反应详情

A mixture of 3-acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-one (3.88 g, 10.0 mmol) in N,N-dimethylformamide dimethyl acetal (38.8 mL) was heated to reflux for 3 h. The mixture was concentrated in vacuo. To the residue were added AcOH (38.8 mL) and phenylhydrazine (1.97 mL, 20.0 mmol). The mixture was heated to reflux for 5 h. The mixture was concentrated in vacuo, 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 triturated with AcOEt/hexane to yield the title compound (2.95 g, 60% yield) as a yellow solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.77 (3H, s), 6.99 (1H, d, J=1.5 Hz), 7.23-7.50 (7H, m), 7.79 (1H, d, J=1.9 Hz), 7.84 (1H, ddd, J=8.7, 4.5, 2.3 Hz), 8.49 (1H, d, J=2.6 Hz).

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 5 h
6. concentrationThe mixture was concentrated in vacuo
7. additiondiluted with 1 M HCl aqueous solution
8. extractionextracted with AcOEt
9. washwashed with saturated NaHCO3 aqueous solution
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated in vacuo
13. custompurified by column chromatography on basic silica gel (hexane/AcOEt=50/50 to 0/100)
14. customtriturated with AcOEt/hexane