A method for synthesizing 2-cyano-5-bromopyridine

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 2-cyano-5-bromopyridine, which comprises the following steps: synthesizing 5-bromo-2-pyridine carboxylic acid by taking 2,5-dibromopyridine as a starting material; synthesizing tert-butyl (5-bromopyridine-2-formyl) carbamate; synthesizing 5-bromo-2-pyridine carboxamide; and synthesizing 2-cyano-5-bromopyridine; compared with the prior art, the synthesis method of 2-cyano-5-bromopyridine is safe, high in yield, high in purity of obtained product, low in cost and friendly to the environment.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic synthesis, and particularly relates to a synthesis method of 2-cyano-5-bromopyridine. BACKGROUND

[0002] The synthesis methods of 2-cyano-5-bromopyridine in the prior art mainly include the following two methods:

[0003] The first method is a diazotization-cyanation method using 5-bromo-2-aminopyridine as a raw material: the 5-bromo-2-aminopyridine is subjected to a diazotization reaction with sodium nitrite at low temperature (0-5 DEG C) to generate a diazonium salt, and then the diazonium salt is subjected to a reaction with a cyanide (such as cuprous cyanide or potassium cyanide) to introduce a cyano group. However, the method has obvious defects: the diazonium salt has poor stability, and the low-temperature condition needs to be strictly controlled, and the operation risk is high; the highly toxic cyanide is used, the equipment corrosion resistance requirement is high, and the waste water generated contains cyanide, the environmental protection treatment cost is high, and the method is not suitable for large-scale industrial production.

[0004] The second method is a direct cyanation method using 2,5-dibromopyridine as a raw material: the cyanide (such as zinc cyanide or potassium ferrocyanide) is directly used to react with 2,5-dibromopyridine under the action of a catalyst (such as tetrakis(triphenylphosphine)palladium(0)) to generate a substitution reaction. Although the method avoids the diazotization step, the highly toxic cyanide is still used, and the catalyst cost is high, and the reaction condition is harsh (high temperature and inert gas protection), which is not conducive to cost control and safe production. SUMMARY

[0005] The application provides a synthesis method of 2-cyano-5-bromopyridine, which aims at the technical problems of using highly toxic cyanide, high operation risk and high cost in the synthesis of 2-cyano-5-bromopyridine in the prior art.

[0006] In order to achieve the above purpose, the technical scheme adopted by the application is as follows: a synthesis method of 2-cyano-5-bromopyridine, comprising the following steps:

[0007] Step one, under the protection of inert gas, the raw material 2,5-dibromopyridine is added into an organic solvent one, methylmagnesium chloride is added dropwise at -60 DEG C to -80 DEG C, stirring reaction is carried out for 2-4 h, dry carbon dioxide is blown in, and 5-bromo-2-pyridine carboxylic acid is obtained by adjusting acid treatment;

[0008] Step two, add 5-bromo-2-pyridinecarboxylic acid obtained in step one into organic solvent two, drop chlorosulfuric acid under temperature control of 0-10℃, after completion of dropping, increase temperature to 35-45℃ and stir for 2-4h, concentrate until no distillate drops out, add organic solvent two until the material dissolves, drop triethylamine and a solution of tert-butyl carbamate under temperature control of 10-20℃, monitor the reaction completion by thin layer chromatography, and then extract, dry and concentrate to obtain tert-butyl (5-bromopyridine-2-formyl) carbamate;

[0009] Step three, react tert-butyl (5-bromopyridine-2-formyl) carbamate obtained in step two with an acid solution, stir for 2-4h under 15-25℃ to remove the tert-butyloxycarbonyl protecting group and obtain 5-bromo-2-pyridinecarboxamide;

[0010] Step four, add 5-bromo-2-pyridinecarboxamide obtained in step three and a dehydrating agent into organic solvent three, stir for 6-8h under 80-100℃ to dehydrate and generate cyano to obtain the target product 2-cyano-5-bromopyridine.

[0011] Preferably, the molar ratio of 2,5-dibromopyridine to methyl magnesium chloride in step one is 1:1.2; the organic solvent one is tetrahydrofuran; and the inert gas is nitrogen or argon.

[0012] Preferably, the molar ratio of 5-bromo-2-pyridinecarboxylic acid to chlorosulfuric acid to tert-butyl carbamate in step two is 1:1.10-1.30:1.01; and the organic solvent two is toluene.

