Phenylhydrazine → 1-[2-(Difluoromethoxy)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1895288Notes

Reaction equation

HRID 1895288 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]1

Participants

4

Reactant 2

HCID 7516PhenylhydrazineHCID 667105041-[2-(Difluoromethoxy)phenyl]-3-[3-(dimethylamino)prop-2-enoyl]-5-methoxypyridazin-4(1H)-one

Product 1

HCID 594362271-[2-(Difluoromethoxy)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 68%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

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: 1H 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.

Workup

  1. concentrationthe mixture was concentrated under reduced pressure
  2. additionThe residue was diluted with AcOEt
  3. washwashed successively with 1 M HCl aqueous solution, saturated NaHCO3 aqueous solution, and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography
  7. washeluting with hexane/AcOEt (7/3-0/10)

Sources & evidence

ORD record
ord-3e4ebe131fd6484b894206968406eeb3
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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