Synthesis of Some Bicyclic Thiazolopyrimidine Derivatives

Thiazolopyrimidine compounds 3(a–d) were synthesized by a simple one-pot condensation reaction of starting pyrimidine derivative 1 and 1,2-dibromoethane 2 in dimethylformamide. In a similar way thiazolopyrimidine compounds 5(a–e) were synthesized by reaction of 1 and 2-bromopropionic acid 4 in dioxane under reflux condition. The yields of products following recrystallization from ethanol were of the order of 70–80%.     

SYNTHESIS OF SOME BICYCLIC THIAZOLO AND THIAZEPINOPYRIMIDINE DERIVATIVES

Thiazolo 3 a–c and oxothialo 5 a–b pyrimidine compounds were synthesized by a simple one-pot condensation reaction of the pyrimidine derivative i 1a and 1,2-dibromoethane i 2 or 2-bromopropanoic acid 4 . In a similar way the thiazepinopyrimidine compounds 7 (a–b) were synthesized by reaction of 1b and 1,4-dichlorobutane 6 in dimethylformamide under reflux condition. The yields of products following recrystallization were of the order of 60–80%.     

SYNTHESIS OF SOME BICYCLIC OXAZOLO- AND OXAZEPINOPYRIMIDINE DERIVATIVES

Oxazolopyrimidine compounds 2(a–c) and 3(a–e) were synthesized by a simple one-pot condensation reaction of the pyrimidine derivative 1 with 1,2-dibromoethane and 2-bromopropanoic acid, respectively. In a similar way the oxazepinopyrimidine compounds 4(a–b) were synthesized by reaction of 1 and 1,4-dichlorobutane in dioxane under reflux condition. The yields of products following recrystallization were of the order of 55–85%.     

Microwave-Assisted Synthesis of Some Pyrimidine Derivatives

Oxo-and thioxopyrimidines 4a–i were synthesized using the Biginelli three-component cyclocondensation reaction of an appropriate β-diketone, arylaldehyde, and (thio)urea under microwave irradiation. Yields of products following recrystallization from ethanol were of the order of 65–90%. ¹H and ¹³C NMR spectroscopy and elemental analysis were used for structural assignment.     

Synthesis of Some New 3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a]-and N-Acetylated Pyrimidines

3-Oxo-2-[(Z)-1-phenylmethylidene]-5H-[1,3]thiazolo[3,2-a] pyrimidine derivatives 2a–f were synthesized by the reaction of an appropriate 3,4-dihydro-2(H)-pyrimidone 1 , chloroacetic acid, sodium acetate and benzaldehyde. Reaction of 1 with acetic anhydride under heating afforded only 3-N-acetylated 3,4-dihydro-2(H)-pyrimidines 3a–f . The yields of the products after recrystallization from ethanol were of the order of 60–92 %. IR, ¹ H NMR spectroscopy, and elemental analysis were used for the identification of these compounds.     

Synthesis of new thiazolo[2,3-b]pyrimidine derivatives of pharmaceutical interest

2H-5-Amino-6-cyano-3,7-dioxothiazolo[2,3-b]pyrimidine was subjected to ring formation affording thiazolo[2,3-b]pyrimidine derivatives. 2H-5-Amino-6-cyano-3,7-dioxo-2-phenylmethylenethiazolo[2,3-b]pyrimidine was also subjected to ring formation affording pyrimido[4,5-d]-, pyrano[2,3-d]-, and pyrido[2,3-d]thiazolo[2,3-b]pyrimidine derivatives. 2-Anilinothiocarbonyl-3,9-dioxo-8-imino-7-phenyl-6-thioxothiazolo[2,3-b]pyrimido[4,5-d]pyrimidine and 8-amino-3,9-dioxo-6-thioxothiazolo[2,3-b]pyrimido[4,5-d]pyrimidine reacted with α-haloactive-methylene compounds to afford heterocyclic compounds containing two, fused and isolated, thiazole moieties, respectively.     

Synthesis and anti-inflammatory activity of imidazo [1,2-a] pyrimidine derivatives

A series of imidazo[1,2-a]pyrimidine derivatives substituted adjacently with two aryls at positions 2 and 3 were designed and synthesized in order to improve their anti-inflammatory activities. Biological tests suggested that these compounds have antiinflammatory activities with COX-2 selectivity to some extent.     

