A method for the catalytic synthesis of 2-cyanoalkenyl indole compounds using trivalent rhodium

Abstract

This invention relates to a method for the trivalent rhodium-catalyzed synthesis of 2-cyanenylindole compounds, belonging to the field of organic chemistry. The method uses [Cp*RhCl2]2 as a catalyst and N-pyrimidine indole compounds and alkynyl-N-cyano-N-phenyl-p-toluenesulfonamide compounds as raw materials. The reaction is carried out in an organic solvent at 60°C with lithium chloride assistance, and the 2-cyanenylindole compounds are obtained after separation and purification. This invention utilizes a cyano group migration strategy to achieve a tandem reaction of indole C-H alkenylation and cyano group introduction, constructing C-C and C-CN bonds in one step, with a target product yield of 31%–82%. Compared with existing technologies, this invention uses a non-toxic cyanide source instead of traditional highly toxic cyaniding reagents, and has advantages such as simple operation, mild reaction conditions, wide substrate applicability, and high atom economy.

Description

Technical Field

[0001] This invention relates to the field of organic chemistry, specifically to a method for the synthesis of 2-cyanenylindole compounds using trivalent rhodium catalysis. Background Technology

[0002] Organic nitriles and their derivatives, as a class of multifunctional structural units, are widely found in pharmaceuticals, natural products, and materials. Among them, α,β-unsaturated nitriles are important building blocks in organic synthesis, capable of being converted into a variety of valuable compounds and serving as key structural units in many bioactive molecules, such as Rilpivirine, Nileprost, and Entacapone. Therefore, the efficient and direct introduction of nitrile groups into organic molecules to construct α,β-unsaturated nitriles has always been an important research direction in the field of organic synthesis.

[0003] In existing technologies, the synthesis of ethylene nitrile mainly includes two types of methods: direct CX nitrification reactions catalyzed by transition metals, and nitrification addition reactions of alkynes. However, these transformations usually require the use of highly toxic cyaniding reagents (such as NaCN, KCN, CuCN, etc.), posing safety risks. In recent years, transition metal-catalyzed CH activation strategies have attracted widespread attention due to their high atom economy and step economy, and have gradually become an efficient route for constructing nitrile compounds.

[0004] To address the toxicity issue of cyanide sources, researchers have developed various non-toxic alternatives to cyanide-based sources. Among these, cyanamide compounds, especially N-cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS), are widely used in CH cyanation and cyanoaddition reactions of alkenes due to their ease of acquisition, relatively low toxicity, and low cost. However, in existing cyanation systems, NCTS is mainly used as a simple cyaniding reagent, and its amide group, acting as a leaving group, results in low atom economy. Therefore, developing novel cyano bifunctional reagents based on cyano migration strategies to construct multiple chemical bonds in a one-step reaction has become a promising research direction.

[0005] In cyano migration strategies, some progress has been made in the bifunctionalization of olefin-linked N-cyanosulfonamides, such as intramolecular aminocyanidation, oxycyanidation, and carbonylation. However, current research is still mainly limited to intramolecular reactions, and intermolecular coupling reactions via cyano functional group migration are rarely reported.

[0006] To address the aforementioned technical problems, this invention provides a method for the efficient synthesis of 2-cyanenylindole compounds under mild conditions by using alkynyl N-cyanosulfonamide as a cyanide source and achieving intermolecular coupling of indole CH alkenylation and cyano group migration via trivalent rhodium catalysis. Summary of the Invention

[0007] In order to solve the problems of the prior art, the present invention provides a method for the synthesis of 2-cyanenylindole compounds by trivalent rhodium catalysis.

[0008] To solve the above-mentioned technical problems, the present invention is achieved through the following technical solution: In a first aspect, a method for synthesizing 2-cyanenylindole compounds by trivalent rhodium catalysis, wherein an indole compound of formula I, an alkyne compound of formula II, a trivalent rhodium catalyst [Cp*RhCl2]2, AgSbF6, and LiCl are added to an organic solvent, and the reaction is carried out at 60°C under nitrogen and closed conditions. After the reaction is completed, the product is separated and purified to obtain the 2-cyanenylindole compound of formula III. Wherein, R is selected from H, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl or aryl; Ar is selected from H, C1-C4 alkyl or halogen-substituted aryl.

[0009] In one specific embodiment of the first aspect, the alkyne compound represented by Formula II is alkynyl N-cyano-N-phenyl-p-toluenesulfonamide or a derivative thereof.

[0010] In one specific embodiment of the first aspect, the molar ratio of the indole compound to the alkyne compound is 1:1.2 to 1.5.

