Preparation methods of three kinds of methyl uric acid compounds, intermediate and preparation method of the intermediate

A compound, methylation technology, applied in the fields of organic chemistry, digestive system, drug combination, etc., can solve the problems of no synthesis report and no industrial value.

Inactive Publication Date: 2018-11-30
NANJING NUTRABUILDING BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Regarding the synthesis of Methylliberine and Liberine, there are basically no synthetic reports in the literature, only the method of O(2)-methyluric acid methylation was reported in Phytochemistry 1975,14,747-750 , but no industrial value

Method used

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  • Preparation methods of three kinds of methyl uric acid compounds, intermediate and preparation method of the intermediate
  • Preparation methods of three kinds of methyl uric acid compounds, intermediate and preparation method of the intermediate
  • Preparation methods of three kinds of methyl uric acid compounds, intermediate and preparation method of the intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] The preparation of embodiment 1 caffeine

[0070] (1) Preparation of 5,6-diamino-2-methoxy-3-methylpyrimidinyl-4-one

[0071]

[0072] 6-Amino-2-methoxy-3-methylpyrimidinyl-4-one (10g, 64.5mmol) was dissolved in tetrahydrofuran, and N-chlorosuccinimide (12.9g , 96.8mmol), after the addition was completed, the reaction was carried out at 20-30°C for 6 hours, and the reaction was basically complete. After concentration, add water and dichloromethane, separate the liquids, wash with sodium thiosulfate solution, sodium bicarbonate solution, and water successively, recrystallize the organic phase after concentration, and obtain off-white solid 6-amino-5-chloro-2- Methoxy-3-methylpyrimidinyl-4-one 10.4 g, yield 85%.

[0073] Suspend 6-amino-5-chloro-2-methoxy-3-methylpyrimidinyl-4-one (10.4g, 54.8mmol) in methanol, add ammonia water (35.8g, 548mmol), and react at 50-60°C After 12 hours, the reaction was substantially complete. Concentrate, add dichloromethane and water...

Embodiment 2

[0078] The preparation of embodiment 2 caffeine

[0079] (1) Preparation of 5,6-diamino-2-methoxy-3-methylpyrimidinyl-4-one

[0080]

[0081] 6-Amino-2-methoxy-3-methylpyrimidinyl-4-one (10 g, 64.5 mmol) was dissolved in tetrahydrofuran, and dibromohydantoin (13.8 g, 48.4 mmol) was added in portions at 20-30°C. After the addition is complete, react at 20-30°C for 6 hours, and the reaction is basically complete. After concentration, add water and dichloromethane, separate the liquids, wash with sodium thiosulfate solution, sodium bicarbonate solution, and water successively, recrystallize the organic phase after concentration, and obtain off-white solid 6-amino-5-bromo-2- Methoxy-3-methylpyrimidinyl-4-one 12.1 g, yield 80%.

[0082] 6-Amino-5-bromo-2-methoxy-3-methylpyrimidinyl-4-one (12.1g, 51.6mmol) was suspended in tetrahydrofuran, ammonia water (16.9g, 258mmol) was added, and sealed at 110-120°C After 1 hour of reaction, the reaction was almost complete. Concentrate,...

Embodiment 3

[0087] The preparation of embodiment 3 caffeine

[0088] (1) Preparation of 5,6-diamino-2-methoxy-3-methylpyrimidinyl-4-one

[0089]

[0090] 6-Amino-2-methoxy-3-methylpyrimidinyl-4-one (10g, 64.5mmol) was dissolved in toluene, and N-bromosuccinimide (51.6mmol ), react at 70-80°C for 1 hour after the addition, and the reaction is basically complete. After concentration, add water and dichloromethane, separate the liquids, wash with sodium thiosulfate solution, sodium bicarbonate solution, and water successively, recrystallize the organic phase after concentration, and obtain off-white solid 6-amino-5-chloro-2- Methoxy-3-methylpyrimidinyl-4-one 10.6 g, yield 87%.

[0091] Suspend 6-amino-5-bromo-2-methoxy-3-methylpyrimidinyl-4-one (10.4g, 54.8mmol) in toluene, add ammonia (54.8mmol), and react at 20-30°C for 24 hours , the reaction is almost complete. Concentrate, add dichloromethane and water solution, concentrate the organic phase, recrystallize with water, and dry to ob...

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PUM

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Abstract

The invention provides preparation methods of three types of compounds which can be extracted from plants such as tea trees and have the effects of resisting depression, tranquilizing and hypnosis, resisting inflammation and easing pain, reducing stress damage of the liver cells and improving the exercise ability, an intermediate and a preparation method of the intermediate. The method is simple and convenient to operate, high in safety, high in atom economy and less in three wastes, and the raw and auxiliary materials are cheap and easy to obtain, low in toxicity, safe and stable; the reaction conditions are mild, the impurities are few, and the yield is high. The product is purified by crystallization, column chromatography is avoided, the operation is simple and feasible, and the process is stable, easy to control and convenient in reaction after-treatment, and can be economically and conveniently used for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a preparation method of three methyluric acid compounds, an intermediate and a preparation method of the intermediate. Background technique [0002] Methyluric acid alkaloids were first discovered from tea trees, and they are mainly found in coffee plants such as Liberica coffee, Abiokuta coffee, Devere coffee and other plants of the genus Coffea and Cocoa. These compounds have the same molecular core structure and can be transformed into each other in the human body or in plants. In recent years, studies have found that Theacrine, Liberine, and Methylliberine have antidepressant, sedative and hypnotic effects, anti-inflammatory and analgesic effects, relieve stress damage to liver cells, and improve exercise It is one of the hot spots in the research of purine alkaloids at present. [0003] [0004] Chemical structure of tetramethyluric acid, methylc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D473/06C07D239/54A61P25/22A61P25/24A61P25/20A61P1/00A61P29/00A61P25/14
CPCA61P1/00A61P25/14A61P25/20A61P25/22A61P25/24A61P29/00C07D239/54C07D473/06
Inventor 张健廖琪林
Owner NANJING NUTRABUILDING BIO TECH CO LTD
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