3-acyl-substituted indolone compound containing hydroxyl group and synthesis method of 3-acyl-substituted indolone compound

Abstract

The invention provides a method for green synthesis of a 3-acyl substituted indolone compound containing a hydroxyl group through visible light driving. The method comprises the following steps: dissolving a hydroxyl-containing N-phenyl acrylamide compound # imgabs 0 # triazine ester # imgabs 1 # alkali and a photosensitizer in a solvent; the preparation method comprises the following steps: under the protection of inert gas, carrying out a driving reaction by adopting visible light, and purifying the obtained reaction liquid to obtain the 3-position acyl substituted indolone compound # imgabs2, in which R1 is any one of methyl, methoxyl, fluorine atom, chlorine atom, bromine atom, tertiary butyl and Boc amino; r2 is any one of hydrogen atom, methyl and phenyl; and R3 is any one of methyl, phenyl and ethyl. According to the method, the 3-acyl substituted indolone compound containing the hydroxyl group can be directly synthesized without a protecting group, the reaction condition is mild, the operation is simple, the yield is high, and the environmental pollution is small.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical synthesis, and in particular to an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group and a synthesis method thereof, in particular to a visible light driven green synthesis method of an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group. Background Art

[0002] Indolinone is a common and important structural unit in natural products. It is widely present in many natural products and is a key intermediate in the synthesis of biological products, agrochemicals and drugs. Therefore, the synthesis of indolinone compounds substituted with 3-acyl has broad application prospects.

[0003] At present, there are reports on methods for constructing 3-acyl-substituted indolone compounds from substituted benzoyl chloride and N-phenylacrylamide compounds under visible light catalysis. For example:

[0004] 1.Xu, Shi-Ming; Chen, Jiang-Qiang; Liu, Dan; Bao, Yun; Liang, Yong-Min; et al. Organic Chemistry Frontiers, (2017), 4(7), 1331-1335.

[0005] 2. Bao, Lei; Wang, Zhi-Xiang; Chen, Xiang-Yu. Organic Letters, (2022), 24(44), 8223-8227.

[0006] 3.Liu, Dan; Jiao, Meng-Jie; Feng, Zhi-Tao; Wang, Xing-Zhi; Xu, Guo-Qiang; et al. Organic Letters, (2018), 20(18), 5700-5704.

[0007] The general reaction formula is as follows:

[0008]

[0009] However, this method cannot be used to directly synthesize indolone compounds containing acyl substituted at the 3rd position of the exposed hydroxyl group. On the one hand, the exposed hydroxyl group will react with the acyl chloride; on the other hand, although the use of protecting groups is feasible, the addition and removal of protecting groups undoubtedly increase the synthetic steps of the reaction. Therefore, it is still challenging to directly, simply and efficiently synthesize indolone functional groups containing acyl substituted at the 3rd position of the hydroxyl group and their derivatives. Summary of the invention

[0010] In view of the defects in the prior art, the present invention aims to provide an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group and a synthesis method thereof. The method has high yield, simple operation, mild conditions and little environmental pollution.

[0011] The object of the present invention is achieved through the following solutions:

[0012] The first aspect of the present invention provides an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group, the structural formula of which is shown below:

[0013] Among them, R1 is any one of methyl, methoxy, fluorine atom, chlorine atom, bromine atom, tert-butyl, and Boc amino group; R2 is any one of hydrogen atom, methyl, and phenyl; R3 is any one of methyl, phenyl, and ethyl.

[0014] The second aspect of the present invention provides a method for synthesizing an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group, comprising the following steps: Triazine esters The base and the photosensitizer are dissolved in a solvent; the reaction is driven by visible light at room temperature under the protection of an inert gas, and the obtained reaction solution is purified to obtain an indole ketone compound containing an acyl group substituted at the 3rd position of the hydroxyl group.

[0015] Wherein, R1 is any one of methyl, methoxy, fluorine, chlorine, bromine, tert-butyl, and Boc amino; R2 is any one of hydrogen, methyl, and phenyl; R3 is any one of methyl, phenyl, and ethyl. The general reaction formula is as follows:

[0016]

[0017] Preferably, the wavelength of the visible light is 450nm-460nm. Preferably, the visible light is LED blue light.

