Acetic Acid → 1-[2-Fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-one

HRID 1407323Notes

Reaction equation

HRID 1407323 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]=[CH:17][CH:16]=[C:15]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[C:14]=2[F:25])[N:5]=1)(=O)[CH3:2].[CH3:26]C(O)=O.[C:30]1([NH:36][NH2:37])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>COC(OC)N(C)C.Cl>[F:25][C:14]1[C:15]([C:19]2[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=2)=[CH:16][CH:17]=[CH:18][C:13]=1[N:6]1[CH:7]=[C:8]([O:11][CH3:12])[C:9](=[O:10])[C:4]([C:1]2[N:36]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[N:37]=[CH:26][CH:2]=2)=[N:5]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 594361833-Acetyl-1-[2-fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one

Product 1

HCID 580723211-[2-Fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 62%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 78373Dimethylformamide dimethyl acetalSolvent

Procedure

A mixture of 3-acetyl-1-[2-fluoro-3-(1-methyl-1H-pyrazol-4-yl)phenyl]-5-methoxypyridazin-4(1H)-one (243 mg, 0.708 mmol) in N,N-dimethylformamide dimethyl acetal (2.4 mL) was heated to reflux for 2 h. The mixture was concentrated in vacuo. To the residue were added AcOH (2.4 mL) and phenylhydrazine (0.139 mL, 1.42 mmol). The mixture was heated to reflux for 2 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=20/80 to 0/100) and recrystallized with EtOH/AcOEt/hexane to yield the title compound (193 mg, 62% yield) as a pale yellow solid: mp 218-221° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.78 (3H, s), 3.91 (3H, s), 6.97 (2H, d, J=1.9 Hz), 7.13-7.50 (6H, m), 7.72-7.84 (2H, m), 7.93 (1H, s), 8.18 (1H, d, J=2.3 Hz), 8.55 (1H, d, J=1.9 Hz).

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. concentrationThe mixture was concentrated in vacuo
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 2 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=20/80 to 0/100)
  12. customrecrystallized with EtOH/AcOEt/hexane

Sources & evidence

ORD record
ord-f53b7eb18aa8404d920c8522344f39b7
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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