A method for preparing quinolinone compounds

Abstract

The application discloses a preparation method of quinolinone compounds, and the preparation method comprises the following steps: contacting a compound shown in formula (I) a ′) or formula (I) b ′) with a catalyst, an oxidant and an organic solvent to react. The method has the advantages of high efficiency, economy and greenness, easy raw material, simple operation, mild reaction condition, good functional group tolerance and substrate universality, no need of additional ligand, excellent chemical selectivity, and is expected to be applied in the synthesis of related pharmaceutical chemistry and natural products.

Description

Technical Field

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

[0002] Quinolinones are used in the preparation of pharmaceuticals, dyes, photosensitive materials, rubber, solvents, and chemical reagents ((a) JMKraus et al. J. Med. Chem. 2010, 53, 3887-3898; (b) I. Kim et al. Angew. Chem., Int. Ed. 2018, 57, 15517-15522; (c) CCZhang, Nat. Prod. Res. 2017, 31, 99-103; (d) I. Kim, et al. J. Am. Chem. Soc. 2019, 141, 9239-9248; (e) Z. Li, et al. Science 2021, 372, 1452-1457), and are closely related to human life. Typical methods for synthesizing quinolinones include Camps quinoline synthesis, Conrad-Limpach reaction, and Friedlander quinoline synthesis. These strategies often employ stoichiometric amounts of corrosive acids and cumbersome synthetic steps, limiting the overall practicality of the synthesis [(a) Jones, CP; J. Org. Chem. 2007, 72, 7968-7973. (b) Chan, BK; J. Org. Chem. 2008, 72, 8489-8495. (c) C.-S. Jia, Org. Biomol. Chem. 2006, 4, 104-110.]. With the development of modern synthetic chemistry techniques, transition metal-catalyzed prefunctionalized aromatic rings undergo C-H bond activation / functionalization / cyclization to synthesize quinolinones (LBRao, C. Sreenivasulu, DRKishore, G. Satyanarayana, Tetrahedron, 2022, 127, 133093). The limitation of this technique lies in the complexity of substrate synthesis and the restriction of functional groups. Another strategy involves the functionalization of ortho-position quinolines through oxidation (S. Mandal, S. Bhuyan, S. Jana, J. Hossain, K. Chhetria and B. Gopal Roy, GreenChem., 2021, 23, 5049-5055), but the substrates are derived from unavailable quinoline oxides, posing a challenge for the diverse synthesis of novel quinolinones. Summary of the Invention

[0003] In view of the shortcomings of existing technologies, this invention provides a method for preparing quinolinone compounds. Using readily available pyridone compounds as raw materials, a one-step reaction is used to construct quinolinone compounds, enabling efficient, economical, and diversified synthesis of compounds containing quinolinones. This method utilizes readily available raw materials, is simple to operate, operates under mild conditions, and has a wide range of applicable substrates. It provides a highly efficient method for synthesizing important drug molecules and natural products containing quinolinone structural units.

[0004] Specifically, the present invention provides a formula (Ⅰ) a ) or formula (Ⅰ) b The method for preparing the quinolinone compound shown in Figure (Ⅰ) includes: under an inert atmosphere, mixing the quinolinone compound of formula (Ⅰ) with... a The compound shown in ') reacts with a catalyst, an oxidant, and an organic solvent to give formula (Ⅰ) a The compound shown in Figure (Ⅰ); or, under an inert atmosphere, the compound of formula (Ⅰ) b The compound shown in ') reacts with a catalyst, an oxidant, and an organic solvent to give formula (Ⅰ) b The compound shown in the figure has the following reaction formula:

[0005]

[0006] Wherein, R1 is selected from one of substituted or unsubstituted aryl or alkyl groups; R2 and R3 may be the same or different, and each is independently selected from one of hydrogen, halogen, alkyl, substituted or unsubstituted aryl, deuterium, or alkoxy groups; R4, R5, and R6 may be the same or different, and each is independently selected from one of hydrogen, aryl, alkyl, or ester groups.

[0007] According to a specific embodiment of the present invention, R1 is selected from one of C6-C10 substituted or unsubstituted aryl groups and C1-C6 alkyl groups, preferably one of benzyl, p-methoxybenzyl, phenyl, and methyl; R2 is selected from one of hydrogen, halogen, C1-C6 alkyl, and C6-C20 substituted or unsubstituted aryl groups, preferably one of hydrogen, fluorine, bromine, methyl, phenyl, halogen-substituted phenyl, naphthyl, and biphenyl; R3 is selected from hydrogen, deuterium, C1-C6 alkyl, and C6-C20 substituted or unsubstituted aryl groups. The R4 is selected from one of unsubstituted aryl and C1-C6 alkoxy groups, preferably one of hydrogen, deuterium, methyl, phenyl, halogen-substituted phenyl, benzyloxy, anthracene, and methoxy groups; the R5 is selected from one of hydrogen, C6-C10 aryl and C1-C6 alkyl groups, preferably one of hydrogen, phenyl, and methyl groups; the R6 is selected from one of hydrogen and C2-C6 ester groups, preferably one of hydrogen and C2-C3 ester groups; the R6 is selected from one of hydrogen and C1-C6 alkyl groups, preferably one of hydrogen and methyl groups.

