Benzamide / benzenesulfonamide compounds containing aryl butyl ketone structure, their preparation methods and applications

Abstract

This invention discloses a benzamide / benzenesulfonamide compound containing an aryl butanone structure, its preparation method, and its application, belonging to the field of medicinal chemistry. The structure of the benzamide compound containing the aryl butanone structure is as follows: R1 is hydrogen, halogen, alkyl, or alkoxy; R2 is tert-butyl, tert-pentyl, tert-octyl, adamantyl, or α,α-dimethylbenzyl; R3 is hydrogen, halogen, alkyl, alkoxy, fused ring, or aryl; R4 is hydrogen, alkyl, or aryl. The structure of the benzenesulfonamide compound containing the aryl butanone structure is as follows: R1 is hydrogen, halogen, or alkyl; R2 is tert-butyl, tert-pentyl, or tert-octyl; R3 is hydrogen, halogen, alkyl, or fused ring. The advantages of this invention are that some of the prepared compounds exhibit strong inhibitory effects on MCF-7 and HCT-116, and can be used as lead compounds for the subsequent preparation and development of antitumor drugs.

Description

Technical Field

[0001] This invention relates to benzamide / benzenesulfonamide compounds, their preparation methods, and applications, specifically to benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures, their preparation methods, and their application in the preparation of antitumor (breast cancer, colon cancer) drugs, belonging to the field of medicinal chemistry technology. Background Technology

[0002] Arylbutyrophenone, as one of the active ingredients in rhubarb, is used industrially as a medium for various organic synthesis and pharmaceutical processes. Some of its derivatives have therapeutic effects in inhibiting positive symptoms of schizophrenia and mania, and are medically known as butyrophenone antipsychotics. Butyrophenone antipsychotics exert their antipsychotic effects by blocking dopamine D2 receptors, reducing transmission from dopaminergic neurons. Common examples of this class of drugs include haloperidol, droperidol, bromoperidol, and tilmipirol.

[0003] Benzamide and benzenesulfonamide, as two important classes of aromatic amide compounds, are key pharmacophores in drug molecules. Due to their unique structural features and reactivity, they occupy an important position in drug development and organic synthesis. Benzamide, relying on the hydrogen bonding of the amide bond and its moderate chemical stability, is widely used in the molecular design of drugs for the central nervous system, gastrointestinal tract, and antitumor purposes, and can effectively bind to various targets. Benzenesulfonamide, due to the strong electron-withdrawing effect of the sulfonyl group and the significant acidity of the NH bond, allows its anion to bind to metal ions at the enzyme's active site, becoming the core framework of sulfonamide antibacterial drugs, carbonic anhydrase inhibitors, and antitumor drugs, exhibiting both high biological activity and good metabolic stability.

[0004] By combining pharmacologically active skeletons, the study of benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures represents both a structural upgrade of classic pharmacophores and an exploration of new targets and mechanisms for drug development. This approach can provide highly efficient, low-toxicity, and highly selective candidate drugs for anti-tumor, antibacterial, CNS disease, and metabolic disease fields, and can also promote the development of organic synthesis methodology and chemical biology, possessing significant theoretical research value and clinical application prospects.

[0005] Currently, the structures and synthetic methods of benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures with good pharmacological activity are rarely reported. Therefore, it is particularly important to establish a simple and practical synthetic methodology and develop a method with mild reaction conditions and fewer operation steps for the direct synthesis of benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures. Summary of the Invention

[0006] The first objective of this invention is to provide benzamide / benzenesulfonamide compounds with aryl butyl ketone structures that have good pharmacological activity.

[0007] The second objective of this invention is to provide a method for preparing the above-mentioned benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures that is simple to operate, has mild reaction conditions, and is highly practical.

[0008] The third objective of this invention is to provide the application of the above-mentioned benzamide / benzenesulfonamide compounds containing the aryl butyl ketone structure in the preparation of antitumor (breast cancer, colon cancer) drugs.

[0009] To achieve the above objectives, the present invention adopts the following technical solution:

[0010] The structures of benzamide compounds containing arylbutanone structures are shown below:

[0011]

[0012] Wherein, R1 is hydrogen, halogen, alkyl or alkoxy; R2 is tert-butyl, tert-pentyl, tert-octyl, adamantyl or α,α-dimethylbenzyl; R3 is hydrogen, halogen, alkyl, alkoxy, cyclohexyl or aryl; and R4 is hydrogen, alkyl or aryl.

[0013] The preparation method of the aforementioned benzamide compounds containing an aryl butyl ketone structure includes the following steps:

[0014] (1) Add the base, copper catalyst, ligand and photosensitizer to a dry reaction vessel in a molar ratio of 1:0.1:0.1:0.02;

[0015] (2) After evacuating and filling the reaction vessel with argon five times, add an organic solvent;

[0016] (3) An N-alkyl-N-fluoro-2-methylaniline compound and a cyclopropanol compound are added sequentially to the reaction mixture, wherein the N-alkyl-N-fluoro-2-methylaniline compound is N-(tert-butyl)-N-fluoro-2-methylaniline, N-(tert-butyl)-N-fluoro-2,4-dimethylaniline, N-(tert-butyl)-N-fluoro-2,5-dimethylaniline, N-(tert-butyl)-N-fluoro-2,3-dimethylaniline, N- (tert-butyl)-N-fluoro-2,6-dimethylaniline, N-(tert-butyl)-N-fluoro-4-chloro-2-methylaniline, N-(tert-butyl)-N-fluoro-4-methoxy-2-methylaniline, N-(tert-butyl)-N-fluoro-2-ethylbenzamide, N-(tert-butyl)-N-fluoro-2-benzylbenzamide, N-fluoro-N-(tert-pentyl)-2-methylaniline, N-fluoro-N-(adamantyl)-2-methylbenzamide Amines, N-fluoro-2-methyl-N-(2,4,4-trimethylpentan-2-yl)aniline, or N-fluoro-2-methyl-N-(2-phenylpropan-2-yl)aniline, wherein the cyclopropanol compound is 1-phenylcyclopropan-1-ol, 1-(p-tolyl)cyclopropan-1-ol, 1-(4-(tert-butyl)phenyl)cyclopropan-1-ol, 1-(4-methoxyphenyl)cyclopropan-1-ol, or 1-(4-chlorophenyl)cyclopropan-1-ol. The molar amounts of 1-(4-bromophenyl)cyclopropane-1-ol, 1-(m-tolyl)cyclopropane-1-ol, 1-(o-tolyl)cyclopropane-1-ol, 1-(3,4-difluorophenyl)cyclopropane-1-ol, 1-(benzo[d][1,3]dioxacyclopentan-5-yl)cyclopropane-1-ol, 1-(naphthyl-2-yl)cyclopropane-1-ol or 1-(4'-propyl-[1,1'-biphenyl]-4-yl)cyclopropane-1-ol, N-alkyl-N-fluoro-2-methylaniline compounds and cyclopropanol compounds are 1 and 2 times that of the base, respectively;

[0017] (4) The mixture was stirred at room temperature for 24 hours under the illumination of a 5W blue LED light;

[0018] (5) After removing the solvent by vacuum concentration, the crude product is purified by column chromatography. The eluent is collected and dried to obtain the final product.

[0019] Preferably, in step (1), the base is K2CO3, CH3COONa, KOH, K2S2O8 or KHCO3; the copper catalyst is [Cu(CH3CN)4]PF6, Cu(OAc)2H2O, Cu(OAc)2, Cu(acac)2, Cu(CF3SO3)2 or CuI; the ligand is 3,4,7,8-tetramethyl-1,10-phenanthroline, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2,2'-bipyridine or 4,4'-di-tert-butyl-2,2'-bipyridine; and the photosensitizer is 4DPAIPN, [Ir(dtbbpy)(ppy)2]PF6, 4CzIPN, 4DPAIPN, Ir(ppy)3 or Rhodamine B.

[0020] The aforementioned benzamide compounds containing the aryl butyl ketone structure are used in the preparation of antitumor drugs, wherein the tumor is breast cancer, and the benzamide compounds containing the aryl butyl ketone structure are:

[0021] , , or .

[0022] The aforementioned benzamide compounds containing the aryl butyl ketone structure are used in the preparation of antitumor drugs, wherein the tumor is colon cancer, and the benzamide compounds containing the aryl butyl ketone structure are:

[0023] , , , , or .

[0024] The structures of benzenesulfonamide compounds containing the arylbutanone structure are shown below:

[0025]

[0026] Wherein, R1 is hydrogen, halogen, or alkyl; R2 is tert-butyl, tert-pentyl, or tert-octyl; and R3 is hydrogen, halogen, alkyl, or cyclic.

