Vinylsulfonyl fluoride compounds and intermediates thereof, methods of preparation and uses

Abstract

The application discloses a vinyl sulfonyl fluoride compound and an intermediate thereof, a preparation method and application, develops an (E)-2-(aziridine-1-yl) ethylene-1-sulfonyl fluoride click reagent, and the reagent uses (E)-2-methoxy-vinyl 1-sulfonyl fluoride and ethylene imine as raw materials. By using (E)-2-(aziridine-1-yl) ethylene-1-sulfonyl fluoride as an intermediate, the synthesis of N-substituted ethylene sulfonyl fluoride compounds can be quickly and reliably completed by amine exchange reaction with amine compounds, the reaction has good selectivity, and the product is easy to separate. The N-substituted ethylene sulfonyl fluoride compound can be used for new drug research and development through late drug modification, and has wide application prospects in the fields of medicinal chemistry, organic synthesis methodology and the like. The structural formula of the N-substituted ethylene sulfonyl fluoride compound is as follows:

Description

Technical Field

[0001] The present invention belongs to the field of chemical synthesis, and in particular relates to vinylsulfonyl fluoride compounds and intermediates thereof, as well as preparation methods and applications. Background Art

[0002] Click chemistry is a synthetic concept first proposed by Professor Sharpless in 1998 and further refined in 2001. Professor Sharpless won the 2022 Nobel Prize in Chemistry for his work on click chemistry. Sulfur-fluoride exchange (SuFEx) chemistry, a new generation of click chemistry introduced in 2014, has been widely applied in a range of important research and production fields, including chemistry, polymer material synthesis, biomolecule labeling, antibody modification, and drug development, and holds broad prospects. Currently, there are over 150 FDA-approved drugs on the market that contain sulfonyl fluoride and sulfonamide structures, which are widely used to treat various types of diseases and have therapeutic potential. This means that N-substituted ethylene sulfonyl fluoride has great potential for application in fields such as medicinal chemistry and organic synthesis methodology. However, general synthetic methods involving N-substituted ethylene sulfonyl fluoride compounds are not widely available. In 1977, Hyatt, JA; Krutak, JJ Synthesis and chemistry of some 2-Aminoethenesulfonylfluorides. An Unusual Manganese Dioxide Oxidation. J. Org. Chem. 1977, 42, 169-170 disclosed that N-substituted ethylene sulfonyl fluoride compounds were first synthesized by oxidation of Michael addition products of amines and ethylene sulfonyl fluoride compounds (ESF) with manganese dioxide. However, this method provided limited examples and, in addition to the use of excess manganese dioxide, gave 2-aliphatic aminoethylene sulfonyl fluoride in low yield (33%). In 2020, Leng, J.; Tang, W.; Fang, W.-Y.; Zhao, C.; Qin, H.-LA Simple Protocol for the Stereoselective Construction of Enaminyl Sulfonyl Fluorides. Org. Lett. 2020, 22, 4316-4321 reported a method for synthesizing N-substituted ethylene sulfonyl fluoride compounds by reacting 1-bromo-2-triazoleethane-1-sulfonyl fluoride reagent with amine. However, this synthetic method still has many shortcomings that need to be overcome: ① The highly toxic and explosive sodium azide (NaN3) is used in the preparation of 1-bromo-2-triazoleethane-1-sulfonyl fluoride reagent; ② A certain amount of 4-phenyl-1H-1,2,3-triazole is generated as a by-product; ③ The separation of the desired product and the by-product is cumbersome; ④ Aromatic amine sulfonyl fluorides cannot be synthesized by this method. Summary of the Invention

[0003] The purpose of the present invention is to overcome the above-mentioned technical deficiencies and provide vinyl sulfonyl fluoride compounds and intermediates thereof, preparation methods and applications. By developing a (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride click reagent, the reaction conditions are mild and there is no need to use highly toxic and explosive sodium azide. The reagent can quickly and reliably complete the synthesis of N-substituted vinyl sulfonyl fluoride compounds with amine compounds, the reaction selectivity is good, and the product is easy to separate.

