A mild, catalyst-free synthesis of 2-aminopyridines

Abstract

Alkylation of 2-mercaptopyridine with 1,2-dibromoethane affords a cyclic dihydrothiazolopyridinium salt that can serve as a precursor of 2-aminopyridines. Its reaction with primary or secondary amines, either neat or in DMSO, under mild conditions gives the title compounds.

Merging C–H Bond Functionalization with Amide Alcoholysis: En Route to 2-Aminopyridines

“…As a result, the design and development of general robust methods for the preparation of substituted 2-aminopyridines is highly significant. Classical methods for 2-alkyl-/2-arylaminopyridines rely on the nucleophilic addition and/or aromatic substitution reaction of pyridine derivatives, including 2-halopyridines, 2-alkoxypyridines, pyridinium, pyridone, pyridine N -oxides, and transition-metal (Pd, Cu, Ni)-catalyzed aminations − (Scheme ). These methods often require multiple synthetic steps for the required pyridine precursors and high temperature and overall offer limited functionalized 2-aminopyridines.…”

Pd‐PEPPSI‐IPentCl: A Useful Catalyst for the Coupling of 2‐Aminopyridine Derivatives

“…N ‐Aryl‐2‐aminopyridine motifs are found in a wide variety of highly useful compounds and notable effort has been expended to develop general approaches for their preparation . Transition‐metal‐catalysed transformations to establish the C−N bond, either to the aryl or pyridyl component, are fraught with the problem of catalyst poisoning, owing to the highly stabilised complexes that form between the aminopyridine and the metal .…”

“…2‐Aminopyridines are structural motifs encountered in a variety of useful compounds, including fluorescent organic materials and therapeutics (see Figure ), thus the development of synthetic methods to assemble this molecular substructure is important. Relative to N ‐alkyl aminopyridines, N ‐aryl derivatives offer an additional challenge for their preparation because direct substitution reactions at the amino group are not possible, and S N Ar with poorly nucleophilic anilines is not favoured . However, metal‐catalysed (hetero)arylation of the amino group provides an alternative for the formation of the C−N bond (Scheme ) .…”

Synthesis of Functionalized Dihydropyrido[2,3-d]pyrimidines in Aqueous Medium

“…5 Methods for the synthesis of 2-aminopyridines involve the reaction of 2-halopyridines with amines using metal catalysts. [6][7][8][9] Since in some cases, amination leads to a mixture of products and the reported methods are often not applicable at large scale, developing new and mild methods for the preparation of 2-aminopyridines is still desirable. Certain 2-amino-3-cyano-pyridines show bioactivity, and different approaches for their synthesis have been reported.…”