Direct Synthesis of Trichloro‐thiazolo[3,2‐a]pyrimidine and Thiazolo[2,3‐b]quinazoline Derivatives

An efficient one‐pot method for synthesis of new biologically active thiazolo[3,2‐a ]pyrimidine and thiazolo[2,3‐b ]quinazoline derivatives is described via reaction of pentachloropyridine with fused pyrimidine‐2(5H )‐thiones or quinazoline‐2(1H )‐thiones. These reactions were carried out in the presence of potassium carbonate as a base in acetonitrile as a solvent to produce products 3a – n in good‐to‐excellent yield. Pentachloropyridine is doubly electrophilic building blocks for the formation of ring annulated thiazolo[3,2‐a ]pyrimidine and thiazolo[2,3‐b ]quinazoline products.     

Unexpected 1,3‐Dipolar Cycloaddition Reaction of Thiazolo[3,2‐a]pyrimidine Derivatives and Nitrilimine

The 1,3‐dipolar cycloaddition reactions of nitrilimine with thiazolo[3,2‐a]pyrimidine derivatives was investigated. Bis‐cycloadducts were obtained through a domino 1,3‐dipolar cycloaddition/ring‐opening/ring‐opening/1,3‐dipolar cycloaddition processes. The structures of the products were characterized thoroughly by NMR, IR, MS, elemental analysis together with X‐ray crystallographic analysis.     

Synthesis of Some New Thiazolo[3,2‐a]pyrimidine Derivatives and Their Applications as Disperse Dyes

A series of novel thiazolo[3,2‐a]pyrimidine derivatives were synthesized by using β‐ketoanilides 1a–c as starting materials and as key intermediates for preparation of new pyrimidinecompounds 3a–e and fused heterocyclic pyrimidine derivatives 5a–c . The new compounds were transformed to disperse dyes 6a,b and 7 . The chemical structures were elucidated by spectroscopic and elemental analyses and found to be in good agreement with the proposed structures. The versatility of compounds 6a,b and 7 for textile dyeing as disperse dyes was reported. The synthesized dyes were applied to polyester fabrics by using high temperature dyeing method at 120°C. The dye uptake expressed as color strength (k/s) of the dyed samples has been measured. Moreover, the color strength was examined in detail. In addition, the position of color in CIELAB coordinates (L*, a*, b*, h, and C*) was assessed. The color fastness of the dyed samples gave excellent results for washing and rubbing; however, the light fastness was moderate. Raman spectra of dyed samples unequivocally excluded ring dyeing and found to match with the proposed structures.     

Synthesis and Anticancer Evaluation of Some Novel Thiophene,Thieno[3,2‐d]pyrimidine,Thieno[3,2‐b]pyridine,and Thieno[3,2‐e][1,4]oxazepine Derivatives Containing Benzothiazole Moiety

In an attempt to establish novel candidate with promising anticancer activity, two derivatives of (benzo[d]thiazol‐2‐yl)thiophene backbone 1 and 14 were synthesized, and they further reacted with various chemical reagents to afford the corresponding substituted thiophene derivatives 6 , 8 , 10 , 15 , 17 , and 20 , thieno[3,2‐d]pyrimidine derivatives 2 – 5 , 7 , 9 , 16 , 21 , 23 , and 24 , thieno[3,2‐b]pyridine derivatives 11 – 13 , and thieno[3,2‐e][1,4]oxazepine derivative 18 . Structures of prepared compounds were affirmed via spectral and elemental data. Among the obtained compounds, seven derivatives 2 , 3 , 4 , 5 , 11 , 12 , and 13 were chosen by National Cancer Institute, USA. Such compounds were screened for their antitumor activity versus 60 cancer cell lines in one‐dose (10 μmol) screening assay. The outcomes showed that all selected compounds exhibited moderate to high anticancer activity towards many cancer cell lines among which compounds 5 and 11 exerted potent antitumor activity against numerous malignant growth cell lines particularly Ovarian Cancer IGROV1.     

