Hydrochloric Acid → HCID 178493675, compound

HRID 2089999Notes

Reaction equation

HRID 2089999 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:28]2[C:32]([OH:33])=[C:31](C(OCC)=O)[CH:30]=[N:29]2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]2[N:21]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[N:20]=[CH:19][CH:18]=2)=[N:9]1.[OH-].[Na+].CCO.Cl>O>[F:1][C:2]1[CH:3]=[C:4]([N:28]2[C:32]([OH:33])=[CH:31][CH:30]=[N:29]2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH:13]=[C:12]([O:14][CH3:15])[C:11](=[O:16])[C:10]([C:17]2[N:21]([C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)[N:20]=[CH:19][CH:18]=2)=[N:9]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 14798Sodium HydroxideHCID 178469983HCID 178469983, compound

Product 1

HCID 178493675HCID 178493675, compoundYield 32%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A mixture of ethyl 1-{3-fluoro-4-[5-methoxy-4-oxo-3-(1-phenyl-1H-pyrazol-5-yl)pyridazin-1(4H)-yl]phenyl}-5-hydroxy-1H-pyrazole-4-carboxylate (1.41 g, 2.73 mmol), 4 M NaOH (40 mL), and EtOH (40 mL) was refluxed for 4 h. After cooling to room temperature, conc. HCl (20 mL) was added slowly. The mixture was stirred for 30 min at room temperature and then refluxed for 1 h. After cooling to room temperature, the reaction mixture was poured into water and extracted with AcOEt. The extract was washed with brine, dried over MgSO4, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography eluting with AcOEt/THF (2/1) and recrystallized from THF/MeOH to give the title compound (387 mg, 32% yield) as a pale yellow solid: mp 221-229° C.; 1H NMR (300 MHz, DMSO-d6): δ ppm 3.78 (3H, s), 5.57 (1H, d, J=1.5 Hz), 6.99 (1H, d, J=1.9 Hz), 7.14 (1H, t, J=9.0 Hz), 7.31-7.51 (6H, m), 7.64-7.68 (1H, m), 7.79-7.84 (2H, m), 8.52 (1H, d, J=1.9 Hz), 12.17 (1H, brs). LC-MS (ESI) m/z 445 [M+H]+.

Workup

  1. temperaturewas refluxed for 4 h
  2. temperaturerefluxed for 1 h
  3. temperatureAfter cooling to room temperature
  4. extractionextracted with AcOEt
  5. washThe extract was washed with brine
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography
  9. washeluting with AcOEt/THF (2/1)
  10. customrecrystallized from THF/MeOH

Sources & evidence

ORD record
ord-48ae70040b8a4fbf90d8c672889afa7d
Source dataset
uspto-grants-2013_05
Patent number
US08435995B2

Reaction notes

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