Method for preparing amino phenethyl alcohol compound through structure reforming of indole compound

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for preparing an amino phenethyl alcohol compound through structure reforming of an indole compound. According to the method for preparing the amino phenethyl alcohol compound through structure reforming of the indole compound, a borane compound serves as a reducing reagent, the indole compound is subjected to boronizing reduction to generate benzo-aza-boride, then the benzo-aza-boride is further subjected to ring-opening oxidation through sodium borate tetrahydrate to generate the amino phenethyl alcohol compound, and the amino phenethyl alcohol compound is prepared. According to the method, efficient synthesis of a series of amino phenethyl alcohol compounds is successfully achieved through structure reforming of the indole compounds, byproducts are few in the reaction process, the selectivity and the yield of the amino phenethyl alcohol compounds are high, and subsequent separation and purification are simple. Moreover, the method provided by the invention is simple in process, green and environment-friendly, simple to operate, low in cost, high in safety and suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing aminophenethanol compounds by structural reforming of indole compounds. Background Art

[0002] Indole compounds are widely found in biologically active natural products, pesticide chemistry and medicinal chemistry. Chemists have been committed to developing new systems for the transformation of indole compounds. Although significant results have been achieved, most catalytic systems keep the indole skeleton unchanged, such as the functionalization of carbon-hydrogen bonds of indole compounds. These catalytic systems have greatly expanded the complexity of the indole skeleton, but it is still very challenging to achieve changes in the indole skeleton and the preparation of new compounds by editing and reorganizing the indole core skeleton.

[0003] Aminophenethanol compounds have potential pharmaceutical activity, but there is still no report on their effective synthesis methods. Summary of the invention

[0004] In view of this, the object of the present invention is to provide a method for preparing aminophenethanol compounds by structural reforming of indole compounds. The present invention successfully realizes the efficient synthesis of a series of aminophenethanol compounds through structural reforming of indole compounds, and the product yield is high.

[0005] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0006] The present invention provides a method for preparing aminophenethanol compounds by structural reforming of indole compounds, comprising the following steps:

[0007] An indole compound and a borane compound are mixed and subjected to a reduction reaction in a protective atmosphere to obtain a benzazaboride;

[0008] The benzazaboride is mixed with sodium perborate tetrahydrate and subjected to a ring-opening oxidation reaction to obtain an aminophenethanol compound.

[0009] Preferably, the indole compound has a structure shown in Formula 1:

[0010]

[0011] In Formula 1, R 1 Including one or more of phenyl, alkyl, cycloalkyl, naphthyl, benzodioxy, benzodioxetane, substituted aryl and substituted alkyl; R 2 It includes one or more of hydrogen, alkyl, methoxy, amino and halogen.

[0012] Preferably, the substituents in the substituted aryl group include methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and One or more of the .

[0013] Preferably, the substituents in the substituted alkyl group include one or more of aryl, alkyl, methoxy and naphthyl.

[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 includes borane dimethyl sulfide complex and / or borane tetrahydrofuran complex.

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

[0017] Preferably, the reduction reaction is carried out at a temperature of 80 to 140° C. and for a time of 12 to 24 hours.

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

[0019] Preferably, the ring-opening oxidation reaction is carried out at a temperature of 30 to 40° C. and for a time of 4 to 6 hours.

[0020] The method for preparing aminophenethanol compounds by structural reforming of indole compounds provided by the present invention uses a borane compound as a reducing agent to borate-reduce the indole compounds to generate a benzazaboride, and then further ring-opening oxidation with sodium borate tetrahydrate to generate aminophenethanol compounds. The efficient synthesis of a series of aminophenethanol compounds is successfully achieved through the structural reforming of the indole compounds, and there are few by-products in the reaction process, the selectivity of aminophenethanol compounds is high, the yield is high, and the subsequent separation and purification is simple. Moreover, the method provided by the present invention has simple process, green and environmental protection, simple operation, low cost, high safety, and is suitable for industrial production. DETAILED DESCRIPTION

[0021] The present invention provides a method for preparing aminophenethanol compounds by structural reforming of indole compounds, which is characterized by comprising the following steps:

[0022] An indole compound and a borane compound are mixed and subjected to a reduction reaction in a protective atmosphere to obtain a benzazaboride;

[0023] The benzazaboride is mixed with sodium perborate tetrahydrate and subjected to a ring-opening oxidation reaction to obtain an aminophenethanol compound.

[0024] Unless otherwise specified, the raw materials used in the present invention are all commercially available products.

