2-oxazolidinone-3-carbamimidate-5-methylene derivatives and processes for their preparation

Abstract

The present application relates to a kind of 2-oxazolidinone-3-carbamimidate-5-methylene derivatives and preparation method thereof, belong to organic synthesis technical field.The structure of 2-oxazolidinone-3-carbamimidate-5-methylene derivatives provided in the present application is as shown in formula (I)-(III).2-Oxazolidinone-3-carbamimidate-5-methylene derivatives of the present application can be applied to the synthesis and activity screening of novel oxazolidinone antibiotics, can provide technical support for the further derivatization and biological activity research of 2-oxazolidinone-3-carbamimidate derivative compound, with wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to a 2-oxazolidinone-3-formamidin-5-methylene derivative and its preparation method. Background Technology

[0002] 2-Oxazolidinones are compounds with an N,O-five-membered ring structure. Besides being important antibiotics (such as linezolid and terdizolid) and chiral ligands, they are also chemical intermediates in the synthesis of other drug molecules such as berberine and carmustine. 2-Oxazolidinone-3-formamidinene compounds are a class of compounds in which the 3-position of the 2-oxazolidinone structure is substituted with a formamidin group; currently, there is limited research on their activity and preparation.

[0003] Patent US20200206233 discovered that 2-oxazolidinone-3-formamidinene compounds can act as inhibitors of mutant isocitrate dehydrogenase (mt-IDH). According to this patent, these compounds are mainly formed by the condensation of 2-oxazolidinone compounds with halogenated derivatives, as shown in the following reaction formula:

[0004]

[0005] Although this method is advantageous for modifying the 3-formamidin site, it makes chemical modification of the core structure of 2-oxazolidinone more difficult, thus limiting the application of 2-oxazolidinone-3-formamidin compounds. Summary of the Invention

[0006] The purpose of this invention is to overcome the problems existing in the prior art and provide a 2-oxazolidinone-3-formamidin-5-methylene derivative and its preparation method.

[0007] This invention is achieved through the following technical solution:

[0008] This invention provides a 2-oxazolidinone-3-formamidin-5-methylene derivative, the structure of which is shown in formulas (I)-(III):

[0009]

[0010] Wherein, R is H, alkyl, aryl, halogen or ether.

[0011] Preferably, the 2-oxazolidinone-3-formamidin-5-methylene derivative has one of the following structures:

[0012]

[0013] Another object of the present invention is to provide a method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative, comprising the following steps:

[0014] (1) Dissolve raw material 1 and raw material 2 in organic solvent A, stir, then add N,N-diisopropylethylamine, and continue stirring to obtain intermediate product;

[0015] (2) Dissolve the intermediate product obtained in step (1) and the silver salt catalyst in organic solvent B, stir the reaction, and obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (1);

[0016] Alternatively, the intermediate product obtained in step (1), the iodine source, and the catalyst are dissolved in organic solvent C and stirred to react, thereby obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (2); and when the iodine source includes elemental iodine, the catalyst is tert-butyl hydroperoxide, and when the iodine source does not include elemental iodine, the catalyst is a silver salt.

[0017] Alternatively, the intermediate product obtained in step (1), the bromine source and the silver salt catalyst are dissolved in organic solvent D and stirred to react, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (3);

[0018] The structure of raw material 1 is shown in formula (1), the structure of raw material 2 is shown in formula (2), and the structure of the intermediate product is shown in formula (3).

[0019]

[0020] The preparation method of this invention uses a propargyloxycarbonyl-substituted guanidine compound as a starting material. Under the catalytic action of a silver salt catalyst, a 2-oxazolidinone-3-formamidin-5-methylene compound can be rapidly generated. Further addition of a bromine source yields its brominated derivatives. Using an iodine source and tert-butyl hydroperoxide (TBHP) or a silver salt as reaction reagents, its iodinated derivatives can be obtained. The raw materials used in the preparation method of this invention are simple and readily available, and the reaction is simple, efficient, and rapid, showing broad application prospects.

[0021] Preferably, the organic solvent A includes at least one of dichloromethane, chloroform, methanol, ethanol, dimethyl sulfoxide, acetone, ethyl acetate, N,N-dimethylformamide, and tetrahydrofuran.

[0022] Preferably, in step (1), the stirring time is 2h-4h; the stirring time is 0.5h-1.5h.

[0023] Preferably, in step (1), the molar ratio of raw material 1 and raw material 2 to N,N-diisopropylethylamine is 1:(1-2):(3-4).

[0024] Preferably, after the reaction in step (1) is completed, the reaction solution is diluted with dichloromethane, washed with water, the organic phase is washed with brine, dried with anhydrous sodium sulfate, filtered, and the filtrate is separated by silica gel column chromatography after vacuum distillation (the eluent is petroleum ether: ethyl acetate = (1-3):1) to obtain the intermediate product.

[0025] Preferably, in step (2), the silver salt includes at least one of AgOTf, AgNO3, AgSbF6, AgBF4, and AgCO2CF3.

[0026] More preferably, in step (2), the silver salt is AgOTf.

