163 results about "Methylpyridinium" patented technology

Provided herein is a process for preparing compound A comprising (a) admixing 2-isopropyl-4-methylpyridin-3-amine (Compound B), or a salt thereof, a first base, and a reactive compound comprising phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanato-2-isopropyl-4-methylpyridine (Compound C); (b) admixing Compound C and 2,6-dichloro-5-fluoronicotinamide (Compound D) to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridin-3-yl)carbamoyl)nicotinamide (Compound E); and (c) admixing Compound E and a second base to form a product mixture comprising Compound A and the second base. Also provided herein is a process for synthesizing AMG 510 comprising using Compound A prepared according to the disclosed processes

The invention relates to the technical field of organic synthesis, in particular to 4-chloro-1-methyl-6H-heterochromene [3, 4-c] pyridine as well as a synthesis method and application of the 4-chloro-1-methyl-6H-heterochromene [3, 4-c] pyridine. The synthesis method comprises the following steps: (1) synthesizing 2-chloro-3-fluoro-4-iodine-5-methylpyridine from 2-chloro-3-fluoro-5-methylpyridine and an iodine elementary substance to obtain 2-chloro-3-fluoro-4-iodine-5-methylpyridine; (2) synthesizing 2-(2-chloro-3-fluoro-5-methylpyridine-4-yl) benzaldehyde from the 2-chloro-3-fluoro-4-iodo-5-methylpyridine, the 1, 1-bis (diphenylphosphine) ferrocene palladium dichloride, the tripotassium phosphate and the (2-formyl phenyl) boric acid, and further synthesizing the 2-(2-chloro-3-fluoro-5-methylpyridine-4-yl) benzaldehyde from the 2-chloro-3-fluoro-4-iodo-5-methylpyridine and the 1, 1-bis (diphenylphosphine) ferrocene palladium dichloride. And (3) synthesizing the 4-chloro-1-methyl-6H-heterochromene [3, 4-c] pyridine by using the 2-(2-chloro-3-fluoro-5-methylpyridine-4-yl) benzaldehyde and sodium tert-butoxide. The 4-chloro-1-methyl-6H-heterochromene [3, 4-c] pyridine compound constructed by the invention can be used for detecting the content of pesticide residue glyphosate.

The invention relates to the technical field of nicotinic acid synthesis, and particularly discloses an efficient nicotinic acid synthesis method based on step-by-step feeding dynamic control, which comprises the following specific steps: step 1, uniformly dividing potassium permanganate into 3 parts, adding the potassium permanganate into an aqueous solution containing 3-methylpyridine every 15 + / -5 minutes, and supplementing 5-8mL of water after each addition; 2, reacting at 70-90 DEG C for 2-4 hours, and filtering while the solution is hot; 3, adding sodium dithionite into the filtrate, wherein the mass of the sodium dithionite is 0.4-0.6 time that of the potassium permanganate; and 4, concentrating the filtrate to 30-50% of the original volume, adjusting the pH value to 3.0-3.5 with acid, and crystallizing to obtain the nicotinic acid. The method has the following effects: the yield is up to 89.52% at most; the cost is reduced: the consumption of hydrochloric acid is reduced by 77%, and the consumption of potassium permanganate is optimized by 16.7%; the efficiency is improved; the reaction time is shortened by 50%; the large fluctuation of the reaction temperature is controlled through step-by-step feeding, the problem that the reaction liquid which is not completely reacted is too alkaline is solved by filtering and adding sodium dithionite, and the false yield is eliminated through the purification and concentration step while the yield is further improved.

The present invention relates to the use of cationic porphyrins such as zinc tetra(N-methylpyridyl)porphyrin tetrachloride and tetra(N-methylpyridyl)porphyrin tetrachloride or a mixture thereof, as selective foliar herbicidal agent.

This invention discloses a method for synthesizing 4-methylpyridine using a Pd / LDH catalyst, belonging to the field of organic chemical synthesis technology. The method includes the following steps: S1, preparing the Pd / LDH catalyst: mixing an aqueous PdCl2 solution with a Mg-Al type LDH support, impregnating at room temperature, drying, and then reducing to obtain the Pd / LDH catalyst; S2, under an inert atmosphere, adding 4-methylpiperidine, the Pd / LDH catalyst, and a low-toxicity solvent to a reaction vessel, stirring the reaction, and then separating and purifying to obtain 4-methylpyridine. This invention, through the combination of a supported Pd / LDH catalyst and a low-toxicity solvent, achieves comprehensive improvements in catalytic efficiency, environmental friendliness, ease of operation, and economy, representing a promising green synthesis route; the reaction conditions are mild, the operation is simple, and the catalyst can be recycled more than 5 times, making it suitable for industrial production.

