Chloroacetone → 1-(6-Bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)propan-2-one

HRID 912473Notes

Reaction equation

HRID 912473 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19].C(=O)([O-])[O-].[Cs+].[Cs+].Cl[CH2:27][C:28](=[O:30])[CH3:29]>CN(C=O)C.O>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:27][C:28](=[O:30])[CH3:29])=[CH:4][C:3]=1[O:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[CH:14][C:13]=1[F:19]

Participants

6

Reactant 3

HCID 6571ChloroacetoneHCID 10796Cesium carbonateHCID 574187616-Bromo-5-(2,4-difluorophenoxy)-1H-indazole

Product 1

HCID 674168791-(6-Bromo-5-(2,4-difluorophenoxy)-1H-indazol-1-yl)propan-2-oneYield 69%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 6-bromo-5-(2,4-difluorophenoxy)-1H-indazole (prepared according to Example 16, Steps A-D; 10.07 g, 31.0 mmol) in DMF (150 mL) at ambient temperature was added cesium carbonate (30.3 g, 92.9 mmol), followed by chloroacetone (5.2 mL, 65.1 mmol). The resulting mixture was vigorously stirred at ambient temperature for 1 hr, then diluted with water (1000 mL). After stirring for 1 hr, the precipitate that formed was collected by filtration, washed with water, and air-dried. This material was dissolved in boiling ethanol (150 mL), and then of water (80 mL) was added. The resulting mixture was cooled at 2° C. for 16 hr. The crystals that formed were collected by filtration, washed with 50/50 water/ethanol, and dried under vacuum to afford the title compound as a light orange powder (8.13 g, 69%).

Workup

  1. stirringAfter stirring for 1 hr
  2. customthe precipitate that formed
  3. filtrationwas collected by filtration
  4. washwashed with water
  5. customair-dried
  6. dissolutionThis material was dissolved
  7. additionof water (80 mL) was added
  8. temperatureThe resulting mixture was cooled at 2° C. for 16 hr
  9. customThe crystals that formed
  10. filtrationwere collected by filtration
  11. washwashed with 50/50 water/ethanol
  12. customdried under vacuum

Sources & evidence

ORD record
ord-fab0902815bc4b6895f46522ed46be9f
Source dataset
uspto-grants-2011_09
Patent number
US08026233B2

Reaction notes

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