[0027] The preparation method of the aforementioned benzenesulfonamide compounds containing an aryl butanone structure includes the following steps:

[0028] (1) Add the base, copper catalyst, ligand and photosensitizer to a dry reaction vessel in a molar ratio of 1:0.1:0.1:0.02;

[0029] (2) After evacuating and filling the reaction vessel with argon five times, add an organic solvent;

[0030] (3) An N-alkyl-N-fluoro-2-methylbenzenesulfonamide compound and a cyclopropanol compound are added sequentially to the reaction mixture, wherein the N-alkyl-N-fluoro-2-methylbenzenesulfonamide compound is N-(tert-butyl)-N-fluoro-2-methylbenzenesulfonamide, N-(tert-butyl)-N,5-difluoro-2-methylbenzenesulfonamide, N-(tert-butyl)-N-fluoro-2,4,6-trimethylbenzenesulfonamide, or N-fluoro-2,4,6-trimethyl-N-( 2,4,4-Trimethylpent-2-yl)benzenesulfonamide or N-fluoro-2,4,6-trimethyl-N-(tert-pentyl)benzenesulfonamide, wherein the cyclopropanol compound is 1-phenylcyclopropane-1-ol, 1-(p-tolyl)cyclopropane-1-ol, 1-(4-(tert-butyl)phenyl)cyclopropane-1-ol, 1-(4-chlorophenyl)cyclopropane-1-ol, 1-(4-bromophenyl)cyclopropane-1-ol or 1-(naphthyl-2-yl)cyclopropane-1-ol, and the molar amounts of the N-alkyl-N-fluoro-2-methylbenzenesulfonamide compound and the cyclopropanol compound are 1 times and 2 times that of the base, respectively;

[0031] (4) The mixture was stirred at room temperature for 24 hours under the illumination of a 5W blue LED light;

[0032] (5) After removing the solvent by vacuum concentration, the crude product is purified by column chromatography. The eluent is collected and dried to obtain the final product.

[0033] Preferably, in step (1), the base is K2CO3, CH3COONa, KOH, K2S2O8 or KHCO3; the copper catalyst is [Cu(CH3CN)4]PF6, Cu(OAc)2H2O, Cu(OAc)2, Cu(acac)2, Cu(CF3SO3)2 or CuI; the ligand is 3,4,7,8-tetramethyl-1,10-phenanthroline, 1,10-phenanthroline, 4,7-diphenyl-1,10-phenanthroline, 2,2'-bipyridine or 4,4'-di-tert-butyl-2,2'-bipyridine; and the photosensitizer is 4DPAIPN, [Ir(dtbbpy)(ppy)2]PF6, 4CzIPN, 4DPAIPN, Ir(ppy)3 or Rhodamine B.

[0034] The aforementioned benzenesulfonamide compounds containing the aryl butyl ketone structure are used in the preparation of antitumor drugs, wherein the tumor is breast cancer, and the benzenesulfonamide compounds containing the aryl butyl ketone structure are:

[0035] .

[0036] The aforementioned benzenesulfonamide compounds containing the aryl butanone structure are used in the preparation of antitumor drugs, wherein the tumor is colon cancer, and the benzenesulfonamide compounds containing the aryl butanone structure are:

[0037] .

[0038] The advantages of this invention are:

[0039] (1) The compounds prepared in this invention showed a certain inhibitory effect on the proliferation of human breast cancer cells MCF-7. Among them, the compounds prepared in Examples 30, 33, 40, 42 and 50 had a strong inhibitory effect on human breast cancer cells MCF-7 and could be used as drug lead compounds for the preparation and development of subsequent anti-tumor drugs. Except for the above 5 compounds, the inhibitory activity of the other compounds on human breast cancer cells MCF-7 was lower than that of the positive control doxorubicin, but they also showed a certain inhibitory activity, which can provide a number of compounds for future new drug development.

[0040] (2) The compounds prepared in this invention showed a certain inhibitory effect on the proliferation of human colon cancer cells HCT-116. Among them, the compounds prepared in Examples 28, 29, 37, 38, 45, 47 and 55 had a strong inhibitory effect on human colon cancer cells HCT-116 and could be used as drug lead compounds for the preparation and development of subsequent anti-tumor drugs. Except for the above 7 compounds, the inhibitory activity of the other compounds on human colon cancer cells HCT-116 was lower than that of the positive control pentafluorouracil, but they also showed a certain inhibitory activity, which can provide a number of compounds for future new drug development.

[0041] (3) The preparation method of the above-mentioned compounds provided by the present invention is simple to operate, has mild reaction conditions, and is highly practical. Detailed Implementation

[0042] The present invention will be described in detail below with reference to specific embodiments.

[0043] I. Structure of Compounds

[0044] 1. Benzamide compounds containing the arylbutanone structure

[0045] The structures of the benzamide compounds containing the aryl butyl ketone structure provided by this invention are shown below:

[0046]

[0047] in:

[0048] R1 is: hydrogen, halogen (e.g., chlorine), alkyl (e.g., methyl) or alkoxy (e.g., methoxy);

[0049] R2 is: tert-butyl, tert-pentyl, tert-octyl, adamantyl, or α,α-dimethylbenzyl;

[0050] R3 can be: hydrogen, halogen (e.g., fluorine, chlorine, bromine), alkyl (e.g., methyl, tert-butyl), alkoxy (e.g., methoxy), fused ring (e.g., benzene ring, 1,3-dioxolane), or aryl (e.g., phenyl).

[0051] R4 is: hydrogen, alkyl (e.g., methyl) or aryl (e.g., phenyl).

[0052] 2. Benzenesulfonamide compounds containing the arylbutanone structure

[0053] The structures of the benzenesulfonamide compounds containing the aryl butyl ketone structure provided by this invention are shown below:

[0054]

[0055] in:

[0056] R1 is: hydrogen, halogen (e.g., fluorine) or alkyl (e.g., methyl);

[0057] R2 is: tert-butyl, tert-pentyl, or tert-octyl;

[0058] R3 is: hydrogen, halogen (e.g., chlorine, bromine), alkyl (e.g., methyl, tert-butyl), or fused ring (e.g., benzene ring).

[0059] II. Preparation methods of compounds

[0060] This invention uses cyclopropanol compounds and N-alkyl-N-fluoro-2-methylaniline / benzenesulfonamide compounds as raw materials, specifically 2,4,5,6-tetra(diphenylamino)-isophthalonitrile (abbreviated as 4DPAIPN), (4,4'-di-tert-butyl-2,2'-bipyridine)bis[(2-pyridyl)phenyl]iridium(III) hexafluorophosphate (abbreviated as [Ir(dtbbpy)(ppy)2]PF6), 2,4,5,6-tetra(9-carbazolyl)-isophthalonitrile (abbreviated as 4CzIPN), and tris(2-phenylpyridine)iridium (abbreviated as Ir). (ppy)3), Eosin Y or Rhodamine B as photosensitizers, copper tetraacetonitrile hexafluorophosphate (chemical formula [Cu(CH3CN)4]PF6), copper acetate (chemical formula Cu(OAc)2), copper acetate monohydrate (chemical formula Cu(OAc)2•H2O), copper trifluoromethanesulfonate (chemical formula Cu(CF3SO3)2), cuprous iodide (chemical formula CuI) or copper acetylacetonate (abbreviated as Cu(acac)2) as copper catalysts, and 3,4,7,8-tetramethyl-1,10-phenanthroline (denoted as L1) or 1,10-phenanthroline as catalysts. (L2), 4,7-diphenyl-1,10-phenanthroline (L3), 2,2'-bipyridine (L4), 4,4'-di-tert-butyl-2,2'-bipyridine (L5), 2,2':6',2''-bipyridine (L6), 4,4,4',4'-tetramethyl-4,4',5,5'-tetrahydro-2,2'-diazolazine (L7) or 4'-phenyl-3,2':6',3''-bipyridine (L8) as ligands, with potassium carbonate (chemical formula K2CO3) and sodium acetate (chemical formula CH3) as ligands. The above-mentioned benzamide / benzenesulfonamide compounds containing aryl butyl ketone structures were synthesized by using COONa, potassium hydroxide (KOH), potassium persulfate (K2S2O8) or potassium bicarbonate (KHCO3) as bases, and dichloromethane (DCM), 1,2-dichloroethane (DCE), tetrahydrofuran (THF), acetonitrile (MeCN) or toluene (PhCH3) as solvents. The reaction mixture was irradiated with a 5W blue LED lamp (wavelength 450-465nm) under an argon atmosphere and stirred at room temperature.

[0061] The reaction formula is shown below:

[0062]

[0063] The structures of each ligand are shown below: .

