Scheme 7.
From: The development of an effective synthetic route of rilpivirine
The improved synthetic procedure of rilpivirine. Reagents and conditions: (i) Pd(OAc)2, P(C6H5CH3)3, CH3COONa, DMAC, N2, 130 °C, 24 h, 51%; (ii) POCl3, 40 °C 8 h; (iii) EtOH, HCl, acetyl chloride, 0 °C, 30 min, total yield of steps (ii) and (iii) 95%; (iv) N2, 160 °C, 2 h, 180 °C, 4 h, 70%; (v) POCl3, reflux 8 h, 89%; (vi) CH3CN, 140 °C, 90 min, 71%