102 results about "Hydrobromide" patented technology

The invention relates to the field of novel medical compounds, in particular to a chiral synthesis method of epigalanthamine hydrobromide which is a key impurity of galanthamine hydrobromide. An intermediate easy for industrial production is used as a raw material, and epigalanthamine hydrobromide is synthesized in one step through a chiral reducing agent. The synthesis method utilizes intermediates in the existing industrial production process, has the advantages of simple steps, low reagent cost, high yield, high optical purity of the product and the like, and greatly facilitates preparation of impurities of galanthamine and further development of a pharmaceutical analysis method of galanthamine.

The invention belongs to the technical field of flame retardants, and particularly relates to a melamine hydrobromide flame retardant and a preparation method thereof. The flame retardant disclosed by the invention has a core-shell structure, the core is hydroxylated melamine hydrobromide subjected to surface modification by a silane coupling agent, and the shell is melamine resin synergistically enhanced by ammonium polyphosphate and oxidized cellulose nanofibrils; through silanization treatment, core-shell interface combination is enhanced, and space-time synergy of gas phase and condensed phase flame retardance is achieved through a composite shell; the obtained flame retardant is high in thermal stability in a polymer matrix, the limit oxygen index of a composite material can be remarkably increased after the flame retardant is added, and the flame retardant has a wide application prospect in the field of flame retardance of high polymer materials through a UL-94 V-0 grade test.

The invention belongs to the field of medicines, and particularly discloses a cystamine derivative impurity of tiagliptin hydrobromide and a control method thereof, and the control method comprises the following steps: dissolving a starting material tetrahydrothiazole in an organic solvent, washing with water, stirring, standing, separating liquid, retaining an organic phase, and spin-drying to obtain purified tetrahydrothiazole. Compared with the prior art, the method has the advantages that cysteamine and cystamine impurities in the thiazolidine are reduced by washing and extracting the starting material thiazolidine, so that the content of cystamine derivative impurities in the tiagliptin API is less than 0.1%, the product purity is effectively improved, and the quality consistency of tiagliptin raw material medicines in multi-batch production is better; repeated recrystallization of API is avoided, the yield is increased to 80% from 36%, and the production cost is reduced; the operation is simple and easy to realize.

The invention discloses preparation and application of an amido-functionalized polyionic liquid catalyst, vinyl imidazole hydrobromide and N-(4-vinyl) benzyl diethylamine are used as monomers, N, N '-methylene bisacrylamide is used as a cross-linking agent, and the amido-functionalized polyionic liquid catalyst is prepared through a free radical copolymerization method. The imidazole / amido functionalized cross-linked PILs with multiple active sites are prepared by one-step synthesis through a hydrothermal polymerization method. The catalyst has catalytic active sites of amido, imidazolyl and Br, so that the catalyst can efficiently catalyze the cycloaddition reaction of CO2 and epoxide at 80 DEG C and normal pressure in the absence of a solvent and a co-catalyst.

The invention discloses a method for detecting genotoxic impurities in vortioxetine hydrobromide orally disintegrating tablets. The method comprises the following steps: mixing phosphate buffer and methanol, wherein the volume ratio of the phosphate buffer to the methanol is 1-20:80-100, to obtain a solvent; grinding the vortioxetine hydrobromide orally disintegrating tablets, adding the mixture into the solvent for dissolution, filtering, and obtaining a test solution; then detecting the test solution by an HPLC method to obtain the content of the genotoxic impurities in the flutioxetine hydrobromide orally disintegrating tablets; the structural formula of the genotoxic impurities is shown in formula (I): The detection method of the invention has accurate and reliable results, is simple and convenient to operate, is rapid, has high stability, good repeatability and durability, can effectively break the difference between solubility and stability, has a recovery rate close to 100%, and has no significant degradation trend of nitrosamine impurities.

