Small-scale 2-chloro-3-amino-4-methylpyridine production control system

Abstract

The utility model provides a small-scale 2-chloro-3-amino-4-methylpyridine production control system, which comprises a reaction unit, a crystallization unit, a detection unit and a control unit, wherein the reaction unit comprises a four-neck flask, a reflux condensing pipe fixed on the four-neck flask, a stirrer, a water bath heating device, a closed pressure tank, a full-automatic extraction instrument and a three-neck flask; the crystallization unit comprises a crystallization reaction kettle and a dryer; the detection unit comprises a thermometer and a high performance liquid chromatograph which are fixed on the four-neck flask; the control unit comprises a controller; the controller is electrically connected with the stirrer, the water bath heating device, the full-automatic extraction instrument, the crystallization reaction kettle, the dryer, the thermometer and the high performance liquid chromatograph respectively. According to the production control system, the controller can be used for operating or adjusting the reaction, so that an operator can conveniently grasp the overall condition of the reaction, the production working efficiency is improved, the labor cost is saved, and the condition that reaction resources are wasted due to inaccurate control of the reaction progress is reduced.

Description

Technical Field

[0001] This invention relates to a small-scale 2-chloro-3-amino-4-methylpyridine production control system, belonging to the field of semi-automated production technology. Background Technology

[0002] With the rapid development of modern society, the demand for various products is increasing. At the same time, various industrial manufacturing industries are studying how to increase output while also improving production efficiency and reducing human resource input. Pharmaceutical companies, in particular, have high standards for sterile environments, precise control of raw material addition, and protection of operator safety during industrial production. Therefore, companies need to improve their operational level in all aspects while ensuring that they obtain products that meet production standards.

[0003] In the production of pharmaceutical compounds such as oseltamivir, remdesivir, and 2-chloro-3-amino-4-methylpyridine, it is often necessary to strictly control factors such as reaction temperature, reaction time, and the degree of agitation during the reaction to ensure the purity and quality of the product. The production of 2-chloro-3-amino-4-methylpyridine involves reaction steps that are time-consuming and at high temperatures. Current production methods incur significant manpower and time costs for monitoring and control. Therefore, this invention relates to a small-scale 2-chloro-3-amino-4-methylpyridine production control system. Utility Model Content

[0004] In view of the shortcomings of the existing technology, the purpose of this utility model is to provide a small-scale 2-chloro-3-amino-4-methylpyridine production control system to solve the problems mentioned in the background technology.

[0005] To achieve the above objectives, this utility model is implemented through the following technical solution, including:

[0006] A small-scale 2-chloro-3-amino-4-methylpyridine production control system includes a reaction unit, a crystallization unit, a detection unit, and a control unit. The reaction unit includes a four-necked flask, a reflux condenser fixed to the four-necked flask, a stirrer, a water bath heating device, a sealed pressure vessel, a fully automatic extractor, and a three-necked flask. The crystallization unit includes a crystallization reactor and a dryer. The detection unit includes a thermometer fixed to the four-necked flask and a high-performance liquid chromatograph. The control unit includes a controller, which is electrically connected to the stirrer, the water bath heating device, the fully automatic extractor, the crystallization reactor, the dryer, the thermometer, and the high-performance liquid chromatograph.

[0007] Preferably, a pressure gauge is installed on the sealed pressure tank, and the pressure gauge is electrically connected to the controller.

[0008] Preferably, the detection unit further includes a pH sensor, which is electrically connected to the controller.

[0009] The beneficial effects of this utility model are as follows: This utility model relates to a small-scale 2-chloro-3-amino-4-methylpyridine production control system. This production control system can use a controller to operate or adjust the reaction. On the one hand, it makes it easier for operators to grasp the overall reaction situation, and on the other hand, it can improve production efficiency, save labor costs, and reduce the waste of reaction resources due to inaccurate control of the reaction progress. Attached Figure Description

[0010] Other features, objects, and advantages of this invention will become more apparent from the following detailed description of non-limiting embodiments with reference to the accompanying drawings:

[0011] Figure 1 This is a schematic diagram of the electrical control structure of the small-scale production control system of this utility model;

[0012] Figure 2 This is a schematic diagram of the production control system involved in Embodiment 1 of this utility model.

[0013] In the diagram: 11 Four-necked flask, 12 Reflux condenser, 13 Stirrer, 14 Water bath heating device, 1401 First water bath heating device, 1402 Second water bath heating device, 15 Sealed pressure vessel, 16 Fully automatic extractor, 17 Three-necked flask, 21 Crystallization reactor, 2101 First crystallization reactor, 2102 Second crystallization reactor, 2103 Third crystallization reactor, 22 Dryer, 2201 First dryer, 2202 Second dryer, 31 Thermometer, 32 High performance liquid chromatograph, 41 Controller, 33 Pressure gauge, 34 pH sensor. Detailed Implementation

[0014] To make the technical means, creative features, objectives and effects of this utility model easier to understand, the present utility model will be further described below in conjunction with specific embodiments.

