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

Process for preparing N-phenyl-2-pyrimidyl amine derivative

An amine derivative and phenyl technology, which is applied in the field of preparation of N-phenyl-2-pyrimidineamine derivatives, can solve the problems of high price, long reaction steps, harsh reaction conditions and the like, and achieve great social and economic benefits , The effect of scientific synthesis route and high product yield

Inactive Publication Date: 2009-09-09
ZHEJIANG ACAD OF MEDICAL SCI
View PDF5 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The above-mentioned preparation method has the disadvantages that the reaction starting materials are difficult to obtain in the Chinese market, some raw materials are highly toxic, expensive, the reaction steps are long, and the reaction conditions are relatively harsh. It is not suitable for domestic production.

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
  • Process for preparing N-phenyl-2-pyrimidyl amine derivative
  • Process for preparing N-phenyl-2-pyrimidyl amine derivative
  • Process for preparing N-phenyl-2-pyrimidyl amine derivative

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1: 2-Chloro-4-(3-pyridyl)pyrimidine

[0031] 2.25 g of 3-bromopyridine was dissolved in 5 mL of anhydrous ether. Under the protection of nitrogen, 3 mL of 1.6M n-butyllithium was added dropwise at a low temperature of -40°C, and stirring was continued for 0.5 h after the dropping. After adding 3.3 g of zinc bromide in 10 mL of anhydrous ether at one time, the reaction was kept and stirred for 1 hour. Warm to room temperature, add a solution of 1.49 g of 2,4-dichloropyrimidine in 5 mL of anhydrous tetrahydrofuran and a catalytic amount of tetrakis(triphenylphosphorus) palladium, and react under reflux for 18 hours. After the reaction is completed, first extract with ethyl acetate, add dilute hydrochloric acid to the extract, and then adjust the pH to 10 with sodium hydroxide to precipitate a flocculent solid. After collection and purification, 1.65g of 2-chloro-4-(3-pyridyl)pyrimidine, mp142-143℃, 1 H-NMR(CDCl 3 ): 748 (1H, m, 5'-H), 7.71 (1H, d, 5-H), 8.45 (1H, m, 4...

Embodiment 2

[0032] Example 2: N-(2-Methyl-4-nitrophenyl)yl-4-(3-pyridyl)-pyrimidin-2-amine

[0033] The above-mentioned 2-chloro-4-(3-pyridyl)pyrimidine 1.91g, p-nitro-o-methylaniline 1.6g, and methanesulfonic acid 0.6g were refluxed and reacted in 10 mL of anhydrous dioxane for 6 hours. After the reaction is complete, the solvent is recovered, a large amount of cold water is added to the residue, and the residue is basified with sodium bicarbonate. Collect the precipitated solid and dry it to give 2.5g, mp 195-196°C. 13 C-NMR: 164.1, 156.2, 155.5, 149.4, 148.8, 148.6, 139.7, 135.4, 132.3, 132.1, 130.2, 121.9, 121.8, 118.5, 108.9, 18.2.

Embodiment 3

[0034] Example 3: N-phenyl-4-(3-pyridyl)-pyrimidin-2-amine

[0035] Using a method similar to Example 2, 1.91 g of 2-chloro-4-(3-pyridyl)pyrimidine, 1.0 g of aniline and 0.6 g of p-toluenesulfonic acid were refluxed in 10 mL of anhydrous dioxane for 6 hours to obtain the target product , Mp.147-148℃. 13 C-NMR: 164.1, 155.5, 154.4, 151.2, 149.3, 148.8, 135.5, 132.3, 130.2, 129.3, 129.3, 122.1, 113.5, 113.5, 108.9.

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 is a new organic chemical synthesis method, especially the key intermediate N-(2-methyl-5-nitrate) of the tyrosine protein kinase inhibitor imatinib for the treatment of diseases such as chronic myelogenous leukemia base) phenyl-4-(3-pyridyl) pyrimidin-2-amine and the preparation method of N-phenyl-pyrimidin-2-amine derivatives similar to its structure, the target product can be obtained by 4-aromatic heterocyclic group- 2-halogenated pyrimidine and substituted aniline are obtained by condensation in the presence of a catalyst. The preparation method has low raw material price, scientific and reasonable synthesis route, high product yield, practical value, great social and economic benefits, and can be used for the prevention and treatment of diseases caused by protein tyrosine kinases. treat.

Description

Technical field [0001] The present invention relates to a new organic chemical synthesis method, in particular to a protein tyrosine kinase inhibitor imatinib key intermediate N-(2-methyl-5-nitro) used to treat diseases such as chronic myelogenous leukemia. ) Preparation method of phenyl-4-(3-pyridyl)pyrimidin-2-amine and its structural analogue N-phenyl-2-pyrimidinamine derivative. Background technique [0002] Imatinib is the first anti-cancer drug invented by Novartis Pharmaceuticals in Switzerland that is rationally designed based on the mechanism of cancer cell action. In May 2001, the US Food and Drug Administration (FDA) approved it as a new oral anti-cancer drug for the treatment of chronic myelogenous leukemia in just two and a half months. In February 2002, the FDA approved it as a drug for the treatment of gastrointestinal stromal tumors. [0003] Imatinib is a new type of tyrosine protein kinase inhibitor that can inhibit the tyrosine kinase activity of abl / bcr, there...

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 Patents(China)
IPC IPC(8): C07D401/04C07D239/00C07D213/00
Inventor 王尊元马臻沈正荣
Owner ZHEJIANG ACAD OF MEDICAL SCI
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