47 results about "Silodosin" patented technology

The invention discloses a preparation method of a silodosin intermediate, wherein the structure of the silodosin intermediate is represented as the formula A. The preparation method, wherein indoline is employed as a start raw material, includes the reactions of Friedel-Crafts acylation, carbonyl reduction, Gabriel reaction and chiral resolution and the like. The preparation method is simple in operation, is low in cost, is high in yield, allows the product to purify easily and is stable in processes, and is suitable for industrial production. The invention also discloses a new intermediate compound which is related in the method.

The invention discloses a novel method for preparing silodosin. In the invention, a complete silodosin synthesizing path is invented. By adopting brand new synthesis methods, intermediates synthesized in each step are brand new compounds, for example, if a Gabriel synthesis method is adopted, primary amine is introduced on the 2-site carbon atom, and chain extending reaction is carried out by utilizing benzyloxy-propyl, and the like. The invention provides the economic and safe path with high purity and high yield, and is suitable for industrial production.

The invention provides a novel optical active compound 5-[(2R)-2-(benzyl amino) propyl]-1-[3-( benzoyloxy) propyl]-7-cyanogroup indoline and a preparation method of the novel optical active compound. The compound can be used as an intermediate for synthesizing silodosin.

The invention provides an optical active compound of 1-(3-benzoyloxy-propyl)-5-(2-(1-phenyl ethyl amine) propyl-7-cyano indoline as well as a preparation method and the application thereof. The optical active compound is shown in a formula (1), comprises a (R,R) configuration and a (S,S) configuration and can be used as an intermediate for synthetizing silodosin. The optical active compound of the single formula (1) can be used for preparing an optical high-purity product and has good yield on the premise of ensuring good optical purity. The preparation method of the optical active compound uses low-cost chiral assistant agent of alpha-phenethylamine and derivatives thereof, has mild reaction conditions, low cost and controllable optical purity and is easy for industrialized production.

The invention discloses a preparation method of a silodosin intermediate. The preparation method comprises the following steps that in an organic solvent, under the action of lewis acid, friedel-crafts acylation reaction occurs between a compound 2 and a compound 3, so as to obtain a compound 4, wherein the lewis acid is one of or more of zinc trifluoromethanesulfonate, bismuth trifluoromethanesulfonate, scandium trifluoromethanesulfonate and aluminum trichloride; under the action of organic acid or boron trifluoride ether complex, the compound 4 reacts with triethyl silicane, so as to obtain a compound 5; the compound 5 reacts with sodium azide, so as to obtain a compound 6; under the action of catalysts, the compound 6 reacts with di-tert-butyl dicarbonate ester and hydrogen, so as to obtain a compound 7; under an acidic condition, the deamination protective reaction of the compound 7 occurs, so as to obtain a compound 8; the compound 8 reacts with L-tartaric acid, so as to obtain a compound 1, namely the silodosin intermediate. The preparation method of the silodosin intermediate has the advantages of simplicity, economy and mild reaction conditions, and chiral resolution is not needed.

The invention provides a preparation method for synthesizing 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline which is a key intermediate of silodosin. The method comprises the following steps: 1-acetylindoline is adopted to serve as the material, and 1-acetyl-7-cyanopyridine-5-(2-amino propyl) indoline can be obtained through the such 7 steps as friedel-crafts acylation reaction, phthalimide amination, alkylsilane reduction, nitrification, reduction, heavy nitrogen cyaniding and deprotection. According to the method, the materials in the whole synthesizing line are cost-saving and easy to obtain, the operation is simple and the operation cost is low. Moreover, the yield rate of each step of reaction is higher than that in the prior art. Therefore, the method provided by the invention is very suitable for industrial production and has larger industrial application value.

The invention relates to a method for preparing silodosin, especially to an industrial preparation method of a silodosin compound, and belongs to the field of pharmaceutical chemical synthesis. The method includes: carrying out salt hydrolysis on 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile tartrate to obtain 5-[(2R)-2-aminopropyl]-2,3-dihydro-1-[3-(benzoyloxy)propyl]-1H-indole-7-nitrile, preparing benzoic acid-R-3-[7-cyano-5-(2-{2-[2-(2,2,2-trifluoro-ethoxy)-phenoxyl]-ethylamino}-propyl)-2,3-dihydro-indole-1-yl]-propylester which is an intermediate, and finally performing a hydrolysis reaction to produce silodosin. According to the provided industrial production method of silodosin, the yield is high, purification becomes easy and the impurity content is low.

The invention discloses a method for preparing and purifying Silodosin intermediates namely 2-(2,2,2-tirfluoroethyoxy) phenol and 2-(2,2,2-tirfluoroethyoxy) phenoxy ethyl methanesulfonate. The method comprises the steps of: A. reacting catechol or a salt thereof, 2-halogenated trifluoroethane or 2,2,2-trifluoroethyl sulfonate as raw materials with alkali metal iodide in an aprotic solvent under the action of basic compound to obtain 2-(2,2,2-trifluoroethoxy) phenol (II), and carrying out steam distillation and purification; and B. reacting 2-(2,2,2-trifluoroethoxy) phenol (II) obtained in the step A with ethylene dimethanesulfonate in the aprotic solvent to obtain 2-(2,2,2-trifluoroethoxy) phenoxy ethyl methanesulfonate (I). The method has the advantages that the starting raw materials are inexpensive and easily available, and the production cost is lowered; complicated column chromatography is not used; and the method is suitable for large-scale industrial production.

The invention provides an oral solution for curing dysuria, which takes silodosin as main active ingredient or silodosin prodrug or pharmaceutically acceptable salt. The oral solution, which is made of water, ethanol or the mixture of the two, overcomes the defects of difficult taking, slow dissolving out and low biological utilization rate in tablet, capsule and other solid preparations. With stable fluid quality, the oral solution has excellent compliance and biologic utilization rate and can be best taken by elder patients.

