Preparation method of piperidyl quinoxalinone derivative
By employing a cross-dehydrogenation coupling reaction of 1-methylquinoxalinone and piperidine in the presence of N-chlorosuccinimide, this method solves the environmental pollution problem caused by the use of expensive catalysts and reagents in existing technologies, and provides an efficient and environmentally friendly method for synthesizing quinoxalinone derivatives.
Patent Information
- Application Number
- CN202511362854.9
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-09-23
- Publication Date
- 2025-12-26
AI Technical Summary
Existing methods for synthesizing quinoxalone derivatives require expensive catalysts and reagents and may lead to environmental pollution and metal residue problems.
Piperidinylquinoxalone derivatives were synthesized in an organic solvent via a cross-dehydrogenation coupling reaction between 1-methylquinoxalone and piperidine in the presence of N-chlorosuccinimide, thus avoiding the use of metal catalysts.
This has enabled an efficient and environmentally friendly synthesis method, which simplifies the operation steps, reduces costs, and minimizes environmental pollution.
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Figure CN121202801A_ABST
Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of medicine synthesis, and particularly relates to a preparation method of a piperidyl quinoxalinone derivative. BACKGROUND
[0002] Quinoxalinone derivatives have wide biological activity and medicinal value, and have attracted more and more attention in the fields of drug research and development and organic synthesis. 1-methyl-3-(piperidin-1-yl) quinoxalin-2(1H)-one, which combines piperidine and quinoxalinone structures, is an important quinoxalinone derivative, and research on a synthesis method thereof is of great significance. The reported synthesis methods of such compounds often need to pre-activate substrates, or use photocatalysts or transition metal catalysts, strong oxidants and the like, which not only increases reaction steps and cost, but also may cause environmental pollution and metal residue problems. Therefore, it is of great practical application value to develop a synthesis method which is efficient, environmentally friendly and does not need metal catalysts. SUMMARY
[0003] In order to solve the problems of the prior art and reduce the use of expensive catalysts and reagents, the purpose of the present application is to provide a synthesis method of a piperidyl quinoxalinone compound.
[0004] In order to achieve the above-mentioned purpose, the technical scheme of the present application is as follows: The present application provides a preparation method of a diphenylmethyl quinoxalinone derivative, comprising the following steps: Under heating conditions, 1-methyl quinoxalinone and piperidine are subjected to cross-dehydrogenative coupling reaction under the action of N-chlorosuccinimide (NCS) in an organic solvent to obtain a piperidyl quinoxalinone derivative, and the reaction equation is shown as formula 1: .
[0005] Preferably, in some embodiments, the reaction temperature is 60-120 DEG C.
[0006] Preferably, the reaction time is 10-24 h.
[0007] Preferably, the reaction solvent is one of toluene, dichloroethane and chloroform.
[0008] Preferably, the molar ratio of 1-methyl quinoxalinone, piperidine and N-chlorosuccinimide is 1.0:1.0-2.0:1.0-2.0.
[0009] The present application has the following beneficial effects: The application provides a preparation method of a piperidyl quinoxalinone derivative. Under heating conditions, 1-methyl quinoxalinone and piperidine are subjected to a dehydrogenation cross-coupling reaction under the action of N-chlorosuccinimide in an organic solvent to obtain the piperidyl quinoxalinone derivative. The reaction has the advantages of high atom economy, no need of a metal catalyst and simple operation. BRIEF DESCRIPTION OF DRAWINGS
[0010] The drawings accompanying the specification of the application form a part of the specification and serve to further illustrate the illustrative embodiments of the application and to explain the principles of the application.
[0011] Figure 1 Reaction equation of the piperidyl quinoxalinone derivative of the application; Figure 2 Nuclear magnetic hydrogen spectrum of the piperidyl quinoxalinone derivative synthesized in example 1 of the application. DETAILED DESCRIPTION
[0012] In order to facilitate the understanding of the application, the application will be described more fully below. The application can be realized in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the disclosure of the application more thorough and comprehensive.
[0013] The experimental methods in the following examples not specifically indicated are usually carried out according to the conventional conditions or according to the conditions suggested by the manufacturers.
