Method for synthesizing indole based on 2-aminophenone and aldehyde

Abstract

The invention discloses a method for synthesizing indole based on 2-aminophenone and aldehyde, which comprises the following steps: by taking 2-aminophenone and aldehyde as reaction raw materials, mixing the 2-aminophenone and aldehyde with a reducing agent in a reductive catalytic system of cheap metal molybdenum, dissolving the mixture in an organic solvent, heating and stirring under an anaerobic condition, and separating and purifying to obtain the corresponding 2, 4-benzpyrole in one step. The invention discloses a 1, 3-disubstituted indole product. The method disclosed by the invention has the characteristics of simple and easily available raw materials, wide functional group compatibility and the like, can realize amplified-scale preparation of the 2, 3-disubstituted indole compound, has good production practicability, and has very high application value in the fields of organic synthesis, drug synthesis and the like.

Description

Technical Field

[0001] This invention belongs to the fields of organic chemistry and pharmaceutical technology, and specifically relates to a method for synthesizing indole based on 2-aminophenyl ketone and aldehyde. Background Technology

[0002] Aromatic indole compounds are widely found in natural products, bioactive molecules, and pharmaceuticals, such as the alkaloid antitumor drugs vincristine and vinblastine, the nonsteroidal anti-inflammatory drug indomethacin, the psychotropic drugs sumatriptan and reserpine, and the antiemetic ondansetron. Given the importance of indole in the chemical pharmaceutical field, developing efficient indole synthesis methods is of great significance and has long been a hot topic in organic synthesis. Common named reactions for indole synthesis include: the Fischer reaction, the Bischler-Möhlau reaction, the Bartoli reaction, the Batcho-Leimgruber reaction, the Cadogan-Sundberg reaction, the Larock reaction, the Fukuyama reaction, and the Gassman reaction, among others.

[0003] Several studies have reported on the construction of indoles using 2-aminophenyl ketone derivatives as substrates and aldehydes via condensation / cyclization strategies. Specifically, the 2-aminophenyl ketone derivatives can be alcohols (…). Org. Biomol. Chem. (2016, 14, 4071) N -Phenylacetylhydrazone ( Org. Chem. Front. , 2018, 5, 1170), Quaternary phosphorus salt ( J. Org. Chem. , 2009, 74,5337; Green Chem. , 2024, 26, 9295). On the other hand, the C(sp) of metal carbene 2 The )-H insertion reaction has been extensively studied, with precursors including palladium, rhodium, ruthenium, and iridium. Common carbene precursors include diazo and sulfonylhydrazones, while the direct deoxygenation of activated ketone carbonyl groups to form carbenes has been less studied but is gradually gaining attention from researchers. J. Am. Chem. Soc. ,2019,141,9832; J. Am. Chem. Soc. ,2023,145,2765; Adv. Synth. Catal. (e.g., 2024, 366, 4661). Furthermore, no method has been reported for the direct synthesis of indole from the reaction of 2-aminophenyl ketone with aldehydes.

[0004] Summary of the Invention

[0005] In view of this, the present invention provides a method for synthesizing indole based on 2-aminophenyl ketone and aldehyde. This method uses inexpensive molybdenum as a catalytic system and successfully converts simple, readily available and stable raw materials into highly functionalized 2,3-disubstituted indole, effectively overcoming the shortcomings of existing indole synthesis technologies.

[0006] This invention provides a method for synthesizing indole based on 2-aminophenyl ketone and aldehyde. Using 2-aminophenyl ketone I and aldehyde II as reactants, in a reducing catalytic system of inexpensive molybdenum, both are mixed with a reducing agent and dissolved in an organic solvent; the reaction is carried out under anaerobic conditions with heating and stirring; after separation and purification, the corresponding 2,3-disubstituted indole product III is obtained. The reaction equation is as follows:

[0007] Among them, R 1 The substituent can be any substituent at any position on the benzene ring, and the number of substituents can be one or more. The substituents are selected from hydrogen, alkyl groups such as methyl, alkoxy groups such as methoxy, halogens such as Br, Cl, and F; Ar is a phenyl group, a substituted phenyl group, a naphthyl group, or a heterocyclic group. The substituents on the substituted phenyl group are mono- or poly-substituted alkyl groups, alkoxy groups, phenyl groups, halogens, etc., at any position on the benzene ring; R 2 It is phenyl, substituted phenyl, naphthyl, heterocyclic, or alkyl; further, R 2 The substituents on the substituted phenyl group are mono- or poly-substituted alkyl, alkoxy, dimethylamino, benzyloxy, phenyl, acetoxy, ester, halogen, trifluoromethyl, etc., at any position on the benzene ring; the heterocyclic group is a benzo[a]heterocyclic ring; and the alkyl group is a cycloalkyl group.

[0008] Further, the preparation method specifically involves: adding molybdenum catalyst and o-quinone ligand sequentially into a pressure-resistant tube; after evacuating and replacing the air with nitrogen, opening the pressure-resistant tube under nitrogen protection and adding an organic solvent to dissolve it; then sealing the pressure-resistant tube and heating and stirring it in a water bath to complete the pretreatment of molybdenum catalyst and o-quinone ligand; after restoring to room temperature, opening the pressure-resistant tube again under nitrogen protection and adding 2-aminophenyl ketone I, aldehyde II, and reducing agent sequentially, and replenishing the organic solvent; resealing the pressure-resistant tube and heating and stirring it in a water bath; after the reaction is complete, evaporating the solvent to dryness, and separating and purifying the crude product by rapid column chromatography to obtain 2,3-disubstituted indole product III.

[0009] Furthermore, the molar ratio of 2-aminophenyl ketone I to aldehyde II is 1:2.

[0010] Furthermore, the molybdenum catalyst is any one of Mo(CO)6, MoO2Cl2, MoO2Cl2(DMF)2, MoO2(acac)2, and MoO2Cl2(bpy).

[0011] Furthermore, the amount of molybdenum catalyst fed is 1 mol% to 20 mol%.

[0012] Furthermore, the ortho-quinone ligand is any one of 3,5-di-tert-butyl-o-benzoquinone, tetrachloro-o-benzoquinone, and 9,10-phenanthrenequinone.

[0013] Furthermore, the amount of the ortho-quinone ligand fed is equal to the molar amount of the molybdenum catalyst, that is, the molar ratio of the ortho-quinone ligand to the molybdenum catalyst is 1:1.

[0014] Furthermore, the pretreatment temperature of the molybdenum catalyst and the ortho-quinone ligand is 120 ~ 180 °C.

[0015] Further, the reducing agent is any one of triphenylphosphine, 1,2-bis(diphenylphosphine)ethane, 1,4-bis(diphenylphosphine)butane, phenylsilane, and phenyldimethylsilane.

[0016] Furthermore, the amount of the reducing agent is 0.6 to 2.0 molar equivalents.

[0017] Furthermore, the organic solvent is any one of toluene, xylene, mesitylene, chlorobenzene, trifluorotoluene, and diethylene glycol dimethyl ether.

[0018] Furthermore, the reaction temperature is 120 ~ 200℃.

[0019] Furthermore, the reaction time is 12 to 48 hours.

[0020] The possible reaction routes of this invention are as follows:

[0021] The reaction process may proceed as follows: condensation and dehydration of I and II to form imine intermediate Int-1; reaction of the divalent molybdenum catalytic species with the carbonyl group of Int-1 to form molybdenum carbene intermediate Int-2; and intramolecular C(sp) of the molybdenum carbene. 2 The )-H insertion reaction constructs the five-membered ring intermediate Int-3, and the resulting tetravalent molybdenum is reduced to regenerate divalent molybdenum; Int-3 isomerizes to generate the stable indole product III.

[0022] This technical solution has at least one of the following beneficial effects: 1. The raw materials are simpler and more readily available. In particular, 2-aminophenyl ketone I is used directly as a reactant, without the need to further convert it into the active raw materials described in the background art, or into traditional carbene precursors such as diazo or hydrazone, which greatly reduces the cost of raw materials.

[0023] 2. A catalytic system was constructed using inexpensive molybdenum and commercially available ortho-quinone ligands, utilizing the intramolecular C(sp) of molybdenum carbene. 2The )-H insertion reaction constructs a five-membered ring, avoiding the use of precious metal catalysts such as palladium, rhodium, ruthenium, and iridium.

[0024] 3. The regeneration of molybdenum catalytic species is achieved using a relatively stable reducing agent, avoiding the use of active reagents and making the reaction operation safer and more convenient.

[0025] 4. The reaction system has broad functional group compatibility and can realize the large-scale preparation of 2,3-disubstituted indole compounds, which has good production practicality and high application value in organic synthesis and drug synthesis. Detailed Implementation

[0026] The present invention will be further described in detail below with reference to specific embodiments. The processes, conditions, and experimental methods for implementing the present invention, except as specifically mentioned below, are all conventional methods, and the raw materials mentioned herein are all available from publicly available commercial sources unless otherwise specified.

[0027] This invention provides a method for synthesizing indole based on 2-aminophenyl ketone and aldehyde as follows: Using 2-aminophenyl ketone I and aldehyde II as reactants, in a reducing catalytic system using inexpensive molybdenum, both are mixed with a reducing agent and dissolved in an organic solvent; the reaction is carried out under anaerobic conditions with heating and stirring; after separation and purification, the corresponding 2,3-disubstituted indole product III is obtained. The reaction equation is as follows:

[0028] Among them, R 1 For hydrogen, alkyl, alkoxy, halogen, Ar is phenyl, substituted phenyl, naphthyl, heterocyclic, R 2 It can be phenyl, substituted phenyl, naphthyl, heterocyclic, or alkyl.

[0029] The specific procedure is as follows: molybdenum catalyst and o-quinone ligand are added sequentially to a pressure-resistant tube; after evacuating the tube to replace the air with nitrogen, the pressure-resistant tube is opened under nitrogen protection, and an organic solvent is added to dissolve the ligand; the pressure-resistant tube is then sealed and placed in a water bath for heating and stirring to complete the pretreatment of the molybdenum catalyst and o-quinone ligand; after returning to room temperature, the pressure-resistant tube is opened again under nitrogen protection, and 2-aminophenyl ketone I, aldehyde II, and reducing agent are added sequentially, along with additional organic solvent; the pressure-resistant tube is then resealed and placed in a water bath for heating and stirring; after the reaction is complete, the solvent is evaporated, and the crude product is separated and purified by rapid column chromatography to obtain 2,3-disubstituted indole product III.

[0030] Specifically, the molybdenum catalyst is any one of Mo(CO)6, MoO2Cl2, MoO2Cl2(DMF)2, MoO2(acac)2, and MoO2Cl2(bpy); the amount of molybdenum catalyst is 1 mol% to 20 mol%; the o-quinone ligand is any one of 3,5-di-tert-butyl-o-benzoquinone, tetrachloro-o-benzoquinone, and 9,10-phenanthrenequinone; the amount of o-quinone ligand is 1 mol% to 20 mol% (equal to the molar amount of the molybdenum catalyst); the pretreatment temperature of the molybdenum catalyst and the o-quinone ligand is 120 to 180 °C; the reducing agent is any one of triphenylphosphine, 1,2-bis(diphenylphosphine)ethane, 1,4-bis(diphenylphosphine)butane, phenylsilane, and phenyldimethylsilane; the amount of the reducing agent is 0.6 to 100 °C. 2.0 molar equivalent; the organic solvent is any one of toluene, xylene, mesitylene, chlorobenzene, trifluorotoluene, and diethylene glycol dimethyl ether; the reaction temperature is 120 ~ 200℃; the reaction time is 12 ~ 48h.

[0031] Raw material I comprises 18 structures, from I-1 to I-18, as follows:

[0032] Material II comprises 21 structures, II-1 to II-21, as follows: Example 1

[0033] 2-(4-methoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-1)

[0034] Mo(CO)6 (5.3 mg, 0.02 mmol) and tetrachloro-o-benzoquinone ligand (4.9 mg, 0.02 mmol) were added sequentially to a pressure-resistant tube. After evacuating the tube and replacing it with nitrogen, the pressure-resistant tube was opened under nitrogen protection, and 1 mL of dry toluene was added to dissolve the ligand. The pressure-resistant tube was then sealed and heated and stirred in a 160°C oil bath for 15 min to complete the pretreatment of the molybdenum catalyst and the o-quinone ligand. After returning to room temperature, the pressure-resistant tube was opened again under nitrogen protection, and 2-aminobenzophenone I-1 (39.4 mg, 0.20 mmol), p-methoxybenzaldehyde II-1 (54.5 mg, 0.40 mmol), and the reducing agent triphenylphosphine (62.9 mg, 0.24 mmol) were added sequentially, and 1 mL of nitrogen was added to the tube. mL of dry toluene; reseal the pressure-resistant tube and heat and stir it in an oil bath at 180℃; after the reaction is complete, evaporate the solvent and separate and purify the crude product by rapid column chromatography to obtain 2,3-disubstituted indole product III-1 (40.7 mg, yield 68%, white solid).

[0035] The NMR data for product III-1 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.19 (br, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.51-7.49 (m, 2H), 7.45-7.26 (m, 7H), 7.22-7.19 (m, 1H), 6.90 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.11, 135.67, 135.20, 134.08, 130.06, 129.41, 128.70, 128.46, 126.03, 125.08, 122.32, 120.29, 119.39, 114.09, 110.75, 55.21. Example 2

[0036] Following the procedure in Example 1, the catalyst Mo(CO)6 was replaced with MoO2(acac)2 (6.5 mg, 0.02 mmol). After the reaction was completed, compound III-1 (11.0 mg, yield 18%) was successfully prepared. Example 3

[0037] Following the procedure in Example 1, the ligand tetrachloro-o-benzoquinone was replaced with 3,5-di-tert-butyl-o-benzoquinone (4.4 mg, 0.02 mmol). After the reaction was completed, compound III-1 (32.3 mg, yield 54%) was successfully prepared. Example 4

[0038] Following the procedure in Example 1, the reducing agent triphenylphosphine was replaced with 1,4-bis(diphenylphosphine)butane (51.2 mg, 0.12 mmol). After the reaction was completed, compound III-1 (35.9 mg, 60% yield) was successfully prepared. Example 5

[0039] Following the procedure in Example 1, the solvent toluene was replaced with mesitylene (2 mL). After the reaction was completed, compound III-1 (38.9 mg, yield 65%) was successfully prepared. Example 6

[0040] Following the procedure in Example 1, the reaction temperature was reduced from 180°C to 140°C. After the reaction was completed, compound III-1 (28.7 mg, yield 48%) was successfully prepared. Example 7

[0041] 2-(4-methoxyphenyl)-3-phenyl-5-methyl-1 H Synthesis of -indole(III-2)

[0042] Following the procedure in Example 1, I-1 was replaced with I-2, and III-2 (40.6 mg, yield 65%, white solid) was successfully prepared.

[0043] The NMR data for product III-2 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.10 (br, 1H), 7.57-7.54 (m, 3H), 7.50-7.46 (m, 2H), 7.39-7.37 (m, 3H), 7.32 (d, J = 8.2 Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 6.90 (d, J = 8.6 Hz, 2H), 3.85 (s, 3H), 2.54 (s, 3H); 13 C NMR (101 MHz, CDCl3) d158.95, 135.41, 134.19, 134.00, 130.08, 129.48, 129.31, 128.92, 128.42, 125.92, 125.19, 123.83, 118.91, 113.98, 113.56, 110.47, 55.11, 21.49. Example 8

[0044] 2-(4-methoxyphenyl)-3-phenyl-6-methyl-1 H Synthesis of -indole (III-3)

[0045] Following the procedure in Example 1, I-1 was replaced with I-3, and III-3 (30.8 mg, yield 49%, colorless oil) was successfully prepared.

[0046] The NMR data for product III-3 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.04 (br, 1H), 7.64-7.62 (m, 1H), 7.51-7.32 (m, 7H), 7.19 (s, 1H), 7.04 (d, J = 8.0 Hz, 1H), 6.88(d, J = 8.3 Hz, 2H), 3.84 (s, 3H), 2.53 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 158.96, 136.13, 135.39, 133.37, 132.14, 129.99, 129.30, 128.42, 126.56, 125.92, 125.27, 122.00, 119.03, 114.03, 110.73, 55.16, 21.69. Example 9

[0047] 2-(4-methoxyphenyl)-3-phenyl-5-methoxy-1 H Synthesis of -indole (III-4)

[0048] Following the procedure in Example 1, I-1 was replaced with I-4, and III-4 (56.3 mg, yield 85%, white solid) was successfully prepared.

[0049] The NMR data for product III-4 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.22 (br, 1H), 7.52-7.45 (m, 4H), 7.36-7.28 (m, 4H), 7.22 (s, 1H), 6.97-6.87 (m, 3H), 3.88 (s,3H), 3.83 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 158.99, 154.56, 135.38, 134.99, 130.87, 129.97, 129.29, 129.09, 128.52, 125.96, 125.11, 113.99, 113.86, 112.41, 111.60, 101.01, 55.83, 55.12. Example 10

[0050] 2-(4-methoxyphenyl)-3-phenyl-5-bromo-1 H Synthesis of -indole (III-5)

[0051] Following the procedure in Example 1, I-1 was replaced with I-5, and III-5 (68.7 mg, yield 91%, white solid) was successfully prepared.

[0052] The NMR data for product III-5 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.22 (br, 1H), 7.80 (s, 1H), 7.42-7.41 (m, 4H), 7.34-7.30 (m, 4H), 7.24-7.22 (m, 1H), 6.85 (d, J = 8.5 Hz, 2H), 3.81 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.31, 135.24, 134.48, 134.26, 130.50, 129.93, 129.36, 128.61, 126.36, 124.99, 124.43, 121.79, 114.13, 113.59, 113.51, 112.21, 55.20. Example 11

[0053] 2-(4-methoxyphenyl)-3-phenyl-5-chloro-1 H Synthesis of -indole (III-6)

[0054] Following the procedure in Example 1, I-1 was replaced with I-6, and III-6 (60.2 mg, 90% yield, white solid) was successfully prepared.

[0055] The NMR data for product III-6 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.03 (br, 1H), 7.48 (s, 1H), 7.24-7.23 (m, 4H), 7.13-6.98 (m, 5H), 6.65 (d, J = 8.3 Hz, 2H), 3.61(s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.24, 135.42, 134.53, 133.98, 129.88, 129.81, 129.33, 128.58, 126.30, 125.85, 124.45, 122.37, 118.67, 114.08, 113.60, 111.79, 55.13.

[0056] The high-resolution mass spectrometry data for product III-6 are as follows: HRMS (EI) m / z: [M+H] + Calcd forC 21 H 17 ClNO + 334.0993; Found 334.0996. Example 12

[0057] 2-(4-methoxyphenyl)-3-phenyl-6-chloro-1 H Synthesis of -indole (III-7)

[0058] Following the procedure in Example 1, I-1 was replaced with I-7, and III-7 (41.5 mg, yield 62%, colorless oil) was successfully prepared.

[0059] The NMR data for product III-7 are as follows: 1 H NMR (400 MHz, CDCl3) d7.98 (br, 1H), 7.41 (d, J = 8.5 Hz, 1H), 7.26-7.22 (m, 4H), 7.17-7.13 (m, 4H), 6.97-6.95 (m, 1H), 6.68 (d, J = 8.6 Hz, 2H), 3.64 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.21, 135.95, 134.62, 129.92, 129.31, 128.55, 127.82, 127.33, 126.29, 124.54, 120.86, 120.21, 114.11, 113.94, 110.64, 55.18. Example 13

[0060] 2-(4-methoxyphenyl)-3-phenyl-5-fluoro-1 H Synthesis of -indole (III-8)

[0061] Following the procedure in Example 1, I-1 was replaced with I-8, and III-8 (46.4 mg, yield 73%, white solid) was successfully prepared.

[0062] The NMR data for product III-8 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.19 (br, 1H), 7.50-7.42 (m, 5H), 7.38-7.34 (m, 3H), 7.30-7.27 (m, 1H), 7.05-7.00 (m, 1H), 6.89(d, J = 8.6 Hz, 2H), 3.84 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.20, 158.32(d, J = 233.0 Hz), 135.89, 134.77, 132.16, 129.79, 129.33, 129.11 (d, J =10.0 Hz), 128.56, 126.19, 124.64, 114.09, 114.06, 111.44 (d, J= 9.0 Hz), 110.39 (d, J = 26.0 Hz), 104.17 (d, J = 24.0 Hz), 55.09; 19 F NMR (376 MHz, CDCl3) d -123.67.

[0063] The high-resolution mass spectrometry data for product III-8 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 21 H 17 FNO + 318.1289; Found 318.1292. Example 14

[0064] 2-(4-methoxyphenyl)-3-(4-methylphenyl)-1 H Synthesis of -indole (III-9)

[0065] Following the procedure in Example 1, I-1 was replaced with I-9, and III-9 (33.8 mg, yield 54%, colorless oil) was successfully prepared.

[0066] The NMR data for product III-9 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.16 (br, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.44-7.40 (m, 5H), 7.32-7.22 (m, 4H), 6.92 (d, J = 8.5Hz, 2H), 3.86 (s, 3H), 2.48 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.02, 135.67, 135.54, 133.84, 132.12, 129.89, 129.35, 129.22, 128.80, 125.21, 122.22, 120.17, 119.43, 114.03, 113.93, 110.73, 55.16, 21.20. Example 15

[0067] 2-(4-methoxyphenyl)-3-(3-methylphenyl)-1H Synthesis of -indole (III-10)

[0068] Following the procedure in Example 1, I-1 was replaced with I-10, and III-10 (44.3 mg, yield 71%, colorless oil) was successfully prepared.

[0069] The NMR data for product III-10 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.17 (br, 1H), 7.79 (d, J = 5.6 Hz, 1H), 7.44-7.22 (m, 9H), 6.92 (d, J = 8.3 Hz, 2H), 3.86 (s, 3H), 2.46 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 158.99, 137.91, 135.66, 135.10, 133.94, 130.65, 129.31, 128.78, 128.33, 127.19, 126.82, 125.11, 122.22, 120.17, 119.41, 114.04, 113.98, 110.75, 55.12, 21.46.

[0070] The high-resolution mass spectrometry data for product III-10 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 22 H 20 NO + 314.1539; Found 314.1543. Example 16

[0071] 2-(4-methoxyphenyl)-3-(2-methylphenyl)-1 H Synthesis of -indole (III-11)

[0072] Following the procedure in Example 1, I-1 was replaced with I-11, and III-11 (16.7 mg, yield 27%, colorless oil) was successfully prepared.

[0073] The NMR data for product III-11 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.06 (br, 1H),7.25-7.06 (m, 9H), 7.00-6.96 (m, 1H), 6.66 (d, J = 8.5 Hz, 2H), 3.61 (s, 3H), 1.91 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 158.84, 137.74, 135.57, 134.64, 133.80, 131.56, 130.21, 129.60, 127.98, 127.02, 125.80, 125.44, 122.12, 119.96, 119.61, 114.12, 113.58, 110.63, 55.12, 20.09. Example 17

[0074] 2,3-Bis(4-methoxyphenyl)-1 H Synthesis of -indole (III-12)

[0075] Following the procedure in Example 1, I-1 was replaced with I-12, and III-12 (32.7 mg, yield 50%, colorless oil) was successfully prepared.

[0076] The NMR data for product III-12 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.20 (br, 1H), 7.72 (d, J = 7.6 Hz, 1H), 7.43-7.38 (m, 5H), 7.29-7.19 (m, 2H), 7.00 (d, J = 8.6Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 3.90 (s, 3H), 3.85 (s, 3H); 13 C NMR (101MHz, CDCl3) d 158.99, 157.92, 135.64, 133.69, 131.09, 129.27, 128.91, 127.50, 125.21, 122.22, 120.14, 119.35, 114.05, 113.96, 110.72, 55.18, 55.16. Example 18

[0077] 2-(4-methoxyphenyl)-3-(4-tert-butylphenyl)-1 H Synthesis of -indole (III-13)

[0078] Following the procedure in Example 1, I-1 was replaced with I-13, and III-13 (49.1 mg, yield 69%, colorless oil) was successfully prepared.

[0079] The NMR data for product III-13 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.12 (br, 1H), 7.81 (d, J = 7.7 Hz, 1H), 7.48-7.39 (m, 7H), 7.31-7.21 (m, 2H), 6.90 (d, J = 8.5Hz, 2H), 3.85 (s, 3H), 1.47 (s, 9H); 13 C NMR (101 MHz, CDCl3) d 158.97, 148.66, 135.68, 133.89, 132.07, 129.54, 129.42, 128.80, 125.32, 125.27, 122.16, 120.10, 119.58, 113.99, 113.84, 110.75, 55.12, 34.44, 31.38. Example 19

[0080] 2-(4-methoxyphenyl)-3-(4-biphenyl)-1 H Synthesis of -indole (III-14)

[0081] Following the procedure in Example 1, I-1 was replaced with I-14, and III-14 (63.8 mg, yield 85%, white solid) was successfully prepared.