[0004] In order to achieve the above technical objectives, the technical solutions of the present invention are as follows:

[0005] In a first aspect, the present invention provides a vinylsulfonyl fluoride compound intermediate, which is (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride, and its structural formula is:

[0006]

[0007] In a second aspect, the present invention provides a method for preparing a vinylsulfonyl fluoride compound intermediate, the specific steps of which are as follows:

[0008] (E)-2-methoxy-vinyl 1-sulfonyl fluoride and ethyleneimine are used as raw materials, mixed in a solvent, subjected to a nucleophilic substitution reaction, and separated and purified to obtain (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride. In a third aspect, the present invention provides an N-substituted ethylene sulfonyl fluoride compound, which is obtained by reacting (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride with an amine compound, and has the following structural formula:

[0009]

[0010] Wherein, R1 and R2 are hydrogen, alkyl or aromatic groups, or R1 and R2 together with the nitrogen atom form a heterocyclic ring.

[0011] In a fourth aspect, the present invention provides a method for preparing an N-substituted ethylene sulfonyl fluoride compound, comprising the following steps:

[0012] An amine compound and (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride are used as raw materials, added into an organic solvent, mixed, reacted at 20-40° C., and separated and purified after the reaction to obtain an N-substituted ethylene sulfonyl fluoride compound.

[0013] In a fifth aspect, the present invention provides an application of an N-substituted ethylene sulfonyl fluoride compound in the preparation of fluoroquinolone drugs.

[0014] Compared with the prior art, the present invention has the following beneficial effects:

[0015] The present invention develops a (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride click reagent, which uses (E)-2-methoxy-vinyl 1-sulfonyl fluoride and ethyleneimine as raw materials, and does not require the use of highly toxic and explosive sodium azide. Using (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride as an intermediate, an amine exchange reaction occurs with different amine compounds to quickly and reliably complete the synthesis of N-substituted ethylene sulfonyl fluoride compounds. The preparation method has the advantages of high yield, wide substrate applicability, easy raw materials, mild reaction conditions, good reaction selectivity, simple operation, and easy product purification, with a yield of more than 90%. N-substituted ethylene sulfonyl fluoride compounds can be used for new drug research and development through late-stage drug modification, and have broad application prospects in the fields of medicinal chemistry, organic synthesis methodology, etc. DETAILED DESCRIPTION

[0016] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention.

[0017] Considering the shortcomings of existing technologies such as purification difficulties, the use of highly toxic and explosive sodium azide, and a narrow substrate range, as well as the importance of N-substituted ethylene sulfonyl fluoride compounds, it is particularly urgent to develop a new method for preparing N-substituted ethylene sulfonyl fluoride compounds.

[0018] The present invention develops a (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride click reagent that undergoes an amine exchange reaction with various amine compounds to rapidly and reliably synthesize N-substituted ethylene sulfonyl fluoride compounds. This preparation method offers advantages such as high yield, a wide range of substrate applications, readily available raw materials, mild reaction conditions, good reaction selectivity, simple operation, and easy product purification. N-substituted ethylene sulfonyl fluoride compounds can be used for new drug development through post-production drug modification and have broad application prospects in fields such as medicinal chemistry and organic synthesis methodology.

[0019] In a first aspect, the present invention provides a (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride reagent, the structural formula of which is as follows:

[0020]

[0021] In a second aspect, the present invention provides a method for preparing a (E)-2-((aziridin-1-yl)ethylene-1-sulfonyl fluoride reagent, comprising the following steps:

[0022] (E)-2-methoxy-vinyl 1-sulfonyl fluoride is mixed with ethyleneimine and a solvent to undergo a nucleophilic substitution reaction, followed by separation and purification to obtain (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride:

[0023]

[0024] Preferably, the molar ratio of (E)-2-methoxy-vinyl 1-sulfonyl fluoride to ethyleneimine is (1-3): 1. More preferably, the molar ratio of (E)-2-methoxy-vinyl 1-sulfonyl fluoride to ethyleneimine is 1:1.

[0025] Preferably, the solvent is a mixture of one or more of ethyl acetate, acetonitrile, water and dichloromethane; more preferably, the solvent is acetonitrile.

[0026] Preferably, the nucleophilic substitution reaction temperature of (E)-2-methoxy-vinyl 1-sulfonyl fluoride and ethyleneimine is 25°C to 80°C; more preferably, the temperature is 50°C.

[0027] In a third aspect, the present invention provides an N-substituted ethylene sulfonyl fluoride compound, the structural formula of which is as follows:

[0028]

[0029] Wherein, R1 and R2 are hydrogen, alkyl or aromatic groups, or R1 and R2 form a heterocyclic ring together with the nitrogen atom.

