Compounds containing a chain carboxylic acid amide structure, and methods of making and using the same, and bactericides

Abstract

The present application relates to the field of pesticide fungicides, discloses a compound containing a chain carboxylic acid amide structure and a preparation method and application thereof, and a fungicide, the compound has a structure shown in formula (I). The compound of the present application has excellent control effect on plant diseases caused by oomycetes such as cucumber downy mildew, phytophthora infestans, pepper phytophthora and the like, is equivalent to the current commercial oomycete disease control agent fluazinam, and has a good market development prospect.

Description

Technical Field

[0001] This invention relates to the field of pesticides and fungicides, specifically to compounds containing chain carboxylic acid amide structures, their preparation methods and applications, and fungicides. Background Technology

[0002] Oomycetes are one of the important pathogens that cause plant diseases. They are characterized by their wide range of parasitic range, strong destructiveness, great harm, and rapid development.

[0003] Downy mildew is one of the most representative oomycetes. It has a short incubation period and can infect multiple times. It can cause a large-scale epidemic of disease in a very short time. For example, the downy mildew of cucumber caused by this fungus can cause all cucumbers to die in just a few days.

[0004] Plant diseases caused by downy mildew can generally be classified into the following three categories: 1) leaf diseases, mainly downy mildew; 2) root and crown diseases of annual and perennial crops, such as soil moisture, seedling wilting, root, neck and stem rot; 3) systemic diseases, which are diseases caused by infection of the roots of soil or seeds, distribution of pathogens in the vascular system of plants and manifestation of symptoms on growing points or leaves.

[0005] In temperate and tropical climates, most annual or perennial agricultural, horticultural, and ornamental crops (such as grapes, cucumbers, potatoes, tobacco, tomatoes, hops, citrus, sunflowers, vegetables, and soybeans) are susceptible to downy mildew, making it a highly destructive plant pathogen. The diseases it causes are difficult to control, resulting in significant losses to agricultural production. Effective control of downy mildew has long been a top priority.

[0006] Controlling oomycete diseases is becoming increasingly difficult. Currently, chemical control remains the simplest and most effective method, with multi-site protective fungicides and single-site systemic fungicides being the main products used in production. However, with the prolonged use of these fungicides and their long-term irrational application, many pathogens have developed serious drug resistance.

[0007] Therefore, developing novel oomycete fungicides that do not exhibit cross-resistance with traditional fungicides has become an urgent development direction in this field. Summary of the Invention

[0008] The purpose of this invention is to overcome the aforementioned deficiencies of the prior art and provide a novel type of oomycete fungicide that does not exhibit cross-resistance with traditional fungicides.

[0009] To achieve the above objectives, a first aspect of the present invention provides a compound containing a chain-like carboxylic acid amide structure, or an agriculturally chemically acceptable salt, hydrate, or solvate thereof, the compound having the structure shown in formula (I).

[0010]

[0011] In equation (I),

[0012] One of X1 and X2 is S, and the other is CH;

[0013] R represents the structure shown in equation (Q1) or the structure shown in equation (Q2);

[0014] In equation (Q1), R 1 R 2 R 3 Each is independently selected from H, C1-C 12 Alkyl, C1-C 12 alkoxy groups, C3-C 12 cycloalkyl, C1-C 12 alkylthio group, C1-C substituted with at least one halogen 12 Alkyl groups, C1-C substituted with phenyl groups 12 The alkoxy, halogen, phenyl, phenyl substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl, pyrazolyl substituted with at least one group from combination A; or, R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group of at least one group in combination A, containing at least one O atom as a cyclizing atom; A is N or CH; and when A is N, R 2 and R 3 One of them does not exist;

[0015] In equation (Q2),

[0016] R 1 R 2 R 3 R 4 Each is independently selected from H, C1-C 12 Alkyl, C1-C 12 alkoxy groups, C3-C 12 cycloalkyl, C1-C 12 alkylthio group, C1-C substituted with at least one halogen 12 Alkyl groups, C1-C substituted with phenyl groups 12 The alkoxy, halogen, phenyl, phenyl group substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl, pyrazolyl group substituted with at least one group from combination A, and R 1 R 2 R 3 R 4 At least one of them is C1-C 12alkoxy or C1-C 12 alkylthio groups; or, R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group of at least one group in combination A containing at least one O atom as a cyclizing atom;

[0017] Combination A consists of C1-C 12 Alkyl groups, halogens, and C1-C atoms substituted with at least one halogen 12 Alkyl, C1-C 12 The alkoxy group composition.

[0018] A second aspect of the present invention provides a method for preparing the compound containing a chain-like carboxylic amide structure as described in the first aspect, or an agriculturally chemically acceptable salt, hydrate, and solvate thereof, the method comprising: contacting the compound represented by formula (II) with the compound represented by formula (III) under condensation reaction conditions.

[0019]

[0020] Furthermore, the definitions of substituents in the compounds shown in formula (II) and formula (III) are the same as those described in the first aspect.

[0021] A third aspect of the invention provides the use of compounds containing a chain-like carboxylic acid amide structure as described in the first aspect, or their agrochemically acceptable salts, hydrates, and solvates, in the control of oomycete diseases in plants.

[0022] The fourth aspect of the invention provides the use of the compounds containing the chain carboxylic acid amide structure described in the first aspect, or their agrochemically acceptable salts, hydrates, and solvates, as agricultural fungicides.

[0023] A fifth aspect of the present invention provides a bactericide comprising an active ingredient and excipients, wherein the active ingredient comprises the compound containing a chain carboxylic acid amide structure as described in the first aspect, or an agriculturally chemically acceptable salt, hydrate, and solvate thereof.

[0024] The compounds of this invention have excellent control effects on plant diseases caused by oomycetes such as cucumber downy mildew, pathogenic Phytophthora, and pepper Phytophthora, and are comparable to the currently commercialized oomycete disease control agent fluthiazopyrone, showing great potential for market development. Detailed Implementation

[0025] The endpoints and any values ​​of the ranges disclosed herein are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of the various ranges, the endpoint values ​​of the various ranges and individual point values, and individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed herein.

[0026] The following provides some exemplary explanations for certain functional groups of the present invention. Unless otherwise specified, the unlisted parts are explained with reference to the following exemplary explanations.

[0027] "Halogen" refers to fluorine, chlorine, bromine, and iodine.

[0028] “C1-C 12 "alkyl" indicates an alkyl group with a total number of carbon atoms of 1-12, including straight-chain alkyl and branched-chain alkyl. For example, it can be a straight-chain alkyl or branched-chain alkyl group with a total number of carbon atoms of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, such as n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl, etc.; "C1-C 10 The definition of "alkyl" is the same as "C1-C". 12 The definition of "alkyl" is similar, but the total number of carbon atoms is different.

[0029] “C1-C 12 The definition of "alkoxy group" is the same as "C1-C". 12 The definition of "alkyl" is similar, but the difference is that "C1-C" is used. 12 The "alkoxy group" is directly connected to the parent nucleus via an O atom, representing an alkoxy group with a total carbon number of 1-12, including straight-chain alkoxy groups and branched-chain alkoxy groups. For example, it can be a straight-chain alkoxy group or a branched-chain alkoxy group with a total carbon number of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. Exemplarily, it can be methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, isobutyloxy, tert-butyloxy, n-pentyloxy, isopentyloxy, or n-hexyloxy. "C1-C 10 The definition of "alkoxy group" is the same as "C1-C". 12 The definition of "alkoxy group" is similar, but the total number of carbon atoms is different.

[0030] “C1-C 12 "alkylthio" and "C1-C" 12 The definition of "alkyl" is similar, but the difference is that "C1-C" is used. 12The "alkylthio" group, where the S atom is directly connected to the parent nucleus, represents an alkylthio group with a total carbon number of 1-12, including straight-chain and branched-chain alkylthio groups. For example, it can be a straight-chain or branched-chain alkylthio group with a total carbon number of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12. Exemplarily, it can be methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, tert-butylthio, n-pentylthio, isopentylthio, or n-hexylthio. "C1-C 10 The definition of "alkylthio" and "C1-C" 12 The definition of "alkylthio" is similar, but the total number of carbon atoms is different.

[0031] “C3-C 12 "Cycloalkyl" refers to a cycloalkyl group with a total number of carbon atoms of 3-12, and all cyclic atoms are carbon atoms. For example, it can be a cycloalkyl group with a total number of carbon atoms of 3, 4, 5, 6, 7, 8, 9, 10, 11, or 12, and the "C3-C" indicates a cycloalkyl group. 12 The cycloalkyl group can be directly attached to the parent nucleus at any substituted position. (C3-C) 10 The definition of "cycloalkyl" and "C3-C" 12 The definition of "cycloalkyl" is similar, but the total number of carbon atoms is different.

[0032] "C1-C substituted by at least one halogen" 12 "alkoxy group" indicates "C1-C 12 At least one H atom in the alkoxy group is substituted with a halogen, and the substituted halogen can be one or more. "C1-C" substituted with at least one halogen 10 The definition of "alkoxy group" is similar, except that the total number of carbon atoms is different.

[0033] "C1-C substituted by at least one halogen" 12 "alkyl" indicates "C1-C 12 At least one H atom in the alkyl group is substituted with a halogen, and the substituted halogen can be one or more. "C1-C" substituted with at least one halogen 10 "alkyl" has a similar definition, only the total number of carbon atoms is different.

[0034] "C1-C substituted with phenyl" 12 "alkoxy group" indicates "C1-C 12 At least one H atom in the alkoxy group is replaced by a phenyl group. "C1-C" groups substituted with phenyl groups 10 The definition of "alkoxy group" is similar, except that the total number of carbon atoms is different.

[0035] “R 2 and R 3"A 3-7 member saturated heterocyclic group containing at least one O atom as a cyclizing atom, which is formed by cyclization of carbon atoms in combination A without substitution or by substitution of at least one group in combination A" means that the total number of cyclizing carbon atoms is 3, 4, 5, 6, or 7 and contains at least one O atom.

[0036] Unless otherwise specified, a group "substituted by at least one group in combination A" means that at least one group in combination A can be substituted at any position where substitution is possible. The dashed lines in the structural formulas shown for the groups indicate the connection points between the groups and the parent nucleus.

[0037] As previously stated, a first aspect of the present invention provides a compound having a chain-like carboxylic acid amide structure or an agriculturally chemically acceptable salt, hydrate, and solvate thereof, the compound having the structure shown in formula (I).

[0038] According to a preferred embodiment, in formula (I),

[0039] One of X1 and X2 is S, and the other is CH;

[0040] R represents the structure shown in equation (Q1);

[0041] In equation (Q1), R 1 R 2 R 3 Each is independently selected from H, C1-C 12 Alkyl, C1-C 12 alkoxy groups, C3-C 12 cycloalkyl, C1-C 12 alkylthio group, C1-C substituted with at least one halogen 12 Alkyl groups, C1-C substituted with phenyl groups 12 The alkoxy, halogen, phenyl, phenyl substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl, pyrazolyl substituted with at least one group from combination A; or, R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group of at least one group in combination A containing at least one O atom as a cyclizing atom;

[0042] A is N or CH; and when A is N, R 2 and R 3 One of them does not exist;

[0043] Combination A consists of C1-C 12 Alkyl groups, halogens, and C1-C atoms substituted with at least one halogen 12 Alkyl, C1-C 12 The alkoxy group composition.

[0044] According to another preferred embodiment, in formula (I),

[0045] One of X1 and X2 is S, and the other is CH;

[0046] R represents the structure shown in equation (Q1);

[0047] In equation (Q1), R 1 R 2 R 3 Each is independently selected from H, C1-C 10 Alkyl, C1-C 10 alkoxy groups, C3-C 10 cycloalkyl, C1-C 10 alkylthio group, C1-C substituted with at least one halogen 10 Alkyl groups, C1-C substituted with phenyl groups 10 The alkoxy, halogen, phenyl, phenyl substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl, pyrazolyl substituted with at least one group from combination A; or, R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group of at least one group in combination A containing at least one O atom as a cyclizing atom;

[0048] A is N or CH; and when A is N, R 2 and R 3 One of them does not exist;

[0049] Combination A consists of C1-C 10 Alkyl groups, halogens, and C1-C atoms substituted with at least one halogen 10 Alkyl, C1-C 10 The alkoxy group composition.

[0050] According to a particularly preferred embodiment, the compound with the structure shown in formula (I) is selected from any one of compound formulas (I-1) to (I-236).

[0051] According to a preferred embodiment, in formula (I),

[0052] One of X1 and X2 is S, and the other is CH;

[0053] R represents the structure shown in equation (Q2); R 1 R 2 R 3 R 4 Each is independently selected from H, C1-C 12 Alkyl, C1-C 12alkoxy groups, C3-C 12 cycloalkyl, C1-C 12 alkylthio group, C1-C substituted with at least one halogen 12 Alkyl groups, C1-C substituted with phenyl groups 12 The alkoxy, halogen, phenyl, phenyl group substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl group substituted with at least one group from combination A; and R 1 R 2 R 3 R 4 At least one of them is C1-C 12 alkoxy or C1-C 12 alkylthio group, or R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group containing at least one O atom 3-7 membered saturated heterocyclic group;

[0054] Combination A consists of C1-C 12 Alkyl groups, halogens, and C1-C atoms substituted with at least one halogen 12 Alkyl, C1-C 12 The alkoxy group composition.

[0055] According to another preferred embodiment, in formula (I),

[0056] One of X1 and X2 is S, and the other is CH;

[0057] R represents the structure shown in equation (Q2); R 1 R 2 R 3 R 4 Each is independently selected from H, C1-C 10 Alkyl, C1-C 10 alkoxy groups, C3-C 10 cycloalkyl, C1-C 10 alkylthio group, C1-C substituted with at least one halogen 10 Alkyl groups, C1-C substituted with phenyl groups 10 The alkoxy, halogen, phenyl, phenyl group substituted with at least one group from combination A, cyano, nitro, pyridyl, pyrazolyl, pyrazolyl group substituted with at least one group from combination A; and R 1 R 2 R 3 R 4 At least one of them is C1-C 10 alkoxy or C1-C 10 alkylthio group, or R 2 and R3 Together they cyclize to form an unsubstituted or substituted group containing at least one O atom 3-7 membered saturated heterocyclic group;

[0058] Combination A consists of C1-C 10 Alkyl groups, halogens, and C1-C atoms substituted with at least one halogen 10 Alkyl, C1-C 10 The alkoxy group composition.

[0059] According to another particularly preferred embodiment, the compound with the structure shown in formula (I) is selected from any one of formulas (II-1) to (II-136).

[0060] The present invention does not impose any particular limitation on the stereostructure of the compound represented by formula (I). The compound represented by formula (I) may exist in different stereoisomers, optical isomers or tautomers. The present invention includes all stereoisomers or optical isomers or tautomers and mixtures thereof in various proportions.

[0061] Any asymmetric atom (e.g., carbon, etc.) in the compounds disclosed in this invention may exist in racemic or enantiomerically enriched forms, such as (R)-, (S)-, or (R,S)- configurations.

[0062] This invention does not impose any particular limitation on the method for preparing the compound containing the chain-like carboxylic amide structure. Those skilled in the art can obtain it by utilizing the characteristics of the structural formula and combining it with known methods in the field of organic synthesis. However, in order to obtain the compound containing the chain-like carboxylic amide structure or its agriculturally acceptable salts, hydrates, and solvates according to this invention in higher yield, this invention provides the following second aspect of the method for preparing the compound containing the chain-like carboxylic amide structure or its agriculturally acceptable salts, hydrates, and solvates; the method includes:

[0063] Under condensation reaction conditions, the compound represented by formula (II) and the compound represented by formula (III) are subjected to a contact reaction.

[0064] Furthermore, the definitions of substituents in the compounds shown in formula (II) and formula (III) are the same as those described in the first aspect.

[0065] Preferably, the condensation reaction is carried out in the presence of an alkaline reagent and in an anhydrous environment.

[0066] In a preferred embodiment, the alkaline reagent is at least one of triethylamine, N,N-diisopropylethylamine, and 4-dimethylaminopyridine.

[0067] The condensation reaction described in this invention is carried out under alkaline conditions.

[0068] Preferably, the contact reaction is carried out in the presence of a solvent, which is preferably selected from at least one of dichloromethane, tetrahydrofuran, N,N-dimethylformamide, acetonitrile, and acetone.

[0069] Preferably, the conditions for the contact reaction include: a reaction temperature of -5°C to 60°C and a reaction time of 1 to 48 hours.

[0070] In this invention, the compounds represented by formula (II) and formula (III) can be commercially available or synthesized using existing methods based on their structural formulas. The present invention provides exemplary methods for preparing the compounds represented by formula (II) in the embodiments, which should not be construed as limiting the invention by those skilled in the art.

[0071] Preferably, in the second aspect of the invention, the molar ratio of the compound represented by formula (II) to the compound represented by formula (III) is 1:(1 to 3); more preferably, it is 1:(1.1 to 2.2).

