A kind of sulphur-containing acetamide compound and its preparation method and application

Abstract

The application discloses a kind of sulphur-containing amide compounds and its preparation method and application;It has the structural formula shown in formula I: Wherein, R1 Selected from H, C 1～6 Alkyl, naphthyl, wherein, R7 Selected from H, C 1～6 Alkyl, halogen, cyano, cyano-substituted phenyl, nitro, C 1‑6 Alkoxy, phenyl, C 1～6 Halogenated alkyl, C 2～6 Ester group;R2 Selected from H, C 1～6 Alkyl;R3 Selected from H, halogen, C 1‑6 Alkoxy;R4 Selected from H, halogen, cyano, nitro, C 1‑6 Alkoxy, C 1～6 Alkyl;R5 Selected from H, C 1～6 Alkyl;R6 Selected from H, C 1～6 Alkyl, wherein R8 Selected from C 1～6 Alkyl.The application develops a kind of novel structure sulphur-containing amide compounds, and the compound has the effect of inhibiting tumour cell activity.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to a sulfur-containing acetamide compound, its preparation method, and its application. Background Technology

[0002] In chemical synthesis, N-alkyl-N-acetamide compounds are commonly used to prepare a variety of organic compounds, including pharmaceuticals, pesticides, and dyes. These compounds have a wide range of applications, such as intermediates in drug synthesis, active ingredients in pesticides, or as research compounds. For the synthesis of sulfide compounds, organosulfur compounds are generally an important category in drug synthesis, materials science, and organic synthesis. They typically possess broad-spectrum biological activities and can be used to develop antibacterial agents, antitumor agents, and anti-inflammatory agents. In organic synthesis, sulfides can be prepared through various methods, either through chemical reactions or by isolation from natural products.

[0003] Therefore, it is necessary to develop a sulfur-containing acetamide compound that has the effect of inhibiting tumor cell activity. Summary of the Invention

[0004] The present invention aims to at least solve one of the technical problems existing in the prior art. To this end, the first aspect of the present invention provides a sulfur-containing acetamide compound that can effectively inhibit tumor cell activity.

[0005] A second aspect of the present invention also provides a method for preparing a sulfur-containing acetamide compound.

[0006] A third aspect of the present invention also provides an application of a sulfur-containing acetamide compound.

[0007] According to a first aspect of the present invention, a sulfur-containing acetamide compound has the structural formula shown in Formula I:

[0008]

[0009] Among them, R1 is selected from H and C. 1～6 alkyl, naphthyl, Among them, R7 is selected from H and C. 1～6 Alkyl, halogen, cyano, cyano-substituted phenyl, nitro, C 1-6 alkoxy, phenyl, C 1～6 Halogenated alkyl, C 2～6 ester group;

[0010] R2 is selected from H and C. 1～6 Alkyl groups;

[0011] R3 is selected from H, halogens, and C. 1-6 alkoxy groups;

[0012] R4 is selected from H, halogen, cyano, nitro, and C. 1-6 alkoxy, C 1～6 Alkyl groups;

[0013] R5 is selected from H and C. 1～6 Alkyl groups;

[0014] R6 is selected from H and C. 1～6 alkyl, R8 is selected from C. 1～6 Alkyl groups.

[0015] The sulfur-containing acetamide compounds according to embodiments of the present invention have at least the following beneficial effects:

[0016] This invention develops a novel sulfur-containing acetamide compound that has the effect of inhibiting tumor cell activity.

[0017] According to some embodiments of the present invention, R7 is selected from H, F, chlorine, bromine, iodine, and C. 1～3 alkyl, C 1～3 alkoxy, C 1～3 Halogenated alkyl, C 2～4 ester, cyano, or cyano-substituted phenyl groups.

[0018] According to some embodiments of the present invention, one of the following structural formulas is selected:

[0019]

[0020]

[0021] The method for preparing a sulfur-containing acetamide compound according to a second aspect embodiment of the present invention includes the following steps:

[0022] Compound 1, compound 2, compound 3, base and oxidant are mixed and reacted to obtain sulfur-containing acetamide compounds with the structural formula shown in Formula I;

[0023] The structural formulas of compounds 1, 2, and 3 are as follows:

[0024]

[0025] Where X is a halogen.

[0026] The method of the present invention has simple preparation steps, good selectivity, high atom economy and high yield.

[0027] According to some embodiments of the present invention, the alkali includes inorganic alkali or organic alkali.

[0028] According to some embodiments of the present invention, the organic base includes at least one of sodium acetate, sodium ethoxide, or sodium tert-butoxide.

[0029] According to some embodiments of the present invention, the inorganic base includes at least one of sodium hydroxide, sodium carbonate, or sodium bicarbonate.