[0011] In one specific embodiment of the first aspect, the amount of the trivalent rhodium catalyst [Cp*RhCl2]2 added is 3 to 5% of the molar amount of the indole compound.

[0012] In one specific embodiment of the first aspect, the amount of AgSbF6 added is 16 to 30% of the molar amount of the indole compound.

[0013] In one specific embodiment of the first aspect, the molar ratio of LiCl to indole compounds is 1 to 1.2:1.

[0014] In one specific embodiment of the first aspect, the organic solvent is selected from any one of 1,2-dichloroethane, dichloromethane, methanol, or tetrahydrofuran.

[0015] In one specific embodiment of the first aspect, the reaction time is 20 to 28 hours.

[0016] In one specific embodiment of the first aspect, the separation and purification are performed using column chromatography, with the eluent being a mixed solvent of petroleum ether and ethyl acetate.

[0017] In one specific embodiment of the first aspect, the indole compound represented by Formula I is N-pyrimidineindole or a substituted derivative thereof.

[0018] The beneficial effects of this invention are as follows: 1. This invention uses [Cp*RhCl2]2, a catalyst with high catalytic activity and controllable site selectivity, as a catalyst. Using N-pyrimidine indole and alkynyl-N-cyano-N-phenyl-p-toluenesulfonamide compounds as raw materials, the reaction is carried out at 60°C and atmospheric pressure with lithium chloride assistance. The 2-cyanenyl indole compound is obtained by column chromatography. This method is simple to operate, uses stable and easy-to-prepare raw materials, and operates under mild reaction conditions. The yield of the target product can reach 31%–82%, with a yield exceeding 79% under optimal conditions. Furthermore, it is applicable to a variety of substituted indole and alkynyl substrates (including those containing alkyl, alkoxy, halogen, trifluoromethyl, aryl, and heterocyclic aryl groups), demonstrating good substrate versatility.

[0019] 2. This invention overcomes the shortcomings of using highly toxic cyaniding reagents (such as NaCN, KCN, etc.) in previous cyanidation reaction systems. It uses non-toxic alkynyl N-cyano-N-phenyl p-toluenesulfonamide as the cyanide source and achieves a tandem reaction of indole CH alkenylation and cyano introduction through a cyano migration strategy. It simultaneously constructs C-C bonds and C-CN bonds in one pot, avoiding the atom economy loss caused by the amide group as the leaving group in traditional methods. It has significant advantages of safety, environmental protection and high atom economy. Detailed Implementation

[0020] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention. Example 1

[0021] Synthesize the following (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. Under a nitrogen atmosphere, add 20.9 mg (0.1 mmol) of 1-(pyrimidin-2-yl)-1H-indole, 44.6 mg (0.12 mmol) of N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide, 2.5 mg (0.004 mmol) of [Cp*RhCl2]2, 5.5 mg (0.016 mmol) of silver hexafluorodiethylate, 4.2 mg (0.1 mmol) of lithium chloride, and 2 mL of dichloromethane to a pressure-resistant tube. Tighten the pressure-resistant tube. 60 0The reaction was stirred at C for 24 h to allow the pyrimidine indole to react substantially completely. After the reaction was complete, dichloromethane was removed by rotary evaporation under reduced pressure to obtain the crude product. The crude product was then subjected to column chromatography on silica gel (petroleum ether: ethyl acetate = 5:1 to 3:1) to give a pale yellow solid product with a yield of 82% (yield calculated based on pyrimidine indole). Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.85 (d, J = 4.8 Hz, 2H), 8.53 (d, J = 8.4 Hz, 1H), 7.80 - 7.66 (m, 2H), 7.63 (d, J = 8.0 Hz, 2H), 7.46 - 7.39 (m, 2H), 7.30 (t,J = 7.5 Hz, 1H), 7.25 - 7.19 (m, 4H), 7.13 (t, J = 7.3 Hz, 1H), 7.07 (t, J =4.9 Hz, 1H), 7.05 - 6.98 (m, 6H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.2, 153.3, 144.3, 138.0, 136.2, 136.2, 135.7, 130.4, 130.2, 130.0, 129.8, 129.7, 128.6, 128.1, 127.5, 125.6, 124.5, 122.9, 121.5, 119.0, 118.6, 117.2, 115.1, 114.2, 106.6, 21.6; HRMS (ESI) theoretical value C 34 H 25 NaN5O2S + [M+Na] + :590.1622, Measured value: 590.1622. Example 2

