Method for synthesizing benzo [h] [1, 6] naphthyridine-5 (6H)-ketone skeleton compound

Abstract

The invention discloses a method for synthesizing a benzo [h] [1, 6] naphthyridine-5 (6H)-ketone skeleton compound, the synthesis method takes N-(2-cyano aryl) acrylamide, aryl sulfonium salt and ketone as raw materials, a series of naphthyridinone derivatives are synthesized under the visible light catalysis condition, and the synthesis method specifically comprises the following steps: under the nitrogen protection and illumination, carrying out a reaction for 2-4 hours at the room temperature to obtain the benzo [h] [1, 6] naphthyridine-5 (6H)-ketone skeleton compound. The method comprises the following steps: adding 0.3 mmol of N-(2-cyanophenyl) acrylamide, 3 mmol of ketone, 0.45 mmol of sulfonium salt, 5 mol% of a photosensitizer and 3 mL of a solvent into a reaction tube, stirring for reaction, monitoring the reaction process by TLC (Thin Layer Chromatography), after the reaction is completed, decompressing and spin-drying the solvent, and purifying residues by adopting silica gel column chromatography to obtain the required product. The method has the advantages of being mild in reaction condition, wide in substrate range, good in tolerance to various functional groups and the like, raw materials are easy to obtain, operation is easy, green synthesis is achieved, and good application prospects are achieved.

Description

Technical Field

[0001] The present invention relates to a synthesis technology of benzonaphthyridine derivatives, in particular to a method for synthesizing a benzo[h][1,6]naphthyridine-5(6H)-one skeleton compound. Background Art

[0002] The naphthyridine heterocyclic skeleton is an important pharmacophore in medicinal chemistry, exhibiting diverse biological activities, such as antiviral, antibacterial, antitumor, anti-inflammatory and analgesic activities ((a) Arch. Pharm., 2015, 348, 837; (b) Chem. Lett. 2015, 25, 3251; (c) J. Med. Chem. 2010, 53, 7146–7155; (d) Eur. J. Med. Chem. 2017, 137, 545-557.).

[0003] Traditional methods for synthesizing naphthyridine heterocycles are through reactions such as the Skraup reaction, Friedlander reaction, and Combes reaction. However, these reactions often require high temperatures and strong acids, produce numerous byproducts, and suffer from drawbacks such as poor functional group tolerance and a narrow substrate range, hindering their widespread application in the chemical and pharmaceutical industries. Therefore, developing green, efficient, and functional group-tolerant synthetic methods is crucial for constructing structurally diverse naphthyridine heterocycle derivatives. Summary of the Invention

[0004] The present invention addresses the deficiencies of the prior art and provides a method for synthesizing benzo[h][1,6]naphthyridin-5(6H)-one skeletal compounds. This method uses N-(2-cyanoaryl)acrylamide, an arylsulfonium salt, and a ketone as raw materials to synthesize a series of naphthyridinone derivatives under visible light catalysis. This method has the advantages of mild reaction conditions, a wide substrate range, and good tolerance to various functional groups. Furthermore, the method utilizes readily available raw materials, is simple to operate, and achieves green synthesis, thus promising promising applications.

[0005] The technical solution for achieving the purpose of the present invention is:

[0006] A method for synthesizing a benzo[h][1,6]naphthyridin-5(6H)-one skeleton compound, wherein the general formula of the synthesis method is:

[0007]

[0008] Among them, R 1 = methyl, methoxy, fluoro, chloro, bromo, aryl or heterocyclyl;

[0009] R 2 =alkyl or alicyclic group;

[0010] R 3 = hydrogen or alkyl;

[0011] R 4 、R 5 =aliphatic group, alicyclic group or halogen;

[0012] Ar = aryl; X = chloride anion, tetrafluoroborate anion, trifluoromethanesulfonate anion;

[0013] The synthetic method comprises the following steps:

[0014] Under nitrogen protection and light, 0.3 mmol N-(2-cyanophenyl)acrylamide, 3 mmol ketone, 0.45 mmol sulfonium salt, 5 mol% photosensitizer and 3 mL solvent were added to the reaction tube, and the reaction was stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to obtain the desired product.

[0015] In the general formula of the synthesis method, the photosensitizer is: 4-CzIPN, Eosin Y, Eosin Y disodium salt, fac-Ir(ppy)3 or Solvents are: trifluorotoluene, chlorobenzene, acetone, 1,2-dichloroethane, acetonitrile, N,N-dimethylformamide or N,N-dimethylacetamide;

[0016] Sulfonium salts are: Ar = aryl, X = chloride anion, tetrafluoroborate anion or trifluoromethanesulfonate anion;

[0017] Lighting: 10-60W white light or 5-60W blue light.

