1-[2-(Difluoromethoxy)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-[2-(difluoromethoxy)phenyl]-5-methoxypyridazin-4(1H)-one

HRID 1624582Notes

Reaction equation

HRID 1624582 reaction equation
[CH3:1][Mg+].[Br-].[F:4][CH:5]([F:28])[O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH:18]=[C:17]([O:19][CH3:20])[C:16](=[O:21])[C:15]([C:22](N(OC)C)=[O:23])=[N:14]1>C1COCC1>[C:22]([C:15]1[C:16](=[O:21])[C:17]([O:19][CH3:20])=[CH:18][N:13]([C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[O:6][CH:5]([F:4])[F:28])[N:14]=1)(=[O:23])[CH3:1]

Participants

4

Reactant 2

HCID 866439291-[2-(Difluoromethoxy)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound

Product 1

HCID 594361723-Acetyl-1-[2-(difluoromethoxy)phenyl]-5-methoxypyridazin-4(1H)-oneYield 80%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

MeMgBr (1 M solution in THF, 40.4 ml, 40.4 mmol) was added dropwise at −78° C. to a solution of 1-[2-(difluoromethoxy)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (4.79 g, 13.48 mmol) in THF (500 mL). After stirring for 1 h, the reaction mixture was quenched with 1 M HCl aqueous solution and warm to room temperature. The reaction mixture was concentrated under reduced pressure and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with hexane/AcOEt (1/1-0/1) and recrystallized from diisopropyl ether/AcOEt to give the title compound (3.33 g, 80% yield) as colorless crystals: 1H NMR (300 MHz, CDCl3): δ ppm 2.68 (3H, s), 3.89 (3H, s), 6.55 (1H, t, J=72.7 Hz), 7.36-7.45 (2H, m), 7.50-7.57 (1H, m), 7.61 (1H, dd, J=7.8, 1.7 Hz), 7.72 (1H, s).

Workup

  1. customthe reaction mixture was quenched with 1 M HCl aqueous solution
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. extractionextracted with AcOEt
  4. washThe extract was washed with brine
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with hexane/AcOEt (1/1-0/1)
  9. customrecrystallized from diisopropyl ether/AcOEt

Sources & evidence

ORD record
ord-be9f73da31b84c6e8108c0618d56f27d
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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