Synthesis of N-Substituted-3-amino-4-halopyridines: a Sequential Boc-Removal/Reductive Amination Mediated by Brønsted and Lewis Acids

摘要

N -Substituted-3-amino-4-halopyridines are valuable synthetic intermediates, as they readily provide access to imidazopyridines and similar heterocyclic systems. The direct synthesis of N-substituted-3-amino-4-halopyridines is problematic, as reductive aminations and base promoted alkylations are difficult in these systems. A high yielding deprotection/alkylation protocol mediated by trifluoroacetic acid and trimethylsilyl trifluoromethanesulfonate is described, providing access to a wide scope of N-substituted-3-amino-4-halopyridines. This protocol furnishes many reaction products in high purity without chromatography. Similar reductive amination conditions were also established for deactivated anilines.