[0022] Synthesize the following (Z)-N-(2-(1-cyano-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)-2-(p-tolyl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-4-methyl-N-(2-(p-tolylethynyl)phenyl)benzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 79%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.84(d, J = 4.9 Hz, 2H), 8.53 (d, J = 8.4 Hz, 1H), 7.92 - 7.57 (m, 4H), 7.45 (d,J = 8.3 Hz, 1H), 7.41 - 7.37 (m, 1H), 7.32 - 7.27 (m, 1H), 7.25 - 7.18 (m,4H), 7.05 (t, J = 4.8 Hz, 1H), 7.03 - 6.97 (m, 2H), 6.86 (d, J = 8.1 Hz, 2H), 6.82 (d, J = 8.2 Hz, 2H), 2.37 (s, 3H), 2.17 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.3, 153.2, 144.2, 140.1, 138.0, 136.4, 136.2, 135.6, 133.3, 130.4, 130.1, 129.9, 129.8, 128.9, 128.6, 127.5, 125.5, 124.5, 122.9, 121.5, 118.7, 117.2, 115.1, 114.1, 105.9, 21.6, 21.3; HRMS (ESI) theoretical value C 35 H 27 NaN5O2S + [M+Na] + : 604.1778, Measured value: 604.1782. Example 3

[0023] Synthesize the following methyl(Z)-4-(2-cyano-2-(2-((4-methylphenyl)sulfonamido)phenyl)-1-(1-(2-pyrimidinyl)-1H-indol-2-yl)vinyl)benzoate ester skeleton compounds. In this embodiment, equimolar amounts of methyl 4-((2-((N-cyano-4-methylphenyl)sulfonamido)phenyl)ethynyl)benzoate were used instead of N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 63%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.83 (d, J = 4.9 Hz, 2H), 8.55 (d, J = 8.4 Hz, 1H), 7.74 - 7.61 (m,6H), 7.49 - 7.38 (m, 2H), 7.31 (t, J = 7.5 Hz, 1H), 7.23 - 7.18 (m, 3H), 7.15(d, J = 7.6 Hz, 1H), 7.10 - 7.04 (m, 4H), 6.99 (t, J = 7.5 Hz, 1H), 3.82 (s,3H), 2.36 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 166.1, 158.5, 157.2, 152.3, 144.4, 140.6, 138.1, 136.2, 135.8, 135.6, 130.7, 130.5, 130.0, 129.8, 129.1, 128.5, 127.5, 125.8, 124.7, 123.1, 121.6, 119.3, 118.2, 117.3, 115.2, 114.5, 107.9, 52.2, 21.6; HRMS (ESI) theoretical value C 36 H 27 NaN5O4S + [M+Na] + : 648.1676, Measured value: 648.1682. Example 4

[0024] Synthesize the following (Z)-N-(2-(1-cyano-2-(3-methoxyphenyl)-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)ethylene)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-N-(2-((3-methoxyphenyl)ethynyl)phenyl)-4-methylbenzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 73%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3)δ 8.86 (d, J = 4.9 Hz, 2H), 8.55 (d, J = 8.5 Hz, 1H), 7.82 - 7.66 (m, 2H),7.64 (d, J = 8.1 Hz, 2H), 7.46 - 7.37 (m, 2H), 7.30 (t, J = 7.5 Hz, 1H), 7.25- 7.19 (m, 4H), 7.08 (t, J = 4.8 Hz, 1H), 7.04 - 6.99 (m, 2H), 6.95 (t, J =8.0 Hz, 1H), 6.70 - 6.65 (m, 1H), 6.58 (d, J = 7.8 Hz, 1H), 6.55 (s, 1H), 3.43 (s, 3H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.9, 158.4, 157.3, 153.2, 144.3, 138.0, 137.3, 136.2, 136.0, 135.7, 130.4, 130.1, 129.9, 129.1, 128.6, 127.4, 125.6, 124.5, 124.3, 122.9, 122.6, 121.6, 119.0, 118.5, 117.2, 116.7, 115.1, 114.5, 114.2, 106.7, 55.1, 21.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O3S + [M+Na] + : 620.1727, Measured value: 620.1728. Example 5

