反应详情

A mixture of 3-acetyl-1-[2-fluoro-5-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one (200 mg, 0.585 mmol) in N,N-dimethylformamide dimethyl acetal (2.0 mL) was heated to reflux for 3 h. The mixture was concentrated in vacuo. To the residue were added AcOH (2.0 mL) and phenylhydrazine (0.115 mL, 1.17 mmol). The mixture was heated to reflux for 3 h. The mixture was diluted with 1 M HCl aqueous solution, extracted with AcOEt, washed with saturated NaHCO3 aqueous solution, dried over Na2SO4, filtered, concentrated in vacuo, purified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC and recrystallized with EtOH/hexane to yield the title compound (118 mg, 46% yield) as a white solid: mp 93-102° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.78 (3H, s), 3.89 (3H, s), 6.91 (1H, d, J=1.9 Hz), 7.20-7.52 (7H, m), 7.63-7.71 (1H, m), 7.78 (1H, d, J=1.9 Hz), 7.83 (1H, s), 8.10 (1H, s), 8.53 (1H, d, J=1.6 Hz). Anal. Calcd for C24H19FN6O2.1.3H2O: C, 61.88; H, 4.67;

1. temperaturewas heated
2. temperatureto reflux for 3 h
3. concentrationThe mixture was concentrated in vacuo
4. temperatureThe mixture was heated
5. temperatureto reflux for 3 h
6. extractionextracted with AcOEt
7. washwashed with saturated NaHCO3 aqueous solution
8. dry with materialdried over Na2SO4
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100) and by HPLC
12. customrecrystallized with EtOH/hexane