A preparation method of 2-hydroxy-indole-3-one compounds

Abstract

The invention discloses a method for preparing a 2-hydroxy-indole-3-ketone compound, comprising the following steps: mixing a compound of formula (I), oxygen, a transition metal catalyst and a solvent for reaction to prepare a 2-hydroxy-indole-3-ketone compound shown in formula (II); wherein the structural formulas of the compound of formula (I) and the 2-hydroxy-indole-3-ketone compound shown in formula (II) are as follows: wherein X is selected from carbon, nitrogen, sulfur and oxygen; n≥0; R1 is selected from hydrogen, halogen, C 1～20 alkyl, nitro; R2 is selected from hydrogen, C 1～20 Alkyl, C 1～10 Alkoxy, halogen, C 2～6 The ester group, C 1～10 or R2 and the benzene ring form an indolyl group; R3 is selected from hydrogen, C 1～20 The preparation raw materials of the present invention are simple and easy to obtain, environmentally friendly and low in price; the reaction conditions are mild, the operation is simple and the yield is high.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for preparing 2-hydroxy-indole-3-one compounds. Background Art

[0002] 2-Hydroxy-indole-3-one is a special oxygen-containing benzoheterocyclic compound that exists in natural products and has significant biological properties, such as antioxidant, anti-inflammatory and anti-cancer properties. Currently, diphenylacetylene is widely used in the synthesis of indolinone skeletons, in which the alkynyl ligands used are high-cost and somewhat dangerous raw materials. It is still a challenge to select a simple, easy-to-obtain and low-cost alkynyl equivalent synthon to achieve efficient construction of indolinone skeletons.

[0003] In summary, it is necessary to provide a method for preparing 2-hydroxy-indole-3-one compounds, which has low cost, high yield and is green. Summary of the invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, the first aspect of the present invention provides a method for preparing 2-hydroxy-indole-3-one compounds. The raw materials for the preparation of the present invention are simple and easy to obtain, environmentally friendly and low in price; the reaction conditions are mild, the operation is simple and the yield is high; the post-reaction treatment is simple and suitable for industrial production.

[0005] According to a first aspect of the present invention, an embodiment provides a method for preparing a 2-hydroxy-indole-3-one compound, comprising the following steps:

[0006] The compound of formula (I), oxygen, a transition metal catalyst and a solvent are mixed and reacted to prepare a 2-hydroxy-indole-3-one compound represented by formula (II);

[0007] The structural formulas of the compounds of formula (I) and 2-hydroxy-indole-3-one compounds of formula (II) are as follows:

[0008]

[0009] Wherein, X is selected from carbon, nitrogen, sulfur, and oxygen; n≥0;

[0010] R1 is selected from hydrogen, halogen, C 1～20 Alkyl, nitro;

[0011] R2 is selected from hydrogen, C 1～20 Alkyl, C 1～10 Alkoxy, halogen, C 2～6 The ester group, C 1～10 or R2 and the benzene ring form an indole group;

[0012] R3 is selected from hydrogen, C 1～20 of alkyl.

[0013] The preparation method according to the embodiment of the present invention has at least the following beneficial effects:

[0014] The present invention utilizes the compound of formula (I) and oxygen to synthesize the indolinone skeleton, which is a more convenient, efficient and environmentally friendly method for constructing the indolinone skeleton. At the same time, the present invention provides various substituted indolinone analogs with medium to excellent yields based on electron transfer free radical reaction under the catalysis of a transition metal catalyst. The preparation raw materials of the present invention are simple and easy to obtain, environmentally friendly and low in price; the reaction conditions are mild, the operation is simple and the yield is high; the post-reaction treatment is simple and suitable for industrial production.

[0015] According to some embodiments of the present invention, R1 is selected from hydrogen, halogen, C 1～10 Alkyl, nitro.

[0016] According to some embodiments of the present invention, R2 is selected from hydrogen, C 1～10 Alkyl, C 1～5 Alkoxy, halogen, C 2～6 The ester group, C 1～10 or R2 and the benzene ring form an indolyl group.

[0017] According to some embodiments of the present invention, R3 is selected from hydrogen, C 1～10 of alkyl.

