Acetic Acid → HCID 58072344, compound

HRID 1407304Notes

Reaction equation

HRID 1407304 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]([Br:19])[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.Cl>[Br:19][C:15]1[C:14]([F:20])=[C:13]([N:6]2[CH:7]=[C:8]([O:11][CH3:12])[C:9](=[O:10])[C:4]([C:1]3[N:31]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=4)[N:32]=[CH:21][CH:2]=3)=[N:5]2)[CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 7516PhenylhydrazineHCID 594362583-Acetyl-1-(3-bromo-2-fluorophenyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 58072344HCID 58072344, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 78373Dimethylformamide dimethyl acetalSolvent

Procedure

A mixture of 3-acetyl-1-(3-bromo-2-fluorophenyl)-5-methoxypyridazin-4(1H)-one (2.98 g, 8.74 mmol) in N,N-dimethylformamide dimethyl acetal (30 mL) was heated to reflux for 3.5 h. The mixture was concentrated in vacuo. To the residue were added AcOH (30 mL) and phenylhydrazine (1.72 mL, 17.5 mmol). The mixture was heated to reflux for 4 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=50/50 to 0/100) and recrystallized with EtOH to yield the title compound (2.29 g, 59% yield) as a yellow solid: mp 186-191° C. 1H NMR (DMSO-d6, 300 MHz): δ ppm 3.77 (3H, s), 6.99 (1H, d, J=1.9 Hz), 7.08-7.15 (1H, m), 7.17-7.26 (1H, m), 7.28-7.47 (5H, m), 7.74-7.86 (2H, m), 8.55 (1H, d, J=2.3 Hz). Anal. Calcd for C20H14BrFN4O2: C, 54.44; H, 3.20; N, 12.70. Found: C, 54.70; H, 3.30; N, 12.82.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 3.5 h
  3. concentrationThe mixture was concentrated in vacuo
  4. temperatureThe mixture was heated
  5. temperatureto reflux for 4 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=50/50 to 0/100)
  12. customrecrystallized with EtOH

Sources & evidence

ORD record
ord-1abf3a6936664d7aaf12ad8c02be2a31
Source dataset
uspto-grants-2014_12
Patent number
US08916566B2

Reaction notes

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