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

Relugolix intermediate compound, preparation method and application thereof

A compound and action technology, applied in the field of chemical drug synthesis, can solve the problems of increased removal difficulty, less urea by-products, and increased impurities.

Pending Publication Date: 2020-06-26
JIANGZI QINGFENG PHARMACEUTICALS INC
View PDF8 Cites 19 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] The overall yield of this route is relatively high, but there is a major defect. The last step of urea reaction generates about 2.0% uret by-products, which are difficult to remove. The increasing trend will further increase the difficulty of removal. Therefore, it will be of great significance to develop a relugoli process route with high yield and less uret by-products

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
  • Relugolix intermediate compound, preparation method and application thereof
  • Relugolix intermediate compound, preparation method and application thereof
  • Relugolix intermediate compound, preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1-2

[0089] Embodiment 1-2: formula B (wherein R 1 is ethyl, R 2 is isobutyl, X is the preparation of intermediate shown in bromine)

[0090]

Embodiment 1

[0092] Weigh 30.14g of compound formula A and add it to a 1000mL three-necked flask, then add 240mL of ethyl acetate, 15.11g of NBS (N-bromosuccinimide) and 0.93g of AIBN (azobisisobutyronitrile), and stir to 70°C, reacted for 18 hours and then lowered to room temperature, added 60mL saturated sodium sulfite solution, then added 200mL water, stirred for 10min, separated the water phase, and washed the organic phase twice with 100mL water. Concentrate the organic phase to about 120 mL under reduced pressure, add 90 mL of ethanol, and concentrate the mixture to about 120 mL, then add 90 mL of ethanol, and then concentrate to 120 mL, add 50 mL of heptane, and stir the mixture at 20 to 30 ° C for 30 Minutes, add n-heptane again, stir at 0 to 10°C for 1 hour, collect the crystals by filtration, wash with ethanol / heptane=1 / 2, and dry under reduced pressure to obtain 31.64g light yellow crystal formula B, yield 91.45%, The chemical purity is 97.80%.

[0093] The NMR data are as foll...

Embodiment 2

[0095] Weigh 30.14g of compound formula A and add it to a 1000mL three-necked flask, then add 240mL of chloroform, 15.11g of NBS (N-bromosuccinimide) and 0.93g of AIBN (azobisisobutyronitrile), and stir to heat up to 60 ℃, reacted for 15 hours and lowered to room temperature, added 60mL of saturated sodium sulfite solution, then added 200mL of water, stirred for 10min and separated the water phase, and the organic phase was washed twice with 100mL of water. Concentrate the organic phase to about 120 mL under reduced pressure, add 90 mL of ethanol, and concentrate the mixture to about 120 mL, then add 90 mL of ethanol, and then concentrate to 120 mL, add 50 mL of heptane, and stir the mixture at 20 to 30 ° C for 30 Minutes, add n-heptane again, stir at 0 to 10°C for 1 hour, collect the crystals by filtration, wash with ethanol / heptane=1 / 2, and dry under reduced pressure to obtain 31.95g light yellow crystal formula B, yield 92.33%, The chemical purity is 97.35%.

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 discloses a brand-new intermediate compound of Relugolix and a preparation method thereof. The intermediate compound is high in purity, and can be used for preparing Relugolix and salts,derivatives or analogues thereof. The invention also discloses a preparation method of Relugolix, the obtained finished product is high in yield and purity, and no uret by-product is detected.

Description

technical field [0001] The invention belongs to the technical field of chemical drug synthesis, and relates to an intermediate compound of relugoli and its preparation method and application. Background technique [0002] Relugoli is a gonadotropin-releasing hormone antagonist (GnRH) developed by Takeda Corporation of Japan. It was launched in Japan in 2018 and is used for bleeding and pain caused by uterine fibroids. Phase III trials for endometriosis-related pain and prostate cancer are ongoing. [0003] Currently, there are only two synthetic routes for relugolis published. J.Med.Chem.2011,54,4998–5012, the disclosed synthetic route is as follows: [0004] [0005] This route is a compound route, and the yield in the last step is only 44%, which is low. [0006] The original research patent CN104703992B discloses another synthetic route, the synthetic route is as follows: [0007] [0008] The overall yield of this route is relatively high, but there is a major ...

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): C07D409/12C07D333/38C07D495/04
CPCC07D409/12C07D333/38C07D495/04
Inventor 刘地发郭正友郭烈平郭训发刘向宇何智斌
Owner JIANGZI QINGFENG PHARMACEUTICALS INC
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