A beta-silylpyridine molecule, synthesis method and application thereof

Abstract

The application discloses a kind of β-silicon-based pyridine molecules, the synthesis method of the compound and the pharmaceutical use of the compound.The β-silicon-based pyridine molecules of the application contain silicon-based and pyridine group, can be used in the late modification of pyridine drug synthesis, has important significance to the excavation of candidate drug, the fast construction nitrogen-containing heterocyclic drug molecule.The β-silicon-based pyridine molecules contain coordination function nitrogen atom, as ligand, the synthesized nitrogen-containing compound can be used for designing metal catalyst and material science.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a β-silylpyridine molecule, its synthesis method, and its application. Background Technology

[0002] Pyridine is an important structural unit in natural products, drug molecules, and functional materials. Pyridine drugs have been extensively studied and applied in recent years, and the pyridine molecular module has become the most frequently occurring nitrogen heterocycle in the approved small molecule drug dataset, mainly for the treatment of cancer and related diseases.

[0003] Pyridine drugs play a crucial role in cancer treatment because they are essential pharmacophores, both synthetically and naturally occurring, in heterocyclic compounds. Many pyridine derivatives can inhibit enzymes, receptors, and other targets, thereby controlling and treating cancer. Furthermore, pyridine scaffolds show great potential in targeted cancer therapy. The ring structure of pyridine significantly influences its pharmacological activity, and the US FDA has approved numerous drugs derived from pyridine. Many researchers are also actively exploring pyridine derivatives as potential therapeutic approaches for targeted cancer treatment, aiming to overcome obstacles encountered in traditional cancer therapies, such as low response rates and drug resistance. Therefore, pyridine and its derivatives possess enormous potential and diverse application prospects in the field of cancer treatment.

[0004] However, the relatively low reactivity of pyridine groups has limited its further development in applied chemistry. Therefore, developing new methods to modify pyridine is of great significance in medicinal chemistry and materials science. Pyridine modification is an important technique in drug design and materials science, which helps to create more effective, safer, and more specific molecular tools, and has a profound impact on the development of the pharmaceutical and materials fields. Summary of the Invention

[0005] The purpose of this invention is to address the above-mentioned shortcomings of the prior art by providing a β-silylpyridine molecule and its synthesis method.

[0006] In a first aspect, the present invention provides a β-silylpyridine molecule, the structural formula of which is as follows:

[0007] Wherein, R1 is an alkyl group, and R2 is any one of ester group, trifluoromethyl group, and H.

[0008] Preferably, the β-silylpyridine molecule is biologically active.

[0009] Secondly, the present invention provides a method for synthesizing β-silylpyridine molecules, characterized in that an olefin of Formula I and an N-methoxypyridinium salt of Formula II are mixed with tris(trimethylsilyl)silane and sodium bicarbonate, an organic solvent is added under an inert gas environment, and the mixture is magnetically stirred under blue light irradiation until the reaction is completed. The mixture is then concentrated under reduced pressure, and the crude product is purified by silica gel column chromatography to obtain compound of Formula III.

[0010] Preferably, the organic solvent includes one or more of dichloromethane, acetonitrile, methanol, and 1,2-dichloroethane.

[0011] Preferably, the blue light irradiation conditions are: wavelength 456nm, light intensity 10 watts, and irradiation duration 12-20 hours.

[0012] Thirdly, the present invention provides the application of β-silylpyridine molecules, characterized in that the β-silylpyridine molecules are used to inhibit tumor cell viability.

[0013] Compared with the prior art, the present invention has the following beneficial effects:

[0014] 1. This invention provides a β-silylpyridine molecule containing silyl and pyridine groups, which can be used for the later-stage modification of pyridine drugs and is of great significance for the discovery of candidate drugs and the rapid construction of nitrogen-containing heterocyclic drug molecules.

[0015] 2. The β-silylpyridine molecule contains a nitrogen atom with coordination function. As a ligand, the synthesized nitrogen-containing compounds can be used to design metal catalysts and in materials science.

