Hydrogen Peroxide → HCID 178438745, compound

HRID 1688702Notes

Reaction equation

HRID 1688702 reaction equation
C([CH:4]1[CH2:7][CH:6]([N:8]2[C:13](=[O:14])[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([C:22]4[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=4)=[CH:18][C:17]=3[F:30])=[C:11]([CH2:31][CH2:32][CH3:33])[N:10]3[N:34]=[CH:35][N:36]=[C:9]23)[CH2:5]1)(=O)C.OO.FC(F)(F)C(OC(=O)C(F)(F)F)=[O:42].C(=O)([O-])O.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(#N)C.C(Cl)(Cl)Cl>[F:30][C:17]1[CH:18]=[C:19]([C:22]2[C:23]([C:28]#[N:29])=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH:20]=[CH:21][C:16]=1[CH2:15][C:12]1[C:13](=[O:14])[N:8]([C@H:6]2[CH2:5][C@@H:4]([OH:42])[CH2:7]2)[C:9]2[N:10]([N:34]=[CH:35][N:36]=2)[C:11]=1[CH2:31][CH2:32][CH3:33]

Participants

9

Reactant 6

HCID 784Hydrogen PeroxideHCID 9845Trifluoroacetic anhydrideHCID 24477Sodium Thiosulfate2×HCID 159087TriacetoxyperiodinaneHCID 516892Sodium Bicarbonate2×HCID 67008964HCID 67008964, compound

Product 1

HCID 178438745HCID 178438745, compoundYield 75%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 4′-{[4-(3-acetylcyclobutyl)-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}-3′-fluorobiphenyl-2-carbonitrile (2.8 g), 30% hydrogen peroxide (48 mL) and chloroform (50 mL) was gradually added dropwise trifluoroacetic acid anhydride (32 mL), and the mixture was heated under reflux for 15 hr. Saturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were gradually added to the reaction mixture, and the mixture was 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, the residue was mixed with tetrahydrofuran (30 mL), methanol (30 mL) and 1 M aqueous sodium hydroxide solution (30 mL), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was neutralized with 1 M hydrochloric acid. After evaporation of the solvent under reduced pressure, the residue was 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. The residue obtained by purification by silica gel column chromatography was mixed with Dess-Martin periodinane (2.8 g) and acetonitrile (15 mL), and the mixture was stirred at room temperature for 2 hr. Saturated aqueous sodium hydrogen carbonate solution and aqueous sodium thiosulfate solution were added to the reaction mixture. After evaporation of the solvent under reduced pressure, the residue was 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. 33% of the residue was dissolved in tetrahydrofuran (3 mL) and methanol (5 mL), sodium tetrahydroborate (0.094 g) was added at 0° C., and the mixture was stirred at room temperature for 14 hr. Saturated aqueous ammonium chloride solution was added to the reaction mixture, the solvent was evaporated under reduced pressure, and the residue was 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 purified by silica gel column chromatography to give the title compound as a colorless solid (0.67 g, 75%).

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 15 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. additionthe residue was mixed with tetrahydrofuran (30 mL), methanol (30 mL) and 1 M aqueous sodium hydroxide solution (30 mL)
  8. customAfter evaporation of the solvent under reduced pressure
  9. extractionthe residue was extracted with ethyl acetate
  10. washThe organic layer was washed with saturated brine
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customThe solvent was evaporated under reduced pressure
  13. customThe residue obtained by purification by silica gel column chromatography
  14. stirringthe mixture was stirred at room temperature for 2 hr
  15. customAfter evaporation of the solvent under reduced pressure
  16. extractionthe residue was extracted with ethyl acetate
  17. washThe organic layer was washed with saturated brine
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customThe solvent was evaporated under reduced pressure
  20. dissolution33% of the residue was dissolved in tetrahydrofuran (3 mL)
  21. additionmethanol (5 mL), sodium tetrahydroborate (0.094 g) was added at 0° C.
  22. stirringthe mixture was stirred at room temperature for 14 hr
  23. additionSaturated aqueous ammonium chloride solution was added to the reaction mixture
  24. customthe solvent was evaporated under reduced pressure
  25. extractionthe residue was extracted with ethyl acetate
  26. washThe organic layer was washed with saturated brine
  27. dry with materialdried over anhydrous magnesium sulfate
  28. customThe solvent was evaporated under reduced pressure
  29. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-36da9fa4448845a68f47dea301bc55e8
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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