Synthesis method and application of a 2-oxazolidinone derivative

Abstract

The present invention discloses a synthesis method and application of 2-oxazolidinone derivatives, belonging to the technical field of organic synthesis. Starting from the p-quinone monoimine shown in Formula Ι and with the action of a specific acid catalyst, 2-oxazolidinone compounds with diverse structures shown in Formula Ⅱ can be obtained. This synthesis method is simple, environmentally friendly, has a wide substrate scope, is convenient for purification and has a high yield. At the same time, the compound shown in Formula Ⅱ obtained in the present invention exhibits certain anti-tumor effects and has development prospects in the field of anti-tumor drug preparation.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 2-oxazolidinone derivatives and applications thereof. Background Art

[0002] 2-Oxazolidinone, belonging to amino acid lactones, is a very important nitrogen-containing five-membered heterocycle, which has attracted strong curiosity and attention from biologists and chemists since 1951. 2-Oxazolidinone compounds are widely used in the fields of medicine, pesticides, chiral auxiliaries, etc. Among them, in the medical field, 2-oxazolidinone compounds have a wide range of applications: for example, (1) linezolid (also known as: morpholine oxazolidone), is an antibiotic containing the 2-oxazolidinone parent nucleus structure, which can inhibit the synthesis of bacterial proteins and shows good antibacterial effects; (2) the nitrosourea drug carmustine, the synthesis substrate of which is 2-oxazolidinone, and this type of drug has broad-spectrum antitumor activity; (3) amoxapine, a new type of 2-oxazolidinone antidepressant, can selectively and reversibly inhibit monoamine oxidase and has obvious curative effects on patients with severe depression. Since its first listing in France in 1985, it has a large application market. Thus, it can be seen that the 2-oxazolidinone skeleton is generally present in drug structures and plays a key role in the function of drugs. However, the current 2-oxazolidinone compounds are relatively single and lack diversity, especially polycyclic compounds containing the 2-oxazolidinone skeleton. Therefore, designing and developing efficient, simple and structurally diverse synthesis methods for 2-oxazolidinone compounds plays an important role in the development of related drugs.

[0003]

[0004] The important value of 2-oxazolidinone in natural products and drug synthesis has attracted many scientific researchers to conduct extensive preparative research on it. The traditional methods for preparing this skeleton mainly include: 1) cyclization of phosgene with amino alcohols; 2) transesterification of amino alcohols with cyclic or linear carbonates; 3) CO 2 insertion into aziridine; 4) addition of amino alcohols to CO 2 ; 5) addition of isocyanates to epoxides. However, these synthesis methods mainly have the following disadvantages: the structures of the obtained compounds are relatively single, expensive transition metal catalysts or highly toxic reagents are used, and there are safety problems during the preparation process, which are not conducive to large-scale production. Summary of the Invention

[0005] The technical problem to be solved by the present invention is to provide a method for synthesizing structurally diverse 2-oxazolidinone compounds in view of the existing synthesis routes that require the use of expensive reagents, have safety problems, and lack structural diversity of compounds. The synthesis method is simple, environmentally friendly, has a wide substrate scope, is convenient for purification and has a high yield, and can obtain structurally diverse and complex 2-oxazolidinone compounds.

[0006] Another object of the present invention is to provide the use of a class of 2-oxazolidinone compounds in the field of preparation of anti-tumor drugs.

[0007] To achieve the above object, the present invention adopts the following technical scheme:

[0008] The present invention provides a method for synthesizing a 2-oxazolidinone derivative, which uses a p-quinoneamine shown in Formula I as a raw material and reacts under the action of a Bronsted acid or a Lewis acid as a catalyst to obtain a 2-oxazolidinone compound shown in Formula II;

[0009]

[0010] Wherein, means or

[0011] R 1 is selected from: C1-C8 straight-chain or branched-chain alkyl containing 0-2 unsaturated double bonds, C1-C8 cycloalkyl, C2-C8 alkynyl;

[0012] R 2 is taken from: unsubstituted or substituted C3-C6 cycloalkyl, 3-6 membered heterocyclic group, aryl; the substitution includes any one of mono-substitution to tri-substitution, and the substituents are selected from halogen (F, Cl, Br, I), nitro, C1-C8 alkyl, C1-C8 alkoxy, halogenated C1-C8 alkyl, phenyl or

[0013] In an embodiment of the present invention, the aryl is selected from: phenyl, naphthyl, thiophenyl, furyl, benzothiophenyl, benzofuryl.

[0014] In an embodiment of the present invention, the 3-6 membered heterocyclic group contains 1-3 heteroatoms, and the heteroatoms are selected from N, O, S. More specifically, it can be selected: tetrahydropyran ring, morpholine ring, piperidine ring, piperazine ring.

[0015] In an embodiment of the present invention, the C2-C8 alkynyl is R 3 is H, C1-C6 alkyl.

[0016] In an embodiment of the present invention, R 1Specifically, it may be a C1-6 linear or branched alkyl group, C n H 2n+1 -C=C-C n H 2n -,

[0017] Most preferably, the 2-oxazolidinone compound has any of the following structures:

[0018]

[0019] In one embodiment of the present invention, the reaction is carried out in an organic solvent; the organic solvent is any one or more of dichloromethane, chloroform, toluene, acetonitrile, and tetrahydrofuran; preferably dichloromethane.