[0018] According to some embodiments of the present invention, the 2-hydroxy-indole-3-one compounds represented by formula (II) include 1-acetyl-2-hydroxy-2-(p-tolyl) indole-3-one, 1-acetyl-2-hydroxy-2-(3-methoxyphenyl) indole-3-one, 1-acetyl-2-hydroxy-2-(m-tolyl) indole-3-one, 1-acetyl-2-hydroxy-2-(m-tolyl) indole-3-one, 1-acetyl-2-(3-chlorophenyl)-2-hydroxyindole-3-one, 1-acetyl-2-(3-chlorophenyl)-2-hydroxyindole-3-one, 1-acetyl-5-bromo-2-hydroxy-2-(p-tolyl)indol-3-one, 1-acetyl-6-fluoro-2-hydroxy-2-(p-tolyl)indol-3-one, 1-acetyl-2-hydroxy-2-(4-methoxyphenyl)indol-3-one, 1-acetyl-2-(4-bromophenyl)-2-hydroxyindol-3-one, 1-acetyl-2-hydroxy-2-(1H-indol-5-yl)indol-3-one, -Hydroxy-2-(p-tolyl)indole-3-one, 1-acetyl-2-hydroxy-4-methyl-2-(p-tolyl)indole-3-one, 2-hydroxy-2-(4-methoxyphenyl)-3-oxoindole-1-carbaldehyde, 1-acetyl-2-hydroxy-2-(thiophen-3-yl)indole-3-one, 1-acetyl-2-hydroxy-6-methyl-2-(p-tolyl)indole-3-one, 4-(1-acetyl-2-hydroxy At least one of 1-acetyl-2-hydroxy-3-oxoindole-2-yl)benzaldehyde, 3-(1-acetyl-2-hydroxy-3-oxoindole-2-yl)benzoic acid methyl ester, 1-acetyl-2-hydroxy-5-methyl-2-(p-tolyl)indol-3-one, 1-acetyl-2-(4-aminophenyl)-2-hydroxyindolin-3-one, and 1-acetyl-2-hydroxy-2-(p-tolyl)-5-(trifluoromethyl)indolin-3-one.

[0019] According to some embodiments of the present invention, the transition metal catalyst is a divalent copper catalyst.

[0020] According to some embodiments of the present invention, the divalent copper catalyst is selected from at least one of copper trifluoromethanesulfonate, copper acetate, copper oxide, and copper bromide.

[0021] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the transition metal catalyst is 1:(0.02-1).

[0022] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the transition metal catalyst is 1:(0.05-1).

[0023] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the transition metal catalyst is 1:(0.05-0.3).

[0024] According to some embodiments of the present invention, the raw materials in the reaction further include Lewis acid and catalyst ligand. The function of Lewis acid is to activate hydrogen atoms and improve the yield.

[0025] According to some embodiments of the present invention, the catalyst ligand includes at least one of 6,6'-dimethyl-2,2'-bipyridine, 2,2'-bipyridine, 4,4'-di-tert-butyl-2,2'-bipyridine, (S)-4-isobutyl-2-(pyridin-2-yl)-4,5-dihydrooxazole, and 4,5-diazofluorene-9-one. The role of the catalyst ligand is to form a bidentate ligand with the transition metal to further improve the catalytic efficiency.

[0026] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the catalyst ligand is 1:(0.2-0.5).

[0027] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the Lewis acid is 1:0.1-1.

[0028] According to some embodiments of the present invention, the molar ratio of the compound of formula (I) to the Lewis acid is 1:0.1 to 0.5.

[0029] According to some embodiments of the present invention, the Lewis acid is selected from at least one of trifluoromethanesulfonate, ferric chloride, and aluminum chloride.

[0030] According to some embodiments of the present invention, the triflate includes at least one of zinc triflate, scandium triflate, and magnesium triflate.

[0031] According to some embodiments of the present invention, the volume molar ratio of the solvent to the compound of formula (I) is 5 mL / mmol to 15 mL / mmol.

[0032] According to some embodiments of the present invention, the solvent includes at least one of acetonitrile, methanol or hexafluoroisopropanol.

[0033] According to some embodiments of the present invention, the reaction temperature is 25°C to 120°C.

[0034] According to some embodiments of the present invention, the reaction time is 6 h to 24 h.

[0035] According to some embodiments of the present invention, after the reaction is completed, the steps further include quenching, a first washing, a first extraction, a second washing, a second extraction, concentration and column chromatography.

[0036] According to some embodiments of the present invention, after the reaction is completed, pure water is added to quench the reaction, ethyl acetate is added for washing, the organic phase is obtained by layering, the aqueous phase is extracted with ethyl acetate, the organic phases are combined, dried, the solvent is removed by distillation under reduced pressure, and then the product is obtained by column chromatography.

[0037] Other features and advantages of the present invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the present invention.

[0038] Definitions and general terms

[0039] “C 1～20 "alkyl" means an alkyl group having 1 to 20 carbon atoms, including C 1～20 Straight chain alkyl, C 1～20 The branched alkyl and C 3～20 The cycloalkyl group may be, for example, a straight chain alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, a branched chain alkyl group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, or a cycloalkyl group having 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, for example, a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a tert-butyl group, an n-pentyl group, an isopentyl group, an n-hexyl group, a cyclopropyl group, a methylcyclopropyl group, an ethylcyclopropyl group, a cyclopentyl group, a methylcyclopentyl group, a cyclohexyl group, etc. 1～10 The "alkyl group" has a similar explanation, except that the number of carbon atoms is different.

