36 results about "CMN pyrazole" patented technology

The compound cis)-N—((S)-1-(6-(4-fluoro-1H-pyrazol-1-yl)pyridin-3-yl)ethyl)-1-methoxy-4-(4 methyl-6-(5-methyl-1H-pyrazol-3-ylamino)pyrimidin-2-yl)cyclohexanecarboxamide can be prepared as a free base in various crystalline solid forms, and in various salt forms each having one or more solid forms.

The present application relates to a kind of preparation method of trifluoromethyl pyrazole compound, belong to the technical field of organic synthesis.The specific method is: (1) trifluoroacetyl ethyl acetate is first with hydrazine hydrate cyclization reaction and generates compound of formula III;(2) under the catalysis of base, compound of formula III is reacted with difluoromethylation reagent and generates compound of formula II;(3) compound of formula II is reacted with methylating agent and obtains compound of formula I;The difluoromethylation reagent is difluoro-monochloromethane or sodium difluoro-monochloroacetate;The methylating agent is chloromethane, bromomethane, iodomethane, dimethyl sulfate or dimethyl carbonate.The present application is prepared by changing reaction route, and the higher-priced raw material methylhydrazine is replaced, and isomer impurity is no longer generated in the product prepared.Not only raw material cost is reduced, but also the purity of product is improved.

The invention belongs to the field of medicine synthesis, and particularly relates to a preparation method of 3-hydroxy-4-fluorobenzoate. According to the preparation method disclosed by the invention, 3-bromo-4-fluorobenzaldehyde is taken as an initial raw material, and the compound 3-hydroxy-4-fluorobenzoate is prepared through four steps of reactions including aldolization, boronation, oxidation and esterification. The 3-hydroxy-4-fluorobenzoate can be used for preparing the acomidid or an intermediate 3-(3-(3, 5-dimethyl-1H-pyrazol-4-yl) propoxy)-4-fluorobenzoate of the acomidid, and the 3-(3, 5-dimethyl-1H-pyrazol-4-yl) propoxy)-4-fluorobenzoate can be used for preparing the acomidid. The preparation method has the advantages of easily available raw materials, mild reaction conditions, simple operation, high yield and purity, and suitableness for industrial production.

The application discloses a method suitable for reducing N2O emission of straw returned to field in medium-weak acidic soil, and relates to the technical field of environmental protection. The medium-weak acidic soil is the straw full amount smashing and burying returned to field soil, and after pre-culturing the medium-weak acidic soil, nitrogen fertilizer and inhibitor are added into the pre-cultured medium-weak acidic soil in sequence, and after culturing, the N2O emission of the medium-weak acidic soil is reduced. The inhibitor is compounded by 3,4-dimethyl pyrazole phosphate and nano carbon solution. The 3,4-dimethyl pyrazole phosphate and the nano carbon solution have a synergistic effect on reducing the total amount of N2O emission in the medium-weak acidic soil. Specifically, compared with the blank treatment group, the N2O emission amount of the inhibitor prepared by combining the 3,4-dimethyl pyrazole phosphate and the nano carbon solution is reduced by 0.422 kg·hm ‑2 .

A low-density, high-temperature, creep-resistant benzoxazine hybrid epoxy paste and its preparation method are disclosed, relating to the field of adhesive technology. The aim is to address the insufficient long-term high-temperature creep resistance of existing lightweight epoxy adhesives. The paste is prepared from the following raw materials: Raw materials are weighed, and amide-containing trifunctional benzoxazine resin, amide-containing difunctional benzoxazine resin, amide-containing monofunctional benzoxazine resin, multifunctional epoxy resin, bisphenol A type epoxy resin, and toughening agent are added to a reaction vessel. The mixture is heated and stirred to obtain a homogeneous resin premix. The mixture is then cooled, and hollow glass microspheres, a coupling agent, and 2-methyl-pyrazolo[1,5-A]pyrimidine-6-carboxylic acid are added, and the mixture is stirred to obtain an intermediate product. Finally, a curing agent is added and stirred to obtain the low-density, high-temperature, creep-resistant benzoxazine hybrid epoxy paste. This invention is applicable to structural bonding applications in aerospace, rail transportation, and electronic packaging where lightweighting and long-term high-temperature reliability are critical.