[0020] In one embodiment of the present invention, the catalyst includes any one of p-toluenesulfonic acid, trifluoroacetic acid, camphorsulfonic acid, ferric chloride, aluminum chloride, indium trifluoromethanesulfonate, and boron trifluoride diethyl ether; preferably boron trifluoride diethyl ether.

[0021] In one embodiment of the present invention, the molar ratio of the catalyst shown in formula Ι to quinoneamine is (0.05 - 1):1, preferably 0.1:1.

[0022] In one embodiment of the present invention, the temperature of the reaction is from -70 °C to 30 °C, preferably 30 °C, and the time is 12 - 24 h.

[0023] The present invention also provides a 2-oxazolidinone derivative, the structure of which is shown as follows:

[0024]

[0025] The present invention also provides the use of the above 2-oxazolidinone derivative in the preparation of anti-cancer drugs.

[0026] In one embodiment of the present invention, the cancers include: lung cancer, bladder cancer, breast cancer, and cervical cancer.

[0027] Compared with the prior art, the present invention has the following beneficial effects:

[0028] The reported methods for synthesizing 2-oxazolidinone compounds have obvious disadvantages. Among them, expensive metal catalysts need to be used, and some require the use of toxic or dangerous reagents, which seriously restricts the industrial production of 2-oxazolidinone compounds. In view of the above situation, the present invention has developed a synthesis method with simple operation, a wide range of substrate applications, a cheap and easily available catalyst with a small dosage of only 0.1 equivalent, and at the same time, it has greatly enriched the types of compounds containing the 2-oxazolidinone skeleton, promoting the drug development of this type of skeleton compound.

[0029] The compounds of the present invention have a certain inhibitory effect on the proliferation of various tumor cells and have potential application prospects in the development of anti-tumor drugs. Detailed Description of the Invention

[0030] The technical solutions of the present invention will be further described in detail below with reference to specific examples.

[0031] The present invention relates to the following chemical abbreviations: Bn is benzyl, Et is ethyl, n Bu is n-butyl, t-Bu is tert-butyl, n hexyl is n-hexyl.

[0032] The p-quinoneamines of formula I involved in the present invention can be prepared according to existing literature, such as Org. Lett. 2021, 23, 7873-7877.

[0033] Example 1

[0034] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0035]

[0036] The preparation method is as follows: Under air conditions, dissolve S1 (0.2 mmol, 62 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2 hours. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1) to obtain the product P1 (48.9 mg, 95%), which is a white solid.

[0037] Characterization data: 1 H NMR (300 MHz, CDCl 3 ) δ 7.43-7.28 (m, 5H), 6.24 (dd, J = 10.5, 1.9 Hz, 1H), 5.96 (d, J = 10.5 Hz, 1H), 4.63-4.58 (m, 1H), 4.54 (d, J = 15.8 Hz, 1H), 4.48 (d, J = 15.7 Hz, 1H), 2.99 (dd, J = 17.8, 2.5 Hz, 1H), 2.68 (dd, J = 17.8, 4.0 Hz, 1H), 1.43 (s, 3H). 13 C NMR (125 MHz, CDCl 3)δ192.5,156.9,143.6,137.8,129.1,128.2,128.1,128.0,79.0,58.9,44.7,37.0,21.5.HRMS(ESI)calculated for C 15 H 15 NNaO 3 [M+Na] + :280.0944,found280.0939.

[0038] Example 2

[0039] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0040]

[0041] The preparation method is as follows: Under air conditions, dissolve S2 (0.2 mmol, 71.8 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1) to obtain the product P2 (53.2 mg, 98%), which is a white solid.

[0042] Characterization data: 1 H NMR (300 MHz, CDCl 3 ) δ 7.24 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 7.7 Hz, 2H), 6.23 (d, J = 10.5 Hz, 1H), 5.95 (d, J = 10.5 Hz, 1H), 4.58 (s, 1H), 4.52 (d, J = 15.6 Hz, 1H), 4.42 (d, J = 15.7 Hz, 1H), 2.98 (d, J = 17.8 Hz, 1H), 2.67 (dd, J = 17.8, 3.8 Hz, 1H), 2.35 (s, 3H), 1.43 (s, 3H). 13 C NMR (75 MHz, DMSO-d 6 ) δ 193.7, 156.3, 144.5, 136.3, 135.3, 128.9, 127.3, 126.9, 78.4, 58.7, 43.0, 36.8, 20.5, 20.0. HRMS(ESI) calculated for C 16 H 17 NNaO3 [M + Na] + : 294.1101, found 294.1095.

[0043] Example 3

[0044] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0045]

[0046] The preparation method is as follows: Under air conditions, dissolve S3 (0.2 mmol, 85.4 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 25 minutes. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1) to obtain the product P3 (52.6 mg, 96%), which is a white solid.

