143 results about "Transmethylation" patented technology

This invention belongs to the field of chemical synthesis and relates to a method for achieving deuterated methylation of a nucleophile. The invention provides a deuterated methylating reagent, which is obtained by reacting formic acid with deuterated methanol under acidic conditions, followed by a second reaction with thiaanthracite and trifluoromethanesulfonic acid. The nucleophile is then reacted with the deuterated methylating reagent described in claim 1, a base, and a solvent to obtain the deuterated methylated product. This invention also provides a method for achieving deuterated methylation of a nucleophile, which involves dissolving the nucleophile and 5-deuterated methyl-5H-thiophene-5-onium trifluoromethanesulfonate in a suitable solvent, adding a base, and then performing the deuterated methylation reaction at room temperature. In the method provided by this invention, the yield of the product after nucleophile methylation can reach 52% to 95%.

The invention relates to an L-proline heterocyclic intermediate, alpha-methyl-L-proline hydrochloride and a preparation method thereof, which comprises the following steps: step 01, cyclization upper protection: taking L-proline as a raw material, which is shown in a formula (1), to react with trichloracetic aldehyde hydrate under an acidic condition, and performing upper protection to obtain a heterocyclic intermediate as shown in a formula (2); the molar weight of chloral hydrate is 1-2.5 times of the molar weight of the L-proline shown in the formula (1), preferably 1.5 times of the molar weight of the L-proline shown in the formula (1). 02, methylation: reacting the heterocyclic intermediate as shown in the formula (2) obtained in the step 01 with lithium diisopropylamide, and after the reaction is completed, adding dimethyl sulfate for methylation to obtain an intermediate as shown in a formula (3); 03, deprotection: adding the intermediate as shown in the formula (3) obtained in the step 02 into a deprotection reagent for hydrolysis so as to obtain the alpha-methyl-L-proline hydrochloride as shown in the formula (4), so that the problems that the preparation cost of the existing alpha-methyl-L-proline hydrochloride is relatively high and the yield is relatively low can be solved.

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 present invention relates to the field of organic chemical synthesis, and specifically relates to a 6-bromonicotine synthesis method. The 6-bromonicotine synthesis method uses 6-hydroxymyosmine (CAS: 70969-38-9) as a starting material, which sequentially undergoes a reduction reaction, an amine methylation reaction and a bromination reaction, to finally obtain the target product 6-bromonicotine. The product purity of the 6-bromonicotine obtained by means of the synthetic route can reach 99.0% or more. The present synthesis method has a simple process and a high yield, and is suitable for industrial scale-up production.

The invention relates to the technical field of cathode electrophoretic paint, and discloses an asymmetric double-blocked isocyanate curing agent as well as a preparation method and application thereof. Based on the reaction activity difference of primary carbon and secondary carbon NCO groups in isophorone diisocyanate molecules, a step-by-step asymmetric sealing strategy is adopted: in the first stage, a hydrophilic chain extender containing a tertiary amine structure is utilized to preferentially react with high-activity primary carbon NCO, and an internal catalytic center and a hydrophilic group are anchored in a molecular skeleton; and in the second stage, the active methylene compound and the bio-based long-chain phenol are used for carrying out hybrid dual-sealing on the residual secondary carbon NCO with relatively large steric hindrance. According to the preparation of the curing agent, the curing agent integrates internal catalysis, stepped curing and self-emulsifying functions, the deblocking energy barrier is effectively reduced, and 140-DEG C low-temperature curing or high-temperature high-performance curing can be realized under the tin-free catalysis condition.

The invention relates to the technical field of biological medicine, in particular to a novel amino acid or polypeptide side chain carbonylation modification reagent which can be used as a novel carbonylation reagent in a method for synthesizing gamma-C (sp3)-H bond carbonylation amino acid or polypeptide through palladium catalysis. Substituting ethylene with a novel carbonylation reagent 1-iodine-2-bromine under the action of a palladium catalyst, an additive and a solvent to realize carbonylation and methylation of the amino acid gamma-C (sp3)-H bond. The method disclosed by the invention has the beneficial effects that a novel carbonylation reagent easy to prepare is developed, substrate raw materials are easy to obtain, the operation is simple and convenient, the condition is mild, the substrate application range is wide, and a plurality of carbonylated amino acids and polypeptide derivatives can be efficiently and accurately synthesized at low cost; and a novel method is provided for modification of unnatural amino acids and polypeptide side chains.

