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.     

Synthesis of (4-methyl-2-oxo-1,2-dihydroquinoline-6-sulfonyl)acetanilides and their effect on blood coagulation system

(4-Methyl-2-oxo-1,2-dihydroquinoline-6-sulfonyl)acetanilides were obtained by either amidation of the respective acid with anilines or the reaction of N-aryl-2-chloroacetamide with 4-methyl-2-oxo-1,2-dihydroquinoline-6-sulfinic acid. Screening of the synthesized compounds revealed their hemostatic activity in vitro.     

Synthesis,nature of electronic transitions,and absorption spectra of the dye based on 4-(methyl-1-{2-[4-(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]-2-oxoethyl}pyridinium bromide

The reaction of 3-(4-bromoacetylphenyl)-1-methylquinolin-2(1Н)-one with pyridine and 4-methylpyridine has afforded the corresponding pyridinium salts. Condensation of 4-methyl-1-{2-[4-(1-methyl-2-oxo-1,2-dihydroquinolin-3-yl)phenyl]-2-oxoethyl}pyridinium bromide with 4-dimethylaminobenzaldehyde has given a new biscyanine dye, 1-{1-[4-(1,2-dihydro-1-methyl-2-oxo-3-quinolinyl)benzoyl]-2-[4-(dimethylamino)-phenyl]ethynyl}-4-{2-[4-(dimethylamino)phenyl]ethynyl}pyridinium bromide. Its electronic spectrum has been analyzed, and quantum-chemical simulation of spatial and electronic structure of its possible isomers has been performed.     

Studies on antibacterial agents. II. Synthesis and antibacterial activities of substituted 1,2-dihydro-6-oxo-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids

A series of substituted 1,2-dihydro-6-oxo-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acids for the treatment of systemic infections was synthesized via 7-bromo-3-ethylthio-4,5-difluoro-2-methylindole (3), which was prepared by Gassman's indole synthesis in excellent yield. The synthesized pyrroloquinolines were tested for their antibacterial activities. 8-Fluoro-1,2-dihydro-2-methyl-9-(4-methyl-1-piperazinyl)-6-oxo-6H- pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid showed a potent antibacterial activity against gram-positive and gram-negative bacteria.     

4-hydroxy-2-quinolones. 96. Synthesis and properties of 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid

Alkaline hydrolysis of the ethyl ester of 4-(cyanoethoxycarbonylmethyl)-2-oxo-1,2-dihydroquinoline-3-carboxylic acid is accompanied by decarboxylation with loss of two molecules of CO₂ and leads to 4-methyl-2-oxo-1,2-dihydroquinoline-3-carboxylic acid. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 887–893, June, 2006.     

Functionalization of substituted 2(1H)- and 4(1H)-pyridones. III. The preparation of substituted 6-Vinyl-1,2-dihydro-2-oxo- and 1,4-dihydro-4-oxo-3-pyridinecarboxylic acids through the chemistry of pyridone dianions

The synthesis of various substituted 6-vinyl-1,2-dihydro-2-oxo-3-pyridinecarboxylic acids from the dianions of 1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile and the corresponding 3-t-butyl ester is reported. The dianions were generated with LDA in THF at low temperature and reacted with various carbonyl substrates. Several conditions for the dehydration and hydrolysis of these adducts to the vinyl pyridone acids are discussed. Employing the conditions used for the 2-pyridone analogs, a series of substituted 6-vinyl-1,4-di-hydro-4-oxo-3-pyridinecarboxylic acids was prepared through the new dianion of 1,4-dihydro-6-methyl-4-oxo-3-pyridinecarboxylic acid, t-butyl ester.     

