Dimethyl Sulfoxide → 2-butyl-3-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-5-(4-fluorophenyl)-6-methylpyrimidin-4(3H)-one

HRID 1673599Notes

Reaction equation

HRID 1673599 reaction equation
[Cl-].O[NH3+:3].[C:4](=[O:7])([O-])[OH:5].[Na+].CS(C)=O.[CH2:13]([C:17]1[N:18]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[C:40]([C:45]#[N:46])=[CH:41][CH:42]=[CH:43][CH:44]=3)=[CH:35][C:34]=2[F:47])[C:19](=[O:31])[C:20]([C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[C:21]([CH3:23])[N:22]=1)[CH2:14][CH2:15][CH3:16]>O>[CH2:13]([C:17]1[N:18]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[C:45]3[NH:3][C:4](=[O:7])[O:5][N:46]=3)=[CH:35][C:34]=2[F:47])[C:19](=[O:31])[C:20]([C:24]2[CH:25]=[CH:26][C:27]([F:30])=[CH:28][CH:29]=2)=[C:21]([CH3:23])[N:22]=1)[CH2:14][CH2:15][CH3:16]

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 21645Hydroxylamine HClHCID 516892Sodium BicarbonateHCID 574600754'-{[2-butyl-5-(4-fluorophenyl)-4-methyl-6-oxopyrimidin-1(6H)-yl]methyl}-3'-fluorobiphenyl-2-carbonitrile

Product 1

HCID 1360267442-butyl-3-{[3-fluoro-2'-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl}-5-(4-fluorophenyl)-6-methylpyrimidin-4(3H)-oneYield 73%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of hydroxylammonium chloride (1.02 g), sodium hydrogen carbonate (1.45 g) and dimethyl sulfoxide (5 mL) was stirred at 40° C. for 30 min, 4′-{[2-butyl-5-(4-fluorophenyl)-4-methyl-6-oxopyrimidin-1(6H)-yl]methyl}-3′-fluorobiphenyl-2-carbonitrile (0.51 g) was added, and the mixture was stirred at 90° C. for 16 hr. The mixture was allowed to cool to room temperature, water was added to the reaction mixture, and the precipitate was collected by filtration. The obtained solid was dissolved in ethyl acetate. The solution was washed with saturated brine and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was dissolved in tetrahydrofuran (15 mL), N,N′-carbonyldiimidazole (0.26 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.24 mL) were added, and the mixture was stirred at room temperature for 30 min. The reaction mixture was diluted with ethyl acetate, washed with 1 M hydrochloric acid and then with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography to give the title compound as colorless crystals (0.41 g, 73%).

Workup

  1. stirringthe mixture was stirred at 90° C. for 16 hr
  2. temperatureto cool to room temperature
  3. filtrationthe precipitate was collected by filtration
  4. dissolutionThe obtained solid was dissolved in ethyl acetate
  5. washThe solution was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated
  8. dissolutionThe residue was dissolved in tetrahydrofuran (15 mL)
  9. additionN,N′-carbonyldiimidazole (0.26 g) and then 1,8-diazabicyclo[5.4.0]undec-7-ene (0.24 mL) were added
  10. stirringthe mixture was stirred at room temperature for 30 min
  11. additionThe reaction mixture was diluted with ethyl acetate
  12. washwashed with 1 M hydrochloric acid
  13. dry with materialwith saturated brine, and dried over anhydrous sodium sulfate
  14. customThe solvent was evaporated under reduced pressure
  15. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-88e54f269d0740d3b27f8acc6a8fb91b
Source dataset
uspto-grants-2011_08
Patent number
US07998968B2

Reaction notes

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