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An efficient synthesis and fluorescent properties of a new series of fused pyrimidine derivatives are described. Condensation of aminopyrimidine derivative 1 with acetophenone leads to olefinic pyrimidine 2, various addition-cyclization reactions of which give the corresponding bicyclic pyrimidines 4, 6, and 8. Cycloaddition reaction of pyrimidine 1 to benzoyl isothiocyanate gives thiourea derivative 9. Intramolecular cyclization of compound 9 with NaOH or Br2 produces pyrimidine derivatives 10 or 12, respectively. Heteroannulation of pyrimidine 1 with ninhydrin or α-carbonyl carboxylic acid 15 gives the tetracyclic pyrimidine 14 and diazepine derivative 18, respectively. Fluorescence properties of pyrimidine derivatives have been tested. [ABSTRACT FROM AUTHOR]

Synthesis of new 8-alkyl-5-aryl-1,3-dimethyl-5,7-dihydro-2H-pyrimido[5′,4′:5,6]pyrano[2,3-d]- pyrimidine-2,4,6(1H,3H)-triones by the high yield reaction of 7-amino-5-aryl-1,3-dimethyl-2,4-dioxo-1,3,4,5- tetrahydro-2H-pyrano[2,3-d]pyrimidine-6-carbonitriles with aliphatic carboxylic acids in the presence of POCl3 is presented. It is probable that synthesis of these new products proceeds via the tandem intramolecular Pinner–Dimroth rearrangement. The products are characterized by FT-IR, 1H, and 13C NMR spectra and evaluated for their antibacterial activity against gram +ve bacteria (Staphylococcus aureus and Staphylococcus epidermidis) and gram–ve bacteria (Escherichia coli and Pseudomonas aeruginosa) using the disc diffusion method. [ABSTRACT FROM AUTHOR]

A new and efficient method for the synthesis of hitherto unreported spiro[benzo[4,5]thiazolo[3,2- a ]chromeno[2,3- d ]pyrimidine-14,3′-indoline]-1,2′,13(2H)-triones was developed via the Domino Knoevenagel condensation–Michael addition–intermolecular cyclization sequences of isatin derivatives, cyclohexane-1,3-diones, and 2-hydroxy-4 H -benzo[4,5]thiazolo[3,2- a ]pyrimidin-4-ones, employing 12-tungstophosphoric acid (H 3 PW 12 O 40 ) as an effective and inexpensive catalyst. [ABSTRACT FROM AUTHOR]

A novel series of imidazoles, pyrimidines, and thiazoles were synthesized using microwave irradiation and conventional method from commercial available p‐aminobenzoic acid. Thus, one‐pot condensation of p‐aminobenzoic acid, urea, and chloroacetic acid have been provided two types of imidazole derivatives as separated mixture 2a and 2b. [3 + 2 + 1] Cyclocondensation of 2a, benzaldehyde, and urea/thiourea in acidic medium afforded imidazolo oxazine derivative 3 and Imidazolothiazine 4. Coupling of 2a with benzene diazonium salt gave the phenyldiazenyl imidazolidine 5. While the reaction of 2a, thiourea, and benzaldehyde in sodium ethoxide afforded imidazolothiazine 6. Oxidative cyclization of thiourea derivative 7 resulted a mixture of benzithiazole derivative 7a and oxathiazole derivative 7b. Cyclocondensation of 7a with phenylenediamine and 4‐methyl phenylenediamine furnished imidazole 8 and 9, respectively. Reaction of P‐aminobenzioc acid with potassium cyanate followed by Biginelli reaction with (acetyl acetone, ethyl acetoacetate, and diethyl malonate) and salicyladehyde in HCl tolerated pyrimidine derivatives 10a–c, respectively. In the same manner, the reactions and short reaction time make microwave technique one of the greenest methodology for synthesis of this class of heterocyclic system. [ABSTRACT FROM AUTHOR]

In this work, the synthesis of oxazolo[4,5‐d]pyrimidines and oxazolo[5,4‐d]pyrimidines is reviewed. The review is focused on the construction of the scaffold rather than on its further modification. Nevertheless, selected examples illustrate some of the most common modifications of these scaffolds. The synthetic part is complemented by an overview of their biological activity. This review covers literature and patents from 1967 until the present. [ABSTRACT FROM AUTHOR]

