1,3-dipolar cycloaddition of diazomethane to quinoid derivatives of pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole

Reactions of diazomethane with quinone mono(di)imines and methylidene quinone imines of pyrido[1,2-a]benzimidazole series occurs by the route of 1,3-dipolar cycloaddition and leads to the formation of quinoid compounds, in particular, previously unknown heterocyclic structures of indazolo[7',6':4,5]imidazo-[2,1-j]quinoline, indazolo[7',6':4,5]imidazo[2,1-e]acridine, indazolo[4',5':4,5]imidazo[2,1-j]quinoline, and indazolo[4',5':4,5]imidazo[2,1-e]acridine.     

Fused Pyrimidine Systems: XVII. Imidazo- and Pyrimidopyrido[3,2-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4(3<Emphasis Type="Italic">H</Emphasis>)-ones

2-(Allylamino)pyrido[3,2-d]pyrimidin-4(3H)-one was converted to linearly fused dihydroimidazo- [1,2-a]pyrido[3,2-d]pyrimidine on heating in polyphosphoric acid, whereas its reactions with molecular iodine and chlorosulfanylarenes afforded mainly angularly fused analogs. 2-(Cinnamylamino)pyrido[3,2-d]pyrimidin- 4(3H)-one reacted with polyphosphoric acid and chlorosulfanylarenes to give linear pyrido[3,2-d]pyrimido-[1,2-a]pyrimidinones, and its iodocyclization led to the formation of angularly fused derivative.     

Synthesis and properties of cyanomethyl derivatives of imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine,imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine,and imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]thiazole

2-Cyanomethyl derivatives were obtained of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[2,1-b]thiazole, and their reactivity was investigated by an example of imidazo[1,2-a]pyridine: It was subjected to nitration, bromination, azo coupling and nitrosation. Acylation of the methylene group effected by amino acids esters with a subsequent addition of the amino group to the cyano group resulted in the formation of 5-amino-4-imidazo[1,2-a]-pyridin-2-yl-1-phenyl-1,2-dihydro-3H-pyrrol-3-one and 2-amino-1-ethyl-3-imidazol[1,2-a]pyridin-2-yl-4(1H)-quinolinone.     

One-stage synthesis of condensed pyrimidines by reaction of substituted 3-(pyrimidin-5-yl)propanoic acids with <Emphasis Type="Italic">ortho</Emphasis>-diamines: Extension of limits

By condensation of 2-aryl-substituted pyrimidin-5-ylpropanoic acids with 1,2-ethanediamine and 1,2-benzenediamine in polyphosphoric acid new derivatives of heterocyclic systems were synthesized: imidazo- and benzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidines. Unlike that the reaction of substituted 2-mercaptopyrimidin-5-ylpropanoic acid with 1,2-benzenediamine in polyphosphoric acid in the presence of equimolar amount of ZnCl₂ proceeds by a tandem mechanism with the formation of 4-methyl-5,6-dihydrobenzo[4',5']imidazo[1',2':1,6]pyrido[2,3-d]pyrimidine-2-thiol and the corresponding disulfide.     

New general synthesis of benzo[4,5]imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine and benzo[4,5]imidazo[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazoline derivatives

The reactions of benzene-1,2-diamine with 5-substituted 2-(alkylsulfanyl)-4-methylpyrimidin-6(1H)-ones and 2-(propylsulfanyl)- and 5-iodo-2-(propylsulfanyl)-3,4-dihydroquinazolines at 175–185°C under solvent-free conditions unexpectedly afforded benzo[4,5]imidazo[1,2-a]pyrimidine, benzo[4,5]imidazo[2,1-b]-quinazoline, and 2,2′-(benzene-1,2-diyldiimino)bis[pyrimidin-4(3H)-ones]. The described reaction is the first example of synthesis of these heterocyclic systems by fusion of benzimidazole to pyrimidine or quinazoline and is likely to follow ANRORC mechanism.     

Synthesis of imidazo[4,5-<Emphasis Type="Italic">e</Emphasis>]benzo[1,2-<Emphasis Type="Italic">c</Emphasis>;3,4-<Emphasis Type="Italic">c</Emphasis>´]difuroxanes

A method for the synthesis of imidazo[4,5-e]benzo[1,2-c;3,4-c´]difuroxanes, potential nitric oxide donors, has been developed. The synthesized compounds were characterized by IR and NMR spectroscopy, high resolution mass spectrometry, and elemental analysis.     

Synthesis of sulfonamide derivatives of pyrido-[2,1-<Emphasis Type="Italic">b</Emphasis>]quinazolin-11-one and pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6-one

Methods were developed of indirect introduction of sulfonamide group in the structures of pyrido-[2,1-b]quinazolin-11-one and pyrido[1,2-a]quinazolin-6-one underlain by cyclocondensation of 2-halo-5-(Rsulfamoyl) benzoyl chlorides with derivatives of 2-aminopyridine. The fact of thermal rearrangement of 8-(morpholin-4-ylsulfonyl)pyrido[1,2-a]quinazolin-6-one into isomeric 2-(morpholine-4-ylsulfonyl)pyrido[2,1-b]-quinazolin-11-one was experimentally registered.     

