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The development of efficient and selective C?N bond-forming reactions from abundant feedstock chemicals remains a central theme in organic chemistry owing to the key roles of amines in synthesis, drug discovery, and materials science. Herein, we present a dual catalytic system for the N-alkylation of diverse aromatic carbocyclic and heterocyclic amines directly with carboxylic acids, by-passing their preactivation as redox-active esters. The reaction, which is enabled by visible-light-driven, acridine-catalyzed decarboxylation, provides access to N-alkylated secondary and tertiary anilines and N-heterocycles. Additional examples, including double alkylation, the installation of metabolically robust deuterated methyl groups, and tandem ring formation, further demonstrate the potential of the direct decarboxylative alkylation (DDA) reaction.

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The present invention is directed to tricyclic indole derivatives, pharmaceutical compositions containing them and their use in the treatment of disorders and conditions modulated by endothelial lipase, for example, cardiovascular disorders.

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With the purpose of expanding the structural variety of chemical compounds available as pharmacological tools for the treatment of Alzheimer’s disease, we synthesized and evaluated a novel series of indole-benzoxazinones (Family I) and benzoxazine-arylpiperazine derivatives (Family II) for potential human acetylcholinesterase (hAChE) inhibitory properties. The most active compounds 7a and 7d demonstrated effective inhibitory profiles with Ki values of 20.3 ± 0.9 muM and 20.2 ± 0.9 muM, respectively. Kinetic inhibition assays showed non-competitive inhibition of AChE by the tested compounds. According to our docking studies, the most active compounds from both series (Families I and II) showed a binding mode similar to donepezil and interact with the same residues.

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[Problems] The present invention provides pharmaceutical composition which is effective for the prophylaxis or treatment of pathology showing involvement of uric acid (hyperuricemia, gouty tophus, acute gout arthritis, chronic gout arthritis, gouty kidney, urolithiasis, renal function disorder, coronary arterial disease, ischemic heart disease and the like) and the like, and is superior in the time-course stability and dissolution property (disintegration property). [Solving Means] The pharmaceutical composition of the present invention is a pharmaceutical composition comprising a nitrogen-containing fused ring compound represented by the following formula [1] or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable additives, wherein the nitrogen-containing fused ring compound or a pharmaceutically acceptable salt thereof is not in contact with a basic additive: wherein each symbol is as described in the specification.

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The syntheses of the thieno[2,3-b][1,4]thiazine derivatives 8 and 9 are described. Reaction of compound 4 with different acyl halides followed by substitution with various ethanamines gave the products 8 and 9. The new 3,4- dihydro-2H-1,4-benzoxazine derivatives 14, 16, 18 and 3,4-dihydro-2H-1,4- benzothiazine derivatives 15 and 17 with an urea moiety have been synthesized. Substitution of 10 respectively 11 with 4-nitrophenyl chloroformate gave the required reactivity for substitution with diamines. Structural modifications of the amino side chain were carried out.

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A conceptually distinct strategy enabling malonylamination of alkenes with abundant amines and iodonium ylides without assistance of any transition metal was developed. Succinimide was identified as a proton shuttle that can not only largely accelerate the process of trapping highly unstable radical ion pairs with alkenes but also significantly improve the chemical yields.

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Reported herein is the development of a simple but practical catalytic system for the selective reduction of amides with hydrosilane or hydrosiloxane. Low-cost and readily available triethylborane (1.0 M in THF), in combination with a catalytic amount of an alkali metal base, was found to catalyze the reduction of all three amide classes (tertiary, secondary, and primary amides) to form amines under mild conditions. In addition, the selective transformation of secondary amides to aldimines and primary amides to nitriles can also be achieved by using a proper combination of BEt3 and base. The scope of these BEt3-base-catalyzed amide hydrosilylation reactions has been explored in depth. Preliminary results of mechanistic studies suggest a modified Piers’ silane Si-H···B activation mode wherein the hydride abstraction by BEt3 is promoted by the coordination of an alkoxide or hydroxide anion to the Si center.

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A simple catalyst- and additive-free method for the N-formylation of amines has been developed. The advantages of this protocol include a wide range of functional group tolerance, high efficiency and a lack of required extra promoters under mild conditions. This convenient strategy will provide a facile synthesis towards N-formamide natural products and pharmaceutical derivatives. A mechanism that involves difluorocarbene is proposed for this reaction.

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A highly efficient and practical Ru-catalyzed direct C-H functionalization of indolines and N-alkylaniline with a simple pivaloyl as a directing group is developed. Broad substrate scopes with respect to N-heteroarenes and olefins are observed. The selective C7-position alkynylation for indoline also proceeds well by using inexpensive ruthenium as a catalyst, and pivaloyl as a directing group.

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The potential utility of polymethylhydrosiloxane (PMHS) as a reducing agent for reductive N-alkylation of aromatic amines and nitro compounds using nitriles as an alkylating agent and Pd(OH)2/C as a catalyst is described. The application of this method for the synthesis of several heterocyclic compounds is also reported.

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