Solid-Phase Synthesis of 1,2,4-Thiadiazoles

Determined on the basis of LC-MS spectrum (integration of diode array 200-400 nm traces) after short-passed silica gel column chromatography. 

As a member of the thiadiazole family, which is a privileged structure for the generation of drug-like libraries, 1,2,4-thiadiazoles have been used as the basic framework for substances of interest in numerous therapeutic areas Recently, we reported the results of a study that led to the development of a solution-phase parallel synthesis of various drug-like 5-amino-1,2,4-thiadiazoles via a three-component nucleophiUc substitution reaction between carbon disulhde, benzamidine, and benzyl chloride, using a key cyclization reaction of a carboxamidine dithiocarbazate induced by TsCl. We also developed a simple and efficient solid-phase parallel synthetic method capable of facilitating the 

Alkylation reactions of 5-amino resin 55 with alkyl halides (R diversity element) provided the desired 3-substituted 5-(iV-alkylamino)-1,2,4-thiadiazole resin 56. In a similar manner, 3-substituted 5-(A-acylamino)-1,2,4-thiadiazole resin 57 was produced by acylation reactions of resins 55 with acid chlorides (R diversity element). More important, resins 56a (R = Ph, R = Bn) and 57a (R = R = Ph) underwent smooth 

Five-step overall isolated yield from BOMBA resin 60 (loading capacity = 1.20mmol/g). 

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