Development of an Industrial Process Based on the Groebke–Blackburn–Bienaymé Multicomponent Reaction: Efficient Preparation of 3-Aminoimidazo[1,2-a]pyrazines

Abstract

3-Aminoimidazo[1,2-<i>a</i>]pyrazine is an important scaffold that is found in many drugs. This scaffold is rapidly accessible through a Groebke–Blackburn–Bienaymé cyclisation starting from an aminopyrazine, an aldehyde and an isocyanide. A scale-up process of this multicomponent reaction has been achieved in high yield and with excellent purity. The scope and limitations of this process leading to various 3-aminoimidazo[1,2-<i>a</i>]pyrazines are disclosed.