An improved synthesis of 1,2,4-oxadiazoles on solid support

• Published in: Bioorganic & medicinal chemistry letters Vol. 11; no. 6; pp. 753 - 755
• Main Authors: Rice, Kenneth D., Nuss, John M.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 26.03.2001; Elsevier
• Subjects: Biological and medical sciences; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Chemistry, Pharmaceutical; Drug Design; Exact sciences and technology; General pharmacology; Life Sciences & Biomedicine; Medical sciences; Organic chemistry; Oxadiazoles - chemical synthesis; Oxadiazoles - chemistry; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Physicochemical properties. Structure-activity relationships; Quaternary Ammonium Compounds - chemistry; Science & Technology; PHASE SYNTHESIS; RECEPTOR; POTENT; OXADIAZOLES; DERIVATIVES; Cyclodehydration; Automation; Five membered ring; Amidoxime; Chemical compound library; Combinatorial chemistry; Oxadiazole derivatives; Benzamide derivatives; Solid phase; Chemical synthesis; Oxygen nitrogen heterocycle
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(01)00028-2

The use of tetra- N-butylammonium fluoride (TBAF) as a mild and efficient reagent for the cyclodehydration of O-acyl amidoximes has been extended to the synthesis of 1,2,4-oxadiazoles on solid support. Argopore MB-CHO resin (Argonaut Technologies) was reductively aminated and subsequently acylated with 4-cyanobenzoyl chloride. Conversion of the nitrile to the amidoxime and acylation with a range of acid chlorides in parallel followed by treatment with TBAF under ambient conditions afforded a library of 3,5-disubstituted 1,2,4-oxadiazoles. The tetra- N-butylammonium fluoride (TBAF) mediated cyclodehydration of O-acyl amidoximes on solid support allows for the mild and efficient synthesis of 2,5-disubstituted 1,2,4-oxadiazole libraries.