Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of dexbudesonide

A single technology of dexbudesonide, which is applied in the field of preparation of dexbudesonide, can solve the problems of high price and high toxicity of intermediate reagents, and achieve the effect of high yield and good separation effect

Active Publication Date: 2016-01-20
云南康健善美制药有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The purpose of the present invention is to overcome the shortcomings of expensive intermediate reagents and high toxicity in the prior art, and provide a synthetic method for dexbudesonide that has mild reaction conditions, good yield, and is suitable for large-scale industrial production

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
  • A kind of preparation method of dexbudesonide
  • A kind of preparation method of dexbudesonide
  • A kind of preparation method of dexbudesonide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Put 11β,21-dihydroxy-16α,17-[(1-methylethylene)-dioxy]pregna-1,4-diene-3,20-dione (desonide ) 5kg, purified water 80kg, ethanol 80kg, reflux to dissolve completely. Cool down to 25°C, add 0.8 kg of n-butyraldehyde dropwise, and keep the reaction for 5 hours after dropping. Concentrate in vacuo at 50°C and centrifuge. The solid was dissolved with 100 kg of ethanol, 2.2 kg of (+)-tartaric acid was added, and the temperature was raised to 65° C. for 2 hours. After the reaction was completed, the temperature was lowered to 5° C., and centrifuged to obtain dexbudesonide tartrate.

[0027] R isomer: 99.2%; S isomer: 0.8%

[0028] [a] D 20° =+116.4°(C=1,CH 2 Cl 2 )

[0029] 1 H-NMR (DCCl 3 , 400MHz): 7.28(t,1H), 6.26(d,1H), 6.02(S,1H), 5.15~5.19(m,1H), 4.48~4.91(m,3H), 4.23(t,1H), 3.01(S, 1H), 2.56(t, 1H), 2.34(d, 1H), 2.07~2.18(m, 3H), 1.47~1.51(m, 1H), 1.46(S, 3H), 1.32~1.43( m, 2H), 1.10~1.18(m, 2H), 0.89~0.99(m, 6H)

[0030] IR(KBr): 3504(-OH), 2956~2872(-C-H)...

Embodiment 2

[0032] Put 3kg of dexbudesonide tartrate in the above example into the reactor, add 10kg of purified water and 10kg of ethanol. Cool down to 0°C, add dropwise 0.5% sodium bicarbonate solution to adjust the pH to 7.5. Concentrate in vacuo to stop flow, centrifuge, and wash with purified water to obtain 1.8 kg of dexbudesonide.

[0033] R isomer: 99.2%; S isomer: 0.8%

Embodiment 3

[0035] Put 11β,21-dihydroxy-16α,17-[(1-methylethylene)-dioxy]pregna-1,4-diene-3,20-dione (desonide ) 5kg, purified water 80kg, ethanol 80kg, reflux to dissolve completely. Cool down to 25°C, add 0.8 kg of n-butyraldehyde dropwise, and keep the reaction for 5 hours after dropping. Concentrate in vacuo and centrifuge. Put the solid matter into the reaction kettle, add 100kg of ethanol, 4kg of (+)-camphorsulfonic acid, and raise the temperature to 65°C for 2 hours. After the reaction was completed, the temperature was lowered to 5° C., and centrifuged to obtain dexbudesonide tartrate.

[0036] R isomer: 99.7%; S isomer: 0.3%

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 relates to a preparation method of adrenocortical hormone agents, and particularly discloses a preparation method of (R)-budesonide. 11beta,21-dihydroxy-16alpha,17- [(1-methylethylidene)bis(oxy)]pregna-1,4-diene-3,20-dione is taken as an initial raw material, and the budesonide (R-isomer) is obtained through exchange and splitting. The preparation method of the (R)-budesonide is simple in process, high in yield and suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of adrenocortical hormone drugs, in particular to a preparation method of dexbudesonide. Background technique [0002] Budesonide is a glucocorticoid with highly effective local anti-inflammatory effect developed by AB Bofors in Sweden. Budesonide is a racemate composed of two isomers 22R and 22S at the C-22 position in a ratio of approximately 1:1. It is clinically used topically to treat skin or respiratory symptoms caused by inflammation and allergies (such as skin diseases, asthma and rhinitis), etc. [0003] Dexbudesonide (R isomer) belongs to adrenocortical hormone drugs, is a single isomer of budesonide C-22 position prepared by chemical synthesis, and its local anti-inflammatory activity (rat auricle swelling method) is 1.4 to 1.7 times that of budesonide, 1.6 to 2 times that of levobudesonide (S isomer), and 13 times that of dexamethasone; the local glucocorticoid effect (human vasoconstriction t...

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 Patents(China)
IPC IPC(8): C07J71/00
Inventor 骆均勇陶长戈
Owner 云南康健善美制药有限公司