Synthesis and thermal decomposition of haloalkoxy-sym-triazines. 8. Synthesis and thermal decomposition of 2-methoxy(methylthio)-4-(2-chloroethylthio)-6-dialkylamino-sym-triazines

New 2-chloroethylthio derivatives of sym-triazine were obtained by the reaction of mercapto-sym-triazines and dichloroethane. It was established that these chlorides undergo cyclization to give 2-dialkylamino-4-oxo(thioxo)-4,5,6,7-tetrahydrothiazolo [1,2-a]-sym-triazines, the structure of which was confirmed by PMR and mass-spectral data, at moderate temperatures.See [7] for Communication 7.Translated f rom Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1275–1278, September, 1981.     

Synthesis and thermal decomposition of haloalkoxy-sym-triazines. 7. Thermal decomposition of 2-dialkylamino-4-(2-chloroethoxy)-6-methoxyamino-sym-triazines

Two 2-dialkylamino-4-(2-chloroethoxy)-6-methoxyamino-sym-triazines were synthesized. It was established that when they are heated at 120° C, the 2-chloroethoxy group undergoes rearrangement with cyclization to give 2-dialkylamino-4-oxo-8-methoxy-6, 7-dihydroimidazo [1,2-a]-sym-triazines, the structure of which was confirmed by data from the IR, PMR, and mass spectra.See [6] for Communication 6.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 8, pp. 1122–1124, August, 1981.     

Synthesis and thermal decomposition of halogenoalkoxy-, halogenoalkylthio-, and halogenoalkoxyamino-sym-triazines 13. Synthesis and thermolysis of 4,6-disubstituted 2-(2-chloroethoxy)- and 2-(2-chloroethylamino)-sym-triazines

4-Amino-, 4-methoxy-, 4-methylthio-, 4-alkylamina-, and 4-dialkylamino-6-alkyl(dialkyl)amino-2-(2-chloro-ethoxy)-sym-triazines and the corresponding 2-(2-chloroethylamino)-sym-triazines were obtained. Their cyclization led to the sym-triazinium chlorides or imidazo-sym-triazines.For Communication 12, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 228–230, February, 1992.     

Unusual reactions of 5,5-dimethyl-2-(indenyl-2)-3-pyrazolidinone with acetylenedicarboxylates

[reaction: see text] Reaction of 5,5-dimethyl-3-pyrazolidinone (1) with 2-indanone (2) gave 5,5-dimethyl-2-(1H-indenyl-2)-3-pyrazolidinone (3) instead of the expected azomethine imine 4. Although reaction of 2-substituted 3-pyrazolidinones with acetylenedicarboxylates usually gives ring expansion products, such as 1,2-diazepines, treatment of 3 with dialkyl acetylenedicarboxylates (5, R = Me; 6 R = Et) resulted in the formation of rel-(7aR,12aS)-6,7-bis(alkoxycarbonyl)-3,4-dihydro-4,4-dimethyl-7aH-indano[1,2-b]pyrrolo[1,2-a]pyrimidin-2-ones (7, R = Me; 9, R = Et) as major products and 3,4-bis(alkoxycarbonyl)-7,7-dimethyl-2-(indenyl-2)-6,7-dihydro-2H,6H-1,2-diazepin-5-ones (8, R = Me: 10, R = Et) as minor products.     

Rearrangements in haloalkoxy (thio,amino)-sym-triazines

The reaction of [2-methoxy-6-dialkylamino-sym-triazin-4-yl]trimethylammonium chlorides with ethylene chlorohydrin gives 2-methoxy-4-(2-chloroethoxy)-6-dialkylamino-sym-triazones, which eliminate CH₃Cl when they are heated to give 2-dialkylamino-4-oxo-4,5,6,7-tetrahydrooxazolo[3,2-a]-sym-triazines. Data from the UV, IR, PMR, and mass spectra are presented.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 989–992, July, 1977.     

Synthesis and some properties of 5-alkylamino-2-(phthalimidoalkyl)-1,3-oxazole-4-carbonitriles

5-Alkylamino-1,3-oxazole-4-carbonitriles containing a 2-phthalimidoethyl or 3-phthalimidopropyl substituent at position 2 of the oxazole ring were synthesized. In the reaction of 5-(morpholin-4-yl)-2-(2-phthalimidoethy)l-1,3-oxazole-4-carbonitrile with hydrazine hydrate, 2-(2-aminoethyl)-5-(morpholin-4-yl)-1,3-oxazole-4-carbonitrile is formed. In the case of the 3-phthalimidopropyl analog, the recyclization product 3-amino-2-(morpholin-4-ylcarbonyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazole is formed.     

