Synthesis method of N-protected 2-benzoyl-3-aryl azo indole

Abstract

The invention discloses a synthesis method of N-protected 2-benzoyl-3-aryl azo indole, which is characterized in that CuNPs (at) HKUST-1 is used as a catalyst, the use of noble metal is abandoned, the use amount is extremely small, and the economical efficiency and the greenness are improved; the synthesis of the 2-aroyl indole compound is efficiently and highly regioselectively realized by using the guiding advantage of the azo substrate of the 2-aroyl indole compound under the nitrogen atmosphere with an equivalent amount of oxidizing agent. The N-protected aryl azo indole which is wide in source and extremely high in research value is used as a raw material, the benzoylformic acid which is rich in reserve is used as an acyl source, and synthesis of the 2-aroyl indole compound is achieved. The raw materials used in the invention are all industrial commodities, and the raw materials are simple to prepare, wide in source, low in price and stable in structure; reaction pollution is small, environmental protection is achieved, and operation is easy.

Description

Technical Field

[0001] The present invention relates to the fields of organic synthesis and heterogeneous catalysis. Specifically, under the heating condition of 80 °C, using CuNPs@HKUST-1 as a catalyst, C3 azoaryl and N-protected indole compounds (1a) and benzoylformic acid compounds (2a) as substrates, the C2 acylation reaction of N-protected aryl azoindole compounds is realized to synthesize N-alkyl-2-benzoyl-3-aryl azoindole products (3a). Background Art

[0002] In the past two decades, transition-metal-catalyzed C–H bond activation and functionalization has been regarded as one of the most efficient and robust methods in organic synthesis (D. J. Abrams, P. A. Provencher, E. J. Sorensen. Chem. Soc. Rev., 2018, 47, 8925–8967. Z. Chen, M.-Y. Rong, J. Nie, X.-F. Zhu, B.-F. Shi, J.-A. Ma. Chem. Soc. Rev., 2019, 48, 4921–4942. S. K. Sinha, S. Guin, S. Maiti, J. P. Biswas, S. Porey, D. Maiti. Chem. Rev., 2022, 122, 5682–5841. J. H. Docherty, T. M. Lister, G. McArthur, M. T. Findlay, P. Domingo-Legarda, J. Kenyon, S. Choudhary, I. Larrosa. Chem. Rev. 2023, 123, 7692–7760. S. K. Sinha, P. Ghosh, S. Jain, S. Maiti, S. A. Al-Thabati, A. A. Alshehri, M. Mokhtar, D. Maiti. Chem. Soc. Rev., 2023, 52, 7461–7503.).Since indole compounds are widely present in natural products, dyes, fragrances, drugs, and other biomolecules (R.D. Taylor, M. MacCoss, A.D. Lawson. J. Med. Chem., 2014, 57, 5845 - 5859. Y. Wan, Y. Li, C. Yan, M. Yan, Z. Tang. Eur. J. Med. Chem., 2019, 183, 111691. T. Cernak, K.D. Dykstra, S. Tyagarajan, P. Vachal, S.W. Krska. Chem. Soc. Rev., 2016, 45, 546 - 576. W. Zeng, C. Han, S. Mohammed, S. Li, Y. Song, F. Sun, Y. Du. RSC Med. Chem., 2024, 15, 788 - 808.), researchers have made great efforts in the direct C - H bond activation and functionalization of indole in recent years (J. Wen, Z. Shi. Acc. Chem., Res. 2021, 54, 1723 - 1736. J.A. Leitch, Y. Bhonoah, C.G. Frost. ACS Catal. 2017, 7, 5618 - 5627. P. Kumar, P.J. Nagtilak, M. Kapur. New J. Chem., 2021, 45, 13692 - 13746.). Due to the good biological activity of acyl indoles, the transition - metal - catalyzed direct selective C - H acylation reaction is considered to be one of the most prominent reactions (Yao SJ, Ren ZH, Guan ZH. Tetrahedron Lett., 2016, 57, 3892 - 3901.). Although the reaction of direct selective C - H bond activation and acylation using acylating reagents, directing groups, and homogeneous metal catalysts has been achieved and made significant progress in the past decade, the use of noble - metal catalysts and other homogeneous metal catalysts in such reactions cannot be recycled and has the drawback of residue, which poses a great limitation to their practical applications.Therefore, to overcome the above problems and improve the sustainability of C-H bond activation, the design, synthesis, and application of heterogeneous catalysts that can be recycled are highly necessary but also challenging (M.B. Gawande, A. Goswami, F.X. Felpin, T. Asefa, X. Huang, R. Silva, X. Zou, R. Zboril, R.S. Varma. Chem. Rev., 2016, 116, 3722 - 3811. S. Hasegawa, K. Motokura. ChemCatChem, 2024, 16. F. Valentini, O. Piermatti, L. Vaccaro. Molecules, 2021, 26.).

[0003] The excellent porosity and large specific surface area of metal-organic frameworks (MOFs) have enabled their widespread application in the field of catalysis (X. Liu, B. Tang, J. Long, W. Zhang, X. Liu, Z. Mirza. Sci. Bull., 2018, 63, 502 - 524.). Among various MOFs, earth-abundant and inexpensive copper MOFs are considered the most attractive catalytic candidates due to their cost-effectiveness and unique catalytic activity. In summary, the binding characteristics of Cu NPs supported by Cu MOFs, such as the high natural abundance of Cu, controllable pore size, and high surface area, have attracted extensive attention. However, most reported Cu MOF-supported NPs are usually prepared by solvothermal methods, that is, synthesizing MOFs using copper salts and organic ligands, and then encapsulating NPs using the porous structure of MOFs (Z. Wang, X. Tang, X. Wang, D. Yang, C. Yang, Y. Lou, J. Chen, N. He. Chem. Commun., 2016, 52, 12210 - 12213.), and in-situ growing a MOF shell containing copper salts and ligands on the NPs core (D. Wang, J. Zhou, R. Chen, R. Shi, C. Wang, J. Lu, G. Zhao, G. Xia, S. Zhou, Z. Liu, H. Wang, Z. Guo, Q. Chen. Chem. Mater., 2017, 29, 3477 - 3489.). This preparation method requires a certain temperature and pressure, and the obtained products are also very small in quantity, thus limiting its industrial production. In addition, traditional solvothermal methods usually use copper salts as metal sources, which are more expensive than copper powder, have poor stability, and have certain corrosiveness and oxidizing properties to equipment. It is difficult to obtain Cu(I)-BTC with monovalent copper having unique and attractive catalytic activity by traditional solvothermal methods. Traditionally, highly dispersed Cu(I)-containing MOF can only be synthesized in-situ by electrodeposition (Y. Li, Z. Wei, J. Hu, T. Deng. New J. Chem., 2023, 47, 4784 - 4789.) by adding Cu(I) active sites to the surface of Cu(II)-BTC, or by plasma reduction treatment of Cu(II)-BTC (N. Zou, T. Qiu, Y. Zheng. Catal. Today, 2023, 421.). However, the lack of atom economy and step economy limits its application. It can be seen that large-scale synthesis of MOFs by classical solvothermal methods is not convenient. Therefore, there is an urgent need to develop a safe and sustainable large-scale production method using cost-effective metals to replace metal salts.To continue the work on developing efficient and sustainable methods for the preparation of MOFs (C. Guo, Y. Zhang, Y. Zhang, J. Wang. Chem. Commun., 2018, 54, 3701 - 3704. C. Guo, Y. Zhang, Y. Guo, L. Zhang, Y. Zhang, J. Wang. Chem. Commun., 2018, 54, 252 - 255. C. Guo, Y. Zhang, L. Zhang, Y. Zhang, J. Wang. CrystEngComm, 2018, 20, 5327 - 5331. C. Guo, J. Guo, Y. Zhang, D. Wang, L. Zhang, Y. Guo, W. Ma, J. Wang.. CrystEngComm, 2018, 20, 7659 - 7665. C. Guo, Y. Zhang, L. Zhang, Y. Guo, N. Akram, J. Wang. ACS Appl. Nano Mater., 2018, 1, 5289 - 5296.), herein, we developed a practical, efficient and sustainable one - pot super - large - scale synthesis strategy, that is, using copper metal and H under normal temperature and pressure. 3 BTC as raw materials, and synthesizing CuNPs@HKUST - 1 under the coordination of nitrogen - containing heterocycles. The synthesized CuNPs@HKUST - 1 catalyst can be used for the regioselective C2 - H acylation reaction of azoindole and benzoylformic acid. Summary of the Invention

[0004] The present invention has synthesized a Cu MOFs material, namely CuNPs@HKUST - 1, on a large scale, and used it as a catalyst to achieve the C2 - arylacylation reaction of indole. This method abandons the use of precious metals, with extremely small amounts of catalyst used, and the catalyst can be recycled, improving the economy and greenness of the reaction. The present invention requires an equivalent amount of oxidant. Under a nitrogen atmosphere, using the abundantly available toluene derivative benzoylformic acid as the acyl source, and relying on the guiding advantage of the self - azo substrate, it efficiently and highly regioselectively realizes the synthesis of 2 - arylacylindole compounds.

[0005] By this method, the N - alkyl - 2 - benzoyl - 3 - arylazoindole products (3a) in the following reaction formula were prepared;

[0006] Wherein, the reaction process is shown in the following reaction formula;

[0007]

[0008] Where R 1 represents different substituents connected to the indole N, specifically groups such as methyl, ethyl, propyl, isopropyl, and benzyl. R 2It means that different substituents are respectively connected to the C4-C7 sites of the indole benzene ring, and the number of substituents is 1-9, which are methyl groups at each site, methoxy groups connected to C5 and C7, and F, Cl, and Br halogen groups on C5. R 3 Independently represents substituted methyl groups at different positions such as the ortho, meta, and para positions of the azobenzene ring or unsubstituted groups with hydrogen, and halogen groups at the para position. R 4 It means the substitution and trisubstitution at the para position of the 2a benzene ring, and the substituents are methyl groups and halogen groups.

