利用串联的氮杂Wittig反应方便合成3-[取代吡啶(噻唑)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮及其除草活性

用串联的氮杂Wittig关环反应合成了一系列3-[取代吡啶(嘧啶)甲基]-1,2,3-三唑[4,5-d]嘧啶-7-酮.膦亚胺4和芳基异氰酸酯发生氮杂Wittig反应生成碳二亚胺5,继而在乙醇钠催化下与各种脂肪伯胺关环,以较好的收率得到目标产物7.初步生物活性测试结果表明:该系列部分化合物在100 mg/L的浓度下对双子叶植物油菜显示出较好的除草活性.     

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.     

顺序一锅法合成5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物

采用顺序一锅法,以4,5,7-三氢-吡喃并[4,3-d]噻吩基三苯基膦亚胺、芳基异氰酸酯和胺类化合物为原料,合成了19个结构新颖的5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物.该方法具有条件温和、操作简便、收率高等特点.所得化合物的结构用1H NMR,IR和MS等手段进行了表征,此外还通过X射线单晶衍射分析法进一步确证了化合物3-(4-氯苯基)-2-二乙胺基-5,6,8-三氢-吡喃并[3’,4’:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮(4a)的结构.     

顺序一锅法合成5,6,8-三氢-吡喃并[3′,4′:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物

采用顺序一锅法,以4,5,7-三氢-吡喃并[4,3-d]噻吩基三苯基膦亚胺、芳基异氰酸酯和胺类化合物为原料,合成了19个结构新颖的5,6,8-三氢吡喃并[3′,4′:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物.该方法具有条件温和、操作简便、收率高等特点.所得化合物的结构用1H NMR,IR和MS等手段进行了表征,此外还通过X射线单晶衍射分析法进一步确证了化合物3-(4-氯苯基)-2-二乙胺基-5,6,8-三氢-吡喃并[3′,4′:4,5]噻吩并[2,3-d]嘧啶-4(3H)-酮(4a)的结构.     

2-芳氧基-3-对氟苯基-3,5,6,7-四氢-4H-环戊二烯并[4,5]噻吩并[2,3-d]-嘧啶-4-酮衍生物的合成及其抑菌活性

利用三组分氮杂Wittig反应, 以三氢环戊二烯并噻吩基三苯基膦亚胺、对氟苯基异氰酸酯和酚, 合成了13个未见文献报道的2-芳氧基-3-对氟苯基-3,5,6,7-四氢-4H-环戊二烯并[4,5]噻吩并[2,3-d]-嘧啶-4-酮衍生物, 产率58%～73%. 通过IR, 1H NMR, MS 和元素分析对目标化合物的结构进行了表征. 初步探讨了所合成化合物的抑菌活性, 结果显示所合成的化合物对真菌(桔青霉菌)的抑制活性优于对细菌的抑制活性.     

苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物的合成

在乙醇钠的催化下,4-[(三苯基膦叶立德)氨基]-2,3-二氢-3-苯基-2-硫代噻唑-5-羧酸乙酯(膦亚胺1)与芳香基二异氰酸酯和亲核试剂的双氮杂Wittig反应制得苯桥连的双[噻唑并[4,5-d]嘧啶-7(6H)-酮]衍生物,产率为56%～92%.产物结构经IR,1H NMR,MS和元素分析确证.     

新型5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d] 嘧啶-4-酮衍生物的合成及其除草活性

以吡唑膦亚胺、芳基异氰酸酯和芳基甲酰肼为原料，通过串联氮杂Wittig反应关环合成了12种新型的5-芳甲酰胺基-6-芳胺基-吡唑并[3,4-d]嘧啶-4-酮衍生物(3a~3l)，其结构经¹H NMR, ¹³C NMR， IR和HR-MS(ESI)表征。对单双子叶除草活性的初步测试结果发现：部分化合物具有优异的除草活性，特别是浓度为100 mg·L^-1时，5-(4-氟苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4(5H)-酮3i和5-(4-吡啶苯甲酰胺基)-6-(4-氯苯胺基)-3-甲硫基-1-苯基-1H-吡唑[3,4-d]-嘧啶-4 (5H)-酮3k对油菜和稗草的茎和根的抑制率高达100%。     

