N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives and processes for their preparation

Abstract

This invention belongs to the field of organic synthesis technology, specifically relating to an N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivative and its preparation method. The method involves mixing compound II (with structural formula), compound III (with structural formula), 1-cyclohexene trifluoromethanesulfonic acid, palladium catalyst, monophosphine ligand, base, and a second solvent in a molar ratio of 1:2:2:0.10–0.15:0.2–0.3:2.0–2.5. The mixture is then heated to 95–105°C under an inert atmosphere and stirred for 10–14 hours to obtain the N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivative (with structural formula). R1 ​​represents phenyl, p-methylphenyl, p-phenylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-methyl formate phenyl, p-cyanophenyl, or n-octyl.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to an N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivative and its preparation method. Background Technology

[0002] 4,5,6,7-Tetrahydroindole compounds are an important class of nitrogen-containing heterocyclic structures, widely found in natural products and bioactive molecules, and have significant applications in medicine, pesticides, and organic synthesis. Furthermore, 4,5,6,7-Tetrahydroindole compounds are valuable synthetic intermediates, particularly in the synthesis of some natural alkaloids, such as Goniomitine, Arcyriacyanin A, and Chuangxinmycin. Therefore, the synthesis of 4,5,6,7-tetrahydroindole derivatives has attracted considerable attention from chemists.

[0003] However, the currently reported synthetic methods for 4,5,6,7-tetrahydroindole derivatives are mainly based on metal-catalyzed cyclization reactions, which still have drawbacks such as stringent reaction conditions or the need for multiple reaction steps. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a method for preparing N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives via olefin CH amination. This method is simple to operate, has few side reactions, and achieves high yields. It can directly prepare a series of N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives via olefin CH amination. The specific preparation scheme is as follows:

[0005] (1) Compound II was obtained by reacting compound IV with N-propyl-4-methylbenzenesulfonamide, wherein the structural formula of compound IV is as follows: The structural formula of compound II is

[0006] R1 represents phenyl, p-methylphenyl, p-phenylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-methyl p-formate phenyl, p-cyanophenyl, or n-octylalkyl;

[0007] (2) The prepared structure is as follows: Compound III;

[0008] (3) Compound II obtained in step (1), compound III obtained in step (2), 1-cyclohexene trifluoromethanesulfonic acid, palladium catalyst, monophosphine ligand, base, and a second solvent were mixed in a molar ratio of 1:2:2:0.10~0.15:0.2~0.3:2.0~2.5. The mixture was then heated to 95~105℃ under an inert atmosphere and stirred for 10~14h to obtain the structure with the following formula: The synthetic route for N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives is as follows:

[0009]

[0010] Taking R1 as a phenyl group as an example, the reaction mechanism of this invention is as follows:

[0011]

[0012] In this diagram, L represents a phosphine ligand. Substrate 1 undergoes oxidative addition to a palladium catalyst to generate intermediate 2, which then undergoes carpalladiumation with acetylinamine II to generate intermediate 3. Following alkenyl CH activation, the corresponding cyclic palladium intermediate 4 is generated. This intermediate 4 then undergoes oxidative addition with a three-membered ring nitrogen-containing reagent III to generate the corresponding cyclic palladium(IV) intermediate 5. After releasing tBuNCO, azinon intermediate 7 is obtained. Substrate 7 is then subjected to successive reductive elimination to yield the N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole product and the palladium catalyst. The acetylinyl group on the acetylinamine II molecule is adjacent to a sulfonyl group. This sulfonyl group, as an electron-withdrawing group, enhances the position selectivity when cyclohexene reacts with this asymmetric acetylinamine II, thus increasing the formation of intermediate 3 as shown in the above reaction mechanism diagram.

[0013] As a preferred method: In step (1), compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-fenolylene, potassium carbonate, and the first solvent are mixed, heated to 80°C under a nitrogen atmosphere, and stirred for 12 hours. After the reaction, the mixture is diluted with ethyl acetate, filtered through diatomaceous earth, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound II (acetylenic amide derivative). The synthetic route is as follows:

[0014]

[0015] Further: In step (1), the molar ratio of compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-fenolylene, and potassium carbonate is 1.1-1.2:1:0.1-0.2:0.2-0.4:2.0-2.5.

[0016] As a preferred option: In step (2), tert-butylamine, triethylenediamine, ditert-butyl dicarbonate and dichloromethane are first mixed and reacted at room temperature (25°C, the same below) to obtain N,N-ditert-butylurea, and then the obtained N,N-ditert-butylurea is mixed and reacted with tert-butyl hypochlorite, potassium tert-butoxide and triethylamine in anhydrous diethyl ether to obtain compound III.

[0017] As a preferred option, in step (3), the palladium catalyst is palladium acetate.

[0018] Preferably, in step (3), the monophosphine ligand is tris(o-methylphenyl)phosphine.

