A method for preparing a 9-aminophenanthrene derivative

Abstract

The application belongs to the technical field of organic synthesis, and particularly relates to a preparation method of 9-aminophenanthrene derivatives. The preparation method comprises the following steps: mixing an alkyne amide derivative, iodobenzene, a palladium catalyst, a diphosphine ligand, a base and a solvent, and performing a ring formation reaction under an inert atmosphere to obtain the 9-aminophenanthrene derivative. The preparation method of the 9-aminophenanthrene derivative provided by the application has the advantages of simple operation, few side reactions, high yield, and the ability to directly synthesize 9-aminophenanthrene derivatives with various types of substituents.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a method for preparing 9-aminophenanthrene derivatives. Background Technology

[0002] 9-Aminophenanthrene compounds are an important class of polycyclic compounds that are widely found in natural products and active molecules. For example, the natural product Piperolactam, Cepharadione A, and the active molecule PSB-16131 all contain the 9-aminophenanthrene structure. They have important applications in the fields of medicine, pesticides, and organic synthesis.

[0003] In the traditional synthesis of 9-aminophenanthrene compounds, they are mainly generated through amination reactions at the C9 position of the phenanthrene ring structure, such as nitration-reduction reactions and metal coupling reactions. Secondly, they are constructed through intramolecular cyclization of biphenyl compounds. However, existing reactions still have limitations such as harsh reaction conditions and a small substrate range. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a method for the tandem cyclization of acetylacetylamine and aromatic iodine, which is simple to operate, has few side reactions, and high yield, and can directly prepare a series of 9-aminophenanthrene derivatives.

[0005] To address the shortcomings of existing technologies, the technical solution provided by this invention is as follows: Compound II, Compound III, palladium catalyst, bisphosphine ligand, additive, base, and organic solvent were mixed and subjected to an amination reaction under an inert atmosphere to obtain the 9-aminophenanthrene derivative shown in Formula I. The synthetic route is shown below:

[0006] Wherein, R1 represents phenyl, p-methylphenyl, p-phenylphenyl, p-cyanophenyl, 3,5-dichlorophenyl, and 2-furanyl; R2 represents hydrogen, phenyl, methoxy, fluorine, chlorine, methyl ester, cyano, etc.

[0007] Preferably, the palladium catalyst is palladium acetate.

[0008] Preferably, the bisphosphine ligand is bisdiphenylphosphine methane.

[0009] Preferably, the additive is potassium pentovaginate.

[0010] Preferably, the alkali is cesium carbonate.

[0011] Preferably, the organic solvent is 1,4-dioxane.

[0012] Preferably, the molar concentration of compound II in the organic solvent is 0.2 to 0.4 mol / L, more preferably 0.3 mol / L.

[0013] Preferably, the molar ratio of compound II, compound III, palladium catalyst, bisphosphine ligand, additive, and base is 1:2.5:0.05:0.05:(0-0.5):2.

[0014] Preferably, the amination reaction is carried out at a temperature of 115-130 °C for 10-14 h.

[0015] Compounds I-a to I-l are some examples of 9-aminophenanthrene derivatives prepared in this invention: .

[0016] Using R1 as a phenyl group and R2 as a hydrogen atom, explain the reaction mechanism of this invention:

[0017] Iodobenzene IIIa undergoes oxidative addition to a palladium catalyst to generate intermediate 1, which reacts with acetylenol IIa via carbopalladium conversion to generate intermediate 2. Subsequent aryl CH activation generates the corresponding cyclic palladium intermediate 3, which undergoes oxidative addition with another molecule of iodobenzene IIIa to generate the corresponding cyclic palladium(IV) intermediate 4, which undergoes reductive elimination to generate 5. Further intramolecular CH activation generates Pd(II) cyclic intermediate 6, which is ultimately reductively eliminated to generate 9-aminophenanthrene compound Ia.

[0018] The beneficial effects of this invention are: The method for preparing 9-aminophenanthrene derivatives provided by this invention has the advantages of readily available initial substrates, a wide substrate range, simple synthesis operation, and excellent yield. It does not require the prior substitution of specific functional groups at the carbon sites to be reacted, and can directly undergo cyclization reaction with aromatic iodine to synthesize 9-aminophenanthrene derivatives with diverse substituent types. Detailed Implementation

[0019] The present invention will be further described below with reference to the embodiments. The following embodiments are only used to more clearly illustrate the technical solution of the present invention, and should not be used to limit the scope of protection of the present invention.