1,3-Dipolar Cycloaddition of Difluoro-Substituted Azomethine Ylides. Synthesis and Transformations of 2-Fluoro-4,5-dihydropyrroles

2-Fluoro-4,5-dihydropyrrole-3,4-dicarboxylic acid derivatives were obtained by reaction of difluorocarbene with N-substituted ketone imines in the presence of fumaronitrile, maleonitrile, or dimethyl maleate. The reaction involves intermediate formation of azomethine ylides and their subsequent cycloaddition at the double bond. 11H-Dibenz[b,e]azepine and 3,4-dihydroisoquinolines react with difluorocarbene in the presence of fumaronitrile to give fluoro-substituted dibenzo[c,f]pyrrolo[1,2-a]azepine and pyrrolo[2,1-a]-isoquinoline derivatives. Treatment of 2-fluoro-4,5-dihydropyrrole-3,4-dicarbonitrile with amines and alkoxides affords the corresponding 2-amino- and 2-alkoxy derivatives, while its reactions with hydrazine hydrate and benzimidamide lead to formation of substituted pyrrolo[2,3-c]pyrazole and pyrrolo[2,3-d]-pyrimidine derivatives.     

Poly(vinylpyrrolidonium) perchlorate catalyzed one-pot synthesis of tricyclic dihydropyrimidine derivatives

A simple and efficient procedure for the synthesis of benzo[4,5]imidazo[1,2-α]pyrimidine and 2-amino-4-substituted-1,4-dihydrobenzo[4,5]imidazolo[1,2-α]pyrimidine-3-carbonitrile derivatives using poly(vinylpyrrolidonium) perchlorate {[PVPH]ClO₄} as a newly reported, modified polymeric catalyst is reported. Some of the advantages of this novel synthetic method are: easy preparation of the catalyst, simple and easy work-up procedure, short reaction times, high to excellent yields of the products and reusability of the catalyst.     

Phosphorylation of Benzimidazole-2-thiones by Chloroethynylphosphonate

The reaction of chloroethynylphosphonates with N-substituted benzimidazole-2-thiones proceeded chemo- and regioselectively with the formation of cyclic zwitterions, namely alkyl (9H-benzo[4,5]imidazo[2,1-b]-thiazol-3-yl-4-ium)phosphonates. Chemo- and regioselective reaction of N-unsubstituted benzimidazole-2-thione with chloroethynylphosphonates led to the production of linear Z-1,2-bis(1H-benzimidazol-2-ylsulfanyl)-ethenylphosphonates.     

Synthesis of nitrogen-containing heterocycles on the basis of 3-(4-acetylphenyl)-1-methylquinolin-2(1<Emphasis Type="Italic">H</Emphasis>)-one

The Meerwein reaction of 1-methylquinolin-2(1H)-one with 4-acetylbenzenediazonium chloride gave 3-(4-acetylphenyl)-1-methylquinolin-2(1H)-one which was brominated to 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one. The latter reacted with pyridine, 4-methylpyridine, quinoline, benzo[f]quinoline, and triphenylphosphine to afford the corresponding quaternary salts, and its reactions with thioacetamide, thiourea, 2-aminopyridine, and 2-aminopyrimidine led to the corresponding thiazole, imidazo[1,2-a]pyridine, and imidazo[1,2-a]pyrimidine derivatives containing a 2-oxoquinoline fragment. 3-(4-{2-[2-(Arylmethylidene)-hydrazinyl]-1,3-thiazol-4-yl}phenyl)-1-methylquinolin-2(1H)-ones were obtained by condensation of 3-[4-(2-bromoacetyl)phenyl]-1-methylquinolin-2(1H)-one with thiosemicarbazide and aromatic aldehydes.     

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.     

Recent synthetic scenario on imidazo[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridines chemical intermediate

Of the biologically important benzene fused heterocycles, the most important are those containing a ring-junction nitrogen. The majority of ring junction systems do not occur naturally, but they have been important from a theoretical viewpoint, for preparation of potentially active analogues. The imidazo[1,2-a] pyridines are an important class of nitrogen ring junction heterocyclic compounds. They have huge applications in medicinal chemistry and drug molecule production. Thus, the initial discussion focuses on synthetic strategies of imidazo[1,2-a] pyridines, and later we disclose the reactivity of the imidazo[1,2-a]pyridines. This review is intended to summarize and discuss the most recent developments of synthesis and reactivity of imidazo[1,2-a]pyridines, mainly the contributions after 2007.     

Synthesis of 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids

Nitration of 2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-one gave its 5-nitro derivative which was subjected to alkylation with dimethyl sulfate, diethyl sulfate, and benzyl(dimethyl)phenylammonium chloride. The resulting 1,3-dimethyl-, 1,3-diethyl-, and 1,3-dibenzyl-5-nitro-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones were reduced to the corresponding 1,3-dialkyl-5-amino-2,3-dihydro-1H-imidazo[4,5-b]pyridin-2-ones, and the latter reacted with itaconic acid to produce 1-(1,3-dialkyl-2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acids. 1-(2-Oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-5-yl)-5-oxopyrrolidine-3-carboxylic acid was obtained by analogous reaction with 5-amino-2,3-dihydro-1H-imidazo[4,5-b]-pyridin-2-one.     

Synthesis of arylmethylpyrimidinetriones and pyrimidoquinolinediones with fluorescent and nonlinear-optical properties

5-Arylmethyl-2,4,6-(1H,3H,5H)pyrimidinetriones and 12-aryl-8,12-dihydrobenzo[f]pyrimido[4,5-b]quinoline-9,11-(7H,10H)diones were synthesized, and their spectral-luminescence and nonlinear-optical properties were examined.     

Synthesis of New Heterocyclic Systems on the Basis of 7-Benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthiridine-4-carbonitrile

Methods have been developed for the synthesis of new 8-amino-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine starting from 7-benzyl-3-chloro-1-(morpholin-4-yl)-5,6,7,8-tetrahydro-2,7-naphthyridine-4-carbonitrile. 8-Hydrazinyl-3-benzyl-5-(morpholin-4-yl)-1,2,3,4-tetrahydropyrimido[4′,5′: 4,5]thieno[2,3-c][2,7]naphthyridine has been converted to isomeric pentacyclic structures with a triazole ring fused through the [c] side of the pyrimidine ring, and their Dimroth rearrangement has been accomplished in both acidic and basic media. New heterocyclic systems containing pyrrolo[1,2-a]pyrimidinone and pyrimido[1,2-a]azepinone fragments were obtained on the basis of the thieno-[2,3-c][2,7]naphthyridine derivative.     

Reactions of 1,3-Dialkyl-5-amino-1,3-dihydro-2<Emphasis Type="Italic">H</Emphasis>-imidazo-[4,5-<Emphasis Type="Italic">b</Emphasis>]pyridin-2-ones with acetylacetone and ethyl acetoacetate

1,3-Dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones reacted with acetylacetone to give the corresponding 4-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)pent-3-en-2-ones which underwent intramolecular cyclization to 1,3-dialkyl-5,7-dimethyl-1,3-dihydro-2H-imidazo[4,5-b]-[1,8]naphthyridin-2-ones on heating in polyphosphoric acid or diphenyl ether. Analogous reaction of 1,3-dialkyl-5-amino-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones with ethyl acetoacetate led to the formation of ethyl 3-(1,3-dialkyl-2-oxo-1,3-dihydro-2H-imidazo[4,5-b]pyridin-5-ylamino)but-2-enoates whose cyclization afforded 1,3-dialkyl-8-hydroxy-7-methyl-1,3-dihydro-2H-imidazo[5,4-b][1,8]naphthyridin-2-ones.     

Synthesis of 9-Substituted 2-Alkyl(aryl)imidazo-[1,2-<Emphasis Type="Italic">a</Emphasis>]benzimidazole-3-carbonitriles

A one-pot preparative synthesis of 9-substituted 2-alkyl(aryl)imidazo[1,2-a]benzimidazole-3-carbonitriles from the corresponding 3-carbaldehydes and hydroxylamine O-sulfonic acid has been developed.     

New donor–acceptor copolymers with ultra-narrow band gap for photovoltaic application

Two novel donor–acceptor (D–A) copolymers P1 and P2 with the thiazoloquinoxaline repeating acceptor moiety and different donor moieties of benzo[1,2-b:4,5-b']dithiophene and isomeric benzo[2,1-b:3,4-b']dithiophene have been prepared. The polymers show light absorption at 300–1200 nm and a band gap width of 0.98 and 1.14 eV, respectively. The energies of the HOMO (–5.42 and–5.29 eV) and LUMO (–3.90 and–3.83 eV) levels of polymers P1 and P2 have been determined. The absorption maximum for polymer P1 in the long-wavelength region is red-shifted by 161 nm, which is caused by stronger charge transfer in P1 as compared with P2. This fact indicates that the benzo[1,2-b:4,5-b']dithiophene structural moiety has a higher electron-donating ability than the benzo[2,1-b:3,4-b']dithiophene moiety. The red shift of the absorption spectrum of polymer P1 in comparison with that of P2 indicates that interchain π–π stacking interactions are more efficient in P1 than in P2.     

Design and synthesis of imidazo[4,5-<Emphasis Type="Italic">c</Emphasis>]pyridine derivatives as promising Aurora kinase A (AURKA) inhibitors

Computer simulation at the PM7 level of theory of the structures of imidazo[4,5-c]pyridine derivatives (deaza analogs of purines) and their complexes with Aurora kinase A (AURKA) indicated prospects for their use as potential AURKA inhibitors in the treatment of oncological diseases. A number of new compounds of the selected imidazo[4,5-c]pyridine series, for which the highest inhibitory activity against AURKA was predicted, were synthesized in high yields for further biological testing.