[0009] As shown in the above reaction formula, in the present invention, under the heating condition of 80 °C, using CuNPs@HKUST-1 as a catalyst, N-protected 3-arylazoindole compounds (1a) and benzoylformic acid compounds (2a) are used as substrates to achieve the C2 acylation reaction of indole compounds, and the product N-methyl-2-benzoyl-3-arylazoindole products (3a) are obtained.

[0010] In the present invention, in the said reaction, the reaction temperature is 80 °C.

[0011] In the present invention, in the said reaction, the reaction oxidant is K 2 S 2 O 8 。

[0012] In the present invention, in the said reaction, the reaction catalyst is CuNPs@HKUST-1.

[0013] In the present invention, in the said reaction, the reaction gas atmosphere is N 2 。

[0014] In the present invention, the reaction solvent is DCE.

[0015] In the present invention, the reaction time of the said reaction is 4 h.

[0016] The synthesis reaction of the present invention includes the following steps:

[0017] 1. The preparation method of the CuNPs@HKUST-1 catalyst material is as follows:

[0018] Disperse 0.15 mol (9.6 g) of Cu powder in 2500 mL of methanol, and successively add 0.225 mol (47.2815 g) of H 3 BTC and 0.25 mol (20.5275 g) of 2-MI. The mixture is stirred publicly at room temperature for 24 h, allowed to stand and filtered by suction, washed several times with DMF and methanol, and dried under vacuum at 60 °C overnight to obtain the material CuNPs@HKUST-1.

[0019] 2. General process for preparing the raw material azoindole

[0020]

[0021] (1) Synthesis of N-alkylindole A

[0022] In a dry 100 mL round-bottom flask, indole (351 mg, 3 mmol), NaOH (180 mg, 4.5 mmol) were added successively, and then ultra-dry DMSO (7 mL) was added. While stirring at room temperature, CH3I (232 μL, 3.6 mmol) was added dropwise. The reaction was monitored by TLC. After the reaction was completed, 15 mL of saturated NH4Cl was added to quench the reaction. The reaction mixture was transferred to a 250 mL separatory funnel, and the mixture was extracted with ethyl acetate. After combining the organic phases, it was dried over anhydrous sodium sulfate, filtered under reduced pressure, and rotary evaporated to obtain the pure N-substituted indole compound.

[0023] (2) Synthesis of aryltriazene B

[0024] Arylamine (10 mmol) was added to a 100 mL round-bottom flask, and then 2 mL of concentrated hydrochloric acid was slowly added, and the mixture was stirred in an ice bath (0 °C). At the same time, an aqueous solution of NaNO 2 (11 mmol) was added dropwise to the reaction system, and the mixture was stirred at 0 °C for 10 min to obtain the diazonium salt product. Then, 10

[0025] mmol of pyrrolidine and 10 mL (1.2 mmol) of K 2 CO 3 solution were added to a beaker, and after stirring evenly, it was added to the above-mentioned aryl diazonium salt solution at one time. The reaction was stirred in an ice-water bath for 30 min and then filtered, and the solid was washed with ice water. The crude product was transferred to a round-bottom flask, and anhydrous ethanol heated to 60 °C was added until it dissolved, and then it was cooled to room temperature or 0 °C, and the pure aryltriazene was obtained by filtration.

[0026] (3) Synthesis of 3-arylazoindole C

[0027] N-substituted indole (1 mmol, 1 eq.), aryltriazene (1.20 mmol, 1.2 eq.), and TFE (10 mL) were added to a dry 100 mL round-bottom flask. During stirring at room temperature, BF 3 ·Et 2O (0.6eq.) and TFE (5mL) mixed system, and then stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was transferred to a 100mL separatory funnel and the aqueous phase was extracted with ethyl acetate. The organic phases were mixed, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The pure N-substituted-3-azoindole was separated by column chromatography (PE:EA = 40:1 to 5:1 gradient elution). (Liu Yonghong. Study on CC and CN bond construction reactions involving aromatic triazenes [D]. Xinjiang University, 2019.)

[0028] 3. Synthesis of N-alkyl-2-benzoyl-3-arylazoindole:

[0029]

[0030] 1a (0.1 mmol), Cu-BTC (2-MI) catalyst (3 mg), 2a (0.3 mmol), oxidant (0.3 mmol), inert atmosphere (N 2 ) and solvent DCE (1 mL), and the reaction was stirred at 80°C to obtain C2 acylindole product 3a.

[0031] The method has the advantages of mild reaction conditions and recyclable catalyst, and the catalyst can be recycled at least 10 times.

[0032] The present invention uses CuNPs@HKUST-1 as a catalyst, abandons the use of precious metals, uses very little, and improves economy and greenness; the present invention requires an equivalent amount of oxidant, and in a nitrogen atmosphere, uses the guiding advantage of its own azo substrate to efficiently and highly regioselectively achieve the synthesis of 2-aroyl indole compounds. The present invention uses N-protected arylazo indole, which has a wide source and great research value, as a raw material, and uses benzoylformic acid, which is rich in reserves, as an acyl source, to achieve the synthesis of 2-aroyl indole compounds. All raw materials used in the present invention are industrialized commodities, and the raw materials are simple to prepare, widely available, cheap, and stable in structure; the reaction has low pollution, is green and environmentally friendly, and is simple to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0034] Figure 1 Schematic diagram of the preparation process of the catalyst CuNPs@HKUST-1 synthesized in Example 1.

[0035] Figure 2(a), (b) SEM images, (c) elemental mapping, and (d), (e) TEM images of the CuNPs@HKUST-1 synthesized in Example 1.

[0036] Figure 3 XPS spectra of (a) C1s, (b) N1s, (c) O1s, and (d) Cu2p of the CuNPs@HKUST-1 prepared in Example 1;

[0037] (e) XRD pattern of CuNPs@HKUST-1; (f) EPR experiment.

[0038] Figure 4 Cyclic experiment diagram of the catalyst CuNPs@HKUST-1 in Example 11.

[0039] Figure 5 1H NMR and 13C NMR spectra of the raw materials prepared in Example 2.

[0040] Figure 6 1H NMR and 13C NMR spectra for the substrate generality study in Example 3. Detailed implementation manners

[0041] In combination with the following specific examples, the present invention will be further described in detail. The protection scope of the present invention is not limited to the following examples. Without departing from the spirit and scope of the inventive concept, changes and advantages that can be conceived by those skilled in the art are included in the present invention, and the appended claims are used as the protection scope. The processes, conditions, reagents, experimental methods, etc. for implementing the present invention are all common knowledge and well-known common sense in the art except for the specifically mentioned content below, and the present invention has no special limiting content. The data given in the following examples include specific operations, reaction conditions, and products. The product purity is identified by NMR and high-resolution mass spectrometry.

[0042] Example 1: As Figure 1 shown, the synthesis method of the catalyst is to disperse 0.15 mol (9.6 g) of Cu powder in 2500 mL of methanol, and then sequentially add 0.225 mol (47.2815 g) of H 3 BTC (benzene-1,3,5-tricarboxylic acid) and 0.25 mol (20.5275 g) of 2-MI (2-methylimidazole). The mixture is stirred in an open container at room temperature for 24 h, allowed to stand and filtered by suction, washed 4 times with DMF and methanol in sequence, and dried overnight under vacuum at 60 °C to obtain the blue powder material CuNPs@HKUST-1. According to the characterization Figure 2It can be seen that the SEM image confirmed the successful synthesis of octahedral Cu-BTC using Cu powder under the promotion of 2-MI, with a size of approximately 3 μm. The distribution of N element in the elemental mapping diagram indicates the presence of partial 2-MI in the catalyst structure, and a large number of Cu nanoparticles with a particle size radius of approximately 5 nm can be seen attached to the catalyst surface from the TEM image. Figure 3 The XRD characterization analysis further confirmed the successful synthesis of Cu-BTC. Characteristic peaks of C=C, C-H, and C=O appeared in the C1s spectrum of the XPS pattern, located at 288.85 eV, 286.28 eV, and 284.80 eV respectively; two characteristic peaks appeared in the O 1s spectrum, with binding energies of 533.38 eV and 532.13 eV respectively, corresponding to -OH and C=O; the appearance of the N element peak in XPS also confirmed the presence of imidazole ligands in the Cu-BTC crystal structure, and the appearance of Cu-N may be attributed to the interaction between Cu 2+ and the nitrogen-containing ligand; Cu2p showed Cu 2+ diffraction peaks, and characteristic peaks of low-valent copper (Cu 1+ / Cu 0 ) appeared at 933.20 eV and 953.10 eV. Figure 3 Figure (f) is the EPR test at different time periods during the preparation of the CuNPs@HKUST-1 catalyst, and the presence of superoxide radicals could be continuously detected in the methanol reaction solution.

[0043] Example 2: Synthesis of raw material 1-methyl-3-[(E)-2-(4-methylphenyl)diazenyl]-indole (1a).

[0044]

[0045] Indole (585 mg, 5 mmol) and NaOH (400 mg, 10 mmol) were successively added to a dry 100 mL round-bottom flask, and then ultra-dry DMSO (12 mL) was added. CH 3 I (387 μL, 6 mmol) was added dropwise with stirring at room temperature, and the mixture was stirred overnight. 25 mL of saturated NH 4 Cl was added to quench the reaction. The reaction mixture was transferred to a 250 mL separatory funnel, and the mixture was extracted with ethyl acetate. After combining the organic phases, they were dried over anhydrous sodium sulfate, filtered under reduced pressure, and rotary evaporated to obtain the pure N-methylindole compound.

