Carbon-nitrogen bond formation in cyclisation by deoxygenation,thermolysis or photolysis of phenylimidazo[1,2-a][1,8]naphthyridines

Triethyl phosphite deoxygenation of 2-(2-nitrophenyl)imidazo[1,2-a][1,8]naphthyridine (3) led to the C-insertion to give the indoloimidazonaphthyridine 5. Our attempt to promote the N-insertion by blocking the C-3 position failed. Triethyl phosphite deoxygenation of 1-nitroso-2-(4-fluorophenyl)imidazo[1,2-a][1,8]-naphthyridine (12) led to the corresponding amine structure (15). Thermolysis and photolysis of 6,8-dimethyl-2-(2-azidophenyl)imidazo[1,2-a][1,8]naphthyridine (17) are also reported.     

Synthesis,structure and reactivity of imidazo[1,2-a][1,8]naphthyridines

The synthesis and reactivity of imidazo[1,2-a][1,8]naphthyridines are reported. Electrophilic substitution reactions were studied and the site of the reaction was established with the aid of high-field ¹H and ¹³C nmr spectra. The experimental C-1 position reaction was correlated with a CNDO/2 calculations.     

Transformations of the pyrido[1,2-a]pyrazine ring system into imidazo[1,2-a]pyridines,imidazo[1,2-a]pyrimidines and 2-oxa-6a, 10c-diazaaceanthrylenes

Transformations of methyl 3-dimethylamino-2-(1-methoxycarbonyl-4-oxo-4H-pyrido[1,2-a]pyrazin-3-yl)acrylate with some cyanomethylenecarbonyl group containing compounds or cyanamide into imidazo-[1,2-a]pyridines, irmdazo[1,2-a]pyrimidines and 2-oxa-6a, 10c-diazaaceanthrylenes are described.     

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.     

The synthesis of 7,8-dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]triazines

Cyclic hydrazino amidines were converted to the corresponding aminopyrazolyl derivatives. Ring closure between the amino groups of pyrazoline moieties and NH groups of cyclic amidines afforded the following ring systems: 7,8-Dihydroimidazo[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines, 8,9-dihydro-7H-pyrimido[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines and 7,8,9,10-tetrahydro[1,3]diazepino[1,2-e]pyrazolo[1,5-a]-1,3,5-triazines.     

A facile synthesis of pyrrolo[1,2-a]pyrimidines and pyrrolo[1,2-a]imidazoles

The one-step synthesis of 8-t-butoxycarbonyl-6,7-dimethyl-2-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrimidine from acetyl methyl carbinol, 3-aminopropionic acid, and t-butyl cyanoacetate is reported. Utilizing a similar technology under basic conditions, 7-substituted 5,6-dimethyl-2-oxo-2,3-dihydro-(1H)-pyrrolo[1,2-a]imidazole is synthesized from acetyl methyl carbinol, ethyl glycinate, and the appropriate acetonitrile.     

A new synthetic approach for imidazo[1,2-a]imidazoles and pyrrolo[1,2-a]imidazoles

Substituted pyrrolo[1,2-a]imidazoles and imidazo[1,2-a]imidazoles are prepared in a simple one pot reaction sequence from esters of heterocyclic or aromatic α-amino acids. The reaction involves condensation with acetoine followed by cyclization with either malonodinitrile, ethyl cyanoacetate or cyanamide.     

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.     

Synthesis of novel imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines

Several 1 1-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines have been used as starting material to prepare a number of derivatives of 9H-imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines and 10H-pyrimido[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepines. The imidazole nucleus was built by reaction of amidines with ethyl bromopyruvate or aminoacetaldehyde dimethylacetal. Several derivatives of imidazo[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine have been prepared by formylation of the pyrrole ring followed by formation of thioamides. Condensation of 11-amino-5H-pyrrolo[2,1-c][1,4]benzodiazepines with diethyl ethoxymethylenemalonate afforded intermediate diesters which were transformed into the corresponding 10H-pyrimido[1,2-a]pyrrolo[2,1-c]-benzodiazepines.     

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.     

Unusual condensation of 4,5-dimethyl-1,2-phenylenediamine with phthalaldehyde in the presence of NiII complexes giving rise to 4,5-dimethyldiisoindolo[2,1-a:1,2-c]quinoxaline-1,8-dione

The reaction of 4,5-dimethyl-1,2-phenylenediamine (1) with phthalaldehyde (2) in the presence of Ni^II complexes afforded 4,5-dimethyldiisoindolo[2,1-a:1,2-c]quinoxaline-1,8-dione (3), whose structure was established by X-ray diffraction analysis.     