[0015] The small-scale 2-chloro-3-amino-4-methylpyridine production control system includes a reaction unit, a crystallization unit, a detection unit, and a control unit. The reaction unit is used to complete each step of the synthesis of 2-chloro-3-amino-4-methylpyridine. The crystallization unit is used to concentrate the product after the reaction to improve its purity for subsequent reactions. The detection unit is used to determine the degree of reaction in each step. The control unit is used to control each experimental device to save labor costs.

[0016] The reaction unit includes a four-necked flask 11, a reflux condenser 12 fixed to the four-necked flask 11, a stirrer 13, a water bath heating device 14, a sealed pressure vessel 15, a fully automated extractor 16, and a three-necked flask 17; the crystallization unit includes a crystallization reactor 21 and a desiccator 22; the detection unit includes a thermometer 31 fixed to the four-necked flask 11 and a high-performance liquid chromatograph 32; the control unit includes a controller 41, which is electrically connected to the stirrer 13, the water bath heating device 14, the fully automated extractor 16, the crystallization reactor 21, the desiccator 22, the thermometer 31, and the high-performance liquid chromatograph 32, respectively, with the electrical connection structure as shown in the figure. Figure 1 As shown.

[0017] In some specific embodiments, a pressure gauge 33 is provided on the sealed pressure tank, and the pressure gauge 33 is electrically connected to the controller 41.

[0018] In some specific embodiments, the detection unit further includes a pH sensor 34, which is electrically connected to the controller 41.

[0019] Example 1

[0020] like Figure 2 As shown, this embodiment provides a small-scale 2-chloro-3-amino-4-methylpyridine production control system, including a reaction unit, a crystallization unit, a detection unit, and a control unit.

[0021] The reaction unit includes a four-necked flask 11, a reflux condenser 12 fixed on the four-necked flask 11, a stirrer 13 fixed on the four-necked flask 11, a first water bath heating device 1401 placed at the bottom of the four-necked flask 11, a sealed pressure vessel 15, a fully automatic extractor 16, a three-necked flask 17, and a second water bath heating device 1402 placed at the bottom of the three-necked flask 17.

[0022] The crystallization unit includes a first crystallization reactor 2101, a second crystallization reactor 2102, a third crystallization reactor 2103, a first dryer 2201, and a second dryer 2202.

[0023] The detection unit includes a thermometer 31 fixed on a four-necked flask 11, a high-performance liquid chromatograph 32, a pressure gauge 33 installed on a sealed pressure vessel 15, and a pH sensor 34.

[0024] The control unit includes a controller 41. In this embodiment, the controller 41 can be a commercially available PLC controller. The controller 41 is electrically connected to the stirrer 13, the water bath heating device 14, the fully automatic extractor 16, the crystallization reactor 21, the dryer 22, the thermometer 31, the high performance liquid chromatograph 32, the pressure gauge 33, and the pH sensor 34.

[0025] In summary, the working principle and operation process of this utility model are as follows: The synthesis of 2-chloro-3-amino-4-methylpyridine includes three main steps: condensation reaction, mixing reaction, and degradation reaction. All three steps involve long-term reactions and crystallization of the product. Some steps also involve drying processes.

