653 results about "Transmethylation" patented technology

The invention concretely relates to a synthetic technology for pyraclostrobin. The synthetic technology comprises: firstly performing cyclization to obtain 1-(4-chlorophenyl)-pyrazol-3-one, oxidizing the pyrazol ring under the effect of an oxidant to generate 1-(4-chlorophenyl)-3-hydroxypyrazole, then using 2-nitrobenzyl bromide to performing etherification to generate 1-(4-chlorophenyl)-3-[2-(nitrophenyl)methoxy]-1H-pyrazole, then using a reducing agent to perform nitro reducing, so as to generate N-hydroxyl-2-[N'-(4-chlorophenyl)pyrazol-3'-yloxymethyl]aniline, then using ClCO2CH3 to perform N-acylation reaction to generate methyl N-hydroxyl-N-2-{[N'-(4-chlorophenyl)pyrazol-3'-yloxymethyl]phenyl}formate, and finally performing hydroxyl methylation under an alkaline condition to generate pyraclostrobin. The technology enables all operations in the pyraclostrobin preparation process to be relatively controllable, helps to improve the stability of the preparation process and improve the product yield, successfully employs low-cost reagents and substantially reduces production cost, and also the employed reagents are relatively small in toxicity, is relatively beneficial for environment protection, and has no corrosivity on plastic pipes, so that the production safety is improved.

A pharmaceutical composition useful as a preventive or therapeutic agent for immune-related diseases. The pharmaceutical composition includes at least HMG-COA reductase inhibitor and at least one amino alcohol compound having the following formula (I), a pharmacologically acceptable salt thereof, or a pharmacologically acceptable ester thereof wherein R1 and R2 each represents hydrogen; R3 represents lower alkyl or hydroxymethyl; R4 represents hydrogen, alkyl, alkoxy or halogen; R5 represents hydrogen, halogeno, cyclohexyl or phenyl; X represents vinylene (CH═CH), oxygen, sulfur or methylated nitrogen; Y represents a single bond, oxygen, sulfur or carbonyl; Z represents a single bond or C1-C8 alkylene; n is 2 or 3.

The present invention pertains to a composition comprising Ibogaine, an indole alkaloid, its active salts and its principal metabolite noribogaine, a demethylated form of ibogaine, for the treatment of hepatitis C and hepatitis C related complications, administered in single or multiple dose regimens effective to reduce somatic complaints, liver enzyme values and viral load caused by chronic hepatitis C in patients, and methods of using the same.

Compounds and compositions of azacytosine analogs and derivatives are provided. In one aspect of the invention, analogs or derivatives of decitabine and azacitidine are provided with modification at the 2-, 4-, or 6-position of the triazine ring, at the 1′-6′position of the ribose ring, or combinations thereof. Methods of using, synthesizing and manufacturing these analogs and derivatives are also provided. These compounds can be formulated into pharmaceutical compositions that can be used for treating any disease associated with aberrant DNA methylation, or a disease or condition that is sensitive to the treatment with decitabine or azacitidine, such as hematological disorders, tumors and cancers.

Alkoxy aromatic compounds are conveniently dealkylated to the corresponding phenolic compounds by treatment with aluminum chloride / N,N-dimethyl aniline complex. Aromatic poly O-demethylation is a unique feature of this invention. This process is applicable to the manufacture of polyphenols such as Resveratrol, Oxyresveratrol, Gnetol.

A process is provided for the production of xylenes from reformate. The process is carried out by methylating under conditions effective for the methylation, the benzene / toluene present in the reformate outside the reforming loop, to produce a resulting product having a higher xylenes content than the reformate. Greater than equilibrium amounts of para-xylene can be produced by the process.