[0019] As a preferred option, in step (3), the base is cesium carbonate.

[0020] Preferably, in step (3), the second solvent is N,N-dimethylformamide.

[0021] As a preferred option, in step (3), the concentration of compound II added to the second solvent is 0.4 mol / L.

[0022] The present invention also provides an N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivative prepared by the above method.

[0023] The beneficial effects of this invention are as follows: the initial substrate, acetylamidoid compound II, on which this preparation method is based is simple and readily available, has a wide substrate range, is easy to synthesize, and has excellent yield. As can be seen from the above reaction mechanism, by reacting acetylamidoid compound II with 1-cyclohexene trifluoromethanesulfonic acid in a palladium-catalyzed next step, the precursor chain segment of the five-membered ring on the target product indole can be directly obtained on the cyclohexene ring structure, and the active group carbon palladium required for subsequent cyclization can also be obtained. Therefore, it is not necessary to pre-substitute specific functional groups at the carbon sites to be reacted, and the double bond of the olefin can be directly aminationed to synthesize N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives with various substituent types.

[0024] This invention uses N,N-di-tert-butyldiazacyclic ketone as a nitrogen source to prepare N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives containing an N-tert-butyl group. The N-tert-butyl group is easily removed and can also serve as a protecting group in the nitrogen of aromatic amines, providing excellent protection in further derivatization reactions of N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives. Detailed Implementation

[0025] A method for preparing an N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivative:

[0026] (1) The structural formula is Compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-fenolylene, and potassium carbonate were mixed with toluene as the first solvent in a molar ratio of 1.1–1.2:1:0.1–0.2:0.2–0.4:2.0–2.5. The mixture was heated to 80°C under a nitrogen atmosphere and stirred for 12 hours. After the reaction, the mixture was diluted with ethyl acetate, filtered through diatomaceous earth, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain the compound with the following structural formula: Compound II (acetylamide derivative):

[0027]

[0028] Wherein, R1 represents phenyl, p-methylphenyl, p-phenylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-methyl p-formate phenyl, p-cyanophenyl or n-octylalkyl;

[0029] (2) Tert-butylamine, triethylenediamine, and di-tert-butyl dicarbonate were added to dichloromethane in a molar ratio of 1:0.5:0.1 and reacted at room temperature for 12 h to obtain N,N-di-tert-butylurea.

[0030] The N,N-di-tert-butylurea obtained above was reacted with tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine in anhydrous diethyl ether at a molar ratio of 1:1.1:1.3:0.02 to obtain the structure with the following formula: Compound III, namely N,N-di-tert-butyldiazepine;

[0031] (3) Compound II obtained in step (1), compound III obtained in step (2), 1-cyclohexene trifluoromethanesulfonic acid, palladium catalyst, monophosphine ligand, base, and a second solvent were mixed in a molar ratio of 1:2:2:0.10~0.15:0.2~0.3:2.0~2.5. The mixture was then heated to 95~105℃ under an inert atmosphere and stirred for 10~14h to obtain the structure with the following formula: N-tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives:

[0032]

[0033] After the reaction was completed, ethyl acetate was added to the resulting reaction system for dilution. The mixture was then filtered through 300-400 mesh silica gel, eluted with ethyl acetate, and the solvent was removed by vacuum filtration. The eluent was then separated by 300-400 mesh silica gel column chromatography. In the silica gel column chromatography, the packing solvent was petroleum ether, and the eluent was petroleum ether or a mixture of petroleum ether and ethyl acetate.

[0034] Unless otherwise specified, all materials and reagents used in the following examples are commercially available or prepared according to existing literature. For example, palladium acetate, tris(o-methylphenyl)phosphine, and N,N-dimethylformamide were purchased from Anaiji Chemical; cesium carbonate was purchased from Leyan.

[0035] Example 1

[0036] 1) Preparation of compound II-a:

[0037]

[0038] Phenylacetylene bromide IV-a (1.9913 g, 11 mmol), N-propyl-4-methylbenzenesulfonamide (2.1329 g, 10 mmol), copper sulfate pentahydrate (0.2497 g, 1.0 mmol), 1,10-phenololine (0.3604 g, 2.0 mmol), and potassium carbonate (2.7640 g, 20 mmol) were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, dry toluene (15 mL) was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through 300–400 mesh silica gel, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-a 2.21 g, with a yield of 70%.

[0039] NMR data of compound II-a: 1 H NMR (400MHz, CDCl3) δ7.84 (d, J = 8.4Hz, 2H), 7.39-7.33 (m, 4H), 7.32-7.26 (m, 3H) ),3.36(t,J=6.8Hz,2H),2.45(s,3H),1.79-1.68(m,2H),0.95(t,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ144.7,134.8,131.4,129.9,128.4,127.8,127.77,123.1,82.5,70.7,53.4,21.7,21.4,11.0.

