A sulfonyl pyridazinone compound and a preparation method and application thereof

Abstract

This invention discloses a sulfonylpyridinone compound, its preparation method, and its applications. The compound is prepared by introducing a sulfonyl group at the 4-position of pyridazin-3(2H)one, giving it multiple functional groups such as sulfone, phenyl, and pyridazinone. The sulfonylpyridinone compound of this invention exhibits a certain antibacterial effect against *Escherichia coli* / *Staphylococcus aureus* and can be used to prepare broad-spectrum antibacterial drugs. Due to its multifunctional nature involving flame retardant groups, this compound is expected to be applied in the flame retardant field. This invention also provides a method for preparing the above-mentioned sulfonylpyridinone compound, achieved through a dehalogenation sulfonation reaction of 4,5-dihalo-2-phenylpyridazin-3(2H)one with sulfonylhydrazine. This reaction process not only avoids transition metal catalysis and the addition of oxidizing or reducing agents, but also features a simple reaction system, a wide range of applicable substrates, and a high yield, which is beneficial for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a sulfonylpyridinone compound and its preparation method and application. Background Technology

[0002] The pyridazine ring is a special six-membered heterocycle containing two adjacent nitrogen atoms, widely found in natural products and drug molecules. Compounds containing the pyridazine ring structure typically exhibit excellent biological activity and are also widely used in various functional materials, such as fluorescent probes and high-energy materials. Among them, pyridazine-3(2H)one is one of the important subtypes of this class of heterocyclic compounds, widely found in various drug molecules, and possesses anti-inflammatory, anticancer, and antibacterial biological activities.

[0003] Meanwhile, due to the multiple functionalization sites on the pyridazine-3(2H)one structure, this compound is also an important synthon in organic synthesis. In recent years, functionalization reactions of pyridazine-3(2H)one compounds have been continuously reported. The most common are electrophilic substitution at the N position 2 or nucleophilic substitution at the C position 5 (reaction formula (a)).

[0004] In contrast, due to the low reactivity of the 4-position carbon in pyridazine-3(2H)ones, functionalization reactions at this position have been less reported and progress has been slow. Furthermore, early studies on the functionalization of the 4-position carbon typically required first functionalizing the 5-position carbon, and then introducing a new functional group into compound B based on compound A in the following two ways (reaction formula (b)): (1) coupling reaction under the action of a metal catalyst or metal reagent; (2) nucleophilic reaction with nitrogen-, oxygen-, or sulfur-containing reagents. Although these methods are significant for the synthesis and modification of pyridazine-3(2H)one functional molecules, problems such as the use of transition metal catalysts, reducing agents, and stringent conditions urgently need to be addressed.

[0005]

[0006] On the other hand, the sulfonyl (sulfone) group is a common functional group found in various natural products and drug molecules. The sulfonyl group can effectively alter the water solubility, acidity, and polarity of a molecule, thereby regulating the activity of the drug molecule. Therefore, sulfonation reactions are of great significance in synthetic chemistry and medicinal chemistry. However, reactions introducing a sulfonyl group at the 4-C position of pyridazine-3(2H)ones are rarely reported. Current limited studies only employ a two-step synthesis method, and the substrate scope is limited. Therefore, it is necessary to develop novel functionalized sulfonylpyridazine-3(2H)ones and their preparation methods. Summary of the Invention

[0007] To overcome the problems existing in the prior art, one objective of the present invention is to provide a sulfonylpyridinone compound. A second objective of the present invention is to provide a method for preparing the above-mentioned sulfonylpyridinone compound. Third and fourth objectives of the present invention are to provide applications of the above-mentioned sulfonylpyridinone compound.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] The first aspect of this invention provides a sulfonylpyridazinone compound, the general structural formula of which is shown in formula (I):

[0010]

[0011] Wherein, R is selected from substituted or unsubstituted aryl groups; the substituted aryl group is monosubstituted or polysubstituted; the substituent on the substituted aryl group is selected from nitro, trifluoromethyl, halogen, cyano, amino, hydroxyl, C1-C4 alkyl, C3-C6 cycloalkyl or C1-C4 alkoxy.

[0012] Preferably, R is selected from one of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 3-methylphenyl, 2-thienyl, 2-naphthyl, and 3-pyridyl.

[0013] A second aspect of the present invention provides a method for preparing the sulfonylpyridinone compounds described in the first aspect, comprising the following steps: 4,5-dihalo-2-phenylpyridin-3(2H)one in the presence of an aromatic heterocyclic organic base and a quaternary ammonium salt tetrabutylammonium iodide. With sulfonyl hydrazine The reaction was carried out to obtain the sulfonylpyridazinone compound;

[0014] Where X is a halogen.

[0015] Preferably, X is Cl or Br.

[0016] Preferably, the R in the sulfonyl hydrazine is selected from one of 4-phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 3-methylphenyl, 2-thienyl, 2-naphthyl, and 3-pyridyl.

[0017] Preferably, the molar ratio of 4,5-dihalo-2-phenylpyridazine-3(2H)one to sulfonylhydrazine is 1:(2-3).

[0018] More preferably, the molar ratio of 4,5-dihalo-2-phenylpyridazine-3(2H)one to sulfonylhydrazine is 1:(2.2-2.6).

[0019] Preferably, the molar ratio of the 4,5-dihalo-2-phenylpyridazine-3(2H) one to the aromatic heterocyclic organic base is 1:(3-5).

