新型环烷烯并嘧啶并噻唑-3-酮类化合物的合成

以环戊酮、环庚酮为起始原料合成的环烷烯并[1,2-d]嘧啶-2-硫酮(2)与氯乙酸、芳香醛反应, 合成具有潜在抗癌活性的稠合杂环化合物5-芳基-2,8-二芳亚甲基-2,3,6,7-四氢-5H,8H-环戊烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(3)以及5-芳基-2,10-二芳亚甲基-2,3,6,7,8,9-六氢-5H,10H-环庚烯并[1,2-d]噻唑并[3,2-a]嘧啶-3-酮(4). 3和4的结构经¹H NMR, IR, MS分析确认.     

Studies on Thiazolopyridines. Part 1: Antimicrobial Activity of Some Novel Fluorinated Thiazolo[3,2-a]Pyridines and Thiazolo[2′,3′:1,6]Pyrido[2,3-d]Pyrimidines

Ternary condensation of aromatic aldehydes, malononitrile and thioglycolic acid (2:2:1 molar ratio) in ethanol/piperidine afforded the corresponding thiazolo[3,2-a]pyridines 1a-d . Thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 4 was obtained by refluxing of compound 1a with acetic anhydride. Also, thiazolopyrido pyrimidine 6 was produced by refluxing of 1a with triethylorthoformate followed by treatment with hydrazine hydrate. Refluxing 1a with formic acid yielded the thiazolopyridopyrimidine 8 which on chlorination with thionyl chloride furnished the chloro derivative 9 . Finally, amino thiazolo[2',3':1,6]pyrido[2,3-d]pyrimidine 10 was obtained by treatment of 1a with formamide. The structures of these compounds were established on the basis of elemental analyses, IR, 1 H NMR, and mass spectral data. Also, the antimicrobial activity of some synthesized compounds is reported.     

1,3-Disubstitutedpyrazole-4-caboxaldehyde in Heterocyclic Synthesis: A Novel Synthesis of Pyridine-2(1H)-thione and Fused Nitrogen and/or Sulfur Heterocyclic Derivatives

Pyridine-2(1H)-thione 5 was synthesized from the reaction of 3-[3-(4-chlorophenyl)-1-phenyl-1H-pyrazol-4-yl]-1-phenylpropenone (3) and cynothioacetamide (4). Compound 5 reacted with halogented compounds 6a–e to give 2-S-alkylpyridine derivatives 7a–e, which could be in turn cyclized into the corresponding thieno[2,3-b]-pyridine derivatives 8a–e. Compound 8a reacted with hydrazine hydrate to give 9. The latter compound reacted with acetic anhydride (10a), formic acid (10b), acetic acid, ethyl acetoacetate, and pentane-2,4-dione to give the corresponding pyrido[3′,2′:4,5]thieno-[3,2-d]pyrimidine 13a,b, pyrazolo[3′,4′:4,5]thieno[3,2-d]pyridine 14 and thieno[2,3-b]-pyridine derivatives 18 and 20, respectively. Alternatively, 8c reacted with 10a,b and nitrous acid to afford the corresponding pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine 24a,b and pyrido[3′,2′:4,5]thieno[3,2-d][1,2,3]triazine 26 derivatives, respectively. Finally compound 5 reacted with methyl iodide to give 2-methylthiopyridine derivative 27, which could be reacted with hydrazine hydrate to yield the corresponding pyrazolo[3,4-b]-pyridine derivative 29.     

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.     

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.     

A Convenient Synthesis for Some New Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused 1,2,4-Triazolo and 1,3,4-Thiadiazolo-derivatives

Diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6 dicarboxylate 1 is a convenient and useful starting matrial for the constructions of heterocyclic systems. It was utilized to synthesize derivatives of the novel heterocyclic systems pyrido[4',3':4,5]thieno[2,3-d]pyrimidine 4 , 10 , pyrido[4',3':4,5]thieno[2,3-d]-[1,2,4]triazolo[1,5-a]pyrimidine 7 , 11a-e and pyrido[4',3':4,5]thieno[2,3-d][1,3,4]thiadiazolo[3,2-a]pyrimidine 12-14 .     

