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.     

A convenient synthesis of linear pyridinoimidazo[1,2-a]pyridine and pyrroloimidazo[1,2-a]pyridine cores

Two new imidazo[1,2-a]pyridine derivatives, pyridinoimidazo[1,2-a]pyridine (10) and pyrroloimidazo[1,2-a]pyridine (16), were synthesised from 2-amino-4-methyl-5-nitropyridine (1) by linear cyclisation, making use of dimethylformamide dimethylacetal (DMFDMA) as an agent of vinylamine functionalisation. This report describes first the formation of pyridine and pyrroloimidazopyridine from (1), and then the formation of pyridine-fused and pyrrolo-fused pyridine by the Friedländer method and reductive cyclisation followed by treatment of the resulting adduct with chloroacetaldehyde.     

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.     

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.     

Grignard reagent-promoted 6-endo-dig cyclization: instantaneous synthesis of original dipyrido[1,2-a:3′,4′-d]imidazole

Dipyrido[1,2-a:3′,4′-d]imidazole derivatives can be readily synthetized from various 3-alkyne-2-cyanoimidazo[1,2-a]pyridines via an efficient Grignard reagent-promoted 6-endo-dig cyclization of nitrile to alkynes. A previous optimization of the Sonogashira coupling reaction at C(3) of the 2-cyanoimidazo[1,2-a]pyridine was necessary as this coupling reaction is known to be largely influenced by the nature of the 2-substituent.     

A new, one-pot, three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines

A new, one-pot and three-component synthesis of 4H-pyrido[1,2-a]pyrimidines, 4H-pyrimido[1,2-a]pyrimidines, and 4H-pyrazino[1,2-a]pyrimidines is described. The reactive 1:1 zwitterionic intermediate, formed by the addition of isocyanides to dialkyl acetylenedicarboxylates, was trapped by N-(2-heteroaryl)amides to yield a ketenimine intermediate, which was cyclized and then rearranged under the reaction conditions to afford the title compounds under mild reaction conditions in good yields. Single-crystal X-ray analysis conclusively confirms the structure of the obtained bridgehead bicyclic 6-6 heterocyclic compounds.     

Expeditious synthesis of 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidin-2-ones and 3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones

A convenient synthesis of new 5,6,7,8-tetrahydro-imidazo[1,2-a]pyrimidin-2-ones and 3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-ones from the Baylis-Hillman adducts of acrylonitrile and their derivatives is described. A common strategy employed to achieve the syntheses of title compounds involved generation of diamines from different Baylis-Hillman derivatives followed by treatment with cyanogen bromide at reflux temperature to trigger a double intramolecular cyclization.     

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.     

Highly efficient synthesis of triazolo[1,2-a]indazole-triones and novel spiro triazolo[1,2-a]indazole-tetraones under solvent-free conditions

A new, convenient, and high yielding procedure for the synthesis of triazolo[1,2-a]indazole-triones by the condensation reaction between dimedone, aryl aldehydes, and ueazoles in the presence of a catalytic amount of sulfonated polyethylene glycol (PEG-SO₃H) as a highly stable and reusable eco-friendly degradable polymeric catalyst is described under solvent-free conditions. This procedure has also been applied successfully for the synthesis of novel spiro triazolo[1,2-a]indazole-tetraones.     

Diversity-oriented decoration of pyrrolo[1,2-a]pyrazines

Diversity-oriented synthesis of a chemical library based on a pyrrolo[1,2-a]pyrazine core is described by using palladium-catalyzed direct C6 arylation of pyrrolo[1,2-a]pyrazines with various aryl bromides. The starting materials, pyrrolo[1,2-a]pyrazines, were easily synthesized by the base-mediated N-alkylation of pyrrole-2-carboxaldehyde with several 2-bromoacetophenones followed by dehydrative cyclization with incorporation of nitrogen by the action of ammonium acetate. Introduction of other functional groups on this chemical scaffold is also discussed herein.     

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.     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

A facile synthesis of pyrrolo[1,2-a]benzimidazoles and pyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazole derivatives

Reaction of 2-cyanomethylbenzimidazole 1 with hydrazonoyl halides 2 led to formation of pyrrolo[1,2-a]benzimidazole derivatives 7. Similar reaction of 1 with halides 3 afforded 5-amino-4-(benzimidazol-2-yl)pyrazole derivatives 11 or 1-amino-2-arylpyrazolo[3,4:4′,3′]pyrrolo[1,2-a]benzimidazol-4-one 14 depending on the reaction conditions. The mechanisms of the studied reactions are discussed.     

An efficient synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines

An efficient synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines is described via a novel multicomponent reaction between 2-aminopyridines, benzaldehydes and imidazoline-2,4,5-trione under solvent-free conditions.     

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.     

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.     

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.     

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.     

Formation of the same pyrimido[1,2-a]indoles from 1-(oxiran-2-ylmethyl)-1H-indole or [1,3]oxazolo[3,2-a]indole derivatives in its reactions with aromatic amines

Reactions of two isomers—2-chloro-1-(oxiran-2-ylmethyl)-1H-indole-3-carbaldehyde or 2-(chloromethyl)-2,3-dihydro[1,3]oxazolo[3,2-a]indole-9-carbaldehyde with aromatic amines lead to the same products in both cases—hydrochlorides of pyrimido[1,2-a]indole derivatives containing two fragments of an amine per one part of the indole nucleus. Its structure was confirmed by X-ray analysis of the crystals base, obtained by alkali treatment of the reaction product (when aryl is 4-MeOC₆H₄).     

A simple approach for the regioselective synthesis of imidazo[1,2-a]pyrimidiones and pyrimido[1,2-a]pyrimidinones

Several imidazo and pyrimido[1,2-a]pyrimidinones of type 1 and 2 were synthesized through intramolecular cyclization of pyrimidines 9 or pyrimidinones 10 bearing a variety of β and γ-aminoalcohols at the 2-position. Ring closure of the pyrimidinones of type 10 under Mitsunobu conditions lead to mixtures of both bicyclic regioisomers 1 and 2. Treatment of pyrimidines of type 9 with H₂SO₄ provided an efficient and operationally simple one-pot hydrolysis-cyclization procedure for obtaining imidazo and pyrimido[1,2-a]pyrimidinones 1 in good yields as the sole regioisomeric bicyclic product.