55 results about "N methylation" patented technology

The invention relates to a new synthesis technology of anti-cancer drug Raltitrexed. The technology comprises the following steps: 1) using L-glutamic acid as raw material to perform esterification with alcohol under the action of halogenating agent and obtain L-glutamic acid diester hydrochloride; 2) using 2-amino-5-methyl-benzoic acid as raw material to prepare 6-bromomethyl-3,4-dihydro-2-methyl-4-oxo-6-quinazoline through cyclization, amination and bromination; 3) using 2-thienyl-propanedioic acid as raw material to prepare N-[5-[N-(tert-butoxycarbonyl)-N-methylamino]-2-thenoyl]-L-glutamic acid diethyl ester through nitrification, esterification, reduction, amino protection, N-methylation and device-esterification; 4) using L-glutamic acid diester hydrochloride and N-[5-[N-(tert-butoxycarbonyl)-N-methylamino]-2-thenoyl]-L-glutamic acid diethyl ester to prepare N-[5-(N-methylamino)-2-thenoyl]-L-glutamic acid diester through dehydrant condensation and deamination protection; and 5) using N-[5-(N-methylamino)-2-thenoyl]-L-glutamic acid diester and 6-bromomethyl-3,4-dihydro-2-methyl-4-oxo-6-quinazoline to perform condensation under the catalysis of alkali, recycling preparative chromatography, purifying, and performing de-esterification to obtain Raltitrexed.

The synthesis of anticancer medicine Raltitrexed with 2, 5-thienyl diformic acid and diethyl glutamate as initial material and through six reaction steps of monocondensation, rearrangement, N-methylation, e;limination of tert-butoxy carbonyl group, condensation with 6-bromomethyl-2-methyl-4-quinbolone and saponification. The present invention has total yield of 18.1%, higher than that of available synthesis line, less reaction steps, mild condition and simple operation, and is suitable for mass production.

The invention discloses a preparation method of dextromethorphan ((+)-3-methoxy-17-methyl-(9 alpha,13 alpha,14 alpha)-levorphane, I). The method comprises the following steps that a dextromethorphan intermediate (+)-1-(4-methoxy) benzyl-1,2,3,4,5,6,7,8-octahydro-isoquinoline (II) conducts N-benzylation reaction with a benzylation reagent under alkaline conditions to form (+)-1-(4-methoxy) benzyl-N-benzyl-1,2,3,4,5,6,7,8-octahydro-isoquinoline (III); the intermediate (III) is subjected to acid cyclization reaction to form (+)-3-hydroxy-17-benzyl-(9 alpha,13 alpha,14 alpha)-levorphane, (IV); the intermediate (IV) reacts with dimethyl sulfate or methine halide, and is subjected to O-methylation and N-methylation reaction to form (+)-3-methoxy group-17-benzyl-17-methyl-(9 alpha,13 alpha,14 alpha)-levorphane quaternary ammonium salt (V); (V) is subjected to catalytic hydrogenation reaction; benzyl is removed; and dextromethorphan (I) is obtained. Therefore, the preparation method can use a common and cheap methylation reagent to substitute an unusual methylation reagent such as phenyltrimethylammonium hydroxide, and the yield of reaction can be increased.

The invention discloses a series of substituted carbazole-imidazolate or benzimidazolium salt compounds with a general structure represented by formula I or II, and a preparation method thereof. According to the preparation method, carbazole is taken as a raw material, and the target compound is obtained via five steps including N-methylation, acylation, reduction, combination with imidazole, and salifying. It is shown by results of in vitro antitumor activity cytotoxicity test that the substituted carbazole-imidazolate or benzimidazolium salt compounds possess excellent cytotoxic activity.

The invention provides a method for catalysis of N-methylation of amines by using an iridium complex with methanol as a carbon source, and belongs to the technical field of energy and homogeneous catalysis. The methanol is used as the carbon source, and under the catalysis of the iridium complex, the reaction of N-methylation of various amine substrates is achieved. The method has the advantages that the methanol is used as the carbon source, toxicity is low, the cost is low, obtaining is easy, and economic applicability is higher; an only by-product is water, and requirements of green chemistry in nowadays society are met; the used preparation method of an iridium complex catalyst is easy, the cost is low, and stability is good; N-methylation of various primary amines and secondary aminescan be high-selectively achieved, and the product yield is excellent. The invention provides a green synthetic method for N-methylation reaction of the amines.

