Preparation method of amidated pyrido [4, 3, 2-gh] phenanthridine compound

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of an amidated pyrido [4, 3, 2-gh] phenanthridine compound. The preparation method comprises the following steps: mixing an N-(2-cyano-1, 1 '-biphenyl) acrylamide compound, N-amido pyridinium salt, a photocatalyst, alkali and a solvent, and carrying out a photocatalytic reaction at room temperature by using visible light as an energy source to obtain the amidated pyrido [4, 3, 2-gh] phenanthridine compound. According to the invention, a pyridine ring and a phenanthridine ring are fused as a parent, and one-step synthesis of the amide-substituted pyrido [4, 3, 2-gh] phenanthridine compound is realized through free radical addition / CN insertion / cyclization cascade reaction. The preparation process is simple, the reaction condition is mild, the application range is wide, and various phenanthridine derivatives can be prepared at medium to good yield.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, in particular to a method for amide-substituted pyrido[4,3,2-gh]phenanthridine compounds. Background Art

[0002] Amidated pyrido[4,3,2-gh]phenanthridine compounds are a type of phenanthridine derivatives, which introduce an amide group into the phenanthridine parent skeleton. They have a phenanthridine ring, a pyridine ring and an amide group, and have broad application value in the fields of biomedicine and materials science.

[0003] However, the existing method for preparing amidated pyrido[4,3,2-gh]phenanthridine compounds requires multi-step synthesis, and has problems such as complicated preparation process, high preparation cost and low preparation efficiency. Summary of the invention

[0004] In view of the above problems, the present invention is proposed to provide a method for preparing an amidated pyrido[4,3,2-gh]phenanthridine compound that overcomes the above problems or at least partially solves the above problems, so as to solve the problems of complicated preparation process, high preparation cost and low preparation efficiency in the existing preparation method.

[0005] The present invention provides a method for preparing an amidated pyrido[4,3,2-gh]phenanthridine compound, comprising:

[0006] S1, mixing an N-(2-cyano-1,1'-biphenyl)acrylamide compound represented by formula II, an N-amidopyridinium salt represented by formula III, a photocatalyst, a base and a solvent, and performing a photocatalytic reaction at room temperature using visible light as an energy source to obtain an amidated pyrido[4,3,2-gh]phenanthridine compound represented by formula I;

[0007] Wherein, Formula III is

[0008] Formula II is

[0009] Formula I is

[0010] R 1 is any one of hydrogen, alkyl, phenyl, C1-C4 alkyl, phenoxy, methylthio, halogen, trifluoromethyl, and methanesulfonyl; R 2 is any one of methyl, benzyl and n-butyl; R 3 It is any one of phenyl, (4- or 3-) halogen-substituted phenyl, (4- or 2-) substituted phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, C1-C6 alkyl, and cycloalkyl; and the photocatalyst is a tris(2-phenylpyridine)iridium compound.

[0011] Optionally, the photocatalytic reaction is carried out under an inert atmosphere.

[0012] Optionally, the molar ratio of the N-(2-cyano-1,1'-biphenyl)acrylamide compound to the N-amidopyridinium salt is 1:1 to 4:1.

[0013] Optionally, the base is any one of anhydrous sodium carbonate, lithium acetate, sodium carbonate, 2,6-di-tert-butyl-4-methylpyridine, 2,6-lutidine, and 2,4,6-tri-tert-butylpyridine.

[0014] Optionally, the molar ratio of the N-(2-cyano-1,1'-biphenylyl)acrylamide compound to the base is 1:1 to 1:3.

[0015] Optionally, the solvent is any one of dimethyl sulfoxide, acetone, 1,4-dioxane, 1,2-dichloroethane, and dichloromethane, or a combination of two or more thereof.

[0016] Optionally, the reaction time of the photocatalytic reaction is 18 to 48 hours; and / or

[0017] The visible light is blue LED light with a power of 5 to 40W.

[0018] Optionally, after S1, the preparation method further comprises:

[0019] S2, separation and purification: the separation and purification includes solvent concentration and column chromatography purification;

[0020] The eluent used for the column chromatography purification is a mixture of ethyl acetate and petroleum ether.

[0021] Optionally, the amount of the photocatalyst is 0.01 to 0.05 times the amount of the N-(2-cyano-1,1'-biphenyl)acrylamide compound.

[0022] In the preparation method of the amidated pyrido [4,3,2-gh] phenanthridine compound of the present invention, the preparation method uses N-(2-cyano-1,1'-biphenyl) acrylamide compounds and N-amido pyridinium salt as raw materials, uses green and sustainable visible light as an energy source, uses tris (2-phenylpyridine) iridium as a photocatalyst, and realizes the one-step synthesis of amide-substituted pyrido [4,3,2-gh] phenanthridine compounds through free radical addition / CN insertion / cyclization cascade reaction, and the preparation process is simple. Compared with the prior art, the preparation steps are reduced, thereby improving the preparation efficiency and reducing the preparation cost.

[0023] Furthermore, the preparation method is carried out at room temperature, the reaction conditions are mild, the operability is strong, and the reaction efficiency is high.

[0024] Furthermore, the above preparation method has a wide range of applications and can prepare a variety of phenanthridine derivatives with moderate to good yields.

[0025] Therefore, based on the following detailed description of specific embodiments of the present invention, those skilled in the art will more clearly understand the above and other objects, advantages and features of the present invention. DETAILED DESCRIPTION

[0026] The invention provides a method for preparing an amidated pyrido[4,3,2-gh]phenanthridine compound, which can be used to prepare a variety of amidated pyrido[4,3,2-gh]phenanthridine compounds.

[0027] A method for preparing an amidated pyrido[4,3,2-gh]phenanthridine compound comprises the following steps: S1, mixing an N-(2-cyano-1,1'-biphenyl)acrylamide compound shown in formula II, an N-amidopyridinium salt shown in formula III, a photocatalyst, a base and a solvent, using visible light as an energy source, and performing a photocatalytic reaction at room temperature to obtain an amidated pyrido[4,3,2-gh]phenanthridine compound shown in formula I.

[0028] The photocatalyst is a tris(2-phenylpyridine)iridium compound as shown in Formula IV.

[0029] Formula IV is Formula III is Formula II is Formula I is

[0030] R 1 It is any one of hydrogen, alkyl, phenyl, C1-C4 alkyl, phenoxy, methylthio, halogen, trifluoromethyl, and methanesulfonyl.

[0031] R 2 It is any one of methyl, benzyl and n-butyl.

