Dimethyl Sulfoxide → 4-[4-(1-hydroxyethyl)benzyl]-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

Temperature

40 °C

A mixture of hydroxylammonium chloride (2.4 g), sodium hydrogen carbonate (3.9 g) and dimethyl sulfoxide (15 mL) was stirred at 40° C. for 30 min, 4′-({4-[4-(1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)benzyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (1.4 g) was added, 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, and the residue was dissolved in tetrahydrofuran (15 mL). N,N′-Carbonyldiimidazole (0.45 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 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 dissolved in tetrahydrofuran (30 mL). Tetrabutylammonium bromide (1.0 M tetrahydrofuran solution, 5.8 mL) was added, and the mixture was stirred at 50° C. for 3 hr. The reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate, and the ethyl acetate layer was washed with saturated brine and concentrated. The residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.72 g, 56%).

1. stirringthe mixture was stirred at 90° C. for 16 hr
2. washwashed with water
3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
4. customThe solvent was evaporated under reduced pressure
5. dissolutionthe residue was dissolved in tetrahydrofuran (15 mL)
6. additionN,N′-Carbonyldiimidazole (0.45 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.38 mL) were added
7. stirringthe mixture was stirred at room temperature for 2 hr
8. additionThe reaction mixture was diluted with ethyl acetate
9. washwashed with saturated aqueous potassium hydrogensulfate solution
10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
11. customThe solvent was evaporated under reduced pressure
12. dissolutionthe residue was dissolved in tetrahydrofuran (30 mL)
13. additionTetrabutylammonium bromide (1.0 M tetrahydrofuran solution, 5.8 mL) was added
14. stirringthe mixture was stirred at 50° C. for 3 hr
15. extractionThe reaction mixture was extracted with 1 N hydrochloric acid and ethyl acetate
16. washthe ethyl acetate layer was washed with saturated brine
17. concentrationconcentrated
18. customThe residue was purified by silica gel column chromatography

ORD record

ord-9d717ca8a19f445ebc3883c28b951ccd

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148383B2