[0072] In a second aspect of the invention, the product obtained after the contact reaction can also be post-processed using post-processing methods conventionally used in the art to obtain a product with higher purity. For example, the post-processing operation methods include: extraction, washing, rotary evaporation, column chromatography, recrystallization, etc. The invention does not have any particular limitations on this, as long as the compound containing the chain carboxylic amide structure described above can be obtained.

[0073] As previously stated, the third aspect of the present invention provides the use of compounds containing a chain-like carboxylic acid amide structure as described in the first aspect, or their agriculturally chemically acceptable salts, hydrates, and solvates, in the control of oomycete diseases in plants.

[0074] Preferably, the plant oomycete disease is selected from at least one of cucumber downy mildew, potato late blight, and pepper blight.

[0075] As previously stated, the fourth aspect of the present invention provides the use of compounds containing a chain carboxylic acid amide structure as described in the first aspect, or their agriculturally chemically acceptable salts, hydrates, and solvates, as agricultural fungicides.

[0076] As previously described, a fifth aspect of the present invention provides a bactericide comprising an active ingredient and excipients, wherein the active ingredient comprises at least one of the compounds containing a chain carboxylic acid amide structure as described in the first aspect above, or an agriculturally chemically acceptable salt, hydrate, and solvate thereof.

[0077] Preferably, the content of the active ingredient is 1-99.9% by weight; more preferably, the content of the active ingredient is 5-95% by weight.

[0078] Preferably, the formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, wettable powder, powder, granule, aqueous solution, poison bait, mother liquor, and mother powder.

[0079] In this invention, the excipients can be various excipients conventionally used in the art, such as surfactants, solvents, etc.

[0080] The present invention will be described in detail below through examples.

[0081] In the following examples, unless otherwise specified, all raw materials used are commercially available and are of chemical purity.

[0082] All room temperatures below are 25±1℃.

[0083] Example 1

[0084]

[0085] Synthesis of Formula (2-2): At 25°C, 790.12 mmol of the compound shown in Formula (2-1) was placed in a 1 L two-necked flask, and 400 mL of 2 M diethyl ether hydrochloride solution was added. 534.62 mmol of tert-butyl nitrite was slowly added dropwise to the reaction flask, and the reaction was allowed to proceed for 3 hours. After the reaction was complete, the reaction mixture was concentrated under reduced pressure to a semi-solid state, washed with 1-chlorobutane, and filtered to obtain a white crystalline solid. The filtrate was concentrated, and the above process was repeated twice. The filtered solids were combined, totaling 81.10 g. This solid was used directly in the next reaction step.

[0086] Synthesis of Formula (2-3): To a 500 mL pear-shaped flask, add a magnetic stir bar, the compound shown in Formula (2-2) (193.48 mmol), 250 mL of acetonitrile, and sodium bicarbonate (1.14 mol). Start stirring and slowly add 2,6-difluorostyrene (193.51 mmol) dropwise using a constant-pressure dropping funnel. Allow the reaction to proceed for 30 minutes, monitoring for completeness by TLC. Filter the system, wash the filter cake three times with acetonitrile, combine the filtrates, and concentrate under reduced pressure to obtain a pale yellow viscous liquid. After standing overnight, a solid precipitates; filter the solid, and then concentrate the filter cake using a V... 石油醚 :V 乙酸乙酯 Wash with a 10:1 solution, remove solvent under reduced pressure to obtain a light yellow solid. Concentrate the filtrate again, and a solid precipitates. Repeat the above operation twice, combine the obtained solids, and obtain 54.39 g of the compound shown in formula (2-3). The mass spectrometry results show a molecular ion peak at 259.30. The 1H NMR data are as follows: 1H NMR (400MHz, CDCl3) δ7.47–7.25(m,1H),6.88(t,J=8.0Hz,2H),6.20–6.08(m,1H),4.67(s,2H),3.60–3.52(m,1H),3.33(dd,J=17.2,8.0Hz,1H).

[0087] Synthesis of Formula (2-4): A magnetic stir bar, the compound shown in Formula (2-3) (38.51 mmol), and 100 mL of anhydrous methanol were added sequentially to a 250 mL pear-shaped flask. While stirring, tert-butyl 4-aminothiocarbonyltetrahydropyridine-1(2H)-carboxylate (38.02 mmol) was added. The mixture was heated to reflux, and the reaction was completed in approximately 4 hours. Most of the methanol was removed by concentration under reduced pressure. 100 mL of water was added, and the mixture was extracted with ethyl acetate. The liquid was separated, and the organic phase was dried over anhydrous sodium sulfate. The mixture was filtered, and the filtrate was concentrated and purified by silica gel column chromatography to obtain the compound shown in Formula (2-4) in 89% yield. The 1H NMR data are as follows: 1 H NMR(400MHz, CDCl3)δ7.71(s,1H),7.29–7.25(m,1H),6.96(t,J=8.0Hz,2H),6.03(dd,J=12.0,9.2Hz,1H),4.21(s,2H),3.77(dd,J=17.6,12.0Hz,1H), 3.60(dd,J=17.6,9.2Hz,1H),3.19(tt,J=12.0,4.0Hz,1H),2.86(t,J=10.4 Hz, 2H), 2.09 (d, J=12.8Hz, 2H), 1.70 (qd, J=12.8, 4.8Hz, 2H), 1.39 (s, 9H).

[0088] Synthesis of Formula (2-5-1): 80 mL of methanol was added to the compound (40.0 mmol) shown in Formula (2-4) to completely dissolve it. Then, 45 mL of hydrochloric acid / methanol (4 M) solution was added, and the mixture was heated to 50 °C and reacted for 4 h. After the reaction was complete, the solvent was removed by concentration under reduced pressure. At this point, the product existed in the form of hydrochloride salt. 2 M sodium hydroxide solution was added to neutralize the solution, making the system alkaline. The mixture was extracted multiple times with ethyl acetate, and the organic phase was dried and concentrated to obtain a yellowish-brown oily crude product. Silica gel column chromatography yielded a light brown solid with a yield of 95%. The 1H NMR data are as follows: 1H NMR (400MHz, CDCl3) δ8.39(s,1H),8.01(s,1H),7.48–7.39(m,1H),7.20(t,J=8.4Hz,2H),5.98(dd,J=12.0,9.2Hz,1H),3.87(dd,J =17.6,12.0Hz,1H),3.61–3.49(m,1H),3.41–3.37(m,3H),3.02(t,J=12.0Hz,2H),2.19(d,J=14.0Hz,2H),1.88(q,J=12.4Hz,2H).

[0089] Example 2

[0090]

[0091] Synthesis of formula (2-7): Ethyl glyoxylate (50% toluene solution, 369 mmol) and hydroxylamine hydrochloride (369 mmol) were dissolved in CH3CN:H2O (9:1, 300 mL), stirred at room temperature for 5 minutes, and then Et3N (51.7 mL, 369 mmol) was added dropwise. The reaction was carried out at room temperature for 1 hour, and then concentrated under reduced pressure. The residue was dissolved in H2O (50 mL) and Et2O (300 mL). The organic layer was washed with saturated NH4Cl (50 mL), dried over Na2SO4, filtered, and concentrated. A colorless crystalline product was obtained in 97% yield.

[0092] Synthesis of formulas (2-8): Ethyl (2)-(hydroxyimine)ethyl acetate (123.2 mmol) was added to a DMF solution at 5 °C. The reaction mixture was stirred at room temperature for 12 hours, water (200 mL) was added, and the mixture was extracted with ethyl acetate (2 × 150 mL). The organic layer was separated, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give the crude product in 74% yield.

[0093] Synthesis of Formula (2-9): To a 500 mL pear-shaped flask, add a magnetic stir bar, the compound shown in Formula (2-8) (1.52 g), 250 mL acetonitrile, and sodium bicarbonate (5.04 g). Start stirring and slowly add 2,6-difluorostyrene (1.4 g) dropwise using a constant-pressure dropping funnel. The reaction was allowed to proceed for 30 minutes, and TLC was used to monitor the reaction until complete. The system was filtered, and the filter cake was washed three times with acetonitrile. The filtrates were combined and concentrated under reduced pressure to obtain a pale yellow viscous liquid. After standing overnight, a solid precipitated. This solid was filtered, and the filter cake was then concentrated using a V... 石油醚 :V 乙酸乙酯 Wash with a 10:1 solution, remove solvent under reduced pressure to obtain a light yellow solid. Concentrate the filtrate again, and a solid precipitates out. Repeat the above operation twice, combine the obtained solids, and obtain the compound shown in formula (2-9).

[0094] Synthesis of Formula (2-10): The compound shown in Formula (2-9) was placed in a sealed tube, dissolved in ethanol, and ammonia monohydrate (5 eq.) was added. The reaction was carried out at room temperature for 24 hours. After the reaction was completed, a solid precipitated out. The solid was filtered, and the filter cake was strained using V... 石油醚 :V 乙酸乙酯 Wash with a 10:1 solution, collect the filter cake, and dry to obtain a white solid.

[0095] Synthesis of Formula (2-11): 1.8 g of the compound shown in Formula (2-10) was dissolved in anhydrous tetrahydrofuran, and 3.55 g of phosphorus pentasulfide was added. The mixture was reacted at 50 °C for 6 hours. Then, ethyl acetate and 1 N hydrochloric acid were added, and the resulting suspension was filtered. The residue was washed with water and ethyl acetate to obtain the compound shown in Formula (2-11).

[0096] Synthesis of formula (2-5-2): 1.69 g of the compound shown in formula 2-11 was dissolved in methanol, and 2.14 g of the compound shown in formula (2-12) was added. The mixture was refluxed for 6 hours. After the reaction was complete, the mixture was cooled to room temperature, and 3 mL of concentrated hydrochloric acid was added. The reaction was monitored by TLC until complete. 2 M sodium hydroxide solution was added to the system to adjust the pH to 10. The mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated to obtain a yellowish-brown oily substance of formula (2-5-2).

[0097] Example 3: Preparation of the compound shown in formula (I)

[0098]

[0099] This embodiment illustrates the method for synthesizing the target compounds shown in formulas (I-1) to (I-236).

[0100] Specifically, the preparation of the compound shown in formula (Ⅰ-1) is taken as an example:

[0101] At room temperature, trans-3-methoxyacrylic acid (1.4 mmol, 1.4 eq.) was added to a 100 mL round-bottom flask and dissolved in 20 mL of dichloromethane. Then, EDCI (2.1 mmol, 2.1 eq.), HOBt (2.10 mmol, 2.1 eq.), and TEA (0.42 mL, 3.0 mmol, 3.0 eq.) were added sequentially. The mixture was stirred and activated for 60 min. Then, the compound of formula (2-5-1) (1.0 mmol, 1.0 eq.) was added to the system. The reaction was continued for 6 h. After the reaction was complete, water was added, and the mixture was extracted twice with dichloromethane. The organic phase was dried, concentrated, and purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to obtain the target compound of formula (Ⅰ-1). It was a white solid with a yield of 78%.

[0102] Example 4

[0103] Synthetic routes and methods for acid intermediates I-1a to I-5a

[0104]

[0105] For certain acid-corresponding ester fragments, the relevant acid intermediates can be obtained by direct ester hydrolysis.

[0106] Taking the synthesis of the compound shown in formula (Ⅰ-1a) as an example: Take a 50 mL round-bottom flask, add methyl trans-3-methoxyacrylate (10.0 mmol, 1 eq.), then add 10 mL of sodium hydroxide solution (20.0 mmol, 2.0 eq.). Raise the reaction temperature to 80 °C and react overnight. Monitor by TLC until hydrolysis is complete, then stop heating. After cooling to room temperature, adjust to acidity with 2 mol / L hydrochloric acid. A white solid precipitates. Filter, wash the filter cake twice with a small amount of water, collect the filter cake, and dry to obtain the acidic pure product, a white solid, with a yield of 56.8%.

[0107] Example 5

[0108] Synthetic routes and methods for acid intermediates I-6a to I-10a

[0109]

[0110] For acid fragments with electron-withdrawing substituents at the 2-position of acrylic acid, the above synthetic route is used to first obtain the corresponding ester, and then hydrolyze it to obtain the acid fragment.

[0111] Taking the preparation of compound I-8a as an example: Take a 100 mL three-necked flask, add 20 mL of ultra-dry dichloromethane under a N2 atmosphere, weigh out methyl bromoacetate (10.0 mmol, 1.0 eq.) and methyl formate (30.0 mmol, 3.0 eq.), dissolve them in the flask, and place it in a low-temperature reactor to cool to -40 °C. Add triethylamine (24.0 mmol, 2.4 eq.) to the system. After the temperature drops back to -40 °C, slowly add TiCl4 (15 mL, 1 mol / L in DCM, 15.0 mmol, 1.5 eq.) dropwise to the reaction system. After the addition is complete, continue the reaction for 10 min, raise the temperature to 5 °C and continue the reaction for 1 h. After the reaction is complete, pour the reaction mixture into ice water, extract twice with dichloromethane, dry the organic phase, concentrate and mix the sample, and purify by column chromatography (V... 石油醚 :V 乙酸乙酯 =20:1), yielding a yellow oily compound in 76.7% yield. Hydrolysis and acidification yield the corresponding acid I-8a.

[0112] Example 6

[0113] Synthetic routes and methods for acid intermediates I-11a to I-14a

[0114]

[0115] For acid fragments of acrylic acid modified with electron-donating substituents such as methyl at the 2-position, the above-described synthetic route is used to first obtain the corresponding ester, and then hydrolyze it to obtain the acid fragment.

[0116] Taking the preparation of compound I-11a as an example: Prepare a 50 mL flask, add zinc powder (90.0 mmol, 3.0 eq.) and 15 mL of diethyl ether, stir to obtain a suspension, then add dichloromethyl methyl ether (30 mmol, 1.0 eq.) and ethyl 2-bromopropionate (60.0 mmol, 2.0 eq.) to a constant pressure dropping funnel, dissolve and dilute with 15 mL of diethyl ether. Control the temperature to reflux the diethyl ether, slowly add the mixture dropwise to the flask, and after the addition is complete, continue to reflux the reaction solution for 20 min, then stop the reaction. Remove the zinc powder by silica gel filtration, wash with dichloromethane, wash the filtrate once with 5v% acetic acid-water solution, wash twice with water, wash with saturated saline and dry, mix the organic phase, and perform silica gel column chromatography (V... 石油醚 :V 乙酸乙酯 =10:1), yielding a transparent oily compound in 57% yield. Hydrolysis and acidification give the corresponding acid I-11a.

[0117] Example 7

[0118] Synthetic routes and methods for acid intermediates I-15a to I-19a, taking the synthetic route and method of acid fragment compound I-15a as an example:

[0119]

[0120] For the acid fragment of acrylic acid with a substituted benzene ring modified at the 2-position, the above synthetic route is used to first obtain a brominated compound, then couple it with phenylboronic acid via Suzuki to obtain the corresponding ester, and then hydrolyze it to obtain the acid fragment.

[0121] Taking the preparation of compound I-15a as an example: In a 100 mL three-necked flask, under a nitrogen atmosphere, add methyl-(Z)-2-bromo-3-methoxyacrylate (10.0 mmol, 1.0 eq.), o-methylphenylboronic acid (30.0 mmol, 3.0 eq.), anhydrous potassium carbonate (50.0 mmol, 5.0 eq.), palladium dichloride (1.0 mmol, 0.1 eq.), and 40 mL of isopropanol. Heat to reflux and react overnight. Monitor the reaction by TLC until complete. Add water, extract twice with ethyl acetate, dry the organic phase, concentrate and mix, and purify by column chromatography (V... 石油醚 :V 乙酸乙酯 =20:1), yielding a pale yellow oily compound with a yield of 92.1%, which was then hydrolyzed and acidified to give the corresponding acid I-15a.

[0122] Example 8

[0123] Synthetic routes and methods for acid intermediates I-20a to I-25a, taking the synthetic route and method of acid fragment compound I-20a as an example:

[0124]

[0125] The introduction of a methoxyoxime structure into a carboxylic acid intermediate is achieved by using the above-mentioned synthetic route, starting from substituted methyl acetoformate, reacting it with methoxyamine hydrochloride to introduce the methoxyoxime structure, and then hydrolyzing it to obtain the acid fragment.

[0126] Taking the preparation of compound I-20a as an example: Take a 50 mL pear-shaped flask, add methyl phenylacetate (11.0 mmol, 1.0 eq.), methoxyamine hydrochloride (22.0 mmol, 2.0 eq.), and 20 mL methanol. Heat the system to reflux and continue the reaction for 8 h. After the reaction is complete, add water, extract with ethyl acetate, dry the organic phase, concentrate and mix the sample, and purify by column chromatography (V... 石油醚 :V 乙酸乙酯 =20:1), yielding a white solid compound in 70.6% yield. Further hydrolysis and acidification yield the corresponding acid I-20a.

[0127] Example 9

[0128] This embodiment illustrates the method for synthesizing the target compounds shown in formulas (II-1) to (II-136).