The invention discloses a method for synthesizing tetrabenazine. The method comprises: step one, using a dimethylamine aqueous solution and a formaldehyde aqueous solution as initial materials to be reacted1 to obtain tetramethyl methane diamine; step two, dissolving the tetramethyl methane diamine obtained in the step one in an organic solvent, dropwise adding acetyl chloride and 5- methyl-2-hexanone, and performing amine methylation to obtain an intermediate 3-[(dimethyl amino) methyl]-5-methyl-2-hexanone; and step three, reacting the 3-[(dimethyl amino) methyl]-5-methyl-2-hexanone obtained in the step two with 6,7-dimethoxy-3,4-dihydroisoquinoline hydrochloride to obtain the tetrabenazine. According to the method for synthesizing tetrabenazine, the cheap and accessible materials are used as the initial materials, imine salts serve as amine methylation reagents to perform amine methylation reaction on the 5- methyl-2-hexanone, and accordingly, the region-selectivity of chemical reactions is improved; and water serves as a reaction solvent to prepare the tetrabenazine, so that the operation is simple and convenient, no complex post-processing process exists, and good industrial application prospects are provided.

The present invention provides a synthetic process for the N-demethylation of N-methyl morphinans. In particular, the invention provides improved synthetic methods for the preparation of N-demethylated morphinan compounds that may be employed as starting materials, for example, commonly available N-methyl opiates such as oripavine and thebaine, and C(3)-protected hydroxy derivatives of oripavine.

The invention relates to a method for preparing Decitabine. The particular proposal for solving the technical problem is as follows: 2-deoxidtion-D-ribose, 10 percent of HCL methanol solution, methoxyacetic acetic anhydride, HMDS, acetic anhydride, tri-silicyl tri-fluorine methane sulfonic acid ester, acetic acid amine, etc. are adopted as raw materials to synthesize the Decitabine; the target product of the Decitabine is obtained through the five steps of reactions, namely, methylation, acylation, trimethyl silication, ammoniation and deacylation with a total yield of above 18.4 percent and a product purity of above 99.7 percent.

Methods are disclosed for producing C8 aromatic hydrocarbons. Representative methods comprise (a) fractionating an aromatic hydrocarbon containing feed stream (e.g., a feed stream comprising C9 and / or C10 aromatic hydrocarbons), to provide at least one methylated aromatic hydrocarbon-enriched fraction; and (b) reacting at least a portion of the at least one methylated aromatic hydrocarbon-enriched fraction in a transalkylation reaction zone to provide a transalkylation effluent comprising the C8 aromatic hydrocarbons. The presence of a methylated aromatic hydrocarbon-enriched fraction in the inlet stream to the transalkylation reaction zone provides a number of advantages as described herein.

Enantiomers of S-adenosyl-l-methionine, their stable salts and their uses are described. These compositions possess potent activity in treating various conditions involving hypomethylation and transulfuration reactions and are valuable for use as active constituents in pharmaceutical compositions.

The invention relates to a chemical synthesis method of ticagrelor key intermediate 2-[[(3aR, 4S, 6R, 6aS)-6-aminotetrahydro-2,2-dimethyl-4H-cyclopenta-1,3-dioxolane-4-yl] oxy]ethanol (a key intermediate A). The method comprises the following steps: taking D-ribose as a raw material, and carrying out ten chemical reaction steps of 1-locus methylation and 2,3-loci isopropylidene protection, 4-locus derivatization, iodination, furan ring-opening, hydroxylamine reaction, palladium on carbon catalytic hydrogenation, amino Cbz protection, hydroxy protection, sodium borohydride reduction ester, Cbz removal protection and the like, thereby obtaining the key intermediate A. The raw materials are cheap and readily available, the preparation process is high in operability, steps of optical resolution, chiral induction and the like are avoided, the total yield is relatively high, and the product quality is better; particularly due to the use of sodium borohydride reduction ester, the preparation cost of ticagrelor is greatly reduced; and the method is suitable for large-scale industrial production.