[0040] 2) Preparation of compound III:

[0041]

[0042] 52.5 mL of tert-butylamine (500.0 mmol), 5.6 g of triethylenediamine (DABCO) (250.0 mmol), and 200.0 mL of dichloromethane were added to the reactor. Then, 57.5 mL of ditert-butyl dicarbonate (50.0 mmol) was dissolved in 50 mL of dichloromethane and added to the reactor. The mixture was stirred at room temperature for 12 h. After the reaction, the reaction solution in the reactor was cooled to 0 °C, and 250 mL of n-hexane was added to facilitate the precipitation of the target product. The mixture was then filtered, and the filter cake was washed successively with supercooled water and diethyl ether to obtain a white solid N,N-ditert-butylurea.

[0043] N,N-di-tert-butylurea (20.0 g, 116.1 mmol) and diethyl ether (200.0 mL) prepared above were added to another reactor. Then, tert-butyl hypochlorite (13.9 mL, 127.7 mmol) was added dropwise, followed by triethylamine (0.16 mL, 2 mmol). The mixture was stirred at room temperature for 30 minutes. After cooling the reaction solution in the reactor to 5°C, potassium tert-butoxide (17.0 g, 150.9 mmol) was slowly added. The mixture was then naturally heated to room temperature and stirred for 12 hours. 150 mL of n-hexane was added to the resulting reaction solution. The mixture was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and distilled under reduced pressure to obtain compound III, a colorless liquid (11.6 g, yield 59%).

[0044] NMR data of compound III: 1 H NMR (400MHz, CDCl3): δ1.30 (s, 18H); 13 C NMR (100MHz, CDCl3): δ158.8, 59.1, 26.8.

[0045] 3) Preparation of compound Ia:

[0046]

[0047] Compound II-a (0.0940 g, 0.3 mmol) prepared in step (1), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Next, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and compound III (0.1022 g, 0.6 mmol) prepared in step (2) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 100 °C for 12 hours to allow the reaction to proceed. After the reaction was completed, the mixture was cooled to room temperature. The resulting reaction solution was diluted with ethyl acetate and filtered through a 300-400 mesh silica gel filter. Eluent was used for elution (the excess compound III three-membered ring that did not participate in the synthesis reaction was degraded and ring-opened to generate urea in the above reaction. Due to the high polarity of ethyl acetate, the urea was eluted along with the compound, and the same applies below). The solvent was removed under reduced pressure, and the mixture was then separated by column chromatography on a 300-400 mesh silica gel filter (the eluent was petroleum ether:ethyl acetate = 50:1 (volume ratio). Since the eluent, which is mainly petroleum ether, has a significantly lower polarity, it was unable to elute the urea along with the compound, thus achieving separation from the target product, and the same applies below). This yielded a pale yellow solid compound Ia (0.0753 g, yield 54%).

[0048] NMR data for compound Ia: 1 H NMR (400MHz, CDCl3) δ7.35(d,J=8.4Hz,1H),7.30-7.26(m,2H),7.25-7.21(m,1H),7.19-7.14(m,2H),7.12(d,J=8.4Hz,2H),3.18-3.09(m,1H), 2.91-2.81(m,3H),2.38(s,3H),2.36-2.24(m,2H),1.91-1.82(m,1H),1 .80-1.57(m,4H),1.37(s,9H),1.30-1.13(m,2H),0.58(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ142.5,138.0,136.6,133.0,132.1,131.7,129.2,128.2,128.0,127. 6,127.3,126.8,119.1,117.6,59.3,52.3,33.2,28.4,24.7,22.9,22.4,21.7,21.6,11.2.

[0049] Example 2

[0050] 1) Preparation of compound II-b:

[0051]

[0052] Weigh out 1.2874 g (6.6 mmol) of p-methylphenylacetylene bromide IV-b, 1.2797 g (6.0 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.1498 g (0.6 mmol) of copper sulfate pentahydrate, 0.2163 g (1.2 mmol) of 1,10-phenololine, and 1.6584 g (12 mmol) of potassium carbonate, and place them in a dry round-bottom flask. After purging the flask with nitrogen, add 10 mL of dry toluene, heat to 80 °C, and stir for 12 h. Dilute with ethyl acetate, filter through 300-400 mesh silica gel, concentrate under reduced pressure to remove the solvent, and separate by column chromatography to obtain 1.61 g of compound II-b, with a yield of 75%.

[0053] NMR data of compound II-b: 1 H NMR (400MHz, CDCl3) δ7.85(d,J=8.0Hz,2H),7.35(d,J=8.4Hz,2H),7.28(d,J=8.0Hz,2H),7.11(d,J=8 .0Hz,2H),3.37(t,J=6.8Hz,2H),2.45(s,3H),2.34(s,3H),1.80-1.68(m,2H),0.96(t,J=7.2Hz,3H); 13 C NMR (400MHz, CDCl3) δ144.6,138.0,134.6,131.5,129.8,129.1,127.7,119.8,81.7,70.5,53.3,21.7,21.5,21.3,10.9.