[0025] An indole compound and a borane compound are mixed and subjected to reduction reaction in a protective atmosphere to obtain a benzazaboride.

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

[0027]

[0028] In the present invention, in Formula 1, R 1 Including one or more of phenyl, alkyl, naphthyl, benzodioxy, benzodioxetane, substituted aryl and substituted alkyl. In the present invention, the alkyl preferably includes methyl, benzyl or long-chain alkyl, and the long-chain alkyl is preferably C8 alkyl. In the present invention, the substituent in the substituted aryl preferably includes phenyl or naphthyl; the substituent in the substituted aryl preferably includes methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and One or more of the above, the alkyl alcohol preferably includes C2 alkyl alcohol; when the substituent or substituents in the substituted aryl are two or more of the above substituents, the present invention has no special restrictions on the specific positions of different types of substituents. In the present invention, the substituents in the substituted alkyl preferably include one or more of aryl, alkyl, methoxy and naphthyl, and the aryl preferably includes phenyl; the alkyl and substituted alkyl independently preferably include C1 to C8 alkyl, more preferably methyl or 1-octyl; when the substituents in the substituted alkyl are two or more of the above substituents, the present invention has no special restrictions on the specific positions of different types of substituents. In the present invention, the R 2 Preferably, it 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; the R 2 It is preferably on the benzene ring or heterocyclic ring of formula 2.

[0029] In the present invention, the indole compounds preferably include 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, -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]dioxane-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-1 H-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 invention, 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 invention, the borane compound preferably includes a borane dimethyl sulfide complex and / or a borane tetrahydrofuran complex.

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

[0032] The present invention has no special limitation on the mixing. The raw materials can be evenly mixed by a mixing method well known to those skilled in the art, such as stirring and mixing.

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

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

[0035]

[0036] In Formula 2, R 1 and R 2 Preferably, R 1 and R 2 The same is not repeated here.

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

[0038]

[0039] After the reduction reaction, the present invention 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 invention mixes the benzazaboride with sodium perborate tetrahydrate and performs a ring-opening oxidation reaction to obtain an aminophenethanol compound.

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

[0042] The present invention has no special limitation on the mixing. The raw materials can be evenly mixed by a mixing method well known to those skilled in the art, such as stirring and mixing.

[0043] In the present invention, the temperature of the ring-opening oxidation reaction is preferably 30 to 40°C, more preferably 35 to 40°C, and the time of the ring-opening oxidation reaction is preferably 4 to 6 hours, more preferably 4 to 5 hours. In the present invention, 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 to 1.2, more preferably 1:1; the ratio of the amount of the boron nitrogen heterocyclic compound to the volume of the solvent is preferably 1 mmol:5 to 20 mL, more preferably 1 mmol:10 to 15 mL.

[0044] After the ring-opening oxidation reaction, the present invention preferably further comprises cooling the obtained ring-opening oxidation reaction liquid to room temperature and purifying it by silica gel column chromatography, and concentrating the obtained eluent to constant weight to obtain aminophenylethanol compounds. In the present invention, the eluent used for the silica gel column chromatography purification 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 present invention does not have any special restrictions on the concentration, and a concentration method well known to those skilled in the art can be used, such as decompression and spin drying.

[0045] In the present invention, the aminophenethanol compound has a structure shown in Formula 3:

[0046]

[0047] In Formula 3, R 1 and R 2 Preferably, R 1 and R 2 The same is not repeated here.

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

[0049]

[0050] The technical solutions in the present invention will be described clearly and completely below in conjunction with the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

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

[0052] The following embodiments 1 When the number of hydrogen atoms in H NMR does not correspond to the structural formula, it is because the hydrogen atoms on the amino group and the hydrogen atoms on the hydroxyl group are not easily observed in the hydrogen spectrum.

[0053] Example 1

[0054] 1-phenyl-1H-indole (denoted as 1a, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3a. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3a (2-(2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 82%.

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

[0056]

[0057] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.34-7.27(m,1H),7.24-7.11(m,4H),6.96(dd,J=7.4,1.2Hz,1H ),6.94-6.88(m,2H),6.84(tt,J=7.3,1.1Hz,1H),3.87(t,J=5.9Hz,2H),2.84(t,J=5.9Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ144.5,142.2,131.0,131.0,129.4,127.5,122.4,120.1,120.0,116.9,64.5,34.9.

[0058] Example 2

[0059] 1-Phenyl-1H-indole (denoted as 1a, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 140°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3a. Then mesitylene was added as an internal standard, and the nuclear magnetic yield was 58%.

