Dimethyl Sulfoxide → 4-[4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)cyclohexyl]-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-one

HRID 520124Notes

Reaction equation

HRID 520124 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[OH:13][C:14]1([CH:48]2[CH2:53][CH2:52][O:51][CH2:50][CH2:49]2)[CH2:19][CH2:18][CH:17]([N:20]2[C:25](=[O:26])[C:24]([CH2:27][C:28]3[CH:33]=[CH:32][C:31]([C:34]4[C:35]([C:40]#[N:41])=[CH:36][CH:37]=[CH:38][CH:39]=4)=[CH:30][CH:29]=3)=[C:23]([CH2:42][CH2:43][CH3:44])[N:22]3[N:45]=[CH:46][N:47]=[C:21]23)[CH2:16][CH2:15]1>O.C(OCC)(=O)C>[OH:13][C:14]1([CH:48]2[CH2:49][CH2:50][O:51][CH2:52][CH2:53]2)[CH2:15][CH2:16][CH:17]([N:20]2[C:25](=[O:26])[C:24]([CH2:27][C:28]3[CH:29]=[CH:30][C:31]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=4[C:40]4[NH:3][C:4](=[O:7])[O:5][N:41]=4)=[CH:32][CH:33]=3)=[C:23]([CH2:42][CH2:43][CH3:44])[N:22]3[N:45]=[CH:46][N:47]=[C:21]23)[CH2:18][CH2:19]1

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670096254'-({4-[4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile

Product 1

HCID 1360637254-[4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)cyclohexyl]-6-{[2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-oneYield 15.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.24 g), sodium hydrogen carbonate (0.38 g) and dimethyl sulfoxide (3 mL) was stirred at 40° C. for 30 min, 4′-({4-[4-hydroxy-4-(tetrahydro-2H-pyran-4-yl)cyclohexyl]-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl}methyl)biphenyl-2-carbonitrile (0.12 g) was added, and the mixture was stirred at 90° C. for 24 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 (2 mL). N,N′-Carbonyldiimidazole (0.045 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.042 mL) were 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 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 purified by silica gel column chromatography to give the title compound as a colorless solid (0.020 g, 14%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 24 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 (2 mL)
  7. additionN,N′-Carbonyldiimidazole (0.045 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.042 mL) were added
  8. stirringthe mixture was stirred at room temperature for 3 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. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-f0ad70ad0e904ba286f6371f7b8e6842
Source dataset
uspto-grants-2015_08
Patent number
US09115136B2

Reaction notes

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