[0018] Preferably, the molar ratio of the hydroxyl-containing N-phenylacrylamide compound, triazine ester, base and photosensitizer is 1:1.5-2:1.5-2:0.01-0.02, and the amount of solvent is 8-15 times the volume of the substrate N-phenylacrylamide.

[0019] Preferably, the base is dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium carbonate or sodium carbonate.

[0020] Preferably, the photosensitizer is Ir(ppy)3 (tris(2-phenylpyridine)iridium(III)).

[0021] Preferably, the solvent is N,N-dimethylformamide, tetrahydrofuran, dioxane or dimethyl sulfoxide.

[0022] Preferably, the purification treatment refers to the concentration of the obtained reaction solution after vacuum distillation or extraction to obtain a concentrate, and the concentrate is subjected to silica gel column chromatography to obtain the indole one compound containing an acyl group substituted at the 3rd position of the hydroxyl group.

[0023] Preferably, the conditions of the reduced pressure distillation are a temperature of 25 to 100° C., a pressure of 0.1 to 20 mmHg, and the extraction solvent is ethyl acetate.

[0024] The technical solution of the present invention uses triazine ester compounds as reaction raw materials. Triazine esters and substrates containing hydroxyl groups are compatible, and there is no need to protect the hydroxyl groups. This solves the technical problem that traditional synthetic routes cannot directly synthesize indole ketone compounds substituted with acyl groups at the 3rd position of the hydroxyl group, and provides an efficient and simple synthetic route for the synthesis of intermediates of drug compounds.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] 1. The synthesis method of the present invention can directly synthesize an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group, without the need to use a protecting group strategy, thereby reducing the synthesis steps and saving production costs.

[0027] 2. The synthesis method of the present invention has very high compatibility with hydroxyl functional groups. At the same time, LED blue light is used as a visible light source, which has little impact on the environment and organisms.

[0028] 3. The synthesis method of the present invention synthesizes an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group in one step by a photochemical method. The entire reaction conditions are mild, the operation is simple, the yield is high, and the substrate applicability is wide.

[0029] 4. The indole ketone compound skeleton containing an acyl group substituted at the 3rd position of the hydroxyl group obtained by the synthesis method of the present invention has potential biological activity and pharmaceutical value and can be used as an important synthetic intermediate. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Other features, objects and advantages of the present invention will become more apparent from the detailed description of non-limiting embodiments made with reference to the following drawings:

[0031] Figure 1 The indole ketone compound 2a containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 1 1 H NMR spectrum.

[0032] Figure 2 The indole ketone compound 2a containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 1 13 C NMR spectrum.

[0033] Figure 3 The indole ketone compound 2b containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 2 1 H NMR spectrum.

[0034] Figure 4 The indole ketone compound 2b containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 2 13 C NMR spectrum.

[0035] Figure 5 The indole ketone compound 2c containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 3 1 H NMR spectrum.

[0036] Figure 6 The indole ketone compound 2c containing an acyl group substituted at the 3rd position of the hydroxyl group prepared in Example 3 13 C NMR spectrum. DETAILED DESCRIPTION

[0037] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several changes and improvements can also be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0038] A method for synthesizing an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group by visible light driven synthesis: the method comprises dissolving a hydroxyl-containing N-phenyl acrylamide compound, a triazine ester, a base and a photosensitizer Ir(ppy)3 in a solvent, and driving the reaction with a visible light of 450nm to 460nm in the atmosphere at room temperature under the protection of an inert gas, and obtaining a reaction solution after 24 hours, and concentrating the reaction solution by vacuum distillation or extraction to obtain a concentrate; the concentrate is subjected to silica gel column chromatography to obtain an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group, and the structural formula thereof is:

[0039]

[0040] The structural formulas of the hydroxyl-containing N-phenylacrylamide compound and the triazine ester compound are respectively:

[0041]

[0042] Where: R 1 is any one of a methyl group, a methoxy group, a fluorine atom, a chlorine atom, a bromine atom, a tert-butyl group, and a Boc amino group; R 2 is any one of a hydrogen atom, a methyl group, and a phenyl group; R 3 It is any one of methyl, phenyl and ethyl.