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

[0061]

[0062] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.34-7.27(m,1H),7.24-7.11(m,4H),6.96(dd,J=7.4,1.2Hz,1H ),6.94-6.88(m,2H),6.84(tt,J=7.3,1.1Hz,1H),3.87(t,J=5.9Hz,2H),2.84(t,J=5.9Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ144.5,142.2,131.0,131.0,129.4,127.5,122.4,120.1,120.0,116.9,64.5,34.9.

[0063] Example 3

[0064] 1-Phenyl-1H-indole (denoted as 1a, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 80°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure 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(400MHz,Chloroform-d)δ7.34-7.27(m,1H),7.24-7.11(m,4H),6.96(dd,J=7.4,1.2Hz,1H ),6.94-6.88(m,2H),6.84(tt,J=7.3,1.1Hz,1H),3.87(t,J=5.9Hz,2H),2.84(t,J=5.9Hz,2H). 13C NMR (101MHz, Chloroform-d) δ144.5,142.2,131.0,131.0,129.4,127.5,122.4,120.1,120.0,116.9,64.5,34.9.

[0068] Example 4

[0069] 1-(p-Tolyl)-1H-indole (denoted as 1b, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3b. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V=4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3b (2-(2-(p-Tolylamino)phenyl)ethane-1-ol), with an isolated yield of 95%.

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

[0071]

[0072] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.25(dd,J=8.0,1.1Hz,1H),7.14(qd,J=7.6,1.5Hz,2H),7.07-7.00(m,2H), 6.92(td,J=7.4,1.2Hz,1H),6.89-6.83(m,2H),3.90(t,J=5.9Hz,2H),2.85(t,J=5.9Hz,2H),2.28(s,3H). 13 C NMR (101MHz, Chloroform-d) δ142.9,141.7,131.0,130.0,129.9,129.8,127.5,121.8,119.0,117.9,64.5,34.9,20.7.

[0073] Example 5

[0074] 1-(4-(tert-butyl)phenyl)-1H-indole (denoted as 1c, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of formula 3c. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of formula 3c (2-(2-((4-(tert-butyl)phenyl)amino)phenyl)ethane-1-ol), with an isolated yield of 84%.

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

[0076]

[0077] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.30(dd,J=8.0,0.9Hz,1H),7.27-7.20(m,2H),7.19-7.0 9(m,2H),6.95-6.86(m,3H),3.90(t,J=5.9Hz,2H),2.85(t,J=5.9Hz,2H),1.30(s,9H). 13 C NMR (101MHz, Chloroform-d) δ143.2,142.7,141.7,131.0,130.1,127.5,126.2,121.9,119.3,117.2,64.5,34.9,34.2,31.6.

[0078] Example 6

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

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

[0081]

[0082] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.14(d,J=7.3Hz,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=5.9Hz,2H),3.77(s,3H),2.86(t,J=5.9Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ154.6,144.0,137.2,131.0,128.6,127.6,120.9,120.9,117.3,114.8,64.3,55.8,34.9.

[0083] Example 7

[0084] 1-(4-phenoxyphenyl)-1H-indole (denoted as 1e, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3e. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3e (2-(2-((4-phenoxyphenyl)amino)phenyl)ethane-1-ol), with an isolated yield of 66%.

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

[0086]

[0087] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.33-7.24(m,3H),7.15(ddd,J=9.4,7.7,2.4hz,2H),7.07-7.00(m,1H) ,6.98(d,J=1.1Hz,1H),6.97-6.96(m,1H),6.93(s,5H),3.92(t,J=5.8Hz,2H),2.87(t,J=5.8Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ158.6,150.2,143.0,140.4,131.1,130.1,129.7,127.6,122.5,121.9,120.8,119.1,118.8,117.8,64.6,34.9.

[0088] Example 8

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

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

[0091]

[0092] The product characterization data are: 1 H NMR (400MHz, Chloroform-d) δ7.29 (dd, J=8.1, 1.3Hz, 1H), 7.23-7.12 (m, 4H), 6.97 (td, J=7. 4,1.3Hz,1H),6.91-6.83(m,2H),3.92(t,J=5.7Hz,2H),2.85(t,J=5.8Hz,2H),2.43(s,3H). 13 C NMR (101MHz, Chloroform-d) δ143.1,142.0,131.1,131.0,130.5,127.5,127.5,122.6,120.0,117.5,64.7,34.8,18.4.

