4-(formoximino)-fluoro-2-quinolinones and a method for their synthesis

Abstract

This invention discloses a 4-(formaldehyde oxime)-fluoro-2-quinolinone compound and its synthetic method, belonging to the fields of organic synthetic chemistry and medicinal chemistry. Using halogen-containing fluoro-N-(2-vinylphenyl)acetamide compounds as starting materials, this invention utilizes a visible light-induced tandem cyclization reaction to obtain 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds in high yield. This invention employs greener and cleaner visible light as an energy source and uses inexpensive and readily available tert-butyl nitrite and trimethylamine borane as dual-role reagents (hydrogen transfer reagent and oxime source) and halogen atom transfer reagent, respectively, avoiding the use of expensive transition metal catalysts. The raw materials are simple and readily available, the process is environmentally friendly, and the target product yield is high.

Description

Technical Field

[0001] This invention belongs to the fields of organic synthetic chemistry and medicinal chemistry, and more specifically relates to a 4-(formaldehyde oxime)-fluoro-2-quinolinone compound and its synthesis method. Background Technology

[0002] 2-Quinolones and their derivatives are a vital class of nitrogen-containing heterocyclic compounds, widely found in numerous natural products and marketed drug molecules. Fluoroquinolones, in particular, as topoisomerase inhibitors, hold an irreplaceable clinical position in the field of anti-infection (especially against Gram-negative bacteria). However, with the widespread use of antibiotics, bacterial resistance has become an increasingly serious problem. To overcome resistance, introducing polar functional groups (such as oxime groups) with strong hydrogen bond donor / acceptor capabilities into the quinolone skeleton has been shown to significantly improve the molecule's water solubility, transmembrane permeability, and targeted binding affinity, thereby restoring or enhancing its antibacterial activity. Therefore, the development of novel 4-(formaldehyde oxime)-fluoro-2-quinolone compounds has extremely high pharmaceutical value.

[0003] Currently, the synthesis of 2-quinolinone compounds mainly relies on classical multi-step condensation reactions or one-pot tandem cyclization strategies. However, these reactions typically involve harsh environments such as strong acids / bases, or are highly dependent on expensive and toxic transition metal catalysts and complex ligands, posing significant challenges to the purification of the final drug molecule (e.g., heavy metal residues). Furthermore, many existing synthetic routes require the introduction of stoichiometric strong oxidants and cumbersome pre-functionalization of starting materials (e.g., pre-halogenation or installation of directing groups), resulting in poor atom and step economy and potential environmental pollution. These harsh reaction conditions, complex post-processing techniques, and environmental pollution risks severely restrict the synthesis and development of these high-value-added compounds.

[0004] Therefore, in order to overcome the above-mentioned shortcomings of the existing technology, it remains an urgent technical problem to be solved in this field to find and develop a new synthetic strategy that does not require metal catalysts, is mild, environmentally friendly, economical, and has broad substrate applicability, so as to achieve the efficient construction of 2-quinolinones and their derivatives with high added value. Summary of the Invention

[0005] The purpose of this invention is to provide a 4-(formaldehyde oxime)-fluoro-2-quinolinone compound and its synthesis method, thereby solving the problems existing in the prior art. This invention provides a simple and low-cost visible light-mediated synthesis method for 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds. This method uses halogen-containing fluoro-N-(2-vinylphenyl)acetamide compounds as starting materials, and utilizes a visible light-induced tandem cyclization reaction to obtain 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds in high yield. This invention uses greener and cleaner visible light as an energy source and employs inexpensive and readily available tert-butyl nitrite and trimethylamine borane as dual-role reagents (hydrogen transfer reagent, oxime source) and halogen atom transfer reagent, respectively, avoiding the use of expensive transition metal catalysts. The raw materials are simple and readily available, the process is environmentally friendly, and the target product yield is high.

[0006] To achieve the above objectives, the present invention provides the following solution: One of the technical solutions of this invention is to provide a 4-(formaldehyde oxime)-fluoro-2-quinolinone compound, the structural formula of which is as follows: ; Among them, R 1 R is alkyl, benzyl, or substituted benzyl. 2 R is hydrogen, alkyl, halogen, or nitro. 3 It is hydrogen or halogen; The alkyl group is selected from one of methyl, ethyl, propyl, cyanomethyl, cyclopropylmethyl, α-naphthylmethyl, and 3-thiophenemethyl; The substituent on the substituted benzyl group is selected from one of cyano, tert-butyl, fluorine, chlorine, bromine, phenyl, acetyl, formyl, trifluoromethyl, and trifluoromethylthio. The halogen is selected from one of fluorine, chlorine, and bromine.

[0007] The second technical solution of the present invention provides a method for preparing the above-mentioned 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds, comprising the following steps: Under a protective atmosphere, 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds, tert-butyl nitrite, trimethylamine borane and solvent were mixed and reacted under ultraviolet light to obtain the 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds. The structural formula of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds is as follows: , where R 1 R is alkyl, benzyl, or substituted benzyl. 2 R is hydrogen, alkyl, halogen, or nitro. 3The alkyl group is hydrogen or halogen; the alkyl group is selected from methyl, ethyl, propyl, cyanomethyl, cyclopropylmethyl, α-naphthylmethyl, 3-thiophenemethyl; the substituent on the substituted benzyl group is selected from cyano, tert-butyl, fluorine, chlorine, bromine, phenyl, acetyl, formyl, trifluoromethyl, trifluoromethylthio; the halogen is selected from fluorine, chlorine, bromine.

[0008] This invention uses tert-butyl nitrite and trimethylamine borane as dual-role reagents (hydrogen transfer reagent and oxime source) and halogen atom transfer reagent, respectively, to obtain the target product in high yield. However, using other nitrogen oxides (such as 4-nitrosomorpholine, 1-nitrosopyrrolidine) or boranes (such as triethylborane, pyridineborane, and nitrogen heterocyclic carbene borane) does not yield the target product or the yield of the target product is low.

[0009] Preferably, the protective atmosphere includes nitrogen, argon, or helium.

[0010] Preferably, the solvent includes acetone, tetrahydrofuran, or 2-methyltetrahydrofuran.

