Methylamine hydrochloride → 1-(4-Fluoro-phenyl)-6-methylamino-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

HRID 2382966Notes

Reaction equation

HRID 2382966 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].Cl.[CH3:34][NH2:35].CC(C)([O-])C.[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O1CCOCC1>[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]([NH:35][CH3:34])[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4]

Participants

6

Reactant 3

HCID 6364545Methylamine hydrochlorideHCID 23676156Sodium t-butoxideHCID 444698036-Bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Product 1

HCID 444684461-(4-Fluoro-phenyl)-6-methylamino-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide (0.05 g, 0.1 mmol), methylamine hydrochloride (0.01 g, 0.2 mmol), palladium(II) acetate di-t-butylbiphenylphosphine (0.005 g, 0.01 mmol) and sodium t-butoxide (0.03 g, 0.25 mmol) was charged in a sealed tube with dioxane (5 mL). The tube was capped, degassed with argon for 5 minutes and warmed at 90° C. for 2 hours. The reaction was cooled to room temperature and filtered through diatomaceous earth, and diluted with water (5 mL) and ethyl acetate (20 mL). The organic layer was separated and washed with brine (10 mL), dried over sodium sulfate, and concentrated. 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. customThe tube was capped
  2. customdegassed with argon for 5 minutes
  3. temperatureThe reaction was cooled to room temperature
  4. filtrationfiltered through diatomaceous earth
  5. additiondiluted with water (5 mL) and ethyl acetate (20 mL)
  6. customThe organic layer was separated
  7. washwashed with brine (10 mL)
  8. dry with materialdried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by reversed-phase HPLC
  11. washeluting with a gradient of 5-100% CH3CN in water
  12. additiondiluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL)
  13. customThe organic layer was separated
  14. dry with materialdried over sodium sulfate
  15. concentrationconcentrated

Sources & evidence

ORD record
ord-dcd73c37f5ad4761b8716ee87043d847
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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