[0129] Specifically, the preparation of the compound shown in formula (II-1) is taken as an example:

[0130] At room temperature, 3,3-dimethoxypropionic acid (1.0 mmol, 1.0 eq.) was added to a 100 mL round-bottom flask and dissolved in 20 mL of dichloromethane. Then, EDCI (1.5 mmol, 1.5 eq.), HOBt (1.5 mmol, 1.5 eq.), and TEA (2.1 mmol, 2.14 eq.) were added sequentially. The mixture was stirred and activated for 60 min. The intermediate shown in formula (2-5-1) obtained previously was then added (0.71 mmol, 0.71 eq.). The reaction was continued for 6 h. After the reaction was complete, water was added, and the mixture was extracted with dichloromethane. The organic phase was dried, concentrated, and purified by column chromatography (V petroleum ether:V ethyl acetate = 2:1) to give the target compound II-1. It was a white solid with a yield of 68%.

[0131] Example 10

[0132] Synthetic routes and methods for acid intermediates II-1a to II-4a, taking the synthetic route and method of compound II-1a as an example:

[0133]

[0134] Synthetic routes and methods for acid intermediates II-1a to II-4a, taking compound II-1a as an example:

[0135] Take a 50 mL round-bottom flask, add ethyl-3,3-dimethoxypropionate (10.0 mmol, 1 eq.), then add 10 mL of 2 mol / L sodium hydroxide solution (20.0 mmol, 2.0 eq.), and add 30 mL of methanol to make the system homogeneous. React overnight, and monitor the hydrolysis by TLC until complete. Stop heating. After cooling to room temperature, acidify with 2 mol / L hydrochloric acid, extract with ethyl acetate, dry and concentrate to obtain the acid product in pure form. Pale yellow oil, yield 85%.

[0136] Example 11

[0137] Synthetic routes and methods for acid intermediates II-5a to II-10a, taking the synthetic route and method of acid fragment compound II-5a as an example:

[0138]

[0139] Synthetic routes and methods for acid intermediates II-5a to II-10a, taking the preparation of compound II-5a as an example:

[0140] In a 50 mL round-bottom flask, add 10.0 mmol (1 eq.) of ethyl-(E)-3-ethoxyacrylate, followed by 7.5 mL (15.0 mmol, 1.5 eq.) of a prepared 2 mol / L sodium hydroxide solution. Add 20 mL of methanol, raise the temperature to 80 °C, and react overnight. TLC monitoring shows complete hydrolysis, at which point heating is stopped. After cooling to room temperature, adjust the pH to 3 with 2 mol / L hydrochloric acid, extract with ethyl acetate, dry the organic phase, and concentrate to obtain crude acid. The crude acid is a clear oil with a yield of 84%. Characterization data of the target compound:

[0141]

[0142] Formula (Ⅰ-1). White solid; mp = 134-136℃. 1H NMR (600MHz, DMSO-d6) δ8.02(d,J=3.0Hz,1H),7.49(t,J=7.8Hz,1H),7.44(d,J=12.0Hz,1 H),7.15(t,J=9.0Hz,2H),6.00(t,J=10.2Hz,1H),5.90(d,J=12.0Hz,1H),4.46(s,1H),4.1 6(s,1H),3.89(dd,J=16.8,12.6Hz,1H),3.67(s,3H),3.53(dd,J=17.4,8.6Hz,1H),3.37(s ,1H),3.15(d,J=12.6Hz,1H),2.74(d,J=12.6Hz,1H),2.08(d,J=13.2Hz,2H),1.57(s,2H). 13 C NMR (100MHz, CDCl3) δ 174.79, 166.03, 162.69, 162.59, 160.13 (d, J = 7.6Hz), 152.28, 145.14, 130.55 (t, J = 10.5Hz), 117.70, 115.77 (t, J = 16.1Hz), 111.98–111.73 (m), 94.83, 72.87 (t, J = 3.3Hz), 57.85, 41.55, 40.71, 32.55. HRMS (MALDI) calculated C 21 H 22 F2N3O3S[M+H] + 434.1344, measured value 434.1342.

[0143]

[0144] Formula (Ⅰ-2). White solid; mp = 141-143℃. 1 H NMR(400MHz,DMSO-d6)δ8.02(s,1H),7.55–7.44(m,1H),7.16(t,J=8.4Hz,2H),6 .83(d,J=21.6Hz,1H),6.00(dd,J=12.0,8.8Hz,1H),4.16(d,J=13.6Hz,2H),3.90 (dd,J=17.2,12.0Hz,1H),3.80(s,3H),3.53(dd,J=17.2,8.6Hz,1H),3.44–3.35 (m,1H),3.07(t,J=12.6Hz,2H),2.12(dd,J=13.6,3.6Hz,2H),1.71–1.57(m,2H). 13C NMR (100MHz, DMSO-d6) δ 175.27, 162.39 (d, J = 7.9Hz), 161.36, 161.15, 159.91 (d, J = 7.8Hz), 152.58, 144.78, 141.29, 141.22, 140.18, 137.65, 131.83 (t, J = 10.8Hz), 120.34, 116.09 (t, J = 16.6Hz), 112.78–112.53 (m), 72.50 (d, J = 3.0Hz), 61.85, 44.33, 41.61, 32.70. HRMS (MALDI) calculated C 21 H 21 F3N3O3S[M+H] + 452.1250, measured value 452.1250.

[0145]

[0146] Formula (Ⅰ-3). White solid; mp = 126-128℃. 1 H NMR(400MHz, CDCl3)δ7.69(s,1H),7.38–7.31(m,1H),7.01(s,1H),6.99–6. 91(m,2H),6.11(dd,J=12.0,9.2Hz,1H),4.36(d,J=13.6Hz,2H),3.91(s,3H ),3.84(dd,J=17.2,12.0Hz,1H),3.67(dd,J=17.2,9.2Hz,1H),3.39–3.30( m,1H),3.15–3.04(m,2H),2.24(dd,J=13.6,3.7Hz,2H),1.95–1.82(m,2H). 13 CNMR (100MHz, DMSO-d6) δ 175.30, 164.12, 162.40 (d, J = 7.7Hz), 159.92 (d, J = 7.8Hz), 152.58, 151.83, 144.79, 131.86 (t, J = 11.0Hz), 120.40, 116.11 (t, J = 16.5Hz), 112.80-112.56 (m), 102.27, 72.51, 61.61, 44.85, 41.63, 32.50. HRMS (MALDI) calculated value C 21 H 21 ClF2N3O3S[M+H] + 468.0955, measured value 468.0953.

[0147]

[0148] Formula (Ⅰ-4). White solid; mp = 76-78℃. 1 H NMR(400MHz, CDCl3)δ7.69(s,1H),7.39–7.32(m,1H),7.04(s,1H),6.99–6. 92(m,2H),6.11(dd,J=12.0,9.2Hz,1H),4.37(d,J=13.6Hz,2H),3.91(s,3H ),3.84(dd,J=17.2,12.0Hz,1H),3.67(dd,J=17.2,9.2Hz,1H),3.39–3.30( m,1H),3.14–3.02(m,2H),2.24(dd,J=13.6,3.6Hz,2H),1.94–1.83(m,2H). 13 CNMR (150MHz, CDCl3) δ 174.47, 164.93, 162.18, 160.52, 152.25, 145.16, 130.55, 117.74, 115.73 (t, J = 15.6Hz), 111.92, 111.77, 91.57, 72.85, 61.39, 45.06, 41.53, 40.46, 32.27. HRMS (MALDI) calculated value C 21 H 21 BrF₂N₃O₃S[M+H] + 514.0431, measured value 514.0434.

[0149]

[0150] Formula (Ⅰ-5). Light yellow solid; mp = 76-78℃. 1 H NMR (400MHz, CDCl3) δ7.69(s,1H),7.38–7.30(m,1H),6.95(t,J=8.0Hz,2H),6.76(s,1H),6.11(dd,J=12.0,9.2Hz,1H),4.36(d,J=13.6Hz,2H),3.90( s,3H),3.84(dd,J=17.2,12.0Hz,1H),3.66(dd,J=17.2,9.2Hz,1H),3.40– 3.30(m,1H),3.07(t,J=12.0Hz,2H),2.27–2.18(m,2H),1.94–1.81(m,2H). 13C NMR (100MHz, CDCl3) δ 174.52, 165.90, 162.61 (d, J = 7.5Hz), 160.11 (d, J = 7.7Hz), 155.16, 152.23, 145.17, 130.59 (t, J = 10.6Hz), 117.82, 115.74 (t, J = 16.2Hz), 112.00-111.75 (m), 72.87 (t, J = 2.8Hz), 63.68, 60.96, 45.22, 41.55 (d, J = 2.3Hz), 40.43, 32.13. HRMS (MALDI) calculated C 21 H 22 F2IN3O3S[M+H] + 560.0311, measured value 560.0308.

[0151]

[0152] Formula (Ⅰ-6). White solid; mp = 87-89℃. 1 H NMR(400MHz, CDCl3)δ7.75(s,1H),7.69(s,1H),7.35–7.28(m,1H),6.92(t, J=8.0Hz,2H),6.08(dd,J=12.0,9.2Hz,1H),4.84(d,J=13.6Hz,1H),3.85–3 .76(m,4H),3.73(d,J=12.8Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.54(t,J =12.0Hz,1H),3.48–3.35(m,2H),2.31(d,J=13.6Hz,2H),2.09–1.94(m,2H). 13 CNMR (100MHz, CDCl3) δ 172.92, 167.29, 162.62 (d, J = 7.6Hz), 160.12 (d, J = 7.6Hz), 155.65, 152.13, 145.38, 130.62 (t, J = 10.7Hz), 117.95, 117.92, 115.73 (t, J = 16.2Hz), 112.02-111.77 (m), 72.94 (t, J = 2.9Hz), 69.71, 56.09, 52.16, 45.68, 41.55, 39.18, 32.73, 31.59. HRMS (MALDI) calculated value C 22 H 21 F2N4O3S[M+H] + 459.1297, measured value 459.1302.

[0153]

[0154] Formula (Ⅰ-7). Yellow oily substance. 1 H NMR (400MHz, CDCl3) δ7.68 (s, 1H), 7.39–7.30 (m, 1H), 6.95 (t, J = 8.0Hz, 2H), 6 .46–6.41(m,1H),6.11(dd,J=12.0,9.2Hz,1H),4.34(d,J=13.6Hz,2H),3.84( dd,J=17.2,12.0Hz,1H),3.74(s,3H),3.66(dd,J=17.2,9.2Hz,1H),3.38–3.2 9(m,1H),3.10–2.98(m,2H),2.22(dd,J=13.6,3.6Hz,2H),1.88–1.74(m,5H). 13 CNMR (100MHz, CDCl3) δ 174.75, 171.37, 162.63 (d, J = 7.0Hz), 160.13 (d, J = 7.0Hz), 152.24, 150.31, 145.18, 130.56 (t, J = 10.0Hz), 117.71, 115.77 (t, J = 16.0Hz), 111.98-111.74 (m), 109.47, 72.86 (t, J = 3.0Hz), 60.33, 44.67, 41.55, 40.77, 32.59, 11.83. HRMS (MALDI) calculated value C 22 H 24 F2N3O3S[M+H] + 448.1501, measured value 448.1502.

[0155]

[0156] Formula (Ⅰ-8). Yellow oily substance. 1H NMR(400MHz, CDCl3)δ7.68(d,J=0.8Hz,1H),7.39–7.31(m,1H),6.95(t,J=8.0Hz,2H),6.2 8(s,1H),6.11(dd,J=12.0,9.2Hz,1H),4.42(d,J=13.6Hz,2H),3.84(dd,J=17.2,12.0Hz, 1H),3.72(d,J=0.8Hz,3H),3.66(dd,J=17.2,9.2Hz,1H),3.40–3.28(m,1H),3.05(t,J=12 .0Hz,2H),2.35(q,J=7.6Hz,2H),2.27–2.19(m,2H),1.87–1.72(m,2H),1.08–1.01(m,3H). 13 C NMR (100MHz, CDCl3) δ 174.77, 170.77, 162.64 (d, J = 7.0Hz), 160.14 (d, J = 8.0Hz), 152.21, 148.54, 145.17, 130.56 (t, J = 10.0Hz), 117.71, 117.69, 116.00, 115.78 (t, J = 16.0Hz), 111.99–111.74 (m), 72.89 (t, J = 3.0Hz), 60.27, 41.56, 40.76, 32.64, 19.64, 12.87. HRMS (MALDI) calculated C 23 H 26 F2N3O3S[M+H] + 462.1657, measured value 462.1660.

[0157]

[0158] Formula (Ⅰ-9). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.65 (s, 1H), 7.35–7.25 (m, 1H), 6.92 (t, J = 8.0Hz, 2H), 6.28 (s, 1H), 6.08(dd,J=12.0,9.2Hz,1H),4.38(d,J=13.6Hz,2H),3.81(dd,J=17.2,12.0Hz,1H),3.68 (s,3H),3.63(dd,J=17.2,9.2Hz,1H),3.35–3.25(m,1H),3.01(s,2H),2.27(dd,J=8.8,6. 4Hz,2H),2.23–2.15(m,2H),1.82–1.69(m,2H),1.47–1.37(m,2H),0.92(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 174.78, 170.93, 162.63 (d, J = 8.0Hz), 160.13 (d, J = 8.0Hz), 152.23, 149.03, 145.18, 130.56 (t, J = 11.0Hz), 117.73, 115.77 (t, J = 16.0Hz), 114.70, 111-111.74 (m), 72.87 (t, J = 3.0Hz), 60.25, 44.70, 41.54, 40.78, 32.62, 28.38, 21.64, 14.10. HRMS (MALDI) calculated C 24 H 28 F2N3O3S[M+H] + 476.1814, measured value 476.1816.

[0159]

[0160] Formula (Ⅰ-10). White solid; mp = 58-60℃. 1 H NMR(400MHz, CDCl3)δ7.65(s,1H),7.31(tt,J=8.4,6.4Hz,1H),6.96–6.88(m,2 H),6.11–6.03(m,2H),4.44(d,J=13.2Hz,2H),3.86–3.76(m,1H),3.66(s,3H),3 .65–3.59(m,1H),3.30(tt,J=11.2,3.6Hz,1H),3.01(t,J=12.8Hz,2H),2.86(p ,J=7.2Hz,1H),2.23–2.15(m,2H),1.81–1.67(m,2H),1.15(s,3H),1.14(s,3H).13 C NMR (100MHz, CDCl3) δ 173.73, 168.89, 161.60 (d, J = 7.3Hz), 159.10 (d, J = 7.5Hz), 151.20, 145.62, 144.14, 129.53 (t, J = 10.6Hz), 118.39, 116.72, 114.73 (t, J = 16.1Hz), 110.95–110.70 (m), 71.85, 59.23, 43.50, 40.53, 39.75, 31.61, 25.77, 20.20. HRMS (MALDI) calculated C 24 H 27 F2N3NaO3S[M+Na] + :498.1633, measured value 498.1632.

[0161]

[0162] Formula (Ⅰ-11). White solid; mp = 69-71℃. 1 H NMR (400MHz, CDCl3) δ7.62(s,1H),7.29(d,J=7.6Hz,1H),7.25(d,J=4.8Hz,1 H),7.26–7.20(m,3H),7.00(s,1H),6.91(t,J=8.0Hz,2H),6.06(dd,J=12.0,9 .2Hz,1H),4.12(s,2H),3.79(s,4H),3.60(dd,J=17.2,9.2Hz,1H),3.26–3.14 (m,1H),2.86–2.74(m,2H),2.27(s,3H),1.95(d,J=13.2Hz,2H),1.45(s,2H). 13 C NMR (100MHz, CDCl3) δ 174.89, 162.63 (d, J = 8.0Hz), 160.13 (d, J = 8.0Hz), 154.80, 152.26, 145.07, 136.52, 133.80, 130.56, 130.55 (t, J = 10.0Hz), 130.15, 127.55, 125.74, 117.63, 115.78 (t, J = 16.0Hz), 114.85, 111.99-111.74 (m), 72.84 (t, J = 3.0Hz), 61.19, 41.55, 40.52, 32.11, 20.13. HRMS (MALDI) calculated C 28 H 28 F2N3O3S[M+H] +524.1814, measured value 524.1819.

[0163]

[0164] Formula (Ⅰ-12). White solid; mp = 71-73℃. 1 H NMR (400MHz, CDCl3) δ7.63 (s, 1H), 7.36–7.24 (m, 3H), 7.22 (dd, J = 8.8, 7.3Hz, 1H ),7.03(d,J=7.2Hz,1H),6.91(t,J=8.0Hz,2H),6.64(s,1H),6.06(dd,J=12.0,9. 2Hz,1H),4.26(s,2H),3.82(s,3H),3.80–3.74(m,1H),3.61(dd,J=17.2,9.2Hz,1 H),3.28–3.15(m,1H),2.96–2.84(m,2H),2.34(s,3H),2.05(s,2H),1.61(s,2H). 13 C NMR (100MHz, CDCl3) δ 174.83, 162.64 (d, J = 8.0Hz), 160.14 (d, J = 8.0Hz), 152.25, 150.58, 145.14, 137.86, 133.69, 130.56 (t, J = 10.0Hz), 128.49, 128.30, 127.71, 125.09, 117.66, 115.79 (t, J = 16.0Hz), 115.22, 111.99-111.75 (m), 72.85, 61.39, 41.58, 40.58, 32.34, 21.60. HRMS (MALDI) calculated C 28 H 28 F2N3O3S[M+H] + 524.1814, measured value 524.1819.