[0020] The following examples illustrate a method for preparing 9-aminophenanthrene derivatives of Formula I, comprising: 1) Preparation of compound II: Compound II was prepared according to the method disclosed in CN117865874A. The specific compound is as follows: , , , , .

[0021] Compound II-e was prepared according to the method disclosed in CN117865874A, and the specific preparation method is as follows:

[0022] Weigh out 1.4995 g of phenylacetylene bromide IV-e (6 mmol). N 1,487 g (6.6 mmol) of 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 placed in a dry round-bottom flask, purged with nitrogen, 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 yield of 99%.

[0023] NMR data of compound II-e: 1 H NMR (400 MHz, CDCl3) d 7.81(d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.25 (t, J = 2.0 Hz, 1H), 7.21 (d, J = 2.0 Hz, 2H), 3.36 (t, J = 7.2 Hz, 2H), 2.46 (s, 3H), 1.77-1.65 (m, 2H), 0.94 (t, J =7.2 Hz, 3H); 13 C NMR (400 MHz, CDCl3) δ 145.0, 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. 2) Preparation of 9-aminophenanthrene derivatives as shown in Formula I Compound II, Compound III, palladium catalyst (palladium acetate), bisphosphine ligand (bisdiphenylphosphinemethane), additive (potassium pivalate), base (cesium carbonate), and solvent (1,4-dioxane) were mixed and subjected to an amination reaction under an inert atmosphere to obtain the 9-aminophenanthrene derivative shown in Formula I. After the reaction was completed, ethyl acetate was added for dilution, and the mixture was filtered through 300-400 mesh silica gel. Ethyl acetate was used as eluting agent, the solvent was removed under reduced pressure, and the mixture was separated by 300-400 mesh silica gel column chromatography. The column packing solvent was petroleum ether; the eluent was petroleum ether or a mixture of petroleum ether and ethyl acetate; and the packing material was 300-400 mesh silica gel.

[0024] In an optional embodiment of the present invention, the concentration of compound II in the solvent is 0.3 mol / L.

[0025] In an optional embodiment of the present invention, the molar ratio of compound II, compound III, palladium catalyst, bisphosphine ligand, additive, and base is 1:2.5:0.05:0.05:(0-0.5):2.

[0026] 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.

[0027] Unless otherwise specified, all materials and reagents used in the following examples are commercially available or prepared according to existing literature.

[0028] All reagents used in the following examples are commercially available. Palladium acetate, bis(diphenylphosphine)methane, and 1,4-dioxane were purchased from Anaiji Chemical; potassium pentovanate and cesium carbonate were purchased from Leyan.

[0029] The following specific examples use compounds II-a~f and compound III as raw materials, and mix them with palladium catalyst, bisphosphine ligand, additives, base and organic solvent, and carry out amination reaction under an inert atmosphere to prepare 9-aminophenanthrene derivatives as shown in Formula I. Example 1

[0030] Preparation of compound Ia:

[0031] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene III-a (0.1530 g, 0.75 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 (0.120 g, 86% yield).

[0032] NMR data for compound Ia: 1 H NMR (400 MHz, CDCl3) d 8.81-8.72 (m, 2H), 8.07 (dd, J = 8.4, 1.2 Hz, 1H), 7.72-7.65 (m, 2H), 7.64-7.61 (m, 1H), 7.57 (ddd, J = 8.0, 6.8, 1.2 Hz, 1H), 7.51-7.41 (m, 6H), 7.34 (dd, J = 8.4, 1.6 Hz, 1H),7.31-7.27 (m, 1H), 7.21 (d, J = 8.0 Hz, 2H), 3.64-3.51 (m, 1H), 3.29-3.17 (m,1H), 2.47 (s, 3H), 1.49-1.37 (m, 1H), 1.32-1.25 (m, 1H), 0.66 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d143.2, 140.8, 137.8, 137.4, 132.9, 132.5, 131.9, 131.5, 131.47, 130.4, 129.9, 129.4, 128.5, 128.4, 128.1, 127.7, 127.5, 127.4, 127.0, 126.9, 126.8, 126.5, 122.9, 122.5, 53.2, 21.6, 21.5, 11.4. Example 2

[0033] Preparation of compound Ib:

[0034] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIb (0.2101 g, 0.75 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 (0.1450 g, 78% yield).