[0011] Preferably, the molar ratio of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compound, tert-butyl nitrite, and trimethylamine borane is 1:(1.5~2):(1.5~2).

[0012] Preferably, the ratio of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compound to the solvent is (0.4~0.5) mmol:4 mL.

[0013] Preferably, the wavelength of the ultraviolet lamp is 390~395nm and the power is 10~30W.

[0014] In this invention, the reaction is carried out under ultraviolet light. Light with smaller or larger wavelengths cannot effectively excite tert-butyl nitrite to undergo homolytic cleavage to generate tert-butyl oxygen free radicals and nitric oxide free radicals, thus failing to obtain the target product, or even if the target product is obtained, the yield is very low.

[0015] Preferably, the reaction temperature is 25~35℃ and the reaction time is 8~12h.

[0016] Preferably, the reaction further includes a purification step, specifically: the product obtained from the reaction is first concentrated under reduced pressure, and then subjected to column chromatography or recrystallization to obtain the 4-(formaldehyde oxime)-fluoro-2-quinolinone compound.

[0017] The technical principle of this invention is as follows: This invention is based on visible light-mediated free radical tandem cyclization reaction. Specifically, it uses the halogen atom transfer (XAT) mechanism initiated by boron free radicals to achieve intramolecular cyclization and bifunctionalization of 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds, thereby constructing 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds.

[0018] Its core reaction mechanism is as follows: Under ultraviolet LED irradiation, tert-butyl nitrite (t-BuONO) undergoes homolytic cleavage to generate tert-butyloxy radicals (t-BuO•) and nitric oxide radicals (•NO). The tert-butyloxy radical (t-BuO•) then undergoes hydrogen atom transfer with trimethylamine borane (Me3N-BH3) in the reaction system, producing a highly reactive boron radical. This boron radical selectively extracts a bromine atom from the bromination site of the starting material 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide via a halogen atom transfer mechanism, generating the corresponding carbon-centered radical intermediate. This radical then undergoes radical addition to the intramolecular vinyl double bond, forming a new carbon-carbon bond, constructing a fluorinated quinolinone ring skeleton, and generating a new cyclized radical intermediate. Subsequently, the nitric oxide radical, acting as a nitrosating agent, combines with the cyclized radical intermediate, introducing the crucial formaldehyde oxime group (-CH=N-OH).

[0019] The synergistic effect of the above processes enables the simultaneous one-step construction of the quinolinone skeleton and the introduction of formaldehyde oxime and fluorine atoms under mild room temperature conditions and visible light induction without transition metal catalysts. This process is characterized by high efficiency, greenness, and high step economy.

[0020] The present invention discloses the following technical effects: This invention utilizes visible light to mediate the tandem cyclization reaction of halogen-containing fluorinated N-(2-vinylphenyl)acetamides, and employs readily available and inexpensive tert-butyl nitrite and trimethylamine borane as dual-role reagents (hydrogen transfer reagent and oxime source) and halogen atom transfer reagents. This makes the preparation of 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds simple, inexpensive, and completely avoids the use of expensive transition metal catalysts. It also results in less environmental pollution and high yield of the target product, achieving relatively ideal results. It is one of the greenest, most direct, and most efficient methods reported to date for the synthesis of this type of compound.

[0021] In addition, the 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds provided by this invention are a series of structurally diverse compounds with potential application value. The formaldehyde oxime group contained therein can not only serve as a versatile conversion platform for further chemical modification, but the introduced fluorine atom and oxime group also greatly improve the physicochemical properties of the molecule. Attached Figure Description

[0022] Figure 1 This is a reaction diagram illustrating the synthesis of 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds according to the present invention; Figure 2 The 1H NMR spectrum of target compound 2a prepared in Example 1; Figure 3 The carbon NMR spectrum of target compound 2a prepared in Example 1; Figure 4 The nuclear magnetic resonance fluorine spectrum of target compound 2a prepared in Example 1; Figure 5 The 1H NMR spectrum of target compound 2b prepared in Example 2; Figure 6 The carbon NMR spectrum of target compound 2b prepared in Example 2; Figure 7 The nuclear magnetic resonance fluorine spectrum of target compound 2b prepared in Example 2. Detailed Implementation

[0023] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0024] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0025] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0026] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0027] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0028] It should be noted that any aspects not described in detail in this invention are conventional practices in the field and are not the focus of this invention.

[0029] The preparation steps and reaction formulas of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compound (compound 1) used in this invention are as follows: In a dried round-bottom flask, a magnetic stir bar was added, and methyltriphenylphosphine bromide (Ph3PMeBr, 10.0 mmol, 2.0 equivalent), potassium tert-butoxide (10.0 mmol, 2.0 equivalent), and anhydrous tetrahydrofuran (20 mL) were added in portions at 0 °C under a nitrogen atmosphere. After stirring for 30 minutes, compound S1 (5.0 mmol, 1.0 equivalent) was added in portions at 0 °C. The reaction mixture was then brought to room temperature and stirred for 4 hours. After the reaction was complete (monitored by TLC), it was quenched with saturated ammonium chloride aqueous solution and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, v / v) to give the target product S2.

[0030] In a dried round-bottom flask, a magnetic stir bar, compound S2 (1.2 mmol, 1.0 equivalent), EDCI (2.4 mmol, 2.0 equivalent), DMAP (0.12 mmol, 10 mol%), and dry dichloromethane (5 mL) were added. Bromodifluoroacetic acid (BrCF₂COOH, 2.4 mmol, 2.0 equivalent) was slowly added with continuous stirring. The reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete (monitored by TLC), the mixture was directly concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, v / v) to give compound S3.

[0031] In a 25 mL pressure-resistant bottle equipped with a magnetic stirrer, S3 (1.0 mmol, 1.0 equivalent), K2CO3 (2.0 mmol, 2.0 equivalent), acetonitrile (5.0 mL), and R were added sequentially. 1 Iodides or bromides (R 1-I / Br, 2.0 mmol, 2.0 equivalents). The reaction mixture was stirred at room temperature. After the reaction was complete, it was quenched with water and extracted with ethyl acetate (3 × 20 mL). The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate = 15:1) to give 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds (compound 1).