The present application relates to a trace neodymium doped phenethylamine lead bromide monocrystal capable of simultaneously enhancing light yield and shortening decay time and application thereof, which solves the technical problem that the prior art is difficult to simultaneously improve light yield and shorten luminescence decay time. The trace neodymium doped phenethylamine lead bromide monocrystal capable of simultaneously enhancing light yield and shortening decay time is prepared by the following steps: 1) weighing; phenethylamine hydrobromide, lead bromide and neodymium bromide are weighed and placed in a glass bottle; the molar ratio of the phenethylamine hydrobromide, lead bromide and neodymium bromide is 2:1:(0.02-0.05); 2) obtaining a precursor solution; N,N-dimethylformamide is added to the glass bottle, heated and stirred until completely dissolved to obtain a precursor solution; 3) obtaining a crystal; the precursor solution is filtered and placed in a glass beaker for crystallization to obtain a neodymium doped phenethylamine lead bromide monocrystal; through adjustment of the crystal band structure by neodymium, the radiation recombination rate is improved.

The present invention provides a pharmaceutically acceptable salt and crystal form of a KIF18A inhibitor, and a preparation method therefor and a use thereof. The pharmaceutically acceptable salt is selected from one or more of a sodium salt, a potassium salt, a hydrochloride, a p-toluenesulfonate, a maleate, a methanesulfonate, an ethanesulfonate, and a hydrobromide of a compound represented by formula (I). The present invention provides the pharmaceutically acceptable salt of the compound represented by formula (I) and a crystal of the salt, which exhibit excellent hygroscopicity, solubility, and / or stability, and are suitable for pharmaceutical use.

The invention provides a method for detecting ethyl chloroformate, 1,3-bromochloropropane and ethyl methylcarbamate impurities in an eptazocine intermediate (-)-(1S-6S)-2,3,4,5,6,7-hexahydro-1,4-dimethyl-1,6-methylene-1hydro-4-phenylin-10-methoxy ether (compound 2). The method is rapid, accurate and has a low detection limit. The method can effectively control the content of ethyl chloroformate, 1,3-bromochloropropane and ethyl methylcarbamate that may remain in compound 2, thereby ensuring the safety of the use of an eptazocine hydrobromide preparation product further prepared from an eptazocine hydrobromide raw material.

The disclosure relates to (2-{4-[(methoxycarbonyl)oxy]-1H-indol-3-yl}ethyl)bis(propan-2-yl)azanium chloride (4-methylcarbonato-N,N-diisopropyltryptramine chloride or 4-methylcarbonato-DiPT chloride), crystalline 4-methylcarbonato-DiPT chloride, [2-(1H-indol-3-yl)ethyl](propan-2-yl)amine (N-isopropyltryptamine or NiPT), crystalline NiPT, N-[2-(1H-indol-3-yl)ethyl]propan-2-amine hydrobromide (N-isopropyltryptamine hydrobromide or NiPT hydrobromide), crystalline NiPT hydrobromide, N-[2-(1H-indol-3-yl)ethyl]cyclohexanamine (N-cyclohexyltryptamine), crystalline N-cyclohexyltryptamine, 2-(1H-in-dol-3-yl)ethanamine (tryptamine), crystalline tryptamine, N-[2-(1H-indol-3-yl)ethyl]cyclohexanamine hydrobromide (N-cyclohexyltryptamine hydrobromide), crystalline N-cyclohexyltryptamine hydrobromide, and specific crystalline forms thereof, including crystalline form 1 of 4-methylcarbonrato-DiPT chloride, crystalline form 1 of NiPT, crystalline form 1 of NiPT hydrobromide, crystalline form 1 of N-cyclohexyltryptamine, crystalline form 1 of tryptamine, and crystalline form 1 of N-cyclohexyltryptamine hydrobromide, to compositions containing the same, and to methods of treatment using them.