[0025] Synthesize the following (Z)-N-(2-(1-cyano-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)-2-(3-(trifluoromethyl)phenyl)ethylene)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-4-methyl-N-(2-((3-(trifluoromethyl)phenyl)ethynyl)phenyl)benzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 60%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.84 (d, J = 4.9 Hz, 2H), 8.57 (d, J = 8.4 Hz, 1H), 7.74 - 7.64 (m,3H), 7.57 (s, 1H), 7.42 (t, J = 7.8 Hz, 1H), 7.37 - 7.30 (m, 3H), 7.29 - 7.20(m, 5H), 7.20 - 7.12 (m, 2H), 7.11 (s, 1H), 7.07 (t, J = 5.0 Hz, 1H), 7.02(t, J = 7.6 Hz, 1H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.2,151.8, 144.4, 138.2, 137.1, 136.3, 135.6, 135.3, 133.1, 130.5, 130.3 (q, J =32.6 Hz), 129.9, 128.6, 128.6, 127.4, 127.0 (q, J = 4.2 Hz), 126.0 (q, J =3.9 Hz), 125.9, 124.9, 124.3, 123.3 (q, J = 272.8 Hz), 123.1, 121.7, 119.9,118.1, 117.3, 115.3, 114.6, 108.0, 21.6; 19 F NMR (376 MHz, CDCl3) δ -62.9; HRMS (ESI) theoretical value C 35 H 24 NaF3N5O2S + [M+Na] + : 658.1496, Measured value: 658.1499. Example 6

[0026] Synthesize the following (Z)-N-(2-(1-cyano-2-(2-methoxyphenyl)-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-N-(2-((2-methoxyphenyl)ethynyl)phenyl)-4-methylbenzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 64%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3)δ 8.75 (d, J = 4.8 Hz, 2H), 8.41 (d, J = 8.4 Hz, 1H), 7.78 (s, 1H), 7.70 (d,J = 8.3 Hz, 2H), 7.65 (d, J = 7.8 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.38 -7.34 (m, 1H), 7.30 - 7.21 (m, 3H), 7.15 - 7.07 (m, 2H), 7.07 - 7.01 (m, 3H),6.95 - 6.91 (m, 1H), 6.88 (t, J = 7.3 Hz, 1H), 6.66 (t, J = 7.4 Hz, 1H), 6.54(d, J = 8.4 Hz, 1H), 3.45 (s, 3H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.1, 157.5, 156.0, 149.9, 144.1, 138.2, 136.9, 136.4, 135.2, 131.5, 131.1, 130.5, 129.8, 129.5, 128.5, 127.5, 125.4, 125.4, 125.3, 123.5, 122.7, 121.5, 120.2, 118.6, 117.1, 114.6, 114.3, 110.9, 107.9, 54.9, 21.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O3S + [M+Na] + : 620.1727, Measured value: 620.1733. Example 7

[0027] Synthesize the following (Z)-N-(5-chloro-2-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)-N-cyano-4-methylbenzenesulfonamide was replaced with an equimolar amount of N-(5-chloro-2-(phenylethynyl)phenyl)-N-cyano-4-methylbenzenesulfonamide in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 51%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ8.85 (d, J = 4.8 Hz, 2H), 8.53 (d, J = 8.5 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J= 7.8 Hz, 1H), 7.64 (d, J = 8.0 Hz, 2H), 7.48 (s, 1H), 7.41 (t, J = 7.7 Hz, 1H), 7.30 (t, J = 7.5 Hz, 1H), 7.26 - 7.22 (m, 2H), 7.16 (t, J = 7.3 Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.10 - 7.03 (m, 3H), 7.02 - 6.95 (m, 4H), 2.39 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.2, 153.9, 144.6, 138.1, 136.9, 136.0, 136.0, 135.9, 135.7, 131.4, 130.0, 129.9, 128.5, 128.2, 127.5, 125.7, 124.5, 123.0, 122.3, 121.6, 118.8, 118.3, 117.3, 115.1, 114.5, 105.4, 21.6; HRMS (ESI) theoretical value C 34 H 24 NaClN5O2S + [M+Na] + : 624.1232, Measured value: 624.1238. Example 8

[0028] Synthesize the following (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(2-pyridyl)-1H-indol-2-yl)ethylene)-4-methylphenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-4-methyl-N-(4-methyl-2-(phenylethynyl)phenyl)benzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 64%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ8.81 (d, J = 4.7 Hz, 2H), 8.51 (d, J = 8.5 Hz, 1H), 7.68 (d, J = 7.7 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.41 - 7.37 (m, 1H), 7.34 - 7.27 (m, 2H), 7.22 (d,J = 8.1 Hz, 2H), 7.16 - 7.09 (m, 1H), 7.08 - 6.95 (m, 9H), 2.38 (s, 3H), 2.21(s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.2, 152.7, 144.1, 138.0, 136.3, 136.3, 136.2, 134.7, 132.9, 130.9, 130.6, 130.0, 129.8, 129.7, 128.6, 128.1, 127.4, 125.5, 122.9, 121.5, 118.7, 117.1, 115.0, 114.1, 106.9, 21.6, 20.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O2S + [M+Na] + : 604.1778, Measured value: 604.1781. Example 9

