Synthesis of ¹⁵N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates.

ABSTRACT: Methods to incorporate stable radioisotopes are integral to pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods to incorporate ¹⁵N atoms within their structures are limited. Here, we present a general approach to pyridine ¹⁵N-labeling that proceeds via ring-opening to NTf-Zincke imines and then ring-closure with commercially available ¹⁵NH₄Cl salts. This process functions on a range of substituted pyridines, from simple building block-type compounds to late-stage labeling of complex pharmaceuticals, and ¹⁵N-incorporation is >95% in most cases. The reactivity of the Zincke imine intermediates also enables deuteration of the pyridine C3- and C5-positions, result

SUBMITTER: Nguyen HMH 

PROVIDER: S-EPMC11446173 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature