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

Preparation method of 2, 4-diamino-6-chloropyrimidine

A technology of diamino and chloropyrimidine, which is applied in the field of preparation of 2,4-diamino-6-chloropyrimidine, can solve the problems of complex operation, high cost and low yield, and achieve high yield and strong repeatability , the effect of reducing risk

Pending Publication Date: 2022-04-26
汉瑞药业(荆门)有限公司
View PDF0 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] As can be seen from the above review, the current preparation schemes for 2,4-diamino-6-chloropyrimidine generally have the following disadvantages: low yield, complicated operation, and high cost

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] A kind of preparation method of 2,4-diamino-6-chloropyrimidine provided by the present invention, first carry out the synthesis of 2,4-diamino-6-hydroxypyrimidine: use methanol as solvent, under the action of sodium methylate, hydrochloric acid Guanidine and ethyl cyanoacetate were heated to reflux for cyclization. After the reaction was complete, the solvent was evaporated to dryness, and then water was added, and the pH was adjusted to 7 with acetic acid, stirred thoroughly and then filtered to obtain 2,4-diamino-6-hydroxypyrimidine. This step can significantly improve the yield: the experimental data results show that when pH=7 is adjusted with hydrochloric acid, because the precipitated 2,4-diamino-6-hydroxypyrimidine is easy to react with hydrochloric acid to form hydrochloride and dissolve in water, while at pH When =9, 2,4-diamino-6-hydroxypyrimidine is not easy to react with hydrochloric acid, so the yield of adjusting pH to below 8 with hydrochloric acid is not...

Embodiment 2

[0021] The preparation method of 2,4-diamino-6-hydroxypyrimidine in this example: add guanidine hydrochloride (100.00 g, 1.00 eq.) and MeOH (300 mL) to the reaction flask, add MeONa (62.21 g, 1.10 eq. .), heated to 60-70°C and stirred for 0.5h. Under stirring at 60-70°C, ethyl cyanoacetate (118.41 g, 1.00 eq.) was added dropwise to the reaction system, and stirring was continued for more than 3 hours after the addition was completed. Cool down to 40-50°C, concentrate, and remove the solvent as much as possible. Add water (800 mL) to the concentrate, and add about 20 mL of glacial acetic acid to adjust the pH to 7 while stirring and controlling the temperature at 0-10 °C. After filtration, the filter cake was rinsed with 100 mL of water, collected and dried to obtain 2,4-diamino-6-hydroxypyrimidine (127.00 g, 96.2% yield).

[0022] 2,4-Diamino-6-chloropyrimidine was prepared by adding 2,4-diamino-6-hydroxypyrimidine (20.00 g, 1.00 eq.) to the reaction flask, followed by caref...

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 discloses a preparation method of 2, 4-diamino-6-chloropyrimidine, which sequentially comprises the following steps: reacting guanidine hydrochloride with ethyl cyanoacetate to obtain 2, 4-diamino-6-hydroxypyrimidine, and adding sodium methoxide in the reaction process; the obtained 2, 4-diamino-6-hydroxypyrimidine generates 2, 4-diamino-6-chloropyrimidine under the action of phosphorus oxychloride, and diisopropylethylamine is added as a catalyst in the reaction process. According to the method, the product purity and yield are improved, the process is simplified, the cost is reduced, and the method has the advantages of high yield and simplicity and reasonability in operation, and is a process suitable for commercial large-scale production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, and in particular relates to a preparation method of 2,4-diamino-6-chloropyrimidine. Background technique [0002] 2,4-Diamino-6-chloropyrimidine is an important raw material for the synthesis of Minoxidil. Some methods for preparing 2,4-diamino-6-chloropyrimidine that have been reported in related literatures mostly have low yield, high cost and complicated operation. [0003] According to the description in Chinese patent CN10566230A: 15g of DAHP is added to 45ml of phosphorus oxychloride to obtain 5.32g of 2,4-diamino-6-chloropyrimidine, the yield is 31%, which is low. [0004] According to "Shandong Pharmaceutical Industry" in 1996, Volume 15, No. 4, "Synthesis Research of Minolidine": Sodium methoxide, guanidine nitrate, and ethyl cyanoacetate were heated and refluxed for 2 hours, methanol was recovered, and pH was adjusted with acetic acid =8, crystallization, yield 81.4...

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): C07D239/48
CPCC07D239/48
Inventor 柴金柱李堃张佳羊智成
Owner 汉瑞药业(荆门)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