8H-indolo [3, 2, 1-DE] phenanthridine-8-ketone compound synthesized from carbazole and o-bromobenzoic acid and synthesis method of 8H-indolo [3, 2, 1-DE] phenanthridine-8-ketone compound

Abstract

The invention discloses an 8H-indolo [3, 2, 1-DE] phenanthridine-8-ketone compound synthesized from carbazole and o-bromobenzoic acid and a synthesis method thereof.The carbazole is used as a raw material, a key nitrogen-containing six-membered ring palladium intermediate is generated under an efficient palladium / norbornene concerted catalysis system, the key nitrogen-containing six-membered ring palladium intermediate reacts with o-bromobenzoic acid, arylation is conducted firstly, a carbon-carbon bond is constructed, and then the compound is synthesized into the 8H-indolo [3, 2, 1-DE] phenanthridine-8-ketone compound. Then, norbornene is subjected to beta carbon elimination leaving, then in-situ coupling is carried out at the N site to construct a carbon-nitrogen bond, and finally, reduction elimination is carried out to obtain a target product. The method is simple to operate, the construction of two chemical bonds is realized by a one-pot method, the steps are economical and efficient, and the target compounds are rich in variety. Meanwhile, the method provides a simple and efficient new path for synthesizing nitrogen-containing tricyclic ring-fused molecules which are very challenging. In addition, the synthesis method has the advantages of simple and easily available raw materials, simple reaction operation, mild reaction conditions, low production cost and high atom utilization rate.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a synthesis method of 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds by using carbazole and o-bromobenzoic acid. Background Art

[0002] Nitrogen-containing tricyclic cyclopentadiene skeletons are widely present in natural products and drug molecules with physiological activity. However, due to the complexity of the structure and the large ring strain, their synthesis has always faced great challenges, and there is currently no efficient synthesis method for such skeletons. The palladium / norbornene synergistic catalytic strategy can sequentially introduce functional groups into the ortho-C−H bond and in-situ C−I bond of aryl iodides, and is an effective strategy for the rapid preparation of polysubstituted aromatics. [a) Catellani, M.; FrignaniF.; Rangoni, A. Angew. Chem. Int. Ed, 1997, 36, 119-122. [b) Della Ca', N.;Fontana, M.; Motti, E. et al. Acc. Chem. Res, 2016, 49, 1389. Since 2000, the palladium / norbornene catalytic strategy has been applied by Lautens, Catellani and other research groups to efficiently construct a variety of aromatic cyclopentadiene skeletons. [c) Lautens, M.; Piguel, S. Angew. Chem. Int. Ed, 2000, 39, 1045. [d) Wang, J.; Dong, G. Chem. Rev, 2019, 119, 7478. In recent years, chemists have used palladium / norbornene synergistic catalysis and coupling reagents such as amides, anilines, imines, aziridines, and hydroxylamines to achieve efficient synthesis of a series of nitrogen-containing heterocyclic compounds, such as polysubstituted carbazoles, indoles, phenanthridines, and isoquinolinones. [e)

[76] FerraccioliR.; Carenzi D.; Rombola O. et al. Org. Lett, 2004, 6, 4759. [f) Candito DA; Lautens M. Angew. Chem. Int. Ed, 2009, 48, 6713. [g) Rago A.; Dong G.Org. Lett. 2021, 23, 3755. [h) Liu F.; Dong Z.; Wang J. et al.Angew. Chem.Int. Ed, 2019, 58, 2144. However, the products synthesized by the above methods are mostly simple nitrogen-containing heterocyclic molecules, and the use of this strategy to construct complex nitrogen-containing tricyclic skeletons has not yet been reported. Summary of the invention

[0003] In view of the problems existing in the prior art, the present invention aims to provide a synthesis of 8H-indole [3,2,1-DE] phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid and a synthesis method thereof, wherein carbazole and o-bromobenzoic acid are used as reaction raw materials, a palladium catalyst and norbornene are used as co-catalysts, and the 8H-indole [3,2,1-DE] phenanthridin-8-one compounds are obtained after heating reaction in an organic solvent and separation and purification. This strategy is used to achieve the efficient construction of complex nitrogen-containing tricyclic ring compounds, which effectively fills the gap in the industry and opens up a new synthesis path.