[0016] 3. This invention provides a method for synthesizing β-silylpyridine molecules. The method uses N-methoxypyridinium salt as a reactant. Under visible light catalysis and in the presence of sodium bicarbonate, methoxy radicals are obtained through N-O bond cleavage. These methoxy radicals then serve as a motive force for capturing active hydrogen and a radical relay reagent, undergoing an intermolecular hydrogen transfer reaction with silanes to obtain silicon radicals. The resulting silicon radicals undergo radical addition with olefins and react with pyridine salts in a tandem manner. This method is innovative and feasible. Attached Figure Description Detailed Implementation

[0017] This invention utilizes methoxy radicals to extract hydrogen atoms from silanes to obtain silicon radicals, and then synthesizes β-silylpyridine via a radical cascade reaction. Using N-methoxypyridinium salt as the reactant, under visible light catalysis and in the presence of sodium bicarbonate, methoxy radicals are obtained through NO bond cleavage. These methoxy radicals further serve as a motive force and radical relay agent for extracting active hydrogen, undergoing an intermolecular hydrogen transfer reaction with silanes to yield silicon radicals. The resulting silicon radicals undergo radical addition with alkenes and react with pyridine salts in a cascade manner to design and synthesize β-silylpyridine molecules.

[0018] Example 1

[0019] In a 10 mL reaction tube, olefin 1a (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to give β-silylpyridine molecule 3a (47.1 mg, 78%).

[0020] 1 H NMR (500 MHz, CDCl3) δ 8.71 (d, J = 4.9 Hz, 1H), 7.95 – 7.92 (m,2H), 7.67 (d, J = 7.2 Hz, 2H), 6.90 – 6.87 (m, 2H), 4.17 (t, J = 6.6 Hz, 2H),3.95 (s, 3H), 3.84 (s, 3H), 3.00 -2.94 (m, 1H), 1.92 – 1.81 (m, 2H), 1.67 –1.58 (m, 1H), 1.40 (dd, J = 14.6, 6.2 Hz, 2H), 1.25 (dd, J = 14.5, 7.7 Hz,1H), 0.12 (s, 27H); 13C {1H} NMR (126 MHz, CDCl3) δ 167.5, 166.3, 165.8, 163.2,150.2, 150.2, 137.8, 131.6, 122.7, 121.5, 120.6, 113.4, 64.6, 55.4, 52.7,47.0, 35.3, 27.2, 15.4, 1.3; IR (ATR) νmax 3419, 2952, 1731, 1724, 1605,1253, 834, 618 cm -1 HRMS (ESI) Calculation for C 29 H 49 NO5Si4: [M+H] + = 603.2688.Found: 604.2753.

[0021] The reaction equation is as follows:

[0022]

[0023] Example 2

[0024] In a 10 mL reaction tube, olefin 1b (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3b (45.5 mg, 75%).

[0025] 1H NMR (500 MHz, CDCl3) δ 8.71 (dd, J = 4.9, 1.0 Hz, 1H), 7.93 – 7.90(m, 2H), 7.66 (d, J = 5.1 Hz, 2H), 7.39 – 7.36 (m, 2H), 4.20 (t, J = 6.5 Hz,2H), 3.95 (s, 3H), 2.99 -2.93 (m, 1H), 1.91 – 1.82 (m, 2H), 1.66 – 1.59 (m,1H), 1.42 – 1.38 (m, 2H), 1.24 (dd, J = 14.6, 7.8 Hz, 1H), 0.12 (s, 27H); 13 C{1H} NMR (126 MHz, CDCl3) 167.4, 165.8, 165.6, 150.2, 139.2, 137.8, 131,128.7, 128.6, 121.5, 120.6, 65.1, 52.7, 47.0, 35.2, 27.1, 15.4, 1.3; IR (ATR)νmax 3437, 2950, ​​2896, 1730, 1595, 1440, 1276, 1107, 836 cm -1 HRMS (ESI) Calculation for C 28 H 46 ClNO4Si4: [M+H] + = 608.2265. Found: 608.2249. The reaction equation is as follows:

[0026]

[0027] Example 3

[0028] In a 10 mL reaction tube, olefin 1c (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3c (48.1 mg, 75%).

