Continuous flow synthesis process of 2-chloro-3-aminopyridine

Abstract

The invention provides a continuous flow synthesis process of 2-chloro-3-aminopyridine, and particularly provides a preparation method of 2-chloro-3-aminopyridine, which comprises the following steps: carrying out continuous flow reaction on a 3-aminopyridine hydrochloride solution and chlorine in a reaction unit to prepare 2-chloro-3-aminopyridine; the concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10-20%, the reaction unit comprises a first feed port and a second feed port, the 3-aminopyridine hydrochloride solution is fed from the first feed port, and the chlorine is fed from the second feed port. The process equipment is low in cost, less in operation, higher in conversion rate and more suitable for industrial production.

Description

Technical Field

[0001] The invention relates to a continuous flow synthesis process of 2-chloro-3-aminopyridine. Background Art

[0002] 2-Chloro-3-aminopyridine is an important pharmaceutical intermediate. Currently, there are mainly the following methods for the continuous preparation of 2-chloro-3-aminopyridine:

[0003] Chinese patent CN 117088807 A discloses a method for preparing 2-chloro-3-aminopyridine. The method adopts a spiral tubular reactor and uses hydrogen peroxide to perform an oxychlorination reaction to prepare 2-chloro-3-aminopyridine. Although this method can improve the yield and purity of the product, the product needs to be completely extracted before it can be used in subsequent reactions because hydrogen peroxide is used as an oxychlorination reagent. In addition, the wastewater contains excessive hydrogen peroxide, which requires additional post-treatment steps.

[0004] Chinese patent CN 110885311 B discloses a method for preparing 2-chloro-3-aminopyridine. The method adopts a multi-stage extraction centrifuge reaction, and sodium hypochlorite is subjected to an oxychlorination reaction to prepare 2-chloro-3-aminopyridine, which can reduce the generation of impurities. However, the process is relatively complicated, and a 4-7-stage extraction centrifuge is used (single-stage reaction time is 3h), and the reaction time is relatively long.

[0005] Chinese patent CN 114716368 B discloses a method for preparing 2-chloro-3-aminopyridine and its hydrochloride. The method adopts a plug flow reactor and directly chlorinates chlorine to prepare 2-chloro-3-aminopyridine. However, the method adopts a three-stream feeding method, and industrialization requires an additional feeding device, which increases investment costs, and the yield is only about 86%.

[0006] Therefore, in order to synthesize 2-chloro-3-aminopyridine more efficiently and economically, it is necessary to develop a new preparation method of 2-chloro-3-aminopyridine that is more suitable for industrial production. Summary of the invention

[0007] The technical problem to be solved by the present invention is to overcome the defects of low conversion rate and high cost in the prior art and to provide a continuous flow synthesis process for 2-chloro-3-aminopyridine which is efficient, safe, rapid, economical and easy to scale up.

[0008] The present invention solves the above technical problems through the following technical solutions:

[0009] The present invention provides a method for preparing 2-chloro-3-aminopyridine, which comprises the following steps:

[0010] 3-aminopyridine hydrochloride solution and chlorine gas are reacted in a continuous flow reaction in a reaction unit to obtain 2-chloro-3-aminopyridine; the concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10-20%,

[0011] The reaction unit comprises a first feed port and a second feed port, the 3-aminopyridine hydrochloride solution is fed through the first feed port, and the chlorine gas is fed through the second feed port.

[0012] In some embodiments, the temperature of the 3-aminopyridine hydrochloride solution before feeding is 30-50°C, for example, 40°C.

[0013] In some embodiments, the gasification temperature of the chlorine gas is 40-60°C; for example, 45°C.

[0014] In some embodiments, the 3-aminopyridine hydrochloride solution is generated by reacting 3-aminopyridine and concentrated hydrochloric acid, and the hydrochloric acid concentration of the concentrated hydrochloric acid is 25-34%, further preferably 27-32%, and further preferably 28-31%.

[0015] In some embodiments, the concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10 to 15%, and further preferably 10 to 13%; the 3-aminopyridine concentration refers to the mass fraction of 3-aminopyridine in the 3-aminopyridine hydrochloride solution.

[0016] In some embodiments, the flow rate of the 3-aminopyridine hydrochloride solution is 20-60 g / min; preferably 30-50 g / min; for example 30, 40 or 50 g / min.

