A method for preparing an amido phenethyl alcohol compound by structural reorganization of an indole compound

Abstract

The present application relates to the technical field of organic synthesis, and in particular to a method for preparing amido phenethyl alcohol compounds by structural reorganization of indole compounds. The method for preparing amido phenethyl alcohol compounds by structural reorganization of indole compounds provided by the present application uses borane compounds as a reducing agent, reduces indole compounds to generate benzazaborinine, and then further opens the ring and oxidizes to generate amido phenethyl alcohol compounds by sodium borate tetrahydrate. The structural reorganization of indole compounds successfully realizes the efficient synthesis of a series of amido phenethyl alcohol compounds, and the reaction process has few by-products, high selectivity and high yield of amido phenethyl alcohol compounds, and simple subsequent separation and purification. Moreover, the method provided by the present application is simple in process, green and environmentally friendly, simple in operation, low in cost, high in safety, and suitable for industrial production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of organic synthesis, and particularly relates to a method for preparing amido phenethyl alcohol compounds by structural reformation of indole compounds. BACKGROUND

[0002] Indole compounds are widely present in natural products, pesticide chemicals and pharmaceutical chemicals with biological activity, and chemists have been committed to developing new systems for conversion of indole compounds. Although remarkable achievements have been made, most of the catalytic systems remain unchanged indole skeleton, for example, carbon-hydrogen bond functionalization of indole compounds, which greatly expands the complexity of indole skeleton, but it is still highly challenging to realize change of indole skeleton and preparation of new compounds by editing and reformation of indole core skeleton.

[0003] The amido phenethyl alcohol compounds have potential drug activity, and currently there is no report on effective synthesis method thereof. SUMMARY

[0004] In view of this, the present application aims to provide a method for preparing amido phenethyl alcohol compounds by structural reformation of indole compounds, which successfully realizes efficient synthesis of a series of amido phenethyl alcohol compounds by structural reformation of indole compounds, and the product has high yield.

[0005] In order to achieve the above-mentioned application purposes, the present application provides the following technical scheme:

[0006] The present application provides a method for preparing amido phenethyl alcohol compounds by structural reformation of indole compounds, comprising the following steps:

[0007] Mixing indole compounds and borane compounds, and performing a reduction reaction in a protective atmosphere to obtain benzazaborinide;

[0008] Mixing the benzazaborinide and sodium perborate tetrahydrate, and performing an open ring oxidation reaction to obtain amido phenethyl alcohol compounds.

[0009] Preferably, the indole compounds have the structure shown in formula 1:

[0010]

[0011] In formula 1, R 1 include one or more of phenyl, alkyl, cycloalkyl, naphthyl, benzodioxyl, benzodioxolyl, substituted aryl and substituted alkyl; R 2 include one or more of hydrogen, alkyl, methoxy, amino and halogen.

[0012] Preferably, the substituent in the substituted aryl group comprises one or more of methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and Preferably, the substituent in the substituted aryl group comprises one or more of methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and

[0013] Preferably, the substituent in the substituted aryl group comprises one or more of methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and

[0014] Preferably, the borane compound is used in the form of a tetrahydrofuran solution of the borane compound, and the concentration of the tetrahydrofuran solution of the borane compound is 2 mol / L.

[0015] Preferably, the borane compound comprises a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex.

[0016] Preferably, the molar ratio of the indole compound to the borane compound is 1:3-5.

[0017] Preferably, the temperature of the reduction reaction is 80-140°C, and the time is 12-24 h.

[0018] Preferably, the molar ratio of the benzazaborine to the sodium perborate tetrahydrate is 1:3-5.

[0019] Preferably, the temperature of the ring-opening oxidation reaction is 30-40°C, and the time is 4-6 h.

[0020] The method for preparing an amido phenethyl alcohol compound by structural reorganization of an indole compound provided by the present application uses a borane compound as a reducing agent, boronizes and reduces an indole compound to generate a benzazaborine, and further ring-opening oxidizes the benzazaborine with sodium perborate tetrahydrate to generate an amido phenethyl alcohol compound. The method successfully realizes the efficient synthesis of a series of amido phenethyl alcohol compounds, and has the advantages of less by-products, high selectivity and high yield of the amido phenethyl alcohol compound, and simple subsequent separation and purification. Moreover, the method provided by the present application has the advantages of simple process, green environmental protection, simple operation, low cost, high safety and suitability for industrial production. DETAILED DESCRIPTION

[0021] The method for preparing an amido phenethyl alcohol compound by structural reorganization of an indole compound provided by the present application has the characteristics that it comprises the following steps:

[0022] Mixing the indole compound and the borane compound, and performing a reduction reaction in a protective atmosphere to obtain a benzazaborine;

[0023] Mixing the benzazaborine and sodium perborate tetrahydrate, and performing a ring-opening oxidation reaction to obtain an amido phenethyl alcohol compound.

[0024] The raw materials used in the present application are commercially available unless otherwise specified.

[0025] The indole compound and borane compound are mixed, and the reduction reaction is carried out in a protective atmosphere to obtain a benzazaborine.

[0026] In the present application, the indole compound preferably has the structure shown in Formula 1:

[0027]

[0028] In the present application, R 1 one or more of phenyl, alkyl, naphthyl, benzo dioxyl, benzo dioxolyl, substituted aryl and substituted alkyl. In the present application, the alkyl preferably includes methyl, benzyl or long chain alkyl, and the long chain alkyl is preferably C8 alkyl. In the present application, the substituent of the substituted aryl preferably includes phenyl or naphthyl; the substituent of the substituted aryl preferably includes one or more of methyl, t-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and alkyl alcohol preferably includes C2 alkyl alcohol; when the substituent or the substituents of the substituted aryl are two or more of the above substituents, the present application does not have a special limitation on the specific position of the different types of substituents. In the present application, the substituent of the substituted alkyl preferably includes one or more of aryl, alkyl, methoxy and naphthyl, and the aryl preferably includes phenyl; the alkyl of the alkyl and the substituted alkyl is independently preferably C1-C8 alkyl, and more preferably methyl or 1-octyl; when the substituent of the substituted alkyl is two or more of the above substituents, the present application does not have a special limitation on the specific position of the different types of substituents. In the present application, R 2 preferably includes one or more of hydrogen, alkyl, methoxy, amino and halogen; the alkyl preferably includes methyl; the halogen preferably includes fluorine, chlorine, bromine or iodine; and R 2 is preferably on the benzene ring or the heterocycle of Formula 2.

