Pyridine → 5-bromo-1-pyridin-3-yl-1H-indazole

HRID 244409

Reaktionsgleichung

Reaktionsgleichung von HRID 244409
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13](B(O)O)[CH:12]=1.N1C=CC=CC=1>ClCCl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([C:13]1[CH:12]=[N:11][CH:16]=[CH:15][CH:14]=1)[N:6]=[CH:5]2

Komponenten

6

Edukt 3

HCID 1049PyridineHCID 7619295-bromo-1H-indazoleHCID 27343783-Pyridinylboronic acid

Produkt 1

HCID 594373015-bromo-1-pyridin-3-yl-1H-indazoleAusbeute 11,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8895Cupric acetateKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A mixture of 2.0 g (10.15 mmol) of 5-bromoindazole, 2.49 g (20.30 mmol) of 3-pyridyl boronic acid, 2.77 g (15.25 mmol) of copper acetate, and 2.4 mL of pyridine were dissolved in dry dichloromethane and stirred at room temperature. Oxygen gas was bubbled into the solution for 3 min and the mix was stirred in a screw top reaction vial in open atmosphere. After stirring overnight at room temperature, the reaction was monitored by LCMS which indicated ˜10-15% conversion. The mixture was then warmed to 70° C. After 24 hours, the mixture was cooled to room temperature, diluted with brine and extracted with EtOAc. The organic was washed with brine, dried over sodium sulfate, and concentrated in vacuo onto silica gel. The crude was then purified by Combiflash chromatography using a 0-70% EtOAc/hexanes gradient (product eluted at 35% EtOAc). The product containing fractions were combined and concentrated in vacuo to afford 0.31 g (11%) of 5-bromo-1-pyridin-3-yl-1H-indazole.

Aufarbeitung

  1. customOxygen gas was bubbled into the solution for 3 min
  2. stirringthe mix was stirred in a screw top reaction vial in open atmosphere
  3. stirringAfter stirring overnight at room temperature
  4. temperatureThe mixture was then warmed to 70° C
  5. temperaturethe mixture was cooled to room temperature
  6. additiondiluted with brine
  7. extractionextracted with EtOAc
  8. washThe organic was washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated in vacuo onto silica gel
  11. customThe crude was then purified by Combiflash chromatography
  12. additionThe product containing fractions
  13. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-69dc3ec10f73440aa4bfbedf448431d6
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658637B2

Verknüpfte Notizen

Wird geladen…