Water → 1-(2,2-Difluoroethyl)-3-(4-{[3-(2-methoxyethyl)-3H-imidazo[4,5-b]pyridin-2-yl]oxy}phenyl)-1H-pyrazolo[4,3-b]pyridine

HRID 573368Notes

Reaction equation

HRID 573368 reaction equation
[F:1][CH:2]([F:20])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]2[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=2)=[N:5]1.[H-].[Na+].[CH3:23][O:24][CH2:25][CH2:26][N:27]1[C:31]2=[N:32][CH:33]=[CH:34][CH:35]=[C:30]2[N:29]=[C:28]1S(C)(=O)=O.O>CN(C=O)C>[F:20][CH:2]([F:1])[CH2:3][N:4]1[C:12]2[C:7](=[N:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]2[CH:18]=[CH:17][C:16]([O:19][C:28]3[N:27]([CH2:26][CH2:25][O:24][CH3:23])[C:31]4=[N:32][CH:33]=[CH:34][CH:35]=[C:30]4[N:29]=3)=[CH:15][CH:14]=2)=[N:5]1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 667277733-(2-methoxyethyl)-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridineHCID 1364090914-(1-(2,2-difluoroethyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)phenol

Product 1

HCID 866890021-(2,2-Difluoroethyl)-3-(4-{[3-(2-methoxyethyl)-3H-imidazo[4,5-b]pyridin-2-yl]oxy}phenyl)-1H-pyrazolo[4,3-b]pyridineYield 29.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-(1-(2,2-difluoroethyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)phenol (50 mg) in DMF (4 mL) was added NaH (60% in oil, 4.80 mg) at room temperature. The mixture was stirred at room temperature for 30 min and then 3-(2-methoxyethyl)-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (52 mg) was added. The mixture was exposed to microwave irradiation at 180° C. for 30 min, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was purified by basic silica gel column chromatography (AcOEt/hexane). The product was crystallized from AcOEt/hexane to give the title compound (24.0 mg).

Workup

  1. customirradiation at 180° C. for 30 min
  2. extractionextracted with AcOEt
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by basic silica gel column chromatography (AcOEt/hexane)
  6. customThe product was crystallized from AcOEt/hexane

Sources & evidence

ORD record
ord-ec6c50b6794949799cc29ac732d5adcf
Source dataset
uspto-grants-2015_05
Patent number
US09029536B2

Reaction notes

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