[0020] Preferably, the molar ratio of the 4,5-dihalo-2-phenylpyridazine-3(2H)one to the quaternary ammonium salt is 1:(0.1-0.5).

[0021] Preferably, the aromatic heterocyclic organic base is selected from 4-dimethylaminopyridine or 2-methylimidazole.

[0022] Preferably, the quaternary ammonium salt is selected from one or more of tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, and benzyltriethylammonium chloride.

[0023] Preferably, the reaction temperature is 50-70°C.

[0024] More preferably, the reaction temperature is 50-70°C.

[0025] Preferably, the reaction time is 7-10 hours.

[0026] More preferably, the reaction time is 7.5-8.5 h.

[0027] Preferably, the reaction is carried out in a solvent composed of an aprotic polar solvent and water;

[0028] More preferably, the aprotic polar solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, and acetone.

[0029] More preferably, the volume ratio of the aprotic polar solvent to water is (8-12):1.

[0030] More preferably, the ratio of the amount of 4,5-dihalo-2-phenylpyridazine-3(2H)one to the solvent is 1 mmol:(5-20) mL.

[0031] More preferably, the method further includes the following steps: after the reaction is complete, the reaction mixture is transferred to a separatory funnel for separation. The aqueous phase is extracted with dichloromethane, and the combined organic phases are washed with saturated sodium chloride solution. The organic phase is then dried with anhydrous sodium sulfate and concentrated under reduced pressure. After separation by column chromatography, the sulfonylpyridinone compound is obtained.

[0032] The third aspect of the present invention provides the use of the sulfonylpyridazinone compounds of the first aspect in the preparation of antibacterial drugs.

[0033] Preferably, the sulfonylpyridazinone compound is used in the preparation of anti-Escherichia coli drugs.

[0034] Preferably, the sulfonylpyridazinone compound is used in the preparation of anti-Staphylococcus aureus drugs.

[0035] The fourth aspect of the present invention provides the use of the sulfonylpyridazinone compounds of the first aspect in the preparation of flame retardants.

[0036] The beneficial effects of this invention are:

[0037] (1) This invention provides a sulfonylpyridinone compound, wherein a sulfonyl group is introduced at the 4-position of pyridazin-3(2H) ketone, giving the compound multiple functional groups such as sulfone, phenyl, and pyridazinone. The sulfonylpyridinone compound of this invention exhibits a certain antibacterial effect against *Escherichia coli* / *Staphylococcus aureus* and can be used to prepare broad-spectrum antibacterial drugs. Furthermore, pyridazinone compounds with aromatic ring structures are important flame retardants, and the sulfone structure is also an important structural unit in flame retardants. Therefore, the sulfonylpyridinone compound of this invention is expected to have important applications in the fields of pharmaceuticals and flame retardants.

[0038] (2) This invention also provides a method for preparing the above-mentioned sulfonylpyridinone compounds, which is achieved through a dehalogenation sulfonation reaction of 4,5-dihalo-2-phenylpyridin-3(2H)one with sulfonyl hydrazine at the C-4 site. This reaction process is not only free of transition metal catalysis and requires no addition of oxidizing or reducing agents, but is also green and efficient, conforming to the development of green synthetic chemistry. Furthermore, it features a simple reaction system, a wide range of applicable substrates, and a high yield, which is beneficial for industrial production. Since the C-4 position of pyridin-3(2H)one has relatively low activity, functionalization reactions (especially sulfonation reactions) are difficult to perform at this position. This invention uses a one-step method to prepare the above-mentioned sulfonylpyridinone compounds. Therefore, the preparation method of this invention is of great significance for expanding the synthetic range of functionalized pyridin-3(2H)ones, especially for sulfonation reactions that construct CS bonds. Attached Figure Description

[0039] Figure 1 This is the X-ray single-crystal diffraction pattern of compound 1 from Example 1. Detailed Implementation

[0040] The present invention will be further described in detail below through specific embodiments. Unless otherwise specified, the raw materials used in the following embodiments can be obtained from conventional commercial channels or prepared and isolated through simple synthesis; unless otherwise specified, the processes employed are conventional processes in the art.

[0041] Example 1

[0042] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0043] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1339 g) of 4-methylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 1, a white solid (0.0734 g, 75%).

[0044] The structural formula and related characterization data of compound 1 are shown below:

[0045]

[0046] 1 H NMR (600MHz, CDCl3), δ, ppm: 2.43 (s, 3H, CH3-15), 7.35 (d, J = 7.8Hz, 2H, ArH-13, 16), 7.40 (t, J = 7.8Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, Ar H-2,3),7.54(d,J=7.8Hz,2H,ArH-12,17),8.04(d,J=8.4Hz,2H,ArH-4,5),8.12(d,J=4.2Hz,1H,ArH-8);8.18(d,J=3.6Hz,1H,ArH-7);

[0047] 13C NMR (150MHz, CDCl3), δ, ppm: 21.8 (C-15), 125.3 (C-4,5), 128.9 (C-12,17), 129.0 (C-1), 129.7 (C-2,3), 129. 9(C-13,16),131.9(C-7),134.8(C-8),135.3(C-11),140.5(C-14),140.8(C-6),145.7(C-9),154.9(C-10);

[0048] ESI-HRMS, m / z: Calculated for C 17 H 15 N₂O₃S[M+H] + :327.0798,Found:327.0793.