[0064] Example 1

[0065]

[0066] The following components were added to a dry Schlenk tube (25 mL): K₂CO₃ (0.1 mmol), Cu(OAc)₂ (0.01 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.01 mmol), and Ir(ppy)₃ (0.002 mmol). After evacuation and argon filling five times, DCM (2.0 mL) was added to the Schlenk tube via syringe. N-(tert-butyl)-N-fluoro-2-methylaniline (0.1 mmol) and 1-phenylcyclopropane-1-ol (0.2 mmol) were added sequentially to the reaction mixture using a microsyringe. The mixture was stirred at room temperature for 24 h under 5 W blue LED illumination. After solvent removal by vacuum concentration, the crude product was purified by column chromatography (300 mesh silica gel, mobile phase: petroleum ether and ethyl acetate mixed in a 25:1 volume ratio). The eluent was collected and dried to give a white solid, yielding 18 mg (56% yield).

[0067] The resulting products 1 HNMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0068] 1 H NMR (500MHz, CDCl3) δ 7.92 (d, J=7.2Hz, 2H), 7.53 (t, 1H), 7.44 (t, J=7.6Hz, 2H), 7.29 (t, J=6.7Hz, 2H), 7.24 (d, J=6.7Hz, 1H), 7.19 (t, J=8.2Hz, 1H), 5.64 (s, 1H), 3.02 (t, J=7.3Hz, 2H), 2.88 (t, J=7.7Hz, 2H), 2.13-2.02 (m, 2H), 1.46 (s, 9H);

[0069] 13 C NMR (126MHz, CDCl3) δ 200.11, 169.75, 139.44, 137.88, 136.99, 132.88, 130.08, 129.49, 128. 51, 128.02, 126.60, 125.97, 51.77, 38.07, 32.39, 29.67, 28.78, 25.71;

[0070] HRMS (ESI): m / z [M+H] + C 21 H 26 NO2: Theoretical value: 324.1959; Calculated molecular weight: 324.1950.

[0071] Examples 2-5

[0072] The preparation methods of Examples 2-5 are basically the same as those of Example 1, except that the solvents are different.

[0073] Table 1 Effect of solvent type on product yield

[0074]

[0075] Examples 6-10

[0076] The preparation methods of Examples 6-10 are basically the same as those of Example 1, except that the types of photosensitizers are different.

[0077] Table 2 Effect of photosensitizer type on product yield

[0078]

[0079] Examples 11-15

[0080] The preparation methods of Examples 11-15 are basically the same as those of Example 1, except that the types of copper catalysts are different.

[0081] Table 3 Effect of copper catalyst type on product yield

[0082]

[0083] Examples 16-22

[0084] The preparation methods of Examples 16-22 are basically the same as those of Example 1, except that the types of ligands are different.

[0085] Table 4 Effect of ligand type on product yield

[0086]

[0087] Examples 23-26

[0088] The preparation methods of Examples 23-26 are basically the same as those of Example 1, except that the types of alkali are different.

[0089] Table 5. Effect of Alkali Type on Product Yield

[0090]

[0091] As can be seen from Examples 1-26, the type of solvent, photosensitizer, copper catalyst, ligand, and base all have a significant impact on the yield of the product. Among them, the highest yield of the product was obtained when 4DPAIPN was used as the photosensitizer, [Cu(CH3CN)4]PF6 was used as the copper catalyst, 3,4,7,8-tetramethyl-1,10-phenanthroline was used as the ligand, K2CO3 was used as the base, and DCM was used as the solvent (78%, Example 15).

[0092] Example 27

[0093]

[0094] The following components were added to a dry Schlenk tube (25 mL): K₂CO₃ (0.1 mmol), [Cu(CH₃CN)₄]PF₆ (0.01 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.01 mmol), and 4DPAIPN (0.002 mmol). After evacuation and argon filling five times, DCM (2.0 mL) was added to the Schlenk tube via syringe. N-(tert-butyl)-N-fluoro-2-methylaniline (0.1 mmol) and 1-(p-tolyl)cyclopropane-1-ol (0.2 mmol) were added sequentially to the reaction mixture using a microsyringe. The mixture was stirred at room temperature for 24 h under 5 W blue LED illumination. After removing the solvent by vacuum concentration, the crude product was purified by column chromatography (silica gel with a particle size of 300 mesh, and the mobile phase being a mixture of petroleum ether and ethyl acetate at a volume ratio of 25:1). The eluent was collected and dried to obtain a white solid with a yield of 23 mg and a yield of 68%.

[0095] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0096] 1 H NMR (500MHz, CDCl3) δ 7.81 (d, J=8.2Hz, 2H), 7.35-7.13 (m, 6H), 5.68 (s, 1H), 2.98 (t, J=7.3Hz, 2H), 2.87 (t, J=7.8Hz, 2H), 2.39 (s, 3H), 2.13-1.99 (m, 2H), 1.45 (s, 9H);

[0097] 13C NMR (126MHz, CDCl3) δ 199.81, 169.78, 143.61, 139.40, 137.81, 134.45, 130.03, 129.44, 129. 16, 128.12, 126.56, 125.91, 51.74, 37.94, 32.37, 28.73, 25.78, 21.56;

[0098] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1934.

[0099] Example 28

[0100]

[0101] The preparation method of Example 28 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-(tert-butyl)phenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 23 mg and a yield of 61%.

[0102] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0103] 1 H NMR (500MHz, CDCl3) δ 7.86 (d, J=8.7Hz, 2H), 7.45 (d, J=8.5Hz, 2H), 7.29 (t, 2H), 7.24 (d, J=6.7Hz, 1H), 7.18 (t, J=8.2Hz, 1H), 5.63 (s, 1H), 2.99 (t, J=7.3Hz, 2H), 2.87 (t, J=7.7Hz, 2H), 2.18-1.97 (m, 2H), 1.45 (s, 9H), 1.33 (s, 9H);

[0104] 13 C NMR (126MHz, CDCl3) δ 199.78, 169.76, 156.58, 139.48, 137.87, 134.42, 130.07, 129.47, 127.99, 126.59, 125.94, 125.45, 51.76, 38.00, 35.05, 32.43, 31.07, 28.78, 25.83;

[0105] HRMS (ESI): m / z [M+Na] + C 25 H 33 NNaO2: Theoretical value: 402.2404; Calculated molecular weight: 402.2405.

[0106] Example 29

[0107]

[0108] The preparation method of Example 29 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-methoxyphenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 25 g and a yield of 71%.

[0109] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0110] 1 H NMR (500MHz, CDCl3) δ 7.90 (d, J=8.9Hz, 2H), 7.29 (t, J=6.8Hz, 2H), 7.24 (d, J=6.6Hz, 1H), 7.18 (t, J=8.1Hz, 1H), 6.91 (d, J=9.0Hz, 2H), 5.65 (s, 1H), 3.84 (s, 3H), 2.96 (t, J=7.3Hz, 2H), 2.87 (t, J=7.7Hz, 2H), 2.15-2.00 (m, 2H), 1.45 (s, 9H);

[0111] 13 C NMR (126MHz, CDCl3) δ 198.71, 169.78, 163.30, 139.45, 137.85, 130.27, 130.08, 130.05, 129. 45, 126.58, 125.92, 113.62, 55.42, 51.75, 37.74, 32.43, 28.76, 25.92;

[0112] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO3: Theoretical value: 376.1884; Calculated molecular weight: 376.1874.

[0113] Example 30

[0114]

[0115] The preparation method of Example 30 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-chlorophenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 32 mg and a yield of 91%.

[0116] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0117] 1 H NMR (500MHz, CDCl3) δ 7.86 (d, J=8.5Hz, 2H), 7.41 (d, J=8.7Hz, 2H), 7.32-7.14 (m, 4H), 5.64 (s, 1H), 2.98 (t, J=7.3Hz, 2H), 2.86 (t, J=7.7Hz, 2H), 2.12-2.02 (m, 2H), 1.45 (s, 9H);

[0118] 13 C NMR (126MHz, CDCl3) δ 198.88, 169.73, 139.32, 139.28, 137.85, 135.26, 130.05, 129.52, 129.46, 128.81, 126.61, 126.03, 51.77, 38.01, 32.32, 28.77, 25.63;

[0119] HRMS (ESI): m / z [M+Na] + C 21 H 24 ClNNaO2: Theoretical value: 380.1388; Calculated molecular weight: 380.1398.

[0120] Example 31

[0121]

[0122] The preparation method of Example 31 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-bromophenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 35 mg and a recovery rate of 87%.