The invention belongs to the field of electrochemical synthesis, and particularly discloses a method for synthesizing N, N, N ', N'-tetramethyl methylenediamine by directly utilizing a dimethylamine aqueous solution through electrochemical amine methylenation. According to the method, a dimethylamine aqueous solution is used as a raw material, and an electrochemical amine methyleneation reaction of dimethylamine is carried out on an anode loaded with a carbon material catalyst in an electrically driven oxidation manner, so that synthesis of N, N, N ', N'-tetramethyl methylenediamine is realized. Different from the existing dimethylamine and formaldehyde condensation method and dimethylamine and methanol electrosynthesis method, the method disclosed by the invention directly adopts the industrial dimethylamine aqueous solution as a raw material to synthesize N, N, N ', N'-tetramethyl methylenediamine, so that the process flow is simplified, and the yield is high. The method has the characteristics of mild process conditions, high system stability, few byproducts, greenness, safety, low cost and suitability for industrial application. The method has wide application potential in the fields of electrochemical organic synthesis, energy storage, pharmaceutical chemical industry and the like.

The invention discloses a liver tissue regeneration regulation and control method based on epigenetic state regulation and control, and relates to the technical field of biology. Comprising the following steps: sampling the liver tissue at a plurality of preset time points after the liver tissue is damaged or partially resected, selecting a target gene related to liver tissue regeneration regulation, and detecting an epigenetic state of a promoter region of the target gene; comparing and analyzing the change of the epigenetic state of the target gene promoter region on the basis of detection results obtained at different time points, and determining epigenetic modification characteristics in the liver tissue regeneration process; according to an analysis result, intervening the expression level of a regulatory factor related to DNA methylation or DNA hydroxymethylation so as to regulate the epigenetic state of the target gene promoter region; after intervention is completed, the transcription expression condition of a target gene and the activity change of a cell signal channel related to liver tissue regeneration are detected, and the liver tissue regeneration process can be effectively regulated and controlled through the method.

The invention discloses an alpha-dideuterium methylated sulfone compound as well as a synthesis method and application thereof, and belongs to the field of organic chemistry. In an air atmosphere, benzyl methyl sulfone and 2-((3, 5-dimethyl-4-methoxypyridine-2-yl) methylsulfonyl)-5-methoxy-1H-benzo [d] imidazole are used as substrates, in the presence of a catalyst [Cp * IrCl2] 2 and cesium carbonate, deuterated paraformaldehyde is used as a carbon source, sodium formate is used as an additive, and the alpha-dideuterium methylated sulfone compound is obtained through a reaction in an acetonitrile solvent at 120 DEG C. The reaction does not need to use a ligand and hydrogen, the reaction is simple and efficient, the potential value of the compound in medicinal chemistry is shown, and the compound has a certain inhibition effect on H3N2 subtype influenza viruses and has remarkable application potential.

The invention discloses a preparation method of an azacyclo-bis (fluorosulfonyl) imide salt derivative, which comprises the following steps of: 1, mixing an azacyclo-compound, a methylation reagent, an ethylation reagent, bis (fluorosulfonyl) imide salt and inorganic alkali in a polar organic solvent, heating, and filtering after complete reaction to obtain crude filtrate containing the azacyclo-bis (fluorosulfonyl) imide salt; the nitrogen heterocyclic compound is selected from one of oxazolidine, 4-cyano piperidine, 4-fluoro piperidine, 4, 4-difluoro piperidine and 3-cyano piperidine; the bis (fluorosulfonyl) imide salt is selected from one of lithium bis (fluorosulfonyl) imide and potassium bis (fluorosulfonyl) imide; and 2, adding an inert organic solvent into the crude product filtrate for crystallization, and performing vacuum drying to obtain a finished product. The method has the advantages that the operation steps are few, the synthesis efficiency is greatly high, the process is greatly simplified, and the preparation cost is effectively reduced.

The invention discloses p-toluenesulfonic acid 8-tert-butyl diphenyl silyloxy-7-methyl octyl ester as well as a synthesis method and application thereof, and relates to the technical field of biopesticides. The preparation method comprises the following steps: taking 8-bromocaprylic acid as an initial raw material, and firstly reacting with t-BuOK and 18-crown ether-6; then reacting with pivaloyl chloride to generate acid anhydride, and then carrying out acylation reaction with 4-benzyl oxazolidine-2-ketone; then carrying out diastereoselective methylation; then, NaBH4 reduction is carried out; carrying out hydroxyl protection; then carrying out hydroboration oxidation reaction; and then carrying out TsCl sulfonylation, so as to synthesize the p-toluenesulfonic acid-8-tert-butyl diphenyl silyloxy 7-methyl octyl ester. The optical purity of the (S)-p-toluenesulfonic acid 8-tert-butyl diphenyl silyloxy-7-methyl octyl ester synthesized in the invention reaches 98%, and the optical purity of the (R)-p-toluenesulfonic acid 8-tert-butyl diphenyl silyloxy-7-methyl octyl ester synthesized in the invention also reaches 98%.