[0054] 2) Preparation of compound III: Same as step 2 in Example 1.

[0055] 3) Preparation of compound Ib:

[0056]

[0057] Compound II-b (0.0982 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Then, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. The solution was then filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, and the solvent was removed under reduced pressure. The solution was then separated by column chromatography on a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ib (0.0660 g, yield 46%).

[0058] NMR data for compound Ib: 1 H NMR (400MHz, CDCl3) δ7.36 (d, J = 8.4Hz, 2H), 7.14-7.08 (m, 3H), 7.03 (s, 2H), 6. 94(d,J=8.4,1H),3.21-3.11(m,1H),2.94-2.87(m,1H),2.84,(t,J=6.8Hz,2H) ,2.38(s,3H),2.36(s,3H),2.40-2.24(m,2H),1.90-1.80(m,1H),1.77-1.69(m ,1H),1.68-1.60(m,2H),1.36(s,9H),1.29-1.17(m,2H),0.61(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ142.4,138.2,136.9,133.4,132.8,132.1,131.5,129.0,128.2,127.89, 127.88,127.5,119.1,117.6,59.3,52.5,33.2,28.4,24.7,22.8,22.3,21.7,21.5,21.4,11.2.

[0059] Example 3

[0060] 1) Preparation of compound II-c:

[0061]

[0062] 2.4684 g (9.6 mmol) of p-phenylphenylacetylene bromide IV-c, 1.8556 g (8.7 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.2172 g (0.87 mmol) of copper sulfate pentahydrate, 0.3136 g (1.74 mmol) of 1,10-phenololine, and 2.4047 g (17.4 mmol) of potassium carbonate were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, 12 mL of dry toluene was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-c 1.81 g, with a yield of 53%.

[0063] NMR data of compound II-c: 1 H NMR(400MHz, CDCl3) δ7.86(d,J=8.4Hz,2H),7.61-7.57(m,2H),7.54(d,J=8.4Hz,2H),7.47-7.42(m, 4H),7.39-7.33(m,3H),3.39(t,J=7.2Hz,2H),2.46(s,3H),1.81-1.70(m,2H),0.97(t,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ144.7,140.6,140.5,134.7,131.9,129.9,129.0,127.8,127.7,127.1,127.08,122.0,83.1,70.6,53.4,21.8,21.5,11.1.

[0064] 2) Preparation of compound III: Same as step 2 in Example 1.

[0065] 3) Preparation of compound Ic:

[0066]

[0067] Compound II-C (0.1169 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Next, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ic (0.0920 g, yield 57%).

[0068] NMR data of compound Ic: 1 H NMR (400MHz, CDCl3) δ7.64 (d, J = 7.2Hz, 2H), 7.51-7.45 (m, 3H), 7.41-7.33 (m, 5H), 7. 22(dd,J=8.0,2.0Hz,1H),7.07(d,J=8.0Hz,2H),3.23-3.15(m,1H),2.99-2.91(m,1H ),2.87(t,J=6.0Hz,2H),2.42-2.27(m,2H),2.32(s,3H),1.92-1.83(m,1H),1.79-1. 72(m,1H),1.70-1.62(m,2H),1.41(s,9H),1.29-1.23(m,2H),0.62(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ142.5,140.9,139.9,138.2,135.7,133.4,132.0,131.7,129.2,128.9,128.4,127. 9,127.5,127.1,126.1,125.4,119.4,117.8,59.4,52.6,33.3,28.4,24.8,22.9,22.4,21.8,21.5,11.3.

[0069] Example 4

[0070] 1) Preparation of compound II-d:

[0071]

[0072] 2.3217 g (11 mmol) of p-methoxyphenylacetylene bromide IV-d, 2.1329 g (10 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.2497 g (1.0 mmol) of copper sulfate pentahydrate, 0.3604 g (2.0 mmol) of 1,10-phenololine, and 2.7640 g (20 mmol) of potassium carbonate were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, 15 mL of dry toluene was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain 3.26 g of compound II-d, with a yield of 95%.

[0073] NMR data of compound II-c: 1 H NMR (400MHz, CDCl3) δ7.83(d,J=8.4Hz,2H),7.35(d,J=8.4Hz,2H),7.31(d,J=8.8Hz,2H),6.82(d,J=8 .8Hz,2H),3.79(s,3H),3.34(t,J=7.2Hz,2H),2.44(s,3H),1.77-1.67(m,2H),0.94(t,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ159.5,144.5,134.6,133.4,129.8,127.7,114.8,113.9,80.9,70.2,55.3,53.3,21.7,21.3,11.0.

