Studies on antiatherosclerotic agents. Synthesis of 5-substituted derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1(2H)-phthalazinone.off.

Several 5-substituted derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1(2H)- phthalazinone were prepared by means of nitration, reductive amination, and diazonium decomposition. The substituents introduced included NO2, NH2, F, Cl, CN. Among the derivatives, the fluorine compound was obtained only in poor yield because intramolecular cyclization occurred predominantly.     

The chemistry of 2H-3,1-benzoxazine-2,4-(1H)dione (isatoic anhydride) 3. One step synthesis of 2,3-dihydro-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones

Reactions of N-haloalkylisatoic anhydrides with amines to produce piperidinobenzamides ( 2 ), pyrrolidinobenzamides ( 4 and 5 ), and 2,3-dihydro-6-methyl-4,1,6-benzoxadiazonine-5,7-(1H,6H)diones ( 10 ) are described. Spectral data are also discussed.     

Studies on antiatherosclerotic agents. Synthesis of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone derivatives and related compounds

Derivatives of 7-ethoxycarbonyl-4-formyl-6,8-dimethyl-1(2H)-phthalazinone and closely related compounds were synthesized using Wittig and epoxidation reactions. Ring opening amination of the epoxides were carried out using dimethylaluminum amide reagents under mild reaction conditions. beta-Keto ester and beta-diketone moieties were introduced through diazo derivatives. These moieties were reacted with hydrazine hydrate to produce 4-pyrazolyl derivatives. The derivatives were tested for their inhibitory effect on platelet aggregation, and their relaxing effect on blood vessels.     

Synthesis, structure, and properties of piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate

Condensation of 4-chlorobenzaldehyde with cyanothioacetamide and dimedone in the presence of piperidine afforded piperidinium 3-(4-chlorophenyl)-2-cyano-3-(2-hydroxy-4,4-dimethyl-6-oxocyclohex-1-enyl)thiopropionimidate. This salt was studied by X-ray diffraction analysis and used in the synthesis of the previously unknown partially hydrogenated 2-alkylthioquinolin-2-ones. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 733–737, April, 2000.     

Three-component condensation in the synthesis of 4-(2-chlorophenyl)-3-cyano-5-ethoxycarbonyl-6-propyl-3,4-dihydropyridine-2(1H)-thione

Condensation of 2-chlorobenzaldehyde with cyanothioacetamide and ethyl butyroylacetate results in 4-(2-chlorophenyl)-3-cyano-5-ethoxycarbonyl-6-propyl-3,4-dihydropyridine-2(1H)-thione, whose further transformation affords the corresponding substituted 2-methylthio-1,4-dihydropyridine. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 173–175, January, 2000.     

Studies on antiatherosclerotic agents. Synthesis and inhibitory activities on platelet aggregation of 4-aryl derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1 (2H)-phthalazinone.

4-Aryl derivatives of 7-ethoxycarbonyl-6,8-dimethyl-1(2H)-phthalazinone and related derivatives were newly synthesized in order to test for their inhibitory activities on platelet aggregation. 4-(2-Anisyl) compound and the corresponding 1-chloro derivative demonstrated significant activity.     

Synthesis of 2,4-(1H,3H)-quinazolinediones

Improved procedures for syntheses of kilogram quantities of quinazolinedione 5 and its intermediates 2,3 and 4 are described. The mechanism of formation of 5 is discussed as well as a side reaction resulting in 7 .     

Synthesis of 3-(aminooxoethyl)-6-methyl-1-(thiethan-3-yl)-pyrimidine-2,4-(1H,3H)-diones

A new approach to prepare 2-chloroacetamides has been developed, based on the reaction of chloroacetyl chloride with excess of secondary amines. Alkylation of 6-methyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-dione with the synthesized 2-chloroacetamides in the presence of potassium carbonate has afforded N ³-acetamido-substituted 6-methyl-1-(thiethan-3-yl)pyrimidine-2,4(1H,3H)-diones.     

Synthesis and antiviral evaluation of 1,3-dimethyl-6-(1H-1,2,3-triazol-1-YL)pyrimidine-2,4(1H,3H)-dione derivatives

Some 6-(1H-1,2,3-triazol-1-yl)pyrimidine-2,4(1H,3H)-dione derivatives were synthesized via the reaction of 6-azido-1,3-dimethyluracil with ethyl acetoacetate in the presence of sodium ethoxide. The antiviral activities of these compounds against Hepatitis A virus (HAV, MBB-cell culture adapted strain) and Herpes simples virus type-1 (HSV-1) were tested.     

Pyrimidines. 65. Synthesis of 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones

Several 6-substituted thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives were synthesized. 6-Ethoxycarbonyl derivatives 3 and 7 were prepared by treatment of 6-chloro-5-formyluracil 1 and 6-chloro-5-cyanouracil 6 with ethyl 2-mercaptoacetate in the presence of a base. Electrophilic substitution reactions (Vilsmeier-Haack reaction, bromination, and nitration) of 5,6-unsubstituted thieno[2,3-d]pyrimidine 9 , prepared by condensation of 6-mercaptouracil 8 with chloroacetaldehyde, afforded the corresponding 6-formyl-, 6-bromo-, and 6-nitrothieno[2,3-d]pyrimidines 10, 15 and 16 , respectively.     

Synthesis of 3-substituted 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines as potential antitumor agents

A series of 3-substituted (chloro, bromo, fluoro or methyl) 7-(3,3-dimethyl-1-triazeno)-10-methylphenothiazines were synthesized as potential antitumor agents. Treatment of p-substituted anilines with ammonium thiocyanate in the presence of bromine gave 6-substituted 2-aminobenzthiazoles which, after methylation with methyl iodide were hydrolyzed in 50% potassium hydroxide to give 5-substituted 2-methylaminothiophenols in moderate yield. Condensation of methylaminothiophenols with 3,4-dichloronitrobenzene in ethanol under an atomsphere of nitrogen gave adducts which were cyclized in dimethylformamide under the catalysis of copper and cuprous iodide to give 3-substituted 7-nitro-10-methylphenothiazines. The nitro group was reduced to the amino function with stannous chloride. Diazotization of the amines followed by coupling with dimethylamine gave the corresponding triazenes.     

Synthesis of derivatives of 1-(2-carboxyethyl)-(1H,3H)-quinazoline-2,4-dione

The action of alkylating agents on 1-(2-carboxyethyl)-(1H,3H)-quinazoline-2,4-dione was utilized to synthesize corresponding esters. The hydrolysis and hydrazinolysis of the last were accomplished. Polyphosphoric acid effected the conversion of 1-(2-carboxyethyl)quinazolinedione to 1,3,7-trioxopyrido[1,2,3-k,j]quinazoline.Kaunas Technological University, Kaunas LT 3028. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 110–112, January, 1997.     

Electron-impact induced fragmentation of 3-hydroxy quinazoline-2,4(1H,3H) dione,pyridopyrimidine-2,4(1H,3H)diones,lumazine and alloxazine

Electron-bombardment of the N-3-hydroxy derivatives of the above-mentioned condensed uracils revealed that the major fragmentations involved the heterocyclic ring. The most intense ion proved to be the M-32 ion which was created by the loss of the NHOH radical from the molecular ion. Mechanisms for this transition are presented. Other fragmentations common to these systems are discussed and compared with those reported for the corresponding N-3 deoxy analogs of the title compounds. The mass spectral fragmentations of the O-methyl-, N-methyl- and O,N-dimethyl derivatives of 3-hydroxyquinazoline-2,4(1H,3H)dione were analyzed and were consistent with those expected from these structures. Electron bombardment of the 3-benzenesulfonyloxy derivatives of the title compounds resulted primarily in the scission of the sulfonate group in preference to that of the heterocyclic dione ring. These sulfonates also showed ions which indicated that a Lossen rearrangement had taken place in the mass spectrometer.     

Synthesis of 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones

The reactions of 1-substituted 2-nitro-3-phenylaminoprop-2-en-1-ones with cyanothioacetamide afforded the corresponding 6-substituted 3-cyano-5-nitropyridine-2(1H)-thiones, which were used for the synthesis of 6-substituted 3-cyano-2-methylthio-5-nitropyridines and 7-substituted 4-hydroxy-8-nitropyrido[2",3":4,5]thieno[2,3-b]pyridin-2(1H)-ones.     

Studies on naphthyridines. Part 2 . Synthesis of 4-substituted and 6-substituted 1,6-naphthyridin-5(6H)-ones

Ethyl 4-substituted 2-methyl-5-oxo-5,6-dihydro-1,6-naphthyridine-3-carboxylates 3a-h were synthetized in a one-step reaction from diethyl 2,6-diraethylpyridine-3,5-dicarboxylates 1a-h by aminomethinylation with 1,3,5-triazine (2). The 6-substitued derivatives 6a-z,aa-ff could be obtained from diethyl 2-[2-(dimethylamino)-vinyl]-6-methylpyridine-3,5-dicarboxylate ( 4 ) either directly or via the isolated intermediate 2-[2-(arylamino)-vinyl]pyridine compounds 5a-i.     

6-三氟甲基嘧啶-2,4(1H,3H)-二酮类化合物的合成及其除草活性

以三氟乙酰乙酸乙酯和单取代脲为原料,设计并合成了10个6-三氟甲基嘧啶-2,4(1H,3H)-二酮类化合物,其结构经1H NMR和元素分析确证。初步生物活性测试表明,部分化合物具有较好的除草活性。在用药量为100μg.mL-1时,3-(4-氟苄基)-6-三氟甲基嘧啶-2,4(1H,3H)-二酮对油菜根长生长抑制率为98%。     

Synthesis of 4,6-(and 5,7-)dimethoxy-3,3-dimethyl-1-indanones

Grignard reaction of ethyl 3-(3,5-dimethoxyphenyl)-propionate (4) followed by cyclodehydration of the carbinol (5) with conc H₂SO₄ gave 4,6-dimethoxy-3,3-dimethylindane (6). Oxidation of the indane (6) with CrO₃-pyridine complex in methylene chloride gave 4,6-dimethoxy-3,3-dimethylindan-1- one (1) in high yield. Conjugate addition of methyl magnesium iodide to methyl α-cyano-β-methyl-3,5-dimethoxycinnamate (11), prepared from 3,5-dimethoxyacetophenone (10) by Knoevenagel condensation, resulted in methyl 2-cyano-3-(3,5-dimethoxyphenyl)-3,3-dimethylpropionate (12). Refluxing the ester (12) with aq DMSO containing sodium chloride gave the corresponding nitrile (15) which underwent Höesch reaction to yield 5,7-dimethoxy-3,3-dimethylindan-1-one (2).