1-(3-Bromo-2-fluorophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-(3-bromo-2-fluorophenyl)-5-methoxypyridazin-4(1H)-one

HRID 1407159Notes

Reaction equation

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

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-(3-bromo-2-fluorophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (4.22 g, 10.9 mmol) in THF (218 mL) was added MeMgBr (1.0 M in THF, 16.4 mL, 16.4 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. The reaction was quenched with saturated NH4Cl aqueous solution at −78° C. The mixture was diluted with 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 50/50) to yield the title compound (3.48 g, 93% yield) as a yellow solid: 1H-NMR (DMSO-d6, 300 MHz): δ ppm 2.50 (3H, s), 3.80 (3H, s), 7.36-7.46 (1H, m), 7.77-7.85 (1H, m), 7.89-7.99 (1H, m), 8.57 (1H, d, J=1.9 Hz).

Workup

customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
additionThe mixture was diluted with NaHCO3 aqueous solution
extractionextracted with EtOAc
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 50/50)

Sources & evidence

ORD record: ord-e5ee8054f97540fcbe380d5d795feb38
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08916566B2

Reaction notes

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