Synthesis of Some Novel Pyrido[2,3‐d]pyrimidine and Pyrido[3,2‐e][1,3,4]triazolo and Tetrazolo[1,5‐c]pyrimidine Derivatives as Potential Antimicrobial and Anticancer Agents

A novel series of pyrido[2,3‐d]pyrimidines 3a – d , 4a – d , 5a – d , 6a – d , and 7a – d ; pyrido[3,2‐e][1,3,4]triazolo; and tetrazolo[1,5‐c]pyrimidines 10a – d and 11a – d was synthesized through different chemical reactions starting from 2‐amino‐3‐cyano‐4,6‐diarylpyridines. The newly synthesized heterocycles were characterized by elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral data. Compounds have been screened for their antibacterial and antifungal activities. The data showed that the presence of electron‐donating group such as p‐methoxyphenyl increases the antimicrobial activity. Also, the compounds have shown anticancer activity for colon and liver cancer cells.     

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.     

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.     

Studies on Synthesis of Novel Pyrido[3,2‐e]tetrazolo[1,5‐c]pyrimidine Derivatives and Their Antimicrobial Activity

A series of novel pyrido[3,2‐e]tetrazolo[1,5‐c]pyrimidine derivative 4 were synthesized starting from 2‐amino‐4‐trifluoromethyl‐6‐phenyl nicotinonitrile 1 via construction of tetrazole followed by fusion of pyrimidine ring. All final products were screened for antibacterial and antifungal activities.     

新型含吡唑的噻唑并[3,2-a]嘧啶类化合物的合成及其抗肿瘤活性

以3-甲基-1-苯基-2-吡唑啉-5-酮为原料,经Vilsmeier-Haack反应和Biginelli反应制得4-(5-氯-3-甲基-1-苯基-唑-4-基)-5-甲酸乙酯-6-甲基-3,4-二氢嘧啶-2(1H)-硫酮(3);3与芳醛经Knoevenagel反应合成了5个新型的含吡唑的噻唑[3,2-a]并嘧啶类化合物(5a~5e),其结构经1H NMR,13C NMR,IR和ESI-MS表征。采用MTT法测定了5a~5e的抗肿瘤活性。结果表明:5a~5e对人前列腺癌PC-3细胞均具有一定的体外抗增殖活性,其中2-【4-{[6-(乙氧羰酯)-5-(5-氯-3-甲基-1-苯基-吡唑-4-基)-3-氧代-7-甲基-噻唑并[3,2-a]嘧啶-2(5H)-亚基]甲基}苯氧基】乙酸(5a)活性最强,其IC50为44.45μM。     

Synthesis of Some New 1,2,3,4‐Tetrahydropyrimidine‐2‐thione and Their Thiazolo[3,2‐a]pyrimidine,Thiazino and Benzothiazepine Derivatives

The starting N‐(2‐pyridyl)‐6‐methyl‐4‐phenyl‐2‐thioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxamide ( 4 ) was used as a key intermediate for the synthesis of new 1,2,3,4‐tetrahydropyrimidine‐2‐thione and their thiazolo[3,2‐a]pyrimidine, thiazino and benzothiazipen derivatives. The reaction of 4 with haloketones in ethanol catalyzed by base afforded the corresponding thiophenopyrimidine and pyrimidothiazipine derivatives 5 , 6 , 7 , 8 , 9 , 10 . Methylation and formylation of 4 led to the pyrimidine derivatives 15 and 16 , respectively. The preventative compounds were established on the basis of elemental and spectral data.     

Synthesis of Novel Fused Thiazolo[3,2‐a]pyrimidin‐3‐ols and Evaluation for their Antibacterial Activity

A series of novel fused thiazolo[3,2‐a]pyrimidin‐3‐ol derivatives have been synthesized by reaction of fused pyrimidine‐thiones with 4‐substituted phenacyl bromide/3(2‐bromoacetyl)coumarin in refluxing acetic acid with good yields. All the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus thuringiensis (Gram positive), Escherichia coli, and Klebsiella pneumoniae (Gram negative) bacterial strains. Activity results revealed that all the compounds were weak to good active against the tested bacterial strains on comparing with the standard drug gentamicin.     

