Synthesis method of 1H-pyrrolo [3, 2-B] pyridine-6-amine

Abstract

The invention relates to a synthesis method of 1H-pyrrolo [3, 2-B] pyridine-6-amine. Comprising the following steps: carrying out a reaction on 5-bromo-2-methyl-3-nitropyridine and N, N-dimethyl formamide dimethyl acetal to obtain (E)-2-(5-bromo-3-nitropyridine-2-yl)-N, N-dimethyl ethylene-1-amine, and carrying out a reaction on the (E)-2-(5-bromo-3-nitropyridine-2-yl)-N, N-dimethyl ethylene-1-amine and the N, N-dimethyl formamide dimethyl acetal to obtain the 5-bromo-2-methyl-3-nitropyridine. Adding the 6-bromine-4-azaindole into acetic acid, and performing reduction and cyclization reaction by using an iron-based catalyst to obtain 6-bromine-4-azaindole; and then adding into ammonia water, and reacting under a copper-based catalyst to obtain the 1H-pyrrolo [3, 2-B] pyridine-6-amine. The 1H-pyrrolo [3, 2-B] pyridine-6-amine is effectively obtained through three-step synthesis. A compound of Fe-coated PMMA-b-PDMAEMA and PE wax coated iron powder is used as an iron-based catalyst, and the ratio of the Fe-coated PMMA-b-PDMAEMA to the PE wax coated iron powder is reasonably adjusted, so that the catalytic effect of the reduction and cyclization reaction is remarkably improved and further optimized, and the conversion rate is improved, thereby realizing high yield of the product.

Description

Technical Field

[0001] This invention relates to a method for synthesizing heterocyclic compounds, specifically a method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine. Background Technology

[0002] Fusion nitrogen heterocyclic compounds are highly favored due to their versatility and structural diversity in pharmaceuticals. These compounds not only enhance drug efficacy and selectivity but also improve bioavailability and stability. The frequency and diversity of fusion nitrogen heterocycles have significantly increased in newly approved drugs, particularly in the field of anticancer research. 1H-pyrrolo[3,2-B]pyridine-6-amine, as a novel fusion nitrogen heterocyclic synthon, holds significant promise for drug screening. However, there are currently no reports on industrial synthesis methods for 1H-pyrrolo[3,2-B]pyridine-6-amine. This leads to a predicament for researchers and related industries when this compound is needed, as they lack an effective synthetic route, limiting its application and development in related fields. Furthermore, the synthetic route needs to achieve high conversion rates to meet industrial requirements; therefore, it is necessary to provide a high-yield synthetic method for 1H-pyrrolo[3,2-B]pyridine-6-amine. Summary of the Invention

[0003] Therefore, in order to synthesize a 1H-pyrrolo[3,2-B]pyridine-6-amine in high yield, this application provides a method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine.

[0004] In a first aspect, this application provides a method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine, comprising the following steps: Step 1: 5-Bromo-2-methyl-3-nitropyridine reacts with N,N-dimethylformamide dimethyl acetal in DMF to give (E)-2-(5-bromo-3-nitropyridine-2-yl)-N,N-dimethylethylene-1-amine; Step 2: (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine is added to acetic acid, reduced and cyclized with an iron-based catalyst to give 6-bromo-4-azaindole; Step 3: 6-bromo-4-azaindole is added to ammonia water and reacted under a copper-based catalyst to give 1H-pyrrolo[3,2-B]pyridine-6-amine; The synthetic route is as follows: .

[0005] This invention provides a three-step synthesis to efficiently obtain 1H-pyrrolo[3,2-B]pyridine-6-amine. It features readily available starting materials, a short synthetic route, simple operation, and high yield.

[0006] Step 1 uses 5-bromo-2-methyl-3-nitropyridine as a raw material and reacts it with N,N-dimethylformamide dimethyl acetal DMF-DMA to attach an alkenyl amine to the pyridine ring, providing an active site for the subsequent ring-closure reaction. This process uses DMF as a solvent, which has good solubility for the reactants and reduces the formation of by-products, resulting in a high yield of (E)-2-(5-bromo-3-nitropyridine-2-yl)-N,N-dimethylethylene-1-amine.

