Synthesis of 5-[2-(Phenoxy)ethyl] Derivatives of 6-Methyluracil, 6-Methyl-2-thioxo-2,3-dihydro-1H-pyrimidin-4-one,and 2-Imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one

A synthesis of novel derivatives of 6-methyluracil, 6-methyl-2-thioxo-, and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one containing a 2-(phenoxy)ethyl substituent at position 5 of the pyrimidine ring has been carried out. It was found that 5-[2-(phenoxy)ethyl] derivatives of 6-methyl-2-thioxo- and 2-imino-6-methyl-2,3-dihydro-1H-pyrimidin-4-one are obtained by the condensation of the corresponding ethyl 3-oxo-2-(2-phenoxyethyl)butanoates with thiourea or guanidine. 6-Methyl-5-[2-(phenoxy)ethyl]uracils can be prepared by treating 6-methyl-5-[2-(phenoxy)ethyl]-2-thioxo-2,3-dihydro-1H-pyrimidin-4-ones with an excess of aqueous monochloroacetic acid solution. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1213–1217, August, 2005.     

Synthesis and Crystal Structure of Tert-butyl 4-[(E)-4-(1,3 -Dioxo-1,3-dihydro-2H-isoindol-2-yl)-1-butenyl] Benzoate

1 INTRODUCTION Phthalimide and its derivatives are synthetic mate- rials, which are widely used as important chemical intermediates of biosensors[1] and many drugs such as Citalopran[2], luminal[3], Beta-Lactam[4] and the No. three generation quinolones[5], and they have been identified as active groups of some drugs and chemical luminescence reagents[6, 7]. Tert-butyl 4- [(E)-4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-1- butenyl] benzoate is an intermediate of a new type of insulin sen…     

4-Oxo-3,4-dihydroquinazolinyl- and Benzimidazolylacetonitriles in Annelation Reactions of a Haloquinoline Ring

The interaction of 4-oxo-3,4-dihydroquinazolinyl- and benzimidazolylacetonitriles with 2,6-dihalobenzaldehydes leads to 3-(2,6-dihalophenyl)-2-(4-oxo-3,4-dihydro-2-quinazolinyl)acrylonitriles and 2-(1H-benzo[d]imidazol-2-yl)-3-(2,6-dihalophenyl)acrylonitriles respectively. As a result of intramolecular cyclization of these nitriles 4-halo-12-oxo-12H-quino[2,1-b]quinazoline-6-carbonitriles and 4-halobenzo[4,5]imidazo[1,2-a]quinoline-6-carbonitriles respectively are formed.     

Synthesis and Crystal Structure of Ethyl 3-（4-Chlorophenyl）-3,4-dihydro-6-methyl-4-oxo-2- （pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate

The crystal structure of the title compound ethyl 3-（4-chlorophenyl）-3,4-dihydro-6- methyl-4-oxo-2-（pyrrolidin-1-yl）furo[2,3-d]pyrimidine-5-carboxylate （C20H20ClN3O4, Mr= 401.84） has been prepared and determined by single-crystal X-ray diffraction. The crystal is of monoclinic, space group P21/n with a = 20.6215（9）, b = 8.5311（4）, c = 21.6886（9） A^°, β = 91.607（1）°, V = 3814.0（3）A^°^3, Z = 8, Dc = 1.400 g/cm^3, F（000） = 1680, μ = 0.233 mm^-1, R = 0.0718 and wR = 0.1545 for 6717 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals two crystallographically independent molecules in the asymmetric unit.     

Synthesis of 4-amino-5-(4,6-diphenyl-2-pyrimidinyl)-3,4-dihydro-2H-1,2,4-triazole-3-thione and its reactions with C-electrophiles

4-Amino-5-(4,6-diphenyl-2-pyrimidinyl)-3,4-dihydro-2H-1,2,4-trazole-3-thione is formed from the reaction of 4,6-diphenylpyrimidinecarboxylic acid or its ethyl ester with thiocarbonyl hydrazide. Alkylation of the product leads to S-alkyl derivaties or 6-substituted 3-(4,6-diphenyl-2-pyriimidinyl)-7H-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazine. Acetylation of 4-amino-5-(4,6-diphenyl-2-pyrimidinyl)-3,4-dihydro-2H-1,2,4-triazole-3-thione gave under different conditions monoacetyl-, diacetyl, and triacetyl derivatives at the amino group and the N₍₂₎ atom, whereas benzoylation gave a benzoyl group at the amino group and 3-(4,6-diphenyl-2-pyrimidinyl)-6-phenyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, 1088–1094, July, 2007.     