It has been discovered that silodosin is effective in treating patients having symptoms associated with prostatitis with silodosin or a pharmaceutically acceptable salt thereof. In a preferred embodiment, patients are treated with 4 mg once daily.

The invention belongs to the field of medicines, and particularly relates to detection method and application of silodosin enantiomer. The method comprises the steps of preparing a silodosin test solution and a contrast solution; preparing a system adaptability solution of silodosin and the silodosin enantiomer; and performing reversed-phase high-performance liquid chromatography on the test solution, the contrast solution and the system adaptability solution, wherein the detection condition is as follows: a chromatographic column comprises a chiral chromatographic column taking silica gel surface covalently bonded with amylase-tri(3-chlorine-5-methyl phenyl carbamate) as a filling agent, a mobile phase comprises diammonium phosphate solution-acetonitrile, the flowing speed of the mobile phase is 0.7mL/min, the detection wavelength is 270 nanometers, and the column temperature of the chromatographic column is not larger than 30 DEG C. The detection method of the silodosin enantiomer, provided by the invention, is relatively good in sensitivity, relatively short in washing time, relatively small in balancing difficulty, favorable in reproducibility and favorable in durability, is convenient to operate and is of important significance to effective quality control of the silodosin.

The invention discloses a preparation method of a silodosin intermediate and relates to the technical field of medical synthesis, aiming at solving the problem in an existing preparation method that the yield of the silodosin intermediate is low. The preparation method of the silodosin intermediate comprises the following steps: carrying out chirally-induced reductive amination on an alpha-substituted acetone compound to obtain an initial intermediate; carrying out amino protection on the initial intermediate to obtain an amino protected intermediate; carrying out hydroformylation on the aminoprotected intermediate to obtain a hydroformylated intermediate; carrying out oximation on the hydroformylated intermediate to obtain an oximated intermediate; carrying out cyaniding on the oximatedintermediate to obtain a cyanated intermediate; carrying out amino deprotection on the cyanated intermediate to obtain free alkali of the silodosin intermediate; carrying out salt forming treatment onthe free alkali of the silodosin intermediate to obtain the silodosin intermediate. The preparation method of the silodosin intermediate, provided by the invention, is used for preparing silodosin.

An agent for the prevention and/or treatment of urine collection disorders associated with lower urinary tract obstructive disease, characterized by containing an indoline derivative represented by the following general formula (I):

wherein R; R¹; and R² are defined in the specification. The derivative and salt are usable as an agent for the prevention and/or treatment of urine collection disorders associated with lower urinary tract obstructive disease. Silodosin is the preferred indoline derivative.

The invention relates to a preparation method of a silodosin intermediate. The preparation method is characterized in that: the intermediate is 1-(3- hydroxypropyl)-5-[(2R)-2-[2-[2-(2,2,2-trifluoroethoxyl] phenoxyl] ethylamino] propyl]-7-nitrile-1H-indoline. The preparation method is shown in the description. The raw materials used in the method are sold on the market, are cheap, and are low in cost. The yield in various step is relatively high, and the post-processing is simple. The preparation method does not use poisonous or hazardous agent, and is convenient for industrialization. The product quality is high, and the optical purity is high.

The invention discloses a preparation method of a silodosin intermediate. The preparation method includes: allowing 5-bromoindoline solution and triethylamine to be in alkylation reaction to obtain asubstance A; allowing a solution of the substance A, ethyl acetoacetate, catalyst and acid-binding agent to be in substitution reaction to obtain a substance B; allowing a solution of the substance Band Lewis acid to be in decarboxylic reaction to obtain a substance C; allowing a solution of the substance C, R-tert butyl sulfonamide, catalyst and reducer to be in amination reaction to obtain a substance D; allowing a solution of the substance D and N-bromosuccinimide solution to be in bromination reaction to obtain a substance E; allowing a solution of the substance E and cuprous cyanide to be in cyanation reaction to obtain a substance F; allowing a solution of the substance F and acid to be in acidolysis reaction to obtain a substance G; preparing the substance G into tartrate to obtainthe silodosin intermediate. The preparation method is simple, high in yield, low in energy consumption and environment-friendly; the silodosin intermediate prepared by the method is high in quality and suitable for large-scale industrial production.

The present invention provides a method for synthesizing a silodosin intermediate with a high enantiomeric purity. The method comprises the steps of using 1-[3-(benzyloxy)propyl]-5-bromoindoline as the raw material, performing a bromine lithium exchange reaction with an organolithium reagent to obtain 1-[3-(benzyloxy)propyl]-5-lithiumindoline, performing a Weinreb amidization reaction with (R)-N-(alkoxycarbonyl)alanine to obtain the silodosin intermediate with a good yield and enantioselectivity. The method has the advantages of simple operation, cheap and easily-available raw materials, highenantiomeric purity of the product and no resolution step, and has extremely high application value for industrial preparation of silodosin.

Provided is a method for preparing silodosin. Also provided is a method for preparing an organic acid salt of a new intermediate 3-(7-cyano-5-((R)-2-((R)-1-phenylethylamino)propyl)-1-hydrogen-indolyl) propyl alcohol (ester or ether), and a new intermediate 3-(7-cyano-5-((R)-2-(((R)-1-phenethyl)(2-(2-(trifluoroethoxy)phenoxy) ethyl)amino)propyl)1-hydrogen-indolyl)propyl alcohol (ester or ether) and a salt thereof. The method has the following advantages: raw materials are cheap and easy to obtain, the operation is simple, the intermediate and product are easy to purify, the yield is high, and the method is applicable to industrial production.