[0007] Preferably, step 1 further includes a post-processing step: cooling after reaction, vacuum concentration, low-temperature water addition and pulping, and filtration to collect the precipitated reddish-brown solid.

[0008] Step 2 uses (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine as a starting material. The intramolecular nitro group is selectively reduced, leading to intramolecular cyclization and yielding 6-bromo-4-azaindole. The auxiliary reaction system in this step is simple and efficient. Acetic acid provides a weakly acidic environment to promote nitro group reduction and accelerate the cyclization rate. The iron-based catalyst has high electron transfer efficiency, further accelerating nitro group reduction and shortening the cyclization induction period. Iron loses electrons in acetic acid to generate ferrous ions, promoting the formation of nitro radical anions, which further abstract protons from acetic acid, achieving a multi-step reaction and ultimately completing the cyclization.

[0009] In step 3, 6-bromo-4-azaindole reacts with a copper-based catalyst to yield 1H-pyrrolo[3,2-B]pyridine-6-amine.

[0010] Preferably, the reaction is followed by post-treatment: cooling, extraction with ethyl acetate, washing with brine, drying with sodium sulfate, filtration, concentration, and recrystallization to obtain the product. A high yield of 1H-pyrrolo[3,2-B]pyridine-6-amine is obtained.

[0011] In some embodiments, the molar ratio of the iron-based catalyst to (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine is 3-5:1.

[0012] In some embodiments, the iron-based catalyst comprises iron powder.

[0013] Iron is an electron donor in the reaction. Compared with iron blocks and iron sheets, iron powder has a larger surface area, and excess iron powder can reduce some of the generated ferric iron to ferrous iron in the reaction, thereby maintaining the redox cycle and promoting the continuous reduction of nitro groups.

[0014] In some embodiments, the iron-based catalyst comprises Fe@PMMA-b-PDMAEMA and PE wax-coated iron powder.

[0015] Preferably, the mass ratio of Fe@PMMA-b-PDMAEMA to PE wax-coated iron powder is 8-12:1.

[0016] While working to improve the yield of the synthetic route in this application, the inventors discovered that the yield of step 1 was as high as 90.7%, and the yield of step 3 was also as high as 81.4%, but the yield of step 2 catalyzed by iron powder was only 61.7%. Therefore, improving the yield of step 2 is key to achieving a high product yield. Based on this, the inventors analyzed that Fe forms Fe... 2+ Fe 3+ Afterwards, ferrous acetate coated the surface of the iron powder, Fe... 3+ Excessive iron powder that cannot be reduced in a timely and effective manner are factors contributing to the low yield in step 2. Furthermore, the large surface area of ​​iron powder makes it more prone to agglomeration, reducing contact with the active reactants, which is also a significant factor. Even with stirring, some agglomeration cannot be resolved. Based on this, this application proposes a composite iron-based catalyst, Fe@PMMA-b-PDMAEMA, and PE wax-coated iron powder. Through the combined action of these two catalysts, highly efficient catalysis of this reaction is achieved, significantly improving the yield of step 2.