[0008] According to a specific embodiment of the present invention, formula (Ⅰ) aThe compound shown in ′) is selected from 1-benzyl-6-buten-1-ylpyridin-2(1H) one, 6-(but-3-en-1-yl)-1-methylpyridin-2(1H)-one, 6-but-3-en-1-yl-1-(4-methoxybenzyl)pyridin-2(1H) one, 6-but-3-en-1-yl-1-phenylpyridin-2(1H) one, 1-benzyl-3-bromo-6-buten-1-ylpyridin-2(1H) one, 1-benzyl-6-buten-1-yl-3-fluoropyridin-2(1H) one, 1-benzyl-6-(but-3-) -en-1-yl)-3-methylpyridin-2(1H)-one, 1-benzyl-6-buten-1-yl-3-phenylpyridin-2(1H)one, 1-benzyl-6-buten-1-yl-3-naphthylpyridin-2(1H)one, 3-(1,1'-biphenyl)-2-yl)-1-benzyl-6-buten-1-ylpyridin-2(1H)one, 1-benzyl-4-benzyloxy-6-but-3-en-1-ylpyridin-2(1H)one, 1-benzyl-6-buten-1-ylpyridin-2(1H)one-4-d, 1-benzyl-6-buten-1-ylpyridin-2(1H)one Alken-1-yl-4-phenylpyridin-2(1H) one, 1-benzyl-6-buten-1-yl-4-(3-chlorophenyl)pyridin-2(1H) one, 1-benzyl-6-buten-1-yl-4-(3,5-difluorophenyl)pyridin-2(1H) one, 4-anthra-9-yl-1-benzyl-6-but-3-en-1-ylpyridin-2(1H) one, 1-benzyl-6-(but-3-en-1-yl)-4-methylpyridin-2(1H)-one, 1-benzyl-3-bromo-6-but-3-en-1-yl-4-phenylpyridin- One of the following: 2(1H) ketone, 1-benzyl-4-benzyloxy-3-bromo-6-buten-1-ylpyridin-2(1H) ketone, 6-(but-3-en-1-yl)-4-methoxy-1-methylpyridin-2(1H)-ketone, (E)-1-benzyl-6-(4-phenylbut-3-en-1-yl)pyridin-2(1H)-ketone, 4-(1-benzyl-6-oxo-1,6-dihydropyridin-2-yl)-2-methylenebutyrate ethyl ester, and 1-benzyl-6-(2-methylbut-3-en-1-yl)pyridin-2(1H)-ketone.

[0009] According to a specific embodiment of the present invention, formula (Ⅰ) bThe compound shown in ′) is selected from one of 1-benzyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-3-bromo-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-3-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-6-(pent-4-en-1-yl)-3-phenylpyridin-2(1H)-one, 1-benzyl-3-(2,4-dichlorophenyl)-6-(pent-4-en-1-yl)pyridin-2(1H)-one, and 1-benzyl-4-benzyloxy-6-(pent-4-en-1-yl)pyridin-2(1H)-one.

[0010] According to a specific embodiment of the present invention, the catalyst is selected from palladium acetate, palladium chloride, palladium neopentanoate, tris(dibenzylindeneacetone)palladium, allyl palladium chloride dimer, tetra(triphenylphosphine)palladium, di(triphenylphosphine)palladium chloride, [1,1'-bis(diphenylphosphino)ferrocene]palladium dichloride, palladium trifluoroacetate, palladium bromide, di(cyanobenzene)palladium dichloride, and bis(acetonitrile)palladium chloride (II).

[0011] According to a specific embodiment of the present invention, the oxidant is selected from at least one of 1,4-benzoquinone, 2,3-dichloro-5,6-dicyanobenzoquinone, ethyl acetoacetate copper, anhydrous copper acetate, copper chloride, anhydrous copper sulfate, silver oxide, silver acetate, and silver carbonate.

[0012] According to a specific embodiment of the present invention, the organic solvent is selected from at least one of N,N-dimethylformamide, dimethyl sulfoxide, acetonitrile, tetrahydrofuran, ethylene glycol dimethyl ether, dichloromethane, 1,2-dichloroethane, 1,4-dioxane, chlorobenzene, trifluorotoluene, toluene, o-xylene, n-heptane, and n-hexane.

[0013] According to a specific embodiment of the present invention, formula (Ⅰ) a ′) or formula (Ⅰ) b The molar volume ratio of the compound, catalyst, oxidant and organic solvent shown in one of the ′) is 0.2–0.4 mmol: 0.02–0.04 mmol: 0.3–0.8 mmol: 1.0–2.0 mL.

[0014] According to a specific embodiment of the present invention, the reaction temperature is 0 to 100°C, and the reaction time is within 50 hours.

[0015] According to a specific embodiment of the present invention, the reaction product is further subjected to post-processing; preferably, the post-processing includes filtration, washing, solvent removal under reduced pressure, and column chromatography separation and purification.

[0016] The method provided by this invention enables the one-step construction of quinolinone-containing compounds from pyridone compounds under the action of a catalytic amount of metal. This method is highly efficient, low-cost, and can be widely used to prepare quinolinone-containing compounds. Compared with existing technologies, this invention has the following advantages:

[0017] (1) The main raw materials of the method of the present invention are readily available pyridone compounds. Most of the raw materials can be commercial reagents, do not require special treatment, are inexpensive, and are easy to prepare for industrial production.