[0027] Preferably, the organic solvent B includes at least one of acetonitrile, dichloromethane, chloroform, dimethyl sulfoxide, methanol, and acetone.

[0028] More preferably, the organic solvent B is acetonitrile.

[0029] Preferably, the iodine source includes at least one of elemental iodine, bis(pyridine)tetrafluoroborate iodine, N-iodosuccinimide, iodine chloride, 1,3-diiodo-5,5-dimethylhydantoin, and N-iodosaccharin.

[0030] Preferably, the organic solvent C includes at least one of dichloromethane, acetonitrile, acetone, and tetrahydrofuran.

[0031] More preferably, the organic solvent C is dichloromethane.

[0032] Preferably, the bromine source includes at least one of N-bromosuccinimide, tribromopyridine, dibromohydantoin, N-bromoacetamide, phosphorus tribromide, carbon tetrabromide, 5,5-dibromomelendronic acid, dibromocyanoacetamide, and dibromoisocyanuric acid.

[0033] Preferably, the organic solvent D includes at least one of acetone, acetonitrile, and dimethylformamide.

[0034] More preferably, the organic solvent D is acetone.

[0035] Preferably, in step (2), the stirring reaction time is 40 min to 120 min.

[0036] The reaction of the present invention can be carried out at room temperature, preferably at a temperature of 20°C-37°C.

[0037] Preferably, in step (2), when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (1), the molar ratio of the intermediate product to the silver salt catalyst is 1:(0.05-0.2).

[0038] Preferably, in step (2), when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (2), the molar ratio of the intermediate product to the iodine source and the catalyst is 1:(1-2):(1-2).

[0039] Preferably, in step (2), when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (3), the molar ratio of the intermediate product to N-bromosuccinimide and the silver salt catalyst is 1:(1-1.5):(0.05-0.2).

[0040] Preferably, after the reaction in step (2) is completed, the reaction solution is concentrated under reduced pressure, and the concentrate is separated by silica gel column chromatography (the polarity range of the eluent is petroleum ether: ethyl acetate = (2-8):1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (1);

[0041] Alternatively, after the reaction is complete, the reaction solution is diluted with dichloromethane, washed with water, and Na2S2O3 is added to the obtained organic phase to quench elemental I2. Then the organic phase is washed with brine, dried with anhydrous sodium sulfate, filtered, and the filtrate is concentrated under reduced pressure and separated by silica gel column chromatography (eluent is petroleum ether: ethyl acetate = (10-13):1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (2).

[0042] Alternatively, after the reaction is complete, the reaction solution is diluted with dichloromethane, washed with water, the organic phase is washed with brine, dried with anhydrous sodium sulfate, filtered, and the filtrate is concentrated under reduced pressure and separated by silica gel column chromatography (the polarity range of the eluent is petroleum ether: ethyl acetate = (10-15):1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (3).

[0043] The present invention has the following beneficial effects:

[0044] (1) The 2-oxazolidinone-3-formamidin-5-methylene derivative obtained in this invention may be applied to the synthesis and activity screening of novel oxazolidinone antibiotics. At the same time, preliminary experimental tests show that the 2-oxazolidinone-3-formamidin-5-methylene derivative of this invention has certain inhibitory activity against CT-26 cells and has good application prospects.

[0045] (2) The raw materials used in the preparation method of the present invention are simple and readily available, and the reaction is simple, efficient and rapid. It can provide technical support for the further derivatization and bioactivity research of 2-oxazolidinone-3-formamidin derivatives and has broad application prospects. Detailed Implementation

[0046] To better illustrate the objectives, technical solutions, and advantages of this invention, the invention will be further described below with reference to specific embodiments. Those skilled in the art should understand that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0047] Unless otherwise specified, the experimental methods used in the examples are conventional methods; the materials and reagents used are commercially available unless otherwise specified.

[0048] The raw material 2 in this invention can be obtained by the preparation method described in the literature (Tian, ​​M.; Yan, M.; Baran, PS11-Step total synthesis of Araiosamines. J. Am. Chem. Soc. 2016, 138, 14234-14237.). The synthetic route of raw material 2 described in the examples and comparative examples is shown below, and the preparation method includes the following steps:

[0049]

[0050] (1) 1H-pyrazole-1-formamidinium hydrochloride (132 mg, 0.9 mmol) was dissolved in CH2Cl2 (5 mL) and DMF (10 mL), and stirred in an ice bath. Then, N,N-diisopropylethylamine (DIPEA, 297 μL, 1.8 mmol) and propargyl chloroformate (160 mg, 1.36 mmol) were added to the solution. The resulting mixture was stirred in an ice bath for 2 hours. After the reaction was completed, the reaction solution was evaporated to dryness, diluted with water, extracted twice with dichloromethane, washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain the intermediate compound (white solid, 126 mg, 0.66 mmol, 72.8%). Its characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ9.01(br,1H),8.46(d,J=2.4Hz,1H),7.71(s,2H),6.44(s,1H),4.77(d,J=2.4Hz,2H),2.49(t,J=2.4Hz,1H); 13 C NMR (101MHz, CDCl3) δ163.19,155.65,143.93,129.01,109.48,78.19,74.73,53.20; HRMS: (ESI)[M+H] + calc.for C8H9N4O2 + ,193.07200,observed193.07162.