The invention discloses a method for preparing pyridine hydrobromide using pyridine hydrochloride mother liquor, belongs to the technical field of pyridine hydrochloride, and is characterized in that it comprises the following steps: adding purified water to pyridine hydrochloride mother liquor, stirring and standing the mixed solution to be layered, and obtaining a lower layer solution; adding calcium hydroxide solution to the lower layer solution, adjusting the pH to neutral, and adding a phase transfer aid to saturation, stirring and standing the mixed solution to be layered, and obtaining an upper layer of recovered pyridine solution; passing hydrogen bromide gas into the recovered pyridine solution, and collecting the reaction solution; the reaction solution is decolorized, concentrated, cooled, crystallized and dried to obtain pyridine hydrobromide. The beneficial effects of the invention are: the mother liquor produced in the production process of pyridine hydrochloride, creatively introduces a phase transfer aid as calcium chloride, and the overall recovery rate of pyridine is increased from 50% to 90%.

The invention belongs to the technical field of medicine synthesis processes, and particularly relates to a preparation method of high-yield and high-purity buspirone hydrochloride. According to the method, 8-(2-pyrimidinyl)-8-aza-5-5-azonium spiro [4.5] decane hydrobromide (pyrimidino piperazine quaternary ammonium salt for short) and 3, 3-tetramethylene glutarimide are taken as raw materials, a mixed solvent of methylbenzene and n-amyl alcohol and / or n-hexanol is taken as a solvent, buspirone can be generated in the presence of sodium carbonate without adding a phase transfer catalyst, and buspirone can be obtained through acid adjustment and extraction. After toluene reverse phase impurity removal, a water phase is adjusted to be alkaline, an ethanol solution of hydrogen chloride is added after toluene extraction, and buspirone hydrochloride solid is directly separated out. The preparation process has a very good cleaning effect on impurities, and the obtained buspirone hydrochloride is high in purity, high in process yield, good in atom economy and low in output of three wastes.

The invention provides various salt forms of deuterated dextromethorphan as shown in a formula (I) as well as a preparation method and application of the various salt forms. The various salt forms comprise tartrate, citrate, hydrobromide and benzoate. Also provided are various crystal forms of the above salts. The salt has excellent effects in the aspects of stability, biological activity, bioavailability, drug effect and the like, and is suitable for development of pharmaceutical preparations.

The present invention provides a salt of a triazine compound which has an inhibitory action against aldosterone synthase and is useful as a drug, and especially as a drug for preventing or treating primary aldosteronism and the like, a crystal thereof, and a method for producing the same. Specifically, the present invention provides a pharmaceutically acceptable salt of 3-[4-[[trans-4-(acetamino)cyclohexyl]carbamoylmethyl]piperazin-1-yl]-5-(p-tolyl)-1,2,4-triazine, wherein the salt is hydrobromide, sulfate, succinate, or tosylate, and the like.

The application provides a preparation method of low-impurity vonerogefumate. The application provides a method for removing impurities A-E in the preparation of vonerogefumate, wherein vonerogefumate is reacted with hydrobromic acid to obtain vonerogefumate hydrobromide, and the method specifically comprises the following steps: (1) dissolving vonerogefumate and hydrobromic acid in a solvent; (2) cooling or directly precipitating a solid; and (3) separating to obtain vonerogefumate hydrobromide. The method can remove impurities A-E which are difficult to remove by a recrystallization refining method, and the method has good selectivity for impurities A-E. The application provides an impurity D, a preparation method thereof and application of the impurity D as an impurity control sample of vonerogefumate.

The invention provides a composition containing picocetinib hydrobromide and a preparation method thereof, the composition is a tablet, the active component picocetinib hydrobromide and a hydrophilic gel framework material (e.g., hydroxypropyl methylcellulose, polyoxyethylene resin or hydroxypropyl methyl cellulose acetate succinate) form a solid dispersion, and the solid dispersion is prepared into the composition containing the picocetinib hydrobromide and the hydrophilic gel framework material (e.g., hydroxypropyl methylcellulose, polyoxyethylene resin or hydroxypropyl methyl cellulose acetate succinate). The solubility of the medicine is improved, and stable release in vivo is realized; according to the present invention, with the addition of the pH value adjusting agent, the solubility of the picetinib hydrobromide can be maintained without limitation in the neutral pH region, the stability is good, and the stable release in the body is achieved so as to achieve the rheumatic arthritis treatment effect, improve the patient comfort and the treatment compliance, reduce the administration frequency and the medical cost, reduce the side effect, and provide the clinical application prospect. The whole preparation method is simple and suitable for industrial production.

