A method for preparing heteroaryl-fused quinolinone compounds

Abstract

The present invention discloses a preparation method of a heteroaryl-fused quinolinone derivative, belonging to the technical field of synthesis. The preparation method is as follows: a substrate shown in Formula I and a photocatalyst are dissolved in an organic solvent, and the reaction is carried out under light irradiation conditions to obtain a heteroaryl-fused quinolinone derivative shown in Formula II. The chemical reaction equation of the preparation method is as follows. The present invention synthesizes a heteroaryl-fused quinolinone derivative from an indole amide derivative, providing new reaction conditions for the synthesis of heteroaryl-fused quinolinone compounds. The reaction conditions are milder, avoiding the use of expensive palladium metal catalysts, high-energy ultraviolet rays, and expensive iridium metal complex catalysts.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and particularly relates to a method for preparing heteroaryl-fused quinolinone compounds. Background Art

[0002] Heteroaryl-fused quinolinone compounds have wide applications in drugs, materials, and synthetic intermediates. For example, as drugs, they have various biological activities, such as anti-tumor activity against osteosarcoma and colorectal cancer, topoisomerase and DYRK1A inhibitory activities, and Tankyrase enzyme inhibitory activity; as synthetic intermediates for synthesizing other drugs or active molecules, such as synthesizing indoloquinoline derivatives with various biological activities; as materials for preparing OLED devices or intermediates for synthesizing such materials, etc. Therefore, methods for preparing heteroaryl-fused quinolinone compounds have application value.

[0003] Currently, the main methods for synthesizing such compounds are as follows: (1) Intramolecular dehydrogenative cyclization catalyzed by noble metals; (2) Intramolecular dehalogenative cyclization catalyzed by metals; (3) Dehalogenative cyclization reaction promoted by ultraviolet light; (4) Oxidative dehydrogenative cyclization promoted by ultraviolet light; (5) Dehydrogenative cyclization catalyzed by metal complexes under visible light conditions. The first two methods both require the use of expensive palladium metal, with an addition amount of 10%, and the reaction needs to be heated to 100 °C; the third method uses chlorine-containing raw materials and is carried out under high-energy ultraviolet light conditions; the fourth method is carried out under high-energy ultraviolet light and oxygen conditions; the fifth method requires a metal iridium complex, and the metal iridium catalyst belongs to a non-renewable resource, with a high price, and the raw material iridium trichloride for preparing and synthesizing this catalyst is expensive.

[0004] The existing methods for preparing heteroaryl-fused quinolinone compounds have deficiencies such as expensive catalysts, low substrate adaptability, high energy consumption, and metal catalyst residues. Therefore, there is an urgent need to develop a method for preparing heteroaryl-fused quinolinone compounds with more green and mild conditions. Summary of the Invention

[0005] The purpose of the present invention is to provide a new method for preparing heteroaryl-fused quinolinone compounds with more green and mild conditions to solve the problems of using expensive metal catalysts (using metal catalysts causes the problem of metal residues in the product) and high-energy ultraviolet light in the prior art.

[0006] To solve the above technical problems, the present invention adopts the following technical scheme:

[0007] A method for preparing heteroaryl-fused quinolinone compounds, comprising the following steps: dissolving the substrate shown in Formula I and a photocatalyst in an organic solvent, reacting under light irradiation conditions, and after the reaction is completed, performing purification and separation to obtain the heteroaryl-fused quinolinone compound shown in Formula II.

[0008] The chemical reaction equation of the preparation method is as follows:

[0009]

[0010] Among them,

[0011] R 1 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, halogen or alkoxy;

[0012] R 2 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, alkoxy, benzyloxy or halogen;

[0013] R 3 is hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, allyl or benzyl;

[0014] n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur;

[0015] Z is N or CH;

[0016] The photocatalyst is 2CzPN or a cyanocarbazole catalyst;

[0017] The light irradiation is blue light, white light or sunlight, preferably blue light.

