Example 6 Synthesis of 3-(5-phenyl-2,4-dimethyl-6-oxo-1,6-dihydropyrimidin-3-yl)benzonitrile Step 1: Preparation of 2-chloro-3-cyano-4,6-dimethylpyridine: In a reaction flask, 3-cyano-4,6-dimethyl-2-hydroxypyridine (4.35 g, 29.39 mmol) was mixed with phosphorus pentachloride (6.92 g, 33.21 mmol) were mixed and heated to 120 °C with continuous stirring. The reaction mixture gradually changed to a clarified solution and stirring was continued for 1 hour to ensure complete reaction. Subsequently, the reaction mixture was slowly poured into a pre-prepared ice/water mixture (250 mL) and allowed to stand for 30 minutes to complete hydrolysis. The aqueous phase was adjusted to pH 6 with sodium bicarbonate and then extracted with dichloromethane (400 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product 2-chloro-3-cyano-4,6-dimethylpyridine (4.60 g, 94% yield) as a brown solid, which was analyzed to contain about 15% impurities. The product was characterized by LC/MS and NMR: LC/MS showed m/e = 167/169 (M + H) with a retention time of 2.98 min; 1H NMR (CDCl3, 400 MHz) δ 7.08 (s, 1H), 2.57 (s, 3H), 2.55 (s, 3H).