[0032] Unless otherwise specified, all reaction materials involved in this invention are commercially available products, and the source of these commercially available products does not affect the technical effect of this invention.

[0033] Unless otherwise specified, the room temperature involved in this invention is calculated as "25~35℃".

[0034] Example 1 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-methyl-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination at a wavelength of 395 nm (power 30 W). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether: EA ethyl acetate volume ratio of 3:1) to obtain target product 2a (62.5 mg; the molar mass of target product 2a is 290 g / mol, therefore, the theoretical mass at 0.4 mmol is 88.1 mg; the yield is (62.5 ÷ 88.1) × 100% = 71%). The structural formula of target product 2a obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 218~219℃. 1 H NMR (400 MHz, DMSO-d6) δ11.88 (s, 1H), 7.86 (d, J = 1.8 Hz, 1H), 7.70 – 7.59 (m, 2H), 7.55 – 7.49 (m,1H), 7.42 – 7.31 (m, 1H), 3.71 (s, 3H). 13C NMR (101 MHz, DMSO-d6) δ 154.7 (d,J = 26.9 Hz), 146.0 (d, J = 251.0 Hz), 137.4, 136.3, 130.0 (d, J = 2.6 Hz), 126.1 (d, J = 6.5 Hz), 123.0, 121.6 (d, J = 15.1 Hz), 116.2, 115.3, 29.8. 19 FNMR (376 MHz, DMSO-d6) δ -124.66 (s, 1F).HRMS (ESI) m / z: [M+H] + calcd forC 11 H 10 FN2O2 + 221.0721; found: 221.0720. The proton, carbon, and fluorine NMR spectra of target product 2a are as follows: Figure 2 , Figure 3 and Figure 4 As shown in the figure. Here, "f1(ppm)" represents the chemical shift.

[0035] Depend on Figures 2-4 It can be seen that the hydrogen spectrum ( Figure 2 In the carbon spectroscopy, δ 11.88 (s, 1H) represents the hydroxyl hydrogen on the oxime, δ 7.86 (d, J = 1.8 Hz, 1H) represents the hydrogen on the formaldehyde oxime, δ 7.70 – 7.59 (m, 2H), 7.55 – 7.49 (m, 1H) and 7.42 – 7.31 (m, 1H) represent the four hydrogens on the benzene ring, and δ 3.71 (s, 3H) represents the hydrogen on the methyl group. The integral ratio is 1:1:2:1:1:3, consistent with the number of hydrogen atoms and substitution pattern of target product 2a; Figure 3 In the fluorine spectrum, δ 154.7 (d, J = 26.9 Hz) represents the carbonyl carbon, which splits due to the influence of fluorine on the adjacent carbon; δ 146.0 (d, J = 251.0 Hz) represents the fluorine-substituted carbon, which splits due to the influence of fluorine, resulting in a large coupling constant; δ 136.3, 130.0 (d, J = 2.6 Hz), 126.1 (d, J = 6.5 Hz), 123.0, 121.6 (d, J = 15.1 Hz), 116.2, and 115.3 represent carbons on the benzene ring, carbons on formaldehyde oxime, and carbons attached to the benzene ring; δ 29.8 represents the carbon on the methyl group, and its carbon signal matches the simulated value; Figure 4In the sample, δ-124.66 (s, 1F) shows only one fluorine signal, indicating that there is only one fluorine atom in the molecule with a specific chemical environment. These data sufficiently demonstrate that the obtained product is the target compound 2a, and that it has good purity.

[0036] Example 2 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-ethyl-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination at a wavelength of 395 nm (power 30 W). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether: EA ethyl acetate volume ratio of 3:1) to obtain the target product 2b (64.9 mg; the molar mass of target product 2b is 340 g / mol, therefore, the theoretical mass at 0.4 mmol is 93.7 mg; the yield is (64.9 ÷ 93.7) × 100% = 69%). The structural formula of the target product 2b obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 216~217℃. 1 H NMR (400 MHz, DMSO-d6) δ11.90 (s, 1H), 7.86 (d, J = 1.7 Hz, 1H), 7.72 – 7.61 (m, 2H), 7.53 (dd, J =7.9, 1.4 Hz, 1H), 7.35 (ddd, J = 8.1, 6.5, 1.7 Hz, 1H), 4.37 (d, J = 7.1 Hz, 2H), 1.26 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 154.8 (d, J = 26.8Hz), 146.3 (d, J = 251.1 Hz), 137.9, 135.7, 130.6 (d, J = 2.3 Hz), 126.9 (d,J = 6.4 Hz), 123.4, 122.3 (d, J = 14.9 Hz), 117.0 (d, J = 4.8 Hz), 115.5,37.9, 13.1. 19 F NMR (376 MHz, DMSO-d6) δ -124.90 (s, 1F). HRMS (ESI) m / z: [M+H]+ calcd for C 12 H 12 FN2O2 + 235.0877; found: 235.0875. The proton, carbon, and fluorine NMR spectra of target product 2b are as follows: Figure 5 , Figure 6 and Figure 7 As shown in the figure. Here, "f1(ppm)" represents the chemical shift.