[0165]

[0166] Formula (Ⅰ-13). White solid; mp = 81-83℃. 1H NMR (600MHz, DMSO-d6) δ8.01 (s, 1H), 7.50 (p, J = 7.2Hz, 1H), 7.31 (d, J = 7.8Hz, 2H),7.21–7.01(m,4H),6.61(s,1H),6.00(dd,J=12.0,8.4Hz,1H),4.11(s,1H) ,3.89(dd,J=17.4,12.0Hz,1H),3.78(s,3H),3.52(dd,J=17.4,8.5Hz,1H),3.3 8(s,2H),2.94(t,J=12.6Hz,2H),2.27(s,3H),2.07–1.95(m,2H),1.51(s,2H). 13 C NMR (150MHz, DMSO-d6) δ 174.82, 162.43 (d, J = 8.0Hz), 160.15 (d, J = 7.8Hz), 152.05, 150.38, 144.88, 137.69, 133.45, 130.22 (t, J = 10.0Hz), 128.29, 128.08, 127.59, 124.42, 117.37, 115.69 (t, J = 16.0Hz), 115.22, 111.98-111.74 (m), 72.87 (t, J = 3.0Hz), 61.28, 41.58, 40.56, 32.31, 21.22. HRMS (MALDI) calculated C 28 H 28 F2N3O3S[M+H] + 524.1814, measured value 524.1816.

[0167]

[0168] Formula (Ⅰ-14). White solid; mp = 79-81℃. 1H NMR (400MHz, CDCl3) δ7.61 (s, 1H), 7.34–7.27 (m, 1H), 7.09 (d, J = 7.6Hz, 1H), 7.05 (s, 1H),6.98(dd,J=7.6,1.6Hz,1H),6.96(s,1H),6.91(t,J=8.0Hz,2H),6.05(dd,J=12.0 ,9.2Hz,1H),4.14(s,2H),3.82–3.71(m,4H),3.60(dd,J=17.2,9.2Hz,1H),3.19–3.09 (m,1H),2.84–2.75(m,2H),2.30(s,3H),2.22(s,3H),2.00–1.87(m,2H),1.45(s,2H). 13 C NMR (100MHz, CDCl3) δ 174.98, 169.86, 162.64 (d, J = 8.0Hz), 160.14 (d, J = 6.0Hz), 154.61, 152.27, 145.07, 135.05, 133.53, 133.33, 130.47, 128.44, 117.61, 115.79 (t, J = 16.3Hz), 114.80, 111.99, 111.75, 72.85, 61.15, 41.55, 40.57, 32.15, 20.98, 19.67. HRMS (MALDI) calculated C 29 H 30 F2N3O3S[M+H] + 538.1970, measured value 538.1976.

[0169]

[0170] Formula (Ⅰ-15). White solid; mp = 94-96℃. 1 H NMR (400MHz, CDCl3) δ7.57 (s, 1H), 7.36 (d, J = 2.4Hz, 1H), 7.25–7.18 (m, 2H), 7.12 ( dd,J=8.8,2.5Hz,1H),6.89(s,1H),6.84(t,J=8.4Hz,2H),6.00(dd,J=12.0,9.2Hz, 1H),4.15(s,2H),3.76(s,3H),3.75–3.68(m,1H),3.55(dd,J=17.2,9.2Hz,1H),3. 22–3.14(m,1H),2.90–2.79(m,2H),1.99(d,J=11.2Hz,2H),1.53(d,J=12.8Hz,2H). 13C NMR (100MHz, CDCl3) δ 174.77, 168.22, 162.63 (d, J = 8.0Hz), 160.13 (d, J = 8.0Hz), 155.83, 152.25, 145.11, 134.77, 132.41, 131.81, 131.75, 130.85, 130.56 (t, J = 10.0Hz), 128.70, 117.71, 115.78 (t, J = 16.0Hz), 111.99, 111.94-111.69 (m), 72.86 (t, J = 2.0Hz), 61.62, 41.57, 40.54, 32.16. HRMS (MALDI) calculated C 27 H 24 Cl2F2N3O3S[M+H] + 578.0878, measured value 578.0881.

[0171]

[0172] Formula (Ⅰ-16). White solid; mp = 119-121℃. 1 H NMR (400MHz, CDCl3) δ7.64(s,1H),7.34–7.25(m,1H),6.95–6.87(m,2H),6.59(dd,J=16.8, 10.4Hz, 1H), 6.28 (dd, J=16.8, 2.0Hz, 1H), 6.06 (dd, J=12.0, 9.2Hz, 1H), 5.70 (dd, J=10.4, 2.0Hz,1H),4.70(s,1H),4.18–3.98(m,1H),3.86–3.73(m,1H),3.62(dd,J=17.2,9.2Hz,1H ),3.38–3.29(m,1H),3.23(s,1H),2.87(s,1H),2.20(d,J=12.0Hz,2H),1.85–1.73(m,2H). 13 C NMR (100MHz, DMSO-d6) δ 175.41, 164.74, 162.38 (d, J = 7.9Hz), 159.90 (d, J = 7.8Hz), 152.58, 144.75, 131.85 (t, J = 10.8Hz), 128.93, 127.64, 120.36, 116.09 (t, J = 16.5Hz), 112.79–112.55 (m), 72.52, 72.49, 72.46, 45.21, 41.61, 40.02, 33.20, 32.33. HRMS (MALDI) calculated C 20 H20 F2N3O2S[M+H] + 404.1239, measured value 404.1241.

[0173]

[0174] Formula (Ⅰ-17). White solid; mp = 78-80℃. 1 H NMR(400MHz, CDCl3) δ7.65(d,J=2.8Hz,1H),7.59(d,J=11.6Hz,1H),7.36–7.26(m,1H),6.91(t,J= 8.4Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),5.68(d,J=12.0Hz,1H),4.36(s,2H),3.95(q,J=7.2Hz,2 H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.40–3.25(m,1H),3.17–2.76(m, 2H), 2.18(dd,J=13.6,3.6Hz,2H),1.85–1.70(m,2H),1.34(t,J=7.2Hz,2H),1.26(t,J=7.2Hz,1H). 13 C NMR (100MHz, CDCl3) δ 174.82, 166.24, 162.63 (d, J = 7.5Hz), 162.01, 160.13 (d, J = 7.5Hz), 152.25, 145.10, 130.54 (t, J = 10.6Hz), 117.71, 117.67, 115.77 (t, J = 16.2Hz), 112.02–111.68 (m), 95.38, 72.87 (t, J = 2.9Hz), 67.51, 41.55, 40.71, 14.75. HRMS (MALDI) calculated C 22 H 24 F2N3O3S[M+H] + :448.1501, measured value 448.1504.

[0175]

[0176] Formula (Ⅰ-18). White solid; mp = 77-79℃. 1H NMR (400MHz, CDCl3) δ7.69–7.60(m,3H),7.41–7.38(m,3H),7.35–7.25(m,1H), 6.98–6.87(m,2H),6.13–6.01(m,1H),4.77(dd,J=35.2,13.6Hz,1H),4.02(d,J =1.6Hz,3H),3.86–3.77(m,1H),3.76–3.66(m,1H),3.61(dd,J=17.6,8.8Hz,1H ),3.38–3.28(m,1H),3.32–2.93(m,2H),2.35–2.07(m,2H),1.99–1.54(m,2H). 13 C NMR (100MHz, CDCl3) δ174.48, 163.25, 162.63 (d, J = 7.4Hz), 160.14 (d, J = 7.6Hz), 15 2.59,152.25,145.24,130.74,130.58(t,J=10.0Hz),130.34,128.88,128.85,126.2 1,126.18,117.77,115.76 (t, J = 16.2 Hz),111.87 (d, J = 24.7 Hz),111.87 (d, J = 14.0 Hz),72.89,62.87,46.07,41.53,40.54,40.26,32.95,31.93,29.69. HRMS (MALDI) calculated value C 26 H 25 F2N4O3S[M+H] + 511.1610, measured value 511.1610.

[0177]

[0178] Formula (Ⅰ-19). White solid; mp = 74-76℃. 1H NMR (400MHz, CDCl3) δ7.66 (s, 1H), 7.36–7.17 (m, 5H), 6.92 (t, J = 8.0Hz, 2H), 6 .08(dd,J=12.0,9.2Hz,1H),4.67(d,J=13.6Hz,1H),4.51–4.43(m,1H),3.94(s ,3H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.31–3.41 (m,2H),3.03–2.91(m,1H),2.33(s,3H),2.29–2.18(m,2H),1.93–1.80(m,2H). 13 C NMR (100MHz, CDCl3) δ174.50, 163.76, 162.65 (d, J = 8.0Hz), 160.15 (d, J = 8.0Hz), 152.26,151.50,145.22,136.49,131.04,130.59(t,J=10.0Hz),130.27,129.38, 127.29, 125.55, 117.80, 115.78 (t, J = 16.0 Hz), 112.01-111.76 (m), 72.91 (t, J = 3.0 Hz), 62.74, 46.77, 41.91, 41.55, 40.54, 32.82, 31.85, 20.21. HRMS (MALDI) calculated value C 27 H 27 F2N4O3S[M+H] + 525.1766, measured value 525.1773.

[0179]

[0180] Formula (Ⅰ-20). White solid; mp = 81-83℃. 1H NMR (400MHz, CDCl3) δ7.69 (d, J = 11.6Hz, 1H), 7.55–7.40 (m, 2H), 7.38–7.28 (m, 2H), 7.26 (s, 1H), 6.9 9–6.91(m,2H),6.15–6.06(m,1H),4.81(dd,J=39.6,13.6Hz,1H),4.05(d,J=1.6Hz,3H),3.84(dd,J=1 7.2,10.8Hz,1H),3.79–3.71(m,1H),3.65(dt,J=17.6,9.6Hz,1H),3.37(dt,J=12.0,5.6Hz,1H),3.33 –2.97(m,2H),2.40(s,3H),2.32(t,J=15.6Hz,1H),2.17(dd,J=27.6,13.2Hz,1H),2.00–1.58(m,2H). 13 C NMR (100MHz, CDCl3) δ174.54, 163.34, 162.63 (d, J = 7.3Hz), 160.13 (d, J = 7.4Hz) ,152.80,152.24,145.23,138.63,131.22,130.59(t,J=10.0Hz),128.78,128.7 5, 126.62, 123.45, 117.77, 115.75 (t, J = 16.1 Hz), 112.00-111.75 (m), 72.89, 62.65, 46.11, 41.52, 40.58, 40.26, 32.97, 31.97, 21.43, 21.41. HRMS (MALDI) calculated value C 27 H 27 F2N4O3S[M+H] + 525.1766, measured value 525.1771.

[0181]

[0182] Formula (Ⅰ-21). White solid; mp = 85-87℃. 1H NMR (400MHz, CDCl3) δ7.66(d,J=11.2Hz,1H),7.52(dd,J=13.2,8.0Hz,2H),7.31(q,J=7.2Hz,1H),7. 19(d,J=8.0Hz,2H),6.96–6.87(m,2H),6.12–6.03(m,1H),4.76(dd,J=32.0,13.6Hz,1H),4.00(d,J=2 .0Hz,3H),3.86–3.76(m,1H),3.76–3.67(m,1H),3.67–3.56(m,1H),3.39–3.29(m,1H),3.28–2.94(m, 2H), 2.36 (d, J=3.6Hz, 3H), 2.28 (t, J=16.8Hz, 1H), 2.13 (dd, J=23.2, 13.6Hz, 1H), 1.99–1.52 (m, 2H). 13 C NMR (150MHz, DMSO-d6) δ 175.14, 162.31, 161.92 (d, J = 7.5Hz), 160.27 (d, J = 7.7Hz), 152.83, 152.53, 144.78, 144.69, 140.76, 131.80 (t, J = 10.6Hz), 130.08, 130.04, 128.12, 126.26, 120.38, 116.03 (t, J = 16.6Hz), 112.69, 112.54, 72.46, 62.74, 45.70, 41.55, 40.19, 39.78, 33.03, 32.11, 21.34. HRMS (MALDI) calculated C 27 H 27 F2N4O3S[M+H] + 525.1766, measured value 525.1775.

[0183]

[0184] Formula (Ⅰ-22). White solid; mp = 123-125℃. 1H NMR(400MHz, CDCl3)δ7.71(s,1H),7.67(s,1H),7.34–7.28(m,1H),6.96–6.88(m,2H),6 .08(dd,J=12.0,9.2Hz,1H),4.67(d,J=14.4Hz,1H),4.35(d,J=14.0Hz,1H),3.98(s,2H) ,3.94(s,1H),3.81(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.42–3.33( m,1H),3.33–3.19(m,1H),2.98–2.89(m,1H),2.23(d,J=13.6Hz,2H),1.92–1.77(m,2H). 13 C NMR (100MHz, CDCl3) δ 174.35, 162.62 (d, J = 7.6Hz), 160.94, 160.12 (d, J = 7.5Hz), 152.23, 145.19, 142.36, 130.60 (t, J = 10.6Hz), 117.81, 115.75 (t, J = 16.1Hz), 112.00-111.76 (m), 72.89, 62.76, 46.13, 41.98, 41.55, 40.39, 32.83, 31.90. HRMS (MALDI) calculated C 20 H 21 F2N4O3S[M+H] + :435.1297, measured value 435.1301.

[0185]

[0186] Formula (Ⅰ-23). ​​White solid; mp = 142-144℃. 1 H NMR (400MHz, CDCl3) δ7.70 (s, 1H), 7.38–7.31 (m, 1H), 6.96 (t, J = 8.0Hz, 2H), 6.12 (dd, J =12.0,9.2Hz,1H),4.69(d,J=13.2Hz,1H),4.24(d,J=13.6Hz,1H),3.97(s,3H),3.85(dd ,J=17.2,12.0Hz,1H),3.67(dd,J=17.2,9.2Hz,1H),3.40(tt,J=11.2,4.0Hz,1H),3.32– 3.22(m,1H),3.01–2.91(m,1H),2.25(d,J=13.2Hz,2H),2.08(s,3H),1.95–1.82(m,2H).13 C NMR (100MHz, CDCl3) δ 174.48, 164.89, 162.62 (d, J = 8.0Hz), 160.12 (d, J = 7.0Hz), 152.24, 151.21, 145.18, 130.57 (t, J = 10.0Hz), 117.75, 115.75 (t, J = 16.0Hz), 111.99–111.74 (m), 72.87 (t, J = 3.0Hz), 62.23, 46.67, 41.76, 41.54 (t, J = 2.0Hz), 40.54, 32.84, 31.88, 12.96. HRMS (MALDI) calculated C 21 H 23 F2N4O3S[M+H] + 449.1453, measured value 449.1454.

[0187]

[0188] Formula (Ⅰ-24). White solid; mp = 58-60℃. 1 H NMR(400MHz, CDCl3)δ7.69(s,1H),7.40–7.30(m,1H),6.96(t,J=8.0Hz,2H),6.11(dd,J=12.0 ,9.2Hz,1H),4.71(d,J=13.6Hz,1H),4.20(d,J=13.6Hz,1H),3.94(s,3H),3.84(dd,J=17.2,1 2.0Hz,1H),3.67(dd,J=17.2,9.2Hz,1H),3.43–3.34(m,1H),3.32–3.22(m,1H),3.02–2.92(m ,1H),2.61(q,J=7.6Hz,2H),2.25(d,J=13.6Hz,2H),1.95–1.79(m,2H),1.13(t,J=7.6Hz,3H). 13 C NMR (100MHz, DMSO-d6) δ 175.16, 163.62, 162.38 (d, J = 8.0Hz), 159.90 (d, J = 8.0Hz), 156.47, 152.55, 144.79, 131.85 (t, J = 11.0Hz), 120.44, 116.08 (t, J = 16.0Hz), 112.79–112.54 (m), 72.50 (t, J = 3.0Hz), 62.18, 46.31, 41.61, 41.13, 39.86, 32.98, 32.18, 20.25, 10.06. HRMS (MALDI) calculated C22 H 25 F2N4O3S[M+H] + 463.1610, measured value 463.1611.