An expeditious synthetic route to access structurally diverse 1,4,5,6-tetrahydropyrimidines via domino ring-opening cyclization of activated aziridines with α-acidic isocyanides has been established. The transformation proceeds via Lewis acid mediated SN2-type ring opening of activated aziridines with α-carbanion of the isocyanides followed by a concomitant 6-endo-dig cyclization in a domino fashion to furnish the 1,4,5,6-tetrahydropyrimidine derivatives in excellent yields (up to 84%) and also in diastereo- and enantiomerically pure form (dr >99:1, ee >99%). [ABSTRACT FROM AUTHOR]

An efficient and facile protocol for the synthesis of azine and azole ring systems was reported. Whereas, reaction of cinnamoyl isothiocyanate with N-nucleophile containing compounds (namely, p-aminophenol (2), N1-phenylbenzene-1,4-diamine (5) and p-aminoacetophenone (8)) tolerated thiourea derivatives 3, 6, and 9, respectively. The later compounds underwent intramolecular cyclization upon treatment with EtONa to give pyrimidinethiones 4, 7, and 10, respectively, in moderate yield (74-79%). Compound 9 underwent intramolecular cyclization and condensation upon reaction with NaOH and benzaldehyde to give pyrimidinethione 12. Thiosemicarbazides 14 and 19 were obtained through reaction of heteroallen 1 with 2,4-dinitrophenylhydrazine 13 and hydrazone 18, respectively. Compound 14 was cyclized to pyrimidinethione 15 and triazine derivatives 17 through its reaction with EtONa at room temperature and refluxing temperature, respectively. Finally, base mediated and oxidative cyclization of thiourea derivative 19 with EtONa, Br2/AcOH, and Pb(OAc)2 afforded thiadiazole 20, benzothiazolotriazole 21, and triazolethione 22 derivatives, respectively. [ABSTRACT FROM AUTHOR]

The review summarizes information on cyclopropane as an independent pharmacophore group and as a fragment for modification of pharmacological activity level of medicines used in practice. The advantages of a cyclopropane fragment over its bioisosteres are that, on the one hand, this fragment imposes conformational rigidity on the molecules of physiologically active compounds and, on the other hand, the replacement of acyclic terminal and “linker” groups with a cyclopropane fragment increases the metabolic stability of the target structures and extends the scope of their therapeutic action. [ABSTRACT FROM AUTHOR]

Various interesting heterocycle skeletons were synthesized via Michael type addition reaction with 1,2; 1,3-bidentate nitrogen and carbon nucleophiles. Cycloaddition of different a,ß-unsaturated systems afforded bromopyrimidinone 3/5, bromothiazine 4 and bromopyrazole 6a/6b pyrazole-1-carboxylate 8, pyridinylmethanone 9, nicotinonitrile 10, pyrazolopyridine 11a/11b, pyran-3-carbonitrile 12/13, chromenopyridine 14 and N-butyrylpyrazolyl-1-butanone 15 derivatives. The structures of the synthesized compounds were elucidated based on IR, NMR and mass spectral analyses. Group of the newly synthesized compounds were screened for their anti-diabetic activities, whereas compounds 8 and 11b exhibited promising anti-diabetic activities at micro molar concentration against a-glucosidase inhibitor with IC50 values ranging between 13.80-500 µM. On the other hand compound 10 showed a week effect as compared to the standard anti-diabetic agent. [ABSTRACT FROM AUTHOR]

A small library containing 3-hydroxyquinazoline-2,4(1 H ,3 H )-dione and 1-hydroxypyrido[2,3- d ]pyrimidin-2(1 H )-one scaffolds was obtained via the copper(I)-catalyzed azidealkyne cycloaddition (CuAAC) reaction and evaluated for their anti-HIV activity in MT-4 cells. Among the synthesized compounds, several 1-hydroxypyrido[2,3- d ]pyrimidin-2(1 H )-one derivatives showed remarkable anti-HIV potency with EC 50 values ranging from 0.92 to 26.85 µM. The most active one, IIA-2 , also showed remarkable and selective potency against HIV type 1 integrase (IN). To the best of our knowledge, this is the first report showing that 1-hydroxypyrido[2,3- d ]pyrimidin-2(1 H )-ones are selective HIV IN inhibitors. Preliminary structure-activity relationship (SAR) studies suggested that the divalent metal ion chelators and the nature and position of substituents around the core are important for antiviral potency. Molecular modeling has been used to predict the binding site of the pyrido[2,3- d ]pyrimidin-2(1 H )-one core in HIV type 1 IN and suggestions are made for improvement of its inhibitory activity. [ABSTRACT FROM AUTHOR]

