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By 1H, 13C, 14N, and 15N NMR the structures were established of bis(3-methylisoxazol-5-yl), some of its derivatives, and related compounds, all synthesized for the first time.

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Trichlorocyclopropenylium tetrachloroaluminate is an electrophilic reagent for the preparative introduction of a cyclopropenyl fragment into heteroaromatic and aromatic substrates. 2005 Pleiades Publishing, Inc.

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The use of I2/AgOAc in dichloromethane constitutes a cheap, mild, and efficient method for the selective iodination of a variety of heterocycles. In a number of cases, this method provides superior yields to other literature methods and affords iodo-functionalized heterocycles that are suitable precursors for carbene complexes.

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Novel compounds of Formula (I) and salts thereof, pharmaceutical compositions containing such compounds and their use in therapy.

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A concise, regiocontrolled route to isoxazoles, based on the condensation of an ester with a metallated imine, has been developed. The intermediate vinylogous amides react smoothly with hydroxylamine to provide, after dehydration, substituted isoxazoles. The method has been used for the multi-kilo scale preparation of ABT-418, a novel cholinergic channel activator.

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The protein kinase MPS1 is a crucial component of the spindle assembly checkpoint signal and is aberrantly overexpressed in many human cancers. MPS1 is one of the top 25 genes overexpressed in tumors with chromosomal instability and aneuploidy. PTEN-deficient breast tumor cells are particularly dependent upon MPS1 for their survival, making it a target of significant interest in oncology. We report the discovery and optimization of potent and selective MPS1 inhibitors based on the 1H-pyrrolo[3,2-c]pyridine scaffold, guided by structure-based design and cellular characterization of MPS1 inhibition, leading to 65 (CCT251455). This potent and selective chemical tool stabilizes an inactive conformation of MPS1 with the activation loop ordered in a manner incompatible with ATP and substrate-peptide binding; it displays a favorable oral pharmacokinetic profile, shows dose-dependent inhibition of MPS1 in an HCT116 human tumor xenograft model, and is an attractive tool compound to elucidate further the therapeutic potential of MPS1 inhibition.

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Several new organometallic isoxazoles, silylated and stannylated in the heterocyclic ring or in a side chain have been made.Their 13C NMR spectra are consistent with the previous conclusions on the electronic effects of MR3 and CH2MR3 (M=Si, Sn) groups, and indicate the importance of the p?-d? and ?-? mechanisms in the various ring positions.

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(Chemical Equation Presented) A short stereoselective total synthesis of the polyketide natural product, tarchonanthuslactone, has been achieved. The key sequence involves the first reported catalytic enantioselective reduction of an N-acyl pyrrole and subsequent use of this stereocenter in a diastereoselective reductive cascade. This proceeded with unprecedentedly high stereocontrol and offered an elegant method of generating the desired syn stereochemistry present in the final target in one step.

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N-Benzyloxyurea was treated various beta-diketones on the presence of sulfuric acid in EtOH to give the corresponding 1-benzyloxy-2(1H)-pyrimidinones. 1-Benzyloxy-2(1H)-pyrimidinonesunderwent the ring transformation with hydroxylamine to afford new 5-N-(benzyloxy)urea-attached 2-isoxazolines in addition to known isoxazoles.The MNDO molecular orbital calculation of 1-benzyloxy-4,6-dimethyl-2(1H)-pyrimidinone and the reaction mechanism are also discussed.

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This chapter focuses on the photochemical isomerization of penta-atomic heterocyclic compounds. The description of the photochemical behavior of pentaatomic heterocyclic compounds is confused. Five mechanisms are invoked to justify the observed behaviors: (1) the ring contraction-ring expansion route (RCRE), (2) the internal cyclization-isomerization route (ICI), (3) the van Tamelen-Whitesides general mechanism (VTW), (4) the Zwitterion-tricycle route (ZT), (5) the fragmentation-readdition route (FR). The direct irradiation of a penta-atomic heterocycle leads to the formation of a singlet-excited state. This excited state can interconvert into the corresponding triplet state or into the corresponding Dewar isomer. The Dewar isomer is the origin of the formation of isomeric heterocyclic derivatives. The excited triplet state obtained via intersystem crossing from the corresponding excited singlet state or via a sensitized reaction can evolve to give a biradical intermediate. This biradical intermediate can be converted into decomposition products or into ring-contraction products. The ring-contraction products can be irradiated under the reaction conditions used to give isomeric heterocyclic derivatives.

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