[0093] Example 9

[0094] 1-([1,1'-biphenyl]-4-yl)-1H-indole (denoted as 1 g, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added into a 15 mL pressure-resistant reaction tube, respectively, and stirred at 100 ° C for 12 h under an argon (1 atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (the volume ratio of tetrahydrofuran to water was 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 3g. The reaction temperature was then lowered to room temperature and purified by silica gel column chromatography using petroleum ether:ethyl acetate (V:V=4:1) as an eluent, and the resulting eluate was dried under reduced pressure to obtain a structural compound (2-(2-([1,1'-biphenyl]-4-ylamino)phenyl)ethane-1-ol) as shown in formula 3g, with an isolated yield of 87%.

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

[0096]

[0097] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.57-7.51(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=5.8Hz,2H),2.86(t,J=5.8Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ144.0,142.0,141.1,132.7,131.2,131.0,128.8,128.0,127.6,126.6,126.5,122.6,120.4,116.9,64.7,34.9.

[0098] Example 10

[0099] 1-(4-fluorophenyl)-1H-indole (denoted as 1h, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3h. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3h (2-(2-((4-fluorophenyl)amino)phenyl)ethane-1-ol), with an isolated yield of 87%.

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

[0101]

[0102] The product characterization data are: 1 H NMR (400MHz, Chloroform-d) δ7.21-7.11(m,3H),6.97-6.85(m,5H),3.91(t,J=5.8Hz,2H),2.85(t,J=5.8Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ 157.5 (d, J = 238.5Hz), 143.0, 140.4 (d, J = 2.2Hz), 131. 1,130.1,127.6,122.0,119.2(d,J=7.6Hz),118.7,115.9(d,J=22.5Hz),64.6,34.8. 19 F NMR (376MHz, Chloroform-d) δ-123.79 (tt, J=8.1, 4.8Hz).

[0103] Embodiment 11

[0104] 1-(4-bromophenyl)-1H-indole (denoted as 1i, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3i. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V=4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3i (2-(2-((4-bromophenyl)amino)phenyl)ethane-1-ol), with an isolated yield of 95%.

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

[0106]

[0107] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.31-7.24(m,3H),7.16(ddd,J=9.2,7.5,1.6Hz,2H),6.98 (td,J=7.4,1.2Hz,1H),6.80-6.74(m,2H),3.88(t,J=5.8Hz,2H),2.82(t,J=5.8Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ143.8,141.6,132.2,131.6,131.1,127.6,123.0,120.5,118.1,111.3,64.7,34.8.

[0108] Example 12

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

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

[0111]

[0112] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.41(d,J=8.4hz,2H),7.35(d,J=8.0Hz,1H),7.22(dd,J=8.5,6.7Hz ,2H),7.07(td,J=7.5,1.2Hz,1H),6.89(d,J=8.4hz,2H),3.98-3.84(m,2H),2.85(t,J=5.7Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ148.07,140.57,132.89,131.23,127.63,126.74(q,J=3.8 Hz), 124.9 (d, J = 271.7Hz), 124.12, 122.18, 126.76 (q, J = 32.3Hz), 114.67, 64.92, 34.70. 19 F NMR (376MHz, Chloroform-d) delta-61.20.

[0113] Embodiment 13

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

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

[0116]

[0117] The product characterization data are: 1 H NMR (400MHz, Chloroform-d) δ7.30-7.24(m,1H),7.13(qd,J=7.7,1.4hz,2H),7.03(d,J=8.4hz,2H),6.93(td,J=7.4,1. 1Hz,1H),6.89-6.83(m,2H),3.85(t,J=5.9Hz,2H),3.75(t,J=6.6Hz,2H),2.82(t,J=5.9Hz,2H),2.74(t,J=6.6Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ142.9,142.4,131.0,130.7,129.9,129.8,127.4,122.1,119.5,117.3,64.3,63.9,38.4,34.9.

[0118] Embodiment 14

[0119] 1-(2-naphthyl)-1H-indole (denoted as 1l, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3l. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V=4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3l (2-(2-(2-naphthylamino)phenyl)ethane-1-ol), and the separation yield was 50%.

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

[0121]

[0122] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.70(dd,J=8.4,3.0Hz,2H),7.58(d,J=8.2Hz,1H),7.42(d,J=8.0Hz,1H),7.39-7.32(m,1H) ,7.28-7.18(m,4H),7.16(dd,J=8.8,2.3Hz,1H),7.02(td,J=7.4,1.1Hz,1H),3.94(t,J=5.8Hz,2H),2.90(t,J=5.8Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ142.4,142.1,134.9,131.4,131.1,129.2,128. 8,127.8,127.6,126.5,126.4,123.1,122.9,120.6,119.7,110.2,64.8,34.9.