[0049] The X-ray single-crystal diffraction pattern of compound 1 is attached. Figure 1 As shown.

[0050] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, high-resolution mass spectrometry (HRMS) and X-ray single-crystal diffraction (XRD) showed that the structure of compound 1 was consistent with the expected structure.

[0051] Example 2

[0052] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0053] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1368 g) of 4-fluorobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 2, a white solid (0.0525 g, 53%).

[0054] The structural formula and related characterization data of compound 2 are shown below:

[0055]

[0056] 1H NMR (600MHz, CDCl3), δ, ppm: 7.19-7.22(m,2H,ArH-2,3),7.40(t,J=7.8Hz,2H,ArH-1),7.44-7.47(m,2H,ArH-13,15),7. 51(d,J=7.8Hz,2H,ArH-4,5),8.13(d,J=4.2Hz,1H,ArH-8),8.16(d,J=3.6Hz,1H,ArH-7),8.17-8.20(m,2H,ArH-12,16);

[0057] 13 C NMR(150MHz, CDCl3), δ, ppm: 116.5(d,J=22.5Hz,C-13,15),125.4(C-4,5),129.1(C-2,3),129.2(C-1),132.2(C-6),133.2(d,J =10.5Hz,C-12,16),133.7(C-7),133.8(C-8),135.4(C-9),140.5(d,J=6.0Hz,C-11),155.0(C-10),166.5(d,J=256.5Hz,C-14);

[0058] 19 F NMR (564MHz, CDCl3), δ, ppm: -101.9;

[0059] ESI-HRMS, m / z: Calculated for C 16 H 12 FN₂O₃S,[M+H] + :331.0547,Found:331.0537.

[0060] High-resolution mass spectrometry results from proton NMR, carbon NMR, and fluorine NMR spectrometry showed that the structure of compound 2 was consistent with expectations.

[0061] Example 3

[0062] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0063] The preparation method is as follows: 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1483 g) of 4-chlorobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added to a Schlenk tube and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction solution was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand for phase separation. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. After separation by column chromatography, compound 3 was obtained as a white solid (0.0571 g, 55%).

[0064] The structural formula and related characterization data of compound 3 are shown below:

[0065]

[0066] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.41 (t, J = 7.2Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, ArH-2, 3), 7.50-7.53 (m, 4H, ArH -12,13,15,16),8.09(d,J=8.4Hz,2H,ArH-4,5),8.13(d,J=4.2Hz,1H,ArH-8),8.16(d,J=4.2Hz,1H,ArH-7);

[0067] 13 C NMR(150MHz, CDCl3), δ, ppm: 125.3(C-4,5),129.1(C-2,3),129.3(C-1),129.5(C-12,16),131.6(C-13,15),132 .3(C-7),135.4(C-8),136.3(C-14),140.3(C-6),140.5(C-11),141.5(C-9),155.0(C-10); ESI-HRMS,m / z:Calcd for C 16 H 12 ClN₂O₃S,[M+H] + :347.0252,Found:347.0242.

[0068] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) show that the structure of compound 3 is consistent with expectations.

[0069] Example 4

[0070] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0071] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1729 g) of 4-trifluoromethylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting product was separated by column chromatography to give compound 4, a white solid (0.0570 g, 50%).

[0072] The structural formula and related characterization data of compound 4 are shown below:

[0073]

[0074] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.41 (t, J=7.2Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, ArH-2,3), 7.51 (d, J=8.4Hz, 2H, ArH-4,5), 7.80 (d,J=8.4Hz,2H,ArH-12,17),8.16(d,J=4.2Hz,1H,ArH-8),8.20(d,J=4.2Hz,1H,ArH-7),8.29(d,J=8.4Hz,2H,ArH-13,16);

[0075] 13 C NMR (150MHz, CDCl3), δ, ppm: 123.2 (q, J=271.5Hz, C-15), 125.3 (C-4,5), 126.2 (q, J=3.0Hz, C-13,16), 129.1 (C-12,17), 129.3 (C -1),130.7(C-2,3),132.7(C-7),135.4(C-8),136.0(q,J=31.5Hz,C-14),139.8(C-6),140.4(C-11),141.4(C-9),154.9(C-10);

[0076] 19 F NMR (564MHz, CDCl3), δ, ppm: -63.3;

[0077] ESI-HRMS, m / z: Calculated for C 17 H 12 F3N2O3S,[M+H] + :381.0515,Found:381.0504.

[0078] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, fluorine nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 4 was consistent with expectations.

[0079] Example 5

[0080] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0081] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1483 g) of 3-chlorobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were dissolved in 2 mL of acetonitrile and 0.2 mL of water, and the mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 5, a white solid (0.0508 g, 49%).