The invention belongs to the technical field of energetic materials, and discloses a synthesis method of a fusion casting carrier explosive 4-methoxy-1-methyl-3, 5-dinitropyrazol, commercially available 1-methylpyrazole-4-boronic acid pinacol ester is used as a raw material, a key intermediate 4-methoxy-1-methyl-1H-pyrazole is synthesized through a one-pot method two-step substitution reaction, and the fusion casting carrier explosive 4-methoxy-1-methyl-3, 5-dinitropyrazol is obtained. The product does not need to be purified, and can be directly nitrified after simple post-treatment, so that the casting carrier explosive product 4-methoxy-1-methyl-3, 5-dinitropyrazole is obtained. Compared with the prior art, the preparation method provided by the invention has the advantages of simplicity, high efficiency, low cost and the like, and has the potential of large-scale synthesis.

The present invention relates to mixtures comprising a solid support comprising a urease inhibitor and another solid support comprising a nitrification inhibitor, such as 3,4-dimethylpyrazole phosphate (DMPP) or 2-(3,4-dimethyl-1H-pyrazol-1-yl)succinic acid (DMPSA), to a method for enhancing the nitrification inhibitory effect or for increasing the health of a plant using mixtures of at least one compound I and at least one compound II; to the use of mixtures comprising compounds I and II for increasing the health of a plant.

This provides a crystalline form of PF-07104091 that has desirable properties such as high crystallinity, high purity, low hygroscopicity, favorable solubility or mechanical properties, improved manufacturability or filterability, and / or favorable stability. [Solution] A crystal (Form 3) of (1R,3S)-3-[3-({[3-(methoxymethyl)-1-methyl-1H-pyrazole-5-yl]carbonyl}amino)-1H-pyrazole-5-yl]cyclopentylpropan-2-ylcarbamate (PF-07104091) monohydrate is provided, having a powder X-ray diffraction (PXRD) pattern including peaks at 2θ values ​​measured using CuKα radiation at 8.4, 10.1 and 21.5°2θ±0.2°2θ.

The present application relates to 1, 3-dimethyl-5-pyrazole carboxylic acid esters and related compounds, methods for their preparation and methods of their use as perfume and flavor ingredients in food, cosmetic, pharmaceutical, consumer and other compositions and products.

The present invention provides a novel 5-fluoro-1-[(2-fluorophenyl)methyl]-1H-pyrazolo [3, 4-b]pyridine-3-carboximidamide formate compound of formula (IV) and process for preparation thereof. The present invention further provides for the use of compound of formula (IV) for the preparation of vericiguat compound of formula I. The present invention also relates to process for the preparation of vericiguat Modification form II, vericiguat Modification form III, vericiguat monohydrate and dihydrate.

The invention relates to the technical field of compound fertilizers, and particularly discloses a low-ammonia volatile nitrogen fertilizer and a preparation process thereof, the low-ammonia volatile nitrogen fertilizer comprises the following raw materials by weight: 40-60 parts of a base nitrogen fertilizer, 2-5 parts of a composite inhibitor, 8-15 parts of a modified coating liquid, and 3-8 parts of an auxiliary agent; a composite inhibitor and a modified coating liquid are added in the process of preparing the low-ammonia volatile nitrogen fertilizer, the composite inhibitor is prepared by mixing n-propyl thiophosphoric triamide, 3-methyl-1H-pyrazole-5-carboxylic acid and a bio-based emulsifier, and the bio-based emulsifier is prepared by chemically bonding spirulina protein and tea polyphenol. Amino groups and carboxyl groups on spirulina protein and phenolic hydroxyl groups on tea polyphenol not only can be combined with hydroxyl groups on n-propyl thiophosphoric triamide and 3-methyl-1H-pyrazole-5-carboxylic acid, but also hydrophobic groups on the spirulina protein and the phenolic hydroxyl groups on the tea polyphenol can form a hydrophobic effect with a flexible long-chain alkane structure on soybean oil in modified coating liquid; the ammonia volatilization inhibition effect and the slow release performance of the nitrogen fertilizer are synergistically improved.

The invention discloses a compound containing a 1-methyl-4-(p-toluoyl)-1H-pyrazol-5-yl carboxylic ester structure and an application of the compound as a herbicide. The structural formula of the compound is shown as a formula I. The preparation method comprises the following steps: taking [3-(4, 5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl) phenyl] (5-hydroxy-1-methyl-1H-pyrazole-4-yl) ketone as a raw material, and carrying out nucleophilic substitution reaction on the [3-(4, 5-dihydro-3-isoxazolyl)-2-methyl-4-(methylsulfonyl) phenyl] (5-hydroxy-1-methyl-1H-pyrazole-4-yl) ketone and an acyl chloride reagent in a solvent to prepare the compound shown in the formula I; the compound has the advantages of novel structure, wide herbicide controlling spectrum, high herbicidal activity, simple preparation method, mild reaction conditions, high product yield, short reaction process and the like.