[0017] In some embodiments, the molar ratio of the chlorine gas and the 3-aminopyridine added to the reaction system for preparing the 3-aminopyridine hydrochloride solution is 1.05 to 1.2, further, preferably 1.05 to 1.15, and further, preferably 1.05 to 1.1.

[0018] In some embodiments, the chlorine gas flow rate is 2 to 6 g / min; preferably 2.9 to 4.85 g / min; for example 2.9, 3.2, 3.9, 4.1, 4.2, 4.4, 4.6, 4.85 g / min.

[0019] In some embodiments, the 3-aminopyridine hydrochloride solution is continuously and stably fed from port a by a pump.

[0020] In some embodiments, the pressure of the reaction system of the reaction is 3 to 15 bar, preferably 3 to 10 bar, and more preferably 3 to 8 bar.

[0021] In some embodiments, the reaction temperature of the reaction is 10 to 40°C, preferably 10 to 30°C, and more preferably 20 to 30°C.

[0022] In some embodiments, the residence time of the reaction unit is 20 s to 120 s, preferably 30 to 100 s, and more preferably 40 to 80 s.

[0023] In some embodiments, the reaction further includes the following post-treatment step: the reaction liquid passes through the reaction unit to reach the receiving kettle, and the reaction liquid in the receiving kettle is purged with nitrogen, and the nitrogen purge flow rate can be 0.5 to 5 L / min, further, preferably 0.5 to 3 L / min, and further, preferably 1 to 3 L / min.

[0024] In some embodiments, the reaction solution is purged with nitrogen and subjected to gas-liquid separation to obtain a crude product, which can be directly used in the next reaction.

[0025] The reactor of the reaction unit is any one or more reactors that can realize continuous flow reaction, including one or more of microchannel reactor, tubular reactor, stacked mixer, static mixer, such as microchannel reactor. Tubular reactor can be a continuous operation reactor with a large aspect ratio and a tubular shape. According to different requirements, the tubular reactor can be a single tube or multiple tubes in parallel, and can be an empty tube or a filled tube.

[0026] In some embodiments, the reaction unit independently comprises one or more reactor modules or reactor module groups, wherein the reactor module group can be composed of multiple reactor modules connected in series or in parallel, and each module can realize feeding, mixing, heat exchange and reaction. The units are connected in series to form a reactor. Each reactor module or module group has one or more material inlets and one or more material outlets.

[0027] The reaction unit can be set to a single temperature zone, or different sub-temperature zones can be set for different reactor modules or reactor module groups. The temperature zones are connected in series.

[0028] In some embodiments, the microchannel reactor includes a plurality of variable diameter cavities connected end to end.

[0029] In some embodiments, the variable diameter cavity includes a wide channel and a narrow channel connected end to end;

[0030] The longitudinal section of the wide channel is heart-shaped, and a transverse Ruyi-shaped flow guide component is arranged in the axial direction of the wide channel; the flow guide component is used to separate the fluid into two streams of fluid, the two streams of fluid flow along the inner side wall of the wide channel and the flow guide component, the two streams of fluid merge at the intersection of the narrow channel and the wide channel in the fluid movement direction, and enter the narrow channel;

[0031] The width of the inlet end of the wide channel is a, the distance between the guide component and the axial center of the inlet end is b, the distance between the guide component and the inner side wall of the wide channel is b, and the distance between the intersection of the narrow channel and the wide channel and the tangent of the nearest outer side wall of the wide channel is e;

[0032] The inner diameter of the outlet end of the narrow channel is a; the width of the narrow channel gradually narrows from width c to width a along length d;

[0033] Wherein, a, b, c, d and e satisfy the following conditions:

[0034] a:b=1:(0.5~2);

[0035] a:c=1:(3~10);

[0036] c: d = 1: (1 to 5);

[0037] a:e=1:(0.5~2.5).

[0038] In some embodiments, in the variable diameter cavity, a:b is 1:(0.7-1.5);

[0039] And / or, the a:c is 1:(3-7);

[0040] And / or, the c:d is 1:(1.5-3);

[0041] And / or, the a:e is 1:(0.5-1.5).

[0042] Preferably, the a:b is 1:(0.8-1.1);

[0043] And / or, the ratio of a:c is 1:(3-5);

[0044] And / or, the c:d is 1:(1.5-2);

[0045] And / or, the a:e is 1:(0.7-1.4).

