A method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate and 3,3'-(pyrazine-2,5-diyl)dipropionate

Abstract

This invention discloses a method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate and the 3,3'-(pyrazine-2,5-diyl)dipropionate, relating to the field of organic synthesis technology. The technical solution of this invention involves mixing a second compound as shown in formula (3), a polar solvent, and a catalyst, and performing a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate, which is then converted in one step into the target product having an aromatic pyrazine ring. The product obtained by this invention not only retains the original carboxylic acid ester active functional groups in each unit, providing possibilities for subsequent derivatization, but more importantly, it introduces a rigid aromatic pyrazine ring core, which can enhance the hydrophobicity and membrane permeability of the molecule; improve chemical and metabolic stability; and its extended conjugated system may bring unique photophysical properties, affecting its efficiency as a photosensitizer in excitation and generation of reactive oxygen species.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate and 3,3'-(pyrazine-2,5-diyl)dipropionate. Background Technology

[0002] 5-Aminolevulinic acid (5-ALA) is a naturally occurring non-protein amino acid that, as a key precursor in the biosynthesis of tetrapyrrole compounds such as heme and chlorophyll, shows broad application prospects in the biomedical and agricultural fields. However, 5-ALA and its simple esters suffer from problems such as poor molecular stability and relatively simple chemical structures in practical applications.

[0003] To overcome these shortcomings, researchers have explored various strategies, primarily including: 1) synthesizing higher-order ester or amide prodrugs to improve lipophilicity and membrane permeability; 2) developing targeted delivery systems based on nanocarriers or chemical conjugates; and 3) synthesizing porphyrin-based direct photosensitizers. However, these strategies either face challenges such as complex synthesis and high costs, or fail to fundamentally alter the properties of the core chromophore. Therefore, from the perspective of molecular structural innovation, the rational design and derivatization of the 5-ALA core framework to construct compounds with novel structures, potentially superior physicochemical properties, and biological activities has significant scientific and application value. Summary of the Invention

[0004] The main objective of this invention is to propose a method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate, aiming to solve the problems of poor molecular stability and relatively simple chemical structure of 5-ALA and its simple esters in practical applications.

[0005] To achieve the above objectives, this invention proposes a method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate, comprising the following steps: Step S10: Mix the monoalkyl succinate as shown in formula (1), the reagent containing the imidazole group and the first organic solvent, and carry out an amidation reaction to obtain the first compound as shown in formula (2); Step S20: Mix the first compound, nitromethane, basic substance and second organic solvent, and carry out nucleophilic substitution reaction to obtain the second compound as shown in formula (3); Step S30: Mix the second compound, polar solvent, and catalyst, and carry out a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate. Equation (1); Equation (2); Equation (3); In formulas (1) to (3), R is a C1-C9 straight-chain alkyl or a C1-C9 branched alkyl.

[0006] Optionally, in step S10, The reagents containing imidazole groups include N,N'-carbonyldiimidazole and / or imidazole; and / or, The first organic solvent includes at least one of dichloromethane, 1,2-dichloroethane, and thionyl chloride; and / or, The molar ratio of the monoalkyl succinate to the reagent containing the imidazole group is 1:(1.0~1.2); and / or, Add 1-3 L of the first organic solvent to each mol of the monoalkyl succinate.

[0007] Optionally, in step S10, the temperature of the amidation reaction is 10~35°C; and / or, The amidation reaction time is 8-12 hours.

[0008] Optionally, in step S20, The alkaline substance includes at least one of potassium tert-butoxide, sodium tert-butoxide, sodium hydroxide, and potassium hydroxide; and / or, The second organic solvent includes at least one of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran; and / or, The nucleophilic substitution reaction is performed at a temperature of 10–35 °C; and / or, The nuclear substitution reaction time is 15-18 hours; and / or, The molar ratio of the first compound, nitromethane, and alkaline substance is 1:(1.2-1.8):(1.0-1.2).

