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

HRID 1412700

Reaction equation

HRID 1412700 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[F:13][C:14]1[CH:15]=[C:16]([C:40]2[C:41]([C:46]#[N:47])=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:17]=[CH:18][C:19]=1[CH2:20][C:21]1[C:22](=[O:39])[N:23]([CH:34]([CH3:38])[CH2:35][O:36][CH3:37])[C:24]2[N:25]([N:30]=[C:31]([CH3:33])[N:32]=2)[C:26]=1[CH2:27][CH2:28][CH3:29]>C(OCC)(=O)C>[F:13][C:14]1[CH:15]=[C:16]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[C:46]2[NH:3][C:4](=[O:7])[O:5][N:47]=2)[CH:17]=[CH:18][C:19]=1[CH2:20][C:21]1[C:22](=[O:39])[N:23]([CH:34]([CH3:38])[CH2:35][O:36][CH3:37])[C:24]2[N:25]([N:30]=[C:31]([CH3:33])[N:32]=2)[C:26]=1[CH2:27][CH2:28][CH3:29]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 670099643'-Fluoro-4'-{[4-(2-methoxy-1-methylethyl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile

Product 1

HCID 1360636766-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-4-(2-methoxy-1-methylethyl)-2-methyl-7-propyl[1,2,4]triazolo[1,5-a]pyrimidin-5(4H)-oneYield 49%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (0.62 g), sodium hydrogen carbonate (0.99 g) and dimethyl sulfoxide (10 mL) was stirred at 40° C. for 30 min, 3′-fluoro-4′-{[4-(2-methoxy-1-methylethyl)-2-methyl-5-oxo-7-propyl-4,5-dihydro[1,2,4]triazolo[1,5-a]pyrimidin-6-yl]methyl}biphenyl-2-carbonitrile (0.28 g) was added, and the mixture was stirred at 90° C. for 16 hr. The reaction mixture was diluted with ethyl acetate, 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 dissolved in tetrahydrofuran (10 mL). N,N′-Carbonyldiimidazole (0.12 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.097 mL) were added, and the mixture was stirred at room temperature for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous potassium hydrogensulfate solution 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 to give the title compound as colorless crystals (0.15 g, 49%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. washwashed with water
  3. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. dissolutionthe residue was dissolved in tetrahydrofuran (10 mL)
  6. additionN,N′-Carbonyldiimidazole (0.12 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.097 mL) were added
  7. stirringthe mixture was stirred at room temperature for 2 hr
  8. additionThe reaction mixture was diluted with ethyl acetate
  9. washwashed with saturated aqueous potassium hydrogensulfate solution
  10. dry with materialwith saturated brine, and dried over anhydrous magnesium sulfate
  11. customThe solvent was evaporated under reduced pressure
  12. customthe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0602ab6d31bc44b280477a1d36674f2e
Source dataset
uspto-grants-2014_12
Patent number
US08921379B2

Linked notes

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