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

Participants

Reaction Steps

At RT, a mixture of 2-bromo-1-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)ethanone (606) (1.01 g, 3.00 mmol) and ethyl 3-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-3-oxopropanoate (604) (0.978 g, 3.60 mmol) in 5 mL of THF and 5 mL of DMF was treated with K2CO3 (1.04 g, 7.51 mmol). After the reaction mixture was stirred at RT for 18 h, it was diluted with 100 mL of EtOAc and filtered. The filtrate was washed with sat. NH4Cl (2×15 mL) followed by brine (10 mL), and concentrated. The crude material was purified by silica gel chromatography (25-50% EtOAc in hexanes) to afford ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate as a yellow amorphous solid (324a). m/z (ESI, +ve) 527.3 (M+H)+. In a glass tube, a solution of ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropanecarbonyl)-4-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-4-oxobutanoate as a yellow amorphous solid (324a) in 5 mL of EtOH and 2.5 mL of AcOH was treated with NH4OAc (1.39 g, 18.02 mmol). The glass tube was sealed, and heated in an oil bath at 55° C. for 8 h. The reaction mixture was concentrated to half of its volume. The residue was diluted with 150 mL of EtOAc and washed sequentially with 15 mL of water, 10 mL of 0.5 N NaOH and 10 mL of brine. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The crude material was purified by silica gel chromatography (25-50% EtOAc in hexanes) to provide ethyl 2-(1-((tert-butoxycarbonyl)amino)cyclopropyl)-5-(3-(tert-butylamino)-2-methylquinoxalin-5-yl)-1H-pyrrole-3-carboxylate (1.4 g, 2.76 mmol, 92% yield) as a yellow amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 11.21 (1H, br.), 7.87 (1H, d, J=7.2 Hz), 7.61 (1H, dd, J=8.0, 1.4 Hz), 7.40 (1H, d, J=2.7 Hz), 7.35 (1H, t, J=7.8 Hz), 6.92 (1H, br.), 5.90 (1H, s), 4.25 (2H, q, J=7.1 Hz), 2.56 (3H, s), 1.58 (9H, s), 1.26-1.39 (14H, m), 1.13 (2H, m). m/z (ESI, +ve) 508.3 (M+H)+.

Provenance & Evidence