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

HRID 244409

反応式

HRID 244409 の反応式
[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

参加物

6

反応物 3

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

生成物 1

HCID 594373015-bromo-1-pyridin-3-yl-1H-indazole収率 11.1%

試薬・触媒・溶媒 2

HCID 8895Cupric acetate触媒HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-69dc3ec10f73440aa4bfbedf448431d6
出典データセット
uspto-grants-2014_02
特許番号
US08658637B2

関連ノート

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