Solid phase synthesis of an extensively focused library of thiadiazole ethers

An approach to combine the advantages of random and of focused combinatorial libraries in pharmaceutical research is described with the example of a solid phase synthesis of 2,5-disubstituted thiadiazole ethers. Key steps of synthesis are the introduction of the heterocycle by selective, sequential nucleophilic double substitution of 2,5-bis(methylsulfonyl)-1,3,4-thiadiazole and the oxidation of the benzylsulfanyl-1,3,4-thiadiazole to the corresponding sulfone using MCPBA on solid phase.