新型4-芳氧基吡啶并[3′,2′∶4,5]噻吩并[3,2-d]嘧啶衍生物的合成

2-氯-3-氰基吡啶与巯基乙酸乙酯经闭环反应制得3-氨基吡啶并[3,′2′∶4,5]噻吩-2-甲酸乙酯(1);1与甲酰胺第二次成环生成吡啶并[3,′2′∶4,5]噻吩并[3,2-d]嘧啶-4-酮(2);2经氯化后与取代苯酚反应合成了12个新型的4-芳氧基吡啶并[3,′2′∶4,5]噻吩并[3,2-d]嘧啶衍生物,其结构经1H NMR,13C NMR,IR和元素分析表征。     

苯并噻吩并[3′,2′:2,3]吡啶并[4,5-d]噻唑并[3,2-a]嘧啶酮类衍生物的有效合成

报道了氨基磺酸作用下,通过Pictet-Spengler反应合成苯并噻吩并[3′,2′:2,3]吡啶并[4,5-d]噻唑并[3,2-a]嘧啶酮衍生物的有效合成方法.其中,该反应关键中间体7-(3-氨基苯并噻吩-2-基)噻唑并[3,2-a]嘧啶-5-酮,经由7-氯甲基噻唑并[3,2-a]嘧啶-5-酮与2-巯基苯甲腈的烷基化及Thorpe-Ziegler环化制得.该合成过程原料易得,反应条件温和,收率高,为新型稠杂环嘧啶类化合物的合成提供了简便的新途径.     

4-(1,3,4-噻二唑-2-巯基)苯并[4,5]呋喃[3,2-d]嘧啶类衍生物合成、晶体结构及抗癌活性

从水杨腈出发,经醚化、两次成环、氯化制得4-氯-苯并[4,5]呋喃[3,2-d]嘧啶(5);5与5-取代-2-巯基-1,3,4-噻二唑反应,合成了7个新的含噻二唑的苯并[4,5]呋喃[3,2-d]嘧啶衍生物.其结构经1HNMR,13CNMR,IR和MS表征,培养并测定化合物6a的晶体结构.采用MTT法进行化合物抑制PC3癌细胞体外活性测试,结果表明所合成的化合物具有不同程度的抑制PC3癌细胞活性,其中化合物6b在10μmol?L-1浓度下对PC3的抑制率为89.2%.     

两种非对称芳基二噻吩并[2,3-b:3',2'-d]噻吩的合成与光谱特性

合成了两种非对称芳基取代的并三噻吩化合物.以2-溴-5-三甲基硅-二噻吩并[2,3-b:3′,2′-d]噻吩为原料,经脱除四甲基硅烷(TMS)和Suzuki偶联两步反应制备了2-噻吩基二噻吩并[2,3-b:3′,2′-d]噻吩,总产率为67.4%;以2-苯基二噻吩并[2,3-b:3′,2′-d]噻吩为原料,经N-溴代琥珀酰亚胺(简称NBS)溴代和Suzuki偶联两步反应制备了2-苯-5-噻吩基二噻吩并[2,3-b:3′,2′-d]噻吩,总产率为27.8%.产物经核磁共振谱(1H NMR,13C NMR)和质谱(MS)分析确认;利用紫外-可见分光光度法(UV-Vis)分析了合成产物的荧光特性.结果表明,由于苯基的存在,2-噻吩-5-苯基二噻吩并[2,3-b:3′,2′-d]噻吩分子的共轭体系增大,导致其吸收峰红移、发光能力减弱.     

香豆素并[4,3-d]噻吩[3,2-b:5,4-b']双吡啶衍生物的合成

以4-氯甲基香豆素为基础物质,通过与3-氰基-2-吡啶硫酮的烷基化及Thorpe-Ziegler反应,得到4-(3-氨基噻吩并[2,3-b]吡啶-2-基)香豆素,接着在对甲苯磺酸作用下,通过Picter-Spengler反应与芳香醛进行缩合,以良好收率合成了一系列香豆素并[4,3-d]噻吩[3,2-b:5,4-b']双吡啶衍生物。该反应操作简单、条件温和、收率良好。产物结构经NMR,IR,MS及元素分析数据得以证实。     

杂环取代苯并[4,5]呋喃[3,2-d]嘧啶类衍生物的合成及其抗癌活性

采用生物活性因子拼接的方法将活性基团1,3,4.三唑等引入苯并[4,5]呋喃[3,2-d]嘧啶化合物中,合成了7个未见文献报道的杂环取代苯并[4,5]呋喃[3,2-d]嘧啶类衍生物,其结构经NMR,IR和MS表征.初步生物活性测试结果表明,部分化合物对人前列腺癌细胞PC3具有一定的抑制活性.     