[0074] 2) Preparation of compound III: Same as step 2 in Example 1.

[0075] 3) Preparation of compound Id:

[0076]

[0077] Compound II-d (0.1030 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Next, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Id (0.0610 g, yield 41%).

[0078] NMR data for compound Id: 1 H NMR(400MHz, CDCl3)δ7.41(d,J=8.4Hz,2H),7.18-7.11(m,3H),7.04(dd,J=8.4,2.0Hz,1H), 6.78(dd,J=8.4,2.8Hz,1H),6.67(dd,J=8.4,2.8Hz,1H),3.83(s,3H),3.20-3.11(m,1H),2. 95-2.87(m,1H),2.84(t,J=6.4Hz,2H),2.39(s,3H),2.32-2.24(m,2H),1.90-1.82(m,1H),1 .75-1.69(m,1H),1.65-1.61(m,2H),1.36(s,9H),1.25-1.17(m,2H),0.61(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ159.0,142.5,138.3,134.1,132.7,131.8,129.1,128.6,127.93,127.9, 119.2,117.5,112.7,112.5,59.3,55.3,52.4,33.2,28.4,24.8,22.9,22.4,21.8,21.6,11.3.

[0079] Example 5

[0080] 1) Preparation of compound II-e:

[0081]

[0082] 2.1892 g (11 mmol) of p-fluorophenylacetylene bromide IV-e, 2.1329 g (10 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.2497 g (1.0 mmol) of copper sulfate pentahydrate, 0.3604 g (2.0 mmol) of 1,10-phenololine, and 2.7640 g (20 mmol) of potassium carbonate were weighed and placed in a dry round-bottom flask. After purging the flask with nitrogen, 15 mL of dry toluene was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-e 2.07 g, with a yield of 63%.

[0083] NMR data of compound II-e: 1 H NMR (400MHz, CDCl3) δ7.83 (d, J = 8.4Hz, 2H), 7.40-7.30 (m, 4H), 7.04-6.91 (m, 2H) ),3.35(t,J=7.2Hz,2H),2.45(s,3H),1.77-1.67(m,2H),0.94(t,J=7.2Hz,3H); 13 C NMR (400MHz, CDCl3) δ162.4 (d, J = 247.4Hz), 144.7, 134.7, 133.6 (d, J = 8.3Hz), 129.9 ,127.8,119.0(d,J=3.6Hz),115.6(d,J=21.9Hz),82.1,69.6,53.3,21.8,21.5,11.0.

[0084] 2) Preparation of compound III: Same as step 2 in Example 1.

[0085] 3) Preparation of compound Ie:

[0086]

[0087] Compound II-e (0.09942 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Then, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ie (0.0610 g, yield 42%).

[0088] NMR data for compound Ie: 1 H NMR (400MHz, CDCl3) δ7.41(d,J=8.4Hz,2H),7.30(ddd,J=8.4,5.6,2.4Hz,1H),7.16(d,J=8.0Hz,2H ),7.10(ddd,J=8.4,5.6,2.0Hz,1H),6.93(td,J=8.4,2.8Hz,1H),6.86(td,J=8.4,2.8Hz,1H),3.19- 3.08(m,1H),3.00-2.90(m,1H),2.83(t,J=2.0Hz,2H),2.40(s,3H),2.25-2.14(m,2H),1.89-1.81( m,1H),1.75-1.67(m,1H),1.65-1.59(m,2H),1.36(s,9H),1.25-1.11(m,2H),0.60(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ162.4 (d, J = 245.1Hz), 142.7, 138.1, 134.8 (d, J = 7.9Hz), 133.2 (d, J = 7.8Hz), 132.4 (d, J = 3.6Hz), 131.1, 129.2 ,128.5,127.9,119.5,117.5,114.4(d,J=20.9Hz),113.8(d,J=21.3Hz),59.4,52.5,33.3,28.4,24.7,22.8,22.3,21.8,21.6,11.2.

[0089] Example 6

[0090] 1) Preparation of compound II-f:

[0091]

[0092] 2.1547 g (10 mmol) of p-chlorophenylacetylene bromide IV-f, 2.3462 g (11 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.2497 g (1.0 mmol) of copper sulfate pentahydrate, 0.3604 g (2.0 mmol) of 1,10-phenololine, and 2.7640 g (20 mmol) of potassium carbonate were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, 20 mL of dry toluene was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-f 3.20 g, with a yield of 92%.

[0093] NMR data of compound II-f: 1 H NMR (400MHz, CDCl3) δ7.82(d,J=8.4Hz,2H),7.35(d,J=8.4Hz,2H),7.32-7.22(m, 4H),3.36(t,J=6.8Hz,2H),2.44(s,3H),1.76-1.67(m,2H),0.94(t,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ144.8,134.7,133.7,132.6,129.9,128.7,128.69,127.7,121.6,83.4,69.8,53.3,21.8,21.5,11.0.

