The invention relates to 2, 3apos; preparation method of-bisindole compound

Abstract

The invention discloses a preparation method of a 2, 3 '-bisindole compound, and belongs to the field of organic synthesis. According to the method, indole and 3-iodo-1-p-toluenesulfonyl-1H-indole are used as initial raw materials and are stirred to react in an organic solvent at 60-80 DEG C under the action of a palladium catalyst, norbornene and alkali, and the 2, 3 '-bisindole compound can be obtained. The raw materials used in the method are cheap and easy to obtain, the reaction process is mild, the substrate universality is good, and the method has high step economy and practicability.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic chemical synthesis, and particularly relates to a preparation method of 2,3'-bisindole compounds. Background Art

[0002] Indole and its derivatives are important skeletons in organic chemical research. Among many indole skeleton-containing compounds, the bisindole skeleton is relatively special. The bisindole skeletons are mainly divided into three types: 2,3'-bisindole, 2,2'-bisindole, and 3,3'-bisindole. In particular, the 2,3'-bisindole skeleton has potential biological activity (Tetrahedron. 2020. 131371).

[0003] Currently, the methods for constructing the 2,3'-bisindole skeleton mainly focus on three types of strategies: acid catalysis, oxidation, and metal catalysis. (1) The catalysis under acidic conditions mainly includes Fischer indole synthesis catalyzed by Lewis acid (Tetrahedron Lett. 2011. 2642), reductive alkylation of α-ketoimine catalyzed by FeCl 3 (J. Org. Chem. 2015. 6381), and direct C3-arylation reaction of 2-indolemethanol with tryptamine and tryptophol catalyzed by acid (Org. Biomol. Chem. 2018. 1536). (2) The oxidative dimerization strategy mediated by iodine and N-bromosuccinimide can also successfully achieve the synthesis of 2,3'-bisindole (J. Org. Chem. 2011. 744, Org. Biomol. Chem. 2017. 9622). (3) The strategies through metal catalysis mainly include palladium catalysis (J. Org. Chem. 2010. 170, J. Org. Chem. 2016. 9337, CN202410893340.5), rhodium catalysis (Org. Lett. 2014. 1244, J. Am. Chem. Soc. 2019. 9527), gold catalysis (Org. Chem. Front. 2021. 1808), cobalt catalysis (Tetrahedron. 2020. 131371), iron catalysis (ChemCatChem. 2025. DOI: 10.1002 / cctc.202401308), all of which can achieve the synthesis of 2,3'-bisindole.

[0004] Although there are currently various methods for the synthesis of 2,3'-bisindole, there are still many challenges in practical applications, including but not limited to issues such as the generality of functional groups, mildness of reaction conditions, economic cost, and environmental protection requirements. Therefore, developing a more efficient, economical, and environmentally friendly synthetic route remains an important research direction in this field. Summary of the Invention

[0005] To solve the problems existing in the prior art, the object of the present invention is to provide a method for preparing 2,3'-biindole compounds.

[0006] To achieve the above object, the technical solution provided by the present invention is as follows:

[0007] Using indole A and 3-iodo-1-p-toluenesulfonyl-1H-indole B as starting materials, under the action of palladium catalyst C, norbornene derivative D, and base E, stirring in an organic solvent F at 60 - 80 °C under heating conditions until the reaction ends, and then subjecting the reaction mixture to suction filtration, concentration, and column chromatography purification to obtain the 2,3'-biindole compound G as shown in the reaction formula. The reaction formula of the reaction is as follows:

[0008]

[0009] Among them, R 1 and R 2 are both substituents on the benzene ring in the indole structure.

[0010] Further, R 1 in the general formula A is selected from one of methoxy, methyl, fluorine, chlorine, bromine, and cyano, and R 2 is one of methyl, bromine, and chlorine.

[0011] Further, the molar ratio of the indole A, 3-iodo-1-p-toluenesulfonyl-1H-indole B, palladium catalyst C, norbornene derivative D, and base E in the feed is 1:(1 - 2):(0.05 - 0.15):(1 - 3):(1 - 3), and the preferred molar ratio of the feed is A:B:C:D:E = 1:1:0.1:2:2.

