A method for preparing biaryl compound

Abstract

The invention discloses a method for preparing a biaryl compound. The method is to use a compound such as indole or indoline containing a directing group and iodinated aromatic hydrocarbon as raw materials in a carbon monoxide atmosphere, and to react a carbon-hydrogen carbonylation / decarbonylation arylation reaction in an organic solvent through the action of a rhodium catalyst, an additive and a base. After the reaction is complete, a series of biaryl compounds are obtained by post-treatment. The invention also provides the application of the same method in the preparation of biaryl compounds by decarbonylation arylation of indoline-derived diaryl ketones. The preparation method is simple to operate, the raw materials and reagents are easily available, the applicability is wide, the reaction yield is high, and it is easy to industrialize.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemical synthesis, and in particular to a method for preparing a biaryl compound. Background Art

[0002] As an important structural unit, biaryl skeletons are not only widely present in natural products, drugs and functional materials (Chem. Rev. 2002, 102, 1359), but also widely used in asymmetric catalysis. The core skeletons of many dominant chiral ligands or chiral catalysts are biaryl compounds (Science. 2003, 299, 1691), such as 1,1′-binaphthol (BINOL) and 1,1′-binaphthyl-2,2′-bis(diphenylphosphine) (BINAP). Therefore, the synthesis and application research of biaryl skeleton compounds has attracted the attention of more and more researchers, and many new synthesis methods and biaryl derivatives have been gradually developed and synthesized.

[0003] Transition metal-catalyzed cross-coupling reactions between aryl halide electrophiles and aryl metal nucleophiles (such as Suzuki-Miyaura coupling, Negishi coupling, Stille coupling, Kumada coupling, etc.) are the most important traditional methods for synthesizing biaryl compounds. However, the two pre-functionalized substrates in this method usually require multi-step synthesis, cumbersome operations, and high waste emissions, resulting in low atomic utilization of the entire reaction. Therefore, people further perfected or improved the traditional cross-coupling reaction, and some new coupling methods continued to emerge (Chem. Rev. 2007, 107, 174; Chem. Rev. 2014, 114, 9219; Chem. Rev. 2015, 115, 12138; Chem. Rev. 2017, 117, 8787), for example, aryl-aryl oxidative coupling between dinucleophiles, aryl-aryl reductive coupling between dielectrophiles, and free radical-type aryl-aryl coupling.

[0004] In addition, unlike the above-mentioned coupling reaction process, the construction of aryl-aryl carbon-carbon bonds by decarbonylation coupling within diaryl ketone molecules and the subsequent synthesis of biaryl compounds (method 1) have attracted increasing attention from scientific researchers in recent years (Angew. Chem. Int. Ed. 2012, 51, 2690; J. Am. Chem. Soc. 2017, 139, 1416; J. Am. Chem. Soc. 2018, 140, 586; Chem. Sci., 2020, 11, 12336; Chem. Rev. 2021, 121, 365; Nat. Commun. 2022, 13, 1805). This method is not only a novel transformation of the ketone functional group, but also an important supplement to the traditional coupling reaction as a novel method for constructing aryl-aryl carbon-carbon bonds. However, this method also has some problems that need to be solved. For example, the ketone substrates required in the reaction, especially heterocyclic-derived diaryl ketone substrates such as indole, need to be synthesized in advance by other methods. This inevitably brings challenges in the selection of reaction substrates and the diversity of product structures.

[0005]

[0006] The present invention realizes the in-situ synthesis of a diaryl ketone intermediate and the further intramolecular decarbonylation arylation tandem reaction of the intermediate by regulating the catalytic system, thereby solving the problem of product structure diversity in the aforementioned diaryl ketone decarbonylation coupling reaction, and the raw materials adopt simple hydrocarbons and halogenated aromatics with a wide range of sources. Therefore, the present invention directly uses heterocyclic compounds such as indole or indoline and iodinated aromatics as raw materials, and realizes the preparation of biaryl compounds through a one-pot hydrocarbon carbonylation / decarbonylation tandem reaction to overcome the shortcomings of the existing synthesis method, which has important theoretical significance and application prospects. Summary of the invention

[0007] The purpose of the present invention is to provide a method for preparing a biaryl compound in view of the deficiencies in the prior art, which is simple, efficient and has strong universality.

[0008] In a first aspect, a method for preparing a biaryl compound is provided. The method comprises the following steps: in a carbon monoxide atmosphere, using an aryl derivative (I) and an iodinated aromatic hydrocarbon (II) as raw materials, and carrying out a carbon-hydrogen carbonylation-decarbonylation arylation tandem reaction in an organic solvent through the combined action of a rhodium catalyst, an additive and a base, to obtain a biaryl compound (III); the aryl derivative (I) includes an indole derivative, an indoline derivative, an arylpyridine and a quinoline; and the reaction formula is as follows:

[0009]

[0010] In the formula, R 1 , R 2 , R3 , R 4 and R 5 Independently selected from one of the following groups: hydrogen, halogen, alkyl, alkoxy, trifluoromethyl, aryl, cyano, nitro, aldehyde, ester;

[0011] Ar is selected from one of the following groups: aryl, heteroaryl;

[0012] DG is selected from one of the following groups: 3-substituted pyridyl, 4-substituted pyridyl, 5-substituted pyridyl, 6-substituted pyridyl, 2-pyrimidinyl, 1-isoquinolyl, N,N-dimethylformyl, N,N-dimethylformamido, pivaloyl, di-tert-butylphosphonyl, p-toluenesulfonyl, N,N-dimethylmethylsulfonyl;

[0013] The amount of the rhodium catalyst added is 0.1-5% of the molar amount of the aromatic derivative (I); the molar ratio of the aromatic derivative (I), iodinated aromatic hydrocarbon, additive and base is 1: (1-1.5): (1-1.5): (1-1.5).

[0014] Preferably, the rhodium catalyst is selected from the following: dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer, bis(hexafluoroantimonate)triacetonitrile(pentamethylcyclopentadienyl)rhodium(III), bis(tetrafluoroborate)triacetonitrile(pentamethylcyclopentadienyl)rhodium(III), bis(trifluoromethanesulfonate)triacetonitrile(pentamethylcyclopentadienyl)rhodium(III), bis(trifluoromethanesulfonate)trihydrate(pentamethylcyclopentadienyl)rhodium(III), rhodium(III) trichloride, rhodium(III) tribromide, rhodium(III) triiodide, rhodium(III) trichloride trihydrate, rhodium(III) trichloride·XH2O, rhodium(III) acetylacetonate, rhodium(III) acetylacetonate, tris(triphenylphosphine) Rhodium(I) chloride, tris(triphenylphosphine)carbonyl rhodium(I) hydride, tetracarbonyl dirhodium(I) dichloride, dicarbonyl acetylacetonato rhodium(I), carbonyl acetylacetonato (triphenylphosphine) rhodium(I), bicyclooctene rhodium(I) chloride dimer, (1,5-cyclooctadiene) rhodium(I) chloride dimer, (1,5-cyclooctadiene) methoxyrhodium(I) dimer, (1,5-cyclooctadiene) hydroxyrhodium(I) dimer, (1,5-cyclooctadiene) trifluoromethanesulfonate rhodium(I) dimer, (1,5-cyclooctadiene) tetrafluoroborate rhodium(I) dimer, bis(acetonitrile)(1,5-cyclooctadiene) rhodium tetrafluoride, carboxylic acid rhodium(II) dimer, carboxylic acid rhodium(III), dodecacarbonyl tetrarhodium, hexadecane hexarhodium.

