- Amide Bond Formation via the Rearrangement of Nitrile Imines Derived from N-2-Nitrophenyl Hydrazonyl Bromides
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We report how the rearrangement of highly reactive nitrile imines derived from N-2-nitrophenyl hydrazonyl bromides can be harnessed for the facile construction of amide bonds. This amidation reaction was found to be widely applicable to the synthesis of primary, secondary, and tertiary amides and was used as the key step in the synthesis of the lipid-lowering agent bezafibrate. The orthogonality and functional group tolerance of this approach was exemplified by the N-acylation of unprotected amino acids.
- Boyle, Mhairi,Livingstone, Keith,Henry, Martyn C.,Elwood, Jessica M. L.,Lopez-Fernandez, J. Daniel,Jamieson, Craig
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p. 334 - 338
(2022/01/20)
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- Design and Scalable Synthesis of N-Alkylhydroxylamine Reagents for the Direct Iron-Catalyzed Installation of Medicinally Relevant Amines**
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Secondary and tertiary alkylamines are privileged substance classes that are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of ten novel hydroxylamine-derived aminating reagents were designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The method has excellent functional group tolerance and a broad scope of alkenes was converted to the corresponding products, including several drug-like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.
- Delcaillau, Tristan,Falk, Eric,Gürtler, Laura,Makai, Szabolcs,Morandi, Bill
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supporting information
p. 21064 - 21071
(2020/09/21)
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- Preparation process of bezafibrate compound
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The invention especially relates to preparation technology for a bezafibrate compound, belonging to the field of pharmaceutical synthesis. The invention provides a preparation process of the bezafibrate compound. The preparation process comprises the following steps: subjecting a compound with a structure as shown in a formula a or a' and a compound with a structure as shown in a formula b to an acylation reaction in an aqueous solution of inorganic base B so as to obtain a bezafibrate intermediate with a structure as shown in a formula c; and then subjecting the bezafibrate intermediate, R1COR2 and methyl halide to a condensation reaction in an aqueous solution of inorganic alkali A to obtain the bezafibrate compound with a structure as shown in a formula d, wherein process flow is as described in the specification, M is a water-soluble inorganic acid, X is a halogen or alkoxy group, and R1 and R2 are the same or different and are selected from a group consisting of H and C1-C3 alkylgroups.
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- Pharmaceutically acceprable salts of aporphine compounds of carboxyl group-containing agents and methods for preparing the same
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The present invention discloses novel pharmaceutically acceptable salts of aporphine compounds and carboxyl-group containing agents. Also, the present invention discloses methods for preparing the pharmaceutically acceptable salts. These pharmaceutically acceptable salts are suitable for use in treating and/or preventing hyperglycemic disease and/or several oxidative stress related diseases.
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- Treatment of skin conditions by use of PPAR alpha activators
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Disorders of the skin and mucous membrane that have a disrupted or dysfunctional epidermal barrier are treated or prevented by topical application of compounds that are either activators of the farnesoid X receptor, activators of the peroxisome proliferator-activated receptor alpha , and oxysterol activators of the LXR alpha receptor. The same compounds are also effective in treating disorders of epidermal differentiation and proliferation.
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- FXR, PPARA and LXRA activators to treat acne/acneiform conditions
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Acne vulgaris and acneiform skin conditions are treated by the application of compounds that is juvenile hormone III, 7-methyl-9-(3,3-dimethyloxiranyl)-3-methyl-2,6-nonadienoic acid methyl ester.
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- Processes for the preparation of tyramine derivatives
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The invention provides a process for the production of N-[2-(p-hydroxyphenyl)ethyl]-p-chlorobenzamide of the formula III: and derivatives thereof, comprising reacting 4-(2-aminoethyl) phenol (Tyramine) of formula I: or the hydrochloride salt thereof, with 1.0 to 1.5 molar equivalent of 4-chlorobenzoyl chloride in the presence of water, in the presence of at least one molar equivalent of base and in the presence of an organic solvent.
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- Method for the preparation of fibrates
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The present invention relates to a method for the preparation of fibrates of the formula I according to the mechanism: STR1 in which R1 represents especially a halogen atom (in particular F, Cl or Br, the preferred halogen atom being Cl) or an acetyl, (4-chlorophenyl)hydroxymethyl, 4-chlorobenzoyl or 2-(4-chlorobenzamido)ethyl group and R2 represents a C1 -C4 alkyl group in which the hydrocarbon chain is linear or branched, the reaction V+VI being carried out without a solvent.
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