含哌嗪基7-溴噻吩并[3,2-d]嘧啶抗癌试剂的设计与合成

为寻找以蛋白酪氨酸激酶为靶点的新型抗癌试剂,本文设计与合成了系列含哌嗪基的7-溴噻吩并[3,2-d]嘧啶衍生物。以巯基乙酸为原料,经六步反应得4-氯-7-溴噻吩并[3,2-d]嘧啶母核,再与不同的哌嗪衍生物在添加三乙胺作碱的条件下反应,制备了五个未见报道的含哌嗪基7-溴噻吩并[3,2-d]嘧啶化合物。结构经1H NMR和HRMS表征。     

Synthesis of Some New Biologically Active Sulfur Compounds Containing Pyrazolo[3,4-d] pyrimidine Moiety

A novel series of the pyrazolo[3,4-d]pyrimidines having biologically active sulfur moieties 3-20 were prepared via reaction of 4-mercapto-1-phenyl-1 H -pyrazolo[3,4-d]pyrimidine 3 with different reagents. Identification of the new compounds was established by elemental analyses, IR, 1 H-NMR, and mass spectral data. Some of the obtained compounds showed the interesting antimicrobial activity comparable to antibiotic chloramphenicol as standard antibacterial agent and Terbinafin as a standard antifungal agent.     

One-Pot Synthesis of Novel Spiro Pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine Derivatives

In a one-pot synthesis, 1′-methyl-2,3″-dioxo-5″-aryl-1,2,5a″,7″,8″,9a″-hexahydro-5″H,6″H-dispiro[indole-3,2′-pyrrolidine-3′,2″-pyrano[2,3-d][1,3]thiazolo[3,2-a]pyrimidine]-4′-carboxylic acid methyl ester was prepared via the sequential reaction of 4-aryl-octahydro-pyrano[2,3-d]pyrimidine-2-thione, dimethyl acetylenedicarboxylate (DMAD), and a mixture of isatin and sarcosine. All the novel spiro compounds, in moderate yields, were characterized thoroughly by infrared, NMR, mass spectromentry, and elemental analysis together with x-ray crystallographic analysis.     

Catalyst-free synthesis of novel 4H-indeno[1,2-b]furan-4-ones and furo[2,3-d]pyrimidines in water

An operationally simple, catalyst-free, and efficient protocol for the synthesis of novel 4H-indeno[1,2-b]furan-4-one and furo[2,3-d]pyrimidine derivatives by a one-pot reaction of 2-aminopyridines, 1,3-indandione, or barbituric acid and phenylglyoxal monohydrate in water at reflux, involving domino aldol condensation, Michael addition, and ring-closing reactions is described. This transformation has several advantages, including high yield, short reaction duration, simple workup, and simple purification.     

Facile and efficient synthesis of 5,7-disubstituted thiazolo[5,4-d] pyrimidine-4,6(5H,7H)-diones

A facile and efficient approach was developed to access 5,7-disubstitued thiazolo[5,4-d]pyrimidine-4,6(5H,7H)-diones through condensation of N-substituted 5-amino-4-carbethoxythiazole with structurally diverse isocyanates in the presence of sodium hydride.The easy availability of substrates and tolerance of structural diversity in this reaction make it attractive to be used for construction of libraries in drug discovery process.     

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.     

Electron Ionization Mass Spectra of Organophosphorus Compounds. Part III: Mass Spectrometric Fragmentation of Diethyl Spiro[Pyrimidino[5,3′][1,2]Oxazole] Phosphonate,Diethyl (Oxazolo[5,4-D]Pyrimidine-4,6-Dione)Phosphonate,and Diethyl (Pyrimidino[4,5-B][1,4]Oxazine)Phosphonate Derivatives

Abstract

Fragmentation pathways of 14 organophosphorus compounds derived from diethyl spiro[pyrimidino[5,3][1,2]oxazole] phosphonates, diethyl (oxazolo[5,4-d]pyrimidine-4,6-dione)phosphonates, and diethyl (pyrimidino[4,5-b][1,4] oxazine)phosphonates were investigated by electron impact mass spectrometry (EI-MS). The intensity of the recorded molecular ion peaks showed various values depending on the nature of the compounds. Characteristic fragment ions were formed by successive loss of simple functional groups followed by decomposition of heterocycles connected to pyrimidine rings.     

Heterocycles from Pyrazoloylhydroximoyl Chloride: Synthesis of Certain Quinoxaline,Benzothiadiazine, Benzoxadiazine,Quinazolinone, Imidazo[1,2-a]pyridine,Imidazo[1,2-a]pyrimidine,Isoxazole, Pyrazolo[3,4-d]pyridazine and Pyrrolidino[3,4-d]isoxazolin-4,6-dione Derivatives

3-Ethoxycarbonyl-5-methyl-1-(4-methylphenyl)-4-pyrazoloylhydroximoyl chloride (1) reacted with o-phenylenediamine, o-aminothiophenol, o-aminophenol and methyl anthranilate to afford 3-nitrosoquinoxaline, benzothiadiazine, benzoxadiazine, and 3-hydroxyquinazoline, respectively. Imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine and isoxazole derivatives were obtained via the reaction of 1 with 2-aminopyridine, 2-aminopyrimidine and the appropriate active methylene compounds, respectively. Pyrazolo[3,4-d]pyridazines, and pyrrolidino[3,4-d]isoxazolines derivatives were also synthesized. The structures of the newly synthesized compounds were established on the basis of spectral data and alternate synthesis whenever possible.     

