Beta-silyl pyridine molecule as well as synthesis method and application thereof

Abstract

The invention discloses a beta-silyl pyridine molecule, a synthesis method of the compound and pharmaceutical application of the compound. The beta-silicon-based pyridine molecule contains a silicon group and a pyridine group, can be used for later transformation of pyridine drug synthesis, and has important significance in the aspects of exploration of candidate drugs and rapid construction of nitrogen-containing heterocyclic ring drug molecules. The beta-silyl pyridine molecule contains a nitrogen atom with a coordination function, and the synthesized nitrogen-containing compound can be used for designing a metal catalyst and material science as a ligand.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and specifically relates to a beta-silyl pyridine molecule and a synthesis method and application thereof. Background Art

[0002] Pyridine is an important structural unit in natural products, drug molecules and functional materials. Pyridine drugs have been widely studied and applied in recent years. The pyridine molecular module has become the most frequently appearing nitrogen heterocycle in the approved small molecule drug data set, mainly used to treat cancer and its related diseases.

[0003] Pyridine drugs play an important role in anticancer therapy because they are one of the essential pharmacophores in heterocyclic compounds that are both synthetic and naturally occurring. Many pyridine derivatives are able to inhibit enzymes, receptors, and other targets, thereby controlling and treating cancer. In addition, pyridine scaffolds have great potential in targeted cancer therapy. The pyridine-based ring structure has a significant impact on pharmacological activity, and the US FDA has approved a variety of drugs derived from pyridine. Many researchers are also working hard to explore pyridine derivatives as potential therapeutics for targeted anticancer therapy to overcome obstacles encountered in traditional anticancer therapy, such as low response rates and drug resistance. Therefore, pyridine and its derivatives have great potential and diverse application prospects in the field of anticancer therapy.

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

[0005] The object of the present invention is to provide a β-silylpyridine molecule and a synthesis method thereof in view of the above-mentioned deficiencies in the prior art.

[0006] In a first aspect, the present invention provides a β-silylpyridine molecule, the structural formula of the molecule is as follows: Wherein, R1 is an alkyl group, and R2 is any one of an ester group, a trifluoromethyl group, and H.

[0007] Preferably, the β-silylpyridine molecule is biologically active.

[0008] In a second aspect, the present invention provides a method for synthesizing a β-silylpyridine molecule, characterized in that the olefin represented by formula I and the N-methoxypyridinium salt represented by formula II are mixed with tri(trimethylsilyl)silane and sodium bicarbonate, an organic solvent is added under an inert gas environment, magnetic stirring is performed under blue light irradiation until the reaction is completed, the mixture is 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. Preferably, the organic solvent includes one or more of dichloromethane, acetonitrile, methanol, and 1,2-dichloroethane.

[0009] Preferably, the blue light irradiation is performed under the following conditions: wavelength 456 nm, light intensity 10 watts, and irradiation time 12-20 hours.

[0010] In a third aspect, the present invention provides an application of a β-silylpyridine molecule, characterized in that the β-silylpyridine molecule is used to inhibit tumor cell viability.

[0011] Compared with the prior art, the present invention has the following beneficial effects: 1. The present invention provides a β-silylpyridine molecule, which contains a silicon group and a pyridine group and can be used for the later modification of the synthesis of pyridine drugs. It is of great significance for the discovery of candidate drugs and the rapid construction of nitrogen-containing heterocyclic drug molecules.

[0012] 2. The β-silylpyridine molecule contains nitrogen atoms with coordination functions. As ligands, the synthesized nitrogen-containing compounds can be used to design metal catalysts and materials science.

[0013] 3. The present invention provides a method for synthesizing β-silylpyridine molecules. The method uses N-methoxypyridinium salt as a reaction raw material, obtains methoxy radicals by breaking N-O bonds under visible light catalysis and in the presence of sodium bicarbonate, and further serves as a power source and free radical relay reagent for capturing active hydrogen, and undergoes intermolecular hydrogen transfer reaction with silane to obtain silicon radicals. The obtained silicon radicals undergo free radical addition with olefins, and react with pyridinium salts in a tandem manner, thereby designing and synthesizing β-silylpyridine molecules. The synthesis method has certain innovation and feasibility. BRIEF DESCRIPTION OF THE DRAWINGS DETAILED DESCRIPTION

[0015] The present invention utilizes methoxy free radicals to capture hydrogen atoms in silane to obtain silicon free radicals, and realizes the synthesis of β-silylpyridine by free radical series connection. The present invention uses N-methoxypyridinium salt as a reaction raw material, and obtains methoxy free radicals by NO bond cleavage under visible light catalysis and in the presence of sodium bicarbonate. The methoxy free radical further serves as a power source and free radical relay reagent for capturing active hydrogen, and undergoes intermolecular hydrogen transfer reaction with silane to obtain silicon free radicals. The obtained silicon free radical undergoes free radical addition with olefins, and reacts with pyridinium salt in series, thereby designing and synthesizing β-silylpyridine molecules.

