Potassium Carbonate → Ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate

Participants

Reaction Steps

A mixture of 2-bromo-1-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)ethanone (616) (300 mg, 0.83 mmol), ethyl 4-((tert-butoxycarbonyl)amino)-3-oxopentanoate (602) (258 mg, 0.99 mmol) and K2CO3 (286 mg, 2.07 mmol) in DMF (2.75 mL) was stirred at RT for 1 h. The reaction mixture was concentrated. Saturated NH4Cl (aq.) and EtOAc was added and the layers were separated. The aq. layer was extracted with EtOAc (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-50% EtOAc in hexanes) to provide ethyl 4-((tert-butoxycarbonyl)amino)-2-(2-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-2-oxoethyl)-3-oxopentanoate (293a) (285 mg, 64% yield). m/z (ESI, +ve) 541.1 (M+H)+. This material was put into a sealed tube with 2 mL of EtOH. AcOH (1 mL) and NH4OAc (511 mg, 6.63 mmol) were added and the mixture was stirred at 60° C. overnight (21 h). The reaction mixture was concentrated. The residue was put into solution with EtOAc and water. The layers were separated and the organic layer was washed with water, 1 M NaOH (aq.) and brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (0-50% EtOAc in hexanes) to provide ethyl 2-(1-((tert-butoxycarbonyl)amino)ethyl)-5-(2-methyl-3-((2,2,2-trifluoroethyl)amino)quinoxalin-5-yl)-1H-pyrrole-3-carboxylate (293b) (215 mg, 0.41 mmol, 50% yield) as a yellow foam. 1H NMR (400 MHz, CDCl3) δ ppm 7.87 (dt, J=7.53, 0.73 Hz, 1H), 7.29-7.44 (m, 2H), 7.12 (d, J=2.54 Hz, 1H), 5.00 (br. s., 1H), 4.25-4.53 (m, 4H), 2.14-2.30 (m, 2H), 1.64 (s, 3H), 1.58 (d, J=7.24 Hz, 3H), 1.36-1.48 (m, 12H). 19F NMR (377 MHz, CDCl3) δ ppm −70.80. m/z (ESI, +ve) 522.2 (M+H)+.

Provenance & Evidence