[0051] (2) The obtained intermediate compound (40 mg, 0.2 mmol) was dissolved in CH2Cl2 (12 mL), stirred in an ice bath, and then trifluoroacetic anhydride (62.70 mg, 0.3 mmol) was added. The resulting mixture was stirred at room temperature for 2 hours. After the reaction was completed, the reaction solution was washed with water, washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to obtain raw material 2. Its characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ8.29(d,J=2.8Hz,1H),7.75(d,J=1.2Hz,1H),6.57(m,1H),4.86(d,J=2.8Hz,2H),2.59(t,J=2.4Hz,1H).

[0052] Example 1

[0053] This embodiment provides a method for preparing a 2-oxazolidinone-3-formamidin-5-methylene derivative, comprising the following steps:

[0054] (1) Raw material 1a (1.0 equivalent) and raw material 2 (1.5 equivalent) were dissolved in dichloromethane (DCM) and stirred at room temperature for 3 hours. Then, N,N-diisopropylethylamine (DIPEA, 3.0 equivalent) was added and stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed with water, the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was separated by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 1:1) after vacuum distillation to obtain intermediate product 3a. Its characterization data are as follows: 1 HNMR (400MHz, CDCl3) δ7.41 (m, 2H), 7.29 (m, 3H), 4.45 (d, J = 2.4Hz, 2H), 2.33 (t, J = 2.4Hz, 1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ162.9,160.9,136.2,129.8,127.0,126.2,79.1,73.6,51.7; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 12 N3O2 218.0924; found 218.0928. The synthesis route is as follows:

[0055]

[0056] (2) The intermediate product 3a (1.0 equivalent) and AgOTf (0.1 equivalent) obtained in step (1) were dissolved in acetonitrile. The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was concentrated under reduced pressure. The concentrate was separated by silica gel column chromatography (the polarity range of the eluent was petroleum ether: ethyl acetate = 2:1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative 4a of this example; the NMR yield was 99%; its characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ7.35(m,2H),7.07(m,1H),6.94(m,2H),6.09(q,J=2.4Hz,1H),5.85(br,2H),4.95(t,J=2.4Hz,2H),4.66(q,J=2.0Hz,1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.3,146.9,145.2,135.7,129.7,123.4,121.8,93.4,67.3; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 12 N3O2 218.0924; found 218.0918. The synthesis route is as follows:

[0057]

[0058] Example 2

[0059] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1b is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3b and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4b of this embodiment. The structures of 1b, 3b, and 4b are shown below:

[0060]

[0061] The characterization data of intermediate product 3b are as follows: 1 H NMR(400MHz, CDCl3)δ7.43(dd,J=7.6,4.0Hz,1H),7.32(m,2H),7.24(m,1H),7.17(m, 1H),7.11(t,J=7.2Hz,1H),6.98(m,3H),4.55(d,J=2.4Hz,2H),2.37(t,J=2.4Hz,1H); 13 C{ 1H}NMR(101MHz, CDCl3)δ162.7,160.3,156.4,151.4,129.8,128.0,127.6,127.4,124.2,123.8,119.7,118.6,79.0,73.7,51.9; HRMS(ESI)m / z:[M+H] + Calcd for C 17 H 16 N3O3 310.1186; found 310.1191.

[0062] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4b in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.24(m,2H),7.16(m,1H),7.08(m,2H),7.03(d,J=7.2Hz,1H),6.99(m,1H) ,6.89(m,2H),5.90(br,2H),5.56(q,J=2.4Hz,1H),4.82(t,J=2.4Hz,2H),4.36(q,J=2.0Hz,1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ158.0,156.1,147.3,144.8,138.7,135.1,129.5,125.4,124.6,123.8,122.3,121.9,117.0,93.4,67.2; HRMS(ESI)m / z:[M+H] + Calcd forC 17 H 16 N3O3 310.1186; found 310.1189. Separation yield 99%.

[0063] Example 3

[0064] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1c is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3c and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4c of this embodiment. The structures of 1c, 3c, and 4c are shown below:

[0065]

[0066] The characterization data of intermediate product 3c are as follows: 1H NMR (400MHz, CDCl3) δ7.21 (m, 2H), 6.93 (m, 2H), 4.49 (d, J = 2.4Hz, 2H), 3.82 (s, 3H), 2.35 (t, J = 2.4Hz, 1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ163.0,161.5,158.8,128.3,128.1,115.0,79.2,73.5,55.5,51.8; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 14 N3O3 248.1030; found 248.1026.

[0067] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4c in this example are as follows: 1 H NMR (400MHz, CDCl3) δ6.88(m,4H),6.07(q,J=2.4Hz,1H),5.84(br,2H),4.94(t,J=2.4Hz,2H),4.64(q,J=2.0Hz,1H),3.79(s,3H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.3,155.8,145.6,139.9,135.8,122.6,115.0,93.2,67.3,55.5; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 14 N3O3 248.1030; found 248.1033. Separation yield was 78%.