[0018] The N-(2-cyanophenyl)acrylamide compounds in the synthesis method are: N-(2-cyanophenyl)-N-methylacrylamide, N-(2-cyano-5-methylphenyl)-N-methylacrylamide, N-(2-cyano-5-methoxyphenyl)-N-methylacrylamide, N-(2-cyano-5-fluorophenyl)-N-methylacrylamide, N-(2-cyano-5-chlorophenyl)-N-methylacrylamide, N-(2-cyano-5-bromophenyl)-N-methylacrylamide, N-(2-cyano-4-methylphenyl)-N-methylacrylamide, N-(4-cyano-4'-fluoro-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, N-(5-acetyl-2-cyanophenyl)-N-isobutylacrylamide, N-(3-cyanothiophene-2-yl)-N-methylacrylamide, (E)-N-(2-cyanophenyl)-N-methylbut-2-enamide, N-(2-cyanophenyl)-N-(cyclopropylmethyl)acrylamide, N-(2-cyanophenyl)-N-(tetrahydro-2H-pyran-4-ylmethyl)acrylamide, N-acryloyl-N-(2-cyanophenyl)glycine ethyl ester.

[0019] The ketone in the synthesis method is: acetone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, ethyl acetoacetate, ethyl propionylacetate, 3-cyclopropyl-3-carbonyl-ethyl propionate, ethyl 3-cyclobutyl-3-oxopropionate, ethyl 3-cyclohexyl-3-oxopropionate, ethyl trifluoroacetoacetate, acetylacetone, 1,3-cyclohexanedione, chloroacetone, 1-chlorobutan-2-one (Example 29), or bromoacetone.

[0020] This technical solution uses a photocatalytic addition / cyclization reaction of ketones with N-(2-cyanophenyl)-N-methylacrylamide to synthesize a series of novel benzonaphthyridinone skeleton compounds with moderate to good yields. This technical solution has the advantages of mild reaction conditions, a wide substrate range, and good tolerance to various functional groups. In addition, the method has readily available raw materials, simple operation, and achieves green synthesis, which has good application prospects. DETAILED DESCRIPTION

[0021] The present invention is further described below with reference to the synthesis and product characterization of the embodiments, but is not intended to limit the present invention.

[0022] Example 1:

[0023] Synthesis of 2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0024]

[0025] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 56.5 mg of a yellow solid product with a yield of 84% (mp 166.6–167.1°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.93(dd,J=7.9,1.7Hz,1H),8.63(d,J=8.2Hz,1H) ,7.62(ddd,J=8.7,7.1,1.7Hz,1H),7.42–7.35(m,3H),3.80(s,3H),2.77(s,3H). 13 C NMR (100MHz, Chloroform-d) δ163.4,161.7,149.7,139.3,136.9,131.1,125.3,123.2,122.7,120.6,118.7,114.5,29.8,25.4.HRMS (ESI): Exact mass calculated for C 14 H 13 N2O([M+H] + ):225.1022,Found:225.1022.

[0026] Example 2:

[0027] Synthesis of 2,6,8-trimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0028]

[0029] Under light conditions, N-(2-cyano-5-methylphenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 57.1 mg of the light yellow solid product 3b in 80% yield (mp 155.3–155.8°C). The product was characterized as follows: 1H NMR(400MHz,Chloroform-d)δ8.71(d,J=8.0Hz,1H),8.53(d,J=8.1Hz,1H),7.25 (d,J=8.1Hz,1H),7.11(d,J=8.3Hz,2H),3.71(s,3H),2.69(s,3H),2.45(s,3H). 13 C NMR (100MHz, Chloroform-d) δ163.3,161.9,149.8,141.7,139.3,136.9,125.2,124.0,122.8,118.2,114.9,29.8,25.4,22.2.HRMS (ESI): Exact mass calculated for C 15 H 15 N2O([M+H] + ):239.1179,Found:239.1178.

[0030] Example 3:

[0031] Synthesis of 8-methoxy-2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0032]

[0033] Under light conditions, N-(2-cyano-5-methoxyphenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 59.4 mg of the yellow solid product 3c in a yield of 78% (mp 141.7–142.8°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.70(d,J=8.8Hz,1H),8.46(d,J=8.1Hz,1H),7.18(d,J=8.2Hz,1 H),6.83(dd,J=8.9,2.3Hz,1H),6.73(d,J=2.3Hz,1H),3.85(s,3H),3.65(s,3H),2.65(s,3H). 13C NMR(100MHz,Chloroform-d)δ163.4,162.1,149.7,140.7,136.8,126.8,122.1,117.2,114.2,109.1,99.8,55.6,29.8,25.4.HRMS(ESI):Exact mass calculated forC 15 H 15 N2O2([M+H] + ):255.1128,Found:255.1128.

[0034] Example 4:

[0035] Synthesis of 8-fluoro-2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0036]

[0037] Under light conditions, N-(2-cyano-5-fluorophenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 57.4 mg of white solid product 3d in a yield of 79% (mp 182.0–182.1°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ8.60–8.44(m,2H),7.35–7.22(m,3H),3.71(s,3H),2.70(s,3H). 13 C NMR(100MHz,Chloroform-d)δ163.6,161.3,158.7(d,J=243.4Hz),148.6(d,J=3.0Hz),137.0,135.6(d,J=2.0Hz),123.8 ,122.0(d,J=8.1Hz),119.0,118.5(d,J=24.2Hz),116.1(d,J=8.1Hz),111.1(d,J=24.2Hz),30.1,25.3.HRMS(ESI):Exact masscalculated for C 14 H 12 FN2O([M+H] + ):243.0928,Found:243.0928.

