Regioselective Copper(I)-Catalyzed Direct C(3)-H (Hetero)arylation of 6-(Hetero)arylated 1,2,4-Triazolo[4,3-]pyridazines: Ligand-Free Approach.

The first efficient Cu(I) catalyzed regioselective C3-(hetero)arylation of 6-(hetero)arylated 1,2,4-triazolo[4,3-]pyridazines has been developed to streamline the synthesis of pharmaceutically important 3,6-diarylated 1,2,4-triazolo[4,3-]pyridazines. This direct (hetero)arylation is compatible with a range of aryl iodides and tolerates a variety of functional groups (23 examples). A series of new 3,6-diarylated 1,2,4-triazolo[4,3-]pyridazines were synthesized with good to excellent yields (up to 98%).

Non-Substituted Imidazolium-Based Electrolytes as Potential Alternatives to the Conventional Acidic Electrolytes of Polyaniline-Based Electrode Materials for Supercapacitors.

Although disubstituted imidazolium cation is sterically crowded, hundreds of ionic liquids based on this cation have been reported as electrolytes for energy storage devices. In contrast to disubstituted imidazolium, non-substituted imidazolium is uncrowded sterically and has not yet been investigated as an electrolyte, to the best of our knowledge. Hence, imidazolium hydrogen sulfate [Imi][HSO], in mixture with water, was studied as an electrolyte for PANI-based electrode materials.

Molecular properties prediction, anticancer and anti-inflammatory activities of some pyrimido[1,2-b]pyridazin-2-one derivatives.

Introduction: The anticancer and anti-inflammatory activities of a novel series of eleven pyrimido[1,2-b]pyridazin-2-one analogues substituted at position 7 were assessed in the current study.

Methods: The physicochemical characteristics were studied using MolSoft software. The antiproliferative activity was investigated by MTT cell viability assay, and cell cycle analysis elucidated the antiproliferative mechanism of action.

Synthesis of Trifluoromethylated Pyrimido[1,2-]indazole Derivatives through the Cyclocondensation of 3-Aminoindazoles with Ketoester and Their Functionalization via Suzuki-Miyaura Cross-Coupling and SN Reactions.

A new series of trifluoromethylated pyrimido[1,2-]indazol-4(1)-one derivatives was synthesized with good to excellent yields through a simple condensation of 3-aminoindazole derivatives with ethyl 4,4,4-trifluoro 3-oxobutanoate. The functionalization of the corresponding chlorinated fused tricyclic scaffolds via Suzuki-Miyaura and aromatic nucleophilic substitution reactions led to the synthesis of highly diverse trifluoromethylated pyrimido[1,2-]indazole derivatives with good yields.

Three Component One-Pot Synthesis and Antiproliferative Activity of New [1,2,4]Triazolo[4,3-]pyrimidines.

A series of new [1,2,4]triazolo[4,3-a]pyrimidine derivatives was prepared using a one-pot three-component synthesis from 5-amino-1-phenyl-1-1,2,4-triazoles, aromatic aldehydes and ethyl acetoacetate. The compound structures were confirmed by IR, H-NMR, C-NMR, HRMS and X-ray analyses. The biological activity of these compounds as antitumor agents was evaluated.

Efficient Synthesis of 1-Benzo[4,5]imidazo[1,2-][1,3]oxazin-1-one Derivatives Using AgCO/TFA-Catalyzed 6- Cyclization: Reaction Scope and Mechanistic Study.

A small library of 1-benzo[4,5]imidazo[1,2-][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a AgCO/TFA-catalyzed intramolecular oxacyclization of -2-alkynylbenzimidazole substrates. In all experiments, the 6-- cyclization was exclusively achieved since the possible heterocycle was not observed, indicating the high regioselectivity of this process. The scope and limitations of the silver catalyzed cyclization of --2-alkynylbenzimidazoles as substrates, bearing various substituents, were investigated.

D-π-A-Type Pyrazolo[1,5-]pyrimidine-Based Hole-Transporting Materials for Perovskite Solar Cells: Effect of the Functionalization Position.

Donor−acceptor (D−A) small molecules are regarded as promising hole-transporting materials for perovskite solar cells (PSCs) due to their tunable optoelectronic properties. This paper reports the design, synthesis and characterization of three novel isomeric D-π-A small molecules PY1, PY2 and PY3. The chemical structures of the molecules consist of a pyrazolo[1,5-a]pyrimidine acceptor core functionalized with one 3,6-bis(4,4′-dimethoxydiphenylamino)carbazole (3,6-CzDMPA) donor moiety via a phenyl π-spacer at the 3, 5 and 7 positions, respectively.

Stepwise synthesis of 2,6-difunctionalized ethyl pyrazolo[1,5-]pyrimidine-3-carboxylate site-selective cross-coupling reactions: experimental and computational studies.