[0123] Embodiment 15

[0124] 1-(1,2-methylenedioxyphenyl)-1H-indole (denoted as 1m, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3m. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3m (2-(2-(1,2-methylenedioxyphenylamino)phenyl)ethane-1-ol, with an isolated yield of 70%).

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

[0126]

[0127] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.19-7.07(m,3H),6.90(td,J=7.4,1.6Hz,1H),6.69(d,J=8.3Hz,1H),6.56 (d,J=2.2Hz,1H),6.40(dd,J=8.3,2.2Hz,1H),5.89(s,2H),3.91(t,J=5.9Hz,2H),2.85(t,J=5.9Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ148.3,143.6,142.1,138.9,131.0,129.4,127.6,121.4,118.3,111.4,108.7,101.4,101.0,64.5,34.9.

[0128] Example 16

[0129] 1-(2,3-Dihydrobenzo[b][1,4]dioxane-6-yl)-1H-indole (denoted as 1n, 0.2mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added into a 15mL pressure-resistant reaction tube, respectively, and stirred at 100°C for 12h under an argon (1atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL of tetrahydrofuran aqueous solution (the volume ratio of tetrahydrofuran to water was 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound having the structure shown in formula 3n. The reaction temperature was then lowered to room temperature and purified by silica gel column chromatography using petroleum ether:ethyl acetate (V:V=4:1) as an eluent, and the resulting eluate was dried under reduced pressure to obtain a structural compound (2-(2-((2,3-dihydrobenzo[b][1,4]dioxane-6-yl)amino)phenyl)ethane-1-ol) represented by formula 3n in an isolated yield of 72%.

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

[0131]

[0132] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.22-7.07(m,3H),6.89(td,J=7.4,1.2Hz,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=5.9Hz,2H),2.85(t,J=5.9Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ144.0,143.3,138.4,138.1,130.9,129.4,127.6,121.4,118.5,117.7,112.2,107.5,64.7,64.4,64.4,34.9.

[0133] Embodiment 17

[0134] 6-methyl-1-phenyl-1H-indole (denoted as 1o, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3o. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and after elution with petroleum ether: ethyl acetate (V:V=4:1) as an eluent, the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3o (2-(4-methyl-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 79%.

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

[0136]

[0137] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.22(tt,J=7.5,2.1Hz,2H),7.16-7.13(m,1H),7.07(d,J=7.6Hz,1H),6.92(dt,J=8.8, 1.7Hz,2H),6.84(tt,J=7.2,1.1Hz,1H),6.81-6.75(m,1H),3.88(t,J=5.9Hz,2H),2.82(t,J=5.9Hz,2H),2.27(s,3H). 13 C NMR (101MHz, Chloroform-d) δ144.7,142.0,137.3,130.9,129.4,127.9,123.4,120.8,119.9,116.9,64.7,34.5,21.3.

[0138] Embodiment 18

[0139] 5-methoxy-1-phenyl-1H-indole (denoted as 1p, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3p. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3p (2-(5-methoxy-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 41%.

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

[0141]

[0142] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.23(d,J=8.6Hz,1H),7.20-7.13(m,2H),6.82-6.78( m,2H),6.77-6.72(m,3H),3.89(t,J=6.0Hz,2H),3.80(s,3H),2.84(t,J=6.0Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ156.4,146.5,135.2,134.5,129.4,125.4,118.8,116.3,115.0,112.7,64.3,55.6,35.1.

[0143] Embodiment 19

[0144] 6-Fluoro-1-phenyl-1H-indole (denoted as 1q, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3q. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3q (2-(4-fluoro-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 84%.

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

[0146]

[0147] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.28-7.20(m,2H),7.06(dd,J=8.3,6.7Hz,1H),7.03-6.95(m,3H), 6.91(t,J=7.4hz,1H), 6.58(td,J=8.2,2.6Hz,1H), 3.87(t,J=5.7Hz,2H), 2.80(t,J=5.7Hz,2H). 13 C NMR(101MHz,Chloroform-d)δ162.4(d,J=243.0Hz),144.3(d,J=10.1Hz),143.2,131.9(d,J=9.5Hz),1 29.5, 125.1 (d, J = 2.9Hz), 121.1, 118.2, 107.9 (d, J = 21.3Hz), 104.8 (d, J = 24.771Hz), 64.7, 64.7, 34.2. 19 FNMR (376MHz, Chloroform-d) δ-114.67 (dt, J=11.4, 7.5Hz).