[0032] R 3 It is any one of phenyl, (4- or 3-) halogen-substituted phenyl, (4- or 2-) substituted phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, C1-C6 alkyl, and cycloalkyl.

[0033] Specifically, the reaction formula of the photocatalytic reaction is as follows:

[0034]

[0035] The preparation method of the amidated pyrido [4,3,2-gh] phenanthridine compounds provided in the present embodiment, using N- (2-cyano -1,1 '- biphenyl) acrylamide compounds, N- amide pyridine salt as raw materials, using green sustainable visible light as an energy source, using tri (2-phenylpyridine) iridium as a photocatalyst, by free radical addition / CN insertion / cyclization cascade reaction, to achieve amide-substituted pyrido [4,3,2-gh] phenanthridine compounds One-step synthesis. That is to say, while achieving amidation by a one-step synthesis method, a pyrido [4,3,2-gh] phenanthridine parent nucleus is also constructed. Specifically, the amidated pyrido [4,3,2-gh] phenanthridine compounds prepared by the above-mentioned one-step synthesis method, with pyridine ring and phenanthridine ring fused as a parent, and an amide group is introduced into the phenanthridine parent skeleton. Compared with the prior art, the preparation steps are simplified, thereby improving the preparation efficiency and reducing the preparation cost.

[0036] Furthermore, the preparation method is carried out at room temperature, the reaction conditions are mild, the operability is strong, and the reaction efficiency is high.

[0037] Furthermore, the above preparation method has a wide range of reaction applications, has good functional group tolerance, and can prepare a variety of phenanthridine derivatives in moderate to good yields.

[0038] In summary, this embodiment provides an amidation method for preparing an amidated phenanthridine derivative, wherein the amidated phenanthridine derivative has a phenanthridine ring, a pyridine ring and an amide group. The above method has the advantages of mild reaction conditions, greenness and high efficiency.

[0039] In some embodiments of the present invention, after S1, the preparation method further comprises: S2, separation and purification. The separation and purification is a conventional separation and purification means in the prior art, such as chromatographic separation.

[0040] The separation and purification includes solvent concentration and column chromatography purification. Further, the separation and purification includes filtration, solvent concentration, and column chromatography purification, and the eluent used for column chromatography purification is a mixture of ethyl acetate and petroleum ether. The ratio of ethyl acetate and petroleum ether can be adjusted according to the polarity of the target compound. This post-treatment method is simple, green and environmentally friendly.

[0041] In some embodiments of the present invention, the photocatalytic reaction is carried out under an inert atmosphere, which may be a conventional atmosphere such as argon or nitrogen.

[0042] In some embodiments of the present invention, the N-amido pyridinium salt is an aromatic hetero-substituted N-amido pyridinium salt. In some alternative embodiments, the N-amido pyridinium salt is an aliphatic alkyl-substituted N-amido pyridinium salt. The reactivity of the above two N-amido pyridinium salts is somewhat different, but both can give the corresponding amidation products.

[0043] To further improve the catalytic efficiency, in some embodiments of the present invention, the base is any one of anhydrous sodium carbonate, lithium acetate, sodium carbonate, 2,6-di-tert-butyl-4-methylpyridine, 2,6-lutidine, and 2,4,6-tri-tert-butyl-pyridine.

[0044] In order to further balance the reaction cost and yield, in some embodiments of the present invention, the molar ratio of N-(2-cyano-1,1'-biphenyl)acrylamide compound to N-amidopyridinium salt is 1:1 to 4:1, more preferably 1:1 to 1.5:1.

[0045] In order to further balance the reaction cost and yield, in some embodiments of the present invention, the molar ratio of N-(2-cyano-1,1'-biphenylyl)acrylamide compound to base is 1:1 to 1:3, and more preferably 1:1 to 1:2.

[0046] There is no special restriction on the choice of solvent during the reaction, as long as it does not affect the normal progress of the reaction. In some optional embodiments of the present invention, the solvent is any one of dimethyl sulfoxide, 1,4-dioxane, 1,2-dichloroethane, acetone, and dichloromethane, or a combination of two or more thereof.

[0047] Furthermore, based on 0.2 mmol of N-(2-cyano-1,1'-biphenyl)acrylamide compound, the amount of solvent used can be 1 to 3 mL.

[0048] To further improve the efficiency of the photocatalytic reaction. In some optional embodiments of the present invention, the photocatalytic reaction is carried out under the irradiation of visible light for 18 to 48 hours. In other words, the photocatalytic reaction time is 18 to 48 hours, for example, 18 hours, 20 hours, 25 hours, 30 hours, 36 hours, 40 hours, 45 hours or 48 hours.

[0049] In some optional embodiments of the present invention, the light source of visible light is a blue LED light source with a power of 5 to 40 W, for example, 5 W, 10 W, 20 W, 30 W or 40 W. Preferably, the power of the blue LED light source is 5 to 10 W. The blue LED light source has the advantages of high efficiency and energy saving, environmental protection, long service life and adjustable brightness. Specifically, the blue LED light source has high luminous efficiency, can convert electrical energy into light energy with an efficiency of more than 90%, has low energy consumption, and can significantly save electrical energy. The blue LED light source does not contain harmful substances such as mercury, does not generate ultraviolet radiation, is environmentally friendly, and meets the requirements of modern green environmental protection. The blue LED light source can control the brightness by adjusting the current to achieve smooth brightness adjustment, which is suitable for various lighting needs.

[0050] In some optional embodiments of the present invention, the amount of the photocatalyst is 0.01 to 0.05 times the amount of the N-(2-cyano-1,1'-biphenyl) acrylamide compound, for example, 0.01 times, 0.02 times, 0.03 times, 0.04 times or 0.05 times. Preferably, the amount of the photocatalyst is 0.02 to 0.03 times the amount of the N-(2-cyano-1,1'-biphenyl) acrylamide compound.

[0051] The embodiments of the present application will be described in detail below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present application and are not intended to limit the scope of the present application. The experimental methods for which specific conditions are not specified in the following examples are preferably referred to the guidance given in the present application, and can also be based on the experimental manual or normal conditions in this area, can also be based on the conditions recommended by the manufacturer, or refer to experimental methods known in the art.