[0018] In some technical solutions, R 1 is hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted cycloalkyl, halogen, methoxy, ethoxy, trifluoromethoxy, difluoromethyl, trifluoromethyl;

[0019] R 2 is hydrogen, substituted or unsubstituted C1-C6 alkyl, trifluoromethyl, difluoromethyl, alkoxy, benzyloxy or halogen;

[0020] R 3 is hydrogen, substituted or unsubstituted C1-C6 alkyl, allyl or benzyl;

[0021] n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur;

[0022] Z is N or CH.

[0023] In some technical solutions, R 1 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, trifluoromethoxy, benzyloxy, trifluoromethyl or chlorine;

[0024] R 2is hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, trifluoromethyl, benzyloxy, trifluoromethyl or chlorine;

[0025] R 3 is hydrogen, methyl, ethyl, isopropyl, cyclobutyl, allyl or benzyl;

[0026] n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur;

[0027] Z is N or CH.

[0028] In some technical solutions, R 1 is hydrogen, methyl, methoxy, trifluoromethyl, fluorine, chlorine, bromine;

[0029] R 2 is hydrogen, methyl, ethyl, isopropyl, methoxy, ethoxy, benzyloxy, trifluoromethyl, fluorine, chlorine, bromine;

[0030] R 3 is hydrogen, methyl, allyl or benzyl;

[0031] n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur;

[0032] Z is CH.

[0033] In some technical solutions, the cyano-carbazole catalyst is a cyano-carbazole catalyst with the structure shown in Formula III:

[0034]

[0035] wherein, R is methyl, ethyl, isopropyl, cyclobutyl, benzyl; preferably methyl, ethyl, cyclobutyl, benzyl; more preferably methyl, benzyl.

[0036] In some technical solutions, the ratio of the substrate, the photocatalyst and the organic solvent is 1 mmol: 0.005 - 0.25 mmol: 10 - 40 mL; preferably 1 mmol: 0.01 - 0.05 mmol: 20 - 40 mL.

[0037] In some technical solutions, the organic solvent is a mixed solvent of a halogenated hydrocarbon solvent and dimethyl sulfoxide. Preferably, the volume ratio of the halogenated hydrocarbon solvent to dimethyl sulfoxide is 9.5:0.5 - 0.5:9; more preferably 9:1.

[0038] In some technical solutions, the halogenated hydrocarbon solvent is at least one of dichloromethane, 1,2-dichloroethane, 1,2-dibromoethane or chloroform; preferably 1,2-dibromoethane or 1,2-dichloroethane; more preferably 1,2-dichloroethane.

[0039] In some technical solutions, the volume ratio of the 1,2-dichloroethane to the dimethyl sulfoxide is 9:1.

[0040] In some specific technical solutions, the preparation method of the heteroaryl-fused quinolinone compound includes the following steps: dissolving an arylamide derivative and a photocatalyst in an organic solvent, and reacting under light irradiation conditions to obtain a heteroaryl-fused quinolinone derivative;

[0041] Wherein, the photocatalyst is 2CzBN or a cyano-carbazole catalyst with the structure shown in Formula III:

[0042]

[0043] Wherein, R is methyl, ethyl, cyclobutyl or benzyl;

[0044] The organic solvent is a mixed solvent of 1,2-dichloroethane and dimethyl sulfoxide or 1,2-dibromoethane;

[0045] The light irradiation conditions are blue light, white light or sunlight;

[0046] The chemical structure of the arylamide derivative is any one of the following compounds:

[0047]

[0048] Preferably, the ratio of the arylamide derivative, the photocatalyst and the organic solvent is 1 mmol: 0.005 - 0.05 mmol: 10 - 40 mL; more preferably 1 mmol: 0.01 - 0.05 mmol: 20 - 40 mL.

[0049] Preferably, the ratio of 1,2-dichloroethane to dimethyl sulfoxide in the organic solvent is 9.5:0.5 - 0.5:9; more preferably 9:1.