New heterocyclic structures. [1,2,5]Thiadiazolo[3′,4′:4,5]pyrimido-[2,1-b][1,3]thiazine and thiazolo[3,2a][1,2,5]thiadiazolo[3,4-d]pyrimidine

Derivatives of two new molecular structures, namely, 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one and 6,7-dihydro-9H-thiazolo[3,2-a][1,2,5]thiadiazolo[3,4-d][pyrimidin-9-one, and derivatives of N-substituted sulfamic acid, namely, (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b][1,3]thiazin-6-on-7-yl)sulfamic acid and (7-amino-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidin-5-on-6-yl)sulfamic acid, were separated out as by-products in the reduction reaction of 8-amino-3,4-dihydro-7-nitroso-2H,6H-pyrimido[2,1- b][1,3]thiazin-6-one and 7-amino-2,3-dihydro-6-nitroso-5H-thiazolo[3,2-a]pyrimidin-5-one derivatives, respectively, with sodium hydrosulfite. A mechanism of reaction, which hypothesizes the action of sodium hydrosulfite in an asymmetic form, is proposed. The results of single-crystal X-ray investigation on 7,8-dihydro-6H,10H-[1,2,5]thiadiazolo[3′,4′:4,5]pyrimido[2,1-b][1,3]thiazin-10-one (R = 0.032 for 863 reflections) and (8-amino-3,4-dihydro-2H,6H-pyrimido[2,1-b]- [1,3]thiazin-6-on-7-yl)sulfamic acid, sodium salt (R = 0.028 for 3507 reflections) are reported.     

Synthesis and Pharmacological Evaluation of Some Novel Imidazo[2,1-b][1,3,4]thiadiazole Derivatives

Synthesis of bis‐1,3‐{6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 3 ), bis‐1,3‐{thiadiazolo[2′,3′:2,1]imidazo[4,5‐b]quinoxalinyl}‐1,2,2‐trimethylcyclopentane ( 5 ) has been achieved by the reaction of bis‐(5′‐amino‐1′,3′,4′‐thiadiazolyl)‐1,2,2‐trimethylcyclopentane with α‐haloketones, 2,3‐dichloroquinoxaline respectively. Bromination of compound 3 furnished bis‐1,3‐{5′‐bromo‐6′‐arylimidazo[2,1‐b][1,3,4]thiadiazol‐2‐yl}‐1,2,2‐trimethylcyclopentane ( 4 ). The structural assignment of these compounds was supported by IR, ¹H NMR and elemental analysis data. The antimicrobial, anti‐inflammatory and antifungal activities of some of the compounds have also been evaluated.     

Synthesis of Pyrazolo[1,5‐a][1,3,5]triazine,Pyrazolo[1,5‐a]pyrimidine,and Imidazo[1,2‐b]pyrazole Derivatives Based on Imidazo[2,1‐b]thiazole Moiety

3(5)‐Aminopyrazole derivative ( 6 ) has been synthesized by the reactions of the versatile unreported 2‐cyano‐N ′‐(1‐(3‐methyl‐6‐phenylimidazo[2,1‐b ]thiazol‐2‐yl)ethylidene)acetohydrazide ( 3 ) with phenyl isothiocyanate in KOH/DMF solution followed by reaction with methyl iodide and hydrazine hydrate. Reaction of compound 6 with some 1,3‐dicarbonyl compounds yielded pyrazolo[1,5‐a ]pyrimidine derivatives ( 14 – 17 ). Alkylation of compound 6 with various halo reagents, followed by intramolecular cyclization, yielded the corresponding imidazo[1,2‐b ]pyrazole derivatives 27 , 29 , 31 , and 33 . All newly synthesized compounds were elucidated by considering the data of both elemental analysis and spectral data.     

Synthesis and In Vitro Antitumor Evaluation of Some New Pyrimido[4,5‐b]quinoxaline 5,10‐Dioxide Derivatives

A new series of tricyclic pyrimidoquinoxaline derivatives were synthesized and evaluated as antitumor assays and compared with standard drug 5‐fluorouracil. These new pyrimidoquinoxaline derivatives were synthesized by the reaction with o‐aminonitrilequinoxaline derivative 3 with various reagents. One from which, the condensation of o‐aminonitrile with potassium cyanate in acetic acid was stated as a new procedure for building the pyrimidine ring incorporate to quinoxaline moiety. Further condensation of aminonitrile 3 with formamide or Vilsmeier reaction followed by transamination or carbon disulphide was applied as procedures for the pyrimidine ring syntheses. Compound 15 achieved significant in vitro antitumor activity, and compounds 9 and 14 have high activities.     