[0015] Preferably, the additive is selected from one of the following: copper acetate, copper propionate, copper butyrate, copper fluoride, copper trifluoroacetate hydrate, cuprous chloride, cuprous bromide, copper isobutyrate, copper pivalate, adamantane ketone, cuprous iodide, silver chloride, silver carbonate, silver fluoride, silver sulfate, bis(trifluoromethanesulfonyl)imide silver, silver hexafluorophosphate, silver trifluoromethanesulfonate, silver benzoate, silver acetate, silver tetrafluoroborate, silver p-toluenesulfonate, silver oxide, silver methanesulfonate, silver hexafluoroantimonate, silver trifluoroacetate, and silver fluoride.

[0016] Preferably, the base is selected from one of the following inorganic bases or organic bases: lithium carbonate, anhydrous lithium acetate, lithium methoxide, lithium tert-butoxide, sodium carbonate, sodium hydroxide, sodium phenol, sodium trifluoromethanesulfonate, sodium methoxide, sodium tert-butoxide, sodium tert-butoxide, sodium propionate, sodium 2,2,2-trifluoroacetate, sodium ethoxide, sodium bicarbonate, sodium acetate, trisodium phosphate dodecahydrate, disodium hydrogen phosphate dodecahydrate, potassium carbonate, potassium hydroxide, potassium benzoate, potassium tert-butoxide, rubidium carbonate, cesium carbonate, silver carbonate, triethylamine, pyridine, 4-dimethylaminopyridine, DBU (1,8-diazobisspiro[5.4.0]undec-7-ene), and triethylenediamine.

[0017] Preferably, the organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, xylene, o-xylene, m-xylene, p-xylene, mesitylene, 1,4-dioxane, 1,2-dichloroethane, 1,2-dichloromethane, acetonitrile, methyl tert-butyl ether, tetrahydrofuran, N-methylpyrrolidone, triethylamine, ethyl ether, ethylene glycol dimethyl ether, trifluorotoluene, dimethyl sulfoxide and tert-butanol.

[0018] Preferably, the conditions for the hydrocarbon carbonylation / decarbonylation arylation reaction are a pressure of 0.1-0.2 MPa and a temperature of 25-140° C. in a carbon monoxide environment.

[0019] In a second aspect, a rhodium catalyst system is provided for use in the preparation of biaryl compounds by decarbonylation, characterized in that the rhodium catalyst system consists of a rhodium source, an additive and a base, and the molar ratio of the rhodium source, the additive and the base is (0.001~0.05):(1~1.5):(1~1.5).

[0020] Compared with the prior art, the present invention has the following advantages:

[0021] 1. The present invention uses indole derivatives, indoline derivatives, arylpyridine or quinoline derivatives and iodinated aromatic hydrocarbons as raw materials for reaction in a carbon monoxide atmosphere, and generates diaryl ketones in situ through carbon-hydrogen carbonylation and decarbonylation arylation of diaryl ketone intermediates in series, so that biaryl compounds can be prepared efficiently in one pot. The present invention first realizes the in-situ synthesis of diaryl ketone intermediates through carbon-hydrogen carbonylation, and then decarbonylation arylation occurs. Unlike the existing method for preparing biaryl compounds by decarbonation coupling, there is no need to pre-synthesize and separate diaryl ketones as reaction substrates.

[0022] 2. The raw materials of the present invention are cheap and readily available, have strong universality, have high product yield, and the entire process has high atomic economy, which meets the requirements of green chemistry.

[0023] 3. The reaction conditions of the present invention are mild, the process is simple, and the reaction mixture can be separated by simple column chromatography to obtain the biaryl compound in high yield; at the same time, it can be scaled up to gram level, and is easy to realize industrialization. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 The product 3aa obtained in the embodiment of the present invention 1 HNMR spectrum.

[0025] Figure 2 The product 3aa obtained in the embodiment of the present invention 13 CNMR image. DETAILED DESCRIPTION

[0026] The specific implementation modes of the present invention will be further described in detail below in conjunction with the accompanying drawings.

[0027] As mentioned above, in view of the shortcomings of the prior art, the inventors of this case proposed the technical solution of the present invention after long-term research and extensive practice: the method of the present invention realizes the in-situ synthesis of the diaryl ketone intermediate by first performing carbonylation of carbon and hydrogen; and then performing decarbonylation arylation, without the need to synthesize and separate the diaryl ketone as a reaction substrate. The reaction mechanism is as follows:

[0028]

[0029] The present invention is described in detail below by way of examples.

[0030] The present invention provides a method for preparing a biaryl compound. The method comprises the following steps: using an indole derivative, an indoleline derivative, an arylpyridine or quinoline derivative (I) and an iodinated aromatic hydrocarbon (II) as raw materials, and reacting the raw materials with a rhodium catalyst, an additive and a base to produce a carbon-hydrogen carbonylation / decarbonylation arylation reaction in an organic solvent to obtain a compound of the general formula The biaryl compound (III); the reaction formula is as follows:

[0031]

[0032] Where R 1 , R 2 , R 3 , R 4 and R 5 independently selected from the following groups: hydrogen, halogen, alkyl, alkoxy, trifluoromethyl, aryl, cyano, nitro, aldehyde, ester; Ar independently selected from the following groups: aryl, heteroaryl; DG independently selected from the following groups: 2-substituted pyridyl, 3-substituted pyridyl, 4-substituted pyridyl, 5-substituted pyridyl, 6-substituted pyridyl, 2-pyrimidinyl, 1-isoquinolyl, N,N-dimethylformyl, N,N-dimethylformamido, tert-butyl ... Valeryl, di-tert-butylphosphonyl, p-toluenesulfonyl, N,N-dimethylmethylsulfonyl; the amount of the rhodium catalyst added is 0.1-5% of the molar amount of the compound containing the directing group such as indole or indoline; the molar ratio of the compound containing the directing group such as indole or indoline to the iodinated aromatic hydrocarbon is 1:1-1:5; the molar ratio of the compound containing the directing group such as indole or indoline to the additive is 1:1-1:5. The molar ratio of the compound containing the directing group such as indole or indoline to the base is 1:1-1:5.

[0033] Wherein: the rhodium catalyst includes but is not limited to one of the following: dichloro (pentamethylcyclopentadienyl) rhodium (III) dimer, bis (hexafluoroantimonate) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III), bis (tetrafluoroborate) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III), bis (trifluoromethanesulfonate) triacetonitrile (pentamethylcyclopentadienyl) rhodium (III), bis (trifluoromethanesulfonate) trihydrate (pentamethylcyclopentadienyl) rhodium (III), rhodium (III) trichloride, rhodium (III) tribromide, rhodium (III) triiodide, rhodium (III) trichloride trihydrate, rhodium (III) trichloride·XH2O, rhodium (III) acetylacetonate, rhodium (III) acetylacetonate, tris (triphenylphosphine) Rhodium chloride (I), tris(triphenylphosphine)carbonyl rhodium hydride (I), tetracarbonyl dichlororhodium (I), dicarbonyl acetylacetonato rhodium (I), carbonyl acetylacetonato (triphenylphosphine) rhodium (I), dicyclooctene rhodium chloride (I) dimer, (1,5-cyclooctadiene) rhodium chloride (I) dimer, (1,5-cyclooctadiene) methoxy rhodium (I) dimer, (1,5-cyclooctadiene) hydroxyl rhodium (I) dimer, (1,5-cyclooctadiene) trifluoromethanesulfonate rhodium (I) dimer, (1,5-cyclooctadiene) tetrafluoroborate rhodium (I) dimer, bis(acetonitrile)(1,5-cyclooctadiene) rhodium tetrafluoride, carboxylic acid rhodium (II) dimer, carboxylic acid rhodium (III), dodecacarbonyl tetrarhodium, hexadecane hexarhodium. The preferred catalyst is rhodium trichloride (III) trihydrate.