[0050] Preferably, the light irradiation conditions are blue light.

[0051] The present invention has the following beneficial effects:

[0052] (1) The present invention provides new reaction conditions for the synthesis of heteroaryl-fused quinolinone compounds. The reaction conditions are milder, which not only avoids the use of high-energy ultraviolet light, but also does not use expensive metal catalysts (eliminating the possibility of metal residues in the product, which is crucial for drugs);

[0053] (2) Metal catalysts are non-renewable. Using the organic catalyst of the present invention is more environmentally friendly;

[0054] (3) The unit price of the catalyst for obtaining cyano-carbazole is lower. Taking fac-Ir(dFppy)3 (CAS No. 391665-84-2, hereinafter referred to as A), 4CzBnBN (hereinafter referred to as B), and 4CzMeBN (hereinafter referred to as C) as examples, the specific analysis is shown in Table 1. Compared with the prior art, the cost of the present invention is lower.

[0055] Table 1 Analysis of the raw material cost for preparing 1 gram of catalyst

[0056] Specific embodiments

[0057] The present invention will be further illustrated by the following examples. The examples are only used to explain the present invention and are not intended to limit the scope of the present invention. For those not specified in the examples, the operations are carried out under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used without indicating the manufacturer are all conventional products that can be obtained by commercial purchase.

[0058] It should be noted that: the substrate (raw material substance) represented by Formula I used in the present invention is prepared by the methods reported in the public literature and its corresponding supporting information. Those skilled in the art can prepare the raw material substances involved in the present invention without adjusting the conditions of the preparation methods in the literature. The reference documents are as follows: J. Org. Chem. 2022, 87, 7955-7967; Org. Lett. 2018, 20, 5696-5699.

[0059] The photocatalyst described in the present invention is obtained by purchase or prepared by the methods reported in the public literature and its corresponding supporting information (such as cyano-carbazole catalysts, referring to the preparation literature Org. Lett. 2021, 23, 3146-3150). Specifically, the structure of the photocatalyst used in the present invention is shown as follows, and other reagents used are all obtained by commercial purchase.

[0060]

[0061] "Substituted" means that one or more hydrogen atoms in an alkyl or cycloalkyl are each independently replaced by a non-hydrogen substituent.

[0062] "Alkyl" is a hydrocarbon containing primary, secondary or tertiary carbon atoms. For example, an alkyl group may have 1 to 10 carbon atoms (i.e., C1-C10 alkyl), 1 to 8 carbon atoms (i.e., C1-C8 alkyl), or 1 to 6 carbon atoms (i.e., C1-C6 alkyl). Examples of suitable alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et), 1-propyl (i-Pr, i-propyl), 2-propyl (i-Pr, i-propyl), 1-butyl (n-Bu, n-butyl), 2-methyl-1-propyl (i-Bu, i-butyl), 2-butyl (s-Bu, s-butyl), 2-methyl-2-propyl (t-Bu, t-butyl), 1-pentyl (n-pentyl), 2-pentyl, 3-pentyl, 2-methyl-2-butyl, 3-methyl-2-butyl, 3-methyl-1-butyl, 2-methyl-1-butyl, 1-hexyl, 2-hexyl, 3-hexyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 3-methyl-3-pentyl, 2-methyl-3-pentyl, 2,3-dimethyl-2-butyl, 3,3-dimethyl-2-butyl, and octyl.

[0063] "Cycloalkyl" is a hydrocarbon of cyclic carbon atoms. For example, a cycloalkyl group may have 1 to 10 carbon atoms (i.e., C1-C10 cycloalkyl), 1 to 8 carbon atoms (i.e., C1-C8 cycloalkyl), or 1 to 6 carbon atoms (i.e., C1-C6 cycloalkyl).

[0064] In the reaction formula of the present invention, "PC" represents a visible light catalyst, "Solvent" represents an organic solvent, "Ar" represents argon, and "rt" represents room temperature.

