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

To a mixture of 1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-N,5-dimethoxy-N-methyl-4-oxo-1,4-dihydropyridazine-3-carboxamide (267 mg, 0.687 mmol) in THF (80 mL) was added MeMgBr (1.0 M in THF, 2.06 mL, 2.06 mmol) at −78° C. under N2. The mixture was stirred at −78° C. for 2 h. To the mixture was added MeMgBr (1.0 M in THF, 0.687 mL, 0.687 mmol) at −78° C. The mixture was stirred at −78° C. for 1 h. To the mixture was added MeMgBr (1.0 M in THF, 1.37 mL, 1.37 mmol) at −78° C. The mixture was stirred at −78° C. for 3 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 and purified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 70/30) to yield the title compound (201 mg, 85% yield) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 2.52 (3H, s), 3.82 (3H, s), 3.87 (3H, s), 7.53 (1H, dd, J=10.6, 8.7 Hz), 7.78 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 7.92-8.00 (2H, m), 8.23 (1H, s), 8.56 (1H, d, J=1.5 Hz).

1. stirringThe mixture was stirred at −78° C. for 1 h
2. stirringThe mixture was stirred at −78° C. for 3 h
3. customThe reaction was quenched with saturated NH4Cl aqueous solution at −78° C
4. additionThe mixture was diluted with saturated NaHCO3 aqueous solution
5. extractionextracted with EtOAc
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. custompurified by column chromatography on silica gel (EtOAc/MeOH=100/0 to 70/30)

ORDレコード

ord-b6328a56bdba46108bd8d96f5c4f0f7b

出典データセット

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08916566B2