[0034] The additive is selected from one of the following: copper acetate, copper propionate, copper butyrate, copper fluoride, copper trifluoroacetate hydrate, cuprous chloride, cuprous bromide, copper isobutyrate, copper pivalate, adamantane ketone, cuprous iodide, silver chloride, silver carbonate, silver fluoride, silver sulfate, silver bis(trifluoromethanesulfonyl)imide, silver hexafluorophosphate, silver trifluoromethanesulfonate, silver benzoate, silver acetate, silver tetrafluoroborate, silver p-toluenesulfonate, silver oxide, silver methanesulfonate, silver hexafluoroantimonate, silver trifluoroacetate, silver fluoride. The preferred additive is cuprous bromide.

[0035] The base is selected from one of the following inorganic or organic bases: lithium carbonate, anhydrous lithium acetate, lithium methoxide, lithium tert-butoxide, sodium carbonate, sodium hydroxide, sodium phenol, sodium trifluoromethanesulfonate, sodium methoxide, sodium tert-butoxide, sodium tert-butoxide, sodium propionate, sodium 2,2,2-trifluoroacetate, sodium ethoxide, sodium bicarbonate, sodium acetate, trisodium phosphate dodecahydrate, disodium hydrogen phosphate dodecahydrate, potassium carbonate, potassium hydroxide, potassium benzoate, potassium tert-butoxide, rubidium carbonate, cesium carbonate, silver carbonate, triethylamine, pyridine, 4-dimethylaminopyridine, DBU (1,8-diazobisspiro[5.4.0]undec-7-ene), triethylenediamine. The preferred base is sodium carbonate.

[0036] The organic solvent is one, two or more of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, xylene, o-xylene, m-xylene, p-xylene, mesitylene, 1,4-dioxane, 1,2-dichloroethane, 1,2-dichloromethane, acetonitrile, methyl tert-butyl ether, tetrahydrofuran, N-methylpyrrolidone, triethylamine, ether, ethylene glycol dimethyl ether, trifluorotoluene, dimethyl sulfoxide and tert-butyl alcohol. The preferred organic solvent is toluene.

[0037] The hydrocarbon carbonylation / decarbonylation arylation reaction conditions refer to a carbon monoxide environment with a pressure of 0.1-0.2 MPa, preferably 0.1 MPa, and a temperature of 25-140° C., preferably 130° C.

[0038] In some embodiments, the synthesis method may further include: after the hydrocarbon carbonylation / decarbonylation arylation reaction is completed, the obtained reaction mixture is post-treated to separate and obtain the biaryl compound, and the post-treatment includes extraction, washing, drying and column chromatography treatment performed in sequence. The implementation methods of these post-treatments are all known in the art. For example, the reagent for extraction can be ethyl acetate, dichloromethane, ether, etc.; the reagent for washing can be saturated salt water, etc.; the reagent for drying can be anhydrous sodium sulfate, etc.; the eluent for column chromatography separation can be a mixture of ethyl acetate and petroleum ether (the volume ratio of the two can be 1:100 to 1:1), etc.

[0039] In order to make the purpose, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not intended to limit the present invention. In addition, the technical features involved in the various embodiments of the present invention described below can be combined with each other as long as they do not conflict with each other.

[0040] Example 1: Preparation of 7-aryl indole derivative 3aa

[0041] Its synthetic route is as follows:

[0042]

[0043] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3aa. The product was a white solid with a yield of 97%.

[0044] 1 HNMR (400MHz, CDCl3) δ7.92(d,J=4.7Hz,2H),7.33(d,J=7.3Hz,2H),7.26(d,J=7.6Hz,1H),7.23–7 .18(m,1H),7.17–7.02(m,4H),6.32(t,J=4.7Hz,1H),4.43(t,J=7.9Hz,2H),3.14(t,J=7.9Hz,2H).

[0045] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.2,156.6,142.3,141.1,135.0,130.4,129.0,128.0,126.7,126.1,123.8,123.7,111.8,52.2,29.6.

[0046] Example 2: Preparation of 7-aryl indole derivative 3aa

[0047] N-pyrimidinyl indole 1a (5mmol), RhCl3·3H2O (0.05mmol), CuBr (10mmol), Na2CO3 (12.5mmol) and iodobenzene 2a (15mmol) were added to 10mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 48 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3aa. The product was a white solid with a yield of 73%.

[0048] Example 3: Preparation of 7-aryl indole derivative 3aa

[0049] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 110°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 66%.

[0050] Example 4: Preparation of 7-aryl indole derivative 3aa

[0051] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.005 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 91%.

[0052] Example 5: Preparation of 7-aryl indole derivative 3aa

[0053] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.4 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 96%.

[0054] Example 6: Preparation of 7-aryl indole derivative 3aa

[0055] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.4 mmol), Na2CO3 (0.4 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 97%.

[0056] Example 7: Preparation of 7-aryl indole derivative 3aa

[0057] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 12 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 91%.

[0058] Example 8: Preparation of 7-aryl indoleline derivative 3aa

[0059] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.2 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 65%.

[0060] Example 9: Preparation of 7-aryl indole derivative 3aa

[0061] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.005 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 12 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 75%.

[0062] Example 10: Preparation of 7-aryl indole derivative 3aa

[0063] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.005 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 110°C for 12 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 51%.

[0064] Example 11: Preparation of 7-aryl indoleline derivative 3aa

[0065] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.002 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and iodobenzene 2a (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was introduced. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. The reaction solution was cooled to room temperature, the solvent was evaporated, and trimethoxybenzene was added as an internal standard. The NMR yield was 63%.

[0066] Example 12: Preparation of 7-aryl indole derivative 3ab

[0067] Its synthetic route is as follows:

[0068]

[0069] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 2-fluoroiodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ab.

[0070] The product was a colorless oil with a yield of 95%.

[0071] 1 HNMR(400MHz, CDCl3)δ7.96(d,J=4.8Hz,2H),7.31–7.19(m,3H),7.13–7.04(m,2H),6 .97–6.87(m,2H),6.38(t,J=4.8Hz,1H),4.42(t,J=8.0Hz,2H),3.18(t,J=8.0Hz,2H).

[0072] 13 C{ 1 H}NMR(101MHz, CDCl3)δ159.0(d,J=247.5Hz),158.9,156.6,141.8,135.0,130.3(d,J=15.2Hz),129.8(d,J=26.3Hz),129.7(d ,J=32.3Hz),128.1(d,J=8.1Hz),124.3(d,J=5Hz),123.6(d,J=4.0Hz),123.2,115.2,115.1(d,J=22.2Hz),111.8,51.9,29.4.

[0073] HRMS(ESI)m / z:CalculatedforC 18 H 14 FN3[M+H] + :292.1172,found:292.1253.

[0074] Example 13: Preparation of 7-aryl indole derivative 3ac

[0075] Its synthetic route is as follows:

[0076]

[0077] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 3-iodotoluene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3ac. The product was a colorless oil with a yield of 98%.

