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Synthesis of N-Substituted 3-Amino-4-halopyridines: A Sequential Boc-Removal/Reductive Amination Mediated by Bronsted and Lewis Acids.

ABSTRACT: 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.

SUBMITTER: Wilhelmsen CA

PROVIDER: S-EPMC5835363 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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

Wilhelmsen Christopher A CA Dixon Alexandre D C ADC Chisholm John D JD Clark Daniel A DA

The Journal of organic chemistry 20180119 3

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 o ...[more]

PMID: 29308898

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