Scheme 5.
From: The development of an effective synthetic route of rilpivirine
Synthesis of intermediate 3 from pyrimidine-2,4(1H,3H)-dione (17) as starting material [14]. Reagents and conditions: (i) C6H5N(CH3)2, POCl3, 0 °C; reflux, 4 h, 43%; (ii) CH3OH, NaOCH3, rt, 14 h, 50%; (iii) 2-Toluene sulfonic acid, dioxane, 100–110 °C, 14 h, 55%; (iv) Pyridine, 150–160 °C, 3 h, 87%; (v) POCl3, 0 °C, reflux, 1 h, 75%