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

Febuxostat impurity

A compound and reaction solvent technology, applied in the field of medicinal chemistry, can solve problems such as no separation and detection methods

Pending Publication Date: 2022-03-08
SUNSHINE LAKE PHARM CO LTD
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] At present, "United States Pharmacopoeia" USP, "European Pharmacopoeia" EP, "Japanese Pharmacopoeia" JP, and "Chinese Pharmacopoeia" Ch.P. do not contain corresponding impurities, nor do they have corresponding separation and detection methods, nor do they disclose impurities in the prior art 3 and preparation and detection methods

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
  • Febuxostat impurity
  • Febuxostat impurity
  • Febuxostat impurity

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0098] The preparation of embodiment 1 compound 2

[0099]

[0100] Add compound 1 (2.00g) and trifluoroacetic acid (6mL) to the reaction flask, cool down to 20°C, add NBS (1.30g) under stirring at 15-35°C, stir for 5h, then raise the temperature to 35°C and stir for 2h. After the reaction, pour into 50mL of cold water at 10°C to quench, add EA (40mL×2) to extract twice, combine the EA layers, wash the EA layer with 20mL of saturated sodium sulfite solution once, and concentrate and remove the EA layer at 40°C under reduced pressure solvent to obtain compound 1 (2.40 g), with a yield of 100% and a purity of 90%.

[0101] LC-MS: m / z(ESI):424.3(M+H+)+

Embodiment 2

[0102] The preparation of embodiment 2 compound 3

[0103] Add compound 2 (2.40 g) prepared according to the method in Example 1, ethanol (20 mL) to the reaction flask, add a mixed solution of NaOH (1.16 g) and water (8 mL) at room temperature, heat up to 40 ° C and stir for 5 h After the reaction is completed, cool down to 25°C, concentrate under reduced pressure, add 40mL of water, stir and clarify, add aqueous hydrochloric acid (8mL, 2mol / L) to adjust the pH to about 1, continue stirring at 25°C for 2h, filter, and filter the cake with 20mL Washed with water and dried under vacuum at 55°C to obtain compound 3 (2.00 g) with a yield of 87.3% and a purity of 99%.

[0104] LC-MS: m / z (ESI): 395,397 1H NMR (600MHz, DMSO) δ13.46(s, 1H), 8.43(d, J=2.2Hz, 1H), 8.33(d, J=2.2Hz, 1H ), 4.04 (d, J=6.2Hz, 2H), 2.66 (s, 3H), 2.19–2.06 (m, 1H), 0.98 (s, 7H).

Embodiment 3

[0105] The detection and analysis of embodiment 3 compound 3

[0106] Instruments and Conditions

[0107]

[0108]

[0109] Experimental procedure

[0110] Solution preparation

[0111] Mobile phase A phase: namely 0.1% trifluoroacetic acid, take 1ml of trifluoroacetic acid and add it to 1000ml ultrapure water, mix well, and filter with 0.2μm water filter membrane to obtain the product;

[0112] Mobile phase B phase: acetonitrile;

[0113] Diluent / blank solution: mixed solution of acetonitrile and water (8:1, V / V);

[0114] Test solution: Take about 25 mg of febuxostat test product, weigh it accurately, put it in a 100ml volumetric flask, add diluent to ultrasonically dissolve and dilute to the mark, shake well, and prepare 2 parts in parallel;

[0115] Control solution: accurately pipette 1ml of the test solution into a 100ml volumetric flask, add diluent to the mark, and shake well; then precisely pipette 5ml of the above solution into a 50ml volumetric flask, dilute...

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 febuxostat impurity, and belongs to the field of medicinal chemistry. The invention provides a structure and a preparation method of the impurity, the impurity is obtained by adopting an ester compound of febuxostat as a starting material through a substitution reaction and a hydrolysis reaction, and the preparation method is simple, easy to operate and high in yield. The invention also provides an analysis method of the impurity, which comprises the following steps: a chromatographic column taking octadecyl bonded silica gel as a filler is adopted, a mobile phase is divided into a phase A and a phase B, the phase A is a trifluoroacetic acid aqueous solution, and the phase B is acetonitrile. The analysis method disclosed by the invention is high in sensitivity, good in specificity and reliable in accuracy.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a febuxostat impurity. Background technique [0002] Febuxostat (febuxostat), its chemical name is: 2-[(3-cyano-4-isobutoxy) phenyl]-4-methyl-5-thiazole carboxylic acid, chemical structural formula such as formula (I ) shown. Febuxostat is a xanthine oxidase (XO) inhibitor indicated for the long-term treatment of hyperuricemia with symptoms of gout. [0003] [0004] 2-(3-bromo-5-cyano-4-isobutoxyphenyl)-4-methylthiazole-5-carboxylic acid is an important impurity in the synthesis of febuxostat, and its chemical structure is shown in formula 3 Shown: [0005] [0006] Patent CN102079731A discloses a synthetic route for preparing febuxostat: a brominating reagent is used to participate in the reaction, but it does not disclose impurity 3, nor does it study impurity 3. In the method for preparing febuxostat, if a brominating reagent is used to participate in the reaction...

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): C07D277/56G01N30/02G01N30/06G01N30/86
CPCC07D277/56G01N30/02G01N30/06G01N30/8634
Inventor 王仲清许国彬廖守主陈夷花胡燕青罗忠华黄芳芳
Owner SUNSHINE LAKE PHARM CO LTD
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