[0040] “C 1～10 "Alkoxy" means an alkoxy group having a total of 1 to 10 carbon atoms, including C 1-10 Straight chain alkoxy, C 1-10 Branched alkoxy and C 2-10 The cycloalkoxy group may be, for example, a straight chain alkoxy group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, a branched chain alkoxy group having 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, or a cycloalkoxy group having 2, 3, 4, 5, 6, 7, 8, 9 or 10 carbon atoms, for example, a methoxy group, an ethoxy group, a n-propoxy group, an isopropoxy group, etc. 1～5 The "alkoxy group" has a similar explanation, except that the number of carbon atoms is different.

[0041] The "halogen" includes any one or two or more of fluorine, chlorine, bromine and iodine.

[0042] “C 2～6 The ester group "means that the total number of carbon atoms is 2 to 6, and the structural formula is Ester groups such as methyl formate, ethyl formate, methyl acetate, ethyl acetate and propyl acetate.

[0043] “C 1～10 The "aldehyde group" means that the total number of carbon atoms is 1 to 10, and the structural formula is Aldehyde groups. For example, formaldehyde, acetaldehyde, propionaldehyde, n-butyraldehyde, isobutyraldehyde. DETAILED DESCRIPTION

[0044] The following are specific embodiments of the present invention, and the technical solutions of the present invention are further described in conjunction with the embodiments, but the present invention is not limited to these embodiments.

[0045] Unless otherwise specified, the reagents, methods and equipment used in the present invention are conventional reagents, methods and equipment in the art.

[0046] If not otherwise specified, in the embodiment of the present invention, Cu(OTf)2 (30 mol%): represents that the molar ratio of the catalyst Cu(OTf)2 to the compound of formula (I) is 0.3:1.

[0047] In the embodiment of the present invention, 6,6'-dimethyl-2,2'-bipyridine (30 mol %) represents that the molar ratio of 6,6'-dimethyl-2,2'-bipyridine to the compound of formula (I) is 0.3:1.

[0048] In the embodiment of the present invention, Zn(OTf)2 (20 mol%): represents that the molar ratio of Zn(OTf)2 to the compound of formula (I) is 0.2:1.

[0049] The yield calculation method of the embodiment of the present invention is: yield = product mass / (molecular weight*amount of material fed).

[0050] The general synthesis method of the compound of formula (I) mentioned in the examples of the embodiments of the present invention is as follows:

[0051] 1. Take a 100mL round-bottom flask, add the corresponding 2-iodoaniline compound (10.0mmol) and dichloromethane (45mL) at room temperature or 0°C, slowly add acetyl chloride (CAS No.: 75-36-5) (12.0mmol) to the solution at room temperature or zero degrees, and then add triethylamine (CAS No.: 121-44-8) 2.1mL (15.0mmol). After complete addition, allow the reaction to continue stirring for 0.5h until all starting materials are completely consumed (monitored by TLC). After the reaction is completed, the mixture is quenched with saturated brine (15mL), extracted with DCM (3×30mL), and the combined organic layer is washed with brine. The organic layer is dried over anhydrous Na2SO4 and concentrated in vacuo. The crude product 2-iodoacetanilide compound is purified by silica gel column chromatography (PE / EA=8:1) to provide for the next step.

[0052] 2. Under argon and room temperature, take a 100 mL round-bottom flask and dissolve 2-iodoacetanilide compounds (10.0 mmol), PdCl2(PPh3)2 (CAS No.: 13965-03-2) 140.4 mg (0.02 equiv) and CuI (CAS No.: 7681-65-4) 76.2 mg (0.04 equiv) in THF (30 mL). After stirring at 60 ° C for 5 minutes, NEt3 (10.0 mL) was added, and the corresponding phenylacetylene compounds (1.5 equivalents) were added dropwise and uniformly to the reaction mixture until the starting material was completely consumed (monitored by TCL, about 4-8 hours). After completion, the reaction mixture was quenched with brine and extracted with ethyl acetate (3x 20 mL). The total organic layer was then collected, washed with brine, dried over Na2SO4 and concentrated in vacuo. The obtained crude N-(2-(p-tolynyl)phenyl)acetamide derivative (compound of formula (I)) was purified by flash chromatography using PE / EA as eluent.

[0053] Example 1

[0054] Example 1 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0055]

[0056] N-(2-(p-Tolyl)phenyl)acetamide was prepared by the general synthetic method for compounds of formula (I) described above.