[0014] Example 1 Into a 50 mL thick-walled pressure-resistant glass bottle, dichloroethane 20 mL, 1-methyl quinoxalinone (3.20 g, 20 mmol), piperidine (2.55 g, 30 mmol) and N-chlorosuccinimide (4.01 g, 30 mmol) are sequentially added, and then the reaction system is stirred at 85°C for 12 hours. After the reaction is completed, the organic solvent is removed by rotary evaporation, and column chromatography is used to separate to obtain 3.94 g of the piperidyl quinoxalinone derivative, with a yield of 81%.
[0015] 1H NMR (400 MHz, CDCl3) δ 7.54-7.50 (m, 1H), 7.24-7.21 (m, 2H), 7.16 (dd, J = 7.3, 2.1 Hz, 1H), 3.87 (d, J = 5.2 Hz, 4H), 3.66 (s, 3H), 1.70 (s, 6H). Example 2 Into a 50 mL thick-walled pressure-resistant glass bottle, chloroform 20 mL, 1-methylquinoxaline-2, 3 (3H)-one (3.20 g, 20 mmol), piperidine (2.55 g, 30 mmol) and N-chlorosuccinimide (4.01 g, 30 mmol) were sequentially added, and then the reaction system was stirred at 85°C for 12 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and piperidinyl quinoxaline-2, 3 (3H)-one derivative 3.45 g was obtained by column chromatography, with a yield of 71%.
[0016] Example 3 Into a 50 mL thick-walled pressure-resistant glass bottle, chloroform 20 mL, 1-methylquinoxaline-2, 3 (3H)-one (3.20 g, 20 mmol), piperidine (2.55 g, 30 mmol) and N-chlorosuccinimide (4.01 g, 30 mmol) were sequentially added, and then the reaction system was stirred at 85°C for 12 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and piperidinyl quinoxaline-2, 3 (3H)-one derivative 3.45 g was obtained by column chromatography, with a yield of 71%.
[0017] Example 4 Into a 50 mL thick-walled pressure-resistant glass bottle, chloroform 20 mL, 1-methylquinoxaline-2, 3 (3H)-one (3.20 g, 20 mmol), piperidine (2.55 g, 30 mmol) and N-chlorosuccinimide (4.01 g, 30 mmol) were sequentially added, and then the reaction system was stirred at 85°C for 12 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and piperidinyl quinoxaline-2, 3 (3H)-one derivative 3.45 g was obtained by column chromatography, with a yield of 71%.
[0018] Example 5 Into a 50 mL thick-walled pressure-resistant glass bottle, chloroform 20 mL, 1-methylquinoxaline-2, 3 (3H)-one (3.20 g, 20 mmol), piperidine (2.55 g, 30 mmol) and N-chlorosuccinimide (4.01 g, 30 mmol) were sequentially added, and then the reaction system was stirred at 85°C for 12 hours. After the reaction was completed, the organic solvent was removed by rotary evaporation, and piperidinyl quinoxaline-2, 3 (3H)-one derivative 3.45 g was obtained by column chromatography, with a yield of 71%.
[0019] The above only describes the preferred embodiments of the present application and is not intended to limit the present application. Various modifications and changes can be made by those skilled in the art based on the principles and technical solutions of the present application. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.
Claims
1. A process for the preparation of a piperidinyl quinoxalinone derivative, characterized by, The method comprises the following steps: under heating conditions, 1-methyl-quinoxaline ketone and piperidine are subjected to cross-dehydrogenative coupling reaction in an organic solvent under the action of N-chlorosuccinimide to obtain a piperidyl quinoxaline ketone derivative, and a reaction equation is shown as formula 1. 。 2. The production method according to claim 1, wherein The temperature of the coupling reaction is 60-120 DEG C.
3. The production method according to claim 1, wherein The coupling reaction time is 10-24 hours.
4. The production method according to claim 1, wherein The solvent of the coupling reaction is one of toluene, dichloroethane and chloroform.
5. The production method according to claim 1, wherein The molar ratio of 1-methyl-quinoxaline ketone, piperidine and N-chlorosuccinimide in the coupling reaction is 1.0:1.0-2.0:1.0-2.0.