[0189]

[0190] Formula (Ⅰ-25). White solid; mp = 72-74℃. 1 H NMR(400MHz, CDCl3)δ7.66(s,1H),7.36–7.26(m,1H),7.20(s,1H),7.13(d,J=8.0Hz,1H),7 .08(dd,J=8.0,1.6Hz,1H),6.91(t,J=8.4Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),4.73(s,1H) ,4.01(s,3H),3.78(dt,J=16.8,10.4Hz,2H),3.62(dd,J=17.2,9.2Hz,1H),3.32(t,J=11.2H z,1H),3.19(s,1H),2.98(s,1H),2.50(s,3H),2.30(s,3H),2.29–2.11(m,2H),1.84(s,2H). 13 C NMR (100MHz, CDCl3) δ 162.64 (d, J = 7.6Hz), 160.14 (d, J = 7.6Hz), 153.59, 152.18, 145.18, 135.50, 134.30, 131.82, 130.59 (t, J = 10.6Hz), 130.29, 129.48, 129.35, 117.74, 115.76 (t, J = 16.2Hz), 112.00-111.75 (m), 72.91 (t, J = 3.0Hz), 62.71, 41.56, 41.54, 40.52, 31.93, 21.75, 20.94. HRMS (MALDI) calculated C 28 H 29 F2N4O3S[M+H] + 539.1923, measured value 539.1925.

[0191]

[0192] Formula (Ⅰ-26). White solid; mp = 70-72℃. 1H NMR (400MHz, CDCl3) δ7.66(s,1H),7.34–7.28(m,1H),7.19(s,1H),7.13(d,J=8.0Hz,1H),7.07(dd,J=8. 0,1.6Hz,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),4.74(d,J=44.0Hz,1H),4.26(q,J=7. 2Hz,2H),3.79(dd,J=17.2,12.0Hz,2H),3.62(dd,J=17.0,9.2Hz,1H),3.38–3.28(m,1H),3.23–2.86(m, 2H),2.50(s,3H),2.30(s,3H),2.29–2.22(m,1H),2.14(s,1H),1.88–1.76(m,2H),1.34(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 162.64 (d, J = 7.5Hz), 160.14 (d, J = 7.5Hz), 153.17, 152.25, 145.23, 135.47, 134.26, 131.81, 130.58 (t, J = 10.7Hz), 130.17, 129.75, 129.29, 117.70, 115.77 (t, J = 16.2Hz), 112.01-111.76 (m), 72.90 (t, J = 3.0Hz), 70.45, 41.55, 40.66, 21.87, 20.96, 14.85. HRMS (MALDI) calculated C 29 H 31 F2N4O3S[M+H] + 553.2079, measured value 553.2083.

[0193]

[0194] Formula (Ⅰ-27). White solid; mp = 69-71℃. 1H NMR (400MHz, CDCl3) δ7.67(s,1H),7.34–7.28(m,1H),7.17(s,1H),7.13(d,J=8.0Hz,1H),7.10– 7.04(m,1H),6.91(t,J=8.4Hz,2H),6.11–6.02(m,1H),4.82(s,1H),4.53–4.42(m,1H),3.79(dd ,J=17.2,11.2Hz,2H),3.62(dd,J=17.2,9.2Hz,1H),3.32(d,J=12.0Hz,1H),3.20–2.84(m,2H), 2.51(s,3H),2.30(s,4H),2.16(d,J=12.8Hz,1H),1.91–1.77(m,2H),1.33(s,3H),1.31(s,3H). 13 C NMR (100MHz, CDCl3) δ 162.64 (d, J = 7.5Hz), 160.14 (d, J = 7.5Hz), 152.27, 145.22, 135.43, 134.24, 131.80, 130.59 (t, J = 10.6Hz), 130.03, 130.00, 129.25, 117.68, 115.77 (t, J = 16.3Hz), 112.00-111.75 (m), 76.52, 72.89, 41.57, 40.81, 22.05, 21.72, 20.97. HRMS (MALDI) calculated C 30 H 33 F2N4O3S[M+H] + 567.2236, measured value 567.2240.

[0195]

[0196] Formula (Ⅰ-28). White solid; mp = 106-108℃. 1H NMR(400MHz, CDCl3)δ7.74(s,1H),7.69(s,1H),7.35–7.28(m,1H),6.92(t,J=8.4 Hz,2H),6.08(dd,J=12.0,9.2Hz,1H),4.84(d,J=13.6Hz,1H),4.24(q,J=7.2Hz,2H ),3.85–3.69(m,2H),3.63(dd,J=17.2,9.2Hz,1H),3.54(t,J=12.0Hz,1H),3.43(d ,J=25.6Hz,2H),2.30(d,J=13.6Hz,2H),2.07–1.95(m,2H),1.31(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 172.95, 166.82, 162.61 (d, J = 8.0Hz), 160.11 (d, J = 8.0Hz), 155.60, 152.18, 145.40, 130.62 (t, J = 10.0Hz), 117.95, 117.92, 115.72 (t, J = 16.0Hz), 112.01-111.76 (m), 72.92 (t, J = 3.0Hz), 70.05, 60.99, 56.05, 45.65, 41.54, 39.21, 32.73, 31.61, 14.45. HRMS (MALDI) calculated C 23 H 22 F2N4NaO3S[M+Na] + :495.1273, measured value 495.1270.

[0197]

[0198] Formula (Ⅰ-29). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.70(s,1H),7.66(s,1H),7.31(dt,J=12.8,6.0Hz,1H),6.92(t,J=8.0H z,2H),6.08(t,J=10.4Hz,1H),4.68(d,J=14.0Hz,1H),4.37(d,J=14.0Hz,1H),4.31–4.20(m, 2H),3.81(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.32(dt,J=33.6,11.6Hz,2 H),2.94(t,J=12.4Hz,1H),2.22(d,J=13.2Hz,2H),1.94–1.73(m,2H),1.29(t,J=6.8Hz,3H). 13 C NMR (100MHz, CDCl3) δ 174.32, 162.61 (d, J = 7.6Hz), 161.18, 160.11 (d, J = 7.6Hz), 152.24, 145.21, 142.10, 130.57 (t, J = 10.6Hz), 117.75, 115.76 (t, J = 16.1Hz), 111.99–111.74 (m), 72.86 (t, J = 3.0Hz), 70.69, 46.14, 41.98, 41.54, 40.42, 32.84, 31.90, 14.55. HRMS (MALDI) calculated C 21 H 23 F2N4O3S[M+H] + 449.1453, measured value 449.1455.

[0199]

[0200] Formula (Ⅰ-30). White solid; mp = 124-126℃. 1 H NMR (400MHz, CDCl3) δ7.65(d,J=3.6Hz,1H),7.36–7.26(m,1H),6.92(t,J=8.4Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),5.17(s,1H),4.39(s ,2H),3.89–3.76(m,3H),3.67–3.55(m,1H),3.36–3.27(m,1H),3.00(s,2H),2.29–2.16(m,5H),1.88–1.71(m,2H),1.34(t,J=6.8Hz,3H). 13C NMR (100MHz, CDCl3) δ 174.94, 167.50, 167.42, 162.64 (d, J = 7.4Hz), 160.14 (d, J = 7.3Hz), 152.26, 145.13, 130.54 (t, J = 10.6Hz), 117.65, 115.79 (t, J = 16.1Hz), 111.99–111.74 (m), 91.45, 72.87, 63.19, 41.57, 40.80, 32.64, 19.05, 14.37. HRMS (MALDI) calculated C 23 H 26 F2N3O3S[M+H] + 462.1657, measured value 462.1658.

[0201]

[0202] Formula (I-53). White solid; mp = 86-88℃. 1 H NMR (400MHz, CDCl3) δ7.66 (s, 1H), 7.36–7.24 (m, 2H), 6.91 (t, J = 8.0Hz, 2H), 6.07 (dd, J = 12 .0,8.0Hz,1H),4.99(dd,J=12.0,8.0Hz,1H),4.62(d,J=12.0Hz,1H),4.51(dd,J=20.0,8.0H z,1H),3.99(d,J=12.0Hz,1H),3.83–3.73(m,2H),3.38–3.20(m,2H),2.87(ddd,J=13.2,12 .0,4.0Hz,1H),2.19(q,J=12.0,8.4Hz,2H),2.02–1.68(m,2H),1.17(td,J=7.2,1.6Hz,3H). 13C NMR (100MHz, CDCl3) δ174.29 (d, J = 11.3Hz), 165.84 (d, J = 20.7Hz), 162.63 (d, J = 7.6Hz), 160.13 (d, J = 7. 6Hz), 152.28, 145.21 (d, J = 2.4Hz), 130.56 (t, J = 10.6Hz), 117.68 (d, J = 8.7Hz), 115.78 (t, J = 16.3Hz), 11 1.97 (d, J = 5.9 Hz), 111.77 (d, J = 5.9 Hz), 103.34 (d, J = 38.4 Hz), 72.87, 65.81 (d, J = 12.4 Hz), 64.21 (d, J = 41.2 Hz), 46.12 (d, J = 32.9 Hz), 42.59, 42.19 (d, J = 38.0 Hz), 41.58, 32.36, 31.65, 15.21. HRMS (MALDI) calculated value C 22 H 23 BrF₂N₃O₃S[M+H] + :526.0606, measured value 526.0604.

[0203]

[0204] Formula (I-59). White solid; mp = 121-123℃. 1 H NMR(400MHz, CDCl3)δ7.55(s,1H),7.21–7.16(m,2H),7.15–7.07(m,3H),7.01( s,1H),6.84(t,J=8.4Hz,2H),5.99(dd,J=12.0,9.2Hz,1H),3.96(m,4H),3.71( dd,J=17.2,12Hz,1H),3.53(dd,J=17.2,9.2Hz,1H),3.15–3.03(m,1H),2.72(t ,J=12.0Hz,2H),2.20(s,3H),1.86(s,2H),1.38(s,2H),1.23(t,J=7.1Hz,3H). 13C NMR (100MHz, CDCl3) δ 174.88, 170.07, 162.55 (d, J = 7.6Hz), 160.05 (d, J = 7.5Hz), 153.67, 152.17, 144.94, 136.42, 133.92, 130.79–130.27 (m), 130.06, 127.32, 125.60, 117.54, 114.22, 111.88 (d, J = 5.8Hz), 111.68 (d, J = 5.6Hz), 72.76 (d, J = 3.8Hz), 69.83, 41.47, 40.44, 32.01, 20.14, 15.32. HRMS (MALDI) calculated C 29 H 29 F2N3NaO3S[M+Na] + :560.1790, measured value 560.1790.

[0205]

[0206] Formula (I-60). White solid; mp = 123-124℃. 1 H NMR (400MHz, CDCl3) δ7.56(d,J=3.5Hz,1H),7.25(dd,J=8.4,6.4Hz,1H),7.19(s,2H),7.18–7.11(m,1H),7.02(s,1H),6.98( t,J=6.2Hz,1H),6.85(t,J=8.0Hz,2H),6.10–5.91(m,1H),4.63(d,J=12.4Hz,1H),3.94–3.82(m,1H),3.73(dd,J=16.4,4.0Hz ,1H),3.66(s,2H),3.54(ddd,J=17.2,9.2,2.4Hz,1H),3.18(tdd,J=14.8,7.2,3.6Hz,1H),3.12–3.02(m,1H),2.81–2.68(m,1 H),2.26(s,3H),2.08(d,J=14.4Hz,1H),1.96(d,J=10.4Hz,1H),1.75–1.52(m,3H),1.50–1.38(m,1H),1.19(t,J=7.2Hz,1H). 13C NMR (100MHz, CDCl3) δ 174.40, 174.16, 165.17, 164.81, 163.91 (d, J = 6.2Hz), 160.00, 159.42, 145.68, 141.94, 134.78, 131.20, 130.08, 129.68, 128.59, 126.78, 125.40, 124.92 (d, J = 8.3Hz), 124.07, 104.20, 61.51, 51.40, 44.95, 42.19–41.80 (m), 40.45, 38.61, 32.52, 31.68, 21.75, 14.37. HRMS (MALDI) calculated C 29 H 29 F2N3NaO3S[M+Na] + :560.1790, measured value 560.1792.

[0207]

[0208] Formula (I-63). White solid; mp = 120-122℃. 1 H NMR(400MHz, CDCl3)δ7.66(s,1H),7.46(d,J=2.8Hz,1H),7.38–7.27(m,2H),7.26–7.16(m,1 H),7.07(s,1H),6.94(t,J=8.4Hz,2H),6.14–6.03(m,1H),4.24(d,J=12.4Hz,1H),4.15-4.06 (m,2H),3.81(dd,J=21.2,8.8Hz,2H),3.63(dd,J=17.6,9.6Hz,1H),3.23(d,J=11.6Hz,1H),2 .94(t,J=12.8Hz,2H),1.63(q,J=12.4Hz,2H),1.34(t,J=7.2Hz,3H),1.26(d,J=16.8Hz,2H). 13 C NMR (100MHz, CDCl3) δ 174.86, 168.68, 162.68 (d, J = 7.5Hz), 160.18 (d, J = 7.4Hz), 154.94, 152.28, 145.12, 135.01, 132.40, 131.87, 130.86, 130.58 (t, J = 10.6Hz), 128.60, 117.70, 112.02, 111.77, 111.25, 72.92, 70.44, 41.60, 40.56, 32.17, 15.42. HRMS (MALDI) calculated C28 H 26 Cl2F2N3O3S[M+H] + :592.1035, measured value 592.1041.

[0209]

[0210] Formula (I-64). White solid; mp = 74-75℃. 1 H NMR (400MHz, CDCl3) δ7.68–7.60(m,3H),7.40–7.36(m,3H),7.30(ddt,J=8.4,6.4,2.0Hz,1H),6.91(td,J= 8.4,2.8Hz,2H),6.07(ddd,J=12.0,9.2,5.2Hz,1H),4.78(dd,J=50.8,13.6Hz,1H),4.33–4.22(m,2H),3.8 6–3.66(m,2H),3.61(dt,J=17.2,8.4Hz,1H),3.39–3.27(m,1H),3.10(tdd,J=14.4,11.6,2.8Hz,1H),3.30 –2.90(m,1H),2.28(dd,J=23.6,13.2Hz,1H),2.12(d,J=10.4Hz,1H),2.01–1.78(m,2H),1.37–1.30(m,3H). 13 C NMR (100MHz, CDCl3) δ174.36 (d, J = 41.1Hz), 163.51, 163.08, 160.14 (d, J = 7.5Hz), 152.18, 151.96, 145.22 (d, J = 2 .0Hz),130.99(d,J=7.6Hz),130.58(t,J=10.6Hz),130.20(d,J=1.6Hz),128.83(d,J=2.9Hz),126.15(d,J=2.7Hz ), 117.70 (d, J = 6.8 Hz), 115.77 (t, J = 16.2 Hz), 111.97 (d, J = 5.8 Hz), 111.78 (d, J = 5.6 Hz), 73.06–72.63 (m), 70.67, 46.11, 45.33, 41.54, 40.52 (dd, J = 38.6, 9.6 Hz), 32.97, 32.50–31.83 (m), 14.76 (d, J = 20.8 Hz). HRMS (MALDI) calculated value C 27 H 26 F2N4NaO3S[M+Na] +:547.1586, measured value 547.1583.

[0211]

[0212] Formula (I-78). White solid; mp = 78-80℃. 1 H NMR (400MHz, CDCl3) δ7.71–7.55(m,1H),7.34–7.20(m,3H),7.12(t,J=6.8Hz,2H),6.91(t,J=8.4Hz, 2H),6.06(q,J=10.4Hz,1H),4.97(dd,J=8.0,1.2Hz,1H),4.65(dd,J=36.0,13.6Hz,1H),4.12–3.93( m,2H),3.88–3.70(m,2H),3.62(dd,J=19.6,9.2Hz,1H),3.21(d,J=11.2Hz,1H),3.15(s,3H),2.76(t ,J=12.4Hz,1H),2.43–2.27(m,3H),2.09(t,J=20.0Hz,2H),1.95–1.70(m,2H),0.91(t,J=6.8Hz,3H). 13 CNMR(100MHz, CDCl3)δ174.84,169.95–169.10(m),162.63(d,J=7.4Hz),160.13(d,J=7.7Hz),152.22,145.02(d,J=14.6H z),137.01,132.23,130.54(t,J=10.6Hz),129.79(d,J=6.1Hz),129.49–129.21(m),128.76(d,J=6.9Hz),128.62(d,J=7. 2Hz), 117.64 (d,J=8.3Hz), 115.86 (d,J=16.2Hz), 111.96 (d,J=5.8Hz), 111.77 (d,J=5.7Hz), 72.86, 64.66 (d,J=8.4Hz), 56.16 (d,J=10.1Hz), 45.43 (d,J=8.2Hz), 41.62 (d,J=14.2Hz), 40.47, 32.19 (t,J=39.6Hz), 21.12, 15.07. HRMS (MALDI) calculated value C 30 H 31 F2N3NaO3S[M+Na] + :574.1946, measured value 574.1947.