[0047] Characterization data: 1 H NMR (300 MHz, CDCl 3 ) δ 7.41 - 7.29 (m, 2H), 7.12 - 6.99 (m, 2H), 6.26 (dd, J = 10.5, 2.0 Hz, 1H), 5.99 (d, J = 10.4 Hz, 1H), 4.65 - 4.56 (m, 1H), 4.48 (s, 2H), 2.99 (dd, J = 17.7, 2.5 Hz, 1H), 2.68 (dd, J = 17.8, 4.0 Hz, 1H), 1.44 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.4, 162.6 (d, J = 245.6 Hz), 156.8, 143.4, 133.61 (d, J = 3.2 Hz), 129.78 (d, J = 8.1 Hz), 128.3, 116.0 (d, J = 21.4 Hz), 79.1, 58.9, 44.0, 37.0, 21.6. HRMS (ESI) calculated for C 15 H 14 FNNaO 3 [M + Na] + : 298.0850, found 298.0845.

[0048] Example 4

[0049] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0050]

[0051] The preparation method is as follows: Under air conditions, dissolve S4 (0.2 mmol, 69.4 mg) in CH 2 Cl 2 (1.0 mL), and add BF 3 ·Et 2 (2.5 μL, 10 mol%) at room temperature. After reacting for 30 minutes, the reaction is terminated. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P4 (54.9 mg, 94%), which is a white solid.

[0052] Characterization data: 1 H NMR (300 MHz, CDCl 3 ) δ 7.39 - 7.26 (m, 4H), 6.28 (dd, J = 10.5, 2.0 Hz, 1H), 6.00 (d, J = 10.4 Hz, 1H), 4.65 - 4.56 (m, 1H), 4.47 (s, 2H), 3.00 (dd, J = 17.8, 2.4 Hz, 1H), 2.69 (dd, J = 17.8, 3.9 Hz, 1H), 1.43 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.3, 156.8, 143.2, 136.3, 134.1, 129.4, 129.3, 128.4, 79.1, 58.9, 44.1, 37.0, 21.6. HRMS (ESI) calculated for C 15 H 14 ClNNaO 3 [M+Na] + : 314.0554, found 314.0551.

[0053] Example 5

[0054] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0055]

[0056] The preparation method is as follows: Under air conditions, dissolve S5 (0.2 mmol, 78.2 mg) in CH 2 Cl 2 (1.0 mL), and add BF 3 ·Et2 O (2.5 μL, 10 mol%), and the reaction ended after 30 minutes. The reaction solution was directly concentrated under reduced pressure, and the crude product was separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 2:1) to obtain product P5 (61.4 mg, 92%), which was a white solid.

[0057] Characterization data: 1 H NMR (300 MHz, CDCl 3 ) δ 7.49 (d, J = 8.2 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H), 6.29 (dd, J = 10.4, 1.4 Hz, 1H), 6.01 (d, J = 10.5 Hz, 1H), 4.66 - 4.57 (m, 1H), 4.52 - 4.37 (m, 2H), 3.00 (dd, J = 17.8, 2.5 Hz, 1H), 2.69 (dd, J = 17.8, 3.8 Hz, 1H), 1.43 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.3, 156.8, 143.2, 136.8, 132.2, 129.7, 128.4, 122.2, 79.1, 58.9, 44.1, 37.0, 21.6. HRMS (ESI) calculated for C 15 H 14 BrNNaO 3 [M + Na] + : 358.0049, found 358.0046.

[0058] Example 6

[0059] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0060]

[0061] The preparation method is as follows: Under air conditions, S6 (0.2 mmol, 68.6 mg) was dissolved in CH 2 Cl 2 (1.0 mL), and BF 3 ·Et 2 O (2.5 μL, 10 mol%) was added at room temperature. The reaction ended after 30 minutes. The reaction solution was directly concentrated under reduced pressure, and the crude product was separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 2:1) to obtain product P6 (55.6 mg, 97%), which was a white solid.

[0062] 11H NMR (300 MHz, CDCl 3 ) δ 7.33 - 7.26 (m, 2H), 6.88 (d, J = 8.5 Hz, 2H), 6.21 (dd, J = 10.4, 1.6 Hz, 1H), 5.94 (d, J = 10.5 Hz, 1H), 4.60 - 4.48 (m, 2H), 4.39 (d, J = 15.6 Hz, 1H), 3.81 (s, 3H), 2.98 (dd, J = 17.8, 2.3 Hz, 1H), 2.67 (dd, J = 17.8, 3.9 Hz, 1H), 1.44 (s, 3H). 13 13C NMR (125 MHz, CDCl 3 ) δ 192.5, 159.6, 156.8, 143.8, 129.8, 129.5, 128.0, 114.5, 79.0, 58.9, 55.4, 44.2, 37.0, 21.5. HRMS (ESI) calculated for C 16 15 17 NNaO 4 [M + Na] + : 310.1050, found 310.1067.

[0063] Example 7

[0064] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0065]

[0066] The preparation method is as follows: Under air conditions, dissolve S7 (0.2 mmol, 65.4 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 2:1) to obtain the product P7 (49.8 mg, 92%), which is a white solid.