A convenient and efficient regioselective synthesis of new pyrimido[4′,5′:4,5] [1,3]thiazino[3,2-a]perimidines is described through intermolecular heterocyclization of 2,4-dichloro-5-(chloromethyl)-6-methylpyrimidine and 1H-perimidine-2(3H)-thione in short reaction times under mild conditions. [ABSTRACT FROM PUBLISHER]

We report new method for preparation of 2-amino-5-aryl-1,3,4-thiadiazoles by reaction of arylaldehyde with thiosemicarbazide and in the next step via cyclization of 2-aryl hydrazinecarbothioamide in the presence of ZnCl2.6H2O or FeCl3.6H2O. Also, in this research, new substituted 1,3,4-thiadiazolo-[3,2-α]pyrimidines were synthesized by the reaction of 2-amino-5-aryl-1,3,4-thiadiazoles derivatives with DMAD or DEAD in the presence of K2CO3 under reflux conditions. The FT-IR, 1H-NMR, 13C-NMR, elemental analysis and single- crystal X-ray analysis confirm the structures of the products. [ABSTRACT FROM AUTHOR]

Methyl 3-(dimethylamino) acrylates containing trifluoromethylsulfenyl-, trifluoromethylsulfinyl-, and trifluoromethylsulfonyl groups were synthesized and their utility demonstrated by reactions with aliphatic and aromatic amidines to produce 2,5-substituted 4(3 H )-pyrimidones. Cyclization reactions of enaminones with urea or thiourea led to 5-substituted uracil or 2-thiouracil derivatives, respectively. [ABSTRACT FROM AUTHOR]

The known methods for synthesis of thioxopyrimidines and their condensed analogs with exocyclic sulfur atom are summarized and discussed. The most popular approaches are based on [3+3], [4+2], [5+1] cyclization processes or domino reactions. The literature data analysis shows that the title compounds possess diverse biological activities, such as antioxidant, radioprotective, analgesic, antiinflammatory, antihypertensive, anxiolytic, anamnestic, anticonvulsant, antimicrobial, fungicidal, herbicidal, antiviral, and anticancer. [ABSTRACT FROM AUTHOR]

5-Bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one was used as an efficient precursor for the synthesis of a new series of (1,2,3-triazol-1-yl)methyl-pyrimidine biheterocycles. For this stepwise synthesis, the 5-bromo-1,1,1-trifluoro-4-methoxypent-3-en-2-one was first converted into 5-azido-1,1,1-trifluoro-4-methoxypent-3-en-2-one through a nucleophilic substitution of the bromine by an azide group. This was then followed by an azide-alkyne cycloaddition reaction (click chemistry) to give the key intermediate 5-[4-alkyl(aryl)-1H-1,2,3-triazol-1-yl]-1,1,1-trifluoro-4-methoxypent-3-en-2-ones. These were cyclocondensed with 2-methylisothiourea sulfate to give a series of 2-(methylthio)-4-(1,2,3-triazol-1-yl)methyl-6-(trifluoromethyl)pyrimidines. Additionally, the 2-methylthiopyrimidine products were used to prepare a new series of 2-amino-4-(1,2,3-triazol-1-yl)methyl-6-(trifluoromethyl)pyrimidines. [ABSTRACT FROM AUTHOR]

Pyrimidinone is one of the important nitrogen containing heterocycles due to their wide range of bioactivities. An efficient silver-catalyzed intermolecular cyclization of 2-aminopyridines with various alkynoates has been developed. 2-Substituted 4 H -pyrido[1,2- a ]pyrimidin-4-ones containing a wide range of functional groups are synthesized in the standard conditions. This transformation is conducted under convenient conditions and affords products in good yields. [ABSTRACT FROM AUTHOR]

Ortho-substituted polymethoxydiarylazolopyrimidines were synthesized using polymethoxysubstituted benzaldehydes and acetophenones as starting material. X-ray crystallography data clearly confirmed that the subsequent cyclization of 3-amino-1,2,4-triazole with ketoaldehydes yielded polymethoxyphenylsubstituted 6,7-diaryl-[1,2,4]triazolo[1,5-a]pyrimidines as single isomers. All compounds were evaluated in vivo using phenotypic sea urchin embryo assay. 6-(4-Methoxyphenyl)-7-(3,4,5-trimethoxyphenyl)pyrazolo[1,5- a]pyrimidine showed antimitotic microtubule destabilizing activity. The importance of aryl rings substituents in diaryltriazolopyrimidines for their antiproliferative antitubulin effect has been suggested. [ABSTRACT FROM AUTHOR]