[0004] The present invention is achieved through the following technical solutions: A method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid comprises the following steps: Carbazole, o-bromobenzoic acid, potassium pivalate, sodium carbonate and other compounds are added to an organic solvent in sequence, palladium catalyst and norbornene are used as catalysts, and after heating and stirring, the obtained 8H-indole [3,2,1-DE] phenanthridin-8-one compound is separated and purified.

[0005] Preferably, the reaction formula for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid is: ; Wherein, R is selected from hydrogen, methyl, tert-butyl, trimethylsilyl, alkoxy, phenyl, furyl or thienyl, and R' is selected from methyl, alkoxy, halogen or trifluoromethyl.

[0006] Preferably, the palladium catalyst is palladium acetate.

[0007] Preferably, the molar ratio of the carbazole compound, the o-bromobenzoic acid compound, palladium acetate, potassium pivalate, norbornene, and sodium carbonate is 10:20:1:20:20:10.

[0008] Preferably, the concentration of the carbazole compound in the organic solvent is 0.1-0.5 mol / L.

[0009] Preferably, the organic solvent is N,N-dimethylformamide.

[0010] Preferably, the carbazole compound includes one of 9H-carbazole, 3,6-dimethyl-9H-carbazole, 3,6-di-tert-butyl-9H-carbazole, 3,6-ditrimethylsilyl-9H-carbazole, 3,6-dimethoxy-9H-carbazole, 3,6-diphenyl-9H-carbazole, 3,6-di(2-furyl)-9H-carbazole and 3,6-di(3-thienyl)-9H-carbazole.

[0011] Preferably, the o-bromobenzoic acid compound includes one of 2-bromobenzoic acid, 2-bromo-5-methoxybenzoic acid, 2-bromo-5-fluorobenzoic acid, 2-bromo-5-trifluoromethylbenzoic acid, 2-bromo-4-methylbenzoic acid, 2-bromo-4-chlorobenzoic acid and 2-bromo-3-methylbenzoic acid.

[0012] Preferably, the heating temperature is 50°C-95°C, and the stirring time is 0.5 h-24 h under oil bath conditions.

[0013] Preferably, the specific steps of separation and purification are: The reaction product was cooled to room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate aqueous solution, and finally concentrated in vacuo and purified by silica gel column chromatography to obtain 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds.

[0014] A 8H-indolo[3,2,1-DE]phenanthridin-8-one compound is synthesized from carbazole and o-bromobenzoic acid. The structural formula of the 8H-indolo[3,2,1-DE]phenanthridin-8-one compound is:

[0015] Wherein, R is selected from hydrogen, methyl, tert-butyl, trimethylsilyl, alkoxy, phenyl, furyl or thienyl, and R' is selected from methyl, alkoxy, halogen or trifluoromethyl.

[0016] Compared with the prior art, the present invention has the following beneficial technical effects: The invention discloses a synthesis method of 8H-indolo[3,2,1-DE]phenanthridine-8-one by catalyzing carbazole and o-bromobenzoic acid with palladium / norbornene, wherein carbazole, o-bromobenzoic acid, potassium pivalate, sodium carbonate and other compounds are sequentially added to an organic solvent, and a palladium catalyst and norbornene are used as catalysts, and after heating and stirring, the obtained 8H-indolo[3,2,1-DE]phenanthridine-8-one compound is separated and purified. The invention uses carbazole as a raw material, generates a key nitrogen-containing six-membered ring palladium intermediate under an efficient palladium / norbornene synergistic catalytic system, and firstly arylates it with o-bromobenzoic acid to construct a carbon-carbon bond, then norbornene undergoes β-carbon elimination and leaves, and then in-situ coupling occurs at the N site to construct a carbon-nitrogen bond, and finally reduction and elimination are performed to obtain the target product. The method is simple to operate, and the one-pot method realizes the construction of two chemical bonds, the steps are economical and efficient, and the target compound types are rich. At the same time, the method provides a simple and efficient new path for synthesizing highly challenging nitrogen-containing tricyclic ring molecules. In addition, the raw materials of this synthesis method are simple and easy to obtain, the reaction operation is simple, the reaction conditions are mild, the production cost is low, and the atomic utilization rate is high.