[0057] Take a 15mL pressure tube, add N-(2-(p-tolyl)phenyl)acetamide 50.0mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile (CAS No.: 75-05-8) / hexafluoroisopropanol (CAS No.: 920-66-1) = 10:1 (2mL), and react for 17 hours under an oxygen environment at 60°C. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 70%.

[0058] The characterization data of the product are:

[0059] 1H NMR(500MHz,DMSO-d6)δ8.59(d,J=8.4Hz,1H),7.97(s,1H),7.83(t,J=7.9Hz,1H),7.7 0(d,J=7.6Hz,1H),7.31(t,J=7.5Hz,1H),7.24–7.19(m,4H),2.28(s,3H),1.91(s,3H).

[0060] 13 C NMR (125MHz, DMSO-d6) δ196.2,169.9,152.5,138.3,138.2,134.2,129.6,125.0,124.7,124.7,120.0,117.4,90.1,24.4,20.7

[0061] ESI-MS: calculated for C 17 H 15 NO3[M+H] - :282.1124,found:282.1120.

[0062] Example 2

[0063] Example 2 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0064]

[0065] Take a 15mL pressure tube, add N-(2-((3-methoxyphenyl)ethynyl)phenyl)acetamide 53.1mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 56%.

[0066] The characterization data of the product are:

[0067] 1H NMR(500MHz,DMSO-d6)δ8.59(d,J=8.4Hz,1H),8.06(s,1H),7.85(t,J=8.4,7.4,1.4Hz,1H),7.73(d, J=7.4Hz,1H),7.35–7.29(m,2H),6.98–6.95(m,2H),6.78(d,J=7.9Hz,1H),3.75(s,3H),1.94(s,3H).

[0068] 13 C NMR (125MHz, DMSO-d6) δ195.8,169.9,159.8,152.6,138.8,138.3,130.3,124.8,124.7,119.9,117.4,116.8,113.8,111.4,89.9,55.2,24.4.

[0069] ESI-MS: calculated for C 17 H 15 NO4[M+H] - :298.1073,found:298.1070.

[0070] Example 3

[0071] Example 3 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0072]

[0073] Take a 15mL pressure tube, add N-(2-(m-tolynyl)phenyl)acetamide 50.0mg (0.20mmol), Cu(OTf)221.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60°C in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 67%.

[0074] The characterization data of the product are:

[0075] 1H NMR (500MHz, DMSO-d6) δ8.60(d,J=8.4Hz,1H),8.01(s,1H),7.85(t,J=7.5Hz,1H),7.72(d,1H),7.32(t,J=7.4Hz ,1H),7.28(t,J=7.9Hz,1H),7.19(s,1H),7.19(d,J=6.7Hz,1H),7.10(d,J=7.7Hz,1H),2.29(s,3H),1.92(s,3H).

[0076] 13 C NMR (125MHz, DMSO-d6) δ196.1,169.9,152.6,138.4,138.3,137.1,129.5,129.0,125.5,124.8,124.7,122.1,120.0,117.4,90.1,24.4,21.1.

[0077] ESI-MS: calculated for C 17 H 15 NO3[M+H] - :282.1124,found:282.1120.

[0078] Example 4

[0079] Example 4 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0080]

[0081] Take a 15mL pressure tube, add N-(2-((3-chlorophenyl)ethynyl)phenyl)acetamide 53.9mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 66%.

[0082] The characterization data of the product are:

[0083] 1H NMR (500MHz, DMSO-d6) δ8.59(d,J=8.4Hz,1H),8.25(s,1H),7.87(td,J=8.6,7.3,1.5Hz,1H),7.74(d,J=7.6Hz, 1H),7.49–7.45(m,2H),7.43(t,J=7.9Hz,1H),7.34(td,J=7.5,0.8Hz,1H),7.20(d,J=7.7Hz,1H),1.94(s,3H).

[0084] 13 C NMR (125MHz, DMSO-d6) δ195.6,169.6,152.6,139.6,138.5,133.9,131.1,129.0,125.3,124.9,124.9,123.6,119.6,117.5,89.4,24.4.

[0085] ESI-MS: calculated for C 16 H 12 ClNO3[M+H] - :302.0578,found:302.0573.

[0086] Example 5

[0087] Example 5 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0088]

[0089] Take a 15mL pressure tube, add 65.6mg (0.20mmol) of N-(4-bromo-2-(p-tolyl)phenyl)acetamide, 21.8mg (30mol%) of Cu(OTf)2, 14.6mg (20mol%) of Zn(OTf)2, 10.9mg (30mol%) of 6,6'-dimethyl-2,2'-bipyridine and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 56%.

