Parallel solution phase synthesis of a library of amino acid derived 2-arylamino-[1,3,4]-oxadiazoles

✍ Scribed by Julia I. Gavrilyuk; Alan J. Lough; Robert A. Batey

• Publisher: Elsevier Science
• Year: 2008
• Tongue: French
• Weight: 272 KB
• Volume: 49
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/j.tetlet.2008.05.110

✦ Synopsis

A mild method for the synthesis of peptidomimetic 2-arylamino 5-substituted 1,3,4-oxadiazoles from Boc-protected a-amino acid derived hydrazides has been developed, and applied in a parallel solutionphase synthesis. The optimized reaction conditions involve a one-pot reaction of Boc-protected amino acid hydrazides with arylisothiocyanates in the presence of either Hg(II) chloride, Mukaiyama's reagent (2-chloro-N-methylpyridinium iodide) or polymer supported Mukaiyama's reagent, with triethylamine in dichloromethane at ambient temperature. The 1,3,4-oxadiazole products were obtained in good to excellent yields without any detectable epimerization. The reactions proceed via initial formation of thiosemicarbazides, followed by dehydrothiolative cyclization to the 1,3,4-oxadiazoles.