Solid Phase Synthesis of Small Heterocyclic Scaffolds
R. Severinsen, J. P. Kilburn, J. F. Lau*
Medicinal Chemistry Research, Novo Nordisk A/S, Denmark
21 September 2005 (online)
2,5-Disubstituted [1,3,4]-thiadiazoles and [1,3,4]-oxadiazoles were prepared via several steps starting with thiosemicarbazide 1 or semicarbazide 2 anchored on the commercially available [2-(3,5-dimethoxy-4-formylphenoxy)ethoxy]methyl polystyrene. 5-Alkylthio-2-alkylamino-[1,3,4]-thiadiazoles 3a (14 variations, 45-82% yield), 5-alkyl-2-alkylamino-[1,3,4]-thiadiazoles 3b (12 variations, 47-76% yield), 5-acylamino-2-alkylamino-[1,3,4]-thiadiazoles 3c (23 variations, 31-86% yield) and 2,5-bis(alkylamino)-[1,3,4]-oxadiazoles 3d (13 variations, 58-89% yield) were readily isolated after TFA-mediated cleavage from the corresponding resin beads.