[0029] Synthesize the following (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)ethylene)-4-(trifluoromethyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-4-methyl-N-(2-(phenylethynyl)-4-(trifluoromethyl)phenyl)benzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 61%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.89 (d, J = 4.9 Hz, 2H), 8.57 (d, J = 8.5 Hz, 1H), 8.16 (s, 1H), 7.69 (d, J = 7.5 Hz, 1H), 7.61 (d, J = 7.7 Hz, 2H), 7.53 - 7.39 (m, 4H), 7.32(t, J = 7.2 Hz, 1H), 7.25 - 7.16 (m, 3H), 7.14 - 7.05 (m, 3H), 7.04 - 6.97(m, 3H), 2.39 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.5, 157.3, 154.4, 144.8,138.9, 138.3, 135.9, 135.8, 135.7, 130.2, 130.0, 130.0, 128.5, 128.3, 127.8(q, J = 4.4 Hz), 127.5, 127.2 (q, J = 4.4 Hz), 125.9, 123.5, 123.4 (q, J =272.2 Hz), 123.1, 121.7, 118.1, 117.7, 117.3, 115.2, 115.0, 104.7, 21.6; 19 FNMR (376 MHz, CDCl3) δ -62.2; HRMS (ESI) theoretical value C 35 H 24 NaF3N5O2S + [M+Na] + :658.1496, Measured value: 658.1498. Example 10

[0030] Synthesize the following (Z)-N-(2-chloro-6-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-(2-chloro-6-(phenylethynyl)phenyl)-N-cyano-4-methylbenzenesulfonamide was used instead of N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 62%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ8.50 (d, J = 4.8 Hz, 2H), 8.43 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 7.7 Hz, 1H),7.66 - 7.52 (m, 4H), 7.41 - 7.34 (m, 1H), 7.32 - 7.27 (m, 1H), 7.24 - 7.17(m, 4H), 7.00 - 6.96 (m, 1H), 6.94 - 6.87 (m, 4H), 6.82 (t, J = 4.8 Hz, 1H), 5.63 (s, 1H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 157.7, 157.0, 151.4, 144.0, 137.9, 137.4, 136.9, 136.9, 136.7, 133.6, 131.3, 130.9, 130.1, 130.0, 129.5, 128.9, 128.8, 128.6, 127.5, 127.4, 125.2, 122.6, 122.0, 120.0, 116.5, 115.5, 114.5, 107.7, 21.6; HRMS (ESI) theoretical value C 34 H 24 NaClN5O2S + [M+Na] + : 624.1232, measured value: 624.1238. Example 11

[0031] Synthesize the following (E)-N-(2-(1-cyano-2-(1-(2-pyrimidinyl)-1H-indol-2-yl)-2-(thiophen-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, an equimolar amount of N-cyano-4-methyl-N-(2-(thiophen-2-ethynyl)phenyl)benzenesulfonamide was used instead of the N-cyano-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide used in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 81%. Characterization data are as follows: 1 H NMR (600 MHz, CDCl3) δ 8.95- 8.82 (m, 2H), 8.60 (d, J = 8.4 Hz, 1H), 8.24 (s, 1H), 7.94 (d, J = 8.4 Hz,1H), 7.76 - 7.66 (m, 3H), 7.52 - 7.40 (m, 2H), 7.38 - 7.23 (m, 2H), 7.23 -7.10 (m, 5H), 7.05 (t, J = 4.9 Hz, 1H), 6.70 - 6.54 (m, 2H), 2.31 (s, 3H); 13 CNMR (151 MHz, CDCl3) δ 158.7, 157.1, 147.1, 144.4, 138.8, 137.2, 135.7, 134.4, 133.0, 132.0, 131.4, 130.3, 129.9, 128.6, 127.5, 126.6, 125.5, 125.3, 123.2, 123.0, 121.6, 120.2, 118.1, 117.1, 115.4, 112.5, 104.8, 21.6; HRMS (ESI) theoretical value C 32 H 23 NaN5O2S2 + [M+Na] + : 596.1186, Measured value: 596.1190. Example 12