[0012] Further, the palladium catalyst C is one of palladium acetate, palladium chloride, and palladium trifluoroacetate, and palladium acetate is preferred.

[0013] Further, the norbornene derivative D is one of norbornene, methyl 5-norbornene-2-carboxylate, and 2-cyano-5-norbornene, and norbornene is preferred.

[0014] Further, the structure of norbornene is The structure of methyl 5-norbornene-2-carboxylate is The structure of 2-cyano-5-norbornene is

[0015] Further, the base E is one of sodium carbonate, potassium carbonate, and cesium carbonate, and potassium carbonate is preferred.

[0016] Further, the solvent F is one of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, and N-methylpyrrolidone, and preferably N,N-dimethylformamide.

[0017] Further, in the preparation method, the heating process can use an oil bath, which is silicone oil or paraffin oil; the suction filtration process uses a sintered glass funnel and is filtered under reduced pressure; the concentration process can use atmospheric distillation or vacuum distillation, and preferably uses a rotary evaporator for concentration under reduced pressure; the purification process obtains a pure product through column chromatography.

[0018] The method of the present invention can efficiently achieve the synthesis of 2,3'-biindole compounds. Compared with the prior art, the present invention has the following advantages:

[0019] 1. The reaction conditions of the present invention are mild: In the prior art, the catalysis under acidic conditions involves the use of strong acids, which requires relatively harsh reaction conditions and has poor functional group generality. The preparation method of the present invention reacts in an organic solvent under heating conditions of 60-80 °C. The reaction conditions are relatively mild, avoiding the use of strong acids, reducing the corrosion of reaction equipment and the impact on the environment, and having better compatibility with more functional groups at the same time;

[0020] 2. The present invention has good functional group generality: Due to the mild reaction conditions and no dependence on strong acids, the method of the present invention can be applied to more types of functional groups, making the method have a wider application prospect in the synthesis of 2,3'-biindole compounds containing different functional groups;

[0021] 3. The present invention reduces the use of harmful reagents: The present invention avoids the use of harmful reagents such as strong acids and halogen oxidants, conforms to the principles of green chemistry, and reduces the environmental burden;

[0022] 4. The method involved in the present invention has short steps and can be completed in one step. Compared with traditional multi-step reactions or complex pre-functionalization, it has step economy and lower industrial production costs. Description of the Drawings

[0023] Figure 1 is the 1 H-NMR (400 MHz, CDCl 3 ) spectrum of compound G-2;

[0024] Figure 2 is the 13 C-NMR (100 MHz, CDCl 3 ) spectrum of compound G-2;

[0025] Figure 3 is the 11H-NMR (400 MHz, CDCl 3 ) spectrum;

[0026] Figure 4 For compound G-15 13 13C-NMR (100 MHz, CDCl 3 ) spectrum. Detailed implementation manners

[0027] The present invention will be further described below in conjunction with embodiments. In the following embodiments, the palladium catalyst is Pd(OAc) 2 as an example, the norbornene derivative is norbornene as an example, and the organic solvent is N,N-dimethylformamide as an example, but does not limit the protection scope of the present invention in any way.

[0028] Example 1: Preparation of compound G-1, and its reaction formula is as follows:

[0029]

