Synthesis of N-alkyl-octahydroisoquinolin-1-one-8-carboxamide libraries using a tandem Diels-Alder/acylation sequence

A synthetic sequence was developed in which a diene containing an attached secondary amine was reacted with maleic anhydride to afford the title structures in one step. The reaction involves a Diels-Alder reaction combined with a transacylation reaction of the imide group. A series of six scaffolds was constructed using this methodology. Each scaffold was subsequently reacted with 12 amines to afford a library containing 72 compounds.