Check patentability & draft patents in minutes with Patsnap Eureka AI!

Preparation and purification methods of fluticasone furoate bulk drug impurity

A technology of fluticasone furoate and purification method is applied in the field of preparation and purification of fluticasone furoate crude drug impurities, can solve the problem of not finding fluticasone furoate crude drug impurities and the like, and achieves easy purification, ensures accuracy, and improves quality standards. Effect

Inactive Publication Date: 2019-08-09
BIONNA (BEIJING) MEDICAL TECH CO LTD
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Fluticasone furoate API impurity (Formula 1) is one of the impurities produced during the synthesis of fluticasone furoate API. In order to ensure the quality of the drug and improve the drugability, it is necessary to identify the impurity, and in order to ensure the control of subsequent substances, it is necessary to study Reasonable method makes the standard substance of this impurity; And does not find the method for making fluticasone furoate crude drug impurity (formula 1) simply and quickly at present

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation and purification methods of fluticasone furoate bulk drug impurity
  • Preparation and purification methods of fluticasone furoate bulk drug impurity
  • Preparation and purification methods of fluticasone furoate bulk drug impurity

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0031] The present invention provides a kind of preparation method of fluticasone furoate crude drug impurity, described fluticasone furoate crude drug impurity has the structure of following formula (1):

[0032]

[0033] figure 1 A schematic diagram of the synthetic route of the impurity in the embodiment of the present invention is shown. like figure 1 Shown, the preparation method of described formula (1) fluticasone furoate crude drug impurity comprises:

[0034] With compound 3(6α,9α-difluoro-17α-[(2-furylcarbonyl)oxy]-11β-hydroxy-16α-methyl-3-oxo-androst-1,4-diene-17β -thiocarboxylic acid) as a raw material, in the presence of a base, protonated or non-protonated solvent, reacts with sulfur chloride to generate a mixture containing compound 1; wherein compound 1 is the generated impurity.

[0035] Specifically, the base includes sodium carbonate, potassium carbonate, cesium carbonate, sodium phosphate, potassium phosphate, 4-dimethylaminopyridine, triethylamine, N...

Embodiment 1

[0053] The method for the preparation of fluticasone furoate crude drug impurities is specifically:

[0054] At room temperature, the intermediate compound 3 (1.2g, 2.4mmol) that generates fluticasone furoate was added to a 100mL three-necked flask, and 25mL of tetrahydrofuran and N-methylmorpholine (0.24g, 2.4mmol) were added, followed by nitrogen gas Protection, the use of nitrogen protection is to extract the air inside the container and fill it with nitrogen gas. The main purpose is to prevent the flammable gas in the container from forming a flammable mixture with the oxygen in the air, which may cause internal combustion or explosion; nitrogen protection is used Nitrogen replacement device.

[0055] After the operation, the temperature was lowered to 0°C, and sulfur chloride (0.16g, 1.2mmol) was weighed and slowly added dropwise. After the addition was completed, it was kept and stirred for 0.5h, and then placed in an ice-water bath, and 25mL of saturated saline was adde...

Embodiment 2

[0057] The preparation method of fluticasone furoate crude drug impurity is specifically:

[0058] Under room temperature conditions, the intermediate 3 (3.1g, 6.1mmol) that will generate fluticasone furoate was added to a 250mL three-necked flask, and 60mL of dichloromethane and triethylamine (1.2g, 6.1mmol) were added, followed by nitrogen protection, The use of nitrogen protection is to extract the air inside the container and fill it with nitrogen gas. The main purpose is to prevent the flammable gas in the container from forming a flammable mixture with the oxygen in the air, which may cause internal combustion or explosion; nitrogen protection uses nitrogen replacement device.

[0059] After the operation, cool down to -20°C, weigh sulfur chloride (0.41g, 3.1mmol) and slowly add it dropwise. After the addition, keep stirring for 20min, then place it in an ice-water bath, add 60mL of water to stir, extract and separate, and the organic phase is decompressed. The residue ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention provides a preparation method of a fluticasone furoate bulk drug impurity. The preparation method of the fluticasone furoate bulk drug impurity comprises the steps that 6alpha,9alpha-difluoro-17alpha-[(2-furyl carbonyl]oxyl]-11beta-hydroxyl-16alpha-methyl-3-oxo-androstane-1,4-diene-17beta-thiocarboxylic acid is taken as a raw material, and reacts with sulfur chloride in the presenceof alkali and a protonation or non-protonation solvent to generate a mixture containing the fluticasone furoate bulk drug impurity. The invention further provides a purification method of the fluticasone furoate bulk drug impurity. The purification method comprises the steps that the mixture is mixed with water and the non-protonation solvent, an organic phase is separated out, and then a solid crude product is obtained through column chromatography purification; the solid crude product is refined through one or more organic solvents to obtain a high-purity product. The fluticasone furoate bulk drug impurity can be prepared simply through one step; meanwhile, the peculiar purification method is utilized for making the impurity easy to purify and high in purity, and the accuracy of impurityreference substance purity and analysis work is effectively guaranteed.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a method for preparing and purifying fluticasone furoate crude drug impurities. Background technique [0002] Fluticasone furoate is a synthetic corticosteroid derived from fluticasone, which has anti-inflammatory properties and can be widely used in the treatment of inflammatory diseases such as asthma and rhinitis; U.S. Patent US4335121 discloses 6α, 9α-difluoro 17α-(1 -oxopropoxy)-11β-hydroxy-16α-methyl-3-oxo-androst-1,4-diene-17β-thiocarboxylic acid-S-fluoromethyl ester (common name is fluticasone propionate) and derivatives thereof, WO2002 / 012265 discloses a new fluticasone derivative, i.e. fluticasone furoate or fluticasone furoate, the structural formula is as follows: [0003] [0004] The chemical name of fluticasone furoate (Formula 2) is: 6α, 9α-difluoro-17α-[(2-furylcarbonyl)oxy]-11β-hydroxyl-16α-methyl-3-oxo-androster- 1,4-diene-17β-thiocarboxylate...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07J31/00
CPCC07J31/006
Inventor 魏相龙王双会马晓光尹鲲李昊
Owner BIONNA (BEIJING) MEDICAL TECH CO LTD
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com