[0017] Furthermore, the palladium acetate used in the present invention as a palladium precursor is the best catalyst obtained through reaction condition screening, and the coordination of its acetate ion can assist the palladium center in activating the carbon-hydrogen bond, thereby effectively improving the catalytic efficiency.

[0018] Furthermore, the present invention uses potassium pivalate as an additive, and the pivalate ion can assist in activating the carbon-hydrogen bond of the substrate.

[0019] Furthermore, the present invention uses sodium carbonate as an alkaline neutralizing agent, which plays a neutralizing role in the reaction process, and carbonate ions can assist palladium in activating the carbon-hydrogen bonds of the substrate. BRIEF DESCRIPTION OF THE DRAWINGS

[0020] Figure 1 The product prepared in Example 1 1 H NMR spectrum; Figure 2 The product prepared in Example 1 13 C NMR spectrum; Figure 3 The product prepared in Example 2 1 H NMR spectra; Figure 4 The product prepared in Example 2 13 C NMR spectrum; Figure 5 The product prepared in Example 3 1 H NMR spectra; Figure 6 The product prepared in Example 3 13 C NMR spectrum; Figure 7 The product prepared in Example 4 1 H NMR spectra; Figure 8 The product prepared in Example 4 13 C NMR spectrum; Fig. 9 The product prepared in Example 5 1 H NMR spectra; Fig.10 The product prepared in Example 5 13 C NMR spectrum; Fig.11 The product prepared in Example 6 1 H NMR spectra; Fig.12 The product prepared in Example 6 13 C NMR spectrum; Fig.13 The product prepared in Example 71 H NMR spectra; Fig.14 The product prepared in Example 7 13 C NMR spectrum; Fig.15 The product prepared in Example 8 1 H NMR spectra; Fig.16 The product prepared in Example 8 13 C NMR spectrum; Fig.17 The product prepared in Example 9 1 H NMR spectra; Fig.18 The product prepared in Example 9 13 C NMR spectrum; Fig.19 The product prepared in Example 10 1 H NMR spectra; Fig. 20 The product prepared in Example 10 13 C NMR spectrum; Fig.21 The product prepared in Example 11 1 H NMR spectra; Fig. 22 The product prepared in Example 11 13 C NMR spectrum; Fig.23 The product prepared in Example 12 1 H NMR spectra; Fig.24 The product prepared in Example 12 13 C NMR spectrum; Fig.25 The product prepared in Example 13 1 H NMR spectra; Fig.26 The product prepared in Example 13 13 C NMR spectrum; Fig. 27 The product prepared in Example 14 1 H NMR spectra; Fig.28 The product prepared in Example 14 13 C NMR spectrum; DETAILED DESCRIPTION The present invention is further described in detail below in conjunction with specific embodiments, which are intended to explain the present invention rather than to limit it.

[0021] The preparation of 8H-indolo[3,2,1-DE]phenanthridine-8-one compounds through six-membered cyclopalladium intermediates with the help of palladium / norbornene synergistic catalysis is a new research direction for this type of molecule, specifically: Carbazole, o-bromobenzoic acid, potassium pivalate, sodium carbonate and other compounds are added to an organic solvent in sequence, palladium catalyst and norbornene are used as catalysts, and after heating and stirring, the obtained 8H-indole [3,2,1-DE] phenanthridin-8-one compound is separated and purified.