[0052] The preparation methods of the following Examples 1 to 32 include: in an argon atmosphere, 0.2 mmol of N-(2-cyano-1,1'-biphenyl) acrylamide compounds shown in formula II, 0.1 mmol of N-amido pyridinium salt shown in formula III, 0.02 mmol of tris(2-phenylpyridine)iridium shown in formula IV, and 2,6-di-tert-butyl-4-methylpyridine are added to a reaction tube, and then 1.0 mL of dichloromethane is added to the reaction tube, and the reaction is carried out at room temperature for 36 hours under the irradiation of a 15W blue LED lamp. After the reaction is completed, the reaction solution is filtered, concentrated under reduced pressure, and purified by column chromatography to obtain the target compound. Among them, the eluent used for column chromatography is a mixed solvent of ethyl acetate and petroleum ether in a volume ratio of 1:1.

[0053] Example 1

[0054] The target compound of Example 1 is N-((9-fluoro-4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and the structural formula is:

[0055]

[0056] In the preparation process, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-fluoro-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0057] The yield of the target compound in Example 1 was 67%. The NMR characterization was as follows: 1H NMR (400 MHz, Chloroform-d) δ8.52 (dd, J = 9.1, 5.8 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.86 (t, J = 8.1 Hz, 1H), 7.81 (dd, J = 9.7, 2.7 Hz, 1H), 7.67 (d, J = 8.0 Hz, 3H), 7.43 (ddd, J = 8.9, 8.0, 2.7 Hz, 1H), 7.23 (dd, J = 8.0, 3.0 Hz, 3H), 4.36 (dd, J = 13.4, 6.1 Hz, 1H), 4.13 (dd, J = 13.4, 5.4 Hz, 1H), 3.60 (s, 3H), 2.39 (s, 3H), 1.81 (s, 3H).13CNMR(101MHz,Chloroform-d)δ172.99,167.39,163.09(d,J=250Hz),159.91, 145.82(d,J=4.0Hz),141.77,138.90,133.31,132.56,131.88,129.19,126.95,124.7 1(d,J=9.1Hz),119.66(d,J=1.0Hz),116.45,116.20,114.29(d,J=20.2Hz),111.48,1 10.93,50.50,47.39,30.04,24.84,21.46.19FNMR(376MHz,Chloroform-d)δ-110.67.

[0058] Example 2

[0059] The target compound of Example 2 is N-((9-chloro-4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0060]

[0061] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-chloro-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0062] The yield of the target compound in Example 2 was 47%, and the NMR characterization was as follows: 1H NMR (400 MHz, Chloroform-d) δ8.44 (d, J = 8.8 Hz, 1H), 8.25-8.14 (m, 2H), 7.86 (t, J = 8.1 Hz, 1H), 7.68-7.58 (m, 4H), 7.28-7.19 (m, 3H), 4.34 (dd, J = 13.4, 6.2 Hz, 1H), 4.12 (dd, J = 13.5, 5.3 Hz, 1H), 3.59 (s, 3H), 2.39 (s, 3 H),1.80(s,3H).13CNMR(101MHz,Chloroform-d)δ172.94,167.41,159.83,145.13,141.80,138.90,135.19,133.09,132. 60,131.82,129.19,128.97,127.67,126.95,124.06,121.43,116.30,111.78,111.37,50.61,47.45,30.06,24.80,21.46.

[0063] Example 3

[0064] The target compound of Example 3 is 4-methyl-N-((4,6,9-trimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0065]

[0066] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl)acrylamide compound is N-[(2-cyano-4'-methyl-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amidopyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0067] The yield of the target compound in Example 3 was 60%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.43(d,J=8.4Hz,1H),8.26(d,J=8.3Hz,1H),8. 00(s,1H),7.87(d,J=5.6Hz,1H),7.83(t,J=8.1Hz,1H),7.70(d,J=7.9Hz,2H), 7.51(d,J=8.4Hz,1H),7.21(t,J=7.8Hz,3H),4.33(dd,J=13.4,5.8Hz,1H),4.1 9(dd,J=13.4,5.5Hz,1H),3.59(s,3H),2.62(s,3H),2.39(s,3H),1.81(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.11,167.48,158.50,141.72,139.87,138.77,133.59,132.13,131.97,1 29.17,128.98,127.04,122.48,120.65,116.29,111.53,110.68,50.26,47.38,30.06,25.04,21.66,21.47.

[0068] Example 4

[0069] The target compound of Example 4 is N-((9-methoxy-4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0070]

[0071] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-methoxy-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0072] The yield of the target compound in Example 4 was 46%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.41(d,J=9.1Hz,1H),8.18(d,J=8.4Hz,1H),7.85 –7.76(m,2H),7.71(d,J=7.8Hz,2H),7.57(d,J=2.7Hz,1H),7.30(dd,J=9.0,2.7Hz ,1H),7.21(d,J=7.9Hz,2H),7.15(d,J=7.9Hz,1H),4.44(dd,J=13.4,6.3Hz,1H), 4.08(dd,J=13.4,5.0Hz,1H),4.01(s,3H),3.58(s,3H),2.39(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.28,167.39,160.69,158.75,146.26,141.70,138.69,133.67,132.09,132.00,1 29.13,127.03,123.84,118.52,116.99,116.03,111.00,109.95,109.27,55.64,50.18,47.38,29.96,25.00,21.47.

[0073] Example 5

[0074] The target compound of Example 5 is N-((4,6-dimethyl-5-oxo-9-phenyl-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0075]

[0076] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl)acrylamide compound is N-[(2-cyano-4'-phenyl-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amidopyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0077] The yield of the target compound in Example 5 was 48%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.57(d,J=8.6Hz,1H),8.41(d,J=2.0Hz,1H),8. 29(d,J=8.3Hz,1H),7.96–7.78(m,5H),7.71(d,J=8.1Hz,2H),7.53(t,J=7.6Hz ,2H),7.44(d,J=7.4Hz,1H),7.23(dd,J=16.6,7.8Hz,3H),4.37(dd,J=13.4,5. 9Hz, 1H), 4.17 (dd, J = 13.4, 5.4Hz, 1H), 3.59 (s, 3H), 2.37 (s, 3H), 1.83 (s, 3H). 13 CNMR(101MHz,Chloroform-d)δ173.06,167.43,158.97,144.80,142.13,141.70,139.96,138.83,133.34,132.27,132.01,129.1 6,129.05,128.00,127.59,127.37,127.03,126.24,123.22,121.96,116.47,111.76,111.09,50.32,47.43,30.04,24.98,21.47.