[0009] Optionally, in step S30, the polar solvent includes at least one of dichloromethane, methanol, and ethanol.

[0010] Optionally, in step S30, the catalyst includes a supported palladium-on-carbon catalyst and / or Raney nickel.

[0011] Optionally, in step S30, the temperature of the catalytic hydrogenation reaction is 15~35℃; and / or, The catalytic hydrogenation reaction takes 10-16 hours; and / or, The catalytic hydrogenation reaction pressure is 0.1-0.5 MPa.

[0012] Optionally, in step S30, the molar ratio of the second compound, the polar solvent, and the catalyst is 1:(20-30):(0.08~0.20).

[0013] The technical solution of this invention is to mix the second compound shown in formula (3), a polar solvent, and a catalyst, and carry out a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate, which is then converted into the target product with an aromatic pyrazine ring in one step. The product obtained by this invention not only retains the original carboxylic acid ester active functional groups in each unit, providing the possibility for subsequent derivatization, but more importantly, it introduces a rigid aromatic pyrazine ring core, which can enhance the hydrophobicity and membrane permeability of the molecule; improve chemical and metabolic stability; and its extended conjugated system may bring unique photophysical properties, affecting its efficiency in excitation and generation of reactive oxygen species as a photosensitizer.

[0014] This invention starts with inexpensive and readily available monoalkyl succinates to prepare the target pyrazine dimer. The synthetic route is rationally designed and has high atom economy. The reaction conditions are mild, with each step carried out at atmospheric or low to medium pressure and at room temperature or near room temperature. The operation is safe and simple, with low equipment requirements. The yield and purity are high: the overall yield can reach more than 65%, the chemical purity of the product is not less than 95.0%, and the quality is stable, which is conducive to industrial production. Attached Figure Description

[0015] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the structures shown in these drawings without creative effort.

[0016] Figure 1 This is a synthetic route diagram of the present invention.

[0017] Figure 2 A schematic diagram of the 1H NMR spectrum of the first organic compound provided by the present invention, namely ethyl 4-(1-imidazolium)-oxobutyrate.

[0018] Figure 3 A schematic diagram of the carbon spectrum of the first organic compound provided by the present invention, namely ethyl 4-(1-imidazolium)-oxobutyrate.

[0019] Figure 4 A schematic diagram of the 1H NMR spectrum of the second organic compound provided by the present invention, namely ethyl 5-nitro-4-oxovalerate.

[0020] Figure 5 A schematic diagram of the carbon spectrum of the second organic compound provided by the present invention, namely ethyl 5-nitro-4-oxovalerate.

[0021] Figure 6The schematic diagram of the proton nuclear magnetic resonance spectrum of the product provided in Example 1 of the present invention, namely ethyl 3,3′-(pyrazine-2,5-diyl)dipropionate.

[0022] Figure 7 A schematic diagram of the carbon spectrum of the product provided in Example 1 of the present invention, namely ethyl 3,3′-(pyrazine-2,5-diyl)dipropionate.

[0023] Figure 8 The schematic diagram of the proton nuclear magnetic resonance spectrum of the product provided in Example 3 of the present invention, namely methyl 3,3′-(pyrazine-2,5-diyl)dipropionate.

[0024] Figure 9 A schematic diagram of the carbon spectrum of the product provided in Example 3 of the present invention, namely methyl 3,3′-(pyrazine-2,5-diyl)dipropionate.

[0025] Figure 10 The ultraviolet absorption spectra of ethyl 3,3′-(pyrazine-2,5-diyl)dipropionate and 5-ALA hydrochloride provided in Example 1 of the present invention.