[0035] NMR data for compound Ib: 1 H NMR (400 MHz, CDCl3) d 9.16–8.87 (m, 2H), 8.16 (d, J = 8.8 Hz, 1H), 7.94-7.73 (m, 5H), 7.72-7.61 (m, 2H), 7.60-7.31 (m,13H), 7.26-7.20 (m, 2H), 3.70-3.53 (m, 1H), 3.33-3.16 (m, 1H), 2.47 (s, 3H),1.53-1.43 (m, 1H), 1.38-1.30 (m, 1H), 0.69 (t, J = 7.2 Hz, 3H); 13 C NMR (100MHz, CDCl3) d143.3, 141.31, 141.26, 140.6, 140.3, 139.9, 137.8, 137.4, 132.4, 131.9, 131.1, 130.8, 129.9, 129.5, 129.14, 129.11, 128.5, 128.2, 127.81, 127.79, 127.6, 127.2, 126.6, 126.4, 121.4, 121.0, 53.2, 21.7, 21.6, 11.5. Example 3

[0036] Preparation of compound Ic:

[0037] The difference between this embodiment and Example 1 is that the reaction temperature is 130 °C; compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (0.0087 g, 0.015 mmol), potassium pentovane (0.0213 g, 0.15 mmol), and cesium carbonate (0.1955 g, 0.6 mmol) were added sequentially to a 5 mL pressure-resistant tube, evacuated and filled with argon gas, and then ultra-dry 1,4-dioxane (1.0 mL) and iodobenzene IIIc (0.1755 g, 0.75 mmol) were added sequentially, sealed and placed in a magnetically heated stirrer at 130 °C for 12 hours. After the reaction was completed, the mixture was cooled to room temperature, diluted with ethyl acetate, filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, the solvent was removed under reduced pressure, and separated by 300-400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ic (0.1190 g, yield 75%).

[0038] NMR data of compound Ic: 1 H NMR (400 MHz, CDCl3) 8.04–7.98 (m, 2H), 7.96 (d, J = 9.2 Hz, 1H), 7.54 (dt, J = 7.6, 0.8, 1H), 7.45-7.40 (m, 4H), 7.38-7.34 (m, 1H), 7.25-7.16 (m, 5H), 7.06 (dd, J= 9.2, 2.4 Hz, 1H), 4.03 (s, 3H), 3.99 (s, 3H), 3.56-3.47 (m, 1H), 3.21-3.12 (m, 1H), 2.43 (s, 3H), 1.45-1.36 (m, 1H), 1.26-1.19 (m, 1H), 0.63 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 158.7, 158.4, 143.1, 138.2, 137.9, 137.7, 132.3, 131.9, 131.3, 130.2, 130.1, 130.0, 129.4, 128.3, 128.2, 128.1, 128.0, 127.5, 127.47, 126.5, 116.5, 116.4, 104.8, 104.4, 55.68, 55.65, 53.2, 21.6, 21.5, 11.4. Example 4

[0039] Preparation of compound Id:

[0040] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (0.0087 g, 0.015 mmol), potassium pentovane (0.0213 g, 0.15 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 filled with argon gas. Then, ultra-dry 1,4-dioxane (1.0 mL) and iodobenzene IIId (0.1665 g, 0.75 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 completed, the mixture was cooled to room temperature, diluted with ethyl acetate, filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, the solvent was removed under reduced pressure, and separated by 300-400 mesh silica gel column chromatography to obtain a pale yellow solid compound Id (0.1290 g, yield 85%).

[0041] NMR data for compound Id: 1 H NMR (400 MHz, CDCl3) d 8.24-8.15 (m, 2H), 8.05 (dd, J= 9.2, 5.6 Hz, 1H), 7.54-7.50 (m, 1H), 7.48-7.43 (m, 2H), 7.43-7.37(m, 3H), 7.34-7.27 (m, 2H), 7.24-7.17 (m, 4H), 3.55-3.47 (m, 1H), 3.19-3.11(m, 1H), 2.45 (s, 3H), 1.43-1.35 (m, 1H), 1.25-1.18 (m, 1H), 0.64 (t, J = 7.2Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 162.0 (d, J = 246.7 Hz), 161.8 (d, J =245.8 Hz), 143.5, 139.6 (d, J = 2.1 Hz), 137.6, 136.9, 132.5 (dd, J = 8.3,4.2 Hz), 131.7, 131.6, 131.5 (dd, J = 8.7, 4.2 Hz), 131.1 (d, J = 8.7 Hz), 130.1 (d, J = 1.5 Hz), 129.8, 129.5, 129.2 (d, J = 8.6 Hz), 128.7 (d, J = 1.6Hz), 128.5, 128.04, 127.96, 127.7, 116.5 (d, J = 23.4 Hz), 116.3 (d, J = 23.2Hz), 108.2 (d, J = 22.4 Hz), 107.9 (d, J = 22.5 Hz), 53.2, 21.6, 21.5, 11.4. Example 5

