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Preparation of substituted quinolinyl and isoquinolinyl sulfonyl chlorides for the synthesis of novel sulfonamides

Novel sulfonyl chlorides of quinolines and isoquinolines have successfully been prepared. This enabled the preparation of the corresponding sulfonamides via reaction with an amine using the “resin-capture and release” methodology.

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Crystal structure and magnetic characteristics of a new 3-methylisoquinolinium tetrachloridoferrate(III)

The crystal structure of a new 3-methylisoquinolinium [3-Me(IsoQH)] salt, [3-Me(IsoQH)][FeCl4], was determined. The iron cation is tetracoordinated by chlorine anions, and it adopts a slightly distorted tetrahedral coordination. In the crystal structure, there are pi-pi stacking interactions between the 3-methylisoquinolinium cations in an ABAB infinite arrangement, N-H-Cl hydro-gen bonds, and C-H-Cl intermolecular interactions. Magnetic measurements of a powdered sample were carried out. A negative Weiss constant as well as the intermolecular exchange parameter for [3-Me(IsoQH)][FeCl4] indicate the occurrence of antiferromagnetic interactions transmitted in the crystal lattice.

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IMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF CYCLIN DEPENDENT KINASES

The invention provides compounds of the formula (I): and salts, tautomers, solvates and N-oxides thereof; wherein Q is CH or N; X is N, N+-O- or CR3; Y is N, N+-O- or CR3a; R1 and R2 are independently selected from hydrogen and various substituents as defined in the claims; or R1 and R2 together with the atoms to which they are attached, link to form an optionally substituted carbocyclic or heterocyclic aromatic or non-aromatic ring of 4 to 7 members; R3 is selected from hydrogen and various substituents; and R3a is selected from hydrogen and various substituents as defined in the claims. Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds. The compounds of formula (I) have activity as inhibitors of CDK kinases and are useful in the treatment of inter alia proliferative diseases such as cancers.

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An efficient synthesis of 2-(trifluoromethyl)-2H-[1,3]oxazino[2,3-a] isoquinolines via a three-component cascade approach using a continuous-flow microreactor

The three-component reaction between an isoquinoline, a dialkyl acetylenedicarboxylate and 2,2,2-trifluoro-1-phenylethanone involving a 1,4-dipolar cycloaddition cascade approach is developed using a continuous-flow microreactor. The reaction conditions (solvent, flow rate and temperature) are optimized leading to the synthesis 2-(trifluoromethyl)-2H-[1,3]oxazino[2,3-a] isoquinoline derivatives in 79-83% isolated yields, whilst eliminating the formation of 11bH-pyrido[2,1-a]isoquinoline-1,2,3,4-tetracarboxylate by-products. The continuous-flow method is also applied to similar reactions using aromatic aldehydes as the carbonyl component. Georg Thieme Verlag Stuttgart ¡¤ New York.

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Lanthanides and actinides: Annual survey of their organometallic chemistry covering the year 2015

This review summarizes the progress in organo-f-element chemistry during the year 2015. The year 2015 witnessed a slight increase of contributions in the fields of organolanthanide and organoactinide chemistry over 2014 (ca. 10% more). A continuing trend for many years which continued into 2015 was the investigation of highly reactive lanthanide alkyl complexes supported by non-cyclopentadienyl ligands (e.g. amidinates, beta-diketiminates etc.). Many of these complexes found useful applications in homogeneous catalysis. Trinuclear rare-earth metal methylidene (CH22-) complexes are an emerging class of compounds that serve as methylidene transfer agents for the methylenation of carbonyl compounds. The range of rare-earth metal alkyl complexes bearing different types of carbene ligands have also been further expanded. Several new lanthanide phosphido and phosphinidene complexes have been stabilized by specially designed N,N’-chelating ligands. The range of fully characterized lanthanide(II) compounds of the type [K(2.2.2-cryptand)][Cp’3Ln] (Cp’=C5H4SiMe3) has again been significantly expanded so that the +2 ions are now available for yttrium and all the lanthanides (except promethium, which was not studied due to its high radioactivity). The first well-defined lutetacyclopentadienes have been synthesized and their reactivity has been studied. The synthesis, structure, and reactivity of the extremely reactive yttrium metallocene ethyl complex Cp*2Y(CH2CH3), including activation of methane, have been reported. Significant progress has also been made in the field of endohedral metallofullerenes. Notably, encapsulation of a large La2C2 cluster inside D5(450)C100 induced a 5% axial compression of the cage, as compared with the structure of La2@D5(450)C100. The number of well-characterized heterometallic organolanthanide complexes has also witnessed a remarkable growth. An impressive number of interesting contributions have been published in the field of organolanthanide catalysis, with an emphasis on Ln-catalyzed olefin and diene polymerization. Approximately 20% of the papers published in 2015 were in the area of organoactinide chemistry. Notable results include the synthesis and characterization of homoleptic uranium(IV) tetrabenzyl complexes and a simple mono(imido) thorium complex and the first bis(imido) thorium complex, K[Th(NDipp))(NR2)3] and K2[Th(NDipp)2)(NR2)2] (Dipp=2,6-diisopropylphenyl, R=SiMe3). The reactivity of the unusual base-free imido complex [eta5-1,2,4-(Me3C)3C5H2]2ThN(p-tolyl) has also been studied. A highly remarkable achievement in 2015 was the synthesis of crystalline molecular complexes of the [{C5H3(SiMe3)2}3Th]- anion containing thorium in the formal +2 oxidation state. Various unusual transformations have been achieved using the Cp*2Th platform. For example, a unique thorium phosphinidene complex obtained from the reaction of Cp*2Th(CH3)2 with H2P(2,4,6-iPr3C6H2) has been prepared and structurally characterized. Other remarkable results include the preparation of novel actinide metallacyclocumulenes and metallacyclopentadienes. The synthesis of [3]thoro- and [3]uranocenophanes, the first structurally authenticated ansa-bridged actinocenes, has also been reported. Finally, significant progress has been made in the field of organoactinide catalysis.