6-溴-N-芳基噻吩[2,3-d]并嘧啶-4-胺类化合物的合成新方法

研究了6-溴-N-[3-氯-4-(3-氟苄氧基)苯基]噻吩[2,3-d]并嘧啶-4-胺的合成新方法.以相对廉价的2,5-二羟基-1,4-二噻烷和丙二腈为原料,依次通过Gewald反应、芳环溴代、缩合、环合以及Dimroth重排四步反应得到目标产物6-溴-N-[3-氯-4-(3-氟苄氧基)苯基]噻吩[2,3-d]并嘧啶-4-胺,总产率为56.9%.用1H NMR,IR,MS和HRMS对产物进行了结构表征.并应用该方法,合成了一系列的6-溴-N-芳基噻吩[2,3-d]并嘧啶-4-胺类化合物.研究表明该方法具有原料易得、操作简便、收率较高,且产物容易分离纯化等优点.     

新型5,6,7,8-四氢苯并噻吩并嘧啶酮衍生物的合成与抗肿瘤活性研究

应用5,6,7,8-四氢苯并噻吩膦亚胺(2)与烷基异氰酸酯的氮杂Wittig反应生成碳二亚胺2,在不同的条件下,2分别与不同的亲核试剂反应,有效地合成了不同取代的新型稠合噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物.所得化合物的结构由1H NMR,IR,MS和元素分析所确证.初步的体外抗肿瘤活性测试,结果显示目标化合物具有抑制肿瘤细胞的生长,其中5d对口腔肿瘤细胞KB2IC50值为19.0μmol/L,表现出潜在的抗肿瘤活性.     

新型的2-烷氨基-3-苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及其抑菌活性

用烯基膦亚胺与苯基异氰酸酯、伯胺的串联aza-W ittig反应合成了8个新型的2-烷氨基-3-苯基-5-甲基-6-(1H-1,2,4-三唑-1-基)-噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物(6a~6h),其结构经1H NMR,MS和元素分析表征。生物活性测试结果表明,部分化合物表现出一定的抑菌活性,其中6 c活性最好,在c(6 c)=5×10-5g.L-1时,对棉花枯萎菌的抑制率达90%。     

Application of bis(iminophosphorane) in heterocyclic synthesis: new entries to symmetrically or unsymmetrically substituted thieno[2,3-d:5,4-d']dipyrimidine-4,5(3H,6H)-diones

The bis(carbodiimides) 4, obtained from bis-aza-Wittig reactions of bis(iminophosphorane) 3 with 2 equiv of aromatic isocyanates, were reacted with secondary amine to give symmetrically substituted 2,7-diaminothieno[2,3-d:5,4-d']dipyrimidine-4,5(3H,6H)-dione 6 in the presence of a catalytic amount of EtO(-)Na(+). Reactions of 4 with phenols or ROH in the presence of a catalytic amount of potassium carbonate or RO(-)Na(+) gave symmetrically substituted 2,7-diaryl(alkyl)oxythieno[2,3-d:5,4-d']dipyrimidine-4,5(3H,6H)-diones 6 in satisfactory yields. However, iminophosphoranes 9 were obtained via reaction of bis(iminophosphorane) 3 with 1 equiv of aromatic isocyanate and subsequent reaction with an amine in the presence of a catalytic amount of EtO(-)Na(+). Further reaction of iminophosphoranes 9 with aromatic isocyanates and various nucleophile generated unsymmetrically substituted thieno[2,3-d:5,4-d']dipyrimidine-4,5(3H,6H)-diones 12 in good yields.     

An efficient route for synthesis of 2-alkylamino benzo[b]thieno[3,2-d]pyrimidin-4(3H)-one

The carbodiimide 2,obtained from the aza-Wittig reactions of iminophosphorane 1 with alkyl isocyanates,reacted with primary amino to give 2-alkylamino benzo[b]thieno[3,2-d]pyrimidin-4(3H)-ones 4 and 5.The formation mechanism of the title compounds has been investigated.     

