Sodium hydride → 2-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrile

HRID 2077454Notes

Reaction equation

HRID 2077454 reaction equation
[H-].[Na+].[CH3:3][C:4]1([CH3:18])[CH2:12][C:11]2[NH:10][N:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[C:7]=2[C:6](=[O:17])[CH2:5]1.[Br:19][C:20]1[CH:27]=[C:26](F)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]>CS(C)=O>[Br:19][C:20]1[CH:27]=[C:26]([N:10]2[C:11]3[CH2:12][C:4]([CH3:18])([CH3:3])[CH2:5][C:6](=[O:17])[C:7]=3[C:8]([C:13]([F:16])([F:15])[F:14])=[N:9]2)[CH:25]=[CH:24][C:21]=1[C:22]#[N:23]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1189392-Bromo-4-fluorobenzonitrileHCID 441904636,6-Dimethyl-3-(trifluoromethyl)-1,5,6,7-tetrahydro-4H-indazol-4-one

Product 1

HCID 118541752-bromo-4-[6,6-dimethyl-4-oxo-3-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-indazol-1-yl]benzenecarbonitrileYield 63.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
45 °C

Procedure

Sodium hydride (168 mg, 7.02 mmol, 1.0 eq.) was added to a solution of 6,6-dimethyl-3-trifluoromethyl-1,5,6,7-tetrahydro-indazol-4-one (1.63 g, 7.02 mmol, 1.0 eq.) in 35 mL of anhydrous dimethyl sulfoxide. After 15 min 2-bromo-4-fluorobenzonitrile (2.25 g, 11.23 mmol, 1.6 eq.) was added as a solid. The reaction mixture was heated at 45° C. After 23 h the reaction mixture was cooled to ambient temperature and quenched with 10 mL of saturated aqueous ammonium chloride. The mixture was diluted with water and extracted with ethyl acetate (4×). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified on a Biotage (SiO2, hexanes-ethyl acetate) to afford 2-bromo-4-(6,6-dimethyl-4-oxo-3-trifluoromethyl-4,5,6,7-tetrahydro-indazol-1-yl)-benzonitrile (1.83 g, 63%) as an off-white powder, LC/MS: (M+H)=412.0.

Workup

  1. temperatureAfter 23 h the reaction mixture was cooled to ambient temperature
  2. customquenched with 10 mL of saturated aqueous ammonium chloride
  3. additionThe mixture was diluted with water
  4. extractionextracted with ethyl acetate (4×)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified on a Biotage (SiO2, hexanes-ethyl acetate)

Sources & evidence

ORD record
ord-18073d20279842868b77ff40d8f3289c
Source dataset
uspto-grants-2011_04
Patent number
US07928135B2

Reaction notes

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