Water → 2,5-Dichloro-4-[3-(4-cyclopropyl-3,4-dihydro-2H-quinoxaline-1-carbonyl)-pyridin-4-yloxy]-benzonitrile

Participants

Reaction Conditions

Reaction Steps

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 evaporated. 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]+.

Provenance & Evidence