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

Novel method for preparing 3-aminopyrazole-4-formamide hemi-sulfate

A technology of hemisulfate and aminopyrazole, applied in the field of pharmaceutical synthesis, can solve the problems of long reaction steps, compressed allopurinol profit space, high cost of malononitrile, etc., and achieves mild reaction conditions, simple preparation method and production cost. low effect

Pending Publication Date: 2022-01-28
HUBEI POLYTECHNIC UNIV +2
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The first method is to use pyridine amidohydrazone and ethoxymethylene malononitrile etc. as raw materials to obtain 3-aminopyrazole-4-carboxamide hemisulfate through addition, cyclization, and salt-forming reactions. But the used main raw material of this method is expensive, and the total reaction yield is not high, and industrialization promotion has certain difficulty (Reuken GJones. -4891)
The second method is to prepare 3-aminopyrazole-4-carboxamide hemisulfate by reactions such as malononitrile, triethyl orthoformate, hydrazine hydrate and sulfuric acid, but the reaction steps of this method are longer, and the propanediol used Nitrile and other raw materials are expensive (Ding Jingmin, Chen Huiru, Zhang Wenwen, et al. Synthesis of 3-aminopyrazole-4-carboxamide hemisulfate[J]. Applied Chemical Industry, 2009,38(1):77-78)
But the product yield of this method is the highest about 80%, produces a large amount of acetonitrile waste liquid and morpholine waste gas etc. in production, and environmental management cost is big, and the price of raw materials such as triethyl orthoformate rises in recent years, has compressed allopurin Profit margin of alcohol production (patents CN 104926728 A, CN101774970 A)

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
  • Novel method for preparing 3-aminopyrazole-4-formamide hemi-sulfate
  • Novel method for preparing 3-aminopyrazole-4-formamide hemi-sulfate
  • Novel method for preparing 3-aminopyrazole-4-formamide hemi-sulfate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0021] The synthesis of embodiment 12-cyano group-3-(dimethylamino)acrylamide

[0022] Dissolve 2.5g (0.03mol) of cyanoacetamide in 30mL (0.35mol) of 1,4-dioxane, then add 3.9g (0.033mol) of N,N-dimethylformamide dimethyl acetal, in Reaction at 50°C for 3h. After the reaction was complete as monitored by TLC, the 1,4-dioxane was evaporated under reduced pressure, and the obtained solid was washed with 5 mL (0.06 mol) of cold 1,4-dioxane, and dried to obtain 4.03 g of a white product, with a yield of 96%. . mp: 145-147°C. IR(KBr), ν / cm -1 : 3461, 3154 (-NH 2 ); 2188 (-CN); 1665 (C=O); 1559 (C=C). 1 HNMR (DMSO-d 6 ): 3.23(s,6H); 5.87(s,2H); 7.75(s,1H).

Embodiment 23

[0023] Synthesis of embodiment 23-aminopyrazole-4-carboxamide hemisulfate

[0024] Add 40mL (0.77mol) of absolute ethanol and 2.0g (0.04mol) of hydrazine hydrate to 4.17g (0.03mol) of 2-cyano-3-(dimethylamino)acrylamide, and then reflux at 80°C for 5h. After TLC monitors that the reaction is complete, adjust the pH 1-2 of the solution with 50% sulfuric acid by mass percentage, continue to stir for 20 min, filter with suction, and wash the filter cake successively with 5 mL of water (0.28 mol) and 5 mL (0.07 mol) of acetone to obtain a white solid powder 3 -Aminopyrazole-4-carboxamide hemisulfate 3.26 g, yield 93%. mp: 224-226°C. IR(KBr), ν / cm -1 : 3447, 3310, 3187(N-H); 1660(C=O); 1563(C=C); 1 HNMR (DMSO-d 6 )δ8.05(s,4H,NH 2 ).

Embodiment 3

[0025] Example 3 One-step synthesis of 3-aminopyrazole-4-carboxamide hemisulfate

[0026] Dissolve 2.5g (0.03mol) of cyanoacetamide in 104mL (1.20mol) of 1,4-dioxane, then add 7.08g (0.06mol) of N,N-dimethylformamide dimethyl acetal, in Reaction at 40°C for 2h. After the completion of the reaction as monitored by TLC, the solvent was distilled off under reduced pressure. The obtained solid was washed with 7.6mL (0.09mol) of cold 1,4-dioxane, and then 52.5mL of absolute ethanol (0.9mol) and 4.5g (0.09mol) of hydrazine hydrate were added to the above reaction system, and refluxed at 70°C 5h. After TLC monitors that the reaction is complete, adjust the pH of the solution to 1-2 with 50% sulfuric acid by mass percent, continue to stir for 25 min, filter with suction, and wash the filter cake successively with 4.3 mL of water (0.24 mol) and 4.4 mL (0.06 mol) of acetone to obtain a white solid Powdered 3-aminopyrazole-4-carboxamide hemisulfate 4.68g, yield 88.8%.

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 provides a novel method for preparing 3-aminopyrazole-4-formamide hemi-sulfate. The method comprises the following steps: by taking cyanoacetamide, N, N-dimethylformamide dimethyl acetal and the like as raw materials, carrying out condensation, cyclization and salt forming reaction to prepare the 3-aminopyrazole-4-formamide hemi-sulfate. According to the invention, the whole reaction process can be completed step by step or continuously in the same reactor, and the preparation method is simple, clean and environment-friendly in process, low in operation difficulty, mild in reaction condition, high in yield and low in production cost.

Description

technical field [0001] The invention belongs to the field of drug synthesis, in particular to a new method for preparing 3-aminopyrazole-4-carboxamide hemisulfate. Background technique [0002] Allopurinol is a classic anti-gout drug, which can effectively inhibit xanthine oxidase, prevent the metabolism of hypoxanthine and xanthine into uric acid, thereby reducing the production of uric acid and reducing the content of uric acid in the body to normal levels. 3-Aminopyrazole-4-carboxamide hemisulfate is an important intermediate for the synthesis of allopurinol, and there are three main methods for its synthesis. The first method is to use pyridine amidohydrazone and ethoxymethylene malononitrile etc. as raw materials to obtain 3-aminopyrazole-4-carboxamide hemisulfate through addition, cyclization, and salt-forming reactions. But the used main raw material of this method is expensive, and the total reaction yield is not high, and industrialization promotion has certain dif...

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): C07D231/38C07D207/34C07C253/30C07C255/30
CPCC07D231/38C07D207/34C07C253/30C07C255/30
Inventor 张勇刘桂琴隋宁徐来卢资左小华
Owner HUBEI POLYTECHNIC UNIV
Features
  • Generate Ideas
  • 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