[0082] The NMR data for product III-14 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.00 (br, 1H), 7.63 (d, J= 7.8 Hz, 1H), 7.55-7.49 (m, 4H), 7.40-7.38 (m, 2H), 7.34-7.31 (m, 2H), 7.25-7.20 (m, 4H), 7.13-7.03 (m, 2H), 6.73 (d, J = 8.6 Hz, 2H), 3.65 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.16, 140.86, 138.49, 135.74, 134.32, 134.25, 130.33, 129.50, 128.73, 128.63, 127.09, 127.05, 126.85, 125.05, 122.35, 120.35, 119.41, 114.12, 113.53, 110.82, 55.18.

[0083] The high-resolution mass spectrometry data for product III-14 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 27 H 22 NO + 376.1696; Found 376.1699. Example 20

[0084] 2-(4-methoxyphenyl)-3-(4-bromophenyl)-1 H Synthesis of -indole (III-15)

[0085] Following the procedure in Example 1, I-1 was replaced with I-15, and III-15 (63.7 mg, yield 84%, white solid) was successfully prepared.

[0086] The NMR data for product III-15 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.18 (br, 1H), 7.73 (d, J = 7.7 Hz, 1H), 7.58-7.56 (m, 2H), 7.43-7.23 (m, 7H), 6.93 (d, J = 8.4Hz, 2H), 3.87 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.18, 135.61, 134.32, 134.18, 131.56, 129.42, 128.22, 124.58, 122.42, 120.44, 119.78, 118.99, 114.13, 112.60, 110.88, 55.16.

[0087] The high-resolution mass spectrometry data for product III-15 are as follows: HRMS (EI) m / z: [M+H] + Calcd forC 21 H 17 BrNO + 378.0488; Found 378.0488. Example 21

[0088] 2-(4-methoxyphenyl)-3-(4-chlorophenyl)-1 H Synthesis of -indole (III-16)

[0089] Following the procedure in Example 1, I-1 was replaced with I-16, and III-16 (62.6 mg, yield 94%, colorless oil) was successfully prepared.

[0090] The NMR data for product III-16 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.21 (br, 1H), 7.74 (d, J = 7.6 Hz, 1H), 7.43-7.23 (m, 9H), 6.93 (d, J = 8.4 Hz, 2H), 3.87 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.20, 135.62, 134.34, 133.72, 131.64, 131.22, 129.42, 128.64, 128.34, 124.65, 122.42, 120.43, 119.02, 114.14, 112.65, 110.88, 55.16. Example 22

[0091] 2-(4-methoxyphenyl)-3-(4-fluorophenyl)-1 H Synthesis of -indole (III-17)

[0092] Following the procedure in Example 1, I-1 was replaced with I-17, and III-17 (53.8 mg, yield 85%, colorless oil) was successfully prepared.

[0093] The NMR data for product III-17 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.17 (br, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.46-7.21 (m, 7H), 7.16-7.12 (m, 2H), 6.91 (d, J = 8.5Hz, 2H), 3.85 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 161.38 (d, J = 243.0 Hz),159.13, 135.58, 134.12, 131.48 (d, J = 8.0 Hz), 131.10 (d, J = 3.0 Hz),129.35, 128.62, 124.81, 122.36, 120.34, 119.08, 115.38 (d, J = 21.0 Hz),114.10, 112.92, 110.83, 55.15; 19 F NMR (376 MHz, CDCl3) d -116.55. Example 23

[0094] 2-(4-methoxyphenyl)-3-(2-naphthyl)-1 H Synthesis of -indole (III-18)

[0095] Following the procedure in Example 1, I-1 was replaced with I-18, and III-18 (53.4 mg, yield 76%, white solid) was successfully prepared.

[0096] The NMR data for product III-18 are as follows: 1 H NMR (400 MHz, CDCl3) d8.22 (br, 1H), 8.11 (s, 1H), 7.95-7.89 (m, 4H), 7.60-7.56 (m, 3H), 7.46-7.26 (m, 5H), 6.87 (d, J = 8.4 Hz, 2H), 3.82 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 159.08, 135.75, 134.37, 133.79, 132.89, 131.96, 129.39, 128.85, 128.80, 128.19, 127.86, 127.75, 127.60, 125.83, 125.37, 124.92, 122.37, 120.36, 119.31, 114.04, 113.77, 110.87, 55.08.

[0097] The high-resolution mass spectrometry data for product III-18 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 25 H 20 NO + 350.1539; Found 350.1543. Example 24

[0098] 2-(3-methoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-19)

[0099] Following the procedure in Example 1, but replacing raw material II-1 with II-2, III-19 (46.3 mg, yield 77%, colorless oil) was successfully prepared.

[0100] The NMR data for product III-19 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.06 (br, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.33-7.32 (m, 2H), 7.27-7.22 (m, 3H), 7.17-7.01 (m, 4H), 6.86 (d, J = 7.6 Hz, 2H), 6.80 (s, 1H), 6.70-7.68 (m, 1H), 3.48 (s, 3H);13 CNMR (101 MHz, CDCl3) d 159.44, 135.73, 135.00, 133.83, 133.78, 130.18, 129.65, 128.68, 128.46, 126.25, 122.68, 120.35, 120.25, 119.61, 115.15, 113.63, 113.37, 110.90, 54.97. Example 25

[0101] 2-(2-methoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-20)

[0102] Following the procedure in Example 1, but replacing raw material II-1 with II-3, III-20 (21.6 mg, yield 36%, colorless oil) was successfully prepared.

[0103] The NMR data for product III-20 are as follows: 1 H NMR (400 MHz, CDCl3) d 9.04 (br, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.52-7.41 (m, 5H), 7.34-7.28 (m, 4H), 7.19 (t, J = 7.5Hz, 1H), 7.05 (d, J = 8.1 Hz, 1H), 6.86 (t, J = 7.5 Hz, 1H), 3.90 (s, 3H); 13 CNMR (101 MHz, CDCl3) d 156.68, 135.81, 135.41, 131.99, 131.13, 130.04, 128.98, 128.41, 127.77, 125.94, 122.35, 120.91, 120.80, 119.86, 119.35, 115.66, 111.54, 110.74, 55.63. Example 26

[0104] 2,3-Diphenyl-1 H Synthesis of -indole (III-21)

[0105] Following the procedure in Example 1, but replacing raw material II-1 with II-4, III-21 (35.7 mg, yield 66%, colorless oil) was successfully prepared.