[0094] 2) Preparation of compound III: Same as step 2 in Example 1.

[0095] 3) Preparation of compound If:

[0096]

[0097] Compound II-f (0.1044 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Then, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and the solution was then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound If (0.0610 g, yield 45%).

[0098] NMR data for compound If: 1 H NMR (400MHz, CDCl3) δ7.38 (d, J=8.4Hz, 2H), 7.49 (dd, J=8.0, 2.0Hz, 1H), 7.21 (dd, J=8.0, 2.4Hz, 1H),7.16(d,J=8.0Hz,2H),7.12(dd,J=8.4,2.4Hz,1H),7.08(dd,J=8.4,2.4Hz,1H),3.21-3.10( m,1H),3.02-2.93(m,1H),2.83(t,J=6.4Hz,2H),2.41(s,3H),2.27-2.12(m,2H),1.89-1.79(m,1 H),1.76-1.66(m,1H),1.66-1.56(m,2H),1.37(s,9H),1.26-1.10(m,2H),0.62(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ142.8,138.1,135.1,134.4,133.4,132.8,130.8,129.2,128.7,1 27.8,127.0,119.6,117.6,59.4,52.6,33.3,28.3,24.7,22.8,22.3,21.9,21.6,11.2.

[0099] Example 7

[0100] 1) Preparation of compound II-g:

[0101]

[0102] Methyl p-formate phenylacetylene bromide IV-g (2.3668g, 9.9mmol), N-propyl-4-methylbenzenesulfonamide (1.9196g, 9.0mmol), copper sulfate pentahydrate (0.2247g, 0.9mmol), 1,10-phenololine (0.3244g, 1.8mmol), and potassium carbonate (2.4876g, 18mmol) were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, dry toluene (13mL) was added. The mixture was heated to 80℃ and stirred for 12h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through 300-400 mesh silica gel, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-g 2.10g, with a yield of 63%.

[0103] NMR data for compound II-g: 1 H NMR (400MHz, CDCl3) δ7.95(d,J=8.8Hz,2H),7.83(d,J=8.0Hz,2H),7.38(d,J=8.4Hz,2H),7.35(d,J=8 .4Hz,2H),3.90(s,3H),3.38(t,J=6.8Hz,2H),2.44(s,3H),1.78-1.68(m,2H),0.95(t,J=7.2Hz,3H); 13 C NMR (400MHz, CDCl3) δ166.7,144.9,134.7,130.6,130.0,129.6,128.8,128.1,127.7,85.8,70.8,53.3,52.3,21.8,21.5,11.0.

[0104] 2) Preparation of compound III: Same as step 2 in Example 1.

[0105] 3) Preparation of compound Ig:

[0106]

[0107] In a 5 mL pressure-resistant tube, compound II-g (0.1115 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially. The tube was then evacuated and filled with argon gas. Then, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted in ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and the solution was then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ig (0.0720 g, yield 46%).

[0108] NMR data for compound Ig: 1 H NMR (400MHz, CDCl3) δ7.90 (dd, J=8.0, 2.0Hz, 1H), 7.66 (dd, J=8.0, 2.0Hz, 1H), 7.45-7.38 (m ,3H),7.22(dd,J=8.0,1.6Hz,1H),7.13(d,J=8.0Hz,2H),3.93(s,3H),3.16-3.08(m,1H),2. 98-2.90(m,1H),2.84(t,J=6.0Hz,2H),2.94(s,3H),2.23-2.10(m,2H),1.90-1.78(m,1H),1 .75-1.67(m,1H),1.63-1.57(m,2H),1.36(s,9H),1.23-1.11(m,2H),0.58(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ167.2,142.8,141.7,138.1,132.7,131.6,131.1,129.3,129.27,128.8,12 8.0,127.8,119.8,117.9,59.5,52.6,52.2,33.2,29.8,28.3,24.6,22.8,22.3,21.9,21.6,11.2.

[0109] Example 8

[0110] 1) Preparation of compound II-h:

[0111]

[0112] 2.0398 g (9.9 mmol) of p-cyanophenylacetylene bromide IV-h, 1.9196 g (9.0 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.2247 g (0.9 mmol) of copper sulfate pentahydrate, 0.3244 g (1.8 mmol) of 1,10-phenololine, and 2.4876 g (18 mmol) of potassium carbonate were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, 13 mL of dry toluene was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-h 3.0 g, with a yield of 98%.

[0113] NMR data of compound II-h: 1 H NMR (400MHz, CDCl3) δ7.80(d,J=8.4Hz,2H),7.53(d,J=8.4Hz,2H),7.38(d,J=8.4Hz,2H),7.35 (d,J=8.4Hz,2H),3.37(t,J=7.2Hz,2H),2.41(s,3H),1.75-1.65(m,2H),0.92(t,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ145.0,134.4,131.9,130.9,129.9,128.2,127.5,118.6,110.3,87.2,70.3,53.1,21.6,21.3,10.8.