[0046] p-Toluidine (10 mmol) was added to a 100 mL round-bottom flask, and then 2 mL of 36% concentrated hydrochloric acid by mass was slowly added, and the mixture was stirred in an ice bath (0 °C). At the same time, NaNO 2An aqueous solution (5 mL) of 2 CO 3 (11 mmol) was stirred at 0 °C for an additional 10 min to obtain a diazonium salt product, yielding an aryl diazonium salt solution. Then, 10 mmol of pyrrolidine and 10 mL (1.2 mmol) of an aqueous solution of K

[0047] were added to a beaker. After stirring evenly, it was added to the above aryl diazonium salt solution all at once. The reaction was stirred in an ice-water bath for 30 min, then filtered by suction and the solid was washed with ice water. The solid crude product was transferred to a round-bottom flask, and anhydrous ethanol (20 mL) heated to 60 °C was added until it dissolved. Then it was cooled to room temperature or 0 °C, and the pure aryltriazene was obtained by suction filtration. 3 ·Et 2 N-methylindole (5 mmol), aryltriazene (6 mmol, 1.2 eq.), and TFE (30 mL, tetrahydrofuran) were added to a dry 100 mL round-bottom flask. A mixed system of BF

[0048]

[0049] (0.6 equiv, 46% aqueous solution of boron trifluoride diethyl etherate) and TFE (10 mL) was added dropwise during stirring at room temperature, and then stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was transferred to a 100 mL separatory funnel and the aqueous phase was extracted with ethyl acetate 3 times. The combined organic phases were dried over anhydrous sodium sulfate, filtered, concentrated under reduced pressure, and separated by column chromatography (eluted with a linear gradient of PE (petroleum ether):EA (ethyl acetate) = 40:1 to 5:1) to obtain the pure product 1-methyl-3-[(E)-2-(4-methylphenyl)diazenyl]-indole (1a). The substrate 1a was an orange solid, with a yield of (72%) and a melting point of: 124.3 - 125.4 °C. The compound was characterized by NMR and high-resolution mass spectrometry, and the spectral parameters were as follows: f (E)-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1a): Eluent: petroleumether / EtOAc = 20:1 (v / v). R 1 H NMR (600 MHz, CDCl 3 ) δ 8.59 (d, J = 7.2 Hz, 1H), 7.83 (s, 1H), 7.80 (d, J = 7.9 Hz, 2H), 7.37 - 7.33 (m, 3H), 7.30 (d, J = 7.9 Hz, 2H), 3.86 (s, 3H), 2.44 (s, 3H).13 C NMR (150 MHz, CDCl 3 ) δ 152.04, 139.12, 137.41, 135.51, 134.28, 129.70, 123.98, 123.27, 122.84, 121.78, 119.70, 109.52, 33.48, 21.48.

[0050] Example 3: Synthesis of 1-methyl-2-benzoyl-3-[(E)-2-(4-methylphenyl)diazenyl]-indole (3a)

[0051]

[0052] 1a (24.9 mg, 0.1 mmol), CuNPs@HKUST-1 catalyst (3.0 mg), 2a (45.0 mg, 0.3 mmol), and oxidant K 2 S 2 O 8 (80.9 mg, 0.3 mmol) were successively added into a glass tube. Then, the inert atmosphere (N 2 ) was evacuated and filled, and the solvent DCE (1 mL, 1,2-dichloroethane) was sucked into the glass tube with a disposable syringe. The mixture was stirred under heating at 80 °C for 4 h to obtain the C2 benzoyl indole product 3a (mass: 33.5 mg, yield: 95%). The product was an orange solid with a melting point of 134.1 - 135.7 °C. The compound was characterized by NMR and high-resolution mass spectrometry, and the parameters of the obtained product were as follows:

[0053]

[0054] (E)-(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3a): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.42 (Developing agent: petroleum ether / EtOAc = 10:1). 33.5 mg, 95% yield. Orange solid. MP: 134.1 - 135.7 °C. 1 H NMR (600 MHz, CDCl 3)δ8.63(d, J = 8.0 Hz, 1H), 7.98(dd, J = 8.1, 1.0 Hz, 2H), 7.62(t, J = 7.4 Hz, 1H), 7.50–7.44(m, 4H), 7.37 - 7.40(m, 1H), 7.21(d, J = 8.3 Hz, 2H), 7.10(d, J = 8.1 Hz, 2H), 4.02(s, 3H), 2.35(s, 3H). 13 C NMR(150 MHz, CDCl 3 )δ190.10, 151.84, 140.28, 140.08, 138.64, 137.35, 136.02, 133.01, 130.86, 129.52, 128.05, 126.36, 124.79, 124.00, 122.25, 117.36, 110.18, 31.82, 21.47. HRMS(ESI)(M + Na + )Calcd. for C 23 H 19 ON 3 : 376.14203, Found: 376.14203.

[0055] The remaining products 3b - 3z were all obtained according to the steps of Example 3. Among them, the product 3j obtained has a structure similar to that of the tubulin inhibitor, and this compound has potential inhibitory effects on tumor cells. (Mahboobi, S.; Pongratz, H. Hufsky, H.; Hockemeyer, J.; Frieser, M.; Lyssenko, A.; Paper, D. H.; Bürgermeister, J.; F.D.; Fiebig, H. H.; Burger, A. M.; Baasner, S.; Beckers, T. Synthetic 2 - aroylindolederivatives as a new class of potent tubulin - inhibitory, antimitotic agents[J]. J. Med. Chem., 2001, 44(26): 4535 - 4553.) The product 3d can be prepared on a large scale, such as in Example 10.

[0056] Example 4: Screening of catalysts.

[0057] 1a (24.9 mg, 0.1 mmol) was successively added into a glass tube, and then the screened catalysts ZIF-8 (5.0 mg), MIL-125(Ti) (5.0 mg), Uio-67 (5.0 mg), Cu-BDC (5.0 mg), Cu-BTC (5.0 mg), CuNPs@HKUST-1 (5.0 mg), CuCl (20 mmol%), CuCl 2 (20 mmol%), etc., 5.0 mg were added respectively. Finally, 2a (45.0 mg, 0.3 mmol) and the oxidant K 2 S 2 O 8 (80.9 mg, 0.3 mmol) were added. Then, under air conditions, 1 mL of the solvent DCE (1,2-dichloroethane) was aspirated with a disposable syringe and added into the glass tube. The mixture was stirred under heating at 80 °C for 4 h to obtain the C2-benzoyl indole product 3a, and the yields were NR, NR, trace, 65%, 70%, 86%, 56% and 63% respectively. It can be concluded that the optimal catalyst for the reaction is CuNPs@HKUST-1.

[0058] Example 5: Screening of temperature.

[0059] 1a (24.9 mg, 0.1 mmol), CuNPs@HKUST-1 catalyst (5.0 mg), 2a (45.0 mg, 0.3 mmol), and the oxidant K 2 S 2 O 8 (80.9 mg, 0.3 mmol) were successively added into a glass tube. Then, under air conditions, 1 mL of the solvent DCE (1,2-dichloroethane) was aspirated with a disposable syringe and added into the glass tube. The mixture was stirred under heating at room temperature, 40 °C, 60 °C, 80 °C or 100 °C for 4 h to obtain the C2-benzoyl indole product 3a, and the yields were NR, trace, 48%, 86% and 87% respectively. It can be concluded that the optimal temperature for the reaction is 80 °C.

[0060] Example 6: Screening of solvent.

[0061] 1a (24.9 mg, 0.1 mmol), CuNPs@HKUST-1 catalyst (5.0 mg), 2a (45.0 mg, 0.3 mmol), and oxidant K2S2O8 (80.9 mg, 0.3 mmol) were successively added into a glass tube. Then, under air conditions, 1 mL of solvents such as 1,2-dichloroethane, acetonitrile, ethanol, toluene, N,N-dimethylformamide, dimethyl sulfoxide, and water were respectively aspirated with a disposable syringe and added into the glass tube. The mixture was stirred under heating at 80 °C for 4 h to obtain the C2-benzoylindole product 3a, and the yields were 86%, 37%, trace, 31%, trace, 25%, and 19% respectively. It can be concluded that the optimal solvent for the reaction is 1,2-dichloroethane.

[0062] Example 7: Screening of oxidants.

[0063] 1a (24.9 mg, 0.1 mmol), CuNPs@HKUST-1 catalyst (5.0 mg), 2a (45.0 mg, 0.3 mmol) were successively added into a glass tube, and then the screened oxidants K 2 S 2 O 8 (0.3 mmol), (NH 4 ) 2 S 2 O 8 (0.3 mmol), PhI(ACO) 2 (0.3 mmol), BPO (0.3 mmol), or TBHP (0.3 mmol) were added respectively. Then, under air conditions, 1 mL of 1,2-dichloroethane was aspirated with a disposable syringe and added into the glass tube. The mixture was stirred under heating at 80 °C for 4 h to obtain the C2-benzoylindole product 3a, and the yields were 86%, 64%, 40%, 13%, and trace respectively. It can be concluded that the optimal oxidant for the reaction is K 2 S 2 O 8 .

[0064] Example 8: Screening of catalyst dosage.

[0065] 1a (24.9 mg, 0.1 mmol) was successively added into a glass tube, and then 5.0 mg, 3.0 mg, and 1.0 mg of CuNPs@HKUST-1 catalyst were added respectively. Finally, 2a (45.0 mg, 0.3 mmol) and oxidant K 2 S 2 O 8 (0.3 mmol) were added. Then, under N 2Under the conditions, 1 mL of the solvent 1,2-dichloroethane was sucked with a disposable syringe and added into a glass tube, and stirred under heating at 80 °C. After reacting for 4 h, the C2-benzoyl indole product 3a was obtained, and the yields were 97%, 95% and 90% respectively. It was thus considered that the optimal amount of the oxidant was 3.0 mg.

[0066] Example 9: Control experiment.

[0067] The operation was as in Example 3, except that the reaction was carried out without adding K 2 S 2 O 8 or without adding the catalyst CuNPs@HKUST-1. Finally, the result of thin layer chromatography detection was trace in both cases, indicating that the presence of the oxidant K 2 S 2 O 8 and the catalyst CuNPs@HKUST-1 are necessary conditions for the reaction to occur.

[0068] Example 10: Gram-scale experiment of 3d product.

[0069] To further verify the practicability of this method, a gram-scale reaction was carried out under improved conditions. As shown in the following chemical formula, under nitrogen conditions, 1d (4 mmol), 2a (12 mmol), the catalyst CuNPs@HKUST-1(0.12 g), the oxidant K 2 S 2 O 8 (12 mmol) and the solvent DCE (30 mL) were added into a 100 mL round-bottom flask, and stirred at 80 °C for 6 h. The target product 3d was successfully obtained with a yield of 71%.

[0070]

[0071] Example 11: Catalyst recycling test.

