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

HRID 1624823Notes

Reaction equation

HRID 1624823 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.Cl.[Cl:30][C:31]1[CH:32]=[C:33]([NH:37][NH2:38])[CH:34]=[CH:35][CH:36]=1>COC(OC)N(C)C>[Cl:30][C:31]1[CH:32]=[C:33]([N:37]2[C:1]([C:4]3[C:9](=[O:10])[C:8]([O:11][CH3:12])=[CH:7][N:6]([C:13]4[CH:18]=[CH:17][C:16]([N:19]5[CH:23]=[CH:22][CH:21]=[N:20]5)=[CH:15][C:14]=4[F:24])[N:5]=3)=[CH:2][CH:25]=[N:38]2)[CH:34]=[CH:35][CH:36]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 75331m-Chlorophenylhydrazine hydrochlorideHCID 594361683-Acetyl-1-(2-fluoro-4-(1H-pyrazol-1-yl)phenyl)-5-methoxypyridazin-4(1H)-one

Product 1

HCID 468490783-[1-(3-Chlorophenyl)-1H-pyrazol-5-yl]-1-[2-fluoro-4-(1H-pyrazol-1-yl)phenyl]-5-methoxypyridazin-4(1H)-oneYield 44%

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 (393 mg, 1.20 mmol) in N,N-dimethylformamide dimethyl acetal (4.0 mL) was stirred at 100° C. for 1 h. The reaction mixture was concentrated in vacuo. To the residue were added AcOH (4 mL) and 3-chlorophenylhydrazine hydrochloride (429 mg, 2.40 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 (242 mg, 44% yield) as an orange solid: mp 186-190° C.; NMR (300 MHz, DMSO-d6): δ ppm 3.80 (3H, s), 6.64 (1H, d, J=1.9 Hz), 7.05 (1H, d, J=1.9 Hz), 7.27-7.34 (1H, m), 7.44 (3H, dd, J=16.6, 10.2 Hz), 7.34-7.52 (1H, m), 7.84 (3H, dd, J=3.6, 1.7 Hz), 8.00 (1H, dd, J=12.3, 2.1 Hz), 8.56 (1H, d, J=1.9 Hz), 8.67 (1H, d, J=2.6 Hz): LC-MS (ESI) m/z 463 [M+H]+. Anal. Calcd for C23H16ClFN6O2.0.03H2O: C, 59.61; H, 3.49; N, 18.14. Found: C, 59.32; H, 3.50; N, 17.92.

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-39c6e839cc0c4472bf8d04c8c18b4ac9
Source dataset
uspto-grants-2014_07
Patent number
US08778944B2

Reaction notes

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