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Transition-Metal-Free Thioamination of Arynes Using Sulfenamides

The insertion of arynes into the S-N sigma-bond of sulfenamides allowing the synthesis of o-sulfanylaniline derivatives with reasonable functional group compatibility is presented. The aryne generated from 2-(trimethylsilyl)aryl triflates using CsF in DME was the key for the success of this transition-metal-free thioamination reaction, which involves new C-N and C-S bond formations in a single step under mild conditions. Moreover, the synthetic potential of this method was demonstrated by the synthesis of the antidepressant drug vortioxetine.

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SYNTHESE D’ARYLAMINO-1 OU-3 OXO-2 PROPYLPHOSPHONATES. PASSAGE AUX INDOLE PHOSPHONATES SELON BISCHLER

The synthesis of indole phosphonates 3, 4, 4′ by Bischler cyclization of 1- or 3-arylamino-2-oxopropylphosphonates 1 and 2 (Fig. 8) is described.Two new reagents are used to prepare the arylaminoketones: the 1-chloro and 3-chloro-2-methoxycarbonylhydrazonopropylphosphonates 6 and 10; these compounds undergo base-catalysed 1,4 elimination of hydrogene chloride leading to azoenes which give Michael type additions with anilines.The arylaminohydrazones thus obtained, when treated with aqueous TiCl3 or under acid-catalyzed exchange with acetone, yield the title compounds arylaminoketones.

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Final Thoughts on Chemistry for 5-Cyclopropyl-3-(2,6-dichlorophenyl)isoxazole-4-methanol

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BRIDGED BICYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS

The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

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A facile protocol for the synthesis of mono-N-methyl anilines via formimidate intermediates

A general procedure for the preparation of mono-N-methyl anilines has been developed with excellent yields. This protocol relies on a NaBH3(OAc) reduction of formimidate intermediates that are quantitatively generated by treatment of primary substituted anilines with triethyl orthoformate under the catalysis of MCM-41-SO3H mesoporous zeolite. The newly developed procedure was facile, efficient, and environmentally benign.

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Top Picks: new discover of 5-(4-Hydroxyphenyl)isoxazole-3-carboxylic acid

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Facile proton transfer reactions of N,N-dimethylaniline cation radicals

Ring-substituted N,N-dimethylaniline (DMA) cation radicals undergo rapid proton transfer reactions with acetate ion or pyridine in acetonitrile. The difference in pKa of the parent DMA and DMA* was estimated to equal 27 using electrode potentials in a thermochemical cycle. Second-order rate constants for the reaction with acetate ion at 298 K ranged from 3.2 ¡Á 106 for the p-methoxy-substituted cation radical to 3 ¡Á 109 M-1 s-1 for the corresponding p-nitro derivative. Rate constants for the reactions of the cation radicals with pyridine were observed to be as much as 106 lower than with acetate ion. Activation parameters for the two series of reactions differed markedly. Enthalpies of activation (DeltaH*) on the order of 20 kcal/mol and large positive activation entropies (DeltaS*), 35-53 eu, were characteristic of the acetate ion reactions, while for pyridine, DeltaH* ranged from 2 to 13 kcal/mol and DeltaS* values were large and negative, -15 to -29 eu. Large kH/kD values for reactions of ArN(CD3)2*+ implicate proton transfer as the rate-determining step in both reaction series. The differences in activation parameters for the two sets of reactions were attributed to differences in the position of the preequilibrium between base and cation radicals. A large equilibrium constant is expected for the reversible ion combination between acetate ion and the cation radicals.

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Synthesis of N4-(substituted phenyl)-N4-alkyl/ desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines and identification of new microtubule disrupting compounds that are effective against multidrug resistant cells

A series of fourteen N4-(substituted phenyl)-N 4-alkyl/desalkyl-9H-pyrimido[4,5-b]indole-2,4-diamines was synthesized as potential microtubule targeting agents. The synthesis involved a Fisher indole cyclization of 2-amino-6-hydrazinylpyrimidin-4(3H)-one with cyclohexanone, followed by oxidation, chlorination and displacement with appropriate anilines. Compounds 6, 14 and 15 had low nanomolar potency against MDA-MB-435 tumor cells and depolymerized microtubules. Compound 6 additionally had nanomolar GI50 values against 57 of the NCI 60-tumor panel cell lines. Mechanistic studies showed that 6 inhibited tubulin polymerization and [3H]colchicine binding to tubulin. The most potent compounds were all effective in cells expressing P-glycoprotein or the betaIII isotype of tubulin, which have been associated with clinical drug resistance. Modeling studies provided the potential interactions of 6, 14 and 15 within the colchicine site.