[0038] Example 5:

[0039] Synthesis of 8-chloro-2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0040]

[0041] Under light conditions, N-(2-cyano-5-chlorophenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 60.4 mg of the product 3e as a light yellow solid in a yield of 78% (mp 219.2–219.8°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.83(d,J=2.5Hz,1H),8.58(d,J=8.2Hz,1H),7.54(dd,J= 8.9,2.6Hz,1H),7.38(d,J=8.2Hz,1H),7.32(d,J=8.9Hz,1H),3.76(s,3H),2.76(s,3H). 13 C NMR (100MHz, Chloroform-d) δ163.7,161.4,148.5,137.7,136.8,130.9,128.6,124.8,123.8,121.9,118.9,115.9,29.9,25.4.HRMS (ESI): Exact mass calculated for C 14 H 12 ClN2O([M+H] + ):259.0633,Found:259.0635.

[0042] Example 6:

[0043] Synthesis of 8-bromo-2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0044]

[0045] Under light conditions, N-(2-cyano-5-bromophenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 64.3 mg of the yellow solid product 3f in a yield of 71% (mp 159.3–159.7°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.73(d,J=8.5Hz,1H),8.57(d,J=8.1Hz,1H),7.53(d,J=1 .5Hz,1H),7.45(dt,J=8.6,1.5Hz,1H),7.37(d,J=8.2Hz,1H),3.75(s,3H),2.75(s,3H). 13 C NMR (100MHz, Chloroform-d) δ163.7,161.6,149.0,140.1,136.8,126.7,125.8,125.4,123.5,119.5,118.5,117.5,29.9,25.4.HRMS (ESI): Exact mass calculated for C 14 H 12 BrN2O([M+H] + ):303.0128,Found:303.0129.

[0046] Example 7:

[0047] Synthesis of 2,6,9-trimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0048]

[0049] Under light conditions, N-(2-cyano-4-methylphenyl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 3 g (57.8 mg) of a yellow solid product with a yield of 81% (mp 129.1–129.5° C.); the product was characterized as follows: 1H NMR(400MHz,Chloroform-d)δ8.66(s,1H),8.59(d,J=8.1Hz,1H),7.42–7.37(m, 1H),7.33(d,J=8.2Hz,1H),7.27(s,1H),3.75(s,3H),2.75(s,3H),2.49(s,3H). 13 C NMR (100MHz, Chloroform-d) δ163.3,161.5,149.6,137.2,136.8,132.3,132.1,125.0,123.0,120.4,118.7,114.4,29.8,25.4,20.8.HRMS(ESI): Exact mass calculated for C 15 H 15 N2O([M+H] + ):239.1179,Found:239.1179.

[0050] Example 8:

[0051] Synthesis of 8-(4-fluorophenyl)-2,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0052]

[0053] Under light conditions, N-(4-cyano-4'-fluoro-[1,1'-biphenyl]-3-yl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to the reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography (SiO2, ethyl acetate: dichloromethane = 1:50 elution) to obtain 73.4 mg of a light yellow solid product 3h with a yield of 77% (mp 164.9–165.6°C); the product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.92(d,J=8.2Hz,1H),8.60(d,J=8.2Hz,1H),7.68–7.62(m,2 H),7.53–7.47(m,2H),7.34(d,J=8.2Hz,1H),7.22–7.15(m,2H),3.83(s,3H),2.76(s,3H). 13C NMR(100MHz,Chloroform-d)δ163.6,162.9(d,J=249.5Hz),161.9,149.5,143.1,139.6,136.8,136.7(d,J=3.0Hz) ,129.1(d,J=8.1Hz),125.8,123.2,121.7,119.6,118.6,115.9(d,J=22.2Hz),112.9,29.9,25.6.HRMS(ESI):Exact mass calculated for C 20 H 16 FN2O([M+H] + ):319.1241,Found:319.1241.

[0054] Example 9:

[0055] Synthesis of 8-acetyl-6-isobutyl-2-methylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0056]

[0057] Under light conditions, N-(5-acetyl-2-cyanophenyl)-N-isobutylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 56.4 mg of white solid product 3i in a yield of 61% (mp 166.6–166.9°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.96(d,J=8.3Hz,1H),8.57(dd,J=8.1,1.4Hz,1H),7.94(d,J=1.6Hz,1H),7.79(dd,J=8.3,1.5Hz,1H),7.36( dd,J=8.2,1.4Hz,1H),4.25(d,J=7.5Hz,2H),2.72(d,J=1.4Hz,3H),2.64(d,J=1.4Hz,3H),2.24(dt,J=13.7,6.9Hz,1H),1.00–0.94(m,6H). 13C NMR(100MHz,Chloroform-d)δ197.6,163.8,161.8,148.7,138.7,138.5,137.1,126.0, 124.3,124.2,122.2,119.6,114.7,49.2,27.3,26.9,25.4,20.2.HRMS(ESI):Exactmass calculated for C 19 H 21 N2O2([M+H] + ):309.1598,Found:309.1598.

