Potassium Carbonate → Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-4-oxobutanoate

Participants

Reaction Steps

A mixture of 2-bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone (616) (700 mg, 1.93 mmol), ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604, 629 mg, 2.32 mmol) and K2CO3 (668 mg, 4.83 mmol) in DMF (7.0 mL) was stirred at RT for 45 min. The reaction mixture was treated with a saturated solution of NH4Cl (aq.) and EtOAc was added and the layers were separated. The organic layer was washed with brine (25 mL), and dried over anhydrous MgSO4, filtered and concentrated. The crude material was purified by chromatography on an ISCO Combiflash RF (40 g SingleStep column, eluted using a gradient of 0-90% EtOAc in hexanes) affording ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-4-oxobutanoate (890 mg, 1.611 mmol, 83% yield) as a light orange viscous oil. m/z (ESI, +ve ion) 553.3 (M+H)+. The light orange viscous oil was added to a sealed tube with EtOH (4 mL). AcOH (2 mL) and NH4OAc (1192 mg, 15.46 mmol) were added and the mixture was stirred at 60° C. for 12 h. The reaction mixture was concentrated. The residue was treated with EtOAc and water. The layers were separated and the organic layer was washed with brine. The organic layer was dried over anhydrous MgSO4, filtered and concentrated. The crude material was purified by chromatography on an ISCO Combiflash RF (40 g Thomson SingleStep column, eluting with a gradient of 0-70% EtOAc in hexanes) to provide the title compound (970 mg, 1.81 mmol, 94% yield) as yellow crystalline solid. 19F NMR (376 MHz, CDCl3) δ ppm −71.24 (3F, s). m/z (ESI, +ve ion) 534.2 (M+H)+.

Provenance & Evidence