[0013] Preferably, the acid solution in step three is hydrogen chloride ethyl acetate solution or a mixed solution of trifluoroacetic acid and dichloromethane with a volume ratio of 1:1.

[0014] Preferably, the dehydrating agent in step four is phosphorus oxychloride, phosphorus pentoxide or thionyl chloride.

[0015] Preferably, the molar ratio of 5-bromo-2-pyridinecarboxamide to the dehydrating agent in step four is 1:1.5-2.0.

[0016] Preferably, the organic solvent three is toluene or chlorobenzene.

[0017] Compared with the prior art, the synthesis method of 2-cyano-5-bromopyridine has the following advantages and positive effects:

[0018] (1) High safety: the present application avoids using highly toxic cyanide (such as potassium cyanide and cuprous cyanide), and uses tert-butyl carbamate (tert-butyloxycarbonyl amine) as the amino source, and then generates cyano through formamide dehydration, so that the toxicity of raw materials and intermediates is low, the operation risk is greatly reduced, and the safety production requirement is met;

[0019] (2) high yield and high purity: the total yield of the four-step reaction is ≥64% (calculated based on 2,5-dibromopyridine), and the purity of the target product is ≥99%, which is higher than the existing diazotization-cyanation method (the total yield is about 50%) and the direct cyanation method (the total yield is about 60%);

[0020] (3) low cost: both 2,5-dibromopyridine and tert-butyl carbamate (tert-butoxycarbonyl amine) are mass-produced industrial products with low prices; there is no need for special catalysts and the organic solvent can be recycled (such as toluene recovery ≥80%), further reducing production costs;

[0021] (4) environmentally friendly: no cyanide-containing wastewater is generated during the reaction process, and the waste gas and waste liquid can be discharged in accordance with the standard through conventional environmental protection treatment processes, which has little impact on the environment and meets the development trend of green chemical industry;

[0022] (5) simple operation: the reaction conditions are mild (no need for ultra-low temperature and ultra-high pressure), the steps are clear, the post-treatment is simple, and it is easy to realize large-scale industrial production;

[0023] (6) Compared with using ammonia gas as the source of amino group, tert-butyl carbamate is used as the source of amino group in step two of the present application, the reaction control is more precise (dropping solution of tert-butyl carbamate), the reaction process is mild, controllable, safe and uniform in heat release, the amide product is a single tert-butyl (5-bromopyridine-2-formyl) carbamate with high purity and high yield; Because if ammonia gas is used in step two of the present application, due to the uneven flow and diffusion of ammonia gas, the reaction process is violent (the reaction of ammonia gas with highly active acyl chloride is a violent exothermic reaction, it is not easy to achieve local heat dissipation by gas inlet, which may cause the reaction temperature to rise instantaneously, causing the solvent to boil violently, the material to splash, and even to overflow, which brings serious safety hazards), the amide product is a mixture of primary amide and over-acylated product with low yield and poor purity;

[0024] (7) Compared with using ammonia water as the source of amino group, the present application also has the advantages of mild, controllable, safe and uniform heat release in the reaction process, and the obtained tert-butyl (5-bromopyridine-2-formyl) carbamate has high purity and high yield; Because if ammonia water is used in step two of the present application, the ammonia water contains a large amount of water, and the acyl chloride is extremely sensitive to water, and its hydrolysis reaction rate is usually much faster than its amination reaction with ammonia; This will cause the main reaction to become a hydrolysis reaction, and most of the expensive acyl chloride raw materials will react with water to generate useless 5-bromo-2-pyridine carboxylic acid; Even if the ammonia water is slowly added, the water in it will immediately react with the acyl chloride to produce a large amount of heat and hydrogen chloride gas, causing local violent boiling, splashing and even overflow, which is very dangerous for experimental operation. BRIEF DESCRIPTION OF DRAWINGS

[0025] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments description:

[0026] Figure 1 The synthesis method of 2-cyano-5-bromo-pyridine is shown in the figure.

