A kind of synthetic method of amino-containing hydroxypyridone compound

A technology for azide hydroxypyridone and ketone compounds, which is applied in the field of synthesis of hydroxypyridone compounds and can solve the problems of harsh reaction conditions, use of metals or toxic reagents, complicated operation and the like

Active Publication Date: 2020-11-13
ZHEJIANG UNIV OF TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In order to solve the problems of harsh reaction conditions, use of metals or toxic reagents, and cumbersome operations in the process of reducing azide to amino groups, the purpose of the present invention is to provide a synthetic method for a novel amino-containing hydroxypyridone iron chelating agent

Method used

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  • A kind of synthetic method of amino-containing hydroxypyridone compound
  • A kind of synthetic method of amino-containing hydroxypyridone compound
  • A kind of synthetic method of amino-containing hydroxypyridone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0065] Embodiment 1: the synthesis of compound 5,6

[0066]

[0067] Add maltol 1 (15.10g, 120mmol) or ethyl maltol 2 (16.80g, 120mmol), methyl iodide (51.10g, 360mmol) into a 500mL single-necked flask, anhydrous K 2 CO 3 (49.70g, 360mmol), acetone (100mL), heated to reflux for 3h. The reaction was monitored by TLC. After the conversion of the raw materials was complete, the reaction was stopped, the reaction solution was concentrated to obtain a solid, 180 mL of water was added, extracted with 180 mL×3 dichloromethane, the organic layers were combined, and the organic layer was washed with 100 mL×2 saturated brine, and anhydrous After drying over sodium sulfate and concentrating, 16.70 g (99.4%) of yellow liquid 3 or 18.40 g (99.5%) of yellow liquid 4 were obtained.

[0068] 3 (7.00g, 50mmol) or 4 (7.70g, 50mmol), ethanolamine (9.15g, 150mmol) or 3-aminopropanol (11.25g, 150mmol), 2M NaOH (5mL), ethanol (100mL ), warming up to reflux reaction 8h. The reaction was monit...

Embodiment 2

[0069] Embodiment 2: raw material Ia, Ib, Ic, the synthesis of Id

[0070]

[0071] Add 5a (3.66g, 20mmol, n=2) or 5b (3.94g, 20mmol, n=3) or 6a (3.94g, 20mmol, n=2) or 6b (4.22g, 20mmol, n=2) or 6b (4.22g, 20mmol, n=2) into a 100mL single-necked flask 3), anhydrous DMF (50mL), sodium azide (6.50g, 100mmol), triphenylphosphine (10.48g, 40mmol), carbon tetrabromide (13.28g, 40mmol) were added successively, and reacted at room temperature for 20min. TLC monitors the reaction, and after the conversion of raw materials is complete, the reaction is stopped, filtered, and the filtrate is concentrated, purified by silica gel column chromatography (dichloromethane:methanol=20:1 as eluent) to obtain 3.26g (78.4%, 78.4%) of yellow oily liquid Ia n=2), Ib 2.93g (66.1%, n=3), Ic 3.15g (71%, n=2), Id 3.71g (78.5%, n=3).

Embodiment 3

[0072] Embodiment 3: the synthesis of compound 12

[0073]

[0074] Add kojic acid 7 (142.00g, 1000mmol) and thionyl chloride (500mL) into a 1000mL single-necked flask, connect the reaction flask to a gas absorption device, and stir at room temperature for 2h. After the reaction, suction filtration was performed, the filter cake was washed with petroleum ether until the filtrate was colorless, and the filter cake was recrystallized with water to obtain 144.50 g (90.3%) of a white solid. Add the above-mentioned white solid (144.50g, 903.13mmol) and distilled water (500mL) into a 1000mL two-necked flask, heat up to 50°C, then add zinc powder (97.5g, 1500mmol), measure concentrated hydrochloric acid (200mL) and place under constant pressure In the liquid funnel, slowly add dropwise, control the temperature between 70 ~ 80 ℃, after dropping, control the temperature at 75 ℃ for 4 hours. After the reaction, the reaction solution was cooled to room temperature, extracted with 100...

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Abstract

The invention discloses a synthetic method for an amino-containing 3-hydroxypyridine-4-ketone iron chelating agent as shown in a formula (III) which is described in the specification. The synthetic method comprises the following steps: with methyl-protected azido hydroxypyridone as shown in a formula (I) which is described in the specification as a raw material, allowing the methyl-protected azido-hydroxypyridine to generate reduction and demethylation reactions under the protection of boron tribromide as shown in a formula (II) which is described in the specification, a solvent A and gas B, after completion of the reactions, carrying out quenching with a solvent C, and carrying out post-treatment so as to obtain the amino-containing 3-hydroxypyridine-4-ketone compound as shown in the formula (III). Compared with a conventional method, the synthetic method provided by the invention adopts a boron tribromide reagent with mild reaction conditions, avoids the use of a metal catalyst, andhas simple and convenient operation and high reaction yield.

Description

technical field [0001] The invention relates to a synthesis method of a novel amino group-containing hydroxypyridone compound, which can be used as an iron chelating agent and belongs to the field of organic synthesis. Background technique [0002] Iron is an essential trace element in the human body and is closely related to human life and health. In normal human body, the content of iron is strictly controlled within a certain range, however, under pathological conditions, if iron overload in the brain increases redox active metal ions, it will lead to a series of pathological reactions such as oxidative stress and protein aggregation , leading to neurodegenerative diseases such as Alzheimer's disease. Therefore, iron ion chelators can be used as potential anti-Alzheimer's drugs. [0003] 3-Hydroxypyridin-4-one compounds have strong iron chelating ability, can chelate ferric ions highly selectively, and have weak chelating ability to other divalent metal ions in organism...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D213/69C07D213/79C07D471/04
CPCC07D213/69C07D213/79C07D471/04
Inventor 谢媛媛蒋筱莹甘兵米治胜张长俊黄应益白仁仁
Owner ZHEJIANG UNIV OF TECH
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