[0029] In the present application, the indole compound preferably includes 1-phenyl-1H-indole, 1-(p-tolyl)-1H-indole, 1-(4-(tert-butyl)phenyl)-1H-indole, 1-(4-methoxyphenyl)-1H-indole, 1-(4-phenoxyphenyl)-1H-indole, 1-(4-(methylthio)phenyl)-1H-indole, 1-([1,1'-biphenyl]-4-yl)-1H-indole, 1-(4-fluorophenyl)-1H-indole, 1-(4-bromophenyl)-1H-indole, 1-(4-(trifluoromethyl)phenyl)-1H-indole, 2-(4-(1H-indol-1-yl)phenyl)ethan-1-ol, 1-(2-naphthyl)-1H-indole, 1-(1,2-methylenedioxyphenyl)-1H-indole, 1-(2,3-dihydrobenzo[b][1,4]dioxan-6-yl)-1H-indole, 6-methyl-1-phenyl-1H-indole, 5-methoxy-1-phenyl-1H-indole, 6-fluoro-1-phenyl-1H-indole, 5-fluoro-1-phenyl-1H-indole, 5-chloro-1-phenyl-1H-indole, 5-bromo-1-phenyl-1H-indole, 5-iodo-1-phenyl-1H-indole, 1-phenyl-1H-indol-5-amine, 3-methyl-1-phenyl-1H-indole, 1-methyl-1H-indole, 1-benzyl-1H-indole, 1-octyl-1H-indole, 5,6-dihydro-4H-pyrrolo[3,2-1-ij]quinoline, or 1-((7-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)naphthalen-2-yl)methyl)-1H-indole.

[0030] In the present application, the borane compound is preferably used in the form of a tetrahydrofuran solution of the borane compound, and the molar concentration of the tetrahydrofuran solution of the borane compound is preferably 2 mol / L. In the present application, the borane compound preferably includes borane dimethyl sulfide complex and / or borane tetrahydrofuran complex.

[0031] In the present application, the molar ratio of the indole compound to the borane compound is preferably 1:3 to 5, more preferably 1:3.5 to 4.5, and further preferably 1:4.

[0032] The mixing in the present application is not particularly limited, and the raw materials can be mixed uniformly by using a mixing method well known to those skilled in the art, such as stirring mixing.

[0033] In the present application, the temperature of the reduction reaction is preferably 80 to 140°C, and more preferably 90 to 100°C, and the time of the reduction reaction is preferably 12 to 24 h, and more preferably 12 to 15 h. In the present application, the protective atmosphere preferably includes nitrogen, argon, or helium, and the pressure of the protective atmosphere is preferably 1 atm.

[0034] In the present application, the benzazaboride preferably has the structure shown in Formula 2:

[0035]

[0036] R 1 and R 2 are preferably the same as R 1 and R 2 in the Formula 1, which are not repeated here.

[0037] In the present application, the reaction formula of the reduction reaction is as follows:

[0038]

[0039] After the reduction reaction, the present application preferably further comprises cooling the obtained reduction reaction solution to room temperature, and then performing a subsequent ring-opening oxidation reaction.

[0040] After obtaining the benzazaboride, the present application mixes the benzazaboride with sodium perborate tetrahydrate to perform a ring-opening oxidation reaction, thereby obtaining an amine-based phenethyl alcohol compound.

[0041] In the present application, the molar ratio of the benzazaboride to sodium perborate tetrahydrate is preferably 1:3-5, and more preferably 1:4-5.

[0042] The mixing in the present application is not particularly limited, and any mixing method known to those skilled in the art can be used to mix the raw materials uniformly, such as stirring mixing.

[0043] In the present application, the temperature of the ring-opening oxidation reaction is preferably 30-40°C, and more preferably 35-40°C, and the time of the ring-opening oxidation reaction is preferably 4-6h, and more preferably 4-5h. In the present application, the solvent used in the ring-opening oxidation reaction preferably includes a tetrahydrofuran aqueous solution, and the volume ratio of tetrahydrofuran to water in the tetrahydrofuran aqueous solution is preferably 1:1-1.2, and more preferably 1:1. The amount-of-substance ratio of the boron-nitrogen heterocyclic compound to the volume of the solvent is preferably 1 mmol:5-20 mL, and more preferably 1 mmol:10-15 mL.

[0044] After the ring-opening oxidation reaction, the application preferably further comprises purifying the obtained ring-opening oxidation reaction solution by silica gel column chromatography after cooling to room temperature, and concentrating the obtained eluent to constant weight to obtain the amine-based phenethyl alcohol compound. In the application, the eluent used in the silica gel column chromatography is preferably a petroleum ether-ethyl acetate mixed solvent, and the volume ratio of petroleum ether to ethyl acetate in the petroleum ether-ethyl acetate mixed solvent is preferably 1:1 to 10:1, more preferably 2:1 to 8:1, and further preferably 4:1 to 5:1. The application does not have any special limitation on the concentration, and any concentration method known to those skilled in the art can be used, such as rotary evaporation under reduced pressure.

[0045] In the application, the amine-based phenethyl alcohol compound has the structure shown in Formula 3:

[0046]

[0047] R 1 and R 2 are preferably the same as R 1 and R 2 in Formula 1, which will not be described here again.