[0027] Figure 2 The purity detection result of 2-cyano-5-bromo-pyridine obtained by using the present application is shown in the figure. DETAILED DESCRIPTION

[0028] In order to more clearly illustrate the technical solutions of the embodiments of the present application, the following will briefly introduce the drawings needed to be used in the embodiments description:

[0029] In the following description, a lot of specific details are set forth in order to provide a thorough understanding of the present application, however, the present application can also be implemented in other ways different from the description herein, therefore, the present application is not limited to the specific embodiments disclosed in the following description.

[0030] Embodiment 1

[0031] The following will be described in combination with Figure 1 The synthesis method of one kind of 2-cyano-5-bromo-pyridine in Embodiment 1 is further described, including the following steps:

[0032] Step one, under the protection of inert gas, the raw material 2,5-dibromopyridine is added into organic solvent one, methyl magnesium chloride is added dropwise at -60~ -80℃, stirring reaction 2-4h, dry carbon dioxide is blown in, and 5-bromo-2-pyridine carboxylic acid is obtained by adjusting acid treatment;

[0033] Step two, 5-bromo-2-pyridine carboxylic acid obtained in step one is added into organic solvent two, and thionyl chloride is added dropwise at 0~10℃, after the addition, the temperature is increased to 35~45℃, stirring 2-4h, and concentrated until no more distillate drops, then organic solvent two is added until the material is dissolved, triethylamine is added at 10~20℃, and the solution of tert-butyl carbamate is added dropwise, after the reaction is completed by monitoring with thin layer chromatography, extraction, drying and concentration are carried out, and tert-butyl (5-bromopyridine-2-formyl) carbamate is obtained;

[0034] Step three, tert-butyl (5-bromopyridine-2-formyl) carbamate obtained in step two is reacted with an acidic solution, stirring reaction 2-4h at 15-25℃, and the tert-butyloxycarbonyl protecting group is removed, and 5-bromo-2-pyridine carboxamide is obtained;

[0035] Step four, add the 5-bromo-2-pyridinecarboxamide obtained in step three, a dehydrating agent into an organic solvent three, stir the reaction at 80-100 °C for 6-8 h, dehydrate to generate cyano, to obtain the target product 2-cyano-5-bromopyridine.

[0036] Step one, synthesis of 5-bromo-2-pyridinecarboxylic acid:

[0037] 1. Experimental purpose: 2,5-dibromopyridine as raw material, through Grignard reaction / carboxylation, to prepare the intermediate 5-bromo-2-pyridinecarboxylic acid.

[0038] 2. Main instruments and equipment: 500 mL three-necked flask, low-temperature constant-temperature stirring bath, magnetic stirrer, constant-pressure dropping funnel, thermometer, gas inlet tube, rotary evaporator and vacuum drying box.

[0039] 3. Reagents and materials:

[0040]

[0041] 4. Experimental steps and phenomenon records:

[0042] (1) Device setup and feeding: Under nitrogen protection, add tetrahydrofuran THF (100 mL) and 2,5-dibromopyridine (23.6 g) into a dry 500 mL three-necked flask in turn. Start stirring and the solid is completely dissolved to obtain a colorless to light yellow clear solution. Cooling: Place the reaction bottle in a low-temperature bath and slowly cool to an internal temperature of -70 °C (actual record: -68 °C to -72 °C). Drop Grignard reagent: Slowly drop methyl magnesium chloride THF solution (40 mL, 3.0 M) through the constant-pressure dropping funnel. Control the dropping speed to maintain the internal temperature at about -70 °C. During the dropping process, the reaction solution has no obvious color change (record: keep clear).

[0043] 2,5-dibromopyridine + methyl magnesium chloride → 5-bromo-2-pyridyl magnesium chloride + bromomethane↑.

[0044] (2) Insulation reaction: After the dropping is completed, continue to stir the reaction at -70 °C for 2 hours. Thin layer chromatography TLC monitoring (developing agent: petroleum ether: ethyl acetate = 3:1, ultraviolet lamp 254 nm coloration) shows that the 2,5-dibromopyridine raw material point (Rf≈0.8) basically disappears and a new point (Rf≈0.1) is generated near the baseline, which is preliminarily judged as Grignard salt. Pass carbon dioxide: Keep low temperature and blow dry carbon dioxide gas into the reaction solution for about 30 minutes. It is observed that the reaction solution gradually becomes turbid suspension.