[0213]

[0214] Formula (I-81). White solid; mp = 82-84℃. 1 H NMR(400MHz, CDCl3)δ7.63(s,1H),7.48(td,J=7.2,1.6Hz,1H),7.34–7.27(m,1H),7.25–7.21(m,1H),7.17 –7.10(m,1H),7.05(ddd,J=10.4,8.0,1.2Hz,1H),6.95–6.87(m,3H),6.06(dd,J=12.0,9.2Hz,1H),4.21(s, 1H), 4.12 (qd, J=7.2, 1.6Hz, 1H), 4.04 (q, J=7.2Hz, 2H), 3.78 (dd, J=17.2, 12.0Hz, 1H), 3.60 (dd, J=17.2, 9. 2Hz,1H),3.26–3.12(m,1H),2.89(t,J=12.4Hz,2H),2.00(s,2H),1.57(s,2H),1.31(td,J=6.8,2.8Hz,3H). 13 C NMR (100MHz, CDCl3) δ174.98, 169.39, 161.38 (dd, J = 251.5, 7.6Hz), 160.49, 158.02 ,153.00,152.26,145.04,131.10(d,J=3.6Hz),130.56(t,J=10.6Hz),128.95(d,J= 8.3Hz), 124.01 (d, J = 3.3Hz), 122.28 (d, J = 14.4Hz), 117.70, 115.98–115.36 (m), 111.99, 111.74, 108.77, 72.86, 70.10, 41.54, 40.57, 32.11, 15.36. HRMS (MALDI) calculated value C 28 H 26 F3N3NaO3S[M+Na] + :564.1539, measured value 564.1534.

[0215]

[0216] Formula (Ⅰ-134). A light yellow, oily substance. 1H NMR(400MHz, CDCl3)δ7.36–7.28(m,1H),7.00(s,1H),6.96–6.89(m,2H),6.61(dd,J=16.8,10.6Hz,1H),6 .28(dd,J=16.8,1.6Hz,1H),6.13(dd,J=12.0,9.2Hz,1H),5.69(dd,J=10.6,2.0Hz,1H),4.81–4.69(m,1H ), 4.15–4.04 (m, 1H), 3.87 (dd, J = 17.6, 12.0 Hz, 1H), 3.68 (dd, J = 17.4, 9.2 Hz, 1H), 3.28–3.13 (m, 1H), 3.07 (tt, J = 11.6, 3.6 Hz, 1H), 2.86–2.73 (m, 1H), 2.12 (d, J = 13.2 Hz, 2H), 1.75–1.64 (m, 2H). HRMS (MALDI) calculated value C 20 H 20 F2N3O2S[M+H] + :404.1239, measured value 404.1242.

[0217]

[0218] Formula (Ⅰ-135). White solid; mp = 81-83℃. 1 H NMR(400MHz, CDCl3)δ7.58(d,J=11.6Hz,1H),7.35–7.27(m,1H),7.01–6.98(m,1H), 6.96–6.89(m,2H),6.12(dd,J=12.0,9.2Hz,1H),5.70(d,J=11.6Hz,1H),4.72(d,J=1 3.6Hz,1H),3.97–3.82(m,3H),3.72–3.64(m,2H),3.26–3.12(m,1H),3.07–3.01(m, 1H),2.83–2.69(m,1H),2.12–2.07(m,2H),1.72–1.65(m,2H),1.33(t,J=7.2Hz,3H). 13C NMR (100MHz, CDCl3) δ 166.21, 162.54 (d, J = 7.6Hz), 161.80, 161.20, 160.04 (d, J = 7.5Hz), 156.72, 153.31, 130.75 (t, J = 10.6Hz), 115.34 (t, J = 16.0Hz), 114.32, 111.96 (d, J = 5.9Hz), 111.77 (d, J = 5.2Hz), 95.55, 73.94, 67.45, 46.44–44.90 (m), 40.56, 38.69, 32.15, 31.33, 27.06, 14.72. HRMS (MALDI) calculated C 22 H 24 F2N3O3S[M+H] + :448.1501, measured value 448.1501.

[0219]

[0220] Formula (Ⅱ-1). White solid; mp = 96-98℃. 1 H NMR (400MHz, CDCl3) δ7.66(s,1H),7.35–7.27(m,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2 Hz,1H),4.84(t,J=5.6Hz,1H),4.69(d,J=13.6Hz,1H),4.02(d,J=13.6Hz,1H),3.80(dd,J=17.2,1 2.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.42(d,J=2.4Hz,6H),3.35–3.27(m,1H),3.20(t,J=12. 8Hz,1H),2.79(t,J=12.8Hz,1H),2.71(t,J=5.2Hz,2H),2.18(t,J=13.6Hz,2H),1.87–1.68(m,2H). 13C NMR (100MHz, CDCl3) δ 174.62, 167.84, 162.62 (d, J = 7.6Hz), 160.12 (d, J = 7.5Hz), 152.26, 145.18, 130.55 (t, J = 10.7Hz), 117.66, 115.77 (t, J = 16.1Hz), 111.98-111.73 (m), 103.33, 72.85 (t, J = 3.0Hz), 54.82, 54.58, 45.76, 41.56 (d, J = 2.4Hz), 41.44, 40.50, 37.75, 32.80, 32.09. HRMS (MALDI) calculated C 22 H 25 F₂N₃NaO₄S[M+Na] + 488.1426, measured value 488.1426.

[0221]

[0222] Formula (Ⅱ-2). Yellow oily substance. 1 H NMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.38–7.30 (m, 1H), 6.95 (t, J = 8.0Hz, 2H), 6.10 ( dd,J=12.0,9.2Hz,1H),4.98(t,J=5.6Hz,1H),4.73(d,J=13.6Hz,1H),4.11(d,J=12 .0Hz,1H),3.89–3.72(m,3H),3.70–3.57(m,3H),3.39–3.29(m,1H),3.23(t,J=12. 8Hz,1H),2.86–2.69(m,3H),2.20(s,2H),1.93–1.71(m,2H),1.25(t,J=7.2Hz,6H). 13 C NMR (100MHz, CDCl3) δ 174.67, 168.07, 162.62 (d, J = 7.6Hz), 160.12 (d, J = 7.7Hz), 152.29, 145.16, 130.55 (t, J = 10.6Hz), 117.60, 115.78 (t, J = 16.1Hz), 111.98-111.73 (m), 101.72, 72.85 (t, J = 3.0Hz), 63.35, 63.15, 45.96, 41.57, 41.45, 40.57, 38.76, 32.81, 32.20, 15.40, 15.38. HRMS (MALDI) calculated C 24 H 29F₂N₃NaO₄S[M+Na] + 516.1739, measured value 516.1738.

[0223]

[0224] Formula (Ⅱ-3). Yellow oily substance. 1 H NMR (400MHz, CDCl3) δ7.66(s,1H),7.35–7.26(m,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2 Hz,1H),4.93–4.87(m,1H),4.73–4.63(m,1H),4.09–4.01(m,1H),3.80(dd,J=17.2,12.0Hz,1H),3 .76–3.68(m,1H),3.67–3.54(m,2H),3.42(d,J=3.2Hz,3H),3.35–3.26(m,1H),3.25–3.16(m,1H), 2.85–2.76(m,1H),2.76–2.66(m,2H),2.23–2.13(m,2H),1.86–1.67(m,2H),1.22(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 174.66, 168.06, 162.63 (d, J = 7.6Hz), 160.13 (d, J = 7.6Hz), 152.27, 145.16, 130.54 (t, J = 10.6Hz), 117.63, 115.77 (t, J = 16.2Hz), 111.98–111.73 (m), 102.54, 72.86 (t, J = 3.0Hz), 63.45, 54.52, 45.90, 41.56, 41.49, 40.52, 38.16, 32.80, 32.10, 15.35 (d, J = 2.9Hz). HRMS (MALDI) calculated values ​​C 23 H 28 F2N3O4S[M+H] + :480.1763, measured value 480.1761.

[0225]

[0226] Formula (Ⅱ-4). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.70 (s, 1H), 7.39–7.31 (m, 1H), 6.95 (t, J = 8.0Hz, 2H), 6.11 (dd, J = 12.0, 9.2Hz,1H),4.98(q,J=4.8Hz,1H),4.77–4.69(m,1H),4.15–4.08(m,1H),3.90–3.73(m,2H),3. 70–3.58(m,3H),3.54–3.46(m,1H),3.39–3.29(m,1H),3.23(t,J=12.8Hz,1H),2.86–2.70(m,3 H),2.20(s,2H),1.84(s,2H),1.64(q,J=7.2Hz,2H),1.25(t,J=7.2Hz,3H),0.99–0.92(m,3H). 13 C NMR (100MHz, CDCl3) δ174.66, 168.08, 162.60 (d, J = 7.7Hz), 160.10 (d, J = 7.5Hz), 152.27, 145.14, 130. 54(t,J=10.6Hz),117.62,115.76(t,J=16.2Hz),111.96-111.71(m),101.80(d,J=7.1Hz),72.82(t,J= 2.9Hz), 69.43 (d,J=16.3Hz), 63.15 (d,J=20.2Hz), 45.95 (d,J=6.2Hz), 41.55, 41.42 (d,J=4.0Hz), 40.55 (d,J=3.1Hz), 38.65, 32.80, 32.17, 23.09, 15.37 (d,J=2.9Hz), 10.63 (d,J=2.2Hz). HRMS (MALDI) calculated value C 25 H 31 F₂N₃NaO₄S[M+Na] + 530.1896, measured value 530.1899.

[0227]

[0228] Formula (Ⅱ-5). Yellow oily substance. 1H NMR(400MHz, CDCl3)δ7.70(s,1H),7.38(t,J=4.8Hz,4H),7.35–7.32(m,2H),6.96(t,J=8.0Hz,2H) ,6.11(dd,J=12.0,9.2Hz,1H),5.15(t,J=5.6Hz,1H),4.81–4.70(m,2H),4.64(dd,J=11.6,4.8Hz,1 H),4.08(d,J=13.6Hz,1H),3.90–3.75(m,2H),3.71–3.60(m,2H),3.31(d,J=4.4Hz,1H),3.19(q,J =12.0Hz,1H),2.92–2.73(m,3H),2.19(d,J=13.6Hz,2H),1.89–1.68(m,2H),1.27(t,J=7.2Hz,3H). 13 CNMR (100MHz, CDCl3) δ174.64, 167.91, 162.64 (d, J = 7.6Hz), 160.14 (d, J = 7.6Hz), 152.30,145.18,137.99,130.55(t,J=10.6Hz),128.40,127.83,127.75,127.69,11 7.60, 115.80 (t, J = 16.2 Hz), 111.99-111.74 (m), 101.52, 72.86 (t, J = 3.2 Hz), 69.35, 63.09, 45.92, 41.58, 40.52, 38.70, 32.69, 32.00, 15.40, 15.38. HRMS (MALDI) calculated value C 29 H 31 F₂N₃NaO₄S[M+Na] + 530.1896, measured value 530.1897.

[0229]

[0230] Formula (Ⅱ-6). White solid; mp = 58-60℃. 1H NMR (400MHz, CDCl3) δ7.66 (s, 1H), 7.34–7.27 (m, 1H), 6.92 (t, J = 8.0Hz, 2H), 6.07 (dd, J = 12.0, 9.2Hz, 1H), 4.7 4(d,J=13.6Hz,1H),4.51(dd,J=15.2,8.0Hz,1H),4.10(dd,J=25.2,13.6Hz,1H),3.81(dd,J=17.2,12.0Hz,1H ),3.63(dd,J=17.2,9.2Hz,1H),3.42(d,J=6.8Hz,6H),3.32(s,1H),3.19(dd,J=22.8,11.4Hz,1H),3.05(q,J= 7.2Hz,1H),2.89–2.69(m,1H),2.21(dd,J=27.9,12.8Hz,2H),1.92–1.65(m,2H),1.16(dd,J=7.2,3.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 175.00, 172.25, 162.64 (d, J = 7.8Hz), 160.14 (d, J = 7.5Hz), 152.27, 145.15, 130.55 (t, J = 10.6Hz), 117.63, 115.79 (t, J = 16.1Hz), 111.99-111.74 (m), 107.72, 72.88, 56.80, 53.75, 45.82, 41.84, 41.59, 40.78, 39.44, 32.95, 32.38, 13.81. HRMS (MALDI) calculated C 23 H 27 F₂N₃NaO₄S[M+Na] + 502.1583, measured value 502.1583.

[0231]

[0232] Formula (Ⅱ-7). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.66(s,1H),7.38–7.24(m,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2H z,1H),4.74(dd,J=32.8,13.6Hz,1H),4.48(dd,J=8.0,5.6Hz,1H),4.23–4.10(m,1H),3.80(dd,J=17 .2,12.0Hz,1H),3.63(dd,J=17.2,9.2Hz,1H),3.45–3.34(m,6H),3.34–3.26(m,1H),3.26–3.15(m, 1H),3.02–2.93(m,1H),2.92–2.73(m,1H),2.29–2.12(m,2H),1.91–1.59(m,4H),0.92–0.81(m,3H). 13 C NMR (100MHz, CDCl3) δ 175.09, 171.50, 162.63 (d, J = 7.5Hz), 160.13 (d, J = 7.6Hz), 152.29, 145.17, 130.55 (t, J = 10.6Hz), 117.61, 115.77 (t, J = 16.1Hz), 111.98-111.73 (m), 107.37, 72.86 (t, J = 3.0Hz), 56.82, 53.99, 46.89, 41.95, 41.56, 40.83, 40.51, 32.99, 32.47, 22.10, 11.63. HRMS (MALDI) calculated C 23 H 27 F₂N₃NaO₄S[M+Na] + 516.1739, measured value 516.1742.

[0233]

[0234] Formula (Ⅱ-8). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.66(d,J=3.6Hz,1H),7.34–7.26(m,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),4.82–4 .63(m,1H),4.46(dd,J=8.4,2.0Hz,1H),4.16(dd,J=18.8,14.4Hz,1H),3.80(dd,J=16.8,12.0Hz,1H),3.63(dd,J=17.2,9.2 Hz,1H),3.41(d,J=2.8Hz,3H),3.37(s,1H),3.34–3.25(m,1H),3.25–3.15(m,1H),3.09–3.00(m,1H),2.93–2.70(m,1H),2.2 8–2.13(m,2H),1.94(s,2H),1.80–1.69(m,2H),1.58–1.47(m,1H),1.43–1.33(m,1H),1.33–1.17(m,2H),0.98–0.88(m,3H). 13 CNMR (100MHz, CDCl3) δ 175.10, 171.63, 162.63 (d, J = 7.5Hz), 160.13 (d, J = 7.7Hz), 152.29, 145.17, 130.54 (t, J = 10.6Hz), 117.68, 115.78 (t, J = 16.2Hz), 111.98-111.73 (m), 107.51, 77.39, 77.07, 76.75, 72.86, 56.86, 53.97, 46.03, 45.19, 41.96, 41.55, 40.84, 33.18, 31.07, 22.61, 20.42, 14.16. HRMS (MALDI) calculated value C 25 H 31 F₂N₃NaO₄S[M+Na] + 530.1896, measured value 530.1899.

[0235]

[0236] Formula (Ⅱ-9). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.66(d,J=4.0Hz,1H),7.34–7.27(m,1H),6.92(t,J=8.0Hz,2H),6.07(dd,J=12.0,9.2Hz,1H),4.73(dd, J=42.0,13.2Hz,1H),4.46(dd,J=8.0,3.6Hz,1H),4.16(t,J=16.7Hz,1H),3.80(dd,J=17.2,12.0Hz,1H),3.63(dd,J=17.2,9.2 Hz,1H),3.47(s,1H),3.44–3.39(m,3H),3.37(s,1H),3.35–3.27(m,1H),3.26–3.15(m,1H),3.06–2.99(m,1H),2.93–2.72(m,1 H),2.18(t,J=15.6Hz,2H),1.98–1.86(m,1H),1.83–1.68(m,2H),1.62–1.52(m,1H),1.40–1.11(m,5H),0.88(t,J=7.2Hz,3H). 13 C NMR (100MHz, CDCl3) δ 174.72, 171.65, 162.63 (d, J = 7.5Hz), 160.14 (d, J = 7.7Hz), 152.28, 145.16, 130.54 (t, J = 10.6Hz), 117.67, 115.78 (t, J = 16.3Hz), 111.98-111.73 (m), 107.52, 72.87, 56.87, 53.95, 46.03, 45.36, 41.98, 41.56, 40.85, 33.01, 32.50, 29.41, 28.71, 22.83, 13.99. HRMS (MALDI) calculated C 26 H 33 F₂N₃NaO₄S[M+Na] + 544.2052, measured value 544.2055.

[0237]

[0238] Formula (Ⅱ-10). White solid; mp = 69-71℃. 1H NMR (400MHz, CDCl3) δ7.68–7.56(m,1H),7.38(d,J=5.6Hz,2H),7.36–7.26(m,4H),6.91(t,J= 8.4Hz,2H),6.05(q,J=11.2Hz,1H),4.98(d,J=8.0Hz,1H),4.65(dd,J=40.0,13.6Hz,1H),4.11 –3.96(m,2H),3.85–3.68(m,1H),3.67–3.55(m,1H),3.54–3.48(m,3H),3.25–3.16(m,2H),3.1 4(d,J=2.4Hz,3H),2.77(s,1H),2.16–2.04(m,1H),1.87(d,J=12.8Hz,1H),1.82–0.77(m,2H). 13 C NMR (100MHz, CDCl3) δ174.72, 169.09, 162.63 (d, J = 7.4Hz), 160.13 (d, J = 7.4Hz) ,152.19,144.95,135.33,130.54(t,J=10.7Hz),128.84,128.76,127.50,117.6 7,117.59,115.78 (t, J=16.0Hz),111.99-111.74 (m),107.42,107.30,72.86,56.56,55.50,53.15,45.43,41.76,41.55,40.44,32.22,31.77.HRMS (MALDI) calculated value C 28 H 29 F₂N₃NaO₄S[M+Na] + 564.1739, measured value 564.1738.

