학술논문
Synthesis of 15 N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates.
Document Type
Academic Journal
Author
Nguyen HMH; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.; Thomas DC; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.; Hart MA; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.; Steenback KR; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.; Levy JN; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.; McNally A; Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523, United States.
Source
Publisher: American Chemical Society Country of Publication: United States NLM ID: 7503056 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1520-5126 (Electronic) Linking ISSN: 00027863 NLM ISO Abbreviation: J Am Chem Soc Subsets: PubMed not MEDLINE; MEDLINE
Subject
Language
English
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 15 N atoms within their structures are limited. Here, we present a general approach to pyridine 15 N-labeling that proceeds via ring-opening to N Tf-Zincke imines and then ring-closure with commercially available 15 NH 4 Cl salts. This process functions on a range of substituted pyridines, from simple building block-type compounds to late-stage labeling of complex pharmaceuticals, and 15 N-incorporation is >95% in most cases. The reactivity of the Zincke imine intermediates also enables deuteration of the pyridine C3- and C5-positions, resulting in higher mass isotopologs required for LCMS analysis of biological fluids during drug development.