Direct arylation of imidazo[1,2-a]pyridine at C-3 with aryl iodides, bromides, and triflates via copper(I)-catalyzed C-H bond functionalization

A convenient method for the copper(I)-catalyzed arylation of substituted imidazo[1,2-a]pyridine has been developed. This method is applicable to a variety of aryl electrophiles, including bromides, iodides, and triflates. It represents the first general process for C-3 arylation of substituted imidazo[1,2-a]pyridine by Cu(I) catalysis to construct various functionalized imidazo[1,2-a]pyridine core π-systems.     

Research on imidazo[1,2-a]benzimidazole derivatives XII. 3-Acyl-substituted imidazo[1,2-a]benzimidazoles

Stable 3-acetyl derivatives of imidazo[1,2-a]benzimidazole were synthesized by the action of acetic anhydride on 2,9-disubstituted imidazo[1,2-a]benzimidazole. The former were also obtained by cyclization of 1-alkyl (aralkyl) -3-acylmethyl-2-iminobenzimidazoline hydrobromides in acetic anhydride in the presence of anhydrous sodium acetate. 3-Benzoyl-substituted imidazo[1,2-a]benzimidazoles, which are unstable in acidic media, were synthesized by the action of benzoyl chloride in the presence of pyridine or excess starting imidazo [1,2-a] benzimidazole.See [1] for communication XI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 121– 125, January, 1976.     

Efficient solid-phase synthesis of a library of imidazo[1,2-a]pyridine-8-carboxamides

A versatile method for the solid-phase synthesis of imidazo[1,2-a]pyridine-based derivatives, imidazo[1,2-a]pyridine-8-carboxamides, has been developed. They were obtained by treatment of the amino group of the polymer-bound 2-aminonicotinate with different alpha-haloketones, followed by halogenation at the 3-position of the polymer-bound imidazo[1,2-a]pyridine. The derived polymer-bound imidazo[1,2-a]pyridines 5, 6, and 7 were finally cleaved from the solid-support with an excess of primary or secondary amines. The final crude products were purified from excess amines by solid-supported liquid-liquid extraction (SLE).     

Easy access to novel substituted 6-aminoimidazo[1,2-a]pyridines using palladium- and copper-catalyzed aminations

Convenient and efficient methods for the preparation of novel 6-aminoimidazo[1,2-a]pyridine derivatives are reported that utilized palladium- or copper-catalyzed methodology. The crystal structure for 6-N-methylanilinoimidazo[1,2-a]pyridine 10 is also described.     

2-(1-Adamantyl)-7-methylimidazo-[1,2-α]pyridine and its reactions with N-bromosuccinimide

In reaction with equimolar amount or twice the amount of N-bromosuccinimide 2-(1-adamantyl)-7-methylimidazo[1,2-a]pyridine, obtained from 2-amino-4-methylpyridine and bromomethyl 1-adamantyl ketone, is converted into 2-(1-adamantyl)-3-bromo-7-methylimidazo[1,2-a]pyridine. With three times the amount of N-bromosuccinimide it gives 2-(1-adamantyl)-3-bromo-7-formylimidazo[1,2-a]pyridine.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1791–1793, December, 2004.     

Nitration of 2-phenylimidazo[1,2-a]pyridine

The addition of 2-phenylimidazo[1,2-a]pyridine to a nitrating mixture forms 3-nitro-2-(p-nitrophenyl)imidazo[1,2-a]pyridine; the position of the nitro groups in it has been shown by chemical reactions and by a determination of the dipole moment.     

Solid-phase synthesis of imidazo[1,2-a]pyridine using sodium benzenesulfinate as a traceless linker

[formula: see text] The preparation of the first library of imidazo[1,2-a]pyridine derivatives on a solid support is described. A sulfone linker strategy was applied in the synthesis. Key steps involved in the solid-phase synthetic procedure include (i) alpha-haloketone resin formation by sulfinate-->sulfone alkylation, (ii) imidazo[1,2-a]pyridine ring formation by treatment with 2-aminopyridine, (iii) sulfone anion alkylation, and (iv) traceless product release by oxidation-elimination. A library of 12 imidazo[1,2-a]pyridines was synthesized.     

a -Oxo Ketene Dithioacetals Chemistry-A Facile Route to the Synthesis of Fused Heterocyclic Compounds

The fused heterocyclic compounds 2 : imidazo [1,2-a] pyridine 2a-c and pyrido [1,2-a] pyrimidine 2d were obtained from the reaction of a -cinnamoyl ketene dibenzylthio acetals 1 with diamine. When a -cinnamoyl -a '-benzoyl ketene N, N-acetals 3a-b were treated by t-BuONa/t-BuOH solution, 8- benzoyl-pyrido[1,2-a] pyrimidine 4 was produced.     