[0058] Example 10:

[0059] Synthesis of 2,6-dimethylthieno[2,3-h][1,6]naphthyridin-5(6H)-one:

[0060]

[0061] Under light conditions, N-(3-cyanothiophene-2-yl)-N-methylacrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 50.4 mg of the product 3j as a pale yellow solid in a 73% yield (mp 106.0–106.8°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ8.52(d,J=8.2Hz,1H),7.84(d,J=5.7Hz,1H),7.22(d,J=8.2Hz,1H),6.98(d,J=5.6Hz,1H),3.69(s,3H),2.68(s,3H). 13 C NMR(100MHz,Chloroform-d)δ163.9,161.8,148.9,147.5,137.5,123.3,121.8,120.0,117.1,116.2,34.1,25.3.HRMS(ESI):Exact mass calculated for C 12 H 11 N2OS([M+H] + ):231.0587,Found:231.0587.

[0062] Example 11:

[0063] Synthesis of 2,4,6-trimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0064]

[0065] Under light conditions, (E)-N-(2-cyanophenyl)-N-methylbut-2-enamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 57.8 mg of the light yellow solid product 3k in an 81% yield (mp 178.8–179.2°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ8.90(d,J=7.8Hz,1H),7.53(t,J=7.8Hz,1H),7.32–7.23(m,2H),7.07(s,1H),3.68(s,3H),2.84(s,3H),2.63(s,3H). 13 C NMR (100MHz, Chloroform-d) δ162.3,161.8,152.0,150.8,139.1,131.1,126.4,126.0,122.5,117.8,114.0,29.6,24.9,23.7.HRMS (ESI): Exact mass calculated for C 15 H 15 N2O([M+H] + ):239.1179,Found:239.1179.

[0066] Example 12:

[0067] Synthesis of 6-(cyclopropylmethyl)-2-methylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0068]

[0069] Under light conditions, N-(2-cyanophenyl)-N-(cyclopropylmethyl)acrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 61 mg of white solid product 31 in a yield of 77% (mp 99.3–99.7°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.93(d,J=7.9Hz,1H),8.56(d,J=8.1Hz,1H),7.56(dd,J=8.8,6.7Hz,1H),7.49(d,J=8.4Hz,1H),7.30( dd,J=8.0,4.2Hz,2H),4.27(d,J=6.8Hz,2H),2.72(s,3H),1.25(dd,J=13.1,6.6Hz,1H),0.53(d,J=4.4Hz,2H),0.48(d,J=7.6Hz,2H). 13 C NMR (100MHz, Chloroform-d) δ163.4,161.7,149.6,138.8,137.2,131.2,125.6,123.2,122.6,120.6,118.8,114.9,46.3,25.3,9.9,4.2.HRMS (ESI): Exact mass calculated for C 17 H 17 N2O([M+H] + ):265.1335,Found:265.1335.

[0070] Example 13:

[0071] Synthesis of 2-methyl-6-((tetrahydro-2H-pyran-4-yl)methyl)benzo[h][1,6]naphthyridin-5(6H)-one:

[0072]

[0073] Under light conditions, N-(2-cyanophenyl)-N-(tetrahydro-2H-pyran-4-ylmethyl)acrylamide (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to the reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 66.6 mg of a white solid product 3m with a yield of 72% (mp 119.7–119.9°C); the product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.92(d,J=7.9Hz,1H),8.55(d,J=8.2Hz,1H),7.55(t,J=7.2Hz,1H),7.31(dt,J=7.9,3.9Hz,3H),4.28(d,J=7.2Hz, 2H),3.91(dt,J=11.3,3.4Hz,2H),3.25(qd,J=8.3,7.5,4.2Hz,2H),2.7 1(s,3H),2.14(dq,J=15.3,7.7Hz,1H),1.55(td,J=9.0,7.9,3.8Hz,4H). 13 C NMR(100MHz,Chloroform-d)δ163.6,162.0,149.6,138.7,137.1,131.1,125.7,1 23.3,122.7,120.8,118.5,114.7,67.6,47.5,34.2,30.8,25.4.HRMS(ESI):Exact mass calculated for C 19 H 21 N2O2([M+H] + ):309.1598,Found:309.1598.

[0074] Example 14:

[0075] Synthesis of ethyl 2-(2-methyl-5-oxobenzo[h][1,6]naphthyridin-6(5H)-yl)acetate:

[0076]

[0077] Under light conditions, acryloyl-N-(2-cyanophenyl)glycine ethyl ester (0.3 mmol), acetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 71.1 mg of the light yellow solid product 3n in an 80% yield (mp 190.7–191.0°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.96(d,J=7.9Hz,1H),8.62(d,J=8.2Hz,1H),7.62–7.55(m,1H),7.38(dt, J=7.7,3.6Hz,2H),7.15(d,J=8.4Hz,1H),5.18(s,2H),4.25(q,J=7.1Hz,2H),2.78(s,3H),1.26(s,3H). 13 C NMR(100MHz,Chloroform-d)δ168.3,163.9,161.7,150.0,138.4,137.0,131.3,12 5.7,123.3,123.1,120.8,118.3,113.9,61.8,44.2,25.5,14.2.HRMS(ESI):Exact mass calculated for C 17 H 17 N2O3([M+H] + ):297.1234,Found:297.1234.

