Preparation method of N-tert-butyl-3-aminoindole derivative and N-tert-butyl-3-aminoindole derivative

Abstract

The application provides a preparation method of N-tert-butyl-3-aminoindole derivatives, and the specific steps are as follows: 1) mixing compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-phenanthroline, potassium carbonate and a first solvent, after reaction, post-treatment is performed to obtain compound II; 2) mixing tert-butylamine, triethylenediamine, di-tert-butyl dicarbonate, dichloromethane at room temperature, and after reaction for 12 hours, N,N-di-tert-butyl urea is obtained; further reaction of the N,N-di-tert-butyl urea is performed to obtain compound III; 3) mixing compound II, compound III, iodobenzene, a palladium catalyst, a biphosphine ligand, a base and a second solvent, and after reaction, the N-tert-butyl-3-aminoindole derivative with the structural formula of the application can be directly subjected to amination and ring reaction with iodobenzene in one-pot reaction.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing N-tert-butyl-3-aminoindole derivatives and the N-tert-butyl-3-aminoindole derivatives. Background Technology

[0002] 3-Aminoindole 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, 3-aminoindole compounds are valuable synthetic intermediates, particularly in the synthesis of some natural alkaloids, such as the total synthesis of natural products (-)-mersicapine and 8-desbromohinckdentine A. Therefore, the synthesis of 3-aminoindole derivatives has received considerable attention from chemists.

[0003] In the traditional synthesis of 3-aminoindole, the 3-position nitration reduction reaction of indole is often used. The nitration reaction is a dangerous process with very strict requirements for equipment and management. Currently, the microchannel reactor is being promoted, but the equipment investment is high. The waste products of nitration are hazardous wastes, and the treatment requirements are strict and the cost is high. Summary of the Invention

[0004] The purpose of this invention is to address the above-mentioned shortcomings by providing a method for preparing N-tert-butyl-3-aminoindole derivatives.

[0005] To address the shortcomings of existing technologies, this invention provides a method for the tandem amination of acetylacetylamine and iodobenzene. This method is simple to operate, has few side reactions, and achieves high molar yield, enabling the direct preparation of a series of N-tert-butyl-3-aminoindole derivatives. The specific steps are as follows:

[0006] 1) Compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-fenolylene, potassium carbonate, and the first solvent were mixed and reacted at 80–90 °C for 8–12 h under a nitrogen atmosphere. After the reaction was completed, 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 structure shown below. Compound II; the synthetic route is shown in the following formula:

[0007]

[0008] 2) Tert-butylamine, triethylenediamine, di-tert-butyl dicarbonate, and dichloromethane were mixed at room temperature and reacted for 12 h to obtain N,N-di-tert-butylurea; N,N-di-tert-butylurea, tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine were mixed in anhydrous diethyl ether, and after the reaction was completed, the following structure was obtained: Compound III.

[0009] 3) Compound II, Compound III, Iodobenzene V, palladium catalyst, bisphosphine ligand, base, and second solvent were mixed and subjected to an amination reaction under an inert atmosphere to obtain the structure with the following formula: N-tert-butyl-3-aminoindole derivatives, wherein R1 represents hydrogen, methyl, phenyl, cyano, or halogen; R2 represents hydrogen, methyl, phenyl, methoxy, chlorine, bromine, trifluoromethyl, cyano, or methyl formate. The synthetic route is shown in the following formula:

[0010]

[0011] Further, in step 1), the molar ratio of compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-phenanthroline, and potassium carbonate is (1.1-1.2):1:(0.1-0.2):(0.2-0.4):(2.0-2.5).

[0012] Furthermore, the method for preparing the N-tert-butyl-3-aminoindole derivative is characterized in that, in step (3), the base is cesium carbonate.

[0013] Furthermore, in step (3), the second solvent is 1,4-dioxane.

[0014] Further, in step (3), the bisphosphine ligand is 4,5-bisdiphenylphosphine-9,9-dimethyloxane.

[0015] Furthermore, in step (2), the concentration of compound II in the second solvent is 0.2 mol / L.

[0016] Further, in step (3), the molar ratio of compound II, compound III, iodobenzene, palladium catalyst, bisphosphine ligand, and base is 1:1.5:1.5:(0.05~0.10):(0.05~0.10):(2.0~2.5).

[0017] Furthermore, in step (3), the reaction temperature of the amination reaction is 115-130°C and the reaction time is 10-14h.

[0018] Furthermore, in step (3), the palladium catalyst is palladium acetate.

[0019] A second aspect of the present invention also provides an N-tert-butyl-3-aminoindole derivative prepared by the above preparation method.

[0020] Beneficial effects of this invention:

[0021] (1) The method for preparing N-tert-butyl-3-aminoindole derivatives provided by the present invention has simple and readily available raw materials, a wide range of substrates, simple synthesis operation, and excellent molar yield. It does not require the prior substitution of specific functional groups at the carbon sites to be reacted, and can directly undergo amination and cyclization reaction with iodobenzene in a one-pot reaction to synthesize N-tert-butyl-3-aminoindole derivatives with diverse substituent types.