[0048] In the application, the reaction formula of the ring-opening oxidation reaction is as follows:

[0049]

[0050] The technical solutions in the application will be described clearly and completely in combination with the embodiments in the application. Obviously, the described embodiments are only some of the embodiments of the application, but not all the embodiments. Based on the embodiments in the application, all other embodiments obtained by those skilled in the art without creative labor fall within the protection scope of the application.

[0051] In the following embodiments, all indole compounds are prepared according to the published literature (Tetrahedron 2011, 67, 5282-5288. Synthesis 2008, 2008(11), 1707-1716), and other raw materials are commercially available products known to those skilled in the art.

[0052] In the following embodiments of the application, 1 In H NMR, when the number of hydrogens does not correspond to the structural formula, it is because the hydrogens on the amino group and the hydrogens on the hydroxyl group are not easy to observe on the hydrogen spectrum.

[0053] Example 1

[0054] A 15 mL pressure tube was charged with 1-phenyl-1H-indole (denoted as 1a, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3a. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3a (2-(2-(phenylamino)phenyl)ethan-1-ol, separation yield 82%).

[0055] The chemical reaction formula of the above preparation process is:

[0056]

[0057] The product characterization data are as follows: 1 H NMR (400 MHz, Chloroform-d) δ 7.34-7.27 (m, 1H), 7.24-7.11 (m, 4H), 6.96 (dd, J = 7.4, 1.2 Hz, 1H), 6.94-6.88 (m, 2H), 6.84 (tt, J = 7.3, 1.1 Hz, 1H), 3.87 (t, J = 5.9 Hz, 2H), 2.84 (t, J = 5.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 144.5, 142.2, 131.0, 131.0, 129.4, 127.5, 122.4, 120.1, 120.0, 116.9, 64.5, 34.9.

[0058] Example 2

[0059] A 15 mL pressure tube was charged with 1-phenyl-1H-indole (denoted as 1a, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3a. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3a (2-(2-(phenylamino)phenyl)ethan-1-ol, separation yield 82%).

[0060] The chemical reaction formula of the above preparation process is:

[0061]

[0062] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.34-7.27 (m, 1H), 7.24-7.11 (m, 4H), 6.96 (dd, J = 7.4, 1.2 Hz, 1H), 6.94-6.88 (m, 2H), 6.84 (tt, J = 7.3, 1.1 Hz, 1H), 3.87 (t, J = 5.9 Hz, 2H), 2.84 (t, J = 5.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 144.5, 142.2, 131.0, 131.0, 129.4, 127.5, 122.4, 120.1, 120.0, 116.9, 64.5, 34.9.

[0063] Example 3

[0064] 1-phenyl-1H-indole (denoted as 1a, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added into 15 mL pressure-resistant reaction tubes respectively, stirred at 80°C under argon (1 atm) atmosphere for 12 h, after the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, stirred at 40°C for 4 h, to obtain a product system containing the compound shown in formula 3a. Then mesitylene was added as an internal standard, and the nuclear magnetic yield was 24%.

[0065] The chemical reaction formula of the above preparation process is:

[0066]

[0067] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.34-7.27 (m, 1H), 7.24-7.11 (m, 4H), 6.96 (dd, J = 7.4, 1.2 Hz, 1H), 6.94-6.88 (m, 2H), 6.84 (tt, J = 7.3, 1.1 Hz, 1H), 3.87 (t, J = 5.9 Hz, 2H), 2.84 (t, J = 5.9 Hz, 2H). 13C NMR (101 MHz, Chloroform-d) δ 144.5, 142.2, 131.0, 131.0, 129.4, 127.5, 122.4, 120.1, 120.0, 116.9, 64.5, 34.9.

[0068] Example 4

[0069] A 15 mL pressure tube was charged with 1-(p-tolyl)-1H-indole (denoted as 1b, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under argon (1 atm) atmosphere, after the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (tetrahydrofuran and water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3b. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted with petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3b (2-(2-(p-tolylamino)phenyl)ethan-1-ol, separation yield 95%).

[0070] The chemical reaction formula of the above preparation process is:

[0071]

[0072] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.25 (dd, J = 8.0, 1.1 Hz, 1H), 7.14 (qd, J = 7.6, 1.5 Hz, 2H), 7.07-7.00 (m, 2H), 6.92 (td, J = 7.4, 1.2 Hz, 1H), 6.89-6.83 (m, 2H), 3.90 (t, J = 5.9 Hz, 2H), 2.85 (t, J = 5.9 Hz, 2H), 2.28 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 142.9, 141.7, 131.0, 130.0, 129.9, 129.8, 127.5, 121.8, 119.0, 117.9, 64.5, 34.9, 20.7.

[0073] Example 5

[0074] A 15 mL pressure-resistant reaction tube was added with 1-(4-(tert-butyl)phenyl)-1H- indole (denoted as 1c, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100°C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, and sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40°C for 4 h to obtain a product system containing a compound with a structure shown in formula 3c. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted with petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound with a structure shown in formula 3c (2-(2-((4-(tert-butyl)phenyl)amino)phenyl)ethan-1-ol, separation yield 84%).

[0075] The chemical reaction formula of the above preparation process is:

[0076]

[0077] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.30 (dd, J = 8.0, 0.9 Hz, 1H), 7.27-7.20 (m, 2H), 7.19-7.09 (m, 2H), 6.95-6.86 (m, 3H), 3.90 (t, J = 5.9 Hz, 2H), 2.85 (t, J = 5.9 Hz, 2H), 1.30 (s, 9H). 13 C NMR (101 MHz, Chloroform-d) δ 143.2, 142.7, 141.7, 131.0, 130.1, 127.5, 126.2, 121.9, 119.3, 117.2, 64.5, 34.9, 34.2, 31.6.