Novel One-Pot Multicomponent Synthesis of Substituted 2,3-Dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones and Substituted 3-[3-(N′-Benzylidene-hydrazino)-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones

A one-pot procedure has been developed for the synthesis of substituted 2,3-dihydro-2-(6-(4-hydroxy-6-methyl-2-oxo-2H-pyran-3-yl)-7H-[1,2,4]triazolo[3,4-b] [1,3,4]thiadiazin-3-yl)phthalazine-1,4-diones by reaction of 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and phthalic anhydrides in acetic acid medium. Similarly, a one-pot, three-component synthetic procedure has been developed for substituted 3-[3-(N¹-benzylidene-hydrazino)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl]-4-hydroxy-6-methyl-pyran-2-ones from 3-(2-bromoacetyl)-4-hydroxy-6-methyl-2H-pyran-2-one, 4-amino-5-hydrazino-4H-[1,2,4]triazole-3-thiol, and various aromatic aldehydes in absolute ethanol and a few drops of glacial acetic acid.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Reaction of 2,3-Dihydro-1,5-benzothiazepines and Phenylacetyl Chloride in the Presence of Triethylamine： A New Aspect on the Formation Mechanism of Dihydro-1,3-oxazin-4-one Derivatives

2a,4-Disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][ 1,5]benzothiazepin-1-ones, as well as 2-substi-tuted 2,3-dihydro-3-phenylacetyl-2-styryl-benzothiazoles and 4a,6-disubstituted 3- .benzyl-4a,5-d/hydro-2-phenyl-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, were obtained from the reaction of 2,4-disubstituted 2,3-dihydro-1,5-benzothiazepines with phenylacetyl chloride in the presence of triethylamine. The mechanism for the formation of 4a,5-dihydro-1H,6H-[1,3]oxazino[2,3-d][1,5]benzothiazepin-1-ones, 2,3-dihydro-1,3-oxazin-4-one derivatives, was suggested.     

Studies on the syntheses of heterocycles from 3-arylsydnone-4-carbohydroximic acid chlorides with N-arylmaleimides, [1,4]naphthoquinone and aromatic amines

3-Arylsydnone-4-carbohydroximic acid chlorides (1) could react with N-arylmaleimides (3a–b) or 2-methyl-N-phenylmale-imide (3c) to give 3-(3-arylsydnon-4-yl)-5-aryl-3a,6a-dihydro-pyrrolo[3,4-d]isoxazole-4,6-diones (4a–h) or 6a-methyl-3-(3-arylsydnon-4-yl)-5-phenyl-3a,6a-dihydro-pyrrolo[3,4-d]isoxazole-4,6-diones (4i–l), respectively. However, 3-(arylsydnon-4-yl)-naphtho[2,3-d]isoxazole-4,9-diones (6a–d) were obtained in good yield by the reaction of carbohydroximic acid chlorides 1 with [1,4]naphthoquinone. Furthermore, 2-(3-arylsydnon-4-yl)benzoxazoles (9a–d) and 2-(3-arylsydnon-4-yl)benzothiazoles (9e–h) were obtained via the reaction of carbohydroximic acid chlorides 1 with ortho-substituted aromatic amines 7a and b.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

Synthesis of Some 3-Substituted 1,2-Dihydroindoles

The reaction of 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-methyl carboxylate 2 with hydrazine hydrate in methanol gave 4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6-carbonylhydrazine 3. Furthermore, the reaction of 3 with carbon disulfide and then hydrazine hydrate afforded 3-[6-(4-amino-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)-4-oxo-1,3-thiazin-2-yl] hydrazone-1,3-dihydroindol-2-one 5. the latest reacted with DMAD to give {6-hydroxy-3-[4-oxo-2-(2-oxo-1,2-dihydroindol-3-ylidene)hydrazone-1,3-thiazin-6yl]-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-7-ylidene}methoxycarbonylmethylene 6.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Synthetic Approach to 6-Benzoyl-2H-[1,2,4]triazine-3,5-dione and 6-Benzyl-5-thioxo-3,4-dihydro-2H-[1,2,4]triazin-3-one and Studies on Their Transformation to Fused[1,2,4]triazine Systems