[0043] Reference for the synthesis method of triazine ester compounds: Bo Yu, Huaming Sun, Zunyuan Xie, Guofang Zhang, Li-Wen Xu, Weiqiang Zhang and Ziwei Gao. Org. Lett., 2015, 17, 3298-3301.

[0044] If the triazine ester compound is replaced with an acyl chloride, the acyl chloride will react with the hydroxyl group in the substrate and the target product cannot be obtained.

[0045] The technical solution of the present invention is further described below in conjunction with specific embodiments.

[0046] Example 1

[0047] 0.1mmol of hydroxyl-containing N-phenylacrylamide compound 0.2mmol triazine ester 0.2mmol potassium dihydrogen phosphate and 0.001mmol photosensitizer Ir(ppy)3 were dissolved in 1.0mL anhydrous DMF, and the reaction was driven by 450nm-460nm LED blue light in the atmosphere under inert gas protection at room temperature. After 24 hours, a reaction solution was obtained. After adding water, the reaction solution was extracted with ethyl acetate. The organic phase was distilled under reduced pressure at a temperature of 25°C and a pressure of 1.3kPa to obtain a concentrate; the concentrate was chromatographed on a silica gel column (200-300 mesh silica gel, eluent was petroleum ether: ethyl acetate = 3mL: 1mL) to obtain a colorless oily compound 5-(hydroxymethyl)-1,3-dimethyl-3-(2-oxo-2-phenylethyl)indole-2-one. (2a, 26.3 mg, 85%);

[0048] 2a hydrogen spectrum Figure 1 As shown: 1 H NMR(400MHz, Methanol-d4)δ7.88–7.85(m,2H),7.58–7.53(m,1H),7.46-7.41(m,2H),7.28–7.25(m,2H), 7.01-6.98(m,1H),4.51(s,2H),4.03(d,J=18.4Hz,1H),3.62(d,J=18.4Hz,1H),3.30(s,3H),1.39(s,3H).

[0049] 2a carbon spectrum Figure 2 As shown: 13C NMR (101MHz, Methanol-d4) δ195.6, 180.7, 144.0, 143.3, 134.9, 134.1, 133.7, 129.1, 128.0, 126.7, 120.8, 107.8, 65.1, 45.8, 45.2, 26.4, 24.9, 21.5.

[0050] 2a Mass spectral data: HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 19 NO3Na 332.1257; Found332.1265.

[0051] Example 2

[0052] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 5-(hydroxymethyl)-1,3-dimethyl-3-(2-oxo-2-(p-tolyl)ethyl)indol-2-one was obtained. (2b, 26.8 mg, 83%);

[0053] 2b hydrogen spectrum Figure 3 As shown: 1 H NMR(400MHz,Chloroform-d)δ7.72(d,J=7.9Hz,2H),7.20–7.14(m,4H),6.83(d,J=7.8Hz,1H),4.54(s,2 H), 3.69 (d, J = 18.0Hz, 1H), 3.61 (d, J = 18.0Hz, 1H), 3.28 (s, 3H), 2.36 (s, 3H), 2.26 (s, 1H), 1.39 (s, 3H).

[0054] 2b carbon spectrum Figure 4 As shown: 13 C NMR (101MHz, Chloroform-d) δ195.7,180.7,144.0,143.3,134.9,134.1,133.7,129.1,128.0,126.7,120.8,107.8,65.1,45.9,45.2,26.4,24.9,21.5.

[0055] 2b Mass spectral data: HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 21NO3Na 346.1414; Found346.1421.

[0056] Example 3

[0057] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The base used was potassium carbonate, and a colorless oily compound 5-(hydroxymethyl)-1,3-dimethyl-3-(2-oxo-2-(o-tolyl)ethyl)indol-2-one was obtained. (2c, 25.6 mg, 79%);

[0058] 2c hydrogen spectrum Figure 5 As shown: 1 H NMR(400MHz,Chloroform-d)δ7.53(dd,J=7.6,1.5Hz,1H),7.31(td,J=8.2,7.5,2.1Hz,1H),7.22(ddd,J=15.9,8.5,1.7Hz,3H),7.12(d,J=8.1H z,1H),6.82(d,J=7.9Hz,1H),4.61(s,2H),3.61(d,J=17.2Hz,1H),3.54 (d,J=17.2Hz,1H),3.22(s,3H),2.12(s,3H),1.83(s,1H),1.40(s,3H).