[0018] (2) The reaction conditions involved in the method of the present invention have good functional group tolerance and substrate universality;

[0019] (3) The method of the present invention is efficient and versatile, and can construct quinolinone compounds in one step, with extremely high step economy and atom economy;

[0020] (4) The method of the present invention does not require the addition of additional ligands and has excellent chemical selectivity. These research advances are expected to be applied in related medicinal chemistry and natural product synthesis. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0022] Example 1: Preparation of 1-benzylquinoline-2(1H)one

[0023]

[0024] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 1-benzyl-6-buten-1-ylpyridin-2(1H)one, 10 mol% palladium chloride, 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 92%). 1H NMR.(600MHz, CDCl3)δ7.74(d,J=9.5Hz,1H),7.56(dd,J=7.7,1.5Hz,1H),7.41(ddd,J=8.7,7.2,1.6Hz, 1H),7.31-7.25(m,3H),7.22(t,J=7.9Hz,3H),7.18(t,J=7.5Hz,1H),6.81(d,J=9.5Hz,1H),5.56(s,2H). 13 C NMR (151MHz, CDCl3) δ162.64,139.71,139.58,136.43,130.74,128.95,128.90,127.37,126.69,122.33,121.75,121.07,115.16,46.04.

[0025] Example 2: 1-Methylquinoline-2(1H)-one

[0026]

[0027] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 6-(but-3-en-1-yl)-1-methylpyridin-2(1H)-one, 10 mol% palladium chloride, 1.5 equiv 1,4-benzoquinone, and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 72%). 1 H NMR.(600MHz, CDCl3) δ7.67(d,J=9.5Hz,1H),7.57(ddd,J=10.5,7.5,1.8Hz,2H),7.37(dd ,J=8.4,1.0Hz,1H),7.23(ddd,J=8.0,7.2,1.0Hz,1H),6.71(d,J=9.4Hz,1H),3.72(s,3H). 13 C NMRδ162.53,140.15,139.13,130.77,128.89,122.26,121.86,120.83,114.29,29.56.

[0028] Example 3: Preparation of 1-(4-methoxybenzyl)quinoline-2(1H)one

[0029]

[0030] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 6-but-3-en-1-yl-1-(4-methoxybenzyl)pyridin-2(1H)one, 10 mol% palladium chloride, 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 81%). 1 H NMR.(600MHz, CDCl3) δ7.72(d,J=9.5Hz,1H),7.55(dd,J=7.7,1.5Hz,1H),7.43(ddd,J=8.7,7.2,1.5Hz,1H),7. 31(d,J=8.5Hz,1H),7.20-7.15(m,3H),6.82(d,J=8.7Hz,2H),6.79(d,J=9.5Hz,1H),5.49(s,2H),3.75(s,3H). 13 C NMR (151MHz, CDCl3) δ162.65,158.91,139.64,139.58,130.71,128.94,128.50,128.10,122.28,121.80,121.09,115.16,114.31,55.36,45.49.

[0031] Example 4: Preparation of 1-phenylquinoline-2(1H)one

[0032]

[0033] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 6-but-3-en-1-yl-1-phenylpyridin-2(1H)one, 10 mol% palladium chloride, 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 88%). 1H NMR.(600MHz, CDCl3) δ7.79(d,J=9.5Hz,1H),7.60(t,J=7.9Hz,3H),7.53(t,J=7.5Hz,1H),7.33(t,J= 7.9Hz,1H),7.29(d,J=7.7Hz,2H),7.20(t,J=7.5Hz,1H),6.79(d,J=9.6Hz,1H),6.65(d,J=8.5Hz,1H). 13 C NMR (151MHz, CDCl3) δ162.49,141.29,139.98,137.78,130.34,130.32,129.07,128.95,128.43,122.46,122.35,120.47,116.11.

[0034] Example 5: Preparation of 1-benzyl-3-bromoquinoline-2(1H)one

[0035]

[0036] Under an inert gas atmosphere, 1-benzyl-3-bromo-6-buten-1-ylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 92%). 1 H NMR.(600MHz, CDCl3)δ8.19(s,1H),7.52(dd,J=7.9,1.5Hz,1H),7.46(ddd,J =8.7,7.1,1.5Hz,1H),7.30(t,J=7.7Hz,3H),7.26-7.19(m,4H),5.61(s,2H). 13 C NMR (151MHz, CDCl3) δ158.83,141.32,138.93,135.96,131.01,128.97,128.29,127.62,126.87,122.94,120.92,117.54,115.35,47.75.

[0037] Example 6: Preparation of 1-benzyl-3-fluoroquinoline-2(1H)one

[0038]

[0039] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-3-fluoropyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 82%). 1 H NMR. (600MHz, CDCl3) δ7.55(d,J=7.8Hz,1H),7.48(dd,J=9.1,1.8Hz,1H),7.44-7.39(m,1H),7.30(d,J=7.9Hz,3H),7.24(q,J=7.5Hz,4H),5.60(s,2H). 13 C NMR (151MHz, CDCl3) δ156.99,156.81,151.51,149.83,136.61,135.80,129.78,129.76,129. 00,128.67,128.63,127.66,126.80,123.28,119.29,119.24,118.83,118.72,115.29,46.58. 19 F NMR (565MHz, CDCl3) δ-127.95 (d, J=8.4Hz).