[0123] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0124] 1 H NMR (500MHz, CDCl3) δ 7.78 (d, J=8.7Hz, 2H), 7.57 (d, J=8.7Hz, 2H), 7.29 (t, J=5.5Hz, 2H), 7.24-7.16 (m, 2H), 5 .65 (s, 1H), 2.97 (t, J=7.3Hz, 2H), 2.86 (t, J=7.6Hz, 2H), 2.15-2.00 (m, 2H), 1.45 (s, 9H);

[0125] 13 C NMR (126MHz, CDCl3) δ 199.06, 169.72, 139.30, 137.83, 135.64, 131.79, 130.04, 129.57, 129.51, 127.99, 126.59, 126.02, 51.76, 37.98, 32.30, 28.76, 25.59;

[0126] HRMS (ESI): m / z [M+Na] + C 21 H 24 BrNNaO2: Theoretical value: 424.0883; Calculated molecular weight: 424.0873.

[0127] Example 32

[0128]

[0129] The preparation method of Example 32 is basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol is replaced with an equimolar amount (0.2 mmol) of 1-(m-tolyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 15 mg and a yield of 45%.

[0130] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0131] 1 H NMR (500MHz, CDCl3) δ 7.71 (d, J=11.6Hz, 2H), 7.38-7.27 (m, 4H), 7.24 (d, J=6.6Hz, 1H), 7.19 (t, J=8.2Hz, 1H), 5.65 (s , 1H), 3.00 (t, J=7.2Hz, 2H), 2.88 (t, J=7.8Hz, 2H), 2.40 (s, 3H), 2.12-2.03 (m, 2H), 1.45 (s, 9H);

[0132] 13 C NMR (126MHz, CDCl3) δ 200.39, 169.78, 139.46, 138.28, 137.84, 137.01, 133.65, 130.08, 129.49, 128. 54, 128.38, 126.59, 125.95, 125.26, 51.77, 38.15, 32.41, 28.77, 25.80, 21.33;

[0133] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1926.

[0134] Example 33

[0135]

[0136] The preparation method of Example 33 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(o-tolyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 18 mg and a yield of 53%.

[0137] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0138] 1 H NMR (500MHz, CDCl3) δ 7.58 (d, J=7.6Hz, 1H), 7.36-7.27 (m, 3H), 7.25-7.16 (m, 4H), 5.65 (s, 1H), 2.93 (t, J=7.3Hz, 2H), 2.86 (t, J=7.8Hz, 2H), 2.45 (s, 3H), 2.08-2.01 (m, 2H), 1.45 (s, 9H);

[0139] 13 C NMR (126MHz, CDCl3) δ 204.28, 169.73, 139.42, 138.09, 137.81, 131.82, 131.04, 130.06, 129.47, 128.34, 126.59, 125.95, 125.60, 51.74, 41.06, 32.38, 28.75, 25.76, 21.17;

[0140] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1927.

[0141] Example 34

[0142]

[0143] The preparation method of Example 34 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(3,4-difluorophenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 33 mg and a yield of 92%.

[0144] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0145] 1 H NMR (500MHz, CDCl3) δ 7.79-7.67 (m, 2H), 7.32-7.26 (m, 2H), 7.24-7.15 (m, 3H), 5.65 (s, 1H), 2.9 5 (t, J=7.2Hz, 2H), 2.86 (t, J=7.6Hz, 2H), 2.12-2.02 (m, 2H), 1.45 (s, 9H);

[0146] 13 C NMR (126MHz, CDCl3) δ 197.50, 169.69, 154.89-148.40 (m), 139.28, 137.85, 135.16-133.42 (m), 130.07, 129.55, 1 26.62, 126.08, 125.41-124.69 (m), 118.13-116.64 (m), 51.78, 37.91, 32.28, 28.77, 25.59;

[0147] HRMS (ESI): m / z [M+Na] + C 21 H 23 F2NNaO2: Theoretical value: 382.1590; Calculated molecular weight: 382.1593.

[0148] Example 35

[0149]

[0150] The preparation method of Example 35 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(benzo[d][1,3]dioxacyclopentan-5-yl)cyclopropane-1-ol. A colorless oil was obtained, with a yield of 33 mg and a recovery rate of 82%.

[0151] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0152] 1 H NMR (500MHz, CDCl3) δ 7.51 (d, J=8.2Hz, 1H), 7.39 (s, 1H), 7.29 (t, J=6.0Hz, 2H), 7.23 (d, J=6.7Hz, 1H), 7.18 (t, J=8.1Hz, 1H), 6.82 (d, J= 8.2Hz, 1H), 6.02 (s, 2H), 5.66 (s, 1H), 2.92 (t, J=7.3Hz, 2H), 2.85 (t, J=7.7Hz, 2H), 2.15-2.00 (m, 2H), 1.45 (s, 9H);

[0153] 13 C NMR (126MHz, CDCl3) δ 198.17, 169.76, 151.55, 148.07, 139.43, 137.84, 131.85, 130.07, 129.48, 126. 59, 125.95, 124.25, 107.86, 107.80, 101.75, 51.76, 37.85, 32.39, 28.78, 25.94;

[0154] HRMS (ESI): m / z [M+Na] + C 22 H 25 NNaO4: Theoretical value: 390.1676; Calculated molecular weight: 390.1666.

[0155] Example 36

[0156]

[0157] The preparation method of Example 36 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(naphthyl-2-yl)cyclopropane-1-ol. A white solid was obtained, with a yield of 27 mg and a yield of 72%.

[0158] The resulting products1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0159] 1 H NMR (500MHz, CDCl3) δ 8.49 (s, 1H), 8.04 (d, J=10.4Hz, 1H), 7.97 (d, J=8.1Hz, 1H), 7.89 (t, J=9.2Hz, 2H), 7.62-7.54 (m, 2H), 7.3 0-7.25 (m, 2H), 7.21-7.14 (m, 2H), 5.63 (s, 1H), 3.20 (t, 2H), 3.10 (s, 2H), 2.15-2.00 (m, 2H), 1.45 (s, 9H);

[0160] 13 C NMR (126MHz, CDCl3) δ 200.00, 169.81, 139.47, 137.85, 135.55, 134.30, 132.55, 130.53, 129.66, 129.56, 129.41, 1 28.44, 128.38, 127.76, 126.74, 126.58, 125.90, 123.89, 51.73, 38.51, 35.15, 28.82, 24.13;

[0161] HRMS (ESI): m / z [M+Na] + C 25 H 27 NNaO2: Theoretical value: 396.1934; Calculated molecular weight: 396.1924.

[0162] Example 37

[0163]

[0164] The preparation method of Example 37 was basically the same as that of Example 27, except that 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4'-propyl-[1,1'-biphenyl]-4-yl)-cyclopropane-1-ol. A white solid was obtained, with a yield of 32 mg and a recovery rate of 72%.

[0165] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0166] 1H NMR (500MHz, CDCl3) δ 7.97 (d, J=8.4Hz, 2H), 7.64 (d, J=8.4Hz, 2H), 7.53 (d, J=8.2Hz, 2H), 7.31-7.23 (m, 5H), 7.18 (t, J=7.3Hz, 1H), 5.65 (s, 1H), 3.03 (t, J =7.3Hz, 2H), 2.89 (t, J=7.7Hz, 2H), 2.63 (t, J=7.7Hz, 2H), 2.16-2.05 (m, 2H), 1.71-1.65 (m, 2H), 1.45 (s, 9H), 0.97 (t, J=7.3Hz, 3H);

[0167] 13 C NMR (126MHz, CDCl3) δ 199.68, 169.75, 145.51, 142.93, 139.44, 137.87, 137.21, 135.39, 130.07, 129.47, 129.04, 128 .59, 127.03, 126.90, 126.59, 125.95, 51.70, 38.08, 37.67, 32.40, 28.77, 25.80, 24.47, 13.82;

[0168] HRMS (ESI): m / z [M+Na] + C 30 H 35 NNaO2: Theoretical value: 464.2560; Calculated molecular weight: 464.2552.

[0169] Example 38

[0170]

[0171] The preparation method of Example 38 was basically the same as that of Example 27, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2-methylaniline, and 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-phenylcyclopropane-1-ol. A white solid was obtained, with a yield of 14 mg and a yield of 45%.

[0172] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0173] 1H NMR (500MHz, CDCl3) δ 7.71 (d, J=11.6Hz, 2H), 7.38-7.27 (m, 4H), 7.24 (d, J=6.6Hz, 1H), 7.19 (t, J=8.2Hz, 1H), 5.65 (s , 1H), 3.00 (t, J=7.2Hz, 2H), 2.88 (t, J=7.8Hz, 2H), 2.40 (s, 3H), 2.12-2.03 (m, 2H), 1.45 (s, 9H);

[0174] 13 C NMR (126MHz, CDCl3) δ 200.39, 169.78, 139.46, 138.28, 137.84, 137.01, 133.65, 130.08, 129.49, 128. 54, 128.38, 126.59, 125.95, 125.26, 51.77, 38.15, 32.41, 28.77, 25.80, 21.33;

[0175] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1926.