[0114] 2) Preparation of compound III: Same as step 2 in Example 1.

[0115] 3) Preparation of compound Ih:

[0116]

[0117] Compound II-h (0.1016 g, 0.3 mmol) prepared in step (1), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Then, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ih (0.0540 g, yield 37%).

[0118] NMR data of compound Ih: 1 H NMR (400MHz, CDCl3) δ7.65(d,J=8.0Hz,1H),7.52(d,J=8.0Hz,2H),7.44(d,J=8.0Hz ,2H),7.25(d,J=6.8Hz,1H),7.19(d,J=8.0Hz,2H),3.11-3.01(m,2H),2.90-2.79(m, 2H),2.42(s,3H),2.14-2.04(m,1H),1.92-1.80(m,2H),1.73-1.61(m,2H),1.54-1. 48(m,1H),1.37(s,9H),1.24-1.20(m,1H),1.15-1.05(m,1H),0.57(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.1,141.9,137.8,133.4,132.2,131.4,130.6,130.4,130.1,129.3,1 27.8,120.3,119.1,117.6,110.8,59.6,52.5,33.2,28.2,24.5,22.7,22.2,21.9,21.6,11.1.

[0119] Example 9

[0120] 1) Preparation of compound II-i:

[0121]

[0122] 2-(2,2-dibromoethylene)furan IV-i (2.2924 g, 9.1 mmol), N-propyl-4-methylbenzenesulfonamide (1.4930 g, 7.0 mmol), cuprous iodide (0.2666 g, 1.4 mmol), 1,10-phenololine (0.5046 g, 2.8 mmol), and cesium carbonate (6.8424 g, 21 mmol) were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, 10 mL of dry tetrahydrofuran was added. The mixture was heated to 55 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through 300–400 mesh silica gel, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-i 1.83 g, with a yield of 86%.

[0123] NMR data of compound II-i: 1 H NMR (400MHz, CDCl3) δ7.82 (d, J = 8.4Hz, 2H), 7.42-7.33 (m, 3H), 6.60 (d, J = 3.6Hz, 1H), 6.39 (dd, J=3.6,2.0Hz,1H),3.36(t,J=7.2Hz,2H),2.46(s,3H),1.75-1.65(m,2H),0.92(d,J=7.6Hz,3H); 13 C NMR (400MHz, CDCl3) δ144.9,144.0,136.9,134.8,130.0,127.7,117.2,111.2,86.5,61.5,53.5,21.8,21.4,11.0.

[0124] 2) Preparation of compound III: Same as step 2 in Example 1.

[0125] 3) Preparation of compound Ii:

[0126]

[0127] Compound II-i (0.0910 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Next, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ii (0.0518 g, yield 38%).

[0128] NMR data for compound Ii: 1 H NMR (400MHz, CDCl3) δ7.59 (d, J = 8.4Hz, 2H), 7.36 (dd, J = 2.0, 0.8Hz, 1H), 7.22 (d, J = 8.0Hz, 2H) ,6.28(dd,J=2.4,2.0Hz,1H),6.14(dd,J=2.4,0.8Hz,1H),3.18-3.10(m,1H),3.09-2.99(m,1H ),2.80(t,J=2.0Hz,2H),2.41(s,3H),2.18-2.09(m,1H),2.01-1.90(m,1H),1.85-1.76(m,1H) ,1.70-1.62(m,1H),1.58-1.49(m,2H),1.40(s,9H),1.33-1.21(m,2H),0.65(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ146.3,142.6,141.2,138.3,130.1,129.2,127.8,122.4,121. 0,117.5,112.9,111.1,59.2,52.7,31.6,28.1,24.5,22.6,22.1,21.9,21.6,11.1.

[0129] Example 10

[0130] 1) Preparation of compound II-j:

[0131]

[0132] Decyne bromide IV-j (1.1943 g, 5.5 mmol), N-propyl-4-methylbenzenesulfonamide (1.0665 g, 5.0 mmol), copper sulfate pentahydrate (0.1249 g, 0.5 mmol), 1,10-phenololine (0.1802 g, 1.0 mmol), and potassium carbonate (1.3820 g, 10 mmol) were weighed separately and placed in a dry round-bottom flask. After purging the flask with nitrogen, dry toluene (5 mL) was added. The mixture was heated to 80 °C and stirred for 12 h. Ethyl acetate was added to dilute the mixture. The mixture was filtered through 300–400 mesh silica gel, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain compound II-j 1.5 g, with a yield of 86%.