The invention belongs to the technical field of organic synthesis, and discloses ketoxime ether as well as a preparation method and application thereof. The preparation method comprises the following steps: mixing a ketoxime compound, tert-butyl alcohol and alkali to obtain a mixed solution; and adding a methylation reagent into the mixed solution, and reacting to obtain ketoxime ether. The preparation method is low in raw material cost and simple in process operation; tert-butyl alcohol is used as a solvent, sodium tert-butoxide is used as an alkali source, no water participates in the reaction process, ketoxime hydrolysis is effectively reduced, side reactions are greatly reduced, the yield of the obtained product is high, and subsequent separation and solvent recycling are facilitated; use of toxic substances such as sulfur dioxide and sodium nitrite is avoided, and emission of toxic gases such as nitrogen oxides is reduced; and the process safety risk is reduced, and the method is safe, reliable, simple and feasible.

The invention discloses a preparation method of N-methyl o-fluoroaniline, which is characterized in that o-fluoroaniline is used as a starting raw material, and a target product is efficiently synthesized through three steps of reaction: step 1, in the presence of a solvent and alkali, o-fluoroaniline and acetyl chloride are acetylated at low temperature to generate 2-fluoro-acetanilide, and the product is directly used for the next step after being roughly purified; 2, under the action of a solvent and alkali, carrying out controllable methylation on the 2-fluorine-acetanilide and dimethyl carbonate to obtain 2-fluorine-N-methylacetanilide; and 3, removing acetyl protection through acidic hydrolysis, and adding sodium thiosulfate to prevent oxidation to finally obtain a high-purity product. According to the method, excessive methylation is avoided through an acetyl protection strategy, the process does not need high-risk operations such as ultralow temperature and high pressure, the operation is simple and convenient, the energy consumption is low, and the product purity is gt; the total yield reaches 79.86%, and the method is green, safe and suitable for industrial production.

The invention relates to the technical field of organic synthesis, and provides a synthesis method of an important organic synthesis intermediate methyl diethyl phosphonate. Comprising the following steps: firstly, adding paraformaldehyde and alkali into a solvent, heating and stirring, and filtering to obtain an intermediate solution; and adding cation exchange resin and the intermediate solution into a reaction flask, dropwise adding diethyl phosphite, carrying out a heat preservation reaction after dropwise adding is completed, filtering to remove the cation exchange resin (which can be recycled for multiple times) after the reaction is completed, and carrying out reduced pressure distillation to remove the solvent and a trace amount of diethyl phosphite residue, so as to obtain the product. The method has the main advantage that paraformaldehyde is used as a methylation reagent and reacts with diethyl phosphite in one step under the action of a catalyst to obtain a target product.

The invention discloses a method for preparing olotoxin, wherein tetramethyl olotoxin is subjected to demethylation to obtain the olotoxin.

This invention discloses a method for synthesizing potassium 4-methoxysalicylate based on supramolecular-assisted methylation, belonging to the field of organic synthesis technology. The process is based on supramolecular chemistry principles and includes the following steps: (1) Preparation of a macrocyclic host molecule-methylating agent complex loaded with a methylating agent: The macrocyclic host molecule and the methylating agent are reacted at pH 7-9 and 25-40℃ to form a complex solution; (2) One-pot preparation of the target product: 2,4-dihydroxybenzoic acid is salted with potassium hydroxide, potassium carbonate is added, and the above complex solution is added dropwise. A selective methylation reaction is carried out at 55-65℃. After the reaction is complete, post-treatment yields the product. This invention utilizes the molecular recognition function of the macrocyclic host to achieve highly selective methylation of the 4-hydroxyl group under mild conditions. This process has the advantages of simple operation, high safety, low waste, and recyclable host molecules. The yield of potassium 4-methoxysalicylate can reach over 85%, and the purity exceeds 99.0%.

The invention provides a preparation method of a rosaxostat impurity. The preparation method specifically comprises the following steps: S1, carrying out a substitution reaction on a compound 14-hydroxy-7-phenoxy isoquinoline-3-methyl formate and NCS under an acidic condition to generate an impurity A; s2, carrying out methylation reaction on the impurity A and a compound 2-methylboronic acid under an alkaline condition to generate an impurity B; s3, carrying out condensation reaction on the impurity B and a compound 3, namely glycine methyl ester hydrochloride to generate an impurity C. The synthesis method adopted by the invention is simple, the obtained sample is high in purity, and the synthesis method has great significance in process research, impurity analysis and quality control of the rosaxostat.