[0029] 1 H NMR (500 MHz, CDCl3) δ 8.71 (d, J = 4.9 Hz, 1H), 8.10 (d, J = 7.9Hz, 2H), 7.68 (d, J = 8.4 Hz, 4H), 4.24 (t, J = 6.5 Hz, 2H), 3.96 (s, 3H),3.04 - 2.94 (m, 1H), 1.92 - 1.85 (m, 2H), 1.69 -1.62 (m, 1H), 1.45 - 1.38 (m,2H), 1.25 (dd, J = 13.9, 8.5 Hz, 1H), 0.14 - 0.10 (m, 27H); 13 C {1H} NMR (151MHz, CDCl3) δ 167.3, 165.7, 165.3, 150.1, 138.0, 134.3 (q, J = 32.5 Hz), 133.5, 130.0, 125.3 (q, J = 3.7 Hz), 123.6 (d, J = 272.6 Hz), 121.6, 120.8(q, J = 26.9 Hz),65.4, 52.7, 46.9, 35.1, 27.0, 15.5, 1.3; IR (ATR) νmax 3722,2952, 2895, 1730, 1562, 1441, 1278, 1117, 837 cm–1; HRMS (ESI) Calcd forC 29 H 46 F3NO4Si4: [M+H] + = 642.2529. Found: 642.2508.

[0030] The reaction equation is as follows:

[0031] Example 4

[0032] In a 10 mL reaction tube, olefin 1d (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3d (35.3 mg, 61%).

[0033] 1 H NMR (600 MHz, CDCl3) δ 8.70 (d, J = 4.1 Hz, 1H), 7.66 (d, J = 9.4Hz, 2H), 3.96 – 3.91 (m, 5H), 2.96 – 2.89 (s, 1H), 2.25 – 2.20 (m, 1H), 1.84(d, J = 11.6 Hz, 2H), 1.80 – 1.75 (m, 2H), 1.73 – 1.71(m, 2H), 1.63 – 1.60(m, 1H), 1.49 – 1.44 (m, 1H), 1.40 – 1.37(m, 3H), 1.26 – 1.20 (m, 5H), 0.13 (s, 27H); 13 C {1H} NMR (151 MHz, CDCl3) δ 176.1, 167.5, 165.8, 150.1, 137.7,121.5, 120.6, 64.0, 52.7, 47.0, 43.2, 35.2, 29.0, 29.0, 27.1, 25.7, 25.4,25.4, 154, 1.3; IR (ATR) νmax 3446, 2938, 2862, 1735, 1597, 1477, 1291, 837cm -1 HRMS (ESI) Calculation for C 28 H 53 NO4Si4: [M+H] + = 580.3124 Found: 580.3110. The reaction equation is as follows:

[0034]

[0035] Example 5

[0036] In a 10 mL reaction tube, olefin 1e (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 2:1) to give β-silylpyridine molecule 3e (45.3 mg, 77%).

[0037] 1 H NMR (600 MHz, CDCl3) δ 8.67 (dd, J = 5.0, 0.9 Hz, 1H), 7.74 (s,1H), 7.65 – 7.62 (m, 3H), 6.88 – 6.85 (m, 2H), 6.38 (s, 1H), 3.94 (s, 3H),3.82 (s, 3H), 3.42 – 3.37 (m, 1H), 3.14 – 3.09 (m, 1H), 3.03 – 2.98 (m, 1H), 2.13 – 2.08 (m, 1H), 1.95 – 1.89 (m, 1H), 1.42 (dd, J = 14.6, 7.1 Hz, 1H),1.23 (dd, J = 14.6, 7.0 Hz, 1H), 0.09 (s, 27H); 13 C {1H} NMR (151 MHz, CDCl3) δ167.3, 166.5, 165.6, 161.9, 150.0, 138.1, 128.5, 126.9, 121.2, 120.8, 113.5,55.3, 52.6, 45.0, 38.7, 38.0, 15.2, 1.2; IR (ATR) νmax 3330, 2948, 2893,1733, 1635, 1298, 11881112, 835 cm -1 HRMS (ESI) Calculation for C 28 H 48N2O4Si4: [M+H]+ = 589.2764. Found: 589.2744.