[0078] Example 6

[0079] A 15 mL pressure-resistant reaction tube was charged with 1-(4-methoxyphenyl)-1H-indole (denoted as 1d, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound with the structure shown in formula 3d. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound with the structure shown in formula 3d (2-(2-((4-methoxyphenyl)amino)phenyl)ethan-1-ol, separation yield 78%).

[0080] The chemical reaction formula of the above preparation process is:

[0081]

[0082] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.14 (d, J = 7.3 Hz, 1H), 7.12-7.07 (m, 2H), 6.98-6.90 (m, 2H), 6.90-6.85 (m, 1H), 6.85-6.79 (m, 2H), 3.92 (t, J = 5.9 Hz, 2H), 3.77 (s, 3H), 2.86 (t, J = 5.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 154.6, 144.0, 137.2, 131.0, 128.6, 127.6, 120.9, 120.9, 117.3, 114.8, 64.3, 55.8, 34.9.

[0083] Example 7

[0084] A 15 mL pressure tube was charged with 1-(4-phenoxyphenyl)-1H-indole (denoted as 1e, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3e. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3e (2-(2-((4-phenoxyphenyl)amino)phenyl)ethan-1-ol, separation yield 66%).

[0085] The chemical reaction formula of the above preparation process is:

[0086]

[0087] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.33-7.24 (m, 3H), 7.15 (ddd, J = 9.4, 7.7, 2.4 Hz, 2H), 7.07-7.00 (m, 1H), 6.98 (d, J = 1.1 Hz, 1H), 6.97-6.96 (m, 1H), 6.93 (s, 5H), 3.92 (t, J = 5.8 Hz, 2H), 2.87 (t, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 158.6, 150.2, 143.0, 140.4, 131.1, 130.1, 129.7, 127.6, 122.5, 121.9, 120.8, 119.1, 118.8, 117.8, 64.6, 34.9.

[0088] Example 8

[0089] A 15 mL pressure-resistant reaction tube was added with 1-(4-(methylthio)phenyl)-1H-indole (denoted as 1f, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100°C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, and sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40°C for 4 h to obtain a product system containing a compound with a structure shown in formula 3f. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound with a structure shown in formula 3f (2-(2-((4-(methylthio)phenyl)amino)phenyl)ethan-1-ol, separation yield 62%).

[0090] The chemical reaction formula of the above preparation process is:

[0091]

[0092] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.29 (dd, J = 8.1, 1.3 Hz, 1H), 7.23-7.12 (m, 4H), 6.97 (td, J = 7.4, 1.3 Hz, 1H), 6.91-6.83 (m, 2H), 3.92 (t, J = 5.7 Hz, 2H), 2.85 (t, J = 5.8 Hz, 2H), 2.43 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 143.1, 142.0, 131.1, 131.0, 130.5, 127.5, 127.5, 122.6, 120.0, 117.5, 64.7, 34.8, 18.4.

[0093] Example 9

[0094] A 15 mL pressure tube was charged with 1-([1,1'-biphenyl]-4-yl)-1H-indole (denoted as 1g, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3g. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3g (2-(2-([1,1'-biphenyl]-4-ylamino)phenyl)ethan-1-ol, separation yield 87%).

[0095] The chemical reaction formula of the above preparation process is:

[0096]

[0097] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.57-7.51 (m, 2H), 7.49-7.42 (m, 2H), 7.42-7.34 (m, 3H), 7.29-7.23 (m, 1H), 7.23-7.13 (m, 2H), 7.02-6.94 (m, 3H), 3.90 (t, J = 5.8 Hz, 2H), 2.86 (t, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 144.0, 142.0, 141.1, 132.7, 131.2, 131.0, 128.8, 128.0, 127.6, 126.6, 126.5, 122.6, 120.4, 116.9, 64.7, 34.9.

[0098] Example 10

[0099] A 15 mL pressure tube was charged with 1-(4-fluorophenyl)-1H-indole (denoted as 1h, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3h. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3h (2-(2-((4-fluorophenyl)amino)phenyl)ethan-1-ol, separation yield 87%).

[0100] The chemical reaction formula of the above preparation process is:

[0101]

[0102] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.21-7.11 (m, 3H), 6.97-6.85 (m, 5H), 3.91 (t, J = 5.8 Hz, 2H), 2.85 (t, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 157.5 (d, J = 238.5 Hz), 143.0, 140.4 (d, J = 2.2 Hz), 131.1, 130.1, 127.6, 122.0, 119.2 (d, J = 7.6 Hz), 118.7, 115.9 (d, J = 22.5 Hz), 64.6, 34.8. 19 F NMR (376 MHz, Chloroform-d) δ -123.79 (tt, J = 8.1, 4.8 Hz).

[0103] Example 11

[0104] 1-(4-bromophenyl)-1H-indole (denoted as 1i, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added into 15 mL pressure-resistant reaction tube respectively, stirred at 100 ℃ for 12 h under argon (1 atm) atmosphere, after the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, stirred at 40 ℃ for 4 h, to obtain a product system containing a compound with the structure shown in formula 3i. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and then the obtained eluent was rotary evaporated under reduced pressure to obtain a compound with the structure shown in formula 3i (2-(2-((4-bromophenyl)amino)phenyl)ethan-1-ol, separation yield 95%).

[0105] The chemical reaction formula of the above preparation process is:

[0106]

[0107] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.31-7.24 (m, 3H), 7.16 (ddd, J = 9.2, 7.5, 1.6 Hz, 2H), 6.98 (td, J = 7.4, 1.2 Hz, 1H), 6.80-6.74 (m, 2H), 3.88 (t, J = 5.8 Hz, 2H), 2.82 (t, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 143.8, 141.6, 132.2, 131.6, 131.1, 127.6, 123.0, 120.5, 118.1, 111.3, 64.7, 34.8.