[0133] NMR data of compound II-j: 1 H NMR (400MHz, CDCl3) δ7.77(d,J=8.4Hz,2H),7.32(d,J=8.0Hz,2H),3.21(t,J=7.2Hz,2H),2.44(s,3H) ,2.24(t,J=6.8Hz,2H),1.68-1.59(m,2H),1.51-1.41(m,2H),1.36-1.23(m,10H),0.94-0.84(m,6H); 13 C NMR (400MHz, CDCl3) δ144.2,134.9,129.7,127.7,73.1,70.2,53.2,32.0,29.4,29.2,29.1,28.9,22.8,21.7,21.3,18.6,14.2,11.0.

[0134] 2) Preparation of compound III: Same as step 2 in Example 1.

[0135] 3) Preparation of compound Ij:

[0136]

[0137] Compound II-j (0.1049 g, 0.3 mmol), palladium acetate (0.0067 g, 0.03 mmol), tris(o-methylphenyl)phosphine (0.0183 g, 0.06 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) prepared in step (1) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and filled with argon gas. Next, ultra-dry N,N-dimethylformamide (0.75 mL), 1-cyclohexene trifluoromethanesulfonic acid (0.1381 g, 0.6 mmol), and the solution from step (2) were added sequentially. Compound III (0.1022 g, 0.6 mmol) prepared in the above method was sealed and placed in a magnetically heated stirrer and stirred at 100 °C for 12 hours. After the reaction was completed, it was cooled to room temperature, and the resulting reaction solution was diluted with ethyl acetate. After filtration through a 300-400 mesh silica gel filter, ethyl acetate was used as eluent. The solvent was removed under reduced pressure, and then separated by column chromatography through a 300-400 mesh silica gel filter (eluent: petroleum ether: ethyl acetate = 50:1 (volume ratio)) to obtain a pale yellow solid compound Ij (0.0680 g, yield 45%).

[0138] NMR data of compound Ij: 1 H NMR (400MHz, CDCl3) δ7.59(d,J=8.0Hz,2H),7.22(d,J=8.0Hz,2H),3.49-3.39(m,1H),3.26-3.17(m,1H),2.81-2.68(m,2H),2.67-2.58(m,1H) ,2.40(s,3H),2.39-2.33(m,1H),2.03-1.93(m,1H),1.79-1.71(m,1H), 1.62(s,9H),1.59-1.48(m,6H),1.33-1.22(m,12H),0.91-0.84(m,6H); 13 C NMR (100MHz, CDCl3) δ142.6,137.8,133.8,129.2,127.8,127.1,118.0,116.5,59.0,53.6,53 .1,32.3,32.2,32.0,30.2,29.5,29.4,28.5,27.4,24.8,22.8,22.79,22.3,21.6,14.3,11.4.

Claims

1. A kind N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: The preparation method is as follows: (1) Through compound IV and N The reaction of propyl-4-methylbenzenesulfonamide yields compound II, wherein the structural formula of compound IV is... The structural formula of compound II is as follows: , R1 represents phenyl, p-methylphenyl, p-phenylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, p-methyl p-formate phenyl, p-cyanophenyl, or n-octylalkyl; (2) The prepared structure is as follows: Compound III; (3) The compound II obtained in step (1), the compound III obtained in step (2), 1-cyclohexene trifluoromethanesulfonic acid, palladium catalyst, monophosphine ligand, base, and a second solvent are mixed in a molar ratio of 1:2:2:0.10~0.15:0.2~0.3:2.0~2.

5. After mixing, the mixture is heated to 95~105℃ under an inert atmosphere and stirred for 10~14h to obtain the structure with the following formula: of N -tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives In step (3), the palladium catalyst is palladium acetate; and the monophosphine ligand is tris(o-methylphenyl)phosphine.

2. As described in claim 1 N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: In step (1), the molar ratio of compound IV, the molar ratio of compound IV to compound 0.1 is 1.1-1.2:1:0.1-0.2:0.2-0.4:2.0-2.

5. N 1,10-Propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-phenanthroline, potassium carbonate, and the first solvent were mixed and heated to 80°C under a nitrogen atmosphere and stirred for 12 h. After the reaction, the mixture was diluted with ethyl acetate, filtered through diatomaceous earth, concentrated under reduced pressure, and purified by silica gel column chromatography to obtain compound II.

3. As described in claim 1 N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: In step (2), tert-butylamine, triethylenediamine, ditert-butyl dicarbonate, and dichloromethane are first mixed and reacted at room temperature to obtain... N,N -di-tert-butylurea, and then the obtained... N,N - The compound III is obtained by reacting di-tert-butylurea with tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine in anhydrous diethyl ether.

4. As described in claim 1 N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: The alkali mentioned in step (3) is cesium carbonate.

5. As described in claim 1 N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: The second solvent mentioned in step (3) is N , N -Dimethylformamide.

6. As described in claim 1 N A method for preparing tert-butyl-3-amino-4,5,6,7-tetrahydroindole derivatives, characterized in that: In step (3), the concentration of compound II added to the second solvent is 0.4 mol / L.

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