[0106] The NMR data for product III-21 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.11 (br, 1H), 7.60 (d, J = 7.9 Hz, 1H), 7.36-7.26 (m, 7H), 7.22-7.12 (m, 5H), 7.08-7.04 (m, 1H); 13 C NMR (101 MHz, CDCl3) d 135.82, 135.00, 134.04, 132.62, 130.11, 128.67, 128.64, 128.49, 128.14, 127.65, 126.19, 122.65, 120.38, 119.65, 114.95, 110.87. Example 27

[0107] 2-(4-methylphenyl)-3-phenyl-1 H Synthesis of -indole (III-22)

[0108] Following the procedure in Example 1, but replacing raw material II-1 with II-5, III-22 (38.4 mg, yield 68%, colorless oil) was successfully prepared.

[0109] The NMR data for product III-22 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.18 (br, 1H), 7.80 (d, J = 7.9 Hz, 1H), 7.56-7.55 (m, 2H), 7.50-7.46 (m, 3H), 7.40-7.31 (m, 4H), 7.27-7.20 (m, 3H), 2.44 (s, 3H); 13 C NMR (101 MHz, CDCl3) d137.51, 135.73, 135.17, 134.19, 130.10, 129.68, 129.34, 128.73, 128.45, 127.99, 126.09, 122.45, 120.30, 119.51, 114.49, 110.81, 21.20. Example 28

[0110] 2-(4-Benzyloxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-23)

[0111] Following the procedure in Example 1, but replacing raw material II-1 with II-6, III-23 (33.6 mg, yield 45%, white solid) was successfully prepared.

[0112] The NMR data for product III-23 are as follows: 1 H NMR (400 MHz, CDCl3) d 7.98 (br, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.34-7.17 (m, 13H), 7.13-7.09 (m, 1H), 7.06-7.02 (m,1H), 6.79 (d, J = 8.6 Hz, 2H), 4.90 (s, 2H); 13 C NMR (101 MHz, CDCl3) d 158.32, 136.62, 135.66, 135.18, 134.00, 130.06, 129.40, 128.68, 128.57, 128.47, 128.04, 127.51, 126.03, 125.30, 122.32, 120.28, 119.39, 114.94, 114.04, 110.77, 69.91.

[0113] The high-resolution mass spectrometry data for product III-23 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 27 H 22 NO + 376.1696; Found 376.1698. Example 29

[0114] 2-(4-ethoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-24)

[0115] Following the procedure in Example 1, but replacing raw material II-1 with II-7, III-24 (45.3 mg, yield 72%, colorless oil) was successfully prepared.

[0116] The NMR data for product III-24 are as follows: 1 H NMR (400 MHz, CDCl3) d 7.96 (br, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.33-7.31 (m, 2H), 7.26-7.22 (m, 3H), 7.19-7.13 (m, 3H), 7.11-7.07 (m, 1H), 7.04-7.00 (m, 1H), 6.71-6.68 (m, 2H), 3.87 (q, J = 7.0 Hz, 2H), 1.28 (t, J = 7.0 Hz, 3H); 13 C NMR (101 MHz, CDCl3) d 158.53, 135.67, 135.24, 134.16, 130.06, 129.40, 128.71, 128.45, 126.00, 124.89, 122.28, 120.27, 119.37, 114.57, 113.96, 110.75, 63.39, 14.77.

[0117] The high-resolution mass spectrometry data for product III-24 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 22 H 20 NO + 314.1539; Found 314.1543. Example 30

[0118] 2-(4-Dimethylaminophenyl)-3-phenyl-1 H Synthesis of -indole (III-25)

[0119] Following the procedure in Example 1, but replacing raw material II-1 with II-8, III-25 (53.7 mg, yield 86%, yellow oil) was successfully prepared.

[0120] The NMR data for product III-25 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.20 (br, 1H), 7.81 (d, J = 6.5 Hz, 1H), 7.62-7.60 (m, 2H), 7.52-7.48 (m, 2H), 7.45-7.37 (m, 4H), 7.31-7.24 (m, 2H), 6.73 (d, J = 7.4 Hz, 2H), 3.03 (s, 6H); 13 C NMR (101 MHz, CDCl3) d 149.66, 135.64, 134.92, 130.09, 128.93, 128.37, 125.77, 121.88, 121.83, 120.34, 120.05, 119.03, 112.20, 110.64, 40.22.

[0121] The high-resolution mass spectrometry data for product III-25 are as follows: HRMS (EI) m / z: [M+H] + Calcd for C 22 H 21 N2 + 313.1699; Found 313.1697. Example 31

[0122] 2-(4-acetoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-26)

[0123] Following the procedure in Example 1, but replacing raw material II-1 with II-9, III-26 (37.6 mg, yield 57%, colorless oil) was successfully prepared.

[0124] The NMR data for product III-26 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.30 (br, 1H), 7.72 (d, J= 7.9 Hz, 1H), 7.45-7.38 (m, 7H), 7.35-7.28 (m, 2H), 7.23-7.20 (m, 1H),7.05 (d, J = 8.5 Hz, 2H), 2.35 (s, 6H); 13 C NMR (101 MHz, CDCl3) d 169.61, 149.91, 135.89, 134.82, 133.11, 130.37, 130.06, 129.13, 128.61, 128.53, 126.23, 122.66, 121.74, 120.34, 119.60, 115.03, 110.98, 21.10.

[0125] The high-resolution mass spectrometry data for product III-26 are as follows: HRMS (EI) m / z: [M+H] + Calcd forC 20 H 18 NO2 + 328.1332; Found 328.1334. Example 32

[0126] 2-(4-tert-butylphenyl)-3-phenyl-1 H Synthesis of -indole (III-27)

[0127] Following the procedure in Example 1, but replacing raw material II-1 with II-10, III-27 (26.4 mg, yield 41%, colorless oil) was successfully prepared.

[0128] The NMR data for product III-27 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.18 (br, 1H), 7.82 (d, J = 7.0 Hz, 1H), 7.62-7.60 (m, 2H), 7.53-7.26 (m, 10H), 1.45 (s, 9H); 13 CNMR (101 MHz, CDCl3) d150.61, 135.71, 135.22, 134.04, 130.17, 129.60, 128.84, 128.46, 127.62, 126.10, 125.54, 122.43, 120.28, 119.50, 114.55, 110.83, 34.54, 31.20. Example 33

[0129] 2-(4-Biphenyl)-3-phenyl-1 H Synthesis of -indole (III-28)

[0130] Following the procedure in Example 1, but replacing raw material II-1 with II-11, III-28 (40.7 mg, yield 59%, white solid) was successfully prepared.