[0022] (2) The halogen-carbon bond is a relatively weak chemical bond. Compared with other chemical bonds, its bond energy is lower. The chemical bond energy of the CI bond in iodobenzene is the lowest among carbon-halogen bonds, making it easier to break and react.

[0023] (3) The present invention uses N,N-di-tert-butyldiazacyclic ketone as nitrogen source to prepare N-tert-butyl-3-aminoindole derivatives containing N-tert-butyl group. N-tert-butyl group is easy to remove and can also be used as a protecting group in indole nitrogen. It has a good protective effect in the further derivatization reaction of N-tert-butyl-3-aminoindole derivatives. Detailed Implementation

[0024] To make the above-mentioned objectives, features and advantages of the present invention more apparent and understandable, the specific embodiments of the present invention will be described in detail below with reference to the examples in the specification. Unless otherwise specified, the methods described are conventional methods, and the raw materials described are available from publicly available commercial sources unless otherwise specified.

[0025] The term "an embodiment" or "embodiment" as used herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the invention. The phrase "in one embodiment" appearing in different places throughout this specification does not necessarily refer to the same embodiment, nor is it a single or selective embodiment that is mutually exclusive with other embodiments.

[0026] The method for preparing N-tert-butyl-3-aminoindole derivatives provided by this invention comprises the following steps:

[0027] 1) Compound IV, N-propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-fenolylene, and carbon

[0028] Potassium sulfate and the first solvent were mixed and reacted at 80–90 °C for 8–12 h under a nitrogen atmosphere. After the reaction was completed, 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 structure with the following formula: Compound II; the synthetic route is shown in the following formula:

[0029]

[0030] 2)a. Tert-butylamine, triethylenediamine, di-tert-butyl dicarbonate, and dichloromethane were mixed at room temperature and reacted for 12 h to obtain N,N-di-tert-butylurea;

[0031] b. N,N-di-tert-butylurea, tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine were mixed in anhydrous diethyl ether. After the reaction was completed, the following structure was obtained: Compound III.

[0032] 3) Compound II, Compound III, Iodobenzene V, palladium catalyst, bisphosphine ligand, base, and second solvent were mixed and subjected to an amination reaction under an inert atmosphere to obtain the structure with the following formula: N-tert-butyl-3-aminoindole derivatives, wherein R1 represents hydrogen, methyl, phenyl, cyano, or halogen; R2 represents hydrogen, methyl, phenyl, methoxy, chlorine, bromine, trifluoromethyl, cyano, or methyl formate. The synthetic route is shown in the following formula:

[0033]

[0034] Using R1 and R2 as hydrogen atoms, explain the reaction mechanism of this invention:

[0035]

[0036] Wherein, L represents the phosphine ligand; iodobenzene 1 undergoes oxidative addition to the palladium catalyst to generate intermediate 2, which reacts with acetylacetin II via carbopalladium conversion to generate intermediate 3; subsequently, aryl CH activation generates the corresponding cyclic palladium intermediate 4, which undergoes oxidative addition with the three-membered ring nitrogen-containing reagent III to generate the corresponding cyclic palladium(IV) intermediate 5, which releases tBuNCO to give nitrobenzene intermediate 6, which undergoes successive reductive elimination to give N-tert-butyl-3-aminoindole product I and the palladium catalyst.

[0037] In an optional embodiment of the present invention, the palladium catalyst is palladium acetate, the bisphosphine ligand is 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene, and the base is cesium carbonate.

[0038] In an optional embodiment of the present invention, the second solvent is 1,4-dioxane.

[0039] In an optional embodiment of the present invention, the concentration of compound II in the second solvent mixture is 0.2 mol / L.

[0040] In an optional embodiment of the present invention, the molar ratio of compound II, compound III, iodobenzene V, palladium catalyst, monophosphine ligand, and base is 1:1.5:1.5:(0.05~0.10):(0.05~0.10):(2.0~2.5).

[0041] In an optional embodiment of the present invention, the reaction temperature of the amination reaction is 115–130°C, preferably 115°C. The reaction time is 10–14 h, preferably 12 h.

[0042] Compounds I-a to I-p are some examples of N-tert-butyl-3-aminoindole derivatives prepared in this invention.

[0043]

[0044] Unless otherwise specified, all materials and reagents used in the following examples are commercially available or prepared according to existing literature.

[0045] All reagents used in the following examples are commercially available. Palladium acetate, 4,5-bis(diphenylphosphine)-9,9-dimethyloxanthracene, and 1,4-dioxane were purchased from Anaiji Chemical; cesium carbonate was purchased from Leyan.

