Imidazole → HCID 9945293, compound

HRID 1793669Notes

Reaction equation

HRID 1793669 reaction equation
[H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[F:8][C:9]1[CH:10]=[C:11]([C:16]2[CH2:20][CH:19]([CH2:21][O:22][C:23]3[CH:27]=[CH:26][O:25][N:24]=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][O:22][C:23]3[CH:27]=[CH:26][O:25][N:24]=3)[O:18][N:17]=2)[CH:12]=[CH:13][C:14]=1[N:3]1[CH:7]=[CH:6][N:5]=[CH:4]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 22022960HCID 22022960, compound

Product 1

HCID 9945293HCID 9945293, compoundYield 41.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A slurry of sodium hydride (60% in oil, 22 mg, 0.55 mM) in anhydrous N,N-dimethylformamide (0.5 ml) was stirred under an atmosphere of nitrogen and treated dropwise with a solution of imidazole (38 mg, 0.55 mM) in anhydrous N,N-dimethylformamide (0.5 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-isoxazol-3-yloxymethyl-4,5-dihydroisoxazole (140 mg, 0.5 mM) in anhydrous N,N-dimethylformamide (1 ml) added, and the mixture stirred at 70° for 16 hours. After cooling, the mixture was partitioned between aqueous sodium bicarbonate solution (20 ml) and ethyl acetate (20 ml), and the organic extract washed with water (20 ml) and brine (20 ml). After drying (magnesium sulfate) and evaporation, the crude product was chromatographed on a 10 g silica Mega Bond Elut® column, eluting with a gradient from 0–2.5% methanol in dichloromethane. Relevant fractions were combined to give the desired product (68 mg). MS (ESP): 329 (MH+) for C16H13FN4O3

Workup

  1. temperatureAfter cooling
  2. customthe mixture was partitioned between aqueous sodium bicarbonate solution (20 ml) and ethyl acetate (20 ml)
  3. extractionthe organic extract
  4. washwashed with water (20 ml) and brine (20 ml)
  5. customAfter drying
  6. custom(magnesium sulfate) and evaporation
  7. customthe crude product was chromatographed on a 10 g silica Mega Bond Elut® column
  8. washeluting with a gradient from 0–2.5% methanol in dichloromethane

Sources & evidence

ORD record
ord-93d531d16a9747fca324270eef0b62eb
Source dataset
uspto-grants-2006_07
Patent number
US07081538B1

Reaction notes

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