2-Aminopyridine → 4-(2-pyridyl)aminomethylnaphthalene-1-carboxylic Acid

HRID 11874Notes

Reaction equation

HRID 11874 reaction equation
Br[CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([O:15]C)=[O:14])=[CH:5][CH:4]=1.C(=O)([O-])[O-].[K+].[K+].[NH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[NH:23][CH2:2][C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([C:13]([OH:15])=[O:14])=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 104392-AminopyridineHCID 11430Potassium CarbonateHCID 103338131-Naphthalenecarboxylic acid, 4-(bromomethyl)-, methyl ester

Product 1

HCID 219736704-(2-pyridyl)aminomethylnaphthalene-1-carboxylic AcidYield 9.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

The compound obtained in Example 17-2 (1.6728 g) was dissolved in DMF (33 ml). After the addition of potassium carbonate (1.66 g) and 2-aminopyridine (0.68 g), the mixture was stirred for 15 hours at room temperature. After the reaction, the solvent was removed by distillation and the residue was dissolved in chloroform. The organic layer was washed with 1 mol/l aqueous solution of hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. Then, the solvent was removed by distillation. The residue was dissolved in DMF (44 ml). Triethylamine. (1.58 ml) and di-t-butyldicarbonate (2.60 ml) were added and the mixture was stirred for 6 hours at room temperature. After the reaction, the solvent was removed by distillation. The residue was dissolved in ethyl acetate. The solution was washed with 0.5 mol/l aqueous solution of hydrochloric acid and saturated brine, and dried over anhydrous sodium sulfate. The solvent was removed by distillation. The residue was dissolved in methanol (6 ml), and 1 mol/l aqueous solution of sodium hydroxide (6 ml) was added. After the reaction for one day, the reaction solution was concentrated. The residue was dissolved again in methanol and neutralized with ion-exchange resin CG50. The resin was removed by filtration. The filtrate was concentrated. The residue was purified by silica gel column chromatography (15 g, chloroform/methanol=5/1) to obtain the title compound (159 mg) as a colorless viscous liquid.

Workup

  1. customAfter the reaction
  2. customthe solvent was removed by distillation
  3. dissolutionthe residue was dissolved in chloroform
  4. washThe organic layer was washed with 1 mol/l aqueous solution of hydrochloric acid and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThen, the solvent was removed by distillation
  7. dissolutionThe residue was dissolved in DMF (44 ml)
  8. addition(1.58 ml) and di-t-butyldicarbonate (2.60 ml) were added
  9. stirringthe mixture was stirred for 6 hours at room temperature
  10. customAfter the reaction
  11. customthe solvent was removed by distillation
  12. dissolutionThe residue was dissolved in ethyl acetate
  13. washThe solution was washed with 0.5 mol/l aqueous solution of hydrochloric acid and saturated brine
  14. dry with materialdried over anhydrous sodium sulfate
  15. customThe solvent was removed by distillation
  16. dissolutionThe residue was dissolved in methanol (6 ml)
  17. addition1 mol/l aqueous solution of sodium hydroxide (6 ml) was added
  18. customAfter the reaction for one day
  19. concentrationthe reaction solution was concentrated
  20. dissolutionThe residue was dissolved again in methanol and neutralized with ion-exchange resin CG50
  21. customThe resin was removed by filtration
  22. concentrationThe filtrate was concentrated
  23. customThe residue was purified by silica gel column chromatography (15 g, chloroform/methanol=5/1)

Sources & evidence

ORD record
ord-ebd70d5959dd40d49b1ca0a2b29a7ea9
Source dataset
uspto-grants-2006_08
Patent number
US07098215B2

Reaction notes

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