Sulfuric Acid → N-{[1-(cyanomethyl)-1H-pyrazol-4-yl]methyl}-3-(3,5-difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxamide

HRID 1522766Notes

Reaction equation

HRID 1522766 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:11]2[CH2:15][C:14]([CH3:25])([C:16]([NH:18][CH2:19][C:20]3[CH:21]=[N:22][NH:23][CH:24]=3)=[O:17])[O:13][N:12]=2)[CH:7]=[C:8]([F:10])[CH:9]=1.Br[CH2:27][C:28]#[N:29].S(=O)(=O)(O)O>CN(C=O)C>[C:28]([CH2:27][N:23]1[CH:24]=[C:20]([CH2:19][NH:18][C:16]([C:14]2([CH3:25])[O:13][N:12]=[C:11]([C:6]3[CH:5]=[C:4]([F:3])[CH:9]=[C:8]([F:10])[CH:7]=3)[CH2:15]2)=[O:17])[CH:21]=[N:22]1)#[N:29]

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 11534BromoacetonitrileHCID 24758Sodium hydrideHCID 683867093-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide

Product 1

HCID 68387195N-{[1-(cyanomethyl)-1H-pyrazol-4-yl]methyl}-3-(3,5-difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxamideYield 64.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

At 0° C., NaH (60% by weight suspension in mineral oil, 30 mg, 0.75 mmol) was added to a solution of 3-(3,5-difluorophenyl)-5-methyl-N-(1H-pyrazol-4-ylmethyl)-4,5-dihydro-1,2-oxazole-5-carboxamide (200 mg, 0.62 mmol) in DMF (10 ml), and the mixture was stirred for 15 min. The mixture was then warmed to RT, and bromoacetonitrile (225 mg, 1.87 mmol) was added. The mixture was stirred at RT for h and then at 60° C. for 4 h. After cooling to RT, sulfuric acid (0.5M, 10 ml) was added, and the mixture was extracted with EtOAc (3×20 ml). The combined organic phases were then dried over Na2SO4, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel using the mobile phase heptane/EtOAc, giving N-{[1-(cyanomethyl)-1H-pyrazol-4-yl]methyl}-3-(3,5-difluorophenyl)-5-methyl-4,5-dihydro-1,2-oxazole-5-carboxamide (144 mg, 64%).

Workup

  1. stirringThe mixture was stirred at RT for h
  2. waitat 60° C. for 4 h
  3. temperatureAfter cooling to RT
  4. extractionthe mixture was extracted with EtOAc (3×20 ml)
  5. dry with materialThe combined organic phases were then dried over Na2SO4
  6. customthe solvent was removed under reduced pressure
  7. customThe residue was chromatographed on silica gel using the mobile phase heptane/EtOAc

Sources & evidence

ORD record
ord-d9af42af55a745ff91fc89a6e47f983b
Source dataset
uspto-grants-2015_07
Patent number
US09078442B2

Reaction notes

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