[0032] Synthesize the following (Z)-N-(2-(1-cyano-2-(5-methoxy-1-(pyrimidin-2-yl)-1H-indol-2-yl)-2-phenylvinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidin-2-yl)-1H-indole was replaced with an equimolar amount of 5-methoxy-1-(2-pyrimidinyl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 52%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.82 (d, J = 4.8 Hz, 2H), 8.46 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.62 (d, J = 8.0 Hz, 2H), 7.40 (d, J = 8.4 Hz, 1H), 7.24 -7.18 (m, 4H), 7.17 - 7.08 (m, 2H), 7.08 - 6.98 (m, 7H), 6.94 (s, 1H), 3.89 (s, 3H), 2.37 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.2, 156.1, 153.3, 144.2, 136.6, 136.2, 136.2, 133.0, 130.4, 130.2, 130.0, 129.8, 129.7, 129.3, 129.2, 128.0, 127.4, 124.4, 118.9, 118.6, 117.0, 116.2, 115.2, 114.0, 106.4, 103.1, 55.8, 21.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O3S + [M+Na] + : 620.1727, Measured value: 620.1733. Example 13

[0033] Synthesize compounds with the following structural formula: methyl(Z)-2-(2-cyano-2-(2-((4-methylphenyl)sulfonamido)phenyl)-1-phenylvinyl)-1-(2-aminopyrimidinyl)-1H-indole-5-carboxylic acid ester skeleton. In this embodiment, 1-(pyrimidinyl)-1H-indole-5-carboxylic acid ester of methyl 1-(2-pyrimidinyl)-1H-indole used in Example 1 was replaced with an equimolar amount of methyl 1-(2-pyrimidinyl)-1H-indole. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 63%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.87 (d, J = 4.8 Hz, 2H), 8.52 (d, J =8.8 Hz, 1H), 8.43 (s, 1H), 8.09 (d, J = 8.9 Hz, 1H), 7.75 - 7.54 (m, 3H),7.43 (d, J = 8.3 Hz, 1H), 7.35 - 7.18 (m, 4H), 7.15 - 7.09 (m, 3H), 7.08 -6.94 (m, 5H), 3.97 (s, 3H), 2.37 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 167.4, 158.6, 156.9, 152.7, 144.4, 140.3, 137.5, 136.1, 135.8, 135.6, 130.4, 130.3, 129.9, 129.8, 128.2, 128.2, 127.5, 126.6, 124.9, 124.6, 124.0, 119.3, 118.4, 117.8, 114.7, 114.2, 107.5, 52.1, 21.6; HRMS (ESI) theoretical value C 36 H 27 NaN5O4S + [M+Na] + : 648.1676, Measured value: 648.1676. Example 14

[0034] Synthesize the following (Z)-N-(2-(1-cyano-2-(6-methoxy-1-(pyrimidin-2-yl)-1H-indol-2-yl)-2-phenylvinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidin-2-yl)-1H-indole was replaced with an equimolar amount of 6-methoxy-1-(2-pyrimidinyl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 68%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.85 (d, J = 4.7 Hz, 2H), 8.12 (s, 1H), 7.73(s, 1H), 7.59 (d, J = 7.9 Hz, 2H), 7.53 (d, J = 8.6 Hz, 1H), 7.34 (d, J = 8.3Hz, 1H), 7.24 - 7.17 (m, 4H), 7.16 - 7.11 (m, 1H), 7.08 - 6.89 (m, 8H), 3.90 (s, 3H), 2.37 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 159.0, 158.4, 157.5, 153.0, 144.2, 139.4, 136.5, 136.3, 135.5, 135.3, 130.6, 130.2, 130.0, 129.8, 129.7, 128.0, 127.4, 124.3, 122.6, 122.1, 118.9, 117.1, 115.0, 112.7, 105.3, 98.9, 55.7, 21.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O3S + [M+Na] + : 620.1727, Measured value: 620.1730. Example 15

[0035] Synthesize the following (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-6-(trifluoromethyl)-1H-indol-2-yl)ethylene)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidinyl)-6-(trifluoromethyl)-1H-indole was replaced with an equimolar amount of 1-(2-pyrimidinyl)-6-(trifluoromethyl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 71%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.95 - 8.69 (m, 3H), 7.78 (d, J = 8.2 Hz,1H), 7.75 - 7.57 (m, 3H), 7.55 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 8.4 Hz, 1H),7.26 - 7.18 (m, 4H), 7.17 - 7.08 (m, 3H), 7.06 - 7.00 (m, 3H), 6.99 - 6.94(m, 2H), 2.37 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.7, 156.8, 152.6, 144.4,138.6, 136.8, 136.1, 135.7, 130.9, 130.4, 130.3, 129.9, 129.9, 129.8, 128.2,127.5, 127.2 (q, J = 31.9 Hz), 124.9 (q, J = 272.2 Hz), 124.7, 121.9, 119.5 (q, J = 3.5 Hz), 118.3, 117.8, 113.1, 112.9 (q, J = 4.6 Hz), 107.9, 21.6; 19 FNMR (376 MHz, CDCl3) δ -60.8; HRMS (ESI) theoretical value C 35 H 24 NaF3N5O2S + [M+Na] + :658.1496, Measured value: 658.1494. Example 16