The invention relates to a method for realizing selective N-methylation of primary amine, which comprises the following steps: in a nitrogen gas protective atmosphere or in the air, adding a primary amine derivative, a metal iridium or ruthenium complex, methanol and alkali into a reaction vessel; reacting the reaction mixture at 100-150 DEG C for several hours, and then cooling to room temperature; and performing rotary evaporation to remove the solvent, and then performing column separation to obtain a target compound. Compared with the prior art, the reaction shows the following remarkable advantages: 1) the methanol is used as an alkylation agent, thereby avoiding the use of virulent haloalkane and dimethyl sulfate; 2) the reaction only generates water as the byproduct, thereby causing no environmental hazard; 3) the reaction is high in atom economy; 4) the reaction shows absolute selectivity, and the reaction only generates mono-methyl products and generates no bis-methyl products; and 5) the reaction shows wide substrate universality and is effective for various primary amine derivatives.

The invention provides a synthetizing method of lacosamide. The method comprises the steps of: based on D-serine as a raw material, performing an acylation reaction with acetic anhydride and then performing a condensation reaction with benzylamine; and finally, performing a methylation reaction with dimethyl sulfate, thereby obtaining lacosamide, wherein N,N' dicyclohexylcarbodiimide (DCC) or N,N' carbonyl diimidazole (CDI) is used as a catalyst in the condensation reaction; and a phase transfer catalyst including triethyl benzyl ammonium chloride (TEBA), tetrabutylammonium chloride (TBAC), tetrabutylammonium bromide (TBAB) or tetrabutylammonium hydrogen sulfate (TBAHS) is adopted in the methylation reaction. The method has the advantages of being simple in synthetizing process, moderate in reaction condition, simple in after-treatment, high in yield and high in product purity.

The invention provides a method for synthesizing methoxyamine hydrochloride and includes the following steps: ethyl acetate and hydroxylamine hydrochloride are added into a reaction vessel and 10 to 30 percent of sodium hydroxide solution is instilled for oximation reaction; then dimethyl sulfate is instilled, and at the same time sodium hydroxide solution with the mass fractions of 10 to 30 percent is instilled for methylation reaction; cold water is added after the temperature is decreased and a halohydrocarbon solvent is adopted for extraction; pressure is reduced under the temperature of 30 to 50 DEG C to recover the halohydrocarbon solvent and the product obtained is added into inorganic acid solution for hydrolysis reaction; after the hydrolysis is over, hydrochloride is used to obtain the product methoxyamine hydrochloride. The synthetic method which is simple improves the operation environment and increases the yield ratio.

Medicinal compositions for treating or preventing diabetes, rheumatoid, diseases wherein inflammation should be inhibited, diseases wherein alpha-glycosidase should be inhibited, diseases wherein the synthesis of prostaglandin should be inhibited, diseases wherein endotoxin shock should be inhibited, diseases wherein the production of interleukin should be inhibited, diseases wherein the production of heme oxygenase should be induced, and diseases wherein the production of tumor necrosis factor or carcinogenesis should be inhibited, which contain as the active ingredient at least one compound selected from the group consisting of 3,6-anhydrogalactopyranose represented by formula (I), its aldehyde, its hydrate and 2-O-methylated derivatives and 2-O-sulfated derivatives thereof.

The invention relates to the field of medicinal chemistry and pharmacotherapeutics and provides a 2-substituted arylethenyl-N-methylated quinoline derivative, a synthesis method thereof and an application of the 2-substituted arylethenyl-N-methylated quinoline derivative to the preparation of a drug for treating Alzheimer disease. The 2-substituted arylethenyl-N-methylated quinoline derivative has the chemical formula shown in the specification, wherein R1 in the formula is hydrogen, methylpiperazine, piperidine, morpholine, ethoxylpiperazine, dimethylaminoethylpiperazine or dimethylaminopropylpiperazine; R2 is para-substituted chlorine, fluorine, hydroxyl, methoxyl, dimethylamino, diethylin, methylpiperazine and morpholine, or ortho-substituted hydroxyl and methoxyl or meta-substituted methoxyl and nitro; R4 is hydrogen, chlorine, fluorine, hydroxyl, methoxyl, dimethylamino, diethylin, methylpiperazine or morpholine; R2 and R6 are hydrogen, hydroxyl or methoxyl; R3 and R5 are hydrogen, methoxyl or nitro. Experiments prove that the 2-substituted arylethenyl-N-methylated quinoline derivative provided by the invention has anticholinesterase activity, anti-Abeta aggregation and antioxidant activity.