[0078] 1 HNMR(400MHz, CDCl3)δ7.93(d,J=4.8Hz,2H),7.26(d,J=7.6Hz,1H),7.23–7.17(m,1H),7.18–7.10(m,2H),7.05(dt,J=2 1.4,7.5Hz,2H),6.89(d,J=7.5Hz,1H),6.34(t,J=4.8Hz,1H),4.43(t,J=7.9Hz,2H),3.15(t,J=7.9Hz,2H),2.19(s,3H).

[0079] 13 CNMR(101MHz,CDCl3)δ159.3,156.5,142.1,141.1,137.4,134.9,130.2,1 29.0,127.8,127.4,126.8,123.9,123.7,123.6,111.8,52.2,29.6,21.3.

[0080] Example 14: Preparation of 7-aryl indole derivative 3ad

[0081] Its synthetic route is as follows:

[0082]

[0083] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 3-iodoanisole 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ad. The product was a white solid with a yield of 88%.

[0084] 1 HNMR(400MHz, CDCl3)δ7.98(d,J=4.8Hz,2H),7.28(d,J=7.7Hz,1H),7.26–7.19(m,1H),7.13–7.00(m,2H),6.99– 6.88(m,2H),6.69–6.58(m,1H),6.39(t,J=4.8Hz,1H),4.45(t,J=7.9Hz,2H),3.67(s,3H),3.17(t,J=7.9Hz,2H).

[0085] 13 CNMR(101MHz, CDCl3)δ159.6,159.4,156.6,143.7,141.1,135.1,130.0,129.0,123.9,123.8,119.5,112.5,112.0,111.6,55.3,52.3,29.6.

[0086] Example 15: Preparation of 7-aryl indole derivative 3ae

[0087] Its synthetic route is as follows:

[0088]

[0089] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 2-iodoanisole 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ae. The product was a yellow solid with a yield of 65%.

[0090] 1 HNMR(400MHz, CDCl3)δ7.91(d,J=4.7Hz,2H),7.30–7.16(m,3H),7.15–7.00(m,2H),6.80(td,J=7.4,1.1Hz,1H) ,6.67(dd,J=8.3,1.1Hz,1H),6.33(t,J=4.8Hz,1H),4.37(t,J=7.9Hz,2H),3.64(s,3H),3.16(t,J=7.9Hz,2H).

[0091] 13 C{ 1 H}NMR(101MHz,CDCl3)δ158.5,156.2,155.5,141.5,134.5,131.6,130.3, 129.1,127.7,126.0,123.5,122.7,120.3,111.4,109.9,55.4,51.8,29.3.

[0092] Example 16: Preparation of 7-aryl indole derivative 3af

[0093] Its synthetic route is as follows:

[0094]

[0095] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 2-iodophenyl trifluoromethanesulfonate 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3af. The product was a yellow oil with a yield of 65%.

[0096] 1 HNMR(400MHz, CDCl3)δ7.94(d,J=4.7Hz,2H),7.52(dd,J=7.7,1.8Hz,1H),7.32-7.28(m,2H),7.26–7.15(m ,2H),7.11(t,J=7.5Hz,1H),7.03(dd,J=8.2,1.2Hz,1H),6.37(t,J=4.8Hz,1H),4.43(s,2H),3.18(s,2H).

[0097] 13 C{ 1 H}NMR(101MHz,CDCl3)δ158.6,156.6,146.4,141.6,136.7,135.2,131.0, 130.1,128.0,125.0,123.8,123.3,120.8,120.0,116.8,111.8,51.5,29.1

[0098] Example 17: Preparation of 7-aryl indole derivative 3ag

[0099] Its synthetic route is as follows:

[0100]

[0101] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 3-bromoiodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3ag. The product was a colorless oil with a yield of 77%.

[0102] 1 HNMR(400MHz, CDCl3)δ8.00(d,J=4.8Hz,2H),7.52(s,1H),7.30–7.16(m,4H),7.09(t,J=7.5Hz, 1H), 6.98 (t, J = 7.8Hz, 1H), 6.42 (t, J = 4.8Hz, 1H), 4.45 (t, J = 8.0Hz, 2H), 3.17 (t, J = 7.9Hz, 2H).

[0103] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.7,144.5,141.1,135.2,129.9,129.4,129.0,128.9,128.8,125.4,124.3,123.9,122.0,112.1,52.2,29.5.

[0104] HRMS(ESI)m / z:CalculatedforC 18 H 14 BrN3[M+H] + :352.0371, found:352.0462. Example 18: Preparation of 7-aryl indole derivative 3ah

[0105] Its synthetic route is as follows:

[0106]

[0107] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 3-nitroiodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ah. The product was a yellow solid with a yield of 96%.

[0108] 1 HNMR (400MHz, CDCl3) δ8.24(t,J=1.7Hz,1H),7.95(d,J=4.8Hz,3H),7.65(d,J=7.7Hz,1H),7.36–7.2 3(m,3H),7.14(t,J=7.5Hz,1H),6.40(t,J=4.8Hz,1H),4.49(t,J=8.0Hz,2H),3.19(t,J=7.9Hz,2H).

[0109] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.8,148.3,144.3,141.3,135.5,132.9,128.8,128.7,128.2,124.9,124.2,121.8,121.0,112.4,52.2,29.5.

[0110] Example 19: Preparation of 7-aryl indole derivative 3ai

[0111] Its synthetic route is as follows:

[0112]

[0113] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-iodocyanobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3ai. The product was a white solid with a yield of 85%.

[0114] 1 HNMR(400MHz, CDCl3)δ7.97(d,J=4.8Hz,2H),7.45(s,4H),7.32–7.26(m,1H),7.22(d,J=7.7Hz, 1H), 7.12 (t, J = 7.5Hz, 1H), 6.44 (t, J = 4.8Hz, 1H), 4.46 (t, J = 8.0Hz, 2H), 3.18 (t, J = 8.0Hz, 2H).

[0115] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.7,147.4,141.1,135.4,131.9,128.6,128.6,127.3,124.9,124.0,119.3,112.5,109.4,52.1,29.4.

[0116] Example 20: Preparation of 7-aryl indole derivative 3aj

[0117] Its synthetic route is as follows:

[0118]

[0119] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-iodotrifluorotoluene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3aj. The product was a white solid with a yield of 87%.

[0120] 1 HNMR(400MHz, CDCl3)δ7.94(d,J=4.8Hz,2H),7.43(q,J=8.4Hz,4H),7.26(t,J=7.9Hz,2H), 7.12(t,J=7.5Hz,1H), 6.39(t,J=4.8Hz,1H), 4.46(t,J=8.0Hz,2H), 3.18(t,J=7.9Hz,2H).

[0121] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.6,146.2,141.2,135.2,128.9,128.7,128.6,128.1( q,J=32.3Hz),126.9,124.8(q,J=3.0Hz),124.1(q,J=83.8Hz),120.3,112.1,52.1,29.4.

[0122] Example 21: Preparation of 7-aryl indole derivative 3ak

[0123] Its synthetic route is as follows:

[0124]

[0125] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-bromoiodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ak. The product was a white solid with a yield of 92%.

[0126] 1 HNMR (400MHz, CDCl3) δ7.99 (d, J=4.8Hz, 2H), 7.32–7.15 (m, 6H), 7.09 (t, J=7. 5Hz, 1H), 6.42 (t, J = 4.8Hz, 1H), 4.44 (t, J = 7.9Hz, 2H), 3.16 (t, J = 7.9Hz, 2H).