[0030] In a fourth aspect, the present invention provides a method for preparing an N-substituted ethylene sulfonyl fluoride compound, the specific steps of which are as follows:

[0031] A secondary amine or a primary amine is used as a raw material, mixed with (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride and an organic solvent, and a nucleophilic substitution reaction is carried out at 20-40°C for 1-12 hours. The reaction is separated and purified to obtain an N-substituted ethylene sulfonyl fluoride compound. The synthetic route is as follows:

[0032]

[0033] Preferably, the organic solvent includes a mixture of one or more of N,N-dimethylformamide, 1,4-dioxane, acetone, and tetrahydrofuran (THF); more preferably, the solvent is THF.

[0034] Preferably, the reaction temperature is 20-40°C; more preferably, the temperature is 25°C.

[0035] Preferably, the reaction time is 1-12 h; more preferably, the reaction time is 6 h.

[0036] Embodiment 1:

[0037] A method for preparing (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride

[0038]

[0039] The specific preparation steps are as follows:

[0040] To an oven-dried 100 mL flask were added ethyleneimine (50 mmol), (E)-2-methoxy-vinyl 1-sulfonyl fluoride (50 mmol) and acetonitrile (50 mL). The reaction mixture was stirred at 50° C. for 12 hours. The progress of the reaction was monitored by TLC. After completion, the solution was concentrated to dryness and the resulting residue was purified by silica gel column chromatography to give the desired product as a white solid (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride (6.0 g, 79% yield).

[0041] 1 H NMR (500MHz, CDCl3) δ7.42 (d, J = 12.5 Hz, 1H), 4.90 (dd, J = 12.5, 4.6 Hz, 1H), 3.38-3.29 (m, 2H), 3.25-3.17 (m, 2H). 19 F NMR (471MHz, CDCl3) δ71.3 (s, 1F). 13 C NMR(126MHz, CDCl3)δ153.0(s),90.9(d,J=29Hz),30.9(s).ESI-MS HRMS.calculatedfor.C4H7FNO2S[M+H] + 152.0176,found 152.0170.

[0042] Example 2:

[0043] A preparation of an N-substituted ethylene sulfonyl fluoride compound, the reaction formula is as follows:

[0044]

[0045] The specific preparation steps are as follows:

[0046] Piperidines (1.0mmol), (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride (1.1mmol) and THF (5mL) are added into oven-dried 20mL reaction tubes.The reaction mixture is stirred at room temperature for 6 hours.The progress of the reaction is monitored by TLC. After completion, the solution is concentrated to dryness, and the residue obtained by silica gel column chromatography is purified, and the required product is (E)-2-(piperidin-1-yl)ethylene-1-sulfonyl fluoride (183mg, 95% yield) as a white solid.

[0047] 1 H NMR (500MHz, CDCl3) δ7.34 (d, J = 12.5 Hz, 1H), 4.89 (dd, J = 12.5, 4.6 Hz, 1H), 3.40-3.32 (m, 2H), 3.22-3.12 (m, 2H), 1.69-1.62 (m, 6H). 19 F NMR (471MHz, CDCl3) δ71.5 (s, 1F).

[0048] Example 3:

[0049] A preparation of an N-substituted ethylene sulfonyl fluoride compound, its reaction formula is as follows:

[0050]

[0051] The specific preparation steps are as follows:

[0052] 4-bromopiperidine (1.0mmol), (E)-2-(aziridine-1-yl) ethylene-1-sulfonyl fluoride (1.1mmol) and THF (5mL) are added into the 20mL reaction tube of oven-drying.The reaction mixture is stirred at room temperature for 6 hours.The progress of the reaction is monitored by TLC. After completing, the solution is concentrated to dryness, and by silica gel column chromatography obtained residue, required product promptly obtains yellow solid (E)-2-(4-bromopiperidin-1-yl) ethylene-1-sulfonyl fluoride (243mg, 90% productive rate).

[0053] 1 H NMR(500MHz, CDCl3)δ7.35(d,J=12.7Hz,1H),4.99(dd,J=12.7,4.6Hz,1H),4.53-4.43(m,1H),3.76-3.5 8(m,1H),3.56-3.40(m,1H),3.38-3.29(m,1H),3.27-3.14(m,1H),2.23-2.13(m,2H),2.12-2.02(m,2H). 19 F NMR (471MHz, CDCl3) δ71.0 (s, 1F).

