Solid Phase Synthesis of 1,2,4-Triazinan-3-ones

Abstract

Solid-phase parallel synthesis is used worldwide to generate libraries of small organic compounds in order to accelerate the drug discovery process [1]. The focus of this field of research, which initially involved the synthesis of peptides and oligonucleotides, is now on the synthesis of small organic molecules on the solid-phase. Heterocycles, such as benzodiazepines, hydantoins, pyrrolidines, and bicyclic guanidines, have received special attention in combinatorial synthesis due to their biological interesting properties [2]. This strategy has permitted the synthesis of large numbers of heterocycles in a short time frame, enabling their use in high-throughput screening. Compounds containing the 1,2,4-triazine moiety are in use as pharmaceuticals, pesticides, herbicides etc. [3]. As part of our ongoing efforts directed toward the solid phase synthesis of small molecule and heterocyclic compounds and the generation of their combinatorial libraries [4], we report here an efficient method for the synthesis of l,2,4-triazinan-3-ones from resin-bound acylated amino acid amides.