65429-42-7

Usage

Uses

Used in Pharmaceutical Industry:
Fluticasone propionate, 17-beta carboxylic acid, is used as an impurity in the synthesis of fluticasone propionate for the development of corticosteroid medications. It plays a role in the production process of these medications, which are used to treat a variety of inflammatory conditions and asthma.
Used in Research and Development:
Fluticasone propionate, 17-beta carboxylic acid, is used as a research compound for studying the properties and effects of corticosteroids. This can help in the development of new medications and therapies for various medical conditions.
Used in Quality Control:
Fluticasone propionate, 17-beta carboxylic acid, is used in the quality control process of corticosteroid medications. It helps ensure the purity and effectiveness of the final product by monitoring the presence of this specific impurity during the manufacturing process.

InChI:InChI=1/C24H30F2O6/c1-5-19(29)32-24(20(30)31)12(2)8-14-15-10-17(25)16-9-13(27)6-7-21(16,3)23(15,26)18(28)11-22(14,24)4/h6-7,9,12,14-15,17-18,28H,5,8,10-11H2,1-4H3,(H,30,31)/t12-,14+,15+,17+,18+,21+,22+,23+,24+/m1/s1

Upstream product

• 79-03-8 propionyl chloride 
• 28416-82-2 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 
• 28416-82-2 6α,9α-difluoro-11β,17α-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carboxylic acid 
• 123-62-6 propionic acid anhydride 
• 90566-53-3 fluticasone 
• 2135-17-3 flumetasone 
• 109-89-7 diethylamine 
• 96-22-0 pentan-3-one 
• 78-93-3 butanone 
• 2557-49-5 11β,17α,21-trihydroxy-6α,9α-difluoro-16β-methylpregna-1,4-diene-3,20-dione 

Downstream Products

• 105638-31-1 17β-[(N,N-dimethylcarbamoyl)thio]formyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-one androstone-1,4-diene 
• 73205-13-7 6α,9α-difluoro-11β-hydroxy-17β-<(methylthio)carbonyl>-17α-(propionyloxy)-16α-methylandrosta-1,4-dien-3-one 
• 80474-67-5 S-iodomethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxo-androsta-1,4-diene-17β-carbothioate 
• 80486-69-7 S-chloromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carbothioate 
• 80474-45-9 17-propionate carbothioic acid 
• 80474-14-2 flixotide 

Relevant academic research and scientific papers

Fluticasone propionate synthesis method

The embodiments of the invention provide a fluticasone propionate synthesis method, which comprises: a thioesterification reaction: adding a first intermediate, an first organic alkali, dimethylaminothioformyl chloride, sodium iodide and a first organic solvent into a reaction kettle, carrying out a reaction, adding a polar aprotic solvent and water after the reaction, carrying out cooling crystallizing, filtering, washing, and drying to obtain a second intermediate; an alcoholysis reaction: adding the second intermediate, a first inorganic alkali and a second organic solvent into a reaction kettle, carrying out a reaction, adding water or water and an extracting agent after the reaction, extracting, taking the water phase, adding hydrochloric acid in a dropwise manner, crystallizing, filtering, washing, and drying to obtain a third intermediate; and a substitution esterification reaction: adding the third intermediate, a second inorganic alkali and a third organic solvent into a reaction kettle, adding fluorobromomethane, adding hydrochloric acid in a dropwise manner, crystallizing, filtering, washing, and drying to obtain fluticasone propionate. According to the embodiments of the invention, the low-cost production can be realized, and the reaction yield and the purity are high.

METHODS OF PREPARING INTERMEDIATE OF FLUTICASONE PROPIONATE

A method of preparing a thioic acid intermediate of fluticasone propionate includes: treating a 17β-[(N,N-dimethyl carbamoyl)thio]carbonyl compound in a solution including an alcohol and an alkali metal hydroxide, an alkaline-earth metal hydroxide, or a mixture thereof to cleave an amide from the 17β-[(N,N-dimethyl carbamoyl)thio]carbonyl compound; treating the solution to separate an aqueous portion; and adding an acid to the aqueous portion to obtain the thioic acid intermediate of fluticasone propionate. A method of preparing fluticasone propionate includes preparing the thioic acid intermediate of fluticasone propionate, and alkylating the thioic acid intermediate of fluticasone propionate to prepare the fluticasone propionate.