The invention belongs to the technical field of photocatalysis synthesis, and particularly relates to a method for implementing amine compound N-methylation by photocatalysis. The method includes the steps: 1) adding photocatalyst TiO2 and N-methylation carbon sources into a photocatalysis reactor to form a reaction system, and stirring the reaction system under ultraviolet irradiation; 2) adding reducing agents and amine compounds into the reaction system obtained in the step 1), and continually stirring mixture under ultraviolet irradiation to obtain N-methylation products. Compared with the prior art, the preparation method has the main advantages that selected raw materials are low in cost and toxicity, reaction conditions are mild, energy consumption is less, used catalysts are low in cost and easy to obtain, reaction operations are simple, and products are high in yield and good in selectivity.

The present invention relates to an improved process for preparation of Rivastigmine of formula (I) or pharmaceutically acceptable salts thereof comprising a step of N-methylation of compound of formula (III), wherein R₁=R₂=H or R₁=H and R₂=CH₃ or an acid addition salt thereof, using paraformaldehyde in the presence of Raney Nickel and hydrogen in a suitable solvent to obtain compound of formula (II).

The invention relates to a binuclear rhodium complex containing an ortho-carborane structure and preparation and application thereof. The preparation method of the rhodium complex comprises the following steps: 1) adding an n-BuLi solution into an ortho-carborane solution, and then reacting for 30-60 min at room temperature; 2) adding selenium and reacting for 1-2h at room temperature; 3) adding [Cp*RhCl2]2, reacting at room temperature for 3-6h, and performing post-treating to obtain the rhodium complex; and the rhodium complex is used to catalyze arylamine N-methylation reaction to prepare arylamine N-methylated derivatives. Compared with the prior art, the preparation method of the binuclear semi-sandwich rhodium complex containing the ortho-carborane structure is simple and green, has excellent selectivity and higher yield, and the prepared rhodium complex has higher catalytic activity at room temperature, can be used for catalyzing aromatic amine N-methylation reaction to prepare the aromatic amine N-methylation derivatives, has high catalytic reaction yield, and has wide industrial application prospect.

The invention discloses a method for preparing dextromethorphan (I), which comprises the following steps: performing N-methylation by an intermediate ent-3-methoxymorphinan (II) to generate the dextromethorphan (I). The preparation method is simple and convenient, and favorable for reducing the production cost of the dextromethorphan and can improve the quality of the product.

The invention discloses a preparation method of pemetrexed disodium, which can directly hydrolyzing into salt after an organic solvent is removed, rather than salifying together with p-toluenesulfonic acid and/or purifying a product by adopting a crystallization method during the preparation process, thus omitting the step of salifying together with p-toluenesulfonic acid and/or crystallization through ethanol, effectively improving the total yield of drugs to 68-75%; in the preparation process, a peptide condensing agent is firstly prepared and is fully reacted with pemedolac in the organic solvent into transient-state acid ester, so that the generation of N-methylation impurities can be effectively inhibited in the reaction together with L-glutamic acid diethyl ester hydrochloride, the defect that the content of N-methylation impurities during the one-pot preparation process in the prior art exceeds 0.1% can be avoided, the advantages for opening up Europe and America markets can be brought, the defect that the raw materials are not reacted thoroughly to cause high cost can also be overcome; the HPLC (High Performance Liquid Chromatograph) of the finished pemetrexed disodium obtained by adopting the method is more than or equal to 99.8%, and the content of single impurities is less than 0.1%.

The invention relates to an improved production process of 1, 3-Dimethyl-3, 4, 5, 6-tetrahydro-2(1H)-pyrimidinone, which is improved on the basis of a prior production process of 1, 3-Dimethyl-3, 4, 5, 6-tetrahydro-2(1H)-pyrimidinone. In the invention, in a step of synthesizing pyrimidone midbody, a carbon dioxide (or urea)high-temperature and high-pressure method is adopted so as to solve the problems of production process of pyrimidone midbody, environmental pollution of organic solvent and production cost; in a step of N-methylation, formaldehyde is used as a reactant to carry out hydrogenation to finish the N-methylation under the condition of an acidic catalyst, so that the problem of corrosion of methanoic acid and the problem of pollution of waste acid and waste water in the prior art are thoroughly solved. The production process is advanced, has no pollution and accords with green high-new fine chemical engineering manufacturing technique which is emphatically supported by the nation.

