Synthesis of Some Bicyclic Thiazolo- and Oxothiazolo-Pyrimidines

Abstract

Oxothiazolopyrimidine compounds 2(a–e) were synthesized under reflux condition by a simple one-pot condensation reaction of the pyrimidine derivative 1 and chloroacetylchloride in the presence of silver acetate as a catalyst. In a similar way the thiazolopyrimidine 3 and oxothiazolopyrimidine 4 were synthesized by reaction of pyrimidine derivative 1 with 1,2-dibromoethane and 2-bromopropanoic acid respectively. The yields of products following recrystallization from ethanol were of the order of 55–89%.      

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 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 and Structure of Thiazolopyrimidine Derivatives

Russian Journal of Organic Chemistry - Three-component condensations of ethyl acetoacetate with 1,3-thiazol-2-amine and aromatic aldehydes in isopropyl alcohol at 20°C under ultrasonic...     

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.     

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 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%.     

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.     

Facile Syntheses of Some Thieno[2,3-d] Pyrimidine Derivatives

In one-pot synthesis 2-arylidene-5,6,7,8-tetrahydrothiazolo[3,2-a] cyclopenteno-thieno[2,3-d] pyrimidine-3,5-diones (3) were prepared via the reaction of a ternary mixture of 2-thioxo-1,3,4,5,6,7-hexahydr cyclopentinothieno [2,3-d]-4-one (2), chloroacetic acid and a proper aldehyde. Compound 2 reacted with 3-chloropent-2, 4-dione in ethanolic potassium hydroxide yielding the S-acetyl acetone derivative 5f . The latter compound reacted with hydrazine hydrate and phenyl hydrazine yielded the 2-pyrazolthio derivative 10a, b. Compound 5f also underwent cyclization on heating with acetic acid—pyridine solution to give 11. The 2-methylthio derivative 5a, when treated with hydrogen peroxide gave the corresponding oxidized product 9.     

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 Antimicrobial Activity of Some New 1,3-Diphenylpyrazoles Bearing Pyrimidine,Pyrimidinethione, Thiazolopyrimidine,Triazolopyrimidine, Thio-and Alkylthiotriazolop-Yrimidinone Moieties at the 4-Position

1,3-diphenyl-1H-pyrazole-4-carboxaldehyde (1) reacted with ethyl cyanoacetate and thiourea to give the pyrimidinethione derivative 2. The reaction of 2 with some alkylating agents gave the corresponding thioethers 3a–e and 7. Thione 2 was cyclized to 5 and 6 upon a reaction with chloroacetic acid and with benzaldehyde, respectively. Thioether 3c was cyclized to 4 upon boiling with sodium acetate in ethanol, and 7 was cyclized to 8 upon boiling in an acetic anhydride-pyridine mixture. The hydrazino derivative 9 was prepared either by boiling 2 and/or 3a with hydrazine. The reaction of 9 with nitrous acid, acetylacetone, triethyl orthoformate, acetic anhydride, and carbon disulfide gave 10–14. The alkylation of 14 with ethyl iodide, phenacyl bromide, and ethyl chloroacetate afforded the alkythiotriazolo pyrimidinone derivatives 15a–c. The dialkyl derivative 16 was produced upon the treatment of 2 with two equivalents of ethyl iodide. Boiling 16 with hydrazine afforded the hydrazino 17. The reaction of 17 with nitrous acid, carbon disulfide, ethyl cyanoacetate, ethyl acetoacetae, and phenacyl bromide gave 18–22, respectively. Some of the newly obtained compounds were tested for their antibacterial and antifungal activities.     

Synthesis and Antitumor Evaluation of Some Newly Synthesized Pyrazolopyrimidine and Pyrazolotriazolopyrimidine Derivatives

A series of novel pyrazolo[3,4-d]pyrimidine 2b, 3, 5b, pyrazolotetrazolopyrimidine 4, and pyrazolotriazolopyrimidine derivatives 6a,b–10a,b have been synthesized and characterized by elemental analysis and spectroscopic data. Furthermore, the cytotoxicity and in vivo antitumor evaluation of some prepared compounds have been assessed, and derivatives 1a and 6b revealed promising activity in comparison to that of Cisplatin.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

A Convenient Synthesis and Pharmacological Activity of Novel Annelated Pyrimidine Derivatives

Simple and convenient synthesis for a series of 2,3‐diglycosylpyrimidine 4 , pyrazolo[3,4‐d]pyrimidine 8 , ditetrazolo[1,5‐a;1′,5′‐c]pyrimidine 9 , 2,9a,10‐triazaanthracene 12 , thieno[2,3‐d]pyrimidine 14 , 1,3,5,7‐tetraazafluorene‐8‐one 15 , 1,3,5‐triazafluorene‐8‐one 16 , 1,3‐diazafluorene 21a,b derivatives have been synthesized via a sequence of heterocyclization reactions of suitably functionalized 6‐[5‐(4‐bromophenyl)ox‐azol‐4‐yl]‐4‐oxo‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile ( 2 ) with different electrophiles and nucleophiles. The new compounds were prepared with the objective to study their pharmacological properties.     

新磺酰脲类化合物的合成及除草活性

新磺酰脲类化合物的合成及除草活性;嘧啶;合成;除草剂     

Synthesis of Some Pyrazolo[3, 4]pyrimidine Derivatives for Biological Evaluation

Abstract

A novel β -enaminonitrile of 1-(6-p-tolyl-pyridazin-3-yl)-pyrazole derivative 2 was formed using (6-p-tolyl-pyridazin-3-yl)-hydrazine ( 1 ) and 2-ethoxymethylenemalononitrile. The β-enaminonitrile derivative 2 was in turn used as a precursor for the preparation of pyrazoles ( 4 , 6 ), pyrazolo[3, 4-d]-pyrimidines ( 3 , 7–12 ) and pyrazolo[4, 3-e][1,2,4]triazolo[4,3-c]pyrimidine ( 13 ). Also, N- and S-acyclic nucleosides 14 and 15 were prepared. Some of the prepared products showed potent antimicrobial activity.     

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.     

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.     

一些新型呋咱衍生物的合成

以歧化松香为原料, 将其纯化得到脱氢松香酸, 然后经甲酯化、溴代、硝化、成环等步骤, 合成了三个新型脱氢松香酸甲酯呋咱的衍生物12,13-氧化呋咱脱异丙基脱氢松香酸甲酯、12,13-呋咱脱异丙基脱氢松香酸甲酯、12-溴-13,14-氧化呋咱脱异丙基脱氢松香酸甲酯. 产物经红外光谱、核磁共振谱和元素分析方法进行了表征.