Synthesis of imidazo[4,5-b]- and [4,5-c]pyridines

2-Arylimidazo[4,5-b]- and [4,5-c]pyridines have been prepared by treatment of the appropriate 2,3- or 3,4-diaminopyridine with an aromatic carboxylic acid in the presence of polyphosphoric acid. Other derivatives have been prepared by similar cyclisation of diaminopyridines using triethyl orthoformate, urea, thiophosgene and thiourea and the properties of some N-oxides have been investigated. A number of the arylimidazopyridines have been screened for mutagenicity.     

Preparation of 2-aryl-substituted imidazo[4,5-b]pyridines and imidazo[4,5-c]pyridines

It is proposed that sulfur be used as the oxidizing agent in the synthesis of 2-arylimidazopyridines from o-diaminopyridines and aromatic (heteroaromatic) aldehydes. Benzyl alcohols and benzylpyridinium salts can be used in place of aldehydes. 2-Phenylimidazopyridines are also formed in the thermal oxidation with sulfur of o-diaminopyridines with a benzyl substituent attached to the ring or exocyclic nitrogen atoms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 639–645, May, 1987.     

Direct hydroxylation of N-substituted [4,5-b]pyridines and imidazo[4,5-c]pyridines

It is shown that when N-methyl (or benzyl) derivatives of imidazo[4,5-b]pyridine and N-methyl-substituted derivatives of imidazo[4,5-c]pyridine are heated with alkalis, the imidazole ring is always hydroxylated to give the corresponding 2-imidazolones.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1252–1254, September, 1976.     

Synthesis and PMR spectra of 2-hetaryl-substituted imidazo[4,5-b]-pyridines and imidazo[4,5-c]pyridines

A simple method for the synthesis of 2-hetarylimidazopyridines based on the oxidation with sulfur of a mixture of p-diaminopyridine and heterocyclic compounds that contain an active methyl group is proposed. The reaction of diamines with N-oxides of of - and -picolines and the intramolecular oxidative cyclization of 3-amino-4-(2-pyridylmethylamino)pyridine lead to the same result. The PMR spectra of the synthesized 2-pyridylimidazopyridines were studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 940–947, July, 1989.     

A novel preparation of thiazolo[5,4-c]pyridines and the synthesis of some imidazo[4,5-c]pyridines and oxazolo[4,5-c]pyridines

Diethoxymethyl acetate was used to cyclize o-disubstituted aminopyridines to oxazolo[4,5-c]pyridines and imidazo[4,5-c]pyridines. All the possible imidazole-methylated imidazo[4,5-c]pyridines were prepared. A novel synthesis of 2-substituted thiazolo[5,4-c]pyridines and 4-amino-3-pyridinethiol was discovered.     

Synthesis of 3,4-diaminopyridine and imidazo[4,5-c]pyridines by nitration of 4-acylaminopyridines

New methods for the preparation of 3,4-diaminopyridine (5) and imidazo[4,5-c]pyridines 7a,7b based on direct nitration of 4-acylaminopyridines 3a, 3b have been explored.     

Imidazo [4,5-c] - and [4,5-6] pyridines

The synthesis of novel imidazo[4,5-c]pyridines 11-13 and imidazo[4,5-b]pyridines 18-20 is described using 2 as the starting material. The synthesis is generally applicable for the introduction of a wide variety of substituents.     

Synthesis of imidazo[4,5-b]pyridines from aminoimidazolecarbaldehydes

4-Amino-1,2-dimethylimidazole-5-carbaldehyde (1) and 5-amino-1-methylimidazole-4-carbaldehydes 3 were prepared by reduction of the corresponding aminoimidazolecarbonitriles 2 and 4. Condensation of 1 and 3 with carbonitriles, ketones and polyfunctional carbonyl compounds bearing the-CH₂CO-moiety afforded to the imidazo[4,5-b]pyridine derivatives.     

The synthesis of imidazo[4,5-c] - and v-triazolo[4,5-c] pyridazines

The parent imidazo[4,5-c]pyridazine (IV) has been prepared for the first time by three different routes. 1-Methylimidazo[4,5-c]pyridazine (XX) and 3-methylimidazo[4,5-c]pyridazine (XXVII) have been prepared by unequivocal syntheses. The constitution of the methylation product of imidazo[4,5-c]pyridazine-2-thiol (VIII) has been shown to be 2-methylthioimidazo[4,5-c]-pyridazine (IX) by the unequivocal syntheses of 1-methylimidazo[4,5-c]pyridazine-2-thiol (XXIII) and 3-methylimidazo[4,5-c]pyridazine-2-thiol (XXXIII). Likewise, the structure of the methylation product (XIII) was shown to be S-methylation by the unequivocal syntheses of 1-methyl-2-methylthio-6-chloroimidazo[4,5-c]pyridazine (XXIV) and 3-methyl-2-methylthio-6-chloroimidazo[4,5-c]pyridazine (XXXI), respectively. Several 7-substituted amino-v-triazolo-[4,5-c]pyridazines (XXXVIII) have been prepared from 7-chloro-v-triazolo[4,5-c]pyridazine (XXXVII).     