[0046] In some embodiments, in the variable diameter cavity, a is 0.5 to 2 mm; preferably 0.9 to 1.5 mm, more preferably 0.9 to 1.1 mm, for example 0.5, 1.2 or 1 mm;

[0047] And / or, said b is 0.25 to 4 mm; preferably 0.63 to 2.25 mm, more preferably 0.72 to 1.21 mm, for example 0.3, 2 or 1 mm;

[0048] and / or, said c is 1.5 to 20 mm; preferably 2.7 to 10.5 mm, more preferably 2.7 to 5.5 mm, for example 2, 10 or 5 mm;

[0049] and / or, said d is 1.5 to 100 mm; preferably 4.05 to 31.5 mm, more preferably 4.05 to 11 mm, for example 3, 30 or 10 mm;

[0050] And / or, said e is 0.25-5 mm; preferably 0.45-2.25 mm, more preferably 0.63-1.54 mm, for example 0.3, 2 or 1.5 mm.

[0051] In some embodiments, in the variable diameter cavity, the length of the wide channel is f, and the f and the d satisfy the condition: f : d = 1: (1-4), for example, f : d = 1: 3;

[0052] And / or, f is 1-12 mm, preferably 1-3 mm, more preferably 1-1.5 mm, for example 1, 3.3 or 10 mm.

[0053] In some embodiments, in the variable diameter cavity, the cross-section of the narrow channel is circular, elliptical or polygonal.

[0054] In some embodiments, the cross-section of the wide channel is rectangular; the short side of the rectangle is 1 to 3 mm, preferably 1 to 1.5 mm, such as 1 mm.

[0055] In some embodiments, the cross section of the fluid channel formed by the wide channel and the flow guide component is rectangular.

[0056] In some embodiments, at least one of the variable diameter cavities is connected end to end to form a variable diameter cavity array; adjacent variable diameter cavity arrays are connected by U-shaped tubes and are arranged in reverse parallel.

[0057] In some embodiments, the wide channel inlet end of the first variable diameter cavity is connected to the feed port of at least one of the microchannel reactors, and the narrow channel outlet end of the last variable diameter cavity is connected to the discharge port of the microchannel reactor.

[0058] In some embodiments, the first feed port is connected to the wide channel inlet end of the first variable diameter cavity through a first pipeline, and the second feed port is connected to the first feed port through a second pipeline. More preferably, the second pipeline is arranged at the periphery of the first pipeline, and the end of the second pipeline is connected to the end of the first pipeline, and then connected to the discharge port of the microchannel reactor after being collected.

[0059] The positive improvement effect of the present invention is that compared with the traditional intermittent kettle process, the continuous flow process has the following beneficial effects:

[0060] (1) The present invention adopts a continuous flow process, and successfully solves the gas-liquid heterogeneous mass transfer and heat transfer problems by dividing the functional single temperature zones, setting and optimizing the temperature and, as well as coupling with the heat transfer and mass transfer advantages of the continuous flow, so that 3-aminopyridine can be directly transported to the continuous flow reactor for reaction at one time, and can run smoothly, and the reaction time is greatly shortened;

[0061] (2) The present invention reduces the generation of 2,6-dichloro-3-aminopyridine during the reaction system, greatly shortens the reaction time, and has fewer operating steps, simple operation, and high stability.

[0062] (3) The present invention takes advantage of the fact that continuous flow can conveniently and accurately control the pressure of the reaction system. By increasing the pressure of the reaction system, the solubility of chlorine in the reaction liquid is greatly increased, so that the reaction rate is greatly accelerated and the reaction time is further shortened.

[0063] (4) The present invention can effectively avoid the generation of hot spots in the exothermic reaction and greatly improve the safety of the process.

[0064] (5) The present invention utilizes the plug flow characteristics of continuous flow to greatly reduce the occurrence of backmixing, reduce side reactions, reduce impurities in the crude product, increase yield, and simplify post-processing.

[0065] (6) There is no scale-up effect, that is, the process can still complete the reaction in a relatively short time on an industrial scale, and the product content and yield are basically the same as those on a laboratory scale.

[0066] (7) Compared with the existing continuous flow process, the process equipment of the present application has low cost, fewer operations, and higher conversion rate, and is more suitable for industrial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0067] Figure 1 This is a diagram of the continuous flow reaction device.

[0068] Figure 2 Schematic diagram of the structure of the microchannel reactor.

[0069] Figure 3 It is a schematic diagram of the structure of the variable diameter cavity.

