Benzo(B)Thiophene-2-Boronic Acid → 3-Benzo[b]thiophen-2-yl-1H-5-indazolecarbonitrile

HRID 503113Notes

Reaction equation

HRID 503113 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.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[F-].[K+].[S:43]1[C:47](B(O)O)=[CH:46][C:45]2[CH:51]=[CH:52][CH:53]=[CH:54][C:44]1=2>O1CCCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[S:43]1[C:47]([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:46][C:45]2[CH:51]=[CH:52][CH:53]=[CH:54][C:44]1=2

Participants

7

Reactant 4

HCID 2359Benzo(B)Thiophene-2-Boronic AcidHCID 522689Potassium FluorideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 22260825tert-Butyl 3-bromo-5-cyano-1H-indazole-1-carboxylate

Product 1

HCID 222607323-Benzo[b]thiophen-2-yl-1H-5-indazolecarbonitrileYield 57.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 600 mg of tert-butyl 3-bromo-5-cyano-1H-1-indazolecarboxylate produced in Production Example I-14-b in 9 ml tetrahydrofuran were added 21 mg of palladium(II) acetate, 57 mg of 2-(di-tert-butylphosphino)biphenyl, 357 mg of potassium fluoride and 498 mg of 2-benzo[b]thiopheneboronic acid, and the mixture was stirred at 50° C. for 1 hour. After removing the solvent by distillation, the residue was dissolved in 2 ml of methylene chloride. 4 ml of trifluoroacetic acid was added and the mixture was stirred at room temperature for one day. After removing the solvent by distillation, the residue was diluted with 50 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 give 294 mg of the title compound as bright yellow crystals.

Workup

  1. customAfter removing the solvent
  2. distillationby distillation
  3. dissolutionthe residue was dissolved in 2 ml of methylene chloride
  4. addition4 ml of trifluoroacetic acid was added
  5. stirringthe mixture was stirred at room temperature for one day
  6. customAfter removing the solvent
  7. distillationby distillation
  8. additionthe residue was diluted with 50 ml of ethyl acetate
  9. washThe mixture was sequentially washed with saturated aqueous sodium hydrogencarbonate solution and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. customthe solvent was evaporated
  12. customThe crude product was purified
  13. customseparated by silica gel column chromatography (ethyl acetate:toluene=1:19)

Sources & evidence

ORD record
ord-adbafc938e9f4ba1884366025cd4c58c
Source dataset
uspto-grants-2010_08
Patent number
US07776890B2

Reaction notes

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