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

Method for using high-dispersion double-metal nano material to prepare drug intermediate for urogenital system

A highly dispersed and versatile technology, applied in chemical instruments and methods, chemical/physical processes, physical/chemical process catalysts, etc., can solve the problems of low yield, high production cost, unsuitable catalyst recovery, etc., and achieve high yield , post-processing is simple, easy to remove the effect

Active Publication Date: 2018-07-24
济南众志康成药物研发有限公司
View PDF9 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] As far as intermediate 5 is concerned, the overall yield of route 4 is 21.4%, and the route change has industrialization prospects; but when compound 17 is used to prepare compound 4, the yield is not high, which affects the application prospect of this process
[0019] In the cyanation reaction, in order to improve the conversion rate, noble metal Pd and corresponding ligands are usually added as a homogeneous catalyst. The production cost of this method is high, and the catalyst is not suitable for recycling; Below the ppm level; therefore, it is of great significance to develop a new preparation method to prepare compound 4 by cyanation reaction of compound 14 to improve the yield and prepare clinical samples

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 using high-dispersion double-metal nano material to prepare drug intermediate for urogenital system
  • Method for using high-dispersion double-metal nano material to prepare drug intermediate for urogenital system
  • Method for using high-dispersion double-metal nano material to prepare drug intermediate for urogenital system

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] The preparation method of the two-component catalyst of supported type highly dispersed Pd / Ni co-doped, comprises the following steps:

[0041] 1) Dissolve 10mmol of 2-aminoterephthalic acid in potassium hydroxide ethanol aqueous solution with pH=8-9, ultrasonically dissolve, add 10mmol of nickel chloride hexahydrate into the system, and then transfer to the polytetrafluoroethylene-lined In a stainless steel reaction kettle, conduct hydrothermal treatment at 150-180°C for 8-12h in a sealed environment, cool down to room temperature naturally, filter, then place in 20ml of absolute ethanol, beat at 40-60°C for 1-2h, and then filter, 50-60 Vacuum drying at ℃ to obtain nickel 2-aminoterephthalate;

[0042] 2) Disperse 100.0 g of nickel 2-aminoterephthalate in 500 ml of deionized water, then adjust the pH of the system to 3.0-3.8 with 1 mol / L hydrochloric acid aqueous solution, and slowly add 40 ml of 2 mol / L potassium tetrachloropalladate aqueous solution dropwise , keep ...

Embodiment 2

[0044] Catalyst performance evaluation, the reaction conditions are as follows:

[0045] Add 2-bromo-5-nitro-3-(trifluoromethyl)pyridine (2.70g, 10mmol, HPLC purity is 99.8%) in 50ml three-necked flask, 10ml solvent NMP, cyanation reagent CuCN 15mmol, catalyst 0.30g 120 DEG C of reaction, when HPLC monitors that the substrate is no longer converted, the reaction is stopped, and the substrate conversion rate and product selectivity of each reaction liquid system are counted. The results are shown in Table 1:

[0046] Table 1 Different catalyst reaction results

[0047] Catalyst type

Conversion rates / %

selectivity / %

Embodiment 1 preparation

89.8

93.1

Pd / C (5%wtPd content)

78.2

96.3

Pd(OAc) 2

65.2

94.3

Pd(PPh 3 ) 4

46.3

—

PD 2 (dba) 3

59.3

—

NA

69.8

91.4

[0048] Note: NA means that no catalyst was added, and "—" means that the selectivity data was not counte...

Embodiment 3

[0051] For the screening of solvent types and cyanation reagents, the reaction conditions are as follows:

[0052] Add 2-bromo-5-nitro-3-(trifluoromethyl)pyridine (2.70g, 10mmol, HPLC purity is 99.8%) in the 50ml three-necked flask, 10ml solvent, cyanation reagent 15mmol, catalyst (embodiment 1 Preparation) 0.30g 120 DEG C of reaction, when HPLC monitoring substrate no longer converts, stop reaction, count the substrate conversion rate and the selectivity of product of each reaction liquid system, the result is as shown in table 2:

[0053] Table 2 The influence of different solvents and cyanation reagents on the reaction

[0054]

[0055]

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 belongs to the technical field of drug preparation, and particularly relates to a preparation method of a drug intermediate for an urogenital system. 2-amino terephthalic acid and nickelchloride hexahydrate serve as raw materials, a metal organic skeleton structure is formed, then the metal organic skeleton structure is loaded with certain Pd, and finally a load type high-dispersionPd / Ni co-doped double-component catalyst is obtained through reduction at high temperature. The catalyst is adopted to catalyze 2-bromo-5-nitro-3-(trifluoromethyl)pyridine to be subjected to a cyanation reaction to prepare the drug intermediate 2-cyano-5-nitro-3-(trifluoromethyl)pyridine for the urogenital system, the yield is high, and post-treatment is simple, the high-purity target product canbe obtained by adopting extraction and concentration, and column chromatography purification is not needed; and the catalyst can be conveniently removed from the system, and can be recycled.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and in particular relates to a method for preparing a medicine intermediate for genitourinary system with highly dispersed bimetallic nanomaterials. Background technique [0002] Prostate cancer is one of the most common tumors of the male genitourinary system, the second most common cause of cancer death in American men, and approximately one in six American men will be diagnosed with the disease during his lifetime . Castration-resistant prostate cancer (CRPC) refers to prostate cancer that still progresses after initial continuous androgen deprivation therapy (ADT). [0003] On February 14, 2018, the U.S. FDA approved Johnson & Johnson's apalutamide for the treatment of patients with prostate cancer that continues to grow and has not spread (non-metastatic) despite hormone (castration-resistant) therapy. This is the first drug approved by the FDA for the treatment of non-metasta...

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): C07D213/84B01J31/04
CPCB01J31/04B01J2231/4205C07D213/84
Inventor 胡鹏刘艳玉赵庆春苏萌
Owner 济南众志康成药物研发有限公司
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