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 1895225Notes

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-e312953a422947758f023ee4e78a0032
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08513251B2

Reaction notes

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