[0072] Since recyclability is one of the advantages of heterogeneous catalysts, in order to determine the recovery rate and reusability of the CuNPs@HKUST-1 catalyst, C2 acylation of indole was carried out under optimized catalytic conditions. After the reaction was completed, the catalyst was centrifuged, washed 3 times with ethyl acetate, and dried under vacuum for the next cycle. As Figure 4 shown, this catalyst can be recovered and reused at least 10 times without significantly reducing the catalytic activity.

[0073] Characterization data of raw materials

[0074] Raw materials 1b - 1u were all prepared according to Example 2, with the same process and conditions as in Example 2. The difference is that 1b - 1d respectively used equimolar amounts of iodoethane, iodopropane, 2 - bromoisopropane, or benzyl bromide to replace CH 3 I, and the subsequent operations were the same as those in Example 2; 1f - 1n respectively used equimolar amounts of 4 - methylindole, 5 - methylindole, 6 - methylindole, 7 - methylindole, 5 - methoxyindole, 7 - methoxyindole, 5 - fluoroindole, 5 - bromoindole, or 5 - chloroindole to replace indole, and the subsequent operations were the same as those in Example 2; 1o - 1u used equimolar amounts of aniline, o - toluidine, m - toluidine, p - methoxyaniline, p - fluoroaniline, p - chloroaniline, or p - bromoaniline to replace p - toluidine, and the subsequent operations were the same as those in Example 2. After characterization by NMR and high - resolution mass spectrometry, the parameters of the obtained raw materials are as follows.

[0075]

[0076] (E)-1 - ethyl - 3-(p - tolyldiazenyl)-1H - indole(1b): Eluent: petroleum ether / EtOAc = 20:1(v / v). New compound. R f = 0.48 (Developing agent: petroleum ether / EtOAc = 5:1). 63% yield. Orange solid. MP: 54.4 - 55.8℃. 1 H NMR(600MHz, CDCl 3 )δ8.62–8.58(m, 1H), 7.92(s, 1H), 7.80(d, J = 8.2Hz, 2H), 7.39–7.32(m, 3H), 7.31(s, 1H),, 7.30(s, 1H), 4.24(q, J = 7.3Hz, 2H), 2.44(s, 3H), 1.56(t, J = 7.3Hz, 3H). 13 C NMR(150MHz, CDCl 3 )δ152.08, 139.10, 136.56, 135.67, 132.51, 129.70, 123.90, 123.40, 122.82, 121.77, 119.93, 109.60, 41.62, 21.49, 15.26. HRMS(ESI)(M + H + ) Calcd. for C 17 H 17 N 3 : 264.14952, Found: 264.14917.

[0077]

[0078] (E)-1-propyl-3-(p-tolyldiazenyl)-1H-indole(1c): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.55 (Developing agent: petroleum ether / EtOAc = 5:1). 68% yield. Orange solid. MP: 75.6 - 77.2 °C. 1 H NMR(600 MHz, CDCl 3 ) δ 8.65–8.61 (m, 1H), 7.90 (s, 1H), 7.83 (d, J = 8.2 Hz, 2H), 7.39–7.33 (m, 3H), 7.33 (s, 1H), 7.31 (s, 1H), 4.14 (t, J = 7.1 Hz, 2H), 2.45 (s, 3H), 1.98–1.92 (m, 2H), 1.00 (t, J = 7.4 Hz, 3H). 13 C NMR(150 MHz, CDCl 3 ) δ 152.07, 139.08, 136.80, 135.48, 133.44, 129.70, 123.86, 123.35, 122.77, 121.76, 119.84, 109.75, 48.62, 23.28, 21.48, 11.54. HRMS(ESI)(M + H + ) Calcd. for C 18 H 19 N 3 : 278.16517, Found: 278.16486.

[0079]

[0080] (E)-1-isopropyl-3-(p-tolyldiazenyl)-1H-indole(1d): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.57 (Developing agent: petroleum ether / EtOAc = 5:1). 60% yield. Orange solid. MP: 130.3 - 132.0 °C. 1 H NMR(600 MHz, CDCl3 ) δ 8.63–8.59 (m, 1H), 8.04 (s, 1H), 7.80 (d, J = 8.2 Hz, 2H), 7.44–7.40 (m, 1H), 7.36 - 7.32 (m, 2H), 7.31 (s, 1H), 7.30 (s, 1H), 4.77–4.70 (m, 1H), 2.44 (s, 3H), 1.62 (d, J = 6.7 Hz, 6H). 13 C NMR (150 MHz, CDCl 3 ) δ 152.09, 139.06, 136.45, 135.82, 129.71, 129.60, 123.81, 123.37, 122.86, 121.74, 119.93, 109.75, 47.72, 22.79, 21.49. HRMS (ESI) (M + H + ) Calcd. for C 18 H 19 N 3 : 278.16517, Found: 278.16483.

[0081]

[0082] (E)-1-benzyl-3-(p-tolyldiazenyl)-1H-indole (1e): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.55 (Developing agent: petroleum ether / EtOAc = 5:1). 70% yield. Orange solid. MP: 120.0 - 121.5 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 8.64–8.57 (m, 1H), 7.91 (s, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.37–7.28 (m, 8H), 5.38 (s, 2H), 2.43 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 152.02, 139.31, 137.04, 136.14, 135.89, 133.62, 129.73, 129.14, 128.27, 127.30, 124.18, 123.43, 123.03, 121.83, 120.07, 110.06, 50.79, 21.51. HRMS (ESI) (M + H +)Calculated for C 22 H 19 N 3 : 326.16517, Found: 326.16476.

[0083]

[0084] (E)-1,4-dimethyl-3-(p-tolyldiazenyl)-1H-indole (1f): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.43 (Developing agent: petroleum ether / EtOAc = 5:1). 78% yield. Orange solid. MP: 142.1 - 143.8 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 7.79 (d, J = 8.2 Hz, 2H), 7.63 (s, 1H), 7.30 (d, J = 8.2 Hz, 2H), 7.24–7.19 (m, 2H), 7.11 (d, J = 6.5 Hz, 1H), 3.83 (s, 3H), 2.95 (s, 3H), 2.44 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 151.81, 139.41, 137.19, 137.01, 132.32, 129.77, 124.78, 123.20, 122.77, 122.10, 117.08, 107.60, 33.65, 21.52, 20.95. HRMS (ESI) (M + H + )Calculated for C 17 H 17 N 3 : 264.14952, Found: 264.14920.

[0085]

[0086] (E)-1,5-dimethyl-3-(p-tolyldiazenyl)-1H-indole (1g): Eluent: petroleum ether / EtOAc = 20:1 (v / v). R f= 0.41 (Developing agent: petroleum ether / EtOAc = 5:1). 64% yield. Orange solid. MP: 114.4 - 116.2 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 8.38 (s, 1H), 7.80 - 7.69 (m, 3H), 7.30 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.3 Hz, 1H), 7.18 (dd, J = 8.3, 1.1 Hz, 1H), 3.84 (s, 3H), 2.53 (s, 3H), 2.43 (s, 3H). 13 C NMR (150 MHz, CDCl 3 ) δ 152.15, 138.96, 135.90, 135.23, 134.42, 132.57, 129.68, 125.48, 122.91, 121.74, 119.87, 109.23, 33.55, 21.77, 21.49.

[0087]

[0088] (E)-1,6-dimethyl-3-(p-tolyldiazenyl)-1H-indole (1h): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.37 (Developing agent: petroleum ether / EtOAc = 5:1). 59% yield. Orange solid. MP: 122.4 - 126.3 °C. 1 H NMR (600 MHz, CDCl 3 ) δ 8.45 (d, J = 8.0 Hz, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.76 (s, 1H), 7.30 (d, J = 8.1 Hz, 2H), 7.16 (d, J = 8.1 Hz, 1H), 7.13 (s, 1H), 3.82 (s, 3H), 2.53 (s, 3H), 2.44 (s, 3H). 13 C NMR (150 MHz, CDCl 3)δ152.10,138.98,137.89,135.64,134.03,129.68,124.45,122.97,121.75,117.54,109.56,33.42,22.06,21.48.HRMS(ESI)(M+H + )Calcd.forC 17 H 17 N 3 :264.14952,Found:264.14917.

[0089]

[0090] (E)-1,7-dimethyl-3-(p-tolyldiazenyl)-1H-indole(1i):Eluent:petroleumether / EtOAc=20:1(v / v).Newcompound.R f =0.34(Developing agent:petroleum ether / EtOAc=5:1).65%yield.Orange solid.MP:166.7-168.8℃. 1 H NMR(600 MHz,CDCl 3 )δ8.48(d,J=7.9 Hz,1H),7.79(d,J=8.2 Hz,2H),7.70(s,1H),7.30(d,J=8.1 Hz,2H),7.18(t,J=7.6 Hz,1H),7.03(d,J=7.1 Hz,1H),4.09(s,3H),2.76(s,3H),2.43(s,3H). 13 C NMR(150 MHz,CDCl 3 )δ152.07,139.04,136.11,135.62,134.93,129.68,126.83,123.04,121.74,121.47,121.16,121.02,37.80,21.48,19.85.HRMS(ESI)(M+H + )Calcd.forC 17 H 17 N 3 :264.14952,Found:264.14908.

[0091]

[0092] (E)-5-methoxy-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1j): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.27 (Developing agent: petroleum ether / EtOAc = 5:1). 73% yield. Orange solid. MP: 128.4 - 129.4 °C. 1 H NMR(600 MHz, CDCl 3 ) δ8.10 (d, J = 2.4 Hz, 1H), 7.79 (s, 1H), 7.77 (d, J = 8.1 Hz, 2H), 7.29 (d, J = 8.1 Hz, 2H), 7.23 (d, J = 8.8 Hz, 1H), 6.98 (dd, J = 8.7, 2.4 Hz, 1H), 3.92 (s, 3H), 3.84 (s, 3H), 2.43 (s, 3H). 13 C NMR(150 MHz, CDCl 3 ) δ156.75, 152.06, 138.99, 135.29, 134.46, 132.55, 129.70, 121.71, 120.18, 113.79, 110.38, 105.01, 55.95, 33.71, 21.49. HRMS(ESI)(M + H + ) Calcd. for C 17 H 17 N 3 O: 280.14444, Found: 280.14413.

