An efficient and flexible route to novel triazolopiperazine scaffolds

[Display omitted] •A simple and fast methodology allows access to novel triazolopiperazines.•Mild conditions and wide availability of starting materials allow a broad scope.•Tsunoda reagent is crucial in enabling final piperazine ring closure.•The first enantiospecific synthesis of these triazolopiperazines is described.•Difficult to access spirocyclic scaffolds are efficiently constructed in two steps. In this work we describe the preparation of novel fused, spirocyclic and chiral triazolopiperazines. We have developed a practical, rapid and robust synthetic route to these scaffolds that allows control of regio- and stereochemistry. This method utilises mild conditions and uses widely available and diverse amino acids and amidines as starting materials. These complex unprecedented 5,6,7,8-tetrahydro-[1–2,4]triazolo[1,5-a]pyrazines represent attractive building blocks for drug discovery.