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

HRID 885073노트

반응식

HRID 885073 반응식
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

참가 물질

4

반응물 3

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

생성물 1

HCID 8177432,6-Naphthyridin-1-ol

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-d52b1be62b8a4fa5a41fcf54b117a89e
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242124B2

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