A versatile solid-phase synthesis of 3-aryl-1,2,4-oxadiazolones and analogues

We report here the first method to load acidic heterocyclic compounds (1,2,4-oxadiazol-5-one, 1,2,4-oxadiazol-5-thione and 1,2,3,5-oxathiadazol-2-oxide) on a polymer. Using Mitsunobu conditions, these heterocycles were anchored on a 4-hydroxymethyl-3-methoxyphenoxybutyric acid benzhydrylamine (HMPB-BHA) resin. After diversification, compounds can be recovered by a simple treatment in diluted TFA. To illustrate the utility of this procedure, iodophenyl derivatives were anchored on the same resin. A HRMAS-NMR analysis shed light on the reactivity of these heterocycles in Mitsunobu conditions. A subsequent diversification using a Sonogashira coupling produced a small array of novel (arylethynyl)-phenyl-1,2,4-oxadiazol-5-ones.