[0037] Depend on Figures 5-7 It can be seen that the hydrogen spectrum ( Figure 5 In the given equation, δ 11.90 (s, 1H) represents the hydroxyl hydrogen on the oxime, δ 7.86 (d, J = 1.8 Hz, 1H) represents the hydrogen on the formaldehyde oxime, δ 7.86 (d, J = 1.7 Hz, 1H), 7.72 – 7.61 (m, 2H), 7.53 (dd, J = 7.9, 1.4 Hz, 1H), 7.35 (ddd, J = 8.1, 6.5, 1.7 Hz, 1H) represent the four hydrogens on the benzene ring, δ 4.37 (d, J = 7.1 Hz, 2H) represents the CH2 hydrogen on the ethyl group, and δ 1.26 (t, J = 7.1 Hz, 1H) represents the hydrogen on the formaldehyde oxime. Hz, 3H) represents the hydrogen atom of CH3 on the ethyl group, with an integral ratio of 1:1:2:1:1:2:3, consistent with the number of hydrogen atoms and substitution pattern of target product 2b; carbon spectrum ( Figure 6 In the fluorine spectrum, δ 154.8 (d, J = 26.8 Hz) represents the carbonyl carbon, which splits due to the influence of fluorine on the adjacent carbon; δ 146.3 (d, J = 251.1 Hz) represents the fluorine-substituted carbon, which splits due to the influence of fluorine, resulting in a large coupling constant; δ 137.9, 135.7, 130.6 (d, J = 2.3 Hz), 126.9 (d, J = 6.4 Hz), 123.4, 122.3 (d, J = 14.9 Hz), 117.0 (d, J = 4.8 Hz), and 115.5 represent carbons on the benzene ring, carbons on formaldehyde oxime, and carbons attached to the benzene ring; δ 37.9 represents the CH2 carbon on the ethyl group; and δ 13.1 represents the CH3 carbon on the ethyl group. The carbon signals are consistent with the simulated values. Figure 7 In the sample, δ -124.90 (s, 1F) shows only one fluorine signal, indicating that there is only one fluorine atom in the molecule with a chemical environment. The above data fully prove that the obtained product is the target compound 2b, and that it has good purity.