[0017] Specifically, Fe@PMMA-b-PDMAEMA is a block copolymer of methyl methacrylate and 2-(dimethylamino)ethyl methacrylate grafted onto the surface of iron powder. The tertiary amine in the 2-(dimethylamino)ethyl methacrylate segment is protonated in acetic acid, becoming positively charged and exhibiting excellent solvent compatibility. On one hand, it can form a positively charged domain near the iron powder, improving dispersion based on charge repulsion. On the other hand, it can also restrict the deposition of ferrous acetate on the iron powder surface based on charge and steric hindrance, thus maintaining good catalyst dispersion and activity. Although PMMA only has steric hindrance and no corresponding charge repulsion, the grafting of PMMA segments in this application demonstrates an improved catalytic effect. This may be because the PMMA segment is located between the iron powder surface and the positively charged segment. Compared to the positively charged segment being directly grafted onto the iron powder surface, it avoids the accumulation of positive charges on the iron powder surface, which would affect the reaction between iron powder and acetic acid and prevent the formation of effective active Fe. 2+ Grafting iron powder with PMMA-b-PDMAEMA effectively improved Fe dispersion and catalytic surface area, thus enhancing the catalytic effect. However, this also increased the amount of Fe generated. 3+ The reduced contact with iron powder leads to Fe 3+The inability to achieve immediate reduction inhibits the redox cycle and affects the reduction reaction of nitro groups. The inventors further added PE wax to coat the iron powder. The PE wax coating restricts the initial catalytic participation of the iron powder in the core layer. As the temperature rises and the reaction time increases, the PE wax solid film forms a liquid oil film, acetic acid molecules permeate, and the reacting gases form channels in the coating film, allowing the iron powder to be released. This released iron powder can then react with Fe in the system. 3+ The reaction regenerates Fe 2+ This promotes the redox cycle, thus the combined effect of Fe@PMMA-b-PDMAEMA and PE wax-coated iron powder significantly enhances the catalytic effect of step 2 and improves the conversion rate. Furthermore, the mass ratio of Fe@PMMA-b-PDMAEMA to PE wax-coated iron powder is within the range of 8-12:1, with a further ratio of 10:1 showing better kinetic matching with the reaction in step 2. This allows for the maintenance of the highly efficient iron powder catalyst while simultaneously removing Fe. 3+ This demonstrates an optimized yield.

[0018] In some embodiments, the preparation method of Fe@PMMA-b-PDMAEMA includes: grafting iron powder with aminosilane and then brominizing it to obtain Fe-Br, and using Fe-Br as a catalyst to sequentially initiate atom transfer radical polymerization of PMMA and PDMAEMA to obtain the product.

[0019] Preferably, the amount of aminosilane used is 0.2-0.5% of the mass of iron powder.

[0020] Aminoation of iron powder provides active sites for subsequent grafting. Controllable chain segment growth is achieved through ATRP polymerization, resulting in target molecular chains with narrow molecular weight distribution and fewer side reactions. By controlling the amount of aminosilane modification, the grafted chain segments can be made to disperse the catalyst and reduce the salt coverage on the iron surface, while maintaining a large exposed area of ​​iron powder, thereby ensuring high catalytic activity of iron powder.

[0021] In some embodiments, the preparation method of PE wax-coated iron powder includes: heating PE wax to 10-15°C above its melting point and stirring, slowly adding iron powder and continuing to stir, cooling down and then gently grinding and vacuum drying.

[0022] In some embodiments, the copper-based catalyst comprises copper sulfate.

[0023] In some embodiments, the molar percentage of the copper-based catalyst, calculated as 6-bromo-4-azaindole, is 20% to 30% mol.

[0024] In some embodiments, the molar ratio of 5-bromo-2-methyl-3-nitropyridine to N,N-dimethylformamide dimethyl acetal is 1:1.1-1.3.

[0025] In some embodiments, the reaction temperature in step 1 is 85-95°C; the reaction temperature in step 2 is 95-105°C; and the reaction temperature in step 3 is 95-105°C.

[0026] In summary, this application includes at least one of the following beneficial technical effects: 1. This application presents a three-step synthetic method for obtaining 1H-pyrrolo[3,2-B]pyridine-6-amine. It features readily available raw materials, a short synthetic route, simple operation, and high yield.

[0027] 2. In this application, a composite of Fe@PMMA-b-PDMAEMA and PE wax-coated iron powder is used as the iron-based catalyst in step 2. By reasonably adjusting the ratio of the two, the catalytic effect of step 2 is significantly improved and further optimized, thereby increasing the conversion rate and achieving a high yield of the product. Attached Figure Description

[0028] Figure 1 The image shows the liquid chromatography-mass spectra of the product from Example 1.