[0067] 1 1H NMR (300 MHz, CDCl 3) δ 7.32 - 7.15 (m, 4H), 6.25 (dd, J = 10.5, 1.9 Hz, 1H), 6.00 (d, J = 10.5 Hz, 1H), 4.66 - 4.59 (m, 1H), 4.56 (s, 2H), 2.99 (dd, J = 17.8, 2.4 Hz, 1H), 2.69 (dd, J = 17.8, 4.0 Hz, 1H), 2.36 (s, 3H), 1.38 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.5, 156.6, 143.5, 136.4, 134.8, 131.0, 128.6, 128.31, 128.27, 126.4, 78.9, 58.9, 43.2, 37.1, 21.6, 19.4. HRMS (ESI) calculated for C 16 H 17 NNaO 3 [M + Na] + : 294.1101, found 294.1101.

[0068] Example 8

[0069] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0070]

[0071] The preparation method is as follows: Under air conditions, dissolve S8 (0.2 mmol, 71.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P8 (50.5 mg, 83%), which is a white solid.

[0072] 1 H NMR (300 MHz, CDCl 3) δ 8.26 - 8.15 (m, 2H), 7.76 (d, J = 7.7 Hz, 1H), 7.63 - 7.52 (m, 1H), 6.40 (dd, J = 10.5, 2.0 Hz, 1H), 6.07 (d, J = 10.4 Hz, 1H), 4.73 - 4.63 (m, 2H), 4.48 (d, J = 16.1 Hz, 1H), 3.03 (dd, J = 17.8, 2.4 Hz, 1H), 2.72 (dd, J = 17.9, 3.9 Hz, 1H), 1.47 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.1, 156.9, 148.6, 142.6, 139.8, 134.1, 130.2, 128.8, 123.2, 122.5, 79.2, 59.0, 44.0, 37.0, 21.8. HRMS (ESI) calculated for C 15 H 14 N 2 NaO 5 [M + Na] + : 325.0795, found 325.0796.

[0073] Example 9

[0074] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0075]

[0076] Preparation method: Under air conditions, dissolve S9 (0.2 mmol, 63.8 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. Directly concentrate the reaction solution under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P9 (41.5 mg, 79%), which is a white solid.

[0077] Characterization data: 1 H NMR (300 MHz, CDCl 3) δ 6.53 (dd, J=10.5, 2.0 Hz, 1H), 6.10 (d, J=10.5 Hz, 1H), 4.62 - 4.52 (m, 1H), 3.22 (dd, J=14.0, 6.8 Hz, 1H), 2.98 (dd, J=17.8, 2.3 Hz, 1H), 2.83 (dd, J=14.0, 7.9 Hz, 1H), 2.69 (dd, J=17.8, 3.9 Hz, 1H), 1.81 - 1.62 (m, 6H), 1.50 (s, 3H), 1.30 - 1.12 (m, 3H), 1.02 - 0.86 (m, 2H). 13 C NMR(125 MHz, CDCl 3 ) δ 192.6, 157.2, 143.3, 128.6, 78.5, 58.9, 47.5, 37.6, 37.1, 31.10, 31.05, 26.5, 25.88, 25.87, 21.7. HRMS(ESI) calculated for C 15 H 21 NNaO 3 [M + Na] + : 286.1414, found 286.1412.

[0078] Example 10

[0079] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0080]

[0081] Preparation method: Under air conditions, dissolve S10 (0.2 mmol, 64.2 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 1.5 hours. Directly concentrate the reaction solution under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P10 (44.6 mg, 84%), which is a yellow solid.

[0082] Characterization data: 1 H NMR(300 MHz, CDCl 3)δ6.52(d, J = 10.4 Hz, 1H), 6.12(d, J = 10.4 Hz, 1H), 4.60(s, 1H), 4.07 - 3.93(m, 2H), 3.44 - 3.25(m, 3H), 2.99(dd, J = 17.8, 2.3 Hz, 1H), 2.83(dd, J = 13.9, 8.4 Hz, 1H), 2.70(dd, J = 17.8, 3.7 Hz, 1H), 2.11 - 1.94(m, 1H), 1.67(t, J = 10.6 Hz, 2H), 1.51(s, 3H), 1.42 - 1.28(m, 2H). 13 C NMR(125 MHz, CDCl 3 )δ192.4, 157.2, 142.9, 128.8, 78.6, 67.6, 67.5, 59.0, 47.1, 37.0, 34.7, 31.0, 30.9, 21.7. HRMS(ESI) calculated for C 14 H 19 NNaO 4 [M + Na] + : 288.1206, found 288.1206.

[0083] Example 11

[0084] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0085]

[0086] Preparation method: Under air conditions, dissolve S11(0.2 mmol, 72.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O(2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P11(57.1 mg, 93%), which is a white solid.

[0087] Characterization data: 1 H NMR(300 MHz, CDCl 3) δ 7.92 - 7.72 (m, 4H), 7.59 - 7.44 (m, 3H), 6.24 (dd, J = 10.4, 1.8 Hz, 1H), 5.93 (d, J = 10.5 Hz, 1H), 4.77 - 4.60 (m, 3H), 3.00 (dd, J = 17.7, 2.2 Hz, 1H), 2.68 (dd, J = 17.8, 3.9 Hz, 1H), 1.45 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.5, 157.0, 143.6, 135.3, 133.4, 133.2, 129.1, 128.1, 127.93, 127.89, 126.8, 126.7, 126.5, 125.9, 79.1, 59.0, 45.0, 37.0, 21.6. HRMS (ESI) calculated for C 19 H 17 NNaO 3 [M + Na] + : 330.1101, found 330.1099.