[0038] Example 3 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(cyanomethyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2c (76.8 mg; the molar mass of target product 2c is 245 g / mol, therefore, the theoretical mass at 0.4 mmol is 98.1 mg; the yield is (76.8 ÷ 98.1) × 100% = 78%). The structural formula of the target product 2c obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 219~220℃. 1 H NMR (400 MHz, DMSO-d6) δ12.01 (s, 1H), 7.89 (d, J = 1.8 Hz, 1H), 7.81 – 7.70 (m, 2H), 7.64 – 7.57 (m,1H), 7.45 (ddd, J = 8.1, 5.9, 2.3 Hz, 1H), 5.55 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 154.9 (d, J = 28.3 Hz), 145.9 (d, J = 252.1 Hz), 137.5, 135.1,131.1 (d, J = 2.6 Hz), 127.3 (d, J = 6.5 Hz), 124.5, 123.7 (d, J = 15.2 Hz), 117.1 (d, J = 4.4 Hz), 116.2, 115.4, 31.3. 19 F NMR (376 MHz, DMSO-d6) δ -124.79(s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 12 H9FN3O2 + 246.0673; found: 246.0672. Example 4 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(cyclopropylmethyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2d (86.7 mg; the molar mass of the target product 2d is 260 g / mol, therefore, the theoretical mass at 0.4 mmol is 104.1 mg; the yield is (86.7 ÷ 104.1) × 100% = 83%). The structural formula of the target product 2d obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 178~179℃. 1 H NMR (400 MHz, DMSO-d6) δ11.92 (s, 1H), 7.86 (s, 1H), 7.77 (d, J = 8.6 Hz, 1H), 7.66 (t, J = 7.8 Hz,1H), 7.53 (d, J = 7.9 Hz, 1H), 7.35 (t, J = 7.5 Hz, 1H), 4.29 (d, J = 6.9 Hz, 2H), 1.28 (hept, J = 6.5 Hz, 1H), 0.48 (d, J = 7.6 Hz, 4H). 13 C NMR (101 MHz, DMSO-d6) δ 155.4 (d, J = 26.3 Hz), 146.4 (d, J = 251.2 Hz), 138.0, 136.1, 130.6 (d, J = 2.7 Hz), 126.8 (d, J = 6.4 Hz), 123.4, 122.4 (d, J = 15.2 Hz), 116.9 (d, J = 4.8 Hz), 115.9, 46.3, 10.3, 4.2. 19 F NMR (376 MHz, DMSO-d6) δ -124.57 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 14 H 14 FN2O2 +261.1034; found: 261.1029. Example 5 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-benzyl-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination at a wavelength of 395 nm (power 30 W). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2e (93.9 mg; the molar mass of the target product 2e is 296 g / mol, therefore, the theoretical mass at 0.4 mmol is 118.5 mg; the yield is (93.9 ÷ 118.5) × 100% = 79%). The structural formula of the target product 2e obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 173~174℃. 1 H NMR (400 MHz, DMSO-d6) δ11.96 (s, 1H), 7.90 (s, 1H), 7.60 – 7.45 (m, 3H), 7.32 (d, J = 6.7 Hz, 3H), 7.25 (t, J = 7.4 Hz, 3H), 5.61 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 155.7 (d,J = 27.0 Hz), 146.4 (d, J = 251.3 Hz), 143.6, 137.9, 136.6, 136.1, 130.5,129.2, 127.8, 127.1 – 126.7 (m), 123.7, 122.9, 117.1 (d, J = 4.6 Hz), 116.2,45.9. 19 F NMR (376 MHz, DMSO-d6) δ -124.37 (s, 1F). HRMS (ESI) m / z: [M+H] + calcdfor C 17 H 14 FN2O2 + 297.1034; found: 297.1029. Example 6 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(2-cyanobenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2f (82.5 mg; the molar mass of the target product 2f is 321 g / mol, therefore, the theoretical mass at 0.4 mmol is 128.5 mg; the yield is (82.5 ÷ 128.5) × 100% = 64%). The structural formula of the target product 2f obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 241~242℃. 1 H NMR (400 MHz, DMSO-d6) δ11.99 (s, 1H), 8.08 – 7.82 (m, 2H), 7.58 (t, J = 9.3 Hz, 3H), 7.53 – 7.32 (m,3H), 6.90 (d, J = 7.9 Hz, 1H), 5.75 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 155.6(d, J = 27.1 Hz), 146.3 (d, J = 251.6 Hz), 139.8, 137.7, 136.2, 134.2, 134.0,130.9, 128.6, 127.1 (d, J = 6.4 Hz), 126.4, 123.9, 123.1 (d, J = 14.9 Hz), 117.5, 117.2 (d, J = 4.8 Hz), 115.8, 110.7, 45.0. 19 F NMR (376 MHz, DMSO-d6) δ-124.44 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 18 H 13 FN3O2 + 322.0986; found: 322.0983. Example 7 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(3-tert-butylbenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (395 nm, 30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3.5:1) to obtain 2 g (106.0 mg) of the target product. The molar mass of the target product 2 g was 352 g / mol, therefore, the theoretical mass at 0.4 mmol was 141.0 mg; the yield was (106.0 ÷ 141.0) × 100% = 75%). The structural formula of the target product 2 g obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 224~225℃. 1 H NMR (400 MHz, DMSO-d6) δ11.95 (s, 1H), 7.54 (dt, J = 4.8, 2.2 Hz, 3H), 7.38 – 7.27 (m, 3H), 7.17 (d,J = 8.3 Hz, 2H), 5.57 (s, 2H), 1.23 (s, 9H). 13 C NMR (101 MHz, DMSO-d6) δ 155.6(d, J = 26.9 Hz), 150.2, 146.4 (d, J = 251.4 Hz), 137.9, 136.1, 133.6, 130.6,126.9, 126.9, 126.0, 123.6, 122.8 (d, J = 15.2 Hz), 117.0 (d, J = 4.5 Hz), 116.2, 45.5, 34.7, 31.5. 19 F NMR (376 MHz, DMSO-d6) δ -124.43 (s, 1F). HRMS(ESI) m / z: [M+H] + calcd for C 21 H 22 FN2O2 + 353.1660; found: 353.1658. Example 8 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(3-chlorobenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2h (99.3 mg; the molar mass of the target product 2h is 330 g / mol, therefore, the theoretical mass at 0.4 mmol is 132.3 mg; the yield is (99.3 ÷ 132.3) × 100% = 75%). The structural formula of the target product 2h obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 208~209℃. 1 H NMR (400 MHz, DMSO-d6) δ11.96 (s, 1H), 7.90 (d, J = 1.6 Hz, 1H), 7.60 – 7.52 (m, 2H), 7.50 – 7.46 (m,1H), 7.44 – 7.23 (m, 5H), 5.60 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 155.7 (d,J = 27.0 Hz), 146.4 (d, J = 251.4 Hz), 137.8, 135.9, 135.6, 132.4, 130.6,129.2, 129.1, 127.0 (d, J = 6.4 Hz), 123.8, 122.9 (d, J = 15.3 Hz), 117.1 (d, J = 4.4 Hz), 116.1, 45.3. 19 F NMR (376 MHz, DMSO-d6) δ -124.35 (s, 1F). HRMS(ESI) m / z: [M+H] + calcd for C 17 H 13 ClFN2O2 + 331.0644; found: 331.0642. Example 9 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(3-bromobenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2i (104.9 mg; the molar mass of the target product 2i is 375 g / mol, therefore, the theoretical mass at 0.4 mmol is 150.1 mg; the yield is (104.9 ÷ 150.1) × 100% = 70%). The structural formula of the target product 2i obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 233~234℃. 1 H NMR (400 MHz, DMSO-d6) δ11.95 (s, 1H), 7.89 (d, J = 1.7 Hz, 1H), 7.58 – 7.44 (m, 5H), 7.33 (t, J =7.5 Hz, 1H), 7.21 (d, J = 8.2 Hz, 2H), 5.58 (s, 2H). 13 C NMR (101 MHz, DMSO-d6)δ 155.5, 146.4 (d, J = 251.4 Hz), 137.8, 136.1, 135.9, 132.1, 130.6, 129.4,127.0, 123.8, 123.0, 120.9, 117.1, 116.1, 45.4. 