Preparation of some substituted imidazo[1,2-a]pyridine derivatives

2-Bromopyridine derivatives 2a-2c were prepared. Compounds 2b and 2c and ammonia yielded aminopyridines 3b and 3c which were converted to imidazo[1,2-a]pyridine derivatives 4b and 4c . Compound 4b was nitrated giving the analogue 5b of metronidazole 1 .     

Imidazo[1,2-a]benzimidazole derivatives

3-Amino derivatives of 9-alkyl(benzyl)-2-arylimidazo[1,2-a]benzimidazoles, obtained by the reduction of the appropriate 3-nitro(nitroso) derivatives, are extremely unstable, and the imidazole ring opens readily resulting in conversion to 2-(-carboxybenzylamino)benzimidazoles. The reaction apparently proceeds through the intermediate formation of 2-(-cyanobenzylamino)benzimidazole, which is a tautomeric form of the 3-amino compound and can react as such to form 3-acylamino derivatives and anils. If there is a methyl group in the 3-position of the ring, the amine is quite stable and can be isolated in free form.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 673–677, May, 1971.     

Mass spectra of pyrrolo [1,2-a]benzimidazole and imidazo[1,2-a]benzimidazole derivatives

The closeness of the electronic structures of the ions formed in the first act of disintegration of the ions is responsible for the monotypic character of the subsequent fragmentation of pyrrolo[1,2-a]benzimidazole and imidazo[1,2-a]benzimidazole derivatives. The mass-spectrometric disintegration of the investigated systems has something in common with the fragmentation of thiazolo[3,2-a]benzimidazole derivatives.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, 1124–1127, August, 1975.     

Synthesis of 7-substituted imidazo[1,2-a]pyrimidin-5(1H)-ones

The synthesis of 7-substituted imidazo[1,2-a]pyrimidin-5(1H)-ones by either of 2 methods is reported.     

Microwave-assisted combinatorial synthesis of polysubstituent imidazo[1,2-a]quinoline, pyrimido[1,2-a]quinoline and quinolino[1,2-a]quinazoline derivatives

A series of unusual fused heterocyclic compound derivatives, consisting of a pyridine and a imidazole or pyrimidine core, with a bridgehead nitrogen, were successfully synthesized by a microwave-assisted, three-component domino reaction of aldehydes, enaminones, and malononnitrile. In this one-pot reaction, up to five new bonds were formed accompanied by generating the lactam group. This method has the advantages of short synthetic route, operational simplicity, increased safety for small-scale high-speed synthesis, and minimal environment impact.     

Improved microwave-assisted catalyst-free synthesis of 9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-dione derivatives

A green regioselective synthesis of some new and known 9-aryl-5,9-dihydropyrimido[4,5-d][1,2,4]triazolo[1,5-a]pyrimidine-6,8(4H,7H)-diones has been described via the microwave-assisted one-pot reaction of 3-amino-1H-1,2,4-triazoles, aromatic aldehydes and barbituric acids under solvent- and catalyst-free conditions. This operationally simple procedure is less laborious and provides a better scope than previously reported procedures.     

Imidazo[1,2-a]pyridines. I. Synthesis and inotropic activity of new 5-imidazo[1,2-a]pyridinyl-2(1H)-pyridinone derivatives

A series of 1,2-dihydro-5-imidazo[1,2-a]pyridinyl-2(1H)-pyridonones was synthesized and evaluated for positive inotropic activity, 1,2-Dihydro-5-imidazo[1,2-a]pyridin-6-yl-6-methyl-2- oxo-3-pyridinecarbonitrile (11a) hydrochloride monohydrate (E-1020) was found to be a potent and selective inhibitor of phosphodiesterase III and a long-acting, potent, orally active positive inotropic agent. Additional imidazo[1,2-a]pyridin-2-yl (3a), -3-yl (16), -7-yl (20) and -8-yl (24a) compounds were also prepared. Altering the pyridine substitution from the 2-position to the 6-position produced a 2-fold increase in the i.v. cardiotonic potency (ED50) from 52 to 23 micrograms/kg, while substitution at the 3-, 7- or 8-position reduced potency. In the 2-positional isomers, introduction of halogen groups enhanced the activity and 3-chloro-1,2-dihydro-5-(6-fluoroimidazo[1,2-a] pyridin-2-yl)-6-methyl-2(1H)-pyridinone (3u) was the most potent (i.v. ED50 11 micrograms/kg) in this series. E-1020 is presently under development for the treatment of congestive heart failure.     