[0078] Example 15:

[0079] Synthesis of 2-ethyl-3,6-dimethylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0080]

[0081] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), 3-pentanone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 58.2 mg of the white solid product 4a in a yield of 77% (mp 160.2–160.6°C). The product was characterized as follows: 1H NMR(400MHz,Chloroform-d)δ8.94(d,J=7.8Hz,1H),8.41(s,1H),7.63–7.55(m,1H),7.37(dd ,J=16.6,8.1Hz,2H),3.80(s,3H),2.99(q,J=7.4Hz,2H),2.47(s,3H),1.45(t,J=7.5Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ166.5,161.9,147.4,138.9,136.5,131.3,130.5,125.0,122.6,121.0,118.8,114.4,29.8,29.1,18.7,12.0.HRMS(ESI): Exact mass calculated for C 16 H 17 N2O([M+H] + ):253.1335,Found:253.1335.

[0082] Example 16:

[0083] Synthesis of 5-methyl-5,8,9,10-tetrahydro-6H-benzo[h]cyclopenta[b][1,6]naphthyridin-6-one:

[0084]

[0085] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), cyclopentanone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 1.5 mg of the yellow solid product 4b in an 82% yield (mp 172.0–172.4°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.93–8.86(m,1H),8.51(s,1H),7.63–7.56(m,1H),7.42–7.3 3(m,2H),3.80(s,3H),3.20(t,J=7.7Hz,2H),3.10(t,J=7.4Hz,2H),2.24(p,J=7.6Hz,2H). 13C NMR (100MHz, Chloroform-d) δ171.5,162.0,149.0,138.7,137.5,131.7,130.7,125.0,122.7,120.8,119.3,114.4,34.9,30.6,29.9,23.3.HRMS (ESI): Exact mass calculated for C 16 H 15 N2O([M+H] + ):251.1179,Found:251.1179.

[0086] Example 17:

[0087] Synthesis of 5-methyl-8,9,10,11-tetrahydrodibenzo[b,h][1,6]naphthyridin-6(5H)-one:

[0088]

[0089] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), cyclohexanone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (SiO2, ethyl acetate:dichloromethane = 1:50) to obtain 64.2 mg of white solid product 4c in 81% yield (mp 166.5–167.1°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.84(dd,J=7.9,1.4Hz,1H),8.37(s,1H),7.57(ddd,J=8.6,7.2,1.6Hz,1H),7.41–7.30(m, 2H), 3.78 (s, 3H), 3.11 (t, J = 6.4Hz, 2H), 2.95 (t, J = 6.3Hz, 2H), 1.99 (qd, J = 6.4, 2.9Hz, 2H), 1.89 (qd, J = 6.3, 2.8Hz, 2H). 13 C NMR(100MHz,Chloroform-d)δ163.0,161.8,147.5,138.9,136.4,132.7,130.6,1 25.0,122.6,120.7,118.9,114.4,33.5,29.8,28.8,23.0,22.7.HRMS(ESI):Exact mass calculated forC17 H 17 N2O([M+H] + ):265.1335,Found:265.1336.

[0090] Example 18:

[0091] Synthesis of 5-methyl-5,8,9,10,11,12-hexahydro-6H-benzo[h]cyclohepta[b][1,6]naphthyridin-6-one:

[0092]

[0093] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), cycloheptanone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (SiO2, ethyl acetate:dichloromethane = 1:50 elution) to obtain 65.1 mg of white solid product 4d in a yield of 78% (mp 212.8–213.0°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.86(d,J=7.7Hz,1H),8.36(s,1H),7.55(t,J=7.4Hz,1H),7.38–7.3 0(m,2H),3.77(s,3H),3.32–3.20(m,2H),2.99–2.89(m,2H),1.96–1.88(m,2H),1.84–1.67(m,4H). 13 C NMR(100MHz,Chloroform-d)δ168.5,161.8,147.2,138.9,138.3,135.7,130.5,125. 0,122.6,120.7,118.9,114.4,40.1,35.2,32.4,29.8,28.2,26.6.HRMS(ESI):Exact mass calculated for C 18 H 19 N2O([M+H] + ):279.1492,Found:279.1493.