19 F NMR (376 MHz, DMSO-d6) δ -124.36 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 17 H 13 BrFN2O2 + 375.0139; found: 375.0136. Example 10 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(2-bromo-5-fluorobenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2j (99.0 mg; the molar mass of the target product 2j is 393 g / mol, therefore, the theoretical mass at 0.4 mmol is 157.3 mg; the yield is (99.0 ÷ 157.3) × 100% = 63%). The structural formula of the target product 2j obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 214~215℃. 1 H NMR (400 MHz, DMSO-d6) δ12.35 (s, 1H), 8.53 (s, 1H), 7.68 – 7.53 (m, 2H), 7.43 – 7.27 (m, 3H), 6.88(t, J = 8.3 Hz, 1H), 5.57 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 160.3 (d, J =249.2 Hz), 155.4, 147.4, 141.4, 136.1, 130.7, 130.0, 128.4, 123.9, 123.0,121.1, 119.6, 119.3, 117.2, 115.7, 29.5.. 19 F NMR (376 MHz, DMSO-d6) δ -114. 62(s, 1F), -128.60 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 17 H 12 BrF2N2O2 + 393.0045; found: 393.0042. Example 11 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(4-phenylbenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2k (126.8 mg; the molar mass of the target product 2k is 372 g / mol, therefore, the theoretical mass at 0.4 mmol is 149.0 mg; the yield is (126.8 ÷ 149.0) × 100% = 85%). The structural formula of the target product 2k obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 210~211℃. 1 H NMR (400 MHz, DMSO-d6) δ11.96 (s, 1H), 7.91 (s, 1H), 7.65 – 7.59 (m, 4H), 7.56 (d, J = 4.2 Hz, 3H), 7.44 (t, J = 7.4 Hz, 2H), 7.33 (d, J = 7.4 Hz, 4H), 5.66 (s, 2H). 13 C NMR (101MHz, DMSO-d6) δ 155.7 (d, J = 26.9 Hz), 146.4 (d, J = 251.6 Hz), 140.2,139.7, 137.9, 136.1, 135.8, 130.6, 129.4, 127.9, 127.7, 127.6, 127.1, 127.0(d, J = 6.5 Hz), 123.7, 122.9 (d, J = 15.0 Hz), 117.1 (d, J = 4.3 Hz), 116.2,45.6. 19 F NMR (376 MHz, DMSO-d6) δ -124.37 (s, 1F). HRMS (ESI) m / z: [M+H] + calcdfor C 23 H 18 FN2O2 + 373.1347; found: 373.1348. Example 12 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(4-acetylbenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2l (93.6 mg; the molar mass of the target product 2l is 338 g / mol, therefore, the theoretical mass at 0.4 mmol is 135.3 mg; the yield is (93.6 ÷ 135.3) × 100% = 69%). The structural formula of the target product 2l obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 227~228℃. 1 H NMR (400 MHz, DMSO-d6) δ11.96 (s, 1H), 7.93 (s, 1H), 7.91 (d, J = 1.6 Hz, 2H), 7.58 – 7.50 (m, 2H), 7.44 (d, J = 8.5 Hz, 1H), 7.39 – 7.29 (m, 3H), 5.69 (s, 2H), 2.53 (s, 3H). 13 CNMR (101 MHz, DMSO-d6) δ 197.9, 155.7 (d, J = 26.9 Hz), 146.4 (d, J = 251.4Hz), 142.0, 137.8, 136.4, 136.0, 130.6, 129.2, 127.2, 127.0 (d, J = 6.6 Hz), 123.8, 123.0 (d, J = 15.2 Hz), 117.1 (d, J = 4.8 Hz), 116.0, 45.8, 27.1. 19 FNMR (376 MHz, DMSO-d6) δ -124.33 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd forC 19 H 16 FN2O3 + 339.1139; found: 339.1136. Example 13 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(4-formylbenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2m (81.9 mg, where the molar mass of the target product 2m is 324 g / mol, therefore, the theoretical mass at 0.4 mmol is 129.7 mg; the yield is (81.9 ÷ 129.7) × 100% = 63%). The structural formula of the target product 2m obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 219~220℃. 1 H NMR (400 MHz, DMSO-d6) δ11.98 (s, 1H), 9.96 (s, 1H), 7.94 – 7.83 (m, 3H), 7.60 – 7.50 (m, 2H), 7.44(d, J = 8.2 Hz, 3H), 7.33 (t, J = 7.5 Hz, 1H), 5.71 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 193.1, 155.7 (d, J = 27.0 Hz), 146.4 (d, J = 251.4 Hz), 143.5,141.5, 137.8, 135.9 (d, J = 9.9 Hz), 130.7, 130.5 (d, J = 4.3 Hz), 127.7,127.0 (d, J = 6.3 Hz), 123.9, 123.0 (d, J = 15.3 Hz), 117.1 (d, J = 4.7 Hz),116.0, 46.0. 19 F NMR (376 MHz, DMSO-d6) δ -124.33 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 18 H 14 FN2O2 + 325.0983; found: 325.0981. Example 14 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(4-trifluoromethylbenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2n (102.2 mg; the molar mass of the target product 2n is 364 g / mol, therefore, the theoretical mass at 0.4 mmol is 145.7 mg; the yield is (102.2 ÷ 145.7) × 100% = 70%). The structural formula of the target product 2n obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 212~213℃. 1 H NMR (400 MHz, DMSO-d6) δ11.97 (s, 1H), 7.91 (d, J = 1.7 Hz, 1H), 7.71 (d, J = 8.1 Hz, 2H), 7.55 (td,J = 7.7, 1.3 Hz, 2H), 7.49 – 7.43 (m, 3H), 7.34 (td, J = 7.5, 1.1 Hz, 1H), 5.71 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 155.7 (d, J = 27.2 Hz), 146.4 (d, J= 251.6 Hz), 141.5, 137.8, 136.0, 130.7 (d, J = 2.4 Hz), 128.5 (d, J = 32.0Hz), 127.8, 127.0 (d, J = 6.3 Hz), 126.1 (d, J = 3.9 Hz), 123.8, 123.0 (d, J= 15.2 Hz), 117.2, 116.0, 45.7. 19 F NMR (376 MHz, DMSO-d6) δ -60.97 (s, 3F), -124.37 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 18 H13 FN2O2 + 365.0908; found: 365.0905. Example 15 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(4-trifluoromethylthiobenzyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2o (106.4 mg; the molar mass of the target product 2o is 396 g / mol, therefore, the theoretical mass at 0.4 mmol is 158.5 mg; the yield is (106.4 ÷ 158.5) × 100% = 67%). The structural formula of the target product 2o obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 250~251℃. 1 H NMR (400 MHz, DMSO-d6) δ11.97 (s, 1H), 7.90 (s, 1H), 7.69 (d, J = 7.9 Hz, 2H), 7.56 (d, J = 7.8 Hz,2H), 7.48 (d, J = 8.6 Hz, 1H), 7.43 – 7.28 (m, 3H), 5.68 (s, 2H). 13 C NMR (101MHz, DMSO-d6) δ 155.7 (d, J = 27.1 Hz), 146.4 (d, J = 250.8 Hz), 140.4,137.8, 137.1, 136.0, 131.6, 130.7, 128.6, 127.0, 123.8, 123.0 (d, J = 15.2Hz), 122.3, 117.2, 116.0, 45.6. 19 F NMR (376 MHz, DMSO-d6) δ -42.13 (s, 3F), -124.36 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 18 H 13 F4N2O2S+ 397.0628; found: 397.0626. Example 16 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(naphthylmethyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2p (122.2 mg; the molar mass of the target product 2p is 346 g / mol, therefore, the theoretical mass at 0.4 mmol is 138.5 mg; the yield is (122.2 ÷ 138.5) × 100% = 88%). The structural formula of the target product 2p obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 237~238℃. 