Bicyclic 5–6 systems with one bridgehead (ring junction) nitrogen atom: One extra heteroatom

Abstract

The bicyclic 5–6 system with one bridgehead nitrogen atom has gained much popularity in the present decade. The best example could be denoted as pyrazolo[1,5-a]pyridine, which is devoted a marketed drug ‘Selpercatinib’ employed against cancer. However, the N-iminopyridinium salts, α,β-unsaturated esters and enynylpyrazoles are positively investigated as best raw materials for construction of pyrazolo[1,5-a]pyridine core. Whereas, isoxazolo[2,3-a]pyridines are much more focused toward the synthesis of partially saturated aromatic analogues. The synthesis and reactivity of imidazo[1,5-a]pyridines are involved with different metal catalysts, most of the synthetic reports are shown substituted aminomethyl pyridines, 1,2-dipyrdyls/2-benzoyl pyridines as emerging starting materials. The oxazolo[3,2-a]-pyridines are obtained from different heterocycles such as pyridines and 1,3 oxazoles, partially saturated oxazolo[3,2-a]-pyridines are accessed by the use of alkynes, alkylidines, malonates and alcohols. The thiazolo[3,2-a]pyridines are synthesized by various approaches involved with numerous heterocyclic derivatives. The synthesis of imidazo[1,2-a]pyridines are mainly associated with aminopyridine analogues, the reactivity has been investigated with multiple catalysts. The imidazo[1,2-a]pyridines are the most reactive substances reported with huge reactivity profile and emerging as potential medicinal scaffold in the current time period. The imidazo[1,2-a]pyridine provided a significant clinical agent GLPG1690 developed based autotaxin enzyme to treat idiopathic pulmonary fibrosis (IPF).