反应详情

温度

120 °C

To a suspension of 0.20 g (0.43 mmol) [4-(4-bromo-2,5-dichloro-phenoxy)-pyridin-3-yl]-(4-cyclopropyl-3,4-dihydro-2H-quinoxalin-1-yl)-methanone (Example 26) in 0.2 mL N,N-dimethylformamide was added 0.044 g (0.38 mmol) L-proline (commercially available, CAS RN 147-85-3) followed by the addition of 0.068 g (0.76 mmol) copper(I)cyanide. The resulting dark brown suspension was stirred at 120° C. for 17 hours. Then another 0.2 mL N,N-dimethylformamide were added and stirring was continued for another 7 hours at 120° C. The reaction was allowed to cool to room temperature, stirred for another 64 hours and then partioned between water and ethyl acetate. The resulting turbid mixture was filtered and washed with ethyl acetate. The layers of the filtrate were separated and the water layer extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over magnesium sulfate, filtered and evaporated to dryness. The remaining light brown oil was dissolved in dichloromethane, treated with silica gel and then evpaorated. The resulting powder was purified by silica gel chromatography using a MPLC system (10 g silica gel column, CombiFlash Companion, Isco Inc.) with a gradient of n-heptane:ethyl acetate (100:0 to 40:60) to afford 0.045 g (25%) of the title compound as a brown solid. MS (ESI): m/z=465.1 [M+H]+.

1. stirringstirring
2. waitwas continued for another 7 hours at 120° C
3. temperatureto cool to room temperature
4. stirringstirred for another 64 hours
5. filtrationThe resulting turbid mixture was filtered
6. washwashed with ethyl acetate
7. customThe layers of the filtrate were separated
8. extractionthe water layer extracted twice with ethyl acetate
9. washThe combined organic layers were washed with brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. customevaporated to dryness
13. dissolutionThe remaining light brown oil was dissolved in dichloromethane
14. additiontreated with silica gel
15. customThe resulting powder was purified by silica gel chromatography