Scheme 4. Synthesis of (A) Meta-Linked or (B) Ortho-Linked Bis-Amidines Containing Bromo (37, 43) or Phenyl Substitution (38, 44) on the Central Aromatic Core.

Reagents and conditions: (a) (i) DIBALH, DCM, 0 °C, 1 h; (ii) Rochelle salt (quench), rt, overnight (96%); (b) PPh₃, CBr₄, DCM, rt, 2 h (55–74%); (c) 4-cyanophenol, NaH, DMF, 80 °C, 1 h (87–99%); (d) phenylboronic acid, Pd(dppf)Cl₂·DCM, THF/Na₂CO₃, 65 °C, 8–18 h (8–80%); (e) (i) LHMDS, THF, rt, 48 h; (ii) HCl (quench), 0 °C–rt, overnight (17–75%); (f) (i) LAH, ZnCl₂, THF, rt, 6 h; (ii) Rochelle salt (quench), rt, overnight (95%); (g) (i) DIPEA, NH₂OH·HCl, EtOH, 85 °C, 6 h; (ii) Ac₂O, AcOH, rt, 4 h; (iii) Zn powder, AcOH, 35 °C, 6 h (7%).