[0131] The NMR data for product III-28 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.22 (br, 1H), 7.79 (d, J = 7.9 Hz, 1H), 7.68-7.66 (m, 2H), 7.62-7.32 (m, 14H), 7.26 (d, J = 7.3Hz, 1H); 13 C NMR (101 MHz, CDCl3) d 140.24, 140.14, 135.91, 135.04, 133.62, 131.47, 130.17, 128.80, 128.56, 128.35, 127.45, 127.20, 126.86, 126.28, 122.73, 120.43, 119.65, 115.20, 110.90. Example 34

[0132] 2-(4-bromophenyl)-3-phenyl-1 H Synthesis of -indole (III-29)

[0133] Following the procedure in Example 1, but replacing raw material II-1 with II-12, III-29 (40.3 mg, yield 58%, colorless oil) was successfully prepared.

[0134] The NMR data for product III-29 are as follows: 1H NMR (400 MHz, CDCl3) d 8.14 (br, 1H), 7.76 (d, J = 7.8 Hz, 1H), 7.48-7.39 (m, 8H), 7.35-7.22 (m, 4H); 13 C NMR (101 MHz, CDCl3) d 135.86, 134.59, 132.72, 131.74, 131.42, 130.00, 129.54, 128.62, 128.57, 126.42, 122.93, 121.66, 120.53, 119.70, 115.43, 110.95. Example 35

[0135] 2-(4-chlorophenyl)-3-phenyl-1 H Synthesis of -indole (III-30)

[0136] Following the procedure in Example 1, but replacing raw material II-1 with II-13, III-30 (23.8 mg, yield 39%, white solid) was successfully prepared.

[0137] The NMR data for product III-30 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.05 (br, 1H), 7.57 (d, J = 7.9 Hz, 1H), 7.32-7.26 (m, 5H), 7.21-7.12 (m, 6H), 7.08-7.04 (m, 1H); 13 C NMR (101 MHz, CDCl3) d 135.88, 134.64, 133.48, 132.76, 131.04, 130.03, 129.30, 128.86, 128.62, 128.58, 126.41, 122.93, 120.54, 119.71, 115.42, 110.93. Example 36

[0138] 2-(4-Fluorophenyl)-3-phenyl-1 H Synthesis of -indole (III-31)

[0139] Following the procedure in Example 1, but replacing raw material II-1 with II-14, III-31 (14.2 mg, yield 25%, colorless oil) was successfully prepared.

[0140] The NMR data for product III-31 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.03 (br, 1H), 7.59 (d, J = 7.9 Hz, 1H), 7.33-7.24 (m, 7H), 7.21-7.13 (m, 2H), 7.08-7.05 (m, 1H), 6.93-6.88 (m, 2H); 13 C NMR (101 MHz, CDCl3) d 162.26 (d, J = 247.0 Hz),135.80, 134.78, 133.11, 130.04, 129.91 (d, J = 8.0 Hz), 128.74 (d, J = 3.0Hz), 128.57, 126.30, 122.75, 120.50, 119.65, 115.72 (d, J = 22.0 Hz), 114.97, 110.88; 19 F NMR (376 MHz, CDCl3) d -113.51. Example 37

[0141] 2-(4-trifluoromethylphenyl)-3-phenyl-1 H Synthesis of -indole (III-32)

[0142] Following the procedure in Example 1, but replacing raw material II-1 with II-15, III-32 (37.5 mg, yield 56%, white solid) was successfully prepared.

[0143] The NMR data for product III-32 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.23 (br, 1H), 7.72 (d, J = 7.9 Hz, 1H), 7.59-7.51 (m, 4H), 7.46-7.30 (m, 7H), 7.24-7.20 (m, 1H);13 C NMR (101 MHz, CDCl3) d 136.11, 134.41, 132.22, 130.10, 129.26 (q, J = 32.0Hz), 128.74, 128.65, 128.09, 126.69, 125.57 (q, J = 4.0 Hz), 124.05 (q, J =270.0 Hz), 123.38, 120.72, 119.97, 116.57, 111.07; 19 F NMR (376 MHz, CDCl3) d -62.48. Example 38

[0144] 2-(4-methoxycarbonylphenyl)-3-phenyl-1 H Synthesis of -indole (III-33)

[0145] Following the procedure in Example 1, but replacing raw material II-1 with II-16, III-33 (25.4 mg, yield 39%, white solid) was successfully prepared.

[0146] The NMR data for product III-33 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.38 (br, 1H), 7.86 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.0 Hz, 1H), 7.38-7.28 (m, 7H), 7.24-7.22(m, 2H), 7.09-7.05 (m, 1H), 3.81 (s, 3H); 13 C NMR (101 MHz, CDCl3) d 166.86, 137.15, 136.23, 134.60, 132.66, 130.11, 129.88, 128.72, 128.70, 128.66, 127.76, 126.59, 123.31, 120.61, 119.92, 116.65, 111.06, 52.16. Example 39

[0147] 2-(3,4-Dimethoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-34)

[0148] Following the procedure in Example 1, but replacing raw material II-1 with II-17, III-34 (51.3 mg, yield 78%, white solid) was successfully prepared.

[0149] The NMR data for product III-34 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.32 (br, 1H), 7.70 (d, J = 7.8 Hz, 1H), 7.50-7.48 (m, 2H), 7.44-7.40 (m, 3H), 7.34-7.25 (m, 2H), 7.20-7.16 (m, 1H), 7.07-7.05 (m, 1H), 6.90-6.86 (m, 2H), 3.91 (s, 3H), 3.61(s, 3H); 13 C NMR (101 MHz, CDCl3) d 148.67, 148.60, 135.68, 135.27, 134.01, 130.25, 128.80, 128.46, 126.17, 125.32, 122.42, 120.31, 119.88, 119.40, 114.32, 111.70, 111.16, 110.74, 55.79, 55.43. Example 40

[0150] 2-(3,4,5-trimethoxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-35)

[0151] Following the procedure in Example 1, but replacing raw material II-1 with II-18, III-35 (23.8 mg, yield 33%, white solid) was successfully prepared.

[0152] The NMR data for product III-35 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.42 (br, 1H), 7.68 (d, J= 7.8 Hz, 1H), 7.51-7.41 (m, 5H), 7.34-7.26 (m, 2H), 7.20-7.16 (m, 1H), 6.65 (s, 2H), 7.07-7.05 (m, 1H), 6.90-6.86 (m, 2H), 3.91 (s, 3H), 3.68 (s, 6H); 13 C NMR (101 MHz, CDCl3) d 153.18, 137.48, 135.74, 135.15, 133.92, 130.32, 128.83, 128.47, 128.03, 126.31, 122.66, 120.39, 119.54, 115.05, 110.85, 105.16, 60.91, 55.82. Example 41

[0153] 2-(3,4-methylenedioxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-36)

[0154] Following the procedure in Example 1, but replacing raw material II-1 with II-19, III-36 (50.3 mg, yield 80%, white solid) was successfully prepared.