[0148] Embodiment 20

[0149] 5-Fluoro-1-phenyl-1H-indole (denoted as 1r, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3r. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3r (2-(5-fluoro-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 48%.

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

[0151]

[0152] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.27-7.22(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=5.8Hz,2H),2.82(t,J=5.8Hz,2H),1.92(s,1H). 13 C NMR(101MHz,Chloroform-d)δ158.9(d,J=241.7Hz),145.4,137.8,134.6(d,J=7.1Hz),129. 5,123.6(d,J=8.2Hz),119.5,117.2(d,J=21.9Hz),115.8,114.1(d,J=22.1Hz),64.1,34.8. 19 F NMR (376MHz, Chloroform-d) δ-120.16 (td, J=8.5, 5.1Hz).

[0153] Embodiment 21

[0154] 5-Chloro-1-phenyl-1H-indole (denoted as 1s, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3s. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3s (2-(5-chloro-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 45%.

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

[0156]

[0157] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.26-7.18(m,3H),7.16(d,J=2.5Hz,1H),7.10(dd,J =8.6,2.5Hz,1H),6.93-6.81(m,3H),3.91(t,J=5.7Hz,2H),2.82(t,J=5.7Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ144.1,141.0,132.8,130.7,129.5,127.4,126.7,121.1,120.3,117.0,64.5,34.6.

[0158] Embodiment 22

[0159] 5-Bromo-1-phenyl-1H-indole (denoted as 1t, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3t. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3t (2-(5-bromo-2-(phenylamino)phenyl)ethane-1-ol, with an isolated yield of 53%).

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

[0161]

[0162] The product characterization data are: 1 H NMR (400MHz, Chloroform-d) δ7.30 (d, J = 2.1Hz, 1H), 7.27-7.14 (m, 4H), 6.94-6.83 (m, 3H), 3.91 (t, J = 5.7Hz, 2H), 2.81 (t, J = 5.7Hz, 2H). 13 C NMR (101MHz, Chloroform-d) δ143.8,141.6,133.5,132.9,130.2,129.4,120.9,120.4,117.2,114.0,64.5,34.5.

[0163] Embodiment 23

[0164] 5-iodo-1-phenyl-1H-indole (denoted as 1u, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3u. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and after elution with petroleum ether: ethyl acetate (V:V=4:1) as an eluent, the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3u (2-(5-iodo-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 58%.

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

[0166]

[0167] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.47(d,J=2.1Hz,1H),7.41(dd,J=8.5,2.1Hz,1H),7.22(td,J=7.4,1.9Hz,2H),7.08(d,J=8.5H z,1H),6.95-6.90(m,2H),6.88(tt,J=7.3,1.1Hz,1H),6.75(s,1H),3.91(t,J=5.7Hz,2H),2.79(t,J=5.7Hz,2H),1.97(s,1H). 13 C NMR (101MHz, Chloroform-d) δ143.6,142.5,139.5,136.2,133.1,129.5,120.9,120.6,117.5,84.0,64.6,34.4.

[0168] Embodiment 24

[0169] 1-phenyl-1H-indole-5-amine (denoted as 1v, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction was completed, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3v. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3v (2-(5-amino-2-(phenylamino)phenyl)ethane-1-ol), with an isolated yield of 61%.

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

[0171]

[0172] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.19-7.09(m,2H),7.06(d,J=8.1Hz,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=6.1Hz,2H),2.72(t,J=6.1Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ147.0,143.3,135.7,132.5,129.3,126.4,118.4,117.5,114.6,114.5,63.9,35.0.

[0173] Embodiment 25

[0174] 3-methyl-1-phenyl-1H-indole (denoted as 1w, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3w. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and after elution with petroleum ether: ethyl acetate (V:V=4:1) as an eluent, the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3w (2-(2-(phenylamino)phenyl)propan-1-ol), with an isolated yield of 66%.

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

[0176]

[0177] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.32(dd,J=8.0,1.1Hz,1H),7.26(dd,J=7.7,1.5Hz,1H),7.24-7.13(m,3H),7.06(td,J=7.5,1.1Hz, 1H),6.92-6.86(m,2H),6.83(t,J=7.3Hz,1H),3.82(dd,J=10.2,5.1Hz,1H),3.59(t,J=9.6Hz,1H),3.42-3.28(m,1H),1.23(s,3H). 13 C NMR (101MHz, Chloroform-d) δ145.1,141.7,136.3,129.4,127.1,126.8,123.3,121.6,119.7,116.5,69.9,35.4,16.8.

