Scheme 3. Synthesis of 1,3,4-Oxadiazole and 1,2,4-Triazole Linker Bioisosteres.

Reagents and conditions: (a) NH₂NH₂·H₂O, EtOH, 78 °C, 24 h, 75%; (b) RCH₂C(O)Cl, N,N-diisopropylethylamine, DCM, rt, 15 min, 75–91%; (c) POCl₃, 100 °C, 1 h; (d) ammonium acetate, acetic acid, 140 °C, 1.5 h, 6% over two steps; (e) TsCl, 1,2,2,6,6 pentamethylpiperidine, DCM, rt, 3 h, 48–65%; (f) TFA, DCM, rt, 2 h, 55–98%.