[0070] Description of reference numerals:

[0071] 1 First feed inlet

[0072] 2 Second feed port

[0073] 3 Discharge port DETAILED DESCRIPTION

[0074] The present invention is further described below by way of examples, but the present invention is not limited to the scope of the examples.

[0075] Examples 1-10

[0076] Continuous flow reaction device Figure 1 As shown, it includes a microchannel reactor, and the structural schematic diagram of the microchannel reactor is shown in Figure 2 As shown, it includes several variable-diameter cavities connected end to end. The variable-diameter cavities are connected end to end to form a variable-diameter cavity array; adjacent variable-diameter cavity arrays are connected by U-shaped tubes and arranged in reverse parallel. The wide channel inlet end of the first variable-diameter cavity is connected to the feed ports of the two microchannel reactors, and the narrow channel outlet end of the last variable-diameter cavity is connected to the discharge port 3 of the microchannel reactor. There are two feed ports, the first feed port 1 is connected to the wide channel inlet end of the first variable-diameter cavity through a first pipeline, and the second feed port 2 is connected to the first feed port 1 through a second pipeline. The second pipeline is arranged on the periphery of the first pipeline, and the narrow channel outlet end at the end of the second pipeline is connected to the end of the first pipeline.

[0077] The structural diagram of the variable diameter cavity is as follows: Figure 3 The variable diameter cavity comprises a wide channel and a narrow channel connected end to end, the longitudinal section of the wide channel is heart-shaped, and a transverse Ruyi-shaped flow guide component is arranged in the axial direction of the wide channel; the flow guide component is used to separate the fluid into two streams of fluid, the two streams of fluid flow along the inner side wall of the wide channel and the flow guide component, the two streams of fluid converge at the intersection of the narrow channel and the wide channel in the direction of fluid movement, and enter the narrow channel;

[0078] The width of the inlet end of the wide channel is a, the distance between the guide component and the axial center of the inlet end is b, the distance between the guide component and the inner side wall of the wide channel is b, and the distance between the intersection of the narrow channel and the wide channel and the tangent of the nearest outer side wall of the wide channel is e;

[0079] The inner diameter of the outlet end of the narrow channel is a; the width of the narrow channel gradually narrows from width c to width a along length d;

[0080] The length of the wide channel is f;

[0081] Among them, a, b, c, d, e, and f meet the following conditions:

[0082] a:b=1:0.6;

[0083] a:c=1:4;

[0084] c:d=1:1.5;

[0085] a:e=1:0.6;

[0086] f:d=1:3.

[0087] Among them: a=0.5mm; b=0.3mm; c=2mm; d=3mm; e=0.3mm; f=1mm.

[0088] The channel depth is 1 mm.

[0089] Set the temperature of the continuous flow reactor reaction section to 10-40°C;

[0090] Dissolve 3-aminopyridine in hydrochloric acid solution, and pump the solution into a continuous flow reactor through a plunger metering pump to adjust the required flow rate; control the 3-aminopyridine solution to be kept warm at 40°C before feeding.

[0091] Liquid chlorine is vaporized by vaporization and then measured by a chlorine flow meter before entering a continuous flow reactor. The required flow rate is adjusted to control the chlorine equivalent to 1.05 to 1.2 eq.

[0092] Adjust the pressure of the reaction system through the back pressure valve at the rear end to control the pressure of the reaction system to 3-15 bar;

[0093] The nitrogen purge flow rate of the receiving kettle is adjusted to 0.5-5L / min;

[0094] After the reaction is completed, the raw material conversion rate is above 98%, the dichloro impurities are within 5%, the reaction liquid is separated by gas and liquid to obtain a crude product, and the waste gas enters the tail gas treatment system;

[0095] The product does not need further treatment and can be directly used as raw material for the next diazotization reaction, with a yield of more than 91%.

[0096]

[0097] Although the specific embodiments of the present invention are described above, it should be understood by those skilled in the art that this is only for illustration and the protection scope of the present invention is defined by the appended claims. Those skilled in the art may make various changes or modifications to these embodiments without departing from the principles and essence of the present invention, but these changes and modifications all fall within the protection scope of the present invention.

Claims

1. A method for preparing 2-chloro-3-aminopyridine, characterized in that: It includes the following steps: 3-aminopyridine hydrochloride solution and chlorine gas are reacted in a continuous flow reaction in a reaction unit to obtain 2-chloro-3-aminopyridine; the concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10-20%, The reaction unit comprises a first feed port and a second feed port, the 3-aminopyridine hydrochloride solution is fed through the first feed port, and the chlorine gas is fed through the second feed port.

