8 results about "Eplerenone" patented technology

The application provides a method for synthesizing an eplerenone intermediate N-1 by one-pot method, and belongs to the technical field of organic synthesis. The method is characterized in that: the eplerenone intermediate N-4 is dissolved in dichloromethane, a potassium carbonate aqueous solution and dibromohydantoin are added to perform an opening ring reaction; after the reaction is completed, hydrochloric acid is directly added to perform a rearrangement reaction; then water is separated and methanol is added in the organic layer to perform an ozonation reaction; then sodium sulfite is added to perform a reduction reaction; then hydrochloric acid is added to perform a methyl esterification reaction, so as to obtain the eplerenone intermediate N-1 crude product, and finally the eplerenone intermediate N-1 fine product is obtained through refining. The method realizes the one-pot synthesis of the eplerenone intermediate N-1 from the eplerenone intermediate N-4 through the continuous reactions of opening ring, rearrangement, ozonation, reduction and methyl esterification, and can avoid column chromatography purification, so that the method becomes a green chemical process route with greatly reduced organic solvent consumption and wastewater.

The invention relates to the technical field of pharmaceutical chemicals, in particular to a refining method of an eplerenone intermediate. The method comprises the following steps: S1, dissolving: sequentially adding an eplerenone methyl ester crude product, an organic solvent and water into a reaction bottle, and stirring and heating to completely dissolve the eplerenone methyl ester crude product, the organic solvent and the water; s2, reaction: adding inorganic alkali into a dissolved reaction system, and stirring for full reaction at controlled temperature; s3, elutriation: cooling the system to room temperature, and slowly dropwise adding water to precipitate a solid product; s4, devitrification: cooling, devitrifying and fully stirring; s5, filtering and drying: filtering the system for solid-liquid separation, and drying to obtain an eplerenone methyl ester fine product. The eplerenone methyl ester refining method provided by the invention is high in product yield and low in cost, the adopted organic solvent is a common solvent and is low in toxicity, and the eplerenone methyl ester refining method has good industrial application value and is very suitable for large-scale industrial application.

The invention discloses a stable eplerenone oral suspension and a preparation method thereof. According to the oral suspension, a buffer pair pH regulator is adopted to regulate the pH value of the oral suspension of the system to 3.0-5.0, so that the stability of the product in the storage process is maintained. Meanwhile, compared with eplerenone tablets, the eplerenone oral suspension provided by the invention has the advantages that the absorption is faster, the in-vivo exposure of the medicine is larger, the bioavailability is obviously improved by about 50%, and a reliable high-stability and high-bioavailability eplerenone oral suspension preparation scheme is provided clinically.

The present invention discloses a composition containing eplerenone, its pharmaceutical preparation, preparation method, and use. The composition comprises 98.5wt% to 99.9wt% of eplerenone and a compound of formula A, wherein the content of the compound of formula A does not exceed 0.1wt%. When the compound of formula A exceeds a certain content in eplerenone, it will affect the clinical safety of the drug. Research results show that related clinical adverse reactions increase significantly. The present invention also discloses a preparation method of the eplerenone composition and its pharmaceutical preparation. Comprehensive research on the compound of formula A has been conducted to control the content of the compound of formula A, thereby improving the quality and safety of eplerenone. #imgabs0# Formula A

The invention discloses a composition containing eplerenone as well as a pharmaceutical preparation, a preparation method and application thereof. The composition comprises 98.5 wt%-99.9 wt% of eplerenone and a compound shown in a formula A, and the content of the compound shown in the formula A does not exceed 0.1 wt%; wherein the clinical safety of the medicine can be influenced when the content of the compound shown in the formula A is higher than a certain content in eplerenone, and the research result shows that related clinical adverse reactions are obviously increased. The invention also discloses a preparation method and a pharmaceutical preparation of the eplerenone composition. The compound in the formula A is perfectly researched, the content of the compound in the formula A is controlled, and the quality and safety of eplerenone are improved. Formula A

The application discloses a purification method of eplerenone, which uses a mixture of alcohol and water as a recrystallization solvent. The technical scheme provided by the application can completely dissolve eplerenone, is friendly to the environment, has low toxicity, has high product yield and purity, has good impurity removal effect, has low dosage, and has a safer refining system, and is more suitable for industrialized and large-scale production.

The invention provides a preparation method of eplerenone, which comprises the following steps: in the presence of acid and / or anhydride, carrying out elimination reaction on 9-hydroxy canrenone (1) to obtain a compound (2); in the presence of an oxidizing agent, carrying out epoxy reaction on the compound (2) to obtain a compound (3); in the presence of alkali and a quaternary ammonium salt catalyst, carrying out cyanidation reaction on the compound (3) and a cyanidation reagent, and hydrolyzing under an acidic condition to obtain a compound (4); in the presence of alkali, the compound (4) is subjected to an esterification reaction to obtain eplerenone (5), and the specific reaction route is as follows. The method provided by the invention has the advantages of simple operation, few side reactions, high yield, low production cost, simple post-treatment, great reduction of industrial three wastes, suitableness for industrial production, and very high application value.

The invention discloses a preparation method of eplerenone and an intermediate of eplerenone, and belongs to the technical field of chemical synthesis of medicines, and the preparation method comprises the following steps: by taking 9 alpha-hydroxy-4-androstene-3, 17-diketone which is low in price and easy to obtain as an initial raw material, firstly, constructing a delta9, 11-double bond with high selectivity through an acidic dehydration reaction; then, a gamma-lactone ring is efficiently constructed through 3-position carbonyl protection, 17-position propynylation and oxidative cyclization reaction, and an intermediate delta 9, 11-canrenone is obtained; further efficiently introducing carboxyl into the C7 site of the intermediate through a photocatalytic flow chemical technology, and finally preparing eplerenone through esterification and 9alpha, 11alpha-stereoselective epoxidation. The method is novel in route design, avoids the difficulty in selectivity and the use of toxic reagents in the traditional method, and is mild in condition in each step, high in yield, high in purity and suitable for industrial production.