Hydrogen Peroxide → 1-(4-Fluoro-phenyl)-6-hydroxy-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

HRID 2382964Notes

Reaction equation

HRID 2382964 reaction equation
[CH3:1][NH:2][S:3]([C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]([C:14]2[C:15]3[CH:16]=[N:17][N:18]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[C:19]=3[CH:20]=[C:21](Br)[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)[O:34]1.C([O-])(=O)C.[K+].OO.O.[OH-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1COCC1>[CH3:1][NH:2][S:3]([C:6]1[CH:32]=[CH:31][C:9]([CH2:10][NH:11][C:12]([C:14]2[C:15]3[CH:16]=[N:17][N:18]([C:24]4[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=4)[C:19]=3[CH:20]=[C:21]([OH:34])[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4]

Participants

9

Reactant 6

HCID 784Hydrogen PeroxideHCID 962WaterHCID 14798Sodium HydroxideHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 444698036-Bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Product 1

HCID 1360530821-(4-Fluoro-phenyl)-6-hydroxy-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide (0.1 g, 0.2 mmol), bis(pinacolato)diboron (0.1 g, 0.4 mmol), PdCl2(dppf) (0.04 g, 0.05 mmol), potassium acetate (0.05 g, 0.5 mmol) was charged in a sealed tube with anhydrous THF (7 mL). The solution was warmed at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and quenched with water (15 mL) and diluted with CH2Cl2 (20 mL). The organic layer was separated and washed with brine (10 mL) and dried over sodium sulfate. The solvent was removed in vacuo. The residue was dissolved in THF (10 mL), and a solution of 30% H2O2 in water (0.15 mL, 0.5 mmol) and NaOH (0.01 g, 0.3 mmol) were added. The mixture was stirred at 10° C. for 3 hours and then quenched with water (10 mL) and diluted with CH2Cl2 (20 mL). The organic layer was washed with brine (10 mL) and dried over sodium sulfate. The solvent was removed in vacuo. The residue was purified by reversed-phase HPLC, eluting with a gradient of 5-100% CH3CN in water. The desired fractions were combined and diluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL). The organic layer was separated, dried over sodium sulfate and concentrated to afford the title compound.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customquenched with water (15 mL)
  3. additiondiluted with CH2Cl2 (20 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed in vacuo
  8. dissolutionThe residue was dissolved in THF (10 mL)
  9. customquenched with water (10 mL)
  10. additiondiluted with CH2Cl2 (20 mL)
  11. washThe organic layer was washed with brine (10 mL)
  12. dry with materialdried over sodium sulfate
  13. customThe solvent was removed in vacuo
  14. customThe residue was purified by reversed-phase HPLC
  15. washeluting with a gradient of 5-100% CH3CN in water
  16. additiondiluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL)
  17. customThe organic layer was separated
  18. dry with materialdried over sodium sulfate
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-e611d5d574c34aef93db43c59e3bc1e7
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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