Hydroxylamine HCl → HCID 136053101, compound

Temperature

50 °C

A mixture of hydroxylammonium chloride (2.7 g), sodium hydrogen carbonate (4.4 g) and dimethyl sulfoxide (25 mL) was stirred at 50° C. for 30 min, 4′-{[4-(2-{[tert-butyl(dimethyl)silyl]oxy}-1-methylpropyl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (1.5 g) was added, and the mixture was stirred at 90° C. for 20 hr. After allowing to cool to room temperature, the reaction mixture was extracted with ethyl acetate and water, and 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 (30 mL). N,N′-Carbonyldiimidazole (0.51 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.43 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 (30 mL). Tetrabutylammonium fluoride (1 M tetrahydrofuran solution, 6.6 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. The residue obtained by silica gel column chromatography was dissolved in acetonitrile (20 mL), Dess-Martin reagent (1.1 g) was added, and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution and sodium thiosulfate were added to the reaction mixture, and the mixture was stirred at room temperature for 2 hr, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was recrystallized from acetone and hexane to give the title compound as colorless crystals (0.5 g, 37%).

1. stirringthe mixture was stirred at 90° C. for 20 hr
2. temperatureto cool to room temperature
3. extractionthe reaction mixture was extracted with ethyl acetate and water
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 (30 mL)
9. additionN,N′-Carbonyldiimidazole (0.51 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.43 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 (30 mL)
16. additionTetrabutylammonium fluoride (1 M tetrahydrofuran solution, 6.6 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
23. customThe residue obtained by silica gel column chromatography
24. stirringthe mixture was stirred at room temperature for 2 hr
25. stirringthe mixture was stirred at room temperature for 2 hr
26. extractionextracted with ethyl acetate
27. washThe organic layer was washed with saturated brine
28. dry with materialdried over anhydrous magnesium sulfate
29. customThe solvent was evaporated under reduced pressure
30. customthe residue was recrystallized from acetone and hexane

ORD record

ord-597fe448d27a48e1a8bc47693b53ddda

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148383B2