Reaction of phenylpyruvic acid with semicarbazide afforded 6-benzyl-2H-[1,2,4]triazine-3,5-dione ( 1 ) which upon oxidation with potassium dichromate furnished 6-benzoyl-2H-[1,2,4]triazine-3,5-dione ( 2 ) in good yield. Constructing pyrazolo[3,4-e][1,2,4]triazine system ( 4 ) was achieved by reacting 2 with arylhydrazines in ethanolic solution. However treatment of 2 with the less reactive heteroarylhydrazines gave only the corresponding hydrazones ( 3 ). Attempt for constructing 1,2,4,5,10-pentaaza-dibenzo[a,d]cyclohept-3-one ( 7 ) from 2 was failed and (benzoimidazol-2-yl) [1,2,4] triazine derivative ( 6 ) was the only product. Reaction of 1 with phosphorus pentasulphide afforded compounds 8 and 9 . Compound 8 was transformed to the hydrazino compound 14 , which led to the construction of triazolo[4,3-d] [1,2,4]triazine system. Thus compounds 15 and 16 were obtained by reacting 14 with carbon disulfide or acetic anhydride respectively. Attempt to couple 8 with chloroacetic acid failed, while it's known isomer 10 led to the formation of thiazolo [2,3-c] [1,2,4]triazine derivative ( 13 ). Simple theoretical calculation using AM1 and PM3 semiempirical Hamitonian provided rational ways to correlate the reactivity with structure proposed.     

The synthesis of 4-(2,6,10-trimethyl-1,3,5,9-undecatetraenyl)benzoic acid based on alkoxy alkene-acetal condensation

4-(2,6,10-Trimethyl-1,3,5,9-undecatetraenyl)benzoic acid (1) was synthesized starting from ethyl 4-formylbenzoate (2) and linalool. The key intermediate, ethyl 4-(2-methyl-3-oxo-1-propenyl)benzoate (5), was obtained by the addition of diethyl acetal (3), prepared from2, to ethyl 1-propenyl ether (EPE) followed by the hydrolysis of the resulting adduct.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 914–915, May, 1993.     

Synthesis and Crystal Structure of Ethyl 2-(6-(1,3-Dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) Butanoate

The title compound ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) butanoate 3 was synthesized by the reaction of ethyl 2-(6-amino-7-fluoro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) butanoate with 4,5,6,7-tetraydrophthalic anhydride,and its structure was determined by X-ray single-crystal diffraction.The crystal belongs to the monoclinic system,space group P21/n with a = 9.3469(2),b = 16.7715(5),c = 13.7153(4) ,β = 104.9680(10)°,μ = 0.107 mm-1,Mr = 430.42,V = 2077.08(10) 3,Z = 4,Dc = 1.376 g/cm3,F(000) = 904,T = 296(2) K,R = 0.0508 and wR = 0.1478.     

Interaction of 3-Chloro-2-halopropenyl Ketones with β-Aminocrotonic Acid Ethyl Ester

The reaction of 3-chloro-2-halo-1-propenyl ketones with β-aminocrotonic acid ethyl ester leads to the formation of ethyl esters of 6-alkyl(aryl, benzyl, cyclohexyl)-4-chloromethyl-2-methylnicotinic acids. It was established that at increased temperatures the compounds obtained are partially converted into the corresponding dihydrofuro[3,4-c]pyridines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1184–1188, August, 2005.     