[0026] The realization of the objective, functional features and advantages of the present invention will be further explained in conjunction with the embodiments and with reference to the accompanying drawings. Detailed Implementation

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer shall apply. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially. Furthermore, the meaning of "and / or" throughout the text includes three parallel solutions; for example, "A and / or B" includes solution A, or solution B, or a solution where both A and B are satisfied simultaneously. In addition, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or cannot be implemented, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed by the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0028] 5-ALA and its ester derivatives (such as methyl and ethyl 5-aminolevulinate) have been widely used as second-generation photosensitizer prodrugs in the photodynamic diagnosis and treatment of tumors. Their mechanism of action involves tumor cells selectively taking up and metabolizing 5-ALA, accumulating in situ large amounts of protoporphyrin IX, which has strong photosensitizing activity. Under irradiation with light of a specific wavelength, this produces reactive oxygen species, thereby selectively killing tumor cells. However, 5-ALA and its simple esters still have significant limitations in practical applications: First, their high molecular polarity and limited cell membrane permeability result in low bioavailability; second, they are rapidly metabolized in vivo and have poor stability, often requiring high doses to achieve effective therapeutic concentrations, potentially causing side effects such as skin phototoxicity; third, their relatively simple chemical structure and limited functional modification sites restrict the potential for further optimization to improve their targeting and efficacy. 5-ALA has been proven to be a highly efficient and non-toxic plant growth regulator that can significantly enhance plant photosynthesis, improve stress resistance, and promote increased crop yield and quality. However, its effectiveness in field applications is easily affected by sunlight, rainwater erosion, and microbial degradation, resulting in a short duration of effectiveness, which limits its large-scale promotion and application.

[0029] In view of this, the present invention provides a method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate, comprising the following steps: Step S10, mixing a monoalkyl succinate as shown in formula (1), a reagent containing an imidazole group and a first organic solvent, and performing an amidation reaction to obtain a first compound as shown in formula (2); Step S20: Mix the first compound, nitromethane, basic substance and second organic solvent, and carry out nucleophilic substitution reaction to obtain the second compound as shown in formula (3); Step S30: Mix the second compound, polar solvent, and catalyst, and carry out a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate. Equation (1); Equation (2); Equation (3); In formulas (1) to (3), R is a C1-C9 straight-chain alkyl or a C1-C9 branched alkyl.

[0030] In the technical solution of this invention, the second compound shown in formula (3), a polar solvent, and a catalyst are mixed and subjected to a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate, which is then converted into the target product with an aromatic pyrazine ring in one step. The product obtained by this invention not only retains the original carboxylic acid ester active functional groups in each unit, providing the possibility for subsequent derivatization, but more importantly, it introduces a rigid aromatic pyrazine ring core, which can enhance the hydrophobicity and membrane permeability of the molecule; improve chemical and metabolic stability; and its extended conjugated system may bring unique photophysical properties, affecting its efficiency in excitation and generation of reactive oxygen species as a photosensitizer.

[0031] This process is not a simple amino reduction, but rather involves nitro reduction, intermolecular condensation cyclization, oxidative aromatization, and other reactions. Under catalytic hydrogenation conditions, the system undergoes in-situ dehydrogenation or aromatization using oxygen from the air, resulting in a multi-step cascade reaction. This one-pot strategy for efficiently constructing pyrazine rings avoids the separation of unstable amino intermediates and improves reaction yield.

[0032] In some embodiments of the present invention, in step S10: The reagent containing an imidazole group includes N,N'-carbonyldiimidazole and / or imidazole, wherein the reagent containing the imidazole group can be any one or a combination of N,N'-carbonyldiimidazole and imidazole; the role of the imidazole group reagent in this reaction is to undergo an amidation reaction with the carboxyl group in the monoalkyl succinate.

[0033] The first organic solvent includes dichloromethane, 1,2-dichloroethane, and thionyl chloride. The first organic solvent can be any one, any combination of, or all of dichloromethane, 1,2-dichloroethane, and thionyl chloride. The first organic solvent can provide a uniform solvent environment for the amidation reaction.