[0155] The NMR data for product III-36 are as follows: 1 H NMR (400 MHz, CDCl3) d 7.99 (br, 1H), 7.58 (d, J = 7.9 Hz, 1H), 7.35-7.26 (m, 5H), 7.20-7.12 (m, 2H), 7.07-7.04 (m, 1H), 6.80 (d, J = 8.0 Hz, 1H), 6.74 (s, 1H), 6.66 (d, J = 8.0 Hz, 1H), 5.83 (s, 2H); 13 C NMR (101 MHz, CDCl3) d147.71, 147.21, 135.58, 134.92, 133.89, 130.04, 128.63, 128.49, 126.57, 126.16, 122.48, 121.93, 120.35, 119.47, 114.38, 110.76, 108.72, 108.58, 101.13. Example 42

[0156] 2-(3,4-ethylenedioxyphenyl)-3-phenyl-1 H Synthesis of -indole (III-37)

[0157] Following the procedure in Example 1, but replacing raw material II-1 with II-20, III-37 (44.3 mg, yield 68%, white solid) was successfully prepared.

[0158] The NMR data for product III-37 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.19 (br, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.52-7.50 (m, 2H), 7.46-7.40 (m, 3H), 7.35-7.32 (m, 1H), 7.29-7.25 (m, 1H), 7.22-7.18 (m, 1H), 7.01 (d, J = 1.8 Hz, 1H), 6.93-6.90 (m,1H), 6.85-6.83 (m, 1H), 4.28-4.24 (m, 4H); 13 C NMR (101 MHz, CDCl3) d 143.49, 143.28, 135.62, 135.06, 133.70, 130.08, 128.74, 128.44, 126.12, 126.03, 122.39, 121.59, 120.27, 119.43, 117.46, 116.78, 114.31, 110.76, 64.32, 64.23.

[0159] The high-resolution mass spectrometry data for product III-37 are as follows: HRMS (EI) m / z: [M+H] + Calcd forC 20 H 18 NO2+ 328.1332; Found 328.1335. Example 43

[0160] 2-Cyclohexyl-3-phenyl-1 H Synthesis of -indole (III-38)

[0161] Following the procedure in Example 1, but replacing raw material II-1 with II-21, III-38 (24.8 mg, yield 45%, colorless oil) was successfully prepared.

[0162] The NMR data for product III-38 are as follows: 1 H NMR (400 MHz, CDCl3) d 8.05 (br, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.53-7.48 (m, 4H), 7.39-7.34 (m, 2H), 7.22-7.19 (m, 1H), 7.15-7.12 (m, 1H), 3.08-3.01 (m, 1H), 2.01-1.98 (m, 2H), 1.88-1.78 (m, 3H), 1.67-1.49 (m, 3H), 1.44-1.38 (m, 2H); 13 C NMR (101 MHz, CDCl3) d 140.66, 135.53, 134.95, 129.74, 128.46, 127.86, 125.86, 121.48, 119.83, 118.94, 113.12, 110.41, 35.46, 33.66, 26.45, 26.02.

[0163] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit them; any simple modifications, equivalent substitutions and alterations made to the above embodiments based on the technical essence of the invention shall fall within the scope of the technical solutions of the present invention.

Claims

1. A method for synthesizing indole based on 2-aminophenyl ketone and aldehyde, characterized in that, In a catalytic system using molybdenum catalyst and ortho-quinone ligands, 2-aminophenyl ketone I and aldehyde II are used as reactants, mixed with a reducing agent and dissolved in an organic solvent; under anaerobic conditions, the reaction is heated and stirred to yield 2,3-disubstituted indole III; the reaction equation is as follows: Among them, R 1 Ar represents hydrogen, alkyl, alkoxy, or halogen substituted at any position on the benzene ring; Ar represents phenyl, substituted phenyl, naphthyl, or heterocyclic group; R represents... 2 It can be phenyl, substituted phenyl, naphthyl, heterocyclic, or alkyl.

2. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde as described in claim 1, characterized in that, Molybdenum catalyst and o-quinone ligand were added sequentially to a pressure-resistant tube. Under nitrogen protection, an organic solvent was added to dissolve them. The pressure-resistant tube was then sealed, and the reaction was carried out by heating and stirring in a water bath to complete the pretreatment of molybdenum catalyst and o-quinone ligand. After returning to room temperature, 2-aminophenyl ketone I, aldehyde II, and reducing agent were added sequentially under nitrogen protection, and organic solvent was added. The reaction was carried out by heating and stirring in a water bath to obtain 2,3-disubstituted indole III.

3. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The molybdenum catalyst is any one of Mo(CO)6, MoO2Cl2, MoO2Cl2(DMF)2, MoO2(acac)2, and MoO2Cl2(bpy); and / or, the amount of molybdenum catalyst fed is 1 mol% to 20 mol%.

4. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The ortho-quinone ligand is any one of 3,5-di-tert-butyl-o-benzoquinone, tetrachloro-o-benzoquinone, and 9,10-phenanthroquinone; and / or, the molar ratio of the ortho-quinone ligand to the molybdenum catalyst is 1:

1.

5. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The reducing agent is any one of triphenylphosphine, 1,2-bis(diphenylphosphine)ethane, 1,4-bis(diphenylphosphine)butane, phenylsilane, and phenyldimethylsilane; and / or, the amount of the reducing agent fed is 0.6 to 2.0 molar equivalents.

6. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The organic solvent is any one of toluene, xylene, mesitylene, chlorobenzene, trifluorotoluene, and diethylene glycol dimethyl ether.

7. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The reaction temperature is 120 ~ 200℃.

8. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 1, characterized in that, The reaction time is 12 to 48 hours.

9. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 2, characterized in that, The pretreatment temperature of the molybdenum catalyst and the ortho-quinone ligand is 120 ~ 180℃.

10. The method for synthesizing indole based on 2-aminophenyl ketone and aldehyde according to claim 2, characterized in that, The method further includes, after the reaction is complete, evaporating the solvent and separating and purifying the crude product by column chromatography.

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