[0088] Example 12

[0089] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0090]

[0091] Preparation method: Under air conditions, dissolve S12 (0.2 mmol, 72.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P12 (57.0 mg, 93%), which is a white solid.

[0092] 1 H NMR (300 MHz, CDCl 3)δ8.16(d, J = 8.0 Hz, 1H), 7.96 - 7.80(m, 2H), 7.65 - 7.38(m, 4H), 6.14(dd, J = 10.5, 1.9 Hz, 1H), 5.86(d, J = 10.5 Hz, 1H), 5.10 - 4.97(m, 2H), 4.64 - 4.55(m, 1H), 2.96(dd, J = 17.7, 2.3 Hz, 1H), 2.65(dd, J = 17.7, 4.1 Hz, 1H), 1.33(s, 3H). 13 C NMR(125 MHz, CDCl 3 )δ192.5, 156.6, 143.4, 134.0, 132.5, 131.4, 129.4, 129.0, 128.2, 127.2, 127.1, 126.4, 125.2, 123.6, 78.9, 59.0, 43.6, 37.0, 21.5. HRMS(ESI) calculated for C 19 H 17 NNaO 3 [M + Na] + : 330.1101, found 330.1099.

[0093] Example 13

[0094] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0095]

[0096] The preparation method is as follows: Under air conditions, dissolve S13(0.2 mmol, 70.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O(2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P13(40.4 mg, 68%), which is a white solid.

[0097] Characterization data: 1 H NMR(300 MHz, CDCl 3) δ 7.55 (d, J = 7.3 Hz, 1H), 7.48 (d, J = 8.0 Hz, 1H), 7.36 - 7.21 (m, 2H), 6.76 (s, 1H), 6.40 (dd, J = 10.5, 2.0 Hz, 1H), 6.01 (d, J = 10.4 Hz, 1H), 4.72 - 4.55 (m, 3H), 3.01 (dd, J = 17.8, 2.3 Hz, 1H), 2.71 (dd, J = 17.8, 4.0 Hz, 1H), 1.59 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.4, 156.3, 154.9, 152.6, 143.1, 128.6, 128.2, 124.9, 123.3, 121.4, 111.4, 106.1, 79.2, 58.7, 38.0, 37.0, 21.3. HRMS (ESI) calculated for C 17 H 15 NNaO 4 [M + Na] + : 320.0893, found 320.0893.

[0098] Example 14

[0099] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0100]

[0101] Preparation method: Under air conditions, dissolve S14 (0.2 mmol, 73.8 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluted with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1) to obtain the product P14 (55.2 mg, 88%), which is a white solid.

[0102] Characterization data: 1 H NMR (300 MHz, CDCl 3)δ 7.84 - 7.77 (m, 1H), 7.76 - 7.69 (m, 1H), 7.41 - 7.31 (m, 2H), 7.30 (s, 1H), 6.40 (dd, J=10.5, 2.0 Hz, 1H), 5.99 (d, J=10.5 Hz, 1H), 4.76 (s, 2H), 4.66 - 4.60 (m, 1H), 3.01 (dd, J=17.8, 2.6 Hz, 1H), 2.70 (dd, J=17.8, 4.0 Hz, 1H), 1.56 (s, 3H). 13 C NMR(125 MHz, CDCl 3 )δ 192.3, 156.4, 143.2, 141.2, 140.2, 139.5, 128.5, 124.9, 124.8, 123.8, 123.4, 122.6, 79.2, 59.0, 40.3, 37.0, 21.4. HRMS(ESI) calculated for C 17 H 15 NNaO 3 S [M + Na] + : 366.0665, found 366.0662.

[0103] Example 15

[0104] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0105]

[0106] Preparation method: Under air conditions, dissolve S15 (0.2 mmol, 77.8 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 30 minutes. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 1:1) to obtain the product P15 (51.2 mg, 77%), which is a white solid.

[0107] Characterization data: 1 H NMR(300 MHz, CDCl 3)δ7.59(d,J=7.9Hz,4H),7.50-7.40(m,4H),7.40-7.32(m,1H),6.32(dd,J=10.5,1.9Hz,1H),5.99(d,J=10.5Hz,1H),4.66-4.59(m,1H),4.55(s,2H),3.01(dd,J=17.8,2.4Hz,1H),2.70(dd,J=17.8,3.9Hz,1H),1.47(s,3H). 13 C NMR(125MHz,CDCl 3 )δ192.5,156.9,143.6,141.2,140.5,136.7,129.0,128.5,128.2,127.73,127.70,127.2,79.1,59.0,44.5,37.0,21.7.HRMS(ESI)calculated forC 21 H 19 NNaO 3 [M+Na] + :356.1257,found356.1257.

[0108] Example 16

[0109] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0110]

[0111] Preparation method: Under air conditions, dissolve S16 (0.2 mmol, 72.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O(2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P16 (44.3 mg, 72%), which is a pale yellow solid.