[0065] The full names of some English abbreviations in the present invention are shown in Table 2.

[0066] Table 2

[0067] Abbreviation Full Name DCE 1,2 - Dichloroethane DMSO Dimethyl Sulfoxide EA Ethyl Acetate DCM Dichloromethane MeOH Methanol EDB 1,2 - Dibromoethane THF Tetrahydrofuran MeCN Acetonitrile 1,4 - Dioxane 1,4 - Dioxane

[0068] Example 1:

[0069]

[0070] Add substrate 1a (0.22 mmol) and 4CzBnBN (2 mol%) to a 10 mL dry Schlenk tube equipped with a magnetic stir bar. Connect the reaction tube to a double manifold, evacuate it - purge it with argon in three cycles, and then add the ultra-dry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to three cycles of liquid nitrogen freezing - argon displacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After completion of the reaction, dilute the reaction mixture with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The crude product is separated by wet loading on a silica gel column chromatography with 100 - 200 mesh (eluent: DCM / MeOH = 100 / 1) to obtain 40.6 mg of a white solid with a yield of 87%.

[0071] 1 H NMR (400 MHz, DMSO) δ 12.37 (s, 1H), 11.89 (s, 1H), 8.51 - 8.42 (m, 2H), 7.67 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.6 Hz, 1H), 7.41 (dd, J = 11.2, 4.1 Hz, 1H), 7.33 (dd, J = 17.4, 7.6 Hz, 2H).

[0072] 13 C NMR (101 MHz, DMSO) δ 156.24, 139.35, 135.45, 128.11, 126.41, 126.15, 123.48, 122.83, 122.75, 121.17, 118.74, 118.55, 116.61, 113.56.

[0073] Example 2:

[0074] The difference between this example and Example 1 is only that the addition amount of the photocatalyst is 1%.

[0075] Add substrate 1a (0.2 mmol) and 4CzBnBN (1 mol%) to a 10 mL dry Schlenk tube equipped with a magnetic stir bar. Connect the reaction tube to a double manifold, evacuate it - purge it with argon in three cycles, and then add the ultra-dry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to three cycles of liquid nitrogen freezing - argon displacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After completion of the reaction, dilute the reaction mixture with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The yield of the crude product is determined by NMR internal standard method to be 68%.

[0076] Example 3:

[0077] In this example compared with Example 1, the only difference is that the dosage of the photocatalyst is 5%.

[0078] Add substrate 1a (0.2 mmol) and 4CzBnBN (5 mol%) into a 10 mL dry Schlenk tube equipped with a magnetic stir bar. Connect the reaction tube to a double manifold, evacuate it - circulate argon 3 times, and then add the ultra-dry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to 3 cycles of liquid nitrogen freezing - argon replacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After the reaction is completed, dilute the reaction solution with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The yield of the crude product is determined to be 83% by the internal standard method of nuclear magnetic resonance.

[0079] Example 4:

[0080] In this example compared with Example 1, the only difference is that the photocatalyst is 4CzMeBN.

[0081] Add substrate 1a (0.2 mmol) and 4CzMeBN (2 mol%) into a 10 mL dry Schlenk tube equipped with a magnetic stir bar. Connect the reaction tube to a double manifold, evacuate it - circulate argon 3 times, and then add the ultra-dry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to 3 cycles of liquid nitrogen freezing - argon replacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After the reaction is completed, dilute the reaction solution with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The yield of the crude product is determined to be 92% by the internal standard method of nuclear magnetic resonance.

[0082] Example 5:

[0083] In this example compared with Example 1, the only difference is that the catalyst is 2CzPN.