Synthesis and Crystal Structure of N—tert—butyl—N′—（2，4—dichlorobenzoyl）—N—[1—（4—chlorophenyl）—1,4—dihydro—6—methylpyridazine—4—oxo—3—carbonyl]hydrazine

1 INTRODUCTIONPyridazinone derivatives represent one of the most active classes of compounds possessing a wide spectra of biological activity. They are widely used in pharmaceuticals and agrochemicals[1,2]. Rohm- Haas Company had reported that N-tert-butyl- dibenzoylhydrazine exhibits excellent insecti- cides[3, 4] and t-butyl plays an important role in the insecticide activity [5]. In the previous paper, we had reported that 1-aryl-1,4-dihydro-3- acylhydrazino- carbonyl-4-one-6-methylpy…     

Facile synthesis and characterization of novel pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one and pyrido[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine incorporating 1,3-diarylpyrazole moiety

4-(3-(4-Hydroxyphenyl)-1-phenyl-1H-pyrazol-4-yl)-6-phenyl-2-thioxo-1,2-di hydro-pyridine-3-carbonitrile (1) reacted with ethyl chloroacetate (2) in ethanolic sodium acetate solution to yield the corresponding ethyl (3-cyanopyridin-2-ylsulphanyl)acetate derivative 3. Intramolecular cyclization of compound 3 was achieved by its heating in DMF containing potassium carbonate to afford the corresponding ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate derivative 4 which reacted with hydrazine hydrate in refluxing pyridine to yield the starting material 3-aminothieno[2,3-b]pyridine-2-carbohydrazide derivative 7. Compound 7 reacted with different reagents such as triethylorthoformate, formic acid, acetic acid and acetic anhydride to afford the target molecules pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives 8–10, 12 and 13 in good to excellent yields. On the other hand, pyridine-2(1H)-thione derivative 1 reacted with hydrazine hydrate in refluxing pyridine to give the other starting material 3-amino-1H-pyrazolo[3,4-b]pyridine derivative 20 which reacted with acetylacetone under reflux to afford the target molecule pyrido[2′,3′:3,4]pyrazolo[1,5-a]-pyrimidine derivative 21 in a good yield. The structures of target molecules were elucidated using elemental analyses and spectral data.     

Synthesis of New 4,5-Dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine–Derived Ureas and Their Anticancer Activity

A new series of 1,2,4-triazolo[4,3-a]-quinoline derivatives were designed and synthesized to meet the structural requirements essential for anticancer activity. N-1-(5-Methylisoxazol-4-yl/4-fluoro-2,3-dihydro-1H-inden-1-yl/aryl)-N’-3-(4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-yl) urea derivatives were accomplished in good yields by the reaction of 4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinolin-7-amine with 3-(3-chloro-5-fluoro-2-methoxyphenyl)-5-methyl-isoxazole-4-carboxylic acid, 4-fluoro-2,3-dihydro-1H-indene-1-carboxylic acid, and various simple aromatic carboxylic acids in the presence of diphenyl phosphoryl azide (DPPA). All the newly synthesized title compounds were characterized by elemental and spectral data. Furthermore, anticancer activity was screened for the title compounds (12a–j) in vitro against human neuroblastoma cell lines (SK N SH) and human colon carcinoma cell lines (COLO 205) by using the MTT cell viability method. A few of them (12a and 12b) possess significant cytotoxicity, and some other compounds 12d-f and 12j displayed moderate cytotoxicity against both cell lines.     

Heterophase N-aminomethylation of 5-arylidenepseudothiohydantoins by arylamines and aqueous formaldehyde in aromatic solvents: Effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process

We have obtained a series of 3-aryl-7-arylidene-3,4-dihydro-2H-[1,3]thiazolo[3,2-a][1,3,5]triazin-6(7H)-ones by means of heterophase aminomethylation of 2-amino-5-arylidene-1,3-thiazol-4(5H)-ones with aqueous formaldehyde and aromatic amines in benzene or toluene. We explain the effect of substituents in the heterocyclic substrate and the aryl amine on the efficiency of the process within a detailed scheme for one of the possible aminomethylation reaction routes. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1095–1104, July, 2006.     

Synthesis of 1,3-Bis[(3-aryl)-S-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes

1,3-bis[(3-aryl)-s-triazolo[3,4-b]-[1,3,4]thiadiazole-6-yl]benzenes 2 were synthesized in high yields by the reaction of 3-aryl 4-amino-5-mercapto-1,2,4-triazole 1 with m-phthalic acid.