[0176] Example 39

[0177]

[0178] The preparation method of Example 39 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,5-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2,4-dimethylaniline. A white solid was obtained, with a yield of 17 mg and a yield of 50%.

[0179] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0180] 1H NMR (500MHz, CDCl3) δ 7.92 (d, J=7.2Hz, 2H), 7.53 (t, J=7.4Hz, 1H), 7.43 (t, J=7.7Hz, 2H), 7.15-7.07 (m, 3H), 5.62 (s, 1H), 3.00 (t, J=7.3Hz, 2H), 2.83 (t, J=7.7Hz, 2H), 2.31 (s, 3H), 2.10-2.01 (m, 2H), 1.45 (s, 9H);

[0181] 13 C NMR (126MHz, CDCl3) δ 200.18, 169.90, 137.75, 136.97, 136.16, 135.56, 132.84, 130.11, 129. 96, 128.47, 128.00, 127.19, 51.69, 38.03, 31.93, 28.76, 25.76, 20.79;

[0182] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1925.

[0183] Example 40

[0184]

[0185] The preparation method of Example 40 is basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,3-dimethylaniline is replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2,4-dimethylaniline. A white solid was obtained, with a yield of 14 mg and a yield of 42%.

[0186] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0187] 1 H NMR (500MHz, CDCl3) δ 7.96 (d, J=8.5Hz, 2H), 7.55 (t, 1H), 7.45 (t, J=7.7Hz, 2H), 7.17 (d, J=7.2Hz, 1H), 7.14-7.06 (m, 2 H), 5.58 (s, 1H), 3.07 (t, J=7.2Hz, 2H), 2.84 (t, 2H), 2.37 (s, 3H), 2.09-1.94 (m, 2H), 1.45 (s, 9H);

[0188] 13 C NMR (126MHz, CDCl3) δ 200.13, 170.40, 138.59, 137.62, 137.42, 137.00, 132.89, 131.42, 128. 52, 128.03, 125.81, 124.22, 51.70, 38.60, 29.54, 28.77, 24.86, 19.51;

[0189] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1926.

[0190] Example 41

[0191]

[0192] The preparation method of Example 41 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,6-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2,4-dimethylaniline. A white solid was obtained, with a yield of 18 mg and a yield of 53%.

[0193] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0194] 1 H NMR (500MHz, CDCl3) δ 7.91 (d, J=7.6Hz, 2H), 7.54 (t, J=8.0Hz, 1H), 7.44 (t, J=7.6Hz, 2H), 7.15 (t, J=7.6Hz, 1H), 7.07-6.97 (m, 2 H), 5.59 (s, 1H), 3.00 (t, J=7.2Hz, 2H), 2.74 (t, J=7.7Hz, 2H), 2.34 (s, 3H), 2.14-2.06 (m, 2H), 1.47 (s, 9H);

[0195] 13C NMR (126MHz, CDCl3) δ 200.11, 169.36, 138.47, 137.71, 136.92, 134.05, 132.89, 128.50, 128. 45, 128.01, 127.79, 126.56, 51.81, 37.93, 32.36, 28.77, 25.68, 19.03;

[0196] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1933.

[0197] Example 42

[0198]

[0199] The preparation method of Example 42 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-4-chloro-2-methylaniline. A white solid was obtained, with a yield of 22 mg and a yield of 62%.

[0200] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0201] 1 H NMR (500MHz, CDCl3) δ 7.91 (d, J=8.7Hz, 2H), 7.54 (t, 1H), 7.44 (t, J=7.7Hz, 2H), 7.25-7.20 (m, 2H), 7.15 (d, J=8.1Hz, 1H), 5.68 (s, 1H), 3.01 (t, J=7.2Hz, 2H), 2.84 (t, J=7.8Hz, 2H), 2.13-2.02 (m, 2H), 1.45 (s, 9H);

[0202] 13 C NMR (126MHz, CDCl3) δ 199.85, 168.75, 141.62, 136.86, 136.20, 135.21, 132.98, 129.99, 128.55, 127.97, 126.07, 51.93, 37.90, 32.22, 28.72, 25.39;

[0203] HRMS (ESI): m / z [M+Na] +C 21 H 24 ClNNaO2: Theoretical value: 380.1388; Calculated molecular weight: 380.1384.

[0204] Example 43

[0205]

[0206] The preparation method of Example 43 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-4-methoxy-2-methylaniline. A white solid was obtained, with a yield of 23 mg and a yield of 65%.

[0207] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0208] 1 H NMR (500MHz, CDCl3) δ 7.92 (d, J=8.1Hz, 2H), 7.54 (t, J=7.4Hz, 1H), 7.44 (t, J=7.7Hz, 2H), 7.25 (d, J=6.4Hz, 1H), 6.75 (s, 1H), 6.69 (d, J=1 1.0Hz, 1H), 5.61 (s, 1H), 3.77 (s, 3H), 3.02 (t, J=7.3Hz, 2H), 2.89 (t, J=7.8Hz, 2H), 2.12-2.04 (m, 2H), 1.44 (s, 9H);

[0209] 13 C NMR (126MHz, CDCl3) δ 200.17, 169.58, 160.30, 141.89, 136.99, 132.89, 130.43, 128.52, 128. 28, 128.02, 115.48, 111.10, 55.23, 51.61, 38.08, 32.66, 28.80, 25.67;

[0210] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO3: Theoretical value: 376.1883; Calculated molecular weight: 376.1879.

[0211] Example 44

[0212]

[0213] The preparation method of Example 44 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2-ethylbenzamide was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2,4-dimethylaniline. A white solid was obtained, with a yield of 31 mg and a yield of 92%.

[0214] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0215] 1 H NMR (500MHz, CDCl3) δ 7.84 (d, J=7.0Hz, 2H), 7.51 (t, J=7.4Hz, 1H), 7.40 (t, J=7.7Hz, 2H), 7.36-7.29 (m, 2H), 7.26 (d, 1H), 7.17 (t, J=7.2Hz, 1H), 5 .64 (s, 1H), 3.35-3.17 (m, 1H), 3.04-2.89 (m, 1H), 2.86-2.69 (m, 1H), 2.15-2.00 (m, 2H), 1.45 (s, 9H), 1.31 (d, J=6.9Hz, 3H);

[0216] 13 C NMR (126MHz, CDCl3) δ 200.37, 169.93, 143.87, 138.25, 136.87, 132.82, 129.65, 128.44, 128. 02, 126.35, 126.22, 125.86, 51.80, 37.02, 34.85, 32.21, 28.79, 22.96;

[0217] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1936.

[0218] Example 45

[0219]

[0220] The preparation method of Example 45 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2-benzyl-benzamide was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2,4-dimethylaniline. A white solid was obtained, with a yield of 25 mg and a recovery rate of 63%.

[0221] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0222] 1 H NMR (500MHz, CDCl3) δ 7.86 (d, J=7.2Hz, 2H), 7.51 (t, J=7.4Hz, 1H), 7.43-7.38 (m, 3H), 7.35 (t, J=7.6Hz, 1H), 7.32-7.26 (m, 5H), 7.22-7.15 (m, 2H), 5.44 (s, 1H), 4.64 (t, J=7.9Hz, 1H), 3.07-2.91 (m, 2H), 2.54-2.45 (m, 2H), 1.39 (s, 9H);

[0223] 13 C NMR (126MHz, CDCl3) δ 199.99, 169.76, 144.42, 141.37, 138.41, 136.83, 132.90, 129.75, 128.53, 128. 47, 128.03, 127.58, 126.99, 126.33, 126.23, 51.79, 45.40, 37.28, 30.19, 28.70;

[0224] HRMS (ESI): m / z [M+Na] + C 27 H 29 NNaO2: Theoretical value: 422.2090; Calculated molecular weight: 422.2098.

[0225] Example 46

[0226]

[0227] The preparation method of Example 46 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-fluoro-N-(tert-amyl)-2-methylaniline. A white solid was obtained, with a yield of 21 mg and a yield of 62%.

[0228] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0229] 1H NMR (500MHz, CDCl3) δ 7.92 (d, J=7.0Hz, 2H), 7.54 (t, J=7.4Hz, 1H), 7.44 (t, J=7.7Hz, 2H), 7.30 (t, 2H), 7.25 (d, J=7.5Hz, 1H), 7.19 (t, J=7.4Hz, 1H), 5. 53 (s, 1H), 3.02 (t, J=7.3Hz, 2H), 2.89 (t, J=7.8Hz, 2H), 2.13-2.05 (m, 2H), 1.89-1.79 (m, 2H), 1.40 (s, 6H), 0.92 (t, J=7.5Hz, 3H);

[0230] 13 C NMR (126MHz, CDCl3) δ 200.09, 169.70, 139.50, 137.88, 136.96, 132.87, 130.06, 129.49, 128.50 , 128.00, 126.61, 125.96, 54.55, 38.07, 32.77, 32.35, 26.43, 25.74, 8.47;

[0231] HRMS (ESI): m / z [M+Na] + C 22 H 27 NNaO2: Theoretical value: 360.1934; Calculated molecular weight: 360.1937.