[0084] Add substrate 1a (0.2 mmol) and 2CzPN (2 mol%) into a 10 mL dry Schlenk tube equipped with a magnetic stir bar. Connect the reaction tube to a double manifold, evacuate it - circulate argon 3 times, and then add the ultra-dry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to 3 cycles of liquid nitrogen freezing - argon replacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After the reaction is completed, dilute the reaction solution with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The yield of the crude product is determined to be 40% by the internal standard method of nuclear magnetic resonance.

[0085] Example 6:

[0086] This example is different from Example 1 only in that the organic solvent is 1,2-dibromoethane (EDB).

[0087] Substrate 1a (0.2 mmol) and 4CzBnBN (2 mol%) were added to a 10 mL dry Schlenk tube equipped with a magnetic stir bar. The reaction tube was connected to a double manifold, evacuated - purged with argon three times, and then 8 mL of ultra-dry solvent EDB was added under an argon atmosphere. After subjecting the reaction tube to three cycles of liquid nitrogen freezing - argon displacement - thawing, the reaction tube was placed in a reactor and irradiated with 30 W blue light at 460 nm for 11 hours. After completion of the reaction, the reaction solution was diluted with EA, washed twice with saturated brine, and the organic phase was rotary evaporated under reduced pressure to obtain the crude product. The yield was determined to be 70% by NMR internal standard method.

[0088] Comparative Example

[0089] As shown in Table 3, the effects of different reaction conditions on the product yield were investigated.

[0090] Operation procedure:

[0091] Substrate 1a (0.1 mmol) and a photocatalyst (2 mol%) were added to a 10 mL dry Schlenk tube equipped with a magnetic stir bar. The reaction tube was connected to a double manifold, evacuated - purged with argon three times, and then an ultra-dry solvent was added under an argon atmosphere. After subjecting the reaction tube to three cycles of liquid nitrogen freezing - argon displacement - thawing, the reaction tube was placed in a reactor and irradiated with 30 W blue light. After completion of the reaction, the reaction solution was diluted with EA, washed twice with saturated brine, and the organic phase was rotary evaporated under reduced pressure to obtain the crude product. The reaction yield of product 2a was determined by NMR internal standard method.

[0092] Table 3 Yield data under different reaction conditions

[0093]

[0094]

[0095] Example 7:

[0096]

[0097] To a dry 10 mL Schlenk tube equipped with a magnetic stir bar, add substrate 1b (0.2 mmol) and photocatalyst (2 mol%). Connect the reaction tube to a double manifold, evacuate it - fill it with argon in a cycle of 3 times, and then add ultradry solvent DCE:DMSO (9:1) (8 mL) under an argon atmosphere. After subjecting the reaction tube to 3 cycles of liquid nitrogen freezing - argon replacement - thawing, place the reaction tube in a reactor and irradiate it with 30 W blue light for 11 hours. After the reaction is complete, dilute the reaction solution with EA, wash it twice with saturated brine, and then rotary evaporate the organic phase under reduced pressure to obtain the crude product. The crude product is separated by wet loading on a silica gel column chromatography with 100 - 200 mesh (eluent: DCM / MeOH = 100 / 1) to obtain 34.7 mg of a white solid with a yield of 69%.

[0098] Results: The product is a white solid with a yield of 69%;

[0099] 1 H NMR (400 MHz, DMSO) δ 11.91 (s, 1H), 8.54 (d, J = 8.1 Hz, 1H), 8.47 (d, J = 7.7 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.57 (t, J = 7.7 Hz, 1H), 7.51 (d, J = 8.0 Hz, 1H), 7.44 - 7.28 (m, 3H), 4.34 (s, 3H).

[0100] 13 C NMR (101 MHz, DMSO) δ 156.88, 140.58, 135.41, 126.57, 126.42, 123.43, 123.00, 122.86, 121.70, 121.56, 119.13, 118.30, 116.30, 111.60, 31.75.

