Synthesis and antiviral evaluation of several 6-(Methylene-carbomethoxy)pteridine-4,7(3H,8H)-diones

The reactions of 5,6-diaminopyrimidin-4(3H)-one derivatives 1a-h , with dimethyl acetylenedicarboxylate are discussed in this paper. 6-Amino-5-(E)(1′,2′-dicarbomethoxyvinyl)aminopyrimidines, 2 , and 6-(methylenecarbomethoxy)pteridinones, 3 , have been obtained as main the products, which can be explained on the basis of a Michael addition on pyrimidine derivatives, and cyclization. Those compounds were evaluated for their in vitro antiviral activity.     

First example of the groebke mcr using hydoxybenzal dehydes and substituted 2‐aminopyrimidines

A three component condensation of 2‐aminopyrimidines, isocyanides and 4‐hydroxybenzaldehydes was studied. 3‐Amino‐2‐(4‐hydroxyphenyl)imidazo[1,2‐a]pyrimidine derivatives were obtained in moderate yields. Using 4‐hydroxy‐3,5‐dimethoxybenzaldehyde and 2‐aminopyrimidine as starting materials in the condensation led to mixtures of isomeric 2‐ and 3‐aminoimidazo[1,2‐a]pyrimidines. It was demonstrated, that the regiospecificity of this reaction is mainly defined by the steric hindrance of substituents on the pyrimidine nucleus and the carbonyl activity of the corresponding aldehydes.     

Synthesis and Antimicrobial Evaluation of some Functionalized Heterocycles Derived from Novel Quinolinyl Chalcone

The reaction of 3‐acetyl‐4‐hydroxyl‐1‐methylquinolin‐2(1H )‐one (1) with 10‐oxo‐4,6,7,8,9,10‐hexahydropyrazolo[1,5‐a ][1]benzothieno[2,3‐d ]pyrimidine‐3‐carbaldehyde (2) afforded the novel enone system 3 . The latter compound was reacted with some 1,2‐binucleophilic reagents to give pyrazoline derivative 4 and isoxazoline derivative 5 . Treatment of chalcone 3 with 1,3‐binucleophilic reagents afforded pyrimidine and thiazine derivatives 6 – 8 . Moreover, reaction of compound 3 with active methylene reagents furnished pyridine, pyran, and cyclohexanone derivatives 9 – 12 . Cyclization of compound 12 by using hydrazine hydrate yielded indazol‐3‐one derivative 13. On the other hand, the cyclocondensation of the enone 3 with 1,4‐dinucleophilic reagents yielded diazepine derivative 14 and triazolothiadiazepine derivative 15 .The characterization of the newly synthesized heterocyles were confirmed on the basis of their elemental analysis and spectral data (IR, NMR, and MS). These compounds were also screened for their antibacterial activities.     

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.     

New access to thiazolo[4,5‐d]pyrimidine derivativess

4‐Amino‐5‐bromo‐2‐substituted‐aminopyrimidines are readily obtained from the newly prepared 5‐bromo‐2,4‐dichloro‐6‐methylpyrimidine by sequential treatment with ethanolic ammonia and secondary amines. These compounds were successfully reacted with various isothiocyanates in the presence of sodamide in DMF to form the new thiazolo[4,5‐d] pyrimidine derivatives.     

5‐Fluoro‐1‐octanoyl­uracil

The crystal structure of 5‐fluoro‐1‐octanoyl­uracil [5‐fluoro‐1‐octanoyl­pyrimidine‐2,4(1H,3H)‐dione, C₁₂H₁₇FN₂O₃], a lipophilic prodrug of 5‐fluoro­uracil, is described. The 5‐fluoro­pyrimidine‐2,4(1H,3H)‐dione moiety is similar to the known structure of 1‐acetyl‐5‐fluoro­uracil. The 1‐octanoyl group and the 5‐fluoro­uracil moiety are essentially coplanar, with the octanoyl carbonyl group oriented towards the the ring C—H group and away from the nearer ring carbonyl group. The torsion angle C—N—C—O (from the ring CH group to the octanoyl carbonyl group) of 9.2 (2)° is similar to the corresponding torsion angles reported for 1‐acetyl‐5‐fluoro­uracil (17.3 and 1.6°) and 1,3‐di­acetyl‐5‐fluoro­uracil (8.8°).     

One‐pot synthesis of pyrido[2,3‐d]pyrimidines via efficient three‐component reaction in aqueous media

A short and facile synthesis of pyrido[2,3‐d]pyrimidine derivatives was accomplished in good yields via the three‐component reaction of aldehydes, alkyl nitriles and aminopyrimidines in water in the presence of triethylbenzylammonium chloride (TEBAC). The structures of these compounds were characterized by elemental analysis, IR and ¹H NMR spectra and further confirmed by single crystal X‐ray diffraction analysis.     