[0112] Characterization data: 1 H NMR(300MHz,CDCl 3) δ 8.02 (dd, J = 7.7, 0.9 Hz, 1H), 7.67 - 7.56 (m, 1H), 7.54 - 7.41 (m, 2H), 7.37 - 7.25 (m, 5H), 4.80 (t, J = 4.2 Hz, 1H), 4.74 (d, J = 16.1 Hz, 1H), 4.37 (d, J = 16.1 Hz, 1H), 3.18 (dd, J = 16.5, 4.4 Hz, 1H), 2.94 (dd, J = 16.5, 3.9 Hz, 1H), 1.61 (s, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.7, 156.9, 139.4, 137.6, 134.4, 131.2, 129.1, 128.8, 127.8, 127.6, 127.4, 127.3, 79.7, 61.0, 45.4, 39.1, 24.5. HRMS (ESI) calculated for C 19 H 17 NNaO 3 [M + Na] + : 330.1100, found 330.1095.

[0113] Example 17

[0114] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0115]

[0116] Preparation method: Under air conditions, dissolve S17 (0.2 mmol, 109.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with dichloromethane and methanol (dichloromethane: methanol = 20:1) to obtain the product P17 (82.3 mg, 94%), which is a white solid.

[0117] Characterization data: 1 H NMR (300 MHz, DMSO - d 6) δ 7.37 (s, 4H), 6.77 (d, J = 10.2 Hz, 2H), 6.01 (d, J = 10.4 Hz, 2H), 4.80 (s, 2H), 4.53 (d, J = 16.1 Hz, 2H), 4.42 (d, J = 16.1 Hz, 2H), 3.33 (s, 2H), 3.10 (dd, J = 17.6, 3.5 Hz, 2H), 2.71 (dd, J = 17.4, 1.7 Hz, 2H), 2.50 (s, 3H), 1.41 (s, 6H). 13 C NMR (125 MHz, DMSO-d 6 ) δ 193.6, 156.3, 144.3, 137.3, 127.5, 127.0, 78.4, 58.7, 42.9, 36.8, 20.0.

[0118] HRMS (ESI) calculated for C 24 H 24 N 2 NaO 6 [M + Na] + : 459.1527, found 459.1525.

[0119] Example 18

[0120] The reaction formula for preparing the 2-oxazolidinone compound in this example is as follows:

[0121]

[0122] Preparation method: Under air conditions, dissolve S18 (0.2 mmol, 109.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 2:1) to obtain the product P18 (34.2 mg, 63%), which is a white solid.

[0123] Characterization data: 1 H NMR (300 MHz, CDCl 3)δ 7.41 - 7.27 (m, 5H), 6.17 (dd, J = 10.5, 1.5 Hz, 1H), 6.02 (d, J = 10.5 Hz, 1H), 4.74 - 4.66 (m, 1H), 4.58 (d, J = 15.7 Hz, 1H), 4.40 (d, J = 15.7 Hz, 1H), 2.99 (dd, J = 17.9, 2.6 Hz, 1H), 2.65 (dd, J = 17.9, 4.4 Hz, 1H), 1.90 - 1.73 (m, 2H), 0.90 (t, J = 7.6 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 )δ 192.9, 157.0, 143.5, 137.8, 129.5, 129.0, 128.2, 128.1, 76.5, 62.0, 44.8, 38.6, 28.2, 8.0. HRMS (ESI) calculated for C 16 H 17 NNaO 3 [M + Na] + : 294.1101, found 294.1097.

[0124] Example 19

[0125] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0126]

[0127] Preparation method: Under air conditions, dissolve S19 (0.2 mmol, 67.9 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Directly concentrate the reaction solution under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P19 (30.6 mg, 54%), which is a white solid.

[0128] Characterization data: 1 H NMR (300 MHz, CDCl 3) δ 7.46 - 7.26 (m, 5H), 6.02 (d, J = 10.6 Hz, 1H), 5.98 - 5.89 (m, 1H), 4.75 - 4.68 (m, 1H), 4.61 (s, 2H), 2.99 (dd, J = 18.0, 2.2 Hz, 1H), 2.68 (dd, J = 18.0, 3.9 Hz, 1H), 1.01 - 0.88 (m, 1H), 0.68 - 0.55 (m, 2H), 0.53 - 0.40 (m, 1H), 0.19 - 0.07 (m, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.8, 156.9, 138.7, 138.3, 131.0, 128.9, 128.14, 128.09, 79.3, 62.3, 45.0, 37.5, 15.0, 0.8, 0.1. HRMS (ESI) calculated for C 17 H 17 NNaO 3 [M + Na] + : 306.1101, found 294.1097.

[0129] Example 20

[0130] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0131]

[0132] The preparation method is as follows: Under air conditions, dissolve S20 (0.2 mmol, 71.1 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 2:1) to obtain the product P20 (38.9 mg, 65%), which is a white solid.