[0101] Example 8:

[0102]

[0103] A 10-mL Schlenk tube equipped with a magnetic stir bar was dried in an oven, charged with 0.2 mmol of the substrate indolecarboxamide substrate 1c and 0.004 mmol of the photocatalyst 4CzBnPN. Then the Schlenk tube was connected to a vacuum line, evacuated, and backfilled with argon three times. Then, under an argon stream, 2 mL of a mixed solvent of 1,2-dichloroethane and dimethyl sulfoxide (volume ratio 9:1) that had been bubbled with argon for 5 min was added. Finally, the sealed tube was placed 2 cm away from a 30-W blue LED (wavelength 460 nm), and the reaction was stirred at room temperature for 11 h. After the reaction was completed, the solvent was removed under reduced pressure and purified by silica gel column chromatography to obtain the heteroaryl-fused indoline compound 2c.

[0104] Result: The product was a green solid with a yield of 59%;

[0105] 1 H NMR (400 MHz, DMSO) δ 12.27 (s, 1H), 8.91 (dd, J = 6.1, 3.0 Hz, 1H), 8.76 (d, J = 8.2 Hz, 1H), 8.26 (dd, J = 5.8, 3.2 Hz, 1H), 7.68 (dd, J = 6.1, 3.1 Hz, 2H), 7.63 - 7.53 (m, 2H), 7.41 (t, J = 7.1 Hz, 1H).

[0106] 13 C NMR (101 MHz, DMSO) δ 158.37, 141.77, 138.08, 136.43, 135.95, 132.69, 129.35, 127.96, 126.41, 126.27, 124.63, 124.07, 123.23, 117.87, 117.20.

[0107] Example 9:

[0108]

[0109] A 10-mL Schlenk tube equipped with a magnetic stir bar was dried in an oven, charged with 0.2 mmol of the substrate indolecarboxamide substrate 1d and 0.004 mmol of the photocatalyst 4CzBnPN. Then the Schlenk tube was connected to a vacuum line, evacuated, and backfilled with argon three times. Then, under an argon stream, 2 mL of a mixed solvent of 1,2-dichloroethane and dimethyl sulfoxide (volume ratio 9:1) that had been bubbled with argon for 5 min was added. Finally, the sealed tube was placed 2 cm away from a 30-W blue LED, and the reaction was stirred at room temperature for 11 h. After the reaction was completed, the solvent was removed under reduced pressure and purified by silica gel column chromatography to obtain the heteroaryl-fused indoline compound 2d.

[0110] Result: The product was a white solid 2d with a yield of 86%.

[0111] 1 H NMR (400 MHz, DMSO) δ 12.41 (s, 1H), 11.93 (s, 1H), 8.48 (dd, J = 11.8, 8.0 Hz, 2H), 7.68 (d, J = 8.2 Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.50 (t, J = 7.5 Hz, 1H), 7.43 (t, J = 7.1 Hz, 1H), 7.35 (dd, J = 17.0, 8.1 Hz, 2H).

[0112] 13 C NMR (101 MHz, DMSO) δ 156.21, 139.33, 135.44, 128.10, 126.41, 126.15, 123.48, 122.83, 122.73, 121.17, 118.71, 118.53, 116.60, 113.55.

[0113] For the preparation of other heteroaryl-fused quinolinone compounds, refer to Example 1 to obtain the compounds shown in Table 4.

[0114] Table 4

[0115]

[0116]

[0117]

[0118]

[0119] The method of the present invention has been described through preferred embodiments. It is obvious that relevant personnel can make changes or appropriate alterations and combinations to the methods and applications described herein within the content, spirit, and scope of the present invention to implement and apply the technology of the present invention. Those skilled in the art can draw on the content of this article and appropriately modify the process parameters to achieve it. It should be particularly noted that all similar substitutions and alterations are obvious to those skilled in the art, and they are all considered to be included in the present invention.