[0178] Embodiment 26

[0179] 1-Methyl-1H-indole (denoted as 1x, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 140°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3x. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V=4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3x (2-(2-(methylamino)phenyl)ethane-1-ol), with an isolated yield of 72%.

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

[0181]

[0182] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.18(td,J=7.9,1.5Hz,1H),7.04(dd,J=7.4,1.4hz,1H),6.72(td,J =7.4,0.9Hz,1H),6.66(d,J=8.1Hz,1H),3.86(t,J=6.2Hz,2H),2.84(s,3H),2.76(t,J=6.2Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ147.8,130.3,128.1,123.9,117.6,110.5,63.2,34.8,31.0.

[0183] Embodiment 27

[0184] 1-Benzyl-1H-indole (denoted as 1y, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and the reaction temperature was lowered to room temperature after the reaction was completed. Sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3y. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V = 4:1) was used as an eluent for elution, and the obtained eluate was decompressed and dried by spin drying to obtain a compound of the structure shown in formula 3y (2-(2-(benzylamino)phenyl)ethane-1-ol), and the isolated yield was 62%.

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

[0186]

[0187] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.37-7.31(m,4H),7.29-7.22(m,1H),7.11(td,J=8.0,1.6Hz,1H),7.05(dd,J=7.4,1.3 Hz,1H),6.71(td,J=7.4,1.2Hz,1H),6.64(d,J=8.0Hz,1H),4.32(s,2H),3.85(t,J=6.3Hz,2H),2.77(t,J=6.2Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ146.6,139.5,130.4,128.8,128.0,127.6,127.3,123.8,117.8,111.3,63.0,48.4,34.9.

[0188] Embodiment 28

[0189] 1-Octyl-1H-indole (denoted as 1z, 0.2mmol) and tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6mmol, 2mol / L) were added to a 15mL pressure-resistant reaction tube, stirred at 100°C for 12h under argon (1atm) atmosphere, and after the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1mmol) and 2mL tetrahydrofuran aqueous solution (tetrahydrofuran to water volume ratio 1:1) were added, and stirred at 40°C for 4h to obtain a product system containing a compound of the structure shown in formula 3z. Then the reaction temperature was lowered to room temperature and purified by silica gel column chromatography, and petroleum ether: ethyl acetate (V:V=4:1) was used as an eluent for elution, and the obtained eluate was decompressed and spin-dried to obtain a compound of the structure shown in formula 3z (2-(2-(octylamino)phenyl)ethane-1-ol), and the separation yield was 46%.

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

[0191]

[0192] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ7.15(td,J=7.9,1.6Hz,1H),7.04(dd,J=7.4,1.5Hz,1H),6.73-6.63(m,2H),3.88(t,J=6.2Hz,2H ),3.10(t,J=7.1Hz,2H),2.77(t,J=6.2Hz,2H),1.65(p,J=7.1Hz,2H),1.46-1.36(m,2H),1.36-1.21(m,8H),0.93-0.82(m,3H). 13 C NMR (101MHz, Chloroform-d) δ147.0,130.4,128.0,123.6,117.4,111.1,63.2,44.2,34.9,32.0,29.7,29.6,29.4,27.4,22.8,14.2.

[0193] Embodiment 29

[0194] 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) were respectively added into a 15 mL pressure-resistant reaction tube, and stirred at 100 ° C for 12 h under an argon (1 atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (tetrahydrofuran: water volume ratio 1:1) were added, and stirred at 40 ° C for 4 h to obtain a product system containing a compound represented by the structure of formula 3aa. The reaction temperature was then lowered to room temperature and the mixture was purified by silica gel column chromatography using petroleum ether:ethyl acetate (V:V=4:1) as an eluent. The resulting eluate was then dried under reduced pressure to obtain a structural compound of formula 3aa (2-(1,2,3,4-tetrahydroquinolin-8-yl)ethane-1-ol) with an isolated yield of 54%.

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

[0196]

[0197] The product characterization data are: 1 H NMR(400MHz,Chloroform-d)δ6.86(dd,J=7.2,3.5Hz,2H),6.60(t,J=7.4hz,1H),3.85(t,J=6.2 Hz,2H),3.36-3.26(m,2H),2.78(t,J=6.4hz,2H),2.70(t,J=6.2Hz,2H),1.91(p,J=6.3Hz,2H). 13 C NMR (101MHz, Chloroform-d) δ143.3,128.3,128.1,123.2,122.3,117.1,63.2,42.4,34.6,27.6,22.1.