[0133] Characterization data: 1 H NMR (300 MHz, CDCl 3)δ 7.42 - 7.27 (m, 5H), 6.18 (dd, J = 10.5, 1.6 Hz, 1H), 6.00 (d, J = 10.5 Hz, 1H), 4.74 - 4.65 (m, 1H), 4.57 (d, J = 15.7 Hz, 1H), 4.41 (d, J = 15.7 Hz, 1H), 2.98 (dd, J = 17.9, 2.5 Hz, 1H), 2.66 (dd, J = 17.9, 4.3 Hz, 1H), 1.78 - 1.68 (m, 2H), 1.30 - 1.13 (m, 4H), 0.84 (t, J = 7.0 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 )δ 192.9, 157.0, 143.7, 137.8, 129.2, 129.0, 128.2, 128.1, 76.8, 61.7, 44.8, 38.4, 35.0, 25.6, 23.0, 13.8. HRMS (ESI) calculated for C 18 H 21 NNaO 3 [M + Na] + : 322.1414, found 322.1412.

[0134] Example 21

[0135] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0136]

[0137] The preparation method is as follows: Under air conditions, dissolve S21 (0.2 mmol, 59.7 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 5:1) to obtain the product P21 (37.7 mg, 58%), which is a white solid.

[0138] Characterization data: 1 H NMR (300 MHz, CDCl 3) δ 7.42 - 7.27 (m, 5H), 6.18 (dd, J = 10.5, 1.4 Hz, 1H), 6.00 (d, J = 10.5 Hz, 1H), 4.73 - 4.66 (m, 1H), 4.57 (d, J = 15.7 Hz, 1H), 4.40 (d, J = 15.7 Hz, 1H), 2.97 (dd, J = 17.9, 2.6 Hz, 1H), 2.65 (dd, J = 17.9, 4.3 Hz, 1H), 1.81 - 1.65 (m, 2H), 1.31 - 1.11 (m, 8H), 0.86 (t, J = 6.6 Hz, 3H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.9, 157.1, 143.7, 137.8, 129.2, 129.0, 128.2, 128.1, 76.7, 61.7, 44.8, 38.4, 35.3, 31.5, 29.5, 23.6, 22.5, 14.1. HRMS (ESI) calculated for C 20 H 25 NNaO 3 [M + Na] + : 350.1727, found 350.1725.

[0139] Example 22

[0140] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0141]

[0142] The preparation method is as follows: Under air conditions, dissolve S22 (0.2 mmol, 70.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 5:1) to obtain the product P22 (40.4 mg, 68%), which is a white solid.

[0143] Characterization data: 1 H NMR (300 MHz, CDCl 3) δ 7.42 - 7.27 (m, 5H), 6.21 (dd, J = 10.5, 1.7 Hz, 1H), 6.02 (d, J = 10.5 Hz, 1H), 5.74 - 5.58 (m, 1H), 4.98 (t, J = 13.6 Hz, 2H), 4.78 - 4.69 (m, 1H), 4.57 (d, J = 15.7 Hz, 1H), 4.43 (d, J = 15.7 Hz, 1H), 2.99 (dd, J = 17.9, 2.7 Hz, 1H), 2.67 (dd, J = 17.9, 4.3 Hz, 1H), 2.03 - 1.92 (m, 2H), 1.89 - 1.77 (m, 2H). 13 C NMR (125 MHz, CDCl 3 ) δ 192.7, 157.0, 143.3, 137.7, 135.9, 129.4, 129.1, 128.3, 128.1, 116.4, 76.5, 61.5, 44.9, 38.3, 34.2, 27.6. HRMS (ESI) calculated for C 18 H 19 NNaO 3 [M + Na] + : 320.1257, found 320.1255.

[0144] Example 23

[0145] The reaction formula for preparing the 2 - oxazolidinone compound in this example is as follows:

[0146]

[0147] The preparation method is as follows: Under air conditions, dissolve S23 (0.2 mmol, 70.6 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (2.5 μL, 10 mol%) at room temperature, and the reaction ends after 2.5 hours. Concentrate the reaction solution directly under reduced pressure, and separate the crude product by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether: ethyl acetate = 5:1) to obtain the product P23 (49.0 mg, 92%), which is a pale yellow solid.

[0148] Characterization data: 1 H NMR (300 MHz, CDCl 3)δ 7.45 - 7.30 (m, 5H), 6.02 (dd, J=10.3, 1.9 Hz, 1H), 5.93 (d, J=10.3 Hz, 1H), 4.98 - 4.93 (m, 1H), 4.83 (d, J=15.3 Hz, 1H), 4.45 (d, J=15.3 Hz, 1H), 3.01 (dd, J=17.6, 2.3 Hz, 1H), 2.89 - 2.80 (m, 2H). 13 C NMR (125 MHz, CDCl 3 )δ 191.6, 155.5, 139.4, 137.1, 129.0, 128.7, 128.4, 128.0, 79.1, 78.1, 76.4, 60.0, 45.9, 37.1. HRMS (ESI) calculated for C 16 H 13 NNaO 3 [M + Na] + : 290.0788, found 290.0788.

