269 results about "Methylpyridinium" patented technology

Provided herein is a process comprising heating a composition comprising (P)-compound A or a salt thereof and a solvent to a temperature of 250° C. to 350° C. to form racemized compound A. Also provided is a process for isolating (P)-compound A from a composition comprising (P)-compound A and a tartrate, as described herein. Further provided herein, is a process for isolating a free acid of a tartrate or a hydrate thereof from a composition comprising a tartrate, (P)-compound A, and an organic solvent.

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

A disulfiram derivative of formula (I)wherein R1 and R2 are independently —CH2CH2COOH, —CH2CH2COOEt, optionally substituted methylenepyridyl, optionally substituted methylenefuranyl, or optionally substituted methylenethiopenyl, may be useful in aldehyde dehydrogenase 1a1 (ALDH1a1) and / or monoacylglycerol lipase (MAGL)-mediated diseases or disorders. Such derivatives may avoid or limit aldehyde dehydrogenase 2 (ALDH2) and / or fatty acid amide hydrolase (FAAH) antagonism.

The invention discloses a 2-methylpyridine ammoxidation fixed bed catalytic reactor and a catalytic reaction system, and belongs to the technical field of efficient catalysis. Comprising a tower body, a mixed gas inlet is formed in the top of the tower body, a mixed gas outlet is formed in the bottom of the tower body, a plurality of catalyst laminar flow pipes and a plurality of baffle plates are arranged in an inner cavity of the tower body, a plurality of arc-shaped jacketed pipes are horizontally arranged on the outer wall of the tower body in a surrounding mode, and one axial end of each arc-shaped jacketed pipe is a closed end; the other axial end of the arc-shaped jacketed pipe is a fused salt inlet, a plurality of communicating holes are formed in the connecting face of the outer wall of the tower body and the arc-shaped jacketed pipe, and a fused salt outlet is further formed in the outer wall of the tower body. Fused salt fluid is annularly and uniformly distributed at the fused salt inlet through the arc-shaped jacketed pipe, the flow field disturbance and bias flow phenomena caused by a traditional tangential inlet are avoided, the flowing stability of the fused salt fluid is improved, formation of a local flowing isolation area is eliminated, heat accumulation is reduced, the heat transfer uniformity is improved, and the catalytic efficiency is improved.

The invention discloses a method for synthesizing 2-vinylpyridine by a one-pot method, which comprises the following step: by taking 2-methylpyridine and paraformaldehyde as raw materials and water as a solvent, synthesizing the 2-vinylpyridine by a one-pot reaction under the catalysis of a basic catalyst. According to the invention, 2-methylpyridine and paraformaldehyde are taken as initial raw materials, the raw materials are simple and easy to obtain, the production cost is reduced, and water is taken as a solvent, so that the use of a large amount of organic solvents is avoided, and the influence on environmental pollution is small. In the reaction, a basic catalyst such as triethylamine is used as a catalyst, a small amount of sodium hydroxide solid is added in the reaction process, the basic catalyst enables the whole system to be in an alkaline environment, and sodium hydroxide improves the depolymerization efficiency of paraformaldehyde and promotes the dehydration process of the reaction, so that the selectivity and yield of 2-vinylpyridine are improved.

Methods are provided for treating or preventing colorectal cancer, related diseases, or symptoms of any of the foregoing, e.g., familial adenomatous polyposis (FAP), in subjects of 55 years or older. The methods include administering 3-[(2R)-2,3-dihydroxypropyl]-6-fluoro-5-(2-fluoro-4-iodoanilino)-8-methylpyrido[2,3-d]pyrimidine-4, 7-dione or a pharmaceutically acceptable salt thereof.

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 discloses an easily degradable modified agricultural mulching film and a preparation method thereof, and relates to the field of high polymer materials. When the easily degradable modified agricultural mulching film is prepared, oyster shell powder sequentially reacts with 3-bromopropyltrimethoxysilane, 4-methylpyridine, 5-(7-bromobenzo [C] [1, 2, 5] thiadiazole-4-yl) thiophene-2-formaldehyde and 4-(diphenylamine) phenylboronic acid pinacol ester, and functionalized oyster shell powder is prepared; and reacting urea with formaldehyde, reacting with monopotassium phosphate and chitosan, mixing with the functionalized oyster shell powder, performing injection molding, and drying to obtain the easily degradable modified agricultural mulching film. The easily-degradable modified agricultural mulching film prepared by the invention has good mechanical properties and capabilities of resisting bacteria, performing photocatalytic degradation, adjusting the pH value of soil and degrading the soil into fertilizers.