The invention is applicable to the technical field of non-porous self-adaptive crystals, and provides an application of a non-porous self-adaptive crystal in adsorption and release of 3-methylpyridine, and the non-porous self-adaptive crystal is methyl tetrafluoro column five Me4FP5. The nonporous self-adaptive crystal methyl tetrafluoro column 5 Me4FP5 prepared by the method is applied to the field of 3-MP, controllable release of 3-MP can be realized only by adding an exogenous competitive object, and the released material can also be used for multiple non-thermal stimulation adsorption-release cycles of 3-MP.

The invention discloses a method for preparing 6-fluoronicotinic acid based on a heterogeneous catalytic system, which comprises the following steps: sequentially adding 2-fluoro-5-methylpyridine and a heterogeneous catalyst into a reaction kettle, and uniformly stirring and mixing; continuously introducing oxygen into the reaction kettle, heating to carry out oxidation reaction, monitoring the reaction by HPLC (High Performance Liquid Chromatography) and TCL until the conversion rate of 2-fluoro-5-methylpyridine in a reaction system is greater than or equal to 95%, then cooling to room temperature, filtering reaction liquid, washing a filter cake, drying and recovering the catalyst; after deionized water is added into the filtrate for dilution, a hydrochloric acid solution is added into the reaction system to adjust the pH value, then standing and precipitating are conducted, finally filtering is conducted, and a filter cake is dried to obtain 6-fluoronicotinic acid; the heterogeneous catalyst is a Zr-MOF (Metal Organic Framework) material loaded with TEMPO (Tetramethylpiperidine Oxide)-Cu. According to the method, 2-fluoro-5-methylpyridine is used as a raw material and a reaction medium at the same time, oxygen is used as an oxidizing agent, the 6-fluoronicotinic acid is efficiently synthesized under the catalysis of the heterogeneous catalyst, and the method is low in cost, high in product purity and yield and environmentally friendly.

This application relates to processes and intermediates for the preparation of the PD-1 / PD-L1 inhibitor (R)-1-((7-cyano-2-(3′-((2-(difluoromethyl)-7-((3-hydroxypyrrolidin-1-yl)methyl)pyrido[3,2-d]pyrimidin-4-yl)amino)-2,2′-dimethyl-[1,1′-biphenyl]-3-yl)benzo[d]oxazol-5-yl)methyl)piperidine-4-carboxylic acid, and salts and crystalline forms thereof, where the PD-1 / PD-L1 inhibitor and solid forms and salt forms thereof are useful in the treatment of various diseases including infectious diseases and cancer.

A pharmaceutical composition comprising Compound 1, (3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid), and at least one excipient selected from: a filler, a disintegrant, a surfactant, a binder, and a lubricant, the composition being suitable for oral administration to a patient in need thereof to treat a CFTR mediated disease such as Cystic Fibrosis. Processes of preparing pharmaceutical compositions comprising Compound 1 are also disclosed.

The invention relates to the technical field of organic synthesis, and particularly discloses a synthesis method of 4, 4 '-methylene bis (N-cyclohexylcyclohexane-1-amine). The method comprises the following steps: mixing cyclohexanone and 2-methylpyridine borane, and heating to a reaction temperature; the preparation method comprises the following steps: reacting 4, 4 '-diaminodicyclohexylmethane with heat preservation, after the reaction is finished, cooling to room temperature, mixing a reaction solution with diluted hydrochloric acid, adding an organic solvent for extraction, collecting a water phase, then adjusting the pH value of the water phase to 8-9, adding an organic solvent for extraction, collecting an organic phase, drying and concentrating to obtain the 4, 4'-methylene bis (N-cyclohexylcyclohexane-1-amine). The synthesis method provided by the invention has the advantages of simple process, no need of high temperature and high pressure, mild and controllable reaction conditions, no influence of water in a reaction system, high conversion rate and good selectivity, conforms to the concept of green and safe production, and has a good development prospect.

The invention discloses an azide modified platinum radiotherapy sensitizer as well as a preparation method and application thereof. The azide modified platinum radiotherapy sensitizer is an azide modified platinum complex, comprises a cis platinum complex and a trans platinum complex, and is characterized in that the structure of the azide modified platinum radiotherapy sensitizer is shown in the specification; in the formula I, R1 is cyclohexylamine or 2-methylpyridine; in the formula II, R2 is ammonia molecules or pyridine. The azide modified platinum radiotherapy sensitizer can generate a platinum-nitrogen-bin free radical under the irradiation of X rays, and by utilizing a nitrogen transfer reaction in organic chemistry, the platinum-nitrogen-bin free radical generated after the compound is irradiated by rays can be covalently coupled with some DNA (Deoxyribose Nucleic Acid) or protein, so that the sensitivity of the radiotherapy sensitizer is improved. The radiotherapy sensitization effect in tumor radiotherapy is achieved by directly damaging DNA and hindering DNA repair.

