4-Pyridinemethanamine → 8-hydroxy-N-(4-pyridinylmethyl)[1,6]naphthyridine-7-carboxamide

HRID 896285Notes

Reaction equation

HRID 896285 reaction equation
[OH:1][C:2]1[C:3]([C:12]([O:14]C)=O)=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2.[N:16]1[CH:21]=[CH:20][C:19]([CH2:22][NH2:23])=[CH:18][CH:17]=1>C1(C)C=CC=CC=1>[OH:1][C:2]1[C:3]([C:12]([NH:23][CH2:22][C:19]2[CH:20]=[CH:21][N:16]=[CH:17][CH:18]=2)=[O:14])=[N:4][CH:5]=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[CH:7]2

Participants

4

Reactant 2

HCID 773174-PyridinemethanamineHCID 22346294Methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate

Product 1

HCID 99217708-hydroxy-N-(4-pyridinylmethyl)[1,6]naphthyridine-7-carboxamide

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of methyl 8-hydroxy-1,6-naphthyridine-7-carboxylate from Example 1, Step 2 (0.05 g, 0.245 mmol) in dry toluene (3 mL) was added 1-pyridin-4-ylmethanamine (0.029 g, 0.270 mmol) and the mixture was heated to reflux for 16 hours. The solution was reduced to a smaller volume and refluxed for 4 additional hours. The solvent was removed under reduced pressure and the residue redissolved in DMF and filtered and the solution solution was purified by preparative HPLC (Gilson semipreparative HPLC system and a YMC Combiprep Column (50×20 mm I.D., C18, S-5 uM, 120 A) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min) to afford the title compound after lyophilization.

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 16 hours
  3. temperaturerefluxed for 4 additional hours
  4. customThe solvent was removed under reduced pressure
  5. dissolutionthe residue redissolved in DMF
  6. filtrationfiltered
  7. customthe solution solution was purified by preparative HPLC (Gilson semipreparative HPLC system
  8. washa YMC Combiprep Column (50×20 mm I.D., C18, S-5 uM, 120 A) eluting with 5-95% acetonitrile/water (0.1% TFA) at 15 ml/min)

Sources & evidence

ORD record
ord-6149e595d48647b1916b90f8df6b9f82
Source dataset
uspto-grants-2005_07
Patent number
US06919351B2

Reaction notes

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