Factors Affecting the Stability of Platinum(II) Complexes with 1,2,4-Triazolo[1,5-a]pyrimidine Derivatives and Tetrahydrothiophene-1-Oxide or Diphenyl Sulfoxide

The platinum(II) complexes of general formula [PtCl₂(dstp)(S-donor)] were dstp 5,7-dimethyl-1,2,4-triazolo[1,5-a]-pyrimidine (dmtp), 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine (dbtp), 5-methyl-7-isobutyl-1,2,4-triazolo[1,5-a]pyrimidine (ibmtp) or 5,7-diphenyl-1,2,4-triazolo[1,5-a]pyrimidine (dptp), whereas S-tetrahydrothio-phene-1-oxide (TMSO) or diphenyl sulfoxide (DPSO) were synthesized in a one-pot reaction. Here, we present experimental data (¹H, ¹³C, ¹⁵N, ¹⁹⁵Pt NMR, IR, X-ray) combined with density functional theory (DFT) computations to support and characterize structure–spectra relationships and determine the geometry of dichloride platinum(II) complexes with selected triazolopyrimidines and sulfoxides. Based on the experimental and theoretical data, factors affecting the stability of platinum(II) complexes have been determined.     

5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-芳磺酸酯新型化合物的合成及生物活性

三唑类化合物具有广泛的生物活性。以2-羟基-5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶为原料,在缚酸剂存在下,于室温分别和苯磺酰氯、对甲苯磺酰氯进行酯化反应,合成了两个新型的5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-芳磺酸酯化合物a和b。产物经质谱、红外光谱、核磁共振谱确证。初步生物活性表明,该化合物具有一定的杀菌活性和除草活性,其中a有较高除草活性,而b对禾本科植物有较好的促进生长活性。     

一类新型三唑并嘧啶联噻二唑杂环化合物的合成及杀菌活性

以5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶-2-甲酰肼为原料,设计合成了8个新型的2-(5,7-二甲基-1,2,4-三唑并[1,5-a]嘧啶)-1,3,4-噻二唑.5.硫醚类化合物.通过1HNMR、MS和元素分析对所合成的化合物进行了结构表征.初步的生物活性测试结果表明,所合成的化合物均具有较好的杀菌活性.     

妥卡替尼的合成研究

以2-氨基-4-氯吡啶为起始原料，经过缩合、取代、环合、乌尔曼反应和水合肼还原硝基5步反应得到中间体4-([1,2,4]三唑并[1,5-a]吡啶-7-氧基)-3-甲基苯胺，总收率28.8%。2-氨基-5-硝基苯腈先与N,N-二甲基甲酰胺二甲基缩醛（DMF-DMA）缩合，再与4-([1,2,4]三唑并[1,5-a]吡啶-7-氧基)-3-甲基苯胺环合得到N-[3-甲基-4-([1,2,4]三唑并[1,5-a]吡啶-7-氧基)苯基]-6-硝基-4-喹唑啉胺，再经硝基还原得到N4-[3-甲基-4-([1,2,4]三唑并[1,5-a]吡啶-7-氧基)苯基]-4,6-喹唑啉二胺，三步收率47.4%。同时，采用二硫化碳和2-氨基-2-甲基-1-丙醇为原料，经两步反应制备4,5-二氢-4,4-二甲基-2-(甲硫基)噁唑三氟甲磺酸盐，收率68.6%。最后，N4-[3-甲基-4-([1,2,4]三唑并[1,5-a]吡啶-7-氧基)苯基]-4,6-喹唑啉二胺和4,5-二氢-4,4-二甲基-2-(甲硫基)噁唑三氟甲磺酸盐以三乙胺为碱进行缩合反应得到妥卡替尼，收率62.8%，HPLC纯度99.08%。采用1HNMR、13CNMR和HRMS等对产物结构进行了表征。该合成路线原料廉价易得，为妥卡替尼的放大生产提供理论依据。     