[0094] Example 19:

[0095] Synthesis of 5-methyl-8,9,10,11,12,13-hexahydrobenzo[h]cycloocta[b][1,6]naphthyridin-6(5H)-one:

[0096]

[0097] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), cyclooctanone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 68.4 mg of the product 4e as a light yellow solid in a yield of 78% (mp 174.1–174.5°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.98–8.83(m,1H),8.40(s,1H),7.62–7.52(m,1H),7.43–7.30(m,2H ),3.79(s,3H),3.20–3.12(m,2H),2.98–2.90(m,2H),1.88(s,2H),1.77(s,2H),1.44–1.36(m,4H). 13 C NMR(100MHz,Chloroform-d)δ166.8,162.0,147.9,138.9,136.7,136.0,130.5,125.1, 122.6,120.9,119.3,114.4,35.3,32.3,31.9,30.9,29.8,26.0,25.9.HRMS(ESI):Exact masscalculated for C 19 H 21 N2O([M+H] + ):293.1648,Found:293.1648.

[0098] Example 20:

[0099] Synthesis of ethyl 2,6-dimethyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0100]

[0101] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl acetoacetate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography (SiO2, ethyl acetate:dichloromethane = 1:50) to obtain 68.4 mg of the product 4f as a light yellow solid in a yield of 77% (mp 181.6–181.9°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ9.15(s,1H),8.86(d,J=7.8Hz,1H),7.63(t,J=7.8Hz,1H),7 .40–7.31(m,2H),4.43(q,J=7.1Hz,2H),3.77(s,3H),3.01(s,3H),1.45(t,J=7.1Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ165.8,164.1,161.1,151.1,140.0,139.6,132.1,12 5.9,124.9,122.9,119.8,118.4,114.6,61.5,29.8,25.7,14.3.HRMS(ESI):Exact mass calculated for C 17 H 17 N2O3([M+H] + ):297.1234,Found:297.1234.

[0102] Example 21:

[0103] Synthesis of ethyl 2-ethyl-6-methyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0104]

[0105] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl propionyl acetate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to the reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 4 g (68.8 mg) of a light yellow solid product with a yield of 74% (mp 153.1–153.3° C.); the product was characterized as follows: 1H NMR(400MHz,Chloroform-d)δ9.15(s,1H),8.92(dd,J=7.9,1.4Hz,1H),7.68–7.59(m,1H),7. 42–7.34(m,2H),4.43(q,J=7.1Hz,2H),3.79(s,3H),3.39(q,J=7.4Hz,2H),1.47–1.42(m,6H). 13 CNMR(100MHz,Chloroform-d)δ168.3,165.9,161.2,151.1,140.0,139.6,132.0,126. 1,124.9,122.9,120.2,118.2,114.6,61.5,30.7,29.9,14.3,13.1.HRMS(ESI):Exact masscalculated for C 18 H 19 N2O3([M+H] + ):311.1390,Found:311.1391.

[0106] Example 22:

[0107] Synthesis of ethyl 2-cyclopropyl-6-methyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0108]

[0109] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl 3-cyclopropyl-3-carbonyl-propionate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to the reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 67.6 mg of a light yellow solid product 4h with a yield of 70% (mp 176.0–176.5° C.); the product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ9.07(s,1H),8.70(dd,J=7.9,1.4Hz,1H),7.64–7.56(m,1H),7.32(dd,J=14.4,7.6Hz,2H) ,4.45(q,J=7.1Hz,2H),3.75(s,3H),3.30(ddd,J=12.7,8.1,4.7Hz,1H),1.49–1.41(m,5H),1.19(dq,J=6.8,3.5Hz,2H).13 C NMR(100MHz,Chloroform-d)δ168.1,166.3,161.1,151.0,140.0,139.2,132.0,125. 7,124.9,122.7,120.0,117.2,114.5,61.5,29.8,15.1,14.3,13.1.HRMS(ESI):Exact mass calculated for C 19 H 19 N2O3([M+H] + ):323.1390,Found:323.1390.

[0110] Example 23:

[0111] Synthesis of ethyl 2-cyclobutyl-6-methyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0112]

[0113] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl 3-cyclobutyl-3-oxopropionate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 72.6 mg of the light yellow solid product 4i in a yield of 72% (mp 142.5–143.2°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ9.12(s,1H),9.03(d,J=7.8Hz,1H),7.72–7.61(m,1H),7.46–7.38(m,2H),4.52(p,J=8.4Hz,1H),4.42(q, J=7.1Hz,2H),3.81(s,3H),2.64(pd,J=9.2,2.2Hz,2H),2.50–2.39(m,2H),2.17–2.08(m,1H),2.02–1.97(m,1H),1.44(t,J=7.1Hz,3H). 13C NMR(100MHz,Chloroform-d)δ168.3,166.0,161.3,150.9,140.0,139.4,132.0,126.1,1 24.6,123.0,120.4,118.0,114.6,61.5,40.9,29.9,27.7,18.2,14.3.HRMS(ESI):Exact mass calculated for C 20 H 21 N2O3([M+H] + ):337.1547,Found:337.1547.