[0127] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.2,156.7,141.3,141.0,135.2,131.0,129.2,128.7,128.4,124.0,123.9,119.9,112.2,52.2,29.5.

[0128] Example 22: Preparation of 7-aryl indole derivative 3a1

[0129] Its synthetic route is as follows:

[0130]

[0131] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-iodotoluene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3al. The product was a white solid with a yield of 87%.

[0132] 1 HNMR(400MHz, CDCl3) δ7.96(d,J=4.8Hz,2H),7.23(dt,J=10.5,8.2Hz,4H),7.08(t,J=7.5Hz,1H),6. 95(d,J=7.9Hz,2H),6.35(t,J=4.8Hz,1H),4.44(t,J=7.9Hz,2H),3.15(t,J=7.9Hz,2H),2.24(s,3H).

[0133] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.3,156.6,141.1,139.3,135.7,135.0,130.4,129.0,128.6,126.5,123.8,123.4,111.8,52.3,29.6,21.1.

[0134] Example 23: Preparation of 7-aryl indole derivative 3am

[0135] Its synthetic route is as follows:

[0136]

[0137] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-iodobiphenyl 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3am. The product was a yellow solid with a yield of 72%.

[0138] 1 HNMR(400MHz, CDCl3)δ7.95(d,J=4.8Hz,2H),7.58–7.50(m,2H),7.40(d,J=3.3Hz,6H),7.34–7.27(m,2H),7 .26–7.21(m,1H),7.11(t,J=7.5Hz,1H),6.33(t,J=4.8Hz,1H),4.46(t,J=7.9Hz,2H),3.18(t,J=7.9Hz,2H).

[0139] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.3,156.6,141.4,141.2,141.0,138.8,135.1,129. 8,128.9,128.8,127.1,127.1,127.0,126.6,123.8,123.8,111.9,52.2,29.6.

[0140] Example 24: Preparation of 7-aryl indole derivative 3an

[0141] Its synthetic route is as follows:

[0142]

[0143] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 1-tert-butyl-4-iodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain the pure 7-aryl indole derivative 3an. The product was a yellow solid with a yield of 59%.

[0144] 1 HNMR(400MHz, CDCl3)δ7.90(d,J=4.8Hz,2H),7.28(dd,J=7.7,1.3Hz,1H),7.25–7.19(m,3H),7.18–7.13(m, 2H),7.08(t,J=7.5Hz,1H),6.31(t,J=4.8Hz,1H),4.43(t,J=7.9Hz,2H),3.17(t,J=7.9Hz,2H),1.25(s,9H).

[0145] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.4,149.3,141.2,139.3,134.9,130.0,128.8,126.4,124.7,123.7,123.5,111.5,52.2,34.5,31.5,29.6.

[0146] Example 25: Preparation of 7-aryl indole derivative 3ao

[0147] Its synthetic route is as follows:

[0148]

[0149] N-pyrimidinyl indole 1a (0.2 mmol), RhCl3·3H2O (0.01 mmol), CuBr (0.4 mmol), Na2CO3 (0.5 mmol) and 4-nitrobromobenzene 2 (0.6 mmol) were added to 2.0 mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1 atm) was added. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ao. The product was a yellow solid with a yield of 42%.

[0150] 1 HNMR (400MHz, CDCl3) δ8.09–8.01(m,2H),7.98(d,J=4.8Hz,2H),7.57–7.47(m,2H),7.32(dd,J=7.3,1.3Hz,1H) ,7.28–7.22(m,1H),7.15(t,J=7.5Hz,1H),6.43(t,J=4.7Hz,1H),4.49(t,J=8.0Hz,2H),3.21(t,J=8.0Hz,2H).

[0151] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.1,156.8,149.5,146.0,141.2,135.5,128.6,128.2,127.3,125.1,124.1,123.5,112.6,52.1,29.4.

[0152] HRMS(ESI)m / z:CalculatedforC 18 H 14 N4O2[M+H] + :319.1117, found:319.1175. Example 26: Preparation of 7-aryl indole derivative 3ap

[0153] Its synthetic route is as follows:

[0154]

[0155] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 4-iodobenzaldehyde 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3ap. The product was a white solid with a yield of 94%.

[0156] 1 HNMR (400MHz, CDCl3) δ9.90 (s, 1H), 7.94 (d, J = 4.7Hz, 2H), 7.74–7.64 (m, 2H), 7.56–7.47 (m, 2H), 7.33– 7.23(m,2H),7.12(t,J=7.5Hz,1H),6.37(t,J=4.8Hz,1H),4.47(t,J=8.0Hz,2H),3.19(t,J=7.9Hz,2H).

[0157] 13 C{ 1 H}NMR (101MHz, CDCl3) δ192.2,159.0,156.7,149.1,141.2,135.4,134.3,129.8,129.2,128.8,127.3,124.8,124.1,112.4,52.2,29.5.

[0158] HRMS(ESI)m / z:CalculatedforC 19 H 15 N3O[M+H] + :302.1215,found:302.1278.

[0159] Example 27: Preparation of 7-aryl indole derivative 3aq

[0160] Its synthetic route is as follows:

[0161]

[0162] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 1,3-dimethyl-5-iodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3aq. The product was a yellow solid with a yield of 99%.

[0163] 1 HNMR(400MHz, CDCl3)δ7.95(d,J=4.8Hz,2H),7.31–7.15(m,2H),7.07(t,J=7.5Hz,1H),6.95(d,J=1.6 Hz,2H),6.73(s,1H),6.37(t,J=4.8Hz,1H),4.43(t,J=7.9Hz,2H),3.16(t,J=7.9Hz,2H),2.16(s,6H).

[0164] 13 C{ 1 H}NMR(101MHz, CDCl3)δ159.3,156.4,142.0,141.1,137.4,134.9,130.1,129.0,127.6,124.6,123.6,123.5,111.7,52.3,29.6,21.2.

[0165] Example 28: Preparation of 7-aryl indole derivative 3ar

[0166] Its synthetic route is as follows:

[0167]

[0168] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 3,5-bis(trifluoromethyl)iodobenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ar. The product was a yellow solid with a yield of 99%.

[0169] 1 HNMR(400MHz, CDCl3)δ7.94(d,J=4.8Hz,2H),7.78(d,J=1.7Hz,2H),7.62(s,1H),7.32(dt,J=7.5,1.3Hz,1H), 7.30–7.24(m,1H),7.15(t,J=7.5Hz,1H),6.43(t,J=4.8Hz,1H),4.50(t,J=8.0Hz,2H),3.21(t,J=8.0Hz,2H).

[0170] 13 C{ 1 H}NMR(101MHz,CDCl3)δ158.8,156.7,144.7,141.3,135.6,131.3(q,J C-F =33.3Hz),128.6,127.2,127.1,125.2,124.1,123.5(q,J C-F =273.7Hz),119.5(q,J C-F =2.0Hz),112.4,52.2,29.3.

[0171] Example 29: Preparation of 7-aryl indole derivative 3as

[0172] Its synthetic route is as follows:

[0173]

[0174] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 2-iodothiophene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3as. The product was a white solid with a yield of 69%.

[0175] 1 HNMR(400MHz, CDCl3)δ8.12(d,J=4.8Hz,2H),7.37(dd,J=7.7,1.2Hz,1H),7.22(dd,J=7.4,1.3Hz,1H),7.15–7.04(m,2H),6 .94(dd,J=3.6,1.2Hz,1H), 6.79(dd,J=5.1,3.5Hz,1H), 6.50(t,J=4.8Hz,1H), 4.48(t,J=7.9Hz,2H), 3.16(t,J=7.8Hz,2H).