[0045] (3) Quenching and post-treatment: Keep the internal temperature ≤-30 °C, slowly add pre-cooled dilute hydrochloric acid solution (100 mL) for quenching. A large amount of bubbles are generated, and the system gradually clarifies. After quenching is completed, remove the cold bath and naturally warm up to room temperature (about 22 °C).

[0046] After the carbon dioxide is introduced, the 5-bromo-2-pyridyl magnesium chloride is acidified to obtain 5-bromo-2-pyridine carboxylic acid. 5-bromo-2-pyridyl magnesium chloride + carbon dioxide + hydrogen ion → 5-bromo-2-pyridine carboxylic acid + magnesium ion + chloride ion.

[0047] (4) Extraction and drying: Transfer the reaction solution to a separatory funnel, extract with ethyl acetate (100 mL × 3 times). Wash the combined organic phase with saturated brine (100 mL × 2 times). Dry the organic phase with anhydrous sodium sulfate for about 30 minutes.

[0048] (5) Concentration and product: Remove the drying agent by filtration, and the filtrate is evaporated under reduced pressure (water bath 60 °C, vacuum degree 0.08 MPa) to remove the solvent. White or white solid crude product is obtained.

[0049] 5. Product data: Appearance: white solid, weight: 17.37 g, yield calculation: (17.37 g / theoretical yield 20.2 g) × 100% ≈ 86.0%, melting point determination: 174-176 °C, thin layer chromatography TLC purity: single main spot (petroleum ether: ethyl acetate = 1:1).

[0050] Experimental summary: The operation of this step is smooth, and the temperature control is the key. The yield and purity of the product meet the expectations and can be used for the next step reaction.

[0051] Step two, synthesis of tert-butyl (5-bromopyridine-2-formyl) carbamate:

[0052] 1. Experimental purpose: Convert 5-bromo-2-pyridine carboxylic acid into the corresponding N-Boc protected amide.

[0053] 2. Main instruments and equipment: (synchronous step one, omit low temperature bath).

[0054] 3. Reagents and materials:

[0055]

[0056] 4. Experimental steps and phenomenon records:

[0057] (1) Acyl chloride: To a dry 500 mL reaction flask, add toluene (100 mL) and 5-bromo-2-pyridinecarboxylic acid (20.2 g). Cool to 0-5 °C with an ice water bath and slowly add thionyl chloride (8.7 mL) dropwise. A pungent gas (hydrogen chloride, sulfur dioxide) is evolved during the addition. After the addition is complete, remove the ice bath and allow the reaction to warm to 40 °C and stir for 3 hours. Thin layer chromatography (TLC) monitoring (petroleum ether: ethyl acetate = 1:1) shows the disappearance of the acid spot and the appearance of a new spot (slightly higher Rf).

[0058] 5-bromo-2-pyridinecarboxylic acid + thionyl chloride → 5-bromo-2-pyridinecarboxylic chloride + sulfur dioxide + hydrogen chloride.

[0059] (2) Concentration to remove thionyl chloride: Concentrate the reaction under reduced pressure until no more distillate is observed. This gives the crude acyl chloride as an oil. Amidation: Dissolve the oil in fresh toluene (100 mL). Cool to 10-15 °C with an ice water bath and add triethylamine (14 mL) followed by a solution of tert-butyl carbamate (11.83 g dissolved in 20 mL toluene) dropwise. White fumes (triethylamine hydrochloride) are evolved during the addition and the system becomes cloudy.

[0060] 5-bromo-2-pyridinecarboxylic chloride + triethylamine + tert-butyl carbamate → tert-butyl (5-bromopyridine-2-carbonyl) carbamate + triethylamine hydrochloride.

[0061] (3) Reaction monitoring: After the addition is complete, continue stirring at 10-15 °C for 1 hour and then at room temperature for 2 hours. High performance liquid chromatography (HPLC) monitoring shows that the peak area of the starting acyl chloride (or its corresponding acid) is < 2%. Work-up: Quench the reaction by adding water (100 mL) and separate the layers. Extract the aqueous phase with ethyl acetate (50 mL x 2). Wash the combined organic phases with 1 M dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine. Dry the organic phase over anhydrous sodium sulfate.

[0062] (4) Concentration and product isolation: Filter and concentrate the filtrate under reduced pressure to give a pale yellow viscous oil which solidifies upon standing at room temperature. Appearance: white solid, weight: 26.4 g, yield calculation: (26.4 g / theoretical yield 30.0 g) x 100% = 88.0%, TLC / HPLC: shows the main product with good purity.