[0016] Example 1 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 5:1) to obtain β-silylpyridine molecule 3a (47.1 mg, 78%).

[0017] 1 H NMR (500 MHz, CDCl 3 ) 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); 13 C {1H} NMR (126 MHz, CDCl 3) 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) Calcd for C 29 H 49 NO 5 Si 4 : [M+H] + = 603.2688.Found: 604.2753. The reaction equation is as follows: Example 2 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3b (45.5 mg, 75%).

[0018] 1 H NMR (500 MHz, CDCl 3) 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, CDCl 3 ) 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)Calcd for C 28 H 46 ClNO 4 Si 4 : [M+H] + = 608.2265. Found: 608.2249. The reaction equation is as follows: Example 3 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 by nitrogen and 1 ml of organic solvent acetonitrile was added. The reaction was irradiated with blue light (wavelength 456 nm, light intensity 10 W) and magnetically stirred for 20 hours. After the reaction was completed, the reaction was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3c (48.1 mg, 75%).

[0019] 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 F 3 NO 4 Si 4 : [M+H] + = 642.2529. Found: 642.2508. The reaction equation is as follows: Example 4 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3d (35.3 mg, 61%).

[0020] 1 H NMR (600 MHz, CDCl 3 ) 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, CDCl 3 ) 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) Calcd for C 28 H 53 NO 4 Si 4 : [M+H] + = 580.3124 Found: 580.3110. The reaction equation is as follows: Example 5 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 2:1) to obtain β-silylpyridine molecule 3e (45.3 mg, 77%).

[0021] 1 H NMR (600 MHz, CDCl 3 ) 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) Calcd for C 28 H 48 N2 O 4 Si 4 : [M+H]+ = 589.2764. Found: 589.2744. The reaction equation is as follows: Example 6 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 by nitrogen and 1 ml of organic solvent acetonitrile was added. The reaction was irradiated with blue light (wavelength 456 nm, light intensity 10 W) and magnetically stirred for 20 hours. After the reaction was completed, the reaction was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3f (40.8 mg, 79%).

[0022] 1 H NMR (600 MHz, CDCl 3 ) 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) Calcd for C 25 H 43 NO 3 Si 4 : [M+H] + = 518.2393.Found: 518.2380. The reaction equation is as follows: Example 7 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 5:1) to obtain 3 g (42.1 mg, 73%) of β-silylpyridine molecule.

[0023] 1 H NMR (500 MHz, CDCl 3) 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, CDCl 3 ) 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 NO 4 SSi 4 : [M+Na] + = 602.2039. Found:602.2020. The reaction equation is as follows: Example 8 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 by nitrogen and 1 ml of organic solvent acetonitrile was added. The reaction was irradiated with blue light (wavelength 456nm, light intensity 10W) ​​and magnetically stirred for 20 hours. After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, ethyl acetate as eluent 100%) to obtain β-silylpyridine molecule 3h (46.9 mg, 73%).

[0024] 1 H NMR (500 MHz, CDCl 3 ) 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, CDCl 3 ) 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) Calcd for C 29 H 51 N 5 O 4 Si 4 : [M+H] + =646.3091. Found: 646.3071. The reaction equation is as follows: Example 9 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, ethyl acetate as eluent 100%) to obtain β-silylpyridine molecule 3i (43.7 mg, 64%, dr = 1:1).

[0025] 1 H NMR (500 MHz, CDCl 3 ) 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 { 1 H} NMR (126 MHz, CDCl 3) 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) Calcd for C 29 H 52 N 2 O 7 SSi 4 : [M + H] + = 685.2645. Found: 685.2623. The reaction equation is as follows: Example 10 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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the solution was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, ethyl acetate as eluent 100%) to obtain β-silylpyridine molecule 3j (44.6 mg, 72%, dr = 1:1).

[0026] 1 H NMR (500 MHz, CDCl 3 ) 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, CDCl 3 ) 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, 837cm –1 ; HRMS(ESI) Calcd for C 31 H 59 NO 4 Si 4 : [M + H] + = 622.3594. Found: 622.3578. The reaction equation is as follows: Embodiment 11 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 by nitrogen and 1 ml of organic solvent acetonitrile was added. The reaction was irradiated with blue light (wavelength 456 nm, light intensity 10 W) and magnetically stirred for 20 hours. After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3k (29.0 mg, 55%).