The application relates to application of C-methylated high isoflavone compounds in preparation of antitumor drugs and belongs to the technical field of drug application. In order to solve the problem that the existing antitumor activity is not much reported, the application of C-methylated high isoflavone compounds in preparation of antitumor drugs is provided, the C-methylated high isoflavone compounds are selected from compounds shown in the following formula 1 or formula 2: the C-methylated high isoflavone compounds or pharmaceutically acceptable salts thereof are used as active ingredients for preparation of antitumor drugs for preventing and / or treating adrenal pheochromocytoma (PC-12) and / or human brain astrocytoma (U-87MG). The C-methylated high isoflavone compounds have the advantages of high activity and high inhibition capacity, can be extracted from polygonatum sibiricum and have good drug safety.

The invention belongs to the technical field of organic chemical synthesis, and particularly relates to a synthetic method of deuterated toluene-D3, which comprises the following steps: reacting deuterated iodomethane with magnesium to obtain a Grignard reagent deuterated methyl magnesium iodide; and then carrying out coupling reaction on the deuterated methyl magnesium iodide and bromobenzene under the catalysis of a nickel metal catalyst to obtain the deuterated toluene-D3. The synthesis method solves the problems of many byproducts, high cost and low utilization rate of deuterated raw materials when the existing toluene synthesis process is used for preparing semideuterated toluene, realizes efficient synthesis of high-purity deuterated toluene-D3, greatly reduces the generation of polymethyl compounds, and is short in production period and simple in post-treatment.

The invention relates to the technical field of compound synthesis, in particular to a synthesis method of N, N-dimethylaminoethoxyethanol. The synthesis method comprises the following steps: mixing diglycolamine, a formaldehyde aqueous solution, a palladium carbon catalyst and hydrogen, and carrying out methylation reaction. The synthesis method is simple to operate, high in reaction conversion rate, high in product purity and good in economical efficiency.

The invention discloses a method for analyzing a pharmacodynamic material basis and metabolites of Longqing capsules. According to the method, an UPLC-Q-Exactive-Orbitrap MS technology is adopted, under the same chromatographic condition and mass spectrum condition, the pharmacodynamic material basis and metabolites of the Longqing capsules are measured and analyzed, 128 compounds are analyzed from the Longqing capsules, 144 exogenous compounds including 61 prototype components and 83 metabolites are analyzed from plasma, urine and excrement of rats in total, and the pharmacodynamic material basis and the metabolites of the Longqing capsules are analyzed to form the Longqing capsules with the pharmacodynamic material basis and the metabolites of the Longqing capsules with the pharmacodynamic material basis and the metabolites of the Longqing capsules with the pharmacodynamic material basis and the metabolites of the Longqing capsules. The main metabolic pathways comprise oxidation, reduction, hydrolysis, methylation, sulfation, glucuronization, composite reactions of various reaction types and the like. The invention provides a scientific basis for quality control and clinical reasonable medication of Longqing capsule medicines.

The application discloses a synthesis method of 4-ethyl-2-methylphenol and 5-ethyl-2-methylphenol. The method uses a small amount of meta-p-ethylphenol mixture and methyl alcohol to carry out fixed-bed catalytic methylation reaction, controls the reaction at a low methanol / ethylphenol ratio, a low ethylphenol conversion rate and a low temperature, and the methylation reaction mainly generates 4-ethyl-2-methylphenol, 5-ethyl-2-methylphenol, 3-ethyl-2-methylphenol, 3-ethyl-4-methylphenol and other products; the 4-ethyl-2-methylphenol / 5-ethyl-2-methylphenol mixture is reacted with formaldehyde to obtain linear methyl ethyl phenolic aldehyde resin and a pesticide intermediate 4-ethyl-2-methylphenol, or the 4-ethyl-2-methylphenol / 5-ethyl-2-methylphenol is subjected to tert-butylization, rectification, tert-butyl removal and rectification to obtain 99% 4-ethyl-2-methylphenol, 99.5% 5-ethyl-2-methylphenol and other products, so that the application field of coal-converted meta-p-ethylphenol mixture is expanded.

The application discloses a synthesis process of guanfacine hydrochloride, and the guanfacine hydrochloride raw medicine is obtained through three chemical reactions of urea methylation, amide condensation and amination reaction and one step of salification and recrystallization by taking 2,6-dichlorobenzoic acid and urea as starting materials. The starting material of the application is urea with lower selection cost, and the advantages are that a genotoxic impurity is easy to detect and the workshop detection cost is reduced; the intermediate is O-methyl isourea p-toluenesulfonate, and the advantages are that the intermediate has high stability and the quality is easy to control; and the amination reaction is performed by using ammonium chloride instead of ammonia water, so that the reaction cost is reduced and the workshop operation is more convenient.