Alkylation of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones

Reaction of 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with dimethyl sulfate and haloalkanes in DMF or DMSO in the presence of potassium hydroxide gives the 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones (N-substituted products) and 9,9a-dihydro-3H-imidazo[1,2-a]indoles (O-substituted products). The latter, on treatment with acids and bases, are converted into 1-alkoxycarbonylmethyl-2,3-dihydro-1H-indoles. 1-Ethoxycarbonyl-methyl-2,3-dihydro-1H-indoles on treatment with lithium aluminohydride undergoes cyclization to 2,3,9,9a-tetrahydrooxazolo[3,2-a]indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 49–53, January, 1988.     

Investigations in the imidazole series

The synthesis of derivatives of 2,3-dihydropyrrolo[1,2-a]imidazole from 1,2-dialkylimidazolines or 1,2-diarylkylimidazolines and phenacyl bromides with subsequent heating of the 1,2-disubstituted 3-phenacyl-imidazolinium bromides in aqueous or ethanolic solution in the presence of bases has been effected.For part XXXVIII, see [7].     

Phosphorylated imidazo[1,2-a]pyridines

The reaction of phosphorus(III) halides with imidazo[1,2-a]pyridines in the presence of bases leads to the formation of 3-phosphorylated imidazo[1,2-a]pyridines. The reaction proceeds in high yield and requires no catalysts. In the compounds obtained, in contrast to phosphorylated indolizines, the phosphorus–heterocycle bond is stable and not cleaved by dry hydrogen chloride, alcohols, or water. Imidazo[1,2-a]pyridines with the phosphinic and phosphinous groups can be alkylated both at the phosphorus and at the nitrogen atom of the heterocycle, the alkylation direction being dependent on the strength of the alkylation reagent used. © 1995 John Wiley & Sons, Inc.     

Copper(I)-mediated preparation of new pyrano[3',4':4,5]imidazo[1,2-a]pyridin-1-one compounds under mild palladium-free conditions

A general and efficient Cu(I)-mediated cross-coupling and heterocyclization reaction of 3-iodoimidazo[1,2-a]pyridine-2-carboxylic acid, and terminal alkynes was developed under very mild conditions. This method allows the introduction in one pot of a third ring fused in positions 2 and 3 of the imidazo[1,2-a]pyridine core with reasonable yields and total regioselectivity. This procedure does not require the use of any expensive supplementary additives, and is palladium-free.     

咪唑并吡啶化合物的合成研究进展

咪唑并吡啶类化合物是一类非常重要的含氮稠杂环化合物, 在医药、农药和染料工业有着广泛的应用. 该类化合物由于其特定的生理活性以及和吲哚、氮杂吲哚等在结构上的类似性, 引起了人们广泛的兴趣. 常见的咪唑并吡啶类化合物有咪唑并[1,2-a]吡啶、咪唑并[1,5-a]吡啶、咪唑并[4,5-b]吡啶和咪唑并[4,5-c]吡啶等类型. 以咪唑并[1,2-a]吡啶和咪唑并[1,5-a]吡啶化合物为例, 阐述该类化合物近十年来的合成研究进展.     

Reaction of β-lactam carbenes with 2-pyridyl isonitriles: a one-pot synthesis of 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines useful as fluorescent probes for mercury ion

The one-pot reaction of β-lactam carbenes with 2-pyridyl isonitriles followed by an acidic hydrolysis was reported, which produced 2-carbonyl-3-(pyridylamino)imidazo[1,2-a]pyridines in moderate to good yields. Among the resulting novel imidazo[1,2-a]pyridine derivatives, 1-(6-chloro-3-(5-chloropyridin-2-ylamino)imidazo[1,2-a]pyridin-2-yl)-2-ethylbutan-1-one was demonstrated to be an efficient fluorescent probe for mercury ion both in acetonitrile and in buffered aqueous solution.     