The invention belongs to the field of chemical synthesis, and particularly relates to a method for clean production of 5-methyl-3-(trifluoromethyl)-1H-pyrazole. Methyl trifluoroacetate is used as a raw material and reacts with acetone under the conditions of a solvent and a catalyst, a reaction solution is subjected to acidification and negative pressure distillation to obtain a trifluoroacetylacetone methanol solution, the trifluoroacetylacetone methanol solution directly reacts with hydrazine hydrate, and 5-methyl-3-trifluoromethyl-lH-pyrazole is obtained. The content of the 5-methyl-3-(trifluoromethyl)-1H-pyrazole obtained through the method reaches 99% or above, the two-step synthesis yield reaches 70%, and the method has the advantages of being high in product content, few in impurities, simple in technological process, convenient in solvent recovery and the like, and meets the requirement of clean production.

The invention belongs to the technical field of organic synthesis and fertilizer additives, and particularly relates to a preparation method of 3, 4-dimethyl pyrazole and phosphate thereof, the method comprises the following steps: step 1) formylation reaction; the method comprises the following steps: in the presence of Lewis acid, carrying out formylation reaction on 2-butanone, formate and sodium alkoxide in an alkali solvent to obtain a reaction mixture; (2) cyclization reaction: enabling the reaction mixture obtained in the step (1) to be in contact with hydrazine hydrate for cyclization reaction to obtain the 3, 4-dimethylpyrazole.The preparation method is simple in process, safe, reliable, high in yield and product purity, simple in three-waste treatment and suitable for industrial production, and the solvent can be recycled and reused.

The invention discloses a preparation method of 3-halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic ester, which is characterized in that 5-halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic ester is used as a raw material, and the 3-halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic ester is synthesized by a transposition reaction in the presence of phosphotriester and a trifluoromethyl halogenated benzene compound. According to the method, the trifluoromethyl halogenated benzene compound is used as the catalyst, the boiling point of the trifluoromethyl halogenated benzene compound is low, obvious ionization is not generated in the reaction process, the trifluoromethyl halogenated benzene compound and the unreacted raw material 5-halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic ester can be steamed out together, and the steamed-out raw material 5-halogenated alkyl-1-methyl-1H-pyrazole-4-carboxylic ester is directly used for next reaction; extra post-treatment steps such as extraction and water washing are not needed, the post-treatment steps are simplified, introduction of exogenous acid is avoided, and the production and post-treatment cost is reduced.

Applicant discloses methods and uses of the heteroaryl ketone fused azadecalin compound relacorilant for treating patients suffering from endogenous hypercortisolism (CS) (including Cushing's syndrome and Cushing's Disease) effective reduce or prevent the loss of tissue lean mass; in embodiments, the methods and uses are effective to increase tissue lean mass as compared to the patient's tissue lean mass prior to administration of relacorilant. The methods and uses of relacorilant for treating patients suffering from CS are further effective to reduce body weight and waist circumference of the patient. Therapeutic amounts of relacorilant may be between about 50 milligrams per day (mg / day) and up to about 800 mg / day, e.g., 100 mg / day, 200 mg / day, 300 mg / day, 400 mg / day, or 500 mg / day. The treatments may be oral treatments, and relacorilant may be administered with food, or without food. Relacorilant is (R)-(1-(4-fluorophenyl)-6-((1-methyl-1H-pyrazol-4-yl)sulfonyl)-4,4a,5,6,7,8-hexahydro-1H-pyrazolo[3,4-g]isoquinolin-4a-yl)(4-(trifluoromethyl)pyridine-2-yl)methanone, which has the structure (A).