[0090] Characterization data of the product:

[0091] 1H NMR(500MHz,DMSO-d6)δ8.54(d,J=8.9Hz,1H),8.07(s,1H),8.00(dd,J=8.9,2 .3Hz,1H),7.87(d,J=2.2Hz,1H),7.24–7.20(m,4H),2.28(s,3H),1.91(s,3H).

[0092] 13 C NMR (125MHz, DMSO-d6) δ195.1,182.8,169.9,151.4,140.4,138.5,133.7,129.7,126.9,125.1,121.9,119.5,116.4,90.4,24.3,20.7.

[0093] ESI-MS: calculated for C 17 H 14 BrNO3[M+H] - :360.0029,found:360.0222.

[0094] Example 6

[0095] Example 6 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0096]

[0097] Take a 15mL pressure tube, add N-(5-fluoro-2-(p-tolyl)phenyl)acetamide 53.5mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 81%.

[0098] Characterization data of the product:

[0099] 1H NMR(500MHz,DMSO-d6)δ8.30(dd,J=11.1,2.3Hz,1H),8.09(s,1H),7.81(dd,J=8.5,6 .0Hz,1H),7.26–7.20(m,4H),7.17(td,J=8.7,2.3Hz,1H),2.28(s,3H),1.92(s,3H).

[0100] 13 C NMR(125MHz,DMSO-d6)δ194.5,170.2,169.0,167.0,154.1,154.0,138.5,133.9, 129.7,127.6,127.5,125.1,116.8,112.7,1125,104.8,104.6,90.9,24.3,20.7.

[0101] ESI-MS: calculated for C 17 H 14 FNO3[M+H] - :300.1030,found:300.1025.

[0102] Example 7

[0103] Example 7 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0104]

[0105] Take a 15mL pressure tube, add N-(2-((4-methoxyphenyl)ethynyl)phenyl)acetamide 53.1mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 71%.

[0106] Characterization data of the product:

[0107] 1H NMR (500MHz, DMSO-d6) δ8.58(d,J=8.4Hz,1H),7.95(s,1H),7.84(td,J=8.5,1.4Hz,1H),7.70(d,J=7.6 Hz,1H),7.32(t,J=7.4Hz,1H),7.25(d,J=8.8Hz,2H),6.96(d,J=9.0Hz,2H),3.73(s,3H),1.93(s,3H).

[0108] 13 C NMR (125MHz, DMSO-d6) δ196.3,169.9,159.6,152.4,138.2,128.9,126.5,124.8,124.7,112.0,117.4,114.5,90.0,55.2,24.4.

[0109] ESI-MS: calculated for C 17 H 15 NO4[M+H] - :298.1073,found:298.1069.

[0110] Example 8

[0111] Example 8 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0112]

[0113] Take a 15mL pressure tube, add 62.8mg (0.20mmol) of N-(2-((4-bromophenyl)ethynyl)phenyl)acetamide, 21.8mg (30mol%) of Cu(OTf)2, 14.6mg (20mol%) of Zn(OTf)2, 10.9mg (30mol%) of 6,6'-dimethyl-2,2'-bipyridine and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 40%.

[0114] Characterization data of the product:

[0115] 1H NMR(500MHz,DMSO-d6)δ8.59(d,J=8.4Hz,1H),8.16(s,1H),7.88–7.84(m,1H),7.73(d,J=7 .4Hz,1H),7.62(d,J=8.6Hz,2H),7.34(t,J=7.4Hz,1H),7.30(d,J=8.4Hz,2H),1.93(s,3H).

[0116] 13 C NMR (125MHz, DMSO-d6) δ195.7,169.7,152.6,138.4,136.6,132.1,127.4,124.9,122.3,119.7,117.5,89.7,24.4.

[0117] ESI-MS: calculated for C 16 H 12 BrNO3[M+H] - :408.0229found:408.0222.

[0118] Example 9

[0119] Example 9 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0120]

[0121] Take a 15mL pressure tube, add N-(2-((1H-indol-5-yl)ethynyl)phenyl)acetamide 54.9mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 42%.

[0122] Characterization data of the product:

[0123] 1H NMR (500MHz, DMSO-d6) δ11.34(s,1H),8.24(d,J=8.2Hz,1H),7.72(s,1H),7.59(d,J=6.9Hz,1H),7.52(d,J=8.3Hz,1H),7.45(t,J=2.7Hz ,1H),7.31(td,J=8.3,7.8,1.5Hz,1H),7.26(td,J=7.4,1.2Hz,1H),7.21(dd,J=8.3,1.6Hz,1H),6.69(s,1H),6.53(s,1H),1.98(s,3H).

[0124] 13 C NMR(125MHz,DMSO-d6)δ171.6,141.6,136.9,135.8,129.0,127.7,126.6,1 24.2,124.2,123.4,122.3,120.6,120.2,115.4,111.7,109.9,101.6,27.4.