[0093]

[0094] (E)-7-methoxy-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1k): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.41 (Developing agent: petroleum ether / EtOAc = 5:1). 70% yield. Orange solid. MP: 175.4 - 177.1 °C. 1 H NMR(600 MHz, CDCl 3)δ8.17(d, J = 8.0 Hz, 1H), 7.77(d, J = 8.2 Hz, 2H), 7.70(s, 1H), 7.28(d, J = 8.2 Hz, 2H), 7.19(t, J = 7.9 Hz, 1H), 6.75(d, J = 7.8 Hz, 1H), 4.13(s, 3H), 3.94(s, 3H), 2.42(s, 3H). 13 C NMR(150 MHz, CDCl 3 )δ152.09, 147.59, 139.00, 135.30, 134.84, 129.67, 126.91, 123.54, 122.07, 121.75, 115.64, 105.01, 55.59, 37.68, 21.49. HRMS(ESI)(M + H + )Calcd. for C 17 H 17 N 3 O: 280.14444, Found: 280.14417.

[0095]

[0096] (E)-5-fluoro-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1l): Eluent: petroleum ether / EtOAc = 20:1(v / v). New compound. R f = 0.29(Developing agent: petroleum ether / EtOAc = 5:1). 78% yield. Orange solid. MP: 116.9 - 117.6℃. 1 H NMR(600 MHz, CDCl 3 )δ8.25(dd, J = 9.6, 2.5 Hz, 1H), 7.83(s, 1H), 7.78(d, J = 8.1 Hz, 2H), 7.29(d, J = 8.0 Hz, 2H), 7.23(dd, J = 8.8, 4.2 Hz, 1H), 7.07(td, J = 8.9, 2.5 Hz, 1H), 3.84(s, 3H), 2.43(s, 3H). 13 C NMR(150 MHz, CDCl 3)δ159.97(d,J=235.5Hz),151.84,139.39,135.37,135.26,135.23,133.94,129.75,121.82,119.89(d,J=11.0Hz),112.13(d,J=25.5Hz),110.35(d,J=9.7Hz),108.62(d,J=25.17Hz),33.78,21.50. 19 F NMR(565MHz,CDCl 3 )δ-43.29.HRMS(ESI)(M+H + )Calcd.forC 16 H 14 FN 3 :268.12445,Found:268.12396.

[0097]

[0098] (E)-5-chloro-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1m):Eluent:petroleum ether / EtOAc=20:1(v / v).New compound.R f =0.22(Developing agent:petroleum ether / EtOAc=5:1).73%yield.Orange solid.MP:123.9-125.2℃. 1 H NMR(600MHz,CDCl 3 )δ8.54(d,J=2.0Hz,1H),7.80–7.77(m,3H),7.31–7.26(m,3H),7.21(d,J=8.7Hz,1H),3.82(s,3H),2.43(s,3H). 13 C NMR(150MHz,CDCl 3 )δ151.81,139.54,135.73,134.98,134.74,129.75,128.56,124.20,122.73,121.88,120.42,110.60,33.69.HRMS(ESI)(M+H + )Calcd.forC 16 H 14 ClN 3 :284.09490,Found:284.09464.

[0099]

[0100] (E)-5-bromo-1-methyl-3-(p-tolyldiazenyl)-1H-indole(1n): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.24 (Developing agent: petroleum ether / EtOAc = 5:1). 67% yield. Orange solid. MP: 123.7 - 125.6 °C. 1 H NMR(600MHz, CDCl 3 ) δ8.70 (d, J = 1.9Hz, 1H), 7.79 - 7.78 (m, 3H), 7.41 (dd, J = 8.6, 2.0Hz, 1H), 7.30 (d, J = 8.2Hz, 2H), 7.17 (d, J = 8.6Hz, 1H), 3.82 (s, 3H), 2.43 (s, 3H). 13 C NMR(150MHz, CDCl 3 ) δ151.80, 139.57, 136.01, 134.77, 134.61, 129.75, 126.81, 125.73, 121.89, 120.99, 116.25, 111.04, 33.68, 21.53. HRMS(ESI)(M + H + ) Calcd. for C 16 H 14 BrN 3 : 328.04439, Found: 328.04407.

[0101]

[0102] (E)-3-((4-bromophenyl)diazenyl)-1-methyl-1H-indole(1u): Eluent: petroleum ether / EtOAc = 20:1 (v / v). New compound. R f = 0.32 (Developing agent: petroleum ether / EtOAc = 5:1). 70% yield. Orange solid. MP: 115.7 - 118.1 °C. 1 H NMR(600MHz, CDCl 3)δ8.54(d, J = 7.4Hz, 1H), 7.86(s, 1H), 7.75(d, J = 8.5Hz, 2H), 7.60(d, J = 8.5Hz, 2H), 7.38–7.33(m, 3H), 3.88(s, 3H). 13 C NMR(150MHz, CDCl 3 )δ152.85, 137.55, 135.66, 135.38, 132.17, 124.31, 123.41, 123.30, 123.25, 122.72, 119.52, 109.67, 33.65. HRMS(ESI)(M + H + )Calcd. for C 15 H 12 BrN 3 : 314.02847, Found: 314.02838.

[0103] Among them, 1g, 1o, 1p, 1q, 1r, 1s, 1t are known substances, and their NMR and high-resolution mass spectrometry data have been reported in the literature.

[0104] Characterization data of the product

[0105] Products 3b - 3u were all prepared according to the above method, and the process and conditions were the same as those in Example 3. The difference was that equimolar amounts of raw materials 1b - 1u (raw materials 1b - 1u were all prepared according to Example 2) were used to replace raw material 1a respectively, and then the remaining steps were the same as those in Example 3; products 3v - 3z were all prepared according to the above method, and the process and conditions were the same as those in Example 3. The difference was that equimolar amounts of raw materials 2v - 2z (raw materials 2v - 2z were all obtained by purchasing from the manufacturer) were used to replace raw material 1a respectively, and the remaining steps were the same as those in Example 3. Products 3b - 3z were characterized by NMR and high-resolution mass spectrometry later, and the parameters of the obtained products are as follows.

[0106]

[0107]

[0108] (E)-(1-ethyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone(3b): Eluent: petroleum ether / EtOAc = 50:1 to 10:1(v / v). New compound. R f= 0.42 (Developing agent: petroleum ether / EtOAc = 10:1). 31.9 mg, 87% yield. Orange solid. MP: 143.4 - 144.2 °C. 1 H NMR (600 MHz, DMSO) δ 8.46 (d, J = 7.9 Hz, 1H), 7.88 (dd, J = 8.3, 1.2 Hz, 2H), 7.80 (d, J = 8.4 Hz, 1H), 7.73–7.69 (m, 1H), 7.55–7.49 (m, 3H), 7.41–7.38 (m, 1H), 7.13 (s, 4H), 4.46 (q, J = 7.1 Hz, 2H), 2.29 (s, 3H), 1.40 (t, J = 7.1 Hz, 3H). 13 C NMR (150 MHz, DMSO) δ 189.76, 151.01, 139.86, 139.36, 137.15, 136.89, 134.80, 133.45, 130.07, 129.53, 128.31, 126.15, 123.99, 123.63, 121.50, 116.70, 111.24, 39.56, 20.81, 15.64. HRMS (ESI) (M+Na + ) Calcd. for C 24 H 21 ON 3 : 390.15768, Found: 390.15768.

[0109]

[0110] (E)-phenyl(1-propyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)methanone (3c): Eluent: petroleum ether / EtOAc = 50:1 to 20:1 (v / v). New compound. R f = 0.47 (Developing agent: petroleum ether / EtOAc = 10:1). 31.6 mg, 83% yield. Orange solid. MP: 78.7 - 80.2 °C. 11H NMR (600 MHz, DMSO) δ 8.46 (dd, J = 8.0, 0.5 Hz, 1H), 7.87 (dd, J = 8.2, 1.1 Hz, 2H), 7.80 (dd, J = 8.2, 5.2 Hz, 1H), 7.72–7.67 (m, 1H), 7.55–7.47 (m, 3H), 7.38 (t, J = 7.5 Hz, 1H), 7.13–7.09 (m, 4H), 4.42 (t, J = 7.2 Hz, 2H), 2.27 (s, 3H), 1.82–1.75 (m, 2H), 0.84 (td, J = 7.3, 3.0 Hz, 3H). 13 13C NMR (150 MHz, DMSO) δ 189.75, 151.02, 139.86, 139.36, 137.46, 137.30, 134.93, 133.44, 130.05, 129.51, 128.31, 126.12, 123.97, 123.59, 121.51, 116.53, 111.46, 45.55, 23.38, 20.81, 11.03. HRMS (ESI) (M+Na + ) Calcd. for C 25 H 23 ON 3 : 404.17333, Found: 404.17297.

[0111] (E)-(1-isopropyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3d): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.44 (Developing agent: petroleum ether / EtOAc = 10:1). 37.3 mg, 98% yield. Orange solid. MP: 136.0 - 136.9 °C. 1 1H NMR (600 MHz, CDCl 3)δ8.63(d,J=7.9Hz,1H),7.98(dd,J=8.2,1.0Hz,2H),7.65(d,J=8.4Hz,1H),7.61(t,J=7.4Hz,1H),7.46(t,J=7.8Hz,2H),7.43–7.40(m,1H),7.36(t,J=7.5Hz,1H),7.24(d,J=8.2Hz,2H),7.08(d,J=8.2Hz,2H),4.94-5.01(m,1H),2.34(s,3H),1.73(d,J=7.0Hz,6H). 13 C NMR(150MHz,CDCl 3 )δ191.25,151.86,139.89,139.77,138.34,136.52,135.47,133.40,130.61,129.49,128.31,125.30,124.61,123.48,122.10,118.72,112.31,49.88,21.96,21.45.HRMS(ESI)(M+Na + )Calcd.for C 25 H 23 ON 3 :404.17333,Found:404.17297.

