Sulfuric Acid → 2-Methyl-1,5-naphthyridine

HRID 868956Notes

Reaction equation

HRID 868956 reaction equation
S(=O)(=O)(O)O.B(O)(O)O.[N+]([C:13]1[CH:14]=C(S([O-])(=O)=O)C=C[CH:18]=1)([O-])=O.[Na+].[NH2:24][C:25]1[CH:26]=[N:27][C:28]([CH3:31])=[CH:29][CH:30]=1.[OH-].[Na+]>O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2].O.OCC(CO)O>[CH3:31][C:28]1[CH:29]=[CH:30][C:25]2[C:26](=[CH:18][CH:13]=[CH:14][N:24]=2)[N:27]=1

Participants

9

Reactant 5

HCID 1118Sulfuric AcidHCID 7628Boric AcidHCID 14798Sodium HydroxideHCID 31389Sodium 3-nitrobenzenesulfonateHCID 2433135-Amino-2-methylpyridine

Product 1

HCID 5890332-Methyl-1,5-naphthyridineYield 55.8%

Reagents, catalysts & solvents 3

HCID 62662Ferrous sulfate heptahydrateCatalystHCID 753GlycerolSolventHCID 962WaterSolvent

Procedure

A mixture of concentrated sulfuric acid (14 mL), boric acid (1.55 g, 39 mmol), sodium m-nitrobenzenesulfonate (11.30 g, 50 mmol), and iron sulfate heptahydrate (0.90 g, 3.23 mmol) was stirred at room temperature. Glycerol (8 mL) was added to the mixture followed by 3-amino-6-picoline (2.79 g, 25 mmol) and water (14 mL). The mixture was heated at 135° C. for 18 h. The reaction mixture was cooled to room temperature, basified using 4 N aqueous sodium hydroxide to pH 8, and extracted with EtOAc (50 mL×3). The organic extracts were combined, concentrated, and the residue was purified by column chromatography to afford 2-methyl-1,5-naphthyridine (2.01 g) as a light brown crystalline solid. MS (ESI): m/z 145 [M+H]+. See, e.g., J. Med. Chem. 2004, 47, 4494-4506.

Workup

  1. temperatureThe mixture was heated at 135° C. for 18 h
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with EtOAc (50 mL×3)
  4. concentrationconcentrated
  5. customthe residue was purified by column chromatography

Sources & evidence

ORD record
ord-e1465dcbc634410c8c42d4b0c9d07c49
Source dataset
uspto-grants-2015_03
Patent number
US08969349B2

Reaction notes

Loading…