Synthesis and Evaluation of Bioactivity of Thiazolo[3,2‐b]‐[1,2,4]‐triazoles and Isomeric Thiazolo[2,3‐c]‐[1,2,4]‐triazoles

Synthesis of 2‐(o‐nitrophenyl)‐6‐arylthiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 and its isomer 3‐(o‐nitrophenyl)‐5‐arylthiazolo[2,3‐c]‐[1,2,4]‐triazoles 6 has been achieved starting from the appropriate 1‐(o‐nitrobenzoyl)‐3‐thiosemicarbazide 1 . Compound 1 on condensation with α‐haloketones gives 2‐(o‐nitrobenzoyl)hydrazino‐4‐arylthiazole hydrobromide 5 , which, on cyclization with POCl₃, affords thiazolo[3,2‐b]‐[1,2,4]‐triazoles 6 and not the isomeric thiazolo[3,2‐b]‐[1,2,4]‐triazoles 4 . This has been established by an unequivocal synthesis of 4 through polyphosphoric acid cyclization of 5‐aroylmethylmercapto‐3‐o‐nitrophenyl‐[1,2,4]‐triazole 3 . Compound 3 was synthesized by condensation of α‐haloketones with 5‐mercapto‐3‐(o‐nitrophenyl)‐[1,2,4]‐triazole 2 , obtained cyclization of 2‐(o‐nitrobenzoyl)hydrazinecarbothioamide 1 with NaOH. The antibacterial and antifungal activities of some of the compounds have also been evaluated.     

Synthesis of 5H-5-oxobenzimidazo[2,1-b]pyrido[3,2-e][1,3]thiazine,A novel ring system

Reaction between 2-chloronicotinic acid chloride and 2-mercaptobenzimidazole afforded 5H-5-oxobenzimidazo[2,1-b]pyrido[3,2-e][1,3]thiazine, a novel heterocyclic ring system. The assigned structure was confirmed by means of mass spectrometry.     

Synthesis of new functionalized imidazo[2,1‐b]thiazoles and thiazolo[3,2‐a]pyrimidines

5‐Oxo‐5H‐[1,3]thiazolo[3,2‐a]pyrimidine‐6‐carboxylic acid ( 4 ), and 6‐methylimidazo[2,1‐b]thiazole‐5‐carboxylic acid ( 17 ) were reacted with amines 6a‐i by the reaction with oxalyl chloride and N, N‐di methyl‐formamide as a catalyst into primary and secondary amide derivatives 7‐14 and 19‐22. From compound 24 N,N'‐disubstituted ureas 26, 27 and perhydroimidazo[1,5‐c]thiazole 29 derivatives of imidazo[2,1‐b]thiazole were prepared. By nmr analysis of compound 29 , the existence of two stereoisomers resulting from both optical, due to centre of chirality at C7′a, and conformational isomerism, due to restricted C5? N6′ bond rotation were proved.     

Synthesis of Some New Pyrimidine and Pyrimido[4,5-d]pyrimidine Derivatives

A convenient synthesis of a series of pyrimidine carbonitrile, thiopyrimidine, and pyrimidopyrimidine derivatives, via the reactions of the versatile, readily accessible 6-aryl-4-oxo-2-thioxo-hexahydro-pyrimidine-5-carbonitrile with the appropriate reagents, is described.     

Synthesis of New Pyrimido[4,5‐e][1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine Derivatives via S/N Smiles Rearrangement

Several new pyrimido[4,5‐e ][1,2,4]triazolo[3,4‐b ][1,3,4]thiadiazine derivatives ( 5a , 5b , 5c , 5d , 5e , 5f , 5g ) were synthesized through the condensation reaction of 5‐bromo‐4,6‐dichloropyrimidine ( 1 ) and 4‐amino‐5‐methyl‐4H‐1,2,4‐triazole‐3‐thiol ( 2 ). The single crystal X‐ray data of one of the derivatives confirmed the occurrence of the S/N type Smiles rearrangement during the course of the reaction.