Selective Synthesis of Polyamine Derivatives: Efficient derivatization of the secondary amino group of N‐monosubstituted 1,3‐diamines

Abstract N‐Monosubstituted 1,3‐diamines were selectively functionalized at the secondary N‐atom via 2‐Ph‐substituted hexahydropyrimidine intermediates. Reaction of the diamines with benzaldehyde, followed by treatment with an electrophile and hydrolysis, provided the desired products with excellent selectivity and in high yields. N4,N9‐bis[3‐phenylprop‐2‐enoyl]spermine (4a), which was further converted to N1,N1 2‐bis[3‐phenylprop‐2‐enoyl]spermine (15) by a transamidation reaction, was prepared by this way in 82% yield from spermine (1). Compound 4a was alternatively synthesized in 83% yield, equally from 1, by a sequence involving intermediary protection of the terminal amino groups.