CN-119431348-B - Preparation method and application of pyridine derivative compound

Abstract

The invention discloses a preparation method and application of a pyridine derivative compound, belonging to the technical field of chemical synthesis, wherein the structural formula of the pyridine derivative compound is shown as follows: Wherein the R 1 group is one of 4-CH 3 、4-OCH 3 , 4-F, 4-Cl and 4-Br, the R 2 group is one of C 5 H 9 、-C 6 H 11 , the R 3 group is one of 3-F, 3-H and 3-CH 3 , and the pyridine derivative compound prepared by the invention has very important medicinal value by taking a pyridine ring as a structural center, and has wide application in the aspects of biological medicines such as anti-tumor, anticancer, antibacterial and the like.

Inventors

• WU ZHIXIONG
• SHEN YONGMIAO
• LEI ZIJUN
• XI ZIWEI
• FAN QIANQIAN
• DONG ZHUOYING
• Mei Kaiyu

Assignees

• 浙江理工大学
• 浙江理工大学嵊州创新研究院有限公司

Dates

Publication Date

20260512

Application Date

20240930

Claims (4)

1. 1. The application of the pyridine derivative compound in the preparation of antibacterial drugs is characterized in that the pyridine derivative compound is selected from one of the following compounds: 。
2. 2. The use of pyridine derivative compound in preparing antibacterial agent according to claim 1, wherein the pyridine derivative compound is prepared by adding 2.0mL of acetone into a 4mL transparent glass bottle with a magnetic stirring rod and a rubber stopper, adding 0.2mmol of 4-cyanopyridine, 0.6mmol of [ Ir (dtbbpy) (ppy) 2 ][PF 6 ] 5.0 mol% and 0.6mmol of 4-methylstyrene, 0.2mmol of K 3 PO 4 , 0.4mmol of cyclopentylboric acid into the bottle, reacting the reaction mixture with 3W blue LED at 420nm at ambient temperature for 24 hours, centrifuging the solid after the reaction, concentrating the organic layer, eluting the crude mixture with EA: PE=1:10, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying to obtain the desired product; 。
3. 3. The use of pyridine derivative compound in preparing antibacterial agent according to claim 1, wherein the pyridine derivative compound is prepared by adding 2.0mL of acetone into a 4mL transparent glass bottle with a magnetic stirring rod and a rubber stopper, adding 0.2mmol of 4-cyanopyridine, 0.6mmol of [ Ir (dtbbpy) (ppy) 2 ][PF 6 ] 5.0 mol% and 0.6mmol of 4-fluorostyrene, 0.2mmol of K 3 PO 4 , 0.4mmol of cyclopentylboric acid into the bottle, reacting the reaction mixture with 3W blue LED at 420nm at ambient temperature for 24 hours, centrifuging the solid after the reaction, concentrating the organic layer, eluting the crude mixture with EA: PE=1:10, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying to obtain the desired product; 。
4. 4. the application of the pyridine derivative compound in preparing antibacterial drugs according to claim 1, wherein the pyridine derivative compound is prepared by the following method: 2.0mL of acetone is added into a 4mL transparent glass bottle with a magnetic stirring rod and a rubber plug, 0.2mmol of 4-cyano-3-fluoropyridine and [ Ir (dtbbpy) (ppy) 2 ][PF 6 ] 5.0 mol% and 0.6mmol of 4-methyl styrene and 0.2mmol of K 3 PO 4 are added into the bottle, the reaction mixture is reacted for 24 hours at the ambient temperature by using a 3W blue LED and 420nm, after the reaction, the solid is centrifuged, the organic layer is concentrated, and the crude mixture is eluted by EA (PE=1:10), dried by anhydrous sodium sulfate, concentrated under reduced pressure and purified to obtain the required product; 。