[0040] Example 7: 1-Benzyl-3-methylquinoline-2(1H)-one

[0041]

[0042] Under an inert gas atmosphere, 1-benzyl-6-(but-3-en-1-yl)-3-methylpyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 1,4-benzoquinone (1.5 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 77%). 1H NMR.(600MHz, CDCl3)δ7.62(s,1H),7.51(dd,J=7.7,1.5Hz,1H),7.36(ddd,J=8.6,7.1,1.6Hz,1H) ,7.29(t,J=7.5Hz,2H),7.26-7.19(m,4H),7.16(td,J=7.6,1.0Hz,1H),5.58(s,2H),2.33(s,3H). 13 CNMR (151MHz, CDCl3) δ163.22,138.72,136.72,136.44,130.16,129.43,128.88,128.02,127.32,126.78,122.22,121.16,114.91,46.43,17.90.

[0043] Example 8: Preparation of 1-benzyl-3-phenylquinoline-2(1H)one

[0044]

[0045] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-3-phenylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 96%). 1 H NMR.(600MHz, CDCl3)δ7.83(s,1H),7.73(d,J=6.9Hz,2H),7.57(dd,J=7.8,1.5Hz,1H),7. 42-7.32(m,4H),7.27-7.22(m,5H),7.19(d,J=8.9Hz,1H),7.17-7.13(m,1H),5.58(s,2H). 13 CNMR (151MHz, CDCl3) δ161.80,139.21,137.46,136.75,136.63,132.45,130.41,129. 15,129.05,128.88,128.29,128.28,127.36,126.90,122.41,121.12,114.93,46.66.

[0046] Example 9: Preparation of 1-benzyl-3-naphthylquinoline-2(1H)one

[0047]

[0048] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-3-naphthylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 90%). 1 H NMR.(600MHz, CDCl3)δ7.92-7.87(m,3H),7.78(d,J=8.3Hz,1H),7.61(dd,J=7.8,1.5Hz,1H),7.56-7.53(m,2H),7.5 0-7.47(m,2H),7.46-7.43(m,1H),7.38(d,J=8.6Hz,1H),7.32(d,J=4.4Hz,4H),7.23(t,J=7.8Hz,2H),5.66(s,2H). 13 C NMR (151MHz, CDCl3) δ162.12,139.80,139.62,136.74,134.96,133.83,132.68,132.12,130.66,129.11,128. 94,128.84,128.55,127.76,127.45,127.06,126.30,125.94,125.78,125.48,122.50,120.94,115.15,46.69.

[0049] Example 10: Preparation of 3-(1,1'-biphenyl)-2-yl)-1-benzylquinoline-2(1H)one

[0050]

[0051] Under inert gas protection, 3-

[0052] (1,1'-Biphenyl)-2-yl)-1-benzyl-6-buten-1-ylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL). The reaction mixture was placed on a reactor and stirred at 100°C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 89%). 1 H NMR.(600MHz, CDCl3)δ7.69(s,1H),7.51-7.38(m,6H),7.36(t,J=7.8Hz,3H),7.25(d,J=5.6Hz,2H),7.22 (d,J=7.4Hz,2H),7.19(dd,J=13.1,7.6Hz,2H),7.14(t,J=7.5Hz,1H),6.89(d,J=7.3Hz,2H),5.42(s,2H). 13 C NMR (151MHz, CDCl3) δ161.22,142.20,142.16,139.25,139.03,136.60,135.74,134.15,130.66,130.21,1 29.22,128.82,128.75,128.50,128.08,127.36,127.17,126.75,126.57,122.17,120.83,114.86,46.28.

[0053] Example 11: Preparation of 1-benzyl-4-benzyloxyquinoline-2(1H)one

[0054]

[0055] Under an inert gas atmosphere, 1-benzyl-4-benzyloxy-6-but-3-en-1-ylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 80%). 1H NMR.(600MHz, CDCl3)δ8.05(dd,J=8.0,1.6Hz,1H),7.50(d,J=6.9Hz,2H),7.46-7.38(m,4H),7.31-7.2 7(m,2H),7.25-7.20(m,4H),7.17(ddd,J=8.1,7.1,1.0Hz,1H),6.24(s,1H),5.53(s,2H),5.21(s,2H). 13 C NMR (151MHz, CDCl3) δ164.05,162.13,139.31,136.78,135.41,131.39,128.89,128.86, 128.65,127.80,127.27,126.60,123.69,121.93,116.92,115.08,97.48,70.67,45.64.

[0056] Example 12: Preparation of 1-benzylquinoline-2(1H)-one-4-d

[0057]

[0058] Under inert gas protection, 1-benzyl-6-buten-1-ylpyridin-2(1H)one-4-d (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 60%). 1 H NMR. (600MHz, CDCl3) δ7.56 (dd, J=7.8, 1.5Hz, 1H), 7.42 (ddd, J=8.3, 6.9, 1.3Hz, 1H), 7.28 (d t,J=12.3,6.4Hz,3H),7.22(t,J=8.2Hz,3H),7.18(t,J=7.5Hz,1H),6.80(s,1H),5.56(s,2H). 13 C NMR (151MHz, CDCl3) δ162.66,139.60,136.44,130.75,128.90,127.38,126.69,122.33,121.64,121.00,115.17,46.04.

