Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

Method for synthesizing 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione

A technology of oxypropoxyl and hydroxypropionyl, applied in the production of steroids, bulk chemicals, organic chemistry, etc.

Inactive Publication Date: 2020-12-04
那路新 +1
View PDF7 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] However, the problems in the lipolysis method include: the catalytic efficiency of the enzyme, the maximum usage of the enzyme substrate per unit amount, the recycling activity of the enzyme, and the reaction time of the enzyme catalysis

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
  • Method for synthesizing 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione
  • Method for synthesizing 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione
  • Method for synthesizing 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0066] Preparation of Intermediate I

[0067]

[0068] where R = DMTr

[0069] Compound 11-deoxycortisol (1.04g, 3.0mmol, 1eq.) was dissolved in 10mL of anhydrous pyridine, and dried DMTrCl (1.2-1.5eq) was dissolved in 5mL of anhydrous dichloromethane, and reacted at room temperature Add the dichloromethane solution of DMTrCl dropwise in the product solution, and react at room temperature for 4 hours; quench the reaction with methanol, evaporate the solvent to dryness in an oil pump, and obtain intermediate product I with a yield of 85% (the next step reaction can be directly carried out without aftertreatment, the following One-step solvent environment and catalyst are similar to this step reaction).

[0070] 1 HNMR (600MHz, CDCl 3 )δ(ppm)7.25-7.31(m,5H,H-DMTr),7.15-7.18(m,4H,H-DMTr),6.81-6.84(m,4H,H-DMTr),5.73(1H,s, H-4),4.65(1H,dd,J=19.8,4.8Hz,H-21),4.30(1H,dd,J=19.8,4.8Hz,H-21),3.80(6H,s),2.71( s,1H,17-OH),2.66-2.71(m,1H,H-16β),2.27-2.45(m,4H),1.19(3H,s,H-19),0.96-...

Embodiment 2

[0074] Preparation of Intermediate II

[0075]

[0076] where R = DMTr

[0077] Under nitrogen protection, the intermediate product I (1eq.) was dissolved in 5mL of anhydrous dichloromethane, DMAP (0.1eq.) was added to the above solution, triethylamine (1.2eq.) and propionic anhydride or propionyl chloride were added dropwise (1.2eq.), after dropping, react at 40°C for 12 hours, and evaporate the solvent to obtain the intermediate product II.

[0078] Or under nitrogen protection, the intermediate product I (1eq.) was dissolved in 5mL of anhydrous pyridine, DMAP (0.1eq.) was added to the above solution, triethylamine (1.2eq.) and propionic anhydride or propionyl chloride were added dropwise (1.2eq.), after dropping, react at 80°C for 4 hours, and evaporate the solvent to obtain the intermediate product II. (This step reaction can be processed without strict purification and evaporated to dryness to directly carry out the next step to remove the DMTr protecting group to ob...

Embodiment 3

[0082] Preparation of target compound 1 (21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione)

[0083]

[0084] The concentrated intermediate product II was dissolved in ethyl acetate solution, slowly added dropwise with 0.5M hydrochloric acid solution or 2% trifluoroacetic acid-ethyl acetate solution at 0°C, and reacted at 0°C for 5 minutes to remove DMTr Protecting group, at 0°C, add 5% aqueous sodium bicarbonate and stir to neutralize the acid in the reaction system. The ethyl acetate organic layer is washed twice with 5% aqueous sodium bicarbonate to remove the organic layer of ethyl acetate. Acid and other water-soluble impurities, the organic layer of ethyl acetate was dried over anhydrous sodium sulfate, part of the ethyl acetate solvent was evaporated, and petroleum ether was added to the remaining small amount of ethyl acetate dissolved, and ethyl acetate-petroleum ether (5:1) Recrystallization was carried out in a system with 10 times the amount of solvent to obta...

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

PropertyMeasurementUnit
melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for synthesizing 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione, which comprises the steps of using 11-deoxypicanol as a raw material, selectively esterifying 17alpha-site secondary hydroxyl of 11-deoxypicanol by a chemical synthesis protective group means, and simultaneously retaining 21st-site primary hydroxyl of 11-deoxypicanol without esterification, thereby obtaining 21-hydroxy-17-(1-oxopropoxy)pregna-4-ene-3,20-dione. The method provided by the invention is a one-kettle reaction intermediate product without separation and purification, is more suitable for large-batch industrial preparation, and has the advantages of mild reaction conditions, high yield, simple post-treatment and the like.

Description

technical field [0001] This application relates to the field of medicinal chemistry, in particular to a method for synthesizing 21-hydroxyl-17-(1-oxopropoxy)pregna-4-ene-3,20-dione (the 17th position is alpha configuration (17α ), 17alpha-propio17-(1-oxopropoxy)pregn-4-ene-3,20-dione, also referred to herein as 21-hydroxy-17-(1-oxopropoxy)pregn-4-ene- 3,20-diketone) method. Background technique [0002] It is known that 21-hydroxy-17-(1-oxopropoxy)pregn-4-ene-3,20-dione (target compound 1) has anti-androgen effect, and it is used in various androgen-related therapeutic fields have a wide range of effects. In order to obtain the synthesis of this compound, existing literature reports (Tetrahedron Letter, 448,1961; Gazz.Chim.IT.63,431,1963) and U.S. Patent No. 3,152,154 use 11-deoxycortexol as a raw material, and use orthoester in an aprotic solvent, After the condensation reaction, the target product is obtained under acidic conditions, but this reaction route will produce...

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): C07J5/00
CPCC07J5/0053Y02P20/55
Inventor 那路新蒋智孙连奇姜海涛张婷婷
Owner 那路新
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com