New method for the annelation of a pyridine ring on derivatives of imidazole and benzimidazole

The interaction of (Z)-1,3-diaryl-4-bromo-2-buten-1-ones with 1-substituted (benz)imidazoles in benzene gave (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-imidazolium bromides and (Z)-1-R-3-(2,4-diaryl-4-oxo-2-butenyl)-1H-benzimidazolium bromides which readily cyclize in the presence of base to form derivatives of 7,9-diarylpyrido[1,2-a]benzimidazole and 6,8-diarylpyrimidazo[1,2-a]pyridine. The effects of the nature of substituents in the benzene ring of the diarylbutenones and the substituent at N(1) in the (benz)imidazoles on the alkylation and cyclization reactions has been studied. The optimum conditions for the synthesis of the 5-R-4-hydroxy-2,4-diphenyl-4,5-dihydro-1H-pyrido[1,2-a]benz-imidazol-10-ium, 5-R-2,4-diaryl-4-hydroxy-4,5-dihydro-3H-pyrido[1,2-a]benzimidazol-10-ium, and 5-R-2,4-diaryl-5H-pyrido[1,2-a]benzimidazol-10-ium have been found.     

Chloral as a formylating agent for some bridge heterosystems

The interaction of condensed nitrogen-containing bridge systems with chloral has been studied and the high sensitivity of the reaction to the -excess of the initial heteroaromatic system has been established. It has been shown that chloral is a convenient formylating agent for systems with a moderate -excess —imidazo[l,2-a]imidazole, 9H-imidazo[1,2-a]benzimidazole, imidazo[1,2-a]pyridine, imidazo[1,2-a]naphtho[2,3-d]imidazole. Heterocycles with a high -excess (indolizine, pyrrolo[1,2-a]benzimidazole) form cyanine dyes under the action of chloral. Systems with a lowered -excess (1H-imidazo[1,2-a]benzimidazole, imidazo[1,2-a]quinoline, imidazo[2,1-a]isoquinoline, imidazo[1,2-a]perimidine, imidazo[5,1-b]benzoxazole, imidazo[1,2-a]benzothiazole, and imidazo[1,2-a]pyrimidine) do not react with chloral in a neutral medium. However, in a number of cases their foraylation can be carried out in an acid medium.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 528–537, April, 1980.     

Reactions of esters of 3-phenyl-3-chloro-2-oxopropionic acid with 2-aminopyridines and 2-aminoquinoline

The reaction of esters of 3-phenyl-3-chloro-2-oxopropionic acid with 2-aminopyridines and 2-aminoquinoline in chloroform at reflux gave derivatives of imidazo[1,2-a]pyridine and imidazo[1,2-a]quinoline in high yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 11, pp. 2627–2629, November, 1990.     

A simple and effective approach to the synthesis of isoquinoline derivatives under solvent-free conditions

An efficient synthesis of dialkyl pyrrolo[2,1-a]isoquinoline-2,3-dicarboxylates, pyrrolo[1,2-a]quinoline-1,2- dicarboxylates and indolizines is described via one-pot reactions of isoquinoline, quinoline or pyridine and phenacyl bromids with dialkyl acetylenedicarboxylates or diaryloylacetylene under solvent-free conditions at 50°C. The mild reaction conditions and high yields of the products exhibit the good synthetic advantage of these methods.     

Alkylation of 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one

A mixture of N- and O-alkylation products is formed in the reaction of 1,2,3,4,10,-10a-hexahydropyrimido[1,2-a]indol-2-ones with ethyl iodide, allyl bromide, or benzyl chloride in DMFA (dimethylformamide) in the presence of potassium hydroxide. In the presence of aqueous solutions of acids with subsequent treatment with bases, the alkylation products are converted to 1-[2-(alkoxycarbonyl)-ethyl]-2-methylene-2,3-dehydro-1H-indoles. The reaction of 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one with triethyloxonium fluoroborate gives 1-[2-(ethoxycarbonyl)ethyl]-2-methylene-2,3-dihydro-1H-indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1224–1227, September, 1989.     

Solvent and catalyst-free synthesis of imidazo[1,2-a]pyridines by grindstone chemistry

The present work describes the solvent and catalyst-free synthesis of imidazo[1,2-a]pyridines in excellent to nearly quantitative yields from 2-aminopyridines and a wide variety of ω-bromomethylketones using a grindstone procedure at 25°C to 30°C for 3 to 5 minutes. The absolute structure of the compound, 2-(3-bromophenyl)-7-methylimidazo[1,2-a]pyridine is determined by X-ray crystallography. This green strategy has several noteworthy advantages such as wide spread substrate scope, short reaction times, water work up and the products do not require any chromatographic purification. Moreover, the method does not require any specialized equipment and is highly economical, environmentally benign and easy to carry out in any laboratory. Hence, the developed method meets the concept of “benign by design” and is greener alternative to the reported procedures for the synthesis of imidazo[1,2-a]pyridines.