Synthesis
The general procedure for the synthesis of 6-chloro-5-methylpyrimidine-2,4(1H,3H)-dione from 5-methylbarbituric acid (CAS:2417-22-3) was as follows: under nitrogen protection, 5-methylbarbituric acid (9.40 g, 0.066 mol) and benzyltriethylammonium chloride (BTAC) (30.14 g, 0.13 mol) were suspended in trichloro phosphorus oxide (POCl3) (154 mL, 1.65 mol) and heated at 50 °C with stirring for 7 hours. Upon completion of the reaction, the mixture was cooled to room temperature and evaporated to dryness under vacuum. The residue was carefully quenched with 285 g of ice water at 0 °C and the slurry was subsequently placed in a refrigerator overnight. The precipitate was collected by filtration, washed with cold water and dried under vacuum in the presence of phosphorus pentoxide to give 6-chloro-5-methylpyrimidine-2,4(1H,3H)-dione (5.60 g, 0.035 mol, 53% yield) as a white solid. The melting point of the product was 270-272 °C. 1H NMR (300 MHz, DMSO-d6) δ (ppm): 11.81 (br s, 1H, NH), 11.32 (br s, 1H, NH), 1.82 (s, 3H, CH3). IR (KBr, ν cm-1): 3158 (NH), 3013,2814 (Csp2-H ), 1711,1647 (C=O), 1625 (C=C), 1491 (NH), 1424 (C-N), 891 (NH), 753 (C-Cl).
References
[1] European Journal of Medicinal Chemistry, 2012, vol. 54, p. 159 - 174