Oxidative cyclocondensation of cyclic thio-and selenoureas. 5. 2-Thioxothieno-and 2-thioxopyrido[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidin-4-ones

A study was carried out on the oxidative cyclocondensation of 2-thioxothieno-and 2-thioxopyrido[2,3-d]pyrimidin-4-ones. The thiophene ring with excess π-electron density facilitates the reaction, while the pyridine ring with diminished π-electron density hinders it. 2-Thioxothieno-[2,3-d]pyridimin-4-ones were converted into previously unreported 7H,13H-[1,2,4]thiadiazolo-[3,2-b:5,4-b′]bis(thieno[2,3-d]pyridimine-7,13-diones). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1424–1427, September, 2007.     

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.     

2-烷(芳)氧基苯并呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物的合成及杀菌活性

应用膦亚胺3与芳基异氰酸酯的氮杂Wittig反应, 生成碳二亚胺4, 4再分别与酚、醇作用, 在碳酸钾或醇钠催化下关环, 以72%～88%的产率合成了2-烷(芳)氧基取代-苯并呋喃并[3,2-d]嘧啶-4(3H)-酮衍生物5和6, 其结构经IR, 1H NMR, MS和元素分析证实. 初步生物活性测试表明该类化合物表现出温和的杀菌活性. 如5f在50 mg/L浓度时, 对黄瓜灰霉菌的抑制率为55%.     

Discovery of novel Thieno[2,3-d]pyrimidin-4-yl hydrazone-based cyclin-dependent kinase 4 inhibitors: synthesis, biological evaluation and structure-activity relationships

The design, synthesis, and evaluation of novel thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as cyclin-dependent kinase 4 (CDK4) inhibitors are described. In continuing our program aim to search for potent CDK4 inhibitors, the introduction of a thiazole group at the hydrazone part has led to marked enhancement of chemical stability. Furthermore, by focusing on the optimization at the C-4' position of the thiazole ring and the C-6 position of the thieno[2,3-d]pyrimidine moiety, compound 35 has been identified with efficacy in a xenograft model of HCT116 cells. In this paper, the potency, selectivity profile, and structure-activity relationships of our synthetic compounds are discussed.     

Understanding the tetrazole ring cleavage reaction with hydrazines: Structural determination and mechanistic insight

A distinction in the behaviour of several hydrazines as N-nucleophiles in the recently developed one-pot method for pyrimidine core annulation via 1H-tetrazole ring cleavage was examined. The product structures, 2,3-diamino- or hydrazino derivatives of thieno[3,2-d]pyrimidin-4(3H)-ones, thieno[2,3-d]pyrimidin-4(3H)-ones and [1]benzofuro[3,2-d]pyrimidin-4(3H)-one, were elucidated based on NMR and single crystal X-ray analysis.     

Synthesis and antibacterial activity of some novel triazolothienopyrimidines

A novel series of some novel 5-substituted-1,2,4-triazolo[4,3-c]8,9,10-trihydrocyclopenta/8,9,10,11,12-pentahydrocyclohepta[b]thieno[3,2-e]pyrimidin-3-thiones has been synthesized. The intermediates 4-chloro-2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidines were prepared by warming 2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidin-4[3H]-ones with oxalyl chloride. Thieno[2,3-d]pyrimidin-4[3H]-ones were prepared by a novel, microwave assisted, solvent free, synthetic route under basic conditions hitherto unreported in the literature from ortho amino ester of thiophene. The chloro derivatives, without further purification, were hydrazinated to yield 2-substituted-4-hydrazino-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidines. These compounds were cyclized with carbon disulphide to give the title compounds in quantitative yields. The final compounds were screened for antibacterial activity by Kirby Bauer's method using ampicillin as the standard against various gram positive and gram negative bacteria. All the compounds showed antibacterial activity comparable with the standard.