[0030] According to some embodiments of the present invention, the reaction temperature is 30–120°C.

[0031] According to some embodiments of the present invention, the reaction time is 8 to 24 hours.

[0032] According to some embodiments of the present invention, the oxidant includes at least one of I2, tert-butyl hydroperoxide, NH4I, or di-tert-butyl hydroperoxide.

[0033] According to some embodiments of the present invention, the molar ratio of compound 1, compound 2, base and oxidant is 1:(1.5-3.0):(1.0-1.5):(1.0-1.5).

[0034] According to some embodiments of the present invention, the molar volume ratio of compound 1 and compound 3 is 1 mol: (9-10) mL.

[0035] According to some embodiments of the present invention, the reaction further includes purification.

[0036] According to some embodiments of the present invention, the purification steps are as follows:

[0037] After the reaction was completed, the mixture was cooled to room temperature, diluted, filtered, and the solvent was removed by rotary evaporation under reduced pressure to obtain the crude product. The crude product was then purified by column chromatography.

[0038] According to some embodiments of the present invention, the eluent used for column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate in a volume ratio of (1-10):1.

[0039] A third aspect of the present invention relates to the use of the sulfur-containing acetamide compounds described in any of the preceding claims in the preparation of antitumor drugs.

[0040] Definitions and general terms

[0041] “C 1-6 "alkyl" indicates an alkyl group with a total number of 1-6 carbon atoms, including C64. 1-6 straight-chain alkyl, C 1-6 Branched alkyl groups and C 3-6The cycloalkyl group can be, for example, a straight-chain alkyl group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; a branched-chain alkyl group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; or a cycloalkyl group with a total of 3, 4, 5, or 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, cyclopropyl, methylcyclopropyl, ethylcyclopropyl, cyclopentyl, methylcyclopentyl, cyclohexyl, etc. Regarding "C 1-3 "alkyl" has a similar interpretation, except that the number of carbon atoms is different.

[0042] “C 1-6 "alkoxy group" refers to an alkoxy group with a total number of 1-6 carbon atoms, including C64 and C64. 1-6 Straight-chain alkoxy, C1-6 branched-chain alkoxy and C 2-6 The cycloalkoxy group can be, for example, a straight-chain alkoxy group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; a branched-chain alkoxy group with a total of 1, 2, 3, 4, 5, or 6 carbon atoms; or a cycloalkoxy group with a total of 2, 3, 4, 5, or 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, etc. A similar explanation applies to "C1-4 alkoxy groups," the difference being the number of carbon atoms.

[0043] “C 1～6 "halogenated alkyl" and "C" 1-6 The definition of "alkyl" is similar, except that "C" is different. 1～6 Any one hydrogen atom in the "halogenated alkyl group" is replaced by any halogen.

[0044] “C 2～6 The structural formula of the "ester group" is -COOR, in which the total number of carbon atoms is 2 to 6. Representative examples include methyl formate, ethyl formate, ethyl acetate, methyl acetate, etc.

[0045] "Halogen" includes any one or more of fluorine, chlorine, bromine, and iodine.

[0046] Other features and advantages of the invention will be set forth in the description which follows, and will be apparent in part from the description, or may be learned by practicing the invention. Attached Figure Description

[0047] The above and / or additional aspects and advantages of the present invention will become apparent and readily understood from the description of the embodiments taken in conjunction with the following drawings, in which:

[0048] Figure 1 The 1H NMR spectrum of compound I-1 obtained in Example 1;

[0049] Figure 2The carbon NMR spectrum of compound I-1 obtained in Example 1;

[0050] Figure 3 The 1H NMR spectrum of compound I-2 obtained in Example 2;

[0051] Figure 4 The carbon NMR spectrum of compound I-2 obtained in Example 2;

[0052] Figure 5 The 1H NMR spectrum of compound I-3 obtained in Example 3;

[0053] Figure 6 The carbon NMR spectrum of compound I-3 obtained in Example 3;

[0054] Figure 7 The 1H NMR spectrum of compound I-4 obtained in Example 4;

[0055] Figure 8 The carbon NMR spectrum of compound I-4 obtained in Example 4;

[0056] Figure 9 The 1H NMR spectrum of compound I-5 obtained in Example 5;

[0057] Figure 10 The image shows the carbon NMR spectrum of compound I-5 obtained in Example 5;

[0058] Figure 11 The nuclear magnetic resonance fluorine spectrum of compound I-5 obtained in Example 5;

[0059] Figure 12 The 1H NMR spectrum of compound I-6 obtained in Example 6;

[0060] Figure 13 The carbon NMR spectrum of compound I-6 obtained in Example 6;

[0061] Figure 14 The 1H NMR spectrum of compound I-7 obtained in Example 7;