[0082] The structural formula and related characterization data of compound 5 are shown below:

[0083]

[0084] 1 H NMR(600MHz, CDCl3), δ, ppm: 7.41(t,J=7.8Hz,1H,ArH-1),7.44-7.50(m,3H,ArH-2,3,15),7.52(d,J=7.8Hz,2H,ArH-4,5),7.61(d,J =7.8Hz,1H,ArH-14),8.06(s,1H,ArH-12),8.09(d,J=8.4Hz,1H,ArH-16),8.14(d,J=4.2Hz,1H,ArH-8),8.17(d,J=4.2Hz,1H,ArH-7);

[0085] 13C NMR (150MHz, CDCl3), δ, ppm: 125.3(C-4,5),128.5(C-16),129.1(C-2,3),129.3(C-12),129.6(C-1),130.4(C-1 5),132.6(C-14),134.7(C-13),135.2(C-7),135.4(C-8),139.7(C-6),140.0(C-11),140.5(C-9),154.9(C-10);

[0086] ESI-HRMS, m / z: Calculated for C 16 H 12 ClN₂O₃S,[M+H] + :347.0252,Found:347.0242.

[0087] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 5 was consistent with expectations.

[0088] Example 6

[0089] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0090] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1454 g) of 4-methoxybenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 6, a white solid (0.0841 g, 82%).

[0091] The structural formula and related characterization data of compound 6 are shown below:

[0092]

[0093] 1H NMR (600MHz, CDCl3), δ, ppm: 3.85 (s, 3H, OCH3-1), 6.98 (d, J = 7.8Hz, 2H, ArH-13, 16), 7.39 (t, J = 7.2Hz, 1H, ArH-1), 7.43-7.46 (m, 2H, Ar H-2,3),7.52(d,J=7.8Hz,2H,ArH-12,17),8.08(d,J=8.4Hz,2H,ArH-4,5),8.10(d,J=3.6Hz,1H,ArH-8),8.14(d,J=4.2Hz,1H,ArH-7);

[0094] 13 C NMR(150MHz,CDCl3),δ,ppm:55.8(C-15),114.4(C-13,16),125.4(C-4,5),129.0(C-2,3),129.1(C-1, 11),131.6(C-7),132.5(C-12,17),135.5(C-8),140.7(C-6),141.2(C-9),155.1(C-11),164.6(C-10);

[0095] ESI-HRMS, m / z: Calculated for C 17 H 15 N₂O₄S[M+H] + :343.0747,Found:343.0742.

[0096] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 6 was consistent with expectations.

[0097] Example 7

[0098] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0099] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1440 g) of 4-ethylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 7, a white solid (0.0663 g, 82%).

[0100] The structural formula and related characterization data of compound 7 are shown below:

[0101]

[0102] 1 H NMR (600MHz, CDCl3), δ, ppm: 1.23 (t, J = 7.8Hz, 3H, CH3-16), 2.70 (q, J = 7.8Hz, 2H, CH2-15), 7.35 (d, J = 8.4Hz, 2H, ArH-13, 17), 7.38 (t, J = 7.8Hz, 1H, ArH-1), 7.42-7.45(m,2H,ArH-2,3),7.52(d,J=8.4Hz,2H,ArH-12,18),8.05(d,J=8.4 Hz,2H,ArH-4,5),8.10(d,J=3.6Hz,1H,ArH-8),8.16(d,J=4.2Hz,1H,ArH-7);

[0103] 13 C NMR (150MHz, CDCl3), δ, ppm: 15.7 (C-16), 29.1 (C-15), 125.4 (C-4,5), 128.6 (C-12,18), 129.0 (C-13,17), 129.1 (C -1),130.1(C-2,3),132.0(C-7),135.0(C-11),135.4(C-8),140.6(C-6),140.8(C-9),151.8(C-14),155.0(C-10);

[0104] ESI-HRMS, m / z: Calculated for C 18 H 17 N₂O₃S[M+H] + :341.0954,Found:341.0945.

[0105] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) show that the structure of compound 7 is consistent with expectations.

[0106] Example 8

[0107] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0108] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1641 g) of 4-tert-butylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 8, a white solid (0.0740 g, 67%).

[0109] The structural formula and related characterization data of compound 8 are shown below:

[0110]

[0111] 1 H NMR (600MHz, CDCl3), δ, ppm: 1.31 (s, 9H, CH3-16, 17, 18), 7.39 (t, J = 7.2Hz, 1H, ArH-1), 7.43-7.45 (m, 2H, ArH-2, 3), 7.52-7 .55(m,4H,ArH-4,5,13,19),8.06(d,J=9.0Hz,2H,ArH-12,20),8.11(d,J=4.2Hz,1H,ArH-8),8.16(d,J=4.2Hz,1H,ArH-7);

[0112] 13 C NMR(150 MHz, CDCl3), δ, ppm: 31.1(C-16,17,18),35.4(C-15),125.4(C-4,5),126.2(C-13,19),129.0(C-12,20),129.1(C- 1),129.9(C-2,3),132.1(C-7),134.7(C-8),135.4(C-11),140.6(C-6),140.8(C-9),155.0(C-14),158.6(C-10);

[0113] ESI-HRMS, m / z: Calculated for C 20 H 21 N2O3S[M+H]+:369.1267,Found:369.1258.

[0114] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) show that the structure of compound 8 is consistent with expectations.

[0115] Example 9

[0116] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0117] 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1238 g) of benzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added to a Schlenk tube and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting product was separated by column chromatography to give compound 9 as a white solid (0.0599 g, 64%).