[0068] Example 4

[0069] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1d is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3d and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4d of this embodiment. The structures of 1d, 3d, and 4d are shown below:

[0070]

[0071] The characterization data of the intermediate product in 3D are as follows: 1H NMR (400MHz, d6-DMSO) δ9.02(br,1H),7.88(d,J=7.6Hz,1H),7.38(m,2H),6.97(m,1H),4.56(d,J=2.4Hz,2H),3.42(t,J=2.4Hz,1H); 13 C{ 1 H}NMR(101MHz,d6-DMSO)δ161.8,158.7,141.0,139.3,129.4,128.1,127.8,97.8,80.2,77.1,52.1; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 11 IN3O2343.9890; found 343.9880.

[0072] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example for 4 days are as follows: 1 H NMR(400MHz, CDCl3) δ7.86(dd,J=8.0,1.6Hz,1H),7.32(m,1H),6.94(dd,J=8.0,1.6Hz,1H),6 .79(m,1H),6.37(q,J=2.0Hz,1H),5.90(br,2H),4.96(t,J=2.4Hz,2H),4.70(q,J=1.6Hz,1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.3,148.7,145.4,139.7,135.2,129.6,125.0,121.7,94.8,93.1,67.4; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 11 IN3O2 343.9890; found 343.9886. Separation yield 85%.

[0073] Example 5

[0074] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1e is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3e and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4e of this embodiment. The structures of 1e, 3e, and 4e are shown below:

[0075]

[0076] The characterization data of intermediate product 3e are as follows: 1 H NMR (400MHz, d6-DMSO) δ8.91 (br, 1H), 7.65 (dd, J = 8.0, 1.6 Hz, 1H), 7.57 (d, J = 8. 0Hz,1H),7.36(m,1H),7.11(m,1H),4.57(d,J=2.4Hz,2H),3.43(t,J=2.4Hz,1H); 13 C{ 1 H}NMR(101MHz,d6-DMSO)δ161.9,159.0,137.4,133.1,128.6,128.2,127.1,119.1,80.2,77.1,52.1; HRMS(ESI)m / z:[M+H] + Calcd forC 11 H 11 BrN3O2 296.0029; found 296.0023.

[0077] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4e in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.63 (dd, J=8.0, 1.6Hz, 1H), 7.30 (m, 1H), 6.97 (m, 2H), 6. 30(q,J=2.4Hz,1H),5.89(br,2H),4.99(t,J=2.4Hz,2H),4.72(q,J=2.0Hz,1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.2,145.4,145.2,135.3,133.5,128.7,124.7,122.9,116.9,94.3,67.4; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 11 BrN3O2 296.0029; found 296.0023. Separation yield was 91%.

[0078] Example 6

[0079] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1f is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3f and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4f of this embodiment. The structures of 1f, 3f, and 4f are shown below:

[0080]

[0081] The characterization data of intermediate product 3f are as follows: 1 H NMR (400MHz, d6-DMSO) δ9.07 (br, 1H), 7.44 (m, 2H), 7.15 (m, 2H), 4.58 (d, J = 2.4Hz, 2H), 3.42 (t, J = 2.4Hz, 1H); 13 C{ 1 H} NMR (101MHz, d6-DMSO) δ162.8, 160.1, 158.9 (d, J = 241.1Hz), 135.0 (d, J = 2.9Hz), 124.4 (d, J = 8.4Hz), 115.8 (d, J = 22.6Hz), 80.4, 77.0, 52.1; 19 F NMR(376MHz,d6-DMSO)δ-119.31(s,1F); HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 11 FN3O2 236.0830; found236.0825.

[0082] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4f in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.04 (m, 2H), 6.89 (m, 2H), 6.06 (q, J = 2.4Hz, 1H), 5.87 (br, 2H), 4.95 (t, J = 2.4Hz, 2H), 4.66 (q, J = 2.0Hz, 1H); 13 C{ 1 H} NMR (101MHz, CDCl3) δ 160.4, 157.1 (d, J = 180.8Hz), 145.7, 142.8 (d, J = 2.9Hz), 135.7, 122.9 (d, J = 8.0Hz), 116.4 (d, J = 22.6Hz), 93.5, 67.3; 19 F NMR (376MHz, CDCl3) δ-120.63 (s, 1F); HRMS (ESI) m / z: [M+H]+ Calcd forC 11 H 11 FN3O2 236.0830; found 236.0825. Separation yield was 76%.

[0083] Example 7

[0084] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of 1g of raw material is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding 3g of intermediate product and 4g of the 2-oxazolidinone-3-formamidin-5-methylene derivative of this embodiment. The structures of 1g, 3g, and 4g are shown below:

[0085]

[0086] The characterization data for 3g of the intermediate product are as follows: 1 H NMR (400MHz, CDCl3) δ7.45 (m, 2H), 7.24 (m, 2H), 4.51 (d, J = 2.4Hz, 2H), 2.36 (t, J = 2.4Hz, 1H), 1.35 (s, 9H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ163.0,161.1,150.2,133.2,126.7,125.7,79.2,73.5,51.7,34.6,31.3; HRMS(ESI)m / z:[M+H] + Calcd for C 15 H 20 N3O2 274.1550; found 274.1548.