[0059] 2c carbon spectrum Figure 6 As shown: 13 C NMR(101MHz,Chloroform-d)δ200.5,180.4,143.4,137.9,137.3,134.9,133.8,13 1.6,131.2,128.3,126.9,125.4,121.2,108.0,65.3,49.0,45.8,26.5,24.9,20.7.

[0060] 2c mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 21 NO3Na 346.1414; Found346.1422.

[0061] Example 4

[0062] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The base used was disodium hydrogen phosphate, and a colorless oily compound 5-(hydroxymethyl)-1,3-dimethyl-3-(2-oxo-2-(m-tolyl)ethyl)indol-2-one was obtained. (2d, 26.4mg, 82%);

[0063] 2D hydrogen spectrum data: 1 H NMR(400MHz,Chloroform-d)δ7.67–7.61(m,2H),7.36–7.28(m,2H),7.23(dd,J=7.9,1.7Hz,1H),7.16(d,J=1.7Hz,1H),6 .87(d,J=7.9Hz,1H),4.59(s,2H),3.73(d,J=18.1Hz,1H),3.66(d,J=18.1Hz,1H),3.31(s,3H),2.35(s,3H),1.43(s,3H).

[0064] 2d carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ196.2,180.7,143.5,138.3,136.1,134.8,134.2,13 4.0,128.5,128.4,126.9,125.2,120.9,107.9,65.4,46.1,45.2,26.5,25.0,21.3.

[0065] 2d mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 21 NO3Na 346.1414; Found346.1419.

[0066] Example 5

[0067] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The base used was sodium carbonate, and a colorless oily compound 3-(2-(4-(tert-butyl)phenyl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2e, 26.9 mg, 74%);

[0068] 2e hydrogen spectrum data: 1H NMR (400MHz, Chloroform-d) δ7.77(d,J=8.3Hz,2H),7.40(d,J=8.3Hz,2H),7.20(dd,J=7.9,1.7Hz,1H),7.14(d,J=1.6Hz,1H ), 6.84 (d, J = 7.9Hz, 1H), 4.55 (s, 2H), 3.71 (d, J = 18.0Hz, 1H), 3.63 (d, J = 18.0Hz, 1H), 3.29 (s, 3H), 1.40 (s, 3H), 1.30 (s, 9H).

[0069] 2e carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ195.7,180.7,156.9,143.3,134.9,134.1,133.5 ,127.9,126.7,125.4,120.8,107.9,65.2,45.9,45.2,35.0,31.0,26.5,25.0.

[0070] 2e mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 23 H 27 NO3Na 388.1883; Found388.1893.

[0071] Example 6

[0072] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 3-(2-([1,1'-biphenyl]-4-yl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2f, 28.2 mg, 73%).

[0073] 2f hydrogen spectrum data: 1H NMR(400MHz,Chloroform-d)δ7.90(d,J=8.5Hz,2H),7.64–7.55(m,4H),7.49–7.41(m,2H),7.43–7.36(m,1H),7.22(dd,J=8.0,1.7Hz,1 H),7.18(d,J=1.6Hz,1H),6.86(d,J=7.9Hz,1H),4.58(s,2H),3.76(d,J=18.0Hz,1H),3.70(d,J=18.0Hz,1H),3.31(s,3H),1.43(s,3H).

[0074] 2f carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ195.7,180.7,145.8,143.4,139.6,134.9,134.8,134.1, 128.9,128.6,128.2,127.2,127.1,126.8,120.9,108.0,65.2,46.0,45.3,26.5,25.0.

[0075] 2f mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 23 NO3Na 408.1570; Found408.1579.

[0076] Example 7

[0077] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 3-(2-(3,5-dimethylphenyl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2g, 26.0mg, 77%).