[0078] Example 6

[0079] The target compound of Example 6 is N-((4,6-dimethyl-9-(methylthio)-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and the structural formula is:

[0080]

[0081] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl)acrylamide compound is N-[(2-cyano-4'-methylthio-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amidopyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0082] The yield of the target compound in Example 6 was 35%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.38(d,J=8.7Hz,1H),8.21(d,J=8.3Hz,1H),7. 91(d,J=2.1Hz,1H),7.82(t,J=8.1Hz,2H),7.70(d,J=8.1Hz,2H),7.52(dd,J=8 .7,2.1Hz,1H),7.21(dd,J=10.8,7.9Hz,3H),4.41(dd,J=13.4,6.3Hz,1H),4.1 0(dd,J=13.4,5.2Hz,1H),3.59(s,3H),2.67(s,3H),2.39(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.17,167.41,159.03,145.09,141.73,141.15,138.77,133.46,132.26,131.97,1 29.16,127.02,125.91,124.25,122.76,119.96,116.19,111.45,110.66,50.26,47.33,29.99,25.01,21.48,15.19.

[0083] Example 7

[0084] The target compound of Example 7 is N-((9-ethyl-4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0085]

[0086] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-ethyl-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0087] The yield of the target compound in Example 7 was 61%. The NMR characterization was as follows: 1H NMR (400 MHz, Chloroform-d) δ8.46 (d, J = 8.4 Hz, 1H), 8.27 (d, J = 8.3 Hz, 1H), 8.03 (s, 1H), 7.91 (t, J = 5.7 Hz, 1H), 7.83 (t, J = 8.1 Hz, 1H), 7.71 (d, J = 7.9 Hz, 2H), 7.55 (d d,J=8.4,1.8Hz,1H),7.21(dd,J=8.0,5.6Hz,3H),4.32(dd,J=13.4,5.8Hz,1H),4.19(dd,J=13.4 ,5.6Hz,1H),3.59(s,3H),2.93(q,J=7.6Hz,2H),2.39(s,3H),1.82(s,3H),1.41(t,J=7.6Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ173.07,167.41,158.45,146.08,141.69,138.77,133.59,132.10,131.97,129.13,1 27.98,127.85,127.04,122.55,120.85,116.31,111.52,110.67,50.20,47.41,30.02,28.88,24.98,21.47,15.32.

[0088] Example 8

[0089] The target compound of Example 8 is N-((4,6-dimethyl-5-oxo-9-phenoxy-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0090]

[0091] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-phenoxy-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0092] The yield of the target compound in Example 8 was 52%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.50(d,J=9.0Hz,1H),8.21(d,J=8.3Hz,1H),7.89(s,1 H),7.82(t,J=8.1Hz,1H),7.65(d,J=6.5Hz,2H),7.59(d,J=2.6Hz,1H),7.48–7.41(m, 3H),7.26(t,J=3.8Hz,1H),7.18(d,J=7.8Hz,3H),7.13(d,J=7.9Hz,2H),4.24(dd,J=1 3.4, 5.6Hz, 1H), 4.15 (dd, J = 13.4, 5.7Hz, 1H), 3.58 (s, 3H), 2.38 (s, 3H), 1.77 (s, 3H). 13 CNMR(101MHz,Ch loroform-d)δ172.97,167.33,159.46,159.02,156.05,145.85,141.60,138.83,133.50,132.36,131.87,130.17,129.1 6,126.92,124.48,124.37,120.16,119.57,118.53,116.12,115.27,111.19,110.47,50.17,47.34,30.02,24.86,21.44.

[0093] Example 9

[0094] The target compound of Example 9 is N-((4,6-dimethyl-5-oxo-9-propyl-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and its structural formula is:

[0095]

[0096] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-propyl-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0097] The yield of the target compound in Example 9 was 54%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.44(d,J=8.4Hz,1H),8.25(d,J=8.3Hz,1H),8.00(s,1H) ,7.91(t,J=5.7Hz,1H),7.82(t,J=8.1Hz,1H),7.71(d,J=7.8Hz,2H),7.52(d,J=6.6Hz,1H ),7.20(t,J=7.9Hz,3H),4.31(dd,J=13.4,5.7Hz,1H),4.18(dd,J=13.4,5.5Hz,1H),3.58 (s,3H),2.85(t,J=7.6Hz,2H),2.39(s,3H),1.82(d,J=4.5Hz,5H),1.03(t,J=7.3Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ173.06,167.37,158.41,144.54,141.66,138.76,133.57,132.07,132.01,129.13,1 28.67,128.38,127.04,122.47,120.87,116.29,111.51,110.66,50.19,47.42,37.98,30.01,24.90,24.34,21.47.

[0098] Example 10

[0099] The target compound of Example 10 is N-((9-(tert-butyl)-4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and the structural formula is:

[0100]

[0101] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-[(2-cyano-4'-tert-butyl-[1,1'-biphenyl]-3-yl)]-N-methylacrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0102] The yield of the target compound in Example 10 was 68%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.47(d,J=8.7Hz,1H),8.26(d,J=8.3Hz,1H),8.17(d,J=2.1Hz,1H),8.08(t,J=5.6Hz,1H),7.83(t,J=8.1Hz,1H),7.79–7. 72(m,3H),7.22(dd,J=10.0,7.9Hz,3H),4.30(dd,J=13.4,5.5Hz,1H),4.21( dd,J=13.4,5.6Hz,1H),3.59(s,3H),2.39(s,3H),1.82(s,3H),1.50(s,9H). 13 CNMR(101MHz,Chloroform-d)δ173.07,167.35,158.49,152.96,144.43,141.67,138.74,133.43,132.08,132.05,129. 15,127.06,125.56,125.54,122.38,120.58,116.33,111.57,110.69,50.01,47.39,35.08,31.31,30.00,25.00,21.49.

[0103] Embodiment 11

[0104] The target compound of Example 11 is 4-methyl-N-((4,6,11-trimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0105]

[0106] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-2'-methyl-[1,1'-biphenyl]-3-yl)-N-methylmethyl acrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0107] The yield of the target compound in Example 11 was 52%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.59(d,J=8.7Hz,1H),8.10(d,J=8.1Hz,1H),7.89( t,J=5.7Hz,1H),7.84(t,J=8.3Hz,1H),7.68(dd,J=14.5,7.7Hz,3H),7.52(d,J=7.2 Hz,1H),7.29(d,J=7.9Hz,1H),7.22(d,J=7.8Hz,2H),4.34(dd,J=13.4,5.8Hz,1H) ,4.21(dd,J=13.4,5.6Hz,1H),3.61(s,3H),3.12(s,3H),2.39(s,3H),1.79(s,3H). 13 CNMR(101MHz,Chloroform-d)δ172.89,167.43,157.89,141.67,138.64,135.55,134.77,131.97,131.41,1 31.21,129.16,128.63,127.00,122.83,121.12,112.68,111.03,49.93,47.10,30.24,26.78,24.92,21.46.

