Water → (1-(2,2-Difluoroethyl)-6-fluoro-1H-pyrazolo[4,3-b]pyridin-3-yl]phenol

HRID 573365Notes

Reaction equation

HRID 573365 reaction equation
C(O[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[C:19]3=[N:20][CH:21]=[C:22]([F:24])[CH:23]=[C:18]3[NH:17][N:16]=2)=[CH:11][CH:10]=1)C1C=CC=CC=1.C([O-])([O-])=O.[Cs+].[Cs+].FC(F)(F)S(O[CH2:37][CH:38]([F:40])[F:39])(=O)=O.[OH2:43]>CN(C=O)C>[F:39][CH:38]([F:40])[CH2:37][N:17]1[C:18]2[C:19](=[N:20][CH:21]=[C:22]([F:24])[CH:23]=2)[C:15]([C:12]2[CH:11]=[CH:10][CH:9]=[CH:14][C:13]=2[OH:43])=[N:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27740892,2-Difluoroethyl trifluoromethanesulfonateHCID 667280483-[4-(Benzyloxy)phenyl]-6-fluoro-1H-pyrazolo[4,3-b]pyridine

Product 1

HCID 136409095(1-(2,2-Difluoroethyl)-6-fluoro-1H-pyrazolo[4,3-b]pyridin-3-yl]phenol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred mixture of 3-[4-(benzyloxy)phenyl]-6-fluoro-1H-pyrazolo[4,3-b]pyridine (100 mg) and Cs2CO3 (204 mg) in DMF (4 mL) was added 2,2-difluoroethyl trifluoromethanesulfonate (73.8 mg) at 0° C. The mixture was stirred at room temperature for 12 h, treated with water, and extracted with AcOEt. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The residue was dissolved in EtOH (8 mL) and 10% Pd—C (50% wet, 100 mg) was added. The mixture was stirred at room temperature for 1 h under H2 atmosphere, filtered and evaporated. The residue was purified by silica gel column chromatography (AcOEt/hexane) to give the title compound (47.0 mg).

Workup

  1. extractionextracted with AcOEt
  2. dry with materialThe organic layer was dried over MgSO4
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in EtOH (8 mL)
  5. addition10% Pd—C (50% wet, 100 mg) was added
  6. stirringThe mixture was stirred at room temperature for 1 h under H2 atmosphere
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by silica gel column chromatography (AcOEt/hexane)

Sources & evidence

ORD record
ord-a9c796384a4b4c2194603e10da6e9270
Source dataset
uspto-grants-2015_05
Patent number
US09029536B2

Reaction notes

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