Abstract

The present application belongs to the technical field of preparation and processing of drugs, and particularly relates to finerenone, a preparation method therefor and a finerenone intermediate. In the preparation method provided by the present application, a compound with a diester structure as represented by formula 2 is used as a reaction raw material to carry out a series of reactions, a chiral catalyst is used in the reaction to obtain a product with an S/R configuration ratio of up to 85:15, and the product is resolved by means of using a tartaric acid derivative, so as to prepare a compound with a structure as represented by formula 7, and then the resulting compound is subjected to hydrolysis and amidation reactions to obtain Finerenone. A finerenone drug substance with an ee value of ＞99.9% and a purity of up to 99.9% can be obtained by means of the preparation method of the present application. Moreover, the reactions during the preparation method provided by the present application are all common reactions, not involving dangerous reaction steps such as hydrogenolysis and high-pressure processes. The method has mild reaction conditions, generates no highly toxic by-products, has low requirements for reaction equipment, has low operational costs, and is simple and convenient to operate. Therefore, the method is suitable for industrial production, and has good market prospects.

IPC Classes  ?

• C07D 471/04 - Ortho-condensed systems
• C07C 255/57 - Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton

Abstract

The present disclosure provides a purification method of progesterone. In this method, aldehyde impurities in a progesterone crude product react with a sulfurated nucleophile to yield highly polar hydroxysulfonates and progesterone to realize solubility differentiation, and highly pure progesterone with a content higher than 99.5% and a total aldehyde impurities content lower than 0.2% is obtained through elutriation, filtration, washing a filter cake with water, and drying. The purification method provided by the present disclosure avoids the technical bottleneck of progesterone purification in the prior art, and all reagents and raw materials used during the reaction are inexpensive and easily available, with low equipment requirement and cost input; the purification process is mild and safe, conditions are easy to control, and the purification and recovery rate of the product is high; reagents used cause little environmental pollution, and particularly highly polluting chromium-containing reagents are not used.

IPC Classes  ?

• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms

Abstract

Disclosed in the present disclosure is a method for preparing 16alpha-hydroxyprednisolone, belonging to the technical field of medicine preparation and processing. In the method, 21-hydroxypregna-1,4,9(11),16-tetraene-3,20-dione-21-acetate is used as a starting material, and subjected to oxidation, bromo-hydroxylation, debromination and alcoholysis, so as to prepare 16alpha-hydroxyprednisolone. The method for preparing 16alpha-hydroxylprednisolone of the present disclosure can effectively control the generation of impurities in the reaction process by improving the disadvantages of traditional processes, and has a mild reaction process and a high overall conversion rate; and the method of the present disclosure has low requirements for a reaction device and low operation costs, is easy to operate, is suitable for industrial production, and has a good market prospect.

IPC Classes  ?

• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms
• C07B 35/06 - Decomposition, e.g. elimination of halogens, water or hydrogen halides

Abstract

Disclosed is a method for purifying progesterone, belonging to the technical field of preparation and processing of steroid hormone medicaments. In the method, aldehyde impurities in crude progesterone are used to react with a sulfur-containing nucleophile reagent to generate highly polar hydroxysulfonates to achieve solubility difference with progesterone, then add water for precipitation, perform filtration, and the filter cake is washed with water and dried, so as to obtain highly pure progesterone having a content higher than 99.5% and the total content of impurity aldehydes lower than 0.2%. The purification method of the present invention avoids the technical bottleneck of progesterone purification in the prior art. Raw materials of reagents used in the reaction process are cheap and easily available. The purification process is simple and convenient to operate, has low requirements on equipment, and has low costs. The purification process is mild and safe, the conditions are easy to control, and the product purification recovery rate is high. The reagents used have low environmental pollution, and particularly, chromium-containing high-pollutive reagents are not used. The purification method satisfy the industry development trend of green chemistry, and have good economic and social benefits.

IPC Classes  ?

• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms

Abstract

Disclosed in the present invention is a method for preparing 16alpha-hydroxyprednisolone, belonging to the technical field of medicine preparation and processing. In the method, 21-hydroxypregna-1,4,9(11),16-tetraene-3,20-dione-21-acetate is used as a starting material, and subjected to oxidation, bromo-hydroxylation, debromination and alcoholysis, so as to prepare 16alpha-hydroxyprednisolone. The method for preparing 16alpha-hydroxylprednisolone of the present invention can effectively control the generation of impurities in the reaction process by improving the disadvantages of traditional processes, has a mild reaction process and a high overall conversion rate; and the method of the present invention has low requirements for a reaction device and low operation costs, is easy to operate, is suitable for industrial production, and has a good market prospect.

IPC Classes  ?

• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms

Abstract

Disclosed is a highly efficient preparation method for progesterone with low pollution, pertaining to the technical field of preparation and processing of steroid hormone drugs. The method uses 21-hydroxy-20-methylpregna-4-en-3-one as a starting material, oxidizing the same into an aldehyde using a TEMPO-NaClO reagent, and subjecting the aldehyde to enamination and copper catalytic oxidation degradation to prepare progesterone. The preparation method for progesterone of the present invention has the following advantages: the raw materials and reagents are cheap and easily available, bringing extremely high market competitiveness in terms of equipment investment and production cost; the reaction is mild and safe, and is easy to control and operate; the reaction yield is high, and the purification is simple and convenient; the reagents used cause low environmental pollution, and especially, high pollution reagents containing chromium are not used, which conforms to the development trend of green chemistry, and therefore has good economic and social benefits.

IPC Classes  ?

• C07J 7/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, substituted in position 17 beta by a chain of two carbon atoms

Abstract

Disclosed is a method for preparing trenbolone acetate, same belonging to the technical fields of preparation and processing of hormone drugs. According to the method, 3-ethylenedioxy-estra-[delta]5,10, [delta]9,11-dien-17-one is used as a starting material, and a keto group at position 17 is reduced into an alcohol, a ketal group at position 3 is hydrolyzed, oxidative dehydrogenation is performed, and acetylation is performed on the alcohol at position 17 to prepare the trenbolone acetate. The synthetic process route of the trenbolone acetate described in the present invention has the advantages of cheap and easily available raw materials, simple and convenient reaction control, few byproducts, easy purification, a high total yield and extremely high competitiveness in production cost and operability, is suitable for industrial large-scale production, and has good economic benefits.

IPC Classes  ?

• C07J 1/00 - Normal steroids containing carbon, hydrogen, halogen, or oxygen, not substituted in position 17 beta by a carbon atom, e.g. oestrane, androstane