[0176] 13 C{ 1 H}NMR (101MHz, CDCl3) δ160.1,156.9,143.8,141.5,135.5,128.9,126.7,124.2,124.1,124.0,112.3,52.8,29.8.

[0177] Example 30: Preparation of 7-aryl indole derivative 3at

[0178] Its synthetic route is as follows:

[0179]

[0180] N-pyrimidinyl indole 1a (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and 1-iodo-3,4-methylenedioxybenzene 2 (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3at. The product was a white solid with a yield of 85%.

[0181] 1 HNMR(400MHz, CDCl3)δ8.05(d,J=4.8Hz,2H),7.25–7.17(m,2H),7.09(t,J=7.5Hz,1H),6.89(d,J=1.7Hz,1H),6.83(dd,J =8.1,1.7Hz,1H),6.62(d,J=8.0Hz,1H),6.45(t,J=4.8Hz,1H),5.85(s,2H),4.45(t,J=7.9Hz,2H),3.16(t,J=7.9Hz,2H).

[0182] 13 C{ 1 H}NMR(101MHz,CDCl3)δ159.4,156.7,147.4,145.9,141.1,136.5,135.1,1 30.2,128.8,123.9,123.5,120.2,112.0,107.9,107.5,100.7,52.3,29.6.

[0183] Example 31: Preparation of 7-aryl indole derivative 3ba

[0184] Its synthetic route is as follows:

[0185]

[0186] 2-Methyl-N-pyrimidinyl indole 1b (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ba. The product was a white solid with a yield of 99%.

[0187] 1 HNMR (400MHz, CDCl3) δ7.93(d,J=4.8Hz,2H),7.38–7.30(m,2H),7.27(d,J=7.6Hz,1H),7.22(d,J=6.9Hz,1H),7.19–7. 04(m,4H),6.33(t,J=4.8Hz,1H),4.95–4.88(m,1H),3.60–3.38(m,1H),2.62(d,J=15.5Hz,1H),1.54(d,J=6.5Hz,3H).

[0188] 13 C{ 1 H}NMR (101MHz, CDCl3) δ158.8,156.6,142.4,139.6,133.8,130.8,128.9,128.0,126.6,126.0,124.2,123.9,111.8,59.6,36.9,21.2.

[0189] Example 32: Preparation of 7-aryl indole derivative 3ca

[0190] Its synthetic route is as follows:

[0191]

[0192] 2-Phenyl-N-pyrimidinyl indole 1c (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3ca. The product was a white solid with a yield of 97%.

[0193] 1 HNMR(400MHz, CDCl3)δ7.93(d,J=4.8Hz,2H),7.58–7.47(m,2H),7.46–7.39(m,2H),7.39–7.29(m,3H),7.29–7.23(m,1H) ,7.23–7.04(m,5H),6.36(t,J=4.8Hz,1H),5.85(dd,J=9.5,1.6Hz,1H),3.95–3.74(m,1H),3.09(dd,J=15.7,1.7Hz,1H).

[0194] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.5,156.7,144.4,142.6,141.1,133.4,130.7,129. 4,128.8,128.1,127.4,126.9,126.2,125.9,124.3,124.1,112.5,66.7,38.5.

[0195] HRMS(ESI)m / z:CalculatedforC 24 H 19 N3[M+H] + :350.1579,found:350.1663.

[0196] Example 33: Preparation of 7-aryl indole derivative 3da

[0197] Its synthetic route is as follows:

[0198]

[0199] 3-Methyl-N-pyrimidinyl indole 1d (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3da. The product was a colorless oil with a yield of 97%.

[0200] 1 HNMR(400MHz, CDCl3)δ7.97(d,J=4.8Hz,2H),7.42–7.34(m,2H),7.34–7.28(m,1H),7.22(dt,J=7.4,1.3Hz,1H),7.20–7.13(m,3H),7.13– 7.07(m,1H),6.38(t,J=4.8Hz,1H),4.63(dd,J=10.9,8.2Hz,1H),4.01(dd,J=10.8,7.0Hz,1H),3.59–3.38(m,1H),1.38(d,J=6.9Hz,3H).

[0201] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.3,156.63,142.2,140.7,140.2,130.3,129.1,128.0,126.8,126.1,124.0,122.5,111.8,60.1,36.3,19.1.

[0202] Example 34: Preparation of 7-aryl indole derivative 3ea

[0203] Its synthetic route is as follows:

[0204]

[0205] 4-Methyl-N-pyrimidinyl indole 1e (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ea. The product was a white solid with a yield of 96%.

[0206] 1 HNMR(400MHz, CDCl3) δ7.94(dd,J=4.8,2.2Hz,2H),7.38–7.26(m,2H),7.21(td,J=7.7,7.1,2.2Hz,1H),7.13(td,J=7.5,1.9Hz,2H),7.09–7 .01(m,1H),6.94(dd,J=7.9,2.1Hz,1H),6.42–6.28(m,1H),4.45(td,J=8.0,2.2Hz,2H),3.07(td,J=7.9,2.1Hz,2H),2.30(d,J=2.1Hz,3H).

[0207] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.4,156.6,142.4,140.7,133.6,133.2,129.0,128.0,127.9,126.8,125.9,125.0,111.8,52.1,28.4,18.7.

[0208] HRMS(ESI)m / z:CalculatedforC 19 H 17 N3[M+H] + :288.1422,found:288.1482.

[0209] Example 35: Preparation of 7-aryl indole derivative 3fa

[0210] Its synthetic route is as follows:

[0211]

[0212] 4-Chloro-N-pyrimidinyl indole 1f (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3fa. The product was a white solid with a yield of 93%.

[0213] 1 HNMR(400MHz, CDCl3)δ7.97(d,J=4.8Hz,2H),7.37–7.26(m,2H),7.23(d,J=8.3Hz,1H),7.19–7.1 2(m,2H),7.12–7.05(m,2H),6.41(t,J=4.8Hz,1H),4.48(t,J=8.0Hz,2H),3.22(t,J=8.0Hz,2H).

[0214] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.0,156.6,142.3,141.4,133.2,130.5,129.5,128.7,128.1,126.6,126.3,123.6,112.4,51.9,29.0.

[0215] Example 36: Preparation of 7-aryl indole derivative 3ga

[0216] Its synthetic route is as follows:

[0217]

[0218] 1g (0.2mmol) of 5-methoxy-N-pyrimidinyl indole, RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain the pure 7-aryl indole derivative 3ga. The product was a brown solid with a yield of 95%.

[0219] 1 HNMR(400MHz, CDCl3)δ7.95(dd,J=4.8,1.8Hz,2H),7.44–7.32(m,2H),7.18(td,J=7.4,1.8Hz,2H),7.15–7.07(m,1H), 6.89–6.81(m,2H),6.34(td,J=4.7,1.9Hz,1H),4.47(td,J=7.8,1.7Hz,2H),3.84(d,J=1.8Hz,3H),3.20–3.06(m,2H).

[0220] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.5,156.8,156.7,142.2,136.8,134.8,131.3,128.1,126.8,126.4,113.5,111.5,110.4,55.9,52.5,30.1.

[0221] Example 37: Preparation of 7-aryl indole derivative 3ha

[0222] Its synthetic route is as follows:

[0223]

[0224] 5-Bromo-N-pyrimidinyl indole 1h (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain the pure 7-aryl indole derivative 3ha. The product was a white solid with a yield of 94%.