An efficient and novel approach using highly versatile but less exploited monofluorinated a-oxoketene N,S-acetals as synthons for the synthesis of novel fluorinated multisubstituted pyrimidines and 1,5-benzodiazepines by cyclization with guanidine nitrate and o-phenylenediamine, respectively, has been developed. The synthesized compounds, which carry additional functional groups that allow further functionalization, are of considerable interest as building blocks in medicinal chemistry. X-ray crystallographic studies confirmed the formation of the desired cyclized product. [ABSTRACT FROM AUTHOR]

A method of convergent and stepwise synthesis of novel 4,6-unsubstituted 5-acyl-2-phenyldihydropyrimidines using the Weinreb amide group is developed. The cyclization of 4-dimethylamino-1,3-diaza-1,3-butadiene having N-protecting groups (Boc) with N -methoxy- N -methylacrylamide gives 6-unsubstituted 4-dimethylamino-2-phenyltetrahydropyrimidine, which is a synthetic intermediate for 4,6-unsubstituted 5-acyl-2-phenyldihydropyrimidines. The transformation of the Weinreb amide group to an acyl group via substitution reaction using organolithium reagents, following the elimination of a dimethylamino group using MeI proceeds smoothly, affording 4,6-unsubstituted 5-acyl-2-phenyldihydropyrimidines in good overall yield. The N-protecting group can be easily removed to obtain N-unsubstituted dihydropyrimidines as a mixture of tautomers, and their tautomeric behaviors were analyzed by 1 H NMR spectroscopy. [ABSTRACT FROM AUTHOR]

Dihydroorotase (DHOase) is the third enzyme in the de novo pyrimidine synthesis pathway and is responsible for the reversible cyclization of carbamyl-aspartate (Ca-asp) to dihydroorotate (DHO). DHOase is further divided into two classes based on several structural characteristics, one of which is the length of the flexible catalytic loop that interacts with the substrate, Ca-asp, regulating the enzyme activity. Here, we present the crystal structure of Class I Bacillus anthracis DHOase with Ca-asp in the active site, which shows the peptide backbone of glycine in the shorter loop forming the necessary hydrogen bonds with the substrate, in place of the two threonines found in Class II DHOases. Despite the differences in the catalytic loop, the structure confirms that the key interactions between the substrate and active site residues are similar between Class I and Class II DHOase enzymes, which we further validated by mutagenesis studies. B. anthracis DHOase is also a potential antibacterial drug target. In order to identify prospective inhibitors, we performed high-throughput screening against several libraries using a colorimetric enzymatic assay and an orthogonal fluorescence thermal binding assay. Surface plasmon resonance was used for determining binding affinity ( K D ) and competition analysis with Ca-asp. Our results highlight that the primary difference between Class I and Class II DHOase is the catalytic loop. We also identify several compounds that can potentially be further optimized as potential B. anthracis inhibitors. [ABSTRACT FROM AUTHOR]

An efficient domino protocol has been developed for the synthesis of new pyrimidine scaffolds, through a one-pot four-component cascade transformation via [Bmim]HSO 4 ionic liquid mediated reaction, using an equimolar mixture of thiochroman-4-one, benzaldehyde, thiourea and 3-bromo-1-phenylpropan-1-one leading to the formation of a double electrophilic pyrimidine-2(5 H )-thione intermediate. The intermediate regioselectively undergoes cyclization through intramolecular N H bond activation followed by C S bond formation leading to highly functionalized thiazolo[3,2- a ]thiochromeno[4,3- d ]pyrimidines. The ionic liquid operates efficiently under mild conditions. The recyclability and scope for recovery of the ionic liquid makes this protocol environmentally benign. Further, the compounds 5d , 5g and 5k showed promising antimicrobial activity against the tested Gram-positive bacterial strains. Among them, the compound 5d was identified as a lead molecule exhibiting promising anti-biofilm activity towards Staphylococcus aureus MTCC 96, Bacillus subtilis MTCC 121, Staphylococcus aureus MLS16 MTCC 2940 and Micrococcus luteus MTCC 2470 with IC 50 values of 2.1, 1.9, 2.4 and 5.3 μg/mL, respectively. Further, the compound 5d showed increased levels of intracellular ROS accumulation in Staphylococcus aureus MTCC 96 suggesting that oxidative stress resulted in bacterial cell lysis and death. [ABSTRACT FROM AUTHOR]