Claims

1. A method for preparing a heteroaromatic ring-fused quinolinone derivative, characterized in that: Dissolve the substrate shown in Formula I and the photocatalyst in an organic solvent, and carry out the reaction under light irradiation conditions to obtain the heteroaryl-fused quinolinone derivative shown in Formula II; The chemical reaction equation of the preparation method is as follows: Wherein, R 1 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, trifluoromethoxy, benzyloxy, trifluoromethyl or halogen; R 2 is hydrogen, methyl, ethyl, isopropyl, tert-butyl, methoxy, ethoxy, trifluoromethoxy, benzyloxy, trifluoromethyl or halogen; R 3 is hydrogen, methyl, ethyl, isopropyl, cyclobutyl, propenyl or benzyl; n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur; Z is N or CH; The photocatalyst is a cyanocarbazole catalyst with the structure shown in Formula III: Wherein, R is methyl or benzyl; The organic solvent is a mixed solvent of 1,2-dichloroethane and dimethyl sulfoxide; The light irradiation condition is blue light.

2. The preparation method according to claim 1, wherein R 1 is hydrogen, methyl, methoxy, trifluoromethyl or halogen; and / or, R 2 is hydrogen, methyl, ethyl, isopropyl, methoxy, ethoxy, benzyloxy, trifluoromethyl or halogen; and / or, R 3 is hydrogen, methyl, allyl or benzyl; n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur; and / or, Z is CH; and / or, the light irradiation condition is blue light.

3. The preparation method according to claim 2, characterized in that, R 1 is hydrogen, methyl, methoxy, trifluoromethyl, fluorine, chlorine, bromine; and / or, R 2 is hydrogen, methyl, ethyl, isopropyl, methoxy, ethoxy, benzyloxy, trifluoromethyl, fluorine, chlorine, bromine; and / or, R 3 is hydrogen, methyl, propenyl or benzyl; n = 0 or 1. When n = 1, X is nitrogen, oxygen or sulfur; when n = 0, Y is nitrogen, oxygen or sulfur; and / or, Z is CH; and / or, the light irradiation condition is blue light.

4. The preparation method according to any one of claims 1 to 3, characterized in that, The volume ratio of 1,2-dichloroethane to dimethyl sulfoxide is 9.5:0.5 - 0.5:

9.

5. The preparation method according to claim 4, characterized in that, The ratio of the substrate, photocatalyst and organic solvent is 1 mmol: 0.005 - 0.05 mmol: 10 - 40 mL.

6. A method for preparing a heteroaromatic ring-fused quinolinone derivative, characterized in that: Dissolve the arylamide derivative and the photocatalyst in an organic solvent, and carry out the reaction under light irradiation conditions to obtain the heteroaryl-fused quinolinone derivative; Wherein, the photocatalyst is a cyanocarbazole catalyst with the structure shown in Formula III: Wherein, R is methyl or benzyl; The organic solvent is a mixed solvent of 1,2-dichloroethane and dimethyl sulfoxide; The light irradiation condition is blue light; The chemical structure of the arylamide derivative is any one of the following compounds:

7. The preparation method according to claim 6, characterized in that, The ratio of the arylamide derivative, photocatalyst and organic solvent is 1 mmol: 0.005 - 0.05 mmol: 10 - 40 mL; and / or, the ratio of 1,2-dichloroethane to dimethyl sulfoxide in the organic solvent is 9.5:0.5 - 0.5:9; and / or, the light irradiation condition is blue light.

8. The preparation method according to claim 7, characterized in that The ratio of the arylamide derivative, photocatalyst and organic solvent is 1 mmol: 0.005 - 0.05 mmol: 10 - 40 mL; The ratio of 1,2-dichloroethane to dimethyl sulfoxide in the organic solvent is 9.5:0.5 - 0.5:9; The light irradiation condition is blue light.

9. The preparation method according to claim 8, characterized in that, The ratio of the arylamide derivative, photocatalyst and organic solvent is 1 mmol: 0.01 - 0.05 mmol: 20 - 40 mL; The ratio of 1,2-dichloroethane to dimethyl sulfoxide in the organic solvent is 9:1; The light irradiation condition is blue light.

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