Hydrogen Bromide → 2,6-Naphthyridin-1-ol

HRID 885073Notes

Reaction equation

HRID 885073 reaction equation
CN(C)/[CH:3]=[CH:4]/[C:5]1[CH:12]=[N:11][CH:10]=[CH:9][C:6]=1[C:7]#[N:8].Br.C([OH:17])C>>[C:7]1(=[O:17])[C:6]2[C:5](=[CH:12][N:11]=[CH:10][CH:9]=2)[CH:4]=[CH:3][NH:8]1

Participants

4

Reactant 3

HCID 260Hydrogen BromideHCID 702EthanolHCID 12884773(E)-3-(2-(Dimethylamino)vinyl)isonicotinonitrile

Product 1

HCID 8177432,6-Naphthyridin-1-ol

Procedure

To a suspension of (E)-3-(2-(dimethylamino)vinyl)isonicotinonitrile (5 g, 28.9 mmol) in ethanol (50 mL) was added 49 mL of HBr (48% in water) dropwise over 20 minutes. The mixture was heated to reflux overnight for 19 h, and cooled to rt. Upon cooling, fine yellow crystals started to form. The mixture was cooled in the refrigerator for 1.5 h. The crystals were collected by filtration and were washed with ether. To the yellow solid was carefully added sat. aq. NaHCO3 until gas evolution ceased. The off-white solid that formed was collected by filtration and was washed with water to give 1.83 g of the expected product. The mother liquors from both filtrations were combined and were concentrated under reduced pressure. The residue was neutralized with sat. aq. NaHCO3, and the solvent removed under reduced pressure. The residue was diluted with 300 mL of dichloromethane and 300 mL of MeOH, and the mixture was warmed to reflux with a heat gun. The solids were removed by filtration, and the organic solution was concentrated under reduced pressure. The residue was purified by BIOTAGE® flash chromatography using a 0-6.5% MeOH in dichloromethane gradient. The expected product, was isolated as an off-white solid (0.96 g) and the two lots were combined to yield 2,6-naphthyridin-1(2H)-one (2.79 g, 19.1 mmol, 66% yield). LC/MS: m/z 147.04 (M+H)+, 1.407 min (method 1). 1H NMR (500 MHz, DMSO-d6) δ ppm 11.63 (br. s., 1H) 9.07 (s, 1H) 8.62 (d, J=5.49 Hz, 1H) 7.98 (d, J=5.49 Hz, 1H) 7.33 (d, J=7.02 Hz, 1H) 6.67 (d, J=7.02 Hz, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux overnight for 19 h
  3. temperatureUpon cooling
  4. customto form
  5. temperatureThe mixture was cooled in the refrigerator for 1.5 h
  6. filtrationThe crystals were collected by filtration
  7. washwere washed with ether
  8. customThe off-white solid that formed
  9. filtrationwas collected by filtration
  10. washwas washed with water

Sources & evidence

ORD record
ord-d52b1be62b8a4fa5a41fcf54b117a89e
Source dataset
uspto-grants-2012_08
Patent number
US08242124B2

Reaction notes

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