Solid-Phase Synthesis of 5-Isoxazol-4-yl-[1,2,4]oxadiazoles

Abstract

A library of isoxazole and 1,2,4-oxadiazole-containing diheterocyclic compounds has been prepared. Our strategy was explored in solution phase first as follows. PMB-protected 3-butyn-2-ol was deprotonated with nBuLi, acylated with methyl chloroformate, and then employed in a nitrile oxide 1,3-dipolar cycloaddition (benzaldehyde oxime in the presence of bleach) to afford the isoxazole-substituted carboxylic acid methyl ester. Ester saponification with aqueous NaOH followed by a two-step condensation with benzamidoxime gave the final isoxazole-oxadiazole diheterocyclic product in good yield. With some modifications, we next explored this chemistry on Wang resin, which led to 18 final products that were cleaved from polymer beads with 50% TFA in dichloromethane.

Efficient Preparation of Aldoximes from Arylaldehydes, Ethylenediamine and Oxone® in Water

“…All of the products except for 3g were known compounds and their structures were confirmed by comparison of their melting points, 1 H-and 13 C-NMR and IR spectra with reported data [5,[14][15][16][17][18]. The use of other amines replacing ethylenediamine was studied under the same conditions.…”

Synthesis of simple molecules prepared as arginase inhibitors and evaluated against Leishmania amazonensis

“…This heterocyclic nucleus has been extensively described as a bioisostere of ester and amide functional groups (Quan et al, 2004;Poulain et al, 2001). Additionally, this heterocyclic acts as a pro-drug of the amidine group (Kitamura et al, 2001).…”

Five‐Membered Heterocycles: 1,2‐Azoles. Part 2. Isoxazoles and Isothiazoles

“…The reaction of nitrile oxides with disubstituted alkynes leads to isoxazoles exclusively via 1,3-dipolar cycloaddition when the alkyne contains at least one electron-withdrawing substituent [6,134]. Table 9.6 Stability of some nitrile oxides towards dimerization to furoxans [123].…”