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

HRID 1624686Notes

Reaction equation

HRID 1624686 reaction equation
[CH3:1][Mg+].[Br-].[F:4][C:5]1[CH:10]=[C:9]([N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)[CH:8]=[CH:7][C:6]=1[N:16]1[CH:21]=[C:20]([O:22][CH3:23])[C:19](=[O:24])[C:18]([C:25](N(OC)C)=[O:26])=[N:17]1>C1COCC1>[C:25]([C:18]1[C:19](=[O:24])[C:20]([O:22][CH3:23])=[CH:21][N:16]([C:6]2[CH:7]=[CH:8][C:9]([N:11]3[CH:15]=[CH:14][CH:13]=[N:12]3)=[CH:10][C:5]=2[F:4])[N:17]=1)(=[O:26])[CH3:1]

Participants

4

Reactant 2

HCID 594362571-[2-Fluoro-4-(1H-pyrazol-1-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound

Product 1

HCID 594361683-Acetyl-1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxypyridazin-4(1H)-oneYield 72.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

MeMgBr (1 M solution in THF, 2.8 mL, 2.8 mmol) was added dropwise at −78° C. to a solution of 1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (351 mg, 0.94 mmol) in THF (100 mL). After stirring for 1 h, the reaction mixture was quenched with 1 M HCl aqueous solution 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 AcOEt and recrystallized from MeOH/H2O to give the title compound (223 mg, 72% yield) as a pale yellow solid: mp 159-161° C.; 1H NMR (300 MHz, CDCl3): δ ppm 2.69 (3H, s), 3.93 (3H, s), 6.56 (1H, dd, J=1.5, 2.3 Hz), 7.64 (1H, ddd, J=1.1, 2.3, 9.0 Hz), 7.71-7.79 (4H, m), 7.99 (1H, d, J=2.6 Hz). Anal. Calcd for C16H13FN4O3: C, 58.54; H, 3.99; N, 17.07. Found: C, 58.42; H, 4.01; N, 16.98.

Workup

  1. customthe reaction mixture was quenched with 1 M HCl aqueous solution
  2. extractionextracted with AcOEt
  3. washThe extract was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with AcOEt
  8. customrecrystallized from MeOH/H2O

Sources & evidence

ORD record
ord-182e6bfb59934819b33e00279fda0d1d
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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