[0112]

[0113] (E)-(1-benzyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone(3e):Eluent:petroleum ether / EtOAc=50:1 to 10:1(v / v).New compound.R f =0.37(Developing agent:petroleum ether / EtOAc=10:1).32.2 mg,75%yield.Orangesolid.MP:160.1-161.7℃. 1 H NMR(600 MHz,CDCl 3)δ8.62(d,J=7.9 Hz,1H),7.86(d,J=7.6Hz,2H),7.56(t,J=7.4 Hz,1H),7.35-7.45(m,5H),7.23-7.26(m,2H),7.17-7.21(m,5H),7.09(d,J=8.2Hz,2H),5.72(s,2H),2.35(s,3H). 13 C NMR(150 MHz,CDCl 3 )δ190.36,151.84,140.36,140.27,138.42,137.26,137.21,136.61,132.88,130.68,129.55,128.86,127.99,127.77,126.85,126.57,124.83,124.13,122.30,117.70,110.89,48.20,21.49.HRMS(ESI)(M+Na + )Calcd.for C 29 H 23 ON 3 :452.17333,Found:452.17300.

[0114]

[0115] (E)-(1,4-dimethyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone(3f):Eluent:petroleum ether / EtOAc=50:1 to 10:1(v / v).New compound.R f =0.37(Developing agent:petroleum ether / EtOAc=10:1).28.3 mg,77%yield.Orangesolid.MP:177.9-178.7℃. 1 1H NMR(600 MHz,DMSO)δ7.77(d,J=7.2 Hz,2H),7.57(d,J=8.3 Hz,1H),7.51(t,J=7.4 Hz,1H),7.40(t,J=7.8 Hz,2H),7.35(t,J=7.8 Hz,1H),7.15-7.20(m,5H),3.80(s,3H),2.83(s,3H),2.28(s,3H). 1313C NMR (150 MHz, DMSO) δ 189.37, 149.84, 139.92, 137.14, 136.94, 135.96, 133.30, 131.60, 129.55, 128.77, 128.19, 125.81, 124.39, 123.85, 121.80, 121.11, 109.16, 30.95, 20.87, 20.45. HRMS (ESI) (M+Na + ) Calcd. for C 24 H 21 ON 3 : 390.15768, Found: 390.15747.

[0116]

[0117] (E)-(1,5-dimethyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3g): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.37 (Developing agent: petroleum ether / EtOAc = 10:1). 32.3 mg, 88% yield. Orange solid. MP: 134.4 - 135.2 °C. 1 1H NMR (600 MHz, DMSO) δ 8.27 (s, 1H), 7.87 (dd, J = 8.2, 1.1 Hz, 2H), 7.69 (t, J = 7.4 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.33 (dd, J = 8.5, 1.4 Hz, 1H), 7.14–7.10 (m, 4H), 3.93 (s, 3H), 2.47 (s, 3H), 2.28 (s, 3H). 13 13C NMR (150 MHz, DMSO) δ 189.44, 151.06, 139.66, 139.49, 137.70, 136.59, 134.43, 133.31, 133.25, 130.19, 129.47, 128.15, 127.76, 122.92, 121.51, 116.55, 110.97, 31.66, 21.32, 20.80. HRMS (ESI) (M+Na + ) Calcd. for C 24 H21 ON 3 : 390.15768, Found: 390.15735.

[0118]

[0119] (E)-(1,6-dimethyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3h): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f R = 0.40 (Developing agent: petroleum ether / EtOAc = 10:1). 30.5 mg, 83% yield. Orange solid. MP: 171.4 - 173.3 °C. 1 H NMR (600 MHz, DMSO) δ 8.32 (d, J = 8.1 Hz, 1H), 7.87 (dd, J = 8.3, 1.1 HZ, 2H), 7.70 (t, J = 7.4 Hz, 1H), 7.56 (s, 1H), 7.53 (t, J = 7.8 Hz, 2H), 7.23 (d, J = 8.2 Hz, 1H), 7.13–7.09 (m, 4H), 3.94 (s, 3H), 2.52 (s, 3H), 2.29 (s, 3H). 13 C NMR (150 MHz, DMSO) δ 189.37, 151.04, 139.79, 139.63, 138.59, 137.45, 136.12, 134.92, 133.22, 130.22, 129.51, 128.13, 125.79, 123.32, 121.54, 114.24, 110.89, 31.60, 21.67, 20.82. HRMS (ESI) (M+Na + ) Calcd. for C 24 H 21 ON 3 : 390.15768, Found: 390.15756.

[0120]

[0121] (E)-(1,7-dimethyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone(3i): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.41 (Developing agent: petroleum ether / EtOAc = 10:1). 28.6 mg, 78% yield. Orange solid. MP: 198.9 - 200.8 °C. 1 H NMR(600 MHz, CDCl 3 ) δ8.50 (d, J = 7.9 Hz, 1H), 7.96 (dd, J = 8.2, 1.1 Hz, 2H), 7.61–7.58 (m, 1H), 7.45 (t, J = 7.8 Hz, 2H), 7.23 (t, J = 7.6 Hz, 1H), 7.15 - 7.19 (m, 3H), 7.07 (d, J = 8.1 Hz, 2H), 4.20 (s, 3H), 2.87 (s, 3H), 2.33 (s, 3H). 13 C NMR(150 MHz, CDCl 3 ) δ190.41, 151.84, 140.22, 139.94, 138.69, 137.75, 135.70, 133.18, 130.78, 129.50, 129.18, 128.17, 123.98, 122.46, 122.17, 122.11, 118.66, 35.28, 21.47, 20.85. HRMS(ESI)(M + Na + ) Calcd. for C 24 H 21 ON 3 : 390.15768, Found: 390.15759.

[0122]

[0123] (E)-(5-methoxy-1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone(3j): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f= 0.26 (Developing agent: petroleum ether / EtOAc = 10:1). 31.2 mg, 83% yield. Orange solid. MP: 159.8 - 160.7 °C. 1 H NMR (600 MHz, DMSO) δ 7.96 (d, J = 2.5 Hz, 1H), 7.87 (d, J = 7.6 Hz, 2H), 7.67 - 7.01 (m, 2H), 7.53 (t, J = 7.7 Hz, 2H), 7.16 (dd, J = 9.0, 2.5 Hz, 1H), 7.14–7.09 (m, 4H), 3.95 (s, 3H), 3.86 (s, 3H), 2.28 (s, 3H). 13 C NMR (150 MHz, DMSO) δ 189.29, 157.12, 150.97, 139.62, 139.52, 137.70, 134.49, 133.23, 130.21, 129.48, 128.13, 121.50, 116.80, 116.38, 112.40, 104.29, 55.42, 31.80, 20.81. HRMS (ESI) (M+Na + ) Calcd. for C 24 H 21 O 2 N 3 : 406.15260, Found: 406.15237.

[0124]

[0125] (E)-(7-methoxy-1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3k): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.35 (Developing agent: petroleum ether / EtOAc = 10:1). 33.7 mg, 88% yield. Orange solid. MP: 167.8 - 168.7 °C. 11H NMR (600 MHz, DMSO) δ 8.04 (d, J = 8.0 Hz, 1H), 7.88 (d, J = 7.4 Hz, 2H), 7.70 (t, J = 7.4 Hz, 1H), 7.53 (t, J = 7.7 Hz, 2H), 7.27 (t, J = 7.9 Hz, 1H), 7.12 (s, 4H), 7.02 (d, J = 7.8 Hz, 1H), 4.13 (s, 3H), 3.98 (s, 3H), 2.29 (s, 3H). 13 13C NMR (150 MHz, DMSO) δ 189.54, 150.96, 147.72, 139.75, 139.13, 138.46, 134.50, 133.58, 130.08, 129.53, 128.36, 127.42, 124.78, 121.43, 118.76, 115.52, 107.36, 55.98, 35.10, 20.81. HRMS (ESI) (M + Na + ) Calcd. for C 24 H 21 O 2 N 3 : 406.15260, Found: 406.15256.

[0126]

[0127] (E)-(5-Fluoro-1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3l): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.27 (Developing agent: petroleum ether / EtOAc = 10:1). 30.1 mg, 81% yield. Orange solid. MP: 119.9 - 120.4 °C. 1 1H NMR (600 MHz, DMSO) δ 8.15 (d, J = 7.1 Hz, 1H), 7.89 (d, J = 3.2 Hz, 2H), 7.81 (s, 1H), 7.71 (s, 1H), 7.54 (s, 2H), 7.39 (s, 1H), 7.13 (d, J = 12.0 Hz, 4H), 3.96 (s, 3H), 2.28 (s, 3H). 13¹³C NMR (150 MHz, DMSO) δ 189.17, 159.69 (d, J = 237.0 Hz), 150.85, 139.98, 139.09, 138.99, 134.68, 134.30, 134.27, 133.54, 130.27, 129.52, 128.25, 121.59, δ 116.45 (d, J = 11.0 Hz), 114.49 (d, J = 26.4 Hz), 113.12 (d, J = 9.5 Hz), 107.99 (d, J = 25.1 Hz), 31.94, 20.82, 9. 19 ¹⁹F NMR (565 MHz, DMSO) δ -40.95 (s). HRMS (ESI) (M + Na + ) Calcd. for C 23 H 18 OFN 3 : 394.13261, Found: 394.13257.

[0128]

[0129] (E)-(5-chloro-1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3m): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.29 (Developing agent: petroleum ether / EtOAc = 10:1). 29.8 mg, 77% yield. Orange solid. MP: 147.8 - 148.4 °C. 1 ¹H NMR (600 MHz, DMSO) δ 8.42 (d, J = 2.0 Hz, 1H), 7.89 (d, J = 7.3 Hz, 2H), 7.80 (d, J = 8.9 Hz, 1H), 7.71 (t, J = 7.4 Hz, 1H), 7.56–7.50 (m, 3H), 7.13 (dd, J = 15.8, 8.4 Hz, 4H), 3.94 (s, 3H), 2.28 (s, 3H). 1313C NMR (150 MHz, DMSO) δ 189.13, 150.85, 140.14, 139.00, 138.73, 136.44, 133.63, 133.60, 130.27, 129.55, 128.34, 128.27, 126.02, 122.25, 121.64, 117.18, 113.26, 31.91, 20.83. HRMS (ESI) (M+Na + ) Calcd. for C 23 H 18 OClN 3 : 410.10306, Found: 410.10281.