2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶的合成及工艺优化

2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶的合成及工艺优化。以4,6-二甲氧基嘧啶-2-胺为主要原料,经两步反应制得2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶;并考察了第二步合成工艺。通过熔点测定和1HNMR确证了2-氨基-5,7-二甲氧基-1,2,4-三嗪并[1,5-a]嘧啶;找到了最佳合成工艺,总收率81%。该合成方法具有反应条件温和、成本低、适合工业生产等优点。     

2-取代-7-苄氧基-4,5-二氢-[1,2,4]三氮唑[4,3-a]喹啉-1(2H)-酮的合成及其抗癫痫活性研究

为了寻找具有更好抗惊厥活性及低神经毒性的化合物,文章以6-羟基-3,4-二氢-2(1H)-喹啉酮为起始原料合成了4个2-取代-7-苄氧基-4,5-二氢-[1,2,4]三氮唑[4,3-a]喹啉-1(2H)-酮衍生物,对目标化合物,采用小鼠最大电惊厥实验(MES),皮下戊四唑实验(sc-PTZ)测定了其抗惊厥活性,采用旋转法测定了神经毒性.药理实验结果显示目标化合物表现出了较强的抗惊厥话性,该结论证明喹啉并三氮唑化合物具有被开发为新型癫痫治疗药的优良品质.     

Heterocyclic synthesis with nitriles: Syntheses of some novel pyrazolo[1,5-a]pyrimidine and Pyrrolo[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine Derivatives

3,5-Diamino-4-phenacylpyrazoles 1a , b react with the cinnamonitriles 2a , b to afford the novel 7-phenacylpyrazolo[1,5-a]pyrimidine derivatives 4a – d , respectively. Compounds 4c , d undergo cyclization with trichloroacetonitrile to afford the novel tricyclic system pyrrolo-[2′,3′:3,4]pyrazolo[1,5-a]pyrimidine derivatives 5e , f , respectively.     

Studies on aminoazoles: Synthesis of Pyrazolo[1,5-a]-pyrimidines and their aza derivatives

The reaction of 4-arylazo-3-aminopyrazol-5-ones ( 1a – i ) with α,β-unsaturated nitriles, active methylene reagents and nitrile imines are reported. They lead to new polyfunctional derivatives of pyrazolo[1,5-a]pyrimidine ( 5a – c , 6 , 10a – i , 13a – c , 14a – c , 17a – d , 15 ), pyrazolo-[5,1-c]-1,2,4-triazine ( 22a – i ) and pyrazolo[5,1-c]-1,2,4-triazole ( 25a – c ). The structures of these products and the mechanisms of their formation are reported.     

Amino-thieno[2,3–c]pyrazole und Amino-thieno[2,3–b]pyrrole

Amino-thieno[2,3–c]pyrazoles and Amino-thieno[2,3–b]pyrroles The synthesis of thieno[2,3–c]pyrazoles and thieno[2,3–b]pyrroles is described. From the dithioliumsalt ( 1 ) and potassium hydroxide the potassium-(2,2-dicyan-1-methylthio-ethen-1-yl)-thiolate ( 2 ) is formed. This reacts with hydrazine hydrate to form the 3-amino-5-thioxo-pyrazol-4-carbonitrile ( 3 ) S-Alkylation with α-chlorocarbonyl compounds yielding ( 6a–c ) leads via Thorpe-Ziegler-cyclization to 3,4-diamino-thieno[2,3–c]pyrazoles ( 9 ) if the position 1 is alkylated ( 8 ). Acetyl acetone yields 2-mercapto-pyrazolo[1,5–a]pyrimidine ( 5 ). After S-alkylation ( 10a–d ) are immediately cyclized to thieno [2′,3′:3,4]pyrazolo[1,5-a]pyrimidine ( 11a–d ). The ketone ( 6a ) can be cyclized to the pyrazolo [5,1–b]thiazole ( 12 ). 3 reacts with oxalyl chloride to form the 2,3-dioxo-6-thioxo-imidazo[1,2-b]pyrazole ( 13 ) of which S-phenacyl derivative ( 14 ) because the NH-proton cannot be cyclized. The 5-amino-3,4-dicyano-pyrrol-2-thiolate ( 16 ) shows the analogous behaviour. The S-alkylation is followed by cyclization, and 3,5-diamino-thieno[2,3–b]pyrroles ( 18a–b ) arise. Reaction of 5-amino-2-alkylthio-pyrrol-3,5-dicarbonitrile ( 17 ) with acetyl acetone provides pyrrolo[1,2-a]pyrimidine ( 20a–c ) which can be cyclized to form thieno[3′,2′:4,6]pyrimidines ( 21a–c ) very easily.     