[0239]

[0240] Formula (Ⅱ-11). White solid; mp = 126-128℃. 1H NMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.38–7.31 (m, 1H), 6.95 (t, J = 8.4Hz, 2H), 6.11 (dd, J = 1 2.0,9.2Hz,1H),4.77(d,J=13.2Hz,1H),4.14(dd,J=14.4,7.4Hz,1H),4.05–3.94(m,4H), 3.84(dd,J=17.2,12.0Hz,1H),3.66(dd,J=17.2,9.2Hz,1H),3.39–3.29(m,1H),3.24(t,J =12.8Hz,1H),2.89–2.75(m,3H),2.22(s,2H),1.81(dd,J=28.8,13.6Hz,2H),1.52(s,3H). 13 C NMR (100MHz, CDCl3) δ 174.79, 167.48, 162.61 (d, J = 7.5Hz), 160.11 (d, J = 7.5Hz), 152.26, 145.15, 130.56 (t, J = 10.7Hz), 117.69, 115.76 (t, J = 16.2Hz), 111.98–111.73 (m), 108.71, 72.85 (t, J = 3.0Hz), 64.78, 64.74, 46.49, 43.10, 41.55, 41.41, 40.51, 32.82, 32.15, 24.66. HRMS (MALDI) calculated C 23 H 25 F₂N₃NaO₄S[M+Na] + 500.1426, measured value 500.1425.

[0241]

[0242] Formula (Ⅱ-12). Yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.69 (s, 1H), 7.37–7.31 (m, 1H), 6.95 (t, J = 8.0Hz, 2H), 6.10 (dd, J = 12.0, 9.2Hz ,1H),4.76(d,J=12.8Hz,1H),4.32–4.18(m,1H),4.14–4.06(m,2H),3.84(dd,J=17.2,12.0Hz,1H),3. 66(dd,J=17.2,9.2Hz,1H),3.54–3.40(m,1H),3.38–3.29(m,1H),3.24(s,1H),2.86(s,1H),2.85–2. 76(m,2H),2.21(s,2H),1.81(dd,J=32.4,12.7Hz,2H),1.52(d,J=21.2Hz,3H),1.32(d,J=6.0Hz,3H). 13 CNMR (100MHz, CDCl3) δ 174.79, 167.64, 162.61 (d, J = 7.6Hz), 160.11 (d, J = 7.5Hz), 152.27, 145.14, 130.56 (t, J = 10.6Hz), 117.68, 115.76 (t, J = 16.1Hz), 111.97-111.72 (m), 108.95, 72.84, 70.98, 46.49, 44.05, 43.30, 41.54, 41.39, 40.49, 32.77, 32.16, 24.83, 18.26. HRMS (MALDI) calculated value C 24 H 27 F₂N₃NaO₄S[M+Na] + 514.1583, measured value 514.1580.

[0243]

[0244] Formula (II-18). A pale yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.65(s,1H),7.31(tt,J=8.4,6.6Hz,1H),6.92(t,J=8.3Hz,2H),6.07( dd,J=12.0,9.2Hz,1H),5.07(q,J=5.6Hz,1H),4.72–4.61(m,1H),4.04–3.90(m,3H),3.80(dd ,J=17.1,12.0Hz,1H),3.63(dd,J=17.1,9.2Hz,1H),3.44(d,J=2.8Hz,3H),3.31(tt,J=11.4, 3.9Hz,1H),3.21(t,J=11.9Hz,1H),2.86–2.68(m,3H),2.24–2.12(m,2H),1.87–1.66(m,2H). 13 C NMR (100MHz, CDCl3) δ 174.53, 167.10 (d, J = 2.5Hz), 162.67 (d, J = 7.6Hz), 160.17 (d, J = 7.5Hz), 152.31, 145.23 ( d,J=3.6Hz),130.61(t,J=10.6Hz),122.47(q,J=278.2Hz),117.77(d,J=3.5Hz),115.80(t,J=16.3Hz),112.00( d,J=5.8Hz), 111.81(d,J=5.9Hz), 102.94(d,J=7.3Hz), 72.90, 64.75–63.33(m), 54.71(d,J=20.6Hz), 45.71(d,J=3.0Hz), 41.57, 41.49(d,J=3.8Hz), 40.47(d,J=8.5Hz), 37.69(d,J=20.2Hz), 32.73, 32.05. HRMS (MALDI) calculated value C 23 H 24 F5N3NaO4S[M+Na] + :556.1300, measured value 556.1301.

[0245]

[0246] Formula (II-19). A pale yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.66 (s, 1H), 7.42–7.19 (m, 1H), 6.92 (t, J = 8.2Hz, 2H), 6.07 (dd, J=11.9,9.1Hz,1H),5.12(q,J=5.2Hz,1H),4.68(d,J=13.3Hz,1H),4.05–3.90(m,3H), 3.86–3.69(m,2H),3.69–3.55(m,2H),3.31(tt,J=11.4,3.9Hz,1H),3.21(t,J=12.6Hz ,1H),2.86–2.67(m,3H),2.19(t,J=13.7Hz,2H),1.88–1.64(m,2H),1.27–1.20(m,3H). 13 C NMR (100MHz, CDCl3) δ174.53, 171.20, 167.21, 162.66 (d, J = 7.6Hz), 160.16 (d, J = 7.7Hz), 152.31, 145.22 (d, J =4.2Hz), 130.59 (t, J = 10.6Hz), 123.87 (q, J = 278.1Hz), 117.73 (d, J = 6.2Hz), 115.81 (t, J = 16.2Hz), 111.99 (d, J=5.7Hz), 111.80(d,J=5.6Hz), 102.01(d,J=9.7Hz), 72.90, 64.58–63.56(m), 63.42(d,J=17.7Hz), 45.80, 41.55(d,J=7.6Hz), 40.51(d,J=6.4Hz), 38.19(d,J=6.6Hz), 32.73(d,J=6.6Hz), 32.10, 15.16. HRMS (MALDI) calculated value C 24 H 26 F5N3NaO4S[M+Na] + :570.1456, measured value 570.1455.

[0247]

[0248] Formula (Ⅱ-21). A light yellow, oily substance. 1H NMR(400MHz, CDCl3)δ7.68(s,1H),7.36–7.30(m,1H),6.99–6.88(m,2H),6.09(dd,J=12.0,9.2Hz, 1H),5.07(t,J=5.2Hz,1H),4.71(d,J=13.4Hz,1H),4.15–4.09(m,2H),4.05(d,J=13.4Hz,1H),3.89 –3.78(m,3H),3.65(dd,J=17.2,9.2Hz,1H),3.32(tt,J=11.6,3.6Hz,1H),3.25–3.16(m,1H),2.85– 2.76(m,1H),2.73(dd,J=5.2,1.6Hz,2H),2.25–2.09(m,3H),1.88–1.70(m,2H),1.43–1.33(m,1H). 13 C NMR (100MHz, CDCl3) δ174.65, 167.33, 162.55 (d, J = 7.6Hz), 160.05 (d, J = 7.6Hz), 1 52.21,145.07,130.47(t,J=10.6Hz),117.60,115.70(t,J=16.2Hz),111.88(d,J= 5.8Hz), 111.69 (d, J = 5.8Hz), 99.82, 72.79 (t, J = 2.9Hz), 66.93 (d, J = 1.9Hz), 45.74, 41.48 (t, J = 2.1Hz), 41.39, 40.45, 39.20, 32.71, 31.96, 25.50. HRMS (MALDI) calculated value C 23 H 25 F₂N₃NaO₄S[M+Na] + :500.1426, measured value 500.1424.

[0249]

[0250] Formula (Ⅱ-22). A light yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.64 (s, 1H), 7.36–7.25 (m, 1H), 6.91 (t, J = 8.4Hz, 2H), 6.07 ( dd,J=12.0,9.2Hz,1H),5.31(t,J=4.8Hz,1H),4.71(d,J=13.6Hz,1H),4.03–3.88(m ,5H),3.79(dd,J=17.1,12.0Hz,1H),3.62(dd,J=16.8,9.2Hz,1H),3.34–3.24(m,1H ),3.24–3.16(m,1H),2.85–2.74(m,3H),2.18(t,J=16.2Hz,2H),1.87–1.70(m,2H). 13 C NMR (100MHz, CDCl3) δ 174.57, 167.24, 162.60–162.51 (m), 160.17–160.00 (m), 152.21, 145.11, 130.50, 117.65, 115.71, 111.91, 111.71, 101.82, 72.82, 64.94, 45.63, 41.50, 41.30, 40.45, 38.29, 32.71, 31.93. HRMS (MALDI) calculated C 22 H 23 F₂N₃NaO₄S[M+Na] + :486.1270, measured value 486.1268.

[0251]

[0252] Formula (Ⅱ-23). ​​A light yellow oily substance. 1 H NMR (400MHz, CDCl3) δ7.65(s,1H),7.35–7.26(m,1H),6.91(t,J=8.0Hz,2H),6.06(t,J=10.4Hz ,1H),4.68(s,1H),4.26(t,J=6.4Hz,1H),4.07–3.96(m,1H),3.91–3.68(m,3H),3.62(dd,J=17 2, 9.2 Hz, 1H), 3.30 (t, J = 11.6 Hz, 1H), 3.19 (s, 1H), 2.83–2.72 (m, 1H), 2.55–2.44 (m, 1H), 2.24–2.02 (m, 4H), 1.90 (t, J = 7.2 Hz, 2H), 1.84–1.69 (m, 2H), 1.64–1.51 (m, 1H). HRMS (MALDI) calculated value C 23 H 25F2N3NaO3S[M+Na] + :484.1477, measured value 484.1476.

[0253]

[0254] Formula (Ⅱ-24). A light yellow oily substance. 1 H NMR(400MHz, CDCl3)δ7.64(s,1H),7.33–7.27(m,1H),6.95–6.87(m,2H),6.06(dd,J=12.0,9.2Hz ,1H),4.66(d,J=13.2Hz,1H),4.02–3.90(m,2H),3.91–3.80(m,1H),3.80–3.71(m,2H),3.62(dd, J=17.2,9.2Hz,1H),3.43(t,J=6.8Hz,1H),3.29(tt,J=11.2,4.0Hz,1H),3.18(t,J=12.8Hz,1H), 2.79(m,1H),2.71(m,1H),2.52–2.39(m,2H),2.25–2.11(m,3H),1.82–1.69(m,2H),1.56(m,1H). 13 C NMR (100MHz, CDCl3) δ 174.45, 170.00, 162.56 (d, J = 7.7Hz), 160.06 (d, J = 7.5Hz), 152.16, 145.12, 130.50 (t, J = 10.6Hz), 117.64, 115.69 (t, J = 16.2Hz), 111.89 (d, J = 5.9Hz), 111.70 (d, J = 5.7Hz), 73.27, 72.80 (t, J = 3.1Hz), 67.58, 45.14, 41.49, 41.32, 40.45, 37.02, 35.49, 32.72, 32.18, 32.05. HRMS (MALDI) calculated C 23 H 25 F2N3NaO3S[M+Na] + :484.1477, measured value 484.1475.

[0255]

[0256] Formula (Ⅱ-25). A light yellow, oily substance. 1H NMR(400MHz, CDCl3)δ7.64(s,1H),7.33–7.26(m,1H),6.94–6.87(m,2H),6.06(dd,J=11.6,9.2Hz,1H ),4.69(t,J=14.8Hz,1H),4.08–3.99(m,1H),3.96–3.91(m,1H),3.84–3.74(m,2H),3.61(dd,J=17.2, 9.2Hz,1H),3.51–3.40(m,1H),3.34–3.21(m,1H),3.23–3.11(m,1H),2.84–2.71(m,1H),2.73–2.61(m ,1H),2.39–2.28(m,1H),2.21–2.10(m,2H),1.85–1.67(m,4H),1.59–1.45(m,3H),1.37–1.26(m,1H). 13 CNMR(100MHz, CDCl3)δ174.88,174.67,169.46,169.30,162.58(d,J=7.5Hz),160.08(d,J=7.6Hz),1 52.21,145.07(d,J=5.0Hz),130.48(t,J=10.7Hz),117.60,115.72(t,J=16.1Hz),111.90(d,J=6.0Hz ), 111.71 (d, J = 5.6 Hz), 75.12 (d, J = 12.7 Hz), 72.81 (t, J = 2.9 Hz), 68.54, 45.74 (d, J = 7.4 Hz), 41.50, 40.53 (d, J = 8.0 Hz), 40.19 (d, J = 13.7 Hz), 32.82, 32.03 (d, J = 9.9 Hz), 25.78, 23.35. HRMS (MALDI) calculated value C 24 H 27 F2N3NaO3S[M+Na] + :498.1633, measured value 498.1634.

[0257]

[0258] Formula (Ⅱ-26). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.68(s,1H),7.39–7.30(m,1H),6.94(t,J=8.5Hz,2H),6.14–6.05(m,1H),4.71(d,J=13 .0Hz,1H),3.99(d,J=11.2Hz,1H),3.94–3.78(m,3H),3.65(dd,J=12.8,9.6Hz,1H),3.53–3.41(m,1H),3.40– 3.27 (m, 1H), 3.23 (t, J = 10.0 Hz, 2H), 2.81 (t, J = 12.4 Hz, 1H), 2.33 (dd, J = 14.8, 6.8 Hz, 1H), 2.29–2.13 (m, 3H), 2.01 (s, 1H), 1.98–1.90 (m, 1H), 1.85–1.70 (m, 2H), 1.69–1.61 (m, 2H), 1.39–1.28 (m, 1H). HRMS (MALDI) calculated value C 24 H 27 F2N3NaO3S[M+Na] + :498.1633, measured value 498.1631.

[0259]

[0260] Formula (Ⅱ-27). A light yellow, oily substance. 1 H NMR (400MHz, CDCl3) δ7.63 (s, 1H), 7.33–7.26 (m, 1H), 6.96–6.80 (m, 2H), 6.05 (dd, J = 12.0, 9.2Hz, 1H), 4. 67(d,J=13.4Hz,1H),4.02–3.90(m,3H),3.78(dd,J=16.8,12.0Hz,1H),3.61(dd,J=17.2,9.2Hz,1H),3.4 6–3.37(m,2H),3.29(tt,J=11.6,4.0Hz,1H),3.18(t,J=12.8Hz,1H),2.77(t,J=12.4Hz,1H),2.27(d,J=7 .2Hz,2H),2.24–2.12(m,2H),2.11–2.03(m,1H),1.81–1.70(m,2H),1.70–1.64(m,2H),1.38-1.26(m,2H). 13C NMR (100MHz, CDCl3) δ 174.49, 169.93, 162.54 (d, J = 7.5Hz), 160.04 (d, J = 7.6Hz), 152.12, 145.10, 130.49 (t, J = 10.6Hz), 117.65, 115.66 (t, J = 16.2Hz), 111.88 (d, J = 5.9Hz), 111.69 (d, J = 5.7Hz), 72.81 (t, J = 3.1Hz), 67.80, 45.38, 41.46, 41.31, 40.45, 39.91, 33.06, 32.82, 32.60, 32.08. HRMS (MALDI) calculated C 24 H 27 F2N3NaO3S[M+Na] + :498.1633, measured value 498.1627.

[0261]

[0262] Formula (Ⅱ-28). A light yellow, oily substance. 1 H NMR (400MHz, CDCl3) δ7.66–7.63(m,1H),7.33–7.26(m,1H),6.94–6.86(m,2H),6.09–6.02(m,1H) ,5.18–5.13(m,1H),4.68(d,J=13.4Hz,1H),4.01(d,J=13.6Hz,1H),3.94–3.86(m,2H),3.84–3.7 4 (m, 1H), 3.72–3.63 (m, 2H), 3.63–3.57 (m, 1H), 3.34–3.24 (m, 1H), 3.18 (t, J = 12.8 Hz, 1H), 2.77 (t, J = 12.8 Hz, 1H), 2.72–2.66 (m, 2H), 2.14 (t, J = 14.8 Hz, 2H), 1.80–1.70 (m, 6H). HRMS (MALDI) calculated value C 24 H 27 F₂N₃NaO₄S[M+Na] + :514.1583, measured value 514.1581.

[0263]

[0264] Formula (Ⅱ-31). White solid; mp = 75-77℃. 1H NMR(400MHz, CDCl3)δ7.62(s,1H),7.50–7.41(m,1H),7.34–7.26(m,1H),7.20–7.12(m,3H),6.91(t, J=8.4Hz,2H),6.11–6.00(m,1H),4.91(d,J=7.6Hz,1H),4.76–4.53(m,1H),4.28–4.17(m,1H),3.91–3 0.68 (m, 2H), 3.67–3.56 (m, 1H), 3.54 (s, 3H), 3.27–3.13 (m, 1H), 3.09 (s, 3H), 2.95–2.83 (m, 1H), 2.82–2.69 (m, 1H), 2.43 (s, 3H), 2.15–1.95 (m, 2H), 1.57–1.45 (m, 1H), 0.73–0.58 (m, 1H). HRMS (MALDI) calculated value C 29 H 31 F₂N₃NaO₄S[M+Na] + :578.1896, measured value 578.1894.

