Acetic Acid → 3-[1-(2-Fluorophenyl)-1H-pyrazol-5-yl]-1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxypyridazin-4(1H)-one

HRID 1895355Notes

Reaction equation

HRID 1895355 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][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][C:14]=2[F:24])[N:5]=1)(=O)[CH3:2].[CH3:25]C(O)=O.[F:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[NH:36][NH2:37]>COC(OC)N(C)C>[F:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[N:36]1[C:1]([C:4]2[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]3[CH:18]=[CH:17][C:16]([N:19]4[CH:23]=[CH:22][CH:21]=[N:20]4)=[CH:15][C:14]=3[F:24])[N:5]=2)=[CH:2][CH:25]=[N:37]1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 4238442-Fluorophenylhydrazine hydrochlorideHCID 594361683-Acetyl-1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 468489183-[1-(2-Fluorophenyl)-1H-pyrazol-5-yl]-1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxypyridazin-4(1H)-oneYield 47%

Reagents, catalysts & solvents 1

HCID 78373Dimethylformamide dimethyl acetalSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 3-acetyl-1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxypyridazin-4(1H)-one (197 mg, 0.600 mmol) in N,N-dimethylformamide dimethyl acetal (2.0 mL) was stirred at 100° C. for 1 h. The reaction mixture was concentrated in vacuo. To the residue were added AcOH (2.0 mL) and 2-fluorophenylhydrazine (151 mg, 1.20 mmol). The mixture was stirred at 100° C. for 1 h. After solvent evaporated, the residue was diluted with saturated NaHCO3 aqueous solution (25 mL) and extracted with AcOEt (25 mL×3). The combined organic phase was washed with brine (40 mL), dried with MgSO4, and evaporated. The residue was crystallized from AcOEt to give a coarse solid, which was recrystallized from EtOH/hexane to give the title compound (125 mg, 47% yield) as a white solid: mp 202-206° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 3.79 (3H, s), 6.64 (1H, d, J=1.9 Hz), 6.96 (1H, t, J=8.5 Hz), 7.23-7.33 (3H, m), 7.41-7.53 (2H, m), 7.71 (1H, d, J=9.1 Hz), 7.84 (2H, dd, J=4.0, 1.7 Hz), 7.94 (1H, dd, J=12.3, 2.5 Hz), 8.48 (1H, d, J=1.9 Hz), 8.65 (1H, d, J=2.6 Hz). LC-MS (ESI) m/z 447 [M+H]+. Anal. Calcd for C23H16F2N6O2.0.4H2O: C, 60.90; H, 3.73; N, 18.53. Found: C, 60.68; H, 3.69; N, 18.39.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. stirringThe mixture was stirred at 100° C. for 1 h
  3. customAfter solvent evaporated
  4. additionthe residue was diluted with saturated NaHCO3 aqueous solution (25 mL)
  5. extractionextracted with AcOEt (25 mL×3)
  6. washThe combined organic phase was washed with brine (40 mL)
  7. dry with materialdried with MgSO4
  8. customevaporated
  9. customThe residue was crystallized from AcOEt
  10. customto give a coarse solid, which
  11. customwas recrystallized from EtOH/hexane

Sources & evidence

ORD record
ord-b5a6bdcdbaec40b09974fadbfc841306
Source dataset
uspto-grants-2013_08
Patent number
US08513251B2

Reaction notes

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