[0038] The reaction equation is as follows:

[0039]

[0040] Example 6

[0041] In a 10 mL reaction tube, olefin 1f (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3f (40.8 mg, 79%).

[0042] 1 H NMR (600 MHz, CDCl3) δ 8.72 (d, J = 5.0 Hz, 1H), 7.83 (s, 1H), 7.70 (d, J = 3.5 Hz, 1H), 7.23 – 7.21 (m, 2H), 6.91 – 6.88 (m, 1H), 6.80 (dd, J =8.7, 1.0 Hz, 2H), 4.14 (t, J = 8.3 Hz, 1H), 4.06 (dd, J = 8.8, 5.7 Hz, 1H), 3.97 (s, 3H), 3.47 - 3.44 (m, 1H), 1.52 (dd, J = 14.7, 8.1 Hz, 1H), 1.41 (dd,J = 14.7, 5.6 Hz, 1H), 0.11 (s, 27H); 13C {1H} NMR (151 MHz, CDCl3) δ 165.8,164.5, 158.7, 150.2, 150.2, 137.5, 129.3, 122.9, 121.1, 120.7, 114.6, 73.4,52.7, 46.8, 9.5, 1.2; IR (ATR) νmax 3448, 2948, 2894, 2468, 2076, 1735, 1597,1293, 1107, 835 cm -1 HRMS (ESI) Calculation for C 25 H 43 NO3Si4: [M+H] + = 518.2393.Found: 518.2380.

[0043] The reaction equation is as follows:

[0044]

[0045] Example 7

[0046] In a 10 mL reaction tube, 1 g of olefin (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 5:1) to give 3 g (42.1 mg, 73%) of β-silylpyridine molecules.

[0047] 1H NMR (500 MHz, CDCl3) δ 8.71 (d, J = 4.8 Hz, 1H), 7.74 (dd, J = 3.7,1.2 Hz, 1H), 7.68 (s, 2H), 7.52 (dd, J = 5.0, 1.2 Hz, 1H), 7.07 (t, 1H), 4.18(td, J = 6.6, 1.3 Hz, 2H), 3.95 (s, 3H), 3.01 – 2.94 (m, 1H), 1.89 – 1.80 (m,2H), 1.65 – 1.59 (m, 1H), 1.40 (dd, J = 14.5, 6.2 Hz, 2H), 1.25 (dd, J =14.5, 7.8 Hz (1H), 0.12 (s, 27H); 13 C {1H} NMR (151 MHz, CDCl3) δ 167.4, 165.7,162.2, 150.0, 137.9, 133.9, 133.3, 132.2, 127.6, 121.6, 120.7, 65.0, 52.7,46.9, 35.1, 27.1, 15.4, 1.3; IR (ATR) νmax 3450, 2952, 1726, 1431, 1268,1096, 837 cm–1; HRMS (ESI) Calcd for C 26 H 45 NO4SSi4: [M+Na] + = 602.2039. Found: 602.2020. The reaction equation is as follows:

[0048]

[0049] Example 8

[0050] In a 10 mL reaction tube, olefin 1h (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate as 100%) to give β-silylpyridine molecules 3h (46.9 mg, 73%).

