Dimethylformamide → 6-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

HRID 2382969Notes

Reaction equation

HRID 2382969 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12](Br)[CH:13]=1)=[O:4].[CH3:22][N:23](C=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].[C-]#N.[Zn+2].[C-]#N.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.[Fe+2].[Zn]>[CH3:1][O:2][C:3]([C:5]1[C:6]2[CH:7]=[N:8][N:9]([C:15]3[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=3)[C:10]=2[CH:11]=[C:12]([C:22]#[N:23])[CH:13]=1)=[O:4]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 581387736-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Product 1

HCID 581388956-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A sealed tube was charged with 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester (1.5 g, 4.3 mmol), Pd2(dba)3 (0.4 g, 0.4 mmol), zinc cyanide (0.6 g, 5 mmol), dppf (0.3 g, 0.4 mmol) and zinc powder (0.2 g, 3 mmol) and DMF (20 mL). The reaction solution was degassed with argon for 15 minutes and warmed at 120° C. for 3 hours. The reaction was cooled to room temperature, diluted with saturated aqueous ammonium chloride (10 mL) and ethyl acetate (50 mL). The organic layer was separated and washed with brine (10 mL), dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 0-20% ethyl acetate in hexanes to afford 6-cyano-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid methyl ester.

Workup

  1. customThe reaction solution was degassed with argon for 15 minutes
  2. temperatureThe reaction was cooled to room temperature
  3. additiondiluted with saturated aqueous ammonium chloride (10 mL) and ethyl acetate (50 mL)
  4. customThe organic layer was separated
  5. washwashed with brine (10 mL)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by silica gel chromatography
  10. washeluting with a gradient of 0-20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b2173039169544e09a02a95572f2316f
Source dataset
uspto-grants-2012_09
Patent number
US08263597B2

Reaction notes

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