The invention discloses a method for preparing a catalyst for synthesizing 2-methylpyridine, comprising the following steps: preparing a catalyst containing Fe 3+ , Cu 2+ 、Ni2 + The three hydrochloride solutions were mixed and the HZMS‑5 molecular sieve was mixed with Fe 3+ , Cu 2+ 、Ni 2+ The invention relates to a method for preparing 2-methylpyridine by reacting acetaldehyde and ammonia as raw materials at 300°C-450°C and 0.5MPa-0.8MPa under the action of the catalyst, and the method has the advantages of simple preparation method, low cost, high-efficiency synthesis of 2-methylpyridine under mild reaction conditions, and more economical and environmentally friendly. The invention solves the problems of high raw material price, use of precious metals, dangerous reaction conditions, etc. in the prior art, has high yield of 2-methylpyridine, good selectivity and good industrial application prospect.

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 provides an acid salt of a Sigma-1 receptor agonist or a crystal form thereof, and a preparation method and application thereof. Specifically, it relates to an acid salt of 5-((2-(cyclopropylmethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)(isopropyl)amino)-1-methylpyridin-2(1H)-one having high affinity for the sigma-1 receptor and a crystal form thereof. The present invention relates to a preparation method of the acid salt and the crystal form and its application in the pharmaceutical field. The acid salt of the compound 5-((2-(cyclopropylmethyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)(isopropyl)amino)-1-methylpyridin-2(1H)-one and the crystal form thereof provided by the present invention have improved physical and chemical properties, such as appearance, hygroscopicity and chemical stability.

The invention provides a preparation method of 3-trifluoromethylpyridine, and relates to the technical field of preparation of trifluoromethylpyridine intermediates. 3-methylpyridine (3MP) and a polar aprotic solvent are mixed and then introduced into a micro-channel reactor to react with fluorine / nitrogen mixed gas, and the product 3-trifluoromethylpyridine (3-TF) is separated from the solvent through a three-stage vacuum distillation process. Compared with the conventional synthesis technology, the method provided by the invention has the advantages of high reaction yield, easiness in operation, low energy consumption, solvent recycling, high economical efficiency and the like.

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 provides a continuous synthesis system and method of 2-chloro-5-methylpyridine, the system comprises a tower reactor, a clinker kettle, a condenser, a first flash tank, a spray absorption tower, a second flash tank and a circulating pump, the synthesis method comprises the following steps: phosgene and an intermediate solution enter the tower reactor for reaction from bottom to top, after discharging, introducing into a clinker kettle for reaction, discharging reaction tail gas out of a system after condensation, after a certain retention time, discharging reaction synthetic liquid, introducing into a first flash tank for gas-liquid separation, introducing a gas-phase material into a spray absorption tower, discharging after absorption treatment, introducing a liquid-phase material into a second flash tank for secondary gas-liquid separation, and discharging after secondary gas-liquid separation; a gas-phase material obtained after secondary gas-liquid separation enters a clinker kettle, and a liquid-phase material is subjected to a post-treatment step to obtain a 2-chloro-5-methylpyridine product. By adopting the synthesis system and the synthesis method, the yield of the 2-chloro-5-methylpyridine is high, and the discharge of a large amount of wastewater with complex components is reduced.

The invention provides a preparation method of 2-chloro-5-methylpyridine, in the preparation method, by controlling the reaction pressure when pyridone chloride and phosgene react to generate 2-chloro-5-methylpyridine to be 0.15-1.1 MPa, the solubility of phosgene in a reaction liquid phase can be effectively improved, and the molar ratio of phosgene in a reaction liquid phase system is increased. According to the method, the pyridone chloride and the phosgene can fully react to generate the 2-chloro-5-methylpyridine, so that the utilization rate of the phosgene is increased; and the phenomenon that the pyrolytic intermediate pyridol of pyridone chloride is converted into other impurities due to insufficient phosgene content in a reaction liquid phase and delayed reaction can be effectively avoided. By adopting the continuous preparation operation of the overflow reaction kettle, the yield of the 2-chloro-5-methylpyridine can be further improved, the production cost can be further reduced, and the production efficiency is improved. The method has obvious progressive significance especially for improving the industrial large-scale production efficiency.