[0087] The characterization data of 4g of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.37(m,2H),6.88(m,2H),6.09(q,J=2.4Hz,1H),5.86(br,2H),4.94(t,J=2.4Hz,2H),4.64(q,J=2.0Hz,1H),1.32(s,9H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.3,146.2,145.2,144.1,135.8,126.5,121.2,93.3,67.3,34.3,31.5; HRMS(ESI)m / z:[M+H] +Calcd for C 15 H 20 N3O2 274.1550; found 274.1546. Separation yield 80%.

[0088] Example 8

[0089] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1h is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3h and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4c of this embodiment. The structures of 1h, 3h, and 4h are shown below:

[0090]

[0091] The characterization data of the intermediate product after 3 hours are as follows: 1 H NMR (400MHz, d6-DMSO) δ9.17 (br, 1H), 6.70 (s, 2H), 4.60 (d, J = 2.4Hz, 2H), 3.76 (s, 6H), 3.64 (s, 3H), 3.40 (t, J = 2.4Hz, 1H); 13 C{ 1 H}NMR(101MHz,d6-DMSO)δ162.8,160.1,153.3,134.7,134.2,100.9,80.5,76.9,60.5,56.3,52.2; HRMS(ESI)m / z:[M+H] + Calcd for C 14 H 18 N3O5 308.1241; found308.1249.

[0092] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example after 4 hours are as follows: 1 H NMR (400MHz, CDCl3) δ6.17(s,2H),6.07(q,J=2.4Hz,1H),5.94(br,2H),4.94(t,J=2.4Hz,2H),4.66(q,J=2.0Hz,1H),3.82(s,6H),3.81(s,3H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.2,154.1,145.7,143.0,135.7,133.9,99.1,93.5,67.3,61.0,56.1; HRMS(ESI)m / z:[M+H] +Calcd for C 14 H 18 N3O5 308.1241; found 308.1236. Separation yield 90%.

[0093] Example 9

[0094] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1i is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3i and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4c of this embodiment. The structures of 1i, 3i, and 4i are shown below:

[0095]

[0096] The characterization data of intermediate product 3i are as follows: 1 H NMR (400MHz, d6-DMSO) δ9.42 (br, 1H), 7.77 (s, 2H), 4.64 (d, J = 2.4Hz, 2H), 3.47 (t, J = 2.4Hz, 1H); 13 C{ 1 H}NMR(101MHz,d6-DMSO)δ162.0,158.6,140.6,133.0,123.3,121.4,80.1,77.4,52.4; HRMS(ESI)m / z:[M+H] + Calcd forC 11 H9Cl3N3O2 319.9755; found 319.9752.

[0097] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4i in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.00 (s, 2H), 6.01 (br, 3H), 4.95 (t, J = 2.4Hz, 2H), 4.67 (q, J = 2.0Hz, 1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.1,146.4,146.0,135.2,134.8,125.6,122.5,94.3,67.3; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H9Cl3N3O2 319.9755; found 319.9724. Separation yield was 69%.

[0098] Example 10

[0099] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that an equal amount of raw material 1j is used to replace raw material 1a. All other preparation methods are the same as in Example 1, yielding intermediate product 3j and the 2-oxazolidinone-3-formamidin-5-methylene derivative 4j of this embodiment. The structures of 1j, 3j, and 4j are shown below:

[0100]

[0101] The characterization data of intermediate product 3j are as follows: 1 H NMR(400MHz,d6-DMSO)δ8.94(br,1H),7.46(s,1H),7.36(d,J=8.0Hz,1H),7.00( dd,J=8.0,2.0Hz,1H),4.58(d,J=2.4Hz,2H),3.43(t,J=2.4Hz,1H),2.29(s,3H); 13 C{ 1 H}NMR(101MHz,d6-DMSO)δ162.0,159.4,137.6,135.4,129.5,128.2,127.4,125.0,80.3,77.1,52.2,20.4; HRMS(ESI)m / z:[M+H] + Calcd forC 12 H 13 ClN3O2 266.0691; found 266.0687.

[0102] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 4j in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.29 (d, J = 8.0Hz, 1H), 6.81 (m, 2H), 6.21 (q, J = 2.4Hz, 1H), 5.84 (br, 2H), 4.96 (t, J = 2.4Hz, 2H), 4.68 (q, J = 2.0Hz, 1H), 2.30 (s, 3H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.2,145.0,143.5,138.0,135.4,130.0,125.3,123.6,122.9,94.0,67.4,20.9; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 13ClN3O2 266.0691; found 266.0689. Separation yield was 91%.

