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

HRID 2090010Notes

Reaction equation

HRID 2090010 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]([I:19])[CH:16]=[CH:15][C:14]=2[F:20])[N:5]=1)(=O)[CH3:2].[CH3:21]C(O)=O.[C:25]1([NH:31][NH2:32])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>COC(OC)N(C)C>[F:20][C:14]1[CH:15]=[CH:16][C:17]([I:19])=[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:31]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[N:32]=[CH:21][CH:2]=2)=[N:5]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 594361593-Acetyl-1-(2-fluoro-5-iodophenyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 580722081-(2-Fluoro-5-iodophenyl)-5-methoxy-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-4(1H)-oneYield 60%

Reagents, catalysts & solvents 1

HCID 78373Dimethylformamide dimethyl acetalSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-223a7aef15634f3f98c4fa4a1235c2e7
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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