反应详情

To a solution of tert-butyl 5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-ylcarbamate (1.00 g, 2.57 mmol, Example #3 Step E) and DMF (13 mL) under nitrogen at about 0° C. was added NaH (60% dispersion in mineral oil, 0.113 g, 2.83 mmol) in one portion. After about 30 min, 2-bromoacetamide (0.391 g, 2.83 mmol) was added in one portion. After about 30 min, the ice bath was removed and the solution was stirred at ambient temperature for about 2 h. Saturated aqueous NH4Cl/water (1:1, 100 mL) was added. After stirring for about 10 min, the mixture was filtered using water to wash the filter cake. The aqueous phase was extracted with EtOAc (50 mL). The filter cake was dissolved in EtOAc and added to the organic layer. The organic layer was dried over Na2SO4, filtered, and concentrated under reduced pressure. The material was purified by silica gel chromatography eluting with a gradient of 20-100% EtOAc/heptane to give tert-butyl 2-amino-2-oxoethyl(5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-yl)carbamate (0.980 g, 82%): LC/MS (Table 1, Method n) Rt=0.70 min; MS m/z 446 (M+H)+.

1. waitAfter about 30 min
2. customthe ice bath was removed
3. additionSaturated aqueous NH4Cl/water (1:1, 100 mL) was added
4. stirringAfter stirring for about 10 min
5. filtrationthe mixture was filtered
6. washto wash the filter cake
7. extractionThe aqueous phase was extracted with EtOAc (50 mL)
8. dissolutionThe filter cake was dissolved in EtOAc
9. additionadded to the organic layer
10. dry with materialThe organic layer was dried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe material was purified by silica gel chromatography
14. washeluting with a gradient of 20-100% EtOAc/heptane