[0029] Figure 2 The NMR spectrum of the product of Example 1 is shown. Detailed Implementation

[0030] The present application will be further described in detail below with reference to embodiments and comparative examples: Iron powder was purchased from Jiangsu Leien Environmental Protection Technology Co., Ltd., 200 mesh; PE wax was purchased from Wuhan Jiyesheng Chemical Co., Ltd., JYS15451, melting point 90-100℃.

[0031] Unless otherwise specified, all raw materials used in the examples and comparative examples are commercially available products. The yields in the examples and comparative examples are calculated as the actual / theoretical product of the corresponding step multiplied by 100%.

[0032] Preparation Example 1 Preparation of Fe@PMMA-b-PDMAEMA: 1000g of iron powder was added to 6L of 1mol / L hydrochloric acid solution and stirred and dispersed for 30min. The solution was then filtered, washed with water until neutral, washed with ethanol, and vacuum dried to obtain activated iron powder. Add 4g of aminopropyltrimethoxysilane to 3L of ethanol aqueous solution (ethanol:water volume ratio 10:1) and stir for 15min at 500r / min. Add 1000g of activated iron powder and continue stirring. Heat to 75℃ and reflux for 4h. Centrifuge, wash with water 3 times, and dry to obtain amino-modified iron powder. Amino-modified iron powder was added to 5L of toluene and stirred for 2 hours at 750 rpm. The mixture was then placed in an ice-water bath, and 3.2g of triethylamine was added, followed by 7g of 2-bromoisobutyryl bromide. The mixture was stirred for 1.5 hours. The mixture was then removed from the ice-water bath and reacted at room temperature for 24 hours. The mixture was then centrifuged, washed with ethanol, and dried to obtain bromine-modified iron powder. Step 2) Add 300g MMA to 4L toluene, replace oxygen with nitrogen; add bromine-modified iron powder, 10g cuprous bromide, and 20g pentamethyldiethylenetriamine, heat to 90℃ and react for 5h, cool, centrifuge, wash 3 times with ethanol, and dry to obtain Fe@PMMA-Br; Step 3) Add 300g DMAEMA to 4mL toluene, replace oxygen with nitrogen, add Fe@PMMA-Br, 10g cuprous bromide and 20g pentamethyldiethylenetriamine, heat to 100℃ and react for 5h, cool, centrifuge, wash 3 times with ethanol and dry to obtain Fe@PMMA-b-PDMAEMA.

[0033] Preparation Example 2 Preparation of Fe@PMMA: 1000g of iron powder was added to 6L of 1mol / L hydrochloric acid solution and stirred and dispersed for 30min. The solution was then filtered, washed with water until neutral, washed with ethanol, and vacuum dried to obtain activated iron powder. Add 4g of aminopropyltrimethoxysilane to 3L of ethanol aqueous solution (ethanol:water volume ratio 10:1) and stir for 15min at 500r / min. Add 1000g of activated iron powder and continue stirring. Heat to 75℃ and reflux for 4h. Centrifuge, wash with water 3 times, and dry to obtain amino-modified iron powder. Amino-modified iron powder was added to 5L of toluene and stirred for 2 hours at 750 rpm. The mixture was then placed in an ice-water bath, and 3.2g of triethylamine was added, followed by 7g of 2-bromoisobutyryl bromide. The mixture was stirred for 1.5 hours. The mixture was then removed from the ice-water bath and reacted at room temperature for 24 hours. The mixture was then centrifuged, washed with ethanol, and dried to obtain bromine-modified iron powder. Add 600g MMA to 8L of toluene, and replace oxygen with nitrogen; add bromine-modified iron powder, 20g cuprous bromide, and 40g pentamethyldiethylenetriamine, heat to 90℃ and react for 5h, cool, centrifuge, wash three times with ethanol, and dry to obtain Fe@PMMA.