[0042] Preparation of compound Ie:

[0043] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (0.0087 g, 0.015 mmol), potassium pentovane (0.0213 g, 0.15 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 filled with argon gas. Then, ultra-dry 1,4-dioxane (1.0 mL) and iodobenzene IIIe (0.1788 g, 0.75 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 completed, the mixture was cooled to room temperature, diluted with ethyl acetate, filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, the solvent was removed under reduced pressure, and separated by 300-400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ie (0.1250 g, yield 78%).

[0044] NMR data for compound Ie: 1 H NMR (400 MHz, CDCl3) d 8.63–8.56 (m, 2H), 7.98 (d, J = 9.2 Hz, 1H), 7.53-7.49 (m, 2H), 7.49-7.45 (m, 2H), 7.45-7.40 (m, 3H), 7.40-7.38 (m, 1H), 7.25-7.20 (m, 4H), 3.54-3.46 (m, 1H), 3.17-3.09 (m, 1H), 2.45 (s, 3H), 1.42-1.33 (m, 1H), 1.26-1.17 (m, 1H), 0.64 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 143.6, 140.6, 137.5, 136.6, 134.1, 133.7, 132.5, 131.8, 131.64, 131.61, 130.5, 130.2, 129.7, 129.6, 128.6, 128.3, 128.2, 128.11, 128.09, 128.0, 127.9, 127.7, 122.6, 122.2, 53.1, 21.7, 21.5, 11.4. Example 6

[0045] Preparation of compound If:

[0046] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (0.0087 g, 0.015 mmol), potassium pentovane (0.0213 g, 0.15 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 filled with argon gas. Then, ultra-dry 1,4-dioxane (1.0 mL) and iodobenzene IIIf (0.1965 g, 0.75 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, filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, the solvent was removed under reduced pressure, and separated by 300-400 mesh silica gel column chromatography to obtain a pale yellow solid compound If (0.1050 g, yield 60%).

[0047] NMR data for compound If: 1 H NMR (400 MHz, CDCl3) d 9.60-9.48 (m, 2H), 8.17 (dd, J = 8.4, 1.6 Hz, 1H), 8.10-8.02 (m, 2H), 7.60 (td, J = 7.6, 1.6 Hz, 1H),7.53-7.43 (m, 5H), 7.40 (d, J = 8.8 Hz, 1H), 7.26-7.20 (m, 3H), 4.07 (s, 3H), 4.04 (s, 3H), 3.58-3.48 (m, 1H), 3.23-3.10 (m, 1H), 2.46 (s, 3H), 1.42-1.34(m, 1H), 1.27-1.21 (m, 1H), 0.64 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d167.11, 167.08, 143.6, 142.8, 137.4, 136.4, 136.0, 134.8, 134.5, 131.6, 131.2, 130.2, 129.6, 129.5, 129.1, 128.9, 128.86, 128.6, 128.2, 128.1, 127.7, 127.3, 127.2, 126.9, 125.4, 125.0, 53.1, 52.6, 21.7, 21.5, 11.4. Example 7

[0048] Preparation of compound Ig:

[0049] Compound II-a (0.0940 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (0.0087 g, 0.015 mmol), potassium pentovane (0.0213 g, 0.15 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 filled with argon gas. Then, ultra-dry 1,4-dioxane (1.0 mL) and iodobenzene III g (0.1718 g, 0.75 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 completed, the mixture was cooled to room temperature, diluted with ethyl acetate, filtered through a 300-400 mesh silica gel filter, eluted with ethyl acetate, the solvent was removed under reduced pressure, and separated by 300-400 mesh silica gel column chromatography to obtain a pale yellow solid compound Ig (0.0960 g, yield 62%).