[0059] Example 13: Preparation of 1-benzyl-4-phenylquinoline-2(1H)one

[0060]

[0061] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-4-phenylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 81%). 1 H NMR.(600MHz, CDCl3) δ7.57(dd,J=8.1,1.5Hz,1H),7.53-7.49(m,3H),7.46(dd,J=7.7,1.8Hz,2H),7.43(ddd,J=8.6,7.1,1.5Hz ,1H),7.36-7.31(m,3H),7.29(d,J=6.8Hz,2H),7.26-7.24(m,1H),7.12(ddd,J=8.1,7.1,1.1Hz,1H),6.78(s,1H),5.63(s,2H). 13 C NMR (151MHz, CDCl3) δ162.27,151.67,139.84,137.18,136.52,130.78,129.06,128. 96,128.89,128.73,127.94,127.42,126.78,122.16,121.25,120.89,115.51,46.14.

[0062] Example 14: Preparation of 1-benzyl-4-(3-chlorophenyl)quinoline-2(1H)one

[0063]

[0064] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-4-(3-chlorophenyl)pyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 86%). 1 HNMR.(600MHz, CDCl3)δ7.54-7.38(m,5H),7.37-7.30(m,4H),7.29-7.23(m,3H),7.16-7.11(m,1H),6.76(s,1H),5.62(s,2H). 13 C NMR (151MHz, CDCl3) δ161.98,150.12,139.87,138.92,136.40,134.73,131.00,130.10,129. 10,129.06,128.97,127.60,127.47,127.24,126.77,122.32,121.51,120.46,115.61,46.16.

[0065] Example 15: Preparation of 1-benzyl-4-(3,5-difluorophenyl)quinoline-2(1H)one

[0066]

[0067] Under an inert gas atmosphere, 1-benzyl-6-buten-1-yl-4-(3,5-difluorophenyl)pyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 79%). 1 HNMR.(600MHz, CDCl3)δ7.51-7.44(m,2H),7.37-7.31(m,3H),7.28-

[0068] 7.24(m,3H),7.16(t,J=7.6Hz,1H),7.02-6.98(m,2H),6.95(tt,J=8.9,2.4Hz,1H),6.76(s,1H),5.61(s,2H). 13 C NMR (151MHz, CDCl3) δ164.00,163.91,162.34,162.25,161.82,149.24,140.31,140.25,140.19,139.90,136.29,131.21,129. 00,127.53,127.33,126.78,122.46,121.58,120.03,115.73,112.41,112.37,112.27,112.23,104.60,104.43,104.26,46.23. 19 F NMR (565MHz, CDCl3) δ-108.49 (t, J=7.3Hz).

[0069] Example 16: Preparation of 4-anthracite-9-yl-1-benzylquinoline-2(1H)one

[0070]

[0071] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 4-anthracite-9-yl-1-benzyl-6-but-3-en-1-ylpyridin-2(1H)one, 10 mol% palladium chloride, 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 49%). 1 H NMR.(600MHz, CDCl3)δ8.61(s,1H),8.10(d,J=8.5Hz,2H),7.65(dd,J=8.8,1.0Hz,2H),7.49(ddd,J=8.5,6.5,1.1Hz,2H),7.46-7 .35(m,8H),7.32(td,J=6.2,3.1Hz,1H),6.96(s,1H),6.86(ddd,J=8.1,6.9,1.2Hz,1H),6.78(dd,J=8.1,1.5Hz,1H),5.76(s,2H). 13C NMR (151MHz, CDCl3) δ162.30,149.36,139.73,136.63,131.39,131.06,130.54,129.81,129.11,128. 75,128.31,128.17,127.59,127.00,126.47,126.07,125.63,124.38,122.54,122.28,115.45,46.42.

[0072] Example 17: Preparation of 1-benzyl-4-methylquinoline-2(1H)-one

[0073]

[0074] Under an inert gas atmosphere, 1-benzyl-6-(but-3-en-1-yl)-4-methylpyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 1,4-benzoquinone (1.5 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 49%). 1 H NMR.(600MHz, CDCl3)δ7.72(dd,J=8.0,1.5Hz,1H),7.42(ddd,J=8.6,7.1,1.5Hz,1H),7 .28(dd,J=15.4,7.8Hz,3H),7.24-7.19(m,4H),6.71(s,1H),5.56(s,2H),2.51(s,3H). 13 C NMR (151MHz, CDCl3) δ162.43,147.23,139.32,136.69,130.59,128.90,127.32,126.67,125.40,122.16,121.84,121.12,115.49,45.84,19.24.

[0075] Example 18: Preparation of 1-benzyl-3-bromo-4-phenylquinoline-2(1H)one

[0076]

[0077] Under an inert gas atmosphere, 1-benzyl-3-bromo-6-but-3-en-1-yl-4-phenylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 70%). 1 HNMR.(600MHz, CDCl3)δ7.58-7.49(m,3H),7.45(ddd,J=8.6,7.1,1.6Hz,1H),7.38-7.29(m,7H) ,7.28-7.25(m,1H),7.16(dd,J=8.1,1.5Hz,1H),7.07(ddd,J=8.1,7.1,1.1Hz,1H),5.69(s,2H). 13 C NMR (151MHz, CDCl3) δ158.78,151.22,138.46,137.49,136.12,130.93,129.00,128. 85,128.79,128.68,128.66,127.64,127.00,122.71,121.75,119.09,115.28,48.00.

