Dimethylformamide → 6-Cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

HRID 2382962Notes

Reaction equation

HRID 2382962 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][N:34](C=O)C>[Cl-].[NH4+].C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[CH-]1C(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N.[Zn]>[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]([C:33]#[N:34])[CH:22]=2)=[O:13])=[CH:8][CH:7]=1)(=[O:5])=[O:4]

Participants

9

Reactant 2

HCID 6228DimethylformamideHCID 444698036-Bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Product 1

HCID 442515866-Cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 152416121,1`-Bis(diphenylphosphino)ferroceneCatalystHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide (0.04 g, 0.08 mmol), Pd2(dba)3 (0.009 g, 0.01 mmol), 1,1-bis(diphenylphosphino)ferrocene (dppf) (0.005 g, 0.01 mmol), zinc cyanide (0.01 g, 0.09 mmol) and zinc powder (0.002 g, 0.02 mmol) were charged in a sealed tube with anhydrous DMF (3 mL) at room temperature. The reaction mixture was heated at 120° C. for 3 hours. The solution was cooled to room temperature and diluted with saturated aqueous ammonium chloride (10 mL) and ethyl acetate (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 purified by silica gel chromatography eluting with a gradient of 20-70% ethyl acetate in hexanes to afford the title compound.

Workup

  1. temperatureThe solution was cooled to room temperature
  2. customThe organic layer was separated
  3. washwashed with brine (10 mL)
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed in vacuo
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a gradient of 20-70% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-6a9792b36ac14c2096c9dbbfc035e3cd
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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