An improved synthesis of 1,2,4-oxadiazoles on solid support.
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.
Department of Medicinal Chemistry, Exelixis, Inc., South San Francisco, CA 94083-0511, USA. krice@exelixis.com
K D
KD
Rice
J M
JM
Nuss
D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*
D010069:Oxadiazoles; D000644:Quaternary Ammonium Compounds; C009405:tetrabutylammonium