2. The method for preparing 2-chloro-3-aminopyridine according to claim 1, characterized in that: It satisfies one or more of the following conditions (1) to (13): (1) The temperature of the 3-aminopyridine hydrochloride solution before feeding is 30-50°C; (2) The gasification temperature of the chlorine gas is 40 to 60°C; (3) The 3-aminopyridine hydrochloride solution is generated by the reaction of 3-aminopyridine and concentrated hydrochloric acid, and the hydrochloric acid concentration of the concentrated hydrochloric acid may be 25 to 34%; (4) The concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10 to 15%; (5) The molar ratio of the chlorine gas to the 3-aminopyridine added to the reaction system is 1.05 to 1.2; (6) The 3-aminopyridine hydrochloride solution is continuously and stably fed from the first feed port by a pump; (7) The pressure of the reaction system of the reaction is 3 to 15 bar; (8) The reaction temperature of the reaction is 10 to 40°C; (9) The residence time of the reaction unit is 20s to 120s; (10) The reaction further comprises the following post-treatment step: the reaction liquid passes through the reaction unit to reach the receiving kettle, and the reaction liquid in the receiving kettle is purged with nitrogen; (11) The reaction solution is purged with nitrogen and the gas-liquid is separated to obtain a crude product, which is directly used in the next reaction; (12) The flow rate of the 3-aminopyridine hydrochloride solution is 20 to 60 g / min; The chlorine gas flow rate in (13) is 2 to 6 g / min.

3. The method for preparing 2-chloro-3-aminopyridine according to claim 2, characterized in that: It satisfies one or more of the following conditions (1) to (11): (1) The temperature of the 3-aminopyridine hydrochloride solution before feeding is 40°C; (2) The gasification temperature of the chlorine gas is 45°C; (3) The hydrochloric acid concentration of the concentrated hydrochloric acid is 27 to 32%; (4) The concentration of 3-aminopyridine in the 3-aminopyridine hydrochloride solution is 10 to 13%; (5) The molar ratio of the chlorine gas to the 3-aminopyridine added to the reaction system is 1.05 to 1.15; (6) The pressure of the reaction system of the reaction is 3 to 10 bar; (7) The reaction temperature of the reaction is 10 to 30°C; (8) The residence time of the reaction unit is 30 to 100 seconds; (9) The nitrogen purge flow rate is 0.5 to 5 L / min; (10) The flow rate of the 3-aminopyridine hydrochloride solution is 30 to 50 g / min; The chlorine gas flow rate in (11) is 2.9 to 4.85 g / min.

4. The method for preparing 2-chloro-3-aminopyridine as claimed in claim 3, characterized in that: It satisfies one or more of the following conditions (1) to (9): (1) The hydrochloric acid concentration of the concentrated hydrochloric acid is 28-31%; (2) the molar ratio of the chlorine gas to the 3-aminopyridine added to the reaction system is 1.05 to 1.1; (3) The pressure of the reaction system of the reaction is 3 to 8 bar; (4) The reaction temperature of the reaction is 20 to 30°C; (5) The residence time of the reaction unit is 40 to 80 seconds; (6) The nitrogen purge flow rate is 0.5 to 3 L / min, preferably 1 to 3 L / min; (7) The flow rate of the 3-aminopyridine hydrochloride solution is 30, 40 or 50 g / min; (8) The chlorine gas flow rate is 2.9, 3.2, 3.9, 4.1, 4.2, 4.4, 4.6, 4.85 g / min; and (9) the feed inlet of the reaction unit is only the first feed inlet and the second feed inlet.

5. The method for preparing 2-chloro-3-aminopyridine according to claim 1, characterized in that: It satisfies one or more of the following conditions (1) to (3): (1) The reactor of the reaction unit is one or more of a microchannel reactor, a tubular reactor, a stacked mixer, and a static mixer; for example, a microchannel reactor; the tubular reactor may be a single tube or multiple tubes in parallel, and may be an empty tube or a filled tube; (2) The reaction unit independently comprises one or more reactor modules or reactor module groups, wherein the reactor module group is composed of multiple reactor modules connected in series or in parallel, and each module can realize feeding, mixing, heat exchange and reaction; the units are connected in series to form a reactor; each reactor module or module group has one or more material inlets and one or more material outlets; A separate temperature zone is set for the reaction unit described in (3), or different sub-temperature zones are set for different reactor modules or reactor module groups; and the temperature zones are connected in series.

