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

HRID 42574

Reaction equation

HRID 42574 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-9811589ee5aa49fc974df1b8e24d6317
Source dataset
uspto-grants-2013_09
Patent number
US08536194B2

Linked notes

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