[0130]

[0131] (E)-(5-bromo-1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3n): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.33 (Developing agent: petroleum ether / EtOAc = 10:1). 30.8 mg, 75% yield. Orange solid. MP: 148.7 - 150.1 °C. 1 1H NMR (600 MHz, DMSO) δ 8.57 (d, J = 1.6 Hz, 1H), 7.89 (d, J = 7.4 Hz, 2H), 7.75 (d, J = 8.8 Hz, 1H), 7.71 (t, J = 7.4 Hz, 1H), 7.63 (dd, J = 8.8, 1.7 Hz, 1H), 7.54 (t, J = 7.7 Hz, 2H), 7.13 (dd, J = 13.3, 8.5 Hz, 4H), 3.94 (s, 3H), 2.29 (s, 3H). 13 13C NMR (151 MHz, DMSO) δ 189.12, 140.16, 138.98, 138.55, 136.68, 133.61, 133.44, 130.26, 129.56, 128.57, 128.28, 125.24, 121.63, 117.78, 116.34, 113.64, 31.88, 20.83. HRMS (ESI) (M+Na + ) Calcd. for C 23 H 18OBrN 3 : 454.05255, Found: 454.05228.

[0132]

[0133] (E)-(1-methyl-3-(phenyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3o): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f R = 0.29 (Developing agent: petroleum ether / EtOAc = 10:1). 29.5 mg, 87% yield. Orange solid. MP: 114.8 - 115.6℃. 1 1H NMR (600 MHz, DMSO) δ8.48 (d, J = 5.8 Hz, 1H), 7.91 (d, J = 6.1Hz, 2H), 7.77 - 7.71 (m, 2H), 7.56 - 7.52 (m, 3H), 7.43 - 7.38 (m, 1H), 7.35 - 7.20 (m, 5H), 3.96 (s, 3H). 13 13C NMR (150 MHz, DMSO) δ189.44, 152.90, 139.24, 138.35, 138.01, 134.65, 133.49, 130.27, 129.80, 129.00, 128.25, 126.17, 124.19, 123.48, 121.54, 116.35, 111.34, 31.69. HRMS(ESI)(M+Na + ) Calcd. for C 22 H 17 ON 3 : 362.12638, Found: 362.12616.

[0134]

[0135] (E)-(1-methyl-3-(o-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3p): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f= 0.29 (Developing agent: petroleum ether / EtOAc = 10:1). 22.2 mg, 63% yield. Orange solid. MP: 147.7 - 149.5 °C. 1 H NMR (600 MHz, DMSO) δ 8.38 (d, J = 7.9 Hz, 1H), 7.91 (dd, J = 8.1, 0.84 Hz, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.71 (t, J = 7.4 Hz, 1H), 7.51 - 7.56 (m, 3H), 7.43 (t, J = 7.5 Hz, 1H), 7.31 (d, J = 7.4 Hz, 1H), 7.22 (t, J = 7.3 Hz, 1H), 6.94 (t, J = 7.6 Hz, 1H), 6.51 (d, J = 8.0 Hz, 1H), 3.97 (s, 3H), 2.63 (s, 3H). 13 C NMR (150 MHz, DMSO) δ 189.51, 150.87, 139.24, 138.24, 137.99, 136.49, 135.35, 133.49, 131.11, 130.28, 129.82, 128.28, 126.13, 124.30, 123.14, 116.30, 114.11, 111.40, 31.68, 17.62. HRMS (ESI) (M + Na + ) Calcd. for C 23 H 19 ON 3 : 376.14203, Found: 376.14169.

[0136]

[0137] (E)-(1-methyl-3-(m-tolyldiazenyl)-1H-indol-2-yl)(phenyl)methanone (3q): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.29 (Developing agent: petroleum ether / EtOAc = 10:1). 27.5 mg, 78% yield. Orange liquid. 11H NMR (600 MHz, DMSO) δ 8.48 (d, J = 8.0 Hz, 1H), 7.91–7.88 (m, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.71 (t, J = 7.4 Hz, 1H), 7.56–7.49 (m, 3H), 7.40 (t, J = 7.5 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.16 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 7.3 Hz, 1H), 6.84 (s, 1H), 3.98 (s, 3H), 2.19 (s, 3H). 13 13C NMR (150 MHz, DMSO) δ 189.46, 153.02, 139.62, 138.29, 138.13, 138.11, 134.74, 133.29, 130.42, 130.29, 128.75, 128.12, 126.23, 124.13, 123.58, 120.69, 120.29, 116.21, 111.29, 31.68, 20.71. HRMS (ESI) (M+Na + ) Calcd. for C 23 H 19 ON 3 : 376.14203, Found: 376.14172.

[0138]

[0139] (E)-(3-((4-methoxyphenyl)diazenyl)-1-methyl-1H-indol-2-yl)(phenyl)methanone (3r): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.21 (Developing agent: petroleum ether / EtOAc = 10:1). 28 mg, 76% yield. Orange solid. MP: 140.6 - 141.2 °C. 1 1H NMR (600 MHz, CDCl 3)δ8.59(d, J = 8.0 Hz, 1H), 7.95(dd, J = 8.2, 1.1 Hz, 2H), 7.62–7.57(m, 1H), 7.49–7.42(m, 4H), 7.38–7.33(m, 1H), 7.26–7.24(m, 2H), 6.80–6.76(m, 2H), 4.00(s, 3H), 3.81(s, 3H). 13 C NMR(150 MHz, CDCl 3 )δ190.14, 161.12, 148.20, 140.39, 138.70, 136.85, 136.11, 132.94, 130.87, 128.04, 126.36, 124.82, 123.95, 123.84, 117.44, 114.03, 110.18, 55.60, 31.83. HRMS(ESI)(M+Na + )Calcd. for C 23 H 19 O 2 N 3 : 392.13659, Found: 392.13684.

[0140]

[0141] (E)-(3-((4-fluorophenyl)diazenyl)-1-methyl-1H-indol-2-yl)(phenyl)methanone(3s): Eluent: petroleum ether / EtOAc = 50:1 to 10:1(v / v). New compound. R f = 0.34(Developing agent: petroleum ether / EtOAc = 10:1). 31.8 mg, 89% yield. Orange solid. MP: 105.5 - 106.4℃. 1 H NMR(600 MHz, CDCl 3 )δ8.56(d, J = 7.9 Hz, 1H), 7.94(dd, J = 8.1, 1.0 Hz, 2H), 7.61 - 7.58(m, 1H), 7.49–7.43(m, 4H), 7.38 - 7.36(m, 1H), 7.28–7.24(m, 2H), 6.97–6.92(m, 2H), 4.00(s, 3H). 13 C NMR(150 MHz, CDCl 3)δ190.00,164.40,162.75,150.28(d,J = 3.1 Hz),140.22(s),138.62(s),136.80(d,J = 298.7 Hz),,133.14,130.84,128.11,126.46,124.65,124.20,124.03(d,J = 8.6 Hz),117.26(s),115.73(d,J = 22.2Hz),,110.28(s),31.87(s). 19 F NMR(565 MHz,DMSO)δ - 33.41(s).HRMS(ESI)(M+Na + )Calcd.for C 22 H 16 OFN 3 :380.11696,Found:380.11670.

[0142]

[0143] (E)-(3-((4-chlorophenyl)diazenyl)-1-methyl-1H-indol-2-yl)(phenyl)methanone(3t):Eluent:petroleumether / EtOAc = 50:1 to 10:1(v / v).New compound.R f =0.35(Developing agent:petroleum ether / EtOAc = 10:1).33.9 mg,91%yield.Orangesolid.MP:145.6 - 147.3℃. 1 H NMR(600 MHz,DMSO)δ8.45(d,J = 7.9 Hz,1H),7.89(dd,J = 8.2,1.1 Hz,2H),7.77(d,J = 8.4 Hz,1H),7.73–7.70(m,1H),7.55–7.51(m,3H),7.42 - 7.40(m,1H),7.39–7.36(m,2H),7.23–7.20(m,2H),3.96(s,3H). 1313C NMR (150 MHz, DMSO) δ 189.33, 151.53, 139.18, 138.75, 138.02, 134.61, 134.06, 133.58, 130.24, 129.08, 128.27, 126.26, 124.36, 123.45, 123.04, 116.29, 111.42, 31.76. HRMS (ESI) (M+Na + ) Calcd. for C 22 H 16 OClN 3 : 396.08741, Found: 396.08749.

[0144]

[0145] (E)-(3-((4-chlorophenyl)diazenyl)-1-methyl-1H-indol-2-yl)(phenyl)methanone (3u): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.36 (Developing agent: petroleum ether / EtOAc = 10:1). 34.2 mg, 82% yield. Orange solid. MP: 147.6 - 148.5 °C. 1 1H NMR (600 MHz, CDCl 3 ) δ 8.56 (d, J = 8.0 Hz, 1H), 7.95 (dd, J = 8.4, 0.84 Hz, 2H), 7.63 - 7.60 (m, 1H), 7.50–7.44 (m, 4H), 7.41–7.38 (m, 3H), 7.14–7.12 (m, 2H), 4.01 (s, 3H). 13 13C NMR (150 MHz, CDCl 3 ) δ 189.95, 152.51, 140.17, 138.64, 138.21, 135.89, 133.22, 132.03, 130.84, 128.12, 126.54, 124.67, 124.39, 123.73, 117.20, 110.32, 31.92. HRMS (ESI) (M+Na + ) Calcd. for C 22 H 16 OBrN 3: 440.03690, Found: 440.03677.

