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METHYLENE LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORgammat activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Cyclotrimerization of phenylethynes to fulvene: Reactivity of cis-dichloro(1, 1?-bis(diphenylphosphino)ferrocene)palladium(II)

In the presence of triethylamine (NEt3) and ethanol (EtOH), phenylethyne (or phenylacetylene, PhC?CH) underwent cyclotrimerization: cis-dichloro(1,1?-bis(diphenylphosphino)ferrocene)palladiuni(II), [PdCl2(dppf)] (1), reacted with phenylethyne to give [Pd(dppf)(2,3,5-triphenylfulvene)] (2). Reaction of 2 with dimethyl acetylenedicarboxylate in dichloromethane gave [Pd(dppl)(CH3O2CC?CCO2CH3)] (3) and a free 2,3,5-triphenylfulvene. Crystallographic data for 2¡¤H2O: triclinic space group P1?, a = 10.658(2), b = 10.896(2), c = 21.080(3) A?, alpha = 85.303(9)?, beta = 76.556(9)?, gamma = 80.447(10)?, Z = 2, R(wR2) = 0.0487(0.1083).

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A METHOD OF INDOLE SYNTHESIS

The present invention relates to methods for the synthesis of indoles. In particular, the invention relates to the coupling of an a-haloenone or a-haloenal with an ortho-halonitroarene to form an ortho-(enone)nitroarene or ortho-(enal)nitroarene. Reductive cyclization of an ortho-(enone)nitroarene or ortho-(enal)nitroarene affords access to indole compounds.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Platinum(II), palladium(II), and nickel(II) thiosalicylate complexes

A series of platinum(II), palladium(II) and nickel(II) complexes containing thiosalicylate ligands have been prepared by the reaction of [MX2L2] complexes [X = halide or acetate; L or L2 = ancillary neutral donor ligand such as a tertiary phosphine or cycloocta-1,5-diene (cod)] with thiosalicylic acid in methanol with added pyridine. Displacement of the cod ligand from [Pt(SC6H4CO2)(cod)] with phosphines and phosphites allows the synthesis of additional derivatives. The complexes [Pt(SC6H4CO2)(PPh3)2] and [Ni(SC6H4CO2)(dppp)] [dppp = 1,3-bis(diphenylphosphino)propane] have been the subjects of single-crystal X-ray diffraction studies. While both complexes contain the expected approximately square-planar metal co-ordination environments, the plane of the thiosalicylate ligand is inclined at an angle of 45.9 to the platinum co-ordination plane, but at only 9.4 to the nickel plane. The results of an electrospray mass spectrometry study of the thiosalicylate complexes and some related thioglycolate, 2-sulfanylpropionate and salicylate derivatives are discussed in terms of the stabilities of the complexes.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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One-pot, two-step synthesis and photophysical properties of 2-(5-phenylindol-3-yl)benzimidazole derivatives

An efficient one-pot, two-step procedure has been successfully applied for the synthesis of a series of 2-(5-phenylindol-3-yl)benzimidazoles. The first step was cyclocondensation-oxidation of 5-bromoindole-3-aldehydes with o-phenylenediamines in 1,4-dioxane, which was promoted by activated carbon and used atmospheric air as a “green” oxidant. The resulting 2-(5-bromoindol-3-yl)benzimidazoles in the pot were in situ coupled with postadded phenylboronic acids, and catalyzed with PdCl2(dppf) in 1,4-dioxane-H2O to afford the desired compounds with satisfactorily high yields. The relationship between the synthesized compounds’ absorption, and fluorescence spectra with molecular structures has been investigated with experimental data and theoretical calculations.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Stereoselective synthesis of a pivotal chiral intermediate for natural salicylic macrolides

As a part of our ongoing research projects on the synthesis of natural salicylic macrolides, the optically active protected salicylate bearing the chiral diene substituent was required as a pivotal synthetic intermediate. The synthesis of the compound was achieved with a high optical purity starting from D-mannitol through Heck coupling reaction and terminal methylenation as key C-C bond forming reactions.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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A novel amphiphilic pincer palladium complex: Design, preparation and self-assembling behavior