[0078] Example 19: Preparation of 1-benzyl-4-benzyloxy-3-bromoquinoline-2(1H)one

[0079]

[0080] Under an inert gas atmosphere, 1-benzyl-4-benzyloxy-3-bromo-6-buten-1-ylpyridin-2(1H)one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 74%). 1H NMR.(600MHz, CDCl3)δ7.88(d,J=8.0Hz,1H),7.60-7.55(m,2H),7.50-7.46(m,1H),7.46-7.42(m,2H),7.42-7 .38(m,1H),7.31(dd,J=12.0,8.0Hz,3H),7.26-7.24(m,3H),7.19(t,J=7.6Hz,1H),5.62(s,2H),5.30(s,2H). 13 C NMR (151MHz, CDCl3) δ161.64,160.39,138.48,136.20,135.96,131.63,128.99,128.90, 128.86,128.61,127.61,126.91,124.18,122.75,118.53,115.37,108.17,75.74,47.68.

[0081] Example 20: Preparation of 4-methoxy-1-methylquinoline-2(1H)-one

[0082]

[0083] Under inert gas protection, 0.1 mmol (1.0 equiv) of 6-(but-3-en-1-yl)-4-methoxy-1-methylpyridin-2(1H)-one, 10 mol% palladium chloride, 1.5 equiv 1,4-benzoquinone, and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 64%). 1 H NMR.(600MHz, CDCl3)δ7.97(d,J=8.0Hz,1H),7.58(t,J=7.9Hz,1H),7.34(d, J=8.5Hz,1H),7.23(t,J=7.6Hz,1H),6.05(s,1H),3.95(s,3H),3.68(s,3H). 13 C NMR (151MHz, CDCl3) δ164.03,162.85,139.94,131.35,123.53,121.79,116.70,114.18,96.66,55.95,29.21.

[0084] Example 21: Preparation of 1-benzyl-5-phenylquinoline-2(1H)-one

[0085]

[0086] Under an inert gas atmosphere, (E)-1-benzyl-6-(4-phenylbut-3-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 37%). 1 HNMR(600MHz, CDCl3)δ7.83(d,J=9.9Hz,1H),7.51-7.47(m,2H),7.47-7.43(m,2H),7.40-7.37(m,2H),7 .34-7.28(m,3H),7.26(d,J=4.7Hz,3H),7.14(dd,J=7.3,1.1Hz,1H),6.74(d,J=9.8Hz,1H),5.62(s,2H). 13 C NMR (151MHz, CDCl3)δ

[0087] 162.39,142.16,140.18,139.31,137.68,136.55,130.24,130.01,128.99,128.61,128.00,127.44,126.74,123.84,121.37,119.07,114.57,46.43.

[0088] Example 22: Preparation of ethyl 1-benzyl-2-oxo-1,2-dihydroquinoline-6-carboxylate

[0089]

[0090] Under an inert gas atmosphere, ethyl 4-(1-benzyl-6-oxo-1,6-dihydropyridin-2-yl)-2-methylenebutyrate (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 74%). 1 H NMR.(600MHz, CDCl3)δ8.27(d,J=2.0Hz,1H),8.07(dd,J=8.9,2.0Hz,1H),7.81(d,J=9.5Hz,1H),7.32-7.28(m,3H),7.24 (t,J=7.4Hz,1H),7.20(d,J=7.1Hz,2H),6.85(d,J=9.5Hz,1H),5.57(s,2H),4.38(q,J=7.1Hz,2H),1.39(t,J=7.1Hz,3H). 13 C NMR (151MHz, CDCl3) δ165.77,162.60,142.56,139.83,135.98,131.47,130.94, 129.04,127.63,126.69,124.57,122.54,120.55,115.17,61.31,46.27,14.48.

[0091] Example 23: Preparation of 1-benzyl-7-methylquinoline-2(1H)-one

[0092]

[0093] Under an inert gas atmosphere, 1-benzyl-6-(2-methylbut-3-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 1,4-benzoquinone (1.5 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 41%). 1H NMR.δ7.70(d,J=9.4Hz,1H),7.45(d,J=7.9Hz,1H),7.30(t,J=7.7Hz,2H),7.25-7.21(m ,3H),7.07(s,1H),7.03-6.99(m,1H),6.74(d,J=9.4Hz,1H),5.54(s,2H),2.37(s,3H).

[0094] Example 24: Preparation of 1-benzyl-5-methylquinoline-2(1H)-one

[0095]

[0096] Under an inert gas atmosphere, 1-benzyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 86%). 1 H NMR.(600MHz, CDCl3)δ7.99(d,J=9.8Hz,1H),7.29(td,J=7.4,4.5Hz,3H),7.24-7.18(m,3H), 7.13(d,J=8.6Hz,1H),7.02(d,J=7.3Hz,1H),6.83(d,J=9.8Hz,1H),5.57(s,2H),2.58(s,3H).