Synthesis and insecticidal evaluation of tetrahydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A series of novel tetrahydroimidazo[1,2-a]pyridine-5(1H)-one derivatives containing a electronegative pharmacophore(=CNO₂) were synthesized via practical aza-ene reaction and characterized by ¹H NMR, ¹³C NMR, ¹⁹F NMR and HRMS. Preliminary bioassays showed that some of the target compounds exhibited good insecticidal activity against brown planthopper(Nilaparvata lugens) and cowpea aphids(Aphis craccivora) at 500 mg L^-1. Among them, compound 11h was active against brown planthopper at 100 mg L^-1. The insecticidal activities varied significantly depending on the types and patterns of the substituents, which provided guidance for further investigation on structure modifications.     

Synthesis of 8,9-dihydro[1,2,4]triazolo[1,5-a]-quinazolin-6(7H)-one derivatives

Regioselectivity of the reactions of 1H-1,2,4-triazol-3-amines with 2-acyl-5,5-dimethylcyclohexane-1,3-diones and 2-dimethylaminomethylidene-5,5-dimethylcyclohexane-1,3-dione was studied. In all cases, the products were substituted 8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones whose structure was determined by ¹H and ¹³C NMR spectroscopy.     

Synthesis and antibacterial activity of some imidazo[1,2-a]pyrimidine derivatives.

A series of 75 imidazo[1,2-a]pyrimidine derivatives were synthesized. The "in vitro" antibacterial activity of these compounds and their corresponding alpha-bromoketones against a variety of gram (+), gram (-) bacteria and Mycobacterium species is reported. Some of the prepared derivatives exhibited potent antimicrobial activity.     

Synthesis of perhydro-2(1H)-quinoxalinones and perhydropyrrolo[1,2-a]quinoxalin-4(5H)-one derivatives

The novel trans-bicyclic-perhydro-2(1H)-quinoxalinones 4, 6 and 7 and the tricyclic-perhydropyrrolo[1,2-a]-quinoxalin-4(5H)-one derivatives 8 and 9 are prepared via a ring opening and spontaneous ring closing reaction of the aziridines 2 and 3 with the α-amino acids glycine, L-alanine, L-proline and L-phenylalanine. This methodology was used to prepare 5 and 10 which are novel rigid analogues of the kappa opioid compound 1. Treatment of aziridine 3 with methyl carbamate gave the cyclic urea 11.     

2,3,5,8(1)-Tetrahydroimidazo[1,2-a]pyrimidine-2,5-dione derivatives

The corresponding ylidene, azomethine, and azo derivatives of 2,3,5,8(1)-tetrahydroimidazo [1,2-a]pyrimidine-2,5-dione were synthesized by reaction of 7-methyl-and 6-bromo-7-methyl-2,3,5,8(1)-tetrahydroimidazo[1,2-a]pyrimidine-2,5-diones with aldehydes, insatin, aromatic nitroso compounds, and arenediazonium salts. Ylidene derivatives of 7-methyl-2,3,5,8(1)-tetrahydroimidazo[1,2-a]pyrimidine-2,5-dione were also obtained by reaction of 2-amino-4-methyl-6-oxo-1,6-dihydro-1-pyrimidylacetic acid with carbonyl compounds.     

3,3′-bi(6,8-dialkyl-2,4-dioxa-7-thia-6,8-diazabicyclo[3.3.0]-octane-7,7-dioxides): Structure and synthesis

Derivatives of a new heterocyclic system, 3,3′-bi(6,8-dialkyl-2,4-dioxa-7-thia-6,8-diazabicyclo[3.3.0]-octane-7,7-dioxides), were synthesized by condensation of 1,3-dialkylsulfamides with glyoxal (as a dihydrate trimer). Their structure was investigated by spectral methods, XRD, and X-ray phase analysis of one among these compounds.     

Protonation of pyrrolo[1,2-a] imidazole derivatives

The protonation of a number of pyrrolo[1,2-a]imidazole derivatives in trifluoroacetic acid was studied by PMR spectroscopy. The 5,7-unsubstituted compounds form a mixture of two forms of cations, the structures of which correspond to the addition of a proton to the C₅ and C₇ atoms of the two-ring system with predominance (60–90%) of the 5-C cation. The introduction of a CH₃ group into the 5 position changes the direction of protonation to favor predominant (95%) formation of the 7-C cation. The 7-methyl derivatives of pyrroloimidazole are protonated exclusively at the C₅ atom. It is demonstrated that the basicity of the pyrroloimidazoles considerably surpasses the basicity of indolicine derivatives. The comparative proton-acceptor capacity of these systems is compared with the energy indexes and the reactivity indexes calculated by the simple MO LCAO method.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 492–497, April, 1972.     

Synthesis and insecticidal bioactivities of 2,3-dihydroimidazo[1,2-a]pyridin-5(1H)-one derivatives

A novel synthesis of 2,3-dihydroimidazo[1,2-a]pyridin-5(1H)-one, and insecticidal derivatives were described.