Synthesis of [1,5-A]Pyrimidinone Ring Derivatives

Cyclodehydrogenation of the benzalhydrazino derivatives 5 and 6 gave 6-cyano-7-(4-methoxyphenyl)- 2-phenyl-5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (8) and 6-cyano-7-(4-methoxyphenyl)-4-methyl-2-phenyl- 5-oxo-1,2,4-triazolo[1,5-a]pyrimidine (9) respectively. Melhylation, acetylation and benzylation of 8 gave the corresponding N-methyl, acetyl and benzyl derivatives 10-12 . Methylation of 5 with dimethylsulfate gave 2-benzalhydrazino-5-cyano-3-methyl-6-(4-methoxyphenyl)-3,4-dihydropyrimidin-4-one (6) , of which the reaction with acetic anhydride in pyridine afforded the N-acetylbenzalhydrazino derivative 15 . The latter was also prepared from acetylation of 5 followed by medthylation with iodomethane. Acetylation of 5 with boiling acetic anhydride afforded the diacetyl derivative 16 , whereas its benzylation gave the mono-N-benzyl derivative 14 .     

Microwave‐assisted Synthesis,Characterization, and Density Functional Theory Study of Biologically Active Ferrocenyl Bis‐pyrazoline and Bis‐pyrimidine as Organometallic Macromolecules

Organometallic macromolecules such as ferrocenyl bis‐pyrazoline ( 2 , 3 ) and bis‐pyrimidine ( 4 , 5 ) derivatives were synthesized by reacting ferrocenyl bis‐chalcone 1 with thiosemicarbazide/phenylhydrazine/guanidine hydrochloride/thiourea, respectively, under microwave irradiation. Ferrocenyl bis‐chalcone 1 was synthesized by reacting acetyl ferrocene with terephthalaldehyde. Synthesized compounds were characterized by using IR, ¹H NMR, ¹³C NMR, EI‐MS, and elemental analysis. In vitro antibacterial activity against two Gram‐negative and two Gram‐positive bacteria was determined by the disc diffusion assay. Moreover, minimum inhibition concentrations were also measured with reference to chloramphenicol. Thioamide functionally containing ferrocenyl bis‐pyrazoline derivative 2 shows the best antibacterial activity on Escherichia coli and Salmonella typhimurium, among all tested compounds including the reference drug chloramphenicol. The structure–activity relationship is also developed by using computational calculations with density functional theory (DFT)/B3LYP method.     

Synthesis and Antimicrobial Activity of New Pyridothienopyrimidines and Pyridothienotriazines

5‐Acetyl‐3‐amino‐4‐aryl‐6‐methylthieno[2,3‐b]pyridine‐2‐carboxamides ( 5a,b ) were reacted with triethyl orthoformate or nitrous acid to give the corresponding pyrimidinones 6a,b and triazinones 7a,b . The reaction of 5a,b with acetic anhydride was carried out and its products were identified as a mixture of 8‐acetyl‐9‐aryl‐2,7‐dimethylpyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine‐4(3H)‐one ( 9a,b ) and related 5‐acetyl‐4‐aryl‐3‐biacetylamino‐6‐methylthieno[2,3‐b]pyridine‐2‐carbonitrile ( 10a,b ). Reaction of 7a with some halocompounds afforded the N‐alkylated triazinones 8a‐c . Chlorination of 6a,b and 9a,b with phosphorus oxychloride produced 4‐chloropyrimidines 11a‐d which were used as precursors for the rest of the target heterocycles. Some of the prepared compounds were tested in vitro for their antimicrobial activities.     

Synthesis and Structure of Novel Thieno[2, 3‐d]Pyrimidine Derivatives Containing 1, 3, 4‐Oxadiazole Moiety

The reaction of 5‐(1‐pyrrolyl)‐4‐methyl‐2‐phenylthieno[2, 3‐d]pyrimidine carbohydrazide 5 with CS₂ in the presence of pyridine afforded the 6‐(2, 3‐dihydro‐2‐mercapto‐1, 3, 4‐oxadiazol‐5‐yl)‐4‐methyl‐5‐(1‐pyrrolyl)‐2‐phenylthieno[2, 3‐d]pyrimidine 6 , which reacted with methyl iodide in the presence of sodium methoxide to yield the 6‐(2‐methylthio‐1, 3, 4‐oxadiazol‐5‐yl)‐4‐methyl‐5‐(1‐pyrrolyl)‐2‐phenyl‐thieno[2, 3‐d]pyrimidine 7. The 6‐(2‐substituted‐1, 3, 4‐oxadiazol‐5‐yl)‐2‐phenylthieno[2, 3‐d]pyrimidine derivatives 9, 11 and 13 were obtained by the condensation of 6‐(2‐methylthio‐1, 3, 4‐oxadiazol‐5‐yl)‐2‐phenylthieno[2, 3‐d]pyrimidine 7 with appropriate secondary amines. The structure of the new compounds was substantiated from their IR, UV‐vis spectroscopy, ¹H NMR, mass spectra, elemental analysis and X‐ray crystal analysis.     