[0125] ESI-MS: calculated for C 18 H 14 N2O3[M+Na] + :329.0896.found:4329.0898.

[0126] Example 10

[0127] Example 10 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0128]

[0129] Take a 15mL pressure tube, add N-(4-fluoro-2-(p-tolyl)phenyl)acetamide 53.5mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60°C in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 50%.

[0130] Characterization data of the product:

[0131] 1 H NMR(500MHz,DMSO-d6)δ8.62(dd,J=9.1,4.3Hz,1H),8.05(s,1H),7.73(td,J=9.1,2 .9Hz,1H),7.56(dd,J=7.0,2.9Hz,1H),7.25–7.20(m,4H),2.29(s,3H),1.90(s,3H).

[0132] 13 C NMR (125MHz, DMSO-d6) δ195.7,169.6,157.6,149.1,138.5,133.8,129.7,125.2(d,J=23.4Hz, 1C), 121.3 (d, J = 7.1Hz, 1C), 119.2 (d, J = 7.8Hz, 1C), 110.3 (d, J = 21.8Hz, 1C), 90.6, 24.2, 20.7.

[0133] 19 F NMR (471MHz, DMSO-d6) δ-117.28 (t, J=9.5Hz).

[0134] ESI-MS: calculated for C 17 H 14 FNO3[M+H] - :300.1030,found:300.1025.

[0135] Embodiment 11

[0136] Example 11 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0137]

[0138] Take a 15mL pressure tube, add N-(3-methyl-2-(p-tolyl)phenyl)acetamide 52.7mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 51%.

[0139] Characterization data of the product:

[0140] 1 H NMR(500MHz,DMSO-d6)δ8.45(d,J=8.4Hz,1H),7.90(s,1H),7.67(t,J=7.8Hz,1H) ,7.23–7.19(m,4H),7.10(d,J=7.5Hz,1H),2.48(s,3H),2.28(s,3H),1.90(s,3H).

[0141] 13 C NMR (125MHz, DMSO-d6) δ196.8,169.8,153.0,139.6,138.2,137.3,134.6,129.6,126.1,125.0,117.6,114.7,89.7,24.5,20.7,18.0.

[0142] ESI-MS: calculated for C 18 H 17 NO3[M+H] - :296.1281,found:296.1282.

[0143] Example 12

[0144] Example 12 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0145]

[0146] Take a 15 nml pressure tube, add N-(2-((4-methoxyphenyl)ethynyl)phenyl)formamide 50.2 mg (0.20 mmol), Cu(OTf)2 21.8 mg (30 mol%), Zn(OTf)2 14.6 mg (20 mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9 mg (30 mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2 mL), and react for 17 hours at 60 °C in an oxygen environment. After the reaction is completed, add 5 mL of water to quench the reaction, then add 10 mL of ethyl acetate and 5 mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 36%.

[0147] Characterization data of the product:

[0148] 1 H NMR(500MHz,DMSO-d6)δ8.48(s,1H),8.37(d,J=8.2Hz,1H),8.07(s,1H),7.89(td,J=1.2,8.4Hz,1H),7 .76(d,J=7.5Hz,1H),7.37(t,J=7.4Hz,1H),7.31(d,J=8.9Hz,2H),6.96(d,J=8.9Hz,2H),3.74(s,3H).

[0149] 13 C NMR (125MHz, DMSO-d6) δ196.1,160.7,159.9,150.1,138.5,128.8,127.1,125.4,125.1,120.3,116.4,114.4,89.3,55.3.

[0150] ESI-MS: calculated for C 16 H 13 NO4[M+Na] + :306.0736,found:306.0736.

[0151] Example 13

[0152] Example 13 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0153]

[0154] Take a 15mL pressure tube, add N-(2-(thiophene-3-ethylidene alkynyl)phenyl)acetamide 48.3mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 50%.

[0155] Characterization data of the product:

[0156] 1 H NMR (500MHz, DMSO-d6) δ8.56(d,J=8.4Hz,1H),7.95(s,1H),7.83(t,J=7.8Hz,1H),7.72(d,J=7. 5Hz,1H),7.56(dt,J=8.0,2.1Hz,2H),7.32(t,J=7.4Hz,1H),6.86(d,J=4.9Hz,1H),2.00(s,3H).

[0157] 13 C NMR (125MHz, DMSO-d6) δ195.5,169.8,152.0,138.7,138.2,128.1,124.7,124.6,123.8,119.8,117.6,89.0,24.2.

[0158] ESI-MS: calculated for C 16 H 13 NO4[M+Na] + :296.0351,found:296.0352.

