Phenylhydrazine → 1-(4-Bromo-2,5-difluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1805730Notes

Reaction equation

HRID 1805730 reaction equation
[C:1]([C:4]1[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]2[CH:18]=[C:17]([F:19])[C:16]([Br:20])=[CH:15][C:14]=2[F:21])[N:5]=1)(=O)[CH3:2].[CH3:22]OC(OC)N(C)C.[C:30]1([NH:36][NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[Br:20][C:16]1[C:17]([F:19])=[CH:18][C:13]([N:6]2[CH:7]=[C:8]([O:11][CH3:12])[C:9](=[O:10])[C:4]([C:1]3[N:36]([C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=4)[N:37]=[CH:22][CH:2]=3)=[N:5]2)=[C:14]([F:21])[CH:15]=1

Participants

4

Reactant 3

HCID 7516PhenylhydrazineHCID 78373Dimethylformamide dimethyl acetalHCID 580723823-Acetyl-1-(4-bromo-2,5-difluorophenyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 580724211-(4-Bromo-2,5-difluorophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 23%

Conditions

Temperature
100 °C

Procedure

A mixture of 3-acetyl-1-(4-bromo-2,5-difluorophenyl)-5-methoxypyridazin-4(1H)-one (3.57 g, 10 mmol) and N,N-dimethylformamide dimethyl acetal (16 mL) was stirred at 100° C. for 5 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in AcOH (20 mL) and added phenylhydrazine (2.0 mL, 20 mmol). This mixture was stirred at 130° C. for 3 h. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with hexane/AcOEt (1/0 to 0/1) and recrystallized from iPr2O/AcOEt to give the title compound (1.05 g, 23% yield) as a pale yellow solid: mp 211-213° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 3.77 (3H, s), 7.02 (1H, d, J=1.9 Hz), 7.09 (1H, dd, J=8.9, 6.6 Hz), 7.22-7.62 (5H, m), 7.80 (1H, d, J=1.9 Hz), 8.07 (1H, dd, J=10.2, 6.0 Hz), 8.49 (1H, d, J=2.3 Hz). LC-MS (ESI) m/z 460 [M+H]+. Anal. Calcd for C20H13BrF2N4O2: C, 52.31; H, 2.85; N, 12.20. Found: C, 52.51; H, 2.95; N, 12.20.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated under reduced pressure
  3. dissolutionThe residue was dissolved in AcOH (20 mL)
  4. stirringThis mixture was stirred at 130° C. for 3 h
  5. temperatureAfter cooling to room temperature
  6. concentrationthe reaction mixture was concentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with hexane/AcOEt (1/0 to 0/1)
  9. customrecrystallized from iPr2O/AcOEt

Sources & evidence

ORD record
ord-c05f655d73d947be8cd2984895c35ed8
Source dataset
uspto-grants-2013_01
Patent number
US08354411B2

Reaction notes

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