Dimethylacetamide → 5-(2,4-Difluorophenoxy)-1-isobutyl-1h-indazole-6-carbonitrile

HRID 2112180Notes

Reaction equation

HRID 2112180 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH2:11][CH:12]([CH3:14])[CH3:13])=[CH:4][C:3]=1[O:15][C:16]1[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=1[F:23].C[C:25]([N:27](C)C)=O>>[F:23][C:17]1[CH:18]=[C:19]([F:22])[CH:20]=[CH:21][C:16]=1[O:15][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][C:2]=1[C:25]#[N:27])[N:8]([CH2:11][CH:12]([CH3:14])[CH3:13])[N:7]=[CH:6]2

Participants

3

Reactant 2

HCID 31374DimethylacetamideHCID 574187626-Bromo-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole

Product 1

HCID 426111415-(2,4-Difluorophenoxy)-1-isobutyl-1h-indazole-6-carbonitrileYield 95%

Conditions

Temperature
150 °C

Procedure

6-Bromo-5-(2,4-difluorophenoxy)-1-isobutyl-1H-indazole (31.2 g, 82 mmol) and Cu(I)CN (13.9 g, 156 mmol) were dissolved in DMA and degassed with nitrogen under vacuum. The reaction mixture was heated to 150° C. for 16 hours. The mixture was cooled to room temperature and diluted with ethyl acetate before washing twice with 7M NH4OH. The organics were washed with brine and degassed with nitrogen before being dried over MgSO4 and concentrated under reduced pressure. The crude product was chromatographed eluting with 10% ethyl acetate in hexanes to afford 25.1 g of product (95% yield).

Workup

  1. customdegassed with nitrogen under vacuum
  2. temperatureThe mixture was cooled to room temperature
  3. additiondiluted with ethyl acetate
  4. washbefore washing twice with 7M NH4OH
  5. washThe organics were washed with brine
  6. customdegassed with nitrogen
  7. dry with materialbefore being dried over MgSO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude product was chromatographed
  10. washeluting with 10% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-2895628f4d8a4a5687fa58477c0f101e
Source dataset
uspto-grants-2009_04
Patent number
US07521447B2

Reaction notes

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