[0046] Preparation of compound Ia:

[0047] 1) Preparation of compound II-a:

[0048]

[0049] Weigh out 1.9913 g (11 mmol) of phenylacetylene bromide IV-a, 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, place them in a dry round-bottom flask, purge with nitrogen, and then add 15 mL of dry toluene. The reaction mixture is reacted at 80 °C for 12 h. After the reaction is complete, dilute with ethyl acetate, filter through a 300–400 mesh silica gel filter, concentrate under reduced pressure to remove the solvent, and separate by column chromatography to obtain 2.21 g of compound II-a, with a molar yield of 70%.

[0050] 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.

[0051] 2) Preparation of compound III:

[0052]

[0053] 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 a reactor. Then, 57.5 mL of ditert-butyl dicarbonate (50.0 mmol) was dissolved in 50.0 mL of dichloromethane, and the reaction was carried out at room temperature for 12 h. After the reaction was completed, the reaction solution was cooled to 0 °C, 250 mL of n-hexane was added, and the mixture was filtered. The solution was washed with supercooled water and then with diethyl ether to obtain a white solid, N,N-di-tert-butylurea.

[0054] N,N-di-tert-butylurea (20.0 g, 116.1 mmol) and diethyl ether (200.0 mL) were added to the 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, then cooled to 5°C. Potassium tert-butoxide (17.0 g, 150.9 mmol) was added in portions, and the mixture was allowed to heat naturally for 12 hours. 150 mL of n-hexane was added to the reaction mixture, and the mixture was washed with water and saturated brine. The solution was dried over anhydrous sodium sulfate, filtered, evaporated to dryness, and distilled under reduced pressure to give compound III as a colorless liquid (11.6 g, molar yield 59%).

[0055] 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.

[0056] 3) Preparation of compound Ia:

[0057]

[0058] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.1022 g, 0.6 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ia (0.1310 g, molar yield 95%).

[0059] NMR data for compound Ia: 1 H NMR(400MHz, CDCl3) δ7.73(d,J=8.4Hz,1H),7.68(dt,J=7.2,1.6Hz,1H),7.53(d,J=8.4 Hz,2H),7.42-7.34(m,2H),7.33-7.28(m,1H),7.23-7.17(m,3H),7.14(ddd,J=8.4,6.8, 1.6Hz,1H),6.93(t,J=7.6Hz,1H),6.90-6.82(dd,J=8.0,1.2Hz,1H),3.37-3.26(m,1H) ,3.25-3.14(m,1H),2.43(s,3H),1.58(s,9H),1.25-1.06(m,2H),0.51(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.0,141.4,137.9,135.5,134.7,132.1,131.2,129.4,128.2,127. 9,126.8,126.1,121.1,119.43,119.35,115.3,114.8,59.8,52.8,32.2,22.0,21.7,11.0.

[0060] Example 2

[0061] Preparation of compound Ib:

[0062] 1) Preparation of compound II-a: Same as in Example 1

[0063] 2) Preparation of compound III: Same as in Example 1

[0064] 3) Preparation of compound Ib:

[0065]

[0066] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vb (0.0981 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ib (0.130 g, molar yield 91%).

[0067] NMR data for compound Ib: 1 H NMR(400MHz, CDCl3)δ7.65(dt,J=7.2,1.6Hz,1H),7.58-7.49(m,3H),7.40-7.33(m,2H),7.32-7.27(m,1H),7.22-7.15(m,3H),6.80- 6.70(m,2H),3.34-3.25(m,1H),3.23-3.13(m,1H),2.48(s,3H),2.44(s,3H),1.56(s,9H),1.23-1.04(m,2H),0.50(t,J=7.6Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.0,140.8,137.9,136.0,134.9,131.9,131.2,130.7,129.4,128.2,12 8.1,127.9,126.8,123.9,121.0,119.1,115.4,114.7,59.6,52.7,32.1,22.3,21.9,21.6,11.0.

[0068] Example 3

[0069] Preparation of compound Ic:

[0070] 1) Preparation of compound II-a: Same as in Example 1

[0071] 2) Preparation of compound III: Same as in Example 1

[0072] 3) Preparation of compound Ic:

[0073]

[0074] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vc (0.1260 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ic (0.1380 g, molar yield 86%).

[0075] NMR data of compound Ic: 1 H NMR (400MHz, CDCl3) δ7.91 (s, 1H), 7.71-7.62 (m, 3H), 7.55 (d, J = 8.4Hz, 2H), 7.51-7.43 (m, 2H), 7.42-7.30 (m, 4H), 7.25-7.14 (m, 4H) ),6.95(d,J=8.4Hz,1H),3.42-3.30(m,1H),3.28-3.14(m,1H),2.44(s,3H),1.62(s,9H),1.26-1.09(m,2H),0.54(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.1,142.8,142.1,137.8,136.1,134.8,134.7,132.0,131.2,129.5,128.9,128.3, 128.2,128.0,127.7,126.9,126.8,125.4,119.6,119.5,114.8,114.2,60.0,52.8,32.3,22.0,21.7,11.1.