[0078] 2g hydrogen spectrum data: 1H NMR(400MHz,Chloroform-d)δ7.44(d,J=1.6Hz,2H),7.19(dd,J=8.0,1.7Hz,1H),7.14(d,J=1.8Hz,2H),6.83(d,J =7.9Hz,1H),4.54(s,2H),3.71(d,J=18.1Hz,1H),3.62(d,J=18.1Hz,1H),3.28(s,3H),2.30(s,6H),1.40(s,3H).

[0079] 2g carbon spectrum data: 13 C NMR (101MHz, Chloroform-d) δ196.4,180.7,143.3,138.0,136.1,134.9,134.8,134.1,126.7,125.7,120.7,107.8,65.1,46.1,45.2,26.4,24.8,21.1.

[0080] 2g mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 21 H 23 NO3Na 360.1570; Found360.1577.

[0081] Example 8

[0082] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 5-(hydroxymethyl)-3-(2-(4-methoxyphenyl)-2-oxoethyl)-1,3-dimethylindol-2-one was obtained. (2h, 25.8mg, 76%);

[0083] 2h hydrogen spectrum data: 1 H NMR(400MHz,Chloroform-d)δ7.80(d,J=8.9Hz,2H),7.20(dd,J=8.0,1.7Hz,1H),7.15(d,J=1.7Hz,2H),6.85(dd,J= 8.4, 3.9Hz, 3H), 4.56 (s, 2H), 3.82 (s, 3H), 3.68 (d, J = 17.9Hz, 1H), 3.61 (d, J = 17.9Hz, 1H), 3.29 (s, 3H), 1.39 (s, 3H).

[0084] 2h carbon spectrum data: 13C NMR (101MHz, Chloroform-d) δ194.5,180.8,163.4,143.3,134.8,134.2,130.2,129.2,126.7,120.8,113.5,107.9,65.2,55.4,45.6,45.2,26.5,25.0.

[0085] 2h mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 21 NO4Na 362.1363; Found362.1370.

[0086] Example 9

[0087] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 3-(2-(4-fluorophenyl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2i, 21.3 mg, 65%);

[0088] 2i hydrogen spectrum data: 1 H NMR(400MHz,Chloroform-d)δ7.89–7.81(m,2H),7.22(dd,J=7.9,1.7Hz,1H),7.16(d,J=1.7Hz,1H),7.06( t,J=8.6Hz,2H),6.86(d,J=7.9Hz,1H),4.58(s,2H),3.663(s,1H),3.658(s,1H),3.30(s,3H),1.41(s,3H).

[0089] 2i carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ194.5,180.6,165.7(d,J=255.1Hz),143.3,134.9,134.0,132.6(d,J= 3.0Hz), 130.6 (d, J = 9.4Hz), 126.8, 120.8, 115.6 (d, J = 21.9Hz), 108.0, 65.2, 45.9, 45.2, 26.5, 25.0.

[0090] 19 F NMR (376MHz, Chloroform-d) δ-104.65.

[0091] 2i mass spectrometry data: HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 18 FNO3Na 350.1163; Found350.1170.

[0092] Example 10

[0093] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 3-(2-(4-chlorophenyl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2j, 23.7 mg, 69%);

[0094] 2j hydrogen spectrum data: 1 H NMR(400MHz,Chloroform-d)δ7.76(d,J=8.3Hz,2H),7.36(d,J=8.3Hz,2H),7.22(d,J=8.0Hz,1H),7 .16(s,1H),6.86(d,J=8.0Hz,1H),4.58(s,2H),3.65(s,2H),3.29(s,3H),1.98(s,1H),1.41(s,3H).

[0095] 2j carbon spectrum data: 13 C NMR (101MHz, Chloroform-d) δ194.9,180.5,143.3,139.7,135.0,134.4,133.9,129.4,128.8,126.9,120.8,108.0,65.2,46.0,45.2,26.5,25.0.

[0096] 2j Mass spectral data: HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 18 ClNO3Na 366.0867; Found 366.0872.

[0097] Embodiment 11

[0098] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 3-(2-(2-chlorophenyl)-2-oxoethyl)-5-(hydroxymethyl)-1,3-dimethylindol-2-one was obtained. (2k, 21.7 mg, 63%).