[0062] Figure 15 The carbon NMR spectrum of compound I-7 obtained in Example 7;

[0063] Figure 16 The nuclear magnetic resonance fluorine spectrum of compound I-7 obtained in Example 7;

[0064] Figure 17 The 1H NMR spectrum of compound I-8 obtained in Example 8;

[0065] Figure 18 The carbon NMR spectrum of compound I-8 obtained in Example 8;

[0066] Figure 19 The 1H NMR spectrum of compound I-9 obtained in Example 9;

[0067] Figure 20 The carbon NMR spectrum of compound I-9 obtained in Example 9;

[0068] Figure 21 The 1H NMR spectrum of compound I-10 obtained in Example 10;

[0069] Figure 22 The carbon NMR spectrum of compound I-10 obtained in Example 10;

[0070] Figure 23 The 1H NMR spectrum of compound I-11 obtained in Example 11;

[0071] Figure 24 The carbon NMR spectrum of compound I-11 obtained in Example 11;

[0072] Figure 25 The 1H NMR spectrum of compound I-12 obtained in Example 12;

[0073] Figure 26 The image shows the carbon NMR spectrum of compound I-12 obtained in Example 12. Detailed Implementation

[0074] The following are specific embodiments of the present invention, and the technical solutions of the present invention will be further described in conjunction with the embodiments, but the present invention is not limited to these embodiments.

[0075] Unless otherwise specified, the reagents, methods and equipment used in this invention are all conventional reagents, methods and equipment in this technical field.

[0076] Example 1

[0077] Example 1 provides a sulfur-containing acetamide compound I-1, having the following structure:

[0078]

[0079] Its preparation method is as follows:

[0080] In a reaction vessel, 4-bromo-benzothiazole salt (2 mmol, 0.76 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-1. Compound I-1 is a red oil.

[0081] The reaction route is as follows:

[0082]

[0083] The proton and carbon spectra of the obtained compound I-1 are as follows: Figure 1 and Figure 2 As shown, the structural characterization data are as follows:

[0084] 1 H NMR(500MHz, CDCl3)δ8.15(s,1H),7.41–7.39(m,2H),7.38–7.36(m,3H),7.36 –7.30(m,3H),7.28(td,J=7.7,1.4Hz,1H),7.13–7.09(m,2H),7.06(td,J=7.6 ,1.5Hz,1H),6.75(dd,J=7.8,1.4Hz,1H),4.84(s,2H),4.47(dd,J=8.4,4.7Hz ,1H),3.46–3.36(m,2H),3.32(dd,J=12.8,8.4Hz,1H),3.09(dd,J=12.8,4.7H z, 1H), 1.20 (t, J = 7.0 Hz, 3H).

[0085] 13 C10 NMR (126MHz, CDCl3) δ 163.1, 140.9, 137.6, 137.4, 135.7, 131.5, 131.0, 129.9, 129.2, 128.7, 128.3, 128.1, 126.6, 125.8, 121.7, 80.6, 64.8, 47.9, 40.5, 15.3. The molecular weight of compound I-1 was determined by high-resolution mass spectrometry (HRMS) of electrospray ionization (ESI): C10 24 H 24 BrNO2SNa[M+Na] + Theoretical value (Calcd): 492.0603; Actual measured value (found): 492.0599.

[0086] Example 2

[0087] Example 2 provides a sulfur-containing acetamide compound I-2, having the following structure:

[0088]

[0089] Its preparation method is as follows:

[0090] In a reaction vessel, 4-iodo-benzothiazole salt (2 mmol, 0.61 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-2. Compound I-2 is a red oil.

[0091] The reaction route is as follows:

[0092]

[0093] The proton and carbon spectra of the obtained compound I-2 are as follows: Figure 3 and Figure 4 As shown, the structural characterization data are as follows:

[0094] 1 H NMR(500MHz, CDCl3)δ8.16(s,1H),7.41–7.36(m,4H),7.35–7.33(m,2H),7.31–7.28( m,1H),7.25–7.22(m,2H),7.16(d,J=8.4Hz,2H),7.07(td,J=7.5,1.5Hz,1H),6.75(d d,J=7.8,1.4Hz,1H),4.94–4.77(m,1H),4.47(dd,J=8.4,4.7Hz,1H),3.47–3.35(m,2 H), 3.32 (dd, J = 12.8, 8.4Hz, 1H), 3.09 (dd, J = 12.7, 4.7Hz, 1H), 1.20 (t, J = 7.0Hz, 3H).

[0095] 13 C NMR (126MHz, CDCl3) δ163.1,140.9,137.6,137.5,135.2,133.5,130.7,129.9, 129.1,128.7,128.6,128.3,128.1,126.6,125.8,80.6,64.8,47.9,40.5,15.2.

