4-Hydroxy-2-quinolones 129. Synthesis and structure of 2-bromomethyl-4-carboxy-5-methyl-1,2-dihydrooxazolo-[3,2-<Emphasis Type="Italic">a</Emphasis>]quinolinium bromide

By analogy with the 4-hydroxy derivatives, the bromination of N-allyl-4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid leads to the closure of a five membered oxazole ring but, in contrast, it forms the 2-bromomethyl-4-carboxy-5-methyl-1,2-dihydrooxazolo[3,2-a]quinolinium bromide salt. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1496–1502, October, 2007.     

4-Hydroxy-2-quinolones. 118. Synthesis,structure, and chemical properties of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo-[3,2-<Emphasis Type="Italic">a</Emphasis>]quinoline-4-carboxylic acid and its ethyl ester

Bromination of N-allyl-substituted 4-hydroxy-2-quinolinones with molecular bromine in acetic acid or carbon tetrachloride occurs with closing of a five membered oxazole ring to give 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 736–749, May, 2007.     

4-hydroxy-2-quinolones. 124. Synthesis and structure of ethyl 2-bromomethyl-5-oxo-1,2,6,7,8,9-hexahydro-5H-oxazolo-[3,2-<Emphasis Type="Italic">a</Emphasis>]quinoline-4-carboxylate

The hydrogenation of the benzene part of the molecule in N-allyl-substituted 4-hydroxy-2-quinolinones does not affect the nature of their bromination by molecular bromine and gives 2-bromomethyl-5-oxo-1,2,6,7,8,9-hexahydro-5H-oxazolo[3,2-a]quinolines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1180–1188, August, 2007.     

4-Hydroxy-2-quinolones 123. Amidation of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-<Emphasis Type="Italic">a</Emphasis>]-quinoline-4-carboxylic acid

The reaction of 2-bromomethyl-5-oxo-1,2-dihydro-5H-oxazolo[3,2-a]quinoline-4-carboxylic acid with thionyl chloride is accompanied by a transformation of the oxazoloquinolone ring to give 4-chloro-1-(2,3-dichloropropyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid chloride. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1034–1042, July, 2007.     

4-Hydroxy-2-quinolones 144. Alkyl-, arylalkyl-, and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-3-carboxylic acid and their diuretic properties

Alkyl-, arylalkyl-, and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid were prepared with a view to establishing a structure-biological activity relationship. A comparative analysis has been made of their diuretic properties and those of the structurally similar 4-hydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 718–729, May, 2008.     

Synthesis and molecular structure of 3-(2-aryl-2-oxoethyl)-3-methoxy-2-oxo-2,3-dihydroimidazo-[1,2-<Emphasis Type="Italic">a</Emphasis>]pyridine hydrochlorides

Reactions between 2-pyridylamides of Z-4-aryl-2-hydroxy-4-oxobut-2-enoic acids with diazomethane have been used to synthesize 3-(2-aryl-2-oxoethyl)-3-methoxy-2-oxo-2,3-dihydroimidazo[1,2-a]pyridines, which form hydrochlorides with hydrochloric acid. The structure of the latter has been demonstrated by XRD for the hydrochloride of 3-methoxy-2-oxo-3-(2-phenyl-2-oxoethyl)-2,3-dihydroimidazo[1,2-a]pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 464–468, 2007.     

4-Hydroxy-2-quinolones 131. Bromination of 3-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline

The bromination of 3-allyl-4-hydroxy-2-oxo-1,2-dihydroquinoline by molecular bromine is accompanied by the closure of a five membered furan ring and gives the corresponding 2-bromomethyl-3,9-dihydro-2H-furo[2,3-b]quinolin-4-one. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1677–1686, November, 2007.     

4-Hydroxy-2-quinolones 143. Synthesis,structure, and spectroscopic characteristics of ethyl 2-hydroxy-4-oxo-4H-pyrazino[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-3-carboxylate

Condensation of aminopyrazine with triethyl methanetricarboxylate gave ethyl 2-hydroxy-4-oxo-4H-pyrazino[1,2-a]pyrimidine-3-carboxylate. According to X-ray analytical data the compound exists in the 2-hydroxy-4-oxo form in the crystal. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 411–419, March, 2008.     

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.     

4-Hydroxy-2-quinolones 120. Synthesis and structure of ethyl 2-hydroxy-4-oxo-4H-pyrido-[1,2-a]pyrimidine-3-carboxylate

An improved method for the preparation and purification of ethyl 2-hydroxy-4-oxo-4H-pyrido[1,2-a]-pyrimidine-3-carboxylates is proposed. According to ¹H and ¹³C NMR spectroscopic data the synthesized compounds exist in DMSO solution in the 2-hydroxy-4-oxo form while in the crystal (at least for the case of the unsubstituted derivative) X-ray analysis shows that it occurs in the bipolar 2,4-dioxo form. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 864–876, June, 2007.     