[0149] Example 24: Scale-up reaction

[0150] Referring to Example 1, under air conditions, dissolve S1 (3 mmol, 939 mg) in CH 2 Cl 2 (1.0 mL), add BF 3 ·Et 2 O (37.5 μL, 10 mol%) at room temperature, and the reaction ends after 2 hours. The reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography, eluting with petroleum ether and ethyl acetate (petroleum ether:ethyl acetate = 1:1) to obtain the product P1 (732 mg, 95%), which is a white solid.

[0151] Example 25: Investigation and comparison of catalysts

[0152] Referring to Example 1, only replace the catalyst with an equimolar amount of other catalysts (shown in Table 1) to prepare the corresponding products. The results are shown in Table 1.

[0153] Table 1 Preparation results of different catalysts

[0154] Catalyst P1 Yield <![CDATA[BF 3 ·Et 2 O(Example 1)]]> 95％ p-Toluenesulfonic acid 47％ Iron(III) chloride anhydrous 34％ Aluminium chloride anhydrous 89％

[0155] Example 26: Antitumor activity test of the compounds of the present invention

[0156] Take the cell line in the logarithmic phase, gently wash it with PBS, digest it with 0.25% trypsin, inoculate it in a 96-well plate at a density of 3×103 cells / well, and place it in CO 2Incubate in an incubator (37 °C, 5% CO 2 ) for 24 h. Then add samples with different concentration gradients to the culture wells respectively, set a blank control, and continue to culture in a cell incubator for another 48 h. After 48 h, add 20 μL of MTT culture solution at 5 mg / mL to the culture medium and stain for 4 h. Remove the MTT solution, add 150 μL of DMSO reagent to each well, shake gently for 10 min, measure the absorbance value of each well at a wavelength of 570 nm with an enzyme-linked immunosorbent assay (ELISA) reader, and calculate the inhibition rate and IC 50 value.

[0157] The effects of all compounds in the present invention on the proliferation inhibition of several tumor cells were measured. The IC 50 value is the inhibitor concentration when the inhibition rate reaches 50%. The results are shown in Table 2:

[0158] Table 2 Anti-tumor activity results of the compounds in each example

[0159]

[0160]

[0161] It can be seen from the above results that the compounds of the present invention have a certain inhibitory effect on the proliferation of various tumor cells. Compound P23 shows good inhibitory effects on A549 cells, T24 cells, MCF-7, and Hela cells. Therefore, the compounds of the present invention have potential application prospects in the development of anti-tumor drugs.

[0162] Finally, it should be noted that the above examples are only used to illustrate the technical solutions of the present invention and are not intended to limit them. Although the present invention has been described in detail with reference to the preferred embodiments, those of ordinary skill in the art should understand that the technical solutions of the present invention can be modified or equivalently replaced without departing from the spirit and scope of the technical solutions of the present invention, and they should all be covered by the scope of the claims of the present invention.

Claims

1. A method for synthesizing a 2-oxazolidinone derivative, characterized in that, using the p-quinoneimine shown in Formula I as a raw material, and reacting under the action of boron trifluoride diethyl ether as a catalyst to obtain a 2-oxazolidinone compound shown in Formula II; ， Among them, refers to or ; R 1 Selected from: C1-C8 linear or branched alkyl groups, C1-C8 cycloalkyl groups, C2-C8 alkynyl groups containing 0-2 unsaturated double bonds; R 2 Selected from: unsubstituted or substituted C3-C6 cycloalkyl, 3- to 6-membered heterocyclic group, aryl; said substitution includes any one of mono-substitution to tri-substitution, and the substituents are selected from halogen, nitro, C1-C8 alkyl, C1-C8 alkoxy, halo-C1-C8 alkyl, phenyl.

2. The method according to claim 1, characterized in that, The aryl group is selected from: phenyl, naphthyl, thienyl, furyl, benzothienyl, benzofuryl.

3. The method according to claim 1, characterized in that, The 3- to 6-membered heterocyclic group contains 1 to 3 heteroatoms, and the heteroatoms are selected from N, O, S.

4. The method according to claim 1, characterized in that, The C2-C8 alkynyl is , R 3 is H, C1-C6 alkyl.

5. The method according to claim 1, characterized in that, The reaction is carried out in an organic solvent; the organic solvent is any one or more of dichloromethane, chloroform, toluene, acetonitrile, tetrahydrofuran.

6. The method according to claim 1, characterized in that, The molar ratio of the catalyst to the p-quinoneimine is 0.05 to 1:1; the reaction temperature is -70 °C to 30 °C, and the time is 12 to 24 h.

7. A method for synthesizing a 2-oxazolidinone derivative, characterized in that, The reaction formula is as follows: The preparation method is as follows: Under air conditions, 0.2 mmol of S17 is dissolved in 1.0 mL of CH 2 Cl 2 , and 10 mol% of BF 3 ·Et 2 O is added at room temperature. After reacting for 2.5 hours, the reaction is terminated; the reaction solution is directly concentrated under reduced pressure, and the crude product is separated by silica gel column chromatography and eluted with dichloromethane and methanol = 20:1 to obtain the product P17.

8. A 2-oxazolidinone derivative, characterized in that, Its structure is as follows: 。 9. Use of the 2-oxazolidinone derivative according to claim 8 in the preparation of anticancer drugs, and the cancers are lung cancer, bladder cancer, breast cancer, cervical cancer.

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