A method for preparing a phenyl ketone amide compound

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of a phenyl ketone amide compound. The preparation method of the phenyl ketone amide compound comprises the following steps: phenyl acylsilicon compound 1 and amide compound 2 are used as raw materials, a catalyst is added, and the phenyl ketone amide compound 3 is prepared by reacting in a first solvent. The reaction steps are short and efficient, the atomic utilization rate is higher, the yield of the obtained product is higher, the reaction condition is mild, the substrate range is wide, and the method is more suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, and specifically relates to a method for preparing phenyl ketamide compounds. Background Technology

[0002] α-Ketoamide derivatives possess excellent biological activity. Their bifunctional and multi-reaction-center characteristics endow them with unique chemical properties, making them promising synthetic intermediates with broad applications in synthetic chemistry, medicinal chemistry, and materials science. For example, tacrolimus, a drug for treating eczema, and telaprevir and boprevir, novel drugs for treating hepatitis C, all contain α-ketoamide structural units. Existing techniques have successfully synthesized α-ketoamides from acetylacetones, keto acids, aryl ketones, aryl iodides, and their derivatives via oxidation and coupling reactions. However, these reactions typically use heavy metals such as palladium and copper, leading to problems such as expensive catalysts and environmental pollution. Furthermore, the product yield is significantly affected by the substrate, limiting the applicability of the reactions. Therefore, exploring universally applicable synthetic methods for α-ketoamide compounds is of great significance. Summary of the Invention

[0003] The technical problem solved by this invention is that the synthesis of α-ketoamide compounds in the prior art usually uses heavy metals palladium and copper, which involves complex reaction conditions, high costs, and limited applicability.

[0004] To address the aforementioned technical problems, the present invention aims to provide a method for preparing phenyl ketamide compounds.

[0005] Specifically, the present invention provides the following technical solution:

[0006] In a first aspect, the present invention provides a method for preparing phenyl ketone amide compounds, comprising the following steps:

[0007] Using phenylsilyl compound 1 and amide compound 2 as raw materials, a catalyst is added, and the mixture is reacted in a first solvent to prepare phenyl ketone amide compound 3. The reaction route can be any one of the following two reaction routes:

[0008] First reaction route:

[0009]

[0010] The second reaction route:

[0011]

[0012] Among them, the R1 group is in The ortho, meta, and / or para positions of the group; n is 1 to 3;

[0013] The R1 group is selected from hydrogen, C1-6 Alkyl, C 1-6 The alkoxy group, halogen substituent, or C substituent is a C group that is substituted with a substituent. 1-6 The alkyl group, wherein the substituent is selected from one or more of methyl, tert-butyl, methoxy, butoxy, -F and -Cl;

[0014] The R2 and R3 groups are independently selected from H or C. 1-6 alkyl;

[0015] The R4 group is a silicon-containing group;

[0016] R5 group is selected from In this configuration, the R6 group is attached to any carbon atom on the nitrogen-containing ring, and the R6 group is selected from H and C. 1-7 alkyl or C 1-7 alkoxy groups.

[0017] Preferably, the silicon-containing group consists of three substituents on the silicon atom, each independently selected from C10. 1-4 alkyl, C 1-4 alkoxy, phenyl, benzyl, C 1-3 Alkyl-substituted phenyl, styrene, hydroxy-substituted styrene, or trimethylsilyl.

[0018] Preferably, the silicon-containing group is trimethylsilyl, triethylsilyl, triisopropylsilyl, dimethylisopropylsilyl, diethylisopropylsilyl, methylbutylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, tribenzylsilyl, tri-p-xylylsilyl, triphenylsilyl, diphenylmethylsilyl, di-tert-butylmethylsilyl, tri(trimethylsilyl)silyl, (2-hydroxystyryl)dimethylsilyl, 2-hydroxystyryldiisopropylsilyl, tert-butyloxymethylphenylsilyl, or tert-butoxydiphenylsilyl.

[0019] Preferably, the silicon-based protecting group is trimethylsilyl or triethylsilyl.

[0020] Preferably, in the first or second reaction route, the R1 group is selected from hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, methoxy, butoxy, or -Cl.

[0021] Preferably, in the first reaction route, the R2 and R3 groups are independently selected from methyl, ethyl, propyl, or n-butyl.

[0022] Preferably, in the second reaction route, the R5 group is selected from...

[0023] Preferably, the molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 1-4:1-3.

[0024] Preferably, the molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 2.5-3.5:1.5-2.5.

[0025] More preferably, the molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 2.7-3.3:1.7-2.3.

[0026] Preferably, the reaction temperature is -110℃ to -40℃; more preferably, the reaction temperature is -100℃ to -70℃.

[0027] Preferably, the reaction time is 0.5 to 5 hours.

[0028] Preferably, the catalyst is selected from one or more of lithium diisopropylamino, lithium di(trimethylsilyl)amino, sodium di(trimethylsilyl)amino and potassium di(trimethylsilyl)amino.

[0029] Preferably, the catalyst is selected from lithium diisopropylamino.

[0030] More preferably, the molar ratio of catalyst to compound 1 is 1-8:1-4.

[0031] More preferably, the molar ratio of catalyst to compound 1 is 6-8:2-4.

[0032] Most preferably, the molar ratio of catalyst to compound 1 is 6.5–7.5:2.5–3.5.

[0033] Preferably, the first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

[0034] Preferably, the first solvent is tetrahydrofuran.

[0035] More preferably, the mole-to-volume ratio of compound 1 to the first solvent is 1:0.5-6, wherein the mole is in mol and the volume is in L.

[0036] More preferably, the mole-to-volume ratio of compound 1 to the first solvent is 1:1 to 5, wherein the mole is in mol and the volume is in L.

[0037] More preferably, the mole ratio of compound 1 to the volume ratio of the first solvent is 1:1 to 3, wherein the mole is in mol and the volume is in L.

[0038] Preferably, after the reaction is complete, a second solvent is added to quench the reaction, yielding phenyl ketamide compound 3.

[0039] Preferably, the second solvent is water or a saturated aqueous solution of ammonium chloride.

[0040] More preferably, the volume ratio of the second solvent to the amount of compound 1 is 1 to 15:1, preferably 5 to 8:1, wherein the unit of amount of substance is mol and the unit of volume is L.

[0041] Preferably, a second solvent is added to quench the reaction, followed by concentration under reduced pressure; more preferably, the concentration is carried out under reduced pressure at 20–50°C; and / or for 10–60 min.

[0042] Preferably, the product after vacuum concentration is purified by column chromatography.

[0043] More preferably, the eluent is petroleum ether and ethyl acetate.

[0044] More preferably, the volume ratio of petroleum ether to ethyl acetate is 2 to 15:1.

[0045] Preferably, the gas atmosphere during the preparation process is an N2 atmosphere or an Ar atmosphere.

