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

HRID 418783Notes

Reaction equation

HRID 418783 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][N:9]=[CH:10][C:11]1[C:16](Br)=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=1[Br:19].P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1(C)C=CC=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.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:19][C:12]1[CH:13]=[C:14]([CH3:18])[CH:15]=[C:16]2[C:11]=1[CH:10]=[N:9][N:8]2[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=1[F:1]

Participants

6

Reactant 2

HCID 62657Potassium Phosphate, TribasicHCID 666488172,6-Dibromo-4-methylbenzaldehyde (2-fluorophenyl)hydrazone2×

Product 1

HCID 576159291h-Indazole,4-bromo-1-(2-fluorophenyl)-6-methyl-Yield 41%

Reagents, catalysts & solvents 3

HCID 634876Binap, (A+-)-CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

2,6-Dibromo-4-methylbenzaldehyde (2-fluorophenyl)hydrazone (Intermediate 25, 767 mg, 1.99 mmol), tripotassium phosphate (1.06 g, 4.98 mmol), tris(dibenzylideneacetone)dipalladium(0) (73 mg, 0.08 mmol) and racemic BINAP (50 mg, 0.08 mmol) were dissolved in toluene (26 mL) and heated under reflux for 16 hours in a nitrogen atmosphere. The mixture was then cooled and evaporated under reduced pressure. The residue purified by silica gel chromatography using the Flashmaster II (100 g cartridge) eluting with a 100:0 to 0:100 cyclohexane:dichloromethane gradient over 40 minutes to give the title compound (249 mg).

Workup

  1. temperatureheated
  2. temperatureunder reflux for 16 hours in a nitrogen atmosphere
  3. temperatureThe mixture was then cooled
  4. customevaporated under reduced pressure
  5. customThe residue purified by silica gel chromatography
  6. washeluting with a 100:0 to 0:100 cyclohexane

Sources & evidence

ORD record
ord-51c0fa6322824035ab4dd1f671af5d9c
Source dataset
uspto-grants-2012_01
Patent number
US08093281B2

Reaction notes

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