[0232] Example 47

[0233]

[0234] The preparation method of Example 47 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-fluoro-N-(adamantyl)-2-methylaniline. A white solid was obtained, with a yield of 32 mg and a recovery rate of 79%.

[0235] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0236] 1H NMR (500MHz, CDCl3) δ 7.93 (d, J=6.9Hz, 2H), 7.54 (t, J=7.4Hz, 1H), 7.44 (t, J=7.7Hz, 2H), 7.29 (t, J=7.9Hz, 2H), 7.24 (d, J=6.3Hz, 1H), 7 .18 (t, 1H), 5.49 (s, 1H), 3.02 (t, J=7.3Hz, 2H), 2.89 (t, J=7.7Hz, 2H), 2.20-2.02 (m, 11H), 1.73 (t, J=13.7Hz, 6H);

[0237] 13 C NMR (126MHz, CDCl3) δ 200.16, 169.51, 139.39, 137.93, 136.97, 132.89, 130.08, 129.45, 128.50, 128.04, 126.60, 125.95, 52.51, 41.58, 38.09, 36.32, 32.38, 29.44, 25.70;

[0238] HRMS (ESI): m / z [M+Na] + C 27 H 31 NNaO2: Theoretical value: 424.2247; Calculated molecular weight: 424.2254.

[0239] Example 48

[0240]

[0241] The preparation method of Example 48 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-fluoro-2-methyl-N-(2,4,4-trimethylpentan-2-yl)aniline. A white solid was obtained, with a yield of 36 mg and a recovery rate of 94%.

[0242] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0243] 1H NMR (500MHz, CDCl3) δ 7.94 (d, J=7.0Hz, 2H), 7.55 (t, J=7.4Hz, 1H), 7.45 (t, J=7.7Hz, 2H), 7.33-7.25 (m, 3H), 7.20 (t, J=7.3Hz, 1H) , 5.63 (s, 1H), 3.03 (t, J=7.3Hz, 2H), 2.90 (t, 2H), 2.15-2.05 (m, 2H), 1.86 (s, 2H), 1.52 (s, 6H), 1.06 (s, 9H);

[0244] 13 C NMR (126MHz, CDCl3) δ 200.11, 169.28, 139.74, 137.91, 136.97, 132.88, 130.17, 129.49, 128.51, 128 .02, 126.30, 125.99, 55.83, 51.87, 38.10, 32.34, 31.69, 31.58, 29.06, 25.77;

[0245] HRMS (ESI): m / z [M+Na] + C 25 H 33 NNaO2: Theoretical value: 402.2404; Calculated molecular weight: 402.2407.

[0246] Example 49

[0247]

[0248] The preparation method of Example 49 was basically the same as that of Example 38, except that N-(tert-butyl)-N-fluoro-2,4-dimethylaniline was replaced with an equimolar amount (0.1 mmol) of N-fluoro-2-methyl-N-(2-phenylprop-2-yl)aniline. A white solid was obtained, with a yield of 20 mg and a yield of 52%.

[0249] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0250] 1H NMR (500MHz, CDCl3) δ 7.90 (d, J=8.1Hz, 2H), 7.53 (t, J=7.4Hz, 1H), 7.48 (d, J=8.4Hz, 2H), 7.43 (t, J=7.9Hz, 2H), 7.38 (d, J=7.5Hz, 1H), 7.35-7.28 (m, 3H), 7 .25 (d, J=7.8Hz, 1H), 7.20 (t, J=7.4Hz, 2H), 6.15 (s, 1H), 2.95 (t, J=7.3Hz, 2H), 2.85 (t, J=7.9Hz, 2H), 2.09-1.99 (m, 2H), 1.80 (s, 6H);

[0251] 13 C NMR (126MHz, CDCl3) δ 200.09, 169.12, 146.64, 140.01, 137.15, 136.93, 132.85, 130.19, 129.70, 128.48, 1 28.38, 127.98, 126.69, 126.66, 125.94, 124.74, 56.23, 38.07, 32.30, 28.94, 25.80;

[0252] HRMS (ESI): m / z [M+Na] + C 26 H 27 NNaO2: Theoretical value: 408.1934; Calculated molecular weight: 408.1936.

[0253] Example 50

[0254]

[0255] The following components were added to a dry Schlenk tube (25 mL): K₂CO₃ (0.1 mmol), [Cu(CH₃CN)₄]PF₆ (0.01 mmol), 3,4,7,8-tetramethyl-1,10-phenanthroline (0.01 mmol), and 4DPAIPN (0.002 mmol). After evacuation and argon filling five times, DCM (2.0 mL) was added to the Schlenk tube using a syringe. N-(tert-butyl)-N-fluoro-2-methylbenzenesulfonamide (0.1 mmol) and 1-phenylcyclopropane-1-ol (0.2 mmol) were added sequentially to the reaction mixture using a microsyringe. The mixture was stirred at room temperature for 24 h under 5 W blue LED illumination. After removing the solvent by vacuum concentration, the crude product was purified by column chromatography (silica gel with a particle size of 300 mesh, and a mobile phase of petroleum ether and ethyl acetate mixed in a volume ratio of 7:1). The eluent was collected and dried to give a white solid with a yield of 4 mg and a yield of 11%.

[0256] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0257] 1 H NMR (500MHz, CDCl3) δ 8.05 (d, J=8.1Hz, 1H), 8.00 (d, J=8.5Hz, 2H), 7.57 (t, 1H), 7.50-7.44 (m, 3H), 7.37 (d, J=9.0Hz, 1 H), 7.30 (t, 1H), 5.71 (s, 1H), 3.17 (t, J=6.3Hz, 2H), 3.10 (t, 2H), 2.17-2.09 (m, 2H), 1.27 (s, 9H);

[0258] 13 C NMR (126MHz, CDCl3) δ 200.15, 141.76, 140.51, 136.82, 133.26, 132.14, 131.36, 129.05, 128.61, 128.11, 126.17, 54.88, 37.83, 31.91, 30.27, 25.41;

[0259] HRMS (ESI): m / z [M+Na] + C 20 H 25 NNaO3S: Theoretical value: 382.1447; Calculated molecular weight: 382.1455.

[0260] Example 51

[0261]

[0262] The preparation method of Example 51 was basically the same as that of Example 50, except that N-(tert-butyl)-N,5-difluoro-2-methylbenzenesulfonamide was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N,5-difluoro-2-methylbenzenesulfonamide. A white solid was obtained, with a yield of 8 mg and a yield of 21%.

[0263] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0264] 1 H NMR (500MHz, CDCl3) δ 8.00 (d, J=9.8Hz, 2H), 7.78 (d, J=9.0Hz, 1H), 7.59 (t, 1H), 7.48 (t, J=7.7Hz, 2H), 7.36-7.31 (m, 1H), 7 .16 (t, J=6.7Hz, 1H), 6.03 (s, 1H), 3.18 (t, J=6.2Hz, 2H), 3.05 (t, 2H), 2.17-2.09 (m, 2H), 1.29 (s, 9H);

[0265] 13 C NMR (126MHz, CDCl3) δ 200.14, 160.24 (d, J=248.2Hz), 143.61 (d, J=6.4Hz), 136.73, 136.12 (d, J=3.7Hz), 133.37, 133.03 (d, J= 7.4Hz), 128.63, 128.11, 119.02 (d, J=20.7Hz), 116.13 (d, J=24.8Hz), 55.13, 37.64, 31.18, 30.26, 25.44;

[0266] HRMS (ESI): m / z [M+Na] + C 20 H 24 FNNaO3S: Theoretical value: 400.1353; Calculated molecular weight: 400.1360.

[0267] Example 52

[0268]

[0269] The preparation method of Example 52 was basically the same as that of Example 50, except that N-(tert-butyl)-N-fluoro-2,4,6-trimethylbenzenesulfonamide was replaced with an equimolar amount (0.1 mmol) of N-(tert-butyl)-N-fluoro-2-methylbenzenesulfonamide, and 1-(p-tolyl)cyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-phenylcyclopropane-1-ol. A white solid was obtained, with a yield of 35 mg and a recovery rate of 88%.