[0046] Preferably, the phenyl ketamide compound 3 is any one of the following compounds:

[0047] Compound 3a: n = 1, R1 is in the para position, R1 is -CH3, R2 is -CH3, R3 is -CH3;

[0048] Compound 3b: n = 1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH3, R3 is -CH2CH3;

[0049] Compound 3c: n=1, R1 is in the para position, R1 is -CH3, R5 is...

[0050] Compound 3d: n = 1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH3, R 3 It is -CH2CH2CH3;

[0051] Compound 3e: n = 1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH2CH3, R3 is -CH2CH2CH2CH3;

[0052] Compound 3f: n=1, R1 is in the para position, R1 is -CH3, R5 is...

[0053] Compound 3g: n=1, R1 is in the para position, R1 is -H, R2 is -CH3, R3 is -CH3;

[0054] Compound 3h: n=1, R1 is in the para position, R1 is -C(CH3)3, R2 is -CH3, R3 is -CH3;

[0055] Compound 3i: n = 1, R1 is in the para position, R1 is -Cl, R2 is -CH3, R3 is -CH3;

[0056] Compound 3j: n = 1, R1 is in the para position, R1 is -OCH3, R2 is -CH3, R3 is -CH3;

[0057] Compound 3k: n=1, R1 is in the para position, R1 is -OCH2CH2CH2CH3, R2 is -CH3, R3 is -CH3;

[0058] Compound 3l: n = 1, R1 is in the ortho position, R1 is -CH3, R2 is -CH3, R3 is -CH3;

[0059] Compound 3m: n = 1, R1 is in the meta position, R1 is -CH3, R2 is -CH3, R3 is -CH3;

[0060] Compound 3n: n = 2, R1 is in the meta position, R1 is -CH3, R2 is -CH3, and R3 is -CH3.

[0061] The beneficial effects of this invention are:

[0062] (1) In this invention, amide compounds are used as nucleophiles to synthesize phenyl α-ketoamide compounds with potential application value in one step. The reaction steps are short and efficient, the atom utilization rate is high, and the yield of the product is high.

[0063] (2) The preparation method of the present invention is low in cost. The raw materials, ketones, amide compounds and catalysts used in the present invention are all simple and readily available.

[0064] (3) The preparation method of the present invention has mild reaction conditions, a wide range of applicable substrates, and is suitable for industrial production. Attached Figure Description

[0065] Figure 1 It is the phenyl ketamide compound (3a) in Example 1. 1 H NMR spectrum.

[0066] Figure 2 It is the phenyl ketamide compound (3a) in Example 1. 13 C NMR spectrum.

[0067] Figure 3 It is the phenyl ketamide compound (3b) in Example 2. 1 H NMR spectrum.

[0068] Figure 4It is the phenyl ketamide compound (3b) in Example 2. 13 C NMR spectrum.

[0069] Figure 5 It is the phenyl ketamide compound (3c) in Example 3. 1 H NMR spectrum.

[0070] Figure 6 It is the phenyl ketamide compound (3c) in Example 3. 13 C NMR spectrum.

[0071] Figure 7 It is the phenyl ketamide compound (3d) in Example 4. 1 H NMR spectrum.

[0072] Figure 8 It is the phenyl ketamide compound (3d) in Example 4. 13 C NMR spectrum.

[0073] Figure 9 It is the phenyl ketamide compound (3e) in Example 5. 1 H NMR spectrum.

[0074] Figure 10 It is the phenyl ketamide compound (3e) in Example 5. 13 C NMR spectrum.

[0075] Figure 11 It is the phenyl ketoamide compound (3f) in Example 6. 1 H NMR spectrum.

[0076] Figure 12 It is the phenyl ketoamide compound (3f) in Example 6. 13 C NMR spectrum.

[0077] Figure 13 It is the phenyl ketoamide compound (3g) in Example 7. 1 H NMR spectrum.

[0078] Figure 14 It is the phenyl ketoamide compound (3g) in Example 7. 13 C NMR spectrum.

[0079] Figure 15 It is the phenyl ketamide compound (3h) in Example 8. 1 H NMR spectrum.

[0080] Figure 16 It is the phenyl ketamide compound (3h) in Example 8. 13 C NMR spectrum.

[0081] Figure 17 It is the phenyl ketamide compound (3i) in Example 9. 1 H NMR spectrum.

[0082] Figure 18 It is the phenyl ketamide compound (3i) in Example 9. 13 C NMR spectrum.

[0083] Figure 19 It is the phenyl ketamide compound (3j) in Example 10. 1 H NMR spectrum.

[0084] Figure 20 It is the phenyl ketamide compound (3j) in Example 10. 13 C NMR spectrum.

[0085] Figure 21 It is the phenyl ketamide compound (3k) in Example 11. 1 H NMR spectrum.

[0086] Figure 22 It is the phenyl ketamide compound (3k) in Example 11. 13 C NMR spectrum.

[0087] Figure 23 It is the phenyl ketamide compound (3l) in Example 12. 1 H NMR spectrum.

[0088] Figure 24 It is the phenyl ketamide compound (3l) in Example 12. 13 C NMR spectrum.

[0089] Figure 25 It is the phenyl ketoamide compound (3m) in Example 13. 1 H NMR spectrum.

[0090] Figure 26 It is the phenyl ketoamide compound (3m) in Example 13. 13 C NMR spectrum.

[0091] Figure 27 It is the phenyl ketamide compound (3n) in Example 14. 1 H NMR spectrum.

[0092] Figure 28 It is the phenyl ketamide compound (3n) in Example 14. 13 C NMR spectrum. Detailed Implementation

[0093] As described above, the purpose of this invention is to provide a method for preparing phenyl ketamide compounds.

[0094] In this invention, phenyl ketone amide compounds are directly synthesized under alkaline conditions using acylsilyl compounds as raw materials and readily available conventional solvents such as formamide and its derivatives as nucleophiles. This method utilizes readily available raw materials, has a broad substrate range, is convenient to operate, and exhibits high atom economy, making it suitable for industrial production.

[0095] In this invention, "C" i～j "" indicates that the number of carbon atoms is an integer from i to j. For example, C 1～6 Alkyl groups refer to alkyl groups containing 1 to 6 carbon atoms (including 1 and 6), C 2-6 The alkenyl group refers to an alkenyl group containing 2 to 6 carbon atoms (including 2 and 6).

[0096] The term "substituted" means that any usable connection point in the structure can be replaced by a substituent. The substituent includes, but is not limited to, carboxyl, amino, nitrosyl, alcohol hydroxyl, halogen, or hydrocarbon groups.