The invention discloses a pyridylamino bifunctional polyion liquid catalyst as well as a preparation method and application thereof. The preparation method comprises the following steps: taking brominated 1-(3-propylamine hydrobromide)-3-vinyl imidazole ionic liquid [PAVIm] Br. HBr and brominated 1-pyridyl-2-vinyl imidazole ionic liquid [PDVIM] Br as comonomers, adding a cross-linking agent and an initiator, and copolymerizing to synthesize a polyionic liquid catalyst I; the pyridylamino bifunctional polyion liquid catalyst provided by the invention has a developed porous structure and abundant ionic groups (carbonate ions and bicarbonate ions), shows relatively high CO2 adsorption performance, can catalyze one-pot synthesis of chain carbonate from CO2, an epoxy compound and methanol under the condition of no solvent and cocatalyst, and has the advantages of simple preparation process and low cost. And efficient utilization of CO2 is realized.

The invention discloses an analysis method for determining halogenated alkane impurities in tigliptin hydrobromide, and relates to the technical field of quality analysis. In order to solve the problem of detection of halogenated alkane impurities in tigliptin hydrobromide, the invention provides a convenient, efficient and accurate detection method. The method comprises the following steps: preparing a test solution and an impurity reference solution, and detecting by adopting a gas chromatographic method; the method can be used for accurately determining the content of halogenated alkane in tigliptin hydrobromide, plays a guiding role in development of a synthesis process, and contributes to establishment of quality standards of tigliptin hydrobromide bulk drugs.

Provided herein is N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl (tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4′-(morpholinomethyl)-[1,1′-biphenyl]-3-carboxamide hydrobromide. Also provided herein is a particular polymorph form of this compound.

The invention provides an X-ray luminescent crystal material containing heavy atoms as well as a preparation method and application thereof, and belongs to the technical field of luminescent materials. The chemical formula of the X-ray luminescent crystal material is 2XL at-AMnBr4, 2XL represents dihalogen substituted p-phenylenediamine hydrobromide, halogen atoms are one or two of Cl, Br and I, and A represents crown ether. According to the invention, heavy atoms are introduced into the organic cation module of the organic-inorganic hybrid metal halide through the multistage supramolecular self-assembly effect for the first time, the luminescence property and stability of the X-ray luminescent material are improved, and the luminescent quantum yield reaches 60% or more. The X-ray luminescent material provided by the invention is used as a scintillator of a core component, can efficiently convert X-rays into visible light signals, and provides more accurate and rapid analysis and detection for multiple fields such as safety inspection, scientific research, medical diagnosis and the like.

The invention provides a crystal form of a compound HIF-117 salt as well as a preparation method and application of the crystal form, and the crystal form is any one or more of the following crystal forms: a hydrochloride crystal form A, a sulfate crystal form B, a 1, 2-ethanedisulfonate crystal form C1, 1, 2-ethanedisulfonate crystal form C2, 1, 2-ethanedisulfonate crystal form C3 and 1, 2-ethanedisulfonate crystal form C4. The crystal form 1, 2-ethanedisulfonate crystal form C2, p-toluenesulfonate crystal form D, mesylate crystal form E1, mesylate crystal form E2, hydrobromide crystal form F1, hydrobromide crystal form F2, sodium salt crystal form G, sylvite crystal form H1, sylvite crystal form H2, calcium salt crystal form I, magnesium salt crystal form J, choline salt crystal form K, lysine salt crystal form L, ammonium salt crystal form M, meglumine salt crystal form N, betaine salt crystal form O1, betaine salt crystal form O2 and diethylamine salt crystal form P1, the invention relates to a diethylamine salt crystal form P1, a diethylamine salt crystal form P2, a diethylamine salt crystal form P3, a diethylamine salt crystal form P4, a diethylamine salt crystal form P5, a tromethamine salt crystal form Q1, a tromethamine salt crystal form Q2 and a tromethamine salt crystal form Q3. The compound has good stability, and has important value for development and production of medicines and preparations.