s-triazolo[4,3-a][1,3]diazacycloalkans. V. Synthesis of new derivatives of 3-oxo-2,3,5,6,7,8-hexahydro-s-triazolo[4,3-a]pyrimidine

1-Ethoxycarbonyl-2-methylthio-1,4,5,6-tetrahydropyrimidine ( 1 ) reacting with acylhydrazines, affords 2-acyl derivatives of 3-oxo-2,3,5,6,7,8-hexahydro-s-triazolo [4,3-a] pyrimidine ( 2 ) or 2-acylhydrazine derivatives of 1 . The acylation of 2 and its 2-phenyl derivative 3 with isothiocyanates give corresponding 3-oxo-2,3,5,6,7,8 nexahydro-s-triazolo [4,3-a] pyrimidine 11a, b, 13a, e and 14 .     

Synthesis,Characterization and Anti-Breast Cancer Activity of New 4-Aminoantipyrine-Based Heterocycles

4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, ¹H- and ¹³C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1-Hpyrazol- 4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3′-(4,4′-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol- 4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC₅₀ values ranging from 30.68 to 60.72 μM compared with Doxorubicin as positive control with the IC₅₀ value 71.8 μM.     

2-巯基-5，7-二甲基-1，2，4-三唑并[1，5—α]嘧啶的合成

2-巯基-5,7-二甲基-1,2,4-三唑并[1,5—α]嘧啶是合成三唑并嘧啶类衍生物的重要中间体。实验研究了以5-氨基-3-巯基-1,2,4-嘧啶为原料,与乙酰丙酮环合制备2-巯基-5,7-二甲基-1,2,4-三唑并[1,5-α]嘧啶的工艺条件,研究结果表明,在AMZ与乙酰丙酮物质的量比为1：1．1、反应温度为120℃、反应时间为10h时,2-巯基-5,7-二甲基-1,2,4-三唑并[1,5-α]嘧啶的收率达到80％。     

Dechema corrosion handbook Vol. 3 Edited by D. Behrens,VCH Verlagsgesellschaft,Weinheim Frankfurt am Main, 1988. pp. ix + 282, price £286.00 (subscription price to series £238.00 per volume) ISBN 3-527-26654-2

4-Phenyl-5-aminopyrazole 2 obtained from phenylcyanoacetaldehyde 1 and hydrazine hydrate reacted with diethyl malonate to give 3-phenyl-5,7-dioxopyrazolo[1,5-a]pyrimidine 3 , used as the key compound in the synthesis of arylazo dyes. The key compound 3 was coupled with various aryldiazonium salts 4 to yield 3-phenyl-7-hydroxy-6-arylazopyrazolo[1,5-a]pyrimid-5-ones 5. The resulting arylazo dyes (5) were refluxed in phosphorus oxychloride to give 3-phenyl-5,7-dichloro-6-arylazo-pyrazolo[1,5-a]pyrimidines 6 , which subsequently reacted with refluxing morpholine and piperidine to yield 3-phenyl-5,7-bis(morpholino and piperidino)-6-aryiazopyrazolo[1,5-a]pyrimidines 7. The arylazo dyes 5 and 7 were applied to polyester fibres as disperse dyes and the arylazo dyes 6 were applied to polyamide fibres as disperse reactive dyes. The spectral and dyeing properties of the dyes were studied.     