Description

Preparation method and application of pyridine derivative compound Technical Field The invention relates to a preparation method and application of a pyridine derivative compound, and belongs to the technical field of chemical synthesis. Background The pyridine core is a key component in artificial and naturally occurring bioactive compounds and is a constituent of several alkaloids. The existence of various functional groups such as chlorine, methoxy, amino, hydroxyl, cyano, nitro, hydrazide and the like on the ring increases the pharmacological activity. Wherein the substituted pyridine has antihypertensive, antipyretic, antiinflammatory and analgesic effects, and can be used as cardiotonic and antibacterial agent and anticancer activity. Therefore, the research has important value for synthesizing pyridine derivative compounds. Early wang et Al reported synthesis of tetrahydropyrido [2,3-d ] pyrimidine from aromatic aldehyde, malononitrile and 4-amino-2, 6-dihydroxypyrimidine starting from synth. Commun.2004,34,4331 in the presence of KF/Al 2O3 catalyst for 5-8 h. Wu et al, bioorg. Med. Chem. Lett.2015,25,3251, reported an improvement to the Skraup synthesis, i.e., synthesis of pyrido [3,2-b ] pyridine at 150 ℃ with m-NO 2PhSO3 Na instead of iodine as an oxidant. Meanwhile, the synthesis of pyridine is expanded by photocatalysis, as Rammal et al in org.Lett.2020,22,19,7671-7675, and the combination of N-alkoxyl pyridine ions and alkane under the conditions of visible light and catalyst is limited by the reaction specificity, and the four-element or more cycloalkanes are only combined, so that the derivatization of pyridine cores can be realized by the preparation method of the traditional pyridine derivative compound generally needing strong Lewis acid, strong alkali, high temperature or very strong substrate design and specificity, and a new scheme for constructing the pyridine derivative compound by a simple, efficient and mild reaction condition is urgently needed. Disclosure of Invention Aiming at the problems in the prior art, the invention aims to provide a simple and efficient method for preparing pyridine derivative compounds. The technical scheme adopted by the invention is as follows: The preparation method of the pyridine derivative compound is characterized by comprising the following steps of taking olefin, alkyl boric acid and cyanopyridine as raw materials, and reacting in an organic solvent under the induction action of visible light to obtain the pyridine derivative compound. The olefin is any one of styrene compound and vinyl thiophene. When the olefin is a styrene compound, the structural formula of the synthesized pyridine derivative compound is shown as follows: wherein: the R 1 group is one of CH 3、OCH3, F, cl and Br; The R 2 group is one of C 5H9、C6H11; the R 3 group is one of F, H, CH 3 and Cl. The reaction equation involved is as follows: when the olefin is vinyl thiophene, the structural formula of the synthesized pyridine derivative compound is shown as follows: The further arrangement is that: The molar ratio of the raw materials of the reaction is alkyl boric acid, olefin and cyanopyridine=1-3:1-3:1. The organic solvent is one of acetone (Acetone), dichloroethane (DCE), N-Dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). The reaction is carried out in the presence of a catalyst, preferably one of [ Ir (dtbbpy) (ppy) 2][PF6]、4CzIPN、Ru(bpy)3(PF6)2 ]. The reaction is carried out in the presence of a base, preferably one of K 3PO4、tBuOK、tBuONa、Cs2CO3、NaHCO3、CH3 COONa, DIPEA. After the reaction is finished, the product is purified by using petroleum ether and ethyl acetate as developing agents, separating by using column chromatography, desolventizing and concentrating, and drying by using anhydrous sodium sulfate. Another object of the invention is to provide the use of pyridine derivative compounds in the preparation of antitumor, anticancer or antibacterial drugs. The pyridine derivative compound prepared by the invention takes the pyridine ring as a structural center, has very important medicinal value, and has been widely applied to biological medicines such as anti-tumor, anticancer, antibacterial and the like. From the above description, it can be seen that the present invention has the following advantages: 1. The invention solves the difficulties of the prior art, and provides a safe, green and simple-operation pyridine preparation method, which realizes rapid derivatization by using visible light mediation. 2. The invention utilizes low-cost substrate alkene, alkyl boric acid and cyanopyridine to synthesize the derivative with high added value under the condition of visible light, and has the advantages of low cost, mild reaction condition, short time, easy treatment and the like. 3. The invention uses visible light to carry out at normal temperature, has mild reaction conditions, avoids potential safety hazard caused by high-temperature reaction, is easy to control