41 results about "Methyl-1H-indole" patented technology

The invention relates to a synthetic method of an anti-tumor medicine, namely N-[2-[[2-(dimethylamino) ethyl] methyl amino]-4-methoxy-5-[[4-(1-methyl-1H-indole-3-yl)-2-pyrimidyl] amino] phenyl]-2-acrylamide (AZD9291) and a key intermediate of the anti-tumor medicine. The synthetic method comprises the following steps: performing Boc acid anhydride protection on 4-fluoro-2-methoxy-5-nitroaniline to obtain 4-fluoro-2-methoxy-5-nitroanilino tert-butyl formate, then reacting with N,N,N'-trimethylethylenediamine to obtain 4-(N,N,N'-trimethylethylenediamino)-2-methoxy-5-nitroanilino tert-butyl formate, then reducing to obtain 2-(N,N,N'-trimethylethylenediamino)-4-methoxy-5-tert-butyl carbamate phenylamine, then completely reacting with acryloyl chloride and directly removing a Boc protecting group to obtain 2-methoxy-4-N,N,N'-trimethylethylenediamino-5-acrylamido phenylamine, and finally reacting with 3-(2-chloropyrimidine-4-yl)-1-methylindole to obtain AZD9291. A process disclosed by the invention is simple in step, relatively high in yield, mild in reaction condition and easy for realization of industrial production.

The present invention provides a therapeutic agent for bile duct cancer comprising 5-((2-(4-(1-(2-hydroxyethyl)piperidin-4-yl)benzamide)pyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide or a pharmacologically acceptable salt thereof.

The present application discloses a therapeutic agent for breast cancer, comprising 5-((2-(4-(1-(2-hydroxyethyl)piperidin-4-yl)benzamide)pyridin-4-yl)oxy)-6-(2-methoxyethoxy)-N-methyl-1H-indole-1-carboxamide or a pharmacologically acceptable salt thereof.

This invention discloses a method for preparing sumatriptan succinate. The method comprises: (1) reacting 4-chlorobutyraldehyde and sodium pyrosulfite aqueous solution, filtering and drying to obtain sodium 4-chlorobutane-1,1-disulfonate; (2) heating and reacting 4-hydrazino-N-methyl phenylmethansulfonamide and 4-chlorobutane-1,1-disulfonate in the presence of inorganic acid or organic acid catalyst, neutralizing with an alkali solution, and extracting with an organic solvent to obtain 3-(2-chloroethyl)-N-methyl-1H-indole-5-methansulfonamide; (3) adding phase transfer catalyst into 3-(2-chloroethyl)-N-methyl-1H-indole-5-methansulfonamide, reacting with dimethylamine, extracting, decolorizing, refining to obtain sumatriptan product, dissolving in a solvent under heating, adding succinic acid, reacting, and precipitating the crystal to obtain white sumatriptan succinate. The method has such advantages as short process, easy operation, high yield, low cost and stable product quality.

The invention relates to the field of organic synthesis, in particular to a novel method for synthesizing osimertinib through molecular sieve catalysis. N-1-[2-(dimethylamino) ethyl]-5-methoxy-N1-methyl-N4-[4-(1-methyl-1H-indole-3-yl-2-pyrimidinyl]-1,2,4-triaminobenzene and acrylic acid as raw materials, acrylic acid is added into an alcohol solvent, reaction is carried out through molecular sievecatalysis and microwave heating, and after the reaction is completed, post-treatment is carried out to obtain the osimertinib. According to the method, the reaction conditions are mild, industrial production is facilitated, the raw materials are environmentally friendly in use, used highly toxic raw materials are decreased, the yield is high, and the reaction efficiency is high.

The invention discloses thermosensitive paper and a preparation method thereof. The thermosensitive paper comprises a base paper layer, a precoating layer and a chromogenic layer, wherein the precoating layer and the chromogenic layer are successively formed on the base paper layer; the chromogenic layer is formed by coating with a chromogenic coating, and a chromogenic coating comprises a dye, wherein the dye is at least one of crystal violet lactone, 10-benzoyl-3,7-bis(dimethylamino)phenothiazine, and 7-[4-(diethylamino)-2-(hexyloxy)phenyl]-7-(1-ethyl-2-methyl-1H-indole-3-yl)furano[3,4-B]pyridine-5(7H)-one. Through the method, the amount of a dye and a color developer in the thermosensitive paper can be substantially reduced, and thus adhesion of the dye and the color developer, on a printing head, in the thermosensitive paper in the printing process is reduced, and the printing head is protected to a certain extent.