[0097] This invention provides a method for preparing phenyl ketone amide compounds, comprising the following steps:

[0098] Using phenylsilyl compound 1 and amide compound 2 as raw materials, a catalyst is added, and the mixture is reacted in a first solvent to prepare phenyl ketone amide compound 3. The reaction route can be any one of the following two reaction routes:

[0099] First reaction route:

[0100]

[0101] The second reaction route:

[0102]

[0103] Among them, the R1 group is in The ortho, meta, and / or para positions of the group; n is 1 to 3;

[0104] The R1 group is selected from hydrogen, C 1-6 Alkyl, C 1-6 The alkoxy group, halogen substituent, or C substituent is a C group that is substituted with a substituent. 1-6 The alkyl group, wherein the substituent is selected from one or more of methyl, tert-butyl, methoxy, butoxy, F and Cl;

[0105] The R2 and R3 groups are independently selected from H or C. 1-6 alkyl;

[0106] The R4 group is a silicon-containing group;

[0107] R5 group is selected from In this configuration, the R6 group is attached to any carbon atom on the nitrogen-containing ring, and the R6 group is selected from H and C. 1-7 Alkyl or alkoxy groups.

[0108] in, The R6 group can be attached to any carbon atom on the ring. For example, express express and / or

[0109] Preferably, the first solvent is tetrahydrofuran; it is easy to recycle and has low environmental pollution.

[0110] Preferably, formamide compounds are used as nucleophiles because the raw materials are inexpensive and readily available, and the reaction is easy to perform.

[0111] Preferably, the phenyl ketamide compound 3 is any one of the following compounds:

[0112]

[0113] Unless otherwise stated, all reagents / instruments used in the embodiments and comparative examples of this invention are conventional commercially available products. Information on the experimental materials and instruments used in this invention is shown in the table below:

[0114] Table 1 Experimental Materials and Manufacturers

[0115]

[0116]

[0117] The acylsilane compound in this invention was prepared according to the method described in the journal (“Nucleophilic Allylation of Acylsilanes in Water: An Effective Alternative to Functionalized Tertiary α-Silylalcohols”, Xiu-Xia Liang, et al., The Journal of Organic Chemistry, 2023, 88, 16, 12087–12099), and the successful preparation of the compound was confirmed by characterization with 1H NMR and 13CNMR.

[0118] To better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments.

[0119] Example 1: Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0120] Example 1-1

[0121] (1) Preparation of p-Tolyl(triethylsilyl)methyl ketone

[0122]

[0123] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of p-tolualdehyde (10.0 mmol) in dichloromethane (10 mL), followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-p-tolyl-1,3-dithiaane.

[0124] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of tetrahydrofuran (THF) containing 10.2mmol of 2-p-tolyl-1,3-dithiophene-2-yl)silane. After stirring at 0°C for 30 min, the reaction mixture was brought to room temperature and stirred for 30 min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40 min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to give triethyl(2-(p-tolyl)-1,3-dithiophene-2-yl)silane.

[0125] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-(p-tolyl)-1,3-dithiophene-2-yl)silane (0.93 g, 2.857 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove moisture, and the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) until dry. The solution was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain p-tolyl(triethylsilyl) methyl ketone.

[0126] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0127]

[0128] Under a nitrogen atmosphere at -78°C, N,N-dimethylformamide (DMF) (0.2 mmol) was added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After the solution was cooled to -78°C, lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) was added. After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (27.51 mg, yield 72% (based on the molar amount of DMF), compound 3a).

[0129] The structural characterization data of compound 3a are as follows:

[0130] from Figure 1 We can obtain: 1 HNMR (600MHz, CDCl3) δ7.84 (d, J = 8.4Hz, 2H), 7.30 (d, J = 7.8Hz, 2H), 3.11 (s, 3H), 2.95 (s, 3H), 2.43 (s, 3H).

[0131] from Figure 2 We can obtain: 13 C NMR (150MHz, CDCl3) δ191.6,167.3,146.1,130.7,129.83,129.80,37.1,34.0,22.0.

[0132] HRMS (ESI): Molecular formula C 11 H 13 NO2, m / z[M+Na] + The theoretical value is 214.0838, and the actual value is 214.0835.

[0133] Examples 1-2

[0134] (1) Step (1) is the same as in Example 1-1.

[0135] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0136] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.1 mL, 0.2 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.2 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 9%).

[0137] Examples 1-3

[0138] (1) Step (1) is the same as in Example 1-1.

[0139] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0140] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and diisopropylaminolithium LDA (2 mol / L, 0.1 mL, 0.2 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.4 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 31%).

[0141] Examples 1-4

[0142] (1) Step (1) is the same as in Example 1-1.

[0143] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0144] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.1 mL, 0.2 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.6 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 32%).

[0145] Examples 1-5

[0146] (1) Step (1) is the same as in Example 1-1.

[0147] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0148] Under a nitrogen atmosphere at -78°C, DMF (0.4 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.1 mL, 0.2 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.2 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 6%).

[0149] Examples 1-6

[0150] (1) Step (1) is the same as in Example 1-1.

[0151] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0152] Under a nitrogen atmosphere at -100°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 67%).

[0153] Examples 1-7

[0154] (1) Step (1) is the same as in Example 1-1.

[0155] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0156] Under a nitrogen atmosphere at -50°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, yield 4%).

[0157] Examples 1-8

[0158] (1) Step (1) is the same as in Example 1-1.

[0159] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0160] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 2 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography. The eluent used was petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 70%).

[0161] Examples 1-9

[0162] (1) Step (1) is the same as in Example 1-1.

[0163] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0164] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium di(trimethylsilyl)amino (0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1 hour, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 3%).

[0165] Examples 1-10

[0166] (1) Step (1) is the same as in Example 1-1.

[0167] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0168] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and sodium di(trimethylsilyl)aminoacetamide (0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1 hour, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 2%).

[0169] Examples 1-11

[0170] (1) Step (1) is the same as in Example 1-1.

[0171] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0172] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and potassium di(trimethylsilyl)amino (0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1 hour, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 2%).

[0173] Examples 1-12

[0174] (1) Step (1) is the same as in Example 1-1.

[0175] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0176] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a methyl tert-butyl ether solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 50%).

[0177] Examples 1-13

[0178] (1) Step (1) is the same as in Example 1-1.

[0179] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0180] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a toluene solution (0.6 mL) of p-toluene (triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-toluylacetamide (compound 3a, 49%).

[0181] Examples 1-14

[0182] (1) Step (1) is the same as in Example 1-1.

[0183] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0184] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a diethyl ether solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 49%).

[0185] Examples 1-15

[0186] (1) Step (1) is the same as in Example 1-1.

[0187] (2) Preparation of N,N-dimethyl-2-oxo-2-p-tolylacetamide

[0188] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and lithium diisopropylaminol LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a dichloromethane solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-p-tolylacetamide (compound 3a, 1%).

[0189] Example 2: Preparation of N,N-diethyl-2-oxo-2-p-tolylacetamide

[0190]

[0191] (1) The preparation steps of p-toluyl (triethylsilyl) methyl ketone are the same as those in Example 1.

[0192] (2) Preparation of N,N-diethyl-2-oxo-2-p-tolylacetamide

[0193] Under a nitrogen atmosphere at -78°C, N,N-diethylformamide (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 4.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-diethyl-2-oxo-2-p-tolylacetamide (35.48 mg, 81%, compound 3b).