[0022]

[0023] Wherein, R is selected from hydrogen, methyl, tert-butyl, trimethylsilyl, alkoxy, phenyl, furyl or thienyl, and R' is selected from methyl, alkoxy, halogen or trifluoromethyl. The organic solvent is N,N-dimethylformamide.

[0024] Example 1 Preparation of 8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 42.1 mg of a light yellow solid with a yield of 78%. The product structure is as follows:

[0025] like Figure 1 and Figure 2 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.50(d, J = 7.6 Hz, 1H), 8.35 (d, J = 7.3 Hz, 1H), 7.96 (d, J = 7.4 Hz, 1H), 7.77 (s,2H), 7.67 (d, J = 6.8 Hz, 2H), 7.50 (dt,J = 14.8, 7.1 Hz, 2H), 7.37 (t, J = 6.7Hz, 1H), 7.27 (d, J = 7.2 Hz, 1H). 13 C NMR (100 MHz, CDCl 3 ): δ 160.8, 138.1,133.8, 133.4, 133.1, 129.0, 128.5, 128.3, 126.6, 126.4, 125.7, 124.7, 124.5,122.4, 121.1, 120.8, 120.3, 117.5, 116.8. Example 2 Preparation of 2,12-dimethyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-dimethyl-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 46.8 mg of a light yellow solid with a yield of 78%. The product structure is as follows:

[0026] like Figure 3 and Figure 4 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.39(d, J = 8.0 Hz, 1H), 8.32 (d, J = 8.3 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.75 (t, J =7.5 Hz, 1H), 7.62 (s, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.52 (s, 1H), 7.49 (s,1H), 7.26 (t, J= 3.9 Hz, 1H), 2.48 (s, 3H), 2.45 (s, 3H). 13 C NMR (100 MHz, CDCl 3 ): δ 161.2, 136.4, 136.2, 135.3, 134.1, 133.7, 131.5, 129.4, 129.1,128.6, 127.2, 126.2, 125.0, 122.6, 122.1, 121.2, 120.9, 117.4, 116.8, 22.1,21.7. Example 3 Preparation of 2,12-di-tert-butyl-8H-indolo[3,2,1-DE]phenanthridin-8-one 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-di-tert-butyl-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid were added to a 15 mL Shrek tube in sequence, and then 2.0 mL of dry N,N-dimethylformamide was added thereto, and the mixture was stirred in a 70 °C oil bath for 12 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 53.3 mg of a light yellow solid with a yield of 70%. The product structure is as follows:

[0027] like Figure 5 and Figure 6 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.70 (d, J = 8.6Hz, 1H), 8.65 (d, J = 7.9 Hz, 1H), 8.33 (d, J = 8.0 Hz, 1H), 8.21 (s, 1H), 8.16(s, 1H), 8.11 (s, 1H), 7.78 (t, J = 7.5 Hz, 1H), 7.66 (d, J = 8.6 Hz, 1H), 7.60(t, J = 7.6 Hz, 1H), 1.57 (s, 9H), 1.50 (s, 9H). 13 C NMR (100 MHz, CDCl3 ): δ159.9, 148.3, 147.7, 136.9, 134.3, 133.0, 132.8, 129.5, 128.2, 128.1, 126.7,125.7, 124.7, 122.4, 118.4, 117.3, 117.3, 116.9, 116.5, 35.7, 35.3, 32.3,32.0. Example 4 Preparation of 2,12-Bis(trimethylsilyl)-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-ditrimethylsilyl-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 57.4 mg of a light yellow solid with a yield of 71%. The product structure is as follows:

[0028] like Figure 7 and Figure 8 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.79 (d, J = 8.0Hz, 1H), 8.64 (d, J = 7.9 Hz, 1H), 8.35 (d, J = 7.9 Hz, 1H), 8.29 (s, 1H), 8.26 –8.22 (m, 2H), 7.85 – 7.72 (m, 2H), 7.62 (t, J = 7.5 Hz, 1H), 0.48 (s, 9H), 0.43(s, 9H). 13 C NMR (100 MHz, CDCl 3 ): 13 C NMR (101 MHz, CDCl 3) δ 160.7, 139.8,137.6, 136.5, 135.6, 134.6, 133.8, 133.6, 130.1, 128.9, 128.5, 126.6, 126.4,126.3, 125.7, 124.8, 123.0, 117.4, 117.3, 0.0. Example 5 Preparation of 2,12-dimethoxy-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-dimethoxy-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 39.6 mg of a light yellow solid with a yield of 60%. The product structure is as follows:

[0029] like Fig. 9 and Fig.10 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.59 (d, J =7.5, 2.8 Hz, 2H), 8.10 (d, J = 7.9 Hz, 1H), 7.74 (t, J = 7.5 Hz, 1H), 7.60 (t, J =7.5 Hz, 1H), 7.51 (s, 1H), 7.39 (s, 1H), 7.34 (s, 1H), 7.10 (d, J = 8.9 Hz,1H), 3.95 (s, 3H), 3.93 (s, 3H). 13 C NMR (100 MHz, CDCl 3): δ 159.2, 157.6,157.6, 133.6, 133.5, 132.7, 129.8, 129.4, 128.5, 128.4, 127.7, 125.2, 122.6,118.2, 117.7, 115.5, 106.8, 106.8, 104.9, 56.5, 56.1. Example 6 Preparation of 2,12-diphenyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-diphenyl-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 56.3 mg of a light yellow solid with a yield of 67%. The product structure is as follows:

[0030] like Fig.11 and Fig.12 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.37(d, J = 8.4 Hz, 1H), 8.28 (d, J = 7.9 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.92 (s,1H), 7.87 (s, 2H), 7.62 (t, J = 7.3 Hz, 1H), 7.56 (t, J = 8.3 Hz, 5H), 7.45 (dq, J = 19.5, 6.1, 5.6 Hz, 7H). 13 C NMR (100 MHz, CDCl 3): δ 160.4, 140.8, 140.6,138.8, 138.5, 137.5, 133.6, 133.4, 132.9, 129.2, 129.2, 129.1, 128.7, 127.8,127.7, 127.6, 127.5, 127.4, 127.1, 126.5, 124.9, 122.4, 120.0, 119.4, 119.1,117.6, 117.0. Example 7 Preparation of 2,12-di(2-furyl)-8H-indolo[3,2,1-DE]phenanthridin-8-one 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-di(2-furyl)-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid were added to a 15 mL Shrek tube in sequence, and then 2.0 mL of dry N,N-dimethylformamide was added thereto, and the mixture was stirred in a 70 °C oil bath for 12 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 48.0 mg of a light yellow solid with a yield of 60%. The product structure is as follows:

[0031] like Fig.13 and Fig.14 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.34(d, J = 8.0 Hz, 2H), 8.03 (d, J = 7.9 Hz, 1H), 7.82 (s, 1H), 7.76 (s, 1H), 7.71(d, J = 7.8 Hz, 4H), 7.55 (d, J = 7.0 Hz, 3H), 7.45 (d, J = 8.4 Hz, 1H), 6.78 –6.68 (m, 2H). 13 C NMR (100 MHz, CDCl 3): δ 160.5, 144.2, 144.1, 144.1, 144.1,139.0, 138.9, 137.3, 133.7, 133.5, 132.8, 130.4, 129.9, 129.4, 128.8, 127.0,126.8, 126.5, 126.4, 126.3, 126.2, 125.0, 122.5, 118.6, 118.0, 117.8, 117.3,109.2, 109.1. Example 8 Preparation of 2,12-di(3-thienyl)-8H-indolo[3,2,1-DE]phenanthridin-8-one 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 3,6-di(3-thienyl)-9H-carbazole, and 0.4 mmol of 2-bromobenzoic acid were added to a 15 mL Shrek tube in sequence, and then 2.0 mL of dry N,N-dimethylformamide was added thereto, and the mixture was stirred in a 70 °C oil bath for 12 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 48.0 mg of a light yellow solid with a yield of 60%. The product structure is as follows:

[0032] like Fig.15 and Fig.16 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.35(d, J = 7.3 Hz, 2H), 8.04 (d, J = 7.6 Hz, 1H), 7.97 (s, 1H), 7.87 (s, 2H), 7.72(t, J = 7.4 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.55 (t, J = 7.4 Hz, 1H), 7.36 (dd, J = 12.9, 5.1 Hz, 3H), 7.30 (s, 1H), 7.15 (dd, J = 11.1, 3.8 Hz, 2H). 13C NMR (100MHz, CDCl 3 ): δ 159.5, 144.1, 144.0, 137.6, 133.7, 133.6, 133.2, 132.6, 132.1,129.5, 129.0, 128.5, 128.4, 128.3, 128.3, 127.1, 126.8, 126.6, 125.4, 125.4,125.1, 123.9, 123.8, 122.7, 118.9, 118.4, 118.0, 117.9, 117.4. Example 9 Preparation of 6-methoxy-8H-indolo[3,2,1-DE]phenanthridin-8-one 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-5-methoxybenzoic acid were added to a 15 mL Shrek tube in sequence, and then 2.0 mL of dry N,N-dimethylformamide was added thereto, and the mixture was stirred in a 70 °C oil bath for 12 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 43.2 mg of a light yellow solid with a yield of 72%. The product structure is as follows:

[0033] like Fig.17 and Fig.18 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.60 (d, J =8.0 Hz, 1H), 7.78 (t, J = 11.1 Hz, 3H), 7.62 (t, J = 8.8 Hz, 2H), 7.47 (t, J = 7.6Hz, 1H), 7.34 (t, J = 7.4 Hz, 1H), 7.20 (t, J = 7.3 Hz, 1H), 7.07 (d, J = 8.4 Hz,1H), 3.87 (d, J = 2.2 Hz, 3H). 13 C NMR (100 MHz, CDCl3 ): δ 159.7, 159.4, 138.5,133.1, 128.9, 127.8, 126.9, 126.6, 124.8, 124.0, 123.8, 123.7, 121.7, 120.6,119.7, 119.4, 117.2, 116.9, 110.3, 55.7. Example 10 Preparation of 6-Fluoro-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-5-fluorobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 43.2 mg of a light yellow solid with a yield of 72%. The product structure is as follows:

[0034] like Fig.19 and Fig. 20 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.42(d, J = 8.0 Hz, 1H), 7.94 (dt, J = 10.1, 5.9 Hz, 2H), 7.78 (d, J = 7.6 Hz, 1H),7.70 (t, J = 7.9 Hz, 2H), 7.47 (t, J = 7.6 Hz, 1H), 7.43 – 7.28 (m, 3H). 13 C NMR (100 MHz, CDCl 3): δ 161.8 (d = 248.8 Hz), 159.8, 137.9, 132.6, 130.2 (d = 2.4Hz), 128.5, 128.3 (d = 7.6 Hz), 126.8, 126.1, 125.2, 124.8 (d = 8.0 Hz),124.7, 121.9, 121.6, 121.1, 121.0, 120.2, 117.6, 116.3. Embodiment 11 Preparation of 6-trifluoromethyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-5-trifluoromethylbenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 42.9 mg of a light yellow solid with a yield of 65%. The product structure is as follows:

[0035] like Fig.21 and Fig. 22 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.64(s, 1H), 8.49 (d, J = 8.1 Hz, 1H), 8.14 (d, J = 8.3 Hz, 1H), 7.87 (dt, J = 21.0,7.4 Hz, 4H), 7.52 (t, J = 7.7 Hz, 1H), 7.43 (q, J = 7.4 Hz, 2H). 13 C NMR (100 MHz, CDCl 3): δ 159.8, 138.0, 136.6, 133.7, 130.7 (q = 33.6 Hz), 129.7, 129.7,128.8, 126.8, 126.7(q = 4.1 Hz), 126.5, 126.2, 125.3, 124.9, 123.4, 122.5,121.1, 121.0, 117.6, 115.9. Example 12 Preparation of 5-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-4-methylbenzoic acid were added to a 15 mL Shrek tube in sequence, and then 2.0 mL of dry N,N-dimethylformamide was added thereto, and the mixture was stirred in a 70 °C oil bath for 12 hours. After the reaction was completed, it was cooled to room temperature, diluted with ethyl acetate, and then washed once with a saturated sodium bicarbonate aqueous solution. Finally, the mixture was concentrated in vacuo and purified by silica gel chromatography to obtain 40.3 mg of a light yellow solid with a yield of 72%. The product structure is as follows:

[0036] like Fig.23 and Fig.24 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.74 (d, J =8.1 Hz, 1H), 8.41 (d, J = 8.1 Hz, 1H), 7.93 (t, J = 8.5 Hz, 2H), 7.87 (d, J = 6.8Hz, 2H), 7.55 (t, J = 7.7 Hz, 1H), 7.41 (q, J = 8.0 Hz, 2H), 7.33 (d, J = 8.1 Hz,1H), 2.49 (s, 3H). 13 C NMR (100 MHz, CDCl 3): δ 160.2, 143.8, 138.8, 134.5,133.9, 129.8, 129.4, 128.2, 126.6, 125.6, 125.0, 124.5, 124.1, 122.8, 121.0,120.9, 120.3, 117.5, 117.3, 22.4. Example 13 Preparation of 5-chloro-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-4-chlorobenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 37.8 mg of a light yellow solid with a yield of 63%. The product structure is as follows:

[0037] like Fig.25 and Fig.26 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 + CF 3 COOD): δ 8.36(d, J = 6.6 Hz, 1H), 8.18 (d, J = 8.9 Hz, 1H), 7.76 (s, 1H), 7.71 (d, J = 8.9 Hz,1H), 7.62 (d, J = 23.2 Hz, 2H), 7.48 – 7.40 (m, 1H), 7.34 (t, J = 7.5 Hz, 2H),7.24 (s, 1H). 13 C NMR (100 MHz, CDCl 3): δ 160.1, 140.7, 140.7, 138.1, 135.2,133.5, 130.7, 129.0, 128.6, 126.6, 126.0, 125.0, 124.8, 122.4, 121.8, 120.9,120.4, 117.6, 115.9. Embodiment 14 Preparation of 4-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-3-methylbenzoic acid to a 15 mL Shrek tube, and then add 2.0 mL of dry N,N-dimethylformamide, and stir in a 70 °C oil bath for 12 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 29.1 mg of a light yellow solid with a yield of 52%. The product structure is as follows:

[0038] like Fig. 27 and Fig.28 As shown, the product NMR characterization: 1 H NMR (400 MHz, CDCl 3 ): δ 8.70 (d, J =8.1 Hz, 1H), 8.48 (d, J = 8.8 Hz, 1H), 8.09 (d, J = 8.1 Hz, 1H), 7.87 (d, J = 7.6Hz, 1H), 7.75 (d, J = 7.5 Hz, 1H), 7.53 (t, J = 7.7 Hz, 1H), 7.45 – 7.35 (m, 3H), 7.29 (t, J = 7.8 Hz, 1H), 2.75 (s, 3H). 13 C NMR (100 MHz, CDCl 3): δ 159.9, 137.9,136.9, 135.9, 134.1, 132.4, 128.9, 127.8, 127.7, 127.4, 126.4, 125.0, 124.7,124.3, 123.4, 120.2, 120.1, 118.6, 117.3, 25.3. Embodiment 15 Preparation of 4-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-3-methylbenzoic acid to a 15 mL Shrek tube, and then add 10.0 mL of dry N,N-dimethylformamide, and stir in a 95°C oil bath for 0.5 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 4-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one; Example 16 Preparation of 4-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one Add 0.1 mmol of palladium acetate, 0.4 mmmol of potassium pivalate, 0.2 mmol of sodium carbonate, 0.2 mmol of 9H-carbazole, and 0.4 mmol of 2-bromo-3-methylbenzoic acid to a 15 mL Shrek tube, and then add 6.0 mL of dry N,N-dimethylformamide, and stir in a 50°C oil bath for 24 hours. After the reaction is completed, cool it to room temperature, dilute it with ethyl acetate, and then wash it once with a saturated sodium bicarbonate aqueous solution. Finally, concentrate the mixture in a vacuum and purify it with a silica gel column to obtain 4-methyl-8H-indolo[3,2,1-DE]phenanthridin-8-one.