The Use of 4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one as “Masked” α-Bromo-α'-Hydroxy Ketone in the Synthesis of Heterocyclic Systems

4-(Bromomethylene)-5,5-dimethyl-1,3-dioxolan-2-one was obtained on the basis of the readily obtainable 4-methylene-5,5-dimethyl-1,3-dioxolan-2-one. It forms 2-imidazo[1,2-a]pyridin-2-yl-2-propanol with 2-aminopyridine, 11a-hydroxy-1,1-dimethyl-3-oxo-1,5,11,11a-tetrahydro[1,3]oxazolo[3,4-a]pyrido[1,2-d]-10-pyrazinium bromide with 2-(aminomethyl)pyridine, and the corresponding derivative of 4-hydroxyoxazolidin-2-one with 2-(3,4-dimethoxyphenyl)ethylamine. The last product was converted by intramolecular amidoalkylation without isolation into 10b-(bromomethyl)-8,9-dimethoxy-1,1-dimethyl-1,5,6,10b-tetrahydro[1,3]oxazolo[3,4-a]isoquinolin-3-one.     

Cycloaddition of 2-acylmethyl-1H-benzimidazoles to 4-arylidene-1,3-oxazol-5-ones

Cycloaddition of 2-phenacyl-1H-benzimidazole to 2-phenyl-or 2-methyl-4-arylidene-1,3-oxazol-5-ones occurs regioselectively to form the previously unknown N-(3-aryl-4-benzoyl-1-oxo-1,2,3,4-tetrahydropyrido[1,2-a]benzimidazol-2-yl)benz-and-acetamides. The analogous cycloaddition of the 2-acetonyl-1H-benzimidazole is complicated by prototropic isomerization and leads to the corresponding 1,2,3,5-tetrahydropyrido[1,2-a]benzimidazole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 78, pp. 1008–1014, July, 2007.     

4-Hydroxy-2-quinolones 139. Synthesis,structure, and antiviral activity of N-R-amides of 2-hydroxy-4-oxo-4H-pyrido[1,2-<Emphasis Type="Italic">a</Emphasis>]pyrimidine-3-carboxylic acids

Dialkylaminoalkylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acids have been obtained as potential antiviral agents. The special features of the spatial structure of one example of the synthesized compounds have been studied. Results are given of the investigation of cytotoxicity and antiviral activity in relation to type 1 herpes virus and coronavirus. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 61–77, January, 2008.     

Synthesis of annelated [a]aza-anthracenones and thieno[3,2-g]aza-naphthalenones through ring transformation of 2H-pyran-2-one followed by photocyclization

A concise synthesis of some new classes of heterocycles (4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a-diaza-cyclopenta[a]anthracen-6-carbonitriles and 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a-diazabenzo[a]anthracene-7-carbonitriles) has been developed by the ring transformation of suitably functionalized 2H-pyran-2-one with α-oxoketene cyclic aminals to intermediates (8-aroyl-5-aryl-2,3-dihydro-1H-imidazo[1,2-a]pyridine-7-ylidene)-acetonitriles and (9-aroyl-6-aryl-1,2,3,4-tetrahydropyrido[1,2-a]pyrimidin-8-ylidene)-acetonitriles) followed by their photocyclization either in CHCl₃ or acetonitrile. This reaction was further explored for the synthesis of methyl 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carboxylate, 4-aryl-11-oxo-1,2,3,11-tetrahydro-1,3a,9-triaza-cyclopenta[a]anthracene-6-carbonitriles, 5-aryl-12-oxo-1,3,4,12-tetrahydro-2H-1,4a,10-triazabenzo[a]anthracene-7-carbonitriles, 4-aryl-10-oxo-1,2,3,10-tetrahydro-9-thia-1,3a-diazadicyclopenta[a,g]naphthalene-6-carbonitriles and 5-aryl-11-oxo-1,3,4,11-tetrahydro-2H-10-thia-1,4a-diazacyclopenta[b]phenanthrene-7-carbonitriles from the similar reactions.     

Exotic Amino Acids. 6. Synthesis of Substituted 4-Oxo-4H-pyrido[1,2-a]pyrimidines

2-Pyridylaminomethyleneisopropylidenemalonates, prepared from ethoxymethyleneisopropylidenemalonate and 2-aminopyridines, form 4-oxo-4H-pyrido[1,2-a]pyrimidines at their melting points and are separated from the reaction mixture by sublimation.     