[0270] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0271] 1 H NMR (500MHz, CDCl3) δ 7.88 (d, J=8.4Hz, 2H), 7.25 (d, 2H), 7.00 (s, 1H), 6.92 (s, 1H), 5.19 (s, 1H), 3.14 (t, 2H), 3. 08 (t, J=6.8Hz, 2H), 2.67 (s, 3H), 2.40 (s, 3H), 2.28 (s, 3H), 2.14-2.06 (m, 2H), 1.24 (s, 9H);

[0272] 13 C NMR (126MHz, CDCl3) δ 199.99, 143.75, 142.36, 141.50, 138.03, 137.48, 134.47, 132.14, 131.24 , 129.20, 128.22, 54.71, 38.06, 33.87, 30.15, 26.62, 23.22, 21.60, 20.88;

[0273] HRMS (ESI): m / z [M+Na] + C 23 H 31 NNaO3S: Theoretical value: 424.1917; Calculated molecular weight: 424.1915.

[0274] Example 53

[0275]

[0276] The preparation method of Example 53 was basically the same as that of Example 52, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-(tert-butyl)phenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 33 mg and a yield of 75%.

[0277] The resulting products 1H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0278] 1 H NMR (500MHz, CDCl3) δ 7.92 (d, J=8.7Hz, 2H), 7.46 (d, J=8.5Hz, 2H), 7.00 (s, 1H), 6.92 (s, 1H), 5.20 (s, 1H), 3.14 (t, 2H ), 3.09 (t, J=6.8Hz, 2H), 2.68 (s, 3H), 2.28 (s, 3H), 2.14-2.06 (m, 2H), 1.34 (s, 9H), 1.24 (s, 9H);

[0279] 13 C NMR (126MHz, CDCl3) δ 200.01, 156.69, 142.37, 141.50, 138.03, 137.48, 134.39, 132.14, 131.25, 12 8.07, 125.45, 54.70, 38.08, 35.05, 33.88, 31.05, 30.15, 26.63, 23.21, 20.87;

[0280] HRMS (ESI): m / z [M+Na] + C 26 H 37 NNaO3S: Theoretical value: 466.2387; Calculated molecular weight: 466.2383.

[0281] Example 54

[0282]

[0283] The preparation method of Example 54 was basically the same as that of Example 52, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-chlorophenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 38 mg and a yield of 91%.

[0284] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0285] 1H NMR (400MHz, CDCl3) δ 7.91 (d, J=8.8Hz, 2H), 7.43 (d, J=8.7Hz, 2H), 6.98 (s, 1H), 6.94 (s, 1H), 4.95 (s, 1H), 3.18-3 .10 (m, 2H), 3.07 (t, J=6.9Hz, 2H), 2.67 (s, 3H), 2.28 (s, 3H), 2.15-2.04 (m, 2H), 1.23 (s, 9H);

[0286] 13 C NMR (101MHz, CDCl3) δ 199.16, 142.25, 141.66, 139.44, 138.14, 137.41, 135.23, 132.26, 131 .29, 129.57, 128.87, 54.76, 38.22, 33.91, 30.16, 26.63, 23.12, 20.89;

[0287] HRMS (ESI): m / z [M+Na] + C 22 H 28 ClNNaO3S: Theoretical value: 444.1371; Calculated molecular weight: 444.1367.

[0288] Example 55

[0289]

[0290] The preparation method of Example 55 was basically the same as that of Example 52, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(4-bromophenyl)cyclopropane-1-ol. A white solid was obtained, with a yield of 37 mg and a yield of 79%.

[0291] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0292] 1 H NMR (500MHz, CDCl3) δ 7.84 (d, J=8.5Hz, 2H), 7.59 (d, J=8.7Hz, 2H), 6.98 (s, 1H), 6.93 (s, 1H), 5.00 (s, 1H), 3.14 (t, 2H), 3.06 (t, J=6.9Hz, 2H), 2.67 (s, 3H), 2.28 (s, 3H), 2.14-2.06 (m, 2H), 1.23 (s, 9H);

[0293] 13 C NMR (126MHz, CDCl3) δ 199.31, 142.21, 141.64, 138.11, 137.38, 135.59, 132.25, 131.84, 131 .27, 129.67, 128.16, 54.75, 38.20, 33.88, 30.15, 26.59, 23.13, 20.90;

[0294] HRMS (ESI): m / z [M+Na] + C 22 H 28 BrNNaO3S: Theoretical value: 488.0866; Calculated molecular weight: 488.0863.

[0295] Example 56

[0296]

[0297] The preparation method of Example 56 was basically the same as that of Example 52, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.2 mmol) of 1-(naphthyl-2-yl)cyclopropane-1-ol. A white solid was obtained, with a yield of 24 mg and a yield of 54%.

[0298] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0299] 1 H NMR (500MHz, CDCl3) δ 8.51 (s, 1H), 8.04 (d, J=10.5Hz, 1H), 7.97 (d, J=8.1Hz, 1H), 7.87 (t, J=8.5Hz, 2H), 7.62-7.52 (m, 2H), 7.02 (s, 1H), 6. 93 (s, 1H), 5.18 (s, 1H), 3.25 (t, J=6.8Hz, 2H), 3.20 (t, 2H), 2.68 (s, 3H), 2.28 (s, 3H), 2.22-2.13 (m, 2H), 1.25 (s, 9H);

[0300] 13C NMR (126MHz, CDCl3) δ 200.33, 142.34, 141.58, 138.08, 137.45, 135.54, 134.20, 132.51, 132.18, 131.26, 129.87, 129 .61, 128.36, 128.32, 127.70, 126.67, 123.86, 54.72, 38.32, 33.95, 30.15, 26.79, 23.19, 20.88;

[0301] HRMS (ESI): m / z [M+Na] + C 26 H 31 NNaO3S: Theoretical value: 460.1917; Calculated molecular weight: 460.1913.

[0302] Example 57

[0303]

[0304] The preparation method of Example 57 was basically the same as that of Example 50, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.1 mmol) of N-fluoro-2,4,6-trimethyl-N-(2,4,4-trimethylpentan-2-yl)benzenesulfonamide. A white solid was obtained, with a yield of 23 mg and a yield of 52%.

[0305] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0306] 1 H NMR (500MHz, CDCl3) δ 7.98 (d, J=7.0Hz, 2H), 7.55 (t, J=7.3Hz, 1H), 7.46 (t, J=7.7Hz, 2H), 7.00 (s, 1H), 6.92 (s, 1H), 4.96 (s, 1H ), 3.17-3.08 (m, 4H), 2.67 (s, 3H), 2.28 (s, 3H), 2.15-2.07 (m, 2H), 1.62 (s, 2H), 1.24 (s, 6H), 1.04 (s, 9H);

[0307] 13C NMR (126MHz, CDCl3) δ 200.33, 142.21, 141.49, 137.91, 136.96, 132.98, 132.17, 131.26, 128.53, 12 8.09, 58.84, 55.42, 38.18, 33.96, 31.68, 31.64, 29.39, 26.59, 23.20, 20.88;

[0308] HRMS (ESI): m / z [M+Na] + C 26 H 37 NNaO3S: Theoretical value: 466.2387; Calculated molecular weight: 466.2384.

[0309] Example 58

[0310]

[0311] The preparation method of Example 58 was basically the same as that of Example 50, except that 1-phenylcyclopropane-1-ol was replaced with an equimolar amount (0.1 mmol) of N-fluoro-2,4,6-trimethyl-N-(tert-amyl)benzenesulfonamide. A white solid was obtained, with a yield of 18 mg and a yield of 46%.

[0312] The resulting products 1 H NMR, 13 The identification data from C NMR and HRMS (ESI) are as follows:

[0313] 1 H NMR (500MHz, CDCl3) δ 7.97 (d, J=9.6Hz, 2H), 7.55 (t, J=7.4Hz, 1H), 7.46 (t, J=7.6Hz, 2H), 7.00 (s, 1H), 6.92 (s, 1H), 4.86 (s, 1H), 3.15 (t, 2H), 3. 10 (t, J=6.8Hz, 2H), 2.67 (s, 3H), 2.28 (s, 3H), 2.22-2.13 (m, 2H), 1.59 (d, J=7.5Hz, 2H), 1.16 (s, 6H), 0.86 (t, J=7.5Hz, 3H);

[0314] 13C NMR (126MHz, CDCl3) δ 200.34, 142.31, 141.58, 138.06, 137.56, 136.98, 132.98, 132.18, 131.27, 12 8.54, 128.11, 57.65, 38.21, 35.65, 34.00, 27.07, 26.63, 23.14, 20.89, 8.29;

[0315] HRMS (ESI): m / z [M+Na] + C 23 H 31 NNaO3S: Theoretical value: 424.1917; Measured molecular weight: 424.1905.

[0316] III. Antitumor Activity of the Compound

[0317] 1. Inhibitory activity of the compound against human breast cancer cells MCF-7

[0318] First, human breast cancer cells MCF-7 in the logarithmic growth phase were taken, digested with trypsin, and then a single-cell suspension with a concentration of 50,000 cells / mL was prepared and seeded into 96-well plates. 100 μL of cell suspension was added to each well, and the 96-well plates were incubated at 37°C, 5% CO2, and 95% relative humidity for 24 h.

