Application of the modified Pictet-Spengler cyclization reaction for the preparation of an imidazopyrazine ring: synthesis of new pyrido- and pyrimido-imidazopyrazines.

An efficient and versatile method for the synthesis of imidazopyrazine ring using the modified Pictet-Spengler strategy has been reported. The two step strategy offers rapid assembly of druglike core templates pyridine or pyrimidine and imidazole into new annulated polycyclic skeletons: pyrido- and pyrimido-imidazopyrazines. The rate of endo cyclization of aryl/heteroaryl-amine substrates has been compared with traditionally used aliphatic amine substrates, and results have been discussed in the light of the pK(a) values of amines present in each substrate.