[0096] The molecular weight of compound I-2 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 24 H 24 Theoretical value (Calcd) of INO2SNa[M+Na]+: 540.0465; Actual measured value (found): 540.0472.

[0097] Example 3

[0098] Example 3 provides a sulfur-containing acetamide compound I-3, having the following structure:

[0099]

[0100] Its preparation method is as follows:

[0101] In a reaction vessel, 4-methylbenzothiazole salt (2 mmol, 0.67 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-3. Compound I-3 is a yellow solid. The reaction route is as follows:

[0102]

[0103] The proton and carbon spectra of the obtained compound I-3 are as follows: Figure 5 and Figure 6 As shown, the structural characterization data are as follows:

[0104] 1 H NMR (500MHz, CDCl3) δ8.16 (s, 1H), 7.39 (dd, J = 14.6, 7.4Hz, 4H), 7.35 (d, J = 7.1Hz, 2H),7.26(d,J=7.9Hz,1H),7.11(d,J=7.6Hz,2H),7.09–7.04(m,3H),6.75(d,J=7. 8Hz, 1H), 4.86 (s, 2H), 4.47 (dd, J=8.4, 4.7Hz, 1H), 3.48–3.35 (m, 2H), 3.31 (dd, J= 12.8,8.4Hz,1H),3.07(dd,J=12.8,4.7Hz,1H),2.32(s,3H),1.21(t,J=7.0Hz,3H);

[0105] 13C NMR (126MHz, CDCl3) δ163.1,141.0,138.0,137.4,137.2,133.7,130.1,129.2,129 .1,128.9,128.7,128.3,128.1,126.6,125.7,80.6,64.8,48.2,40.5,21.2,15.2.

[0106] The molecular weight of compound I-3 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 25 H 27 Theoretical value (Calcd) of NO2SNa[M+Na]+: 428.1654; Actual measured value (found): 428.1653.

[0107] Example 4

[0108] Example 4 provides a sulfur-containing acetamide compound I-4, having the following structure:

[0109]

[0110] Its preparation method is as follows:

[0111] In a reaction vessel, 4-methoxybenzothiazole salt (2 mmol, 0.67 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-4. Compound I-4 is a red oil.

[0112] The reaction route is as follows:

[0113]

[0114] The proton and carbon spectra of the obtained compound I-4 are as follows: Figure 7 and Figure 8 As shown, the structural characterization data are as follows:

[0115] 1H NMR(500MHz, CDCl3)δ8.14(s,1H),7.39(t,J=1.2Hz,1H),7.38–7.36(m,3H), 7.36–7.33(m,2H),7.26(dd,J=7.9,1.4Hz,1H),7.15–7.12(m,2H),7.06–7.0 2(m,1H),6.81–6.77(m,2H),6.73(dd,J=7.8,1.5Hz,1H),4.83(s,2H),4.47( dd,J=8.4,4.7Hz,1H),3.77(s,3H),3.48–3.35(m,2H),3.31(dd,J=12.8,8.5

[0116] Hz,1H),3.08(dd,J=12.8,4.7Hz,1H),1.20(t,J=7.0Hz,3H);

[0117] 13 C NMR (126MHz, CDCl3) δ163.1,159.0,140.9,137.9,137.5,130.6,130.1,128.9,128 .9,128.7,128.3,128.1,126.6,125.7,113.7,80.6,64.8,55.2,47.8,40.5,15.2.

[0118] The molecular weight of compound I-4 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 25 H 27 NO3SNa[M+Na] + Theoretical value (Calcd): 444.1603; Actual measured value (found): 444.1600.

[0119] Example 5

[0120] Example 5 provides a sulfur-containing acetamide compound I-5, having the following structure:

[0121]

[0122] Its preparation method is as follows:

[0123] In a reaction vessel, 4-trifluoromethylbenzothiazole salt (2 mmol, 0.71 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-5. Compound I-5 is a red oil.

[0124] The reaction route is as follows:

[0125]

[0126] The proton, carbon, and fluorine spectra of the obtained compound I-5 are shown below. Figures 9-11 As shown, the structural characterization data are as follows:

[0127] 1 H NMR (500MHz, CDCl3) δ8.19 (s, 1H), 7.52 (d, J = 7.7Hz, 1H), 7.46 (dd, J = 7.3, 1.5Hz, 2H), 7. 43–7.37(m,5H),7.36–7.33(m,2H),7.31–7.28(m,1H),7.07(td,J=7.6,1.5Hz,1H),6.76 (dd,J=7.8,1.4Hz,1H),4.94(d,J=22.5Hz,2H),4.48(dd,J=8.4,4.7Hz,1H),3.46–3.37( m,2H),3.33(dd,J=12.8,8.4Hz,1H),3.10(dd,J=12.8,4.7Hz,1H),1.20(t,J=7.0Hz,3H);

[0128] 13 C NMR (126MHz, CDCl3) δ163.2,140.8,137.7,137.5,137.5,132.6,130.7(q,J=32.2Hz),129.8,129.2,128.9,1 28.7,128.3,128.1,126.6,125.9–125.8(m),125.1,124.5(q,J=3.8Hz),122.9,80.6,64.8,48.1,40.4,15.2.

