Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines as synthons for the preparation of polycondensed heterocycles: reaction with chlorocarboxylic acid chlorides

Partially hydrogenated 2-amino[1,2,4]triazolo[1,5-a]pyrimidines and 2-amino[1,2,4]triazolo[5,1-b]quinazolines react with the chlorides of chloroacetic, 3-chloropropanoic, and 4-chlorobutanoic acids at 0–5 °C to give amides through acylation of the 2-amino group. Heating the corresponding 3-chloropropanoyl derivatives at 80–90 °C in DMF leads to selective intramolecular alkylation at N-3 to form the chlorides of partially hydrogenated [1,2,4]triazolo[1,5-a:4,3-a′]dipyrimidin-5-ones and pyrimido[2′,1′:3,4][1,2,4]triazolo[5,1-b]quinazolin-12-ones. It may be more convenient to prepare such compounds through one-pot processes. Some reactions of the synthesized chlorides of polycondensed heterocycles have been studied. Conditions have been found to effect the selective synthesis of free bases, oxidative aromatization or hydrolysis of the dihydropyrimidine cycle, and the selective hydrolytic cleavage or elimination of the pyrimidone ring. Some of the resulting compounds represent new mesoionic heterocycles.     

Water-Mediated Selective Synthesis of Pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]Triazolo[1,5-a]quinazolin-5(4H)-one via Copper-Catalyzed Cascade Reactions

A convenient and sustainable synthesis of pyrazolo[1,5-a]quinazolin-5(4H)-ones and [1,2,4]triazolo[1,5-a]quinazolin-5(4H)-one through copper-catalyzed cascade reactions of 2-bromobenzoates with 1H-pyrazol-5-amines or 1H-1,2,4-triazol-5-amine under ligand-free conditions in water is presented. It is notable that aqueous medium turned out to be crucial for the chemoselective formation of the title compounds. Compared with literature protocols, this new method showed advantages such as simple and sustainable procedure, commercially available starting materials, and convenient reuse of the reaction medium together with the copper catalyst.     

Pyrolytic desulfurization ring contraction of condensed thiadiazines as a general route towards pyrazoloazines and pyrazoloazoles with a bridgehead (ring junction) nitrogen atom

Pyrolytic conversion of [1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-ones, [1,3,4]thiadiazino[2,3-b]quinazolin-10-ones and [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines into their corresponding pyrazolo[5,1-c][1,2,4]triazin-4-ones, pyrazolo[4,3-b]quinazolin-9-ones and pyrazolo[5,1-b][1,2,4]triazoles via desulfurization ring contraction is described. The starting condensed 1,3,4-thiadiazines were prepared from the corresponding readily available 4-amino-3-thioxo-1,2,4-triazin-5(4H)-ones, 3-amino-2,3-dihydro-2-thioxoquinazolin-4(1H)-one and 4-amino-3(2H)-thioxo-1,2,4-triazoles upon reaction with the appropriate α-haloketones in two steps, or directly in one step in ethylpyridinium tetrafluoroborate (ionic liquid, IL).     

Stereoselective synthesis of dihydrothiadiazinoazines and dihydrothiadiazinoazoles and their pyrolytic desulfurization ring contraction

Intramolecular base catalyzed C-C bond formation led to exclusive stereoselective syntheses of trans-6,7-dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines, trans-7,8-dihydro-6H-[1,2,4]triazino[3,4-b][1,3,4]thiadiazin-4-ones, and trans-3,4-dihydro-2H-[1,3,4]thiadiazino[2,3-b]quinazolin-10-one. trans-6,7-Dihydro-5H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines isomerize slowly in CDCl₃ and more rapidly in DMSO-d₆ into the corresponding cis-stereoisomers. The other trans-6,7-dihydro-[1,3,4]thiadiazines isomerize also in DMSO-d₆ into the corresponding cis-stereoisomers. Pyrolytic conversion of these heterocyclic condensed dihydrothiadiazines into their corresponding pyrazolo[5,1-b][1,2,4]triazoles, pyrazolo[5,1-c][1,2,4]triazin-4-ones and pyrazolo[4,3-b]quinazolin-9-ones via desulfurization ring contraction is described.     

Synthesis of [1,2,4]triazoloquinazoline and [1,2,4]-triazolo-1,4-benzodiazepine derivatives

Some [1,2,4]triazolo[1,5-c]quinazolin-5(6H)-ones 7 , the corresponding isomers [1,2,4]triazolo[4,3-c]quinazo-lin-5(6H)-ones and the 5-amino derivatives 8, 9 and 11 have been synthesized starting from the acylamidrazones 5 . The preparation of 5H-[1,2,4]triazolo[1,5-d]-1,4-benzodiazepin-6(7H)-ones 15 and of 5-cyclicaminomethyl-[1,2,4]triazolo[1,5-c]quinazolines 16 and 17 is also reported.     