The present invention is related to a novel process for the preparation of amisulpride (I) which involves: methylation of 4-amino-salicylic-acid (VI) with dimethyl sulphate and base, optionally in presence of TBAB to obtain 4-amino-2-methoxy methyl benzoate (VII) and (ii) oxidation of 4-amino-2-methoxy-5-ethyl thio benzoic acid (IX) or 4-amino-2-methoxy-5-ethyl thio methyl benzoate (X) with oxidizing agent in the presence of sodium tungstate or ammonium molybdate to give 2-methoxy-4-amino-5-ethyl-sulfonyl benzoic acid (IV) or 2-methoxy-4-amino-5-ethyl-sulfonyl methyl benzoate (XI) respectively.

The invention relates to a synthetic method of 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid, which belongs to the synthetic methods of heterocyclic compounds containing 1,3-thiazole ring. The synthetic method is characterized by comprising the following operation steps: 1) homogeneous oximation reaction: preparing 2-hydroxamic ethyl acetoacetate; 2) methylation reaction: preparing 2-methoxyimino ethyl acetoacetate; 3) triphosgene chlorination reaction: preparing 4-chloro-2-methoxyimino ethyl acetoacetate; 4) cyclization reaction: preparing 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid ethyl ester; 5) hydrolysis: preparing a crude product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid; and 6) refining: preparing a product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid. The invention provides an oximating agent system which is applicable to homogeneous nitrosification reaction. The invention provides a triphosgene chlorinating agent which has the advantages of small toxicity, safe and convenient storage, transportation and use, easy control of process operation and high yield. The yield of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid ethyl ester is not less than 95.4%; the yield of the crude product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 94.4%; and the yield of the finished product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 90.5%. The purity of the finished product of the 2-(2-amino-4-thiazolyl)-2-(Z)-methoxyimino acetic acid is not less than 99.06%, and the melting point is 182.1 DEG C-183.9 DEG C. The synthetic method is used for synthesizing raw materials of the third generation of cephalosporins.

The invention discloses a novel method for synthesizing a 1,2,3-thiadiazole-5-formamidine compound. The target compound shown in general formula TDCA is prepared from a compound as shown in general formula M by virtue of a methylation reaction. The target component as shown in the general formula M is prepared from a compound as shown in general formula A and a compound as shown in general formula N by virtue of a condensation reaction, wherein during the methylation reaction, preferably, a catalyst is an organic metallic catalyst consisting of cuprous iodide and a ligand, namely 2,2,6,6-tetramethyl-3,5-heptadione; during the reaction, preferably, dimethylbenzene is taken as a solvent, and the optimum reaction temperature is 100-140 DEG C. The method disclosed by the invention is high in yield and more environment-friendly (as shown in Specification).

The present invention provides a synthetic process for the N-demethylation of N-methyl morphinans. In particular, the invention provides improved synthetic methods for the preparation of N-demethylated morphinan compounds that may be employed as starting materials, for example, commonly available N-methyl opiates such as oripavine and thebaine, and C(3)-protected hydroxy derivatives of oripavine.

The invention provides a new technology for recycling metribuzin methylated mother liquor. The technology uses bromomethane as methylating agent to react with triazone under alkaline condition and obtain metribuzin; and methylated mother and bromine are recycled for cyclic utilization, thus achieving the aim of the reutilization of wastewater. The inorganic salt content and discharge amount of waste water in methylating working section can be effectively reduced, and the difficulty and cost of treating waste water are largely reduced. The invention has good environmental benefit, social benefit and economic benefit.