[0146]

[0147] (E)-(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)(p-tolyl)methanone (3v): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f R = 0.35 (Developing agent: petroleum ether / EtOAc = 10:1). 31.6 mg, 86% yield. Orange solid. MP: 133.6 - 135.3℃. 1 H NMR (600 MHz, DMSO) δ8.46 (d, J = 7.9 Hz, 1H), 7.79 (d, J = 8.2 Hz, 2H), 7.74 (d, J = 8.4 Hz, 1H), 7.52–7.48 (m, 1H), 7.40–7.37 (m, 1H), 7.34 (d, J = 8.0 Hz, 2H), 7.19 - 7.14 (m, 4H), 3.92 (s, 3H), 2.42 (s, 3H), 2.29 (s, 3H). 13 C NMR (150 MHz, DMSO) δ188.95, 151.04, 144.22, 139.75, 138.34, 137.86, 136.66, 134.37, 130.48, 129.53, 128.79, 125.94, 123.94, 123.44, 121.54, 116.49, 111.23, 31.59, 21.26, 20.83. HRMS (ESI) (M+Na + ) Calcd. for C 24 H 21 ON 3 : 390.15768, Found: 390.15750.

[0148]

[0149] (E)-(4-fluorophenyl)(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)methanone(3w): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.36 (Developing agent: petroleum ether / EtOAc = 10:1). 28.9 mg, 78% yield. Orange solid. MP: 139.5 - 141.2 °C. 1 H NMR (600 MHz, DMSO) δ 8.47 (d, J = 8.0 Hz, 1H), 8.00 - 7.98 (m, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.53 - 7.50 (m, 1H), 7.41–7.35 (m, 3H), 7.19–7.15 (m, 4H), 3.96 (s, 3H), 2.30 (s, 3H). 13 C NMR (150 MHz, DMSO) δ 187.86, 165.20 (d, J = 251.2 Hz), 150.97, 140.01, 138.08, 137.52, 136.05 (d, J = 2.1 Hz), 134.67, 133.33 (d, J = 9.6 Hz), 129.58, 126.23, 124.07, 123.56, 121.49, 116.37, 115.26 (d, J = 30.0 Hz), 111.31, 31.67, 20.82. 19 F NMR (565 MHz, DMSO) δ -27.40 (s). HRMS (ESI) (M + Na + ) Calcd. for C 23 H 18 OFN 3 : 394.13261, Found: 394.13254.

[0150]

[0151] (E)-(4-chlorophenyl)(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)methanone(3x): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f= 0.38 (Developing agent: petroleum ether / EtOAc = 10:1). 29.4 mg, 76% yield. Orange solid. MP: 133.2 - 135.1 °C. 1 H NMR (600 MHz, DMSO) δ 8.46 (d, J = 8.0 Hz, 1H), 7.90 (dt, J = 14.0, 2.4 Hz, 2H), 7.76 (d, J = 8.4 Hz, 1H), 7.62–7.59 (m, 2H), 7.54–7.50 (m, 1H), 7.41–7.38 (m, 1H), 7.16–7.13 (m, 4H), 3.97 (s, 3H), 2.30 (s, 3H). 13 C NMR (150 MHz, DMSO) δ 188.24, 150.95, 140.07, 138.28, 138.23, 138.18, 137.14, 134.89, 132.06, 129.55, 128.23, 126.37, 124.12, 123.63, 121.56, 116.28, 111.33, 31.72, 20.85. HRMS (ESI) (M+Na + ) Calcd. for C 23 H 18 OClN 3 : 410.10306, Found: 410.10278.

[0152]

[0153] (E)-(4-bromophenyl)(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)methanone (3y): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.38 (Developing agent: petroleum ether / EtOAc = 10:1). 33.2 mg, 77% yield. Orange solid. MP: 113.4 - 114.7 °C. 11H NMR (600 MHz, DMSO) δ 8.46 (d, J = 7.9 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.80 - 7.74 (m, 3H), 7.52 (t, J = 7.6 Hz, 1H), 7.39 (t, J = 7.5 Hz, 1H), 7.14 (q, J = 8.3 Hz, 4H), 3.98 (s, 3H), 2.31 (s, 3H). 13 13C NMR (150 MHz, DMSO) δ 188.45, 150.95, 140.06, 138.68, 138.19, 137.08, 134.92, 132.12, 131.17, 129.54, 127.33, 126.39, 124.13, 123.64, 121.59, 116.25, 111.33, 31.73, 20.87. HRMS (ESI) (M+Na + ) Calcd. for C 23 H 18 OBrN 3 : 454.05255, Found: 454.05243.

[0154]

[0155] (E)-mesityl(1-methyl-3-(p-tolyldiazenyl)-1H-indol-2-yl)methanone (3z): Eluent: petroleum ether / EtOAc = 50:1 to 10:1 (v / v). New compound. R f = 0.42 (Developing agent: petroleum ether / EtOAc = 10:1). 32.8 mg, 83% yield. Orange solid. MP: 153.8 - 155.2 °C. 1 1H NMR (600 MHz, DMSO) δ 8.44 (d, J = 6.7 Hz, 1H), 7.79 (d, J = 6.8 Hz, 1H), 7.53 (s, 1H), 7.37 (s, 1H), 7.14 (s, 2H), 7.05 (d, J = 6.2 Hz, 2H), 6.94 (s, 2H), 4.17 (s, 3H), 2.35 (s, 3H), 2.33 (s, 3H), 2.08 (s, 6H). 1313C NMR (150 MHz, DMSO) δ 193.53, 151.15, 140.34, 139.88, 138.66, 138.40, 136.04, 135.58, 134.14, 129.38, 128.16, 127.14, 124.48, 124.42, 122.10, 115.54, 111.45, 32.35, 20.91, 20.80, 19.27. HRMS (ESI) (M+Na + ) Calcd. for C 26 H 25 ON 3 : 418.18898, Found: 418.18884.

[0156] The above are only the embodiments of the present invention, and do not thus limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made by using the content of the specification and drawings of the present invention, or directly or indirectly applied in other related technical fields, shall equally be included in the patent protection scope of the present invention.

Claims

1. A method for synthesizing N-protected 2-benzoyl-3-arylazoindole, characterized in that: Using N-methyl-3-arylazoindole compound (I) and benzoylformic acid (II) as substrates, the C2 acylation reaction of N-methyl-3-arylazoindole compound is promoted by heat to synthesize N-protected 2-benzoyl-3-arylazoindole compound (III).

2. The synthesis method according to claim 1, characterized in that: The reaction process is shown in the following reaction formula: R1 represents a different substituent attached to the indole N, specifically one or more of hydrogen, C1-C10 alkyl (preferably one or more of methyl, ethyl, propyl, isopropyl) and benzyl; R2 represents that different substituents are connected to the C4-C7 positions of the indole benzene ring, the number of which is 1-4, and can be one or more of hydrogen, C1-C10 alkyl, halogen (one or more of F, Cl, Br, I); preferably, each position is connected to a methyl group, or C5 and C7 are connected to a methoxy group, and the remaining positions are connected to hydrogen, or one or more of F, Cl, Br halogen groups on C5, and the remaining positions are connected to hydrogen; R3 independently represents substitution at one or more different positions of the ortho, meta, para, etc. of the azobenzene ring, and the number of substituents is 1-5, which may be one or more of hydrogen, C1-C10 alkyl, halogen (one or more of F, Cl, Br, I); preferably, it is methyl or an unsubstituted hydrogen, or one or more of a halogen group (one or more of F, Cl, Br, I) at the para position (the rest of the positions are connected to hydrogen); R4 represents a substitution at the para position of the benzene ring or a trimethyl substitution on the benzene ring, and the substituent is one or more of a C1-C10 alkyl group, a halogen (one or more of F, Cl, Br, I); preferably, the substituent is a methyl group and a halogen group (one or more of F, Cl, Br, I).

3. The synthesis method according to claim 1, characterized in that: The reaction must be carried out at a certain temperature, and the screened temperature is room temperature-100°C, preferably 60-90°C, wherein the optimal reaction temperature is 75-85°C.

4. The synthesis method according to claim 1, characterized in that: The reaction is carried out in a solvent, and the screened solvents are 1,2-dichloroethane, acetonitrile, methanol, toluene, N,N-dimethylformamide, dimethyl sulfoxide, water, etc., and the optimal solvent is 1,2-dichloroethane; based on 0.1 mmol of N-methyl-3-arylazoindole compound (I), the amount of the solvent is 0.5-5 mL, preferably 1-3 mL.

5. The synthesis method according to claim 1, characterized in that: The reaction is carried out in the presence of an oxidant, and the screened oxidants are K2S2O8, (NH4)2S2O8, PhI(ACO)2, BPO, and TBHP, among which the optimal oxidant is K2S2O8; based on 0.1mmol N-methyl-3-arylazoindole compound (I), the amount of the oxidant is 0.1-2mM, preferably 0.3-0.5mM.

6. The synthesis method according to claim 1, characterized in that: The reaction is carried out in the presence of a catalyst, and the screened catalysts include ZIF-8, MIL-125(Ti), Uio-67, Cu-BDC, Cu-BTC, CuNPs@HKUST-1, CuCl, CuCl2, Cu, H3BTC, 2-MI, Cu+2-MI, Cu+H3BTC, 2-MI+H3BTC, Cu+2-MI+H3BTC; among which CuNPs@HKUST-1 is the best; Based on 0.1 mmol of N-methyl-3-arylazoindole compound (I), the amount of the catalyst to be screened is 1-5 mg, and optimally 3-4 mg.

7. The synthesis method according to claim 1, characterized in that: In the reaction, the molar ratio of the N-methyl-3-p-toluene azoindole compound (1a) to the benzoylformic acid (2a) is 1:2-6, preferably 1:2.5-3.5; the amount of oxidant added was investigated and it was found that the yield of 3 eq was better, that is, 1:

3.

8. The synthetic method according to claim 1, wherein the reaction comprises the following steps: The reaction is carried out under an inert atmosphere (eg nitrogen) for 1-10 h, preferably 2-6 h, more preferably 3-5 h.

9. The synthesis method according to claim 8, characterized in that: In a sealed container (e.g., a quartz tube), 1a (0.1 mmol), catalyst (3 mg), 2a (0.3 mmol), oxidant (0.3 mmol), inert atmosphere (N2) and solvent DCE (1 mL) were added in sequence, and the reaction was stirred at 80°C for 4 h to obtain C2 acylindole product 3a.

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