Synthesis of Alkyl and Aryl Substituted Benzo[h]Naphtho[1,2-b][1,6]naphthyridines

The reaction of 4-chloro-2-methylquinolines and 1-naphthylamine under neat conditions yielded 2-methyl-N-(1-naphthyl)quinolin-4-amines. These potential intermediates on reaction with aliphatic and aromatic carboxylic acids yielded the respective 7-alkyl and -aryl substituted benzo[h]naphtho[1,2-b][1,6]naphthyridines. The highly deshielded protons in the final compounds were assigned on the basis of 2D NMR studies.     

新型非对称二苯并[b,f][1,5]二氮杂环辛四烯的合成

以两种不同取代的2-氨基二苯甲酮为原料,氯苯为溶剂,BF3-Et2O为脱水剂,通过分子间脱水一步环化缩合制备非对称二苯并[b,f][1,5]二氮杂环辛四烯衍生物。运用HPLC监控反应过程,优化合成工艺,得到最佳反应条件为:等物质的量的两种不同取代2-氨基二苯甲酮和BF3-Et2O,在氯苯中回流反应12 h。化合物4a^4c为新化合物,其结构经1H NMR,13C NMR和MS(ESI)表征。     

Synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3-e][1,6]naphthyridine-8-ones via Pictet–Spengler cyclization

An efficient method for the synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet–Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe–Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF_3·OEt_2 gives pyrimidothieno[1,6]naphthyridines in good yields.     

Synthesis,Reactions, and Structure of 5-Cyano-4-ethoxy-1-ethoxycarbonyl-2-methylazuleno[1,8-b,c]pyran

Bicyclic azulene compounds, ethyl 4-(cyanoethoxycarbonylmethyl)-2-methylazulene-1-carboxylate (2) and ethyl 4-(cyanoethoxycarbonylmethyl)azulene-1-carboxylate (3) were prepared from ethyl 4-chloro-2-methylazulene-1-carboxylate (7) and ethyl 4-ethoxyazulene-1-carboxylate (8), respectively. Oxidation of 2 with DDQ gave the title compound, 5-cyano-4-ethoxy-1-ethoxycarbonyl-2-methylazuleno[1,8-b,c]pyran (1) and a minor compound, ethyl 4-cyanomethyl-2-methylazulene-1-carboxylate (9). Oxidation of 3 by DDQ produced only ethyl 4-cyanomethylazulene-1-carboxylate (10), Reaction of 1 with 100% H₃PO₄ at room temperature and 100 °C gave 5-cyano-4-ethoxy-2-methylazuleno[1,8-b,c]pyran (11) and 2-methyl-4,5-dihydrozuleno[1,8-b,c]pyran-4-one (12), respectively. All the new compounds were characterized by IR, UV-vis, NMR and Mass spectra, and the structure of 1 was determined by X-ray crystallography. Crystal data for 1; space group P2₁/n, a = 7.391(1), b = 9.660(5), c = 22.859(1) Å, B = 97.01(1)°, V = 1620.0(3) ų, Z = 4, with final residuals R = 0.047 and Rw = 0.055.     

Simple and one-pot synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one moiety from the Baylis-Hillman adducts

A facile synthesis of tri and tetracyclic frameworks containing [1,8]naphthyridin-2-one skeleton from the Baylis-Hillman alcohols via the Johnson-Claisen rearrangement, followed by the treatment with Fe/AcOH in simple one-pot multi-step process is described.     

二苯并[b,f][1,5]二氮杂芳辛四烯衍生物的合成及拆分

以邻氨基二苯甲酮为原料,经自身缩合环化合成了3种二苯并[1,5]二氮杂芳辛四烯衍生物(1a~1c);以邻苯二甲酸酐和溴苯为原料经傅-克反应制得中间体2-(4-溴苯甲酰溴)苯甲酸(M1);M1经叠氮化后自缩合制得6,12-二(4-溴苯基)二苯并[b,f][1,5]二氮杂环辛四烯(1d);以邻氨基苯甲酸甲酯为原料,经自身缩合环化制得中间体二苯并[b,f][1,5]二氮杂环辛四烯-6,12(5H,11H)-二酮(M2);M2经氯化合成6,12-二氯二苯并[b,f][1,5]二氮杂环辛四烯(1e),化合物1a~1e的结构经~1H NMR,~(13)C NMR和ESI-MS表征,其中化合物1c为新化合物。利用超临界色谱(SFC)技术对化合物1a~1e实现了手性拆分,获得5对具有高旋光度的光学活性异构体(ee99%)。     

Synthesis,Characterization and In Vitro Evaluation of Novel 5-Ene-thiazolo[3,2-b][1,2,4]triazole-6(5H)-ones as Possible Anticancer Agents

The present paper is devoted to the search for drug-like molecules with anticancer properties using the thiazolo[3,2-b][1,2,4]triazole-6-one scaffold. A series of 24 novel thiazolo-[3,2-b][1,2,4]triazole-6-ones with 5-aryl(heteryl)idene- and 5-aminomethylidene-moieties has been synthesized employing three-component and three-stage synthetic protocols. A mixture of Z/E-isomers was obtained in solution for the synthesized 5-aminomethylidene-thiazolo[3,2-b]-[1,2,4]triazole-6-ones. The compounds have been studied for their antitumor activity in the NCI 60 lines screen. Some compounds present excellent anticancer properties at 10 μM. Derivatives 2h and 2i were the most active against cancer cell lines without causing toxicity to normal somatic (HEK293) cells. A preliminary SAR study had been performed for the synthesized compounds.     

