Pyrazole → HCID 9922774, compound

HRID 1793850Notes

Reaction equation

HRID 1793850 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][CH:5]=[N:4]1.[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1F>CN(C)C=O>[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][N:22]3[CH:26]=[CH:25][N:24]=[N:23]3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1[N:3]1[CH:7]=[CH:6][CH:5]=[N:4]1

Participants

5

Reactant 3

HCID 1048PyrazoleHCID 24758Sodium hydrideHCID 11334553HCID 11334553, compound

Product 1

HCID 9922774HCID 9922774, compoundYield 45.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A slurry of sodium hydride (60% in oil, 44 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) was stirred under an atmosphere of nitrogen and treated dropwise with a solution of pyrazole (76 mg, 1.1 mM) in anhydrous N,N-dimethylformamide (1 ml) at 0°. The mixture was allowed to warm to ambient temperature over 20 minutes, then a solution of (5RS)-3-(3,4-difluorophenyl)-5-(1,2,3-triazol-1-yl-methyl)-4,5-dihydroisoxazole (264 mg, 1 mM) in anhydrous N,N-dimethylformamide (2 ml) added, and the mixture stirred at 70° for 16 hours. After cooling, the mixture was partitioned between aqueous sodium bicarbonate solution (40 ml) and ethyl acetate (40 ml), and the organic extract washed with water (40 ml) and brine (40 ml). After drying (magnesium sulfate) and evaporation, the crude product was chromatographed on a 20 g silica Mega Bond Elut® column, eluting with ethyl acetate. Relevant fractions were combined to give the desired product (141 mg).

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between aqueous sodium bicarbonate solution (40 ml) and ethyl acetate (40 ml)
  3. extractionthe organic extract
  4. washwashed with water (40 ml) and brine (40 ml)
  5. customAfter drying
  6. custom(magnesium sulfate) and evaporation
  7. customthe crude product was chromatographed on a 20 g silica Mega Bond Elut® column
  8. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-6b45f7acb0cb4c51a2a1f2c8e6002d39
Source dataset
uspto-grants-2006_04
Patent number
US07022705B2

Reaction notes

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