[0034] Preparation Example 3 Preparation of Fe@PDMAEMA: 1000g of iron powder was added to 6L of 1mol / L hydrochloric acid solution and stirred and dispersed for 30min. The solution was then filtered, washed with water until neutral, washed with ethanol, and vacuum dried to obtain activated iron powder. Add 4g of aminopropyltrimethoxysilane to 3L of ethanol aqueous solution (ethanol:water volume ratio 10:1) and stir for 15min at 500r / min. Add 1000g of activated iron powder and continue stirring. Heat to 75℃ and reflux for 4h. Centrifuge, wash with water 3 times, and dry to obtain amino-modified iron powder. Amino-modified iron powder was added to 5L of toluene and stirred for 2 hours at 750 rpm. The mixture was then placed in an ice-water bath, and 3.2g of triethylamine was added, followed by 7g of 2-bromoisobutyryl bromide. The mixture was stirred for 1.5 hours. The mixture was then removed from the ice-water bath and reacted at room temperature for 24 hours. The mixture was then centrifuged, washed with ethanol, and dried to obtain bromine-modified iron powder. Add 600g of DMAEMA to 8L of toluene, replace oxygen with nitrogen, add bromine-modified iron powder, 20g of cuprous bromide, and 40g of pentamethyldiethylenetriamine, heat to 100℃ and react for 5h, cool, centrifuge, wash three times with ethanol, and dry to obtain Fe@PDMAEMA.

[0035] Preparation Example 4 Preparation of PE wax-coated iron powder: The preparation method of PE wax coated iron powder includes: heating PE wax to 15°C above its melting point and stirring for 25 minutes to form a solution, slowly adding iron powder and continuing to stir, with the mass ratio of iron powder to PE wax being 8:1, stirring for 35 minutes, cooling, grinding, and vacuum drying to obtain PE wax coated iron powder. Example 1

[0036] Step 1: Under nitrogen protection, 248 g of 2-methyl-3-nitro-5-bromopyridine, 2.5 L of DMF, and 750 g of DMF-DMA were added sequentially to a 5 L reactor. The reaction mixture was refluxed and heated to 90 °C and stirred at 700 rpm for 4 h. After cooling to room temperature, the mixture was concentrated under vacuum. The residue was mixed with water at 0 °C until it became a paste without clumping. The precipitated solid was collected by filtration and dried to obtain a brownish-red solid (E)-2-(5-bromo-3-nitropyridine-2-yl)-N,N-dimethylethylene-1-amine (yield 90.7%).

[0037] Step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (the mass ratio of Fe@PMMA-b-PDMAEMA from Preparation Example 1 to PE wax-coated iron powder from Preparation Example 4 was 10:1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping. Filtration yielded a grayish-brown solid, 6-bromo-4-azaindole (yield 75.8%).

[0038] Step 3: At room temperature, 125 g of 6-bromo-4-azaindole, 1 L of ammonia, and 310 g of copper sulfate were added sequentially to a 5 L three-necked flask. The mixture was refluxed and heated to 100 °C, and stirred for 20 h. After cooling to room temperature, it was extracted with ethyl acetate 1 L x 5 times. The combined organic layers were washed with 500 mL of saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was recrystallized from a mixture of petroleum ether and ethyl acetate (volume ratio 1:1) to give a brownish-red solid 1H-pyrrolo[3,2-B]pyridine-6-amine (yield 81.4%). Example 2

[0039] The difference between Example 2 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (the mass ratio of Fe@PMMA in Example 2 to PE wax-coated iron powder in Example 4 was 10:1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping, and filtered to obtain a grayish-brown solid, 6-bromo-4-azaindole (yield 65.4%). Example 3

[0040] The difference between Example 3 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (the mass ratio of Fe@PDMAEMA in Example 3 to PE wax-coated iron powder in Example 4 was 10:1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping, and filtered to obtain a grayish-brown solid, 6-bromo-4-azaindole (yield 68.5%). Example 4

[0041] The difference between Example 4 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (the mass ratio of Fe@PMMA-b-PDMAEMA from Example 1 to PE wax-coated iron powder from Example 4 was 5:1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping, and filtered to obtain a grayish-brown solid, 6-bromo-4-azaindole (yield 70.3%). Example 5

[0042] The difference between Example 5 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (the mass ratio of Fe@PMMA-b-PDMAEMA from Example 1 to PE wax-coated iron powder from Example 4 was 15:1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping, and filtered to obtain a grayish-brown solid, 6-bromo-4-azaindole (yield 73.2%). Example 6