3-Oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide derivatives. I. Reaction of esters with alkoxides

Reaction of 3-oxo-1,2-benzoisothiazoline-2-acetic acid alkyl esters 1,1-dioxide ( 1a-d ) with alkaline alkoxides was carried out under various conditions. Under mild conditions, o-(N-carboxymethylsulfamyl)benzoic acids dialkyl esters ( 2a-d ) were obtained with good yields. Reaction of 1a-d or 2a-d with sodium alkoxides under drastic conditions afforded 4-hydroxy-2H-1,2-benzothiazine-3-carboxylic acid alkyl esters 1,1-dioxide ( 3a-d ). Transesterification was observed when esters 1b-d were treated with sodium methoxide in methanol. Esters 3a-d were hydrolyzed in concentrated aqueous sodium hydroxide affording the acid 6 . Attempts to recrystallize 6 from water resulted in its decarboxylation to give 2H-1,2-benzothiazine-4-(3H)one 1,1-dioxide (7). Compound 6 could not be obtained by acid hydrolysis of esters 3a-d or by rearrangement of 3-oxo-1,2-benzoisothiazoline-2-acetic acid 1,1-dioxide ( 8 ). Different experimental evidence supports the suggestion that rearrangement took place by ethanolysis of the carboxamide linkage affording the open sulfonamides (fast step) followed by a Dieckmann cyclization (slow step). It was demonstrated that transesterification took place in the open sulfonamides 2 .     

Synthesis and evaluation of novel 2-oxo-1,2-dihydro-3-quinolinecarboxamide derivatives as serotonin 5-HT4 receptor agonists

A series of N-azabicycloalkyl-1-alkyl-2-oxo-1,2-dihydro-3-quinolinecarboxamides were synthesized and tested for serotonin 5-HT4 receptor-stimulating effects in the regulation of electrically-evoked contraction in guinea pig muscle. Among them, N-azabicycloalkyl-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, 9c, 10c, 11c, 12c) exhibited potent serotonin 5-HT4 receptor-stimulating activity. The most potent compound, N-(endo-8-methyl-8-azabicyclo[3.2.1 oct-3-yl)-1-isopropyl-2-oxo-1,2-dihydro-3-quinolinecarboxamide (8c, ED50 = 36.3 nMi), was seven times as active as cisapride, while 8c had no affinity for 5-HT1A, 5-HT1D, D2, muscarinic M2 or muscarinic M3 receptors even at 10 microM. Compound 8c stimulated digestive tract motility in conscious fed dogs (1.0 mg/kg p.o.).     

A facile and novel synthesis of 1,6-naphthyridin-2(1H)-ones

A new and convenient procedure for the synthesis of 1,6-naphthyridin-2(1H)-ones and their derivatives is described. In the first scheme 5-acetyl-6-[2-(dimethylamino)ethenyl]-1,2-dihydro-2-oxo-3-pyridinecarbonitrile ( 4 ) obtained by the reaction of N,N-dimethylformamide dimethyl acetal with 5-acetyl-1,2-dihydro-6-methyl-2-oxo-3-pyridinecarbonitrile ( 3 ) was cyclized to 1,2-dihydro-5-methyl-2-oxo-1,6-naphthyridine-3-carbonitrile ( 5 ) by the action of ammonium acetate. Thermal decarboxylation of acid 7 obtained from the hydrolysis of nitrile 5 led to a mixture of 5-methyl-1,6-naphthyridin-2(1H)-one ( 8 ) and its dimer 9 . Hydrazide 11 obtained from nitrile 5 in two steps was converted to 3-amino-5-methyl-1,6-naphthyridin-2(1H)-one ( 12 ) by the Curtius rearrangement. The amino group of 12 was readily replaced by treatment with aqueous sodium hydroxide to yield 3-hydroxy-5-methyl-1,6-naphthyridin-2(1H)-one ( 13 ). In the second scheme, Michael reaction of enamines of type 20 with methyl propiolate, followed by ring closure gave 5-acyl(aroyl)-6-methyl-2(1H)-pyridinones ( 21 ) which in turn were treated with Bredereck's reagent to produce 5-acyl(aroyl)-6-[2-(dimethylamino)ethenyl]-2(1H)-pyridinones ( 22 ). Treatment of 22 with ammonium acetate led to the formation of 1,6-naphthyridin-2(1H)-ones 23 .     