This invention relates to a method for enriching arginine dimethylated peptides based on boric acid affinity chromatography. First, diketone compounds are used to selectively block unmodified and monomethylated guanidinium groups on the arginine side chains in a whole protein enzymatic digest. Then, an ortho-dicarbonyl compound and boron affinity chromatography material are simultaneously added to the peptide solution. The boron affinity chromatography material selectively captures the cis-ortho-diol intermediate generated by the reaction of the ortho-dicarbonyl compound with dimethylated arginine residues, thereby enriching the arginine dimethylated peptides. This method, combined with mass spectrometry detection and software analysis, allows for large-scale identification of arginine dimethylation modification sites in proteins. Compared with traditional immunoaffinity enrichment methods, this invention has advantages such as high enrichment specificity, good identification effect, and low experimental cost.

The invention relates to a method for efficiently preparing flurbiprofen based on a Suzuki-Miyaura coupling reaction. The preparation method comprises the following steps: taking ethyl cyanoacetate as a raw material, and carrying out methylation reaction on the ethyl cyanoacetate and methyl iodide or dimethyl sulfate to prepare racemic ethyl 2-cyanopropionate; the racemic ethyl 2-cyanopropionate and 4-bromine-2-fluorobiphenyl are subjected to a similar Suzuki-Miyaura reaction under the combined action of a zero-valent palladium metal catalyst, a metal stabilizer phosphine ligand and alkali, and the racemic ethyl 2-cyano-2-(2-fluoro4-biphenyl) propionate is obtained; and carrying out hydrolysis and decarboxylation on the racemic 2-cyano-2-(2-fluoro-4-biphenyl) ethyl propionate to obtain racemic 2-(2-fluoro-4-biphenyl) propionic acid, namely, the flurbiprofen. The process route comprises three steps of reaction, materials are cheap and easy to obtain, operation is simple, aftertreatment is convenient, and the obtained product is high in purity.

The application belongs to the technical field of compound synthesis, and particularly relates to a preparation method of dipyrone with controlled content of 4-N methylene sulfonic acid sodium dipyrone impurity, which comprises the following steps: dissolving 4-formylaminoantipyrine in water, and then adding dimethyl sulfate and lye to react to obtain a methylation liquor; the obtained methylation liquor is hydrolyzed and neutralized, and then is left to stand and separate into layers, the upper 4-methylaminoantipyrine oil is cooled and crystallized to obtain 4-methylaminoantipyrine solid; the obtained 4-methylaminoantipyrine solid, ethanol, sodium pyrosulfite, activated carbon and formaldehyde are mixed to react to obtain dipyrone; the mass percentage of 4-aminoantipyrine in the 4-formylaminoantipyrine is not more than 1.5%. The content of 4-N methylene sulfonic acid sodium dipyrone (unknown impurity) in the prepared dipyrone is less than or equal to 0.05%, which meets the requirements of the European Pharmacopoeia.

This invention relates to the field of organic synthesis technology, specifically to a method for preparing methylated aminocaprolactam and its application, as well as a cleaning / sterilizing material. In the presence of a catalyst, aminocaprolactam and / or its derivatives are contacted with methanol and subjected to a methylation reaction to obtain methylated aminocaprolactam; wherein the methylated aminocaprolactam includes methylaminocaprolactam and / or dimethylaminocaprolactam. This preparation method uses only aminocaprolactam and / or its derivatives with methanol as the reaction system, without alkylating agents, and has advantages such as controllable selectivity of the target product and a green and safe reaction process.

This invention discloses a desmethylmenoprenone methyltransferase mutant, its construction method, and its applications, belonging to the field of biotechnology. Desmethylmenoprenone methyltransferase is a key enzyme in the MK-7 biosynthetic pathway, responsible for catalyzing the methylation reaction of desmethylmenoprenone to generate a series of methylnaphthoquinone (MK) products, ultimately forming MK-7. This invention, through metabolic network regulation and rational design, successfully obtained 19 single-point mutants, among which 5 mutants showed significantly higher catalytic efficiency than the wild-type enzyme. Experimental results show that the recombinant engineered bacteria constructed based on these mutants exhibit significant advantages in the whole-cell catalytic production of vitamin K2 (MK-7), with MK-7 yield increased by more than 20% compared to the wild-type strain. The excellent catalytic performance of the menG mutant provided by this invention provides strong technical support for the industrial production of vitamin K2, and has broad application prospects and market value.