Pd-catalyzed oxidative cross-coupling of imidazo[1,2-a]pyridine with arenes

A facile method for direct Pd(OAc)₂-catalyzed oxidative cross-coupling of unactivated imidazo[1,2-a]pyridine with simple arenes has been developed. The reaction shows good reaction efficiency, high regioselectivity, and good functional-group compatibility. This approach provides a useful protocol for the preparation of imidazo[1,2-a]pyridine–arene structure of interest in biological and pharmaceutical materials.     

Synthesis of carbamoylpyridine and imidazo[1,5-a]pyridin-1,3-diones via ortho-acetalhydantoin intermediates

A new method for preparing carbamoylpyridine and imidazo[1,5-a]pyridin-1,3-dione rings from an ortho-acetalmethylideneimidazolidin-2,4-dione is described.     

Novel one pot synthesis of polysubstituted pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidines

We have described a convenient regioselective one-pot approach to pyrazolo[1,5-a]- and imidazo[1,2-a]pyrimidine derivatives from α,β-unsaturated imines generated in situ and amino heterocycles. Reaction is general with respect to all three components, namely (i) nitrile, (ii) aldehyde, and (iii) amino heterocycle reagents. Good yields (52-77%), convenient isolation of the targeted molecules are the distinct characteristics of the developed protocol.     

Short and efficient access to imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives

Access to N-protected or N-free imidazo[1,2-a]pyrrolo[3,2-c]pyridine derivatives as potential antiviral compounds was achieved in good yields from N-protected 7-amino-8-halo-2-methylimidazo[1,2-a]pyridines by catalytic coupling of terminal acetylenes under mild conditions using [PdCl₂(PPh₃)₂] or [Cu(Phen)(PPh₃)₂]NO₃.     

An efficient microwave-assisted Suzuki cross-coupling reaction of imidazo[1,2-a]pyridines in aqueous medium

A new simple, rapid and high yielding synthesis of various 6-aryl-2-arylsulfonylmethyl-3-nitroimidazo[1,2-a]pyridines by Suzuki cross-coupling reaction is described using microwave irradiation in aqueous medium without organic co-solvent in the presence of tetrabutylammonium bromide.     

Water mediated deprotective intramolecular hydroamination of N-propargylaminopyridines: synthesis of imidazo[1,2-a]pyridines

Metal-free synthesis of substituted imidazole [1,2-a]pyridines from deprotective N-(prop-2-yn-1-yl)pyridin-2-amines in water is elucidated. Electron releasing substituents on pyridine ring provided pure products in quantitative yields without separation by column chromatography.     

Pyrazolo[1,5-a]pyridines: synthetic approaches to a novel class of antiherpetics

Synthesis of a novel class of 7-amino-3-pyrimidinyl-pyrazolo[1,5-a]pyridine antiherpetic compounds is described. The synthetic methodology is designed to allow for rapid analog synthesis around the C-3 and C-7 positions of the pyrazolo[1,5-a]pyridine. The 7-chloropyrazolo[1,5-a]pyridine D, produced through an azirine rearrangement, served as a key building block. Two complementary methodologies for construction of the C-3 pyrimidine are described. These methods include the development of a novel cyclization utilizing alkynyl ketones or enones to give highly substituted pyrimidines. The outlined strategies facilitated late stage manipulation of either the C-3 or C-7 positions providing flexibility for rapid analog synthesis.     

A novel three-component reaction of N-fluoropyridinium salts: a facile approach to imidazo[1,2-a]pyridines

The reaction of N-fluoropyridinium triflate with isonitriles in acetonitrile and propionitrile in the presence of NaBH(OAc)₃ led to the formation of the corresponding imidazo[1,2-a]pyridines in 44-73% yields. The proposed reaction mechanism involves the intermediate formation of a highly reactive carbene species and apparent reduction of the pyridinium intermediate with NaBH(OAc)₃ to yield the targeted heterocycles.     

Exploration of versatile reactions on 2-chloro-3-nitroimidazo[1,2-a]pyridine: expanding structural diversity of C2- and C3-functionalized imidazo[1,2-a]pyridines

Alternative strategies for functionalizing 2-chloro-3-nitroimidazo[1,2-a]pyridine have been developed. Suzuki–Miyaura cross-coupling reaction provided easily the corresponding 2-arylated compounds, and herefrom the nitro group was reduced into amine which afforded amides, anilines, and ureas in the 3-position. The amination of the key compound using a metal-catalyzed reaction was reported. This study highlighted the importance of the nitro group to facilitate the chlorine displacement. Other nucleophilic aromatic substitutions open a route to various products derived from imidazo[1,2-a]pyridine.     

Novel synthesis of 2,4-bis(2-pyridyl)-5-(pyridyl)imidazoles and formation of N-(3-(pyridyl)imidazo[1,5-a]pyridine)picolinamidines: nitrogen-rich ligands

Heating a neat 1:2 mixture of 2-picolylamine and 2-cyanopyridine followed by treatment of the resultant red gummy substance with aqueous KOH resulted in the isolation of 2,4,5-tris(2-pyridyl)imidazole (1a) as the major product and N-(3-(2-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2a) in small amounts. Similarly, by using 3-picolylamine, 2,4,-bis(2-pyridyl)-5-(3-pyridyl)imidazole (1b) and N-(3-(3-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2b) were isolated, and by using 4-picolylamine, 2,4,-bis(2-pyridyl)-5-(4-pyridyl)imidazole (1c) and N-(3-(4-pyridyl)imidazo[1,5-a]pyridine)picolinamidine (2c) were isolated. The plausible mechanism of the formation of 1a-c and 2a-c is delineated.     