[0129] 19 F NMR (471MHz, CDCl3) δ-62.56.

[0130] The molecular weight of compound I-5 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 25 H 24 Theoretical value (Calcd) of F3NO2SNa[M+Na]+: 482.1372; Actual measured value (found): 482.1370.

[0131] Example 6

[0132] Example 6 provides a sulfur-containing acetamide compound I-6, having the following structural formula:

[0133]

[0134] Its preparation method is as follows:

[0135] In a reaction vessel, methyl 4-carboxylate benzothiazole salt (2 mmol, 0.73 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-6. Compound I-6 is a red oil.

[0136] The reaction route is as follows:

[0137]

[0138] The proton and carbon spectra of the obtained compound I-6 are as follows: Figure 12 and Figure 13 As shown, the structural characterization data are as follows:

[0139] 1 H NMR(500MHz, CDCl3)δ8.19(s,1H),7.96–7.93(m,2H),7.41–7.37(m,3H),7.36(s,2H) ,7.35–7.34(m,1H),7.30(d,J=8.3Hz,2H),7.26(dd,J=7.8,1.5Hz,1H),7.04(td,J=7 .5,1.4Hz,1H),6.74(dd,J=7.8,1.4Hz,1H),4.94(d,J=21.3Hz,2H),4.46(dd,J=8.4, 4.7Hz,1H),3.91(s,3H),3.47–3.34(m,3H),3.33–3.29(m,1H),1.19(t,J=7.0Hz,3H);

[0140] 13C NMR (126MHz, CDCl3) δ166.9,163.2,141.8,140.8,137.6,137.4,129.8,129.7,129.4, 129.1,128.7,128.6,128.3,128.2,126.6,125.8,80.6,64.8,52.1,48.2,40.5,15.2.

[0141] The molecular weight of compound I-6 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 26 H 28 NO4S[M+H] + Theoretical value (Calcd): 450.1733; Actual measured value (found): 450.1733.

[0142] Example 7

[0143] Example 7 provides a sulfur-containing acetamide compound I-7, having the following structure:

[0144]

[0145] Its preparation method is as follows:

[0146] In a reaction vessel, benzothiazole salt (2 mmol, 0.61 g), 4-fluorostyrene (3 mmol, 0.37 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain N-benzyl-N-(2-((2-ethoxy-2-(4-fluorophenyl)ethyl)thio)phenyl)formamide, i.e., compound I-7. Compound I-7 is a red oil.

[0147] The reaction route is as follows:

[0148]

[0149] The proton, carbon, and fluorine spectra of the obtained compound I-7 are as follows: Figures 14-16 As shown, the structural characterization data are as follows:

[0150] 1H NMR(500MHz, CDCl3)δ8.17(s,1H),7.35-7.33(m,2H),7.33-7.31(m,1H),7.28-7 .24(m,4H),7.22(dd,J=7.4,2.2Hz,2H),7.10-7.05(m,3H),6.76(dd,J=7.8,1.4 Hz,1H),4.89(s,2H),4.45(dd,J=8.1,5.0Hz,1H),3.39(qq,J=9.2,7.0Hz,2H),3 .29(dd,J=12.8,8.2Hz,1H),3.04(dd,J=12.8,5.0Hz,1H),1.20(t,J=7.0Hz,3H);

[0151] 13 C NMR(126MHz, CDCl3)δ163.1,162.6(d,J=246.4Hz),138.0,137.2,136.6,130.0,129 .2,128.4,128.3,128.2,127.6,125.9,115.7,115.5,80.0,64.8,48.5,40.5,15.2;

[0152] 19 F NMR (471MHz, CDCl3) δ-113.88.

[0153] The molecular weight of compound I-7 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 24 H 24 FNO2SNa[M+Na] + Theoretical value (Calcd): 432.1403; Actual measured value (found): 432.1411.

[0154] Example 8

[0155] Example 8 provides a sulfur-containing acetamide compound I-8, having the following structure:

[0156]

[0157] Its preparation method is as follows:

[0158] In a reaction vessel, benzothiazole salt (2 mmol, 0.61 g), 4-cyanostrene (3 mmol, 0.39 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-8. Compound I-8 is a red oil.