The present invention relates to: a tablet comprising 6-((5-methyl-3-(6-methylpyridin-3-yl) isoxazol-4-yl) methoxyl)-N-(tetrahydropyran-4-yl) pyridazine-3-carboxamide; and a pharmaceutical composition comprising the tablet. A process for the preparation of the tablet; a cartridge containing the tablet; and the use of the tablet in medical treatment.

The application relates to the technical field of chemical synthesis, and particularly discloses a production method of 2-amino-5-methylpyridine. The production method obtains 2-amino-5-methylpyridine with high yield and high selectivity through (1) an amination reaction and (2) post-treatment, and has the advantages of short cycle, high equipment utilization, large batch yield, low total production cost, less waste and the like.

The present invention belongs to the technical field of biological catalysis and organic synthesis, and in particular, relates to an imine reductase mutant, application thereof and an application method therefor. The imine reductase mutant has an amino acid sequence derived by a mutation occurring to an amino acid sequence as set forth in SEQ ID NO. 1, and an mutation site includes one of the following sites: position 44 with G mutating into V, or position 89 with L mutating into V, or positions 44 and 89 with G and L simultaneously mutating into V, respectively. The imine reductase mutant of the present invention binds to glucose dehydrogenase to prepare an intermediate (S)-2-methyl-5-(pyrrol-2-yl)pyridine through asymmetric hydrogenation reduction by taking β-nicotinamide adenine dinucleotide disodium salt as a coenzyme and 5-(3,4-dihydro-2H-pyrrol-5-yl)-2-methylpyridine as a substrate, with a chemical conversion rate up to above 99.5% and e.e. % up to 99.6%.

The present invention discloses a pinanyl fluorescent probe for detecting the organophosphorus pesticide methyl parathion based on an enzyme inhibition mechanism, as well as its preparation method and application. The fluorescent probe is: 4-(2-(4-(cyclopropylformyloxy-4′-(6,6-dimethyl-2-(4-nitrophenyl)-4,5,6,7-tetrahydro-2H-5,7-methyleneindazole-3-yl)-[1,1′-biphenyl]-3-yl)vinyl)-1-methylpyridinium iodide (abbreviated as: THIP-OCP). The compound can undergo enzymatic hydrolysis reaction with butyrylcholinesterase and, under irradiation with ultraviolet light at a wavelength of 365nm, The solution's fluorescence color changes from colorless to orange-yellow. Since methyl parathion effectively inhibits butyrylcholinesterase activity, when methyl parathion is added to the solution, the solution's fluorescence gradually changes from orange-yellow to colorless under ultraviolet irradiation at a wavelength of 365 nm. Therefore, this compound can be used as a fluorescent probe for detecting methyl parathion. This compound has many advantages, including a low detection limit (0.79 μg / mL) and a wide pH range (5-10), and has great application prospects.

The application discloses a new method for preparing a lumacaftor intermediate. The method uses 5-bromo-6-chloropyridin-2-amine as a starting material, methyl boronic acid, palladium acetate and a ligand L1 to obtain a methylation product. Then, the methylation product is subjected to a Suzuki coupling reaction with m-tert-butoxycarbonyl phenyl boronic acid under the catalysis of tris(dibenzylideneacetone)dipalladium and a ligand L2 to synthesize 3-(6-amino-3-methylpyridin-2-yl)benzoic acid tert-butyl ester. The method can synthesize 3-(6-amino-3-methylpyridin-2-yl)benzoic acid tert-butyl ester at a high yield, and the method uses a small amount of catalyst, has mild reaction conditions and is easy to separate, so that the method is beneficial to industrial implementation and application promotion.

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.

The present invention relates to a method for efficiently producing a compound derived from the commercially available and readily available 3-((3S)-7-bromo-2-((2-hydroxypropyl)amino)-5-(pyridin-2-yl)-3H-benzo[e][1,4]diazepine-3-yl)propionate methyl ester, namely, the compound 3-[(4S)-8-bromo-1-methyl-6-(2-pyridinyl)-4H-imidazo[1,2-a][1,4]benzodiazepine-4-yl]propionate methyl ester benzenesulfonate (remimazolam besylate).

