LAUSR

Abstract 1,2,4-Triazolo[1,5-a]pyridines emerge as promising pharmacophores whose properties depend critically on 2- and 5-positioned substituents. We synthesized three new 1,2,4-triazolo[1,5-a]pyridine derivatives with different 2-substituents in combination with a morpholinomethylphenyl group at 5-position. Due to their unique electronic and intermolecular interactional characteristics, 2-substituents exert distinct influences on their crystal structures by forming diverse supramolecular synthons. Within the triazolopyridine cores, two non-conventional types of intermolecular hydrogen bonds are adopted by compound 1, bifurcated hydrogen bond motifs are formed through the two faces of 2-amino group substituted compound 2, and an anti-parallel self-complementary pairwise hydrogen bond motif is formed by 2-nitro group substituted compound 3. In the single crystal, compound 3 displays different conformational dynamics around the side chains compared to that of 1 and 2. The elucidating and understanding of their structural chemistry information is valuable for both their pharmaceutical development and application in crystal engineering.