[0050] NMR data for compound Ig: 1 H NMR (400 MHz, CDCl3) d 9.06–8.97 (m, 2H), 8.20 (d, J = 8.8 Hz, 1H), 7.81 (dd, J = 8.8, 1.6, 1H), 7.69 (dd, J= 8.4, 1.6 Hz,1H), 7.53-7.39 (m, 7H), 7.25-7.19 (m, 3H), 3.57-3.48 (m, 1H), 3.17-3.09 (m,1H), 2.47 (s, 3H), 1.42-1.33 (m, 1H), 1.26-1.16 (m, 1H), 0.66 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 144.1, 143.4, 137.1, 135.7, 135.4, 135.2, 134.8, 131.3, 130.3, 129.9, 129.7, 129.6, 129.4, 129.3, 129.2, 128.9, 128.7, 128.1, 128.05, 128.0, 127.7, 118.7, 112.0, 111.7, 53.1, 21.7, 21.6, 11.4. Example 8

[0051] Preparation of compound Ih:

[0052] Compound II-b (0.0982 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIa (0.1530 g, 0.75 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 (0.1250 g, 87% yield).

[0053] NMR data of compound Ih: 1 H NMR (400 MHz, CDCl3) d 8.80-8.71 (m, 2H), 8.05 (d, J= 8.4 Hz, 1H), 7.71-7.63 (m, 2H), 7.55 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H),7.49-7.42 (m, 4H), 7.36 (dd, J = 8.0, 1.2 Hz, 1H), 7.29-7.25 (m, 1H), 7.22-7.14 (m, 4H), 3.66-3.54 (m, 1H), 3.30-3.19 (m, 1H), 2.49 (s, 3H), 2.46 (s,3H), 1.50-1.39 (m, 1H), 1.34-1.24 (m, 1H), 0.66 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 143.1, 140.8, 138.1, 137.3, 134.3, 133.1, 132.6, 131.7, 131.4, 130.4, 129.7, 129.3, 129.0, 128.6, 128.2, 128.1, 127.3, 126.95, 126.92, 126.7, 126.5, 122.9, 122.5, 53.3, 21.7, 21.54, 21.5, 11.5. Example 9

[0054] Preparation of compound Ii:

[0055] Compound II-c (0.1169 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIa (0.1530 g, 0.75 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 (0.1190 g, 73% yield).

[0056] NMR data for compound Ii: 1 H NMR (400 MHz, CDCl3) d 8.82-8.72 (m, 2H), 8.18 (dd, J = 8.4, 1.2 Hz, 1H), 7.74-7.66 (m, 5H), 7.64-7.56 (m, 3H), 7.53 (t, J =7.6 Hz, 1H), 7.50-7.39 (m, 5H), 7.34 (dt, J = 8.0, 1.2 Hz, 1H), 7.14 (d, J =8.0 Hz, 2H), 3.70-3.59 (m, 1H), 3.35-3.24 (m, 1H), 2.36 (s, 3H), 1.54-1.44(m, 1H), 1.35-1.27 (m, 1H), 0.68 (t, J = 7.6 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 143.1, 140.8, 140.4, 138.0, 136.5, 132.9, 132.7, 132.2, 131.6, 131.5, 130.5, 130.2, 129.4, 129.0, 128.5, 127.9, 127.6, 127.5, 127.2, 127.1, 127.0, 126.96, 126.8, 126.6, 126.1, 122.9, 122.6, 53.5, 21.59, 21.56, 11.5. Example 10

[0057] Preparation of compound Ij:

[0058] Compound II-c (0.1015 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIa (0.1530 g, 0.75 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 (0.1150 g, 78% yield).

[0059] NMR data of compound Ij: 1 H NMR (400 MHz, CDCl3) d 8.83-8.69 (m, 2H), 7.84-7.78 (m, 2H), 7.76 (dd, J = 7.6, 1.6 Hz, 1H), 7.74-7.66 (m, 3H), 7.53-7.44(m, 4H), 7.40 (dd, J = 8.0, 1.6 Hz, 1H), 7.27-7.24 (m, 2H, CDCl3 residueinside), 7.18 (dd, J = 8.4, 1.2 Hz, 1H), 3.60-3.50 (m, 1H), 3.28-3.17 (m,1H), 2.45 (s, 3H), 1.43-1.34 (m, 1H), 1.27-1.22 (m, 1H), 0.66 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d143.8, 142.7, 139.1, 137.6, 133.1, 132.9, 132.2, 131.9, 131.7, 131.2, 130.9, 130.5, 129.6, 128.0, 127.9, 127.8, 127.6, 127.2, 127.1, 126.3, 123.1, 122.8, 119.0, 111.9, 53.6, 21.74, 21.72, 11.5. Example 11

[0060] Preparation of compound Ik:

[0061] Compound II-e (0.1147 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIa (0.1530 g, 0.75 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 (0.120 g, 75% yield).