A supplement composition for enhancement of methylation process is provided, which contains vitamin B6 (as pyridoxine HCl), folic acid, vitamin B12 (as cyanocobalamin), betaine HCl, and methylsulfonylmethane; and also contains S-adenosylmethionine. The supplement composition further includes silymarin (from milk thistle seed extract), N-acetyl L-cysteine, and cruciferious blend which includes broccoli (brassica oleracea var. talica), kale (brassica oleracea var. acephala), and radish (raphanus sativus). Further provided is a method of using the supplement composition for enhancement of methylation process.

The invention discloses a method for preparing epsilon-caprolactone. After cyclohexanone, co-oxidation agents, catalysts, radical initiators and solvents are mixed, reaction is performed in air atmosphere, the co-oxidation agents are methylbenzene compounds, the catalysts are at least one of nitrates or oxides of Co, Fe and Cu, the solvents are at least one selected from 1, 2-dichloroethane, ethyl acetate and acetonitrile, and the method for preparing the caprolactone further co-produces aromatic aldehyde and aromatic acid. The method for preparing the epsilon-caprolactone takes aromatic methyl compounds as the co-oxidation agents, benzaldehyde is replaced, production cost is remarkably reduced, industrial production of the epsilon-caprolactone prepared by an oxygen / air oxidation method is possible, and the aromatic aldehyde and the aromatic acid are further co-produced when the epsilon-caprolactone is prepared by the method, so that the method had higher values in industrial application.

The invention discloses a novel synthesizing method of dapoxetine, wherein a series of reactions are carried out on trans-cinnamaldehyde and N-carbobenzoxy hydroxylamine which serve as initiative raw materials under the action of a self-prepared catalyst (s)-alpha-alpha-diisopropyl dimethyl tert-butyl silicon oxygroup prolinol, so that an important intermediate of the dapoxetine, namely an important chiral intermediate (S)-3-amino-3-phenyl propyl alcohol (compound 4), is obtained. The invention further discloses a preparation method of capecitabine, wherein the compound serving as a raw material is methylated and protected by hydroxyl and then reacts with 1-naphthol to form a salt, so that the capecitabine is obtained. The preparation method is easy in raw material obtainment, good in stereoselectivity and high in yield, thereby being suitable for industrial production.

The present invention relates to DOT1L inhibitors. The present invention also relates to pharmaceutical compositions containing these compounds and methods of treating disorders in which DOT1-mediated protein methylation plays a part, such as cancer, by administering these compounds and pharmaceutical compositions to subjects in need thereof.

The invention relates to methods for preparing and using laminine and pharmaceutically acceptable salts thereof. L-lysine is used an initiative material, and the method comprises the following steps of: protecting alpha-amino groups and carboxyl with metallic salts under an alkaline condition to form a chelate complex; performing separation and purification to obtain the chelate complex with the purity of 99 to 100 percent, and performing methylation on the chelate complex on epsilon-amino groups under the action of a phase transfer catalyst with a methylating agent to generate trimethyl lysine salts; removing metallic ions with a precipitator or chelating agent to obtain crude laminine and crude pharmaceutically acceptable salts thereof; and re-crystallizing the crude laminine and the crude pharmaceutically acceptable salts thereof with a solvent to obtain the medicinal laminine and the pharmaceutically acceptable salts thereof. The methylation of the separated and purified L-lysine metallic ion chelate complex and the phase transfer catalyst are simultaneously adopted, so the method remarkably reduces the generation of monomethyl substances, dimethyl substances and other byproducts, improves the yield and achieves the product purity of over 98.5 percent (HPLC).

The present invention relates to a method comprising the step of contacting under hydroaminomethylation conditions, an olefin, an amine, a rhodium-phosphorous ligand, and synthesis gas (syngas). In particular, it has been discovered that, under some circumstances, a neutral rhodium-monodentate phosphite ligand is prescribed. The invention provides a simple way of making, in high yields and regiospecificity, a variety of products, including pharmacologically active products such as ibutilide, terfenadine, and fexofenadine, and derivatives thereof.