure
14. customthe residue was purified by silica gel column chromatography

ORD-Eintrag

ord-0f41e6da99a3481e9cbed0bc7dce3eed

Quelldatensatz

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07803940B2