[0043] The difference between Example 6 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (Fe@PMMA-b-PDMAEMA from Preparation Example 1) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping. Filtration yielded a grayish-brown solid, 6-bromo-4-azaindole (yield 67.4%). Example 7

[0044] The difference between Example 7 and Example 1 lies in step 2: Under nitrogen protection, 280 g of (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine, 2800 mL of acetic acid, and 230 g of iron-based catalyst (iron powder) were added sequentially to a 5 L three-necked flask. The mixture was then refluxed and heated to 100°C, and stirred at 400 rpm for 18 h. After cooling to room temperature, the mixture was filtered, and the filtrate was concentrated under vacuum. The residue was then slurried with petroleum ether until it became a paste without clumping. Filtration yielded a grayish-brown solid, 6-bromo-4-azaindole (yield 61.7%).

[0045] In conjunction with Example 1, Figure 1-2 It can be seen that this application successfully synthesized 1H-pyrrolo[3,2-B]pyridine-6-amine, obtaining the target product. Regarding the yield investigation in step 2, referring to Examples 1-3, it can be seen that compared to grafting PMMA or PDMAEMA alone, the combined effect of Fe@PMMA-b-PDMAEMA obtained by grafting block copolymer chains onto the iron powder surface and PE wax-coated iron powder significantly improved the yield; demonstrating the catalytic advantage of Fe@PMMA-b-PDMAEMAPE combined with wax-coated iron powder in this reaction. Combining Examples 1 and 4-7, it can be seen that Fe@PMMA-b-PDMAEMAPE without wax-coated iron powder, or outside the ratio range of this application, exhibits a deterioration in catalytic effect. This indicates that the Fe@PMMA-b-PDMAEMAPE and PE wax-coated iron powder of this application can promote the catalysis of the system based on multiple factors during catalysis, and further optimize the catalytic effect under certain ratios.

[0046] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine, characterized in that: Includes the following steps: Step 1: 5-Bromo-2-methyl-3-nitropyridine reacts with N,N-dimethylformamide dimethyl acetal in DMF to give (E)-2-(5-bromo-3-nitropyridine-2-yl)-N,N-dimethylethylene-1-amine; Step 2: (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine is added to acetic acid, reduced and cyclized with an iron-based catalyst to give 6-bromo-4-azaindole; Step 3: 6-bromo-4-azaindole is added to ammonia water and reacted under a copper-based catalyst to give 1H-pyrrolo[3,2-B]pyridine-6-amine; The synthetic route is as follows: .

2. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The molar ratio of the iron-based catalyst to (E)-2-(5-bromo-3-nitropyridin-2-yl)-N,N-dimethylethylene-1-amine is 3-5:

1.

3. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The iron-based catalyst includes iron powder.

4. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The iron-based catalyst comprises Fe@PMMA-b-PDMAEMA and PE wax-coated iron powder.

5. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 4, characterized in that: The mass ratio of Fe@PMMA-b-PDMAEMA to PE wax-coated iron powder is 8-12:

1.

6. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 4, characterized in that: The preparation method of Fe@PMMA-b-PDMAEMA includes: grafting iron powder with aminosilane and then brominizing it to obtain Fe-Br, and using Fe-Br as a catalyst to sequentially initiate atom transfer radical polymerization of PMMA and PDMAEMA to obtain the product.

7. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The copper-based catalyst contains copper sulfate.

8. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The molar percentage of the copper-based catalyst, calculated as 6-bromo-4-azaindole, is 20%-30% mol.

9. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The molar ratio of 5-bromo-2-methyl-3-nitropyridine to N,N-dimethylformamide dimethyl acetal is 1:1.1-1.

3.

10. The method for synthesizing 1H-pyrrolo[3,2-B]pyridine-6-amine according to claim 1, characterized in that: The reaction temperature in step 1 is 85-95℃; the reaction temperature in step 2 is 95-105℃; the reaction temperature in step 3 is 95-105℃.

Images