[0118] The structural formula and related characterization data of compound 9 are shown below:

[0119]

[0120] 1 H NMR (600 MHz, CDCl3), δ, ppm: 7.39 (t, J = 7.2 Hz, 1H, ArH-1), 7.42-7.45 (m, 2H, ArH-2, 3), 7.50-7.52 (m, 2H, ArH-13, 15), 7.54 (d, J = 8.4 Hz,2H,ArH-4,5),7.64(t,J=7.2Hz,1H,ArH-14),8.11(d,J=4.2 Hz,1H,ArH-8),8.15(d,J=7.2 Hz,2H,ArH-12,16),8.17(d,J=4.2 Hz,1H,ArH-7);

[0121] 13 C NMR(150 MHz, CDCl3), δ, ppm:125.3(C-4,5),128.9(C-12,16),129.0(C-2,3),129.1(C-1,14),130.0 (C-13,15),132.3(C-7),134.5(C-8),135.4(C-6),137.9(C-11),140.6(C-9),155.0(C-10);

[0122] ESI-HRMS, m / z: Calculated for C 16 H 13N2O3S[M+H]+:313.0641,Found:313.0636.

[0123] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) show that the structure of compound 9 is consistent with expectations.

[0124] Example 10

[0125] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0126] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1807 g) of 4-bromobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 10, a white solid (0.0679 g, 58%).

[0127] The structural formula and related characterization data of compound 10 are shown below:

[0128]

[0129] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.41 (t, J=7.2Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, ArH-2,3), 7.51 (d, J=7.8Hz, 2H, ArH-4,5), 7.67 (d,J=9.0Hz,2H,ArH-12,16),8.00(d,J=9.0Hz,2H,ArH-13,15),8.13(d,J=4.2Hz,1H,ArH-8),8.16(d,J=4.2Hz,1H,ArH-7);

[0130] 13C NMR (150MHz, CDCl3), δ, ppm: 125.3(C-4,5),129.1(C-2,3),129.3(C-1),130.3(C-14),131.6(C-12,1 6),132.3(C-7),132.4(C-13,15),135.4(C-8),136.8(C-6),140.3(C-11),140.5(C-9),154.9(C-10);

[0131] ESI-HRMS, m / z: Calculated for C 16 H 12 BrN₂O₃S,[M+H] + :390.9747,Found:390.9742.

[0132] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 10 was consistent with expectations.

[0133] Example 11

[0134] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0135] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.2146 g) of 4-iodobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 11, a white solid (0.0815 g, 62%).

[0136] The structural formula and related characterization data of compound 11 are shown below:

[0137]

[0138] 1H NMR (600MHz, CDCl3), δ, ppm: 7.40 (t, J=7.8Hz, 1H, ArH-1), 7.44-7.48 (m, 2H, ArH-2,3), 7.51 (d, J=7.8Hz, 2H, ArH-4,5), 7.84 (d,J=8.4Hz,2H,ArH-12,16),7.89(d,J=8.4Hz,2H,ArH-13,15),8.13(d,J=3.6Hz,1H,ArH-8),8.15(d,J=4.2Hz,1H,ArH-7);

[0139] 13 C NMR(150MHz,CDCl3),δ,ppm:103.2(C-14),125.3(C-4,5),129.1(C-2,3),129.2(C-1),131.3(C-12,1 6),132.3(C-7),135.4(C-8),137.5(C-6),138.4(C-13,15),140.2(C-11),140.5(C-9),154.9(C-10);

[0140] ESI-HRMS, m / z: Calculated for C 16 H 12 IN₂O₃S, [M+H] + :438.9608,Found:438.9596.

[0141] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 11 was consistent with expectations.

[0142] Example 12

[0143] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0144] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1562 g) of 4-nitrobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 12, a pink solid (0.0482 g, 45%).

[0145] The structural formula and related characterization data of compound 12 are shown below:

[0146]

[0147] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.42 (t, J=7.2Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, ArH-2.3), 7.50 (d, J=7.8Hz, 2H, ArH-4,5),8.18(d,J=4.2Hz,1H,ArH-8),8.21(d,J=4.2Hz,1H,ArH-7),8.33-8.37(m,4H,ArH-12,13,15,16);

[0148] 13 C NMR(150MHz,CDCl3),δ,ppm:124.2(C-4,5),125.3(C-13,15),129.1(C-2,3),129.5(C-1),131.6(C-1 2,16),132.9(C-7),135.4(C-8),139.5(C-6),140.3(C-9),143.5(C-11),151.2(C-14),154.9(C-10);

[0149] ESI-HRMS, m / z: Calculated for C 16 H 12 N3O5S, [M+H] + :358.0492,Found:358.0480.

[0150] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 12 was consistent with expectations.

[0151] Example 13

[0152] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0153] 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1339 g) of 3-methylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added to a Schlenk tube and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting product was separated by column chromatography to give compound 13 as a white solid (0.0606 g, 62%).

[0154] The structural formula and related characterization data of compound 13 are shown below:

[0155]

[0156] 1 H NMR (600MHz, CDCl3), δ, ppm: 2.41 (s, 3H, CH3-1), 7.38 (t, J = 7.8Hz, 1H, ArH-1), 7.41-7.45 (m, 4H, ArH-2, 3, 15, 16), 7.52 (d, J = 7.8 Hz,2H,ArH-4,5),7.90(s,1H,ArH-12),7.95(d,J=7.2Hz,1H,ArH-17),8.11(d,J=4.2Hz,1H,ArH-8),8.17(d,J=3.6Hz,1H,ArH-7);

[0157] 13 C NMR(150MHz,CDCl3),δ,ppm:21.5(C-14),125.3(C-4,5),127.2(C-17),128.9(C-2,3),129.0(C-12),129.9(C-1) ,132.2(C-16),135.3(C-7),135.6(C-8),137.8(C-15),139.3(C-6),140.60(C-11),140.62(C-13),154.9(C-10);

[0158] ESI-HRMS, m / z: Calculated for C 17 H 15 N₂O₃S, [M+H] + :327.0798,Found:327.0788.

