Scheme 4.
From: The development of an effective synthetic route of rilpivirine
Synthesis of intermediate 3 from 1-(4-cyanophenyl)guanidine (14) and diethyl 2-(ethoxymethylene)malonate (15) as starting materials [18]. Reagents and conditions: (i) NMP, AcONa, 100 °C, 1 h; (ii) H2O, 155–160 °C; AcOH, 130–150 °C, 76%; (iii) POCl3, reflux, 20 min, 77%