[0099] 2k hydrogen spectrum data: 1 H NMR(400MHz,Chloroform-d)δ7.36–7.30(m,2H),7.28–7.17(m,4H),6.84(d,J=7.8Hz,1H ), 4.61 (s, 2H), 3.70 (d, J = 17.6Hz, 1H), 3.60 (d, J = 17.6Hz, 1H), 3.25 (s, 3H), 1.40 (s, 3H).

[0100] 2k carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ199.3,180.1,143.3,138.4,135.0,133.4,131.8, 130.8,130.3,129.1,127.0,126.7,121.5,108.0,65.2,50.0,45.8,26.5,24.7.

[0101] 2k mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 19 H 18 ClNO3Na 366.0867; Found 366.0876.

[0102] Example 12

[0103] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The obtained colorless oily compound was tert-butyl (4-(2-(5-(hydroxymethyl)-1,3-dimethyl-2-oxoindole-3-yl)acetyl)phenyl)carbamate (2l, 33.4mg, 79%).

[0104] 2l hydrogen spectrum data: 1H NMR(400MHz,Chloroform-d)δ7.65(d,J=8.7Hz,2H),7.52(s,1H),7.34(d,J=8.5Hz,2H),7.17(dd,J=8.0,1.7Hz,1H),7.12(d,J=1.7 Hz,1H),6.81(d,J=7.9Hz,1H),4.54(s,2H),3.63(d,J=18.1Hz,1H),3.53(d,J=18.1Hz,1H),3.27(s,3H),1.49(s,9H),1.35(s,3H).

[0105] 2l carbon spectrum data: 13 C NMR(101MHz,Chloroform-d)δ194.6,181.0,152.3,143.3,143.0,135.0,134.1,13 0.2,129.3,126.6,120.6,117.3,107.9,80.9,64.9,45.6,45.2,28.2,26.5,24.9.

[0106] 2l Mass spectral data: HRMS (ESI) m / z: [M+Na] + Calcd for C 24 H 28 N2O5Na 447.1890; Found447.1896.

[0107] Embodiment 13

[0108] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 5-(1-hydroxyethyl)-1,3-dimethyl-3-(2-oxo-2-phenylethyl)indol-2-one was obtained. (2m, 29.8mg, 92%); the product contains two chiral carbons and is a mixture of two pairs of corresponding isomers.

[0109] 2m hydrogen spectrum data: 1H NMR(400MHz,Methanol-d4)δ7.90–7.83(m,2H),7.65–7.49(m,1H),7.49–7.39(m,2H),7.3 2–7.22(m,2H),6.98(dd,J=8.5,1.7Hz,1H),4.76(q,J=6.5Hz,0.5H),4.73(q,J=6.3Hz,0.5 H),4.07(s,0.5H),4.02(s,0.5H),3.63(d,J=7.5Hz,0.5H),3.58(d,J=7.4Hz,0.5H),3.29( s, 3H), 1.393 (s, 1.5H), 1.389 (s, 1.5H), 1.36 (d, J = 6.6Hz, 1.5H), 1.34 (d, J = 6.3Hz, 1.5H).

[0110] 2m carbon spectrum data: 13 C NMR(101MHz,Methanol-d4)δ198.4,198.3,183.5,183.4,144.1,144.1,142.2,142.2,137.7,137.6,135.4,135.3,134.5,1 29.7,129.0,126.3,126.2,120.4,120.2,109.3,109.2,70.8,70.7,47.0,46.9,46.88,46.9,25.5,25.4,25.3,20.9,14.5.

[0111] 2m mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 20 H 21 NO3Na 346.1414; Found346.1419.

[0112] Embodiment 14

[0113] The preparation method is the same as that of Example 1, except that: the hydroxyl-containing N-phenylacrylamide compound is The structural formula of the triazine ester compound is The colorless oily compound 5-(hydroxy(phenyl)methyl)-1,3-dimethyl-3-(2-oxo-2-phenylethyl)indol-2-one was obtained. (2n, 34.5 mg, 90%); the product contains two chiral carbons and is a mixture of two pairs of corresponding isomers.

