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Peptide deformylase inhibitors

The present invention relates to a compound of Formula (I): or a pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

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

The Absolute Best Science Experiment for [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II)

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DIHYDRO-PYRROLOPYRIDINONE INHIBITORS

The present invention provides for compounds of formula (I) wherein R1, R2, R3, R4, and R5 have any of the values defined in the specification, and pharmaceutically acceptable salts thereof, that are useful as agents in the treatment of diseases and conditions, including inflammatory diseases, cancer, and AIDS. Also provided are pharmaceutical compositions comprising one or more compounds of formula (I).

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

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Palladium-catalyzed decarboxylative coupling of alpha,beta-unsaturated carboxylic acids with aryl tosylates

We report a general method for selective cross-coupling of alpha,beta-unsaturated carboxylic acids with aryl tosylates enabled by versatile Pd(II) complexes. This method features the general cross-coupling of ubiquitous alpha,beta-unsaturated carboxylic acids by decarboxylation. The transformation is characterized by its operational simplicity, the use of inexpensive, air-stable Pd(II) catalysts, scalability and wide substrate scope. The reaction proceeds with high trans selectivity to furnish valuable (E)-1,2-diarylethenes.

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

Discovery of Bis(dibenzylideneacetone)palladium

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Palladium-catalysed amination of aryl- and heteroaryl halides using tert-butyl tetraisopropylphosphorodiamidite as an easily accessible and air-stable ligand

The phosphorus compound tert-butyl tetraisopropylphosphorodiamidite, prepared from bis(diisopropylamino)chlorophosphine, is an excellent ligand for palladium-catalysed Buchwald-Hartwig amination of aryl- and heteroaryl chlorides and bromides. Based on its ready accessibility and air-stability, this amination protocol is a practical approach to the synthesis of industrially important aryl- and heteroarylamines. 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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Design and Enantioresolution of Homochiral Fe(II)-Pd(II) Coordination Cages from Stereolabile Metalloligands: Stereochemical Stability and Enantioselective Separation

The stereochemistry of chiral-at-metal complexes is much more abundant, albeit complicated, than chiral-at-carbon compounds, but how to make use of stereolabile metal-centers remains a formidable challenge due to the highly versatile coordination geometry of metal ions and racemization/epimerization problem. We demonstrate herein a stepwise assembly of configurationally stable [Pd6(FeL3)8]28+ (Delta/-MOCs-42) homochiral octahedral cages from unstable D3-symmetry tris-chelate-Fe type metalloligands via strong face-directed stereochemical coupling and facile chiral-induced resolution processes based on stereodifferentiating host-guest dynamics. Kinetic studies reveal that the dissociation rate of MOC-42 cages is 100-fold slower than that of Fe-metalloligands and the racemization is effectively inhibited, making the cages retain their chirality over extended periods of time (>5 months) at room temperature. Recyclable enantioseparation of atropisomeric compounds has been successfully achieved, giving up to 88% ee.

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

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Asymmetric Allylation of Furfural Derivatives: Synergistic Effect of Chiral Ligand and Organocatalyst on Stereochemical Control

An asymmetric allylation reaction at the benzylic position of furfurals that are easily accessed from 5-HMF, which is a biomass derivative, has been established by palladium and amine cooperative catalysis. The high levels of enantioselectivity of up to 97% enantiometric excess (ee) were enabled by the synergistic stereochemical control of a chiral TADDOL-based phosphoramidite ligand and a chiral diphenylprolinol silyl ether. The product could be feasibly transformed to chiral aryl-substituted spiroacetal via a four-step reaction sequence.