6. The method for preparing 2-chloro-3-aminopyridine according to claim 5, characterized in that: The microchannel reactor comprises a plurality of variable diameter cavities connected end to end.

7. The method for preparing 2-chloro-3-aminopyridine according to claim 6, characterized in that: The variable diameter cavity includes a wide channel and a narrow channel connected end to end; The longitudinal section of the wide channel is heart-shaped, and a transverse Ruyi-shaped flow guide component is arranged in the axial direction of the wide channel; the flow guide component is used to separate the fluid into two streams of fluid, the two streams of fluid flow along the inner side wall of the wide channel and the flow guide component, the two streams of fluid merge at the intersection of the narrow channel and the wide channel in the fluid movement direction, and enter the narrow channel; The width of the inlet end of the wide channel is a, the distance between the guide component and the axial center of the inlet end is b, the distance between the guide component and the inner side wall of the wide channel is b, and the distance between the intersection of the narrow channel and the wide channel and the tangent of the nearest outer side wall of the wide channel is e; The inner diameter of the outlet end of the narrow channel is a; the width of the narrow channel gradually narrows from width c to width a along length d; Wherein, a, b, c, d and e satisfy the following conditions: a:b=1:(0.5~2); a:c=1:(3~10); c: d = 1: (1 to 5); a:e=1:(0.5~2.5).

8. The method for preparing 2-chloro-3-aminopyridine according to claim 7, characterized in that: The variable diameter cavity satisfies one or more of the following conditions (1) to (5): (1) a is 0.5 to 2 mm; preferably 0.9 to 1.5 mm, more preferably 0.9 to 1.1 mm, for example 0.5, 1.2 or 1 mm; (2) b is 0.25 to 4 mm; preferably 0.63 to 2.25 mm, more preferably 0.72 to 1.21 mm, for example 0.3, 2 or 1 mm; (3) c is 1.5 to 20 mm; preferably 2.7 to 10.5 mm, more preferably 2.7 to 5.5 mm, such as 2, 10 or 5 mm; (4) The distance d is 1.5 to 100 mm; preferably 4.05 to 31.5 mm, more preferably 4.05 to 11 mm, such as 3, 30 or 10 mm; and (5) said e is 0.25 to 5 mm; preferably 0.45 to 2.25 mm, more preferably 0.63 to 1.54 mm, for example 0.3, 2 or 1.5 mm.

9. The method for preparing 2-chloro-3-aminopyridine according to claim 7, characterized in that: The variable diameter cavity satisfies one or both of the following conditions (1) and (2): (1) The length of the wide channel is f, and f and d satisfy the condition: f:d=1:(1-4), for example, f:d=1:3; and (2) said f is 1 to 12 mm, preferably 1 to 3 mm, more preferably 1 to 1.5 mm, for example 1, 3.3 or 10 mm; Preferably, the reactor satisfies one or more of the following conditions (1) to (3): (1) The cross section of the narrow channel is circular, elliptical or polygonal; (2) The cross section of the wide channel is a rectangle; the short side length of the rectangle is 1 to 3 mm, preferably 1 to 1.5 mm, for example 1 mm; and (3) the cross-section of the fluid channel formed by the wide channel and the flow guide component is rectangular.

10. The method for preparing 2-chloro-3-aminopyridine according to claim 7, characterized in that: The variable diameter cavity satisfies one or more of the following conditions (1) to (3): (1) At least one of the variable diameter cavities is connected end to end to form a variable diameter cavity array; adjacent variable diameter cavity arrays are connected by U-shaped tubes and arranged in reverse parallel; (2) The wide channel inlet end of the first variable diameter cavity is connected to the feed port of at least one of the microchannel reactors, and the narrow channel outlet end of the last variable diameter cavity is connected to the discharge port of the microchannel reactor; (3) The first feed port is connected to the wide channel inlet end of the first variable diameter cavity through a first pipeline, and the second feed port is connected to the first feed port through a second pipeline; more preferably, the second pipeline is arranged on the periphery of the first pipeline, and the end of the second pipeline is connected to the end of the first pipeline, and then connected to the discharge port of the microchannel reactor after being combined.

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