Pyrazol-3-ylamine → 4,6-Bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine

HRID 42567

Reaction equation

HRID 42567 reaction equation
[NH2:1][C:2]1[NH:3][N:4]=[CH:5][CH:6]=1.FC1C=CC(C(O[C:15]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)=[CH:16][C:17]2[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=2)=O)=CC=1>CCO.Cl.C(Cl)(Cl)Cl.CO>[F:29][C:26]1[CH:25]=[CH:24][C:23]([C:15]2[C:16]([C:17]3[CH:18]=[CH:19][N:20]=[CH:21][CH:22]=3)=[C:15]([C:23]3[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=3)[N:1]=[C:2]3[NH:3][N:4]=[CH:5][C:6]=23)=[CH:28][CH:27]=1

Participants

7

Reactant 2

HCID 74561Pyrazol-3-ylamineHCID 684458621-(4-Fluorophenyl)-2-(4-pyridyl)vinyl 4-fluorobenzoate

Product 1

HCID 119613744,6-Bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridineYield 23%

Reagents, catalysts & solvents 4

HCID 313Hydrochloric AcidCatalystHCID 702EthanolSolventHCID 887MethanolSolventHCID 6212ChloroformSolvent

Procedure

To a solution of 3-amino-2H-pyrazole (60 mg, 71.8 mmol) in EtOH (2 mL) and 1 drop of 37% HCl, 1-(4-fluorophenyl)-2-(4-pyridyl)vinyl 4-fluorobenzoate (0.22 g, 65.0 mmol, obtained in reference example 4) was added under argon atmosphere. This was heated to reflux for 3 days. The mixture was diluted with CHCl3 and MeOH. It was washed with saturated NaHCO3. The aqueous phase was extracted with CHCl3 (×2). The organic phase was dried over Na2SO4 and concentrated to dryness. The crude product obtained was purified by chromatography on silica gel using hexane-EtOAc mixtures of increasing polarity as eluent, to afford 58 mg of the desired product in a solid white form (yield: 23%).

Workup

  1. temperatureThis was heated
  2. temperatureto reflux for 3 days
  3. washIt was washed with saturated NaHCO3
  4. extractionThe aqueous phase was extracted with CHCl3 (×2)
  5. dry with materialThe organic phase was dried over Na2SO4
  6. concentrationconcentrated to dryness
  7. customThe crude product obtained
  8. customwas purified by chromatography on silica gel
  9. temperatureof increasing polarity as eluent

Sources & evidence

ORD record
ord-4cbd8a706b52416aa85386b5b15613c0
Source dataset
uspto-grants-2013_09
Patent number
US08536194B2

Linked notes

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