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

HRID 418775Notes

Reaction equation

HRID 418775 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][N:10]=[CH:11][C:12]2[C:17](Br)=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=2[Br:20])=[CH:5][CH:4]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].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>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]>[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:6]1[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 634876Binap, (A+-)-HCID 666484422,6-Dibromo-4-methylbenzaldehyde [4-(methyloxy)phenyl]hydrazone2×

Product 1

HCID 576159621h-Indazole,4-bromo-1-(4-methoxyphenyl)-6-methyl-Yield 23.9%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Procedure

Crude 2,6-dibromo-4-methylbenzaldehyde[4-(methyloxy)phenyl]hydrazone (Intermediate 14 prepared from 2.62 g of 2,6-dibromo-4-methylbenzaldehyde) was dissolved in toluene (100 mL) and treated with tripotassium phosphate (5 g, 23.55 mmol), tris(dibenzylideneacetone)dipalladium(0) (196 mg, 0.214 mmol) and racemic BINAP (122 mg, 0.196 mmol). The mixture was heated under reflux for 17 hours and then cooled, filtered through celite and evaporated under reduced pressure. The residue was purified by silica gel chromatography using the Flashmaster II (100 g cartridge) eluting with a 100:0 to 0:100 cyclohexane:dichloromethane gradient over 60 minutes to give crude product (801 mg). Further purification by silica gel chromatography using the Flashmaster II (50 g cartridge) eluting with a 100:0 to 75:25 cyclohexane:ethyl acetate gradient over 50 minutes gave the title compound as a colourless solid (499 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureunder reflux for 17 hours
  3. temperaturecooled
  4. filtrationfiltered through celite
  5. customevaporated under reduced pressure
  6. customThe residue was purified by silica gel chromatography
  7. washeluting with a 100:0 to 0:100 cyclohexane
  8. customdichloromethane gradient over 60 minutes to give crude product (801 mg)
  9. customFurther purification by silica gel chromatography
  10. washeluting with a 100:0 to 75:25 cyclohexane

Sources & evidence

ORD record
ord-b5476161f0a74d0295c18a53194ab963
Source dataset
uspto-grants-2012_01
Patent number
US08093281B2

Reaction notes

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