[0097] Example 25: Preparation of 1-benzyl-5-methylquinoline-2(1H)-one

[0098]

[0099] Under an inert gas atmosphere, 0.1 mmol (1.0 equiv) of 1-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 10 mol% palladium chloride, 1,4-benzoquinone (1.5 equiv), and 0.5 mL of dried dioxane were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 67%). 1 H NMR.(600MHz, CDCl3)δ7.91(d,J=9.7Hz,1H),7.45(t,J=8.0Hz,1H),7.24(d,J= 8.6Hz,1H),7.08-7.06(m,1H),6.74(d,J=9.7Hz,1H),3.73(s,3H),2.57(s,3H).

[0100] Example 26: Preparation of 1-benzyl-3-bromo-5-methylquinoline-2(1H)-one

[0101]

[0102] Under an inert gas atmosphere, 1-benzyl-3-bromo-6-(pent-4-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 79%). 1 H NMR. 1 HNMR(600MHz, CDCl3)δ8.43(s,1H),7.34(t,J=8.0Hz,1H),7.30(t,J=7.5Hz,2H),7.25 -7.20(m,3H),7.16(d,J=8.6Hz,1H),7.05(d,J=7.3Hz,1H),5.62(s,2H),2.57(s,3H).

[0103] Example 27: Preparation of 1-benzyl-3,5-dimethylquinoline-2(1H)-one

[0104]

[0105] Under an inert gas atmosphere, 1-benzyl-3-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 1,4-benzoquinone (1.5 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 69%). 1 H NMR. (600MHz, CDCl3) δ7.85 (s, 1H), 7.28 (t, J = 7.5Hz, 2H), 7.23 (d, J = 7.9Hz, 1H), 7.19 (q, J = 5.4Hz, 3H),7.11(d,J=8.6Hz,1H),7.00(d,J=7.3Hz,1H),5.59(s,2H),2.57(s,3H),2.36(d,J=1.3Hz,3H).

[0106] Example 28: Preparation of 1-benzyl-5-methyl-3-phenylquinoline-2(1H)-one

[0107]

[0108] Under an inert gas atmosphere, 1-benzyl-6-(pent-4-en-1-yl)-3-phenylpyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 83%). 1 H NMR (600MHz, CDCl3) δ8.10 (s, 1H), 7.81-7.76 (m, 2H), 7.46 (dd, J = 8.4, 6.9Hz, 2H), 7.42-7.38 (m, 1H), 7.34-7 .26(m,5H),7.25-7.21(m,1H),7.17(d,J=8.6Hz,1H),7.05(dt,J=7.2,0.9Hz,1H),5.64(s,2H),2.62(s,3H).

[0109] Example 29: Preparation of 1-benzyl-3-(2,4-dichlorophenyl)-5-methylquinoline-2(1H)-one

[0110]

[0111] Under an inert gas atmosphere, 1-benzyl-3-(2,4-dichlorophenyl)-6-(pent-4-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 2,3-dichloro-5,6-dicyanobenzoquinone (2.0 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 82%). 1 H NMR.(600MHz, CDCl3)δ8.03(s,1H),7.52(d,J=2.1Hz,1H),7.43(d,J=8.2Hz,1H),7.36-7.32(m,2H),7.30(t,J=7.6Hz, 2H),7.27-7.25(m,2H),7.23(d,J=7.2Hz,1H),7.19(d,J=8.6Hz,1H),7.06(d,J=7.3Hz,1H),5.62(s,2H),2.58(s,3H).

[0112] Example 30: Preparation of 1-benzyl-4-benzyloxy-5-methylquinoline-2(1H)-one

[0113]

[0114] Under an inert gas atmosphere, 1-benzyl-4-benzyloxy-6-(pent-4-en-1-yl)pyridin-2(1H)-one (0.1 mmol, 1.0 equiv), palladium chloride (10 mol%), 1,4-benzoquinone (1.5 equiv), and dried dioxane (0.5 mL) were added to a dry 4 mL reaction flask equipped with a magnetic stirrer. The reaction mixture was placed on a reactor and stirred at 100 °C for 12 hours. The reaction was monitored by TLC. After the reaction was complete, the mixture was cooled to room temperature, filtered through diatomaceous earth, washed with ethyl acetate, and the solvent was removed under reduced pressure. The crude product was purified by direct column chromatography to obtain the target product (white solid, 77%). 1H NMR.(600MHz, CDCl3)δ7.49-7.46(m,2H),7.45-7.41(m,2H),7.41-7.37(m,1H),7.28(t,J=7.6Hz,2H),7.25-7 .16(m,4H),7.10(d,J=8.6Hz,1H),6.92(d,J=7.3Hz,1H),6.22(s,1H),5.53(s,2H),5.17(s,2H),2.68(s,3H).

[0115] The preferred embodiments of the present invention have been described in detail above. However, the present invention is not limited to the specific details in the above embodiments. Within the scope of the technical concept of the present invention, various simple modifications can be made to the technical solution of the present invention, and these simple modifications all fall within the protection scope of the present invention.