[0062] NMR data for compound Ik: 1 H NMR (400 MHz, CDCl3) d 8.75 (dd, J = 8.4, 5.2Hz, 2H), 7.93 (dd, J = 8.4, 1.2 Hz, 1H), 7.74-7.66 (m, 2H), 7.61 (t, J = 1.6Hz, 1H), 7.59-7.48 (m, 4H), 7.47 (t, J = 2.0 Hz, 1H), 7.31 (dd, J = 8.4, 1.6Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.17 (t, J= 1.6 Hz, 1H), 3.66-3.53 (m,1H), 3.39-3.26 (m, 1H), 2.47 (s, 3H), 1.47-1.38 (m, 1H), 1.33-1.26 (m, 1H),0.69 (t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 143.6, 140.6, 138.1, 137.5, 135.2, 134.0, 133.2, 131.9, 131.7, 131.0, 130.7, 130.5, 129.6, 128.5, 128.0, 127.95, 127.9, 127.8, 127.5, 127.2, 127.1, 126.4, 123.0, 122.8, 53.5, 21.7, 21.66, 11.5. Example 12

[0063] Preparation of compound Il:

[0064] Compound II-f (0.0910 g, 0.3 mmol), palladium acetate (0.0034 g, 0.015 mmol), dppm (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) and iodobenzene IIIa (0.1530 g, 0.75 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 (0.0810 g, 59% yield).

[0065] NMR data for compound Il: 1 H NMR (400 MHz, CDCl3) d 8.75-8.69 (m, 2H), 7.73 (dd, J = 8.4, 1.2 Hz, 1H), 7.71-7.62 (m, 4H), 7.57-7.51 (m, 2H), 7.48 (dd,J = 8.4, 1.6 Hz, 1H), 7.43 (ddd, J = 8.4, 6.8, 1.2 Hz, 1H), 7.27 (d, J = 8.8Hz, 2H), 6.78 (dd, J = 3.6, 0.8 Hz, 1H), 6.56 (dd, J = 7.2, 1.6 Hz, 1H),3.57-3.49 (m, 1H), 3.44-3.35 (m, 1H), 2.47 (s, 3H), 1.44-1.31 (m, 2H), 0.69(t, J = 7.2 Hz, 3H); 13 C NMR (100 MHz, CDCl3) d 148.7, 143.3, 142.4, 137.9, 135.1, 132.6, 132.1, 131.1, 130.8, 130.4, 129.5, 128.2, 127.9, 127.71, 127.67, 127.2, 126.8, 126.5, 123.0, 122.5, 113.2, 111.0, 53.6, 21.8, 21.7, 11.4. The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a 9-amino phenanthrene derivative, characterized by, The process involves mixing compound II, compound III, a palladium catalyst, a bisphosphine ligand, an additive, a base, and an organic solvent, and then carrying out an amination reaction under an inert atmosphere to obtain the 9-aminophenanthrene derivative shown in Formula I. The synthetic route is shown below: Wherein, R1 represents phenyl, p-methylphenyl, p-phenylphenyl, p-cyanophenyl, 3,5-dichlorophenyl, and 2-furanyl; R2 represents hydrogen, phenyl, methoxy, fluorine, chlorine, methyl ester, or cyano. The palladium catalyst is palladium acetate, the bisphosphine ligand is bis(diphenylphosphine)methane, the additive is potassium pentovanate, and the base is cesium carbonate.

2. The method for preparing 9-aminophenanthrene derivatives according to claim 1, characterized in that, The organic solvent is 1,4-dioxane.

3. The method for preparing 9-aminophenanthrene derivatives according to claim 1, characterized in that, The molar concentration of compound II in the organic solvent is 0.2~0.4 mol / L.

4. The method for preparing 9-aminophenanthrene derivatives according to claim 1, characterized in that, The molar ratio of compounds II and III, palladium catalyst, bisphosphine ligand, additive, and base is 1:2.5:0.05:0.05:(0-0.5):

2.

5. The method for preparing 9-aminophenanthrene derivatives according to claim 1, characterized in that, The amination reaction is carried out at a temperature of 115-130 °C for 10-14 h.

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