[0114] Example 24:

[0115] Synthesis of ethyl 2-cyclohexyl-6-methyl-5-oxo-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0116]

[0117] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl 3-cyclohexyl-3-oxopropionate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 77.6 mg of white solid product 4j in a yield of 71% (mp 142.4–143.2° C.); the product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ9.10(s,1H),8.96(dd,J=7.9,1.6Hz,1H),7.69–7.61(m,1H),7.44–7.35(m,2 H),4.44(q,J=7.1Hz,2H),3.80(s,3H),3.72(td,J=11.2,3.2Hz,1H),2.06–1.73(m,8H),1.52–1.42(m,5H). 13 C NMR(100MHz,Chloroform-d)δ170.7,166.4,161.3,151.0,140.0,139.4,132.0,126.1,125 .0,123.9,120.4,117.9,114.5,61.6,43.5,32.7,29.9,26.6,26.2,14.3.HRMS(ESI):Exact mass calculated for C22 H 25 N2O3([M+H] + ):365.1860,Found:365.1860.

[0118] Example 25:

[0119] Synthesis of ethyl 6-methyl-5-oxo-2-trifluoromethyl-5,6-dihydrobenzo[h][1,6]naphthyridine-3-carboxylate:

[0120]

[0121] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), ethyl trifluoroacetoacetate (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 71.4 mg of the light yellow solid product 4k in a yield of 68% (mp 192.0–192.5°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ9.15(s,1H),8.92–8.83(m,1H),7.75–7.67(m,1H) ),7.47–7.39(m,2H),4.49(q,J=7.1Hz,2H),3.82(s,3H),1.45(t,J=7.2Hz,3H). 13 C NMR (100MHz, Chloroform-d) δ164.7, 160.0, 150.6, 148.6 (q, J = 36.4Hz), 140.4, 140. 0,133.1,126.3,123.5,121.6,120.8(q,J=276.7Hz),119.1,114.8,62.7,30.2,14.0. 19 F NMR(376MHz,Chloroform-d)δ-64.4.HRMS(ESI): Exact mass calculated for C 17 H 14 F3N2O3([M+H] + ):351.0951,Found:351.0950.

[0122] Example 26:

[0123] Synthesis of 2,6-dimethyl-3-acetylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0124]

[0125] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), acetylacetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 60.7 mg of the light yellow solid product 41 in a yield of 76% (mp 224.1–224.9°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ9.01(s,1H),8.91(dd,J=7.9,1.6Hz,1H),7.72–7.62(m,1H),7.45–7.35(m,2H),3.80(s,3H),2.96(s,3H),2.72(s,3H). 13 C NMR(100MHz,Chloroform-d)δ199.2,163.3,161.1,150.8,140.0,138.3,132.3,131.4,126.0,123.1,119.8,118.2,114.6,29.9,29.2,26.0.HRMS(ESI): Exact mass calculated for C 16 H 15 N2O2([M+H] + ):267.1128,Found:267.1128.

[0126] Example 27:

[0127] Synthesis of 6-methyl-5,8,9,10-tetrahydrodibenzo[b,h][1,6]naphthyridine-6,11-dione:

[0128]

[0129] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), 1,3-cyclohexanedione (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to the reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 66.7 mg of a light yellow solid product 4m, with a yield of 80% (mp 264.3–264.6°C); the product was characterized as follows: 1H NMR(400MHz,Chloroform-d)δ9.26(s,1H),8.94–8.78(m,1H),7.74–7.60(m,1H),7.42–7 .32(m,2H),3.77(s,3H),3.32(t,J=6.2Hz,2H),2.83–2.75(m,2H),2.28(p,J=6.4Hz,2H). 13 C NMR(100MHz,Chloroform-d)δ196.6,167.2,161.1,152.4,140.2,137.0,132.5,12 7.6,126.3,122.9,119.9,119.8,114.7,38.7,33.4,29.9,21.5.HRMS(ESI):Exact mass calculated forC 17 H 15 N2O2([M+H] + ):279.1128,Found:279.1128.

[0130] Example 28:

[0131] Synthesis of 2,6-dimethyl-3-chlorobenzo[h][1,6]naphthyridin-5(6H)-one:

[0132]

[0133] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), chloroacetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%), and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure, and the residue was purified by column chromatography to obtain 57.3 mg of the product 4n as a light yellow solid with a yield of 74% (mp 214.1–214.7°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ8.81(dd,J=7.9,1.4Hz,1H),8.59(s,1H),7.65–7.56(m,1H),7.42–7.31(m,2H),3.77(s,3H),2.82(s,3H). 13C NMR(100MHz,Chloroform-d)δ161.1,160.7,147.5,139.1,136.0,131.3,130.9,125.3,122.9,120.0,120.0,114.5,29.9,23.7.HRMS(ESI):Exact masscalculated for C 14 H 12 ClN2O([M+H] + ):259.0633,Found:259.0633.

[0134] Example 29:

[0135] Synthesis of 2-ethyl-3-chloro-6-methylbenzo[h][1,6]naphthyridin-5(6H)-one:

[0136]

[0137] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), 1-chlorobutan-2-one (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 54.7 mg of light yellow solid product 4o in a yield of 67% (mp 166.4–167.1°C). The product was characterized as follows: 1 H NMR(400MHz,Chloroform-d)δ8.87(d,J=7.9Hz,1H),8.60(s,1H),7.62(t,J=7.7Hz,1H), 7.38(dd,J=13.6,7.7Hz,2H),3.79(s,3H),3.14(q,J=7.4Hz,2H),1.46(t,J=7.4Hz,3H). 13 C NMR(100MHz,Chloroform-d)δ164.8,160.8,147.6,139.1,136.0,131.3,130.5,125.4,122.9,120.3,119.8,114.5,29.9,29.4,11.7.HRMS(ESI): Exact mass calculated for C 15 H 14 ClN2O([M+H] + ):273.0789,Found:273.0788.