Cyclization of 1-hydroxy-2-(oxoalkynyl)anthraquinones

Procedures were developed for the heterocyclization of 2-benzoylethynyl-1-hydroxy-and 1-hydroxy-2-(1-oxo-3-phenylpropynyl)anthraquinone. The regioselective preparation of 2-substituted anthra[1,2-b]pyran-4,7,12-triones was demonstrated to be possible under mild conditions.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2686–2692, December, 2004.     

4-Hydroxy-2-quinolones 141. Synthesis and structure of 5R-3-hydroxy-1,5-dihydropyrazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]quinolin-4-ones

Treatment of 1R-4-chloro-3-ethoxycarbonyl-2-oxo-1,2-dihydroquinolines with p-toluenesulfonylhydrazide in refluxing ethanol and in the presence of triethylamine gives the 3-hydroxy-5R-1,5-dihydropyrazolo[4,3-c]quinolin-4-ones. The possible mechanism of formation, features of the steric structure of the synthesized compounds, and their NMR and mass spectra are discussed. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 233–238, February, 2008.     

Synthesis of derivatives of a new heterocyclic system, 9-oxo-1,3,4-thiadiazolo[3,2-a]pyrido[3,2-e]pyrimidine

Reaction of 2-substituted 5-imino-7-oxo-1,3,4-thiadiazolo[3,2-a]pyrimidines with pentane-2,4-dione in polyphosphoric acid yields 9-oxo-1,3,4-thiadiazolo[3,2-a]pyrido[3,2-e]pyrimidines.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2037–2038, October, 1995.The authors are grateful to V. A. Dorokhov for the skilled preparation of the paper for publication.     

Synthesis of 6′-carbamoylmethylthio-5′-cyano-1′,4′-dihydro-3,4′-bipyridine-3′-carboxylic and 6′-carbamoylmethylthio-5′-cyano-1′,4′-dihydro-4,4′-bipyridine-3′-carboxylic esters and investigation of their stability. 2. Esters of 6′-carbamoylmethyl-thio-5′-cyano-1′,4′-dihydro-4,4′-bipyridine-3-carboxylic acids

The stability of solutions of esters of 6′-carbamoylmethylthio-5′-cyano-2′-methyl-1′,4′-dihydro-4,4′-bipyridine-3′-carboxylic acids was investigated by HPLC. The corresponding esters of 6′-carbamoylmethylthio-5′-cyano-4,4′-bipyridine-3′-carboxylic acids,esters of 8-cyano-5-methyl-3-oxo-7-(4-pyridyl)-2,3-dihydro-7H-thiazolo-[3,2-a]pyridine-6-carboxylic acids, methyl 3-amino-2-carbamoyl-6-methyl-4-(4-pyridyl)-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate, and methyl 3-amino-2-carbamoyl-6-methyl-4-(4-pyridyl)-thieno[2,3-b]pyridine-5-carboxylate were synthesized as standard compounds (typical impurities). Analysis by HPLC was realized under the conditions of reverse-phase chromatography. It was established that solutions of the investigated compounds (with mixtures of acetonitrile with phosphate buffer, having pH values of not less than 3 and not more than 5, as solvents) are stable for one month when the solutions are stored in a place protected against light. It is also necessary to use chromatographic systems in which the aqueous components have pH 3–5 during determination of the purity of the esters of 6′-carbamoylmethylthio-5′-cyano-2′-methyl-1′,4′-dihydro-4, 4′-bipyridine-3′-carboxylic acid by HPLC in order to separate the analyzed sorbates and their typical impurities more completely. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 841–848, June, 2007.     

Condensed isoquinolines 26. Oxidation reactions of 6,11-dihydro-13H-isoquino-[3,2-<Emphasis Type="Italic">b</Emphasis>]quinazolin-13-one derivatives

Oxidation of the hydrobromide of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one with dimethyl sulfoxide leads to 11-hydroxy-11H-isoquino[3,2-b]quinazoline-6,13-dione, and with hydrogen peroxide to the hydrobromide of 2-[(4-oxo-3,4-dihydro-2-quinazolinyl)carbonyl]benzoic acid. Salts of 5-and 6-alkyl-substituted isoquino[3,2-b]quinazolines are readily oxidized on boiling in nitrobenzene, which leads to aromatization of the isoquino[3,2-b]quinazoline system to 5-methyl-13-oxo-5H,13H-isoquino[ 3,2-b]quinazolinium perchlorate and 6-benzyl-13H-isoquino[3,2-b]quinazolin-13-one. The structures of the dehydrogenation products were established from ¹H NMR and UV spectra. The interaction of the obtained compounds with NaBH₄ has been studied. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1833–1840, December, 2007.