[0108] Example 12

[0109] A 15 mL pressure-resistant reaction tube was charged with 1-(4-(trifluoromethyl)phenyl)-1H-indole (denoted as 1j, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C under an argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3j. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3j (2-(2-((4-(trifluoromethyl)phenyl)amino)phenyl)ethan-1-ol, separation yield 80%).

[0110] The chemical reaction formula of the above preparation process is:

[0111]

[0112] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.41 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 1H), 7.22 (dd, J = 8.5, 6.7 Hz, 2H), 7.07 (td, J = 7.5, 1.2 Hz, 1H), 6.89 (d, J = 8.4 Hz, 2H), 3.98-3.84 (m, 2H), 2.85 (t, J = 5.7 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 148.07, 140.57, 132.89, 131.23, 127.63, 126.74 (q, J = 3.8 Hz), 124.9 (d, J = 271.7 Hz), 124.12, 122.18, 126.76 (q, J = 32.3 Hz), 114.67, 64.92, 34.70. 19 F NMR (376 MHz, Chloroform-d) δ -61.20.

[0113] Example 13

[0114] 2-(4-(1H-indol-1-yl)phenyl)ethan-1-ol (denoted as 1k, 0.2 mmol) and tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex were added into 15 mL pressure-resistant reaction tube respectively, stirred at 100 °C for 12 h under argon (1 atm) atmosphere, after the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, stirred at 40 °C for 4 h, to obtain a product system containing the compound represented by formula 3k. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted with petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain the compound represented by formula 3k (2-(2-((4-(2-hydroxyethyl)phenyl)amino)phenyl)ethan-1-ol, separation yield 62%).

[0115] The chemical reaction formula of the above preparation process is:

[0116]

[0117] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.30-7.24 (m, 1H), 7.13 (qd, J = 7.7, 1.4 Hz, 2H), 7.03 (d, J = 8.4 Hz, 2H), 6.93 (td, J = 7.4, 1.1 Hz, 1H), 6.89-6.83 (m, 2H), 3.85 (t, J = 5.9 Hz, 2H), 3.75 (t, J = 6.6 Hz, 2H), 2.82 (t, J = 5.9 Hz, 2H), 2.74 (t, J = 6.6 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 142.9, 142.4, 131.0, 130.7, 129.9, 129.8, 127.4, 122.1, 119.5, 117.3, 64.3, 63.9, 38.4, 34.9.

[0118] Example 14

[0119] A 15 mL pressure tube was charged with 1-(2-naphthalenyl)-1H-indole (denoted as 1l, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3l. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3l (2-(2-(2-naphthalenylamino)phenyl)ethan-1-ol, separation yield 50%).

[0120] The chemical reaction formula of the above preparation process is:

[0121]

[0122] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.70 (dd, J = 8.4, 3.0 Hz, 2H), 7.58 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.39-7.32 (m, 1H), 7.28-7.18 (m, 4H), 7.16 (dd, J = 8.8, 2.3 Hz, 1H), 7.02 (td, J = 7.4, 1.1 Hz, 1H), 3.94 (t, J = 5.8 Hz, 2H), 2.90 (t, J = 5.8 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 142.4, 142.1, 134.9, 131.4, 131.1, 129.2, 128.8, 127.8, 127.6, 126.5, 126.4, 123.1, 122.9, 120.6, 119.7, 110.2, 64.8, 34.9.

[0123] Example 15

[0124] A 15 mL pressure tube was charged with 1-(1,2-methylenedioxyphenyl)-1H-indole (denoted as 1m, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3m. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3m (2-(2-(1,2-methylenedioxyphenylamino)phenyl)ethan-1-ol, separation yield 70%).

[0125] The chemical reaction formula of the above preparation process is:

[0126]

[0127] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.19-7.07 (m, 3H), 6.90 (td, J = 7.4, 1.6 Hz, 1H), 6.69 (d, J = 8.3 Hz, 1H), 6.56 (d, J = 2.2 Hz, 1H), 6.40 (dd, J = 8.3, 2.2 Hz, 1H), 5.89 (s, 2H), 3.91 (t, J = 5.9 Hz, 2H), 2.85 (t, J = 5.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 148.3, 143.6, 142.1, 138.9, 131.0, 129.4, 127.6, 121.4, 118.3, 111.4, 108.7, 101.4, 101.0, 64.5, 34.9.

[0128] Example 16

[0129] A 15 mL pressure tube was charged with 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H- indole (denoted as 1n, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3n. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3n (2-(2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)amino)phenyl)ethan-1-ol, separation yield 72%).

[0130] The chemical reaction formula of the above preparation process is:

[0131]

[0132] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.22-7.07 (m, 3H), 6.89 (td, J = 7.4, 1.2 Hz, 1H), 6.75 (d, J = 8.6 Hz, 1H), 6.55-6.42 (m, 2H), 4.28-4.14 (m, 4H), 3.91 (t, J = 5.9 Hz, 2H), 2.85 (t, J = 5.9 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 144.0, 143.3, 138.4, 138.1, 130.9, 129.4, 127.6, 121.4, 118.5, 117.7, 112.2, 107.5, 64.7, 64.4, 64.4, 34.9.

[0133] Example 17

[0134] Into a 15 mL pressure tube, 6-methyl-l-phenyl-lH-indole (denoted as lo, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added respectively, and stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3o. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3o (2-(4-methyl-2-(phenylamino)phenyl)ethan-l-ol, separation yield 79%).

[0135] The chemical reaction formula of the above preparation process is:

[0136]

[0137] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.22 (tt, J = 7.5, 2.1 Hz, 2H), 7.16-7.13 (m, 1H), 7.07 (d, J = 7.6 Hz, 1H), 6.92 (dt, J = 8.8, 1.7 Hz, 2H), 6.84 (tt, J = 7.2, 1.1 Hz, 1H), 6.81-6.75 (m, 1H), 3.88 (t, J = 5.9 Hz, 2H), 2.82 (t, J = 5.9 Hz, 2H), 2.27 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 144.7, 142.0, 137.3, 130.9, 129.4, 127.9, 123.4, 120.8, 119.9, 116.9, 64.7, 34.5, 21.3.

