Pd-catalyzed regiocontrolled Sonogashira and Suzuki cross-coupling reaction of 3,6-dihalogenoimidazo[1,2-a]pyridines: one-pot double-coupling approach

New and efficient regioselective Sonogashira and Suzuki-Miyaura palladium-catalyzed coupling reactions of 3,6-dihalogenoimidazo[1,2-a]pyridines followed by another cross-coupling has been successfully developed. Various solvents, palladium species and bases were tested. Scope and limitations of this regiocontrolled palladium-catalyzed reaction were investigated. The synthesis of 3,6-disubstituted imidazo[1,2-a]pyridine derivatives using one-pot regioselective double-coupling approach was developed. This procedure affords convergent syntheses of polysubstituted compounds in high yields in a very few steps.     

Synthesis of novel fluorescent 3-aryl- and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines by Suzuki cross-coupling reactions

Two series of compounds, 3-aryl- (series A, compounds 2a-j) and 3-methyl-7-aryl-[1,2,3]triazolo[1,5-a]pyridines (series B, compounds 3a-j) have been synthesized by Suzuki cross-coupling reactions, with a triazolopyridine halide and an aryl or heteroaryl boronic acid in moderate to good yields. All compounds obtained are fluorescents, the quantum yields, particularly those of compounds 3f-j, are very high.     

Synthesis of substituted [1,2,4]oxadiazino[2,3-a]indole-7,8-dicarbonitriles

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First synthesis of 7-amido-[1,2,4]triazolo[1,5-a]pyrimidines using halogen-metal exchange

A new and efficient methodology for the preparation of novel 7-carboxyl-triazolopyrimidine derivatives via the halogen-metal exchange is described. In addition, we showed that this new method can be useful for the synthesis of amides, esters, and ketones by using different carbamoyl chlorides, isocyanides or acyl chlorides as electrophile.     

An efficient microwave-assisted Suzuki cross-coupling reaction of imidazo[1,2-a]pyridines in aqueous medium

A new simple, rapid and high yielding synthesis of various 6-aryl-2-arylsulfonylmethyl-3-nitroimidazo[1,2-a]pyridines by Suzuki cross-coupling reaction is described using microwave irradiation in aqueous medium without organic co-solvent in the presence of tetrabutylammonium bromide.     

One-pot palladium-catalyzed synthesis of functionalized 10H-pyrido[1,2-a]quinoxalin-10-ones under copper-free conditions

Reactions of 3-substituted-2-chloroquinoxalines, terminal alkynes, and 1,3-dicarbonyl compounds in the presence of palladium catalyst afforded a number of 6,8,9-trisubstituted-10H-pyrido[1,2-a]quinoxalin-10-ones in 60–86% reaction yields. This one-pot protocol provided an efficient, practical, and direct method for the synthesis of pyrido[1,2-a]quinoxalines from readily available starting materials in the absence of a copper salt.     

Parallel iterative solution-phase synthesis of 5-amino-1-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid amide derivatives

The parallel iterative solution-phase synthesis of 5-amino-1-aryl-[1,2,4]triazolo[1,5-a]pyridine-7-carboxylic acid amide derivatives is described. The key intermediate 2,6-bis-aminopyridine-4-carboxylic acid methyl ester was synthesised in a two step procedure in 64% overall yield and elaborated to a variety of triazolopyridine-5-carboxylic acid methyl ester by selective pyridine-N-amination, condensation of the adduct with a wide selection of aldehydes and subsequent cyclisation and oxidation. The desired esters were obtained in yields up to 70%. The final transformation to the amide derivatives was accomplished by application of carefully optimised reaction conditions thus giving access to a library of total 500 triazolopyridine amide derivatives. Iterative synthetic cycles (12-48 library members each) allowing for maximal flexibility in chemistry and maximal efficiency in in vitro biological activity optimisation guided by molecular modelling efforts constitute a synergistic procedure for rapid lead optimisation.     

Triazolopyridines. Part 26: The preparation of novel [1,2,3]triazolo[1,5-a]pyridine sulfoxides

The regioselective synthesis of new triazolopyridine halides and sulfoxides with the substituent in all different ring positions of [1,2,3]triazolo[1,5-a]pyridines is presented. The triazolo ring opening reaction of some representative sulfoxides to obtain disubstituted pyridines is also studied.     

Cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine with hydroxylamine and hydrazine

The cyclocondensation of 6-acetyl-4,7-dihydro-5-methyl-7-phenyl[1,2,4]triazolo[1,5-a]pyrimidine (3) with hydroxylamine or hydrazine leads to 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenylisoxazolo-[5,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4a ) and 3a,4,9,9a-tetrahydro-3,9a-dimethyl-4-phenyl-1H-pyrazolo[3,4-d][1,2,4]triazolo[1,5-a]pyrimidine ( 4b ), respectively. In the presence of methanolic hydrogen chloride, 4b undergoes a cleavage of the pyrimidine ring to yield (5-amino-1,2,4-triazol-1-yl)(3,5-dimethylpyrazol-4-yl)phenylmethane ( 5 ). The structure determination of the compounds obtained is based on ¹H and ¹³C nmr spectra including NOE measurements.     

Synthesis, spectroscopic characterization and in vitro antimicrobial activity of diorganotin(IV) dichloride adducts with [1,2,4]triazolo-[1,5-a]pyrimidine and 5,7-dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidine

The heterocyclic ligands [1,2,4]triazolo-[1,5-a]pyrimidine (tp) and 5,7-dimethyl-[1,2,4]triazolo-[1,5-a]pyrimidine (dmtp), react with diorganotin dichlorides giving the addition compounds Me₂SnCl₂(tp)₂, Et₂SnCl₂(tp)₂, Me₂SnCl₂(dmtp)₂, Et₂SnCl₂(dmtp)₂, Bu₂SnCl₂(dmtp), Ph₂SnCl₂(dmtp). The organotin:ligand stoichiometry goes from 1:2 to 1:1 by increasing the steric hindrance of the organic groups bound to tin. The compounds have been characterized by means of infrared, ¹¹⁹Sn Mössbauer and ¹H AND ¹³C NMR spectroscopy.The ligands presumably coordinate to tin classically through the nitrogen atom at the position 3. The 1:1 complexes adopt trigonal bipyramidal structures, with the organic groups on the equatorial plane and the ligand in the apical position. All-trans octahedral structures are inferred for the 1:2 complexes, except for Et₂SnCl₂(tp)₂, characterized by a skew-trapezoidal structure.¹¹⁹Sn Mössbauer measurements, at room temperature, in concomitance with DFT calculations, performed on isomeric structures of R₂SnCl₂(tp)₂ (R = Me, Et), allowed us to conclude that the all-trans octahedral coordination induces self-assembly in the solid state, possibly accomplished through π-π stacking interactions among the planar ligands coordinated to the organotin(IV) compound, while the skew-trapezoidal structure attributed to Et₂SnCl₂(tp)₂, induces the formation of monomeric adducts in the solid state.In vitro antimicrobial tests showed that [n-Bu₂SnCl₂(dmtp)] has interesting properties as anti Gram-positive and antibiofilm agent.     

Highly efficient blue emission from boron complexes of 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine

Two boron complexes of 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine, which were named as BOHPIP, have been synthesized. These complexes exhibited blue emission in solution with high quantum yields (ΦFL?=?up to 0.71). In addition, 1-(o-hydroxyphenyl)imidazo[1,5-a]pyridine-BPh2 complex showed the strong blue emission even in the solid state (ΦFL?=?0.58).     

Solvent-controlled dehydration and diastereoselective formation of indenone-fused thiazolo[3,2-a]pyridines via a one-pot four-component reaction

A solvent-controlled four-component reaction has been described for the preparation of either hydroxy-tetrahydro-thiaza-cyclopenta[c]fluoren-6-one or dihydro-thiaza-cyclopenta[c]fluoren-6-one from nitroketene dithioacetals, cysteamine hydrochloride, 1,3-indandione and aromatic aldehydes starting materials by changing solvent systems. These reactions proceed under catalyst-free conditions affording a range of two types of skeletally distinct thiazolo[3,2-a]pyridines-based heterocycles. Hydroxy-tetrahydro-thiaza-cyclopenta[c]fluoren-6-one was obtained in H₂O/EtOH (3:1, v/v) in high yield and diastereoselectivity but in contrast dihydro-thiaza-cyclopenta[c]fluoren-6-one was synthesised in EtOH in moderate to good yields and in the longer reaction time. The structural diversities have been confirmed spectroscopically, by IR ¹H and ¹³C NMR, and EI-MS spectra, which agree with the proposed structures.     