[0194] The structural characterization data of compound 3b are as follows:

[0195] from Figure 3 We can obtain: 1 HNMR(600MHz, CDCl3)δ7.80(d,J=8.4Hz,2H),7.27(d,J=8.4Hz,2H),3.53(q,J=7.2Hz, 2H), 3.21 (q, J = 7.2Hz, 2H), 2.40 (s, 3H), 1.26 (t, J = 7.2Hz, 3H), 1.12 (t, J = 7.2Hz, 3H).

[0196] from Figure 4 We can obtain: 13C NMR (150MHz, CDCl3) δ191.5,167.0,145.8,130.9,129.79,129.75,42.2,38.8,21.9,14.2,12.9.

[0197] HRMS (ESI): Molecular formula C 13 H 17 NO2, m / z[M+H] + The theoretical value is 220.1332, and the actual value is 220.1332.

[0198] Example 3: Preparation of 1-(piperidin-1-yl)-2-p-tolylethane-1,2-dione

[0199]

[0200] (1) The preparation steps of p-toluyl (triethylsilyl) methyl ketone are the same as those in Example 1.

[0201] (2) Preparation of 1-(piperidin-1-yl)-2-(p-tolyl)ethane-1,2-dione

[0202] Under a nitrogen atmosphere at -78°C, piperidine-1-carboxaldehyde (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (1.0 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 1-piperidine-1-yl-2-p-tolylethane-1,2-dione (37.42 mg, 81%, compound 3c).

[0203] The structural characterization data of compound 3c are as follows:

[0204] from Figure 5 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.84(d,J=8.4Hz,2H),7.31(d,J=7.8Hz,2H),3.70(s,2H),3.28(t,J=6.6Hz,2H),2.43(s,3H),1.69(s,4H),1.54(s,2H).

[0205] from Figure 6 We can obtain: 13C NMR (150MHz, CDCl3) δ191.8,165.8,146.0,131.0,129.83,129.81,47.2,42.2,26.3,25.6,24.5,22.0.

[0206] HRMS (ESI): Molecular formula C 14 H 17 NO2, m / z[M+H] + The theoretical value is 232.1332, and the actual value is 232.1331.

[0207] Example 4: Preparation of 2-oxo-N,N-dipropyl-2-(p-tolyl)acetamide

[0208]

[0209] (1) The preparation steps of p-toluyl (triethylsilyl) methyl ketone are the same as those in Example 1.

[0210] (2) Preparation of 2-oxo-N,N-dipropyl-2-(p-tolyl)acetamide

[0211] Under a nitrogen atmosphere at -78°C, N,N-dipropylformamide (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1 hour, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-oxo-N,N-dipropyl-2-(p-tolyl)acetamide (41.99 mg, 85%, compound 3d).

[0212] The structural characterization data of compound 3d are as follows:

[0213] from Figure 7 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.83(d,J=8.4Hz,2H),7.29(d,J=7.8Hz,2H),3.46(t,J=7.8Hz,2H),3.11(t,J=7.8 Hz, 2H), 2.43 (s, 3H), 1.74–1.6 (m, 2H), 1.60–1.54 (m, 2H), 1.00 (t, J = 7.8Hz, 3H), 0.78 (t, J = 7.8Hz, 3H).

[0214] from Figure 8 We can obtain: 13C NMR (150MHz, CDCl3) δ191.5,167.5,145.8,131.1,129.9,129.8,49.5,45.9,22.0,21.9,20.8,11.6,11.2.

[0215] HRMS (ESI): Molecular formula C 15 H 21 NO2, m / z[M+H] + The theoretical value is 248.1645, and the actual value is 248.1648.

[0216] Example 5: Preparation of N,N-dibutyl-2-oxo-2-p-tolylacetamide

[0217]

[0218] (1) The preparation steps of p-toluyl (triethylsilyl) methyl ketone are the same as those in Example 1.

[0219] (2) Preparation of N,N-dibutyl-2-oxo-2-p-tolylacetamide

[0220] Under a nitrogen atmosphere at -78°C, N,N-dibutylformamide (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 2 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dibutyl-2-oxo-2-p-tolylacetamide (47.85 mg, 87%, compound 3e).

[0221] The structural characterization data of compound 3e are as follows:

[0222] from Figure 9 The following values ​​were obtained for H NMR (600MHz, CDCl3): δ 7.81 (d, J = 8.4Hz, 2H), 7.29 (d, J = 7.8Hz, 2H), 3.48 (t, J = 7.8Hz, 2H), 3.13 (t, J = 7.8Hz, 2H), 2.42 (s, 3H), 1.68–1.63 (m, 2H), 1.54–1.49 (m, 2H), 1.43–1.37 (m, 2H), 1.20–1.14 (m, 2H), 0.98 (t, J = 7.2Hz, 3H), 0.80 (t, J = 7.2Hz, 3H).

[0223] from Figure 10 We can obtain:13 C NMR (150MHz, CDCl3) δ191.5,167.4,145.8,131.1,129.82,129.75,47.5,44.1,30.7,29.6,22.0,20.4,19.9,14.0,13.7.

[0224] HRMS (ESI): Molecular formula C 17 H 25 NO2, m / z[M+H] + The theoretical value is 276.1958, and the actual value is 276.1960.

[0225] Example 6: Preparation of 1-azaphen-1-yl-2-p-tolylethane-1,2-dione

[0226]

[0227] (1) The preparation steps of p-toluyl (triethylsilyl) methyl ketone are the same as those in Example 1.

[0228] (2) Preparation of 1-azaphen-1-yl-2-p-tolylethane-1,2-dione

[0229] Under a nitrogen atmosphere at -78°C, hexahydro-1H-azaphen-1-carboxaldehyde (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of p-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 1-azaphen-1-yl-2-p-tolylethane-1,2-dione (39.69 mg, 81%, compound 3f).

[0230] The structural characterization data of compound 3f are as follows:

[0231] from Figure 11 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.84(d,J=8.4Hz,2H),7.30(d,J=8.4Hz,2H),3.67(t,J=6.0Hz,2H),3 .33(t,J=6.0Hz,2H),2.43(s,3H),1.86–1.82(m,2H),1.69–1.64(m,4H),1.60–1.57(d,2H).

[0232] from Figure 12 We can obtain:13 C NMR (150MHz, CDCl3) δ191.7,167.5,145.9,131.0,129.9,129.8,48.1,45.2,29.2,27.8,27.4,26.7,22.0.

[0233] HRMS (ESI): Molecular formula C 15 H 19 NO2, m / z[M+H] + The theoretical value is 246.1489, and the actual value is 246.1489.

[0234] Example 7: Preparation of N,N-dimethyl-2-oxo-2-phenylacetamide

[0235] (1) Preparation of phenyl(triethylsilyl) methyl ketone

[0236]

[0237] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of benzaldehyde (10.0 mmol) in dichloromethane (10 mL), followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-phenyl-1,3-dithiaane.

