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A method for the facile synthesis of ethene-bridged terthiophenes (EBTTs) in two steps has been developed. The first step is a double Sonogashira coupling between 3?,4?-dibromo-2,2?:5?,2?-terthiophene and terminal alkynes to give dialkynylated terthiophenes, and the second step is a cyclization reaction to afford EBTTs. The fundamental physical properties of EBTTs were also studied.

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

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A new three-component coupling reaction of benzyne is described that uses two intermolecular carbopalladation reactions to produce 1,2-functionalized benzene derivatives. Copyright

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

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Phosphoinositide 3-kinase (PI3K) is deregulated in a wide variety of human tumors and triggers activation of protein kinase B (PKB/Akt) and mammalian target of rapamycin (mTOR). Here we describe the preclinical characterization of compound 1 (PQR309, bimiralisib), a potent 4,6-dimorpholino-1,3,5-triazine-based pan-class I PI3K inhibitor, which targets mTOR kinase in a balanced fashion at higher concentrations. No off-target interactions were detected for 1 in a wide panel of protein kinase, enzyme, and receptor ligand assays. Moreover, 1 did not bind tubulin, which was observed for the structurally related 4 (BKM120, buparlisib). Compound 1 is orally available, crosses the blood-brain barrier, and displayed favorable pharmacokinetic parameters in mice, rats, and dogs. Compound 1 demonstrated efficiency in inhibiting proliferation in tumor cell lines and a rat xenograft model. This, together with the compound’s safety profile, identifies 1 as a clinical candidate with a broad application range in oncology, including treatment of brain tumors or CNS metastasis. Compound 1 is currently in phase II clinical trials for advanced solid tumors and refractory lymphoma.

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

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

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We report herein the preparation of ortho-vinylaryl S-trifluoromethylated sulfoximines through cross-coupling reactions. Two efficient palladium-catalyzed procedures (Stille and Suzuki) were developed, with use of ortho-iodo aryl sulfoximines as substrates, to give various vinyl derivatives in good yields. The difference in reactivity of the fluorinated derivatives, compared to nonfluorinated counterparts, allowed the use of free NH sulfoximines in the coupling processes, where they proved to be inert to cyclization. Finally, further transformations have been explored, such as metathesis coupling reactions, after post-functionalization of the nitrogen atom by another vinyl group.

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

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A facile one pot synthesis of cyclic silyl enol ethers, 1-sila-2-oxacyclohex-3-enes has been achieved by coupling reactions of strained 1,1-dimethyl-1-silacyclobutane with organic halides in CO atmosphere (1 atm) in the presence of palladium catalysts.

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

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Mg for B: An atom-economical one-pot synthesis by direct magnesium insertion in the presence of B(OBu)3 and LiCl allows a broad range of functionalized (hetero)aryl and alkenyl bromides to be converted into magnesium diorganoboronates 2, which undergo Suzuki-Miyaura cross-coupling reactions with various aryl (pseudo)halides (see scheme). Both aryl groups of 2 are transferred and furnish the products in good to excellent yields. Copyright

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

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The spirastrellolides are a novel family of structurally unprecedented marine macrolides which show promising anticancer properties due to their potent inhibition of protein phosphatase 2A. In the preceding paper, a modular strategy for the synthesis of spirastellolide A methyl ester which allowed for the initial stereochemical uncertainties was outlined, together with the synthesis of a series of suitably functionalised fragments. In this paper, the realisation of this synthesis is described. Two alternative coupling strategies were explored for elaborating the C26-C40 DEF bis-spiroacetal fragment: a modified Julia olefination of a C26 aldehyde with a C17-C25 sulfone, and a Suzuki coupling of a C25 trialkylborane with a C17-C24 vinyl iodide, which also required the development of a double hydroboration reaction to install the C23/C24 stereocentres. The latter proved a significantly superior strategy, and was fully optimised to provide a C17 aldehyde which was coupled with a C1-C16 alkyne fragment to afford the C1-C40 carbon framework. The BC spiroacetal was then installed within this advanced intermediate by oxidative cleavage of two PMB ethers with spontaneous spiroacetalisation, which also led to unanticipated deprotection of the C23 TES ether. The ensuing truncated seco-acid was cyclised in high yield to construct the 38-membered macrolactone under Yamaguchi macrolactonisation conditions, suggesting favourable conformational pre-organisation. Exhaustive desilylation provided a crystalline macrocyclic pentaol, revealing much about the likely conformation of the macrolactone in solution. Attachment of the remainder of the side chain proved challenging, potentially due to steric hindrance by this macrocycle; an olefin cross-metathesis to install an electrophilic allylic carbonate and subsequent pi-allyl Stille coupling with a C43-C47 stannane achieved this goal. Global deprotection completed the first total synthesis of (+)-spirastrellolide A methyl ester which, following detailed NMR correlation with an authentic sample, validated the full configurational assignment. A series of simplified analogues of spirastrellolide incorporating the C26-C47 region were also prepared by pi-allyl Stille coupling reactions.

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

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This disclosure relates to the field of molecules having pesticidal utility against pests in Phyla Arthropoda, Mollusca, and Nematoda, processes to produce such molecules, intermediates used in such processes, compositions containing such molecules, and processes of using such molecules and compositions against such pests. These molecules and compositions may be used, for example, as acaricides, insecticides, miticides, molluscicides, and nematicides. This document discloses molecules having the following formula (?Formula One?).

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

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Rhinoviruses (RVs) have been linked to exacerbations of many pulmonary diseases, thus increasing morbidity and/or mortality in subjects at risk. Unfortunately, the wide variety of RV genotypes constitutes a major hindrance for the development of Rhinovirus replication inhibitors. In the current investigation, we have developed a novel series of pyrazole derivatives that potently inhibit the Rhinovirus replication. Compounds 10e and 10h behave as early stage inhibitors of Rhinovirus infection with a broad-spectrum activity against RV-A and RV-B species (EC50 < 0.1 muM). We also evaluate the dynamics of the emerging resistance of these promising compounds and their in vitro genotoxicity. Molecular docking experiments shed light on the pharmacophoric elements interacting with residues of the drug-binding pocket. A reaction mechanism is the microscopic path by which reactants are transformed into products. Each step is an elementary reaction. In my other articles, you can also check out more blogs about 95464-05-4 Reference:
Chapter 1 An introduction to palladium catalysis,
Palladium/carbon catalyst regeneration and mechanical application method