To a solution of ethyl 5-[(4-fluorophenyl)methyl]-3-3-[(2-methylpropyl)amino]-3-2-pyridinecarboxylate and ethyl 5-[(4-fluorophenyl)methyl]-3-[(2-methyl-1-propen-1-yl)amino]-2-pyridinecarboxylate (˜1.7:1 mixture, 419 mg, 1.3 mmol) in 1,2-dichloroethane (15 mL) was added ethyl 3-chloro-3-oxopropanoate (0.25 mL, 90%, 1.9 mmol). The resultant solution was heated at 85° C. for 5 hours. Upon cooling to room temperature, dichloromethane and saturated aqueous sodium bicarbonate were added and the layers separated. The organic layer was washed with brine. The aqueous layers were extracted with dichloromethane and the combined organics dried over sodium sulfate. Filtration and concentration followed by silica gel chromatography provided ethyl 3-[[3-(ethyloxy)-3-oxopropanoyl](2-methylpropyl)amino]-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (309 mg, 55%). 1H NMR (CDCl3) δ 8.56 (s, 1 H), 7.45 (s, 1 H), 7.10 (m, 2 H), 6.99 (m, 2 H), 4.39 (q, J=7.2 Hz, 2 H), 4.02-3.97 (m, 5 H), 3.15 (d, J=15.6 Hz, 1 H), 3.04 (d, J=15.6 Hz, 1 H), 2.81 (dd, J=13.6, 6.0 Hz, 1 H), 1.62 (m, 1 H), 1.36 (t, J=7.2 Hz, 3 H), 1.16 (t, J=6.8 Hz, 3 H), 0.90 (d, J=6.4 Hz, 3 H), 0.81 (d, J=6.4 Hz, 3 H); MS: m/z 445 (M+1). Further elution provided ethyl 3-[[3-(ethyloxy)-3-oxopropanoyl](2-methyl-1-propen-1-yl)amino]-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate (115 mg, 21%). 1H NMR (CDCl3) δ 8.37 (s, 1 H), 7.32 (s, 1 H), 7.07 (m, 2 H), 6.97 (m, 2 H), 6.15 (s, 1 H), 4.39 (q, J=7.2 Hz, 2 H), 4.18 (q, J=7.2 Hz, 2 H), 3.48 (s, 2 H), 1.70 (s, 3 H), 1.59 (s, 3 H), 1.38 (t, J=7.2 Hz, 3 H), 1.25 (t, J=7.2 Hz, 3 H); MS: m/z 445 (M+1).
