Dimethyl Sulfoxide → HCID 178438512, compound

Temperature

50 °C

A mixture of hydroxylammonium chloride (0.46 g), sodium hydrogen carbonate (0.74 g) and dimethyl sulfoxide (10 mL) was stirred at 50° C. for 30 min, 4′-({4-[trans-4-(2-{[tert-butyl(dimethyl)silyl]oxy}butoxy)cyclohexyl]-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.29 g) was added, and the mixture was stirred at 90° C. for 20 hr. After allowing to cool to room temperature, ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was 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 purified by silica gel column chromatography, and dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.086) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.073 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 N hydrochloric acid 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 (10 mL). Tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 1.1 mL) was added, and the mixture was stirred at room temperature for 3 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was 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 solidified with diisopropyl ether to give the title compound as a colorless solid (0.12 g, 45%).

1. stirringthe mixture was stirred at 90° C. for 20 hr
2. temperatureto cool to room temperature
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with water
5. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
6. customThe solvent was evaporated under reduced pressure
7. customthe residue was purified by silica gel column chromatography
8. dissolutiondissolved in tetrahydrofuran (10 mL)
9. additionN,N′-Carbonyldiimidazole (0.086) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.073 mL) were added
10. stirringthe mixture was stirred at room temperature for 2 hr
11. additionThe reaction mixture was diluted with ethyl acetate
12. washwashed with 1 N hydrochloric acid
13. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
14. customThe solvent was evaporated under reduced pressure
15. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
16. additionTetrabutylammonium fluoride (1 M tetrahydrofuran solution, 1.1 mL) was added
17. stirringthe mixture was stirred at room temperature for 3 hr
18. additionEthyl acetate and water were added to the reaction mixture
19. extractionthe mixture was extracted with ethyl acetate
20. washThe organic layer was washed with water
21. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
22. customThe solvent was evaporated under reduced pressure

ORD record

ord-014915042af241bb94368027c1d6ae9e

Source dataset

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09115136B2