[0159] The reaction route is as follows:

[0160]

[0161] The proton and carbon spectra of the obtained compound I-8 are as follows: Figure 17 and Figure 18 As shown, the structural characterization data are as follows:

[0162] 1 H NMR (500MHz, CDCl3) δ8.17 (s, 1H), 7.71-7.67 (m, 2H), 7.47 (d, J = 8.3Hz, 2H), 7. 33(dd,J=8.1,1.5Hz,1H),7.26(tdd,J=6.0,4.2,1.3Hz,4H),7.21(dd,J=7.4,2 .2Hz,2H),7.08(td,J=7.6,1.5Hz,1H),6.79(dd,J=7.8,1.4Hz,1H),4.89(d,J= 17.2Hz, 2H), 4.50 (dd, J=7.8, 5.0Hz, 1H), 3.41 (qd, J=7.0, 1.4Hz, 2H), 3.25 (dd,

[0163] J=13.0,7.9Hz,1H),3.03(dd,J=13.0,5.0Hz,1H),1.20(t,J=7.0Hz,3H);

[0164] 13 C NMR (126MHz, CDCl3) δ163.0,146.4,138.3,136.6,136.5,132.5,130.1,129.2,129 .0,128.5,128.4,127.7,127.3,126.3,118.6,112.1,80.1,65.4,48.6,40.2,15.2.

[0165] The molecular weight of compound I-8 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 25 H 24N₂O₂SNa[M+Na] + Theoretical value (Calcd): 439.1450; Actual measured value (found): 439.1458.

[0166] Example 9

[0167] Example 1 provides a sulfur-containing acetamide compound I-9, having the following structure:

[0168]

[0169] Its preparation method is as follows:

[0170] In a reaction vessel, benzothiazole salt (2 mmol, 0.71 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-9. Compound I-9 is a red oil.

[0171] The reaction route is as follows:

[0172]

[0173] The proton and carbon spectra of the obtained compound I-9 are as follows: Figure 19 and Figure 20 As shown, the structural characterization data are as follows:

[0174] 1 H NMR(500MHz, CDCl3)δ8.23(s,1H),7.86-7.79(m,1H),7.80–7.72(m,2H),7.64(d,J=1.7Hz,1H),7.5 0–7.44(m,2H),7.44–7.36(m,3H),7.35(d,J=7.1Hz,4H),7.25(td,J=7.7,1.4Hz,1H),6.98(td,J=7 .5,1.4Hz,1H),6.74(dd,J=7.8,1.4Hz,1H),5.05(d,J=21.5Hz,2H),4.45(dd,J=8.4,4.7Hz,1H),3. 47–3.35(m,2H),3.33(dd,J=12.8,8.4Hz,1H),3.08(dd,J=12.8,4.7Hz,1H),1.21(t,J=7.0Hz,3H);

[0175] 13C NMR (126MHz, CDCl3) δ163.3,140.9,137.8,137.4,134.2,133.2,132.8,130.0,129.0,128.7,128.3, 128.2,128.1,128.1,127.9,127.7,127.1,126.6,126.1,126.0,125.8,80.6,64.8,48.6,40.5,15.2.

[0176] The molecular weight of compound I-9 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 28 H 27 NO2SK[M+K] + Theoretical value (Calcd): 480.1394; Actual measured value (found): 480.1384.

[0177] Example 10

[0178] Example 10 provides a sulfur-containing acetamide compound I-10, having the following structure:

[0179]

[0180] Its preparation method is as follows:

[0181] In a reaction vessel, benzothiazole salt (2 mmol, 0.81 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-10. Compound I-10 is a red oil.

[0182] The reaction route is as follows:

[0183]

[0184] The proton and carbon spectra of the obtained compound I-10 are as follows: Figure 21 and Figure 22 As shown, the structural characterization data are as follows:

[0185] 1H NMR(500MHz, CDCl3)δ8.21(s,1H),7.76(dd,J=7.8,1.4Hz,1H),7.64(td,J=7.7,1.4Hz, 1H),7.50–7.42(m,4H),7.40–7.35(m,7H),7.34–7.29(m,2H),7.09(td,J=7.6,1.5Hz,1 H),6.83(dd,J=7.8,1.4Hz,1H),4.96(s,1H),4.50(dd,J=8.4,4.7Hz,1H),3.47–3.38(m ,2H),3.34(dd,J=12.8,8.4Hz,1H),3.11(dd,J=12.8,4.7Hz,1H),1.20(t,J=7.0Hz,3H);

[0186] 13 C NMR (126MHz, CDCl3) δ163.2,145.0,140.9,137.8,137.4,137.4,133.8,132.9,130.0,130.0,129.5,129 .2,128.9,128.9,128.7,128.3,128.1,127.6,126.6,125.9,118.7,111.2,80.6,64.8,48.3,40.4,15.3.