Microwave-assisted three component synthesis of novel bis-fused quinazolin-8(4H)-ones linked to aliphatic or aromatic spacer via amide linkages

Abstract

A novel series of bis(tetrahydro[1,2,4]triazolo[5,1-b]quinazolin-8-ones) and bis(tetrahydrobenzo[4,5]imidazo[2,1-b]quinazolinones) containing amide linkages were regionselectively prepared via a three-component reaction of bis(aldehydes) with dimedone and 3-amino-1,2,4-triazole (or 2-aminobenzimidazole) under conventional heating as well as under microwave irradiation.     

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their analogues

Reductions of (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones and their lactone analogues, prepared from (1R)-(+)-camphor, were studied. Catalytic hydrogenation selectively led to partial saturation of the [1,2,4]triazolo[4,3-x]azine residue, while in reactions with borane–methylsulfide coordination of borane to the 1-position of [1,2,4]triazolo[4,3-x]azine system took place. On the other hand, activation of the carbonyl group in (1R,3R,4R)-3-([1,2,4]triazolo[4,3-x]azin-3-yl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ones with boron trifluoride etherate followed by reaction with borane–methylsulfide furnished the corresponding isoborneols, stereoselectively. The structures of all representative compounds were confirmed by X-ray diffraction.     

Regioselective Synthesis of 2-Substituted [1,2,4]Triazolo[5,1-b][1,3]thiazin-7-ones by Heteropolyacids

2-Substituted [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones 3 were synthesized via regioselective cyclization of 4H-[1,2,4]triazol-3-ylsulfanyl-acrylic acids 2 in the presence of catalytic amounts of heteropolyacids at room temperature in very good yields and rates.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Synthesis and reactions of 3-thioxo[1,2,4]-triazino[3,2-b]quinazolin-10-ones

Thiation of [1,2,4]triazino[3,2-b]quinazoline-3,10-dione 1 proceeds selectively to give the 3-thioxo-analog 3 . The latter was converted to the corresponding 3-methylthio derivative 4 which was reacted with aniline and hydrazine to give the corresponding anilino- and hydrazino derivatives 5 and 7 . Compound 7 was converted to the hydrazones 8a,b and into the novel heterocyclic ring systems [1,2,4]triazolo[4′,3′:4,5][1,2,4]triazino-[3,2-b]quinazolin-7-ones 9, 10a,b and tetrazolo[1′,5′:4,5][1,2,4]triazino[3,2-b]quinazolin-7-one 11 .     

A Facile and Efficient Synthesis of Novel 1,2,4-Triazolo[5,1-b]quinazolin-9-one Derivatives

Summary.  A facile and efficient synthesis of a series of novel 1,2,4-triazolo[5,1-b]quinazolines is described. 2,3-Diaryl-2,3-dihydro-1H-1,2,4-triazolo[5,1-b]quinazolin-9-ones were obtained by reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic aldehydes as well as by ring closure of the corresponding anils. Treatment of 3-amino-2-arylamino-3H-quinazolin-4-ones with aromatic carboxylic acids afforded 2,3-diaryl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones which could also be synthesized by dehydrogenation of the corresponding dihydro derivatives. Reaction of 3-amino-2-arylamino-3H-quinazolin-4-ones with diethyl malonate and acetylacetone gave 3-aryl-3,9-dihydro-9-oxo-1,2,4-triazolo[5,1-b]quinazolin-2-yl-acetic acid ethyl ester and 3-aryl-2-methyl-3H-1,2,4-triazolo[5,1-b]quinazolin-9-ones, respectively. The latter compounds were also prepared via reaction with acetic anhydride, whereas acetylation with acetic anhydride in the presence of pyridine afforded the acetyl derivatives. Received March 22, 2001. Accepted (revised) May 11, 2001     

Synthesis of 2-Aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-Aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones

The reaction of 2-mercaptobenzimidazole, 5-ethoxy-2-mercaptobenzimidazole, and 2-mercaptoimidazoline with cinnamoyl chloride, its derivatives, and heteroanalogs was studied. Convenient methods were found for the synthesis of 2-aryl-2,3-dihydro-4H-[1,3]thiazino[3,2-a]benzimidazol-4-ones and 7-aryl-2,3,6,7-tetrahydro-5H-imidazo[2,1-b]-1,3-thiazin-5-ones.     

