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Palladium-catalyzed cyanomethylation of aryl halides through domino Suzuki coupling-isoxazole fragmentation

A one-pot protocol for the cyanomethylation of aryl halides through a palladium-catalyzed reaction with isoxazole-4-boronic acid pinacol ester was developed. Mechanistically, the reaction proceeds through (1) Suzuki coupling, (2) base-induced fragmentation, and (3) deformylation as shown by characterization of all postulated intermediates. Under optimized conditions (PdCl2dppf, KF, DMSO/H2O, 130 C) a broad spectrum of aryl bromides could be converted into arylacetonitriles with up to 88% yield.

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

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Palladium complexes with metallocene-bridged bidentate diphosphine ligands: Synthesis, structure, and catalytic activity in amination and cross-coupling reactions

The syntheses and characterization of series of new metallocene-bridged diphosphines and the structures of complexes of some of them with Pd(II) are reported. These complexes were examined as the catalysts in amination reactions of halogenoarenes and in the Suzuki reaction. The complexes based on ruthenocene (2) and osmocene (3) showed lower activities then the palladium complex with dppf in amination reactions and the same activities in the Suzuki reaction. New palladium complexes with the bidentate bulky and electron-rich ligands Fe(eta5-C5H4P(o-PriC 6H4)2)2 (6) and Feeta5- C5H4P(o-MeOC6H4)2) 2 (5) showed a very high catalytic activity in amination and Suzuki coupling of aryl bromides. A complex with ligand 6 was used in the amination of 4-bromotoluene by primary and secondary amines and showed excellent activity.

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

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NOVEL 4-AMINO-6-(PYRIDYL AND 2-SUBSTITUTEDPHENYL)-PICOLINATES AND 6-AMINO-2-(PYRIDYL AND 2-SUBSTITUTEDPHENYL)-PYRIMIDINE-4-CARBOXYLATES AND THEIR USE AS HERBICIDES

4-amino-6-(pyridyl and 2-substitutedphenyl)-picolinic acids and their derivatives; 6-amino-2-(pyridyl and 2-substitutedphenyl)-pyrimidine-4-carboxylates and their derivatives; and methods of using the same as herbicides.

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

Archives for Chemistry Experiments of [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)

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Discovery of LSZ102, a potent, orally bioavailable selective estrogen receptor degrader (SERD) for the treatment of estrogen receptor positive breast cancer

In breast cancer, estrogen receptor alpha (ERalpha) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERalpha positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERalpha positive breast cancer.

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

Properties and Exciting Facts About [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)

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Synthesis and properties of dinuclear Ru(II)/Os(II) complexes based on a heteroditopic phenanthroline-terpyridine bridging ligand

The synthesis and characterization of a series of mono- and dinuclear ruthenium(II) and osmium(II) polypyridyl complexes based on the heteroditopic bridging ligand PT are reported. This ligand incorporates bidentate phen (1,10-phenanthroline) and terdentate tpy (2,2?:6?,2?- terpyridine) units directly connected by their 3 and 5 positions, respectively. The dinuclear complexes have been synthesized via a Pd(0) catalyzed cross-coupling reaction between a bromo-substituted Ru-phen complex and a tpy derivative incorporating a boronate ester, followed by Ru(II) or Os(II) complexation. The compounds obtained are fully characterized using spectroscopic and electrochemical measurements. The electrochemical studies do not yield any evidence for interaction between the two metal centers in the dinuclear compounds. Emission studies indicate, however, energy transfer from the phen moiety to the tpy center. For the ruthenium/osmium species, this process is relatively slow, resulting in a dual emission. The emission of the mononuclear ruthenium compound is enhanced by the addition of Zn(II).

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

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Fused tricyclic compounds as inhibitors of 17beta-hydroxysteroid dehydrogenase 3

Fused tricyclic compounds, methods of using such compounds in the treatment of hormone sensitive diseases such as prostate cancer, and pharmaceutical compositions containing such compounds.

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

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Derisking the Cu-Mediated 18F-Fluorination of Heterocyclic Positron Emission Tomography Radioligands

Molecules labeled with fluorine-18 (18F) are used in positron emission tomography to visualize, characterize and measure biological processes in the body. Despite recent advances in the incorporation of 18F onto arenes, the development of general and efficient approaches to label radioligands necessary for drug discovery programs remains a significant task. This full account describes a derisking approach toward the radiosynthesis of heterocyclic positron emission tomography (PET) radioligands using the copper-mediated 18F-fluorination of aryl boron reagents with 18F-fluoride as a model reaction. This approach is based on a study examining how the presence of heterocycles commonly used in drug development affects the efficiency of 18F-fluorination for a representative aryl boron reagent, and on the labeling of more than 50 (hetero)aryl boronic esters. This set of data allows for the application of this derisking strategy to the successful radiosynthesis of seven structurally complex pharmaceutically relevant heterocycle-containing molecules.

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

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Ligand-free Suzuki coupling reaction with highly recyclable ionic palladium catalyst, Ti1-xPdxO2-x (x?=?0.03)

We synthesized a recyclable palladium ionic catalyst, Ti0.97Pd0.03O1.97, using a solution combustion method (SCM), and characterized by XRD and Rietveld refinement. The synthesized Pd ionic catalyst is stable, insensitive to moisture and air, and easy to handle. The new catalyst has exhibited a phenomenal result for the Suzuki-Miyaura cross-coupling reaction with a broad substrate scope, and the reaction proceeds in an aqueous medium. The new catalyst proved beneficial and produced excellent yields irrespective of aryl halide used in the reaction (electron-rich or electron-poor or heterocyclic compounds) and shown a turnover frequency (TOF) of 14?25 h?1 for different reactions. The catalyst was coated on a cordierite monolith (Mg2Al4Si5O18), which enhanced the applicability of the catalyst, and made the handling and recycling of the catalyst very easy. Suzuki Miyaura reaction was carried out using both Pd-powder catalysts as well as the Pd-coated honeycomb, which gave almost similar results. We have demonstrated the recyclability of Pd coated cordierite monolith and shown the superiority of the catalyst over the other Pd catalysts for the Suzuki-Miyaura reaction.

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

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ALKYL-AMIDE-SUBSTITUTED PYRIDYL COMPOUNDS USEFUL AS MODULATORS OF IL-12, IL-23 AND/OR IFNalpha RESPONSES

Compounds having the following formula (I): or a stereoisomer or pharmaceutically-acceptable salt thereof, where R1, R2, R3, R4, and R5 are as defined herein, are useful in the modulation of IL-12, IL-23 and/or IFNalpha, by acting on Tyk-2 to cause signal transduction inhibition.

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

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A Pd(II)-catalyzed ring-expansion reaction of cyclic 2-azidoalcohol derivatives: Synthesis of azaheterocycles

(Chemical Equation Presented) A Pd(II)-catalyzed ring expansion-reaction of cyclic 2-azidoalcohol derivatives was found to proceed via an unprecedented C-C bond cleavage-C-N bond formation sequence, providing substituted azaheterocycles.

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