[0108] Example 12

[0109] The target compound of Example 12 is 4-methyl-N-((4,6,8,10-tetramethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0110]

[0111] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-3',5'-dimethyl-[1,1'-biphenyl]-3-yl)-N-methylmethyl acrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0112] The yield of the target compound in Example 12 was 47%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.28(d,J=8.4Hz,1H),8.18(s,1H),7.80(t,J=8.1Hz,1H),7.62(d,J=6.3Hz,2H),7.47(s,2H),7.19(t,J= 7.9Hz,3H),4.42(dd,J=13.4,6.3Hz,1H),4.10(dd,J=13.4,5.1Hz,1H),3.59(s,3H),2.84(s,3H),2.59(s,3H),2.37(s,3H),1.81(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.44,167.60,155.60,141.64,138.60,137.32,136.59,133.52,132.03,131.89,1 31.53,129.10,127.00,122.61,119.89,116.74,111.70,110.67,50.58,47.51,30.00,24.90,21.99,21.45,18.44.

[0113] Embodiment 13

[0114] The target compound of Example 13 is 4-methyl-N-((4,6,10-trimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0115]

[0116] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-3'-methyl-[1,1'-biphenyl]-3-yl)-N-methylmethyl acrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0117] The yield of the target compound in Example 13 was 55%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.40(d,J=8.2Hz,1H),8.29(d,J=8.3Hz,1H),7.82(t,J=8.1Hz,1H),7.62(d,J=8.0Hz,3H),7.56(t,J=7.6Hz,1H),7.46(d,J =5.8Hz,1H),7.20(dd,J=15.2,7.9Hz,3H),4.45(dd,J=13.3,6.4Hz,1H),4.10 (dd,J=13.3,5.0Hz,1H),3.60(s,3H),2.88(s,3H),2.37(s,3H),1.82(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.41,167.60,156.68,143.27,141.67,138.66,137.74,133.83,131.99,131.82,1 30.04,129.11,127.00,126.74,122.70,120.41,116.75,111.63,110.83,50.76,47.49,30.01,24.97,21.45,18.58.

[0118] Embodiment 14

[0119] The target compound of Example 14 is 4-methyl-N-((4,6,8-trimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0120]

[0121] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-3'-methyl-[1,1'-biphenyl]-3-yl)-N-methylmethyl acrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0122] The yield of the target compound in Example 14 was 17%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.47–8.19(m,2H),8.09(d,J=8.4Hz,1H),7.99–7.87(m,1H),7.84(t,J=8.1Hz,1H),7.71(d,J=7.9Hz,2H),7.62(d,J =8.3Hz,1H),7.23(d,J=7.7Hz,3H),4.31(dd,J=13.4,5.8Hz,1H),4.19(dd ,J=13.4,5.6Hz,1H),3.59(s,3H),2.64(s,3H),2.39(s,3H),1.81(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.39,167.84,157.79,141.74,138.61,137.45,133.54,132.02,131.38,1 29.43,129.24,127.20,127.08,122.19,116.50,111.97,111.06,50.17,47.41,30.11,25.05,22.01,21.52.

[0123] Embodiment 15

[0124] The target compound of Example 15 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-benzo[a]pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and the structural formula is:

[0125]

[0126] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl)acrylamide compound is N-(2-cyano-3-(naphthalen-1-yl)phenyl)-N-methylacrylamide, and the N-amidopyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0127] The yield of the target compound in Example 15 was 49%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ9.04(d,J=8.4Hz,1H),8.77(s,1H),8.08(d,J=3.7Hz,3H),7.87(t,J=8.1Hz,2H),7.70(q,J=7.4,6 .6Hz,4H),7.25–7.18(m,3H),4.40(dd,J=13.4,5.9Hz,1H),4.20(dd,J=13.4,5.4Hz,1H),3.62(s,3H),2.38(s,3H),1.83(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.05,167.41,157.67,144.49,141.69,138.54,133.48,133.27,131.98,131.71,130.52,129.7 1,129.18,128.92,127.97,127.56,127.00,126.86,126.61,121.20,119.64,113.13,110.30,50.02,47.32,30.15,25.04,21.46.

[0128] Example 16

[0129] The target compound of Example 16 is N-((4,6-dimethyl-9-(methylsulfonyl)-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methylbenzamide, and the structural formula is:

[0130]

[0131] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-4'-(methylsulfonyl)-[1,1'-biphenyl]-3-yl)-N-methylmethyl acrylamide, and the N-amido pyridinium salt is 2,4,6-trimethyl-1-(4-methylbenzamido)pyridin-1-ium tetrafluoroborate.

[0132] The yield of the target compound in Example 16 was 39%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.77(d,J=2.0Hz,1H),8.71(d,J=8.6Hz,1H),8.33(d,J=8 .3Hz,1H),8.13(dd,J=8.7,2.0Hz,1H),7.95(t,J=8.1Hz,1H),7.61(d,J=7.9Hz,2H),7.4 3(d,J=5.9Hz,1H),7.37(d,J=8.0Hz,1H),7.21(d,J=7.9Hz,2H),4.36(dd,J=13.4,6.5Hz ,1H),4.08(dd,J=13.4,5.3Hz,1H),3.62(s,3H),3.18(s,3H),2.38(s,3H),1.85(s,3H). 13 CNMR(101MHz,Chloroform-d)δ172.72,167.42,160.77,143.96,141.92,140.85,139.11,133.05,132.43,131.62,1 29.92,129.22,126.91,126.64,124.47,123.87,116.89,112.81,112.71,51.06,47.88,44.55,30.13,24.43,21.46.

[0133] Embodiment 17

[0134] The target compound of Example 17 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-fluorobenzamide, and its structural formula is:

[0135]

[0136] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(4-fluorobenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0137] The yield of the target compound in Example 17 was 65%, and the NMR characterization was: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=9.7Hz,1H),8.30(d,J=8.3Hz,1H),8.15(d,J=8.2Hz,1H),7.96(d,J=5.7Hz,1H),7.88–7.76(m,4H),7.68(td,J= 7.6,7.0,1.4Hz,1H),7.25(d,J=10.0Hz,1H),7.10(t,J=8.6Hz,2H),4.36(dd ,J=13.4,5.9Hz,1H),4.18(dd,J=13.5,5.5Hz,1H),3.60(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.09,166.42,164.47(d,J=252.5Hz),158.47,144.39,138.72,133.53,132.20,131.02(d,J=3.03Hz),12 9.72,129.55,129.29(d,J=9.09Hz),127.20,122.94,122.70,116.52,115.53(d,J=22.22Hz),111.75,111.18,50.10,47.20,30.05,25.17. 19 FNMR(376MHz,Chloroform-d)δ-108.64.

