反应详情

温度

80 °C

A solution of ethyl 2-chloro-3-oxopropanoate (1.60 g, 7.65 mmol, prepared as described in US2009005359A1) and 1,4-dioxane (10.0 mL) was added to 5-tosyl-5H-pyrrolo[3,2-b]pyrazin-2-amine (1.45 g, 5.03 mmol, Preparation #E.1.1) under nitrogen. Anhydrous butan-1-ol (30.0 mL) was added, a reflux condenser was attached, and the system was sealed. After about 30 min, the mixture was warmed to about 80° C. The solution was allowed to cool to ambient temperature. A solution of ethyl 2-chloro-3-oxopropanoate (2.78 g, 13.3 mmol) and 1,4-dioxane (5 mL) was added. After about 30 min, the reaction mixture was warmed to about 80° C. After about 30 min, the mixture was warmed to about 125° C. After about 48 h, the brown solution was allowed to cool to ambient temperature. The volatiles were removed under reduced pressure. The residue was purified by silica gel chromatography eluting with a gradient of 5-50% EtOAc in heptane to give ethyl 3-tosyl-3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazine-8-carboxylate (1.16 g, 60%): LC/MS (Table 1, Method b) Rt=2.52 min; MS m/z 385 (M+H)+.

1. customa reflux condenser was attached
2. customthe system was sealed
3. temperatureto cool to ambient temperature
4. waitAfter about 30 min
5. temperaturethe reaction mixture was warmed to about 80° C
6. waitAfter about 30 min
7. temperaturethe mixture was warmed to about 125° C
8. waitAfter about 48 h
9. temperatureto cool to ambient temperature
10. customThe volatiles were removed under reduced pressure
11. customThe residue was purified by silica gel chromatography
12. washeluting with a gradient of 5-50% EtOAc in heptane