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

HRID 1805578Notes

Reaction equation

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

Participants

Conditions

Temperature: -78 °C

Procedure

A solution of 1-(4-bromo-2,5-difluorophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (5.0 g, 12 mmol) in THF (100 mL) was added dropwise to MeMgBr (1.0 M in THF, 50 mL, 50 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 1 h. The reaction was quenched with 1 M HCl aqueous solution (70 mL) at −78° C. The mixture warmed up to room temperature and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated under reduced pressure to give the title compound (3.6 g, 80% yield) as a yellow solid: 1H NMR (300 MHz, DMSO-d6): δ ppm 2.50 (3H, s), 3.80 (3H, s), 8.03 (1H, dd, J=8.9, 6.6 Hz), 8.17 (1H, dd, J=10.0, 6.2 Hz), 8.52 (1H, d, J=1.5 Hz). LC-MS (ESI) m/z 360 [M+H]+.

Workup

customThe reaction was quenched with 1 M HCl aqueous solution (70 mL) at −78° C
temperatureThe mixture warmed up to room temperature
extractionextracted with AcOEt
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-21a2621b40f8440cbfb5cb4e5ef0d07a
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08354411B2

Reaction notes

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