Synthesis and some heterocyclization reactions of new diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate and ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate

A new CF₂X-analogue of 1,1-bis(trifluoromethyl)-2,2-dicyanoethylene (X = P(O)(OEt)₂), diethyl (1,1-difluoro-3,3-dicyano-2-trifluoromethylallyl)phosphonate, has been synthesized from diethoxyphosphoryl pentafluoroacetone 1. A similar phosphoryl analogue of ethyl 3,3-dicyano-2-trifluoromethylacrylate, ethyl 3,3-dicyano-2-[(diethoxyphosphoryl)difluoromethyl]acrylate, has been obtained from ethyl 3-(diethoxyphosphoryl)-3,3-difluoro-2-oxopropionate 2. By heterocyclization of these new ethylenes with 3-methyl-2-pyrazoline-5-ones, 3(5)-aminopyrazoles, dimedone, 2-aminopyridines, 1-aryl-3-methyl-5-aminopyrazoles, 1,3,3-trimethylisoquinolines, as well as by condensation with anilines and ketones, the difluoromethylphosphonate-substituted derivatives of 1,4-dihydropyrano[2,3-c]pyrazole, 4,5-dihydropyrazolo[1,5-a]pyrimidine, 5,6,7,8-tetrahydro-4H-chromene, 2H-pyrido[1,2-a]pyrimidine, 4,7-dihydro-1H-pyrazolo[3,4-b]pyridine, 1,4-dihydropyridine, 4,5,6,7-tetrahydro-1H-[1]pyrindine, 1,4,5,6,7,8-hexahydroquinoline, and 6,7-dihydro-2H-pyrido[2,1-a]isoquinoline have been obtained in one stage.     

New data on the alkylation of cyclic thioureas with á-halocarboxylic acids and their esters. 2. Alkylation of tetrahydropyrimidine-2(1h)-thione and 5,5-dimethyltetrahydropyrimidine-2(1h)-thione

In the absence of bases all the attempted variations for the alkylation of tetrahydropyrimidine-2(1H)-thione with á-halocarboxylic acids gave only the bicyclic product-2-R-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one hydrohalide. However the hydrohalide of the “ open” S-ethoxycarbonyl derivative of propyleneisothiourea can be obtained by treatment of tetrahydropyrimidine-2(1H)-thione with ethyl chloro-or bromoacetate in anhydrous acetone at room temperature. Alkylation of 5,5-dimethyltetrahydro-2(1H)-pyrimidinethione with chloro-or bromoacetic acid in anhydrous acetone at room temperature gave the hydrohalide of the “open” S-carboxymethyl derivative of dimethylpropyleneisothiourea. All remaining variations for the alkylation of this substrate with á-halocarboxylic acids or their esters gave only the corresponding bicyclic compounds-the hydrohalide of 2-R-6,6-dimethyl-6,7-dihydro-5H-[1,3]thiazolo[3,2-a]pyrimidin-3(2H)-one-independently of the reaction conditions. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 593–604, April, 2006.     

Reaction of dihalocarbenes with 2-(benzylideneamino)pyridines. Cyclization of 2-(benzylideneamino)pyridinium dihalomethylids to give 2-aryl-3-haloimidazo[1,2-α]pyridines

Pyridinium dichloromethylids, formed in the reaction of dichlorocarbene with 2-(benzylideneamino)pyridines, undergo intramolecular 1,5-cyclization to give 2-aryl-3-chloroimidazo[1,2-a]pyridines, which undergo partial conversion to 2-aryl-3-chloro-4H-pyrido[1,2-a]pyrimidin-4-ones under the reaction conditions. 2-Aryl-3-bromoimidazo[1,2-a]pyridines and 2-[N-(1-aryl-2,2,2-tribromoethyl)amino]pyridines, respectively, are obtained in the reaction of dibromocarbene and the tribromomethyl onion generated in the reaction of bromoform with potassium hydroxide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 810–816, June, 1991.     

Heterocyclization of 1,1-dicyano-2-(trifluoromethyl)ethylenes with 1,3,3-trimethyl-3,4-dihydroisoquinoline and its derivatives

1,3,3-Trimethyl-3,4-dihydroisoquinolines react with 1,1-dicyano-2,2-bis(trifluoromethyl)ethylene to give 4-amino-6,6-dimethyl-2,2-bis(trifluoromethyl)-3-cyano-6,7-dihydro-2H-benzo[a]quinolizines. The reaction of 3,3-dimethyl-1-cyanomethylidene-1,2,3,4-tetrahydroisoquinoline and the methyl ester of 3,3-dicyano-2-(trifluoromethyl)acrylic acid leads to 5,5-dimethyl-3-oxo-2-(trifluoromethyl)-2-(dicyanomethyl)-2,3,5,6-tetrahydropyrrolo[2,1-a]isoquinoline.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1888–1892, August, 1992.     

