Ammonium → 3-Methoxy-4-(6-methylpyridazin-4-yl)aniline

HRID 59124

Reaction equation

HRID 59124 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[C:10]([CH3:14])[N:11]=[N:12][CH:13]=2)=[C:4]([O:15][CH3:16])[CH:3]=1.CC(C)([O-])C.[Na+].C(=[NH:36])(C1C=CC=CC=1)C1C=CC=CC=1.CC([O-])=O.[Na+].[NH4+].C(=O)([O-])[O-].[Na+].[Na+]>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.C1(C)C=CC=CC=1>[CH3:16][O:15][C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[C:8]1[CH:9]=[C:10]([CH3:14])[N:11]=[N:12][CH:13]=1)[NH2:36]

Participants

10

Reactant 6

HCID 223AmmoniumHCID 10340Sodium CarbonateHCID 136809Benzophenone imineHCID 517045Sodium AcetateHCID 23676156Sodium t-butoxideHCID 1178214665-(4-Bromo-2-methoxyphenyl)-3-methylpyridazine

Product 1

HCID 668590663-Methoxy-4-(6-methylpyridazin-4-yl)anilineYield 93%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
80 °C

Procedure

5-(4-Bromo-2-methoxyphenyl)-3-methylpyridazine (1.72 g, 6.20 mmol), Pd2(dba)3 (57 mg, 0.062 mmol), BINAP (116 mg, 0.19 mmol), sodium tert-butoxide (833 mg, 8.68 mmol), benzophenone imine (1.25 mL, 7.44 mmol) and toluene (30 mL) were added into a sealed tube. The flask was purged with N2 three times. The reaction was stirred at 80° C. overnight and then cooled down, filtered through a pad of diatomaceous earth and the filter was washed with MTBE. The filtrate was concentrated. The residue was dissolved in MeOH (60 mL). NaOAc (1.22 g, 14.90 mmol) and ammonium hyxroxide hydrochloride (776 mg, 11.2 mmol) was added. The mixture was stirred at room temperature for 1 hour. Sodium carbonate (1.23 g, 11.60 mmol) was added, and the mixture was stirred at room temperature for 10 minutes and then concentrated under reduced pressure. The residue was taken up in dichloromethane. The organic phase was washed with water, brine, dried over sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by flash chromatography on silica gel, eluting with 0% to 1% methanol in ethyl acetate to afford the title compound 1.24 g (93%) as a solid.

Workup

  1. customThe flask was purged with N2 three times
  2. temperaturecooled down
  3. filtrationfiltered through a pad of diatomaceous earth
  4. washthe filter was washed with MTBE
  5. concentrationThe filtrate was concentrated
  6. dissolutionThe residue was dissolved in MeOH (60 mL)
  7. stirringThe mixture was stirred at room temperature for 1 hour
  8. stirringthe mixture was stirred at room temperature for 10 minutes
  9. concentrationconcentrated under reduced pressure
  10. washThe organic phase was washed with water, brine
  11. dry with materialdried over sodium sulfate
  12. customthe solvent was removed under reduced pressure
  13. customThe residue was purified by flash chromatography on silica gel
  14. washeluting with 0% to 1% methanol in ethyl acetate

Sources & evidence

ORD record
ord-7769ddb901f04ee8a320d5418ebd8ce3
Source dataset
uspto-grants-2016_09
Patent number
US09439904B2

Linked notes

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