Step 2: Synthesis of 4,6-dichloro-2-methoxypyrimidine; 2.25 g (7.92 mmol) of 4,6-dihydroxy-2-methoxypyrimidine and 10.0 mL (108.92 mmol) of phosphorus trichloride were mixed and the reaction was heated to reflux for 2 hours. Upon completion of the reaction, the reaction mixture was slowly poured into pre-cooled alkaline ice water and the pH was adjusted to alkaline with sodium hydroxide solution. Subsequently, the aqueous phase was extracted with dichloromethane. The organic phase was separated, dried with anhydrous sodium sulfate and concentrated under reduced pressure to remove the solvent. A product of 0.20 g was obtained in 14% yield. The product was analyzed by ESI-MS showing m/z = 179 ([M + H]+) and an HPLC retention time (Method B) of 1.38 min.
