Sodium Carbonate → 1-(4-Fluoro-phenyl)-6-methyl-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

HRID 1677711Notes

Reaction equation

HRID 1677711 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].[CH3:33]B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[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]([CH3:33])[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 139377Methylboronic AcidHCID 444698036-Bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Product 1

HCID 581387941-(4-Fluoro-phenyl)-6-methyl-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °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), methylboronic acid (0.01 g, 0.2 mmol), tetrakis(triphenylphosphine)palladium (0.06 g, 0.05 mmol) and a solution of 2 N aqueous sodium carbonate (0.1 mL, 0.2 mmol) was added in a sealed tube with DMF (5 mL). The tube was capped and the resulting solution was degassed with argon for 5 minutes. The reaction was heated to 120° C. by microwave irradiation for 2.5 hours. The reaction was cooled to room temperature and quenched with saturated aqueous ammonium chloride (5 mL) and diluted with ethyl acetate (20 mL). The organic layer was separated, washed with brine (10 mL) and dried over sodium sulfate and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 20-50% ethyl acetate in hexanes to afford the title compound.

Workup

  1. customThe tube was capped
  2. customthe resulting solution was degassed with argon for 5 minutes
  3. temperatureThe reaction was cooled to room temperature
  4. customquenched with saturated aqueous ammonium chloride (5 mL)
  5. additiondiluted with 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 silica gel chromatography
  11. washeluting with a gradient of 20-50% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-d53ac19aae1941c18d4ab2d043b8d49b
Source dataset
uspto-grants-2011_08
Patent number
US08008327B2

Reaction notes

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