[0238] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (1.71mL, 10.2mmol) were added to 10.0mL of THF containing 2-phenyl-1,3-dithiane (2.0g, 10.2mmol). After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched with water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain triethyl(2-phenyl-1,3-dithiaphen-2-yl)silane.

[0239] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-phenyl-1,3-dithiophene-2-yl)silane (2.87 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was carried out for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove water, and the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min). The mixture was then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain phenyl(triethylsilyl) methyl ketone.

[0240] (2) Preparation of N,N-dimethyl-2-oxo-2-phenylacetamide

[0241]

[0242] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of phenyl (triethylsilyl) methyl ketone (0.3 mmol). After stirring for 2 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-phenylacetamide (27.26 mg, 77%, compound 3 g).

[0243] The structural characterization data of compound 3g are as follows:

[0244] from Figure 13 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.89 (d, J=7.2Hz, 2H), 7.59 (t, J=7.2Hz, 1H), 7.46 (t, J=7.2Hz, 2H), 3.06 (s, 3H), 2.90 (s, 3H).

[0245] from Figure 14 We can obtain: 13 C NMR (150MHz, CDCl3) δ191.8,167.0,134.7,133.0,129.6,129.0,37.0,33.9.

[0246] HRMS (ESI): Molecular formula C 10 H 11 NO2, m / z[M+Na] + The theoretical value is 200.0682, and the actual value is 200.0687.

[0247] Example 8: Preparation of 2-(4-tert-butyl)phenyl-N,N-dimethyl-2-oxoacetamide

[0248] (1) Preparation of ((4-tert-butyl)phenyl)(triethylsilyl)methyl ketone

[0249]

[0250] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of 10.0 mmol of 4-(tert-butyl)benzaldehyde in 10 mL of dichloromethane, followed by the addition of 3 mmol of boron trifluoride diethyl ether. The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-(4-tert-butyl)phenyl-1,3-dithiaane.

[0251] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of THF containing 10.2mmol of 2-(4-tert-butyl)phenyl-1,3-dithiophene-2-yl)triethylsilane. After stirring at 0°C for 30 min, the reaction mixture was brought to room temperature and stirred for 30 min. The reaction was then quenched by adding water (2mL). After concentration under reduced pressure (evaporation at 35°C for 40 min), the mixture was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-(4-tert-butyl)phenyl-1,3-dithiophene-2-yl)triethylsilane.

[0252] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to 2-(4-tert-butyl)phenyl-1,3-dithiophene-2-yl)triethylsilane (2.857 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove water, and the mixture was concentrated under reduced pressure (evaporation at 35°C for 40 min). The mixture was then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (4-tert-butyl)phenyl(triethylsilyl) methyl ketone.

[0253] (2) Preparation of 2-(4-tert-butyl)phenyl-N,N-dimethyl-2-oxoacetamide

[0254]

[0255] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of (4-tert-butyl)phenyl(triethylsilyl) ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-(4-tert-butyl)phenyl-N,N-dimethyl-2-oxoacetamide (36.81 mg, 79%, compound 3 h).

[0256] The structural characterization data of compound 3h are as follows:

[0257] from Figure 15 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.87 (d, J = 9.0 Hz, 2H), 7.51 (d, J = 9.0 Hz, 2H), 3.11 (s, 3H), 2.95 (s, 3H), 1.34 (s, 9H).

[0258] from Figure 16 We can obtain: 13 C NMR (150MHz, CDCl3) δ191.7,167.4,158.9,130.7,129.8,126.2,37.2,35.5,34.1,31.1.

[0259] HRMS (ESI): Molecular formula C 14 H 19 NO2, m / z[M+H] + The theoretical value is 234.1489, and the actual value is 234.1485.

[0260] Example 9: Preparation of 2-(4-chlorophenyl)-N,N-dimethyl-2-oxoacetamide

[0261] (1) Preparation of (4-chlorophenyl)(triethylsilyl) methyl ketone

[0262]

[0263] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of p-chlorobenzaldehyde (10.0 mmol) in dichloromethane (10 mL), followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-(4-chlorophenyl)-1,3-dithiaane.

[0264] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of THF containing 2-(4-chlorophenyl)-1,3-dithiaran (2.35g, 10.2mmol). After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (2-(4-chlorophenyl)-1,3-dithiaran-2-yl)triethylsilane.

[0265] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to (2-(4-chlorophenyl)-1,3-dithiadin-2-yl)triethylsilane (0.98 g, 2.857 mmol), followed by the addition of NBS (2.0 g, 11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove the water, and the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min). The solution was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (4-chlorophenyl)(triethylsilyl) methyl ketone.

[0266] (2) Preparation of 2-(4-chlorophenyl)-N,N-dimethyl-2-oxoacetamide

[0267]

[0268] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of (4-chlorophenyl)(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 2 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-(4-chlorophenyl)-N,N-dimethyl-2-oxoacetamide (36.29 mg, 86%, compound 3i).

[0269] The structural characterization data of compound 3i are as follows:

[0270] from Figure 17 We can obtain: 1H NMR (600MHz, CDCl3) δ7.89 (d, J = 8.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 3.11 (s, 3H), 2.96 (s, 3H).

[0271] from Figure 18 We can obtain: 13 C NMR (150MHz, CDCl3) δ190.4,166.6,141.5,131.6,131.2,129.5,37.2,34.2.

[0272] HRMS (ESI): Molecular formula C 10 H 10 ClNO2, m / z[M+H] + The theoretical value is 212.0473, and the actual value is 212.0470.

[0273] Example 10: Preparation of 2-(4-methoxyphenyl)-N,N-dimethyl-2-oxoacetamide

[0274] (1) Preparation of (4-methoxyphenyl)(triethylsilyl) methyl ketone

[0275]

[0276] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of 10.0 mmol of 4-methoxybenzaldehyde in 10 mL of dichloromethane, followed by the addition of 3 mmol of boron trifluoride diethyl ether. The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to give 2-(4-methoxyphenyl)-1,3-dithiaane.

[0277] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of THF containing 10.2mmol of 2-(4-methoxyphenyl)-1,3-dithiophene-2-ylsilane. After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain triethyl(2-(4-methoxyphenyl)-1,3-dithiophene-2-ylsilane).

[0278] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-(4-methoxyphenyl)-1,3-dithiophene-2-ylsilane) (0.97 g, 2.857 mmol), followed by the addition of NBS (2.0 g, 11.24 mmol), and the reaction was carried out for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). After removing the water with anhydrous sodium sulfate, the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min). The mixture was then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (4-methoxyphenyl)(triethylsilyl) methyl ketone.

[0279] (2) Preparation of 2-(4-methoxyphenyl)-N,N-dimethyl-2-oxoacetamide

[0280]

[0281] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of (4-methoxyphenyl)(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-(4-methoxyphenyl)-N,N-dimethyl-2-oxoacetamide (37.26 mg, 90%, compound 3j).