Amphiphilic pincer palladium complexes bearing hydrophilic and hydrophobic side chains on the planar NCN palladium pincer backbone were designed and prepared via the ligand introduction route. The complexes self-assembled under aqueous conditions to form vesicles with bilayer membranes containing palladium species. The catalytic activity of the vesicles in the Miyaura-Michael reaction in water was investigated. The Royal Society of Chemistry 2011.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Reaction of 2-(2,2,2-Trifluoroethylidene)-1,3-dithiane 1-Oxide with ketones under pummerer conditions and its application to the synthesis of 3-Trifluoromethyl-Substituted five-membered heteroarenes

(Figure Presented) Easy as pie: With the aid of triflic anhydride, the title reaction resulted in nucleophilic attack of the carbonyl oxygen atom onto the activated cationic sulfur center and subsequent [3,3]-sigmatropic rearrangement (see scheme). The products are precursors of the difficult-to-synthesize five-membered 3-trifluoromethyl heteroarene compounds.

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Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method

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Structural Characterization of Heterodimetallic Zr/Pd and Zr/Rh Catalyst Precursors Containing the C5H4PPh2 Ligand

(Cp-PPh2)2ZrCl2 (5) reacts with (PhCN)2PdCl2 to yield the early-late heterodimetallic complex [(Cp-PPh2)2ZrCl2/PdCl2], 7, which was characterized by an X-ray crystal structure analysis. The phosphine-substituted bent metallocene moiety in 7 serves as a conformationally flexible chelate phosphine ligand (angle P-Pd-P: 96.46(3)). Complex 7 is an active catalyst for the cross-coupling of sec-butylmagnesium bromide with bromobenzene, leading to excellent regioselectivity and moderate reactivity. Complex 5 reacts with dicarbonylrhodium chloride dimer (0.5 equiv) to yield the triply bridged complex 12, [ClZr(mu-Cp-PPh2)2-(mu-Cl)Rh(CO)Cl], which was also characterized by X-ray diffraction (the angle P-Rh-P is 158 at the distorted square-pyramidal pentacoordinated rhodium center). (Cp-PPh2)2Zr-(CH3)2 (13) reacts with [H(CO)Rh(PPh3)3] (14) with loss of two PPh3 ligands and instantaneous liberation of methane to form complex 15, [CH3Zr(mu-Cp-PPh2)2Rh(CO)PPh 3](Zr-Rh), which probably contains a metal-metal bond between the early and late transition metal. Complex 15 is a very active 1-hexene hydroformylation catalyst (TOF > 600, n/iso ? 3 at 80C).

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Reference£º
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Palladium/carbon catalyst regeneration and mechanical application method

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Total synthesis of kendomycin: A macro-C-glycosidation approach

Kendomycin, also known as (-)-TAN 2162, is a novel polyketide-derived ansamycin isolated from Streptomyces sp., which exhibits potent antagonist and agonist activities at the endothelin and calcitonin receptors, respectively. This bacterial metabolite also possesses a strong antibiotic activity against a range of gram-positive and -negative bacteria and cytostatic effects on the growth of human cancer cell lines. When a novel macroglycosidation reaction is employed as the key step, the first enantioselective total synthesis of kendomycin has been accomplished. A Friedel-Crafts-type ring closure of the acyclic precursor containing tetrahydropyran and benzofuran moieties produces the macrocycle as a single stereoisomer in good yield, thus establishing the aryl C-glycosidic linkage of the ansa core. This reaction requires a phenolic glycosyl acceptor and appears to proceed through a rapid O-glycosidation followed by a slow rearrangement to an aryl C-glycoside. The requisite secomacrocycle is prepared by the Pd(0)-catalyzed B-alkyl Suzuki-Miyaura cross-coupling of two subunits, which in turn can be expeditiously assembled from readily available building blocks in a modular fashion. Copyright

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Reference£º
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method