[0054] Example 4:

[0055] The preparation of an N-substituted ethylene sulfonyl fluoride compound has the following reaction formula:

[0056]

[0057] The specific preparation steps are as follows:

[0058] To an oven-dried 20 mL reaction tube was added diethylamine (1.0 mmol), (E)-2-(aziridin-1-yl)ethene-1-sulfonyl fluoride (1.1 mmol), and THF (5 mL). The reaction mixture was allowed to stir at room temperature for 6 hours. The progress of the reaction was monitored by TLC. Upon completion, the solution was concentrated to dryness and the resulting residue was purified by silica gel column chromatography to give the desired product as a colorless liquid (E)-2-(diethylamino)ethene-1-sulfonyl fluoride (144 mg, 80% yield).

[0059] 1 H NMR (500 MHz, CDC13) δ 7.38 (d, J = 12.5 Hz, 1H), 4.86 (dd, J = 12.5, 4.7 Hz, 1H), 3.32 (q, J = 7.1 Hz, 2H), 3.18 (q, J = 7.2 Hz, 2H), 1.24 (t, J = 7.3 Hz, 3H), 1.19 (t, J = 7.7 Hz, 3H). 19 F NMR (471 MHz, CDC13) δ 71.5 (d, J = 5.8 Hz, 1F).

[0060] Example 5:

[0061] One preparation of N-substituted ethenesulfonyl fluoride compounds, the reaction formula is as follows:

[0062]

[0063] The specific preparation steps are as follows:

[0064] To an oven-dried 20 mL reaction tube was added diethylamine (1.0 mmol), (E)-2-(aziridin-1-yl)ethene-1-sulfonyl fluoride (1.1 mmol), and THF (5 mL). The reaction mixture was allowed to stir at room temperature for 6 hours. The progress of the reaction was monitored by TLC. Upon completion, the solution was concentrated to dryness and the resulting residue was purified by silica gel column chromatography to give the desired product as a colorless liquid (E)-2-(diethylamino)ethene-1-sulfonyl fluoride (144 mg, 80% yield).

[0065] 1 H NMR (500 MHz, CDC13) δ 7.38 (d, J = 12.5 Hz, 1H), 4.86 (dd, J = 12.5, 4.7 Hz, 1H), 3.32 (q, J = 7.1 Hz, 2H), 3.18 (q, J = 7.2 Hz, 2H), 1.24 (t, J = 7.3 Hz, 3H), 1.19 (t, J = 7.7 Hz, 3H). 13C NMR(126MHz, CDCl3)δ152.8(s),151.4(s),135.2(s),130.4(s),120.8(s),11 6.8(s),114.8(s),83.3(d,J=25.4Hz),52.6(s),49.4(s),47.7(s),45.2(s). 19 F NMR(471MHz, CDCl3)δ71.0(s,1F).ESI-MS HRMS calculated forC 12 H 15 ClFN2O2[M+H] + 305.0521,found 305.0515.

[0066] Example 6:

[0067] The preparation of an N-substituted ethylene sulfonyl fluoride compound has the following reaction formula:

[0068]

[0069] The specific preparation steps are as follows:

[0070] N-methylaniline (1.0mmol), (E)-2-(aziridine-1-yl)ethylene-1-sulfonyl fluoride (1.1mmol), and THF (5mL) were added to an oven-dried 20mL reaction tube. The reaction mixture was stirred at room temperature for 6 hours. The progress of the reaction was monitored by TLC. After completion, the solution was concentrated to dryness, and the residue obtained by silica gel column chromatography was purified to give the desired product as a white solid (E)-2-methyl(phenyl)aminoethylene-1-sulfonyl fluoride (172mg, 80% yield).

[0071] 1 H NMR (500MHz, CDCl3) δ7.85 (d, J = 10.4Hz, 1H), 7.42 (t, J = 7.2Hz, 2H), 7.31-7.26 (m, 1H), 7.18 (d, J = 7.5Hz, 2H), 5.35-5.16 (m, 1H), 3.32 (s, 3H). 13 C NMR (126MHz, CDCl3) δ 151.4 (s), 145.7 (s), 129.9 (s), 126.4 (s), 121.0 (s), 87.9 (d, J = 25.4Hz), 37.6 (s). 19 F NMR(471MHz,CDCl3)δ70.3(s,1F).MS m / z calcd for C9H 10 FNO2S[M+H] +216.05, found 216.10.