[0103] Example 11

[0104] This embodiment provides a method for preparing a 2-oxazolidinone-3-formamidin-5-methylene derivative, comprising the following steps:

[0105] (1) Same as Example 1;

[0106] (2) The intermediate product 3a (1.0 equivalent), elemental I2 (1.5 equivalent), and tert-butyl hydroperoxide (TBHP, 1.5 equivalent) obtained in step (1) were dissolved in dichloromethane (DCM). The mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed with water, and Na2S2O3 was added to the obtained organic phase to quench elemental I2. Then, the organic phase was washed with brine, dried with anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and separated by silica gel column chromatography (eluent: petroleum ether: ethyl acetate = 10:1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative 5a of this example; the separation yield was 85%; its characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ7.40(t,J=2.4Hz,1H),7.36(m,2H),7.09(t,J=7.6Hz,1H),6.92(dd,J=8.4,1.2Hz,2H),5.91(br,2H),4.86(d,J=2.8Hz,2H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.5,146.3,145.2,134.6,129.8,123.7,121.8,71.7,60.7; HRMS(ESI)m / z:[M+H] + Calcdfor C 11 H 11 IN3O2 343.9890; found 343.9878. The synthesis route is as follows:

[0107]

[0108] Example 12

[0109] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3f is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 5b of this embodiment; the structure of 5b is shown below:

[0110]

[0111] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 5b in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.38(t,J=2.8Hz,1H),7.05(m,2H),6.87(m,2H),5.92(br,2H),4.86(d,J=2.8Hz,2H); 13 C{ 1 H} NMR (101MHz, CDCl3) δ 160.5, 157.3 (d, J = 171.4Hz), 145.7, 142.2 (d, J = 2.6Hz), 134.5, 123.0 (d, J = 7.7Hz), 116.5 (d, J = 22.3Hz), 71.7, 60.7; 19 F NMR (376MHz, CDCl3) δ-120.13 (s, 1F); HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 10 FIN3O2 361.9796; found361.9799. Separation yield was 85%.

[0112] Example 13

[0113] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3b is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 5c of this embodiment; the structure of 5c is shown below:

[0114]

[0115] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 5c in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.27(m,2H),7.18(m,1H),7.12(m,2H),7.03(m,2H),6.86(m,2H),6.72(t,J=2.8Hz,2H),5.95(br,2H),4.72(d,J=2.8Hz,2H); 13 C{ 1H}NMR(101MHz, CDCl3)δ157.8,156.3,147.2,144.8,138.2,133.7,129.5,125.6,124.9,123.8,122.7,122.4,116.6,71.5,60.6; HRMS(ESI)m / z:[M+H] + Calcd for C 17 H 15 IN3O3436.0153; found 436.0146. Separation yield was 83%.

[0116] Example 14

[0117] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3j is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 5d of this embodiment; the structure of 5d is shown below:

[0118]

[0119] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example for 5 days are as follows: 1 H NMR(400MHz, CDCl3) δ7.46(t,J=2.8Hz,1H),7.29(d,J=8.4Hz,1H),6.85(dd,J=8.4, 2.0Hz,1H),6.78(d,J=2.0Hz,1H),5.89(br,2H),4.87(d,J=2.8Hz,2H),2.30(s,3H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.4,145.0,142.9,138.1,134.3,130.0,125.5,123.6,123.4,71.7,61.0,20.9; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 12 ClIN3O2 391.9657; found 391.9649. Separation yield 90%.

[0120] Example 15

[0121] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3c is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 5e of this embodiment; the structure of 5e is shown below:

[0122]

[0123] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 5e in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.39 (t, J = 2.8 Hz, 1H), 6.88 (m, 4H), 5.90 (br, 2H), 4.86 (d, J = 2.8 Hz, 2H), 3.80 (s, 3H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.5,156.0,145.6,139.2,134.6,122.6,115.1,71.7,60.6,55.6; HRMS(ESI)m / z:[M+H] + Calcd for C 12 H 13 IN3O3373.9996; found373.9989. Separation yield was 71%.

[0124] Example 16

[0125] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3d is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 5f of this embodiment; the structure of 5f is shown below:

[0126]

[0127] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 5f in this example are as follows: 1 H NMR(400MHz, CDCl3) δ7.87(dd,J=8.0,1.6Hz,1H),7.61(t,J=2.8Hz,1H),7.32(m,1 H),6.93(dd,J=8.0,1.6Hz,1H),6.81(m,1H),5.93(br,2H),4.88(d,J=2.8Hz,2H); 13 C{ 1H}NMR(101MHz, CDCl3)δ156.4,148.0,145.3,139.8,134.1,129.7,125.2,121.6,93.3,71.7,61.8; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 10 I₂N₃O₂ 469.8857; found 469.8844. Separation yield was 91%.

[0128] Example 17

[0129] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 11 in that intermediate product 3i is used to replace the raw material intermediate product 3a, yielding 5g of the 2-oxazolidinone-3-formamidin-5-methylene derivative of this embodiment; the structure of 5g is shown below:

[0130]

[0131] The characterization data of 5g of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.30 (t, J = 2.8Hz, 1H), 6.98 (s, 2H), 6.08 (br, 2H), 4.87 (d, J = 2.8Hz, 2H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.3,146.0,145.7,134.9,134.0,125.9,122.5,71.7,61.1; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H8Cl3N3O2 445.8721; found 445.8712. Separation yield was 81%.