[0282] The structural characterization data of compound 3j are as follows:

[0283] from Figure 19 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.90 (d, J = 9.0 Hz, 2H), 6.96 (d, J = 9.0 Hz, 2H), 3.87 (s, 3H), 3.09 (s, 3H), 2.94 (s, 3H).

[0284] from Figure 20 We can obtain: 13 C NMR (150MHz, CDCl3) δ190.6,167.5,165.0,132.2,126.3,114.4,55.8,37.2,34.1.

[0285] HRMS (ESI): Molecular formula C 11 H 13 NO3, m / z[M+H] +The theoretical value is 208.0968, and the actual value is 208.0966.

[0286] Example 11: Preparation of 2-(4-butoxyphenyl)-N,N-dimethyl-2-oxoacetamide

[0287] (1) Preparation of (4-butoxyphenyl)(triethylsilyl) methyl ketone

[0288]

[0289] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of 10.0 mmol of 4-butoxybenzaldehyde in 10 mL of dichloromethane, followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-(4-butoxyphenyl)-1,3-dithiaane.

[0290] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of THF containing 10.2mmol of 2-(4-butoxyphenyl)-1,3-dithiophene-2-ylsilane. After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL). After concentration under reduced pressure (evaporation at 35°C for 40min), the mixture was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to give triethyl(2-(4-butoxyphenyl))-1,3-dithiophene-2-ylsilane.

[0291] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-(4-butoxyphenyl))-1,3-dithiophene-2-ylsilane (2.857 mmol), followed by the addition of NBS (2.0 g, 11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove the water, and the mixture was evaporated to dryness. The solution was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (4-butoxyphenyl)(triethylsilyl) methyl ketone.

[0292] (2) Preparation of 2-(4-butoxyphenyl)-N,N-dimethyl-2-oxoacetamide

[0293]

[0294] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of (4-butoxyphenyl)(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-(4-butoxyphenyl)-N,N-dimethyl-2-oxoacetamide (43.33 mg, 87%, compound 3k).

[0295] The structural characterization data of compound 3j are as follows:

[0296] from Figure 21 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.89 (d, J = 9.0Hz, 2H), 6.95 (d, J = 8.4Hz, 2H), 4.04 (t, J = 6.6Hz, 2H) ,3.10(s,3H),2.95(s,3H),1.81–1.76(m,2H),1.52–1.46(m,2H),0.98(t,J=7.2Hz,3H).

[0297] from Figure 22 We can obtain: 13 C NMR (150MHz, CDCl3) δ190.6,167.6,164.6,132.2,126.1,114.9,68.3,37.2,34.1,31.2,19.3,13.9.

[0298] HRMS (ESI): Molecular formula C 14 H 19 NO3, m / z[M+Na] + The theoretical value is 272.1257, and the actual value is 272.1255.

[0299] Example 12: Preparation of N,N-dimethyl-2-oxo-2-(o-tolyl)acetamide

[0300] (1) Preparation of o-tolyl(triethylsilyl) methyl ketone

[0301]

[0302] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of o-tolualdehyde (10.0 mmol) in dichloromethane (10 mL), followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain o-tolyl-1,3-dithiaane.

[0303] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to THF (10.0mL) containing o-tolyl-1,3-dithiaran (10.2mmol). After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain triethyl(2-(o-tolyl)-1,3-dithiaran-2-yl)silane.

[0304] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-(o-tolyl)-1,3-dithiadin-2-yl)silane (2.857 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove water, and the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min). The solution was purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain o-tolyl(triethylsilyl) methyl ketone.

[0305] (2) Preparation of N,N-dimethyl-2-oxo-2-(o-tolyl)acetamide

[0306]

[0307] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of o-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 2 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-(o-tolyl)acetamide (17.95 mg, 47%, compound 3l).

[0308] The structural characterization data of compound 3l are as follows:

[0309] from Figure 23 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.67 (d, J = 7.8Hz, 1H), 7.44-7.47 (m, 1H), 7.28-7.29 (m, 2H), 3.09 (s, 3H), 2.95 (s, 3H), 2.64 (s, 3H).

[0310] from Figure 24 We can obtain: 13 C NMR (150MHz, CDCl3) δ193.9,167.9,141.5,133.8,132.72,132.66,131.6,126.3,37.1,34.1,21.8.

[0311] HRMS (ESI): Molecular formula C 11 H 13 NO2, m / z[M+H] + The theoretical value is 192.1019, and the actual value is 192.0986.

[0312] Example 13: Preparation of N,N-dimethyl-2-oxo-2-(m-tolyl)acetamide

[0313] (1) Preparation of m-Tolyl(Triethylsilyl)Methylketone

[0314]

[0315] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of m-tolualdehyde (10.0 mmol) in dichloromethane (10 mL), followed by the addition of boron trifluoride diethyl ether (3 mmol). The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain m-tolyl-1,3-dithiaane.

[0316] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to THF (10.0mL) containing m-tolyl-1,3-dithiaran (10.2mmol). After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain triethyl(2-(m-tolyl)-1,3-dithiaran-2-yl)silane.

[0317] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to triethyl(2-(m-tolyl)-1,3-dithiadin-2-yl)silane (2.857 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was allowed to proceed for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove water, and the mixture was concentrated under reduced pressure (evaporation at 35°C for 40 min). The mixture was then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain m-tolyl(triethylsilyl) methyl ketone.

[0318] (2) Preparation of N,N-dimethyl-2-oxo-2-(m-tolyl)acetamide

[0319]

[0320] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of m-tolyl(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1 hour, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give N,N-dimethyl-2-oxo-2-(m-tolyl)acetamide (27.89 mg, 73%, compound 3 m).

[0321] The structural characterization data of compound 3m are as follows:

[0322] from Figure 25 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.72-7.73(m,2H),7.43-7.44(m,1H),7.36-7.39(m,1H),3.10(s,3H),2.94(s,3H),2.40(s,3H).

[0323] from Figure 26 We can obtain: 13 C NMR (150MHz, CDCl3) δ192.1,167.3,139.0,135.7,133.2,130.1,129.0,127.0,37.1,34.1,21.3.

[0324] HRMS (ESI): Molecular formula C 11 H 13 NO2, m / z[M+H] + The theoretical value is 192.1019, and the actual value is 192.1013.

[0325] Example 14: Preparation of 2-(3,5-dimethylphenyl)-N,N-dimethyl-2-oxoacetamide

[0326] (1) Preparation of (3,5-dimethylphenyl)(triethylsilyl) methyl ketone

[0327]

[0328] 1) Under a nitrogen atmosphere at 0°C, 1,3-propanedithiol (11.0 mmol) was added to a solution of 10.0 mmol of 3,5-dimethylbenzaldehyde in 10 mL of dichloromethane, followed by the addition of 3 mmol of boron trifluoride diethyl ether. The mixture was stirred at room temperature for 3 hours. The reaction solution was filtered through diatomaceous earth, concentrated under reduced pressure, and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) as the eluent to obtain 2-(3,5-dimethylphenyl)-1,3-dithiaane.