新型叶酸拮抗剂吡啶并嘌呤衍生物的环合反应研究

将6-取代-2,4-二氨基哌啶并[3,2-d]嘧啶衍生物与N,N-二甲基甲酰胺、三氯乙酰氯在25℃反应2h,"一锅法"环合反应生成7-取代-2-氨基-7,8-二氢-6H-吡啶并[1,2,3-gh]嘌呤衍生物,利用NMR、HRMS确定目标化合物的结构。考察了不同底物、反应底物比例、反应时间、温度对反应产率的影响,并提出可能的反应机理。该反应条件温和、效率高、操作简单。     

3,4-二胺-1H-吡唑并[5,4-d]嘧啶的固相合成

用固相合成技术合成了吡唑并[5,4-d]嘧啶的一类衍生物8.以Merrifield树脂为原料,与化合物3反应得到树脂4.4经过还原胺化、取代、分子内亲核加成反应得到树脂7,再由三氟醋酸断裂得到化合物3,4-二胺-1H-吡唑并[5,4-d]嘧啶.     

6-溴代呋喃[2,3-d]嘧啶双环核苷的合成新方法研究

6-溴代呋喃[2,3-d]嘧啶双环核苷是合成具有显著抗病毒活性的呋喃并嘧啶双环核苷衍生物的重要中间体.该类化合物的文献制备方法合成步骤多,并需使用钯配合物作催化剂.以易得的5-甲酰基嘧啶核苷为原料,先经与四溴化碳缩合得5-(2,2-二溴乙烯基)嘧啶核苷类似物,然后在碘化亚铜催化下发生环化反应生成目标产物,不仅缩短了合成路线,而且避免了贵金属试剂的使用,是一种经济实用的新方法.     

新型4-(5-N-取代-1,3,4-噻二唑-2-巯基)-苯并[4,5]呋喃[3,2-d]嘧啶类衍生物的合成及其抗癌活性

将5-取代胺基-2-巯基-1,3,4-噻二唑引入苯并[4,5]呋喃[3,2-d]嘧啶中,设计并合成了10个新型的4-(5-N-取代-1,3,4-噻二唑-2-巯基)-苯并[4,5]呋喃[3,2-d]嘧啶类衍生物(3a～3j),其结构经1H NMR,13C NMR,IR和MS确认。用MTT法测定了3a～3j对人胃腺癌细胞体(MGC)的体外增殖活性。结果表明,3a～3j均具有不同程度的抑制MGC的活性,其中4-(5-N-2’-甲氧基苯基-1,3,4-噻二唑-2-巯基)-苯并[4,5]呋喃[3,2-d]嘧啶(3j)在10μmol·L-1的浓度下对MGC的抑制率为86.4%。     

Synthèse des pyrido[2,3-d] el [3,2-d] -s-triazolo[3,4-f] pyrimidines el de (pyrazolyl-1')-4 pyrido[2,3-d] et [3,2-d] pyrimidines

The synthesis of two new heterocycles is described: pyrido-[2,3-d]-.s-triazolo[ 3,4-f] pyrimidine and pyrido[3,2-d]-.s-triayzolo-[3,4-f] pyrimidine. 4-[I'-Pyrazolyl]pyrido[2,3-d]pyrimidines and 4-[1′-pyrazoly1] pyrido[ 3,2-d] pyrimidine are obtained by the action of 4-hydrazinopyrido[2,3-d]pyrimidine and 4-hydrazinopyrido-[3,2-d]pyrimidine with several β-diketones.     

New efficient route to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines via regioselective cross-coupling reactions

The first access to dissymmetric 2,4-di(het)aryl-pyrido[3,2-d]pyrimidines III is reported. Two mild alternative routes led to the rarely targeted compounds from 2,4-dichloro- and 2-chloro-4-isopropylsulfanyl-pyrido[3,2-d]pyrimidine by two successive palladium-catalyzed reactions involving an original regioselective chlorine discrimination. Alternatively, type III compounds were elaborated from 2 by C-2 chlorine further displacement of the C-4 isopropylsulfanyl group, which acted as a temporary C-4 protecting group. These results open the way to innovative synthesis strategies of various bis-functionalized pyrimidine series.     

Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines

A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-amino)]5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines were obtained by irradiating 2-substituted-4-chloro-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with 1-amino-propanol under basic conditions in a microwave oven. 4-Chlorothieno[2,3-d]pyrimidines were synthesized by microwave irradiation of equimolar mixture of 4-hydroxythieno[2,3-d]pyrimidines and phosphorus oxychloride. The final compounds were screened for antibacterial activity by Kirby Bauer's method using amicacin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.     

Deazapurine solid-phase synthesis: construction of 3-substituted pyrrolo[3,2-d]pyrimidine-6-carboxylates on cross-linked polystyrene bearing a cysteamine linker

The first solid-phase methodology for the preparation of pyrrolo[3,2-d]pyrimidines is presented. Merrifield resin bearing a cysteamine "traceless" linker was treated with 4-oxo-N-(PhF)proline benzyl ester (10; PhF = 9-(9-phenylfluorenyl)) to provide resin-bound aminopyrrole 20, which was treated with ethyl, phenyl, 4-phenoxyphenyl, and 2,4-dimethoxyphenyl isocyanates to furnish resin-bound ureidopyrroles 21a-d. Resin-bound pyrrolo[3,2-d]pyrimidines 22a-d were then obtained by acylation of 21 using trichloroacetyl chloride in dioxane followed by treatment with Cs2CO3 in DMF. Cleavage of pyrrolo[3,2-d]pyrimidines 22a-d from the resin was achieved in two steps, by oxidation of the sulfur to the sulfone followed by beta-elimination in the presence of t-BuONa. Four pyrrolo[3,2-d]pyrimidines, 24a-d, with different alkyl and aryl substituents at the N3 pyrimidine nitrogen, were thus obtained in overall yields of 42-50% and purities of 90-100%.     

