Tetrahydrobenzofuran Mannich alkali compounds, and preparation method and application thereof

A technology for benzofuran and compounds, which is applied in the field of tetrahydrobenzofuran Mannich base compounds, can solve environmental pollution and other problems, and achieve the effects of simple post-processing, low environmental pollution, and good functional group tolerance

Active Publication Date: 2020-02-18
CHINA THREE GORGES UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The traditional Mannich reaction mostly uses protonic acid or Lewis acid catalysts, but these acid cat

Method used

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  • Tetrahydrobenzofuran Mannich alkali compounds, and preparation method and application thereof
  • Tetrahydrobenzofuran Mannich alkali compounds, and preparation method and application thereof
  • Tetrahydrobenzofuran Mannich alkali compounds, and preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Example Embodiment

[0020] Example 1

[0021] Preparation of Mannich base of tetrahydrobenzofurocyclohexanone

[0022] Using tetrahydrobenzofuran-4-one oxime ether as the raw material, the reaction route of the long-chain Mannich base by reacting with secondary amine and formaldehyde on the terminal alkyne is as follows:

[0023]

[0024] Table 1 Experimental equipment

[0025]

[0026] Experimental reagent

[0027] Table 2 Experimental reagents

[0028]

[0029] The reagents used are all domestically-available commercially available analytical grades. The column chromatography silica gel (200-300 mesh) uses Qingdao Ocean Chemical products. All reagents in the reaction are pretreated with reference to the "Reagent Purification Manual" before use.

[0030] Synthesis of intermediates

[0031]

[0032] Dissolve 3-methyl-6,7-dihydrobenzofuran-4(5H)-one (Compound 1a, 1.78 g, 10.0 mmol) and hydroxylamine hydrochloride (0.834 g, 12.0 mmol) in 30 mL of anhydrous methanol, and then Anhydrous sodium acetate (0.984 g, ...

Example Embodiment

[0088] Example 2

[0089] Preparation of heterocyclic Mannich base 5

[0090]

[0091] Put Intermediate 3b (1.0 mmol), p-chloroaniline (1.5 mmol) and 30% aqueous formaldehyde solution (4.0 mmol) into a 50 mL round bottom flask, add 10 mL of ethylene glycol to dissolve and a catalytic amount of glacial acetic acid, and heat to 80°C, Stir at a constant temperature for a certain period of time, stirring, and TLC monitoring until the reaction is complete. The reaction solution was poured into 30 mL of water, extracted with ethyl acetate (3×20 mL), dried, and the organic phase was distilled under reduced pressure to remove the solvent. The resulting crude product was purified by column chromatography ( Petroleum ether: ethyl acetate = 10:1) to obtain heterocyclic Mannich base 5a.

[0092] (E)-2-(((4-Chlorophenyl)amino)methyl)-3,6,6-trimethyl-6,7-dihydrobenzofuran-4(5H)-one O-prop-2-yn-1-yl oxime (5a):Yellow oil, yield 61%; R f 0.45(ethyl acetate / petroleum ether=1: 30,v / v); 1 H NMR(CDCl...

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Abstract

The invention provides tetrahydrobenzofuran Mannich alkali compounds. The structural formula of the tetrahydrobenzofuran Mannich alkali compounds is shown in the specification, wherein R is hydrogen or methyl, R2 and R3 comprise any one of methyl, ethyl, n-propyl, isopropyl, n-butyl, hydroxyethyl, a C4 or C5 methylene chain and an N atom-containing C4 or C5 methylene chain. A preparation method comprises the steps: taking cuprous iodide as a catalyst, dimethyl sulfoxide as a solvent, and a formaldehyde aqueous solution (preferably 30% formaldehyde aqueous solution), secondary amine and furanocyclohexanone oxime ethers as raw materials, and preparing a series of long-chain tetrahydrobenzofuranone Mannich alkalis through a one-pot reaction. The reaction product is single, no side reaction occurs, good functional group tolerance is achieved, and secondary amine containing hydroxyl and heteroatoms has no influence on the reaction. The prepared product is applied to anti-gastric cancer drugs, and a remarkable effect is achieved.

Description

technical field [0001] The invention relates to a tetrahydrobenzofuran Mannich base compound and its application in the preparation of anti-gastric cancer drugs. Background technique [0002] As one of the global public health problems, malignant tumors have become the number one killer of human health in the 21st century. According to the statistics of the World Health Organization (WHO) in 2008, gastric cancer (Gastric Cancer) is one of the common malignant tumors of the digestive tract. , there are more than 1 million new cases of gastric cancer every year in the world, and about 800,000 deaths. The incidence of gastric cancer in my country accounts for more than 30% of the total incidence of upper gastrointestinal tumors in the world, and it is one of the countries with higher incidence and mortality of gastric cancer. Therefore, the development of efficient anti-gastric cancer drugs has important social significance and economic value. Mannich reaction, also known as...

Claims

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Application Information

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IPC IPC(8): C07D307/79C07D307/52A61P35/00
CPCC07D307/79C07D307/52A61P35/00
Inventor 黄年玉金蕾刘明国姚辉邓张双郭志勇汪鋆植张雪晴
Owner CHINA THREE GORGES UNIV
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