Claims

1. Formula (Ⅰ) a ) or formula (Ⅰ) b The method for preparing quinoline ketone compounds shown in the figure is characterized in that, The preparation method includes: Under an inert atmosphere, equation (Ⅰ) a The compound shown in (I) reacts with a catalyst, an oxidant, and an organic solvent to yield the product of formula (I). a The compound shown in the figure; or, Under an inert atmosphere, equation (Ⅰ) b The compound shown in (I) reacts with a catalyst, an oxidant, and an organic solvent to yield the product of formula (I). b The compound shown in the figure has the following reaction formula: in, R1 is selected from benzyl, p-methoxybenzyl, phenyl, and C1-C6 alkyl; R2 is selected from hydrogen, halogen, C1-C6 alkyl, C6-C20 aryl, and halogen-substituted phenyl. R3 is selected from one of hydrogen, deuterium, C1-C6 alkyl, C6-C20 aryl, halogen-substituted phenyl, benzyloxy, and C1-C6 alkoxy. R4 is selected from hydrogen, C6-C10 aryl, and C1-C6 alkyl; R5 is selected from hydrogen or C2-C6 ester groups; R6 is selected from hydrogen and C1-C6 alkyl groups; The catalyst is selected from palladium chloride and palladium bromide; The oxidant is selected from 1,4-benzoquinone and 2,3-dichloro-5,6-dicyanobenzoquinone; The organic solvent is 1,4-dioxane.

2. The preparation method according to claim 1, characterized in that, R1 is one of benzyl, p-methoxybenzyl, phenyl, and methyl; R2 is one of hydrogen, fluorine, bromine, methyl, phenyl, halogen-substituted phenyl, naphthyl, and biphenyl; R3 is one of hydrogen, deuterium, methyl, phenyl, halogen-substituted phenyl, benzyloxy, anthracene, and methoxy; R4 is one of hydrogen, phenyl, and methyl; R5 is one of hydrogen and C2-C3 ester group; and R6 is one of hydrogen and methyl.

3. The preparation method according to claim 1, characterized in that, The formula (Ⅰ) a The compound shown is selected from 1-benzyl-6-buten-1-ylpyridin-2(1H)one, 6-(but-3-en-1-yl)-1-methylpyridin-2(1H)-one, 6-but-3-en-1-yl-1-(4-methoxybenzyl)pyridin-2(1H)one, 6-but-3-en-1-yl-1-phenylpyridin-2(1H)one, 1-benzyl-3-bromo-6-buten-1-ylpyridin-2(1H)one, 1-benzyl-6-buten-1-yl-3-fluoropyridin-2(1H)one, 1-benzyl-6-(but-3-) -en-1-yl)-3-methylpyridin-2(1H)-one, 1-benzyl-6-buten-1-yl-3-phenylpyridin-2(1H)-one, 1-benzyl-6-buten-1-yl-3-naphthylpyridin-2(1H)-one, 3-(1,1'-biphenyl)-2-yl)-1-benzyl-6-buten-1-ylpyridin-2(1H)-one, 1-benzyl-4-benzyloxy-6-but-3-en-1-ylpyridin-2(1H)-one, 1-benzyl-6-buten-1-ylpyridin-2(1H)-one-4-d, 1-benzyl-6-buten-1-ylpyridin-2(1H)-one Alken-1-yl-4-phenylpyridin-2(1H) one, 1-benzyl-6-buten-1-yl-4-(3-chlorophenyl)pyridin-2(1H) one, 1-benzyl-6-buten-1-yl-4-(3,5-difluorophenyl)pyridin-2(1H) one, 4-anthra-9-yl-1-benzyl-6-but-3-en-1-ylpyridin-2(1H) one, 1-benzyl-6-(but-3-en-1-yl)-4-methylpyridin-2(1H)-one, 1-benzyl-3-bromo-6-but-3-en-1-yl-4-phenylpyridin- One of the following: 2(1H) ketone, 1-benzyl-4-benzyloxy-3-bromo-6-buten-1-ylpyridin-2(1H) ketone, 6-(but-3-en-1-yl)-4-methoxy-1-methylpyridin-2(1H)-ketone, (E)-1-benzyl-6-(4-phenylbut-3-en-1-yl)pyridin-2(1H)-ketone, 4-(1-benzyl-6-oxo-1,6-dihydropyridin-2-yl)-2-methylenebutyrate ethyl ester, and 1-benzyl-6-(2-methylbut-3-en-1-yl)pyridin-2(1H)-ketone.

4. The preparation method according to claim 1, characterized in that, The formula (Ⅰ) b The compound shown is selected from one of the following: 1-benzyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-3-bromo-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-3-methyl-6-(pent-4-en-1-yl)pyridin-2(1H)-one, 1-benzyl-6-(pent-4-en-1-yl)-3-phenylpyridin-2(1H)-one, 1-benzyl-3-(2,4-dichlorophenyl)-6-(pent-4-en-1-yl)pyridin-2(1H)-one, and 1-benzyl-4-benzyloxy-6-(pent-4-en-1-yl)pyridin-2(1H)-one.

5. The preparation method according to claim 1, characterized in that, Formula (Ⅰ) a ´) or formula (Ⅰ) b The molar volume ratio of the compound, catalyst, oxidant and organic solvent shown in one of the formulas is 0.2~0.4 mmol:0.02~0.04 mmol:0.3~0.8 mmol:1.0~2.0 mL.

6. The preparation method according to claim 1, characterized in that, The reaction temperature is 0~100 ℃, and the reaction time is within 50 h.

7. The preparation method according to claim 1, characterized in that, It also includes post-processing of the reaction products.

8. The preparation method according to claim 7, characterized in that, The post-processing includes filtration, washing, solvent removal under reduced pressure, and column chromatography for separation and purification.

Images