[0138] Example 30:

[0139] Synthesis of 2,6-dimethyl-3-bromobenzo[h][1,6]naphthyridin-5(6H)-one:

[0140]

[0141] Under light conditions, N-(2-cyanophenyl)-N-methylacrylamide (0.3 mmol), bromoacetone (3 mmol), sulfonium salt (0.45 mmol), 4-CzIPN (5 mol%) and trifluorotoluene (3 mL) were added to a reaction tube and stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by column chromatography to obtain 56.2 mg of the light yellow solid product 4p in a yield of 62% (mp 176.0–176.5°C). The product was characterized as follows: 1 H NMR (400MHz, Chloroform-d) δ8.87–8.70(m,2H),7.62(t,J=7.8Hz,1H),7.41–7.32(m,2H),3.77(s,3H),2.85(s,3H). 13 CNMR(100MHz,Chloroform-d)δ162.2,160.5,148.1,139.5,139.1,131.4,125.2,122.9,120.6,120.1,120.0,114.6,29.9,26.0.HRMS(ESI):Exact mass calculated forC 14 H 12 BN2O([M+H] + ):303.0128,Found:303.0126.

Claims

1. A method for synthesizing a benzo[h][1,6]naphthyridin-5(6H)-one skeleton compound, characterized in that: The general formula of the synthesis method is: Among them, R 1 = methyl, methoxy, fluoro, chloro, bromo, aryl or heterocyclyl; R 2 =alkyl or alicyclic group; R 3 = hydrogen or alkyl; R 4 、R 5 =aliphatic group, alicyclic group or halogen; Ar = aryl; X = chloride anion, tetrafluoroborate anion, trifluoromethanesulfonate anion; The synthetic method comprises the following steps: Under nitrogen protection and light, 0.3 mmol N-(2-cyanophenyl)acrylamide, 3 mmol ketone, 0.45 mmol sulfonium salt, 5 mol% photosensitizer and 3 mL solvent were added to the reaction tube, and the reaction was stirred. The reaction progress was monitored by TLC. After the reaction was complete, the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography to obtain the desired product.

2. The method for synthesizing a benzo[h][1,6]naphthyridin-5(6H)-one skeleton compound according to claim 1, characterized in that: In the general formula of the synthesis method, Photosensitizers are: 4-CzIPN, Eosin Y, Eosin Y disodium salt, fac-Ir(ppy)3 or Solvents are: trifluorotoluene, chlorobenzene, acetone, 1,2-dichloroethane, acetonitrile, N,N-dimethylformamide or N,N-dimethylacetamide; Sulfonium salts are: Ar = aryl, X = chloride anion, tetrafluoroborate anion or trifluoromethanesulfonate anion; Lighting: 10-60W white light or 5-60W blue light.

3. The method for synthesizing a benzo[h][1,6]naphthyridin-5(6H)-one skeleton compound according to claim 1, characterized in that: The N-(2-cyanophenyl)acrylamide compounds in the synthesis method are: N-(2-cyanophenyl)-N-methylacrylamide, N-(2-cyano-5-methylphenyl)-N-methylacrylamide, N-(2-cyano-5-methoxyphenyl)-N-methylacrylamide, N-(2-cyano-5-fluorophenyl)-N-methylacrylamide, N-(2-cyano-5-chlorophenyl)-N-methylacrylamide, N-(2-cyano-5-bromophenyl)-N-methylacrylamide, N-(2-cyano-4-methylphenyl)-N-methylacrylamide, N-(4-cyano-4'-fluoro-[1,1'-biphenyl]-3-yl)-N-methylacrylamide, N-(5-acetyl-2-cyano- N-(2-cyanophenyl)-N-(cyclopropylmethyl)acrylamide, N-(2-cyanophenyl)-N-(tetrahydro-2H-pyran-4-ylmethyl)acrylamide, and N-acryloyl-N-(2-cyanophenyl)glycine ethyl ester.

4. The method for synthesizing a benzo[h][1,6]naphthyridin-5(6H)-one skeleton compound according to claim 1, characterized in that: The ketone in the synthesis method is: acetone, 3-pentanone, cyclopentanone, cyclohexanone, cycloheptanone, cyclooctanone, ethyl acetoacetate, ethyl propionylacetate, 3-cyclopropyl-3-carbonyl-ethyl propionate, ethyl 3-cyclobutyl-3-oxopropionate, ethyl 3-cyclohexyl-3-oxopropionate, ethyl trifluoroacetoacetate, acetylacetone, 1,3-cyclohexanedione, chloroacetone, 1-chlorobutan-2-one (Example 29), or bromoacetone.

Images