Sodium hydride → HCID 118093919, compound

HRID 1056974Notes

Reaction equation

HRID 1056974 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].[Br:12][C:13]1[C:14]([CH3:24])=[N:15][C:16]2[N:17]([N:20]=[C:21]([CH3:23])[CH:22]=2)[C:18]=1Cl>O1CCCC1>[Br:12][C:13]1[C:14]([CH3:24])=[N:15][C:16]2[N:17]([N:20]=[C:21]([CH3:23])[CH:22]=2)[C:18]=1[O:9][C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 118093858HCID 118093858, compound

Product 1

HCID 118093919HCID 118093919, compoundYield 95.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2,4-difluorophenol (0.156 mL, 0.960 mmol) in tetrahydrofuran (3.0 mL) was treated with sodium hydride (0.0242 g, 0.960 mmol) at 0° C. The resultant reaction mixture was warmed to RT and stirred at that temperature for 30 min. The reaction mixture was then cooled to 0° C., treated with 6-bromo-7-chloro-2,5-dimethylpyrazolo[1,5-a]pyrimidine (0.125 g, 0.480 mmol), warmed to RT and stirred at RT for 14 h. The reaction mixture was cooled to 0° C., quenched with saturated ammonium chloride solution, and diluted with ethyl acetate. Layers were separated and the organic layer was washed with water and brine, dried with sodium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 30% Et2O/hexanes) gave the desired product (162 mg, 95%) as a white solid. LCMS calculated for C14H11BrF2N3O (M+H)+: m/z=354.0, 356.0. found: 353.9, 356.0.

Workup

  1. customThe resultant reaction mixture
  2. temperatureThe reaction mixture was then cooled to 0° C.
  3. temperaturewarmed to RT
  4. stirringstirred at RT for 14 h
  5. temperatureThe reaction mixture was cooled to 0° C.
  6. customquenched with saturated ammonium chloride solution
  7. additiondiluted with ethyl acetate
  8. customLayers were separated
  9. washthe organic layer was washed with water and brine
  10. dry with materialdried with sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a crude residue
  14. customPurification by flash column chromatography (100% hexanes to 30% Et2O/hexanes)

Sources & evidence

ORD record
ord-9986e338ad16420791d712e9bb79d424
Source dataset
uspto-grants-2016_07
Patent number
US09399640B2

Reaction notes

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