[0026] The synthesis of 2-chloro-3-amino-4-methylpyridine was carried out using the production control system described in Example 1. This production control system can pre-set the working parameters for each step, or pre-set parameters before each reaction stage and provide prompts after the reaction is completed. The operation process provided here adopts the pre-setting method: the controller 41 pre-sets the reaction steps, reaction conditions, required instruments, and various parameters for the production of 2-chloro-3-amino-4-methylpyridine, places the required instruments, and completes the corresponding preparations; appropriate amounts of the reaction substrate toluene, 4,4-dimethoxybutanone, and cyanoacetyl are added sequentially to the four-necked flask 11. Amine and ammonium acetate are reacted, and then the reaction program is started by controller 41. Controller 41 transmits signals to stirrer 13 and the first water bath heating device 1401. Stirrer 13 starts running, and the first water bath heating device 1401 heats up to 75°C. The thermometer built into the first water bath heating device 1401 detects the water temperature and sends the temperature information back to controller 41. Controller 41 starts timing after determining that the internal water bath temperature of the first water bath heating device 1401 has reached the preset standard, and performs a heat preservation condensation reaction. After the reaction time is completed, controller 41 reminds the operator by playing a notification or other means. In this embodiment, the operator... Sampling is performed manually, and the content of the reaction substrate is detected using a high-performance liquid chromatograph (HPLC) 32. The HPLC 32 sends the detection results back to the controller 41. Upon receiving the signal, the controller 41 sends a new signal to the stirrer 13 and the first water bath heating device 1401, causing the stirrer 13 and the first water bath heating device 1401 to stop working, and the reaction stops. The reaction solution is then transferred to the first crystallization reactor 2101 manually or with the aid of a robotic arm, and a signal is input to the controller 41. The controller 41 controls the first crystallization reactor 2101 to work according to preset parameters, concentrating the toluene solvent in the reaction solution under reduced pressure and crystallizing it. After obtaining the crude first mixture, the controller 41 prompts the operator to transfer the reactants after the crystallization stage is completed. Upon receiving the prompt, the operator adds the crude first mixture and ethanol solution to the sealed pressure vessel 15, introduces hydrogen chloride gas, slowly raises the temperature to 80°C, and controls the pressure at 0.3 MPa. After the pressure gauge 33 detects that the internal pressure of the sealed pressure vessel 15 has reached the preset range, the timing is started to maintain the temperature for the reaction. During the reaction, the pH sensor 34 continuously monitors the acidity and alkalinity of the reaction solution in the sealed pressure vessel 15 and feeds it back to the controller 41. After about 8 hours of reaction, a liquid phase sample is taken and the content of the crude first mixture is found to be less than 0.The reaction is stopped at 5%. The pressure vessel 15 is sealed and slowly cooled. The reaction solution is transferred to the second crystallization reactor 2102 for crystallization. The solid 2-chloro-4-methyl-nicotinamide is obtained by filtration. The filtered reaction solution is transferred to the fully automatic extractor 16 for extraction, and the organic phase is concentrated. It is then combined with the filtered solid and sent to the first dryer 2201 for drying to obtain 2-chloro-4-methyl-nicotinamide. The dried 2-chloro-4-methyl-nicotinamide and other reactants are added to the three-necked flask 17 manually or with the help of a robotic arm. A signal is input to the controller 41 to control the reaction. The temperature of the second water bath heating device 1402 is controlled by device 41 to be maintained within the range of 3℃-5℃ for 1 hour and then at 70℃ for 2 hours. After the preset reaction time, the reaction is stopped when the content of the reactant raw material is found to be less than 0.3% by manual sampling. The reactants are then transferred to the third crystallization reactor 2103 for crystallization, filtered, and dried in the second dryer 2202 to obtain crude 2-chloro-3-amino-4-methylpyridine. In actual operation, the crude 2-chloro-3-amino-4-methylpyridine can be recrystallized as needed to obtain 2-chloro-3-amino-4-methylpyridine with higher purity.

[0027] The foregoing has shown and described the basic principles, main features, and advantages of this utility model. It will be apparent to those skilled in the art that this utility model is not limited to the details of the exemplary embodiments described above, and that it can be implemented in other specific forms without departing from the spirit or basic characteristics of this utility model. Therefore, the embodiments should be considered exemplary and non-limiting in all respects. The scope of this utility model is defined by the appended claims rather than the foregoing description, and thus all variations falling within the meaning and scope of equivalents of the claims are intended to be included within this utility model.

[0028] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.

Claims

1. A small-scale 2-chloro-3-amino-4-methylpyridine production control system, characterized in that: Includes reaction unit, crystallization unit, detection unit, and control unit. The reaction unit includes a four-necked flask (11), a reflux condenser (12) fixed on the four-necked flask (11), a stirrer (13), a water bath heating device (14), a sealed pressure vessel (15), a fully automatic extractor (16), and a three-necked flask (17); The crystallization unit includes a crystallization reactor (21) and a dryer (22); The detection unit includes a thermometer (31) and a high-performance liquid chromatograph (32) fixed on the four-necked flask (11); The control unit includes a controller (41), which is electrically connected to the stirrer (13), the water bath heating device (14), the fully automatic extractor (16), the crystallization reactor (21), the dryer (22), the thermometer (31), and the high performance liquid chromatograph (32).

2. The small-scale 2-chloro-3-amino-4-methylpyridine production control system according to claim 1, characterized in that: The sealed pressure tank (15) is equipped with a pressure gauge (33), which is electrically connected to the controller (41).

3. The small-scale 2-chloro-3-amino-4-methylpyridine production control system according to claim 1, characterized in that: The detection unit also includes a pH sensor (34), which is electrically connected to the controller (41).

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