[0076] Example 4

[0077] Preparation of compound Id:

[0078] 1) Preparation of compound II-a: Same as in Example 1

[0079] 2) Preparation of compound III: Same as in Example 1

[0080] 3) Preparation of compound Id:

[0081]

[0082] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vd (0.1053 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Id (0.0808 g, molar yield 55%).

[0083] NMR data for compound Id: 1 H NMR (400MHz, CDCl3) δ7.65-7.58(m,1H),7.52(d,J=8.4Hz,2H),7.39-7.32(m,2H),7.32-7.27(m,1H),7.23-7.16(m,4H),6.76(d,J=8.8Hz,1H),6. 63(dd,J=8.8,2.4Hz,1H),3.88(s,3H),3.36-3.23(m,1H),3.22-3.11(m, 1H),2.43(s,3H),1.56(s,9H),1.25-1.04(m,2H),0.51(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ155.2,143.0,140.4,137.8,136.4,134.9,132.0,131.3,129.4,128.2,12 8.1,127.9,126.8,120.6,119.9,114.7,108.4,100.2,59.6,56.0,52.8,32.0,21.9,21.7,11.0.

[0084] Example 5

[0085] Preparation of compound Ie:

[0086] 1) Preparation of compound II-a: Same as in Example 1

[0087] 2) Preparation of compound III: Same as in Example 1

[0088] 3) Preparation of compound Ie:

[0089]

[0090] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vd (0.1053 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ie (0.0808 g, molar yield 55%).

[0091] NMR data for compound Ie: 1 H NMR (400MHz, CDCl3) δ7.71(d,J=1.6Hz,1H),7.59(dt,J=7.2,1.6Hz,1H),7.59(d,J=8.0Hz,2H),7.40-7.29(m,3H),7.22-7.17(m,3H),6.91(dd,J= 8.4,1.6Hz,1H),6.79(d,J=8.4Hz,1H),3.32-3.24(m,1H),3.20-3.11(m, 1H),2.44(s,3H),1.55(s,9H),1.23-1.06(m,2H),0.52(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.3,142.1,137.6,135.8,134.2,131.9,131.1,129.5,128.4,128.1, 128.0,127.0,126.95,124.7,120.2,120.1,115.1,114.9,60.2,52.8,32.1,21.9,21.7,11.0.

[0092] Example 6

[0093] Preparation of compound If:

[0094] 1) Preparation of compound II-a: Same as in Example 1

[0095] 2) Preparation of compound III: Same as in Example 1

[0096] 3) Preparation of compound If:

[0097]

[0098] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene V-fb (0.1273 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound If (0.0808 g, molar yield 55%).

[0099] NMR data for compound If: 1 H NMR (400MHz, CDCl3) δ7.87(d,J=1.6Hz,1H),7.60(dt,J=7.2,1.6Hz,1H),7.49(d,J=8.0Hz,2H),7.40-7.29(m,3H),7.21-7.15(m,3H),7.03(dd,J= 8.4,1.2Hz,1H),6.74(d,J=8.4Hz,1H),3.31-3.23(m,1H),3.19-3.11(m, 1H),2.44(s,3H),1.55(s,9H),1.22-1.06(m,2H),0.52(t,J=7.2Hz,3H); 13C NMR (100MHz, CDCl3) δ143.2,142.0,137.6,136.2,134.2,131.9,131.0,129.5,128.5,128.1, 128.0,126.9,125.0,122.7,120.5,118.0,115.0,114.8,60.2,52.7,32.1,21.9,21.7,11.0.

[0100] Example 7

[0101] Preparation of compound Ig:

[0102] 1) Preparation of compound II-a: Same as in Example 1

[0103] 2) Preparation of compound III: Same as in Example 1

[0104] 3) Preparation of compound Ig:

[0105]

[0106] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vg (0.1224 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ig (0.1060 g, molar yield 67%).

[0107] NMR data for compound Ig: 1 H NMR (400MHz, CDCl3) δ7.99 (s, 1H), 7.60 (dt, J = 7.6, 2.0Hz, 1H), 7.49 (d, J = 8.4Hz, 2H), 7.44-7.31 (m, 3H), 7.23-7.16 (m, 4H), 7. 01(d,J=8.4Hz,1H),3.35-3.25(m,1H),3.21-3.10(m,1H),2.44(s,3H),1.59(s,9H),1.23-1.08(m,2H),0.53(t,J=7.2Hz,3H);13 C NMR (100MHz, CDCl3) δ144.1,143.4,137.5,134.3,133.9,131.8,130.9,129.6,128.7,128.1,128.06,127.0,125.3(q,J=2 69.9Hz), 123.1 (q, J = 31.4Hz), 119.8, 116.2 (q, J = 3.6Hz), 115.0, 112.6 (q, J = 4.7Hz), 60.5, 52.8, 32.3, 22.0, 21.7, 11.0.