[0030] Indole (0.43 mmol, 50.0 mg), 3-iodo-1-p-toluenesulfonyl-1H-indole (0.43 mmol, 170.5 mg, 1 equiv.), norbornene (0.86 mmol, 80.0 mg, 2 equiv.), potassium carbonate (0.86 mmol, 119.0 mg, 2 equiv.), Pd(OAc) 2 (0.043 mmol, 10.0 mg, 10 mol%.) and N,N-dimethylformamide (3 mL, 0.15 mol / L) were successively added to a reaction tube (10 mL) pre-equipped with a magnetic stir bar. After the above reagents were added, the air in the reaction tube was replaced with oxygen, and the reaction tube was transferred to an oil bath at 70 °C and stirred for another 16 h. The reaction was terminated after TLC detection showed complete conversion of the starting materials. After cooling to room temperature, 30 mL of water was added, and the mixture was extracted with 20 mL of ethyl acetate. The organic phase was collected, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain a crude product. The target product G-1 (145.2 mg, yield 88%) as a white solid was obtained by column chromatography purification (ethyl acetate: petroleum ether = 1:30, V:V). 1 1H NMR (400 MHz, CDCl 3 ) δ 8.48 (s, 1H), 8.09 (d, J = 8.2 Hz, 1H), 7.98–7.92 (m, 1H), 7.90 (s, 1H), 7.83 (d, J = 8.5 Hz, 2H), 7.68 (d, J = 7.8 Hz, 1H), 7.47–7.32 (m, 3H), 7.25–7.12 (m, 4H), 6.89 (d, J = 2.0 Hz, 1H), 2.31 (s, 3H). 1313C NMR (101 MHz, CDCl 3 ) δ 145.42, 136.41, 135.54, 134.95, 130.44, 130.13, 129.12, 128.70, 126.98, 125.49, 124.04, 122.62, 122.22, 120.90, 120.58, 120.38, 116.14, 113.96, 110.97, 101.71, 21.65.

[0031] Example 2: Preparation of Compound G-2

[0032]

[0033] The operation steps and conditions were the same as those in Example 1, except that the indole substrate used was 5-methoxyindole (0.43 mmol, 63.2 mg), and the reaction temperature was 60 °C, to obtain Compound G-2 (white solid, 88.0 mg, yield 50%). 1 1H NMR (400 MHz, CDCl 3 ) δ 8.29 (s, 1H), 8.09–8.03 (m, 1H), 7.95–7.88 (m, 1H), 7.87–7.77 (m, 3H), 7.44–7.26 (m, 3H), 7.20 (d, J = 8.1 Hz, 2H), 7.12 (d, J = 2.4 Hz, 1H), 6.89 (dd, J = 8.8, 2.4 Hz, 1H), 6.79 (d, J = 2.1 Hz, 1H), 3.88 (s, 3H), 2.32 (s, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 154.68, 145.40, 135.58, 135.09, 131.63, 131.21, 130.14, 129.67, 128.72, 127.02, 125.48, 124.02, 122.17, 120.87, 116.20, 114.01, 112.82, 111.65, 102.43, 101.64, 56.02, 21.68. Figure 1 is its 1 1H-NMR (400 MHz, CDCl 3 ) spectrum, Figure 2 is its 13 13C-NMR (100 MHz, CDCl 3 ) spectrum.

[0034] Example 3: Preparation of Compound G-3

[0035]

[0036] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 5-methylindole (0.256 mmol, 33.5 mg), and compound G-3 (white solid, 80.4 mg, yield 80%) is obtained. 1 H NMR (400 MHz, CDCl 3 ) δ 8.22 (s, 1H), 8.06 (dt, J = 8.3, 1.0 Hz, 1H), 7.92 (dd, J = 8.2, 1.2 Hz, 1H), 7.85–7.77 (m, 3H), 7.47–7.28 (m, 4H), 7.23 (d, J = 8.1 Hz, 2H), 7.04 (dd, J = 8.3, 1.7 Hz, 1H), 6.77 (dd, J = 2.1, 0.9 Hz, 1H), 2.46 (s, 3H), 2.34 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 145.37, 135.56, 135.03, 134.75, 130.51, 130.12, 129.60, 129.42, 128.75, 126.99, 125.45, 124.25, 124.00, 122.09, 120.92, 120.25, 116.28, 113.97, 110.60, 101.32, 21.66, 21.59.