1 H NMR (400 MHz, DMSO-d6) δ12.02 (s, 1H), 8.33 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.96 (d, J= 1.4 Hz, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.75 – 7.68 (m, 1H), 7.67 – 7.59 (m,2H), 7.52 – 7.43 (m, 1H), 7.33 (td, J = 7.7, 3.6 Hz, 1H), 7.26 (d, J = 8.5Hz, 1H), 6.64 (d, J = 6.9 Hz, 1H), 6.06 (s, 2H). 13C NMR (101 MHz, DMSO-d6) δ155.6 (d, J = 27.1 Hz), 146.4 (d, J = 251.4 Hz), 137.9, 136.3, 133.9, 131.1,130.7, 130.6, 129.2, 128.0, 127.1, 126.9 (d, J = 6.4 Hz), 126.7, 125.9,123.8, 123.5, 123.0 (d, J = 15.1 Hz), 122.0, 117.1 (d, J = 4.7 Hz), 116.2,44.5. 19 F NMR (376 MHz, DMSO-d6) δ -124.41 (s, 1F). HRMS (ESI) m / z: [M+H] + calcdfor C 21 H 16 FN2O2 + 347.1190; found: 347.1187. Example 17 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-(3-thiophenemethyl)-N-(2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2q (105.5 mg; the molar mass of the target product 2q is 302 g / mol, therefore, the theoretical mass at 0.4 mmol is 120.9 mg; the yield is (105.5 ÷ 120.9) × 100% = 87%). The structural formula of the target product 2q obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 215~216℃. 1H NMR (400 MHz, DMSO-d6) δ11.93 (s, 1H), 7.87 (d, J = 1.7 Hz, 1H), 7.68 (d, J = 8.5 Hz, 1H), 7.61 –7.47 (m, 3H), 7.42 (dd, J = 3.0, 1.3 Hz, 1H), 7.33 (t, J = 7.5 Hz, 1H), 7.07 (dd, J = 4.9, 1.3 Hz, 1H), 5.56 (s, 2H). 13 C NMR (101 MHz, DMSO-d6) δ 155.4 (d,J = 27.3 Hz), 146.4 (d, J = 251.4 Hz), 137.9, 137.2, 135.9, 130.5, 127.6,127.4, 126.9 (d, J = 6.6 Hz), 123.6, 123.5, 122.7 (d, J = 15.2 Hz), 117.0 (d,J = 4.6 Hz), 116.0, 42.0. 19 F NMR (376 MHz, DMSO-d6) δ -124.42 (s, 1F). HRMS(ESI) m / z: [M+H] + calcd for C15H 12 FN2O2S + 303.0598; found: 303.0596. Example 18 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-methyl-N-(4-isopropyl-2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2r (80.0 mg; the molar mass of the target product 2r is 332 g / mol, therefore, the theoretical mass at 0.4 mmol is 104.9 mg; the yield is (80.0 ÷ 104.9) × 100% = 76%). The structural formula of the target product 2r obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 179~180℃. 1 H NMR (400 MHz, DMSO-d6) δ11.87 (s, 1H), 7.87 (d, J = 1.7 Hz, 1H), 7.56 (d, J = 1.7 Hz, 2H), 7.34 (d, J= 1.4 Hz, 1H), 3.69 (s, 3H), 2.99 (hept, J = 6.9 Hz, 1H), 1.23 (d, J = 6.9Hz, 6H). 13 C NMR (101 MHz, DMSO-d6) δ 155.1 (d, J = 26.9 Hz), 146.6 (d, J =250.7 Hz), 143.5, 138.0, 135.1, 129.0 (d, J = 2.7 Hz), 123.6 (d, J = 6.1 Hz), 122.0 (d, J = 14.9 Hz), 116.6 (d, J = 4.5 Hz), 115.9, 33.2, 30.3, 24.3. 19 F NMR(376 MHz, DMSO-d6) δ -124.52 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd forC 14 H 16 FN2O2 + 263.1190; found: 263.1188. Example 19 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-methyl-N-(4-fluoro-2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2S (74.6 mg; the molar mass of the target product 2S is 238 g / mol, therefore, the theoretical mass at 0.4 mmol is 95.3 mg; the yield is (74.6 ÷ 95.3) × 100% = 78%). The structural formula of the target product 2S obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 210~211℃. 1 H NMR (400 MHz, DMSO-d6) δ11.95 (s, 1H), 7.85 (s, 1H), 7.58 – 7.47 (m, 2H), 7.24 (td, J = 8.6, 2.2 Hz,1H), 3.68 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 163.3 (d, J = 246.3 Hz), 155.4 (d, J = 27.0 Hz), 145.9 (d, J = 250.3 Hz), 138.5 (d, J = 11.5 Hz), 137.7,129.0 (dd, J = 10.3, 6.7 Hz), 121.9 (d, J = 15.6 Hz), 113.3 (d, J = 2.9 Hz), 111.4 (d, J = 23.2 Hz), 102.9 (d, J = 27.7 Hz), 30.6. 19 F NMR (376 MHz, DMSO-d6) δ -108.81 (s, 1F), -125.99 (d, J = 5.8 Hz, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 11 H9F2N2O2 + 239.0627; found: 239.0621. Example 20 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-methyl-N-(4,5-difluoro-2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The reaction was carried out under UV light (395 nm, 30 W) at room temperature with stirring for 10 h. After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2t (83.3 mg; the molar mass of the target product 2t is 256 g / mol, therefore, the theoretical mass at 0.4 mmol is 102.5 mg; the yield is (83.3 ÷ 102.5) × 100% = 81%). The structural formula of the target product 2t obtained in this example is as follows: ; Its main physicochemical properties are as follows: white solid, melting point 220~221℃. 1 H NMR (400 MHz, DMSO-d6) δ12.03 (s, 1H), 7.86 – 7.77 (m, 2H), 7.52 (dd, J = 11.1, 8.6 Hz, 1H), 3.68 (s,3H). 13 C NMR (101 MHz, DMSO-d6) δ 155.1 (d, J = 27.1 Hz), 148.9 (dd, J = 142.5,3.4 Hz), 147.3 – 145.5 (m), 144.7, 137.3, 134.4, 121.2 (d, J = 16.8 Hz), 114.5 (d, J = 19.2 Hz), 113.4, 105.6 (d, J = 23.3 Hz), 31.1. 19 F NMR (376 MHz, DMSO-d6) δ -122.83 (d, J = 6.9 Hz, 1F), -133.31 (dd, J = 23.8, 7.2 Hz, 1F), -144.16 (d, J = 23.7 Hz, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 11 H8F3N2O2 + 257.0532; found: 257.0531. Example 21 Under a nitrogen atmosphere, 2-bromo-2,2-difluoro-N-methyl-N-(4-nitro-2-vinylphenyl)acetamide (0.4 mmol), tert-butyl nitrite (0.8 mmol), trimethylamine borane (0.8 mmol), and acetone (4 mL) were added sequentially to a 10 mL Shrek flask containing a magnetic magnet. The mixture was stirred at room temperature for 10 h under UV-LED illumination (395 nm wavelength, 30 W power). After the reaction, the mixture was concentrated under reduced pressure, and the crude product was purified by silica gel column chromatography (PE petroleum ether / EA ethyl acetate volume ratio 3:1) to obtain the target product 2u (47.9 mg; the molar mass of the target product 2u is 265 g / mol, therefore, the theoretical mass at 0.4 mmol is 106.1 mg; the yield is (47.9 ÷ 106.1) × 100% = 45%). The structural formula of the target product 2u obtained in this example is as follows: ; Its main physical and chemical properties are as follows: white solid, melting point 223~224℃. 1 H NMR (400 MHz, DMSO-d6) δ12.16 (s, 1H), 8.44 (dd, J = 9.3, 2.7 Hz, 1H), 8.27 (d, J = 2.6 Hz, 1H), 7.98(d, J = 1.8 Hz, 1H), 7.85 (d, J = 9.4 Hz, 1H), 3.77 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 155.3, 147.7 (d, J = 253.6 Hz), 142.7, 141.1, 137.1, 124.8, 122.5 (d, J = 7.2 Hz), 122.0, 117.3, 116.6 (d, J = 5.8 Hz), 31.1. 19 F NMR (376 MHz, DMSO-d6) δ -121.40 (s, 1F). HRMS (ESI) m / z: [M+H] + calcd for C 11 H9FN3O4 + 266.0572; found: 266.0568. Comparative Example 1 Compared to Example 1, Comparative Example 1 differed only in that 4-nitrosomorpholine was used instead of tert-butyl nitrite as the dual-role reagent; the other procedures were the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 1 was 0.

