A Three-Component Path to Amino Thiadiazoles and Amino Oxadiazoles via a Nitrilium Ylide
Kane A C Bastick1, Matthew Diamandas1, Yang Daniel Ou1
1Department of Chemistry, University of Toronto, Toronto, Ontario M5S 3H6, Canada.
Abstract:
A novel multicomponent reaction to 2-amino-1,3,4-thiadiazoles has been developed using 5-substituted-1H-tetrazoles, amines, and TCDI as the key C═S donor. This modular process, inspired by the Huisgen reaction to obtain 1,3,4-oxadiazoles from acylated tetrazoles, proceeds via a key nitrilium ylide generated from tetrazole cycloreversion/nitrogen extrusion. This strategy allows for the rapid, facile, and scalable assembly of numerous 2-amino-1,3,4-thiadiazoles and 2-amino-1,3,4-oxadiazoles using CDI as a C═O donor, without the requirement for cross-coupling methodologies. The limitations to the amine scope were explored, and the developed reaction was showcased by the strategic modification of a nonsteroidal anti-inflammatory drug (NSAID), crisaborole.
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