[0034] The molar ratio of the monoalkyl succinate to the reagent containing the imidazole group is 1:(1.0-1.2); this reagent ratio facilitates a more complete amidation reaction and improves the yield; the molar ratio of the monoalkyl succinate to the activating reagent can be any ratio within the range of 1:1, 1.1 or 1:1.2. Add 1-3L of the first organic solvent per mol of the monoalkyl succinate. The amount of solvent added per mol of the monoalkyl succinate can be 1L, 2L or 3L. The amount of solvent added within this range can provide a uniform environment for the reaction, which is conducive to the rapid occurrence and completion of the reaction.

[0035] In some embodiments of the present invention, in step S10: the temperature of the acylation reaction is 10-35°C, and the temperature can be 10°C, 20°C, 25°C, 30°C or 35°C; the acylation reaction time is 8-12h, and the reaction time can be 8h, 9h, 10h, 11h or 12h. It can be understood that this step of the present invention has high reactivity, does not require high temperature conditions, and the reaction rate is also relatively fast.

[0036] In some embodiments of the present invention, in step S20: The basic substance includes at least one of potassium tert-butoxide, sodium tert-butoxide, sodium hydroxide, and potassium hydroxide. The basic agent can be any one, any combination of, or all of potassium tert-butoxide, sodium tert-butoxide, sodium hydroxide, and potassium hydroxide. The basic substance facilitates the dehydrogenation of nitromethane to form a negative ion, followed by a nucleophilic substitution reaction. The second organic solvent includes at least one of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran. The second organic solvent can be any one, any combination of, or all of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran. The nucleophilic substitution reaction is carried out under the following conditions: temperature... The temperature is 10-35℃, where the temperature can be 10℃, 20℃, 25℃, 30℃, or 35℃; the nucleophilic substitution reaction time is 15-18h, where the reaction time can be 15h, 16h, 17h, or 18h; the molar ratio of the second compound, nitromethane, and basic substance is 1:(1.2-1.8):(1.0-1.2), and the molar ratio of the second compound, nitromethane, and basic substance can be any combination within the range of 1:1.2:1.0, 1:1.2:1.2, 1:1.8:1.0, 1:1.8:1.2, or 1:1.5:1.1.

[0037] In some embodiments of the present invention, the polar solvent includes at least one of dichloromethane, methanol, and ethanol, and the polar solvent may be any one, any two, or any three of dichloromethane, methanol, and ethanol; the catalyst includes a supported palladium-on-carbon catalyst and / or Raney nickel, and the catalyst may be a supported palladium-on-carbon catalyst, Raney nickel, or a combination thereof. The reaction conditions are as follows: the reaction temperature is 15~35℃; the reaction time is 10~16h; the catalytic hydrogenation reaction pressure is 0.1-0.5MPa, and the hydrogen pressure can be 0.1MPa, 0.2MPa, 0.3MPa, 0.4MPa or 0.5MPa; the molar ratio of the first compound, polar solvent and catalyst is 1:(20-30):(0.08-0.20), and the molar ratio of the first compound, polar solvent and catalyst can be any combination within the range of 1:20:0.08, 1:20:0.12, 1:30:0.08, 1:30:0.12 or 1:25:0.20.

[0038] Understandably, the synthetic route for obtaining the target pyrazine dimer from monoalkyl succinates is rationally designed and highly atom-economical. The reaction conditions are mild, with each step carried out at atmospheric or low-to-medium pressure and at or near room temperature, making the operation safe, simple, and requiring minimal equipment. The yield and purity are high: the overall yield can reach over 60%, the chemical purity of the product is not less than 95.0%, and the quality is stable, which is beneficial for industrial production. The product obtained by this invention not only retains the original carboxylic acid ester active functional groups in each unit, providing possibilities for subsequent derivatization, but also introduces a rigid aromatic pyrazine ring core, which can enhance the molecule's hydrophobicity and membrane permeability; improve chemical and metabolic stability; its extended conjugated system may bring unique photophysical properties, affecting its efficiency as a photosensitizer in excitation and generation of reactive oxygen species.