[0037] Example 4: Preparation of compound G-4

[0038]

[0039] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 6-methylindole (0.256 mmol, 33.5 mg), and compound G-4 (white solid, 68.2 mg, yield 66%) is obtained. 1 H NMR (400 MHz, CDCl 3 ) δ 8.37 (s, 1H), 8.13–8.06 (m, 1H), 7.95 (dt, J = 7.7, 1.0 Hz, 1H), 7.89 (s, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.56 (d, J = 8.0 Hz, 1H), 7.38 (dddd, J = 23.2, 8.4, 7.3, 1.2 Hz, 2H), 7.22–7.15 (m, 3H), 7.00 (dd, J = 8.0, 1.5 Hz, 1H), 6.85 (dd, J = 2.1, 0.9 Hz, 1H), 2.49 (s, 3H), 2.30 (s, 3H). 13 C NMR (101 MHz, CDCl3 ) δ 145.35, 136.88, 135.54, 134.96, 132.47, 130.09, 129.76, 128.75, 126.95, 126.92, 125.41, 123.98, 122.12, 121.92, 120.94, 120.18, 116.32, 113.93, 110.93, 101.55, 21.91, 21.61.

[0040] Example 5: Preparation of Compound G-5

[0041]

[0042] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 7-methylindole (0.43 mmol, 56.0 mg), and Compound G-5 (white solid, 91.5 mg, yield 60%) is obtained. 1 H NMR (400 MHz, CDCl 3 ) δ 8.26 (s, 1H), 8.06 (d, J = 8.3 Hz, 1H), 7.94 (dd, J = 7.3, 1.4 Hz, 1H), 7.90 (s, 1H), 7.83 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.38 (dtd, J = 20.6, 7.2, 1.2 Hz, 2H), 7.23 (d, J = 8.1 Hz, 2H), 7.06 (dt, J = 14.3, 7.1 Hz, 2H), 6.88 (d, J = 2.1 Hz, 1H), 2.57 (s, 3H), 2.34 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 145.43, 135.99, 135.53, 135.03, 130.16, 128.80, 128.68, 127.03, 125.50, 124.03, 123.25, 122.17, 120.92, 120.64, 120.18, 118.35, 116.21, 113.97, 102.36, 21.72, 16.96.

[0043] Example 6: Preparation of Compound G-6

[0044]

[0045] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 5-fluoroindole (0.256 mmol, 34.5 mg), and the reaction temperature is 80 °C, and Compound G-6 (white solid, 78.0 mg, yield 77%) is obtained. 11H NMR (400 MHz, CDCl 3 ) δ 8.37 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 7.87–7.78 (m, 3H), 7.45–7.26 (m, 4H), 7.23 (d, J = 8.1 Hz, 2H), 6.96 (td, J = 9.1, 2.5 Hz, 1H), 6.81 (d, J = 2.1 Hz, 1H), 2.34 (s, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 158.39 (d, J = 234.8 Hz), 129.59 (d, J = 10.4 Hz), 111.48 (d, J = 9.6 Hz), 110.92 (d, J = 26.4 Hz), 105.43 (d, J = 23.6 Hz), 101.86 (d, J = 4.5 Hz).

[0046] Example 7: Preparation of Compound G-7

[0047]

[0048] The operation steps and conditions were the same as those in Example 1, except that the indole substrate used was 5-chloroindole (0.43 mmol, 65.0 mg), and Compound G-7 (white solid, 145.0 mg, yield 81%) was obtained. 1 1H NMR (400 MHz, CDCl 3 ) δ 8.36 (s, 1H), 8.06 (dt, J = 8.3, 1.0 Hz, 1H), 7.89 (dt, J = 7.8, 1.1 Hz, 1H), 7.85–7.78 (m, 3H), 7.60 (d, J = 2.0 Hz, 1H), 7.45–7.30 (m, 3H), 7.24 (d, J = 8.4 Hz, 2H), 7.16 (dd, J = 8.6, 2.0 Hz, 1H), 6.79 (dd, J = 2.1, 0.9 Hz, 1H), 2.34 (s, 3H). 13 13C NMR (101 MHz, CDCl 3 ) δ 145.52, 135.57, 135.15, 134.79, 132.01, 130.30, 130.21, 128.53, 127.08, 126.12, 125.66, 124.14, 122.92, 122.61, 120.73, 120.00, 115.56, 114.09, 111.84, 101.38, 21.74.