[0225] 1 HNMR(400MHz, CDCl3)δ7.96(d,J=4.8Hz,2H),7.42(d,J=2.0Hz,1H),7.39–7.28(m,3H),7.14 (dt,J=14.3,7.0Hz,3H),6.39(t,J=4.8Hz,1H),4.45(t,J=7.9Hz,2H),3.16(t,J=8.0Hz,2H).

[0226] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.0,156.6,141.0,140.5,137.3,131.9,131.6,128.1,126.7,126.6,116.1,112.3,52.3,29.4.

[0227] Example 38: Preparation of 7-aryl indole derivative 3ia

[0228] Its synthetic route is as follows:

[0229]

[0230] 5-Chloro-N-pyrimidinyl indole 1i (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3ia. The product was a white solid with a yield of 96%.

[0231] 1 HNMR(400MHz, CDCl3)δ7.94(d,J=4.8Hz,2H),7.34–7.27(m,2H),7.25(t,J=2.5Hz,1H), 7.21–7.06(m,4H),6.38(t,J=4.8Hz,1H),4.45(t,J=8.0Hz,2H),3.14(t,J=7.9Hz,2H).

[0232] 13 C{ 1 H}NMR (101MHz, CDCl3) δ157.9,155.4,139.9,135.8,130.2,128.5,128.4,127.9,126.5,126.4,121.5,111.0,51.2,28.3.

[0233] Example 39: Preparation of 7-aryl indole derivatives 3ja and 3ja'

[0234] Its synthetic route is as follows:

[0235]

[0236] N-pyrimidinylcarbazole 1j (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivatives 3ja and 3ja'. The product 3ja was a white solid with a yield of 26%. The product 3ja' was a white solid with a yield of 28%.

[0237] 3ja

[0238] 1 HNMR(400MHz, CDCl3)δ8.30(t,J=4.2Hz,2H),8.11(td,J=7.1,5.7,2.7Hz,3H),7.50-7.43(m, 3H),7.36(td,J=7.6,3.2Hz,1H),7.28-7.24(m,2H),7.14–7.02(m,3H),6.80(q,J=4.5Hz,1H).

[0239] 13 C{ 1 H}NMR (101MHz, CDCl3) δ157.6,157.3,141.4,140.9,137.1,128.7,128.5,128. 1,127.6,126.9,126.8,126.2125.2,122.4,122.1,120.2,119.3,117.1,112.2.

[0240] 3ja'

[0241] 1 HNMR (400MHz, CDCl3) δ8.22(dd,J=7.7,1.4Hz,2H),7.78(d,J=4.8Hz,2H),7.39(t,J =7.5Hz,2H),7.32(dd,J=7.4,1.3Hz,2H),7.03–6.89(m,10H),6.52(t,J=4.8Hz,1H).

[0242] 13 C{ 1H}NMR (101MHz, CDCl3) δ157.5,156.5,140.4,137.3,129.5,128.4,127.7,126.9,125.7,125.0,120.7,119.4,118.2.

[0243] Example 40: Preparation of 7-aryl indole derivative 3ka

[0244] Its synthetic route is as follows:

[0245]

[0246] 5-Nitro-N-pyrimidinyl indole 1k (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added and reacted in an oil bath at 130℃ for 24 hours. The reaction was stopped and the reaction solution was cooled to room temperature. Ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3ka. The product was a yellow solid with a yield of 64%.

[0247] 1 HNMR(400MHz, CDCl3) δ8.21(d,J=2.4Hz,1H),8.08(dd,J=2.5,1.3Hz,1H),8.00(d,J=4.8Hz,2H),7.31 –7.21(m,2H),7.20–7.08(m,3H),6.52(t,J=4.8Hz,1H),4.52(t,J=8.2Hz,2H),3.29(t,J=8.2Hz,2H).

[0248] 13 C{ 1 H}NMR (101MHz, CDCl3) δ158.3,156.6,147.1,143.3,140.2,136.0,128.9,128.2,127.0,126.5,126.3,119.1,113.6,52.7,28.5.

[0249] Example 41: Preparation of 7-aryl indole derivative 31a

[0250] Its synthetic route is as follows:

[0251]

[0252] 5-Fluoro-N-pyrimidinyl indole 1l (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130°C for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 7-aryl indole derivative 3la. The product was a white solid with a yield of 97%.

[0253] 1 HNMR(400MHz, CDCl3)δ7.96(d,J=4.8Hz,2H),7.40–7.31(m,2H),7.20–7.08(m,3H),7 .04–6.92(m,2H),6.38(t,J=4.8Hz,1H),4.48(t,J=7.9Hz,2H),3.15(t,J=7.8Hz,2H).

[0254] 13 C{ 1 H}NMR(101MHz, CDCl3)δ159.8(d,J=242.4Hz),159.3,156.6,141.2,137.2(d,J=2.0Hz),137.1(d,J=9.1Hz ), 131.6 (d, J = 8.1Hz), 128.1, 126.6, 126.6, 115.0 (d, J = 24.2Hz), 111.9, 110.9 (d, J = 24.2Hz), 52.5, 29.9.

[0255] Example 42: Preparation of 7-aryl indole derivative 3ma

[0256] Its synthetic route is as follows:

[0257]

[0258] 6-Chloro-N-pyrimidinyl indole 1m (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3ma. The product was a white solid with a yield of 52%.

[0259] 1 HNMR(400MHz, CDCl3)δ7.95(d,J=4.7Hz,2H),7.36–7.27(m,2H),7.22–7.11(m,4H), 7.11–7.03(m,1H),6.38(t,J=4.8Hz,1H),4.40(t,J=7.9Hz,2H),3.16–3.09(m,2H).

[0260] 13 C{ 1 H}NMR (101MHz, CDCl3) δ158.9,156.6,143.7,138.3,133.9,132.3,129.6,128.7,127.4,126.8,124.7,124.4,112.2,53.2,29.4.

[0261] Example 43: Preparation of 7-aryl indole derivative 3na

[0262] Its synthetic route is as follows:

[0263]

[0264] 6-Fluoro-N-pyrimidinyl indole 1n (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 7-aryl indole derivative 3na. The product was a white solid with a yield of 72%.

[0265] 1 HNMR(400MHz, CDCl3)δ7.94(d,J=4.8Hz,2H),7.32(dt,J=8.2,1.5Hz,2H),7.22–7.05(m,4H), 6.82(dd,J=10.4,8.2Hz,1H), 6.38(t,J=4.8Hz,1H), 4.45(t,J=8.0Hz,2H), 3.18–3.08(m,2H).

[0266] 13 C{ 1 H} NMR (101MHz, CDCl3) δ 159.6 (d, J = 243.4Hz), 158.8, 156.5, 143.1 (d, J = 7.1Hz), 135.3, 130.2 (d, J = 3.0Hz), 128. 6(d,J=2.0Hz),127.7,126.7,124.0(d,J=10.1Hz),118.5(d,J=19.2Hz),112.2,110.1(d,J=24.2Hz),53.2,29.1.

[0267] Example 44: Preparation of 2-aryl indole derivative 3oa

[0268] Its synthetic route is as follows:

[0269]

[0270] N-pyrimidinyl indole 1o (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 2-aryl indole derivative 3oa. The product was a white solid with a yield of 69%.

[0271] 1 HNMR(400MHz, CDCl3)δ8.61(d,J=4.8Hz,2H),8.16–8.08(m,1H),7.69–7.59( m,1H),7.36–7.18(m,7H),7.03(td,J=4.8,1.1Hz,1H),6.80(d,J=1.1Hz,1H).