[0159] Embodiment 14

[0160] Example 14 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0161]

[0162] Take a 15mL pressure tube, add N-(5-methyl-2-(p-tolyl)phenyl)acetamide 52.7mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 73%.

[0163] Characterization data of the product:

[0164] 1 H NMR(500MHz,DMSO-d6)δ8.44(s,1H),7.95(s,1H),7.59(d,J=7.8Hz,1H),7.2 1(d,J=2.2Hz,4H),7.16–7.14(m,1H),2.48(s,3H),2.28(s,3H),1.90(s,3H).

[0165] 13 C NMR (125MHz, DMSO-d6) δ195.4,169.9,152.8,149.6,138.2,134.4,129.6,125.8,125.0,124.6,117.8,117.6,90.5,40.0,24.4,22.5,20.7.

[0166] ESI-MS: calculated for C 18 H 17 NO3[M+H] - :296.1281,found:296.1275.

[0167] Embodiment 15

[0168] Example 15 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0169]

[0170] Take a 15mL pressure tube, add N-(2-((4-formylphenyl)ethynyl)phenyl)acetamide 52.7mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60°C in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 64%.

[0171] Characterization data of the product:

[0172] 1 H NMR (500MHz, DMSO-d6) δ10.01(s,1H),8.61(d,J=8.4Hz,1H),8.29(s,1H),7.96(d,J=8.5Hz,2H),7.88( td,J=7.4,1.4Hz,1H),7.75(d,J=7.6Hz,1H),7.59(d,J=8.1Hz,2H),7.35(t,J=7.9Hz,1H),1.91(s,3H).

[0173] 13 C NMR (125MHz, DMSO-d6) δ195.5,192.7,169.6,152.7,143.3,138.6,136.4,130.3,126.0,124.9,119.7,117.6,89.8,24.4.

[0174] ESI-MS: calculated for C 17 H 13 NO4[M+H] - :296.0917,found:296.0921.

[0175] Example 16

[0176] Example 16 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0177]

[0178] Take a 15mL pressure tube, add 3-((2-acetylaminophenyl)ethynyl)benzoic acid methyl ester 58.7mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction is completed, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 35%.

[0179] Characterization data of the product:

[0180] 1 H NMR(500MHz,DMSO-d6)δ8.61(d,J=8.4Hz,1H),8.28(s,1H),8.01–7.97(m,2H),7.88(td,J=8.6,1.4Hz,1H ),7.74(dd,J=7.4,1.1Hz,1H),7.59–7.56(m,2H),7.36(td,J=7.6,0.8Hz,1H),3.84(s,3H),1.90(s,3H).

[0181] 13 C NMR (125MHz, DMSO-d6) δ195.8,169.7,165.8,152.7,138.6,138.0,130.5,129.9,129.8,129.7,125.9,125.0,119.7,117.5,89.6,52.4,24.4.

[0182] ESI-MS: calculated for C 18 H 15 NO5[M+H] - :326.1022,found:326.1018.

[0183] Embodiment 17

[0184] Example 17 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0185]

[0186] Take a 15mL pressure tube, add N-(4-methyl-2-(p-tolyl)phenyl)acetamide 52.7mg (0.20mmol), Cu(OTf)2 21.8mg (30mol%), Zn(OTf)2 14.6mg (20mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9mg (30mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours at 60℃ in an oxygen environment. After the reaction, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 75%.

[0187] Characterization data of the product:

[0188] 1 H NMR (500MHz, DMSO-d6) δ8.48(d,J=8.5Hz,1H),7.95(s,1H),7.66(d,J=8.7Hz,1H),7.5(S,1H),7.20(s,4H),2.35(s,3H),2.28(s,3H),1.89(s,3H).

[0189] 13 C NMR (125MHz, DMSO-d6) δ196.2,169.6,150.7,139.0,138.2,134.4,134.2,129.6,125.0,124.2,120.1,117.2,90.3,24.3,20.7,20.2.

[0190] ESI-MS: calculated for C 18 H 17 NO3[M+Na] + :318.1100,found:318.1100.

[0191] Embodiment 18

[0192] Example 18 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0193]

[0194] Take a 15 nml pressure tube, add N-(2-((4-aminophenyl)ethynyl)phenyl)acetamide 50.0 mg (0.20 mmol), Cu(OTf)2 21.8 mg (30 mol%), Zn(OTf)2 14.6 mg (20 mol%), 6,6'-dimethyl-2,2'-bipyridine 10.9 mg (30 mol%) and acetonitrile / hexafluoroisopropanol = 10:1 (2 mL), and react for 17 hours at 60 °C in an oxygen environment. After the reaction is completed, add 5 mL of water to quench the reaction, then add 10 mL of ethyl acetate and 5 mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5 mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, distill under reduced pressure to remove the solvent, and then obtain the product by column chromatography with a yield of 23%.

