Formylation of Furyl-substituted Imidazo[1,2-a]pyridine, Imidazo[1,2-a]pyrimidine and Imidazo[2,1-b]thiazole

Vilsmeier formylation of 2-(2-furyl)-substituted imidazo[1,2-a]pyridine and imidazo[1,2-a]pyrimidine, and also 6-(2-furyl)imidazo[2,1-b]thiazole with 1 mole of reagent occurs at the free position of the imidazole ring, while with an excess of the reagent it also occurs at the position 5 of the furyl group.     

Properties of 8-Cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

The alkylation, acylation, halogenation, nitration, oxidation, and hydrolysis reactions of 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine have been studied. It was found that the 6-halo derivatives add alcohol to give covalent solvates. X-ray analysis has been carried out on one of the solvates (6-chloro-8-cyano-7-ethoxy-5-phenyl-7-trifluoromethyl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine) as well as on 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine trifluoroacetate.     

Synthesis of 5-Phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

Syntheses are reported for a series of 2-alkylamino-6-phenyl-4-trifluoromethylpyridines. The reaction of 3-cyano-2-(hydroxyalkylamino)-6-phenyl-4-trifluoromethylpyridines with thionyl chloride gave the corresponding 2-(chloroalkylamino)pyridines, 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydro-imidazo[1,2-a]pyridines, and 9-cyano-6-phenyl-8-trifluoromethyl-2,3,4-trihydropyrido[1,2-a]-pyrimidines. X-ray diffraction structural analysis was used to study 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine.     

Formylation of 3,4-Dihydropyrrolo[1,2-a]pyrazines

Formylation of 3,4-dihydropyrrolo[1,2-a]pyrazines containing alkyl or aryl substituents at position 1 has been studied under the conditions of the Vilsmeier reaction. The direction of the reaction depends on the structure of 3,4-dihydropyrrolo[1,2-a]pyrazine starting materials. Formylation of 1-methyl-substituted 3,4-dihydropyrrolo[1,2-a]pyrazines occurs at the methyl group.     

Acylation of 3,4-Dihydropyrrolo[1,2-a]pyrazines

The direction of trifluoroacetylation with trifluoroacetic anhydride of 3,4-dihydropyrrolo[1,2-a]pyrazines containing an alkyl or aralkyl substituent in position 1 depends on both the structure of the 3,4-dihydropyrrolo[1,2-a]pyrazine starting materials and on the ratio of reagent:substrate. It may lead to both mono- and disubstituted products. Trifluoroacetylation of 1-methyl-3,4-dihydropyrrolo[1,2-a]pyrazines occurs at the methyl group. Acetylation of 3,4-dihydropyrrolo[1,2-a]pyrazines leads only to N-acetyl-substituted reaction products.     

Dipyrrolo[1,2-a:2',1'-c]pyrazines. 8. Electrophilic Substitution in Dipyrrolo[1,2-a:2',1'-c]pyrazines and 5,6-Dihydrodipyrrolo[1,2-a:2',1'-c]pyrazines. Acylation of Dipyrrolo[1,2-a:2',1'-c]pyrazines

Esters, nitriles, and amides of dipyrrolo[1,2-a:2',1'-c]pyrazines have been synthesized by the acylation of dipyrrolo[1,2-a:2',1'-c]pyrazines and 5,6-dihydrodipyrrolo[1,2-a:2',1'-c]pyrazines with trichloroacetic acid chloride, p-tosyl isocyanate, and isocyanatophosphoric acid dichloride (Kirsanov isocyanate).     

Condensation of 1-Substituted 1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indol-2-one Derivatives with Aromatic Aldehydes

Condensation of 1-alkyl-, 1-allyl-, and 1-benzyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with benzaldehydes in acetic acid and subsequent treatment of the reaction mixture with potassium hydroxide afforded 1-substituted 9a-(2-phenylethenyl)-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one derivatives. 1-Methyl- and 1-ethyl-9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones were synthesized by alkylation of 9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one with methyl- and ethyl iodides in DMF in the presence of a strong base.     

Fluorine-containing pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6-ones

Reactions of 2-aminopyridine and 2-amino-5-methylpyridine with 2,3,4,5-tetrafluorobenzoyl chloride afforded N,N’-diaroylpyridinium salts, which were converted into 6H-pyrido[1,2-a]quinazolin-6-ones by refluxing in toluene in the presence of triethylamine. The angular structure of the tricyclic derivatives obtained was confirmed by ¹⁹F and ¹³C NMR spectroscopy and 2D heteronuclear HetCOR and HMBC experiments.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2216–2220, October, 2004.     

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 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.     

Stereoselective synthesis of 4-substituted 1,2,3,4,10,10a-hexahydropyrazino[1,2-<Emphasis Type="Italic">a</Emphasis>]indoles

4-Substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles were synthesized from 2-cyanoindole. (R)-4-Methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indole was obtained by the Mitsunobu reaction. Stereoselective reduction of 4-substituted 1,2,3,4-tetrahydropyrazino[1,2-a]indoles gave 4-substituted 1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indoles. (4R, 10aR)-4-Methyl-1,2,3,4,10,10a-hexahydropyrazino[1,2-a]indole was synthesized.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 221–225, January, 2005.     