[0051] 1 H NMR (500 MHz, CDCl3) δ 8.66 (d, J = 4.9 Hz, 1H), 7.63 (d, J = 7.1Hz, 2H), 7.46 (s, 1H), 3.94 (dd, J = 4.2, 1.5 Hz, 6H), 3.89 – 3.80 (m, 2H),3.51 (s, 3H), 2.92 – 2.86 (m, 1H), 1.73 – 1.70 (m, 2H), 1.58 – 1.50 (m, 2H),1.39 (dd, J= 15.1, 6.5 Hz, 1H), 1.21 (dd, J = 14.5, 7.0 Hz, 2H), 1.05 – 0.97(m, 1H), 0.08 (s, 27H); 13 C {1H} NMR (126 MHz, CDCl3) δ 167.8, 165.9, 155.1,151.3, 150.0, 148.6, 141.3, 137.6, 121.5, 120.4, 107.6, 52.6, 47.4, 41.2,39.2, 33.5, 29.6, 28.1, 25.3, 14.8, 1.2; IR (ATR) νmax 3429, 3110, 2945,1706, 1658, 1552, 1292, 836 cm -1 HRMS (ESI) Calculation for C 29 H 51 N5O4Si4: [M+H]+ = 646.3091. Found: 646.3071. The reaction equation is as follows:

[0052]

[0053] Example 9

[0054] In a 10 mL reaction tube, olefin 1i (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate as 100%) to obtain β-silylpyridine molecule 3i (43.7 mg, 64%, dr = 1:1).

[0055] 1 H NMR (500 MHz, CDCl3) δ 8.70 (t, 1H), 7.68 (d, J = 12.2 Hz, 2H), 4.58(dt, J = 4.3, 2.3 Hz, 1H), 4.32 (s, 1H), 4.15 – 4.09 (m, 1H), 4.07 – 4.01 (m,1H), 3.96 (s, 3H), 3.47 (dd, J = 16.2, 4.2 Hz, 1H), 3.41 (d, J = 16.2 Hz, 1H),2.97 – 2.91 (m, 1H), 1.79 (q, J = 7.9 Hz, 2H), 1.55 (d, J = 4.6 Hz, 3H), 1.42 –1.37 (m, 1H), 1.33 (d, J = 6.2 Hz, 3H), 1.21 (dd, J = 14.5, 7.6 Hz, 1H), 0.12 (s,27H); 13 C { 1H} NMR (126 MHz, CDCl3) δ 170.6, 166.9, 166.9 (166.8), 165.6,150.0, 138.0, 121.5 (121.0), 120.8, 66.3 (66.2), 63.2, 62.6, 61.1, 52.8,46.8, 38.3, 35.0 (35.0), 26.9 (26.8), 20.3 (20.3), 18.6 (18.6), 15.4 (15.3),1.2; IR (ATR) νmax 2948, 2901, 1800, 1739, 1601, 1445, 1193, 837cm –1 HRMS(ESI) Calculation for C 29 H 52 N₂O₇SSi₄: [M + H] + = 685.2645. Found: 685.2623.

[0056] The reaction equation is as follows:

[0057]

[0058] Example 10

[0059] In a 10 mL reaction tube, olefin 1j (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluting with ethyl acetate as 100%) to give β-silylpyridine molecule 3j (44.6 mg, 72%, dr = 1:1).

[0060] 1 H NMR (500 MHz, CDCl3) δ 8.70 (d, J= 4.1 Hz, 1H), 7.65 (s, 2H), 4.66 –4.60 (m, 1H), 3.95 (s, 3H), 2.97 – 2.91 (m, 1H), 2.12 – 2.05 (m, 2H), 2.00 –1.87 (m, 3H), 1.81-1.74 (m, 1H), 1.67-1.60 (m, 2H), 1.48-1.39 (m, 2H), 1.32-1.21 (m, 2H), 1.05-0.97 (m, 1H), 0.92-0.83 (m, 8H), 0.70 (dd, J =10.1, 7.0 Hz, 3H), 0.12 (s, 27H); 13 C { 1 H} NMR (126 MHz, CDCl3) δ 172.6(172.5), 167.0 (166.9), 165.7, 150.3, 137.8, 121.7 (121.6), 120.7, 74.0(74.0), 52.7, 47.0 (46.9), 46.6, 40.9, 34.2 (34.2), 33.9 (33.7), 33.0 (32.9),31.3, 26.2 (26.1), 23.3 (23.3), 22.0 (22.0), 20.7 (20.7), 16.2, 15.2 (15.0),1.2; IR (ATR) νmax 2952, 2897, 1733, 1642, 1446, 1291, 1127, 837 cm –1 HRMS(ESI) Calculation for C 31 H 59 NO4Si4: [M + H] + = 622.3594. Found: 622.3578.

