Synthesis of Substituted 1,3-Cyclohexadienes,Pyridine-2(1H)-thiones,and Thieno[2,3-d]pyrimidine- 4(3H)-thiones by the Michael Reaction

Cyclopentylidene- and cyclohexylidene(cyano)acetamides reacted with malononitrile and cyano-(thioacetamide) according to the Michael pattern with exchange of the methylene components to give substituted 1-amino-2,6,6-tricyano-1,3-cyclohexadienes and thieno[2,3-d]pyrimidine-4(3H)-thiones. Condensation of cyclopentylidene- and cyclohexylidene(cyano)acetamide with 1,3-dicarbonyl compounds afforded 4,6-di-methyl-3-cyanopyridine-2(1H)-thione and morpholinium 4-methyl-6-oxo-3-cyano-1,6-dihydropyridine-2-thiolate which were converted into substituted 2-alkylsulfanylpyridines, thieno[2,3-b]pyridines, thiazolo[3,2-a]pyridine, and 2H-[1,3]thiazino[3,2-a]pyridine.     

Synthesis of functionalized 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones and their recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones

By the reaction of 6-aryl(alkyl)amino-5-cyano-2,3-dihydro-1,3-thiazin-4(10)-ones with α-halogenoketones in the presence of triethylamine, 2,3-dihydrothieno[2,3-d]pyrimidin-4(1H)-ones have been synthesized and their acid-catalyzed recyclization to 2,3-dihydrothieno[3,4-d]pyrimidin-4(1H)-ones has been found and studied. © 2006 Wiley Periodicals, Inc. Heteroatom Chem 17:104–111, 2006; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20181     

Synthesis of functionalized pyrimidine-4-thiones and derivatives of pyrido[2,3-d]pirimidine-5-one from monoacylketene aminals

Monoacylketene aminals containing an unsubstituted NH₂ group react as C-nucleophiles with benzoyl isothiocyanate to give the corresponding thioamides which undergo cyclization by sodium methoxide in methanol to afford 6-R-amino-5-acetyl-2-phenyl-3H-pyrimidine-4-thiones. A scheme for constructing the pyrido[2,3-d]pyrimidine system from keteneaminals is offered. The reaction of 6-R-amino-5-acetyl-2-phenyl-3H-pyrimidine-4-thiones with dimethylformamide dimethylacetal leads to 8-R-N-4-methylthio-8H-pyrido-[2,3-d]pyrimidine-5-ones. Cyclization of 5-acetyl-6-benzoylamino-4-methylthio-2-phenylpyrimidine by sodium methoxide yields N-unsubstituted 4-methylthio-8H-pyrido-[2,3-d]pyrimidine-5-one.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 1932–1937, November, 1993     

Synthesis of 5-Amino-4-imino-3,4-dihydropyrido[3,4-d]pyridazin-1(2H)-one Derivatives

Russian Journal of Organic Chemistry -     

SYNTHESIS AND SOME REACTIONS OF 2-MERCAPTO-3,5,7-TRIPHENYLPYRIDO[2,3-d]-PYRIMIDINE-4(3H)-ONE

Abstract

2-Mercapto-3,5,7-triphenylpyrido[2,3-d]pyrimidine-4(3H)-one (II) was synthesized by the interaction of ethyl-2-amino-4,6-diphenylincotinate (I) with phenyl isothiocyanate in pyridine. The reaction of II with different reagents was carried out to give some condensed heterocyclic systems.     

Synthesis of 4-amino-6-hetarylthieno[2,3-d]pyrimidines from 5-acetyl-6-aminopyrimidine-4(3H)-thiones

Russian Chemical Bulletin - An efficient method for the synthesis of functionalized thieno[2,3-d]pyrimidines and 2-(thieno[2,3-d]pyrimidin-6-yl)pyrido[2,3-d]pyrimidines from...     

Synthesis of Pyrano[2,3-d]pyrimidine-2,4-diones and Pyridino[2,3-d]pyrimidine-2,4,6,8-tetraones: Evaluation Antitumor Activity

A series of some novel pyrano[2,3-d]pyrimidine 4 – 10 with 75–95% yields and pyridino[2,3-d]pyrimidine derivatives 11 – 16 with 75–92% yields is reported. The building structures have been achieved by reaction of 5-arylidene barbituric acid 2 and active nucleophile carbon or nitrogen as examples barbituric acid and acetyl acetone or refluxing of bispyrimidine-2,4,6-trione derivative 3 with cyclizing reagents such as phosphorous pentoxide, hydrazine hydrate and aminothiazole. The newly synthesized structures have been elucidated on the basis of their spectral analysis. Some selected members were screened for antitumor activity. Among the screened compounds 9 , 16 , 7 , 10 and 8 exhibited high antitumor activity.     

A facile one-pot synthesis of new thieno- [2,3-d]pyrimidine-2,4（1H,3H）-dione derivatives

A facile one-pot synthesis of new 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones via base-catalyzed cyclocondensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryi isocyanates is described.     