The invention discloses a preparation method of an apelisib intermediate 4-methylpyridine compound. According to the method, 2-halogen-4-methylpyridine is used as an initiator to prepare the apelisib intermediate 4-methylpyridine compound. 2-halo-4-methylpyridine shown as a compound I is used as an initiator and reacts with 1, 1, 1-trifluoroacetone under the condition of a reducing agent to obtain the 4-methylpyridine compound shown as a compound II, and the method is easy to operate, high in yield and more suitable for industrialization.

The present application provides a preparation method of racemic nicotine, including the following steps: Nicotinyl chloride and methylamine are reacted under alkaline conditions to obtain methylnicotinamide, then condensed with monochloroacetone to obtain N-methyl-N-(2-oxopropyl) nicotinamide, then self-aldol condensed to obtain 1-methyl-5-(pyridin-3-yl)-1,2-dihydro-3H-pyrrol-3-one, and finally reduced to obtain racemic nicotine.

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 discloses a PBT composite material and a preparation method thereof, and relates to the technical field of modified PBT composite materials. The invention provides a polybutylene terephthalate composite material. The polybutylene terephthalate composite material is prepared from the following components in parts by weight: 50-85 parts of polybutylene terephthalate, 1-10 parts of a titanium dioxide coloring agent, 1-10 parts of an acrylic acid toughening agent, 6-20 parts of ionic liquid and 0.1-1.5 parts of an antioxidant, the ionic liquid is composed of positive ions and negative ions, the positive ions comprise at least one of 1-methylpyridinium ions, 1-butylpyridinium ions, 1-butyl-4-methylpyridinium ions, 1-allyl-1-methylpyrrolidinium ions and 1-butyl-1-methylpyrrolidinium ions, and the negative ions comprise at least one of 1-methylpyridinium ions, 1-butylpyridinium ions, 1-butyl-4-methylpyridinium ions, 1-allyl-1-methylpyrrolidinium ions and 1-butyl-1-methylpyrrolidinium ions. The anions comprise at least one of chloride ions, bromide ions, iodide ions and bis (trifluoromethylsulfonyl) imine ions. Through the special compounding effect of all the components, the polybutylene terephthalate composite material with good fluidity and excellent hydrolysis resistance is prepared.

Crystalline forms and pharmaceutical compositions of the PRMT5 inhibitor of formula (I), methods for preparing the PRMT5 inhibitor of formula (I) and its crystalline form, methods for preparing pharmaceutical compositions of the PRMT5 inhibitor of formula (I), and methods of using the PRMT5 inhibitor of formula (I) or crystalline solid form and pharma- ceutically acceptable compositions thereof. TIFF2025501503000207.tif42165

The invention relates to the technical field of anode materials, in particular to a modified carbon anode and a preparation method thereof, and the preparation method comprises the following steps: S1, crushing pretreatment; s2, mixing; s3, extrusion forming; s4, strengthening treatment; the performance of the modified carbon anode in the aspects of conductivity, density, breaking strength and the like can be remarkably improved by matching a unique preparation process with specific components. The double modified asphalt plays a key role in bonding and performance optimization. In the first modification, 2, 3, 5-trimethylpyridine reacts with asphalt, so that the aromaticity and the crosslinking degree of the asphalt are increased, and the softening point and the thermal stability of the asphalt are greatly improved. And the asphalt can stably wrap the asphalt coke particles to form a compact structure, so that the density of the anode is effectively improved. In the second modification, a boron-containing compound is introduced and further reacts with the first modified asphalt to form a boron-containing cross-linked structure, so that not only is the intermolecular force enhanced, but also the crystal structure of the anode is optimized.

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.

A method for preparing 2,3-dichloro-5-trifluoromethylpyridine, comprising at a temperature of 100˜150° C. and a pressure of 0.5˜5.0 MP, in presence of at least one catalyst selected from supported metal chloride, supported zeolite molecular sieve and supported heteropolyacid, 2-chloro-5-trifluoromethylpyridine reacts with chlorine gas to obtain 2,3-dichloro-5-trifluoromethylpyridine. The preparing method provided by the present invention has advantages such as high selectivity of desired product, high utilization rate of chlorine gas, moderate process condition, simple operation and less three wastes. The present invention also discloses a preparing method for preparing 2-chloro-5-trifluoromethylpyridine, which is capable of reducing unit consumption, reducing separation cost, and improving safety compared to the prior art.