PROCESS FOR PREPARING FLUTICASONE PROPIONATE/FUROATE

The present invention relates to an improved process for the preparation of substituted Fluticasone derivatives. The invention also reveals the processes for the purification of Fluticasones and related intermediates to provide the highly pure product.

Improved synthesis of fluticasone propionate

A novel process for the preparation of fluticasone propionate (1), a corticosteroid, is reported. In this paper, compound 2 was used as starting material to prepare 6 by using NaClO or NaBrO which was much cheaper than H 5IO6 as an oxidizing agent. Furthermore, toxic, expensive, and pollutive BrCH2F was replaced by AgNO3 and Selectfluor in decarboxylative fluorination.

METHOD FOR PREPARATION OF FLUTICASONE PROPIONATE

Taught is a method for preparing S-fluoromethyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxoandrosta-1,4-diene-17β-carbothioate (fluticasone propionate). The present method is simple, convenient, and mild, yields highly pure product, and is suitable for use commercially on a large scale.

METHOD FOR THE PREPARATION OF FLUTICASONE PROPIONATE

Taught is a method for preparing S-fluoromethyl-6α,9α- difluroro-11β-hydroxy-16α-methyl-17α- propionyloxy-3-oxoandrosta-1,4-diene-17β-carbothioate (fluticasone propionate). The present method is simple, convenient, and mild, yields highly pure product, and is suitable for use commercially on a large scale.

Novel crystalline forms of 6alpha, 9alpha -difluoro-11beta-hydroxy-16alpha-methyl-3-oxo-17alpha-propionyloxy-androsta-1,4-diene 17beta-carboxylic acid and processes for preparation thereof

Novel crystalline forms II, III, IV, V, VI, VII and VIII of 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17α-propionyloxyandrosta-1,4-diene-17β-carboxylic acid, a chemical intermediate useful in the preparation of fluticasone propionate, and novel methods of making these forms, substantially free of water, are disclosed.

Convenient synthesis of s-fluoromethyl 6alpha, 9alpha-difluoro-11beta-hydroxy-16alpha-methyl-17alpha-propionyloxy-3-oxoandrosta-1,4-diene-17beta-carbothioate

The present invention provides a convenient process for the preparation of S-fluoromethyl 6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxoandrosta-1,4-diene-17β-carbothioate, a compound of formula 1, comprising (a) treating 17β-[(N,N-dimethylcarbamoyl)thio]carbonyl-6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxoandrosta-1,4-diene, a compound of formula 3 with alkali metal carbonate-alcohol system to obtain 6α,9α-difluoro-11β-hydroxy-16α-methyl-17α-propionyloxy-3-oxoandrosta-1,4-diene-17β-carbothioic acid, a compound of formula 4; (b) reacting the compound of formula 4 with bromofluoromethane to yield the compound of formula 1. The present invention also provides an improved process for preparation of compound of formula 1 comprising (a) reacting 6α,9α-difluoro-11β-hydroxy-16α-methyl-3-oxo-17-(propionyloxy)androsta-1,4-dien-17β-carboxylic acid, a compound of formula 2, with N,N-dimethylthiocarbamoyl chloride in an inert aprotic solvent in the presence of an iodide catalyst and a base to give a compound of formula 3, (b) reacting the compound of formula 3 with a hydrosulfide reagent and bromofluromethane to obtain a compound of formula 1.

Process for the preparation of steroidal 17 beta-carbothioates

A novel method for the conversion of steroidal 17β-carboxylic acids to carbothioates such as fluticasone propionate via novel in situ generated 17β-carboxy imidazolyl- or succinimidyl esters.