新型噻唑并[3,2-a]嘧啶类化合物的合成

5-乙氧羰基-4-芳基-6-甲基-3,4-二氢嘧啶-2-酮与丁炔二酸二甲酯反应, 合成了系列新的噻唑并[3,2-a]嘧啶类化合物, 反应具有时间短、收率高、后处理简单等优点. 采用NMR (1H, 13C, COSY, HSQC和HMBC), IR等多种谱学技术, 结合元素分析对产物进行详细表征, 通过对目标产物的1,3-偶极环加成的衍生化产物进行X射线单晶衍射而确定目标产物的结构.     

MICROWAVE ASSISTED SYNTHESIS OF SOME FUSED THIAZOLOPYRIMIDINES

A simple and fast synthesis of some fused thiazolopyrimidine compounds 2(a–g) in high yield has been developed using microwave assisted cyclocondensation reaction of 1 with chloroacetic acid, anhydrous sodium acetate, and corresponding aldehyde. Yields of products following recrystallization from ethanol were of the order of 88–94%. IR and ¹ H NMR spectrscopies and elemental analysis were used for identification of these compounds.     

6-烷基-7-亚胺基-2-硫代-2,3,6,7-四氢噻唑并[4,5-d]嘧啶的合成、晶体结构与生物活性

通过3-苯基-5-氰基-2-硫代-2,3-二氢-4-乙氧亚甲胺基噻唑(5)与伯胺反应, 经中间体甲脒关环, 合成了10种新的噻唑并[4,5-d]嘧啶类化合物6a～6j. 所有化合物的结构均经1H NMR, IR和元素分析进行了表征, 并且采用X射线单晶衍射分析方法进一步测定了化合物6i的结构. 初步的生物活性试验表明, 部分标题化合物具有一定的杀菌或除草活性.     

Synthesis of N1-Substituted 1,2,3,6-Tetrahydropyrimidin-2-ones via an Unexpected Reaction of Thiazolo[3,2-a]-pyrimidine Derivatives and Nitrile Oxide

A new class of N1‐substituted 1,2,3,6‐tetrahydropyrimidin‐2‐ones was prepared in moderate yields by the reaction of nitrile oxide with thiazolo[3,2‐a]pyrimidine derivatives via a domino 1,3‐dipolar cycloaddition/ring‐opening/ substitution process. The structures of the products were characterized thoroughly by IR, elemental analysis, MS, NMR together with X‐ray crystallographic analysis.     

Synthesis and spectroscopic characterization of novel 2-amino-4,5,6,7-tetrahydro-3H-cyclopenta[d]pyrimidine and pyrimido[1,2-a]pyrimidine derivatives

2-Aminocyclopenta[d]pyrimidines 3a-c were achieved via a one-pot, three-component reactions of cyclopentanone 1, aromatic aldehyde and guanidine hydrochloride (1:2:1 molar ratio). Also, cyclization of 2,5-bis-(arylmethylidene)cyclopentanones 2 with guanidine hydrochloride (1:1 molar ratio) in methanol in the presence of sodiummethoxide afforded cyclopenta-[d]pyrimidines 3. Compound 3a has been shown to be a useful building block for the synthesis of some novel pyrimido[1,2-a]pyrimidines 5, 7 and 12. The structures of the newly synthesized compounds were confirmed on the basis of analytical and spectral data.     

Facile green one‐pot synthesis of novel thiazolo[3,2‐a]pyrimidine derivatives using Fe3O4@l‐arginine and their biological investigation as potent antimicrobial agents

Thiazolopyrimidine derivatives are well known because of their excellent therapeutic properties. In this investigation, an effective one‐pot three‐component method is described for the synthesis of novel 2‐[(Z )‐1‐(substituted phenyl)methylidine]‐7‐methyl‐3‐oxo‐5‐(substituted phenyl)‐2,3‐dihydro‐5H ‐thiazolo[3,2‐a]pyrimidine‐6‐carboxilic acid tert ‐butyl ester derivatives by condensation reaction of 3,4‐dihydropyrimidine‐2(1H )‐thiones, various aromatic aldehydes and chloroacetyl chloride under reflux conditions in the presence of Fe₃O₄@l ‐arginine nanoparticles as a magnetically reusable and eco‐friendly catalyst with short reaction times and moderate yields. The chemical structures of all synthesized compounds were determined using infrared, ¹H NMR and ¹³C NMR spectroscopies. In vitro antimicrobial activities of 3,4‐dihydropyrimidine‐2(1H )‐thiones and newly fused thiazolo[3,2‐a]pyrimidine derivatives were examined using the well diffusion method against diverse pathogenic strains, namely Staphylococcus aureus ATCC 6538, S. epidermidis ATCC 12228, Escherichia coli ATCC 8739 and Pseudomonas aeruginosa ATCC 9027 (bacteria), Candida albicans ATCC 10231 (yeast) and Aspergillus niger ATCC 16404 (fungus). The compounds having 2‐hydroxy, 4‐hydroxy, 2‐chloro and 4‐chloro groups attached to the phenyl ring on the pyrimidine and 4‐CH₃, 4‐OCH₃ and 3‐NO₂ groups attached to benzylidine on the thiazolo moiety showed significant antibacterial activity.     