[0138] Example 18

[0139] Into a 15 mL pressure tube, 5-methoxy-1-phenyl-1H-indole (denoted as 1p, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added respectively, and stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3p. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3p (2-(5-methoxy-2-(phenylamino)phenyl)ethan-1-ol, separation yield 41%).

[0140] The chemical reaction formula of the above preparation process is:

[0141]

[0142] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.23 (d, J = 8.6 Hz, 1H), 7.20-7.13 (m, 2H), 6.82-6.78 (m, 2H), 6.77-6.72 (m, 3H), 3.89 (t, J = 6.0 Hz, 2H), 3.80 (s, 3H), 2.84 (t, J = 6.0 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 156.4, 146.5, 135.2, 134.5, 129.4, 125.4, 118.8, 116.3, 115.0, 112.7, 64.3, 55.6, 35.1.

[0143] Example 19

[0144] Into a 15 mL pressure tube, 6-fluoro-1-phenyl-1H-indole (denoted as 1q, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added respectively, and stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3q. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted with petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3q (2-(4-fluoro-2-(phenylamino)phenyl)ethan-1-ol, separation yield 84%).

[0145] The chemical reaction formula of the above preparation process is:

[0146]

[0147] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.28-7.20 (m, 2H), 7.06 (dd, J = 8.3, 6.7 Hz, 1H), 7.03-6.95 (m, 3H), 6.91 (t, J = 7.4 Hz, 1H), 6.58 (td, J = 8.2, 2.6 Hz, 1H), 3.87 (t, J = 5.7 Hz, 2H), 2.80 (t, J = 5.7 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 162.4 (d, J = 243.0 Hz), 144.3 (d, J = 10.1 Hz), 143.2, 131.9 (d, J = 9.5 Hz), 129.5, 125.1 (d, J = 2.9 Hz), 121.1, 118.2, 107.9 (d, J = 21.3 Hz), 104.8 (d, J = 24.771 Hz), 64.7, 64.7, 34.2. 19 F NMR (376 MHz, Chloroform-d) δ -114.67 (dt, J = 11.4, 7.5 Hz).

[0148] Example 20

[0149] Into a 15 mL pressure tube, 5-fluoro-1-phenyl-1H-indole (denoted as 1r, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex were added respectively, and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3r. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3r (2-(5-fluoro-2-(phenylamino)phenyl)ethan-1-ol, separation yield 48%).

[0150] The chemical reaction formula of the above preparation process is:

[0151]

[0152] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.27-7.22 (m, 1H), 7.22-7.15 (m, 2H), 6.95-6.84 (m, 2H), 6.84-6.77 (m, 3H), 6.33 (s, 1H), 3.89 (t, J = 5.8 Hz, 2H), 2.82 (t, J = 5.8 Hz, 2H), 1.92 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 158.9 (d, J = 241.7 Hz), 145.4, 137.8, 134.6 (d, J = 7.1 Hz), 129.5, 123.6 (d, J = 8.2 Hz), 119.5, 117.2 (d, J = 21.9 Hz), 115.8, 114.1 (d, J = 22.1 Hz), 64.1, 34.8. 19 F NMR (376 MHz, Chloroform-d) δ -120.16 (td, J = 8.5, 5.1 Hz).

[0153] Example 21

[0154] Into a 15 mL pressure tube, 5-chloro-1-phenyl-1H-indole (denoted as 1s, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added respectively, and stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound with the structure shown in formula 3s. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain the compound with the structure shown in formula 3s (2-(5-chloro-2-(phenylamino)phenyl)ethan-1-ol, separation yield 45%).

[0155] The chemical reaction formula of the above preparation process is:

[0156]

[0157] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.26-7.18 (m, 3H), 7.16 (d, J = 2.5 Hz, 1H), 7.10 (dd, J = 8.6, 2.5 Hz, 1H), 6.93-6.81 (m, 3H), 3.91 (t, J = 5.7 Hz, 2H), 2.82 (t, J = 5.7 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 144.1, 141.0, 132.8, 130.7, 129.5, 127.4, 126.7, 121.1, 120.3, 117.0, 64.5, 34.6.

[0158] Example 22

[0159] Into a 15 mL pressure tube, 5-bromo-1-phenyl-1H-indole (denoted as 1t, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex were added respectively, and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3t. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3t (2-(5-bromo-2-(phenylamino)phenyl)ethan-1-ol, separation yield 53%).

[0160] The chemical reaction formula of the above preparation process is:

[0161]

[0162] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.30 (d, J = 2.1 Hz, 1H), 7.27-7.14 (m, 4H), 6.94-6.83 (m, 3H), 3.91 (t, J = 5.7 Hz, 2H), 2.81 (t, J = 5.7 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 143.8, 141.6, 133.5, 132.9, 130.2, 129.4, 120.9, 120.4, 117.2, 114.0, 64.5, 34.5.

[0163] Example 23

[0164] Into a 15 mL pressure tube, 5-iodo-1-phenyl-1H-indole (denoted as 1u, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added respectively, and stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was reduced to room temperature, sodium peroxoborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3u. Then the reaction temperature was reduced to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3u (2-(5-iodo-2-(phenylamino)phenyl)ethan-1-ol, separation yield 58%).

[0165] The chemical reaction formula of the above preparation process is:

[0166]

[0167] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.47 (d, J = 2.1 Hz, 1H), 7.41 (dd, J = 8.5, 2.1 Hz, 1H), 7.22 (td, J = 7.4, 1.9 Hz, 2H), 7.08 (d, J = 8.5 Hz, 1H), 6.95-6.90 (m, 2H), 6.88 (tt, J = 7.3, 1.1 Hz, 1H), 6.75 (s, 1H), 3.91 (t, J = 5.7 Hz, 2H), 2.79 (t, J = 5.7 Hz, 2H), 1.97 (s, 1H). 13 C NMR (101 MHz, Chloroform-d) δ 143.6, 142.5, 139.5, 136.2, 133.1, 129.5, 120.9, 120.6, 117.5, 84.0, 64.6, 34.4.

