Heterocycle library synthesis multicomponent condensation reactions

Heterocyclic chemistry has been a major beneficiary of MW-expedited solvent-lfee chemistry utilizing mineral supported reagents. It has been exploited for parallel synthesis, a strategy that is adaptable for multicomponent reactions, such as Ugi " and Biginelli reactions " , for rapid assembly of a library of compoimds. A representative multi-component condensation reaction to create a small-molecule library of imidazo[l,2-a]pyridines, imidazo[l,2-a] pyrazines, and imidazo[l,2-a]pyrimidines is depicted in Scheme 3. 

Multicomponent condensations such as the Ugi reaction [44] and the Big-inelli condensation [45] are especially useful for the creation of diverse chemical libraries on the solid phase. Four-component condensations have been reviewed by Mjalli and Toyonaga [46] for the synthesis on the solid phase of small-ring heterocycles [47]. For example, the one-pot condensation of an amine (derived from amino acids) and an aldehyde, followed by the addition of an isocyanide and a carboxylic acid, provides a dipeptidomimetic iV-alky 1-A-acyl- a-amino amide 10 that can serve as a useful starting point for the synthesis of imidazoles 11 and pyrroles 12, which are pharmaceutically useful compounds (Fig. 4). 

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