Tert-Butylamine → 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine

HRID 1056105노트

반응식

HRID 1056105 반응식
[Br:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[NH:10][C:9](=O)[C:8]([CH3:13])=[N:7]2.[C:15]([NH2:19])([CH3:18])([CH3:17])[CH3:16]>CS(C)=O.CCOC(C)=O.C([O-])(O)=O.[Na+]>[Br:1][C:2]1[C:3]([F:14])=[CH:4][CH:5]=[C:6]2[C:11]=1[N:10]=[C:9]([NH:19][C:15]([CH3:18])([CH3:17])[CH3:16])[C:8]([CH3:13])=[N:7]2

참가 물질

6

반응물 2

HCID 6385Tert-ButylamineHCID 897842068-bromo-7-fluoro-3-methylquinoxalin-2(1H)-one

생성물 1

HCID 897819348-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine수율 83%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 8857Ethyl Acetate용매HCID 516892Sodium Bicarbonate용매

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온도
100 °C

실험 절차

A mixture of 5-bromo-3-chloro-6-fluoro-2-methylquinoxaline (600) (5.00 g, 18.15 mmol) and tert-butylamine (Alfa-Aesar, Ward Hill, Ma) (9.62 mL, 91 mmol) in DMSO (50 mL) in a sealed tube was heated at 100° C. for 2 h. After cooling to RT, the mixture was diluted with EtOAc and saturated NaHCO3 (aq.). The layers were separated and the aq. layer was extracted with EtOAc (3×). The combined organic layers were washed with water and brine and dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by silica gel chromatography (0-20% EtOAc in hexanes) to provide 8-bromo-N-(tert-butyl)-7-fluoro-3-methylquinoxalin-2-amine (605a) (4.70 g, 15.06 mmol, 83% yield) as an orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.71 (1H, dd, J=9.0, 5.7 Hz), 7.14 (1H, t, J=8.6 Hz), 4.82 (1H, br. s.), 2.51 (3H, s), 1.64 (9H, s). 19F NMR (376 MHz, CDCl3) δ ppm −103.85 (s, 1F). m/z (ESI, +ve) 312.0, 314.0 (M+H)+.

후처리

  1. temperatureAfter cooling to RT
  2. customThe layers were separated
  3. extractionthe aq. layer was extracted with EtOAc (3×)
  4. washThe combined organic layers were washed with water and brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material was absorbed onto a plug of silica gel
  9. custompurified by silica gel chromatography (0-20% EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-3102c133fc9b4b848d2a7f4636973603
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394297B2

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