[0072] Comparative Example 1:

[0073]

[0074] The specific preparation steps are as follows:

[0075] Into an oven-dried 20 mL reaction tube was added N-methylaniline (1.0 mmol), ethylene sulfonyl fluoride (1.1 mmol), and 1,4-dioxane (5 mL). The reaction mixture was stirred at room temperature for 12 hours. The result showed that no reaction occurred.

[0076] Comparative Example 2:

[0077]

[0078] The specific preparation steps are as follows:

[0079] Into an oven-dried 20 mL reaction tube was added N-methylaniline (1.0 mmol), 1-bromo-2-triazole ethane-1-sulfonyl fluoride (1.1 mmol), and 1,4-dioxane (5 mL). The reaction mixture was stirred at room temperature for 12 hours. The result showed that no reaction occurred.

[0080] From Example 6, Comparative Example 1, and Comparative Example 2, it can be seen that when other raw materials (such as ethylene sulfonyl fluoride or 1-bromo-2-triazole ethane-1-sulfonyl fluoride) are used to replace (E)-2-(aziridin-1-yl) ethylene-1-sulfonyl fluoride, the reaction cannot proceed, and the target product cannot be generated.

[0081] In order to avoid repetition, reference is made to the preparation of N-substituted ethylene sulfonyl fluoride compounds in Examples 2-6 above, and the typical structures and reaction yield statistics of the N-substituted ethylene sulfonyl fluoride compounds obtained by the present application are as follows:

[0082]

[0083] Comparative Example 3

[0084] The difference between Comparative Example 3 and Example 6 is only that (E)-2-methoxy ethylene-1-sulfonyl fluoride is used to replace (E)-2-(aziridin-1-yl) ethylene-1-sulfonyl fluoride to prepare the same product 3e.

[0085] It was found that the reaction needed to be stirred at room temperature for 12 hours, and the yield of (E)-2-methyl(phenyl)amino ethylene-1-sulfonyl fluoride (3e) was only about 50%.

[0086] Similarly, when preparing products such as 3a, 3f, and 3h, using the (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride of the present invention as a raw material can effectively reduce the reaction time and significantly improve the product yield.

[0087] Application Example 1

[0088] Three fluoroquinolone drugs (lomefloxacin, ciprofloxacin, and norfloxacin) were used as raw materials for the amine compound reaction with (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride. The other steps and conditions were the same as those in Example 2. The synthetic route, the structural reaction, and the yield of the modified fluoroquinolone drugs are shown below:

[0089]

[0090] Comparative Application Example 1

[0091] Ethylenesulfonyl fluoride was used to replace (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride, and the other steps and conditions were the same as those in Application Example 1. The synthetic route and the structural reaction and yield of the modified fluoroquinolone drug are shown below:

[0092]

[0093] Biological activity test

[0094] The products obtained in the above-mentioned Application Example 1 and Comparative Example 1 were respectively subjected to biological activity tests, with the main test item being the minimum inhibitory concentration (MICs). The results are shown in Table 1 below.

[0095] Determination of Minimum Inhibitory Concentration (MIC): The antibacterial potential of three antibiotics and their fluorosulfonyl vinyl products 3j-3l and fluorosulfonyl ethyl products 5a-5c was evaluated against a panel of bacteria in Mueller-Hinton (MH) broth, including two Gram-positive bacteria (Staphylococcus aureus SA (ATCC 9454) and methicillin-resistant Staphylococcus aureus MRSA). The MICs of the title compounds were determined in Mueller-Hinton (MH) broth according to the Clinical Laboratory Standards Institute (CLSI) method using a microbroth dilution method in a 96-well microplate. The bacterial inoculum was prepared by culturing colonies from MH agar in MH broth. The final test concentration of the compounds ranged from 0.019-80 μg / mL, and the bacterial inoculum was 10 5 CFU / mL. The lowest concentration of the test compound that inhibited visible bacterial growth after incubation at 37°C for 18-20 hours was recorded as the minimum inhibitory concentration (MICs). Each compound was sampled at least twice, and the average value was recorded as the minimum inhibitory concentration (MICs) of the compound. Each sample was tested in triplicate, and each experiment was repeated three times.