N,N′-Linked 1,2-benzisothiazol-3(2H)-one 1,1-dioxides: synthesis, biological activity, and derived radicals

A number of N,N′-linked benzoannelated isothiazol-3(2H)-one 1,1-dioxides, not available via oxidation of isothiazolium salts, were obtained with good yields by reaction of N-amino heterocycles with 2-chlorosulfonylbenzoyl chloride and evaluated for their inhibitory activity toward human leukocyte elastase (HLE) and acetylcholinesterase (AChE). 2-(Phthalimid-1-yl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide and 2-(2-methyl-4-oxo-3(4H)-quinazolinyl)-1,2-benzisothiazol-3(2H)-one 1,1-dioxide were found to be inhibitors of HLE and tested as potential precursors of nitrogen-centered radicals using 266 nm laser flash photolysis.     

A convenient synthesis of 3-formyl-2-oxo-1,2-dihydroquinoxaline chlorophenylhydrazones: Novel tautomeric equilibria between hydrazone imine and diazenyl enamine forms with long-range pSSrototropy

3-Formyl-2-oxo-1,2-dihydroquinoxaline chlorophenylhydrazones 4a-c were synthesized from the reactions of 3-methyl-2-oxo-1,2-dihydroquinoxaline 3 with chlorophenyl diazonium salts, and 4b,c were found to exhibit the tautomeric equilibria between the hydrazone imine and diazenyl enamine forms in the dimethylsulfoxide solutions.     

Synthesis of 1-substituted 1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones

1-R-9,9,9a-Trimethyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones and the corresponding 2-methylene-2,3-dihydroindoles were obtained by the reaction of 2,3,3-trimethyl-3H-indole with a number of N-substituted chloroacetic acid amides and subsequent reaction of the resulting quaternary salts with bases. The kinetics of intramolecular cyclization of 1-(N-alkylcarbamoylethyl)-2-methylene-2,3-dihydroindoles under the influence of acetic acid were studied. Under the influence of strong protic acids 1-R-imidazo[1,2-a]indol-2-ones undergo decyclization and are converted to 3H-indolium salts.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1485–1489, November, 1986.     

Synthesis of pyridazino[4,5-b]indole derivatives from 2-(3-carboxy-1-methylindole)acetic acid anhydride

2-(3-Carboxy-1-methylindole)acetic acid anhydride ( 1 ) reacts with aryldiazonium salts to give 85–95% of the corresponding α-hydrazono anhydrides 2 . Treating 2 with boiling hydrazine hydrate in xylene, the respective 2-aryl-4-carbohydrazido-5-methyl-1-oxo-1,2-dihydro-5H/-pyridazino[4,5-b]indoles 3 were obtained (47–67%), and these compounds characterized as the respective benzylidene derivatives 4 . Compounds 2 react with amines (aniline, morpholine, piperidine) to give the respective 2-(3-carboxy-1-methylindole)aceta-mide 5 or the respective 2-aryl-4-carboxamido-5-methyl-5H-pyridazino[4,5-b]indole 6 , the product obtained depending on the structure of the aryl substituent. Boiling 2b (aryl = 4-chlorophenyl) with 5% sodium hydroxide gave (80%) 2-(3-carboxy-1-methylindole)acetic acid ( 7 ). Hydrolysis of 2b gave a mixture of 7 and 2-(3-carboxy-1-methylindolyl)-2-(4-chlorophenylhydrazono)acetic acid ( 8 ).     

Synthesis of 1,2-azaphospholanes containing an amino acid fragment

2-Oxo-1,2-azaphospholanes and 1,2-azaphospholanium salts containing an amino acid fragment were synthesized by intramolecular P-alkylation of N-3-chloropropyl-substituted tricoordinate phosphorus amides. Hydrolysis of 2-oxo-1,2-azaphospholanes at the P-N bond gives rise to γ-aminopropylphosphonic acid derivatives. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2557–2562, November, 2005.     

Synthesis of (2-oxo-1-pyrrolidinyl)pyrimidines

(2-Oxo-1-pyrrolidinyl)pyrimidines have been synthesized by thermal cyclization of certain N-(pyrimidinyl)--aminobutyric acids. Reaction of 2-methyl-4-chloro-6-(2-oxo-1-pyrrolidinyl)pyrimidine with the sodium salts of acetone or acetophenone oximes gave the corresponding pyrimidinylketoximes. The iodomethylation of pyrrolidinylpyrimidines is reported.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1540–1544, November, 1993.     

