Skip to main content
. 2014 Mar 5;57(6):2773–2788. doi: 10.1021/jm500066b

Scheme 2. Synthesis of Two Regioisomers of 1,2,4-Oxadiazole Bioisosteres.

Scheme 2

Reagents and conditions: (a) NH2OH·H2O, EtOH, rt, 5 h, 98–99%; (b) 2, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, hydroxybenzotriazole, DMF, 140 °C, 3 h, 10–31%; (c) 10% TFA in DCM (v/v), rt, 2 h, 13–99%; (d) bromoacetonitrile, t-BuOK, THF, 0 °C to rt, 15 min, 88%; (e) tert-butyl 4-hydroxypiperidine-1-carboxylate, diisopropyl azodicarboxylate, PPh3, THF, rt 1.5 h, 78%; (f) RCH2CO2H, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, hydroxybenzotriazole, MeCN, rt, 18 h; (g) 4 Å molecular sieves, toluene, 18 h, 110 °C, 54–68% over two steps.