Synthesis of derivatives of a new heterocyclic system pyrazolo[3,4-b]pyrido[1′,2′: 1,2]imidazo[4,5-d]pyridine

1-[4-Aminoarylpyrazolo[3,4-b]pyridin-5-yl]pyridinium chlorides undergo cyclization under reflux in tert-butanol in the presence of an excess of potassium tert-butoxide to form tetracyclic derivatives of pyrazolo[3,4-b]pyrido[1′,2′:1,2]imidazo[4,5-d]pyridine. The reaction scheme of the processes is proposed. The structures of the reaction products were confirmed by physicochemical methods. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 710–714, April, 2006.     

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.     

Condensed Imidazo-1,2,4-azines. 31. Synthesis and Chemical Transformations of Substituted 1,2,4-Triazepino[2,3-a]benzimidazoles

By reaction of 1,2-diaminobenzimidazole with 1,3-diketones, acetoacetic ester and its derivatives, we have synthesized substituted 1,2,4-triazepino[2,3-a]benzimidazole and 5H-1,2,4-triazepino[2,3-a]benzimidazol-4-one. By reaction of 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazol-4-one with aromatic aldehydes or phenyldiazonium chloride, we have obtained 3-arylidene(phenylazo) derivatives of this compound, and by reaction with P₂S₅ we have obtained 5H-2-methyl-1,2,4-triazepino[2,3-a]benzimidazole-4-thione. We have shown that when reacted with ammonia, primary or secondary amines, the latter forms 4-amino-substituted 2-methyl-1,2,4-triazepino[2,3-a]benzimidazole.     

Synthesis,Antibacterial and Antifungal Activity of New 3-Aryl-5H-pyrrolo[1,2-a]imidazole and 5H-Imidazo[1,2-a]azepine Quaternary Salts

A series of novel 3-aryl-5H-pyrrolo[1,2-a]imidazole and 5H-imidazo[1,2-a]azepine quaternary salts were synthesized in 58–85% yields via the reaction of 3-aryl-6, 7-dihydro-5H-pyrrolo[1,2-a]imidazoles or 3-aryl-6,7,8,9-tetrahydro-5H-imidazo[1,2-a]azepines and various alkylating reagents. All compounds were characterized by ¹H NMR, ¹³C NMR, and LC-MS. The conducted screening studies of the in vitro antimicrobial activity of the new quaternary salts derivatives established that 15 of the 18 newly synthesized compounds show antibacterial and antifungal activity. Synthesized 3-(3,4-dichlorohenyl)-1-[(4-phenoxyphenylcarbamoyl)-methyl]-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-1-ium chloride 6c possessed a broad activity spectrum towards Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, and Cryptococcus neoformans, with a high hemolytic activity against human red blood cells and cytotoxicity against HEK-293. However, compound 6c is characterized by a low in vivo toxicity in mice (LD₅₀ > 2000 mg/kg).     

Research on heterocyclic compounds,XXXV. Synthesis of 2-phenylimidazo[1,2-a]pyrazine-3-acetates

Summary Prompted by the remarkable pharmacological activity shown by the corresponding carboxylic acids and other analogues, a series of 2-phenylimidazo[1,2-a]pyrazine-3-acetic acids has been prepared. A multi-step method similar to a synthetic procedure used to obtain Zolpidem, an imidazo[1,2-a]pyridine with hypnotic properties has been developed.

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Untersuchungen an heterocyclischen Verbindungen, 35. Mitt. Synthese von 2-Phenylimidazo[1,2-a]pyrazin-3-acetaten

Zusammenfassung Angeregt durch die bemerkenswerte pharmakologische Aktivität der entsprechenden Carbonsäuren, wurde eine Reihe von 2-Phenylimidazo[1,2-a]pyrazin-3-acetaten synthetisiert. Zu diesem Zweck wurde eine mehrstufige Methode analog zu jener zur Herstellung von Zolpidem, einem Imidazo[1,2-a]pyridin mit hypnotischen Eigenschaften, entwickelt.

     

Efficient synthesis of novel dipyridoimidazoles and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives

Novel dipyrido[1,2-a;3′,4′-d]imidazoles 7a-d, dipyrido[1,2-a;4′,3′-d]imidazoles 8a,c and pyrido[1′,2′;1,2]imidazo[4,5-d]pyridazine derivatives 9a-d were synthesized by two pathways: thermal electrocyclic reaction of 3-alkenylimidazopyridine-2-oximes 10 and direct condensation of ethyl glycinate (or hydrazine) with 2,3-dicarbonylimidazo[1,2-a]pyridines 11.     

Reactions of 1-Substituted Benzo[4,5]imidazo[1,2-a]pyridines

Bromination of 1-oxo(imino, amino)benzo[4,5]imidazo[1,2-a]pyridines gave the corresponding 2-bromo derivatives. Acylation using the Vilsmeier complex in acetic anhydride gave the N-formyl and N-acetyl derivatives. The reaction of the amine with the Vilsmeier complex, acetyl acetone, ethyl acetoacetate, and 2,5-dimethoxytetrahydrofuran occurs at the amino group.     

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.     

4a-Alkyl Derivatives of 5-Oxo-4H-4a,5-dihydroindeno[1,2-b]pyridine

High selectivity has been discovered for the C-alkylation of ambident anions of 5-oxo-1H-4,5-dihydroindeno[1,2-b]pyridines with ethyl bromoacetate, allyl, propargyl, and phenacyl bromides, which leads to the formation of the corresponding 4a-substituted 5-oxo-4H-4a,5-dihydroindeno[1,2-b]pyridines in high yield.