Hydrogen Peroxide → HCID 52933353, compound

HRID 1423076Notes

Reaction equation

HRID 1423076 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]=[CH: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]=[CH: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 67195929HCID 67195929, compound

Product 1

HCID 52933353HCID 52933353, compound

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-fluorophenyl)-1H-indole-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) is charged in a sealed tube with anhydrous THF (7 mL). The solution is warmed at 80° C. for 16 hours. The reaction mixture is cooled to room temperature and quenched with water (15 mL) and diluted with CH2Cl2 (20 mL). The organic layer is separated and washed with brine (10 mL), dried over sodium sulfate and concentrated in vacuo. The residue is 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) is added. The mixture is stirred at 10° C. for 3 hours and is then quenched with water (10 mL) and diluted with CH2Cl2 (20 mL). The organic layer is washed with brine (10 mL) and dried over sodium sulfate and concentrated in vacuo. The residue is purified by reversed-phase HPLC eluting with a gradient of 5-100% CH3CN in water. The desired fractions are combined and diluted with saturated aqueous NaHCO3 (20 mL) and EtOAc (20 mL). The organic layer is separated, dried over sodium sulfate and concentrated to afford the title compound.

Workup

  1. temperatureThe reaction mixture is cooled to room temperature
  2. customquenched with water (15 mL)
  3. additiondiluted with CH2Cl2 (20 mL)
  4. customThe organic layer is separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated in vacuo
  8. dissolutionThe residue is dissolved in THF (10 mL)
  9. customis then quenched with water (10 mL)
  10. additiondiluted with CH2Cl2 (20 mL)
  11. washThe organic layer is washed with brine (10 mL)
  12. dry with materialdried over sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue is 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 EtOAc (20 mL)
  17. customThe organic layer is separated
  18. dry with materialdried over sodium sulfate
  19. concentrationconcentrated

Sources & evidence

ORD record
ord-aac515a949b74f1e8bd77e15c4597974
Source dataset
uspto-grants-2015_01
Patent number
US08927550B2

Reaction notes

Loading…