The invention provides a preparation method of arecoline. On the presence of organic base, reaction raw materials such as nicotinic acid and the like have esterification and alkylation reactions with a compound capable of providing alkyl in the organic solvent, and arecoline can be prepared through a reduction reaction and aftertreatment. Two procedures including esterification and N-methylation are combined, and the process route of preparation of arecoline is shortened. According to the method, the operation conditions are simple, and the intermediate treatment is more convenient; expensive alkyl halide (such as methyl iodide) cannot be used as a reaction raw material, cheaper sulfolipid or phosphate ester compounds are selected, a good implementation effect is also obtained, and the product has a cost advantage.

The invention relates to preparation of important chemical products by using methoxyl groups in lignin. According to a method, methyl provided by the lignin reacts with carbon monoxide and water underthe catalysis effects of catalysts to obtain acetic acid; reaction is performed with aminated compounds to obtain N-methylation products. The methoxyl groups in the lignin are used for preparing important chemical products for the first time; an important and continuous production path is provided for the preparation of various important chemical products.

The invention relates to a 5-methyl-7-amino-5H,7H-dibenzo[b,d]azepin-6-ketone preparation method, wherein the method takes bromoaniline and phenylboronic acid as raw materials, a Suzuki coupling reaction is conducted to get 2-aminobphenyl, amino is protected with ethyl chloroformate, then potassium tert-butoxide is used as an acid-binding agent, the 2-aminobphenyl is subjected to N-methylation with methyl iodide, deprotected with amino, reacted with chloracetyl, and subjected to a Friedel Craft cyclizing hydrocarbylation to get the target product. The 5-methyl-7-amino-5H,7H-dibenzo[b,d]azepin-6-ketone preparation method has the advantages of simple process, high overall yield and low production cost, and is applicable to industrial mass production.

The present invention discloses a production method for 1,2-N,N'dimethylcyclohexanediamine. According to the method, N single protection is performed on o-phenylene diamine and aromatic benzene sulfonyl chloride; methyl iodide or dimethyl sulphate is adopted to carry out a N methylation reaction; N single protection is performed on 1,2-diaminocyclohexane and aromatic benzene sulfonyl chloride, then methyl iodide or dimethyl sulphate is adopted to carry out a N methylation reaction, a hydrolysis reaction is performed in the presence of sulphuric acid to remove aromatic benzenesulfonyl to obtain the target product 1,2-N,N'dimethylcyclohexanediamine. The process of the present invention is simple and easy to operate, and the high purity target product can be obtained with the method of the present invention.

The invention relates to application of a dinuclear rhodium complex in a fatty amine N-methylation reaction. The dinuclear rhodium complex is taken as a catalyst, CH3I is taken as a methylation reagent, and the fatty amine N-methylation reaction is catalyzed in an organic solvent for preparing a fatty amine N-methylation derivative. Compared with the prior art, according to the application of thedinuclear rhodium complex, the dinuclear rhodium complex has high catalytic activity at the indoor temperature and can be used for catalyzing the fatty amine N-methylation reaction for preparing the fatty amine N-methylation derivative, according to the catalytic reaction, the yield (90-97%) is high, and the reaction conditions are mild; participation of strong alkali is not needed, all the reagents have stable performance for air and water, the requirements for reaction equipment are low, and the dinuclear rhodium complex has a wide industrial application prospect.

The present invention relates to the field of cancer. More specifically, the present invention provides compositions

and methods useful for detecting and treating esophageal cancer. In a specific embodiment, a method for identifying a subject having esophageal squamous cell carcinoma (ESCC) comprises (a) extracting genomic DNA from a sample obtained from the subject; (b)

performing a conversion reaction on the genomic DNA in vitro to convert unmethylated cytosine to uracil by deamination; and (c)

detecting nucleic acid methylation of one or more genes in the converted genomic DNA, wherein detecting nucleic acid methylation e identifies the subject as having ESCC. The one or more genes can comprise ZNF542, ZNF132, cg20655070, TAC1 and SLC35F1. In a

more specific embodiment, the one or more genes comprise ZNF542 and ZNF132 and can further comprise detecting the nucleic acid N methylation of one or more of cg20655070, TAC1 and SLC35F1.