[0114] 2n hydrogen spectrum data: 1H NMR(400MHz, Methanol-d4)δ7.83(ddd,J=8.5,4.6,1.3Hz,2H),7.60–7.48(m,1H),7.41(td,J=7.8,7.3,1.4Hz,2H),7.36–7.08(m,7H),6.95(dd, J=8.1,1.4Hz,1H),5.704(s,0.5H),5.696(s,0.5H),4.02(d,J=1.4Hz,0 .5H), 3.97 (d, J = 0.5Hz, 1H), 3.26 (s, 3H), 1.36 (s, 1.5H), 1.35 (s, 1.5H).

[0115] 2n carbon spectrum data: 13 C NMR(101MHz,Methanol-d4)δ198.5,198.4,183.4,145.9,145.9,144.2,140.6,140.6,137.6,137.6,135.4,135.3,134.5,129.7,129.7 ,129.2,129.2,129.0,128.1,127.7,127.6,127.5,127.5,121.5,121.4,109.3,109.2,76.8,76.7,46.9,46.9,46.8,26.8,25.3,25.2.

[0116] 2n mass spectrum data: HRMS (ESI) m / z: [M+Na] + Calcd for C 25 H 23 NO3Na 408.1570; Found408.1579.

[0117] The above describes the specific embodiments of the present invention. It should be understood that the present invention is not limited to the above specific embodiments, and those skilled in the art can make various changes or modifications within the scope of the claims, which does not affect the essence of the present invention. In the absence of conflict, the embodiments of the present application and the features in the embodiments can be combined with each other arbitrarily.

Claims

1. An indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group, characterized in that: The structural formula is as follows: Among them, R1 is any one of methyl, methoxy, fluorine atom, chlorine atom, bromine atom, tert-butyl, and Boc amino group; R2 is any one of hydrogen atom, methyl, and phenyl; R3 is any one of methyl, phenyl, and ethyl.

2. A method for synthesizing the indole ketone compound containing an acyl group substituted at the 3rd position of the hydroxyl group according to claim 1, characterized in that: The method comprises the following steps: Triazine esters The base and the photosensitizer are dissolved in a solvent; under the protection of an inert gas, the reaction is driven by visible light, and the obtained reaction solution is purified to obtain an indole ketone compound containing an acyl group substituted at the 3rd position of the hydroxyl group. Among them, R1 is any one of methyl, methoxy, fluorine atom, chlorine atom, bromine atom, tert-butyl, and Boc amino group; R2 is any one of hydrogen atom, methyl, and phenyl; R3 is any one of methyl, phenyl, and ethyl.

3. The method for synthesizing an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2, characterized in that: The wavelength of the visible light is 450nm-460nm.

4. The method for synthesizing an indolinone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2 or 3, characterized in that: The visible light is LED blue light.

5. The method for synthesizing an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2, characterized in that: The molar ratio of the hydroxyl-containing N-phenylacrylamide compound, triazine ester, base and photosensitizer is 1:1.5-2:1.5-2:0.01-0.02, and the amount of solvent is 8-15 times the volume of the substrate N-phenylacrylamide.

6. The method for synthesizing an indolinone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2 or 5, characterized in that: The alkali is dipotassium hydrogen phosphate, disodium hydrogen phosphate, potassium carbonate or sodium carbonate.

7. The method for synthesizing an indolinone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2 or 5, characterized in that: The photosensitizer is Ir(ppy)3.

8. The method for synthesizing an indolinone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2 or 5, characterized in that: The solvent is N,N-dimethylformamide, tetrahydrofuran, dioxane or dimethyl sulfoxide.

9. The method for synthesizing an indole ketone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 2, characterized in that: The obtained reaction solution is concentrated after vacuum distillation or extraction to obtain a concentrate, and the concentrate is chromatographed on a silica gel column to obtain an indole ketone compound containing an acyl group substituted at the 3rd position of the hydroxyl group.

10. The method for synthesizing an indolone compound containing an acyl group substituted at the 3rd position of a hydroxyl group according to claim 9, characterized in that: The conditions for the reduced pressure distillation are a temperature of 25 to 100° C. and a pressure of 0.1 to 20 mmHg.

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