[0049] Example 8: Preparation of Compound G-8

[0050]

[0051] The operation steps and conditions were the same as those in Example 1, except that the indole substrate used was 5-bromoindole (0.43 mmol, 84.0 mg), and compound G-8 (white solid, 149.5 mg, yield 76%) was obtained. 1 H NMR (400 MHz, CDCl 3 ) δ 8.49 (s, 1H), 8.06 (d, J = 8.2 Hz, 1H), 7.89 (d, J = 6.6 Hz, 2H), 7.85–7.79 (m, 2H), 7.78–7.73 (m, 1H), 7.38 (dtd, J = 15.5, 7.6, 6.3 Hz, 2H), 7.28 (t, J = 1.6 Hz, 2H), 7.22 (d, J = 8.2 Hz, 2H), 6.78 (d, J = 2.1 Hz, 1H), 2.33 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 145.54, 135.59, 135.14, 135.09, 131.84, 130.98, 130.21, 128.54, 127.07, 125.66, 125.46, 124.16, 123.08, 122.64, 120.75, 115.56, 114.08, 113.63, 112.30, 101.23, 21.71.

[0052] Example 9: Preparation of Compound G-9

[0053]

[0054] The operation steps and conditions were the same as those in Example 1, except that the indole substrate used was 6-bromoindole (0.43 mmol, 84.0 mg), and compound G-9 (white solid, 127.1 mg, yield 64%) was obtained. 1 H NMR (400 MHz, CDCl 3 ) δ 8.44 (s, 1H), 8.06 (dt, J = 8.3, 1.0 Hz, 1H), 7.93–7.86 (m, 2H), 7.85–7.79 (m, 2H), 7.59–7.51 (m, 1H), 7.49 (d, J = 8.4 Hz, 1H), 7.44–7.32 (m, 2H), 7.23 (ddd, J = 8.5, 4.4, 1.2 Hz, 3H), 6.82 (dd, J = 2.2, 0.9 Hz, 1H), 2.33 (s, 3H). 13 C NMR (101 MHz, CDCl 3)δ145.51,137.26,135.63,135.23,131.28,130.21,128.56,128.14,127.10,125.65,124.13,123.87,122.55,121.81,120.72,116.03,115.56,114.12,113.83,101.86,21.72.

[0055] Example 10: Preparation of Compound G-10

[0056]

[0057] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 4-cyanoindole (0.256 mmol, 36.4 mg), and Compound G-10 (white solid, 45.7 mg, yield 43%) is obtained. 1 H NMR(400MHz,DMSO-d 6 )δ12.18(s,1H),8.48(s,1H),8.16–8.09(m,1H),8.06–7.99(m,1H),7.97–7.89(m,2H),7.77(dt,J=8.2,1.0Hz,1H),7.55(dd,J=7.4,0.9Hz,1H),7.50–7.36(m,4H),7.29(dd,J=8.2,7.4Hz,1H),7.10(dd,J=2.1,0.9Hz,1H),2.30(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ145.85,136.10,134.61,133.71,133.67,130.38,129.50,127.37,126.82,125.55,124.94,124.65,124.35,121.71,121.04,118.74,116.15,114.23,113.45,100.81,98.09,21.01.

[0058] Example 11: Preparation of Compound G-11

[0059]

[0060] The operation steps and conditions are the same as those in Example 1, except that the indole substrate used is 5-cyanoindole (0.256 mmol, 36.4 mg), and Compound G-11 (white solid, 100.1 mg, yield 95%) is obtained. 1 H NMR(400MHz,DMSO-d6 )δ12.14(s,1H),8.44(s,1H),8.11–8.05(m,2H),8.05–8.00(m,1H),7.95–7.87(m,2H),7.58(dt,J=8.4,0.8Hz,1H),7.53–7.35(m,5H),7.15(d,J=2.0Hz,1H),2.29(s,3H). 13 C NMR(101MHz,DMSO-d 6 )δ145.81,138.14,134.67,133.72,132.91,130.36,128.42,127.47,126.77,125.54,125.32,124.61,124.27,124.08,120.89,120.64,114.40,113.51,112.09,101.42,100.73,20.99.