The application provides a gamma-polyglutamic acid modified nitrification inhibitor and a preparation method and application thereof. A natural high molecular material gamma-polyglutamic acid (gamma-PGA) is used for structural modification of 3,4-dimethylpyrazole phosphate (DMPP), so that a gamma-polyglutamic acid modified nitrification inhibitor (DMPP-gamma-PGA conjugate) is obtained, and the thermal stability and storage stability of the nitrification inhibitor are significantly improved. The modified product can be applied to stable nitrogen fertilizer. Through soil culture experiments, it is shown that the modification of gamma-PGA not only enhances the nitrification inhibition effect of DMPP, but also significantly reduces the N2O emission flux and cumulative emission amount. In addition, the slow-release effect of gamma-PGA effectively prolongs the persistence period of DMPP, improves the nitrogen regulation capacity of DMPP, and provides a more environmentally friendly and efficient nitrification inhibition scheme for agricultural production.

The application discloses a preparation method of fluoxapyroxad, which comprises the following steps: mixing 1-methyl-3-difluoromethyl-1H-pyrazole-4-carbonyl chloride, a catalyst and a first organic solvent and heating to 83 DEG C-140 DEG C, then adding a mixed solution composed of 3', 4', 5'-trifluoro-2-aminobiphenyl and a second organic solvent, keeping warm after adding, continuously releasing hydrogen chloride during the reaction, adding an aqueous solution of inorganic base after the reaction is completed, stirring and standing, separating the water layer, cooling and crystallizing the organic phase, filtering and drying to obtain the fluoxapyroxad product. The preparation method does not need to add an acid-binding agent, has the advantages of high yield, less waste, low cost, simple operation and good safety.

The application provides a synthesis method of metrafenone, and belongs to the technical field of organic synthesis, and comprises the following steps: firstly, subjecting 5-hydroxy-1-methyl-3-(trifluoromethyl)-1H-pyrazole to a hydroxymethylation reaction to obtain 4-(hydroxymethyl)-5-hydroxy-1-methyl-3-(trifluoromethyl)-1H-pyrazole; then, reacting with difluorobromoacetic acid to obtain 4-(hydroxymethyl)-5-(difluoromethoxy)-1-methyl-3-(trifluoromethyl)-1H-pyrazole; then, subjecting to a mesylation reaction to obtain a mesylate intermediate; simultaneously, preparing 3-acetylthio-5,5-dimethyl-4,5-dihydroisoxazole from 3-chloro-5,5-dimethyl-4,5-dihydroisoxazole; then, subjecting the intermediate to a thioetherization reaction with the mesylate intermediate to obtain a thioether coupling intermediate; finally, performing an oxidation reaction in the presence of a catalyst to obtain metrafenone. By adopting the mesylate activated intermediate and combining a continuous flow fixed bed oxidation process, the method is favorable for improving the purity and total yield of the target product and reducing the tungsten residue in the product.

The invention discloses a 3, 4-dimethyl pyrazole salt as well as a preparation method and application thereof, and the 3, 4-dimethyl pyrazole salt is 3, 4-dimethyl pyrazole mesylate. The preparation method comprises the following steps: firstly, dispersing a 3, 4-dimethylpyrazole solid in an inert solvent, and diluting methanesulfonic acid with the inert solvent for later use; slowly adding the diluted methanesulfonic acid solution into a mixture of 3, 4-dimethyl pyrazole and an inert solvent; and after the reaction is finished, cooling materials after the reaction, separating out crystals, filtering and drying to obtain the 3, 4-dimethyl pyrazole mesylate. The 3, 4-dimethylpyrazole mesylate provided by the invention is low in use loss rate, strong in storage stability and good in nitrification inhibition effect.

The application relates to the technical field of materials, and provides a new method for synthesizing 3,6-dinitropyrazolo[4,3-c]pyrazole. The method comprises the following steps: performing a nitrosation reaction on compound 1 (3,5-dimethylpyrazole) and a first nitrosating agent in a first solvent to obtain compound 2, and then reducing the nitroso group of the compound 2 by using a reducing agent to obtain compound 3; performing an acetylation reaction on the compound 3 and an acetylating agent in a second solvent to obtain compound 4, and then adding a first alkali and a second nitrosating agent to perform a nitrosation reaction to obtain compound 5 and compound 6; and performing a reaction on the compound 5 and the compound 6 in a third solvent to obtain compound 7 (DNPP), wherein the third solvent contains a second alkali or an acid solution. The process of the application does not involve accumulation of dangerous intermediates, has the advantages of simple operation, high safety, excellent yield, convenient post-treatment and the like, and is easy to scale up.