[0195] Characterization data of the product:

[0196] 1 H NMR(500MHz,Chloroform-d)δ8.36(d,J=8.4Hz,1H),7.53(d,J=7.7Hz,1H),7.32(td,J=7.0,1.2Hz,1H),7. 27(td,J=7.6,1.0Hz,1H),7.25–7.23(m,2H),6.75(d,J=8.5Hz,2H),6.54(s,1H),3.89(s,2H),2.11(s,3H).

[0197] 13 C NMR (125MHz, Chloroform-d) δ171.9,147.0,140.2,137.5,130.2,129.2,124.6,124.0,123.6,123.5,120.1,116.0,115.0,110.4,27.9.

[0198] ESI-MS: calculated for C 16 H 14 N2O3[M+Na] + :305.0897,found:305.0891.

[0199] Embodiment 19

[0200] Example 19 provides a method for preparing a 2-hydroxy-indole-3-one compound, the structural formula and steps of which are as follows:

[0201]

[0202] Take a 15mL pressure tube, add 65.3mg (0.20mmol) of N-(2-(p-tolylethynyl)-4-(trifluoromethyl)phenyl)acetamide, 21.8mg (30mol%) of Cu(OTf)2, 14.6mg (20mol%) of Zn(OTf)2, 10.9mg (30mol%) of 6,6'-dimethyl-2,2'-bipyridine and acetonitrile / hexafluoroisopropanol = 10:1 (2mL), and react for 17 hours under an oxygen environment at 60°C. After the reaction, add 5mL of water to quench the reaction, then add 10mL of ethyl acetate and 5mL of saturated brine for washing, collect the organic phase by layers, extract the aqueous phase with ethyl acetate twice, each time with 5mL of ethyl acetate, combine the organic phases, add anhydrous sodium sulfate to dry, remove the solvent by reduced pressure distillation, and then obtain the product by column chromatography with a yield of 31%.

[0203] Characterization data of the product:

[0204] 1 H NMR(500MHz,Chloroform-d)δ8.57(d,J=8.3Hz,1H),8.10(s,1H),7.74(s,1H),7.56(d ,J=8.7Hz,1H),7.44(d,J=8.0Hz,2H),7.22(d,J=7.8Hz,2H),2.41(s,3H),2.27(s,3H).

[0205] 13 C NMR(125MHz,Chloroform-d)δ168.4,141.4,139.9,131.5,129.5,128.7,128.7,126 .4,126.4,125.5,125.3,124.8,122.6,119.0,118.6,112.3,98.0,82.3,25.1,21.6.

[0206] 19 F NMR(471MHz,Chloroform-d)δ-62.34.

[0207] ESI-MS: calculated for C 18 H 14 F3NO3[M+Na] + :372.0818,found:372.0816.

[0208] The above is a detailed description of the embodiments of the present invention, but the present invention is not limited to the above embodiments. Various changes can be made within the knowledge scope of ordinary technicians in the relevant technical field without departing from the purpose of the present invention.

Claims

1. A method for preparing 2-hydroxy-indole-3-one compounds, characterized in that: The steps include: The compound of formula (I), oxygen, a transition metal catalyst and a solvent are mixed and reacted to prepare a 2-hydroxy-indole-3-one compound represented by formula (II); The structural formulas of the compounds of formula (I) and 2-hydroxy-indole-3-one compounds of formula (II) are as follows: ； Wherein, X is selected from carbon, nitrogen, sulfur, and oxygen; n≥0; R1 is selected from hydrogen, halogen, C 1~20 Alkyl, nitro; R2 is selected from hydrogen, C 1~20 Alkyl, C 1~10 Alkoxy, halogen, C 2~6 The ester group, C 1~10 or R2 and the benzene ring form an indole group; R3 is selected from hydrogen, C 1~20 The alkyl group; The transition metal catalyst is a divalent copper catalyst, and the divalent copper catalyst is selected from copper trifluoromethanesulfonate, The raw materials in the reaction also include Lewis acid and catalyst ligand, the Lewis acid is selected from Zn(OTf)2, the catalyst ligand is 6,6'-dimethyl-2,2'-bipyridine, the solvent is selected from at least one of acetonitrile and hexafluoroisopropanol, the reaction temperature is 25°C to 120°C, and the reaction time is 6h to 24h.

2. The method for preparing 2-hydroxy-indole-3-one compounds according to claim 1, characterized in that: The molar ratio of the compound of formula (I) to the transition metal catalyst is 1:(0.02-1).

3. The method for preparing 2-hydroxy-indole-3-one compounds according to claim 1, characterized in that: The volume molar ratio of the solvent to the compound of formula (I) is 5 mL / mmol to 15 mL / mmol.

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