4-Fluorophenylboronic acid → 3-(4-Fluorophenyl)-1H-indazole-5-carbonitrile

HRID 1610068Notes

Reaction equation

HRID 1610068 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=2)[N:4](C(OC(C)(C)C)=O)[N:3]=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[F-].[K+].[F:47][C:48]1[CH:53]=[CH:52][C:51](B(O)O)=[CH:50][CH:49]=1>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:47][C:48]1[CH:53]=[CH:52][C:51]([C:2]2[C:10]3[C:5](=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[CH:9]=3)[NH:4][N:3]=2)=[CH:50][CH:49]=1

Participants

7

Reactant 4

HCID 2856454-Fluorophenylboronic acidHCID 522689Potassium FluorideHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 22260825tert-Butyl 3-bromo-5-cyano-1H-indazole-1-carboxylate

Product 1

HCID 222606703-(4-Fluorophenyl)-1H-indazole-5-carbonitrileYield 74%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 2.0 g of tert-butyl 3-bromo-5-cyano-1H-1-indazolecarboxylate in 30 ml tetrahydrofuran were added 70 mg of palladium(II) acetate, 218 mg of 2-(dicyclohexylphosphino)biphenyl, 1.19 g of potassium fluoride and 1.30 g of 4-fluorophenylboronic acid, and the mixture was stirred at 50° C. for one day. After removing the solvent by distillation, the residue was diluted with 40 ml of ethyl acetate. The mixture was sequentially washed with water and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The residue was dissolved in 25 ml of methylene chloride, and 5 ml of trifluoroacetic acid was added, followed by stirring at room temperature for 1 hour. After removing the solvent by distillation, the residue was diluted with 40 ml of ethyl acetate. The mixture was sequentially washed with saturated aqueous sodium hydrogencarbonate solution and brine, dried over anhydrous magnesium sulfate and the solvent was evaporated. The crude product was purified and separated by silica gel column chromatography (ethyl acetate:toluene=1:19 to 1:9), to give 1.09 g of the title compound as bright yellow crystals.

Workup

  1. customAfter removing the solvent
  2. distillationby distillation
  3. additionthe residue was diluted with 40 ml of ethyl acetate
  4. washThe mixture was sequentially washed with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated
  7. dissolutionThe residue was dissolved in 25 ml of methylene chloride
  8. addition5 ml of trifluoroacetic acid was added
  9. stirringby stirring at room temperature for 1 hour
  10. customAfter removing the solvent
  11. distillationby distillation
  12. additionthe residue was diluted with 40 ml of ethyl acetate
  13. washThe mixture was sequentially washed with saturated aqueous sodium hydrogencarbonate solution and brine
  14. dry with materialdried over anhydrous magnesium sulfate
  15. customthe solvent was evaporated
  16. customThe crude product was purified
  17. customseparated by silica gel column chromatography (ethyl acetate:toluene=1:19 to 1:9)

Sources & evidence

ORD record
ord-6be7ef4dfee34194ba67517618fa8828
Source dataset
uspto-grants-2006_01
Patent number
US06982274B2

Reaction notes

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