[0159] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 13 was consistent with expectations.

[0160] Example 14

[0161] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0162] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1454 g) of 3-methoxybenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 14, a white waxy solid (0.0718 g, 70%).

[0163] The structural formula and related characterization data of compound 14 are shown below:

[0164]

[0165] 1 H NMR (600MHz, CDCl3), δ, ppm: 3.86 (s, 3H, OCH3-13), 7.40 (t, J = 7.8Hz, 1H, ArH-1), 7.42-7.46 (m, 4H, ArH-2, 3, 15, 16), 7.53 (d, J = 7. 8Hz,2H,ArH-4,5),7.64(s,1H,ArH-12),7.71(d,J=7.8Hz,1H,ArH-17),8.12(d,J=4.2Hz,1H,ArH-8),8.16(d,J=4.2Hz,1H,ArH-7);

[0166] 13 C NMR (150MHz, CDCl3), δ, ppm: 55.9 (C-13), 114.1 (C-12), 121.2 (C-15), 122.1 (C-17), 125.4 (C-4,5), 129.0 (C-2,3), 129 .2(C-1),130.2(C-16),132.3(C-7),135.3(C-8),139.1(C-9),140.5(C-6),140.6(C-11),155.0(C-14),159.8(C-10);

[0167] ESI-HRMS, m / z: Calculated for C 17 H 15 N₂O₄S, [M+H] + :343.0747,Found:343.0737.

[0168] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 14 was consistent with expectations.

[0169] Example 15

[0170] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0171] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1368 g) of 3-fluorobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 15, a white solid (0.0505 g, 70%).

[0172] The structural formula and related characterization data of compound 15 are shown below:

[0173]

[0174] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.33-7.36 (m, 1H, ArH-15), 7.41 (t, J=7.8Hz, 1H, ArH-1), 7.44-7.47 (m, 2H, ArH-2, 3), 7.51-7.54 (m, 3H, A rH-4,5,12),7.84(d,J=7.8Hz,1H,ArH-14),7.96(d,J=7.8Hz,1H,ArH-16),8.14(d,J=4.2Hz,1H,ArH-8),8.17(d,J=4.2Hz,1H,ArH-7);

[0175] 13C NMR (150MHz, CDCl3), δ, ppm: 117.3 (d, J=25.5Hz, C-12), 121.9 ((d, J=21.0H z,C-14),125.3(C-4,5),125.9(d,J=3.0Hz,C-16),129.1(C-2,3),129.3(C- 1),130.9(d,J=7.5Hz,C-15),132.6(C-7),135.4(C-8),139.4(d,J=6.0Hz, C-11),140.1(C-6),140.5(C-9),154.9(C-10),162.2(d,J=250.5Hz,C-13);

[0176] 19 F NMR (564MHz, CDCl3), δ, ppm: -109.3;

[0177] ESI-HRMS, m / z: Calculated for C 16 H 12 FN₂O₃S,[M+H] + :331.0547,Found:331.0537.

[0178] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, fluorine nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 15 was consistent with expectations.

[0179] Example 16

[0180] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0181] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1807 g) of 3-bromobenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 16, a white solid (0.0620 g, 53%).

[0182] The structural formula and related characterization data of compound 16 are shown below:

[0183]

[0184] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.39-7.43 (m, 2H, ArH-1,15), 7.44-7.47 (m, 2H, ArH-2, 3), 7.52 (d, J=8.4Hz, 2H, ArH-4, 5),7.76(d,J=7.8Hz,1H,ArH-16),8.13-8.15(m,2H,ArH-7,14),8.16(d,J=3.6Hz,1H,ArH-8),8.19(s,1H,ArH-12);

[0185] 13 C NMR(150MHz,CDCl3),δ,ppm:122.9(C-13),125.3(C-4,5),129.0(C-16),129.1(C-2,3),129.2(C-1),130.6(C-1 2),132.3(C-15),132.6(C-14),135.4(C-7),137.6(C-8),139.8(C-6),140.0(C-11),140.5(C-9),154.9(C-10);

[0186] ESI-HRMS, m / z: Calculated for C 16 H 12 BrN₂O₃S,[M+H] + :390.9747,Found:390.9734.

[0187] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 16 was consistent with expectations.

[0188] Example 17

[0189] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0190] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1729 g) of 3-trifluoromethylbenzenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 17, a white solid (0.0524 g, 46%).