[0096] Table 1 Minimum inhibitory concentration data of fluoroquinolones and their derivatives

[0097]

[0098] The antimicrobial assays in Table 1 show that:

[0099] (1) 3j-3l and 5a-5c have the same antibacterial spectrum as fluoroquinolones (lomefloxacin, ciprofloxacin, and norfloxacin);

[0100] (2) It is noteworthy that the MIC values ​​of 3j-3l against Staphylococcus aureus (SA) decreased by 4-fold (0.156 μM), 4-fold (0.039 μM), and 3-fold (0.052 μM), respectively, while those against methicillin-resistant Staphylococcus aureus (MRSA) remained essentially unchanged;

[0101] The MIC values ​​of 5a-5c against Staphylococcus aureus (SA) were significantly increased by 4-fold (2.5 μM), 64-fold (10 μM), and 51-fold (8 μM); while those against methicillin-resistant Staphylococcus aureus (MRSA) were significantly increased by 8-fold (10 μM), 16-fold (20 μM), and 16-fold (20 μM);

[0102] The results showed that the anti-Gram-positive bacterial activity of sulfonyl fluoride vinyl fluoroquinolones 3j-3l was significantly increased, while the anti-Gram-positive bacterial activity of sulfonyl fluoride ethyl fluoroquinolones 5a-5c was significantly decreased.

[0103] Compared to existing technologies, the present invention develops a (E)-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride click reagent that undergoes an amine exchange reaction with various amine compounds to rapidly and reliably synthesize N-substituted ethylenesulfonyl fluoride compounds. This preparation method offers advantages such as a wide range of substrate applicability, high yield, readily available raw materials, mild reaction conditions, good reaction selectivity, simple operation, and easy product purification.

[0104] N-substituted ethylene sulfonyl fluoride compounds can be used for new drug development through post-drug modification, and have broad application prospects in medicinal chemistry, organic synthesis methodology, and other fields. Further biological activity studies have shown that the antibacterial activity of fluoroquinolones functionalized with N-substituted ethylene sulfonyl fluoride compounds is significantly enhanced by four times compared to the active pharmaceutical ingredient.

[0105] The specific embodiments of the present invention described above do not limit the scope of protection of the present invention. Any other corresponding changes and modifications made based on the technical concept of the present invention should be included in the scope of protection of the claims of the present invention.

Claims

1. A vinylsulfonyl fluoride compound intermediate, characterized in that: The intermediate is ( E )-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride, the structural formula of which is: 。 2. The method for preparing a vinylsulfonyl fluoride intermediate according to claim 1, wherein The following steps are involved: by( E )-2-methoxy-vinyl-1-sulfonyl fluoride and ethyleneimine are used as raw materials, mixed in a solvent, and subjected to nucleophilic substitution reaction, separated and purified to obtain ( E )-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride.

3. The method for preparing a vinylsulfonyl fluoride intermediate according to claim 2, wherein: ( E The molar ratio of )-2-methoxy-vinyl-1-sulfonyl fluoride to ethyleneimine is (1-3):

1.

4. The method for preparing a vinylsulfonyl fluoride intermediate according to claim 2, wherein: The solvent is a mixture of one or more of ethyl acetate, acetonitrile, water and dichloromethane.

5. The method for preparing the vinylsulfonyl fluoride intermediate according to claim 2, wherein The temperature of the nucleophilic substitution reaction is 25 o C~80 o C.

6. A method for preparing an N-substituted ethylene sulfonyl fluoride compound, characterized in that: The following steps are involved: With amine compound and claim 1 ( E )-2-(aziridin-1-yl)ethylene-1-sulfonyl fluoride as a raw material, adding it to an organic solvent and mixing it, reacting it at 20-40° C. After the reaction is completed, separation and purification are performed to obtain an N-substituted ethylene sulfonyl fluoride compound; The amine compound is lomefloxacin, ciprofloxacin or norfloxacin; the organic solvent is tetrahydrofuran; The structure of the N-substituted ethylene sulfonyl fluoride compound is selected from: 。 7. The method for preparing the N-substituted ethylene sulfonyl fluoride compound according to claim 6, wherein The ratio between the amine compound and the organic solvent is 1mmol: (3-8) mL; The reaction time is 1 to 12 hours.

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