3-(Cyanomethyl)pyridine-2-carbonitrile → 6-Methoxy-1,7-naphthyridin-8-amine

HRID 1881765Notes

Reaction equation

HRID 1881765 reaction equation
[C:1]([CH2:3][C:4]1[C:5]([C:10]#[N:11])=[N:6][CH:7]=[CH:8][CH:9]=1)#[N:2].[CH3:12][O-:13].[Na+]>CO>[CH3:12][O:13][C:1]1[CH:3]=[C:4]2[C:5](=[C:10]([NH2:11])[N:2]=1)[N:6]=[CH:7][CH:8]=[CH:9]2

Participants

4

Reactant 2

HCID 46725983-(Cyanomethyl)pyridine-2-carbonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 130013406-Methoxy-1,7-naphthyridin-8-amineYield 9.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a 1 L round bottom flask was added 3-(cyanomethyl)picolinonitrile (63.6 mmol), MeOH (500 mL), followed by sodium methoxide (76.3 mmol). The mixture was heated at reflux for 18 h, after which time the solvent was removed. The residue was diluted with water (400 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated. The resultant crude residue was purified by silica gel to yield 6-methoxy-1,7-naphthyridin-8-amine (1.05 g, 5.99 mmol, 9.4%) as an off-white solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 8.50 (d, J=2.75 Hz, 1H), 7.95 (d, J=8.24 Hz, 1H), 7.48 (dd, J=8.25, 4.40 Hz, 1H), 7.05 (s, 2H), 6.16 (s, 1H), 3.79 (s, 3H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 18 h
  3. customafter which time the solvent was removed
  4. additionThe residue was diluted with water (400 mL)
  5. extractionextracted with ethyl acetate (2×200 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customThe resultant crude residue was purified by silica gel

Sources & evidence

ORD record
ord-15689a4add9a46aea0325fb7612d0304
Source dataset
uspto-grants-2012_11
Patent number
US08318941B2

Reaction notes

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