A series of novel pyrimidines ( 6a-6i) has been synthesized from corresponding chalcones and isonicotinimidamide.HCl in the presence of potassium carbonate involving Michael addition followed by cycloaddition. All newly synthesised chalcones and pyrimidines were screened for in vitro antimicrobial activity against various Gram positive, Gram negative bacterial and fungal strains. Most of compounds displayed high antimicrobial activity compared to standard drugs Penicillin, Streptomycin and Ampothericin-B. [ABSTRACT FROM AUTHOR]

A silver catalyzed cyclization of acetylene amine was developed to synthesize 4,6-substituted pyrrolo[3,2- d ]pyrimidine, a bioactive isosteric scaffold of purine. Starting from simple commercially available acetylenes and pyrimidines, the method was found to be compatible with wide chemical functionalities, leading to a series of pyrrolo[3,2- d ]pyrimidines in 84–91% yields. [ABSTRACT FROM AUTHOR]

An efficient Au-catalyzed domino intramolecular cyclization reaction has been developed for the construction of pyrimidine derivatives from ynals and amidines at room temperature for 3 h. This transformation provides a new method for the formation of C–C and C–N bonds via intramolecular cyclization. [ABSTRACT FROM AUTHOR]

The synthesis of triaryl methanols was investigated by reacting different 4-metalated 2-substituted pyrimidines with diaryl ketones, the latter being generated by deprotocupration-aroylation of azine and diazine substrates. Cyclization of the triaryl methanols thus obtained afforded pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidines, which were evaluated for kinase inhibition and antiproliferative activities in melanoma cells. [ABSTRACT FROM AUTHOR]

A series of new phosphonylated 1,2,3-triazolo[4,5-d]pyrimidines (8-azahypoxanti-nes) was synthesized employing the 1,3-dipolar cycloaddition of corresponding ω-azidoalkylphosphonates and 2-cyanoacetamide followed by the pyrimidine ring closure with triethyl orthoformate. All compounds were evaluated in vitro for inhibitory activity against a broad variety of DNA and RNA viruses but none was found active below 100 μM. They were not cytostatic at 250 μM. [ABSTRACT FROM PUBLISHER]

The acid-catalyzed condensation between 2-aminosubstituted [1,2,4]triazolo[1,5-a]pyrimidines and their analogues with various saturation of the pyrimidine ring and 1,3-diketones or 1,1,3,3-tetramethoxypropane was evaluated as a new approach for the synthesis of diversely substituted polycyclic derivatives of triazolopyrimidine. The reaction of 4,5,6,7-tetrahydro- or aromatic aminotriazolopyrimidines results in selective formation of the corresponding [1,2,4]triazolo[1,5-a:4,3-a′]dipyrimidin-5-ium salts, and the condensation of substrates containing the 4,7-dihydro-[1,2,4]triazolo[1,5-a]pyrimidine fragment is accompanied by a cascade rearrangement with unusual recyclization of the dihydropyrimidine ring to yield partially hydrogenated [1,2,4]triazolo[1,5-a:4,3-a′]dipyrimidin-5-ium or pyrimido[1′,2′:1,5][1,2,4]triazolo[3,4-b]quinazolin-5-ium salts. The proposed methodology exhibits a wide scope, providing rapid access to polycondensed derivatives of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold. DFT calculations of the Gibbs free energies of possible isomers were performed to rationalize the experimentally observed reactivity and selectivity. [ABSTRACT FROM AUTHOR]

The reaction of thioxopyrimidine derivative 1a with chloroacetic acid and p-chlorobenzaldehyde gave compound 2. Alkylation of 1b using chloroacetonitrile gave N-alkylated derivative 6 which was reacted with hydrazine hydrate to give 7. Compound 7 was cyclized with formic and nitrous acid to give 8 and 9, respectively. The reaction of 1b with phosphorous oxychloride gave chloropyrimidine derivative 10 which was reacted and cyclized with different reagents to give compounds 11- 23. The antimicrobial activity was studied against examples of Gram-positive and Gram-negative bacteria. [ABSTRACT FROM AUTHOR]

