Potassium Hydroxide → 4,6-Bis(4-fluorophenyl)-1-(4-methylsulfanylbenzyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine

HRID 2376733

Reaction equation

HRID 2376733 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:11]=[C:10]3[NH:27][N:28]=[CH:29][C:9]=23)=[CH:4][CH:3]=1.[OH-].[K+].Cl[CH2:33][C:34]1[CH:39]=[CH:38][C:37]([S:40][CH3:41])=[CH:36][CH:35]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]3[C:10](=[N:27][N:28]([CH2:33][C:34]4[CH:39]=[CH:38][C:37]([S:40][CH3:41])=[CH:36][CH:35]=4)[CH:29]=3)[N:11]=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[C:13]=2[C:14]2[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=2)=[CH:4][CH:3]=1.[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]3[CH:15]=[CH:16][N:17]=[CH:18][CH:19]=3)=[C:12]([C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[N:11]=[C:10]3[N:27]([CH2:33][C:34]4[CH:39]=[CH:38][C:37]([S:40][CH3:41])=[CH:36][CH:35]=4)[N:28]=[CH:29][C:9]=23)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 701281-(Chloromethyl)-4-(methylthio)benzeneHCID 119613744,6-Bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine

Product 2

HCID 684435974,6-Bis(4-fluorophenyl)-2-(4-methylsulfanylbenzyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridineYield 25%HCID 684460364,6-Bis(4-fluorophenyl)-1-(4-methylsulfanylbenzyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridineYield 47%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
60 °C

Procedure

In a volumetric flask, 4,6-bis(4-fluorophenyl)-5-(4-pyridyl)-1H-pyrazolo[3,4-b]pyridine (0.30 g, 78.0 mmol, obtained in example 1) and DMF (3.5 mL) were introduced under argon atmosphere. KOH (0.06 g, 1.1 mmol) was added followed by a solution of 1-chloromethyl-4-(methylsulfanyl)benzene (0.15 g, 0.9 mmol, obtained in section a) in DMF (0.4 mL). This was heated to 60° C. overnight. It was allowed to cool and concentrated. The residue was dissolved in a mixture of water and EtOAc. The two phases were separated. 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 0.10 g of 4,6-bis(4-fluorophenyl)-2-(4-methylsulfanylbenzyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine (yield: 25%) and 0.19 g of 4,6-bis(4-fluorophenyl)-1-(4-methylsulfanylbenzyl)-5-(4-pyridyl)pyrazolo[3,4-b]pyridine (yield: 47%).

Workup

  1. temperatureto cool
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in a mixture of water and EtOAc
  4. customThe two phases were separated
  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-297b10a226cf44138abded43bd5e471b
Source dataset
uspto-grants-2008_12
Patent number
US07468376B2

Linked notes

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