5,7-二甲基-N-芳基-1,2,4-三唑[1,5-a]嘧啶-2-磺酰胺的合成

以5-氨基-3-巯基-1,2,4-三唑为原料,经氧氯化后分别与6个芳胺反应,得到5氨基-N-芳基1,2,4-三唑-3-磺酰胺,继而和乙酰丙酮于乙酸中环合,制得6个取代的1,2,4-三唑[1,5-a]嘧啶-2-磺酰胺衍生物,同时讨论了胺解反应和环合反应的影响因素。所有目标产物的结构均经IR和1HNMR谱验证。     

2-取代-7-苄氧基-4，5-二氢-[1，2,4]-氮唑[4，3-a]喹啉-1（2H）-酮的合成及其抗癫痫活性研究

为了寻找具有更好抗惊厥活性及低神经毒性的化合物,文章以6-羟基-3,4-二氢-2（1忉-喹啉酮为起始原料合成了4个2-取代-7-苄氧基-4,5-二氢-[1,2,4】三氮唑[4,3-a】喹啉-1（2H）-酮衍生物,对目标化合物,采用小鼠最大电惊厥实验（MES）,皮下戊四唑实验（sc-PTZ）测定了其抗惊厥活性,采尉旋转法测定了神经毒性。药理实验结果显示目标化合物表现出了较强的抗惊厥活性,该结论证明喹啉并三氮唑化合物具有被开发为新型癫痫治疗药的优良品质。     

7-苄氨基-9,10-二氢-1,2,4-三氮唑并[4,3-a]喹啉衍生物的合成及环合反应的探讨

以6-氨基-3,4-二氢-2(1H)-喹啉酮为起始原料,经缩合、还原、硫代、环合等反应合成了5个7-苄氨基-9,10-二氢-1,2,4-三氮唑并[4,3-a]喹啉衍生物。产物的结构经核磁共振谱和质谱确证。     

三唑并嘧啶磺酰胺类化合物的合成及除草活性

以5-氨基-3-巯基-1,2,4-三唑为起始原料,经氧氯化、胺解和环合,制得了9个1,2,4-三唑[1,5-a]嘧啶磺酰胺类化合物,产物结构经IR和1H NMR验证,并测定了它们的除草活性。     

2-{[5-（取代吡唑-5-基）-1，3，4-噁二唑-2-基]甲巯基）-5，7-二甲基-1，2，4-三唑[1，5-a]嘧啶类化合物合成及生物活性

设计并合成了七个2-{[5-（取代吡唑-5-基）-1,3,4-噁二唑-2-基]甲巯基）-5,7-二甲基-1,2,4-三唑[1,5-a]嘧啶类化合物,均为未见文献报道的新化合物。目标产物的结构经元素分析、IR、MS和^1H NMR测定确证,初步生物活性测试表明标题化合物具有一定的除草活性。     

α,β-Unsaturated nitriles in heterocyclic synthesis. II. Synthesis of Pyrazolo[3,4-b]pyridine and Pyrazolo[1,5-a]pyrimidine derivatives of antipyrine

5-Amino-3-antipyrinyl-pyrazole ( 1 ) reacted with cinnamonitriles 2a and 2c , d to afford 5-amino-4-benzylidene-pyrazole derivatives 3a , b . Compound 1 reacted with two moles of 2a to yield pyrazolo[3,4-b]pyridine derivative 7a which could be also obtained from the reaction of 3a with 2a . The reaction of 1 with α-cyanochalcone 2e resulted in the formation of pyrazolo-[1,5-a]pyrimidine derivative 8 .     

7-苄氨基-9,10-二氢-1,2,4-三氮唑并[4,3-a]喹啉衍生物的合成

以6-氨基-3，4-二氢-2(1H)-喹啉酮为起始原料，经缩合、还原、硫代、环合等反应合成了5个未见报道的7-苄氨基-9，10-二氢-1，2，4-三氮唑并[4，3-a]喹啉衍生物。产物及中间产物的结构经红外光谱和核磁共振谱确证。