[0063] (5) Experimental summary: The acyl chloride and amidation reactions are complete and the work-up procedure is standard. The product state and yield are as expected.

[0064] Step three, synthesis of 5-bromo-2-pyridinecarboxamide (Boc deprotection):

[0065] Key Operation: Dissolve tert-butyl (5-bromopyridine-2-carbonyl)carbamate (30.0 g, 0.10 mol) in a small amount of ethyl acetate (10 mL) and bubble dry hydrogen chloride gas into the solution until saturated (about 0.4 mol) at room temperature. The system gradually becomes turbid and solid precipitates. Reaction Monitoring: TLC (petroleum ether: ethyl acetate = 1:1) shows that the Boc-protected product spot disappears and a new strongly polar spot (formamide hydrochloride) appears near the origin. Key of Work-up: After the reaction is completed, filter to obtain white solid (hydrochloride salt). Dissolve the solid in water and carefully adjust the pH to 8-9 with 5% sodium hydroxide solution. A large amount of white solid reprecipitates. Filter, wash with water, and dry under vacuum at 50 °C.

[0066] tert-butyl (5-bromopyridine-2-carbonyl)carbamate + hydrogen chloride → 5-bromo-2-pyridinecarboxamide hydrochloride + carbon dioxide↑+ isobutene↑;

[0067] 5-bromo-2-pyridinecarboxamide hydrochloride + 5% sodium hydroxide solution → 5-bromo-2-pyridinecarboxamide + sodium chloride + water.

[0068] Result: Product: 5-bromo-2-pyridinecarboxamide, Appearance: white crystalline powder, Weight: 19.0 g, Yield: 95.0%, Melting point: 219-221 °C.

[0069] Step Four, Synthesis of 2-cyano-5-bromopyridine (dehydration to nitrile):

[0070] (1) Key Operation: Add 5-bromo-2-pyridinecarboxamide (20.0 g, 0.10 mol) and toluene (100 mL) into a reaction flask, and then add phosphorus oxychloride (15.3 g, 0.10 mol) with stirring. Heat to 90 °C and reflux for 7 hours. Reaction Monitoring: HPLC monitoring shows that the formamide peak area is <1% and the main product peak appears at a shorter retention time.

[0071] 5-bromo-2-pyridinecarboxamide + phosphorus oxychloride → 2-cyano-5-bromopyridine + phosphoric acid + 3 hydrogen chloride↑.

[0072] (2) Key of Work-up: Slowly pour the cooled reaction liquid into 200 g crushed ice / ice water with vigorous stirring under good ventilation. Carefully neutralize to pH 7-8 with 2 M sodium hydroxide solution. Extract with ethyl acetate, dry, and concentrate to obtain the crude product.

[0073] (3) Purification: Purify the crude product by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1).

[0074] (4) Result: Final product: 2-cyano-5-bromopyridine, appearance: white needle-like crystal, weight: 15.98 g, yield: 89.8% (calculated based on formamide), purity (HPLC) as shown: 99.3%, melting point: 129-131 °C, total yield of four steps (calculated based on 2,5-dibromopyridine): 0.860 x 0.880 x 0.950 x 0.898 ≈ 64.6%. Figure 2

[0075] Experiment summary: This experiment successfully completed the four-step synthesis of 2-cyano-5-bromopyridine according to the established route.

[0076] Example 2

[0077] The difference between this example and Example 1 is that in Step 2 of this example, 0.11 mol or 0.13 mol of thionyl chloride is used. Since the theoretical molar ratio of 5-bromo-2-pyridinecarboxylic acid to thionyl chloride participating in the reaction is 1:1, a slight excess of thionyl chloride is used to ensure complete reaction.

[0078] Example 3

[0079] The difference between this example and Example 1 is that in Step 3, the acidic solution is a mixture of trifluoroacetic acid and dichloromethane in a volume ratio of 1:1 to obtain trifluoroacetate; the solid is dissolved in water, and the pH is carefully adjusted to 8-9 with 5% sodium hydroxide solution, and a large amount of white solid reprecipitates. Filter, wash with water, and dry under vacuum at 50°C.