The application discloses a preparation method of a catalyst for synthesizing pyridine from 3-methylpyridine and relates to the technical field of catalysts. The catalyst comprises the following steps: ZSM-5 is used as a carrier, V2O5, CoO and Ag are used as active components, molecular sieve ZSM-5, citric acid, ammonium metavanadate, cobalt nitrate, silver nitrate and deionized water are mixed, and then are filtered, dried and calcined to obtain a supported high-efficiency catalyst; the catalyst is filled in a fixed bed, 50% 3-methylpyridine is used as raw material, and a demethylation reaction is carried out under the action of high temperature, the catalyst and air to produce pyridine. The catalyst used in the application does not need to be frequently activated, the activation frequency is low, the catalyst stability is good, the catalyst is not prone to deactivation, can continue to operate stably after activation, catalyst loss is greatly reduced, 3-methylpyridine can be efficiently converted into pyridine by using the prepared catalyst, and the dilemma of waste caused by small demand for 3-methylpyridine in the market is solved.

The invention relates to the field of organic synthesis, in particular to a method for continuously preparing 5-(trifluoromethyl)-1H-tetrazole sodium salt. The method comprises the following steps: mixing trifluoroacetamide and 3-methylpyridine to obtain a mixture I; phosphorus oxychloride and 3-methylpyridine are mixed, and a second mixture is obtained; a continuous feeding mode is adopted, the first mixture and the second mixture are mixed, a steady-state reaction is maintained, and reaction liquid is continuously obtained; performing gas-liquid separation on the reaction liquid to obtain liquid and gas, quenching the liquid, performing gas washing on the gas through 3-methylpyridine, then introducing the gas into a mixed solution of sodium azide and acetone for absorption and filtration to obtain a filter cake, and performing drip washing to obtain the 5-(trifluoromethyl)-1H-tetrazole sodium salt. The purity of the product prepared by the method is greater than or equal to 99.3%, the yield is 84-91%, and the method is easy for industrial production.

The invention discloses a photo-induced self-sacrifice stripping photocatalyst and a preparation method and application thereof, and belongs to the technical field of catalysts.The preparation method of the photocatalyst comprises the following steps that 2, 4, 6-trimethylpyridine and alkyl halide are placed in a first solvent for a reaction, and a monomer ETMP-X is obtained; x is any one of Cl, Br and I; and in an inert atmosphere, putting the monomer ETMP-X, TAPB and a base catalyst into a second solvent, and heating to 100-150 DEG C for reaction to obtain the photocatalyst. The prepared photocatalyst is an ionic covalent organic framework material and has high crystallinity and long-range orderliness, the particle size and thickness of the material can be remarkably reduced by conducting photoinduced self-sacrifice stripping on the photocatalyst, and the stripping process of the material is successfully achieved; in addition, the stripped material is applied to the field of photocatalytic hydrogen peroxide production and is coupled with aerobic oxidation of the benzyl alcohol compound, so that ultrahigh hydrogen peroxide generation rate and higher conversion selectivity of the benzyl alcohol compound are realized.

The invention relates to the technical field of high polymer materials, and particularly discloses a chemical method PI preparation method for a graphite heat-conducting film and application of the chemical method PI preparation method, and the chemical method PI preparation method comprises the following steps: adding an inorganic filler into a first solvent to obtain a filler dispersion liquid; adding a diamine monomer, a dianhydride monomer and the inorganic filler dispersion liquid into a first solvent, and carrying out condensation polymerization to obtain PAA resin; and defoaming the resin, adding a dehydrating agent and a catalyst, carrying out continuous coating, segmented drying and two-way stretching, and carrying out chemical imidization to obtain the polyimide film. According to the invention, the molecular linearity and ductility of the film are ensured by controlling the adding proportion and the block mode of the rigid monomer and the flexible monomer; 3-methylpyridine with a low boiling point is adopted as a catalyst, and a dehydrating agent AA and resin are added according to the ratio, so that the stable production of the ultra-thick PI film is ensured, and the thickness, molecular orientation and dry film quality stability control of the PI film is realized by adopting temperature zone setting of a film forming section and stretching ratio and tension adjustment of a stretching section.

The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of terminal alkyne. The method comprises the following steps: mixing a 2-methylpyridine compound as shown in a formula 1 and N, N-dimethylformamide as shown in a formula 2 with an organic solvent (cyclopentyl methyl ether or tetrahydrofuran) in the presence of lithium bis (trimethylsilyl) amide, cesium fluoride, perfluorobutyl sulfonyl fluoride and 1, 8-diazabicyclo [5.4. 0] undec-7-ene, and reacting to synthesize the terminal alkyne as shown in a formula 3. The raw materials adopted by the invention are common chemicals in the market. The method is wide in application range, common terminal alkyne compounds can be synthesized, reaction substrates can be adjusted according to needs, and a series of terminal alkyne derivatives can be synthesized. Certain support is provided for research in the fields of medicine, material science and the like. The invention provides biological activity of an iso-terminal alkyne compound on oomycetes plant pathogens and a determination method of the iso-terminal alkyne compound.

