N-bromobutanimide → 2-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

HRID 1056133ノート

反応式

HRID 1056133 の反応式
[CH:1]1([NH:4][C:5]2[C:6]([CH3:19])=[N:7][C:8]3[C:13]([N:14]=2)=[C:12]([C:15](=[O:17])[CH3:16])[C:11]([F:18])=[CH:10][CH:9]=3)[CH2:3][CH2:2]1.FC(F)(F)S(O[Si](C(C)(C)C)(C)C)(=O)=O.C1C(=O)N([Br:42])C(=O)C1>C(Cl)Cl.C([O-])(O)=O.[Na+]>[Br:42][CH2:16][C:15]([C:12]1[C:11]([F:18])=[CH:10][CH:9]=[C:8]2[C:13]=1[N:14]=[C:5]([NH:4][CH:1]1[CH2:2][CH2:3]1)[C:6]([CH3:19])=[N:7]2)=[O:17]

参加物

6

反応物 3

HCID 67184N-bromobutanimideHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonateHCID 897822001-(3-(Cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone

生成物 1

HCID 897821632-Bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone収率 63.4%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 516892Sodium Bicarbonate溶媒2 回

反応条件

温度
0 °C

実験手順

To a stirred solution of 1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283b) (1.44 g, 5.55 mmol) in DCM (13.88 mL) at 0° C. was added TEA (0.91 mL, 6.54 mmol) and tert-butyldimethylsilyl trifluoromethanesulfonate (Sigma-Aldrich) (1.40 mL, 6.11 mmol). The overall mixture was stirred at 0° C. for 1 h, while under inert atmosphere. The reaction mixture was treated with saturated NaHCO3 (20 mL) and the layers were separated. The aq. layer was extracted with DCM (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. m/z (ESI, +ve) 374 (M+H). The residue was treated with THF (13.88 mL) and water (1.6 mL). The resulting mixture was chilled to 0° C. in an ice/water bath. NBS (Alfa Aesar, Ward Hill, Mass.) (0.99 g, 5.55 mmol) was added into the mixture and the overall mixture was stirred at 0° C. for 30 min. The mixture was diluted with DCM (40 mL) and saturated NaHCO3 (10 mL). The layers were separated and the aq. layer was extracted with DCM (3×). The organic extracts were combined, dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography through a SiliCycle SiliaSep pre-packed silica-gel column (120 gram), eluting with a gradient of 0-25% EtOAc in DCM, to provide 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283c) (1.19 g, 3.52 mmol, 63% yield) as light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.94 (dd, J=9.00, 5.87 Hz, 1H), 7.65-7.84 (m, 1H), 7.32 (t, J=9.39 Hz, 1H), 5.18 (s, 2H), 2.69-2.91 (m, 1H), 2.51 (s, 3H), 0.76-0.95 (m, 2H), 0.60-0.76 (m, 2H). m/z (ESI, +ve) 338/341 (M+H).

後処理

  1. customthe layers were separated
  2. extractionThe aq. layer was extracted with DCM (3×)
  3. dry with materialThe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe residue was treated with THF (13.88 mL) and water (1.6 mL)
  7. temperatureThe resulting mixture was chilled to 0° C. in an ice/water bath
  8. stirringthe overall mixture was stirred at 0° C. for 30 min
  9. customThe layers were separated
  10. extractionthe aq. layer was extracted with DCM (3×)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo
  14. customThe crude material was purified by chromatography through a SiliCycle SiliaSep pre-packed silica-gel column (120 gram)
  15. washeluting with a gradient of 0-25% EtOAc in DCM

出典と根拠

ORDレコード
ord-985896403b0341ad8a1e100afdd59929
出典データセット
uspto-grants-2016_07
特許番号
US09394297B2

反応ノート

読み込み中…