[0036] Synthesize the following (Z)-N-(2-(1-cyano-2-(4-methoxy-1-(pyrimidin-2-yl)-1H-indol-2-yl)-2-phenylvinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidin-2-yl)-1H-indole was replaced with an equimolar amount of 4-methoxy-1-(2-aminopyrimidinyl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 51%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.83 (d, J = 4.9 Hz, 2H), 8.10 (d, J = 8.4Hz, 1H), 7.69 (s, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.3 Hz, 1H),7.32 (t, J = 8.2 Hz, 1H), 7.24 - 7.18 (m, 4H), 7.15 - 7.10 (m, 2H), 7.07 -6.97 (m, 6H), 6.71 (d, J = 7.9 Hz, 1H), 3.98 (s, 3H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.4, 157.4, 153.5, 153.0, 144.3, 139.4, 136.3, 136.2, 135.5, 134.7, 130.5, 130.1, 129.9, 129.7, 128.1, 127.4, 126.6, 124.5, 124.2, 119.4, 119.2, 118.6, 117.3, 111.8, 108.0, 106.1, 102.8, 55.5, 21.6; HRMS (ESI) theoretical value C 35 H 27 NaN5O3S + [M+Na] + : 620.1727, Measured value: 620.1727. Example 17

[0037] Synthesize the following (Z)-N-(2-(1-cyano-2-(7-methyl-1-(2-pyrimidinyl)-1H-indol-2-yl)-2-phenylvinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidin-2-yl)-1H-indole was replaced with an equimolar amount of 7-methyl-1-(2-pyrimidinyl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 37%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.66 (d, J = 4.4 Hz, 2H), 7.77 (d, J = 7.8 Hz,2H), 7.60 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 8.3 Hz, 1H), 7.48 (s, 1H), 7.25 -7.21 (m, 3H), 7.21 - 7.12 (m, 2H), 7.09 (d, J = 7.2 Hz, 1H), 7.06 (d, J = 7.6Hz, 1H), 7.02 - 6.93 (m, 3H), 6.86 (t, J = 7.6 Hz, 2H), 6.64 (d, J = 8.1 Hz,2H), 2.37 (s, 3H), 2.04 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 158.2, 157.4, 152.3, 144.4, 136.8, 136.6, 136.1, 135.7, 135.0, 130.3, 130.3, 129.9, 129.5, 129.3, 128.6, 128.0, 127.9, 127.6, 124.9, 122.7, 122.1, 120.3, 119.7, 118.6, 118.3, 110.8, 109.7, 21.6, 20.9; HRMS (ESI) theoretical value C 35 H 27 NaN5O2S + [M+Na] + :604.1778, Measured value: 604.1783. Example 18

[0038] Synthesize the following (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(pyridin-2-yl)-1H-indazol-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton compound. In this embodiment, 1-(pyrimidin-2-yl)-1H-indole used in Example 1 was replaced with an equimolar amount of 1-(pyridin-2-yl)-1H-indole, and the other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 35%. The characterization data are as follows: 1HNMR (600 MHz, CDCl3) δ 8.70 (d, J = 3.9 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.72 - 7.68 (m, 1H), 7.67 - 7.62 (m, 3H), 7.53 (d, J = 8.2 Hz, 1H), 7.39 (d,J = 8.0 Hz, 1H), 7.34 - 7.29 (m, 2H), 7.26 - 7.22 (m, 3H), 7.20 - 7.12 (m,3H), 7.10 - 7.05 (m, 2H), 6.99 - 6.93 (m, 3H), 6.88 - 6.84 (m, 2H), 2.39 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 151.8, 150.7, 149.6, 144.1, 138.3, 137.9, 136.8, 136.5, 136.4, 135.2, 130.8, 130.0, 130.0, 129.8, 129.5, 128.0, 127.9, 127.4, 125.0, 124.8, 124.6, 122.0, 121.9, 121.8, 120.5, 120.1, 118.7, 111.5, 110.7, 107.9, 21.6; HRMS (ESI) theoretical value C 35 H 26 NaN4O2S + [M+Na] + : 589.1669, Measured value: 589.1669. Example 19