[0108] Example 8

[0109] Preparation of compound Ih:

[0110] 1) Preparation of compound II-a: Same as in Example 1

[0111] 2) Preparation of compound III: Same as in Example 1

[0112] 3) Preparation of compound Ih:

[0113]

[0114] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vh (0.1031 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ih (0.1060 g, molar yield 67%).

[0115] NMR data of compound Ih: 1H NMR (400MHz, CDCl3) δ8.06(s,1H),7.57(dt,J=7.6,2.0Hz,1H),7.47(d,J=8.4Hz,2H),7.44-7.39(m,1H),7.39-7.32(m,2H),7.22-7.15( m,4H),6.99(d,J=8.0Hz,1H),3.32-3.24(m,1H),3.18-3.09(m,1H),2.44(s,3H),1.58(s,9H),1.22-1.06(m,2H),0.54(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ145.3,143.5,137.4,134.1,133.4,131.8,130.7,129.6,129.4,128.9,128 .1,128.09,127.1,122.3,120.9,120.1,120.0,115.6,103.8,60.9,52.8,32.3,22.0,21.7,11.0.

[0116] Example 9

[0117] Preparation of compound Ii:

[0118] 1) Preparation of compound II-a: Same as in Example 1

[0119] 2) Preparation of compound III: Same as in Example 1

[0120] 3) Preparation of compound Ii:

[0121]

[0122] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vi (0.1179 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ii (0.1320 g, molar yield 85%).

[0123] NMR data for compound Ii: 1 H NMR(400MHz, CDCl3)δ8.50(s,1H),7.72-7.66(m,1H),7.60(dd,J=8.4,1.2Hz,1H),7.51(d,J=8.4Hz,2H),7.44-7.36(m,2H),7.35-7.30(m,1H) ,7.23-7.16(m,3H),6.83(d,J=8.4Hz,1H),3.95(s,3H),3.35-3.15(m,2 H),2.44(s,3H),1.61(s,9H),1.24-1.05(m,2H),0.52(t,J=7.6Hz,3H); 13 C NMR (100MHz, CDCl3) δ168.2,144.9,143.3,137.6,134.7,134.0,131.9,130.9,129.6,128.6,12 8.2,128.0,127.0,122.7,120.5,118.8,117.6,115.2,60.5,52.8,52.2,32.4,21.9,21.7,11.0.

[0124] Example 10

[0125] Preparation of compound Ij:

[0126] 1) Preparation of compound II-a: Same as in Example 1

[0127] 2) Preparation of compound III: Same as in Example 1

[0128] 3) Preparation of compound Ij:

[0129]

[0130] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Vj (0.1260 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ij (0.1310 g, molar yield 81%).

[0131] NMR data of compound Ij: 1 H NMR (400MHz, CDCl3) δ7.88(dt,J=7.2,1.6Hz,1H),7.77(d,J=8.8Hz,1H),7.61(d,J=8.4Hz,2H),7.46-7.36(m,7H),7.34-7.27(m,2H ),7.22-7.15(m,3H),6.70(d,J=2.0Hz,1H),3.45-3.28(m,2H),2.28(s,3H),1.60(s,9H),1.22-1.06(m,2H),0.51(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.4,142.6,141.7,138.1,135.1,134.5,132.4,132.1,131.3,129.6,128.7,128.3, 128.2,128.0,127.2,126.7,126.5,125.9,120.5,117.5,115.6,115.2,60.0,53.0,32.2,22.1,21.4,11.0...

[0132] Example 11

[0133] 1) Preparation of compound II-b:

[0134]

[0135] Weigh out 1.2874 g (6.6 mmol) of phenylacetylene 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, place them in a dry round-bottom flask, purge with nitrogen, and then add 10 mL of dry toluene. React the reaction mixture at 80 °C for 12 h. After the reaction is complete, dilute with ethyl acetate, filter through a 300–400 mesh silica gel filter, concentrate under reduced pressure to remove the solvent, and separate by column chromatography to obtain 1.61 g of compound II-a, with a molar yield of 75%.

[0136] NMR data of compound II-a: 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.

[0137] 2) Preparation of compound III: Same as in Example 1.

[0138] 3) Preparation of compound Ik:

[0139]

[0140] Compound II-b (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ik (0.1250 g, molar yield 88%).

[0141] NMR data for compound Ik: 1 H NMR (400MHz, CDCl3) δ7.71(d,J=8.4Hz,1H),7.57-7.48(m,3H),7.20-7.09(m,5H),7.07(dd,J=7.6,2.0Hz,1H),6.91(td,J=7.6,0.6Hz,1H),6.8 6(dd,J=8.4,1.6Hz,1H),3.36-3.27(m,1H),3.24-3.15(m,1H),2.44(s, 3H),2.42(s,3H),1.57(s,9H),1.24-1.08(m,2H),0.53(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ142.9,141.5,138.0,137.9,135.4,131.8,131.6,131.0,129.4,128.5,12 8.2,127.5,126.1,120.9,119.3,119.2,115.2,114.6,59.7,52.8,32.1,22.0,21.6,21.5,11.1.

