Biaryl sulfonamides from O‐acetyl amidoximes: 1,2,4‐Oxadiazole cyclization under acidic conditions

Abstract

A series of 4‐cyanobenzenesulfonamides (1a, 1b, 1c, 1d, 1e, 1f, 1g, 1h) was converted to the corresponding O‐acetylated amidoximes (2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h). The reaction of 1a was exemplarily investigated with respect to the formation of a byproduct, which was identified as 1,2,4‐oxadiazole derivative 3a. This observation led to the development of an improved procedure for the preparation of 2a, 2b, 2c, 2d, 2e, 2f, 2g, 2h. Compounds 2 could be transformed to 1,2,4‐oxadiazoles 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h in high yields and purity upon heating in acetic acid. J. Heterocyclic Chem., (2011).

Limiting the Number of Potential Binding Modes by Introducing Symmetry into Ligands: Structure‐Based Design of Inhibitors for Trypsin‐Like Serine Proteases

“…For this purpose, Boc-protected glycine was treated with 3-or 4-cyanobenzylamine and, after deprotection,c oupled to 3-or 4-cyanophenylacetic acid using HATU for amide couplingi nb oth steps. The corresponding bisbenzonitriles (27)(28)(29)(30)w ere subsequently converted into bisbenzamidines following the Judkinsp rocedure, [43] by treatment with hydrox-ylaminet oo btain the corresponding hydroxyamidines 51-54, which were acetylated with acetic anhydride, followed by apalladium-catalyzed hydrogenolysis to bisbenzamidines 1-4.T o suppress the formation of 1,2,4-oxdiazole byproducts, [44] the reaction conditions were individually adjusted. The bisbenzamidines were purified using preparative HPLC and collected as bis-hydrochlorides after lyophilization.…”

Design and Synthesis of N1,N5-bis[4-(5-Alkyl-1,2,4-oxadiazol-3-yl)phenyl]glutaramides as Potential Antifungal Prodrugs

“…Bora et al . [35] reported the 1,2,4-oxadiazole synthesis by the reaction of amidoximes with acid chlorides in refluxing toluene medium in presence of molecular sieves, while O -acetylated amidoximes, upon heating in acetic acid, yielded the 1,2,4-oxadiazoles [36]. The oxadiazolones are conveniently prepared by cyclizing the amidoxime with 1,1'-carbonyldiimidazole in 1,4-dioxane [11] or with methylchloroformate in chloroform [21] or ethylchloroformate in xylene [24].…”