[0039] Synthesize the following methyl(Z)-5-(2-cyano-2-(2-((4-methylphenyl)sulfonamido)phenyl)-1-phenylethylene)-1-(2-aminopyrimidinyl)-1H-pyrrole-3-carboxylic acid ester skeleton compounds. In this embodiment, 1-(pyrimidinyl)-1H-pyrrole-3-carboxylic acid ester of methyl 1-(2-pyrimidinyl)-1H-indole used in Example 1 was replaced with an equimolar amount of methyl 1-(2-pyrimidinyl)-1H-pyrrole-3-carboxylic acid ester. Other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 31%. Characterization data are as follows: 1H NMR (600 MHz, CDCl3) δ 8.84 (d, J = 4.9 Hz, 2H), 8.56 (d, J = 1.8Hz, 1H), 7.94 (s, 1H), 7.44 (d, J = 8.2 Hz, 2H), 7.29 (d, J = 7.6 Hz, 1H),7.26 - 7.16 (m, 6H), 7.14 - 7.06 (m, 4H), 7.03 (t, J = 7.5 Hz, 1H), 6.85 (d,J = 1.9 Hz, 1H), 3.86 (s, 3H), 2.38 (s, 3H); 13 C NMR (151 MHz, CDCl3) δ 164.1, 159.0, 155.9, 151.3, 144.2, 136.6, 136.2, 135.0, 130.9, 130.7, 130.2, 130.0, 129.8, 129.6, 128.3, 127.2, 124.1, 123.2, 119.0, 118.5, 118.2, 107.3, 51.5, 21.6; HRMS (ESI) theoretical value C 32 H 25 NaN5O4S + [M+Na] + : 598.1520, Measured value: 598.1523. Example 20

[0040] Synthesize compounds with the following structural formula: (Z)-N-(2-(1-cyano-2-phenyl-2-(1-(2-pyrimidinyl)-1H-pyrrolo-2-yl)vinyl)phenyl)-4-methylbenzenesulfonamide skeleton. In this embodiment, equimolar amounts of 2-(1H-pyrrolo-1-yl)pyrimidine were used to replace 1-(pyrimidin-2-yl)-1H-indole in Example 1. The other steps were the same as in Example 1, yielding a pale yellow solid with a yield of 35%. Characterization data are as follows: 1HNMR (600 MHz, CDCl3) δ 8.80 (d, J = 4.9 Hz, 2H), 8.19 (s, 1H), 7.97 (dd, J =3.1, 1.8 Hz, 1H), 7.43 (d, J = 8.4 Hz, 2H), 7.33 - 7.29 (m, 1H), 7.24 - 7.08(m, 10H), 7.03 - 6.98 (m, 1H), 6.49 - 6.40 (m, 2H), 2.37 (s, 3H); 13 C NMR (151MHz, CDCl3) δ 158.7, 156.6, 152.2, 144.0, 137.3, 136.4, 135.2, 130.8, 130.5, 130.3, 129.9, 129.8, 129.7, 128.1, 127.2, 126.0, 123.8, 123.4, 120.2, 119.0, 118.0, 117.8, 111.3, 105.4, 21.6; HRMS (ESI) theoretical value C 30 H 23 NaN5O2S + [M+Na] + :540.1465, Measured value: 540.1467.

[0041] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing 2-cyanenylindole compounds using trivalent rhodium catalysis, characterized in that: The indole compound shown in Formula I, the alkyne compound shown in Formula II, the trivalent rhodium catalyst [Cp*RhCl2]2, AgSbF6, and LiCl were added to an organic solvent and reacted at 60°C under nitrogen and sealed conditions. After the reaction was completed, the product was separated and purified to obtain the 2-cyanenylindole compound shown in Formula III. Wherein, R is selected from H, C1-C4 alkyl, C1-C4 alkoxy, halogen, trifluoromethyl or aryl; Ar is selected from H, C1-C4 alkyl or halogen-substituted aryl.

2. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The alkyne compound represented by Formula II is alkynyl N-cyano-N-phenyl-p-toluenesulfonamide or its derivative.

3. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The molar ratio of the indole compound to the alkyne compound is 1:1.2 to 1.

5.

4. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The amount of the trivalent rhodium catalyst [Cp*RhCl2]2 added is 3 to 5% of the molar amount of the indole compound.

5. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The amount of AgSbF6 added is 16-30% of the molar amount of the indole compound.

6. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The molar ratio of LiCl to indole compounds is 1 to 1.2:

1.

7. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The organic solvent is selected from any one of 1,2-dichloroethane, dichloromethane, methanol, or tetrahydrofuran.

8. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The reaction time is 20 to 28 hours.

9. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The separation and purification were performed using column chromatography, with the eluent being a mixture of petroleum ether and ethyl acetate.

10. The method for synthesizing 2-cyanenylindole compounds catalyzed by trivalent rhodium according to claim 1, characterized in that: The indole compound represented by Formula I is N-pyrimidineindole or its substituted derivative.

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