[0319] Then, 100 μL of a 10 μM solution of the test compound (doxorubicin, the compound prepared in Example 1, and the compounds prepared in Examples 27-58) was added to each well in the experimental group, and the same volume (100 μL) of complete culture medium was added to each well in the control group. Each group had 3 parallel wells and was incubated at 37°C in a 5% CO2 incubator for 72 h.

[0320] Next, 20 μL of 5 mg / mL MTT solution (filtered through a 0.2 μm membrane) was added to each well. The 96-well plate was then placed in a 37°C, 5% CO2 incubator and incubated for 4 h. The supernatant was aspirated, and 150 μL of DMSO was added to each well to dissolve formazan crystals. The plate was shaken on a shaker for 10 min in the dark until fully mixed. The optical density (OD) of each well was measured using a microplate reader at a detection wavelength of 570 nm.

[0321] Finally, the inhibition rate of each test compound against human breast cancer cells MCF-7 was calculated using the following formula:

[0322] Cell inhibition rate (%) = (1 - average OD value of experimental group / average OD value of control group) × 100%

[0323] The calculated inhibition rates of each test compound on human breast cancer cells MCF-7 are shown in Table 6.

[0324] Table 6. Inhibition rate of each test compound on human breast cancer cells MCF-7

[0325]

[0326] As shown in Table 6, the compounds prepared in Example 1 and the compounds prepared in Examples 27-58 all showed certain inhibitory effects on the proliferation of human breast cancer cells MCF-7. Among them, the compounds prepared in Examples 30, 33, 40, 42 and 50 had strong inhibitory effects on human breast cancer cells MCF-7 and can be used as lead compounds for the preparation and development of subsequent anti-tumor drugs. Except for the above 5 compounds, the inhibitory activity of the other compounds on human breast cancer cells MCF-7 was lower than that of the positive control doxorubicin, but they still showed certain inhibitory activity, which can provide a number of compounds for future new drug development.

[0327] 2. Inhibitory activity of the compound against human colon cancer cells HCT-116

[0328] First, human colon cancer cells HCT-116 in the logarithmic growth phase were taken, digested with trypsin, and then a single-cell suspension with a concentration of 50,000 cells / mL was prepared and seeded into 96-well plates. 100 μL of cell suspension was added to each well, and the 96-well plates were incubated at 37°C, 5% CO2, and 95% relative humidity for 24 h.

[0329] Then, 100 μL of the test compound (5-fluorouracil, the compound prepared in Example 1, and the compounds prepared in Examples 27-58) was added to each well in the experimental group, and the same volume (100 μL) of complete culture medium was added to each well in the control group. Each group had 3 parallel wells and was incubated at 37°C in a 5% CO2 incubator for 72 h.

[0330] Next, 20 μL of 5 mg / mL MTT solution (filtered through a 0.2 μm membrane) was added to each well. The 96-well plate was then placed in a 37°C, 5% CO2 incubator and incubated for 4 h. The supernatant was aspirated, and 150 μL of DMSO was added to each well to dissolve formazan crystals. The plate was shaken on a shaker for 10 min in the dark until fully mixed. The optical density (OD) of each well was measured using a microplate reader at a detection wavelength of 570 nm.

[0331] The calculated inhibition rates of each test compound against human colon cancer cells HCT-116 are shown in Table 7.

[0332] Table 7. Inhibition rates of each test compound against human colon cancer cells HCT-116

[0333]

[0334] As shown in Table 7, the compounds prepared in Example 1 and the compounds prepared in Examples 27-58 all showed certain inhibitory effects on the proliferation of human colon cancer cells HCT-116. Among them, the compounds prepared in Examples 28, 29, 37, 38, 45, 47 and 55 had strong inhibitory effects on human colon cancer cells HCT-116 and can be used as lead compounds for the preparation and development of subsequent anti-tumor drugs. Except for the above 7 compounds, the inhibitory activity of the other compounds on human colon cancer cells HCT-116 was lower than that of the positive control pentafluorouracil, but they also showed certain inhibitory activity, which can provide a number of compounds for future new drug development.

[0335] It should be noted that the above embodiments are merely examples for clearly illustrating the present invention, and are not intended to limit the implementation of the present invention. Those skilled in the art can make other variations or modifications based on the above description. It is impossible to exhaustively list all possible implementations here. All obvious variations or modifications derived from the technical solutions of this invention are still within the scope of protection of this invention.

Claims

1. A benzamide compound containing an arylbutanone structure, characterized in that, The structures of the benzamide compounds containing the aryl butyl ketone structure are shown below: , , , , , , , , or .

2. The method for preparing the benzamide compound containing the arylbutanone structure according to claim 1, characterized in that, Includes the following steps: (1) K2CO3, [Cu(CH3CN)4]PF6, 3,4,7,8-tetramethyl-1,10-phenanthroline and 4DPAIPN were added to a dry reaction vessel in a molar ratio of 1:0.1:0.1:0.02; (2) After evacuating and filling the reaction vessel with argon five times, add an organic solvent; (3) An N-alkyl-N-fluoro-2-methylaniline compound and a cyclopropanol compound are added sequentially to the reaction mixture, wherein the N-alkyl-N-fluoro-2-methylaniline compound is N-(tert-butyl)-N-fluoro-2-methylaniline, N-(tert-butyl)-N-fluoro-2,4-dimethylaniline, N-(tert-butyl)-N-fluoro-2,3-dimethylaniline, N-(tert-butyl)-N-fluoro-4-chloro-2- ... The compound is 1-(4-(tert-butyl)phenyl)cyclopropane-1-ol, 1-(4-methoxyphenyl)cyclopropane-1-ol, 1-(4-chlorophenyl)cyclopropane-1-ol, 1-(o-tolyl)cyclopropane-1-ol, or 1-(4'-propyl-[1,1'-biphenyl]-4-yl)cyclopropane-1-ol, wherein the molar amounts of the N-alkyl-N-fluoro-2-methylaniline compound and the cyclopropane compound are 1 times and 2 times that of the base, respectively. (4) The mixture was stirred at room temperature for 24 hours under the illumination of a 5W blue LED light; (5) After removing the solvent by vacuum concentration, the crude product is purified by column chromatography. The eluent is collected and dried to obtain the final product.

3. The use of the benzamide compound containing the arylbutanone structure according to claim 1 in the preparation of antitumor drugs, characterized in that, The tumor is breast cancer, and the benzamide compound containing the aryl butyl ketone structure is: , , or .

4. The use of the benzamide compound containing the arylbutanone structure according to claim 1 in the preparation of antitumor drugs, characterized in that, The tumor is colon cancer, and the benzamide compound containing the aryl butyl ketone structure is: , , , , or .

5. A benzenesulfonamide compound containing an arylbutanone structure, characterized in that, The structures of the benzenesulfonamide compounds containing the aryl butyl ketone structure are shown below: or .

6. The method for preparing the benzenesulfonamide compound containing the arylbutanone structure according to claim 5, characterized in that, Includes the following steps: (1) K2CO3, [Cu(CH3CN)4]PF6, 3,4,7,8-tetramethyl-1,10-phenanthroline and 4DPAIPN were added to a dry reaction vessel in a molar ratio of 1:0.1:0.1:0.02; (2) After evacuating and filling the reaction vessel with argon five times, add an organic solvent; (3) Add N-alkyl-N-fluoro-2-methylbenzenesulfonamide and cyclopropanol compound sequentially to the reaction mixture, wherein the N-alkyl-N-fluoro-2-methylbenzenesulfonamide is N-(tert-butyl)-N-fluoro-2-methylbenzenesulfonamide or N-(tert-butyl)-N-fluoro-2,4,6-trimethylbenzenesulfonamide, and the cyclopropanol is 1-phenylcyclopropane-1-ol or 1-(4-bromophenyl)cyclopropane-1-ol, wherein the molar amounts of the N-alkyl-N-fluoro-2-methylbenzenesulfonamide and the cyclopropanol compound are 1 times and 2 times that of the base, respectively; (4) The mixture was stirred at room temperature for 24 hours under the illumination of a 5W blue LED light; (5) After removing the solvent by vacuum concentration, the crude product is purified by column chromatography. The eluent is collected and dried to obtain the final product.

7. The use of the benzenesulfonamide compound containing the arylbutanone structure according to claim 5 in the preparation of antitumor drugs, characterized in that, The tumor is breast cancer, and the benzenesulfonamide compound containing an arylbutanone structure is: 。 8. The use of the benzenesulfonamide compound containing the arylbutanone structure according to claim 5 in the preparation of antitumor drugs, characterized in that, The tumor is colon cancer, and the benzenesulfonamide compound containing the arylbutanone structure is: 。

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