Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Impurities of baricitinib and preparation and detection methods thereof

A baricitinib and impurity technology, which is applied to medical preparations containing active ingredients, measuring devices, and pharmaceutical formulas, can solve problems such as optimization and selection, and achieve the effects of ensuring safety and reliability, simple operation, and high yield

Pending Publication Date: 2018-12-11
NANJING YOUKE BIOLOGICAL MEDICAL RES +3
View PDF8 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The inventor found during the research and experiment of process route selection that no matter it is based on the preparation method disclosed in the above patent text or the self-developed process, there will be at least three kinds of impurities in the final baricitinib product, and their production Difficult to avoid through process optimization

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
  • Impurities of baricitinib and preparation and detection methods thereof
  • Impurities of baricitinib and preparation and detection methods thereof
  • Impurities of baricitinib and preparation and detection methods thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0050] The preparation of embodiment 1 impurity A

[0051] Weigh baricitinib (1.0g, 2.7mmol) into a 100ml reaction flask, add 20ml DMSO, stir to dissolve, add potassium carbonate (0.6g, 4.3mmol), cool to below 10°C, slowly drop into 4.0ml 30% hydrogen peroxide, naturally warmed up to room temperature after dripping, stirred for about 10 minutes, after TLC confirmed that the reaction was complete, added 100ml of water, extracted with ethyl acetate (30ml×3), combined organic phases, washed with water (30ml×2), saturated saline Washed, dried over anhydrous sodium sulfate for 30 min, filtered, and the filtrate was concentrated to dryness under reduced pressure to obtain 500 mg of a white solid product with a yield of 47.7% and an HPLC purity of 96.96%.

[0052] MS-ESI(M+1): m / z 391.1;

[0053] 1 H NMR (500MHz, d 6 -DMSO)δ:12.07(s,1H),10.17(s,1H),8.68(d,2H),8.40(s,1H),7.58(d,1H),7.47(d,1H),6.98(d ,2H),4.53(d,2H),4.37(d,2H),3.30(s,2H),3.15-3.22(m,2H),3.00(s,2H),1.24(t,3H).

Embodiment 2

[0054] The preparation of embodiment 2 impurity A

[0055]Take baricitinib (1.0g, 2.7mmol) and put it into a 50ml reaction flask, add 15ml methanol and 1ml DMSO, then add 6ml of 1mol / L NaOH solution and 2ml H at room temperature 2 o 2 . The reaction mixture was heated at 50° C. for 3 h. After TLC confirmed that the reaction was complete, it was cooled to room temperature, 100 ml of water was added, extracted with ethyl acetate (30 ml × 3), the organic phases were combined, washed with water (30 ml × 2), and washed with saturated brine. Dry over sodium sulfate for 30 min, filter, and concentrate the filtrate to dryness under reduced pressure to obtain 612 mg of a white solid product with a yield of 58.4% and a purity of 95.98% by HPLC.

Embodiment 3

[0056] Example 3 Preparation of Impurity B

[0057] Weigh baricitinib (2.0g, 5.4mmol) into a 100ml reaction bottle, slowly add 30ml of concentrated hydrochloric acid, heat up to 100°C, react for 1-2h, after TLC confirms that the reaction is complete, add 30ml of water, cool to 0 ℃, use 30% NaOH solution to adjust the pH to about pH9~10, extract with ethyl acetate (50ml×3), combine the organic layers, wash with water (50ml×2), dry over anhydrous sodium sulfate for 30min, filter, and put the filtrate at 45℃ Concentrate to dryness under reduced pressure to obtain 800 mg of off-white solid with a yield of 38.1% and an HPLC purity of 94.67%.

[0058] MS-ESI(M+1): m / z 391.1

[0059] 1 H NMR (300MHz, d 6 -DMSO)δ:13.19(brs,1H),9.20(s,1H),8.94(s,1H),8.75(s,1H),7.96(s,1H),7.61(t,1H),7.44(s ,1H),4.85(d,1H),4.69(d,1H),3.68(s,2H),3.27-3.51(m,2H),2.95(q,2H),1.03-1.15(m,3H).

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 belongs to the field of drug synthesis, and in particular relates to three impurities of baricitinib: impurities A, B and C, a preparation method, structural characterization and a detection method of the three impurities and an application of controlling purity of a baricitinib raw material or a preparation as an impurity reference substance as well. The invention can provide a standard reference substance for quality control and clinical medication safety detection of baricitinib, so that the clinical medication safety and reliability can be guaranteed.

Description

technical field [0001] The present invention relates to the field of medicine and chemical industry, in particular to the impurity of baricitinib, its preparation method, detection method and composition containing the impurity. Background technique [0002] Baricitinib (Olumiant, I) is a selective JAK1 and JAK2 inhibitor jointly developed by Eli Lilly and its partner Incyte, which can inhibit IL-6 and IL-23 and other inflammatory cytokines Intracellular signaling of the chemical name 1-(ethylsulfonyl)-3-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl ]-3-azetidine acetonitrile, its structural formula is as shown in formula (I). This product has been approved by the European Union in 2017 for the treatment of adults with moderate to severe rheumatoid arthritis who do not respond or are intolerant to current rheumatoid arthritis drugs. It can be used as a single drug or combined with a wide range of drugs Used in conjunction with methotrexate. [0003] [0004] Exi...

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
IPC IPC(8): C07D487/04A61K31/519A61P19/02A61P29/00G01N30/02
CPCA61K31/519C07D487/04G01N30/02G01N2030/027Y02P20/55
Inventor 张峰张鹏赵国权杨谋伟朱素华薛峪泉刘春猛
Owner NANJING YOUKE BIOLOGICAL MEDICAL RES
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap 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