Potassium Carbonate → Ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-4-oxobutanoate

Participants

Reaction Steps

At RT, to a mixture of 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (283c) (1.18 g, 3.49 mmol) and ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604) (1.14 g, 4.19 mmol) dissolved in DMF (10.26 mL) was added K2CO3 (1.21 g, 8.72 mmol). The overall mixture was stirred overnight. The mixture was diluted with saturated NaHCO3 (100 mL) and CHCl3 (100 mL). The layers were separated and the aq. layer was extracted with CHCl3 (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated in vacuo. The crude material was purified by chromatography through an Interchim puriFlash UP (25 micron) pre-packed silica-gel column (80 grams), eluting with a gradient of 0-30% EtOAc in DCM, to provide ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-4-oxobutanoate (0.69 g, 1.30 mmol, 37% yield) as a yellow oil. The yellow oil was put into a sealed tube with 2:1 mixture of EtOH/AcOH (3 mL) and NH4OAc (Sigma) (0.80 g, 10.5 mmol) was added and the mixture was stirred at 60° C. overnight. The precipitate solid was filtered and washed with Et2O (3×2 mL) to give ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (0.41 g, 23% yield) as a yellow solid. m/z (ESI, +ve) 510 (M+H).

Provenance & Evidence