[0039] The above description is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any ordinary technician in the industry can smoothly implement the present invention as shown in the drawings and described above. However, any equivalent changes, modifications and evolutions made by technicians familiar with the profession without departing from the scope of the technical solution of the present invention using the technical content disclosed above are all equivalent embodiments of the present invention. At the same time, any equivalent changes, modifications and evolutions made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the technical solution of the present invention.

Claims

1. A method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid, characterized in that: The following steps are involved: A carbazole compound, a palladium catalyst, an o-bromobenzoic acid compound, potassium pivalate, sodium carbonate and norbornene are sequentially added to an organic solvent, and after heating and stirring, the obtained 8H-indolo[3,2,1-DE]phenanthridin-8-one compound is separated and purified.

2. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The reaction formula for synthesizing 8H-indolo[3,2,1-DE]phenanthridine-8-one compounds by using carbazole and o-bromobenzoic acid is: ； Wherein, R is selected from hydrogen, methyl, tert-butyl, trimethylsilyl, alkoxy, phenyl, furyl or thienyl, and R' is selected from methyl, alkoxy, halogen or trifluoromethyl.

3. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The palladium catalyst is palladium acetate.

4. A method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The molar ratio of the carbazole compound, the o-bromobenzoic acid compound, the palladium catalyst, potassium pivalate, norbornene and sodium carbonate is 10:20:1:20:20:10; the concentration of the carbazole compound in the organic solvent is 0.1-0.5 mol / L.

5. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The o-bromobenzoic acid compound includes one of 2-bromobenzoic acid, 2-bromo-5-methoxybenzoic acid, 2-bromo-5-fluorobenzoic acid, 2-bromo-5-trifluoromethylbenzoic acid, 2-bromo-4-methylbenzoic acid, 2-bromo-4-chlorobenzoic acid and 2-bromo-3-methylbenzoic acid.

6. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The carbazole compound includes one of 9H-carbazole, 3,6-dimethyl-9H-carbazole, 3,6-di-tert-butyl-9H-carbazole, 3,6-ditrimethylsilyl-9H-carbazole, 3,6-dimethoxy-9H-carbazole, 3,6-diphenyl-9H-carbazole, 3,6-di(2-furyl)-9H-carbazole and 3,6-di(3-thienyl)-9H-carbazole.

7. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The organic solvent is N,N-dimethylformamide.

8. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The specific process of the heating and stirring is that the heating temperature is 50°C-95°C, and the stirring time is 0.5 h-24 h under oil bath conditions.

9. The method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid according to claim 1, characterized in that: The specific steps of separation and purification are: The reaction product was cooled to room temperature, diluted with ethyl acetate, washed with saturated sodium bicarbonate aqueous solution, and finally concentrated in vacuo and purified by silica gel column chromatography to obtain 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds.

10. A method for synthesizing 8H-indolo[3,2,1-DE]phenanthridin-8-one compounds from carbazole and o-bromobenzoic acid, characterized in that: The 8H-indolo[3,2,1-DE]phenanthridin-8-one compound is prepared based on the synthesis method according to any one of claims 1 to 9, and the structural formula is: Wherein, R is selected from hydrogen, methyl, tert-butyl, trimethylsilyl, alkoxy, phenyl, furyl or thienyl, and R' is selected from methyl, alkoxy, halogen or trifluoromethyl.

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