The 1,3-dipolar cycloaddition reaction of ethyl 5-aryl-2-(2-methoxy-2-oxoethylidene)-7-methyl-3-oxo-2,3-dihydro-5 H-[1,3]thiazolo[3,2-a] pyrimidine-6-carboxylate and azomethine ylide, which was generated in situ by the reaction of 11H-indeno[1,2-b]quinoxalin-11-one and l-proline, afforded novel 6″ethyl 1′-methyl 5″aryl-7″methyl-3″oxo-5′,6′,7′7a′-tetrahydro-1′ H,3″ H,5″ H-dispiro[indeno[1,2-b]quinoxaline-11,3′-pyrrolizine-2′,2″-[1,3]thiazolo[3,2-a]pyrimidine-1′,6″-dicarboxylates in good yields. The structures of all the products were characterised thoroughly by NMR, IR and HRMS together with X-ray crystallographic analysis. [ABSTRACT FROM AUTHOR]

[3+2] Cycloaddition of CF 3 -ynones with azides proceeds regioselectively to give 1-R-4-trifluoroacetyl-1 H -1,2,3-triazoles as the major products. [ABSTRACT FROM AUTHOR]

A series of 5H-thiazolo[3,2-a]pyrimidin-5-ones were synthesized by the cyclization reactions of S-alkylated derivatives in concentrated H2SO4. Upon treatment of S-alkylated derivatives at different temperatures, intramolecular cyclization to 7-(substituted phenylamino)-5H-thiazolo[3,2-a]pyrimidin-5-ones or sulfonation of cyclized products to sulfonic acid derivatives occurred. The structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and HRMS studies. The compounds were evaluated for their preliminary in vitro antibacterial activity against some Gram-positive and Gram-negative bacteria and screened for antitubercular activity against Mycobacterium tuberculosis by the broth dilution assay method. Some compounds showed good antibacterial and antitubercular activities. [ABSTRACT FROM AUTHOR]

The examination of the cycloaddition reactions of 1,2,3-triazines 17-19, bearing electron-donating substituents at C5, are described. Despite the noncomplementary 1,2,3-triazine C5 substituents, amidines were found to undergo a powerful cycloaddition to provide 2,5-disubstituted pyrimidines in excellent yields (42-99%; EDG = SMe > OMe > NHAc). Even select ynamines and enamines were capable of cycloadditions with 17, but not 18 or 19, to provide trisubstituted pyridines in modest yields (37-40% and 33% respectively). [ABSTRACT FROM AUTHOR]

A one-pot four-component synthesis of thieno[2,3- d]pyrimidin-4-amines via sequential Gewald/cyclocondensation reactions is described. 2-Aminothiophene-3-carbonitriles obtained from the Gewald reaction between cyclic ketones, malononitrile, and sulfur underwent a condensationcyclization reaction with benzonitriles under solvent-free conditions to afford the title compounds in excellent yields. [ABSTRACT FROM AUTHOR]

Novel conjugates of pyridothienopyrimidinones and carbohydrates or other moieties linked by 1,2,3-triazoles were synthesized. After establishing the pyridothienopyrimidone ring systems by ring closure, propargyl group was introduced by or . Cu-catalyzed of the propargyl product with azido group gave the corresponding 1,2,3-triazoles in high yields. A remarkable case of the catalyzed ring closure to build a pyrimidinone moiety with two diastereomers was observed. Theoretical calculations were performed on the studied diastereomers, and it was found that the S-isomer is more stable than the corresponding R-isomer by about 2 kcal/mol. [ABSTRACT FROM AUTHOR]

The reaction of thione 3 or its 2-methylthio derivative 4 with hydrazonoyl halides 5a-l, in the presence of triethylamine, yielded the corresponding triazolo[4,3-a]pyrimidin-5(1H)-ones 8a-l. The structure of compounds 8a-l was further confirmed by the reaction of 3 with the appropriate active chloromethylenes 11a-c followed by coupling of the products with benzenediazonium chloride to afford the azo-coupling products 6b, f, and j, which were converted in situ to 8b, f, and j. 2-Hydrazinyl-pyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one (13) was prepared and condensed with different aldehydes 14a-f to give the corresponding hydrazone derivatives 15a-f. Oxidative cyclization of the hydrazones 15a-f give the corresponding triazolo[4,3-a] pyrimidin-5(1H)-one derivatives 16a-f. The antimicrobial activity of the products was evaluated and the results revealed that compounds 8f and 15f showed strong activity against gram-positive bacteria while compound 15d showed the highest activity against gram-negative bacteria. Moreover, compounds 15b, 8d, 8e, 8c, 8l, and 8j exhibited significant antifungal activity. In addition, the antitumoral activity of the synthesized products against different cancer cell lines was determined and the results revealed that compound 12c was the most active against MCF-7, HepG-2, HCT-116, and HeLa with IC50 values of 0.51, 0.72, 0.95, and 0.95, respectively, as compared with doxorubicin as positive control. [ABSTRACT FROM AUTHOR]