[0061] The reaction equation is as follows:

[0062]

[0063] Example 11

[0064] In a 10 mL reaction tube, olefin 1k (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2a (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3k (29.0 mg, 55%).

[0065] 1 H NMR (600 MHz, CDCl3) δ 8.71 (d, J = 5.0 Hz, 1H), 7.65 (d, J = 16.0Hz, 2H), 7.21 (t, J = 7.5 Hz, 2H), 7.14 – 7.12 (m, 1H), 7.06 (d, J = 6.8 Hz,2H), 3.96 (s, 3H), 2.98 – 2.94 (m, 1H), 2.58 – 2.48 (m, 2H), 1.81 – 1.73 (m,2H), 1.51 – 1.45 (m, 1H), 1.35 (dd, J = 14.5, 5.9 Hz, 1H), 1.28 – 1.22 (m,2H), 0.13 (s, 27H); 13 C {1H} NMR (126 MHz, CDCl3) δ 167.9, 165.8, 149.9, 142.2,137.8, 137.8, 128.3, 128.2, 125.7, 121.6, 120.5, 52.7, 47.2, 38.5, 36.0,30.0, 15.4, 1.3; IR (ATR) νmax 3439, 2948, 1738, 1595, 1442, 1291, 834 cm -1 HRMS (ESI) Calculation for C 27 H 46 N2O3Si4: [M+H] + = 530.2757. Found: 530.2743.

[0066] The reaction equation is as follows:

[0067]

[0068] Example 12

[0069] In a 10 mL reaction tube, 1 L of olefin (0.1 mmol, 1.0 equiv.), 2b of N-methoxypyridinium salt (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give 3 L of β-silylpyridine molecules (28.8 mg, 53%).

[0070] 1 H NMR (500 MHz, CDCl3) δ 8.58 (d, J = 4.5 Hz, 1H), 7.94 (d, 2H), 7.63 (d, J = 7.8 Hz, 1H), 7.17 – 7.06 (m, 2H), 6.90 – 6.87 (m, 2H), 4.20 – 4.15(m, 2H), 3.85 (s, 3H), 2.96 – 2.83 (m, 1H), 1.90 – 1.80 (m, 2H), 1.67 – 1.58(m, 1H), 1.42 (dt, J = 13.8, 6.9 Hz, 2H), 1.24 (dd, J = 14.5, 7.6 Hz, 1H), 0.12 (s, 28H); 13 C {1H} NMR (126 MHz, CDCl3) δ 166.3, 165.9, 163.2, 149.1,136.9, 131.6, 122.8, 122.7, 121.5, 113.5, 64.7, 55.4, 46.7, 35.4, 27.2, 15.3,1.3;IR(ATR) νmax 3434, 2951, 1716, 1602, 1257, 1111, 838 cm–1; HRMS (ESI)Calcd for C 27 H 47NO3Si4 : [M+H] + = 546.2706. Found: 546.2691. The reaction equation is as follows:

[0071]

[0072] Example 13

[0073] In a 10 mL reaction tube, olefin 1m (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2c (0.15 mmol, 1.5 equiv.), tris(trimethylsilyl)silane (0.3 mmol, 3.0 equiv.), and sodium bicarbonate (0.15 mmol, 1.5 equiv.) were added. The reaction solution was protected with nitrogen and 1 mL of acetonitrile was added as organic solvent. The reaction was carried out under blue light (wavelength 456 nm, light intensity 10 W) with magnetic stirring for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to give β-silylpyridine molecule 3m (43.3 mg, 71%).