[0061] Example 12: Preparation of Compound G-12

[0062]

[0063] The operation steps and conditions were the same as those in Example 1, except that the iodinated indole substrate used was 5-bromo-3-iodo-1-(p-toluenesulfonyl)-1H-indole (0.256 mmol, 122 mg), to obtain Compound G-12 (white solid, 86.8 mg, yield 73.1%). 1 HNMR(400MHz,CDCl 3 )δ8.34(s,1H),8.03(d,J=1.9Hz,1H),7.92(d,J=8.8Hz,1H),7.83–7.76(m,3H),7.66(d,J=7.8Hz,1H),7.49(dd,J=8.9,1.9Hz,1H),7.42(d,J=8.1Hz,1H),7.23(t,J=7.9Hz,3H),7.19–7.11(m,1H),6.85–6.80(m,1H),2.35(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.79,136.45,134.71,134.21,130.40,130.29,129.62,129.04,128.46,127.01,123.63,123.21,122.89,120.74,120.59,117.69,115.50,115.40,110.96,102.04,21.77.

[0064] Example 13: Preparation of Compound G-13

[0065]

[0066] The operation steps and conditions are the same as those in Example 1, except that the iodoindole substrate used is 5-chloro-3-iodo-1-(p-toluenesulfonyl)-1H-indole (0.43 mmol, 185.3 mg), and Compound G-12 (white solid, 113.8 mg, yield 63%) is obtained. 1 HNMR(400MHz,CDCl 3 )δ8.33(s,1H),7.97(d,J=8.9Hz,1H),7.88(d,J=2.1Hz,1H),7.83(s,1H),7.79(d,J=8.4Hz,2H),7.66(d,J=7.8Hz,1H),7.42(d,J=8.1Hz,1H),7.35(dd,J=8.9,2.1Hz,1H),7.26–7.19(m,3H),7.19–7.11(m,1H),6.82(d,J=2.1Hz,1H),2.35(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.75,136.52,134.89,133.94,130.28,130.11,129.97,129.71,129.12,127.03,125.82,123.43,122.91,120.76,120.62,115.67,115.07,110.97,102.07,21.74.

[0067] Example 14: Preparation of Compound G-14

[0068]

[0069] The operation steps and conditions are the same as those in Example 1, except that the iodoindole substrate used is 6-methyl-3-iodo-1-(p-toluenesulfonyl)-1H-indole (0.256 mmol, 105.0 mg), and Compound G-14 (white solid, 87.1 mg, yield 85%) is obtained. 1 H NMR(400MHz,CDCl 3)δ8.34(s,1H),7.87(s,1H),7.80(dd,J=8.1,5.5Hz,3H),7.76(s,1H),7.64(d,J=7.8Hz,1H),7.41(d,J=8.0Hz,1H),7.25–7.10(m,5H),6.85(d,J=2.1Hz,1H),2.52(s,3H),2.34(s,3H). 13 C NMR(101MHz,CDCl 3 )δ145.29,136.46,136.07,135.81,135.38,130.71,130.15,129.22,127.01,126.49,125.61,122.64,121.65,120.62,120.45,120.43,116.04,114.12,110.88,101.73,22.08,21.70.

[0070] Example 15: Preparation of Compound G-15

[0071]

[0072] The operation steps and conditions were the same as those in Example 1, except that the iodoindole substrate used was 5-methyl-3-iodo-1-(p-toluenesulfonyl)-1H-indole (0.85 mmol, 363.0 mg), and Compound G-15 (white solid, 224.3 mg, yield 66%) was obtained. 1 H NMR(400MHz,CDCl 3 )δ8.56(s,1H),7.96(d,J=9.1Hz,1H),7.85(s,1H),7.79(d,J=8.5Hz,2H),7.68(dd,J=7.8,1.2Hz,1H),7.44(dd,J=8.0,1.1Hz,1H),7.36(d,J=2.5Hz,1H),7.29–7.21(m,1H),7.21–7.12(m,3H),7.02(dd,J=9.1,2.5Hz,1H),6.84(dd,J=2.1,0.9Hz,1H),3.87(s,3H),2.30(s,3H). 13 C NMR(101MHz,CDCl 3)δ 157.02, 145.30, 136.38, 134.86, 130.48, 130.20, 130.07, 129.76, 129.08, 126.88, 123.01, 122.59, 120.51, 120.35, 116.18, 114.82, 114.41, 111.01, 103.43, 101.42, 55.88, 21.61. Figure 3 For it 1 H-NMR (400 MHz, CDCl 3 ) spectrum Figure 4 For it 13 C-NMR (100 MHz, CDCl 3 ) spectrum

