A novel three-component, one-pot condensation yielding 3-amino-substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrazines and imidazo[1,2-a]pyrimidines from aldehydes, isonitriles and 2-aminopyridine, 2-amino-pyrazine or 2-amino-pyrimidine is described.Combinatorial chemistry has recently gained much attention in pharmaceutical research. 1 The discovery of highly versatile and efficient synthetic methods for a broad variety of chemical structures is a prerequisite for the synthesis of large and diverse compound libraries. Multicomponent condensations (MCC's) constitute an especially attractive synthetic strategy for rapid and efficient library generation since the number of possible products grows exponentially with the number of the components involved and also because of their convergent nature. 2Here we present a facile three-component, one-pot condensation reaction yielding 3-amino-substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrazines and imidazo[1,2-a]pyrimidines.The imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrazine and imidazo [1,2-a]pyrimidine structural moieties can be found in pharmacologically active compounds such as benzodiazepine receptor agonists, 3 antiinflammatory agents, 4 inhibitors of gastric acid secretion, 5 calcium channel blockers 6 and antibacterials. 7 The classical synthesis of imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrazines and imidazo[1,2-a]pyrimidines involves the condensation of α-haloketones with 2-amino-pyridines, 2-amino-pyrazines or 2-amino-pyrimidines, respectively. 8 Being only a two-component condensation, this reaction is less suitable for the generation of a large compound library. To our knowledge only a single example for the formation of one of the said heterocyclic systems by a three-component reaction is reported in the literature, namely the synthesis of 3-amino-imidazo[1,2-a]pyrazine by condensation of 2-aminopyrazine, formaldehyde and sodium cyanide. 9The use of Ugi-type multicomponent reactions for the generation of compound libraries both by solution and solid phase chemistry has been reported by several groups. 2,10-15 Various heterocycles have been synthesized by this highly versatile condensation, including benzodiazepines, 11 pyrroles, 12 lactams, 13 hydantoins, 2,14 tetrazoles 14 and diketopiperazines. 15 In the course of our own studies of the Ugireaction using a broad variety of isonitriles 1, aldehydes 2, amines 3 and carboxylic acids we observed that the structure of the product formed depends strongly on the structure of the primary amine involved. We found now that the condensation with 6-membered heteroaromatic amines containing a H 2 N-C=N substructure leads smoothly to the generation of imidazo[1,2-a]-annulated heterobicyclic compounds. Thus, 2-amino-pyridine, 2-amino-pyrazine or 2-amino-pyrimidine gave 3-amino-imidazo[1,2-a]pyridines 4, 3-amino-imidazo[1,2-a]pyrazines 5 and 3-amino-imidazo[1,2-a]pyrimidines 6, respectively (Scheme 1).This reaction may be regarded as a special type of the Ugi four component reaction. 2 Thus, the reaction proce...

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