[0191] The structural formula and related characterization data of compound 17 are shown below:

[0192]

[0193] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.41 (t, J = 7.2Hz, 1H, ArH-1), 7.44-7.48 (m, 2H, ArH-2, 3), 7.52 (d, J = 7.8Hz, 2H, ArH-4, 5), 7.69-7.72 (m, 1H, ArH-16 ),7.91(d,J=7.8Hz,1H,ArH-17),8.16(d,J=4.2Hz,1H,ArH-8),8.21(d,J=4.2Hz,1H,ArH-7),8.30(s,1H,ArH-12),8.47(d,J=7.8Hz,1H,ArH-15);

[0194] 13 C NMR (150MHz, CDCl3), δ, ppm: 123.2 (q, J=271.5Hz, C-14), 125.3 (C-4,5), 126.6 (q, J=3.0Hz, C-12), 129.1 (C-2,3), 129.3 (C-1), 129.9 (C-16), 131 .2(q,J=4.5Hz,C-15),131.7(q,J=34.5Hz,C-13),132.7(C-7),134.1(C- 8),135.4(C-6),139.2(C-17),139.8(C-11),140.5(C-9),154.9(C-10);

[0195] 19 F NMR (564MHz, CDCl3), δ, ppm: -62.7;

[0196] ESI-HRMS, m / z: Calculated for C 17 H 12 F3N2O3S,[M+H] + :381.0515,Found:381.0511.

[0197] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, fluorine nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 17 was consistent with expectations.

[0198] Example 18

[0199] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0200] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1282 g) of 2-thienylsulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 18, a white waxy solid (0.0506 g, 53%).

[0201] The structural formula and related characterization data of compound 18 are shown below:

[0202]

[0203] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.12-7.14 (m, 1H, ArH-13), 7.41 (t, J=7.2Hz, 1H, ArH-1), 7.56 (d, J=7.2Hz, 2H, ArH-4,5),7.75(d,J=3.6Hz,1H,ArH-12),8.06(d,J=3.6Hz,1H,ArH-14),8.11-8.13(m,2H,ArH-7,8);

[0204] 13 C NMR (150MHz, CDCl3), δ, ppm: 125.3 (C-4,5), 128.1 (C-14), 128.9 (C-2,3), 129.1 (C-11), 131. 6(C-12,13),135.4(C-1),136.1(C-7),137.5(C-8),140.4(C-6),140.5(C-9),154.9(C-10);

[0205] ESI-HRMS, m / z: Calculated for C 14 H 11 N₂O₃S₂, [M+H] + :319.0206,Found:319.0196.

[0206] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 18 was consistent with expectations.

[0207] Example 19

[0208] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0209] In a Schlenk tube, 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1598 g) of 2-naphthalenesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine, and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction mixture was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand to separate the layers. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Separation by column chromatography yielded compound 19, a white solid (0.0662 g, 61%).

[0210] The structural formula and related characterization data of compound 19 are shown below:

[0211]

[0212] 1 H NMR (600MHz, CDCl3), δ, ppm: 7.37 (t, J = 7.8Hz, 1H, ArH-1), 7.41-7.43 (m, 2H, ArH-2, 3), 7.49 (d ,J=7.8Hz,2H,ArH-4,5),7.59-7.61(m,1H,ArH-19),7.64-7.67(m,1H,ArH-18),7.90(d,J=8.4H z,1H,ArH-20),7.96(d,J=8.4Hz,1H,ArH-17),8.01(d,J=8.4Hz,1H,ArH-12),8.07(d,J=8.4Hz ,1H,ArH-13),8.14(d,J=4.2Hz,1H,ArH-8),8.24(d,J=4.2Hz,1H,ArH-7),8.74(s,1H,ArH-14).

[0213] 13C NMR(150MHz,CDCl3),δ,ppm:124.1(C-1),125.4(C-4,5),127.7(C-18),128.1(C-19),129.0(C-2,3),129.1(C-17),129.3(C-20),129.8(C-1 2),130.0(C-14),132.1(C-13),132.2(C-7),132.5(C-8),134.8(C-15 ),135.4(C-6),135.9(C-16),140.6(C-11),140.8(C-9),155.1(C-10).

[0214] ESI-HRMS, m / z: Calculated for C 20 H 15 N₂O₃S, [M+H] + :363.0798,Found:363.0787.

[0215] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) showed that the structure of compound 19 was consistent with expectations.

[0216] Example 20

[0217] This embodiment provides a sulfonylpyridazinone compound, the preparation method of which is as follows:

[0218] The preparation method is as follows: 0.3 mmol (0.099 g) of 4,5-dibromo-2-phenylpyridazin-3(2H)one, 0.72 mmol (0.1246 g) of 3-pyridinesulfonylhydrazine, 1.2 mmol (0.1464 g) of 4-dimethylaminopyridine and 0.009 mmol (0.0033 g) of tetrabutylammonium iodide were added to a Schlenk tube and dissolved in 2 mL of acetonitrile and 0.2 mL of water. The mixture was stirred at 60 °C for 8 h. After the reaction was complete, the reaction solution was completely transferred to a separatory funnel with dichloromethane, washed with saturated sodium chloride solution, and allowed to stand for separation. The organic phase was dried over anhydrous sodium sulfate and concentrated under reduced pressure. After separation by column chromatography, compound 20 was obtained as a white waxy solid (0.0338 g, 36%).