[0138] Embodiment 18

[0139] The target compound of Example 18 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and its structural formula is:

[0140]

[0141] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-benzamido-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0142] The yield of the target compound in Example 18 was 70%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(dd,J=8.3,1.4Hz,1H),8.30(d,J=8.3Hz,1 H),8.18(dd,J=8.2,1.4Hz,1H),7.96(t,J=5.7Hz,1H),7.88–7.76(m,4H),7.68 (ddd,J=8.3,7.0,1.4Hz,1H),7.51–7.41(m,3H),7.24(d,J=7.9Hz,1H),4.36(d d,J=13.4,5.9Hz,1H),4.21(dd,J=13.4,5.6Hz,1H),3.60(s,3H),1.82(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.08,167.48,158.53,144.42,138.75,134.83,133.51,132.18,131.34,12 9.77,129.51,128.53,127.16,127.01,122.94,122.68,116.47,111.77,111.15,50.21,47.25,30.05,25.09.

[0143] Embodiment 19

[0144] The target compound of Example 19 is 4-bromo-N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0145]

[0146] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(4-bromobenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0147] The yield of the target compound in Example 19 was 64%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=6.8Hz,1H),8.30(d,J=8.3Hz,1H),8 .15(d,J=8.2Hz,1H),8.03(t,J=5.7Hz,1H),7.86(t,J=8.1Hz,1H),7.82–7.76( m,1H),7.71–7.66(m,3H),7.56(d,J=8.4Hz,2H),7.25(d,J=8.0Hz,1H),4.34(d d,J=13.5,5.8Hz,1H),4.19(dd,J=13.5,5.5Hz,1H),3.60(s,3H),1.79(s,3H). 13 CNMR(101MHz,Chloroform-d)δ144.36,138.71,133.68,133.53,132.23,131.74,129.69,129.58 ,128.65,127.23,125.99,122.95,122.71,116.53,111.74,111.20,50.02,47.17,30.06,25.25.

[0148] Embodiment 20

[0149] The target compound of Example 20 is 4-chloro-N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0150]

[0151] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(4-chlorobenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0152] The yield of the target compound in Example 20 was 68%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.55(d,J=9.7Hz,1H),8.31(d,J=8.3Hz,1H),8.15(d,J=8.2Hz,1H),8.02(t,J=5.6Hz,1H),7.86(t,J=8.1Hz,1H),7.83–7 .74(m,3H),7.72–7.64(m,1H),7.41(d,J=8.5Hz,2H),7.26(s,1H),4.35(dd, J=13.5,5.8Hz,1H),4.20(dd,J=13.5,5.5Hz,1H),3.60(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.04,166.41,158.47,144.36,138.71,137.53,133.53,133.22,132.23,12 9.69,129.57,128.77,128.45,127.22,122.95,122.71,116.52,111.74,111.19,50.05,47.19,30.06,25.22.

[0153] Embodiment 21

[0154] The target compound of Example 21 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-(trifluoromethyl)benzamide, and its structural formula is:

[0155]

[0156] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(4-trifluoromethylbenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0157] The yield of the target compound in Example 21 was 68%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.55(d,J=8.3Hz,1H),8.31(d,J=8.3Hz,1H),8.17(dd,J=12.9,6.9Hz,2H),7.93(d,J=8.1Hz,2H),7.87(t,J=8.1Hz,1H) ,7.83–7.76(m,1H),7.70(d,J=8.3Hz,3H),7.26(d,J=7.9Hz,1H),4.38(dd, J=13.5,5.8Hz,1H),4.24(dd,J=13.5,5.5Hz,1H),3.61(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.01,166.19,158.44,144.34,138.68,138.11,133.54,133.04(d,J=32.3Hz),132.28,129.64,129.6 0,127.49,127.27,126.28(q,J=250.8Hz),125.59(d,J=4.04Hz),122.96,122.74,116.57,111.73,111.25,49.99,47.16,30.07,25.37. 19 FNMR(376MHz,Chloroform-d)δ-62.83.

[0158] Embodiment 22

[0159] The target compound of Example 22 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-4-methoxybenzamide, and the structural formula is:

[0160]

[0161] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amidopyridinium salt is 1-(4-methoxybenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0162] The yield of the target compound in Example 22 was 41%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=8.2Hz,1H),8.29(d,J=8.3Hz,1H),8.18(d,J=8.1Hz,1H),7.80(dd,J=25.0,8.4Hz,5H),7.72–7.63(m,1H ),7.24(d,J=7.9Hz,1H),6.92(d,J=8.9Hz,2H),4.34(dd,J=13.4,5.9Hz, 1H), 4.17 (dd, J=13.4, 5.5Hz, 1H), 3.84 (s, 3H), 3.59 (s, 3H), 1.81 (s, 3H). 13 CNMR(101MHz,Chloroform-d)δ173.11,167.02,162.07,158.58,144.43,138.77,133.48,132.16,129.76,12 9.49,128.78,127.13,122.93,122.68,116.44,113.69,111.79,111.13,55.42,50.30,47.34,30.04,24.93.

[0163] Embodiment 23

[0164] The target compound of Example 23 is 3-chloro-N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)benzamide, and the structural formula is:

[0165]

[0166] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(3-chlorobenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0167] The yield of the target compound in Example 23 was 45%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.55(d,J=8.4Hz,1H),8.31(d,J=8.3Hz,1H),8.19(d,J=8.2Hz,1H),8.11(t,J=5.8Hz,1H),7.87(t,J=8.1Hz,1H),7.83 –7.77(m,2H),7.69(t,J=8.3Hz,2H),7.46(d,J=8.9Hz,1H),7.37(t,J=7.8H z,1H),7.26(d,J=8.0Hz,1H),4.32–4.21(m,2H),3.60(s,3H),1.81(s,3H). 13 CNMR(101MHz,Chloroform-d)δ172.91,166.10,158.51,144.31,138.73,136.63,134.68,133.55,132.27,131.37,12 9.88,129.73,129.60,127.33,127.25,125.16,122.96,122.71,116.53,111.73,111.20,49.97,47.25,30.07,25.21.

