Cesium fluoride → 4'-Hydroxy-3'-pyridazin-4-ylbiphenyl-3-carbonitrile

HRID 1619720Notes

Reaction equation

HRID 1619720 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=2)=[CH:4][C:3]=1I.C([Sn](CCCC)(CCCC)[C:22]1[CH:27]=[CH:26][N:25]=[N:24][CH:23]=1)CCC.[F-].[Cs+]>CN(C)C=O.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].[Cu]I>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]#[N:15])[CH:9]=2)=[CH:4][C:3]=1[C:22]1[CH:27]=[CH:26][N:25]=[N:24][CH:23]=1

Participants

7

Reactant 3

HCID 25953Cesium fluorideHCID 64097334-(Tributylstannyl)pyridazineHCID 580423194'-Hydroxy-3'-iodobiphenyl-3-carbonitrile

Product 1

HCID 1362008814'-Hydroxy-3'-pyridazin-4-ylbiphenyl-3-carbonitrileYield 58.3%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 4′-hydroxy-3′-iodobiphenyl-3-carbonitrile (Preparation 120, 715 mg, 2.23 mmol), 4-(tributylstannyl)pyridazine (904 mg, 2.45 mmol) and cesium fluoride (677 mg, 4.46 mmol) in N,N-dimethylformamide (5 mL) was degassed under nitrogen. Then tetrakistriphenylphosphinepalladium (0) (258 mg, 0.22 mmol) and copper (I) iodide (85 mg, 0.45 mmol) were added, the reaction mixture was further degassed and then heated at 60° C. for 4 hours. The cooled reaction mixture was quenched with 10% ammonia (0.88M) in water (10 mL), diluted with ethyl acetate (20 mL) and then the mixture was stirred for 20 minutes. The resulting mixture was further diluted with ethyl acetate (10 mL) and the layers were separated. The organic layer was dried over anhydrous MgSO4, filtered and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel eluting with 10% dichloromethane in ethyl acetate to give the title compound (355 mg, 55%).

Workup

  1. customwas degassed under nitrogen
  2. customthe reaction mixture was further degassed
  3. customThe cooled reaction mixture
  4. customwas quenched with 10% ammonia (0.88M) in water (10 mL)
  5. additiondiluted with ethyl acetate (20 mL)
  6. additionThe resulting mixture was further diluted with ethyl acetate (10 mL)
  7. customthe layers were separated
  8. dry with materialThe organic layer was dried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationthe filtrate was concentrated in vacuo
  11. customThe residue was purified by flash chromatography on silica gel eluting with 10% dichloromethane in ethyl acetate

Sources & evidence

ORD record
ord-47badeadc1b24e4cb3e5ab2040ca939a
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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