8 results about "Bilastine" patented technology

The invention discloses a preparation method of a bilastine intermediate, which comprises the following steps: reacting a compound 5 with thionyl chloride under the conditions that dichloromethane is used as a solvent and DMF (Dimethyl Formamide) is used as a catalyst to generate acyl chloride, and then reacting the acyl chloride with diethylamine to prepare a compound 6; taking dichloromethane as a solvent, and carrying out Friedel-Crafts acylation on the compound 6 and ethyl oxalyl chloride under the condition of anhydrous aluminum trichloride to obtain a compound 7; reducing the compound 7 by using sodium borohydride, liquid caustic soda and a water system to prepare a compound 8; taking dichloromethane as a solvent, and reducing the compound 8 by TMDS under the condition of anhydrous aluminum trichloride to prepare a compound 9; hydrolyzing the compound 9 under the hydrochloric acid condition to obtain a compound 10; and under the condition of thionyl chloride, carrying out esterification reaction on the compound 10 and methanol to prepare the bilastine intermediate TM. The preparation method of the bilastine intermediate, provided by the invention, has the advantages of economical and easily available raw materials, mild reaction conditions, efficient reaction and simple operation, and is suitable for industrial application.

The application discloses a preparation process of bilastine, and belongs to the technical field of medicinal chemistry. The target compound is prepared through three-step chemical reactions by using a folding process, intermediate products do not need to be purified or only need to be simply extracted to remove impurities to meet production requirements; compound I is condensed with compound II in water to prepare compound III; then, a proton acid is added to deprotect to prepare a compound IV aqueous solution; after dichloromethane back extraction to remove impurities; the compound IV aqueous solution is subjected to a substitution reaction with compound V to prepare compound VI. The raw material adopted by the application is clear, cheap and easy to obtain, market supply is stable, the preparation process is simple, water is used as a solvent in the three-step reaction, and no special equipment is required, the production efficiency is improved, the production cycle is shortened, and the generation of three wastes is reduced, and the application is suitable for industrial production; the purity of each intermediate prepared is more than 99%, the purity of the final product can reach 99.88%, and the impurity spectrum is stable and clear.

This application discloses a method for preparing bilastin and its impurities. The method for preparing bilastin includes a reaction step using a compound of formula (I) and / or a salt of a compound of formula (I) as an intermediate, wherein the content of the compound of formula (II) in the intermediate product is not higher than 0.1 wt%. The method of this application yields bilastin with a purity higher than 99.5%, and the content of a single impurity is not more than 0.1%. The purity of the bilastin product meets the quality standards specified in the pharmacopoeia, with a high product qualification rate, which is conducive to large-scale production.

The disclosure relates to an aqueous ophthalmic pharmaceutical composition including: a) at least 0.4% w / v of bilastine, of formulaor a pharmaceutically acceptable salt or solvate thereof, wherein the bilastine salt or solvate thereof is completely dissolved in the pharmaceutical composition; b) at least one β-cyclodextrin; and c) at least one pharmaceutically acceptable water-soluble gelling agent; and wherein the pH is comprised between 4 and 9. Use of the composition is described for the treatment and / or prevention of conditions mediated by H1 histamine receptor, such as allergic disorders or diseases. The treatment and / or prevention of allergic conjunctivitis is described.

The invention relates to the technical field of chemical analysis, in particular to a method for separating a bilastine intermediate and related substances thereof. The method comprises the following steps: detecting a to-be-detected sample by using a high performance liquid chromatography to obtain a chromatogram; wherein the chromatographic conditions of the high performance liquid chromatography are as follows: octadecylsilane chemically bonded silica is used as a filling agent of a chromatographic column; the mobile phase comprises a mobile phase A and a mobile phase B, the mobile phase A and the mobile phase B are used for gradient elution, the mobile phase A is a sodium hexanesulfonate solution, the mobile phase B is acetonitrile, and the bilastine intermediate and the related substances thereof are subjected to gradient elution and HPLC (High Performance Liquid Chromatography) detection. According to the method disclosed by the invention, the bilastine intermediate and the related substances thereof can be effectively separated, so that the peaks of the related substances and the peaks of the bilastine intermediate are not overlapped, the peak shape is good, the separation requirement is met, and the quality control of drugs taking bilastine as a raw material can be effectively realized.

The invention discloses a synthetic route of a bilastine intermediate, which comprises the following steps: S1, dissolving 2-(4-(2-chloroethyl) phenyl)-2-methyl-methyl propionate in acetic acid, and adding sodium acetate for reaction to obtain a compound B; s2, the compound B is placed in a mixed system of sodium hydroxide, water and ethyl alcohol to react, and a compound C is obtained; s3, mixing the compound C with methanol, and reacting under the catalysis of concentrated sulfuric acid to obtain a compound D; s4, the compound D reacts with paratoluensulfonyl chloride in the presence of triethylamine, and a target product is obtained. The method is mild in reaction condition, simple and controllable in step and high in repeatability, the total yield from the initial raw material A to the product E reaches up to 85.58%, the product purity is verified to meet the requirement through thin-layer chromatography and nuclear magnetic hydrogen spectrum, the problems that in the prior art, when the bilastine key intermediate is synthesized, the yield is low, the process is complex, the condition is harsh, and the environmental protection property is poor are solved, and the method is suitable for industrial production. The method is suitable for industrial large-scale production.

The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a bilastine intermediate; namely, a new preparation method of 4-[2-[4-[1-(2-ethoxyethyl)-1H-2-benzimidazolyl]-1-piperidyl]-ethyl]-alpha,alpha-dimethylphenylacetic acid methyl (or ethyl) ester is provided. In the method, 2-(1-(2-bromoethyl)piperidin-4-yl)-1-(2-ethoxyethyl)-1H-benzo[d]imidazole is used as a starting material, and after being activated by iodine / zinc, the starting material is subjected to a cross-coupling reaction with 2-(4-bromophenyl)-2-methylpropionic acid methyl (or ethyl) ester to obtain the target product. The whole synthesis method is simple in operation and suitable for industrial production.