[0142] Example 12

[0143] Preparation of compound Il:

[0144] 1) Preparation of compound II-c:

[0145]

[0146] 2.4684 g (9.6 mmol) of phenylacetylene 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 and placed in a dry round-bottom flask. Nitrogen gas was introduced to purge the mixture, followed by the addition of 12 mL of dry toluene. The reaction mixture was reacted at 80 °C for 12 h. After the reaction was complete, the mixture was diluted with ethyl acetate, filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain 1.81 g of compound II-c, with a molar yield of 53%.

[0147] 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 CNMR(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.

[0148] 2) Preparation of compound III: Same as in Example 1.

[0149] 3) Preparation of compound Il:

[0150]

[0151] Compound II-c (0.1169 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Il (0.1524 g, molar yield 94%).

[0152] NMR data of compound Il: 1 H NMR (400MHz, CDCl3) δ7.80-7.72(m,2H),7.71-7.66(m,2H),7.62(d,J=8.0,2.0Hz,1H),7.5 6(dd,J=8.0,2.0Hz,1H),7.54-7.45(m,4H),7.39(tt,J=7.6,1.2Hz,1H),7.28-7.24(m,1H), 7.20-7.12(m,3H),6.93(td,J=8.0,0.8Hz,1H),6.88(dd,J=8.0,1.2Hz,1H),3.40-3.31(m, 1H),3.30-3.21(m,1H),2.40(s,3H),1.62(s,9H),1.25-1.08(m,2H),0.53(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.0,141.1,140.8,140.7,137.9,135.7,133.7,132.4,131.6,129.4,129.0,128.2, 127.6,127.2,126.4,126.1,125.4,121.1,119.4,119.39,115.3,115.0,59.8,52.9,32.2,22.0,21.6,11.1.

[0153] Example 13

[0154] Preparation of compound Im:

[0155] 1) Preparation of compound II-d:

[0156]

[0157] Weigh out 2.0398 g (9.9 mmol) of phenylacetylene bromide IV-d, 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, place them in a dry round-bottom flask, purge with nitrogen, and then add 13 mL of dry toluene. React the reaction mixture at 80 °C for 12 h. After the reaction is complete, dilute with ethyl acetate, filter through a 300–400 mesh silica gel filter, concentrate under reduced pressure to remove the solvent, and separate by column chromatography to obtain 3.0 g of compound II-d, with a molar yield of 98%.

[0158] NMR data of compound II-d: 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 CNMR (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.

[0159] 2) Preparation of compound III: Same as in Example 1.

[0160] 3) Preparation of compound Im:

[0161]

[0162] Compound II-c (0.1015 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Il (0.1320 g, molar yield 91%).

[0163] NMR data for compound Im: 1 H NMR (400MHz, CDCl3) δ8.06 (dd, J=8.0, 1.6Hz, 1H), 7.77-7.70 (m, 2H), 7.62 (dd, J=8.0, 2.0Hz ,1H),7.56(d,J=8.4Hz,2H),7.32(dd,J=8.0,2.0Hz,1H),7.23(d,J=8.0Hz,2H),7.16(ddd,J= 8.4,7.2,1.2Hz,1H),6.86(ddd,J=8.0,6.8,0.8Hz,1H),6.57(d,J=7.6Hz,1H),3.39-3.31(m ,1H),3.29-3.21(m,1H),2.45(s,3H),1.58(s,9H),1.13-0.96(m,2H),0.50(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.5,139.8,139.4,137.4,136.2,132.7,131.9,131.87,130.4,129.6,12 8.2,125.2,121.8,119.7,119.5,118.9,115.9,115.5,112.0,60.1,52.8,32.3,22.1,21.7,10.9.

[0164] Example 14

[0165] Preparation of compound In:

[0166] 1) Preparation of compound II-e:

[0167]

[0168] 1.4995 g (6 mmol) of phenylacetylene bromide IV-e, 1.487 g (6.6 mmol) of N-propyl-4-methylbenzenesulfonamide, 0.1498 g (0.6 mmol) of copper sulfate pentahydrate, 0.2162 g (1.2 mmol) of 1,10-phenololine, and 1.6584 g (12 mmol) of potassium carbonate were weighed and placed in a dry round-bottom flask. Nitrogen gas was purged, and then 12 mL of dry toluene was added. The reaction mixture was reacted at 80 °C for 12 h. After the reaction was complete, the mixture was diluted with ethyl acetate, filtered through a 300–400 mesh silica gel filter, concentrated under reduced pressure to remove the solvent, and separated by column chromatography to obtain 2.29 g of compound II-e, with a molar yield of 99%.