[0272] 13 C{ 1 H}NMR (101MHz, CDCl3) δ158.3,158.2,140.6,138.2,134.0,129.4,128.2,127.2,123.7,122.2,120.8,117.7,112.9,108.3.

[0273] Example 45: Preparation of 2-arylpyridine derivative 3pa

[0274] Its synthetic route is as follows:

[0275]

[0276] Phenylpyridine 1p (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 130℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain the pure 2-arylpyridine derivative 3pa. The product was a white solid with a yield of 72%.

[0277] 1 HNMR (400MHz, CDCl3) δ8.62(dt,J=4.9,1.3Hz,1H),7.69(dt,J=7.1,3.5Hz,1H),7.45(tt,J=5.8,2.9Hz,3H),7.36(t d,J=7.7,1.8Hz,1H),7.22(dd,J=5.3,1.9Hz,3H),7.16(dt,J=6.7,2.2Hz,2H),7.1–7.06(m,1H),6.92–6.82(m,1H).

[0278] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.3,149.5,141.4,140.7,139.6,135.3,130.6,129.8,128.6,128.2,127.7,126.8,125.5,121.4.

[0279] Example 46: Preparation of 2-arylisoquinoline derivative 3qa

[0280] Its synthetic route is as follows:

[0281]

[0282] Naphthylisoquinoline 1q (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol), Na2CO3 (0.5mmol) and iodobenzene 2a (0.6mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added. After reacting in an oil bath at 150℃ for 24 hours, the reaction was stopped. After the reaction solution was cooled to room temperature, ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10-1:1) was performed to obtain pure 2-arylisoquinoline derivative 3qa. The product was a yellow solid with a yield of 70%.

[0283] 1 HNMR (400MHz, CDCl3) δ8.55(d,J=5.7Hz,1H),8.05(d,J=8.5Hz,1H),7.90(d,J=8.2Hz,1H) ,7.71(d,J=8.3Hz,1H),7.57(d,J=8.5Hz,1H),7.53(d,J=5.7Hz,1H),7.50(td,J=7.5Hz,1. 3Hz,1H),7.45(td,J=7.4,1.1Hz,1H),7.40(d,J=8.4Hz,1H),7.30(td,J=7.6Hz,1.3Hz,1H) ,7.22(td,7.2Hz,1.0Hz,1H),7.20(d,J=8.6Hz,1H),7.16-7.11(m,2H),7.07-6.99(m,3H).

[0284] 13 C{ 1 H}NMR (101MHz, CDCl3): δ161.0,143.0,140.3,137.3,136.9,133.3,133.8,132.8,130.9,129. 3,128.8,128.6,128.0,127.9,127.5,127.3,127.0,126.7,126.5,126.4,126.3,125.8,122.0.

[0285] Example 47: Preparation of 7-aryl indoleline derivative 3aa

[0286] Its synthetic route is as follows:

[0287]

[0288] N-pyrimidinyl indole derivative 1r (0.2mmol), RhCl3·3H2O (0.01mmol), CuBr (0.4mmol) and Na2CO3 (0.5mmol) were added to 2.0mL of toluene. After replacing carbon monoxide three times in a Young's tube, carbon monoxide (1atm) was added and reacted in an oil bath at 130℃ for 24 hours. The reaction was stopped and the reaction solution was cooled to room temperature. Ethyl acetate and saturated brine were added for multiple washing and extraction. Anhydrous sodium sulfate was added to the organic phase for drying and filtration. The solvent was evaporated and column chromatography with ethyl acetate / petroleum ether (1:10~1:1) was performed to obtain pure 7-aryl indole derivative 3aa. The product was a white solid with a yield of 84%.

[0289] 1 HNMR (400MHz, CDCl3) δ7.92(d,J=4.7Hz,2H),7.33(d,J=7.3Hz,2H),7.26(d,J=7.6Hz,1H),7.23–7 .18(m,1H),7.17–7.02(m,4H),6.32(t,J=4.7Hz,1H),4.43(t,J=7.9Hz,2H),3.14(t,J=7.9Hz,2H).

[0290] 13 C{ 1 H}NMR (101MHz, CDCl3) δ159.2,156.6,142.3,141.1,135.0,130.4,129.0,128.0,126.7,126.1,123.8,123.7,111.8,52.2,29.6.

Claims

1. A method for preparing a biaryl compound, characterized in that: The method is to use an aryl derivative (I) and an iodinated aromatic hydrocarbon (II) as raw materials in a carbon monoxide atmosphere, and to carry out a carbon-hydrogen carbonylation-decarbonylation arylation cascade reaction in an organic solvent through the combined action of a rhodium catalyst, an additive and a base to obtain a biaryl compound (III); the reaction formula is as follows: In the formula, R 1 , R 2 , R 3 , R 4 and R 5 Independently selected from one of the following groups: hydrogen, halogen, alkyl, alkoxy, trifluoromethyl, aryl, cyano, nitro, aldehyde, ester; Ar is selected from one of the following groups: aryl, heteroaryl; DG is selected from one of the following groups: 3-substituted pyridyl, 4-substituted pyridyl, 5-substituted pyridyl, 6-substituted pyridyl, 2-pyrimidinyl, 1-isoquinolyl, N,N-dimethylformyl, N,N-dimethylformamido, pivaloyl, di-tert-butylphosphonyl, p-toluenesulfonyl, N,N-dimethylmethylsulfonyl; The amount of the rhodium catalyst added is 0.1-5% of the molar amount of the aryl derivative (I); the molar ratio of the aryl derivative (I), iodinated aromatic hydrocarbon, additive and base is 1: (1-1.5): (1-1.5): (1-1.5); The rhodium catalyst is rhodium (III) chloride; The additive is selected from cuprous chloride, cuprous bromide and cuprous iodide.

2. The preparation method according to claim 1, characterized in that: The base is selected from one of the following inorganic bases or organic bases: lithium carbonate, anhydrous lithium acetate, lithium methoxide, lithium tert-butoxide, sodium carbonate, sodium hydroxide, sodium phenol, sodium trifluoromethanesulfonate, sodium methoxide, sodium tert-butoxide, sodium propionate, sodium 2,2,2-trifluoroacetate, sodium ethoxide, sodium bicarbonate, sodium acetate, trisodium phosphate dodecahydrate, disodium hydrogen phosphate dodecahydrate, potassium carbonate, potassium hydroxide, potassium benzoate, potassium tert-butoxide, rubidium carbonate, cesium carbonate, silver carbonate, triethylamine, pyridine, 4-dimethylaminopyridine, DBU (1,8-diazobisspiro[5.4.0]undec-7-ene), and triethylenediamine.

3. The preparation method according to claim 1, characterized in that: The organic solvent is one or more of N,N-dimethylformamide, N,N-dimethylacetamide, toluene, o-xylene, m-xylene, p-xylene, mesitylene, 1,4-dioxane, 1,2-dichloroethane, dichloromethane, acetonitrile, methyl tert-butyl ether, tetrahydrofuran, N-methylpyrrolidone, triethylamine, ethyl ether, ethylene glycol dimethyl ether, trifluorotoluene, dimethyl sulfoxide and tert-butyl alcohol.

4. The preparation method according to claim 1, characterized in that: The reaction conditions of the hydrocarbon carbonylation-decarbonylation arylation tandem reaction are a carbon monoxide environment, a pressure of 0.1-0.2 MPa, and a temperature of 25-140° C.

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