Synthesis of 8,8-R,R-8,9-dihydro[1,2,4]triazolo[1,5-<Emphasis Type="Italic">a</Emphasis>]quinazolin-6(7<Emphasis Type="Italic">H</Emphasis>)-ones

Three-component condensation of 3-amino-1,2,4-triazole (or its 5-methyl and 5-methylthio derivatives), dimedone (or cyclohexane-1,3-dione), and dimethylformamide dimethyl acetal afforded 8,8-R, R-8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2805–2807, December, 2005.     

New [g]-fused [1,2,4]triazolo[1,5-c]pyrimidines: Synthesis of pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidine,pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-c]pteridine derivatives

A number of 2-aryl-substituted pyrido[3,2-e] and [4,3-e][1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-c]pteridines 11,12a,b,e , their corresponding 5-carbonyl derivatives 7,8a,b,e and some pyrimido[5,4-e][1,2,4]triazolo[1,5-c]pyrimidin-5-ones 7,8c,d have been synthesized, according to different pathways. The new tricyclic heterocycles were prepared with the aim of studying their possible benzodiazepine receptors affinity.     

Synthesis of 8,9-dihydro[1,2,4]triazolo[1,5-a]-quinazolin-6(7H)-one derivatives

Regioselectivity of the reactions of 1H-1,2,4-triazol-3-amines with 2-acyl-5,5-dimethylcyclohexane-1,3-diones and 2-dimethylaminomethylidene-5,5-dimethylcyclohexane-1,3-dione was studied. In all cases, the products were substituted 8,9-dihydro[1,2,4]triazolo[1,5-a]quinazolin-6(7H)-ones whose structure was determined by ¹H and ¹³C NMR spectroscopy.     

An Efficient and Convenient Synthesis of 2-Thio[1,2,4]triazolo[1,5-c]quinazoline and its Derivatives

Summary. 4-Hydrazinoquinazoline with carbon disulfide underwent a recyclization reaction. The title compound 2-thio[1,2,4]triazolo[1,5-c]quinazoline was obtained after treatment of 4-hydrazinoquinazoline with potassium ethylxanthogenate via a facile in situ Dimroth-like rearrangement of the expected [4,3-c] system. Its structure was established by X-ray diffraction study and confirmed by an independent synthesis, starting from o-aminobenzonitrile.     

A new strategy for the synthesis of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines and pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines

A series of pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of aldehyde N-(1,3-diphenylpyrazolo[3,4-d]pyrimidin-4-yl)hydrazones. Dimroth rearrangement of such a series yielded pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidines.     

2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones

A novel method for synthesis of 2-R-5-Ar(Het)-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 3-R-4,5-dihydro-1H-1,2,4-triazole-5-thiones with 3-aryl(heteryl)-2-propenoyl chlorides is proposed.     

Synthesis of pyrazolo[4,3-<Emphasis Type="Italic">e</Emphasis>][1,2,4]triazolo[4,3-<Emphasis Type="Italic">c</Emphasis>]pyrimidines

Starting from 1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-ones, a synthesis pathway to the tricyclic pyrazolo[4,3-e][1,2,4]triazolo[4,3-c]pyrimidines is described. Reaction of 1,5-dihydro-4H-pyrazolo[3,4-d] pyrimidin-4-ones with phosphoryl chloride afforded the corresponding 4-chloro-1H-pyrazolo[3,4-d]pyrimidines. Treatment of these compounds with hydrazine hydrate at reflux temperature gave the hydrazino derivatives, which were subsequently cyclized to the titled compounds on heating with orthoesters in ethanol. Correspondence: Abolghasem Davoodnia, Department of Chemistry, School of Sciences, Islamic Azad University, Mashhad Branch, Mashhad 91735-413, Iran.     

Synthesis,design, and antimicrobial activity of pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinones based on quinoline derivatives

The pyrido[2,3-d]pyrimidine moieties are one of the most biologically widespread heterocyclic compounds as antimicrobial, antioxidant, antitubercular, antiviral and anti-inflammatory. Hence, we synthesized an efficient new series of 2-thioxo-pyrido[2,3-d]pyrimidinone, 2-hydrazinyl-(quinolin-2-yl)pyrido[2,3-d]pyrimidinone,N′-(quinolin-2-yl)-pyrido[2,3-d]pyrimidine-(formo/aceto)-hydrazide and substituted-(quinolin-2-yl)pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidinone derivatives. The characterization of new compounds was corresponded by using spectroscopic techniques, IR, NMR and Mass spectra. In vitro, all compounds were evaluated as antimicrobial activity compared with cefotaxime sodium and nystatin as the standard drug. This work deals with the exploration of the new heterocyclic compounds and medicinal diversity of quinoline-pyrido[2,3-d][1,2,4]triazolo[4,3-a]pyrimidine derivatives that might pave the way for long in the discovery of therapeutic medicine for future drug design.