反应详情

To a stirred solution of 1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606a) (14.96 g, 58.1 mmol) and TEA (12.15 mL, 87 mmol) in DCM (100 mL) at 0° C. was added tert-butyldimethylsilyl trifluoromethanesulfonate (13.18 mL, 57.4 mmol) dropwise. After the addition, the reaction mixture was stirred at RT for 3 h. It was cooled with an ice bath and quenched with 50 mL of saturated NaHCO3. The layers were separated. The aq. layer was extracted with DCM (2×50 mL). The combined DCM extracts were dried over Na2SO4 and concentrated. The remaining light brown oil was dissolved in THF (100 mL) and H2O (10 mL), cooled with an ice bath, and treated with NBS (10.35 g, 58.1 mmol) in a single portion. The resulting mixture was stirred at 0° C. for 2 h, quenched with 50 mL of saturated NaHCO3, and extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with 20 mL of brine, dried over MgSO4 and concentrated. The resulting yellow solid was treated with 100 mL of MeOH and stirred for 10 min. The yellow solid was filtered, rinsed with MeOH (2×5 mL), collected and dried in a vacuum oven at RT for 18 h to give 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (15.5 g, 79% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.91 (1H, dd, J=8.0, 1.6 Hz), 7.75 (1H, dd, J=7.3, 1.5 Hz), 7.41 (1H, t, J=7.6 Hz), 6.18 (1H, s), 5.15 (2H, s), 2.58 (3H, s), 1.52 (9H, s). m/z (ESI, +ve) 336/338 (M+H)+.

1. additionAfter the addition
2. temperatureIt was cooled with an ice bath
3. customquenched with 50 mL of saturated NaHCO3
4. customThe layers were separated
5. extractionThe aq. layer was extracted with DCM (2×50 mL)
6. dry with materialThe combined DCM extracts were dried over Na2SO4
7. concentrationconcentrated
8. dissolutionThe remaining light brown oil was dissolved in THF (100 mL)
9. temperatureH2O (10 mL), cooled with an ice bath
10. stirringThe resulting mixture was stirred at 0° C. for 2 h
11. customquenched with 50 mL of saturated NaHCO3
12. extractionextracted with EtOAc (3×100 mL)
13. washwashed with 20 mL of brine
14. dry with materialdried over MgSO4
15. concentrationconcentrated
16. additionThe resulting yellow solid was treated with 100 mL of MeOH
17. stirringstirred for 10 min
18. filtrationThe yellow solid was filtered
19. washrinsed with MeOH (2×5 mL)
20. customcollected
21. customdried in a vacuum oven at RT for 18 h