109113-72-6

White to yellow powder

2-(Chloromethyl)-4-methylquinazoline, is a building block used for the preparation of Linagliptin (L465900), and its impurities, acting as type 2 diabetes drugs.

Journal of Heterocyclic Chemistry, 23, p. 1263, 1986 DOI: 10.1002/jhet.5570230458

Notclassified

Into a 500ml reaction flask, add o-aminoacetophenone, chloroacetonitrile, 1,4-dioxane, and N-methyl-3(3-sulfopropyl)imidazolium hydrogen sulfate prepared above. Stir to dissolve, cool the reaction system to 8°C, and dropwise add hydrochloric acid to the reaction system. The reaction temperature was kept unchanged during the dropwise addition. After that, the reaction was continued at 8°C for 18 hours to complete the reaction process. After the reaction, ammonia water (the concentration of ammonia water was 10wt%) at 5°C was added to the reaction system. After stirring and crystallizing at 5 for 30 minutes, filter to obtain a filter cake, washing the filter cake with water. Recrystallized with 200ml of dichloromethane to obtain 2-(chloromethyl)-4-methylquinazoline. yield: 85.14%