1194-74-7

609-08-5

1194-74-7

The general procedure for the synthesis of 6-hydroxy-2,5-dimethyl-4(1H)-pyrimidinone from diethyl methylmalonate is as follows: Example 4.1 Synthesis of 2,5-dimethyl-4,6-dihydroxypyrimidine To a single neck flask 40 mL of methanol was added and cooled to 0°C with an ice bath under nitrogen atmosphere. To the reaction mixture was added 9.72 g of sodium methanol (i.e., a solution with a concentration of 3 mol/L), followed by the slow addition of 5 g (53 mmol) of acetamidine hydrochloride at 0 °C. The reaction mixture was stirred at room temperature for about 20 minutes, then 8.3 mL of diethyl methylmalonate was added dropwise. Stirring was continued for 3 hours. After completion of the reaction, the methanol was concentrated under reduced pressure (2 kPa). The crude product was dissolved in a minimal amount of water, cooled to 0 °C, and then acidified with pure acetic acid to pH 4-5. The white precipitate formed was collected by filtration and washed sequentially with water, ether, and pentane. Finally, the white product was dried over P2O5 under reduced pressure (0.2 kPa) to give 3.3 g (49% yield) of the target product. TLC analysis: Rf = 0.2 (silica gel, eluent: dichloromethane-methanol-water-acetic acid, 85:15:2:2). 1H-NMR (DMSO-d6): δ 1.68 (s, 3H, OH-CH2C-CH3); 2.18 (s, 3H, N-C-CH3).