1-[2-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one

HRID 1805536Notes

Reaction equation

HRID 1805536 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)=[CH:4][C:3]=1[N:14]1[CH:19]=[C:18]([O:20][CH3:21])[C:17](=[O:22])[C:16]([C:23](N(OC)C)=[O:24])=[N:15]1.[CH3:29][Mg+].[Br-]>C1COCC1>[C:23]([C:16]1[C:17](=[O:22])[C:18]([O:20][CH3:21])=[CH:19][N:14]([C:3]2[CH:4]=[C:5]([C:8]3[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=3)[CH:6]=[CH:7][C:2]=2[F:1])[N:15]=1)(=[O:24])[CH3:29]

Participants

4

Reactant 2

HCID 594362241-[2-Fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound3×

Product 1

HCID 594362133-Acetyl-1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-oneYield 85.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (267 mg, 0.687 mmol) in THF (80 mL) was added MeMgBr (1.0 M in THF, 2.06 mL, 2.06 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. To the mixture was added MeMgBr (1.0 M in THF, 0.687 mL, 0.687 mmol) at −78° C. The mixture was stirred at −78° C. for 1 h. To the mixture was added MeMgBr (1.0 M in THF, 1.37 mL, 1.37 mmol) at −78° C. The mixture was stirred at −78° C. for 3 h. The reaction was quenched with saturated NH4Cl aqueous solution at −78° C. The mixture was diluted with saturated NaHCO3 aqueous solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 70/30) to yield the title compound (201 mg, 85% yield) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.52 (3H, s), 3.82 (3H, s), 3.87 (3H, s), 7.53 (1H, dd, J=10.6, 8.7 Hz), 7.78 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 7.92-8.00 (2H, m), 8.23 (1H, s), 8.56 (1H, d, J=1.5 Hz).

Workup

  1. stirringThe mixture was stirred at −78° C. for 1 h
  2. stirringThe mixture was stirred at −78° C. for 3 h
  3. customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
  4. additionThe mixture was diluted with saturated NaHCO3 aqueous solution
  5. extractionextracted with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. custompurified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 70/30)

Sources & evidence

ORD record
ord-3c6f0d0642e74668850dd084759b1f8c
Source dataset
uspto-grants-2013_01
Patent number
US08354411B2

Reaction notes

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