4-Hydroxybenzaldehyde → 4-[6-(4-Fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]phenol

HRID 2376745

Reaction equation

HRID 2376745 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[NH2:17][C:18]1[NH:19][N:20]=[CH:21][CH:22]=1.[OH:23][C:24]1[CH:31]=[CH:30][C:27]([CH:28]=O)=[CH:26][CH:25]=1.Cl.C([O-])(O)=O.[Na+]>COCCO.C(Cl)(Cl)Cl.CO>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:17]=[C:18]3[NH:19][N:20]=[CH:21][C:22]3=[C:28]([C:27]3[CH:30]=[CH:31][C:24]([OH:23])=[CH:25][CH:26]=3)[C:9]=2[C:10]2[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=2)=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 1264-HydroxybenzaldehydeHCID 313Hydrochloric AcidHCID 74561Pyrazol-3-ylamineHCID 516892Sodium BicarbonateHCID 103308811-(4-Fluorophenyl)-2-(pyridin-4-yl)ethan-1-one

Product 1

HCID 1363678394-[6-(4-Fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridin-4-yl]phenolYield 41.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6212ChloroformSolventHCID 80192-MethoxyethanolSolvent2×

Procedure

To a solution of 1-(4-fluorophenyl)-2-(4-pyridyl)ethanone (0.30 g, 1.4 mmol, obtained in reference example 1) in 2-methoxyethanol (2 mL), 3-amino-2H-pyrazole (0.13 g, 1.5 mmol), 4-hydroxybenzaldehyde (0.17 g, 1.4 mmol), 2-methoxyethanol (2 mL) and 37% HCl (0.04 g, 0.4 mmol) were added under argon atmosphere. The mixture was heated to reflux overnight. It was allowed to cool and concentrated. The solid obtained was dissolved in CHCl3 and some drops of MeOH. Saturated NaHCO3 was added and the aqueous phase was extracted 3 times with CHCl3. The combined organic phases were dried over Na2SO4 and concentrated to dryness. The crude product was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 0.22 g of the desired compound (yield: 41%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight
  3. temperatureto cool
  4. concentrationconcentrated
  5. customThe solid obtained
  6. extractionthe aqueous phase was extracted 3 times with CHCl3
  7. dry with materialThe combined organic phases were dried over Na2SO4
  8. concentrationconcentrated to dryness
  9. customThe crude product was purified by chromatography on silica gel
  10. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-2d4f46cb3478409d8d0a7db1a2f3388c
Source dataset
uspto-grants-2008_12
Patent number
US07468376B2

Linked notes

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