Synthesis of new thieno[2,3‐d]pyrimidines,thieno[3,2‐e]pyridines,and thieno[2,3‐d][1,3]oxazines

o‐Aminothiophene dicarbonitrile 1 on neat reaction with cyclic ketones in anhydrous ZnCl₂ yielded mixture of fused aminopyridine 3 and iminospirooxazine 4 derivatives. Similarly, pyrimidine derivatives 5 and 8 were obtained by the reaction of this intermediate 1 with formic acid and DMF‐DMA followed by hydrazine hydrate, respectively. The reaction of o‐amino‐thiophene dicarboxamide 2 at ambient temperature with cyclic ketones yielded spiropyrimidine 10 as a sole product in quantitative yield. The regioselective anellated pyrimidine 9 , 11 , and dihydropyrimidine 12 derivatives were also obtained by the reaction with aromatic aldehydes in presence of piperidine and iodine respectively. J. Heterocyclic Chem., (2012).     

Synthesis and reactions of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidin‐5‐carbonitrile

The synthesis of 6‐methylsulfanyl‐2,4‐dithioxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carbonitrile 4 is described. Compound 4 was reacted with various alkylants. The reaction with chloroacetic acid derivatives results in the formation of thieno[2,3‐d]pyrimidines 8 . When methyl iodide was used 2,4,6‐tris(methylsul‐fanyl)pyrimidine‐5‐carbonitrile 5 was obtained. The substitution of the methylsulfanyl groups in compound 5 by several N‐nuclophiles leads to amino substituted pyrimidines.     

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 properties of O‐2‐[2‐(2‐methoxyethoxy)ethoxy]acetyl cellulose

In this article, a series of O‐2‐[2‐(2‐methoxyethoxy)ethoxy]acetyl celluloses with different degree of substitution (DS) values was synthesized by a homogeneous reaction of cellulose with 2‐[2‐(2‐methoxyethoxy)ethoxy]acetyl chloride in a 10% (w/w) dimethylacetamide/lithium chloride solution, combined with pyridine as the acid acceptor. The total DS values of the derivatives in anhydroglucose units was determined by ¹H and ¹³C NMR spectra, and ranged from 0.4 to 3.0, depending on the amount of acid chloride in the reaction. The effects of the total DS values and the O‐2‐[2‐(2‐methoxyethoxy)ethoxy]acetyl substituent distribution on the solubility of the derivatives were investigated. The lowest limit of the DS value for water‐soluble O‐2‐[2‐(2‐methoxyethoxy)ethoxy]acetyl cellulose was approximately 0.5, which is lower than that of methylcellulose. The amphiphilic derivatives with higher DS values than 1.7 exhibited a good solubility in both water and organic solvents, such as dimethyl sulfoxide, tetrahydrofuran, and chloroform. Sol‐gel transition in aqueous solution was observed for the amphiphilic derivatives with a higher DS value than 1.7; the precipitation temperature (T_p) decreased as the DS value increased, showing that the derivatives are highly temperature sensitive. The thermal properties of the fully substituted derivative were measured using polarized microscopy, DSC, and X‐ray diffraction; and are discussed in terms of phase transition of the sample derivatives. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 376–382, 2001     

A convenient synthesis of pyrazolo[3,4‐d]pyrimidine‐4,6‐dione and pyrazolo[4,3‐d]pyrimidine‐5,7‐dione derivatives

Pyrazolo‐[3,4‐d]pyrimidine‐4,6‐diones 5 and pyrazolo[4,3‐d]pyrimidine‐5,7‐diones 7 were synthesized by Curtius rearrangement of pyrazolic mono‐esters 2 and 3 followed by hetero‐cyclization via the ureas derivatives 4 and 6 under alkaline conditions.     

An Efficient Synthesis of Pyrido[2,3‐d][6,5‐d]dipyrimidine and 5,5′‐Arylmethylenebis(2,6‐diaminopyrimidinone) Derivatives under Microwave Irradiation

A series of pyrido[2,3‐d][6,5‐d]dipyrimidine and 5,5′‐arylmethylenebis(2,6‐diaminopyrimidinone) derivatives have been synthesized through a rapid reaction of aromatic aldehydes with aminopyrimidines in acetic acid under microwave irradiation. This method has the advantages of simple operation, high yields, short reaction time, and easy work‐up.     

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.     

Novel synthesis of some new pyrimido[1,6‐a]pyrimidine and pyrazolo[1,5‐a]pyrimidine derivatives

An easy and efficient route for synthesis of some pyrimido[1,6‐a]pyrimidine and pyrazolo[1,5‐a]pyrimidine derivatives was described through the reaction of sodium salts of formyl ketones with 6‐aminothiouracil and 5‐aminopyrazole derivatives, respectively. The characterization of the reaction products was confirmed by using elemental analysis and spectral data. J. Heterocyclic Chem., (2012).     

Hydroxypyrimidines Condensation with Carbonyl Compounds: II. Hydroxy-, Sulfanyl-, and Aminopyrimidines

The first part of review treated condensation of barbituric acids with carbonyl compounds both in the absence and in the presence of third components [1]. In so doing we discussed only the reactions involving the C ⁵ atom of the pyrimidine ring. The second part concerns similar transformations of other hydroxy- and aminopyrimidines and thioanalogs thereof.