The invention relates to a polymorphic form of hydrobromide or hydrochloride of 5-(6-(4-(cyclopropylmethyl) piperazine-1-yl)-2-methylpyridine-3-yl)-N-((4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl) methyl)-3-(N-ethylcyclopropanecarboxamide)-2-methylbenzamide, a pharmaceutical composition of the polymorphic form and application of the polymorphic form and the pharmaceutical composition of the hydrobromide or hydrochloride of the 5-(6-(4-(cyclopropylmethyl) piperazine-1-yl)-2-methylpyridine-3-yl)-N-(4, 6-dimethyl-2-oxo-1, 2-dihydropyridine-3-yl)-3-(N-ethylcyclopropanecarboxamide.

This application discloses an analytical method for N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, belonging to the field of pharmaceutical impurity analysis. The method employs high-performance liquid chromatography (HPLC), with the following chromatographic conditions: a 4.6 mm × 250 mm column packed with octadecylsilane-bonded silica gel, with a particle size of 5 μm; mobile phase A is a 90:10 water-acetonitrile mixture containing 0.025%–0.035% trifluoroacetic acid (v / v); mobile phase B is acetonitrile; gradient elution; column temperature 38–42 °C; flow rate 0.9–1.1 ml / min; injection volume 50 μl; and detection wavelength 226 nm. This analytical method effectively eliminates excipient interference and exhibits excellent detection performance (specificity, sensitivity, linearity, precision, accuracy, and robustness), accurately detecting the content of N-nitrosamine vortioxetine in vortioxetine hydrobromide tablets, meeting quality control requirements.

The invention discloses a preparation method of hydrobromic acid vortioxetine, and belongs to the technical field of organic synthesis. The method comprises the following steps: by taking o-aminothiophenol and Boc2O as initial raw materials, carrying out amino protection to obtain an intermediate 1; reacting the intermediate 1 with 2, 4-dimethyl bromobenzene under an alkaline condition to form a thioether bond, and acidifying to obtain an intermediate 2; carrying out high-temperature cyclization on the intermediate 2 and bis (2-bromoethyl) amine hydrobromide in mesitylene, so as to obtain a crude product of the hydrobromic acid vortioxetine; and recrystallizing the crude product with 95% ethanol to obtain a high-purity final product. The route is simple, only three-step reaction is needed, a noble metal catalyst is not needed in the whole process, and the problem of metal residues is fundamentally avoided; the selected raw materials are easy to obtain, the reaction condition is mild, the operation is simple and convenient, the process is stable, the total yield is good, the product purity is as high as 99.9%, and the method is suitable for large-scale production.

The present invention relates to polymorphs of the hydrobromide salt of 5-{2-[({8-[(2,6-dimethylbenzyl)amino]-2,3-dimethylimidazo[1,2-a]pyridin-6-yl}carbonyl)-amino]ethoxy}-5-oxopentanoic acid (linaprazangrate), more specifically Form A, Form B, and Form C of the HBr salt of linaprazangrate. The present invention also relates to pharmaceutical compositions containing such polymorphs and to the use of these polymorphs in the treatment or prevention of gastrointestinal inflammatory or gastric acid-related diseases, particularly erosive gastroesophageal reflux disease (eGERD).