[0168] Example 24

[0169] A 15 mL pressure tube was charged with 1-phenyl-1H-indol-5-amine (denoted as 1v, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3v. The reaction temperature was then lowered to room temperature, and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3v (2-(5-amino-2-(phenylamino)phenyl)ethan-1-ol, separation yield 61%).

[0170] The chemical reaction formula of the above preparation process is:

[0171]

[0172] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.19-7.09 (m, 2H), 7.06 (d, J = 8.1 Hz, 1H), 6.73 (tt, J = 7.3, 1.1 Hz, 1H), 6.70-6.66 (m, 2H), 6.57-6.51 (m, 2H), 3.77 (t, J = 6.1 Hz, 2H), 2.72 (t, J = 6.1 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 147.0, 143.3, 135.7, 132.5, 129.3, 126.4, 118.4, 117.5, 114.6, 114.5, 63.9, 35.0.

[0173] Example 25

[0174] A 15 mL pressure tube was charged with 3-methyl-l-phenyl-lH-indole (denoted as 1w, 0.2 mmol) and a tetrahydrofuran solution (denoted as 2a, 0.6 mmol, 2 mol / L) of borane dimethyl sulfide complex, stirred at 100 °C under argon (1 atm) atmosphere for 12 h. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3w. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3w (2-(2-(phenylamino)phenyl)propan-l-ol, separation yield 66%).

[0175] The chemical reaction formula of the above preparation process is:

[0176]

[0177] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.32 (dd, J = 8.0, 1.1 Hz, 1H), 7.26 (dd, J = 7.7, 1.5 Hz, 1H), 7.24-7.13 (m, 3H), 7.06 (td, J = 7.5, 1.1 Hz, 1H), 6.92-6.86 (m, 2H), 6.83 (t, J = 7.3 Hz, 1H), 3.82 (dd, J = 10.2, 5.1 Hz, 1H), 3.59 (t, J = 9.6 Hz, 1H), 3.42-3.28 (m, 1H), 1.23 (s, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 145.1, 141.7, 136.3, 129.4, 127.1, 126.8, 123.3, 121.6, 119.7, 116.5, 69.9, 35.4, 16.8.

[0178] Example 26

[0179] A 15 mL pressure tube was charged with 1-methyl-1H-indole (denoted as 1x, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 140 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3x. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3x (2-(2-(methylamino)phenyl)ethan-1-ol, separation yield 72%).

[0180] The chemical reaction formula of the above preparation process is:

[0181]

[0182] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.18 (td, J = 7.9, 1.5 Hz, 1H), 7.04 (dd, J = 7.4, 1.4 Hz, 1H), 6.72 (td, J = 7.4, 0.9 Hz, 1H), 6.66 (d, J = 8.1 Hz, 1H), 3.86 (t, J = 6.2 Hz, 2H), 2.84 (s, 3H), 2.76 (t, J = 6.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 147.8, 130.3, 128.1, 123.9, 117.6, 110.5, 63.2, 34.8, 31.0.

[0183] Example 27

[0184] A 15 mL pressure tube was charged with 1-benzyl-1H-indole (denoted as 1y, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran:water = 1:1 by volume) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3y. Then the reaction temperature was lowered to room temperature, and purified by silica gel column chromatography, eluted using petroleum ether:ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3y (2-(2-(benzylamino)phenyl)ethan-1-ol, separation yield 62%).

[0185] The chemical reaction formula of the above preparation process is:

[0186]

[0187] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.37-7.31 (m, 4H), 7.29-7.22 (m, 1H), 7.11 (td, J = 8.0, 1.6 Hz, 1H), 7.05 (dd, J = 7.4, 1.3 Hz, 1H), 6.71 (td, J = 7.4, 1.2 Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H), 4.32 (s, 2H), 3.85 (t, J = 6.3 Hz, 2H), 2.77 (t, J = 6.2 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 146.6, 139.5, 130.4, 128.8, 128.0, 127.6, 127.3, 123.8, 117.8, 111.3, 63.0, 48.4, 34.9.

[0188] Example 28

[0189] A 15 mL pressure tube was charged with 1-octyl-1H-indole (denoted as 1z, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3z. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3z (2-(2-(octylamino)phenyl)ethan-1-ol, separation yield 46%).

[0190] The chemical reaction formula of the above preparation process is:

[0191]

[0192] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.15 (td, J = 7.9, 1.6 Hz, 1H), 7.04 (dd, J = 7.4, 1.5 Hz, 1H), 6.73-6.63 (m, 2H), 3.88 (t, J = 6.2 Hz, 2H), 3.10 (t, J = 7.1 Hz, 2H), 2.77 (t, J = 6.2 Hz, 2H), 1.65 (p, J = 7.1 Hz, 2H), 1.46-1.36 (m, 2H), 1.36-1.21 (m, 8H), 0.93-0.82 (m, 3H). 13 C NMR (101 MHz, Chloroform-d) δ 147.0, 130.4, 128.0, 123.6, 117.4, 111.1, 63.2, 44.2, 34.9, 32.0, 29.7, 29.6, 29.4, 27.4, 22.8, 14.2.

[0193] Example 29

[0194] A 15 mL pressure tube was charged with 5,6-dihydro-4H-pyrrolo[3,2-1-ij]quinoline (denoted as 1aa, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), and stirred at 100 °C for 12 h under an argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, and sodium perborate tetrahydrate (1 mmol) and 2 mL of a tetrahydrofuran aqueous solution (tetrahydrofuran to water in a volume ratio of 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3aa. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted using petroleum ether: ethyl acetate (V:V = 4:1) as the eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3aa (2-(1,2,3,4-tetrahydroquinolin-8-yl)ethan-1-ol, separation yield 54%).

