Acetone → 1,8-Naphthyridine, 2-methyl-

HRID 868955Notes

Reaction equation

HRID 868955 reaction equation
[NH2:1][C:2]1[N:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.N1CC[CH2:15][C@H:11]1[C:12](O)=O.CC(C)=O>CCO>[CH3:15][C:11]1[CH:12]=[CH:4][C:3]2[C:2](=[N:9][CH:8]=[CH:7][CH:6]=2)[N:1]=1

Participants

5

Reactant 3

HCID 180AcetoneHCID 145742L-ProlineHCID 7376333-Pyridinecarboxaldehyde, 2-amino-

Product 1

HCID 740731,8-Naphthyridine, 2-methyl-Yield 887.8%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 2-aminonicotinaldehyde (732 mg, 6 mmol) and L-proline (69 mg, 0.6 mmol) in EtOH (15 mL) was added acetone (1.74 g, 30 mmol). Then the mixture was heated at reflux and stirred for 8 h. The resulting mixture was concentrated under reduced pressure to give a residue, which was washed with water (10 mL) and extracted with DCM (15 mL×3). The combined organic layers were washed with brine (10 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford the crude product 2-methyl-1,8-naphthyridine as a yellow solid (768 mg). MS (ESI): m/z 145 [M+H]+. See e.g., Bioorg. Med. Chem. Lett., 2005, 15, 2679-84.

Workup

  1. temperatureThen the mixture was heated
  2. temperatureat reflux
  3. concentrationThe resulting mixture was concentrated under reduced pressure
  4. customto give a residue, which
  5. washwas washed with water (10 mL)
  6. extractionextracted with DCM (15 mL×3)
  7. washThe combined organic layers were washed with brine (10 mL)
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-019d8b9c12dc4272a77f2296ce555c9c
Source dataset
uspto-grants-2015_03
Patent number
US08969349B2

Reaction notes

Loading…