[0187] The molecular weight of compound I-10 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 31 H 28 N₂O₂SNa[M+Na] + Theoretical value (Calcd): 515.1763; Actual measured value (found): 492.0599.

[0188] Example 11

[0189] Example 11 provides a sulfur-containing acetamide compound I-11, having the following structure:

[0190]

[0191] Its preparation method is as follows:

[0192] In a reaction vessel, benzothiazole salt (2 mmol, 0.61 g), trans-β-methylstyrene (3 mmol, 0.36 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-11. Compound I-11 is a red oil.

[0193] The reaction route is as follows:

[0194]

[0195] The proton and carbon spectra of the obtained compound I-11 are as follows: Figure 23 and Figure 24 As shown, the structural characterization data are as follows:

[0196] 1 H NMR(500MHz, CDCl3)δ8.18(s,1H),7.42–7.39(m,1H),7.38–7.33(m,4H),7.31( dd,J=6.6,1.7Hz,1H),7.26(dt,J=7.1,4.5Hz,4H),7.21(dd,J=7.3,2.1Hz,2H) ,7.06(t,J=7.8Hz,1H),6.75(d,J=7.8Hz,1H),4.90(s,2H),4.43(d,J=5.1Hz,1 H),3.53–3.44(m,2H),3.44–3.37(m,1H),1.32(d,J=6.9Hz,3H),1.24(t,J=7.0H z,3H).

[0197] 13 C NMR (126MHz, CDCl3) δ163.1,140.0,139.2,136.7,136.2,130.5,130.1,129.2,128 .8,128.4,128.3,127.9,127.5,127.2,126.4,83.9,65.2,48.8,48.7,16.2,15.2.

[0198] The molecular weight of compound I-11 was determined by high-resolution mass spectrometry (HRMS) using electrospray ionization (ESI): C 25 H 27 NO2SNa[M+Na] + Theoretical value (Calcd): 414.1498; Actual measured value (found): 414.1505.

[0199] Example 12

[0200] Example 12 provides a sulfur-containing acetamide compound I-12, having the following structure:

[0201]

[0202] Its preparation method is as follows:

[0203] In a reaction vessel, 2-methylbenzothiazole salt (2 mmol, 0.63 g), styrene (3 mmol, 0.31 g), sodium acetate (3 mmol, 0.25 g), iodine (1 mmol, 0.50 g), and ethanol (10 mL) were mixed thoroughly and reacted at 100 °C for 10 hours. After the reaction was completed, the mixture was cooled to room temperature, filtered, and subjected to rotary evaporation under reduced pressure to remove unreacted substances, yielding the crude product. The crude product was purified by column chromatography to obtain compound I-12. Compound I-12 is a red oil.

[0204] The reaction route is as follows:

[0205]

[0206] The proton and carbon spectra of the obtained compound I-12 are as follows: Figure 25 and Figure 26 As shown, the structural characterization data are as follows:

[0207] 1 H NMR (500MHz, CDCl3) δ7.43–7.37(m,4H),7.35(ddd,J=8.6,5.5,2.5Hz,1H),7.30(d,J=1.7Hz,1H),7.26(dt ,J=4.1,1.7Hz,4H),7.24–7.21(m,2H),6.97(td,J=7.3,1.2Hz,1H),6.62(ddd,J=7.8,2.5,1.4Hz,1H),5.6 5(dd,J=14.3,11.1Hz,1H),4.51(dt,J=8.3,5.0Hz,1H),3.96(dd,J=14.4,7.5Hz,1H),3.48–3.39(m,2H),3 .39–3.32(m,1H),3.14(ddd,J=12.7,11.5,4.8Hz,1H),1.84(d,J=4.4Hz,3H),1.22(td,J=7.0,1.6Hz,3H).

[0208] 13C NMR(126MHz, CDCl3)δ170.8(d,J=13.3Hz),141.0,139.1(d,J=3.2Hz),137.9–137.3(m),130.1(d,J=7.7Hz),129.4(d ,J=3.2Hz),128.8,128.7,128.3(d,J=2.5Hz),128.3,127.3,126.6(d,J=2.3Hz),126.2,126.1,125.1,80.5(d,J=6.6H z), 64.8 (d, J = 2.7 Hz), 50.5, 39.3 (d, J = 12.8 Hz), 22.3 (d, J = 2.7 Hz), 15.2. The molecular weight of compound I-12 obtained by high-resolution mass spectrometry (HRMS) by electrospray ionization (ESI) was determined as follows: C 25 H 27 NO2SNa[M+Na] + Theoretical value (Calcd): 428.1655; Actual measured value (found): 428.1652.

[0209] Performance testing

[0210] The compounds prepared in Examples 1-12 were tested for their antitumor cell activity.