[0132] Example 18

[0133] This embodiment provides a method for preparing a 2-oxazolidinone-3-formamidin-5-methylene derivative, comprising the following steps:

[0134] (1) Same as Example 1;

[0135] (2) The intermediate product 3a (1.0 equivalent), N-bromosuccinimide (NBS, 1.2 equivalent), and AgOTf (0.1 equivalent) obtained in step (1) were dissolved in acetone and stirred at room temperature for 1 hour. After the reaction was completed, the reaction solution was diluted with dichloromethane, washed with water, the organic phase was washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure and separated by silica gel column chromatography (the polarity range of the eluent was petroleum ether: ethyl acetate = 10:1) to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative 6a of this example; the separation yield was 77%; its characterization data are as follows: 1 H NMR (400MHz, CDCl3) δ7.49(t,J=2.8Hz,1H),7.38(m,2H),7.11(t,J=7.6Hz,1H),6.94(m,2H),5.96(br,2H),4.97(d,J=2.8Hz,2H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.1,146.3,145.0,132.3,129.8,123.7,121.8,90.8,68.1; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 11 BrN3O2 296.0029; found 296.0032. The synthesis route is as follows:

[0136]

[0137] Example 19

[0138] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 18 in that intermediate product 3b is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 6b of this embodiment; the structure of 6b is shown below:

[0139]

[0140] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 6b in this example are as follows: 1 H NMR (400MHz, CDCl3); δ7.26(m,2H),7.18(m,1H),7.11(m,2H),7.01(m,2H),6.86(m,2H),6.79(t,J=2.8Hz,1H),5.99(br,2H),4.82(d,J=2.8Hz,2H); 13 C{1 H}NMR(101MHz, CDCl3)δ157.8,155.9,147.3,144.6,138.1,131.6,129.5,125.5,124.9,123.7,122.6,122.3,116.6,90.8,68.0; HRMS(ESI)m / z:[M+H] + Calcd for C 17 H 15 BrN3O3388.0291; found388.0297. Separation yield was 70%.

[0141] Example 20

[0142] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 18 in that intermediate product 3f is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 6c of this embodiment; the structure of 6c is shown below:

[0143]

[0144] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 6c in this example are as follows: 1 H NMR (400MHz, CDCl3) δ7.44(t,J=2.8Hz,1H),7.05(m,2H),6.86(m,2H),5.95(br,2H),4.95(d,J=2.8Hz,2H); 13 C{ 1 H}NMR (101MHz, CDCl3) δ 160.5, 157.1 (d, J = 212.6Hz), 145.5, 142.2 (d, J = 2.9Hz), 132.3, 123.0 (d, J = 8.0Hz), 116.5 (d, J = 22.3Hz), 90.9, 68.1; 19 F NMR (376MHz, CDCl3) δ-120.15 (s, 1F); HRMS (ESI) m / z: [M+H] + Calcd for C 11 H 10 FBrN3O2 313.9935; found 313.9938. Separation yield was 73%.

[0145] Example 21

[0146] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 18 in that intermediate product 3d is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 6d of this embodiment; the structure of 6d is shown below:

[0147]

[0148] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative in this example for 6 days are as follows: 1 H NMR(400MHz, CDCl3) δ7.87(dd,J=8.0,1.6Hz,1H),7.66(t,J=2.8Hz,1H),7.33(m,1 H),6.93(dd,J=8.0,1.6Hz,1H),6.81(m,1H),5.96(br,2H),4.98(d,J=2.8Hz,1H); 13 C{ 1 H}NMR(101MHz, CDCl3)δ156.0,148.0,145.1,139.8,131.9,129.7,125.3,121.6,93.3,91.7,68.2; HRMS(ESI)m / z:[M+H] + Calcd for C 11 H 10 BrIN3O2 421.8996; found 421.8984. Separation yield was 56%.

[0149] Example 22

[0150] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 18 in that intermediate product 3g is used to replace the raw material intermediate product 3a, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative 6e of this embodiment; the structure of 6e is shown below:

[0151]

[0152] The characterization data of the 2-oxazolidinone-3-formamidin-5-methylene derivative 6e in this example are as follows: ¹H NMR (400MHz, CDCl₃) δ 7.47 (t, J = 2.8Hz, ¹H), 7.37 (m, 2H), 6.86 (m, 2H), 5.95 (br, 2H), 4.95 (d, J = 2.8Hz, 1H), 1.32 (s, 9H); ¹³C{¹H}NMR (101MHz, CDCl₃) δ 156.1, 146.5, 145.0, 143.4, 132.4, 126.6, 121.2, 90.8, 68.1, 34.3, 31.5; HRMS (ESI) m / z: [M+H]+Calcd for C₁₅H₁₉BrN₃O₂ 352.0655; found 352.0661. The separation yield was 82%.

[0153] Example 23

[0154] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), an equal amount of AgCO2CF3 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 70%.

[0155] Example 24

[0156] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), an equal amount of AgNO3 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 90%.

[0157] Example 25

[0158] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), an equal amount of AgSbF6 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 98%.

[0159] Example 26

[0160] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), an equal amount of AgBF4 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 98%.

