1-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide → 3-Acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-one

HRID 1624684Notes

Reaction equation

HRID 1624684 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([I:8])=[CH:4][C:3]=1[N:9]1[CH:14]=[C:13]([O:15][CH3:16])[C:12](=[O:17])[C:11]([C:18](N(OC)C)=[O:19])=[N:10]1.[CH3:24][Mg+].[Br-]>C1COCC1>[C:18]([C:11]1[C:12](=[O:17])[C:13]([O:15][CH3:16])=[CH:14][N:9]([C:3]2[CH:4]=[C:5]([I:8])[CH:6]=[CH:7][C:2]=2[F:1])[N:10]=1)(=[O:19])[CH3:24]

Participants

4

Reactant 2

HCID 594362381-(2-Fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamideHCID 178418689HCID 178418689, compound

Product 1

HCID 594361593-Acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-oneYield 92.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a mixture of 1-(2-fluoro-5-iodophenyl)-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (4.33 g, 10.0 mmol) in THF (1.0 L) was added MeMgBr (1.0 M in THF, 20.0 mL, 20.0 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 saturated NaHCO3 aqueous solution, extracted with EtOAc, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 0/100) and triturated with EtOAc/hexane to yield the title compound (3.58 g, 92% yield) as a pale yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.50 (3H, s), 3.80 (3H, s), 7.38 (1H, dd, J=11.0, 8.7 Hz), 7.95 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 8.15 (1H, dd, J=7.2, 2.3 Hz), 8.52 (1H, d, J=1.5 Hz).

Workup

  1. customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
  2. additionThe mixture was diluted with saturated NaHCO3 aqueous solution
  3. extractionextracted with EtOAc
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. custompurified by column chromatography on silica gel (hexane/EtOAc=50/50 to 0/100 and EtOAc/MeOH=100/0 to 0/100)
  8. customtriturated with EtOAc/hexane

Sources & evidence

ORD record
ord-cb93b8ae78e741ef86f7b209c1a3e131
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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