[0073] Example 16: Preparation of Compound G-16

[0074]

[0075] The operation steps and conditions are the same as those in Example 1, except that the iodinated indole substrate used is 6-chloro-3-iodo-1-p-toluenesulfonyl-1H-indole (0.85 mmol, 366.0 mg), to obtain Compound G-16 (white solid, 230.5 mg, yield 65%). 1 HNMR (400 MHz, CDCl 3 ) δ 8.33 (s, 1H), 7.97 (d, J = 8.9 Hz, 1H), 7.88 (d, J = 2.1 Hz, 1H), 7.83 (s, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.66 (d, J = 7.8 Hz, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.35 (dd, J = 8.9, 2.1 Hz, 1H), 7.26–7.19 (m, 3H), 7.19–7.11 (m, 1H), 6.82 (d, J = 2.1 Hz, 1H), 2.35 (s, 3H). 13 C NMR (101 MHz, CDCl 3 ) δ 145.75, 136.52, 134.89, 133.94, 130.28, 130.11, 129.97, 129.71, 129.12, 127.03, 125.82, 123.43, 122.91, 120.76, 120.62, 115.67, 115.07, 110.97, 102.07, 21.74.

[0076] The specific embodiments described herein are only the preferred specific embodiments of the present invention, but the scope of protection of the present invention is not limited thereto. Any modifications, equivalent substitutions, improvements, etc. made by those skilled in the art within the technical scope disclosed by the present invention shall be included within the scope of protection of the invention.

Claims

1. A method for preparing a 2,3'-bisindole compound, characterized in that: The preparation method is as follows: indole A and 3-iodo-1-toluenesulfonyl-1H-indole B are used as starting materials, and under the action of palladium catalyst C, norbornene derivative D, and base E, the mixture is stirred in an organic solvent F at 60-80° C. until the reaction is completed, and the reaction mixture is filtered, concentrated, and purified by column chromatography to obtain a 2,3'-bisindole compound G as shown in the reaction formula. The reaction formula of the reaction is shown as follows: Among them, R 1 , R 2 All are substituents on the benzene ring in the indole structure.

2. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: R in Formula A 1 is selected from the group consisting of methoxy, methyl, fluorine, chlorine, bromine, and cyano, R 2 It is one of methyl, bromine and chlorine.

3. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: The molar ratio of indole A, 3-iodo-1-toluenesulfonyl-1H-indole B, palladium catalyst C, norbornene derivative D, and base E is 1:(1-2):(0.05-0.15):(1-3):(1-3).

4. The method for preparing 2,3'-bisindole compounds according to claim 3, characterized in that: The molar ratio of indole A, 3-iodo-1-toluenesulfonyl-1H-indole B, palladium catalyst C, norbornene derivative D, and base E is 1:1:0.1:2:

2.

5. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: The palladium catalyst C is one of palladium acetate, palladium chloride and palladium trifluoroacetate.

6. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: The norbornene derivative D is one of norbornene, 5-norbornene-2-carboxylic acid methyl ester and 2-cyano-5-norbornene.

7. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: The base E is one of sodium carbonate, potassium carbonate and cesium carbonate.

8. The method for preparing 2,3'-bisindole compounds according to claim 1, characterized in that: The solvent F is one of dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide and N-methylpyrrolidone.

9. The method for preparing the 2,3'-bisindole compound according to any one of claims 1 to 8, characterized in that: In the preparation method, the heating process can adopt an oil bath, which can be silicone oil or paraffin oil; the filtration process uses a sand core funnel and filters under reduced pressure; the concentration process can adopt atmospheric distillation or reduced pressure distillation, preferably using a rotary evaporator to concentrate under reduced pressure; the purification process is to obtain a pure product through column chromatography.

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