[0161] Example 27

[0162] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), chloroform is used instead of acetonitrile as the organic solvent, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 66%.

[0163] Example 28

[0164] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), the organic solvent is not acetonitrile but dimethyl sulfoxide, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 81%.

[0165] Example 29

[0166] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this embodiment differs from that in Example 1 in that, in step (2), methanol is used instead of acetonitrile as the organic solvent, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 64%.

[0167] Comparative Example 1

[0168] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of Ag2CO3 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 0%.

[0169] Comparative Example 2

[0170] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of AgF is used to replace AgOTf, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 20%.

[0171] Comparative Example 3

[0172] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of PdCl2 is used to replace AgOTf, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 3%.

[0173] Comparative Example 4

[0174] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of PdCl2(dppf)·DCM is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 0%.

[0175] Comparative Example 5

[0176] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of PdCl2 (dppf) is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 0%.

[0177] Comparative Example 6

[0178] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of Pd(OAc)2 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 20%.

[0179] Comparative Example 7

[0180] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of PdCl2(PPh3)2 is used to replace AgOTf, and the rest of the preparation method is the same as in Example 1. The NMR yield of product 4a is 0%.

[0181] Comparative Example 8

[0182] The preparation method of the 2-oxazolidinone-3-formamidin-5-methylene derivative provided in this comparative example differs from that in Example 1 in that, in step (2), an equal amount of CuI is used to replace AgOTf, while the rest of the preparation method is the same as in Example 1, and the NMR yield of product 4a is 5%.

[0183] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention and are not intended to limit the scope of protection of the present invention. Although the present invention has been described in detail with reference to preferred embodiments, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention.

Claims

1. A 2-oxazolidinone-3-formamidin-5-methylene derivative, characterized in that, The structures of the 2-oxazolidinone-3-formamidin-5-methylene derivatives are shown in formulas (I)-(III): Wherein, R is H, alkyl, aryl, halogen or ether.

2. The 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 1, characterized in that, The 2-oxazolidinone-3-formamidin-5-methylene derivative has one of the following structures: 。 3. A method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative as described in claim 1 or 2, characterized in that, Includes the following steps: (1) Dissolve raw material 1 and raw material 2 in organic solvent A, stir, then add N,N-diisopropylethylamine, and continue stirring to obtain intermediate product; (2) Dissolve the intermediate product obtained in step (1) and the silver salt catalyst in organic solvent B, stir and react to obtain the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (I); the silver salt includes at least one of AgOTf, AgNO3, AgSbF6, AgBF4, and AgCO2CF3. Alternatively, the intermediate product obtained in step (1), the iodine source, and the catalyst are dissolved in organic solvent C and stirred to react, thereby obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (II); and when the iodine source includes elemental iodine, the catalyst is tert-butyl hydroperoxide, and when the iodine source does not include elemental iodine, the catalyst is a silver salt. Alternatively, the intermediate product obtained in step (1), the bromine source, and the silver salt catalyst are dissolved in organic solvent D and stirred to react, thus obtaining the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (III); The structure of raw material 1 is shown in formula (1), the structure of raw material 2 is shown in formula (2), and the structure of the intermediate product is shown in formula (3). 。 4. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, In step (1), the stirring time is 2h-4h; the stirring time is 0.5h-1.5h.

5. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, In step (1), the molar ratio of raw material 1 and raw material 2 to N,N-diisopropylethylamine is 1:(1-2):(3-4).

6. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, The organic solvent A includes at least one of dichloromethane, chloroform, methanol, ethanol, dimethyl sulfoxide, acetone, ethyl acetate, N,N-dimethylformamide, and tetrahydrofuran; And / or, the organic solvent B includes at least one of acetonitrile, dichloromethane, chloroform, dimethyl sulfoxide, methanol, and acetone; And / or, the organic solvent C includes at least one of dichloromethane, acetonitrile, acetone, and tetrahydrofuran; And / or, the organic solvent D includes at least one of acetone, acetonitrile, and dimethylformamide.

7. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, In step (2), the iodine source includes at least one of elemental iodine, bis(pyridine)tetrafluoroborate, N-iodosuccinimide, iodine chloride, 1,3-diiodo-5,5-dimethylhydantoin, and N-iodosaccharin; and / or, the bromine source includes at least one of N-bromosuccinimide, tribromopyridine, dibromohydantoin, N-bromoacetamide, phosphorus tribromide, carbon tetrabromide, 5,5-dibromomelinic acid, dibromocyanoacetamide, and dibromoisocyanuric acid.

8. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, In step (2), the stirring reaction time is 40 min to 120 min.

9. The method for preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative according to claim 3, characterized in that, In step (2), when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative shown in formula (I), the molar ratio of the intermediate product to the silver salt catalyst is 1:(0.05-0.2). And / or, when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative of formula (II), the molar ratio of the intermediate to the iodine source and the catalyst is 1:(1-2):(1-2); And / or, when preparing the 2-oxazolidinone-3-formamidin-5-methylene derivative of formula (III), the molar ratio of the intermediate to N-bromosuccinimide and the silver salt catalyst is 1:(1-1.5):(0.05-0.2).

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