Synthesis of a Heterocyclic Amine and Acid Receptor

The synthesis of a molecule able to bind both with an amine and a carboxylic acid is described. This new host consists in a pyrroloisoquinoline structure possessing a side arm with an acetamidopyridine moiety. The pyrroloisoquinoline part was obtained after improvement of the previously published route involving regioselective reduction of appropriate 3-arylalkylaminosuccinimides followed by ring closure using iminium chemistry. The tricyclic structure was then functionalized by cross-coupling reaction under Pd0 catalysis of its triflate derivative with the trimethylsilyl ketene acetal of methyl acetate. The so-obtained ester was then reacted with 2-amino-4,6-dimethylpyridine leading to the targeted host. The association constants of this latter compound with some carboxylic acids and amines were determined by 1H NMR titration. NOESY experiments and molecular modeling calculations were performed in order to precise the actual host–guest interactions.