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Alkylation of quinoline and isoquinoline in the presence of LiCl

The in situ generated EEDQ and EEDI reacted with alkylating reagents such as diethyl malonate, ethyl acetoacetate etc. in the presence of a 0.5 equiv of LiCl in acetonitrile to provide the corresponding products in high yields. EEDQ and EEDI generated in situ by the reaction of quinoline and isoquinoline with diethyl pyrocarbonate was treated with alkylating reagents having an activated carbon such as diethyl malonate, ethyl acetoacetate etc. in the presence of 0.5 equiv of LiCl in acetonitrile to provide the corresponding alkyl dihydroquinolines and alkyl dihydroisoquinolines in high yields.

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NOUVELLE SYNTHESE DU SQUELETTE DIHYDRO-1,2 ISOQUINOLEINE PAR REACTION DE SUBSTITUTION NUCLEOPHILE RADICALAIRE EN CHAINE (SRN1)

The SRN1 reaction between ortho-iodo-benzylamine and ketone enolates affords the 1,2-dihydroisoquinoline ring system from which the 3-substituted isoquinolines or the 1,2,3,4-tetrahydroisoquinoline are obtained.

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Metal-Free Direct C?H beta-Carbonyl Alkylation of Heteroarenes with Cyclopropanols Mediated by K2S2O8

Direct C?H beta-carbonyl alkylation of heteroarenes under metal-, acid- and photo-catalyst free conditions has been achieved. A wide scope of substrates, such as various substituted quinolines and isoquinolines, pyridines, pyridazine, benzo[d]thiazole and phenanthroline, underwent the beta-carbonyl alkylation efficiently via K2S2O8-mediated ring-opening of cyclopropanols. The corresponding beta-heteroarylated ketones were obtained in moderate to excellent yields and gram-scale experiments further demonstrated the practicality of this synthetic protocol. The readily available reagents, mild and environmentally benign conditions make the method extremely attractive. The reaction mechanism is also proposed.

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Asymmetric synthesis of a TRPV1 antagonist via tert -butanesulfinamide- directed reductive amination with a chromanone

An expedient asymmetric synthesis of TRPV1 antagonist 1 has been developed and demonstrated on multikilogram scale. The enabling route to 1 is detailed herein and characterized by the following key transformations: an aldol-cyclodehydration sequence to install the chromanone, and an auxiliary-mediated diastereoselective reductive amination.

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Copper(II) salicylideneglycinate complexes as potential antimicrobial agents

The reaction of an ethanolic solutions of N-salicylideneglycinatoaquacopper(II) hemihydrate with urea, pyridine, 2,4-dimethylpyridine, 3,5-dimethylpyridine, quinoline, 4-methylquinoline, isoquinoline, or 3-methylisoquinoline in an equimolar ratio resulted in solid products containing complexes of the type Cu(salgly)L with distorted square pyramidal coordination polyhedra. The products were characterized by elemental analysis, electronic and EPR spectra, and magnetic susceptibility measurements. Moreover, the crystal and molecular structure of N-salicylideneglycinatoureacopper(II) dimer was determined by single crystal X-ray diffraction methods. The copper(II) atoms are bridged by two phenolic oxygen atoms with a Cu-Cu distance of 3.1093(11) A and Cu-O-Cu angle of 94.47(12). The antimicrobial effects have been tested on various strains of bacteria, yeasts and filamentous fungi.

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