[0168] Embodiment 24

[0169] The target compound of Example 24 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-2-methylbenzamide, and the structural formula is:

[0170]

[0171] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(2-methylformamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0172] The yield of the target compound in Example 24 was 30%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.56(d,J=8.3Hz,1H),8.30(d,J=8.3Hz,1H),8.15( d,J=8.0Hz,1H),7.86(t,J=8.1Hz,1H),7.81–7.74(m,1H),7.74–7.64(m,1H),7.39 –7.31(m,1H),7.21(d,J=7.9Hz,1H),7.16–7.02(m,2H),6.94–6.81(m,1H),6.35(s ,1H),5.60(s,1H),3.50(s,3H),2.96–2.84(m,1H),2.81–2.57(m,3H),1.73(s,3H). 13 CNMR(101MHz,Chlorofor md)δ173.83,171.89,159.40,144.80,138.78,138.54,135.45,133.33,132.05,130.26,129.76,129.40,12 9.36,127.77,126.82,126.06,122.83,122.80,116.29,112.43,110.95,51.21,42.41,30.51,29.79,29.39.

[0173] Embodiment 25

[0174] The target compound of Example 25 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)acetamide, and the structural formula is:

[0175]

[0176] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-acetamido-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0177] The yield of the target compound in Example 25 was 68%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=8.2Hz,1H),8.30(d,J=8.3Hz,1H),8.17(d,J=8.2Hz,1H),7.85(t,J=8.1Hz,1H),7.77(t,J=7.6Hz,1H),7.71 –7.61(m,1H),7.25(d,J=7.9Hz,1H),6.68(s,1H),4.26(dd,J=13.4,6.7Hz ,1H),3.93(dd,J=13.4,5.1Hz,1H),3.58(s,3H),1.94(s,3H),1.73(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.07,170.27,158.07,144.55,138.69,133.46,132.05,129.8 9,129.41,127.08,122.87,122.60,116.42,111.88,111.03,50.59,46.99,30.01,25.05,23.46.

[0178] Embodiment 26

[0179] The target compound of Example 26 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)isonicotinamide, and the structural formula is:

[0180]

[0181] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(isonicotinamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0182] The yield of the target compound in Example 26 was 30%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.57(d,J=8.3Hz,1H),8.33(d,J=8.3Hz,1H),8.28(d,J=5.9Hz,1H),8.17(d,J=8.2Hz,1H),7.88(t,J=8.1Hz,1H),7.85– 7.78(m,1H),7.76–7.67(m,3H),7.58–7.45(m,1H),7.29(s,1H),4.41(dd,J =13.5,5.8Hz,1H),4.25(dd,J=13.5,5.5Hz,1H),3.62(s,3H),1.79(s,3H). 13 CNMR(101MHz,Chloroform-d)δ173.00,165.47,158.36,150.44,144.32,141.96,138.64,133.58,132.30 ,129.65,128.95,128.69,127.32,122.97,122.74,116.63,111.70,111.27,49.83,46.90,30.07,25.63.

[0183] Embodiment 27

[0184] The target compound of Example 27 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)nicotinamide, and the structural formula is:

[0185]

[0186] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(nicotinamide)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0187] The yield of the target compound in Example 27 was 24%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ9.05(s,1H),8.71(s,1H),8.56(d,J=8.2Hz,1H),8.32(d,J=8.3Hz,1H),8.18(d,J=8.2Hz,3H),7.88(t,J=8 .1Hz,1H),7.80(t,J=6.9Hz,1H),7.70(t,J=7.0Hz,1H),7.41(s,1H),7.27(d,J=4.0Hz,1H),4.41–4.27(m,2H),3.61(s,3H),1.80(s,3H). 13 CNMR(101MHz,Chloroform-d)δ172.91,165.53,158.50,152.07,147.90,144.31,138.70,135.28,133.57,132.28 ,129.71,129.67,128.96,128.67,127.28,122.94,122.70,116.56,111.72,111.21,49.99,47.01,30.08,25.54.

[0188] Embodiment 28

[0189] The target compound of Example 28 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)isobutyramide, and the structural formula is:

[0190]

[0191] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(isobutylamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0192] The yield of the target compound in Example 28 was 21%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.55(d,J=9.8Hz,1H),8.30(d,J=8.2Hz,1H),8.16( d,J=9.6Hz,1H),7.85(t,J=8.1Hz,1H),7.81–7.72(m,1H),7.72–7.62(m,1H),7.24 (d,J=7.9Hz,1H),6.81(s,1H),4.15(dd,J=13.4,6.2Hz,1H),3.93(dd,J=13.4,5.6 Hz,1H),3.58(s,3H),2.33(hept,J=6.9Hz,1H),1.77(s,3H),1.09(t,J=7.1Hz,6H). 13 CNMR(101MHz,Chloroform-d)δ177.05,173.08,158.38,144.49,138.79,133.43,132.07,129.80,129. 43,127.06,122.87,122.62,116.36,111.88,111.01,50.49,47.35,35.85,29.98,24.43,19.61,19.55.

[0193] Embodiment 29

[0194] The target compound of Example 29 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)cyclopropanecarboxamide, and its structural formula is:

[0195]

[0196] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(cyclopropanecarboxamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0197] The yield of the target compound in Example 29 was 45%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.53(d,J=9.7Hz,1H),8.29(d,J=8.3Hz,1H),8.16(d,J=8.2 Hz,1H),7.84(t,J=8.1Hz,1H),7.80–7.71(m,1H),7.71–7.58(m,1H),7.24(d,J=7.9Hz,1H), 6.83(s,1H),4.27(dd,J=13.4,6.8Hz,1H),3.91(dd,J=13.4,5.2Hz,1H),3.58(s,3H),1.76 (s,3H),1.31(ddd,J=12.5,7.9,4.6Hz,1H),0.88(dd,J=4.5,2.8Hz,2H),0.70–0.61(m,2H). 13 CNMR(101MHz,Chloroform-d)δ173.75,173.12,158.22,144.55,138.74,133.41,132.03,129.87,129 .37,127.03,122.87,122.59,116.35,111.93,111.01,50.72,47.41,29.99,24.68,14.90,7.12,7.08.

