Synthesis
Diethyl 2-aminomalonate hydrochloride (20 g, 90 mmol) and ethyl 2-cyano-3-ethoxyacrylate (16 g, 94 mmol) were dissolved in ethanol (250 mL). Sodium ethoxide (21 g, 310 mmol) was added to the solution and the reaction mixture was heated to reflux for 14 hours. Upon completion of the reaction, the reaction solution was neutralized with acetic acid (20 mL) and subsequently concentrated. The concentrated mixture was partitioned between dichloromethane and water for liquid-liquid separation. The aqueous layer was extracted twice with dichloromethane. All organic layers were combined, washed with brine, dried over anhydrous sodium sulfate and concentrated. The resulting solid was ground overnight with a mixture of heptane and dichloromethane (10:1 v/v). The suspension was filtered to give 12.5 g of diethyl 3-amino-1H-pyrrole-2,4-dicarboxylate as a solid in 80% yield. The product was characterized by 1H NMR (400 MHz, DMSO-d6): δ 11.53 (s, 1H), 7.20 (d, J = 4.0 Hz, 1H), 5.57 (s, 2H), 4.27-4.11 (m, 4H), 1.32-1.19 (m, 6H).