[0039] Comparative Example 2 Compared to Example 1, Comparative Example 2 differed only in that 1-nitrosopyrrolidine was used instead of tert-butyl nitrite as the dual-role reagent; the other procedures were the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 2 was 0.

[0040] Comparative Example 3 Compared with Example 1, Comparative Example 3 differs only in that triethylborane is used instead of trimethylamineborane as the halogen atom transfer reagent; the other processes are the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 3 is 23%.

[0041] Comparative Example 4 Compared to Example 1, Comparative Example 4 differs only in that pyridineborane is used instead of trimethylamineborane as the halogen atom transfer reagent; the other processes are the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 4 was 14%.

[0042] Comparative Example 5 Compared to Example 1, Comparative Example 5 differs only in that it uses a nitrogen-containing heterocyclic carbene borane instead of trimethylamine borane as the halogen atom transfer reagent; the other processes are the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 5 was 0.

[0043] Comparative Example 6 Compared with Example 1, Comparative Example 6 differs only in that a light source with a wavelength of 356 nm (30 W) is used instead of a light source with a wavelength of 395 nm (30 W). All other processes are the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 6 is 0.

[0044] Comparative Example 7 Compared with Example 1, Comparative Example 7 differs only in that a light source with a wavelength of 456 nm (30 W) is used instead of a light source with a wavelength of 30 W (356 nm). All other processes are the same as in Example 1. The yield of the white solid compound 2a prepared in Comparative Example 7 is 7%.

[0045] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0046] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A 4-(formaldehyde oxime)-fluoro-2-quinolinone compound, characterized in that, The structural formula of the 4-(formaldehyde oxime)-fluoro-2-quinolinone compound is as follows: ； Among them, R 1 R is alkyl, benzyl, or substituted benzyl. 2 R is hydrogen, alkyl, halogen, or nitro. 3 It is hydrogen or halogen; The alkyl group is selected from one of methyl, ethyl, propyl, cyanomethyl, cyclopropylmethyl, α-naphthylmethyl, and 3-thiophenemethyl; The substituent on the substituted benzyl group is selected from one of cyano, tert-butyl, fluorine, chlorine, bromine, phenyl, acetyl, formyl, trifluoromethyl, and trifluoromethylthio. The halogen is selected from one of fluorine, chlorine, and bromine.

2. The method for preparing the 4-(formaldehyde oxime)-fluoro-2-quinolinone compound according to claim 1, characterized in that, Includes the following steps: Under a protective atmosphere, 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds, tert-butyl nitrite, trimethylamine borane and solvent were mixed and reacted under ultraviolet light to obtain the 4-(formaldehyde oxime)-fluoro-2-quinolinone compounds. The structural formula of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compounds is as follows: , where R 1 R is alkyl, benzyl, or substituted benzyl. 2 R is hydrogen, alkyl, halogen, or nitro. 3 The alkyl group is hydrogen or halogen; the alkyl group is selected from methyl, ethyl, propyl, cyanomethyl, cyclopropylmethyl, α-naphthylmethyl, 3-thiophenemethyl; the substituent on the substituted benzyl group is selected from cyano, tert-butyl, fluorine, chlorine, bromine, phenyl, acetyl, formyl, trifluoromethyl, trifluoromethylthio; the halogen is selected from fluorine, chlorine, bromine.

3. The preparation method according to claim 2, characterized in that, The protective atmosphere includes nitrogen, argon, or helium.

4. The preparation method according to claim 2, characterized in that, The solvent includes acetone, tetrahydrofuran, or 2-methyltetrahydrofuran.

5. The preparation method according to claim 2, characterized in that, The molar ratio of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compound, tert-butyl nitrite, and trimethylamine borane is 1:(1.5~2):(1.5~2).

6. The preparation method according to claim 2, characterized in that, The ratio of the 2-bromo-2,2-difluoro-N-(2-vinylphenyl)acetamide compound to the solvent is (0.4~0.5) mmol:4 mL.

7. The preparation method according to claim 2, characterized in that, The ultraviolet lamp has a wavelength of 390~395nm and a power of 10~30W.

8. The preparation method according to claim 2, characterized in that, The reaction is carried out at a temperature of 25-35°C for 8-12 hours.

9. The preparation method according to claim 2, characterized in that, After the reaction is completed, a purification step is also included, specifically: the product obtained from the reaction is first concentrated under reduced pressure, and then subjected to column chromatography or recrystallization to obtain the 4-(formaldehyde oxime)-fluoro-2-quinolinone compound.

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