[0080] tert-butyl (5-bromopyridine-2-formyl)carbamate + trifluoroacetic acid → trifluoroacetate + carbon dioxide↑ + isobutene↑;

[0081] trifluoroacetate + 5% sodium hydroxide solution → 5-bromo-2-pyridinecarboxamide + sodium trifluoroacetate + water.

[0082] Example 4

[0083] The difference between this example and Example 1 is that in Step 4, the dehydrating agent is phosphorus pentoxide. The reaction equation is:

[0084] 5-bromo-2-pyridinecarboxamide + phosphorus pentoxide → 2-cyano-5-bromopyridine + 2 metaphosphoric acid.

[0085] Example 5

[0086] The difference between this example and Example 1 is that in Step 4, the dehydrating agent is thionyl chloride. The reaction equation is:

[0087] 5-bromo-2-pyridinecarboxamide + thionyl chloride → 2-cyano-5-bromopyridine + sulfur dioxide↑ + 2 hydrogen chloride↑. ​

[0088] The above merely describes preferred embodiments of the present application, but is not intended to limit the present application in other forms. Any person skilled in the art can make changes or modifications to the above disclosed technical contents into equivalent embodiments with equivalent changes, and apply to other fields. However, any simple modification or equivalent change made to the above embodiments without departing from the technical solution of the present application, and according to the technical essence of the present application, still belongs to the protection scope of the technical solution of the present application.

Claims

1. A method for synthesizing 2-cyano-5-bromopyridine, characterized in that, Includes the following steps: Step 1: Under inert gas protection, 2,5-dibromopyridine is added to organic solvent 1, and methyl magnesium chloride is added dropwise at -60~-80℃. The mixture is stirred and reacted for 2-4 hours. Dry carbon dioxide is bubbled in, and the mixture is treated with acid to obtain 5-bromo-2-pyridinecarboxylic acid. Step 2: Add the 5-bromo-2-pyridinecarboxylic acid obtained in Step 1 to Organic Solvent 2, and add thionyl chloride dropwise while controlling the temperature at 0~10℃. After the addition is complete, raise the temperature to 35~45℃ and stir for 2-4 hours. Concentrate until no more distillate drips out, add Organic Solvent 2 until the material is completely dissolved, add triethylamine while controlling the temperature at 10~20℃, and add a solution of tert-butyl carbamate dropwise. After monitoring the completion of the reaction by thin-layer chromatography, extract, dry and concentrate to obtain tert-butyl (5-bromopyridine-2-carboxy) carbamate. Step 3: The tert-butyl (5-bromopyridine-2-carboxylic acid) carbamate obtained in Step 2 is reacted with an acidic solution and stirred at 15-25°C for 2-4 hours to remove the tert-butoxycarbonyl protecting group, yielding 5-bromo-2-pyridinecarboxamide. Step four: Add the 5-bromo-2-pyridine carboxamide obtained in step three and the dehydrating agent to organic solvent three, and stir the reaction at 80-100℃ for 6-8 hours to dehydrate and generate cyano group, thus obtaining the target product 2-cyano-5-bromopyridine.

2. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, In step one, the molar ratio of 2,5-dibromopyridine to methylmagnesium chloride is 1:1.2; the organic solvent is tetrahydrofuran; and the inert gas is argon.

3. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, In step two, the molar ratio of raw materials 5-bromo-2-pyridinecarboxylic acid: thionyl chloride: tert-butyl carbamate is 1:1.10~1.30:1.01; the organic solvent is toluene.

4. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, The acidic solution mentioned in step three is an ethyl acetate solution of hydrogen chloride or a mixed solution of trifluoroacetic acid and dichloromethane in a volume ratio of 1:

1.

5. The method for synthesizing 2-cyano-5-bromopyridine according to claim 1, characterized in that, The dehydrating agent mentioned in step four is phosphorus oxychloride, phosphorus pentoxide, or thionyl chloride.

6. The method for synthesizing 2-cyano-5-bromopyridine according to claim 5, characterized in that, In step four, the molar ratio of 5-bromo-2-pyridinecarboxamide to the dehydrating agent is 1:1.5-2.

0.

7. The method for synthesizing 2-cyano-5-bromopyridine according to claim 6, characterized in that, The organic solvent is toluene or chlorobenzene.

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