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1,4-Diazabicyclo[2.2.2]octane (DABCO) as an efficient reagent for the synthesis of isoxazole derivatives from primary nitro compounds and dipolarophiles: The role of the base

The dehydration of primary nitro compounds can be performed by bases in the presence of dipolarophiles. The reactivity of several tertiary amines or azaheteroaromatic compounds containing one or two basic centres is shown to be related to the ability of the protonated base to establish H-bonded ion pairs with the adduct that is formed from the nitronate and the dipolarophile in chloroform. Among the organic bases examined, caged tertiary diamine 1,4-diazabicyclo[2.2.2]octane (DABCO) gave the best results. The reaction is applicable to activated nitro compounds and to phenylnitromethane and affords isoxazoline derivatives in higher yields compared with those of other methods. The reaction, however, is not compatible with nitroalkanes. The proposed mechanism of the reaction is based on the collapse of the H-bonded ion pair. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

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Heterocyclic french Nepal ester derivatives X receptor modulators (by machine translation)

The invention relates to a heterocyclic compound and contains the same component composition preparation method and its as french Nepal ester X receptor (FXR) derivatives of the active use of the regulator, the regulator shown in formula I of the heterocyclic compound, or its pharmaceutically acceptable salt, prodrug, compound solvent, polymorphism body, isomer, and stable isotope derivatives. The invention relates to compounds can be used for the treatment or prevention of the diseases related to the FXR-mediated by, the related disease is due to the carbohydrate, lipid or bile metabolism caused by abnormal. (by machine translation)

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GOLD CATALYZED HYDROAMINATION OF ALKYNES AND ALLENES

Methods are provided for the catalytic hydroamination of compounds having an alkyne or allene functional group, in which the compound is contacted with ammonia or an amine in the presence of a catalytic amount of a gold complex under conditions sufficient for hydroamination to occur.

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Awesome Chemistry Experiments For 5-Methyl-3,4-diphenylisoxazole

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Chemistry of Four-Membered Cyclic Nitrones. 3. Reaction with Nucleophilic Reagents and Stereospecific Conversion into 1-Hydroxyazetidines

Four-membered cyclic nitrones (1) react with a variety of nucleophiles (MeMgI, CN-, OH-, MeO-, and H-) by stereospecific addition to the C=N bond.Reaction of 1a with potassium cyanide and with methylmagnesium iodide yields the 1-hydroxyazetidines 2a and 2b, respectively.Reduction of 1b with lithium aluminum hydride and with sodium borohydride affords the 1-hydroxyazetidine derivatives 3 and 4, respectively.Sodium hydroxide in methanol-water reacts with 1a to give a mixture of two isomeric 5-hydroxyisoxazolidines 5a and 5b, but under similar reaction conditions 1b and 1c rearrange to the oximes 6 and 7.In acetic acid at room temperature 6a cyclizes to the 6H-1,2-oxazin-6-one derivative 8, whereas 6b yields 5-methyl-3,4-diphenylisoxazole (9) after being refluxed in acetic acid, probably by carbon monoxide elimination from the intermediate oxazin-6-one derivative.Reaction of 1a with sodium hydroxide for 2 min gives exclusively the 1-hydroxy-4-methoxyazetidine 13a, whereas prolonged reaction gives the isomeric azetidine 13b together with 5 (mixture of 5a and 5b in a ratio 4:1).Single-crystal X-ray analysis of 13b reveals that all three relatively bulky substituents at C-2, C-3, and C-4 are on the same face of the azetidine ring.Treatment of 13b with acetic acid at room temperature gives the 5-methoxyisoxazolidine 15.The 1-hydroxyazetidines 2-4 are oxidized with yellow mercury(II) oxide to the corresponding four-membered cyclic nitrones 1b, 16 and 17.

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