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

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Multimetallic complexes of group 10 and 11 metals based on polydentate dithiocarbamate ligands

The ligands KS2CN(Bz)CH2CH2N(Bz)CS 2K (K2L1), N(CH2CH 2N(Me)CS2Na)3 (Na3L2), and the new chelates {(CH2CH2)NCS2Na} 3 (Na3L3) and {CH2CH 2N(CS2Na)CH2CH2CH 2NCS2Na}2 (Na4L4), react with the gold(I) complexes [ClAu(PR3)] (R = Me, Ph, Cy) and [ClAu(IDip)] to yield di-, tri-and tetragold compounds. Larger metal units can also be coordinated by the longer, flexible linker, K2L1. Thus two equivalents of cis-[PtCl2(PEt3)2] react with K2L1 in the presence of NH4PF 6 to yield the bimetallic complex [L1{Pt(PEt 3)2}2](PF6)2. The compounds [NiCl2(dppp)] and [MCl2(dppf)] (M = Ni, Pd, Pt; dppp = 1,3-bis(diphenylphosphino)propane, dppf = 1,1′-bis(diphenylphosphino) ferrocene) also yield the dications, [L1{Ni(dppp)}2] 2+ and [L1{Ni(dppf)}2]2+ in an analogous fashion. In the same manner, reaction between [(L?2) (AuCl)2] (L?2 = dppm, dppf; dppm = bis(diphenylphosphino)methane) and KS2CN(Bz)CH2CH 2N(Bz)CS2K yield [L1{Au2(L? 2)}2]. The molecular structures of [L1{M(dppf)} 2](PF6)2 (M = Ni, Pd) and [L 1{Au(PR3)}2] (R = Me, Ph) are reported.

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

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Synthesis of tetrasubstituted pyrazoles containing pyridinyl substituents

A synthesis of tetrasubstituted pyrazoles containing two, three or four pyridinyl substituents is described. Hence, the reaction of 1,3-dipyridinyl-1,3-propanediones with 2-hydrazinopyridine or phenylhydrazine, respectively, affords the corresponding 1,3,5-trisubstituted pyrazoles. Iodination at the 4-position of the pyrazole nucleus by treatment with I2/HIO3 gives the appropriate 4-iodopyrazoles which served as starting materials for different cross-coupling reactions. Finally, Negishi cross-coupling employing organozinc halides and Pd catalysts turned out to be the method of choice to obtain the desired tetrasubstituted pyrazoles. The formation of different unexpected reaction products is described. Detailed NMR spectroscopic investigations (1H, 13C, 15N) were undertaken with all products prepared. Moreover, the structure of a condensation product was confirmed by crystal structure analysis.

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

Simple exploration of 1,1′-Bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex

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Selectivity Controlled Palladium-Catalyzed Carbonylative Synthesis of Propiolates and Chromenones from Phenols and Alkynes

An interesting selectivity-controlled palladium-catalyzed oxidative carbonylation procedure for the synthesis of propiolates and chromenones has been developed. Starting from phenols and alkynes, under slightly different conditions, various propiolates and chromenones can be isolated in moderate to good yields. Additionally, this also presents the first example of direct carbonylative annulation of nonpreactivated phenols and terminal alkynes to produce chromenones.

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

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MYELIN DETECTION USING BENZOFURAN DERIVATIVES

The present invention relates to methods for the detection of myelin and a quantitative measurement of its local concentration in a sample using a benzofuran compound or its radioisotope derivatives. In one embodiment a method of myelin detection comprises identifying a subject at risk of or diagnosed with a myelin-associated neuropathy, parenterally administering to the subject the benzofuran compound, or a derivative of the compound, and determining myelination in the subject by detecting binding in the sample. In one embodiment, the invention provides a method of imaging myelinated tissue in a surgical field of mammalian tissue comprising the steps of contacting the surgical site with the benzofuran compound or a radioisotope derivative of the compound, and detecting binding in the surgical site. In yet another embodiment, a method of imaging spinal cord and spinal nerve root tissue is provided comprising the steps of parenteral administration of a radioisotope derivative of the benzofuran compound and detecting the radioisotope derivative within the spinal canal and intervertebral foramen. Methods of quantification of binding of the benzofuran compound or its derivatives are also provided.

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