[0211] (1) Test method: Each compound (Ⅰ-1~Ⅰ-12) was prepared into a solution of 100 μg·mL -1 The methanol solution, and the positive control drugs 5-fluorouracil (5-FU) and docetaxel were prepared to a concentration of 100 μg / mL. -1 The inhibitory effects of each compound on K562 cells, HL-60 cells, and HeLa cells were tested using DMSO solution, with methanol and DMSO solvent as blank controls, respectively, and the MTT assay was used.

[0212] (2) Preparation of cell culture medium: Pour one packet of RPMI-1640 culture medium powder (Net wt 10.4g) into a clean beaker, dissolve it in 900mL of ultrapure water, and add 100mg·mL⁻¹ -11 mL of streptomycin, 0.5 mL of penicillin, and 2 g of NaHCO3 were mixed magnetically and then filtered through a 0.22 μm filter in a clean bench using a pre-sterilized Zeiss filter. The filtrate was stored directly in a 450 mL / bottle after moist heat sterilization. Before using the culture medium, frozen serum was inactivated at 56 °C for 30 min and then added to the prepared RPMI-1640 culture medium (50 mL serum in 450 mL of culture medium). The mixture was gently shaken, capped, sealed with aluminum foil, and stored at 4 °C. MTT solution preparation: 50 mg of MTT (3-(4,5-dimethylthiazol-2)-2,5-diphenyltetrazolium bromide) powder was dissolved in 10 mL of PBS solution, filtered through a 0.22 μm filter, and stored at 4 °C.

[0213] (3) Antitumor activity test: K562 cells, HL-60 cells, and HeLa cells in the logarithmic growth phase were centrifuged at 3000 rpm for 3 min at 4℃. The supernatant was removed, and the cells were diluted with fresh RPMI-1640 medium to a concentration of 1×10⁻⁶. 5 Cell suspension at 200 μL / mL was seeded into each well of a 96-well plate and incubated at 37°C with 5% CO2 for 1 h. Then, 2 μL of sample solution was added to each well, with three parallel wells per sample. Two blank control groups of three wells each were also included. Cells were incubated under the same conditions for 24 h. After 24 h, morphological changes were observed under a light microscope to preliminarily determine the cytotoxic activity of the sample. Photographs were taken if necessary. 5 mg / mL of the solution was added to each well. -1 Add 20 μL of MTT solution to each well and incubate for 4 h. Centrifuge the 96-well plate (4℃, 2000 rpm, 20 min) to remove the supernatant. Add 150 μL of DMSO to each well and shake thoroughly to completely dissolve the purple precipitate. Measure the optical density (OD) at 570 nm using a microplate reader. Take the average value for each sample and calculate IR% = (OD). 空白 -OD 样品 ) / OD 空白 The inhibition rate (IR%) is calculated using the formula ×100%.

[0214] The inhibitory activity of compound 3a-3h on the proliferation of four types of tumor cells was tested using the MTT assay. The results are shown in Table 1.

[0215] Table 1. MTT assay results of the inhibitory activity of the compounds against the proliferation of three types of tumor cells.

[0216]

[0217]

[0218] As shown in Table 1, the sulfur-containing acetamide compound prepared in this invention has a certain inhibitory effect on K562 cells, HL-60 cells and HeLa cells, indicating that it has certain anti-tumor cell activity and has potential application value in anti-tumor cell drugs.

[0219] The present invention has been described in detail above with reference to the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention.

Claims

1. A sulfur-containing acetamide compound, characterized in that, Selected from the following structural formulas: 、 、 、 、 、 、 、 、 、 、 、 。 2. A method for preparing the sulfur-containing acetamide compound of claim 1, characterized in that, Includes the following steps: Compound 1, compound 2, compound 3, base and oxidant are mixed and reacted to obtain sulfur-containing acetamide compounds with the structural formula shown in Formula I; The structural formulas of compounds 1, 2, and 3 are as follows: 、 ； Wherein, X is a halogen; the substituents R1 to R6 correspond to the segments of the structural formula in claim 1.

3. The preparation method according to claim 2, characterized in that, The alkali includes inorganic alkali or organic alkali.

4. The preparation method according to claim 2, characterized in that, The reaction temperature is 30~120℃.

5. The preparation method according to claim 2, characterized in that, The reaction time is 8-24 hours.

6. The preparation method according to claim 2, characterized in that, The oxidant includes at least one of I2, tert-butyl hydroperoxide, NH4I, or di-tert-butyl hydroperoxide.

7. The preparation method according to claim 2, characterized in that, The molar ratio of compound 1, compound 2, base and oxidant is 1:(1.5~3.0):(1.0~1.5):(1.0~1.5).

8. The use of the sulfur-containing acetamide compound according to claim 1 in the preparation of antitumor drugs.

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