[0169] NMR data of compound II-e: 1 H NMR (400MHz, CDCl3) δ7.81(d,J=8.4Hz,2H),7.37(d,J=8.4Hz,2H),7.25(t,J=2.0Hz,1H),7.21 (d,J=2.0Hz,2H),3.36(t,J=7.2Hz,2H),2.46(s,3H),1.77-1.65(m,2H),0.94(t,J=7.2Hz,3H); 13 C NMR (400MHz, CDCl3) δ145.0,134.9,134.6,130.0,129.1,127.9,127.7,126.1,85.1,69.0,53.3,21.8,21.5,11.0.

[0170] 2) Preparation of compound III: Same as in Example 1.

[0171] 3) Preparation of compound In:

[0172]

[0173] Compound II-e (0.1147 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound In (0.1300 g, molar yield 82%).

[0174] NMR data for compound In: 1 H NMR (400MHz, CDCl3) δ7.73(d,J=8.8Hz,1H),7.67(t,J=1.6Hz,1H),7.59(d,J=8.4H z,2H),7.40(t,J=1.6Hz,1H),7.23(d,J=8.0Hz,2H),7.17(ddd,J=8.4,6.8,1.6Hz, 1H),7.10(t,J=1.6Hz,1H),6.94(td,J=8.0,0.8Hz,1H),6.87(d,J=8.0Hz,1H),3.4 1-3.26(m,2H),2.44(s,3H),1.61(s,9H),1.25-1.08(m,2H),0.55(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ143.4,138.1,137.7,137.3,135.9,134.6,133.3,130.5,129.6,129 .5,128.4,128.2,125.6,121.8,119.8,115.8,115.4,60.1,52.7,32.3,22.0,21.7,10.9.

[0175] Example 15

[0176] Preparation of compound Io:

[0177] 1) Preparation of compound II-e:

[0178]

[0179] Alkenyl bromide VI (2.2924 g, 9.1 mmol), N-propyl-4-methylbenzenesulfonamide (1.4930 g, 7.0 mmol), copper sulfate pentahydrate (0.1250 g, 0.5 mmol), 1,10-phenololine (0.1802 g, 1.0 mmol), and potassium carbonate (1.3820 g, 10 mmol) were weighed and placed in a dry round-bottom flask. Nitrogen gas was introduced to purge the atmosphere, followed by the addition of 10 mL of dry tetrahydrofuran. The reaction mixture was reacted at 55 °C for 12 h. After the reaction was complete, the mixture was diluted with ethyl acetate, 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 1.83 g, with a molar yield of 86%.

[0180] NMR data of compound II-e: 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.

[0181] 2) Preparation of compound III: Same as in Example 1.

[0182] 3) Preparation of compound Io:

[0183]

[0184] Compound II-f (0.0910 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Io (0.1346 g, molar yield 99%).

[0185] NMR data for compound Io: 1 H NMR (400MHz, CDCl3) δ7.73 (dt, J=8.4, 0.8Hz, 1H), 7.64 (d, J=8.4Hz, 2H), 7.50 (dd, J=2.0, 0.8Hz ,1H),7.24(d,J=8.0Hz,2H),7.14(ddd,J=8.8,7.2,1.6Hz,1H),6.86(ddd,J=7.6,6.8,0.8Hz,1H) ,6.73(dd,J=3.2,0.8Hz,1H),6.64(dt,J=8.0,0.8Hz,1H),6.48(dd,J=3.2,1.6Hz,1H),3.46-3.3 5(m,1H),3.31-3.21(m,1H),2.45(s,3H),1.63(s,9H),1.22-1.09(m,2H),0.61(t,J=7.2Hz,3H); 13 C NMR (100MHz, CDCl3) δ144.8,143.1,142.0,138.0,135.8,130.8,129.5,128.0,125.0, 122.0,119.6,119.3,117.3,115.3,114.1,111.7,59.6,52.7,30.5,21.9,21.7,10.9..

[0186] Example 16

[0187] Preparation of compound Ip:

[0188] 1) Preparation of compound II-g:

[0189]

[0190] Alkenyl bromide VI (1.0950 g, 5 mmol), N-propyl-4-methylbenzenesulfonamide (1.2390 g, 5.5 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 and placed in a dry round-bottom flask. Nitrogen gas was purged, and then 10 mL of dry toluene was added. The reaction mixture was reacted at 80 °C for 12 h. After the reaction was complete, the mixture was diluted with ethyl acetate, 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-g 1.25 g, with a molar yield of 71%.

[0191] NMR data for compound II-g: 1 H NMR (400MHz, CDCl3) δ7.78(d,J=8.4Hz,2H),7.33(d,J=8.0Hz,2H),5.49(s,1H),3.76(d,J=11.2Hz,2H),3.41(d, J=11.2Hz,2H),3.27(t,J=7.2Hz,3H),2.43(s,3H),1.72-1.61(m,2H),0.97(d,J=14Hz,6H),0.89(t,J=7.2Hz,3H) 13 CNMR (400MHz, CDCl3) δ144.8,134.7,129.9,127.7,90.6,79.2,74.7,65.7,53.0,30.5,22.7,22.5,21.8,21.4,11.0.