[0219] The structural formula and related characterization data of compound 20 are shown below:

[0220]

[0221] 1H NMR (600MHz, CDCl3), δ, ppm: 7.41 (t, J = 7.2 Hz, 1H, ArH-1), 7.45-7.47 (m, 2H, ArH-2, 3), 7.49-7.52 (m, 3H, ArH-4, 5, 14), 8.17 (d, J = 4 .2Hz,1H,ArH-8),8.20(d,J=4.2Hz,1H,ArH-7),8.57(d,J=8.4Hz,1H,ArH-15),8.85(d,J=6.0Hz,1H,ArH-13),9.22(s,1H,ArH-12);

[0222] 13 C NMR(150MHz,CDCl3),δ,ppm:123.7(C-14),125.3(C-4,5),128.9(C-11),129.1(C-2,3),129.4(C-1),132 .5(C-7),135.4(C-8),138.8(C-15),140.0(C-6),140.4(C-12),150.4(C-9),154.7(C-13),154.9(C-10);

[0223] ESI-HRMS, m / z: Calculated for C 15 H 12 N3O3S, [M+H] + :314.0584,Found:314.0594.

[0224] The results of proton nuclear magnetic resonance (NMR) spectroscopy, carbon nuclear magnetic resonance (NMR) spectroscopy, and high-resolution mass spectrometry (HRMS) show that the structure of compound 20 is consistent with expectations.

[0225] Experimental Analysis

[0226] The antibacterial properties of the products from Examples 1-5 were tested, and the specific test methods and results are as follows:

[0227] 1. Experimental strains

[0228] The bacterial strains used in the experiment were: Escherichia coli ATCC 43894 and Staphylococcus aureus ATCC 25923.

[0229] 2. Experimental Procedure

[0230] 2.1 Activation of bacterial strains and preparation of bacterial culture

[0231] Escherichia coli ATCC 43894 and Staphylococcus aureus ATCC 25923, stored at -80℃, were dispersed on LB agar medium using the streak method and incubated at 37℃ for 24 h. Single colonies were picked from the medium using an inoculation loop and inoculated into 2 mL of liquid broth, incubated for 12 h. Then, 50 μL of the bacterial culture was diluted 1:100 and cultured to the logarithmic growth phase.

[0232] 2.2 Minimum Inhibitory Concentration (MIC) Test

[0233] The bacterial culture that has reached logarithmic growth was diluted to OD using LB medium. 600 =0.1 for later use. Weigh 8 mg of the compound to prepare a stock solution with a concentration of 4 mg / mL. Serially dilute this stock solution with LB broth in a 96-well plate to prepare solutions of different concentrations (180 μL). Add an equal volume (20 μL) of the diluted bacterial suspension to each 96-well plate, controlling the final polymer concentrations to be 2000, 1000, 500, 250, 125, 62.5, 31.25, and 16.125 μg / mL. Then incubate at 37°C (18 h for E. coli, 18-20 h for Staphylococcus aureus). The minimum concentration at which no significant increase in bacterial concentration is taken as the MIC of the compound. Use a bacterial suspension without the compound as a negative control and LB broth without the compound and bacteria as a positive control. Set up three parallel controls for each concentration and perform three technical replicates to confirm the MIC value for each bacterium (Table 1).

[0234] 3. Experimental Results

[0235] As shown in Table 1, all selected compounds possess certain antibacterial properties. Compared with similar tests, the representative compounds in this invention show better results than those reported in existing literature (Wang YL; Liu ZH, Liu T, et al. Chemistryselect, 2024, 9, e202401299).

[0236] Table 1 shows the minimum antibacterial activity of some compounds.

[0237]

[0238]

[0239] In addition, the compounds of Examples 6 to 20 also have the potential to have certain antibacterial effects.

[0240] The above description represents the preferred embodiments of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and these improvements and modifications are also considered to be within the scope of protection of the present invention.

Claims

1. A sulfonylpyridazinone compound, characterized in that, The general structural formula of the sulfonylpyridazinone compounds is shown in formula (Ⅰ): Equation (Ⅰ); Wherein, R is selected from one of phenyl, 4-methylphenyl, 4-ethylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-iodophenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 3-fluorophenyl, 3-chlorophenyl, 3-bromophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 3-methylphenyl, 2-thienyl, 2-naphthyl or 3-pyridyl.

2. The method for preparing the sulfonylpyridazinone compound according to claim 1, characterized in that, The process includes the following steps: in the presence of an aromatic heterocyclic organic base and a quaternary ammonium salt, 4,5-dihalo-2-phenylpyridazine-3(2 H )ketone With sulfonyl hydrazine The reaction was carried out to obtain the sulfonylpyridazinone compound; Where X is Cl or Br; The aromatic heterocyclic organic base is selected from 4-dimethylaminopyridine; The quaternary ammonium salt is selected from tetrabutylammonium iodide.

3. The method for preparing sulfonylpyridazinone compounds according to claim 2, characterized in that, The 4,5-dihalo-2-phenylpyridazine-3(2) H The molar ratio of ketone to sulfonyl hydrazine is 1:(2-3).

4. The method for preparing sulfonylpyridazinone compounds according to claim 2, characterized in that, The reaction temperature is 50-70℃; And / or, the reaction time is 7-10 h.

5. The method for preparing sulfonylpyridazinone compounds according to claim 2, characterized in that, The 4,5-dihalo-2-phenylpyridazine-3(2) H The molar ratio of ketone to aromatic heterocyclic organic base is 1:(3-5).

6. The method for preparing sulfonylpyridazinone compounds according to claim 2, characterized in that, The reaction is carried out in a solvent consisting of an aprotic polar solvent and water.

7. The use of the sulfonylpyridazinone compound of claim 1 in the preparation of antibacterial drugs, characterized in that, The antibacterial drug is an anti-Escherichia coli drug or an anti-Staphylococcus aureus drug.

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