Synthesis and Anticancer Activity of Novel Nonfused Bicyclic Thiazolidinone Derivatives

A series of new 2-{4-oxo-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-arylacetamides ( 4a–e ), 5-(2-oxo-2-aryl-ethyl)-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidine-4-ones ( 5a–d ), 2-(4-oxo-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidin-5-yl)-N-arylacetamides ( 7a–e ), and 5-(2-oxo-2-aryl-ethyl)-2-[(2-oxothiazolidin-4-ylidene)-hydrazono]-thiazolidine-4-ones ( 8a–d ) have been synthesized starting from 2-thioxothiazolidin-4-one and 4-thioxothiazolidin-2-one through a multistep reaction sequence. 2-Thioxothiazolidin-4-one was alkylated via the intermediate formation of the triethylammonium salt 1 by ethyl chloroacetate. Compound 2 and 4-thioxothiazolidin-2-one reacted with thiosemicarbazides to give the 1-(4-thiazolidinone-2-ylidene)-4-R-thiosemicarbazones ( 3a,b ) and 1-(2-thiazolidinone-4-ylidene)thiosemicarbazones ( 6a,b ), respectively. Following [2+3]-cyclization of thiazolidinone-substituted thiosemicarbazones ( 3a,b and 6a,b) with N-arylmaleimides and aroylacrylic acids as equivalents of dielectrophilic synthon [C₂]^{2 +}, novel non-fused bicyclic thiazolidinones ( 4a–e, 5a–d, 7a–e, 8a–d ) were synthesized. The structures of the new compounds ( 4a–e, 5a–d, 7a–e, 8a–d ) were established on the basis of their elemental analysis and ¹H NMR and mass spectral data. Eight of the synthesized compounds were tested, and three of them displayed different levels of antitumor activity. The most efficient antitumor agent—2-{4-oxo-3-furylmethyl-2-[(4-oxothiazolidin-2-ylidene)-hydrazono]-thiazolidin-5-yl}-N-4-chlorophenylacetamide ( 4d ) was found to be active against leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate, and breast cancer cell lines with mean lgGI₅₀ and lgTGI values of –5.35 and –4.78, respectively.     

1,2-Dibromoethane and KI mediated α-acyloxylation of ketones with carboxylic acids

The 1,2-dibromoethane-and Kl-mediatedα-acyloxylation of ketones is reported in moderate to good yield without the use of transition metals and strong oxidants.Various acids are well tolerated with wide functional group compatibility.An 1,2-dibromoethane-and Kl-catalysed reaction mechanism is proposed based on the results of control experiments.     

2-(4-正戊氧基苯基)-5-氯-嘧啶的合成

以氯乙酸为原料制得高氯酸盐，产率84％，进而与对正戊氧基苯甲脒盐酸盐相对接，全盛了2-(4-正戊氧基苯基）－5－氯－嘧啶，收率90％。通过元素分析，核磁共振谱证实了其结构。总产率75％（以氯乙酸计算）。     

Microwave Irradiation for Accelerating Synthesis of 5,6-Diphenylimidazo[1,2-a]pyrimidines Based on Isoflavones

Microwave irradiation was used to accelerate the cyclocondensation of isoflavones with 2-aminoimidazole to synthesize 5,6-diphenylimidazo[1,2-a]pyrimidines. A series of 17 new compounds were characterized by Fourier transform infrared, NMR, and elemental analysis. 5-(2-Hydroxyl-4-isopropoxyphenyl)-6-phenylimidazo-[1,2-a]pyrimidine was determined by x-ray diffraction. A variety of substrates can participate in the process with good yields and purities, making this methodology suitable for library synthesis in drug discovery.      

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.     

Synthesis and Characterization of Some Thallium Cyclopentadienide Fused Ring Pyridazines

Thallium cyclopentadiene (Cp) salts are important precursors for the synthesis of a variety of compounds having materials and commercial applications. The synthesis of 5,6-fused ring thallium Cp pyridazines 2a–d from previously reported 5,6-fused ring pyridazines is described herein. This route was quite general, and features an efficient and convenient two-step synthesis of a series of TlCp salts in a THF solution of thallium ethoxide. Full characterization of newly formed TlCp salts 3a–d are reported.