[0039] The technical solution of the present invention will be further described in detail below with reference to specific embodiments and accompanying drawings. It should be understood that the following embodiments are only used to explain the present invention and are not intended to limit the present invention.

[0040] Example 1 A method for synthesizing ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate, comprising the following steps: Step S10: In a dry 500 mL three-necked flask, add monoethyl succinate (15.0 g, 0.10 mol) and dichloromethane (200 mL). After stirring to dissolve, add N,N'-carbonyldiimidazole (17.8 g, 0.11 mol) in two portions at room temperature, and stir the reaction at 25 °C for 10 hours to obtain a dichloromethane solution containing formula (2). The reaction process can be monitored by TLC. This solution can be used directly for the next reaction. Step S20: Transfer the dichloromethane solution containing formula (2) into a dropping funnel. In another dry 1 L three-necked flask, add N,N-dimethylformamide (200 mL), cool to 0°C in an ice-water bath, and add nitromethane (0.18 mol) and potassium tert-butoxide (12.3 g, 0.11 mol) sequentially. Keep at 0°C, slowly add the dichloromethane solution containing formula (2) dropwise with stirring, and complete the addition in about 1 hour. Remove the ice bath, allow the reaction solution to naturally warm to room temperature (about 25°C), and continue stirring for 16 hours. After the reaction is complete, slowly pour the reaction solution into ice water (500 mL) and extract three times with ethyl acetate (200 mL). Combine the organic phases, wash sequentially with saturated brine (100 mL), dry with anhydrous sodium sulfate, concentrate under reduced pressure, and obtain a pale yellow oily crude compound II. The crude product can be further purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 4:1, v / v) to obtain a purer second compound.

[0041] Step S30: The purified second compound (approximately 12.0 g) was dissolved in methanol (150 mL) and transferred to a high-pressure hydrogenation reactor. 10% palladium catalyst on carbon (containing 50% water, 1.2 g) was added. The air in the reactor was replaced three times with hydrogen, and then hydrogen was introduced to a pressure of 0.3 MPa. The reaction was stirred at room temperature (approximately 25 °C) for 8 hours. After the reaction was complete, hydrogen was released, and the reaction solution was carefully filtered to recover the catalyst (washed with methanol). The filtrates were combined and concentrated under reduced pressure to remove most of the solvent, yielding a pale yellow oily crude product. The crude product was further purified by silica gel column chromatography (eluent: dichloromethane / methanol = 30:1, v / v) to give the target product—ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate—in a colorless to pale yellow liquid, with an overall yield of 65%.

[0042] Example 2 A method for synthesizing ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate, differing from Example 1 only in that the catalyst is replaced with Raney nickel, with an overall yield of 61% for ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate.

[0043] Example 3 A method for synthesizing methyl 3,3'-(pyrazine-2,5-diyl)dipropionate, the difference being that the starting material is replaced with monomethyl succinate, and the overall yield of methyl 3,3'-(pyrazine-2,5-diyl)dipropionate is 62%.

[0044] Comparative Example 1 A method for synthesizing ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate, differing from Example 1 in that the activation step S10 is omitted, and the overall yield of ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate is 0.

[0045] Comparative Example 2 A method for synthesizing ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate differs from Example 1 in that it is not a hydrogen reduction method, but uses zinc powder and concentrated hydrochloric acid as catalysts for reduction. The overall yield of ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate is extremely low (<5%).

[0046] Performance testing The lipid solubility and UV absorption of ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate prepared in Example 1 and the control sample 5-ALA were detected, and the results are shown in Table 1: Table 1. Comparison of ethyl 3,3'-(pyrazine-2,5-diyl)dipropionate with control sample 5-ALA

[0047] Examples 1-3, Comparative Examples 1-2, and Table 1 and... Figure 5 It is known that constructing dimers from 5-ALA or its esters typically requires a multi-step protection-deprotection strategy or the use of highly toxic and expensive condensation reagents. This invention takes a different approach, designing 5-nitro-4-oxovalerate as a key intermediate and utilizing its bifunctional properties to efficiently construct pyrazine rings via a one-pot tandem reductive cyclization process, simplifying the operation and reducing costs.