This invention discloses a continuous catalytic synthesis system for highly selective 4-methylpyridine and its application method, belonging to the field of chemical production technology. The system includes a raw material pretreatment and plasma activation unit, a microchannel catalytic reaction unit, an online analysis unit, a control unit, and a product separation and recycling unit. The method uses pyridine and methanol as raw materials. After plasma activation pretreatment, the raw materials enter a microchannel reactor packed with a Co-La / ZSM-5 catalyst for reaction, and the reaction conditions are controlled by online analysis feedback. This invention achieves highly selective and high-yield synthesis of 4-methylpyridine at 300-370℃ through the synergistic effect of plasma activation for directional regulation of raw material activity, microreactor-enhanced mass and heat transfer, and shape-selective 4-methylation catalysis by a specific bimetallic catalyst. Simultaneously, it extends catalyst lifetime and solves the technical problems of low selectivity, numerous side reactions, and easy catalyst deactivation in traditional processes.

The application provides a preparation method of 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride, which comprises the following steps: S1: 2-acetyl-3-chloro-5-trifluoromethylpyridine is reacted with hydroxylamine and p-toluenesulfonyl chloride under alkaline conditions in a solution to obtain 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino p-toluenesulfonate; S2: 1-(3-chloro-5-(trifluoromethyl)pyridin-2-yl)ethylamino p-toluenesulfonate is reacted under alkaline conditions at low temperature in a solution to obtain 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethanone; S3: 2-amino-1-(3-chloro-5-trifluoromethylpyridin-2-yl)ethanone is reduced by a reducing agent under the action of a catalyst in a solution, and finally salification is carried out to obtain 2-aminoethyl-3-chloro-5-trifluoromethylpyridine hydrochloride. The application has the beneficial effects that the total yield of three steps is 82%, the product purity is greater than 99%, the solvent can be recycled and reused, the reaction route is short, the reaction yield is high, the product purity is high, no special process is needed, and the application can be popularized in industry.

This invention provides a process for preparing compound A, which is used to synthesize a KRAS inhibitor. [Solution] A process for preparing compound A as shown below is provided, comprising: (a) mixing a reactive compound containing 2-isopropyl-4-methylpyridine-3-amine or a salt thereof, a first base, and phosgene or a phosgene equivalent in an organic solvent to form 3-isocyanate-2-isopropyl-4-methylpyridine (compound C); (b) mixing compound C and 2,6-dichloro-5-fluoronicotinamide to form 2,6-dichloro-5-fluoro-N-((2-isopropyl-4-methylpyridine-3-yl)carbamoyl)nicotinamide (compound E); and (c) mixing compound E and a second base to form a product mixture containing compound A and the second base. A process for synthesizing AMG 510 using compound A is also provided. JPEG2026071310000032.jpg35150

The application provides a supercritical extraction process of 2-cyanopyridine, and the specific process steps comprise ammonia oxidation of 2-methylpyridine, supercritical extraction, and separation and purification. The extraction process can effectively solve the problems of general separation efficiency, poor product quality, and low yield in the current mainstream 2-cyanopyridine preparation process. The extraction process of the application avoids the use of sulfuric acid, and the production process is more environmentally friendly. The hydrolysis of 2-cyanopyridine is inhibited, the product yield is improved, the yield of 2-cyanopyridine reaches 88%, only a small amount of solvent material is left in the supercritical extraction extract, and the product quality is higher. The supercritical extraction achieves the purpose of extraction by changing the pressure and temperature, and the process is simple and the extraction speed is fast.

The invention discloses a 2-(imidazo [1, 5-a] pyridine-1-yl)-1-methylpyridine-1-onium compound as well as a preparation method and an antibacterial and mildew-proof application thereof. The structural formula of the 2-(imidazo [1, 5-a] pyridine-1-yl)-1-methylpyridine-1-onium compound is shown as a formula (II), and the 2-(imidazo [1, 5-a] pyridine-1-yl)-1-methylpyridine-1-onium compound is easy to synthesize, shows good antibacterial and mildew-proof activity, has good antibacterial activity on staphylococcus aureus, escherichia coli, candida albicans and aspergillus fumigatus, serves as a novel antibacterial and mildew-proof agent, and has good application prospects. The method has great application value in the technical field of antibiosis. Formula (II)