The Synthesis of 2‐Amino‐4‐(4‐imidazolyl)pyridines

A general synthetic scheme for the preparation of 2‐amino‐4,(4‐imidazolyl)pyridines, potential histamine H2 antagonists, is described. The synthesis is based on the Neber rearrangement of l,(4‐pyridyl)l‐alkanone oxime 0‐tosylates to the appropriate α‐aminoketones or α‐aminoketals, which are then converted to the corresponding imidazoles. The reaction of Grignard reagents with 2‐chloroisonicotinonitrile, as well as nucleophilic displacement of chloride by amines on 2‐chloroisonicotinonitrile and derivatives, are discussed in relation to the preparation of the ketone intermediates.