[0195] The chemical reaction formula of the above preparation process is:

[0196]

[0197] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 6.86 (dd, J = 7.2, 3.5 Hz, 2H), 6.60 (t, J = 7.4 Hz, 1H), 3.85 (t, J = 6.2 Hz, 2H), 3.36-3.26 (m, 2H), 2.78 (t, J = 6.4 Hz, 2H), 2.70 (t, J = 6.2 Hz, 2H), 1.91 (p, J = 6.3 Hz, 2H). 13 C NMR (101 MHz, Chloroform-d) δ 143.3, 128.3, 128.1, 123.2, 122.3, 117.1, 63.2, 42.4, 34.6, 27.6, 22.1.

[0198] Example 30

[0199] A 15 mL pressure tube was charged with 1-((7-(3-((3r,5r,7r)-adamantan-1-yl)-4- methoxyphenyl)naphthalen-2-yl)methyl)-1H-indole (denoted as 1ab, 0.2 mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L), stirred at 100 °C for 12 h under argon (1 atm) atmosphere. After the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (volume ratio of tetrahydrofuran to water 1:1) were added, and stirred at 40 °C for 4 h to obtain a product system containing a compound represented by formula 3ab. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, eluted with petroleum ether: ethyl acetate (V:V = 4:1) as eluent, and the obtained eluent was rotary evaporated under reduced pressure to obtain a compound represented by formula 3ab (2-(2-(((7-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)naphthalen-2-yl)methyl)amino)phenyl)ethan-1-ol) with an isolated yield of 29%.

[0200] The chemical reaction formula of the above preparation process is:

[0201]

[0202] The product characterization data are: 1 H NMR (400 MHz, Chloroform-d) δ 7.97 (d, J = 1.8 Hz, 1H), 7.90-7.77 (m, 3H), 7.72 (dd, J = 8.5, 1.9 Hz, 1H), 7.58 (d, J = 2.4 Hz, 1H), 7.51 (td, J = 8.6, 2.0 Hz, 2H), 7.17-7.04 (m, 2H), 6.98 (d, J = 8.5 Hz, 1H), 6.78-6.65 (m, 2H), 4.50 (s, 2H), 3.92 (t, J = 6.2 Hz, 2H), 3.89 (s, 3H), 2.84 (t, J = 6.2 Hz, 2H), 2.18 (d, J = 2.5 Hz, 6H), 2.10 (s, 3H), 1.80 (s, 6H). 13 C NMR (101 MHz, Chloroform-d) δ 158.7, 146.7, 139.0, 136.7, 133.3, 132.4, 130.4, 128.7, 128.2, 128.1, 126.2, 126.1, 126.0, 125.9, 125.7, 125.0, 123.9, 117.9, 112.2, 111.5, 63.2, 55.3, 48.7, 40.8, 37.3, 37.3, 35.0, 29.3.

[0203] Comparative Example 1

[0204] Compound 3a was prepared according to the method of Example 1, except that the borane dimethylsulfide complex was replaced by 9-BBN. Compound 3a was not detected and only 1a was detected in the reaction solution.

[0205] Comparative Example 2

[0206] Compound 3a was prepared according to the method of Example 1, except that the borane dimethylsulfide complex was replaced by HBpin. Compound 3a was not detected and only 1a was detected in the reaction solution.

[0207] The above only describes the preferred embodiments of the present application, it should be noted that for those skilled in the art, without departing from the principles of the present application, can also make a number of improvements and refinements, these improvements and refinements should also be considered within the scope of the present application.

Claims

1. A method for preparing an amine-based phenethyl alcohol compound by structural reorganization of an indole compound, comprising the following steps: mixing the indole compound and a borane compound, and performing a reduction reaction in a protective atmosphere to obtain a benzoazaborinine compound; mixing the benzoazaborinine compound with sodium perborate tetrahydrate, and performing an open ring oxidation reaction to obtain the amine-based phenethyl alcohol compound; a reaction formula of the reduction reaction is as follows: a reaction formula of the open ring oxidation reaction is as follows: the borane compound is selected from a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex; the temperature of the reduction reaction is 80-140 ℃. The substituent in the substituted aryl group includes one or more of a methyl group, a tert-butyl group, a methoxy group, a phenoxy group, a methylthio group, a phenyl group, fluorine, bromine, and a trifluoromethyl group. The substituent in the substituted alkyl group includes one or more of an aryl group, an alkyl group, and a methoxy group. The substituent in the substituted alkyl group includes a naphthyl group. ； The borane compound is used in the form of a tetrahydrofuran solution of the borane compound, and the concentration of the tetrahydrofuran solution of the borane compound is 2 mol / L. ； Among them, R 1 Selected from phenyl, alkyl, cycloalkyl, naphthyl, benzodioxane, substituted aryl, or substituted alkyl; R 2 It is selected from one or more of hydrogen, alkyl, methoxy, amino and halogen; The molar ratio of the indole compound to the borane compound is 1:3-5. The time of the reduction reaction is 12-24 h.

2. The production method according to claim 1, characterized by, The molar ratio of the benzoazaborinine compound to sodium perborate tetrahydrate is 1:3-5.

3. The preparation method according to claim 1, characterized in that, The temperature of the open ring oxidation reaction is 30-40 ℃, and the time is 4-6 h.

4. The method of claim 1, wherein, ​ 5. The preparation method according to claim 1, characterized in that, ​ 6. The method of claim 1, wherein, ​ 7. The method of any one of claims 1 to 6, wherein the method further comprises the step of: ​ ​ 8. The method of claim 1, wherein, ​ 9. The production method according to claim 1 or 8, characterized by, ​

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