225 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 invention relates to a suzertraline intermediate as well as a preparation method and application thereof, and particularly provides a suzertraline intermediate 3, 4-difluoro-2-methoxyphenylacetic acid compound and a preparation method thereof, and the suzertraline intermediate can be used for preparing 3, 4-difluoro-2-methoxyphenylacetic acid. Specifically, 2, 3, 4-trifluoronitrobenzene which is low in price and easy to obtain serves as a starting raw material, 3, 4-difluoro-2-methoxyphenylacetic acid is prepared through a substitution reaction, a methylation reaction, a reduction reaction, a Meerwein arylation reaction and a hydrolysis reaction, the method is mild in reaction condition, a reaction substrate better meets the economic and environment-friendly requirements, reaction operation and a post-treatment process are safe and simple, and the method is suitable for industrial production. The purification steps are simple and convenient, byproducts are few, a target product with high purity can be obtained conveniently, corrosion to equipment is small, special equipment is not needed, and the method is suitable for industrial production.

The invention belongs to the technical field of synthesis and preparation of high-molecular optical materials, and particularly relates to a multi-mercaptothiol composition as well as a preparation method and application thereof. According to the present invention, the three-step synthesis route of the tetrahydroxymethylation reaction, the thiol precursor introduction and the deprotection is adopted, the reaction conditions are mild, the steps are clear, the yield is high, the complexity of the traditional synthesis route is avoided, the production cost is reduced, and the industrial production is easily achieved. In the aspect of refractive index regulation and control, the compound contains a plurality of sulfur atoms, the coating is endowed with the characteristic of high refractive index, accurate regulation of the refractive index can be realized by adjusting the formula of the composition, the requirements of different optical applications are met, and the application range of the material is widened. The prepared optical coating has excellent light transmittance, light loss can be reduced to the maximum extent, and the efficient performance of an optical device is ensured; meanwhile, the haze value of the coating is low, the light scattering phenomenon is effectively avoided, and the imaging definition and the precision of an optical system are guaranteed.

The invention provides a method for synthesizing N-methylated polypeptide, which comprises the following steps: dissolving a carboxylic acid compound, N-methyl amino-acid ester hydrochloride or N-methyl amino-acid ester, an alkaline substance and pivaloic anhydride in an organic solvent, reacting at 15-80 DEG C for 3-10 hours, and post-treating the obtained reaction liquid to obtain an N-methyl dipeptide compound, the method comprises the following steps: removing a protecting group in an N-methyl dipeptide compound to obtain a free-state N-methyl dipeptide compound, and condensing the free-state N-methyl dipeptide compound and amino acid or N-methyl amino-acid ester protected by amino to obtain the N-methylated polypeptide, the mixed anhydride intermediate is formed in situ, and the reaction is completed in one step; according to the method, trimethylacetic anhydride is used as a condensing agent, the structure is simple, the reaction is safe, cheap and non-toxic, a large amount of nitrogen-containing byproducts are not generated in the reaction, and purification is convenient; the method is high in stereoselectivity, and racemization is avoided; according to the method, environment-friendly solvents such as ethyl acetate can be used, the reaction condition is mild, and the reaction time is short.

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 provides a preparation method of (S)-(+)-1-methoxy-2-propylamine hydrochloride, which comprises the following steps: taking (S)-(+)-2-amino-1-propanol as a raw material, carrying out halogenation reaction and amino protection, then carrying out methylation reaction with methanol, and finally carrying out amino deprotection by using hydrochloric acid to obtain the product (S)-(+)-1-methoxy-2-propylamine hydrochloride. The method is suitable for industrial production.

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 relates to a method for producing mecobalamin by using a micro-channel reactor, which comprises the following steps: firstly, introducing a reaction mixed solution of cyanocobalamin, cobalt chloride, sodium borohydride and purified water into a first micro-channel reactor for reduction reaction; the obtained cyanocobalamin solution in the reduction state is introduced into a second microchannel reactor to be subjected to a methylation reaction with a trimethylsulfoxide iodide solution, and finally, an obtained mecobalamin solution is subjected to post-treatment to obtain a finished product. Compared with the prior art, the micro-channel reactor is used for continuous production, the mass and heat transfer effect is good, the reaction temperature can be accurately controlled, side reactions are further reduced, and the product quality is effectively improved.