The present invention relates to polymorphs of the hydrobromate of 5-{2-[({8-[(2, 6-dimethylbenzyl) amino]-2, 3-dimethylimidazo [1, 2-a] pyridin-6-yl} carbonyl)-amino] ethoxy}-5-oxovaleric acid (linaraben glutarate), and more particularly to Form A, Form B and Form C of the HBr salt of linaraben glutarate. The present invention also relates to pharmaceutical compositions comprising the polymorphs, and to the use of these polymorphs in the treatment or prevention of gastroenteritis diseases or gastric acid related diseases, in particular erosive gastroesophageal reflux disease (eGERD).

The invention relates to guanidine-containing hydrobromide electrolyte for a high-energy-density zinc-bromine-iodine battery as well as a preparation method and application of the guanidine-containing hydrobromide electrolyte, and belongs to the technical field of aqueous zinc-bromine-iodine batteries. The guanidine hydrobromide-containing electrolyte for the high-energy-density zinc-bromine-iodine battery comprises guanidine hydrobromide, zinc salt and deionized water. According to the guanidine-containing hydrobromide electrolyte for the high-energy-density zinc-bromine-iodine battery, provided by the invention, redox of iodine valence state I-I0I < + > and redox of bromine valence state BrBr0 can be realized at the same time, and six-electron transfer of halogen compounds in the zinc-bromine-iodine battery is realized. On one hand, the energy density of the battery is increased to 3-4 times of the initial value, and on the other hand, the zinc-bromine-iodine battery containing the zinc-bromine-iodine battery has the advantages of being easy to manufacture and easy to industrially popularize.

The present invention provides a pharmaceutically acceptable salt and crystal form of a KIF18A inhibitor, and a preparation method therefor and a use thereof. The pharmaceutically acceptable salt is selected from one or more of a sodium salt, a potassium salt, a hydrochloride, a p-toluenesulfonate, a maleate, a methanesulfonate, an ethanesulfonate, and a hydrobromide of a compound represented by formula (I). The present invention provides the pharmaceutically acceptable salt of the compound represented by formula (I) and a crystal of the salt, which exhibit excellent hygroscopicity, solubility, and / or stability, and are suitable for pharmaceutical use.

The present invention relates to a process for the industrial-scale production of 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol hemifumarate, a salt consisting of two molecules of 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol and one molecule of fumaric acid, and having the following formula: 5-{2-[benzyl-(1-(4-hydroxyphenyl)-1-methylethyl)amino]-1-hydroxyethyl}benzene-1,3-diol hemifumarate is a useful intermediate in the synthesis of 5-[(1RS)-2-[(1RS)-2-(4-hydroxyphenyl)-1-methylethyl]-amino-1-hydroxyethyl]benzene-1,3-diol hydrobromide, which is used in the pharmaceutical field under the is known by the common name fenoterol hydrobromide.

Novel crystalline forms of Nirogacestat dihydrobromide and preparation methods thereof, pharmaceutical compositions containing the crystalline forms, and uses of the crystalline forms for preparing γ-secretase inhibitor drugs and drugs for treating desmoid tumors.

The preparation method comprises the following specific steps: firstly, taking copper bromide and 1-butyl-3-methylimidazole hydrobromide as raw materials, and reacting to prepare a copper complex ionic liquid; ultrasonically dispersing cerium nitrate and lanthanum-doped lithium titanate into the copper complexing ionic liquid to obtain ionic liquid mixed liquid; stirring and heating tetraethoxysilane to 130-150 DEG C, continuously adding the ionic liquid mixed solution, uniformly stirring and mixing, immediately adding tetrabutyl titanate, concentrated hydrochloric acid, deionized water and methanol, carrying out heat-preservation stirring for 30-40 minutes under the condition of a pulsed magnetic field, finally, carrying out heat-preservation standing for 8-10 hours, and carrying out post-treatment, so as to obtain the ionic liquid. The composite denitration agent disclosed by the invention can be used for flue gas treatment of the lime rotary kiln, can realize a relatively good denitration effect under the condition of low temperature (100-120 DEG C), and has a good popularization prospect.