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

Synthesis method of 2-fluoro-5-trifluoromethylpyrimidine

A technology of trifluoromethylpyrimidine and synthesis method, which is applied in the field of drug synthesis, and can solve the problems of high cost of raw materials, complicated process, and high cost of antimony pentafluoride

Active Publication Date: 2021-10-19
KINGCHEM LIAONING CHEMICAL CO LTD
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The disadvantage of this method is that carbon tetrachloride, which is prohibited by the "Montreal Protocol", is used as a solvent, and sulfone chloride is used for chlorination. The cost of sulfone chloride is much higher than that of chlorine, and the cost of antimony pentafluoride is also very high. and heavy metal pollution
[0010] In a word, the methods for synthesizing 2-fluoro-5-trifluoromethylpyrimidine in the present art have problems such as complex process, high cost of raw materials, low yield, etc.

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
  • Synthesis method of 2-fluoro-5-trifluoromethylpyrimidine
  • Synthesis method of 2-fluoro-5-trifluoromethylpyrimidine
  • Synthesis method of 2-fluoro-5-trifluoromethylpyrimidine

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0029] The invention provides a kind of synthetic method of 2-fluoro-5-trifluoromethylpyrimidine, comprising the following steps:

[0030] Mix 5-methyluracil, phosphorus oxychloride and phosphorus pentachloride for ring chlorination to obtain 2,4-dichloro-5-methylpyrimidine;

[0031] Mixing the 2,4-dichloro-5-methylpyrimidine and zinc powder for reduction reaction to obtain 2-chloro-5-methylpyrimidine;

[0032] The 2-chloro-5-methylpyrimidine is mixed with the initiator, and chlorine gas is introduced to perform a chlorination reaction to obtain 2-chloro-5-trichloromethylpyrimidine;

[0033] The 2-chloro-5-trichloromethylpyrimidine and hydrogen fluoride are mixed for fluorination reaction to obtain 2-fluoro-5-trifluoromethylpyrimidine.

[0034] In the invention, 5-methyluracil, phosphorus oxychloride and phosphorus pentachloride are mixed for ring chlorination reaction to obtain 2,4-dichloro-5-methylpyrimidine. In the present invention, the molar ratio of said 5-methyluracil...

Embodiment 1

[0057] Take 75g (0.59mol) of 5-methyluracil, 236g of phosphorus oxychloride, and 16.5g (0.12mol) of triethylamine hydrochloride, add them into the reaction flask, raise the temperature to 100°C to 110°C, and reflux for 5h. Cool down to 40°C, add phosphorus pentachloride 248 (1.19mol), and keep the reaction for 2h. After the reaction was completed, phosphorus oxychloride was recovered by vacuum distillation, and the vacuum distillation was continued to obtain 88 g (0.54 mol) of 2,4-dichloro-5-methylpyrimidine, with a yield of 91.5%.

Embodiment 2

[0059] Take 70g (0.43mol) of 2,4-dichloro-5-methylpyrimidine obtained in Example 1, 84g (1.28mol) of zinc powder, and 700g of water, put them into the reaction bottle, and reflux at 95°C to 105°C for 5h , after the reaction was completed, the product material liquid was extracted with dichloromethane, and the dichloromethane phase was distilled to reclaim the dichloromethane, and the crude product obtained was recrystallized with petroleum ether to obtain 45 g of 2-chloro-5-methylpyrimidine (0.35 mol ), yield 81.4%.

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 medicine synthesis, and provides a synthesis method of 2-fluoro-5-trifluoromethylpyrimidine. According to the invention, 5-methyl uracil is used as a raw material, and a target product is obtained through a cyclic chlorination reaction, a reduction reaction, a chlorination reaction and a fluorination reaction, the process is simple, the raw material is cheap and easy to obtain, the yield is high, and heavy metal pollution is not generated in the whole process; and according to the method, phosphorus oxychloride is used for chlorination in the cyclochlorination reaction, chlorine is used for chlorination in the chlorination reaction, the cost of phosphorus oxychloride and chlorine is low, phosphorus pentachloride is used for recycling phosphorus oxychloride in the cyclochlorination reaction, and the reaction cost can be further reduced.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of 2-fluoro-5-trifluoromethylpyrimidine. Background technique [0002] 2-Fluoro-5-trifluoromethylpyrimidine is an important intermediate in the synthesis of medicine, which can be used to synthesize fused ring dihydrofuran compounds, which can be used as G protein-coupled receptor GPR119 regulators, For the treatment of diabetes, obesity and dyslipidemia diseases. In addition, 2-fluoro-5-trifluoromethylpyrimidine can also be used as an intermediate in the synthesis of drugs for the treatment of Alzheimer's disease and schizophrenia. [0003] At present, the synthetic methods of 2-fluoro-5-trifluoromethylpyrimidine reported in the art mainly contain the following types: [0004] Patent WO2009150240A introduces a method for synthesizing fluoro-5-trifluoromethylpyrimidine, in which 2,4-dichloro-5-trifluoromethylpyrimidine is used as raw material, and zinc...

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): C07D239/30
CPCC07D239/30
Inventor 付立民何秉恕胡珍珠宋桐集王新宇
Owner KINGCHEM LIAONING CHEMICAL CO LTD
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