New Facile Route to Synthesize Furo[3,2-e][1,2,4]triazolo[4,3-c]pyrimidine and Furo[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine Derivatives

A new facile route for synthesis of 3-(aryl)-8,9-diphenylfuro[3,2-e][1,2,4]triazolo pyrimidines derivative from the same starting material, 2-amino-4,5-diphenylfuran-3-carbonitrile, has been developed through heterocyclization of the corresponding arylidene-hydrazono-5,6-diphenylfuro[2,3-d]pyrimidine and N-(arylmethylene)-4-imino-5,6-diphenylfuro[2,3-d]pyrimidin-3(4H)-amine under refluxing condition with acetic anhydride followed by air oxidation. The products were obtained in good yield with an easy workup along with the purification of products by a nonchromatographic method. This general synthetic procedure can be extended to the preparation of a wide range of isomeric triazoles using 2-amino 3-carbonitrile bifunctional derivatives.     

Synthesis and Anticonvulsant Activity of 9-Alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3[5H]-ones

A series of novel 9-alkoxy-6,7-dihydro-2H-benzo[c][1,2,4]triazolo[4,3-a]azepin-3(5H)-one derivatives was designed and synthesized starting from 2,3,4,5-tetrahydro-7-hydroxy-1H-2-benzazepin-1-one. The structures of these compounds were confirmed by mass, ¹H NMR infrared spectra, and elemental analysis. Their anticonvulsant activity was evaluated by maximal electroshock (MES) test, and their neurotoxic effects were determined by the rotarod neurotoxicity test. The results shown that 3k was the most active compound with median effective dose (ED₅₀) of 27.3 mg/kg, median toxicity dose (TD₅₀) of 118.3 mg/kg, and protective index (PI) of 4.3. Possible structure–activity relationship is discussed.     

Synthesis of 5-Hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano[2,3-c]pyridin-2-ones and Their Esters

New 5-hydroxymethyl-8-methyl-3-(3-aryl-[1,2,4]oxadiazol-5-yl)-2H-pyrano-[2,3-c]pyridin-2-ones and their esters were synthesized. The structure of obtained compounds was determined through a complete ¹H NMR analysis.     

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.     

An efficient synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6]naphthy-ridine-8-ones

An efficient method for the synthesis of novel benzo[b]pyrido[3',2':4,5] thieno[2,3-e][1,6] naphthyridine-8-one derivatives has been developed using a Pictet-Spengler reaction between 4-(3-aminothieno[2,3-b]pyridin-2-yl)quinoline-2-ones, which could be obtained from the alkylation of 4-bromomethylquinoline-2-ones with 3-cyanopyridine-2-thione followed by a Thorpe-Ziegler isomerization, and aromatic aldehydes under p-TsOH as catalysis in good yields.     

[5C+1N]成环反应：吡啶-4(1H)酮类化合物的一种简便合成方法

用N,N-二甲基丙烯酰基二硫缩烯酮类化合物2与各种脂肪胺类化合物3在N,N-二甲基甲酰胺溶剂中60 ℃条件下,氮乙烯基发生分子内的亲核取代反应,通过[5C+1N]成环反应,合成了系列吡啶-4(1H)酮类化合物4,产率在75%~95%之间。     

Modified Coumarins. 8. Synthesis of Substituted 5-(4-Methoxyphenyl)-7H-furo[3,2-g]chromen-7-ones

The MacLeod method was used to synthesize a series of substituted 5-(4-methoxyphenyl)-7H-furo[3,2- g]chromen-7-ones, modified analogs of psoralen, from 7-hydroxy-4-(4-methoxyphenyl)coumarins.     

Facile and Convenient Synthesis of Pyrazole,Pyridine, Pyridazine,Pyrazolo[3,4-b]pyridine,and Pyrazolo[5,1-c][1,2,4]triazine Derivatives

Abstract

A convenient synthesis of a series of pyrazole, pyridine, pyridinethione, pyridazine, pyrazolo[3,4-b]pyridine, imidazo[1,2-a]pyrimidine, and pyrazolo[5,1-c][1 Kumar , R. 5-(1-Substituted)alkyl pyrimidine nucleosides as antiviral (herpes) agents . Curr. Med. Chem. 2004 , 11 , 2749 – 2766 . [Google Scholar] 2 Holy , A. ; Günter , J. ; Dvoráková , H. ; Masojídková , M. ; Andrei , G. ; Snoeck , R. ; Balzarini , J. ; De Clercq , E. Structure–antiviral activity relationship in the series of pyrimidine and purine N-[2-(2-phosphonomethoxy)ethyl] nucleotide analogues, 1: Derivatives substituted at the carbon atoms of the base . J. Med. Chem. 1999 , 42 , 2064 – 2086 . [Google Scholar] 4 Brandes , W. ; Daum , W. ; Krauss , P. Fungicidal oxime ethers. Ger. Patent 2,623,847, 1977; Chem. Abstr . 1978 , 88 , 120822h . [Google Scholar]]triazine derivatives incorporating a pyrimidine moiety, via the reactions of the versatile, readily accessible 3-oxo-N-(pyrimid-2-yl)butanamide with the appropriate reagents, is described.     

