Synthesis of 4,7-dihydro[1,2,4]triazolo-[1,5-a]pyrimidine-6-sulfonamide derivatives

Abstract

There is a large body of publications on the synthesis and chemical properties of various derivatives of 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine, including those containing an acceptor substituent at position 6. At the same time, derivatives of 4,7-dihydro[1,2,4]triazolo[1,5-a]pyrimidine-6-sulfonamides which are of interest due to their biological properties are still not well studied. The goal of this work was the synthesis of these substances. The starting β-ketosulfonamides 3а,b were prepared by us according to a literature method using 1-(methylsulfonyl)piperidine (1) as the starting material (Scheme 1). Compound 1 was metalated at –15 °C in THF solution by the action of 2.5 M solution of n-butyllithium in hexane; the resulting lithium salt was treated with a solution of the corresponding aliphatic aldehyde in THF with cooling. Work-up of the reaction mixture afforded the corresponding β-sulfoalcohols 2а,b, which were further oxidized by Jones reagent affording the required β-sulfoketones 3a,b. The yield of compounds 3а,b (based on compound 1) was 86 and 98%, respectively. The reaction of compounds 3a,b, aromatic aldehydes, and 3-amino-1,2,4-triazole in boiling DMF led to the formation of the target compounds 4a–e in 18–42% yields (Scheme 2). The low yields were probably due to both the Chemistry of Heterocyclic Compounds 2015, 51(7), 691–694