[MediaObject not available: see fulltext.]6-Nitroazolo[1,5- а]pyrimidines were used as dipolarophiles in a reaction with sodium azide providing previously unknown 2 Н-azolo[1,5- а]-[1,2,3]triazolo[4,5- е]pyrimidines. [ABSTRACT FROM AUTHOR]

A series of pteridine derivatives have been synthesised through intramolecular cyclisation of 2,4-dichloro-6-methyl-5-nitro pyrimidine with various esters of amino acids. The subsequently reaction of pteridines with hydrazine hydrate and then with triethylorthoesters obtained quantitatively the desired [1,2,4]triazolo[3,4-b]pteridine derivatives as a novel heterocyclic system. [ABSTRACT FROM AUTHOR]

The reaction of 6-amino-2-(prop-2-yn-1-ylsulfanyl)pyrimidin-4(1H)-one with various iodobenzenes in the presence of a Pd-Cu catalyst leads to the regioselective cyclization to 5-amino-3-benzyl-7H-[1,3]thiazolo[3,2-a]pyrimidin-7-ones. This one-pot procedure is very simple, and affords good-to-high yields. [ABSTRACT FROM AUTHOR]

A facile method for the synthesis of steroidal D-ring fused pyrazolo[1,5- a ]pyrimidines through a microwave mediated reaction between steroidal β-bromovinyl aldehydes and pyrazoloamines using palladium(II) catalyst has been described. [ABSTRACT FROM AUTHOR]

Various fused pyrimidines, such as furo[2,3-d]pyrimidine, triazolo-[1,5-a]pyrimidine and tetrazolo[1,5-a]pyrimidine, were synthesized in the reactions of thioxopyrimidine-6(1H)-ones with ethyl chloroacetate (under different reaction conditions), thiourea and sodium nitrite. Pyrimidine thiones reacted with POCl3/PCl5 to give the chloro derivatives which reacted with sodium azide and thiourea to give tetrazolo[1,5-c]pyrimidines, and pyrimido pyrimidines. Thioxopyrimidine-6(1H)-ones reacted with benzylamine to give pyrrolo[2,3-d]pyrimidinethiones. Theoretical calculation using MIDO/3, Fukui indices and the heat of formation of some compounds were carried out. The pharmacological and antimicrobial activities of some of the synthesized products were also evaluated. [ABSTRACT FROM AUTHOR]

A new and efficient synthesis of pyrimido[4,5-d]pyrimidine-2,4-dione derivatives through the reaction of 6-aminouracils and N,N'-bis(arylmethylidene) arylmethane in the presence of molecular iodine as a readily available and feasible catalyst. [ABSTRACT FROM AUTHOR]

A new and efficient method for the synthesis of quinazolines has been developed. Thus, N-[2-(1-azidoalkyl)phenyl]formamides 1 are dehydrated with POCl3 to give the corresponding 2-(1-azidoalkyl)phenyl isocyanides 2, which are then treated with NaH in DMF at 0° to give quinazolines 6 in satisfactory yields via cyclization of 1-(2-isocyanophenyl)alkylideneamine intermediates 4. This methodology can be applied to the synthesis of the 7-azaanalogs of quinazolines, i.e., pyrido[3,4- d]pyrimidines 9. [ABSTRACT FROM AUTHOR]

Abstract: Several 6-substituted-8-nitrothiazolo[3,2-c]pyrimidine derivatives have been obtained very efficiently by a multicomponent cyclisation of 2-(nitromethylene)thiazolidine, formaldehyde and various aliphatic or aromatic amines in water, using both microwave irradiation and conventional heating. Reaction yields were considerably higher and the reaction times very much reduced using microwave heating when compared to conventional heating, resulting in the definition of a rapid and efficient synthetic protocol. [Copyright &y& Elsevier]