[0027] 1 H NMR (600 MHz, CDCl 3 ) 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, CDCl 3 ) 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) Calcd for C 27 H 46 N 2 O 3 Si 4: [M+H] + = 530.2757. Found: 530.2743. The reaction equation is as follows: Example 12 In a 10 ml reaction tube, olefin 1l (0.1 mmol, 1.0 equiv.), N-methoxypyridinium salt 2b (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 by nitrogen and 1 ml of acetonitrile was added. The reaction was stirred magnetically for 20 hours under blue light (wavelength 456 nm, light intensity 10 W). After the reaction was completed, the mixture was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3l (28.8 mg, 53%).

[0028] 1 H NMR (500 MHz, CDCl 3 ) 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, CDCl 3 ) 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 H47 NO 3 Si4 : [M+H] + = 546.2706. Found: 546.2691. The reaction equation is as follows: Embodiment 13 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 by nitrogen and 1 ml of organic solvent acetonitrile was added. The reaction was irradiated with blue light (wavelength 456nm, light intensity 10W) ​​and magnetically stirred for 20 hours. After the reaction was completed, the reaction was concentrated to dryness under reduced pressure. The concentrated crude product was separated and purified by silica gel column chromatography (eluent, petroleum ether: ethyl acetate as eluent = 10:1) to obtain β-silylpyridine molecule 3m (43.3 mg, 71%).

[0029] 1 H NMR (600 MHz, CDCl 3 ) 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); 13 C {1H} NMR (126 MHz,CDCl 3) 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, 840 cm -1 ; HRMS (ESI) Calcd for C 28 H 46 F 3 NO 3 Si 4 : [M+Na] += 636.2399. Found: 636.2380. The reaction equation is as follows: Embodiment 14 The compounds obtained in Examples 1-13 were configured into a certain concentration gradient (0.015 mM - 100 mM) and (0.015 μM - 100 μM), and the effects of the compounds on the viability of liver cancer cells (HepG2) were determined by MTT colorimetry. The cytotoxicity of these compounds was studied by Cell Counting Kit-8 (CCK-8) assay. The specific steps are as follows: Tumor cells were inoculated in a 96-well plate (3000 cells / well) and cultured overnight, and then incubated with these 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. Subsequently, 20 microliters of CCK-8 solution (Beyotime, Shanghai Biyuntian Biotechnology Co., Ltd.) was added to each well and incubated for 4 hours. The absorbance of each sample was measured at 450 nm by a microplate reader (Tecan infinite M1000 Pro). The relative cell viability of each sample was normalized with a DMSO control. IC50 is used to measure the level of inhibition or activity of a compound or drug on a biological system. The present invention calculates the IC50 value of a compound on tumor cells by cell viability. (Cell viability % = OD570 of sample treatment group / average OD570 of blank control group × 100%).

[0030] The statistical results of the activities of the compounds obtained in Examples 1-13 are shown in Table 1, which shows that the compounds obtained in Examples 1-13 have biological activity and can inhibit the activity of liver cancer cells.

[0031] Table 1 Activity statistics of compounds obtained in Examples 1-13 The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as 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: ; Wherein, R1 is an alkyl group, and R2 is any one of an ester group, a trifluoromethyl group, and H.

2. The β-silylpyridine molecule according to claim 1, characterized in that The β-silylpyridine molecule has biological activity.

3. A method for synthesizing a β-silylpyridine molecule, characterized in that: The olefin represented by formula I and the N-methoxypyridinium salt represented by formula II are mixed with tri(trimethylsilyl)silane and sodium bicarbonate, and an organic solvent is added under an inert gas environment. The mixture is magnetically stirred under blue light irradiation until the reaction is completed, and the mixture is concentrated under reduced pressure. The concentrated crude product is separated and purified by silica gel column chromatography to obtain a compound of formula III. .

4. The synthesis method according to claim 3, characterized in that The organic solvent includes one or more of dichloromethane, acetonitrile, methanol, and 1,2-dichloroethane.

5. The synthesis method according to claim 3, characterized in that The conditions of the blue light irradiation are: wavelength 456nm, light intensity 10 watts, and irradiation time 12-20 hours.

6. The use of the β-silylpyridine molecule according to claim 1, characterized in that: The β-silylpyridine molecule is used to inhibit tumor cell activity.

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