Synthesis of 6-Alkyl Carbamato/Alkyl Thiocarbamato-2,10-dichloro-12-trichloromethyl-12 H -dibenzo[d,g][1,3,2]-dioxaphosphocin 6-Oxides

6-Alkylcarbamato/alkylthiocarbamato-2,10-dichloro-12-trichloromethyl-12 H -dibenzo [d,g][1,3,2]-dioxaphosphocin 6-oxides have been synthesized by the condensation of 2,2-bis(2-hydroxy-5-chlorophenyl)-1,1,1-trichloroethane with dichlorophosphinyl carbamates of different alcohols/thiols in the presence of triethylamine in dry toluene and were characterized by different spectral studies.     

从Baylis-Hillman加成物合成1，2，3，4-四氢苯并萘啶-2-酮衍生物

本文介绍了（2）通过还原、两次环化的一锅串联反应制备了一系列1,2,3,4-四氢苯并萘啶-2-酮衍生物,反应条件温和,环境友好,产品易于分离,反应收率中等。起始原料可由Baylis－Hillman加成物通过Johnson-Claisen重排制备。     

Synthesis of substituted 4H-thiazolo[4,5-b][1]benzothiopyran-4-ones as possible schistosomicidal agents

Summary Interaction of ethyl 2-acetamido-5-bromothiazole-4-carboxylate (2) with 2-methyl-5-chlorothiophenol (3) afforded the thioether4, which was hydrolysed to the corresponding carboxylic acid5. Attempted cyclization of5 to6 yielded the decarboxylated product7. On the other hand, interaction of 2-acetamido-5-bromothiazole (9) with thiosalicylic acid (10) yielded the thioether11, which was cyclized to compound12. Acid hydrolysis of12 yielded the amino derivative13, which was reacted with certain selected alkyl halides using sodium hydride to afford compounds14–18.

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Synthese von substituierten 4H-Thiazolo[4,5-b][1]benzothiopyran-4-onen als mögliche schistosomicide Wirkstoffe

Zusammenfassung Die Reaktion von Ethyl 2-Acetamido-5-bromthiazol-4-carboxylat (2) mit 2-Methyl-5-chlorthiophenol (3) ergab den Thioether4, der zur entsprechenden Carbonsäure5 hydrolysiert wurde. Die versuchte Cyclisierung von5 zu6 ergab das Decarboxylierungsprodukt7. Andererseits ergab die Reaktion von 2-Acetamido-5-bromthiazol (9) mit Thiosalizylsäure (10) den Thioether11, der zu Verbindung12 cyclisiert werden konnte. Saure Hydrolyse von12 ergab das Aminoderivat13, das mit geeigneten Alkylhalogeniden unter Verwendung von Natriumhydrid zu den Verbindungen14–18 führte.

     

Facile synthesis of [1,2,4]triazino[4,3-b][1,2,4,5]tetrazepin derivatives by a one-pot reactions using 4-amino-3-hydrazinyl-6-methyl-1,2,4-triazin-5 (4H)-one

<正>4-Amino-3-mercapto-6-methyl-l,2,4-triazin-5(4H)-one 1 converted to 4-amino-6-methy-3-(methylthio)-1,2,4-triazin-5(4H)-one by methylation with methyl iodide.Controlled hydrazination of the resulting compound afforded 4-amino-3-hydrazinyl-6- methyl-l,2,4-triazin-5(4H)-one 2 as a building block,to the synthesis of some novel derivatives of[1,2,4]triazino- [4,3,b][1,2,4,5]tetrazepine 3-6,by the reaction with 3-chloropentane-2,4-dione,chloro acetonitrile,1,3-dichloroacetone,and methyl bromoacetate.This general synthetic procedure can be extended to the preparation of wide variety of tetrazepines using 1,2- bielectrophiles derivatives.     

A Facile Synthesis of 5‐Phenyl‐Dibenzo[b,g][1,8]Napthyridines

The Vilsmeier Haack heterocyclization of 2‐aryl amino‐4‐phenyl quinolines quinoline yielded the hitherto unknown 5‐phenyl‐dibenzo[b,g][1,8]naphthyridines in quantitative yield. The synthesis of aryl amines was achieved by the action of anilines on 2‐chloro‐4‐phenyl quinoline, which in turn was sourced through the combes reaction of benzoyl acetanilides.