Synthetic studies on diuretics. 5-(3,3-N,S-substituted-2-propenoyl)-2,3-dihydro-2- benzo[b]furancarboxylic acids

6,7-Dichloro-2,3-dihydro-2-benzo[b]furancarboxylic acid derivatives having a 3,3-N,S-disubstituted-2-propenoyl group at the 5-position were prepared by alkylation of 5-(thiocarbamoyl)acetyl derivatives of the 2,3-dihydro-2-benzo[b]furancarboxylic acid ester or by acetal exchange reaction of 5-[3,3-bis(alkylthio)-2-propenoyl] derivatives. Synthesis of 5-[4 and/or 5-(di)substituted-4-thiazolin-2-ylidene]acetyl-2,3- dihydro-2-benzo[b]furancarboxylic acids was also achieved by the reaction of 2-halo-1-methoxyethyl isothiocyanate with the 5-acetyl derivative in the presence of base or through sulfide contraction of 2-[[6,7-dichloro-2-methoxycarbonyl-2,3-dihydrobenzo[b]furan-5-yl) carbonyl)-methylthio]thiazolium bromide. Some of the compounds which were synthesized showed potent natriuretic activities in rats and mice. The structure-activity relationship is also discussed.     

Synthesis of 2-methyl(phenyl)-6-methyl-7-phenylindolisine and 2-methyl(phenyl)indolisino-[6,7-a]indene

Substituted indolisines were obtained from 2-methyl-, 2-ethoxymethyl-, and 2-phenoxymethyl-5-methyl-4-phenylpyridines. 3-Methyl-2-azafluorene was used in the syntheses of a four-ring condensed system — substituted indolisino[6,7-a]indene.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1395–1397, October, 1971.     

Reactions of 3-methyl-1-(2-pyridyl)-4-chloro-5-formyl-6,7-dihydroindazole

The reactions of 3-methyl-1-(2-pyridyl)-, 3-methyl-1-phenyl-, and 3-methyl-1,6-diphenyl-4-chloro-5-formyl-6,7-dihydroindazoles with guanidine and benzo- and 3- and 4-pyridinecarbamidines gave the corresponding 8-substituted 1-methyl-3-(2-pyridyl)-and 1-methyl-3-phenyl-4,5-dihydropyrazolo[5,4-h]quinazolines. With acetic anhydride the same indazole derivatives gave the 4-acetoxy-5-formyl derivatives, and with hydroxylamine they gave4-chloro-5-hydroxyiminomethyl-6,7-dihydroindazoles. Thereactionof4-acetoxyl-1-(2-pyridyl)-5-formyl-6,7-dihydroindazole with hydroxylamine gave 8-methyl-6-(2-pyridyl)-4,5-dihydroisoxazolo[5,4-e]indazole, while dehydration of 5-hydroxyiminomethyl-3-methyl-4-chloro-6,7-dihydroindazole gave the 4-chloro-5-cyano derivative. The reaction of the latter with nucleophilic reagents was investigated.Riga Technical University, Riga, Latvia LV-1658. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1209–1213, September, 1998.     

Molecular structure and tautomeric conversions of 5-(4-dimethylaminophenyl)-7-phenyl-6,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine

The x-ray structure is solved and the three-dimensional structure is analyzed for 5-(4-dimethylaminophenyl)-7phenyl-6,7-dihydro-1,2,4-triazolo[1,5-a]pyrimidine. Its reverse isomerization into the 4,7-dihydro species is studiedTranslated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 933–936, July, 1992.     

The reaction of 2-hetarylacetonitriles with heterocyclic haloaldehydes

The reaction of 4-oxo-3,4-dihydroquinazolyl-and benzimidazolylacetonitriles with 2-chloro-2-quinolinecarbaldehydes and 1-aryl-5-chloro-3-methyl-1H-pyrazole-4-carbaldehydes gave the corresponding 3-(2-chloro-3-quinolyl)-2-(4-oxo-3,4-dihydro-2-quinazolyl)-2-propenenitriles and 3-(1-aryl-5-chloro-3-methyl-1H-4-pyrazolyl)-2-hetaryl-2-propenenitriles. Intramolecular cyclization of these compounds gives 15-oxo-15H-benzo[6,7][1,8]naphthyridino[2,1-b]quinazoline-6-carbonitriles, 1-aryl-3-methyl-11-oxo-1,11-dihydropyrazolo[4′,3′:5,6]pyrido[2,1-b]quinazoline-5-carbonitriles, and 1-aryl-3-methyl-1H-benzo[4,5]imidazo[1,2-a]pyrazolo[4,3-e]pyridine-5-carbonitriles.     