Abstract: A synthetic method for novel 4-unsubstituted 2-phenyldihydropyrimidines having acyl and alkoxycarbonyl groups at the 5- and 6-positions was developed. The cyclization of 4-dimethylamino-1,3-diaza-1,3-butadiene having N-protecting groups (Boc, Cbz) with 1,2-disubstituted ethylenes, such as diethyl maleate, diethyl fumarate, (Z)-hex-3-ene-2,5-dione, (E)-1,4-diphenylbut-2-ene-1,4-dione, and unsymmetrical (E)-ethyl 4-oxo-4-phenylbut-2-enoate, following the elimination of a dimethylamino group proceeded smoothly, producing the corresponding dihydropyrimidines in good overall yield. The N-protecting group (Boc) could be easily removed to obtain N-unsubstituted dihydropyrimidines as a mixture of tautomers, and their tautomeric behavior was analyzed by 1H NMR spectroscopy. [Copyright &y& Elsevier]

Abstract: An innovative synthetic pathway for the preparation of a new series of triazole-decorated dihydropyrimidinone peptidomimetics with skeletal α or β-amino acid residue is reported. The protocol involves two synthetic steps with an initial solvent-free and catalyst-free synthesis of propargylated dihydropyrimidinone precursors using Biginelli condensations. The subsequent cycloaddition reactions of pyrimidinone alkynes with small peptide like azides prepared from Ugi or alternate Mannich type multi-component reactions afforded the triazole decorated pyrimidinone peptide conjugates in excellent yield with high regio and stereospecificities. In total, a scaffold diversity contains 11 new pyrimidinone alkynes and 18 new pyrimidinone peptidomimetics were introduced into the chemical space. [Copyright &y& Elsevier]

During the N-benzoylation reaction for the synthesis of N-substituted aminopyrimidines, an undesired N,N-diacylation reaction took place. The extension of this N-acylation reaction to a series of several 2-aminopyrimidines, aminopyrazines and highly deactivated anilines produced analogous results. The possible mechanism responsible for that behavior is investigated and an advantageous alternative procedure for the clean formation of the desired amides is suggested. [ABSTRACT FROM AUTHOR]

A novel simple five-step synthesis of 1,6-disubstituted tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones has been developed. The synthetic protocol starts with 'ring switching' transformation of commercially available 5,6-dihydro-2H-pyran-2-one into the 5-(2-hydroxyethyl)pyrazolidin-3-one, followed by addition of the latter to isocyanates, Appel bromination, cyclization, and N(1)-alkylation with alkyl halides to give the title compounds. In comparison to a 12-step synthesis reported recently, the present method is clearly superior with respect to the number of synthetic steps and versatility of substituents at position 6. [ABSTRACT FROM AUTHOR]

Potentially bioactive pyrimidine-annulated spiroheterocyclic compounds are synthesized in good to excellent yields using readily available, cheap and environmentally friendly iron(III) chloride (FeCl3) as the catalyst. The process is straightforward and provides a diverse range of spiropyrimidine derivatives via the 5-endodig mode of cyclization, starting from simple and easily available starting materials. [ABSTRACT FROM AUTHOR]

A simple protocol was introduced to prepare several enantiomerically pure heterocycles by using (-)-(1 R,2 R,3 S,4 S)-3-aminonorbornene-2-carboxylic acid as a chiral auxiliary. The protocol is based on a domino ring-closure reaction, in which the relative configuration of the new asymmetric center is controlled by the stereochemistry of the amino acid, followed by a microwave-induced retro-Diels-Alder reaction. [ABSTRACT FROM AUTHOR]

Abstract: A convenient and efficient procedure for the preparation of 3,4-dihydro-2H-pyran derivatives containing a sugar moiety is described. The reaction sequence is: Knoevenagel condensation of unprotected sugars and CH acids, acetylation of C-glycosides and hetero-Diels–Alder reaction. O-Acetylated 1,3-dimethyl-2,4,6-trioxo-pyrimidin-5-ylidene derivatives were used as new heterodienes in the synthesis of fused uracils—pyrano[2,3-d]pyrimidines with a sugar moiety. Solvent-free hetero-Diels–Alder cycloadditions of O-acetylated pyrimidin-5-ylidene alditols with enol ethers and cyclic enol ether were investigated at room temperature. New, enantiomerically pure cis and trans diastereoisomers of pyrano[2,3-d]pyrimidines and cis–cis, trans–cis diastereoisomers of pyrano[3′,2′:5,6]pyrano[2,3-d]pyrimidines with alditol moiety were obtained. The same pyrimidin-5-ylidene alditols underwent conjugate Michael addition–cyclizations with malononitrile at room temperature to afford optically active diastereoisomers of pyrano[2,3-d]pyrimidine-6-carbonitriles with a sugar moiety. [Copyright &y& Elsevier]