Synthesis of Substituted Imidazo[1,5-a]pyridines Starting from N-2-Pyridyl- methylamides Using Lawesson’s Reagent and Mercury(II) Acetate Synthesis of Imidazo[1,5-a]pyridines from N-2-Pyridylmethylamides (original) (raw)

A revised approach to the synthesis of 3-acyl imidazo[1,2-a] pyridines

Heterocyclic Communications, 2010

3-Acyl imidazo[l,2-a]pyridines with no substituent at position 2 were obtained in moderate to good yields in an improved version of the Tisler protocol for the synthesis of imidazo[l,2-x]azines. It was found that yields are significantly improved if the reaction is carried out in the presence of DMF or in some cases in the absence of a solvent. INTRODUCTION The fused heterocyclic system imidazo[l,2-a]pyridine is an important pharmacophore, as is demonstrated by the broad variety of pharmacological activities shown by its derivatives.' The most common approach to the synthesis of the imidazo[l,2-o]pyridine ring is based on the condensation reaction of 2-aminopyridines with a-halocarbonyl compounds. 2 This methodology allows the direct construction of 2 or 2,3-substituted imidazo[l,2-a]pyridines, but is not usefiil for the synthesis of 3-acyl imidazo[l,2-a]pyridines with no substituent at position 2. The interesting aspect of 3-aroyl imidazo[l,2-a]pyridines is their potential biological activity. Thus, derivatives of 2-amino-3-aroyl imidazo [l,2-a]pyridines have been evaluated as antiviral agents. 3 A useful method of synthesis of 3-acyl imidazo[l,2-a]azines is the intramolecular cyclization of alkylated iV-heteroaryl formamidines, described by Tisler. 4,5 Direct thermal regiospecific acylation of 7-methyl imidazo[l,2-a]pyridine has also been reported. 6 Since our research program required 3-aroyl imidazo[l,2-a]pyridines unsubstituted at position 2 to carry out several studies, the Tisler method was the best option to synthesize them. However, in the Tisler protocol the related derivative 2-methyl-3-benzoylimidazo[l,2-a]pyridine 2 was obtained in only 16% yield via condensation of formamidine 1, with the corresponding α-bromoketone. The results of an adaptation of such methodology to the synthesis of 3-acyl imidazo[l,2-a]pyridines unsubstituted at position 2 are presented herein. RESULTS AND DISCUSSION The study began with a multicomponent approach to the 3-acyl imidazo[l ,2-a]pyridine heterocyclic system, employing 2-aminopyridine, 2-bromoacetophenone and formaldehyde. However, from this experiment only 2-phenylimidazo[l,2.a]pyridine was obtained. Then DMFDMA, a well known one carbon synthon useful in the synthesis of heterocycles, 7 was used in place of formaldehyde. This attempt was also unsuccessful, giving only traces of 3-(4'-chlorobenzoyl imidazo[l,2-a]pyridine. Therefore, it was decided to directly treat the jV'-pyridylformamidine 3

Various Synthesis of Imidazo[1,2-a]pyridines Derivatives and Therapeutic Significance: A Review

Bio web of conferences/BIO web of conferences, 2024

The synthesis of bicyclic heterocycles, notably nitrogen-containing imidazopyridines, holds immense appeal due to their structural diversity and pivotal role in biological systems. These compounds are ubiquitously found in nature and are prized for their significance in both chemical and biological contexts. Imidazopyridine derivatives, among nitrogen heterocycles, serve as fundamental structures in various applications spanning pharmaceuticals to food additives. Consequently, their synthesis and modification represent a focal point in both natural and synthetic organic chemistry. This review aims to comprehensively explore conventional methodologies alongside innovative synthesis approaches, while also delving into the diverse biological properties exhibited by these versatile heterocycles. Through this examination, we endeavor to provide valuable insights that will contribute to further advancements in the synthesis and utilization of imidazopyridines in various fields.

SYNTHESIS OF SOME NEW SUBSTITUTED IMIDAZO(1,2-a)PYRIDINES AND THEIR 2-ONE DERIVATIVES

IUG Journal of Natural Studies, 2016

2,3-diaminopyridine (11) (a tri-nitrogen nucleophile) undergoes regioselective cyclocondensation reaction with nitrilimines (2,10) affording 8-aminoimidazo[1,2-a]pyridines (12) and 8-aminoimidazo[1,2a]pyridine-2-ones (13), respectively. The structures of the new compounds (12,13) were deduced from their IR, MS and NMR spectral data.

Improved method for the preparation of 3-aryl- and 3-styrylimidazo[1,5-a]pyridines

Chemistry of Heterocyclic Compounds, 2000

A new convenient method is proposed./or the preparation o/ 3-ao 'l-and 2-stvn.,limidazo[l,5-a]pyridines involving the cvclocondensation 0/ 2-(acylaminobenzyl)pyridines in acetic anhydride with adding of p-toluenesul[onic acid. Imidazo[1,5-a]pyridines display physiological activity and are used in antiviral [1] and cardiotonic drugs [2]. These compounds are also employed as inhibitors for certain enzymes [3] and as fluorophors [4, 5].

Recent Progress in Metal-Free Direct Synthesis of Imidazo[1,2-a]pyridines

ACS Omega

This Mini-Review highlights the most effective protocols for metal-free direct synthesis of imidazo[1,2-a]pyridines, crucial target products and key intermediates, developed in the past decade. The emphases is given on the ecological impact of the methods and on the mechanistic aspects as well. The procedures efficiently applied in the preparation of important drugs and promising drug candidates are also underlined.