Halogenation of imidazo[4,5-c]pyridinones

Unsubstituted imidazo[4, 5-c]pyridine does not react with chlorine, bromine, or iodine at room temperature or even upon heating to 160°C. The introduction of an oxo group activates the system such that halogenation proceeds readily. Imidazo[4, 5-c]pyridin-4-one gives 7-halo derivatives, while imidazo[4, 5-c]pyridin-2-ones give 4, 7-dihalo products.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1076—1081, August, 1994.     

Synthesis of imidazo[4,5-c]pyrazoles via copper-catalyzed amidine cyclization

A new synthetic approach to 4-substituted imidazo[4,5-c]pyrazoles is proposed on the basis of the N'-(4-halopyrazol-5-yl)amidine cyclization under the conditions of copper-catalyzed cross-coupling reactions. Using 5-aminopyrazoles and copper catalysts as starting materials, the method is inexpensive and convenient and allows a wide range of substituents at all positions of the imidazo[4,5-c]pyrazole nucleus.     

Electronic structure and physico-chemical characteristics of imidazo[4,5-b]- and [4,5-c]pyridines and their protonated and deprotonated derivatives

Dipole moments, diamagnetic permeabilities,¹H,¹³C and¹⁵N chemical shifts, and the energies of the lowest singlet-singlet transitions for imidazo[4,5-b]- and [4,5-c]pyridines, the corresponding protonated species and anions have been calculated using the bonding variant of the PPP perturbation method. The aromaticity of the compounds is given based on the results obtained.L. M. Litvinenko Physico-Chemical and Coal Chemistry Institute, Ukraine National Academy of Sciences, Donetsk. 340114. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1411–1419, October, 1994. Original article submitted June 8, 1994.     

Synthesis and anticonvulsant activity of 1-benzyl-4-alkylamino-1H-imidazo[4,5-c]pyridines

Four 3-deaza analogues of the potent anticonvulsant purine, BW A78U, were synthesized and tested for anticonvulsant activity. The imidazo[4,5-c]pyridines 9–12 were prepared in two steps from 4-chloro-1H-imidazo[4,5-c]pyridine ( 2 ). The compounds were potent anticonvulsant agents against maximal electroshock-induced seizures in rats with i.p. ED₅₀ ranging from 2 to 3.5 mg/kg. However, these 3-deazapurines were appreciably more toxic than BW A78U, which precluded their development as potential antiepileptic agents.     

Synthesis of imidazo[4,5-b]pyridines and imidazo[4,5-b]pyrazines by palladium catalyzed amidation of 2-chloro-3-amino-heterocycles

A facile synthesis of imidazo[4,5-b]pyridines and -pyrazines is described using a Pd-catalyzed amide coupling reaction. This reaction provides quick access to products with substitution at N1 and C2. A model system relevant to the natural product pentosidine has been demonstrated, as well as the total synthesis of the mutagen 1-Me-5-PhIP.     

2-formylimidazo[4,5-b]- and 2-formylimidazo[4,5-c]pyridines

The corresponding aldehydes were obtained by oxidation of N-substituted 2-methylimidazo-[4,5-b]- and 2-methylimidazo[4,5-c]pyridines with selenium dioxide. Some of their properties and transformations were studied.     

Synthesis and some reactions of 4-nitro derivatives of imidazo[4,5-c]pyridin-2-ones

Imidazo[4,5-c]pyridine and its N-methyl derivatives do not undergo nitration, but the 2-oxo derivatives of these compounds are easily nitrated when heated. Some properties of the resulting 4-nitroimidazo[4,5-c]pyridin-2-ones have been studied.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 97–102, January, 1986.     

s-Triazolo[4,3-b]pyridazines and imidazo[4,5-c]pyridazines

8-Amino-s-triazolo[4, 3-b]pyridazine (I), an adenine analog has been prepared by two different routes. Likewise 8-amino-3-phenyl-s-triazolo[4,3-b]pyridazine (V) has been prepared. Both of these compounds have been prepared utilizing 3,4,5-trichloropyridazine and 3,4,6-trichloropyridazine as the starting materials thus interrelating the 3,4,5-and the 3,4,6-series. A variety of other transformations have been carried out.     

Synthesis of imidazo[1,2- a] pyridines directly from methyl or methylene ketones. iodination of imidazo[1,2-a] pyridines

Imidazo[1,2-a]pyridines were obtained by direct reaction of acetophenone, propiophenone, and their furan analogs and ring-substituted derivatives with an equimolar amount of iodine and and excess 2-aminopyridine or its substituted derivatives. The effect of substituents in the ketones and 2-aminopyridine, the reagent molar ratios, the character of the solvents, and replacement of iodine by other halogenating agents on the course of the reaction and the yields of products was studied. The formation of 3-iodo- and 6-iodoimidazopyridines as side products was noted in the case of ketones that do not have electron-acceptor substituents in the ring. These and other iodo-substituted imidazopyridines were synthesized for chromatographic comparison.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1396–1405, October, 1976.