Cesium carbonate → 3-(3-Methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamine

HRID 425885Notes

Reaction equation

HRID 425885 reaction equation
[C:1]1([C:7]2[CH:8]=[C:9]([OH:33])[C:10]([NH:13]C(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)=[N:11][CH:12]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Cs+].[Cs+].[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45]Br>C1COCC1.ClCCl>[CH3:40][O:41][C:42]1[CH:43]=[C:44]([CH:47]=[CH:48][CH:49]=1)[CH2:45][O:33][C:9]1[C:10]([NH2:13])=[N:11][CH:12]=[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH:8]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 40672073-Methoxybenzyl bromideHCID 211114995-Phenyl-2-(trityl-amino)-pyridin-3-ol

Product 1

HCID 104252613-(3-Methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamineYield 60%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-phenyl-2-(trityl-amino)-pyridin-3-ol (100 mg, 0.24 mmol) in THF (3 mL) was added Cs2CO3 (79 mg, 0.24 mmol). The mixture was stirred at room temperature for 20 minutes, and then 3-methoxybenzylbromide (0.037 mL, 0.26 mmol) was added. The reaction was stirred at room temperature overnight, diluted with dichloromethane (5 mL), and filtered to remove the salts. The solvents were evaporated, and the residue was dissolved in 10% trifluoroacetic acid in dichloromethane (2 mL). The reaction was stirred for 2 hr, and evaporated. The residue was dissolved in dichloromethane, washed by sat. NaHCO3, and dried over Na2SO4. After filtration and concentration, the crude product was purified on a silica gel column eluting with methanol-dichloromethane (from 3% to 15% gradient) to provide 3-(3-methoxy-benzyloxy)-5-phenyl-pyridin-2-ylamine as a white solid (43.5 mg, 60% yield).

Workup

  1. stirringThe reaction was stirred at room temperature overnight
  2. filtrationfiltered
  3. customto remove the salts
  4. customThe solvents were evaporated
  5. dissolutionthe residue was dissolved in 10% trifluoroacetic acid in dichloromethane (2 mL)
  6. stirringThe reaction was stirred for 2 hr
  7. customevaporated
  8. dissolutionThe residue was dissolved in dichloromethane
  9. washwashed by sat. NaHCO3
  10. dry with materialdried over Na2SO4
  11. filtrationAfter filtration and concentration
  12. customthe crude product was purified on a silica gel column
  13. washeluting with methanol-dichloromethane (from 3% to 15% gradient)

Sources & evidence

ORD record
ord-2822b20c7a53402f90b56ef70620b2b2
Source dataset
uspto-grants-2012_01
Patent number
US08106197B2

Reaction notes

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