Dimethyl Sulfoxide → HCID 178438452, compound

HRID 1689065Notes

Reaction equation

HRID 1689065 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[C:13]([C:16]1[CH:56]=[CH:55][C:19]([O:20][C@@H:21]2[CH2:26][CH2:25][C@H:24]([N:27]3[C:32](=[O:33])[C:31]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([C:41]5[C:42]([C:47]#[N:48])=[CH:43][CH:44]=[CH:45][CH:46]=5)=[CH:37][CH:36]=4)=[C:30]([CH2:49][CH2:50][CH3:51])[N:29]4[N:52]=[CH:53][N:54]=[C:28]34)[CH2:23][CH2:22]2)=[CH:18][CH:17]=1)(=[O:15])[CH3:14]>O.C(OCC)(=O)C>[C:13]([C:16]1[CH:17]=[CH:18][C:19]([O:20][C@@H:21]2[CH2:26][CH2:25][C@H:24]([N:27]3[C:32](=[O:33])[C:31]([CH2:34][C:35]4[CH:40]=[CH:39][C:38]([C:41]5[CH:46]=[CH:45][CH:44]=[CH:43][C:42]=5[C:47]5[NH:3][C:4](=[O:7])[O:5][N:48]=5)=[CH:37][CH:36]=4)=[C:30]([CH2:49][CH2:50][CH3:51])[N:29]4[N:52]=[CH:53][N:54]=[C:28]34)[CH2:23][CH2:22]2)=[CH:55][CH:56]=1)(=[O:15])[CH3:14]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 178438582HCID 178438582, compound

Product 1

HCID 178438452HCID 178438452, compoundYield 17.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.88 g), sodium hydrogen carbonate (1.4 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-({4-[cis-4-(4-acetylphenoxy)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.50 g) was added, and the mixture was stirred at 90° C. for 40 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 saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was dissolved in tetrahydrofuran (4 mL). N,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.15 mL) were added, and the mixture was stirred at room temperature for 50 hr. Ethyl acetate and water were added to the reaction mixture, and the mixture was acidified with 1 M hydrochloric acid 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 heated under reflux in ethanol (10 mL)-20% sulfuric acid (5 mL) for 16 hr. The solvent was evaporated under reduced pressure, 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 and the residue was purified by silica gel column chromatography to give the title compound as a colorless solid (0.097 g, 17%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 40 hr
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customThe solvent was evaporated under reduced pressure
  6. dissolutionthe residue was dissolved in tetrahydrofuran (4 mL)
  7. additionN,N′-Carbonyldiimidazole (0.16 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.15 mL) were added
  8. stirringthe mixture was stirred at room temperature for 50 hr
  9. additionEthyl acetate and water were added to the reaction mixture
  10. extractionextracted with ethyl acetate
  11. washThe organic layer was washed with saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customThe solvent was evaporated under reduced pressure
  14. temperaturethe residue was heated
  15. temperatureunder reflux in ethanol (10 mL)-20% sulfuric acid (5 mL) for 16 hr
  16. customThe solvent was evaporated under reduced pressure
  17. extractionthe mixture was extracted with ethyl acetate
  18. washThe organic layer was washed with saturated brine
  19. dry with materialdried over anhydrous magnesium sulfate
  20. customThe solvent was evaporated under reduced pressure
  21. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-bec63cb7e61c47c1ab53fd8605b8d4a1
Source dataset
uspto-grants-2012_04
Patent number
US08148383B2

Reaction notes

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