[0192] 2) Preparation of compound III: Same as in Example 1.

[0193] 3) Preparation of compound Ip:

[0194]

[0195] Compound II-g (0.1054 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), Xantphos (0.0087 g, 0.015 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 15 mL pressure-resistant tube. The tube was then evacuated and purged with argon gas. Next, ultradry 1,4-dioxane (1.0 mL), iodobenzene Va (0.0918 g, 0.45 mmol), and compound III (0.0766 g, 0.45 mmol) were added sequentially. The tube was sealed and placed in a magnetically heated stirrer at 115 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, diluted with ethyl acetate, and filtered through a 300–400 mesh silica gel filter. Eluent was used as elution, the solvent was removed under reduced pressure, and the mixture was separated by 300–400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ip (0.1166 g, molar yield 78%).

[0196] NMR data for compound Ip: 1 H NMR (400MHz, CDCl3) δ7.72(d,J=8.4Hz,1H),7.60(d,J=8.0Hz,2H),7.18(d,J=7.6Hz,2H) ,7.07(ddd,J=8.8,7.2,1.6Hz,1H),6.70(t,J=7.6Hz,1H),6.35(d,J=8.0Hz,1H),6.05(s ,1H),3.90-3.75(m,3H),3.72-3.62(m,2H),3.37-3.28(m,1H),2.41(s,3H),1.98(s,9H) ,1.65-1.57(m,1H),1.50-1.41(m,1H),1.28(s,3H),0.86(t,J=7.2Hz,3H),0.80(s,3H); 13 C NMR (100MHz, CDCl3) δ143.2,137.5,135.6,135.5,129.5,127.9,124.1,121.8,119.1,118 .8,117.5,116.0,99.0,79.4,79.1,59.9,53.6,31.5,30.6,24.9,22.6,22.58,21.6,11.3.

[0197] The above embodiments are only used to illustrate the technical solutions of the present invention, and are not intended to limit it. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that modifications can still be made to the technical solutions described in the foregoing embodiments, or equivalent substitutions can be made to some of the technical features. Such modifications or substitutions do not cause the essence of the corresponding technical solutions to deviate from the spirit of the technical solutions of the embodiments of the present invention.

Claims

1. A kind N The method for preparing tert-butyl-3-aminoindole derivatives is characterized by, The specific steps include: 1) Compound IV , N 1,10-Propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, potassium carbonate, and the first solvent were mixed and reacted at 80-90°C for 8-12 h under a nitrogen atmosphere. After the reaction was completed, 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 structure [structure omitted]. Compound II, wherein the first solvent is any one of toluene, ethylbenzene, and benzene; 2) Tert-butylamine, triethylenediamine, di-tert-butyl dicarbonate, and dichloromethane were mixed at room temperature and reacted for 12 hours to obtain... N, N -Di-tert-butylurea; N,N - Di-tert-butylurea, tert-butyl hypochlorite, potassium tert-butoxide, and triethylamine are mixed in anhydrous diethyl ether. After the reaction is complete, the following structure is obtained: Compound III; 3) Compound II, Compound III, iodobenzene, palladium catalyst, bisphosphine ligand, base, and second solvent were mixed and subjected to an amination reaction under an inert atmosphere to obtain the structure with the following formula: of N -tert-butyl-3-aminoindole derivatives, wherein R1 represents hydrogen, methyl, phenyl, cyano, or halogen; R2 represents hydrogen, methyl, phenyl, methoxy, chlorine, bromine, trifluoromethyl, cyano, or methyl formate, and the second solvent is 1,4-dioxane. In step 3), the base is cesium carbonate; the bisphosphine ligand is 4,5-bisdiphenylphosphine-9,9-dimethyloxanthracene. The palladium catalyst is palladium acetate; the amination reaction temperature is 115~130 ℃, and the reaction time is 10~14 h.

2. The method for preparing N-tert-butyl-3-aminoindole derivatives as described in claim 1, characterized in that, In step 1), compound IV, N The molar ratio of propyl-4-methylbenzenesulfonamide, copper sulfate pentahydrate, 1,10-phenanthroline, and potassium carbonate is (1.1~1.2):1:(0.1~0.2):(0.2~0.4):(2.0~2.5).

3. The method for preparing N-tert-butyl-3-aminoindole derivatives as described in claim 1, characterized in that, In step 3), the concentration of compound II in the second solvent is 0.2 mol / L.

4. The method for preparing N-tert-butyl-3-aminoindole derivatives as described in claim 1, characterized in that, In step 3), the molar ratio of compound II, compound III, iodobenzene, palladium catalyst, bisphosphine ligand, and base is 1:1.5:1.5:(0.05~0.10):(0.05~0.10):(2.0~2.5).

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