[0329] 2) Under a nitrogen atmosphere at 0°C, n-BuLi (2.5M, 6.08mL, 15.2mmol) and TESCl (10.2mmol) were added to 10.0mL of THF containing 10.2mmol of 2-(3,5-dimethylphenyl)-1,3-dithiaran (2.2mmol). After stirring at 0°C for 30min, the reaction mixture was brought to room temperature and stirred for 30min. The reaction was then quenched by adding water (2mL), concentrated under reduced pressure (evaporated at 35°C for 40min), and purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (2-(3,5-dimethylphenyl)-1,3-dithiaran-2-yl)triethylsilane.

[0330] 3) Under an air atmosphere at 0°C, acetone and water (acetone:water volume ratio 6:7) were added to (2-(3,5-dimethylphenyl)-1,3-dithiadin-2-yl)triethylsilane (2.857 mmol), followed by the addition of NBS (11.24 mmol), and the reaction was carried out for 30 min. The mixture was diluted with water (10 mL) and extracted with EtOAc (10 mL). Anhydrous sodium sulfate was added to remove water, and the mixture was concentrated under reduced pressure (evaporated at 35°C for 40 min). The mixture was then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 100:1) to obtain (3,5-dimethylphenyl)(triethylsilyl) methyl ketone.

[0331] (2) Preparation of 2-(3,5-dimethylphenyl)-N,N-dimethyl-2-oxoacetamide

[0332]

[0333] Under a nitrogen atmosphere at -78°C, DMF (0.2 mmol) and LDA (2 mol / L, 0.35 mL, 0.7 mmol) were added to a THF solution (0.6 mL) of (3,5-dimethylphenyl)(triethylsilyl) methyl ketone (0.3 mmol). After stirring for 1.5 hours, water (2 mL) was added to quench the reaction. The solution was concentrated under reduced pressure (evaporated at 35°C for 40 min) and then purified by column chromatography using petroleum ether / ethyl acetate (v / v = 5:1) to give 2-(3,5-dimethylphenyl)-N,N-dimethyl-2-oxoacetamide (34.85 mg, 85%, compound 3n).

[0334] The structural characterization data of compound 3n are as follows:

[0335] from Figure 27 We can obtain: 1 H NMR (600MHz, CDCl3) δ7.46(s,2H),7.19(s,1H),3.04(s,3H),2.87(s,3H),2.29(s,6H).

[0336] from Figure 28 We can obtain: 13 C NMR (150MHz, CDCl3) δ192.4,167.4,138.9,136.6,133.2,127.4,37.1,34.0,21.2.

[0337] HRMS (ESI): Molecular formula C 12 H 15 NO2, m / z[M+H] + The theoretical value is 206.1176, and the actual value is 206.1173.

[0338] While the specific embodiments of the present invention have been described above, they are not intended to limit the scope of protection of the present invention. Based on the technical solutions of the present invention, various modifications or variations that can be made by those skilled in the art without creative effort are still within the scope of protection of the present invention.

Claims

1. A method for preparing a phenyl ketone amide compound, characterized in that, It includes the following steps: Using phenylsilyl compound 1 and amide compound 2 as raw materials, a catalyst is added, and the mixture is reacted in a first solvent to prepare phenyl ketone amide compound 3. The catalyst is selected from one or more of lithium diisopropylamino, lithium di(trimethylsilyl)amino, sodium di(trimethylsilyl)amino, and potassium di(trimethylsilyl)amino; the reaction route is any one of the following two reaction routes: First reaction route: ； The second reaction route: ； Among them, the R1 group is The ortho, meta, and / or para positions of the group; n is 1 to 3; The R1 group is selected from hydrogen, C 1-6 Alkyl, C 1-6 The alkoxy group, halogen substituent, or C substituent is a C group that is substituted with a substituent. 1-6 The alkyl group, wherein the substituent is selected from one or more of methyl, tert-butyl, methoxy, butoxy, -F and -Cl; The R2 and R3 groups are independently selected from H or C. 1-6 alkyl; The R4 group is trimethylsilyl, triethylsilyl, or tert-butyldimethylsilyl; R5 group is selected from ; ; ; ; or The R6 group is selected from H and C. 1-7 alkyl or C 1-7 alkoxy groups.

2. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, In either the first or second reaction route, the R1 group is selected from hydrogen, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, methoxy, butoxy, or -Cl; And / or, in the first reaction route, R2 and R3 groups are independently selected from methyl, ethyl, propyl, or n-butyl; or, in the second reaction route, R5 group is selected from... , or .

3. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 1~4: 1~3.

4. The method for preparing phenyl ketone amide compounds according to claim 2, wherein, The molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 1~4: 1~3.

5. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 2.5~3.5:1.5~2.

5.

6. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The molar ratio of the phenylsilyl compound 1 to the amide compound 2 is 2.7~3.3: 1.7~2.

3.

7. The method for preparing phenyl ketamide compounds according to claim 1, wherein, The reaction temperature is -110℃ to -40℃; And / or, the reaction time is 0.5~5h.

8. The method for preparing phenyl ketone amide compounds according to claim 2, wherein, The reaction temperature is -110℃ to -40℃; And / or, the reaction time is 0.5~5h.

9. The method for preparing phenyl ketone amide compounds according to claim 3, wherein, The reaction temperature is -110℃ to -40℃; And / or, the reaction time is 0.5~5h.

10. The method for preparing phenyl ketone amide compounds according to claim 7, wherein, The reaction temperature is -100℃ to -70℃.

11. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The catalyst was selected from lithium diisopropylamino.

12. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The molar ratio of catalyst to compound 1 is 1~8:1~4.

13. The method for preparing phenyl ketone amide compounds according to claim 2, wherein, The molar ratio of catalyst to compound 1 is 1~8:1~4.

14. The method for preparing phenyl ketone amide compounds according to claim 3, wherein, The molar ratio of catalyst to compound 1 is 1~8:1~4.

15. The method for preparing phenyl ketone amide compounds according to claim 7, wherein, The molar ratio of catalyst to compound 1 is 1~8:1~4.

16. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The molar ratio of catalyst to compound 1 is 6~8:2~4.

17. The method for preparing phenyl ketamide compounds according to claim 1, wherein, The molar ratio of catalyst to compound 1 is 6.5~7.5:2.5~3.

5.

18. The method for preparing phenyl ketamide compounds according to claim 1, wherein, The first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

19. The method for preparing phenyl ketone amide compounds according to claim 2, wherein, The first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

20. The method for preparing phenyl ketone amide compounds according to claim 3, wherein, The first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

21. The method for preparing phenyl ketone amide compounds according to claim 7, wherein, The first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

22. The method for preparing phenyl ketone amide compounds according to claim 12, wherein, The first solvent includes one or more of tetrahydrofuran, methyl tert-butyl ether, toluene, diethyl ether, and dichloromethane.

23. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The first solvent is tetrahydrofuran.

24. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

25. The method for preparing phenyl ketone amide compounds according to claim 2, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

26. The method for preparing phenyl ketone amide compounds according to claim 3, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

27. The method for preparing phenyl ketone amide compounds according to claim 7, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

28. The method for preparing phenyl ketone amide compounds according to claim 12, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

29. The method for preparing phenyl ketone amide compounds according to claim 18, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:0.5~6, where the mole is in mol and the volume is in L.

30. The method for preparing phenyl ketone amide compounds according to claim 1, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:1~5, where the mole is in mol and the volume is in L.

31. The method for preparing phenyl ketamide compounds according to claim 1, wherein, The mole ratio of compound 1 to the volume ratio of the first solvent is 1:1~3, where the mole is in mol and the volume is in L.

32. The method for preparing the phenyl ketone amide compound according to any one of claims 1-31, wherein, After the reaction was complete, a second solvent was added to quench the reaction, yielding phenyl ketamide compound 3.

33. The method for preparing phenyl ketone amide compounds according to claim 32, wherein, The second solvent is water or a saturated aqueous solution of ammonium chloride; And / or, add a second solvent to quench the reaction, then concentrate under reduced pressure; And / or, the product concentrated under reduced pressure is purified by column chromatography.

34. The method for preparing phenyl ketone amide compounds according to claim 32, wherein, The volume ratio of the second solvent to the amount of compound 1 is 1 to 15:1, where the unit of amount of substance is mol and the unit of volume is L.

35. The method for preparing phenyl ketone amide compounds according to claim 33, wherein, The volume ratio of the second solvent to the amount of compound 1 is 5-8:1, where the unit of amount of substance is mol and the unit of volume is L.

36. The method for preparing phenyl ketone amide compounds according to claim 33, wherein, The temperature for vacuum concentration is 20~50℃; and / or the time is 10~60min.

37. The method for preparing phenyl ketone amide compounds according to claim 34, wherein, The temperature for vacuum concentration is 20~50℃; and / or the time is 10~60min.

38. The method for preparing phenyl ketone amide compounds according to claim 33, wherein, The eluent was petroleum ether and ethyl acetate.

39. The method for preparing phenyl ketone amide compounds according to claim 34, wherein, The eluent was petroleum ether and ethyl acetate.

40. The method for preparing phenyl ketone amide compounds according to claim 36, wherein, The eluent was petroleum ether and ethyl acetate.

41. The method for preparing phenyl ketone amide compounds according to claim 38, wherein, The volume ratio of petroleum ether to ethyl acetate is 2~15:

1.

42. The method for preparing the phenyl ketone amide compound according to any one of claims 1-31, wherein, The gas atmosphere during the preparation process is either N2 or Ar.

43. The method for preparing phenyl ketone amide compounds according to claim 32, wherein, The gas atmosphere during the preparation process is either N2 or Ar.

44. The method for preparing the phenyl ketone amide compound according to any one of claims 1-31, wherein, The phenyl ketamide compound 3 is any one of the following compounds: Compound 3a: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3b: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH3, R3 is -CH2CH3; Compound 3c: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3d: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH3, R3 is -CH2CH2CH3; Compound 3e: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH2CH3, R3 is -CH2CH2CH2CH3; Compound 3f: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3g: n=1, R1 is in the para position, R1 is -H, R2 is -CH3, R3 is -CH3; Compound 3h: n=1, R1 is in the para position, R1 is -C(CH3)3, R2 is -CH3, R3 is -CH3; Compound 3i: n=1, R1 is in the para position, R1 is -Cl, R2 is -CH3, R3 is -CH3; Compound 3j: n=1, R1 is in the para position, R1 is -OCH3, R2 is -CH3, R3 is -CH3; Compound 3k: n=1, R1 is in the para position, R1 is -OCH2CH2CH2CH3, R2 is -CH3, R3 is -CH3; Compound 3l: n=1, R1 is in the ortho position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3m: n=1, R1 is in the meta position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3n: n=2, R1 is in the meta position, R1 is -CH3, R2 is -CH3, and R3 is -CH3.

45. The method for preparing phenyl ketone amide compounds according to claim 32, wherein, The phenyl ketamide compound 3 is any one of the following compounds: Compound 3a: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3b: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH3, R3 is -CH2CH3; Compound 3c: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3d: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH3, R3 is -CH2CH2CH3; Compound 3e: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH2CH3, R3 is -CH2CH2CH2CH3; Compound 3f: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3g: n=1, R1 is in the para position, R1 is -H, R2 is -CH3, R3 is -CH3; Compound 3h: n=1, R1 is in the para position, R1 is -C(CH3)3, R2 is -CH3, R3 is -CH3; Compound 3i: n=1, R1 is in the para position, R1 is -Cl, R2 is -CH3, R3 is -CH3; Compound 3j: n=1, R1 is in the para position, R1 is -OCH3, R2 is -CH3, R3 is -CH3; Compound 3k: n=1, R1 is in the para position, R1 is -OCH2CH2CH2CH3, R2 is -CH3, R3 is -CH3; Compound 3l: n=1, R1 is in the ortho position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3m: n=1, R1 is in the meta position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3n: n=2, R1 is in the meta position, R1 is -CH3, R2 is -CH3, and R3 is -CH3.

46. ​​The method for preparing phenyl ketone amide compounds according to claim 42, wherein, The phenyl ketamide compound 3 is any one of the following compounds: Compound 3a: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3b: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH3, R3 is -CH2CH3; Compound 3c: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3d: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH3, R3 is -CH2CH2CH3; Compound 3e: n=1, R1 is in the para position, R1 is -CH3, R2 is -CH2CH2CH2CH3, R3 is -CH2CH2CH2CH3; Compound 3f: n=1, R1 is in the para position, R1 is -CH3, R5 is... ; Compound 3g: n=1, R1 is in the para position, R1 is -H, R2 is -CH3, R3 is -CH3; Compound 3h: n=1, R1 is in the para position, R1 is -C(CH3)3, R2 is -CH3, R3 is -CH3; Compound 3i: n=1, R1 is in the para position, R1 is -Cl, R2 is -CH3, R3 is -CH3; Compound 3j: n=1, R1 is in the para position, R1 is -OCH3, R2 is -CH3, R3 is -CH3; Compound 3k: n=1, R1 is in the para position, R1 is -OCH2CH2CH2CH3, R2 is -CH3, R3 is -CH3; Compound 3l: n=1, R1 is in the ortho position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3m: n=1, R1 is in the meta position, R1 is -CH3, R2 is -CH3, R3 is -CH3; Compound 3n: n=2, R1 is in the meta position, R1 is -CH3, R2 is -CH3, and R3 is -CH3.

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