Preparation method and application of hylagolil intermediate 1 and hylagolil intermediate 2

A technology of elagolix and intermediates, which is applied in the field of compound preparation, can solve the problems of difficult refining, difficult refining, unfavorable scale-up production, etc., and achieve the effects of guaranteed purity, simple synthesis and operation, and easy industrial production

Pending Publication Date: 2022-07-01
SHIJIANGZHUANG ZHIHENG PHARMACY TECH CO LTD
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the crude products of intermediate 1 and intermediate 2 are all foamy solids, which are difficult to refine, and if high-purity intermediate 1 and intermediate 2 cannot be obtained, it will bring about cumbersome post-treatment operations and impurities Technical problems unsuitable for industrial production such as excessive content and difficult refining
The post-treatment method of intermediate 1 recorded in the prior art includes column chromatography purification, but column chromatography purification is not conducive to industrial scale-up production, and how to obtain high-purity intermediate 2 has not been reported in the literature

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
  • Preparation method and application of hylagolil intermediate 1 and hylagolil intermediate 2
  • Preparation method and application of hylagolil intermediate 1 and hylagolil intermediate 2
  • Preparation method and application of hylagolil intermediate 1 and hylagolil intermediate 2

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] This embodiment provides a preparation method of Elagoli Intermediate 2.

[0032] 1. Preparation of intermediate 1 crude product:

[0033]

[0034] Intermediate 6 (50 g, 117 mmol) and D-Boc-phenylglycinol mesylate (59 g, 188 mmol) were dissolved in 300 mL of DMF, potassium carbonate (41 g, 293 mmol) was added under stirring, and the temperature was raised to 40 ± 5 °C for reaction 16h, stop heating;

[0035] The reaction solution was concentrated to about 200g, heated to 60±5℃, slowly added 800mL of water and stirred to dissolve, continued to grow crystals for 0.5h, slowly cooled to room temperature, continued to stir for 1h, and the filter cake was washed with 100mL of water; dried at 50℃ for 4- 8h, the crude product of Intermediate 1 was obtained, weighing 100.5g.

[0036] 2. Purification of crude intermediate 1

[0037] Take 100 g of the crude intermediate 1 and add it to 300 mL of ethanol, heat to 60±5°C, stir to dissolve, add 10 mL of water and continue to st...

Embodiment 2

[0041] This embodiment provides a purification method of Elagoli Intermediate 1.

[0042] 1. Preparation of crude intermediate 1: the same as in Example 1.

[0043] 2. Purification of crude intermediate 1

[0044] Take 10 g of the above-mentioned crude intermediate 1 and add it to 30 mL of ethanol, heat to 60 ± 5 °C, stir to dissolve, add 5 mL of water and continue to stir for 30 min, add 0.1 g of seed crystals (that is, intermediate 1 crystals); Slowly cool down to 10 ± 5°C, stirring was continued overnight. The next day was filtered, and the filter cake was washed with 10 mL of water; dried at 50° C. to obtain 6.3 g of a white solid with a yield of 84.2% and a purity of 99.46%.

Embodiment 3

[0046]This example provides a purification method of Elagoli Intermediate 1.

[0047] 1. Preparation of crude intermediate 1: the same as in Example 1.

[0048] 2. Purification of crude intermediate 1

[0049] Add 10 g of the crude intermediate 1 to 30 mL of tetrahydrofuran, heat to 60 ± 5 °C, stir to dissolve, add 60 mL of water and continue stirring for 30 min; slowly cool down to 20 ± 5 °C, continue stirring overnight. The next day, filtered, and the filter cake was washed with 10 mL of water; dried at 50° C. to obtain 6.6 g of a white solid with a yield of 87.3% and a purity of 99.13%.

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 technical field of compound preparation, in particular to a preparation method and application of an intermediate 1 and an intermediate 2 of hylagolil. The preparation method comprises the following steps: firstly, heating and dissolving a crude product of the hylagolil intermediate 1 in a solvent, cooling to room temperature or adding water, uniformly mixing, then adding a seed crystal, cooling and crystallizing to obtain the refined hylagolil intermediate 1. According to the preparation method of the hylagolil intermediate 2 provided by the invention, the hylagolil intermediate 2 is obtained by reacting a refined hylagolil intermediate 1 in an acidic reaction solution. The preparation method has the advantages that the purity of the prepared hylagoride intermediate 1 and hylagoride intermediate 2 is high, the purity of the prepared hylagoride raw material medicine can be effectively guaranteed, the synthesis operation of the hylagoride raw material medicine is simpler, more convenient, more coherent, safer and controllable, and the industrial production is easy.

Description

technical field [0001] The invention belongs to the technical field of compound preparation, and in particular relates to a preparation method and application of an Elagoli intermediate 1 and an intermediate 2. Background technique [0002] Elagolix is ​​currently the only orally administered non-peptide small molecule gonadotropin-releasing hormone (GnRH) receptor antagonist, which inhibits endogenous binding to GnRH receptors in the pituitary gland Sexual GnRH signaling. Administration produces dose-dependent inhibition of luteinizing hormone and follicle-stimulating hormone, and reduces plasma concentrations of ovarian sex hormones, estradiol, and progesterone. In July 2018, the drug was approved by the FDA for the treatment of women with moderate-to-severe endometriosis pain. It is worth mentioning that Elagolix is ​​the first oral therapy approved by the FDA for this indication in ten years. [0003] The medicine has many advantages, such as safety, effectiveness, or...

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): C07D239/54
CPCC07D239/54
Inventor 陈金萍赵军旭何清超王颖
Owner SHIJIANGZHUANG ZHIHENG PHARMACY TECH CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap