Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of IDO1 inhibitor Epacadostat intermediate

An intermediate and reducing agent technology, applied in the field of pharmaceutical synthesis, can solve the problems of difficult to scale up production, high toxicity, unfavorable labor protection, etc., and achieve the effects of mild reaction conditions, easy and difficult to obtain raw materials

Active Publication Date: 2018-06-01
CHINA PHARM UNIV
View PDF7 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the route is short, the aziridine used in the fifth step is a highly toxic and flammable reagent, which is not conducive to labor protection; the sixth step requires high-temperature microwave reaction, which is difficult to scale up production
[0020] To sum up, considering factors such as raw material cost, reaction steps, reaction conditions, industrial scale-up, and labor protection, route 1 has comprehensive advantages and is a process route with better industrialization prospects, but it also has shortcomings that need to be improved

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 of IDO1 inhibitor Epacadostat intermediate
  • Preparation method of IDO1 inhibitor Epacadostat intermediate
  • Preparation method of IDO1 inhibitor Epacadostat intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] Preparation of 4-amino-N'-hydroxy-1,2,5-oxadiazole-3-carboxamidine (II)

[0040] Add malononitrile (25.0g, 378.4mmol) into a 500mL three-necked flask, add water (75mL), heat and stir at 45°C to dissolve, put it in an ice bath, add glacial acetic acid (21.6mL, 378.4mmol), and cool to At 0°C, add NaNO dropwise 2 (28.7 g, 416.2 mmol) was dissolved in 50 mL of water, and after the addition was completed, it was stirred at room temperature for about 2 hours (the reaction was complete as monitored by TLC). At 0°C, add NH dropwise 2 OH·HCl (65.7g, 946.12mmol) was dissolved in 80mL of water, and the pH of the reaction solution was adjusted to 9-10 with NaOH solution. After the addition was completed, the reaction was carried out at room temperature for about 4 hours (the reaction was complete as monitored by TLC); heated to reflux React for about 8 hours (TLC monitors that the reaction is complete); stop heating, cool, filter with suction, and dry at 45° C. to obtain 39.1 g o...

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 drug synthesis field, specifically to a preparation method of an IDO1 (indoleamine-2, 3-dioxygenase 1) inhibitor Epacadostat intermediate 4-(3-bromo-4-fluorophenyl)-3-(4-((2-bromoethyl)amino)-1, 2, 5-oxadiazole-3-yl)-1, 2, 4-oxadiazole-5(4H)-one (VI). The method provided by the invention has the characteristics of: easily available raw materials, mild reaction conditions and the like, and is beneficial to industrial production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a preparation method of an IDO1 inhibitor Epacadostat (I) intermediate. Background technique [0002] Indoleamine-2,3-dioxygenase (IDO for short) is a monomeric enzyme containing heme, which contains two subtypes, namely indoleamine-2, 3-dioxygenase 1 (Indoleamine-2,3-dioxygenase 1, referred to as IDO1) and indoleamine 2,3-dioxygenase 2 (Indoleamine-2,3-dioxygenase 2, referred to as IDO2). IDO can catalyze the conversion of tryptophan into N-formylkynurenine through oxidation reaction. When IDO is overexpressed, it will lead to a large amount of tryptophan degradation and accumulation of N-formylkynurenine in the body. Studies have found that IDO is closely related to the pathogenesis of many diseases, such as: cancer, depression, Alzheimer's disease, etc. [0003] Epacadostat (INCB-24360, I), the chemical name is (Z)-N-(3-bromo-4-fluorophenyl)-N'-hydroxyl-4-(2-(aminosulfonylamino...

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): C07D413/04
CPCC07D413/04
Inventor 朱启华何光超董仲夏单金曦王俊杰许可馨徐云根
Owner CHINA PHARM UNIV
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com