A variety of novel disubstituted 2-(alknyl, aryl and arylamine)-6-alkynylpyrazolo[1,5-]pyrimidine derivatives was prepared sequential site-selective cross-coupling reactions from 2,6-dibromopyrazolo[1,5-]pyrimidine 3. The regio-controlled Sonogashira-type coupling of 3 with a wide range of terminal alkynes proceeded smoothly with excellent selectivity in favor of the C6-position through careful adjustment of the coupling conditions, followed by the subsequent introduction of alkynyl, aryl or arylamine groups at the C2-position the Sonogashira, Suzuki-Miyaura and Buchwald-Hartwig coupling reactions, respectively. These promising results allow for further use and diversification of the chemically and biologically interesting pyrazolo[1,5-]pyrimidine scaffold.

Simple and Expedient Access to Novel Fluorinated Thiazolo- and Oxazolo[3,2-]pyrimidin-7-one Derivatives and Their Functionalization via Palladium-Catalyzed Reactions.

An efficient, versatile, and one-pot method for the preparation of novel fluorinated thiazolo- and oxazolo[3,2-]pyrimidin-7-ones is described from 2-aminothiazoles or 2-amino-oxazoles and fluorinated alkynoates. This transformation, performed under transition-metal-free conditions, offers new fluorinated cyclized products with good to excellent yields. Moreover, the functionalization of these -fused scaffolds via the Suzuki-Miyaura and Sonogashira cross-coupling reactions led to the synthesis of highly diverse thiazolo- and oxazolo[3,2-]pyrimidin-7-ones.

A AgCO/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-][1,3]oxazin-5-one derivatives.

A series of 2,7-disubstituted 3-methylimidazo[1,2-][1,3]oxazin-5-ones were synthesized in good yields AgCO/TFA-mediated intramolecular annulation of -Boc-2-alkynyl-4-bromo(alkynyl)-5-methylimidazoles. This methodology was carried out in the presence of a catalytic amount of silver carbonate and trifluoroacetic acid in dichloroethane at 60 °C. In all experiments, only the six-membered ring product was obtained since the possible five-membered compound was not observed, proving the high regioselectivity of this approach.

Enhanced Storage Performance of PANI and PANI/Graphene Composites Synthesized in Protic Ionic Liquids.

Polyaniline (PANI) was synthesized using oxidative polymerization in a mixture of water with pyrrolidinium hydrogen sulfate [Pyrr][HSO], which is a protic ionic liquid PIL. The obtained PANI (PANI/PIL) was compared with conventional PANI (PANI/HCl and PANI/HSO) in terms of their morphological, structural, and storage properties. The results demonstrate that the addition of this PIL to a polymerization medium leads to a fiber-like morphology, instead of a spherical-like morphology, of PANI/HSO or an agglomerated morphology of PANI/HCl.

Efficient microwave-assisted Suzuki-Miyaura cross-coupling reaction of 3-bromo pyrazolo[1,5-]pyrimidin-5(4)-one: towards a new access to 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-]pyrimidine derivatives.

A convenient and efficient synthetic route to C3-arylated 7-trifluoromethylpyrazolo[1,5-]pyrimidin-5-one derivatives has been reported starting from 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-]pyrimidin-5-one through a Suzuki-Miyaura cross-coupling reaction. The arylation (heteroarylation) strategy can be performed using a wide variety of aryl and heteroaryl boronic acids and requiring a tandem catalyst XPhosPdG2/XPhos to avoid the debromination reaction. These optimized conditions were successfully extended to the synthesis of 7-, 8- and 9-arylated pyrimido[1,2-]indazol-2-ones from their corresponding brominated starting materials.

A Direct and an Efficient Regioselective Synthesis of 1,2-Benzothiazine 1,1-dioxides, β-Carbolinones, Indolo[2,3-]pyran-1-ones, Indolo[3,2-]pyran-1-ones, Thieno[2,3-]pyran-7-ones and Pyrano[3',4':4,5]imidazo[1,2-]pyridin-1-ones via Tandem Stille/Heterocyclization Reaction.

A general regioselective one-pot synthesis of 1,2-benzothiazine 1,1-dioxides from 2-iodo benzenesulfonamide moieties and allenylstannanes is described using a domino Stille-like/Azacyclization reaction. The conditions developed also opened a novel access to β-carbolinones, indolopyranones, thienopyranones and pyrano-imidazopyridines.

Pyrimido[1,2-b]indazole derivatives: Selective inhibitors of human monoamine oxidase B with neuroprotective activity.

Structurally diverse heterotricyclic compounds are recognized as monoamine oxidase (MAO) inhibitors and thus represent an appealing scaffold in development and optimization of novel MAO inhibitors. Herein we explored the chemical space of pyrimido[1,2-b]indazoles as MAO inhibitors by preparing a small library of (hetero)aryl derivatives. An efficient synthetic strategy was developed starting from commercially available 1H-indazol-3-amines, which were converted to various 3-bromoheterotricyclic derivatives and further functionalized via Suzuki-Miyaura coupling reaction.

Efficient Access to 3,5-Disubstituted 7-(Trifluoromethyl)pyrazolo[1,5-]pyrimidines Involving SAr and Suzuki Cross-Coupling Reactions.

An efficient and original synthesis of various 3,5-disubstituted 7-(trifluoromethyl)pyrazolo[1,5-]pyrimidines is reported. A library of compounds diversely substituted in C-3 and C-5 positions was easily prepared from a common starting material, 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-]pyrimidin-5-one. In C-5 position, a SAr type reaction was achieved by first activating the C-O bond of the lactam function with PyBroP (Bromotripyrrolidinophosphonium hexafluorophosphate), followed by the addition of amine or thiol giving monosubstituted derivatives, whereas in C-3 position, arylation was performed via Suzuki-Miyaura cross-coupling using the commercially available aromatic and heteroaromatic boronic acids.

Synthesis and evaluation of the anticoccidial activity of trifluoropyrido[1,2-a]pyrimidin-2-one derivatives.

Screening of our chemical library to discover new molecules exhibiting in vitro activity against the invasion of host cells by Eimeria tenella revealed a lead compound with an IC50 of 15μM. Structure-activity relationship studies were conducted with 34 newly synthesized compounds to identify more active molecules and enhance in vitro activity against the parasite. Four compounds were more effective in inhibiting MDBK cell invasion in vitro than the lead compound.

Synthesis and physicochemical properties of unsaturated trifluoromethylated sodium carboxylates in aqueous media.

Structural modifications of unsaturated sodium carboxylate surfactants in terms of trifluoromethylation associated with the hydrocarbon chain length have been studied, the synthesis is described, and aggregation properties have been examined by conductimetry and vapor pressure osmometry between 30°C and 45°C. No strong effect of adding a CF3 group was observed on the Critical Micellar Concentrations. However, the thermodynamic study shows the specific effect exerted by the CF3 group through the enhancement of the entropic contribution.

QSAR study and synthesis of new phenyltropanes as ligands of the dopamine transporter (DAT).

The dopamine transporter (DAT) plays a pivotal role in the regulation of dopamine neurotransmission, and is involved in a number of physiological functions and brain disorders. Furthermore the DAT analysis by molecular imaging techniques is a useful tool for the diagnosis and follow up treatment of diseases involving the DAT. In order to predict the affinity of new derivatives for the DAT, different QSAR molecular modeling models based on cocaine were compared.

Regioselective copper-mediated synthesis of thieno[2,3-c]pyrane-7-one, indolo[2,3-c]pyrane-1-one, and indolo[3,2-c]pyrane-1-one.

In the presence of copper(I) iodide, heteroaromatic β-iodo-α,β-unsaturated carboxylic acid systems opposed to terminal alkyne afford selectively 6-endo-dig cyclization products via a tandem coupling oxacyclization reaction.

Copper(I)-mediated preparation of new pyrano[3',4':4,5]imidazo[1,2-a]pyridin-1-one compounds under mild palladium-free conditions.

A general and efficient Cu(I)-mediated cross-coupling and heterocyclization reaction of 3-iodoimidazo[1,2-a]pyridine-2-carboxylic acid, and terminal alkynes was developed under very mild conditions. This method allows the introduction in one pot of a third ring fused in positions 2 and 3 of the imidazo[1,2-a]pyridine core with reasonable yields and total regioselectivity. This procedure does not require the use of any expensive supplementary additives, and is palladium-free.

Domino allylic amination/Sonogashira/heterocyclisation reactions: palladium-catalysed three-component synthesis of pyrroles.

Three-component reactions with 3,4-diiodoalk-2-enoic derivatives, primary amines, and terminal alkynes proceeded to give trisubstituted pyrroles in fair to good yields in the presence of palladium and copper catalysts under mild reaction conditions.

Improvements of TArgeted multiplex mass spectrometry IMaging.

MALDI mass spectrometers have become popular tools for imaging histological sections. Currently this technology is primarily used for imaging naturally occurring molecules. Here we report on the improvement of TArgeted multiplex MS IMaging (TAMSIM) technology.

Synthesis of isocoumarins and alpha-pyrones via tandem Stille reaction/heterocyclization.

A general route to alpha-pyrones and 3-substituted isocoumarins from (Z)-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c is described, including compounds bearing a substituent on the aromatic ring. Treatment of (Z)-beta-iodovinylic acids 1a-f or 2-iodobenzoic acids 4a-c with various allenyltributyltin reagents in the presence of palladium acetate, triphenylphosphine, and tetrabutylammonium bromide in dimethylformamide provided good yields of the corresponding alpha-pyrones 3a-k or 3-substituted isocoumarins 5a-g via tandem Stille reaction and 6-endo-dig oxacyclization.

New stereoselective preparation of (Z)-3-perfluoroalkyl-3-magnesiated enoates by an iodine-magnesium exchange reaction.

(Z)-Ethyl-3-perfluoroalkyl-3-magnesiated crotonates were prepared from (Z)-ethyl-3-perfluoroalkyl-3-iodo enoates by iodine-magnesium exchange reaction with isopropylmagnesium bromide in THF at -78 degrees C. These new reagents reacted with a range of electrophiles, leading to polyfunctional products bearing a perfluoroalkyl group.