[0074] 1 H NMR (600 MHz, CDCl3) δ 8.76 (d, J = 5.1 Hz, 1H), 7.95 – 7.93 (m,2H), 7.37 (d, J = 5.0 Hz, 1H), 7.35 (s, 1H), 6.90 – 6.88 (m, 2H), 4.19 (td, J= 6.5, 2.5 Hz, 2H), 3.84 (s, 3H), 3.02 – 2.97 (m, 1H), 1.94 – 1.88 (m, 1H), 1.86 (dd, J = 12.5, 8.2 Hz, 1H), 1.68 – 1.60 (m, 1H), 1.41 (dd, J = 14.6, 6.3Hz, 2H), 1.26 (dd, J = 14.6, 7.6 Hz, 1H), 0.12 (s, 27H); 13C {1H} NMR (126 MHz, CDCl3) δ 167.8, 166.2, 163.3, 149.9, 139.2 (q, J = 34.4 Hz), 131.6, 122.7 (q,J = 273.4 Hz), 122.7, 118.1 (q, J = 3.7 Hz), 117.37(q, J = 3.42 Hz), 113.5,64.4, 55.5, 47.0, 35.2, 27.1, 15.4, 1.2; IR (ATR) νmax 3729, 2950, ​​2900,1714, 1608, 1410, 1168, 840cm -1 HRMS (ESI) Calculation for C 28 H 46 F3NO3Si4: [M+Na] += 636.2399. Found: 636.2380.

[0075] The reaction equation is as follows:

[0076]

[0077] Example 14

[0078] The compounds obtained in Examples 1-13 were prepared in concentration gradients (0.015 mM - 100 mM) and (0.015 μM - 100 μM). The effects of the compounds on the viability of hepatocellular carcinoma cells (HepG2) were determined using the MTT assay. The cytotoxicity of these compounds was studied using the Cell Counting Kit-8 (CCK-8) assay. The specific steps were as follows: Tumor cells were seeded in 96-well plates (3000 cells / well) and cultured overnight, then incubated with the compounds at concentrations of 0, 0.015, 0.046, 0.14, 0.41, 1.23, 3.7, 11.11, 33.33, and 100 mM / μM for 72 hours, respectively. Subsequently, 20 μL of CCK-8 solution (Beyotime, Shanghai Beyotime Biotechnology Co., Ltd.) was added to each well and incubated for 4 hours. The absorbance of each sample was measured at 450 nm using a microplate reader (Tecan Infinite M1000 Pro). The relative cell viability of each sample was normalized using DMSO control. IC50 is used to measure the inhibitory or active level of a compound or drug on a biological system. In this invention, the IC50 value of a compound against tumor cells was calculated using cell viability. (Cell viability % = OD570 of the sample treatment group / mean OD570 of the blank control group × 100%).

[0079] The statistical results of the activity of the compounds obtained in Examples 1-13 are shown in Table 1, indicating that the compounds obtained in Examples 1-13 have biological activity and can inhibit the activity of liver cancer cells.

[0080] Table 1. Statistical analysis of the activity of compounds obtained in Examples 1-13

[0081]

[0082] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A β-silylpyridine molecule, characterized in that, The structural formula of the molecule is as follows: 、 、 、 、 、 、 、 、 、 、 、 、 。 2. A method of synthesizing a beta-silicon-based pyridine molecule according to claim 1, characterized in that, The olefin shown in formula I, the N-methoxypyridinium salt shown in formula II, and tris(trimethylsilyl)silane and sodium bicarbonate are mixed, an organic solvent is added under inert gas environment, and magnetic stirring is carried out under blue light irradiation until the reaction is completed, then concentrated under reduced pressure, and the concentrated crude product is separated and purified by silica gel column chromatography to obtain a compound of formula III, which is selected from the specific compounds of claim 1: 。 3. The method of synthesis of claim 2, wherein, The organic solvent is selected from one or more of dichloromethane, acetonitrile, methanol, and 1,2-dichloroethane.

4. The method of synthesis of claim 2, wherein, The blue light irradiation is under the conditions of wavelength 456 nm, light intensity 10 watts, and irradiation time 12-20 hours.

5. Use of the β-silicon-based pyridine molecule according to claim 1, characterized in that The beta-silylpyridine molecule is used in the preparation of an antitumor drug.

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