Dichloromethane → Ethyl 3-{[3-(ethyloxy)-3-oxopropanoyl][2-(2-oxo-1-pyrrolidinyl)ethyl]amino}-5-[(4-fluorophenyl)methyl]-2-pyridinecarboxylate

Participants

Reaction Steps

A solution of ethyl 5-(4-fluorobenzyl)-3-{[2-(2-oxopyrrolidin-1-yl)ethyl]amino}pyridine-2-carboxylate (2.445 g, 6.34 mmol) and ethyl malonyl chloride (1.25 mL, 9.5 mmol) was heated under nitrogen at reflux for 1 hour. Additional ethyl malonyl chloride (0.25 mL, 1.9 mmol) was added and the reaction was maintained for another hour at reflux. The reaction mixture was cooled, diluted with CH2Cl2, and treat with saturated aqueous NaHCO3. After phase separation, the aqueous phase was extracted twice with CH2Cl2. The combined organic layers were dried over MgSO4, filtered, evaporated in vacuo and purified on silica gel eluting with 3% MeOH in CH2Cl2 to provide an oil: 1H NMR (CDCl3) δ 8.57 (1H, d, J=2 Hz), 8.23 (1H, d, J=2 Hz), 7.23 (2H, dd, J=6, 8 Hz), 7.00 (2H, t, J=8 Hz), 4.66-4.76 (1H, m), 4.41 (2H, q, J=7 Hz), 3.98-4.08 (4H, m), 3.80-3.90 (2H, m), 3.24-3.31 (1H, m), 3.02 (2H, dd, J=16, 32 Hz), 2.86-2.96 (2H, m), 2.30-2.48 (2H, m), 1.92-2.11 (2H, m), 1.38 (3H, t, J=7 Hz), 1.17 (3H, t, J=Hz); ES+ MS: 500 (M+H+).

Provenance & Evidence