Synthesis
Acetic anhydride (130 mL, 1.37 mol) was slowly added dropwise to 180 mL of acetic acid solution containing malonic acid (80 g, 0.79 mol) and N-methylurea (50 g, 0.68 mol) at 70 °C. After the dropwise addition was completed, the reaction mixture was warmed up to 90 °C with continuous stirring for 3 hours. After completion of the reaction, the mixture was cooled to room temperature. The solvent was removed by distillation under reduced pressure and the resulting residue was treated with 350 mL of ethanol to precipitate a pale yellow solid. The solid was purified by recrystallization from ethanol to give 63.1 g of 1-methylpyrimidine-2,4,6(1H,3H,5H)-trione as a final crystalline solid (yield: 65.8%). The melting point was measured to be 131.2-133.1 °C (literature value: 130-131.5 °C).
References
[1] Journal of Heterocyclic Chemistry, 2014, vol. 51, # 3, p. 594 - 597
[2] Journal of Medicinal Chemistry, 1989, vol. 32, # 6, p. 1231 - 1237
[3] Patent: WO2009/73210, 2009, A1. Location in patent: Page/Page column 76
[4] Patent: WO2006/133261, 2006, A2. Location in patent: Page/Page column 30
[5] Patent: WO2007/143705, 2007, A2. Location in patent: Page/Page column 23