3-acyl-1,5-benzodiazepines in the reactions of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with certain 1,2-diaminobenzenes

Reaction of 5,5-dimethyl-2-formylcyclohexane-1,3-dione with 4-methyl-, 4-benzoyl-, and 4-nitro-1,2-diaminobenzenes gave the corresponding 2-(2-amino-4-methylphenylaminomethylene)-, 2-(2-amino-5-benzoylphenylaminomethylene)-, and 2-(2-amino-5-nitrophenylaminomethylene)-5,5-dimethylcyclohexane-1,3-diones. When treated with hydrochloric acid, they cyclize to 7-methyl-, 8-benzoyl-, and 8-nitro-3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinon hydrochlorides. Under hydrolytic conditions the salts of 3,3,7-trimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone and 3,3-dimethyl-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinone undergo the C₁₁−N₁₀ bond cleavage to give N-(2-aminophenyl)- and N-(2-amino-5-methylphenyl)-substituted 3-amino-2-formyl-5,5-dimethylcyclohex-2-enones. Ring opening of the hydrochlorides of 8-benzoyl-, and 3,3-dimethyl-8-nitro-2,3,4,5-tetrahydro-1H-dibenzo[b,e][1,4]diazepinones occurs at the C−N₅ bond and gives the starting enamines. Riga Technical University, Riga LV-1658, Latvia; Translated from Khimiya Geterotsiklicheskikh Soedinenii, N. 5, pp. 696–700, May, 1999.     

Synthesis and antioxidant activities of 2-methyl-5-oxo-1,4-dihydroindeno[1,2-b]pyridines

Cycloalkyl esters of 4-aryl- and 4-cinnamyl-2-methyl-5-oxo-1,4-dihydroindeno[1,2-b]pyridine-3-carboxylic acids were synthesized. Their antioxidant activities, which are most pronounced for the 4-(2-nitrophenyl) derivatives, were determined with respect to the inhibition of the autooxidation of methyl oleate.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1528–1531, November, 1982.     

Preparation of N-phosphorylated 2-oxo-1,3-oxazolidines and 6-methyl-2-oxo-1,3-tetrahydrooxazine

Conclusions N-Phosphorylated 2-oxo-1,3-oxazolidines and 6-methyl-3-(diethoxyphosphinyl)-2-oxo-1,3-tetrahydro-oxazine were prepared by allowing N-(diethoxyphosphinyl)imidocarbonyl dichloride to react with ethylene glycol, 1,2-propylene glycol, and 1,3-butylene and 2,3-butylene glycols in the presence of triethylamine in a dioxane medium.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 396–399, February, 1970.     

Skeletal transformations of pentafluorophenylation products of perfluorinated 1,2-dialkyl-1,2-dihydrocyclobutabenzenes in SbF5

Perfluorinated 1-ethyl-2-methyl- and 1-isopropyl-2-methyl-1,2-dihydrocyclobutabenzenes reacted with pentafluorobenzene in SbF₅ to generate perfluoro(1-ethyl-2-methyl-2-phenyl- and perfluoro(1-izopropyl-2-methyl-2-phenyl-1,2-dihydrocyclobutabenzen-1-yl) cations. These cations in SbF₅ at 20°C underwent opening of the four-membered ring and its expansion to five-membered. After hydrolysis, perfluorinated 4-[1-(2-propylphenyl)ethylidene]- and 4-[1-(2-isobutylphenyl)ethylidene]-2,5-cyclohexadien-1-ones were obtained together with perfluoro(3-ethyl- and perfluoro(3-isopropyl-2-phenylinden-1-ones).     

Novel and Efficient Synthesis of Pyrimidine Derivatives

A new series of 1-alkyl-2-oxo-1,2-dihydro-pyrimidine-5-carboxalic acid amides is described. The reaction of N-((E)-3-(dimethylamino)-2-formylacryloyl) formamidine, an intermediate obtained by Vilsmeier–Haack formylation of acetonitrile with various mono-substituted ureas, provides such compounds in good yields.