Phenylhydrazine → 1-[2-(Difluoromethoxy)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one
Reaction equation
[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH:15]=[C:14]([O:16][CH3:17])[C:13](=[O:18])[C:12]([C:19](=O)[CH:20]=[CH:21][N:22](C)C)=[N:11]1.[C:27]1([NH:33]N)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1>CC(O)=O>[F:1][CH:2]([F:26])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[N:10]1[CH:15]=[C:14]([O:16][CH3:17])[C:13](=[O:18])[C:12]([C:19]2[N:33]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:22]=[CH:21][CH:20]=2)=[N:11]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
A solution of 1-[2-(difluoromethoxy)phenyl]-3-[3-(dimethylamino)prop-2-enoyl]-5-methoxypyridazin-4(1H)-one (0.50 g, 1.369 mmol) and phenylhydrazine (0.269 mL, 2.74 mmol) in AcOH (5 mL) was refluxed for 2 h. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was diluted with AcOEt, washed successively with 1 M HCl aqueous solution, saturated NaHCO3 aqueous solution, and brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with hexane/AcOEt (7/3-0/10) to give the title compound (0.38 g, 68% yield) as an off-white amorphous solid: NMR (300 MHz, CDCl3): δ ppm 3.88 (3H, s), 6.37 (1H, t, J=72.3 Hz), 6.57 (1H, dd, J=8.1, 1.7 Hz), 7.09-7.16 (1H, m), 7.22-7.25 (2H, m), 7.34-7.42 (6H, m), 7.76-7.78 (2H, m). LC-MS (ESI) m/z 411 [M+H]+. Anal. Calcd. for C21H16F2N4O3: C, 61.15; H, 4.07; N, 13.79. Found: C, 61.23; H, 4.11; N, 13.71.