[0198] Embodiment 30

[0199] 1-((7-(3-((3r,5r,7r)-adamantan-1-yl)-4-methoxyphenyl)naphthalen-2-yl)methyl)-1H-indole (denoted as 1ab, 0.2 mmol) and a tetrahydrofuran solution of borane dimethyl sulfide complex (denoted as 2a, 0.6 mmol, 2 mol / L) were added into a 15 mL pressure-resistant reaction tube, respectively, and stirred at 100 ° C for 12 h under an argon (1 atm) atmosphere. After the reaction, the reaction temperature was lowered to room temperature, sodium perborate tetrahydrate (1 mmol) and 2 mL of tetrahydrofuran aqueous solution (the volume ratio of tetrahydrofuran to water was 1:1) were added, and stirred at 40 ° C for 4 h to obtain a product system containing a compound represented by the structure of formula 3ab. The reaction temperature was then lowered to room temperature and the product was purified by silica gel column chromatography using petroleum ether:ethyl acetate (V:V=4:1) as an eluent, and the eluate was decompressed and spin-dried to obtain a structural compound (2-(2-(((7-(3-((3r,5r,7r)-adamantane-1-yl)-4-methoxyphenyl)naphthalen-2-yl)methyl)amino)phenyl)ethane-1-ol) represented by formula 3ab in 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(400MHz,Chloroform-d)δ7.97(d,J=1.8Hz,1H),7.90-7.77(m,3H),7.72(dd,J =8.5,1.9Hz,1H),7.58(d,J=2.4hz,1H),7.51(td,J=8.6,2.0Hz,2H),7.17-7.04(m, 2H),6.98(d,J=8.5Hz,1H),6.78-6.65(m,2H),4.50(s,2H),3.92(t,J=6.2Hz,2H),3 .89(s,3H),2.84(t,J=6.2Hz,2H),2.18(d,J=2.5Hz,6H),2.10(s,3H),1.80(s,6H). 13 C NMR(101MHz,Chloroform-d)δ158.7,146.7,139.0,136.7,133.3,132.4,130.4,128.7,128.2,128.1,126.2,1 26.1,126.0,125.9,125.7,125.0,123.9,117.9,112.2,111.5,63.2,55.3,48.7,40.8,37.3,37.3,35.0,29.3.

[0203] Comparative Example 1

[0204] Compound 3a was prepared according to the method of Example 1. The only difference from Example 1 was that borane dimethyl sulfide 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. The only difference from Example 1 was that borane dimethyl sulfide complex was replaced by HBpin. Compound 3a was not detected, and only 1a was detected in the reaction solution.

[0207] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing aminophenethanol compounds by structural reforming of indole compounds, comprising the following steps: An indole compound and a borane compound are mixed and subjected to a reduction reaction in a protective atmosphere to obtain a benzazaboride; The benzazaboride is mixed with sodium perborate tetrahydrate and subjected to a ring-opening oxidation reaction to obtain an aminophenethanol compound.

2. The preparation method according to claim 1, characterized in that: The indole compound has a structure shown in Formula 1: In Formula 1, R 1 Including one or more of phenyl, alkyl, cycloalkyl, naphthyl, benzodioxy, benzodioxetane, substituted aryl and substituted alkyl; R 2 It includes one or more of hydrogen, alkyl, methoxy, amino and halogen.

3. The preparation method according to claim 2, characterized in that: The substituents in the substituted aryl group include methyl, tert-butyl, methoxy, oxyphenyl, methylthio, phenyl, fluorine, bromine, trifluoromethyl, alkyl alcohol and One or more of the .

4. The preparation method according to claim 2, characterized in that: The substituents in the substituted alkyl group include one or more of aryl, alkyl, methoxy and naphthyl.

5. The preparation method according to claim 1, characterized in that: 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.

6. The preparation method according to claim 1 or 5, characterized in that: The borane compounds include borane dimethyl sulfide complex and / or borane tetrahydrofuran complex.

7. The preparation method according to claim 1, characterized in that: The molar ratio of the indole compound to the borane compound is 1:3-5.

8. The preparation method according to claim 1, 2, 3, 4, 5 or 7, characterized in that: The temperature of the reduction reaction is 80-140° C. and the time is 12-24 hours.

9. The preparation method according to claim 1, characterized in that: The molar ratio of the benzazaboride to sodium perborate tetrahydrate is 1:3-5.

10. The preparation method according to claim 1, characterized in that: The temperature of the ring-opening oxidation reaction is 30-40° C. and the time is 4-6 hours.

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