Potassium Phosphate, Tribasic → 1h-Indazole,4-bromo-1-(2,4-difluorophenyl)-6-methyl-

HRID 418773Notes

Reaction equation

HRID 418773 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[NH:9][N:10]=[CH:11][C:12]1[C:17](Br)=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=1[Br:20].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.ClCCl.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].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>[Br:20][C:13]1[CH:14]=[C:15]([CH3:19])[CH:16]=[C:17]2[C:12]=1[CH:11]=[N:10][N:9]2[C:3]1[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=1[F:1]

Participants

7

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 666483952,6-Dibromo-4-methylbenzaldehyde (2,4-difluorophenyl)hydrazone2×

Product 1

HCID 576159461h-Indazole,4-bromo-1-(2,4-difluorophenyl)-6-methyl-Yield 33%

Reagents, catalysts & solvents 4

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

2,6-Dibromo-4-methylbenzaldehyde (2,4-difluorophenyl)hydrazone (Intermediate 12, 67.4 g, 0.167 mol), tripotassium phosphate (88.8 g, 0.418 mol), tris(dibenzylideneacetone)dipalladium(0) (3.4 g, 3.71 mmol) and racemic BINAP (2.09 g, 3.27 mmol) were heated in degassed 1,4-dioxane (1.125 L) under reflux for 4 days. The mixture was filtered through Celite, washing through with dichloromethane. The filtrate was evaporated under reduced pressure to give a dark brown residue which was dissolved in dichloromethane, absorbed onto silica gel, applied to a silica gel column (1 kg) and eluted with a gradient of 10 to 35% dichloromethane in hexane. Product containing fractions were combined and evaporated to give the title compound as a red solid (17.8 g).

Workup

  1. temperatureunder reflux for 4 days
  2. filtrationThe mixture was filtered through Celite
  3. washwashing through with dichloromethane
  4. customThe filtrate was evaporated under reduced pressure
  5. customto give a dark brown residue which
  6. customabsorbed onto silica gel
  7. washeluted with a gradient of 10 to 35% dichloromethane in hexane
  8. additionProduct containing fractions
  9. customevaporated

Sources & evidence

ORD record
ord-97cd849d1af24c84aa33f0ec8459b624
Source dataset
uspto-grants-2012_01
Patent number
US08093281B2

Reaction notes

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