Synthesis,crystal structure,DFT, molecular docking and antitumor activity of 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin-1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one

Research on Chemical Intermediates - In this study, the compound 4-(2-chlorobenzyl)-1-(5-fluoro-2-hydroxy-3-((4-methylpiperidin -1-yl)methyl)phenyl)-[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one (1)...     

Chemistry of acyl(imidoyl)ketenes. 8*. Thermolysis of 3-alkoxycarbonyl- 5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]- quinoxaline-1,2,4-triones. Structure of 2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)- 2,4-di(ethoxycarbonyl)-6-phenyl-2,3,5,6-tetrahydro- 1h-pyrido[1,2-a]quinoxaline-1,3,5-trione

3-Alkoxycarbonylmethylene-1-phenyl-1,2,3,4-tetrahydro-2-quinoxalones, obtained by the interaction of dialkyl esters of oxaloacetic acid and N-phenyl-o-phenylenediamine, react with oxalyl chloride with the formation of 3-alkoxycarbonyl-5-phenyl-1,2,4,5-tetrahydropyrrolo[1,2-a]quinoxaline-1,2,4-triones. Alkoxycarbonyl(2-oxo-1-phenyl-1,2-dihydro-3-quinoxalinyl)ketenes, generated on thermal decarbonylation of the latter, are stabilized by participation in a [4+2] cyclodimerization reaction with the formation of 2,4-di(alkoxycarbonyl)-2-(3-oxo-4-phenyl-3,4-dihydro-2-quinoxalinyl)-6-phenyl-2,3,5,6-tetrahydro-1H-pyrido[1,2-a]quinoxaline-1,3,5-triones. The crystal and molecular structure of the di(ethoxycarbonyl) derivative have been investigated by X-ray structural analysis.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1501–1506, October, 2004.     

Imine-enamine tautomerization of dihydroazolopyrimidines 4. Synthesis and tautomerization of 5-(2-hydroxyphenyl)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines

The condensation of 3-amino-1,2,4-triazole with 2-hydroxychalcones gives 7-aryl-5-(2-hydroxyphenyl)-4,7(6,7)-dihydro-1,2,4-triazolo[1,5-a]pyrimidines. Both tautomeric forms were isolated for a number of these compounds. PMR spectroscopy was used to show that the enamine form is predominant in DMSO in contrast to the case in CHCl₃.For Communication 3, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1353–1356, October, 1993.     

SYNTHESIS,CRYSTAL STRUCTURE,AND DFT STUDY OF 1-(PYRROLIDIN-1- YL-METHYL)-4-(THIOPHEN-2-YL-METHYL)- [1,2,4]TRIAZOLO[4,3-a]QUINAZOLIN-5(4H)-ONE

Journal of Structural Chemistry - In this paper, the triazoloquinazolinone derivative 1-(pyrrolidin-1-yl-methyl)-4-(thiophen-2-yl-methyl)[1,2,4]triazolo[4,3-a]quinazolin-5(4H)-one is synthesized...     

Synthesis,Structure and Cytotoxicity Testing of Novel 7-(4,5-Dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-Imine Derivatives

The appropriate 1-arylhydrazinecarbonitriles 1a–c are subjected to the reaction with 2-chloro-4,5-dihydro-1H-imidazole (2), yielding 7-(4,5-dihydro-1H-imidazol-2-yl)-2-aryl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-imines 3a–c, which are subsequently converted into the corresponding amides 4a–e, 8a–c, sulfonamides 5a–n, 9, ureas 6a–I, and thioureas 7a–d. The structures of the newly prepared derivatives 3a–c, 4a–e, 5a–n, 6a–i, 7a–d, 8a–c, and 9 are confirmed by IR, NMR spectroscopic data, as well as single-crystal X-ray analyses of 5e and 8c. The in vitro cytotoxic potency of these compounds is determined on a panel of human cancer cell lines, and the relationships between structure and antitumor activity are discussed. The most active 4-chloro-N-(2-(4-chlorophenyl)-7-(4,5-dihydro-1H-imidazol-2-yl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)benzamide (4e) and N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-(p-tolyl)-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-[1,1′-biphenyl]-4-sulfonamide (5l) inhibits the growth of the cervical cancer SISO and bladder cancer RT-112 cell lines with IC₅₀ values in the range of 2.38–3.77 μM. Moreover, N-(7-(4,5-dihydro-1H-imidazol-2-yl)-2-phenyl-6,7-dihydro-2H-imidazo[2,1-c][1,2,4]triazol-3(5H)-ylidene)-4-phenoxybenzenesulfonamide (5m) has the best selectivity towards the SISO cell line and induces apoptosis in this cell line.