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

HRID 1895177Notes

Reaction equation

[F:1][C:2]1[C:7]([C:8]2[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=2)=[CH:6][CH:5]=[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]=[CH:5][CH:6]=[C:7]([C:8]3[CH:9]=[N:10][N:11]([CH3:13])[CH:12]=3)[C:2]=2[F:1])[N:15]=1)(=[O:24])[CH3:29]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 1-[2-fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (345 mg, 0.890 mmol) in THF (100 mL) was added MeMgBr (1.0 M in THF, 2.67 mL, 2.67 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 100 min. The reaction was quenched with saturated NH4Cl aqueous solution at −78° C. The mixture was 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 (243 mg, 80% yield) as a white solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.51 (3H, brs), 3.81 (3H, s), 3.91 (3H, s), 7.38-7.46 (1H, m), 7.54-7.64 (1H, m), 7.86-7.95 (1H, m, J=15.0, 1.7 Hz), 7.98 (1H, s), 8.25 (1H, d, J=2.3 Hz), 8.58 (1H, d, J=1.9 Hz).

Workup

customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
extractionThe mixture was extracted with EtOAc
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 70/30)

Sources & evidence

ORD record: ord-ddeb0ee077e84e449923e2eb57d36ba1
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513251B2

Reaction notes

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