[0048] The product of this invention exhibits significantly enhanced lipid solubility, which substantially increases its ability to permeate biological membranes, thereby greatly improving bioavailability. Its molar extinction coefficient is approximately six times higher than that of 5-ALA, a result that cannot be predicted by simple structural assembly. This significantly enhanced photophysical property is directly related to its potential application as a photosensitizer prodrug or a photofunctional material.

[0049] Compared with the chemical reduction method (Zn / HCl) in Comparative Example 2, the method of the present invention has a higher yield (>60% vs <5%), purer product, is more environmentally friendly, and safer to operate, representing a significant technological advancement.

[0050] The above are merely preferred embodiments of the present invention and do not limit the patent scope of the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the patent protection scope of the present invention.

Claims

1. A method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate, characterized in that, Includes the following steps: Step S10: Mix the monoalkyl succinate as shown in formula (1), the reagent containing the imidazole group and the first organic solvent, and carry out an amidation reaction to obtain the first compound as shown in formula (2); Step S20: Mix the first compound, nitromethane, basic substance and second organic solvent, and carry out nucleophilic substitution reaction to obtain the second compound as shown in formula (3); Step S30: Mix the second compound, polar solvent, and catalyst, and carry out a catalytic hydrogenation reaction to obtain the 3,3'-(pyrazine-2,5-diyl)dipropionate. Equation (1); Equation (2); Equation (3); In formulas (1) to (3), R is a C1-C9 straight-chain alkyl or a C1-C9 branched alkyl.

2. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S10, The reagents containing imidazole groups include N,N'-carbonyldiimidazole and / or imidazole; and / or, The first organic solvent includes at least one of dichloromethane, 1,2-dichloroethane, and thionyl chloride; and / or, The molar ratio of the monoalkyl succinate to the reagent containing the imidazole group is 1:(1.0~1.2); and / or, Add 1-3 L of the first organic solvent to each mol of the monoalkyl succinate.

3. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S10, the amidation reaction is carried out at a temperature of 10~35℃; and / or, The amidation reaction time is 8-12 hours.

4. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S20, The alkaline substance includes at least one of potassium tert-butoxide, sodium tert-butoxide, sodium hydroxide, and potassium hydroxide; and / or, The second organic solvent includes at least one of N,N-dimethylformamide, dimethyl sulfoxide, and tetrahydrofuran; and / or, The nucleophilic substitution reaction is performed at a temperature of 10–35 °C; and / or, The nuclear substitution reaction time is 15-18 hours; and / or, The molar ratio of the first compound, nitromethane, and alkaline substance is 1:(1.2-1.8):(1.0-1.2).

5. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S30, the polar solvent includes at least one of dichloromethane, methanol, and ethanol.

6. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S30, the catalyst includes a supported palladium-on-carbon catalyst and / or Raney nickel.

7. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S30, the temperature of the catalytic hydrogenation reaction is 15~35℃; and / or, The catalytic hydrogenation reaction takes 10-16 hours; and / or, The catalytic hydrogenation reaction pressure is 0.1-0.5 MPa.

8. The method for synthesizing 3,3'-(pyrazine-2,5-diyl)dipropionate as described in claim 1, characterized in that, In step S30, the molar ratio of the second compound, the polar solvent, and the catalyst is 1:(20-30):(0.08~0.20).

9. A 3,3'-(pyrazine-2,5-diyl)dipropionate, characterized in that, It is prepared by the synthetic method of 3,3'-(pyrazine-2,5-diyl)dipropionate according to any one of claims 1-8.

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