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

Temperature

40 °C

A mixture of hydroxylammonium chloride (1.2 g), sodium hydrogen carbonate (1.7 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 4′-{[2-ethyl-1-(3-fluoro-4-isopropoxyphenyl)-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.43 g) was added, and the mixture was stirred at 90° C. for 24 hr. The mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the precipitated solid was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was dissolved in tetrahydrofuran (10 mL). N,N′-carbonyldiimidazole (0.25 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.23 g, 48%).

1. stirringthe mixture was stirred at 90° C. for 24 hr
2. temperatureto cool to room temperature
3. filtrationthe precipitated solid was collected by filtration
4. dissolutionThe obtained solid was dissolved in ethyl acetate
5. washThe solution was washed with saturated brine
6. dry with materialdried over anhydrous sodium sulfate
7. customThe solvent was evaporated
8. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
9. additionN,N′-carbonyldiimidazole (0.25 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.23 mL) were added
10. stirringthe mixture was stirred at room temperature for 30 min
11. additionThe reaction mixture was diluted with ethyl acetate
12. washwashed with 1 M hydrochloric acid
13. dry with materialwith saturated brine, and dried over anhydrous sodium sulfate
14. customThe solvent was evaporated under reduced pressure
15. customThe residue was purified by silica gel column chromatography

ORD record

ord-40194baf8fe54021b61c0e2fbef4ffa6

Source dataset

uspto-grants-2010_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07803940B2