The invention discloses a method for preparing Osimertinib mesylate. The method comprises the steps that after 3-(2-chlorine-4-pyrimidinly)-1-methyl-1H-indole is subjected to substitution reaction with 4-fluorine-2-methoxy-5-nitroaniline, 3-(2-chlorine-4-pyrimidinly)-1-methyl-1H-indole is subjected to substitution reaction with N,N,N'-trimethyl-ethylenediamine, nitro is restored after catalytic hydrogenation, then 3-(2-chlorine-4-pyrimidinly)-1-methyl-1H-indole is subjected to coupling reaction with 3-chloropropionyl-chloride, osimertinib is obtained after elimination with sodium hydroxide, and osimertinib reacts with salt mesylate in acetone and water to obtain osimertinib mesylate, wherein a catalyst for restoring nitro by the catalytic hydrogenation is raney nickel, palladium carbon or palladium-carbon hydroxide. The method for preparing osimertinib mesylate is low in cost, high in yield, little in environmental pollution, simple and easy in production process operation and suitable for industrialized production.

The invention discloses an industrial production method for bazedoxifene acetate. The production method comprises the following steps: taking p-hydroxy benzaldehyde as a starting material, substituting with chloracetyl-hexamethyleneimine, reducing with borohydride and chlorinating with a chlorinating agent to obtain a compound 4; reacting the compound 4 with 5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole to obtain a compound 5; and carrying out debenzylation to obtain a compound 6, and salifying with acetic acid to obtain a target compound which is the bazedoxifene acetate. The defective workmanship of preparation in the prior art is solved, the used reagent is low in cost and easy to obtain, environmental pollution is small, safety is high, an operation process is simple, and thus, the bazedoxifene acetate is suitable for being produced industrially.

The invention relates to compounds of formula (X), and salts thereof, and their use as intermediates in improved manufacturing processes for the synthesis of pharmaceutical compound of formula (I): X is =0, =N-0H or =N-OC(O)Me; Y is hydrogen, PhS- or p-chlorophenylsulfanyl; Z is hydrogen or -CH2COOR1 wherein R1 is selected from hydrogen, optionally substituted hydrocarbyl and optionally substituted heterocyclyl.

The present invention is related to a process for the preparation of 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-Indole (formula-1, a useful intermediate for the synthesis of bazedoxifene) using 4-benzyloxy propiophenone and 4-benzyloxy phenyl hydrazine hydrochloride.

The invention discloses a preparation method of bazedoxifene. The preparation method comprises the following steps: (a) taking 1-(4-(2-(azepane-1-yl)ethoxy)benzyl)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indole, adding a polar organic solvent, an aprotic lewis acid organic solution and a hydrogen ion provider, and stirring at 0-40 DEG C to obtain a reaction liquid; and (b) separating and purifying the reaction liquid obtained in the step (a) to obtain bazedoxifene. In the method disclosed by the invention, the low-cost and easily available aprotic lewis acid such as boron trifluoride is adopted as a catalyst for preparing bazedoxifene, the reaction conditions are mild, the operation is convenient, the safety is high, and the energy consumption is low; the obtained bazedoxifene has high yield and high purity, and the preparation difficulty and production cost of bazedoxifene are lowered; and the method brings a remarkable positive effect and is very suitable for industrialized use.

A pharmaceutical composition for oral administration comprising a compression coated solid dosage form of a bitter or unpleasant tasting pharmaceutically active agent. Included are compression coated oral dosage forms of 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulphonamide or a pharmaceutically acceptable salt or solvate thereof as active ingredient. The compression coated solid dosage forms are of use in the treatment of conditions associated with cephalic pain, in particular migraine.

The invention belongs to the technical field of medicine and relates to 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione as well as a medical application, a stereoisomer and pharmaceutically acceptable salt thereof. The structural formula of 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl] butyl]piperazine-2,3-dione is represented in the specification; 1-ethyl-4-[4-[5-hydroxy-2-(4-hydroxyphenyl)-3-methyl-1H-indole-1-yl]butyl]piperazine-2,3-dione and pharmaceutically acceptable acid addition salt of the compound can be combined with existing drugs or can be independently used as an estrogen receptor modulator for treating or preventing various estrogen function related diseases such as bone loss, fracture, osteoporosis, hectic fever, LDL cholesterol level rise, cardiovascular disease, cognitive impairment, brain degeneration disease and anxiety, as well as depression, sexual dysfunction, hypertension, retinal degeneration and cancer caused by estrogen deficiency, especially osteoporosis.

The invention provides quinoline for treating cholangiocarcinoma, and an application thereof to preparation of a medical composition for treating tumors, and particularly relates to an application ofquinoline derivative 1-[[[4-(4-fluoro-2-methyl-1H-indole -5-)oxy-6-methoxyquinolin-7-yl]oxy]methyl cyclopropylamine to treatment cholangiocarcinoma: as shown in the description.