One-pot approach to the synthesis of novel 12H-chromeno[2′,3′:4,5]imidazo[1,2-a]pyridines in aqueous media

The chromeno-imidazo[1,2-a]pyridine scaffold was generated in an one pot condensation/cyclization reaction involving a salicylaldehyde and 1-(cyanomethyl)pyridinium chloride, in aqueous sodium carbonate solution. These novel compounds were isolated in 47-71% yield. The reaction pathway was followed by ¹H NMR spectroscopy allowing a clear understanding of the side reactions involved in the process.Different mono-substituted pyridinium chlorides were synthesized and reacted with mono-substituted salicylaldehydes and a detailed discussion of the scope of the synthetic method is also presented.     

A one-pot synthesis of polysubstituted imidazo[1,2-a]pyridines

A series of 5,7,8-polysubstituted imidazo[1,2-a]pyridines were synthesized regioselectively from in situ generated α,β-unsaturated imines and dianions derived from methyl azolyl acetates in a one-pot procedure. The targeted molecules were conveniently isolated in analytically pure form (ca. 50-70% yields) by trituration of the concentrated reaction mixtures with cold ether.     

A general and efficient method for the copper-catalyzed cross-coupling of amides and thiophenols with 6-halogenoimidazo[1,2-a]pyridines

Convenient and efficient methods for the preparation of novel 6-amido and 6-phenylsulfanylimidazo[1,2-a]pyridine derivatives that utilize copper-catalyzed methodologies are reported. These methods are particularly noteworthy because of their experimental simplicity and the low cost of the catalyst system.     

Ionic liquid promoted one-pot synthesis of 3-aminoimidazo[1,2-a]pyridines

3-Aminoimidazo[1,2-a]pyridines have been synthesized in good to excellent yields in the presence of the ionic liquid 1-butyl-3-methylimidazolium bromide [bmim]Br, the reaction workup is simple and the ionic liquid can be easily separated from the product and reused.     

A new, one-pot, multi-component synthesis of imines of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines

An efficient, one-pot, multi-component synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines, 3-amino-2-arylimidazo[1,2-a]pyrazines, and 3-amino-2-arylimidazo[1,2-a]pyrimidines is described. Heating a mixture of a 2-aminopyridine, 2-aminopyrazine or 2-aminopyrimidine, a benzaldehyde, and imidazoline-2,4,5-trione under solvent-free conditions afforded imine derivatives of the title compounds in excellent yields. Single-crystal X-ray analysis conclusively confirms the structure of these bridgehead bicyclic 5-6 heterocycles.     

Multicomponent synthesis of imidazo[1,2-a]pyridines using catalytic zinc chloride

The novel use of zinc chloride to catalyze the one-pot, three component synthesis of imidazo[1,2-a]pyridines from a range of substrates using either conventional heating or microwave irradiation is described. This methodology affords a number of imidazo[1,2-a]pyridines in reasonable yields and short reaction times without any significant optimization of the reaction conditions.     

A one-pot four-component synthesis of N-arylidene-2-aryl-imidazo[1,2-a]azin-3-amines

N-Arylidene-2-aryl-imidazo[1,2-a]azin-3-amines were synthesized via a one-pot, four-component condensation reaction using a 2-aminoazine, toluene-4-sulfonylmethyl isocyanide (TsCH₂NC), and two equivalents of readily available aromatic aldehydes. The reaction was performed in diethyl ether as the solvent, with p-toluenesulfonic acid (p-TSA) as the catalyst at reflux temperature.     

Novel synthesis of C-3-(hetero)aryl [1,2,3]triazolo[1,5-a]pyridines using the Stille reaction

Herein, we report a novel and high yielding approach for the preparation of the first C-3-organometallic substituted [1,2,3]triazolo[1,5-a]pyridine and its application to the Stille reaction using MAOS.     

Pd-catalyzed regiocontrolled Sonogashira and Suzuki cross-coupling reaction of 3,6-dihalogenoimidazo[1,2-a]pyridines: one-pot double-coupling approach

New and efficient regioselective Sonogashira and Suzuki-Miyaura palladium-catalyzed coupling reactions of 3,6-dihalogenoimidazo[1,2-a]pyridines followed by another cross-coupling has been successfully developed. Various solvents, palladium species and bases were tested. Scope and limitations of this regiocontrolled palladium-catalyzed reaction were investigated. The synthesis of 3,6-disubstituted imidazo[1,2-a]pyridine derivatives using one-pot regioselective double-coupling approach was developed. This procedure affords convergent syntheses of polysubstituted compounds in high yields in a very few steps.     

One pot synthesis of imidazo[2,1-b]thiazoles and benzo[d]thiazolo[3,2-a]imidazoles

A series of imidazo[2,1-b]thiazole and benzo[d]thiazolo[3,2-a]imidazole analogues were synthesized by stirring an equimolar mixture of dibenzoylacetylene with imidazole/thiazole derivatives in toluene or acetonitrile at room temperature. The products were generated in good yields and characterized by standard analytical techniques such as IR, ¹H NMR, ¹³C NMR and mass spectrometry. The structure of products 19, 20, 22, 24 and 25 were also unambiguously confirmed by single crystal X-ray analysis.