Diversification of the three-component coupling of 2-aminoheterocycles, aldehydes, and isonitriles: Efficient parallel synthesis of a diverse and druglike library of imidazo- and tetrahydroimidazo[1,2-d] heterocycles

Due to their diverse range of biological activities, imidazoheterocycles are recognized as privileged structures making these structural motifs attractive targets for library preparation-We report herein the synthesis of a sizable collection of imidazo[ 1,2-a] heterocycle scaffolds well-suited for divergent library preparation by virtue of amine functional handles with diverse positioning and connectivities. Partial reduction of imidazo[1,2-a]pyrazines to the tetrahydroimidazo[1,2-a]pyrazines and regiospecific Mannich-type bond formation at the C-3 of imidazo[1,2-a]pyridine under mild conditions achieved additional topological and connective diversity within the scaffold collection. Subsequent parallel reaction of the functionalized imidazoheterocycles with polystyrene-tetrafluorophenol esters and sulfonates produced a 7500 compound library in high purity.