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 provides an aminomethylation reaction method based on a pyrazolo [1, 5-a] pyrimidine nitrogen-containing fused heterocycle substrate, a product and application, and belongs to the technical field of chemistry. Pyrazolo [1, 5-a] pyrimidine nitrogen-containing fused heterocycle, secondary amine and glyoxylic acid are used as raw materials, an aminomethylation reaction is achieved at the C3 site of pyrazolo [1, 5-a] pyrimidine through heating for the first time, a transition metal catalyst or a chemical oxidizing agent is not needed, the drug purification problem caused by metal residues and oxidation byproduct pollution are avoided, and the purity of the product is improved. The method is a novel efficient, simple, convenient and environment-friendly nitrogen-containing fused heterocyclic aromatic hydrocarbon functionalization strategy, the reaction can be directly carried out at the temperature of 100-120 DEG C, shielding gas does not need to be filled, and compared with some reactions needing high-temperature or high-pressure conditions, the mild reaction conditions are easier to control, side reactions are reduced, and the yield of the target product is increased. Meanwhile, the reaction conditions are also beneficial to reducing energy consumption, and conform to the concept of green chemistry.

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%.

A preparation method of the methacrylated gelatin with the dual functions comprises the following steps: firstly, preparing collagen methylated polymethacrylate, then mixing 5% of collagen methylated polymethacrylate, 0.2% of trimethylbenzoyl phosphonate, 10 mg / ml of a herba houttuyniae extract and 20 micrograms / ml of nifedimab, and carrying out uniform mixing, so as to obtain the methacrylated gelatin with the dual functions, the collagen methylated polymethacrylate and the trimethylbenzoyl phosphonate, the herba houttuyniae extract, the nifedimab and the collagen methylated polymethacrylate, the herba houttuyniae extract and the nifedimab. The methacrylated gelatin is prepared under ultraviolet irradiation, and the loose cross-linked network structure of the methacrylated gelatin can realize continuous release of drugs, so that the demand of continuous and stable drug delivery is met; in addition, the gelatin methacrylamide, the herba houttuyniae extract and the nintedanib are combined to relieve hemorrhagic intestinal adhesion and can regulate inflammation and anti-fibrosis functions.

The invention particularly relates to 4 '-thiosugar and a preparation method thereof. The preparation method comprises the following steps: taking D-ribose as a raw material, firstly carrying out methylation protection on C1-site hydroxyl, and then carrying out benzylation protection on other hydroxyl; the preparation method comprises the following steps: firstly, carrying out hydrolysis on a glucosidic bond at a C1 site, carrying out reduction through hydroboron to obtain open-loop ribitol (formula V), carrying out sulfonic acid esterification and bromination substitution on hydroxyl of the ribitol, forming a sulfur bridge bond by taking sodium sulfide as a nucleophilic reagent to obtain benzyl-protected thiosugar, oxidizing a thioether bond into sulfoxide, rearranging to obtain acetoxy thioether, and carrying out debenzylation reaction and hydroxybenzoylation reaction to obtain the high-purity acetoxy thioether. According to the present invention, the multi-step intermediate reaction only needs simple purification, the key intermediate can be obtained through recrystallization, the method is simple, the yield is high, the amplification production is convenient, and the obtained 4 '-thiosugar as the basic sugar can participate in the reaction with a variety of basic groups to form the sulfur-containing nucleoside so as to provide the good foundation for the subsequent drug development or activity screening.

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 present invention relates to the combination of a compound of formula (I) as described herein with an hypomethylating agent (HMA) for use for the prevention and / or treatment of cancer, in particular acute myeloid leukemia (AML), and AML-related myeloid diseases. The present invention further relates to a pharmaceutical composition comprising a compound of formula (I) as described herein with an HMA.

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.