262368-30-9Relevant articles and documents
Refining method of amino intermediate
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, (2021/03/03)
The invention relates to a tefining method of an amino intermediate represented by formula (I). Through the refining method, the concentrations of a genotoxic impurity 1 (N-(4-nitrophenyl)-N-methyl-2-(4-methylpiperazin-1-yl) acetamide) and an impurity 2 (N-(4-(hydroxyamino) phenyl)-N-methyl-2- (4-methylpiperazin-1-yl) acetamide) can be controlled to 4 ppm or less. According to the present invention, the contents of the genotoxic impurity 1 and the genotoxic impurity 2 in the formula (I) are significantly reduced, such that the process guarantee is provided for the industrial preparation of high-quality nintedanib ethanesulfonate, and the medication safety is ensured.
Preparation method of nintedanib key intermediate
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Paragraph 0005; 0026-0039; 0045, (2021/09/08)
The invention provides a preparation method of a nintedanib key intermediate, and belongs to the technical field of synthesis of medical intermediates. The first preparation method comprises the following steps: carrying out a nitro reduction reaction on a compound IV by taking an alcohol reagent or tetrahydrofuran as a solvent, taking hydrazine hydrate as a reducing agent and taking palladium carbon (Pd/C) as a catalyst until the nitro reduction reaction is complete, performing filtering to remove the catalyst under the protection of nitrogen, performing desolventizing to remove the solvent, performing dissolving by using dichloromethane, performing filtering to remove impurities, and performing desolventizing to obtain a compound I; the second method comprises the following steps: carrying out a nitro reduction reaction on a compound IV by taking hydrazine hydrate as a reducing agent and anhydrous ferric trichloride and activated carbon as catalysts until the nitro reduction reaction is complete, performing performing filtering to remove the catalyst, performing desolventizing to remove the solvent, dissolving dichloromethane, drying anhydrous sodium sulfate, performing filtering, and performing desolventizing to obtain a compound I. The preparation method provided by the invention is high in yield, strong in operability and high in safety, belongs to an environment-friendly process, and is suitable for industrial large-scale production.
INDOLINONE COMPOUNDS FOR USE AS MAP4K1 INHIBITORS
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, (2020/05/15)
The present disclosure is directed to compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein ring A, ring C, X1, X2, L1, R1, R2, R3, R4, R5, R6, R7, m and n are as defined herein, which are useful as MAP4K1 inhibitors, processes for their preparation, pharmaceutical compositions comprising the compounds, and the use of the compounds or the compositions in the treatment or prevention of various diseases, conditions and/or disorders mediated by MAP4K1.