Synthesis and Crystal Structure of 2-Ethoxy-3-n-butyl-benzofuro[2,3-d]pyrimidin-4（3H）-one

The crystal structure of the new title compound 2-ethoxy-3-n-butyl- benzofuro[2,3d]pyrimidin-4（3H）-one （C16H18N2O3, Mr = 286.32） has been prepared and determined by singlecrystal X-ray diffraction. The crystal is of monoclinic, space group P21/c with a = 13.7167（14）, b = 13.113（1）, c = 8.378（1） A, β = 98.992（2）^o, V = 1488.4（3） A^3, Z = 4, Dc = 1.278, F（000） = 608, μ = 0.089 mm^-1, MoKa radiation （2 = 0.71073）, R = 0.0498, wR = 0.1238 for 2336 observed reflections with I 〉 2σ（I）. X-ray diffraction analysis reveals that all ring atoms in the benzo[4, 5]furo [2,3-d] pyrimi- dinone moieties are almost coplanar.     

2,6-二(对氨基苯)苯并[1,2-d;5,4-d']二噁唑的合成

以4,6-二氨基间苯二酚二磷酸盐和对氨基苯甲酸为原料,在多聚磷酸中,添加还原剂SnCl_2·2H_2O,经缩聚反应合成了有机二胺单体——2,6-二(对氨基苯)苯并[1,2-d;5,4-d']二噁唑(DIABO),其结构经~1H NMR和FT-IR确证。最佳反应条件为:1 0.01 mol,PPA中P_2O_5质量分数为84%,SnCl_2·2H_2O用量为8 wt%,在氮气保护下于200℃反应4 h,产率97%。TG研究结果表明:DIABO的起始分解温度为401.0℃。     

Synthesis of thiopyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]furo[3,2-d]pyrimidines

<正>Reactions of the 6-hydroxy-thiopyrano[3,4-c]pyridine-5-carbonitrile derivative 1 withα-halo-carbonyl compounds gave the ortho-substituted intermediates 2a-c which were converted into furo[2,3-b]thiopyrano[4,3-d]pyridines 3a-c by fusion of a furan moiety under basic conditions.Further cyclization of 3a-c led to a fusion of a pyrimidine ring,yielding the tetracyclic products 6,7 and 8.In addition,condensation of 6 with various aromatic aldehydes afforded the corresponding imines 9a,b.Mannich reaction of 7 gave products 10a,b.     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

2-[4-(2-Thienyl)-1,3-thiazol-2-yl]ethanenitrile in Heterocyclic Synthesis of Biological Interist

Abstract

Thiazolylacetonitrile was used in the synthesis of coumarin, pyrazolo[4,3]pyrimidines, 1,3,4-thiadiazolines, aminothiophenes, and thiazoles in a good yields. Also, pyrazolo[4,5-d]triazolino[4,5-a]pyrimidines, pyrazolo[4,5-d]thiazolino[3,2-a]pyrimidines, and pyrazolo[4,5-d]tetrazolino[1,5-a]pyrimidines were synthesized from pyrazolo[4,5-d]pyrimidine. Structures of the newly synthesized were elucidated by elemental analysis, spectral data, and alternative synthesis routes whenever possible. Some synthesized compounds were tested for their antimicrobial activity.     

SYNTHESIS AND ANTIMICROBIAL SCREENING OF SOME NEW 4-IMINO-3,5,7-TRISUBSTITUTED PYRIDO[2,3-d]PYRIMIDINES AND THEIR RIBOFURANOSIDES AS POTENTIAL CHEMOTHERAPEUTIC AGENTS

Some new nucleosides, viz. 4-imino-3,5,7-trisubstituted-1-(2′,3′,5′-tri-O-kbenzyl–β-D-ribofuranosyl)pyrido[2,3-d]pyrimidin/e–2(1H)-ones/ thiones(VII/VIII), have been synthesized by condensation of trimethylsilyl derivatives of 4-imino-3,5,7-trisubstituted pyrido[2,3-d]pyrimidin/e-2(1H)-ones/thiones (III/IV) with β-D-ribofuranosyl1-acetate-2,3,5-tribenzoate. Compounds III/IV have been synthesized by refluxing 2-amino-3-cyano-4,6-disubstituted pyridine (II) with substituted an arylisocyanate or an isothiocyanate respectively. The structure of all the synthesized compounds have been established by IR and ¹H NMR studies. These compounds have been screened for antimicrobial activities in order evaluate. The possibility of the derivatives to be used as potential chemotherapeutic agents.