MgO nanopowders catalyzed synthesis of pyrano[4,3-d]thiazolo[3,2-a]pyrimidine derivatives

A cubic phase of pure MgO nanopowders was prepared in an aqueous solution containing freshly squeezed orange juice with pulp and characterized by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and Fourier transform infrared (FT-IR) spectroscopic techniques. The catalytic potential of MgO nanopowders was evaluated in preparation of pyrano[4,3-d]thiazolo[3,2-a]pyrimidine and chromeno[4,3-d]thiazolo[3,2-a]pyrimidines derivatives using the three simple methods including thermal, ultrasonic irradiation, and high-speed ball milling (HSBM) technique under solvent-free conditions. All products were successfully formed in high yields.     

Diversity-oriented synthesis of functionalized pyrrolo[3,2-d]pyrimidines with variation of the pyrimidine ring nitrogen substituents

Nine 2,4-dioxo-2,3,4,5-tetrahydro-1H-pyrrolo[3,2-d]pyrimidine-6-carboxylic acid benzyl esters 12 were synthesized in four steps from 4-oxo-N-(PhF)proline benzyl ester 7 by a general method in which elements of molecular diversity were readily added onto the pyrimidine nitrogens. Conversion of 4-oxoproline 7 into the corresponding aminopyrrole 8 using benzyl-, allyl-, and isopropylamine followed by treatment with phenyl, allyl, and ethyl isocyanate gave nine different ureas 9. 4-Ureido-1H-pyrrole-2-carboxylic acid benzyl esters 9 were then converted into the respective pyrrolo[3,2-d]pyrimidines 12 using trichloroacetyl chloride in acetonitrile followed by treatment with Cs(2)CO(3). Crystallization from toluene gave the desired deazapurines in 37-55% overall yield from proline 7.     

Transformations of 5-methyl-6-carbethoxy-3,4-dihydrothieno-[2,3-d]pyrimidine for synthesis of 4-methoxy-, 4-alkylamino-, and other derivatives of thieno[2,3-d]pyrimidine

4-Chloro derivatives of thieno[2,3-d]pyrimidine are formed by the action of phosphorus oxychloride on 5-methyl- and 5-methyl-6-carbethoxythieno[2,3-d]pyrimidin-4-ones. Action of nucleophilic reagents (methanol, sodium methylate, primary and secondary amines) on these chloro derivatives gave 4-methoxy-, 4-alkylamino-, and 4-dialkylamino substituted thieno[2,3-d]pyrimidines. It was found that 4-methoxy derivatives of thieno[2,3-d]pyrimidines undergo a thermal rearrangement into 3-methyl-substituted thieno[2,3-d]pyrimid-4-ones. In the bromination of 5-methyl-4-chloro- and 5-methyl-4-methoxy-substituted thieno[2,3-d]pyrimidines by N-bromosuccinimide, 5-bromomethyl derivatives of thieno[2,3-d]pyrimidine are formed, from which, by the action of primary and secondary amines, 5-aminomethyl-substituted thieno[2,3-d]pyrimidines were obtained. A synthesis of 1,2,3,4-tetrahydro-1,3-diazepino[4a,10-d,e] thieno[2,3-d]pyrimidines was also carried out.Deceased.Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 7, pp. 925–928, July, 1985.     

Access and regioselective transformations of 6-substituted 4-aryl-2,8-dichloropyrido[3,2-d]pyrimidine compounds

We report herein an efficient route for the synthesis of 2,4,8-trichloropyrido[3,2-d]pyrimidines 1 with R(1) substituents at C-6. The potential of such scaffolds was demonstrated by the possibility to displace regioselectively each aromatic chloride to introduce diversity. Sequential sulfur nucleophilic addition followed by Liebeskind-Srogl cross-coupling reaction yielded unprecedented aryl introduction at C-4 on a trichloropyrido[3,2-d]pyrimidine derivative. The reactivity difference of the remaining two chlorides toward S(N)Ar reactions was investigated. Amination yielded high C-2 regioselectivity, while thiolation was influenced by C-6 substituents, resulting in medium to high C-2 versus C-8 regioselectivity. The last chloride was efficiently displaced by S(N)Ar, Suzuki-Miyaura cross-coupling reaction, or reduction. C-2 arylation as a final step was also possible by Liebeskind-Srogl cross-coupling reaction on the previously introduced C-2 thioether. A concise and highly divergent synthetic use of 1 was developed, thereby providing an efficient approach to explore the structure-activity relationship of pyrido[3,2-d]pyrimidine derivatives such as 9, 10, 15, and 16.     

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 .     

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.