Dimethyl Sulfoxide → HCID 178440089, compound

Temperature

40 °C

A mixture of hydroxylammonium chloride (0.82 g), sodium hydrogen carbonate (1.2 g) and dimethyl sulfoxide (5 mL) was stirred at 40° C. for 30 min, 4′-{[1-(4-{[trans-4-(1-{[tert-butyl(dimethyl)silyl]oxy}-1-methylethyl)cyclohexyl]oxy}phenyl)-2-ethyl-6-oxo-4-propyl-1,6-dihydropyrimidin-5-yl]methyl}biphenyl-2-carbonitrile (0.48 g) was added, and the mixture was stirred at 90° C. for 8 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 (5 mL). N,N′-carbonyldiimidazole (0.17 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 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 dissolved in 1,4-dioxane (5 mL), tetrabutylammonium fluoride (2.1 mL, 1.0 M tetrahydrofuran solution) was added and the mixture was heated under reflux for 24 hr. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate, and 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 (0.094 g, 21%).

1. stirringthe mixture was stirred at 90° C. for 8 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 (5 mL)
9. additionN,N′-carbonyldiimidazole (0.17 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.16 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. dissolutionThe residue was dissolved in 1,4-dioxane (5 mL)
16. additiontetrabutylammonium fluoride (2.1 mL, 1.0 M tetrahydrofuran solution) was added
17. temperaturethe mixture was heated
18. temperatureunder reflux for 24 hr
19. additionThe reaction mixture was diluted with ethyl acetate
20. washwashed with 1 M hydrochloric acid and saturated brine
21. dry with materialdried over anhydrous sodium sulfate
22. customthe solvent was evaporated under reduced pressure
23. customThe residue was purified by silica gel column chromatography

ORD record

ord-c159b11617dc48468e1a46f91f35eb26

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07998968B2