Cesium carbonate → N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine

HRID 473613Notes

Reaction equation

HRID 473613 reaction equation
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[CH:6][CH:7]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CS(C)=O.O>[Br:1][C:2]1[C:3]([O:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]=3)=[CH:21][CH:20]=2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 6933243-Bromo-2-chloropyridineHCID 212625714-(Pyridin-2-ylamino)phenol

Product 1

HCID 59373954N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Procedure

To a 50 mL round-bottomed flask was added 3-bromo-2-chloropyridine (4.1292 g, 21.46 mmol), 4-(pyridin-2-ylamino)phenol (4.7912 g, 25.75 mmol), and cesium carbonate (2.082 mL, 25.75 mmol) in dimethyl sulfoxide at 80° C. to stir. Reaction was monitored by LCMS to completion. The reaction mixture was diluted with water (15 mL) and extracted with DCM (3×10 mL). The organic extract was washed with water (2×10 mL), satd sodium chloride solution (2×10 mL), dried with magnesium sulfalte, filtered, and concentrated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (40M), eluting with a gradient of 0.5% to 4% methanol in DCM, to provide N-(4-(3-bromopyridin-2-yloxy)phenyl)pyridin-2-amine. MS (ESI, pos. ion) m/z: 343.0 (M+1). IC50 (uM) 0.96.

Workup

  1. customReaction
  2. extractionextracted with DCM (3×10 mL)
  3. extractionThe organic extract
  4. washwas washed with water (2×10 mL), satd sodium chloride solution (2×10 mL)
  5. dry with materialdried with magnesium sulfalte
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customchromatographed through a Biotage™ pre-packed silica gel column (40M)
  9. washeluting with a gradient of 0.5% to 4% methanol in DCM

Sources & evidence

ORD record
ord-b436b97ad6154b17b3504fe3734d46c1
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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