Synthesis of 4-alkyl-2-aryl-1,3-oxazole[5,4-d]pyrimidine-7(4H)-thiones and 6-alkyl-2-aryl-1,3-oxazole[5,4-d]pyrimidin-7(6H)-ones from 2-aroylamino-3,3-dichloroacrylonitriles

The sequential treatment of accessible 2-aroylamino-3,3-dichloroacrylonitriles with excess of amine, triethyl orthoformate, and hydrogen sulfide results in 4-substituted oxazole[5,4-d]pyrimidine-7(4H)-thione. The sequential reactions of the same reagents with sodium methylate, trifluoroacetic acid, triethyl orthoformate, and amines give rise to the 6-substituted oxazole[5,4-d]pyrimidin-7(4H)-one.     

Pyrido[2,3-d]pyrimidines 4. Synthesis and some transformations of oxo(hydroxy)pyrido[2,3-d]pyrimidines

The cyclization of 5-cyanoacetyl-6-aminouracils in acidic media was accomplished. The structures of the pyrido[2,3-d]pyrimidines obtained and their properties are discussed.See [1] for Communication 3.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 674–680, May, 1991.     

Convenient Synthesis of 3-(1-Carboxyalkyl)pyrido[2,3-d]pyrimidine-2,4-diones

A cheap and safe synthetic route to obtain 3-(1-carboxyalkyl)pyrido[2,3-d]pyrimidinediones (carboxyalkyl = -CHRCO₂H; R = H; CH₂; CH₂Ph; Ph; CH₂ (C₃H₃N₂); (CH₂)₂CO₂H; CH₂CO₂H) starting from 2,3-pyridinedicarboxylic acid is described. A process scheme consistent with empirical observations is proposed.     

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 new pyrimido[4,5-d]pyrimidine derivatives from 5-acetyl-6-methyl-4-methylsulfanylpyrimidine-2(1H)-thiones and guanidine

Reactions of 5-acetyl-1-aryl(alkyl)-6-methyl-4-methylsulfanylpyrimidine-2(1H)-thiones (prepared from diacetylketene N,S-acetal) with guanidine afforded 3-alkyl- and 3-aryl-7-amino-5-methyl-4-methylidene-3,4-dihydropyrimido[4,5-d]pyrimidine-2(1H)-thiones. By-products of these reactions (5-acetyl-1-alkyl(aryl)-6-methyl-2-thiouracils) can also be obtained from the starting pyrimidinethiones and EtONa in EtOH. Pyrimidopyrimidinethiones can react with MeOH at the methylidene group in the presence of MeONa.     

Isolation of Intermediates in the Synthesis of Thieno[2,3-d]pyrimidine-2,4(1H,3H)-diones Using Microwave Irradiation

A simple and fast method for the isolation of intermediates in the synthesis of 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones has been developed by microwave-assisted condensation of ethyl 2-amino-4,5-dimethylthiophene-3-carboxylate with aryl isocyanates. The intermediates, subsequently, underwent cyclization in t-butanol in the presence of potassium t-butoxide on heating to reflux to give the desired bicyclic products, 3-arylthieno[2,3-d]pyrimidine-2,4(1H,3H)-diones.     

Facile Synthesis of 2-Alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones

Isothiocyanate 2, obtained from aza-Wittig reaction of iminophosphorane 1 with CS₂, reacted with amine to give 2-thioxo-2,3,5,6,7,8-hexahydrobenzothieno[2,3-d]pyrimidin-4(1H)-ones 4 in the presence of sodium ethoxide. S-Alkylation of 4 produced 2-alkylthio-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 5 in good yields.     

选择性合成双[噻吩并[2,3-d]嘧啶-4(3H)-酮]

以2-氨基-4-三氟甲基-5-甲基-噻吩-3-羧酸乙酯(1)为起始原料制得膦亚胺2.在碳酸钾的催化下,膦亚胺2与芳基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上2,2’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]3;膦亚胺2与烷基异氰酸酯和伯二胺的氮杂Wittig反应制得嘧啶环上3,3’取代的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]4.化合物3的核磁共振氢谱表明关环反应在嘧啶环的2,2’位;化合物4的核磁共振氢谱表明关环反应在嘧啶环的3,3’位.对合成反应机理的推导及目标产物核磁共振氢谱数据的分析解释了此合成反应的选择性.     

桥连的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]的合成

2-氨基-4-三氟甲基-5-甲基-噻吩-3-羧酸乙酯(1)与三苯基膦、六氯乙烷及三乙胺反应,以84％的产率得到膦亚胺2.在碳酸钾的催化下,膦业胺2与芳基异氰酸酯和双官能亲核试剂的串联氮杂Wittig反应制得新型桥连的双[噻吩并[2,3-d]嘧啶-4(3H)-酮]3,产率为58％～82％.所有产物结构经IR,1HNMR,MS表征和元素分析确证.