Rearrangement reactions of heterocycles. 12. Rearrangement of 6-substituted pyrido[1,2-a]pyrimidines to isomeric 1,8-naphthyridines and some of their further reactions

2-Amino-6-methylpyridine ( 4 ) reacts with active malonates 2a-d or 3a-d either in acetone solution with triethylamine as catalyst at room temperature or with active malonates 2a-d in acetone solution at reflux temperature to yield the pyrido[1,2-a]pyrimidines 5a-d . 2,6-Diaminopyridine ( 8 ) already reacts without triethylamine with 2a-d at room temperature to afford the pyrido[1,2-a]pyrimidines 9a-d . At higher temperatures pyrido[1,2-a]pyrimidines 5 and 9 are rearranged via ketene intermediates [1] to yield the 1,8-naphthyridines 6a-d , and 10a-d , respectively. The naphthyridines 6 and 10 can also be synthesized directly from 4 or 8 using either diethyl malonates 1 or — with better results — the active malonates 2 at 240–250°. Further reaction of 10a-e with 2c,d leads to the pyridonaphthyridines 12a-f . Nitration of 6c yields the nitro derivative 16 and chlorination of 6c,d gives 15c,d , while the chlorination of 10c affords the di-chloro derivative 17 .     

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).     

Nitrogen bridgehead compounds VIII . Ring transformations IV . Synthesis and reactions of 2,3-Cycloalkylene-4H-pyrido [1,2-a] pyrimidin-4-ones

By condensing alicyclic β-ketocarboxylates with substituted 2-aminopyridines in polyphosphoric acid or phosphoryl chloride-polyphosphoric acid, numerous 2,3-tri-, tetra-, penta- and hexamethylene-4H-pvrido[1,2-a]pyrimidin-4-ones were synthesized for pharmacological purposes. The stability and several reactions of the title compounds were studied. The 6-substituted-4H-pyrido[1,2-a]pyrimidin-4-ones were transformed into 1,8-naphthyridines in good yields independent of the ring size of ring C . The characteristic differences in the ir and uv spectra of the pyrido-pyrimidines and the corresponding naphthyridines are discussed. Catalytic hydrogenation of the pyrido[1,2-a]pyrimidin-4-ones furnished the corresponding 6,7,8,9-tetrahydropyrido-[1,2-a]pyrimidin-4-one derivatives. It was found that the A and C rings attached to the pyrirnidinone ring in solutions of unsubstituted tetrahydropyrido[1,2-a]pyrimidin-4-ones are flexible, whereas in the 6-methyl derivatives the conformer containing the 6-methyl group in axial position predominates.     

3-Methylpyrazolo [1,2-a] pyridazin-1-one. Selenium derivatives of 5,8-dihydropyrazolo[1,2-a]pyridazine

The dehydrogenation of the known 3-methyl-5,8-dihydropyrazolo[1,2-a]pyridazin-1-one (2) to the ten π electron heteroaromatic 3-methylpyrazolo[1,2-a]pyridazin-1-one ( 3 ) is reported. Conversions of the pyrazolone 2 to the pyrazoloselenone 6 via the chloropyrazolium chloride 7 , and of pyrazolones 2 and 3 and pyrazoloselenone 6 into the corresponding O or Se ethyl pyrazolium fluoroborates 5, 4 , and 8 by triethyloxonium fluoroborate are also described.     

Ionic liquids on the basis of 2,3,4,6,7,8,9,10-octahydropyrimido-[1,2-a]azepine (1,8-diazabicyclo[5.4.0]undec-7-ene)

New ionic liquids containing alkyl and polyfluoroalkyl substituents and various anions were synthesized from 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepinium ion (1,8-diazabicyclo[5.4.0]undec-7-en-8-ium). Their NMR spectra and miscibility with water and organic solvents were studied.     

Stepwise approach to the 2,3-dihydroimidazo[1,2-a]pyridine and 5-oxo-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine ring systems

The syntheses of 2,3-dihydro-8-fluoro-6-trifluoromethylimidazo[1,2-a]pyridine-3-carbonitrile ( 2 ), 8-fluoro-6-trifluoromethylimidazo[1,2-a]pyridine-3-carbonitrile ( 9 ) and 5-oxo-8-trifluoromethyl-1,2,3,5-tetrahydroimidazo[1,2-a]pyridine-3-carbonitrile ( 3 ) are described. These compounds are constructed in a stepwise approach starting from the properly substituted 2-halopyridines.     

3-Substituted 2-trifluoromethylimidazo [1,2-a] pyridines

3-Fluoro-2-trifluoromethylimidazo[1,2-a]pyridines were obtained by reactions of hexafluoroacetone 2-pyridylimines with trimethyl phosphite and studied in reactions with sodium methoxide. This gave the corresponding 3-methoxy-2-trifluoromethylimidazo[1,2-a]pyridines.     

Pyrimido[1,2-a]benzimidazolocyanines

Cyanine dyes containing a pyrimido[1,2-a]benzimidazole chromophore are described.     

Synthesis of Structurally Related Purines: Benzimidazo[1,2-a]pyridines, Benzimidazo-[1,2-c]pyrimidines, and Pyrazolo-[1,5-a]pyrimidines

Summary.  Reactions of sodium salts of 3-hydroxymethylene-2-alkanones with 2-cyanomethylbenzimidazole afforded benzimidazo[1,2-a]pyridines. Analogues reactions with 2-aminobenzimidazole and 5-aminopyrazoles afforded benzimidazo[1,2-c]pyrimidines and pyrazolo[1,5-a]pyrimidines. Received December 12, 1999. Accepted (revised) February 12, 2000