The application belongs to the technical field of organic chemistry and specifically relates to a preparation method of zanabe Ronast. The method comprises the following steps: 1,3-dimethylpyrazole-4-formaldehyde is used as raw material, 4-bromo-piperidine, sodium cyanoborohydride and zinc chloride are used to carry out Borch reduction amination reaction to obtain 4-bromo-1-((1,3-dimethyl-1-H-pyrazole-4-yl)methyl)piperidine; then, 4-methyl 4-cyanobenzoate is used to carry out electrocatalytic synthesis to obtain 4-(1-((1,3-dimethyl-1H-pyrazole-4-yl)methyl)piperidin-4-yl)benzoic acid methyl ester; finally, o-phenylenediamine and potassium tert-butoxide are stirred at room temperature to obtain zanabe Ronast. The application is synthesized through three steps, the reaction condition is mild, the raw material is simple and easy to obtain, the method is green and environment-friendly, the synthesis efficiency is high, the cost is low, and the method is suitable for industrial production.

The present disclosure provides, in part, compounds of formula (A) and formula (D), which are intermediate compounds that can be used to prepare the compound N-(5-(difluoromethoxy)-1H-pyrazol-3-yl)-1-((tetrahydro-2H-pyran-4-yl)methyl)-1H-pyrazolo[3,4- b]pyrazin-6-amine (compound of formula (I)) and processes for the preparation of the compound of formula (I).

The present invention relates to salts and polymorphic forms of Compound A (6-chloro-7-(4-(4-chlorobenzyl)piperazin-1-yl)-2-(1,3-dimethyl-1H-pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine), an inhibitor of Aurora kinase and FMS-like tyrosine kinase 3 (FLT3) activity. The present invention also relates to processes for the preparation of the salts and polymorphic forms of the compound, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, as well as other diseases or conditions in which Aurora kinase and / or FLT3 activity is implicated.

The application belongs to the technical field of pesticide synthesis, and particularly relates to a difluoromethyl pyrazole formyl benzidine compound, a synthesis method and application thereof. The difluoromethyl pyrazole formyl benzidine compound is synthesized by first preparing DFPA acyl chloride through 3-difluoromethyl-1-methyl-1H-pyrazole-4-carboxylic acid (referred to as DFPA), then docking the obtained DFPA acyl chloride with benzidine with different substituents, and measuring that the difluoromethyl pyrazole formyl benzidine compound has excellent activity in resisting pathogenic bacteria. The compound can be used for preparing a pathogenic bacteria resisting pharmaceutical preparation.

The invention discloses a continuous preparation method of 1-methyl-1H-pyrazole-5-carboxylic acid in the technical field of compound preparation, aiming at solving the problems that a lithium salt intermediate generated by intermittent production is unstable and has a relatively large thermal runaway risk. The preparation method comprises the following steps: dissolving 1-methyl-1H-pyrazole to obtain a raw material solution; continuously pumping the raw material solution and the n-butyllithium solution into a first continuous reactor according to a preset proportion, and carrying out lithiation reaction to generate a lithiation reaction solution; introducing the lithiation reaction liquid into a second continuous reactor, introducing carbon dioxide, and carrying out carboxylation reaction to generate carboxylation reaction liquid; and carrying out quenching and treatment on the carboxylation reaction solution to obtain the 1-methyl-1H-pyrazole-5-carboxylic acid. The method is suitable for continuous production of 1-methyl-1H-pyrazole-5-carboxylic acid, rapid and continuous production of 1-methyl-1H-pyrazole-5-carboxylic acid can be achieved, and the problem that the retention time of a lithium salt intermediate in intermittent reaction is too long is solved.

This invention belongs to the field of pharmaceutical synthesis technology, specifically relating to a method for preparing naphamostat mesylate. The method uses 6-formamidinylnaphth-2-yl-4-aminobenzoate as a starting material, reacting it with 3,5-dimethyl-1-pyrazoleformamidin nitrate to form a salt, thereby obtaining the target product, naphamostat mesylate. Compared with products obtained by existing technologies, this method has higher yield and purity, and is simpler, safer, and suitable for industrial production.

Processes for preparing 3- [ (3aS, 6aR) -5- {5-chloro-2-[ (1-methyl-1H-pyrazol-4-yl) amino] pyrimidin-4-yl} -3a-methyl-octahydropyrrolo [3, 4-c]pyrrole-2-yl] -3-oxopropionitrile (Compound I) on a scale of over 1 kg.