[0198] Embodiment 30

[0199] The target compound of Example 30 is N-((4,6-dimethyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)cyclohexanecarboxamide, and the structural formula is:

[0200]

[0201] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-(2-cyano-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, and the N-amido pyridinium salt is 1-(cyclohexanecarboxamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0202] The yield of the target compound in Example 30 was 23%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=9.8Hz,1H),8.29(d,J=8.3Hz,1H),8.16(d,J=8.2Hz,1H),7.85( t,J=8.1Hz,1H),7.78(td,J=8.3,7.6,1.4Hz,1H),7.68(ddd,J=8.3,7.0,1.4Hz,1H),7.24(d,J=7.5Hz,1H) ,6.80(s,1H),4.17(dd,J=13.4,6.4Hz,1H),3.89(dd,J=13.4,5.4Hz,1H),3.58(s,3H),2.06(tt,J=11.7, 3.4Hz,1H),1.82(d,J=14.4Hz,2H),1.76(s,3H),1.73–1.60(m,2H),1.43–1.30(m,2H),1.30–1.14(m,4H). 13 CNMR(101MHz,Chloroform-d)δ176.21,173.14,158.32,144.51,138.76,132.04,129.81,129.42,127.05, 122.87,122.62,116.37,111.88,111.02,50.48,47.25,45.64,29.98,29.72,29.63,25.81,25.75,24.37.

[0203] Embodiment 31

[0204] The target compound of Example 31 is N-((4-benzyl-6-methyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-2-methylbenzamide, and its structural formula is:

[0205]

[0206] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-benzyl-N-(2-cyano-[1,1'-biphenyl]-3-yl) methacrylamide, and the N-amido pyridinium salt is 1-((4-methylbenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0207] The yield of the target compound in Example 31 was 41%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=8.2Hz,1H),8.27(d,J=8.3Hz,2H),7.8 9(d,J=5.7Hz,1H),7.84–7.76(m,1H),7.75–7.65(m,4H),7.30(d,J=6.9Hz,5H),7 .22(d,J=8.0Hz,2H),7.16(d,J=8.0Hz,1H),5.44(dd,J=65.0,15.6Hz,2H),4.48 (dd,J=13.5,5.9Hz,1H),4.33(dd,J=13.5,5.4Hz,1H),2.39(s,3H),1.91(s,3H). 13 CNMR(101MHz,Chloroform-d)δ167.51,158.38,141.76,135.91,133.68,131.85,129.61,129.37,129.18,12 9.03,127.48,127.29,127.03,126.31,122.99,122.63,116.57,112.31,50.54,47.23,46.43,25.53,21.46.

[0208] Embodiment 32

[0209] The target compound of Example 32 is N-((4-butyl-6-methyl-5-oxo-5,6-dihydro-4H-pyrido[4,3,2-gh]phenanthridin-6-yl)methyl)-2-methylbenzamide, and the structural formula is:

[0210]

[0211] In the preparation process of the target compound, the N-(2-cyano-1,1'-biphenyl) acrylamide compound is N-butyl-N-(2-cyano-[1,1'-biphenyl]-3-yl) methacrylamide, and the N-amido pyridinium salt is 1-((4-methylbenzamido)-2,4,6-trimethylpyridin-1-ium tetrafluoroborate.

[0212] The yield of the target compound in Example 32 was 39%, and the NMR characterization was as follows: 1HNMR(400MHz,Chloroform-d)δ8.54(d,J=8.3Hz,1H),8.29(d,J=8.3Hz,1H),8.18(d,J=8.2Hz,1H),7.97–7.81(m,2H),7.81–7.75(m,1H),7.69(dd,J=17.7,7.5Hz,3H),7.23(dd,J=8.1,2.8Hz,3H),4.34(dd,J=13.4,5.8Hz,1H),4.25–4.19(m,1H),4.19–4.08(m,2H),2.39(s,3H),1.79(s,3H),1.73(dq,J=13.7,6.4,5.9Hz,2H),1.49(h,J=7.4Hz,2H),1.00(t,J=7.3Hz,3H). 13 CNMR(101MHz,Chloroform-d)δ172.87,167.42,158.63,144.36,141.69,137.82,133.76,132.14,131.97,129.73,129.47,129.17,127.11,127.01,122.98,122.63,116.26,112.03,111.16,50.16,47.17,42.56,28.87,25.01,21.46,20.26,13.89。

Claims

1. A method for preparing an amidated pyrido[4,3,2-gh]phenanthridine compound, characterized in that: include: S1, mixing an N-(2-cyano-1,1'-biphenyl)acrylamide compound represented by formula II, an N-amidopyridinium salt represented by formula III, a photocatalyst, a base and a solvent, and performing a photocatalytic reaction at room temperature using visible light as an energy source to obtain an amidated pyrido[4,3,2-gh]phenanthridine compound represented by formula I; Wherein, Formula III is Formula II is Formula I is R 1 is any one of hydrogen, alkyl, phenyl, C1-C4 alkyl, phenoxy, methylthio, halogen, trifluoromethyl, and methanesulfonyl; R 2 is any one of methyl, benzyl and n-butyl; R 3 It is any one of phenyl, (4- or 3-) halogen-substituted phenyl, (4- or 2-) substituted phenyl, 4-methoxyphenyl, 4-trifluoromethylphenyl, C1-C6 alkyl, and cycloalkyl; and the photocatalyst is a tris(2-phenylpyridine)iridium compound.

2. The preparation method according to claim 1, characterized in that: The photocatalytic reaction is carried out under an inert atmosphere.

3. The preparation method according to claim 1, characterized in that: The molar ratio of the N-(2-cyano-1,1'-biphenylyl)acrylamide compound to the N-amidopyridinium salt is 1:1 to 4:

1.

4. The preparation method according to claim 1, characterized in that: The base is any one of anhydrous sodium carbonate, lithium acetate, sodium carbonate, 2,6-di-tert-butyl-4-methylpyridine, 2,6-lutidine, and 2,4,6-tri-tert-butyl-pyridine.

5. The preparation method according to claim 1, characterized in that: The molar ratio of the N-(2-cyano-1,1'-biphenylyl)acrylamide compound to the base is 1:1 to 1:

3.

6. The preparation method according to claim 1, characterized in that: The solvent is any one of dimethyl sulfoxide, acetone, 1,4-dioxane, 1,2-dichloroethane, and dichloromethane, or a combination of two or more thereof.

7. The preparation method according to claim 1, characterized in that: The reaction time of the photocatalytic reaction is 18 to 48 hours; and / or The visible light is blue LED light with a power of 5 to 40W.

8. The preparation method according to claim 1, characterized in that: After S1, the preparation method further comprises: S2, separation and purification: the separation and purification includes solvent concentration and column chromatography purification; The eluent used for the column chromatography purification is a mixture of ethyl acetate and petroleum ether.

9. The preparation method according to claim 1, characterized in that: The amount of the photocatalyst is 0.01 to 0.05 times the amount of the N-(2-cyano-1,1'-biphenyl) acrylamide compound.

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