Novel synthesis of C-3-(hetero)aryl [1,2,3]triazolo[1,5-a]pyridines using the Stille reaction

Herein, we report a novel and high yielding approach for the preparation of the first C-3-organometallic substituted [1,2,3]triazolo[1,5-a]pyridine and its application to the Stille reaction using MAOS.     

A synthetic approach to new polycyclic ring system of biological interest through domino reaction: indolo[2,3-e][1,2,3]triazolo[1,5-a]pyrimidine

The title indolo-triazolo-pyrimidines were obtained from 3-azidoindoles and can be used as models for the design of DNA-interactive compounds. Hetero-domino reaction of azidoindoles/pyrroles and acetonitriles constitutes the synthetic entry to annelated 1,2,3-triazolo[1,5-a]pyrimidines.     

PdCu/Al2O3 catalyst for Sonogashira cross-coupling: effect of a Pd/Cu ratio on the catalytic performance

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Visible-light mediated regioselective approach towards synthesis of 7-aroyl-6-methyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines

The first visible-light mediated, simple, efficient and ecofriendly protocol for the regioselective synthesis of novel [1,2,4]triazolo[3,4-b][1,3,4]thiadiazines has been developed by the reaction of α-bromodiketones, generated in situ by the bromination of a diverse array of β-diketones with N-bromosuccinimide, with 4-amino-[1,2,4]triazole-3-thiols. The methodology does not require the presence of any additives and this reaction proceeded in the presence of EDG (OMe), EWG (Cl) and heteroarenes (thiophenyl) giving the expected products in good to excellent yields. A solvent free protocol was also established to accomplish the synthesis of target compounds but it required PTSA as a catalyst and yields are comparatively poor. The structure of the regioisomer has been confirmed unambiguously by heteronuclear 2D-NMR [(¹H-¹³C) HMBC, (¹H-¹⁵N) HMBC, (¹H-¹³C) HMQC] spectroscopic and X-ray crystallographic studies.     

Copper(II) complexes with 1,2,4-triazolo[1,5-a] pyrimidine and its 5,7-dimethyl derivative

Several Cu(II) complexes with 1,2,4-triazolo[1,5-a]pyrimidine (tp) and its 5,7-dimethyl derivative (dmtp) have been isolated and structurally characterized. Five of them are mononuclear and contain 1,10-phenanthroline (phen) or ethylenediamine (en) as auxiliary ligands, their formula being [Cu(H₂O)(phen)(tp)₂](ClO₄)₂ · H₂O, [Cu(H₂O)(phen)(dmtp)₂](ClO₄)₂, [Cu(NO₃)(H₂O)(phen)(tp)](NO₃), [Cu(H₂O)₂(en)(tp)₂](ClO₄)₂ and [Cu(H₂O)₂(en)(dmtp)₂](ClO₄)₂. In all these compounds the tp or dmtp ligand is monodentately coordinated via the nitrogen atom in position 3. The auxiliary ligand influences the coordination number, which is five when this ligand is phen and six when it is en whereas the number of triazolopyrimidine ligands linked to the metal seems to be influenced by the nature of the counteranion. A dinuclear compound with tp has also been isolated, its formula being [Cu₂(OH)(H₂O)_2.5(tp)₅](ClO₄)₃·(H₂O)_1.5, with both metal atoms linked by an hydroxydo group and by a tp bridging ligand, coordinated to one of the copper atoms via N3 and to the other via N4. This compound has several unusual features among the metal complexes with triazolopyrimidine derivatives: the presence of two different kinds of bridging moieties, the coexistence of bridging and terminal ligands and the formation of a N3–N4 bridge for a Cu(II) dinuclear compound for a derivative without exocyclic oxygen atoms.     

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.     

Metal-free protocol for the synthesis of novel 6-(het)aryl-5-aryl-5H-imidazo[4,5-b][1,2,5]oxadiazolo[3,4-e]pyrazines

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