A novel process of preparation of a compound of 3-(2-Dimethylamino)-N-methyl-1H-indole-5-methane sulfonamide, which comprises of a reaction 4-hydrazino-N-methyl benzene methane sulfonamide with 4-dimethyl amino butyraldehyde diethyl acetal in a chlorinated solvent in the presence of ethyl poly phosphate and conversion of the crude product to a product of 3-(2-Dimethylamino)-N-methyl-1H-indole-5-methane sulfonamide succinate of extra high purity and colour.

The invention discloses a preparation method for 5-benzyloxy-2-(4-benzyloxyphenyl)-3-methyl-1H-indole as shown in the specification. The preparation method comprises the following steps: (1) subjecting a compound II and a compound III to a condensation reaction in an alcohol solvent under the action of alkali; and (2) mixing a reaction solution obtained in the step (1) with protonic acid and carrying out Bischler-Mohlau indole cyclization. Compared with the prior art, the invention has the following advantages: the condensation reaction in the first step and Bischler-Mohlau indole cyclization at the second step are integrated into a one-pot reaction, so operation is simple and convenient; a reaction product I is directly precipitated from the reaction solvent, so reaction post-treatment is substantially simplified, and high purity and high reaction yield are realized; and the method is applicable to enlarged production.

The invention relates to a preparation method of a biomass derived palladium catalyst and application to synthesis of an anti-tumor drug osimertinib. The preparation method comprises the following process: enabling chitosan and palladium salt to react in the presence of a solvent to form a complex; then cooling to room temperature; drying a solid in vacuum to remove a solvent; under the protectionof argon gas, carbonizing at high temperature to obtain the catalyst; dissolving a raw material N-(2-dimethylamino-ethyl-2-methoxy-N-methyl-N-[4-(1-methyl-1H-indole-3-yl-pyrimidine-2-yl)-5-nitryl-benzene-1,4-diamine and adding the catalyst; stirring at temperature of 0 to 120 DEG C for 5 to 12h; dropwise adding hydrazine hydrate; after completely reacting, cooling to room temperature and filtering; spinning and drying the solvent to obtain a faint yellow solid. The preparation method provided by the invention has the advantages of wide raw material source, relatively low price, moderate reaction conditions and high yield; the catalyst has high activity, high stability, high dispersity of active components and long service life; the catalyst can be repeatedly used for a plurality of timesand the preparation method also has the advantages of short flow, easiness for controlling reaction and simple equipment requirements; complicated post-treatment is avoided and environment pollution is avoided.

The invention discloses a crystal form of N-{2-{[2-(dimethylamino)ethyl](methyl)amido}-6-(2,2,2-trifluoroethoxy)-5-{[4-(1-methyl-1H-indole-3-yl)pyrimidine-2-yl]amido}pyridine-3-yl}acrylamide as well as a preparation method and an application thereof, wherein the X-ray powder diffraction pattern of the crystal form has characteristic peaks when diffraction angles 2[theta] are 6.5 +/-0.2 degrees, 8.2 +/-0.2 degrees, 9.8 +/-0.2 degrees, 11.9 +/-0.2 degrees, 16.4 +/-0.2 degrees, 17.2 +/-0.2 degrees, 19.6 +/-0.2 degrees and 20.3 +/-0.2 degrees. The crystal form is good in stability, simple in preparation method, good in repeatability and suitable for industrial production.

The invention discloses a preparation method for 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine succinate (I), which belongs to the field of preparation of medicament intermediates. The preparation method comprises the following steps of: undergoing a condensation reaction on 3-(2-aminoethyl)-N-methyl-1H-indole-5-methanesulfonamide (III) and a methanol aqueous solution in the presence of ammonium carbonate and methanol, and directly reducing an intermediate product by performing palladium/carbon catalytic hydrogen without separating to obtain 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine (II); at the end of the reaction, recovering a solvent, performing post-treatment to obtain a crude product (II); and recrystallizing to obtain refined 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine (II), undergoing a salt-forming reaction on the refined product and succinic acid in purified water, clarifying the reaction liquid, and adding activecarbon for decolorizing to obtain 3-[2-(dimethylamino)ethly]-N-methylindole-5-methyl sulfonylamine succinate (I). The preparation method has the characteristics of stable process and easiness for controlling.

The invention belongs to the field of medicine synthesis, and particularly relates to a synthesis method of a panobinostat key intermediate. The key intermediate is (E)-3-[4-[[[2-(2-methyl-1H-indole-3-yl)ethyl] amino] methyl] phenyl] methyl acrylate hydrochloride. The method has the advantages that the yield is as high as 85 percent or higher; the impurities are few; the purity is 99.5 percent orhigher; meanwhile, the operation is simple and convenient.