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

Method for synthesizing enzalutamide

A synthetic method, enzalutamide technology, applied in the field of enzalutamide synthesis, can solve the problems of low overall yield and high toxicity, and achieve the effects of simple operation, reduced environmental and human hazards, and reduced raw material costs

Inactive Publication Date: 2015-06-17
CHINA PHARM UNIV
View PDF6 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] This route also uses thiophosgene, which is more toxic and has a lower overall yield

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 enzalutamide
  • Method for synthesizing enzalutamide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add compound 1 (15.5g, 0.10mol) and 200mL water into a 500mL three-necked flask, add potassium permanganate (36.4g, 0.23mol) in batches, and then reflux for 8h. TLC detected that the reaction was complete, and after the purple color of the reaction solution faded, it was suction filtered while it was hot. If the purple color of the reaction solution does not fade, add an appropriate amount of saturated sodium bisulfite solution to completely fade the reaction solution. The filtrate was cooled with an ice-water bath, and the pH was adjusted to 1 with concentrated hydrochloric acid. The solvent was evaporated under reduced pressure. Recrystallization from water gave compound 2 (10.2 g, 55%) as white needle crystals.

Embodiment 2

[0033] Add compound 1 (15.5g, 0.10mol), 100ml acetic acid, 50ml sulfuric acid into a 500mL three-necked flask, add chromium trioxide-acetic anhydride (30.3g, 0.15mol) in batches, then raise the temperature to 50°C for 5h. It was detected by TLC that the reaction was complete. 300 ml of water was added to the reaction solution, extracted three times with 150 ml of dichloromethane, washed three times with 150 ml of saturated sodium chloride, and the organic layer was dried with anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Column chromatography yielded compound 2 (10.2 g, 63%) as white needle crystals. 1 H NMR (300MHz, CDCl 3 )δ: 10.59 (s, 1H), 8.28-8.05 (m, 3H); EI-MS m / Z: 83, 131, 185 [M] + .

[0034] Synthesis of compound 3

Embodiment 3

[0036] Compound 2 (3.7g, 0.02mol), 50mL DMF was added to a 250mL three-necked flask, and thionyl chloride (9.5g, 0.08mol) was slowly added dropwise to the reaction solution under nitrogen protection, and reacted at room temperature for 12h, then, 40 Evaporate excess thionyl chloride under reduced pressure at ℃, pass methylamine gas into the reaction solution, control the temperature below 30 ℃, stop when the reaction solution is detected to be neutral. Extracted three times with 300ml ethyl acetate, washed three times with 150ml saturated sodium chloride, and dried the organic layer with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and recrystallized from ethanol to obtain compound 3 (3.6 g, 91%) as a yellow solid. 1 H NMR (300MHz, CDCl 3 )δ: 8.33-8.31(m, 1H), 8.13(d, J=2.7Hz, 1H), 8.04(d, J=8.3Hz, 1H), 6.75(s, 1H), 3.09(s, 3H); EI-MS m / Z: 94, 122, 168, 198 [M] + .

[0037] Synthesis of Compound 4

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 the field of chemical synthesis and in particular relates to synthesis of a medicine enzalutamide for treating male late castration-resistant prostate cancer. The method is characterized by comprising the following steps: by taking 2-fluoro-4-nitrotoluene as a raw material, sequentially performing oxidation, acylation and reduction, thereby obtaining N-methyl-2-fluoro-4-aminobenzamide; carrying out a nucleophilic reaction between N-methyl-2-fluoro-4-aminobenzamide and ethyl 2-bromoisobutyrate, condensing the generated 2-(3-fluoro-4-methylamino formyl phenyl) amino aniline-2-methylethyl propionate and 4-isothiocyanic-2-trifluoromethylbenzonitrile in the presence of a condensing agent, thereby obtaining the enzalutamide. The method disclosed by the invention is easy to operate, stable, reliable and mild in conditions, application of a toxic reagent is reduced, the total reaction yield is more than 20 percent, the purity of the synthesized product is high and is larger than 99.0 percent.

Description

technical field [0001] The invention relates to the field of chemical synthesis, in particular, the invention relates to the synthesis of enzalutamide. Background technique [0002] Prostate cancer is a very important type of male reproductive system tumors. It ranks second among common malignant tumors in Europe and the United States. In the United States, the incidence of prostate cancer ranks first among all malignant tumors, and its mortality rate ranks second. Although the incidence of prostate cancer in my country is far lower than that in western countries, it has shown a significant increase trend with the aging population in recent years. Because androgens play a pivotal role in the development of the prostate and prostate cancer, the androgen receptor is an essential target for systemic treatment of prostate cancer. [0003] Enzalutamide is a novel structural non-steroidal androgen receptor antagonist with a structure of formula (I). [0004] [0005] Enzaluta...

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): C07D233/86
CPCC07D233/86
Inventor 孙迎迎李永韧孙丽萍
Owner CHINA PHARM UNIV
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