[0265]

[0266] Formula (Ⅱ-32). White solid; mp = 89-91℃. 1 H NMR (400MHz, CDCl3) δ7.62(s,1H),7.34–7.27(m,1H),7.23–7.14(m,3H),7.07(t,J=6.8Hz,1H),6.91(td,J=8.0,3.2Hz ,2H),6.05(dd,J=11.2Hz,J=20.8Hz,1H),4.98(d,J=8.0Hz,1H),4.72–4.57(m,1H),4.03–3.96(m,1H),3.80–3.72(m,1 3.66–3.56 (m, 1H), 3.51 (s, 3H), 3.26–3.18 (m, 1H), 3.15 (s, 3H), 2.99 (t, J = 11.6 Hz, 1H), 2.81–2.72 (m, 1H), 2.33 (s, 3H), 2.16–2.06 (m, 1H), 1.93–1.80 (m, 1H), 1.81–1.73 (m, 1H), 1.58–1.48 (m, 1H), 0.93–0.81 (m, 1H). HRMS (MALDI) calculated value C 29 H 31 F₂N₃NaO₄S[M+Na] + :578.1896, measured value 578.1895.

[0267]

[0268] Formula (Ⅱ-33). Light yellow solid; mp = 90-92℃. 1 H NMR (400MHz, CDCl3) δ7.67–7.56(m,1H),7.33–7.26(m,3H),7.13(d,J=7.6Hz,2H),6.91(t,J=8.0Hz,2H),6.05(dd, J=20.4Hz, J=10.0Hz, 1H), 4.96 (dd, J=8.0, 2.0Hz, 1H), 4.73–4.55 (m, 1H), 4.05–3.96 (m, 1H), 3.85–3.69 (m, 1H), 3.6 6–3.54(m, 1H), 3.51(d, J = 2.0Hz, 3H), 3.27–3.17(m, 1H), 3.15(s, 3H), 2.97(t, J = 12.4Hz, 1H), 2.76(t, J = 12.4Hz, 1H), 2.35–2.27(m, 3H), 2.16–2.02(m, 2H), 1.91–1.78(m, 1H), 1.59–1.46(m, 1H), 0.96–0.81(m, 1H). HRMS (MALDI) calculated value C 29 H 31 F₂N₃NaO₄S[M+Na] + :578.1896, measured value 578.1897.

[0269]

[0270] Formula (Ⅱ-34). White solid; mp = 93-95℃. 1H NMR (400MHz, CDCl3) δ7.66–7.56(m,1H),7.34–7.26(m,2H),7.06(d,J=7.6Hz,1H),6.99–6.86(m,3H),6.1 0–6.01(m,1H),4.90(d,J=8.0Hz,1H),4.76–4.56(m,1H),4.22–4.09(m,1H),3.90–3.60(m,3H),3.54(d,J= 6.4Hz, 3H), 3.26–3.14 (m, 1H), 3.10 (d, J = 4.8Hz, 3H), 2.93–2.68 (m, 1H), 2.38 (d, J = 3.2Hz, 3H), 2.28 (d, J = 4.0Hz, 3H), 2.16–2.05 (m, 1H), 1.92–1.72 (m, 2H), 1.56–1.44 (m, 1H), 0.68–0.56 (m, 1H). HRMS (MALDI) calculated value C 30 H 33 F₂N₃NaO₄S[M+Na] + :592.2052, measured value 592.2044.

[0271]

[0272] Formula (Ⅱ-35). White solid; mp = 90-92℃. 1 H NMR (400MHz, CDCl3) δ7.66–7.56(m,1H),7.37–7.28(m,2H),7.00–6.95(m,2H),6.94–6.87(m,2H),6.10–6 .00(m,1H),4.92–4.86(m,1H),4.74–4.54(m,1H),4.23–4.13(m,1H),3.91–3.68(m,2H),3.67–3.56(m,1H) ,3.53 (d, J = 2.8 Hz, 3H), 3.23–3.12 (m, 1H), 3.10 (s, 3H), 2.94–2.68 (m, 1H), 2.39 (d, J = 2.8 Hz, 3H), 2.30–2.24 (m, 3H), 2.19–1.96 (m, 2H), 1.91–1.72 (m, 1H), 1.57–1.44 (m, 1H), 0.75–0.63 (m, 1H). HRMS (MALDI) calculated value C 30 H 33 F₂N₃NaO₄S[M+Na] + :592.2052, measured value 592.2044.

[0273]

[0274] Formula (Ⅱ-37). White solid; mp = 98-100℃. 1 H NMR (400MHz, CDCl3) δ7.67–7.56(m,1H),7.53–7.46(m,1H),7.34–7.27(m,1H),7.25–7.20(m,1H),6.98–6. 87(m,4H),6.10–6.00(m,1H),5.13–5.04(m,1H),4.72–4.52(m,2H),4.21(t,J=15.6Hz,1H),3.86(s,3H),3. 82–3.70(m, 1H), 3.67–3.53(m, 1H), 3.50(s, 3H), 3.28–3.19(m, 1H), 3.15(s, 3H), 3.02–2.93(m, 1H), 2.80–2.68(m, 1H), 2.15–2.07(m, 1H), 1.91–1.72(m, 1H), 1.52–1.40(m, 1H), 0.88–0.76(m, 1H). HRMS (MALDI) calculated value C 29 H 31 F₂N₃NaO₅S[M+Na] + :594.1845, measured value 594.1843.

[0275]

[0276] Formula (Ⅱ-39). White solid; mp = 113-115℃. 1 H NMR (400MHz, CDCl3) δ7.71–7.62(m,2H),7.33–7.28(m,2H),7.21–7.16(m,1H),6.95–6.87(m ,2H),6.12–6.02(m,1H),5.00(dd,J=8.0,2.8Hz,1H),4.72–4.58(m,2H),4.27–4.10(m,1H),3 .88–3.55(m,2H), 3.51(d,J=4.0Hz,3H), 3.39–3.24(m,1H), 3.21(s,3H), 3.16–3.08(m,1H), 2.88–2.75(m,1H), 2.20–2.09(m,2H), 1.97–1.72(m,1H), 1.64–1.05(m,1H). HRMS (MALDI) calculated value C 28 H 27 Cl2F2N3NaO4S[M+Na] +:632.0960, measured value 632.0963.

[0277]

[0278] Formula (Ⅱ-70). A light yellow, oily substance. 1 H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),6.98(s,1H),6.92(t,J=8.4Hz,2H),6.12(t,J= 10.8Hz,1H),4.97–4.92(m,1H),4.72(d,J=13.6Hz,1H),4.06(d,J=13.6Hz,1H),3.90–3 .80(m,1H),3.77–3.65(m,3H),3.61–3.53(m,2H),3.15(t,J=12.8Hz,1H),3.02(t,J=12 .4Hz,1H),2.79–2.65(m,3H),2.12–2.02(m,2H),1.77–1.58(m,2H),1.26–1.16(m,6H). 13 C NMR (100MHz, CDCl3) δ167.97,162.51(d,J=7.6Hz),161.10,160.00(d,J=7.6Hz),156.72,153 .29,130.74(t,J=10.6Hz),115.30(t,J=16.2Hz),114.27,111.94(d,J=5.9Hz),111.74(d,J= 5.5Hz), 101.67, 73.89 (t, J = 3.0Hz), 63.17 (d, J = 17.2Hz), 46.24, 41.76, 40.50 (d, J = 2.3Hz), 38.71, 38.50, 32.14 (d, J = 4.1Hz), 31.30 (d, J = 4.7Hz), 15.31 (d, J = 2.6Hz). HRMS (MALDI) calculated value C 24 H 30 F2N3O4S[M+H] + :494.1920, measured value 494.1923.

[0279]

[0280] Formula (Ⅱ-71). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),6.98(s,1H),6.92(t,J=8.4Hz,2H),6.12( t,J=10.8Hz,1H),4.90(s,1H),4.72(d,J=13.2Hz,1H),4.03(d,J=13.6Hz,1H),3.9 0–3.81(m,1H),3.76–3.55(m,3H),3.41(s,3H),3.16(t,J=12.8Hz,1H),3.01(t,J= 12.0Hz,1H),2.71(s,3H),2.14–2.02(m,2H),1.76–1.58(m,2H),1.26–1.18(m,3H). 13 C NMR (100MHz, CDCl3) δ167.85,162.52(d,J=7.5Hz),161.08,160.02(d,J=7.4Hz),156.74,153.30,130.75(t ,J=10.6Hz),115.32(t,J=16.2Hz),114.30,111.95(d,J=5.8Hz),111.76(d,J=5.7Hz),102.49,73.90(d,J=2 0.9Hz), 63.28 (d,J=15.2Hz), 54.59 (d,J=24.3Hz), 46.15 (d,J=2.2Hz), 41.77 (d,J=1.9Hz), 40.53, 38.49 (d,J=2.9Hz), 38.22 (d,J=17.6Hz), 32.18 (d,J=3.8Hz), 31.34–31.19 (m), 15.30 (d,J=3.1Hz). HRMS (MALDI) calculated value C 23 H 28 F2N3O4S[M+H] + :480.1763, measured value 480.1760.

[0281]

[0282] Formula (Ⅱ-79). A light yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),7.00(s,1H),6.96–6.89(m,2H),6.13(dd ,J=12.0,9.2Hz,1H),4.77(d,J=11.6Hz,1H),4.11–4.04(m,1H),3.99–3.84(m,5H) ,3.69(dd,J=17.6,9.2Hz,1H),3.23–3.12(m,1H),3.05(tt,J=12.0,3.6Hz,1H),2 .81(s,2H),2.76–2.67(m,1H),2.14–2.06(m,2H),1.74–1.61(m,2H),1.48(s,3H). 13 C NMR (100MHz, CDCl3) δ167.42,162.51(d,J=7.6Hz),161.15,160.01(d,J=7.4Hz),156.71,153.29,13 0.75(t,J=10.7Hz),115.30(t,J=16.2Hz),114.47–114.15(m),111.95(d,J=5.8Hz),111.75(d,J=5.9 Hz), 108.70, 73.91 (t, J = 3.1 Hz), 64.69 (d, J = 4.7 Hz), 46.87–46.49 (m), 43.00, 41.97–41.70 (m), 40.52 (d, J = 2.5 Hz), 38.52–38.26 (m), 32.30–31.91 (m), 31.40–31.02 (m), 30.17, 24.64. HRMS (MALDI) calculated value C 23 H 26 F2N3O4S[M+H] + :478.1607, measured value 478.1611.

[0283]

[0284] Formula (Ⅱ-81). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),6.99(s,1H),6.96–6.89(m,2H),6.13(dd,J=12.0, 9.2Hz,1H),4.87(d,J=7.2Hz,1H),4.73(d,J=13.6Hz,1H),3.98(d,J=13.2Hz,1H),3.87(dd, J = 17.2, 12.0 Hz, 1H), 3.68 (dd, J = 17.2, 9.2 Hz, 1H), 3.42 (s, 3H), 3.18 (t, J = 12.8 Hz, 1H), 3.09–2.97 (m, 2H), 2.80–2.70 (m, 2H), 2.17–2.05 (m, 5H), 1.74–1.61 (m, 2H). HRMS (MALDI) calculated value C 22 H 26 F2N3O3S2[M+H] + :482.1378, measured value 482.1380.

[0285]

[0286] Formula (Ⅱ-82). A light yellow oily substance. 1 H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),7.00(s,1H),6.96–6.89(m,2H),6.13(dd,J=12.0,9.2Hz,1H ),4.95–4.90(m,1H),4.73(d,J=13.2Hz,1H),3.98(d,J=13.2Hz,1H),3.89(dd,J=17.2,12.0Hz,1H),3 .69 (dd, J = 17.2, 9.2 Hz, 1H), 3.42 (s, 3H), 3.18 (t, J = 12.8 Hz, 1H), 3.10–2.99 (m, 2H), 2.82–2.72 (m, 2H), 2.68–2.61 (m, 2H), 2.16–2.05 (m, 2H), 1.74–1.61 (m, 2H), 1.28 (t, J = 7.6 Hz, 3H). HRMS (MALDI) calculated value C 23 H 28 F2N3O3S2[M+H] + :496.1535, measured value 496.1530.

[0287]

[0288] Formula (Ⅱ-85). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.27(m,1H),6.99(s,1H),6.96–6.89(m,2H),6.13(dd,J=12.0,9 .2Hz,1H),4.97–4.92(m,1H),4.78–4.68(m,1H),4.05–3.96(m,1H),3.91–3.78(m,2H),3.68 (dd, J = 17.2, 9.2 Hz, 1H), 3.51–3.45 (m, 1H), 3.18 (t, J = 12.8 Hz, 1H), 3.09–2.99 (m, 2H), 2.81–2.69 (m, 2H), 2.13–2.06 (m, 5H), 1.75–1.62 (m, 2H), 1.20 (t, J = 7.2 Hz, 3H). HRMS (MALDI) calculated value C 23 H 28 F2N3O3S2[M+H] + :496.1535, measured value 496.1536.

[0289]

[0290] Formula (Ⅱ-87). A light yellow oily substance. 1 ¹H NMR (400MHz, CDCl₃) δ 7.36–7.27 (m, 1H), 6.99 (s, 1H), 6.96–6.89 (m, 2H), 6.12 (dd, J = 12.0, 9.2Hz, 1H), 5.14–5.09 (m, 1H), 4.71 (d, J = 13.4Hz, 1H), 4.03–3.82 (m, 4H), 3.78–3.57 (m, 3H), 3.18 (t, J = 12.8Hz, 1H), 3.09–3.00 (m, 1H), 2.78–2.68 (m, 3H), 2.14–2.05 (m, 2H), 1.74–1.62 (m, 2H), 1.24–1.19 (m, 3H). HRMS (MALDI) calculated C 24 H 27 F5N3O4S[M+H] + :548.1637, measured value 548.1642.

[0291]

[0292] Formula (Ⅱ-92). A light yellow oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.28(m,1H),7.00(s,1H),6.96–6.89(m,2H),6.13(dd,J=12. 4,9.2Hz,1H),4.72(d,J=13.4Hz,1H),4.01–3.92(m,2H),3.91–3.83(m,2H),3.79–3.74(m ,1H),3.73–3.64(m,1H),3.48–3.42(m,1H),3.22–3.12(m,1H),3.08–2.98(m,1H),2.76– 2.67(m,2H),2.53–2.40(m,2H),2.21–2.06(m,3H),1.71–1.61(m,2H),1.60–1.52(m,1H). 13 C NMR (100MHz, CDCl3) δ 169.98, 162.53 (d, J = 7.3Hz), 160.97, 160.03 (d, J = 7.6Hz), 156.80, 153.28, 130.76 (t, J = 10.7Hz), 115.24 (d, J = 16.4Hz), 114.38, 111.96 (d, J = 5.7Hz), 111.77 (d, J = 5.5Hz), 73.93, 73.31, 67.61, 45.56, 41.72, 40.56, 38.52, 37.05, 35.56, 32.28, 32.21, 31.25. HRMS (MALDI) calculated C 29 H 31 F2N3NaO5S[M+H] + :594.1845, measured value 594.1843.

[0293]

[0294] Formula (Ⅱ-93). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.37–7.29(m,1H),6.99(s,1H),6.97–6.89(m,2H),6.17–6.08(m,1H),4 .78–4.69(m,1H),4.04(d,J=13.6Hz,1H),3.98–3.89(m,1H),3.88–3.76(m,2H),3.68(dd,J=17 .4,9.2Hz,1H),3.50–3.42(m,1H),3.21–3.09(m,1H),3.08–2.98(m,1H),2.79–2.63(m,2H),2 .39–2.31(m,1H),2.14–2.03(m,2H),1.86–1.60(m,4H),1.58–1.46(m,3H),1.37–1.27(m,1H). 13 C NMR (100MHz, CDCl3) δ169.22 (d, J = 8.4Hz), 162.51 (d, J = 7.5Hz), 161.16 (d, J = 8.8Hz), 160.01 (d, J = 7.5Hz), 156.69 (d, J = 3 .0Hz),153.29,130.73(t,J=10.6Hz),115.31(t,J=16.2Hz),114.29(d,J=5.0Hz),111.94(d,J=5.8Hz),111.74(d,J=5.9H z), 75.06 (d, J = 5.9 Hz), 73.90 (t, J = 3.0 Hz), 68.52 (d, J = 1.8 Hz), 46.04 (d, J = 2.3 Hz), 41.78 (d, J = 2.0 Hz), 40.53, 40.16 (d, J = 13.0 Hz), 38.52, 32.37–32.20 (m), 32.00 (d, J = 8.4 Hz), 31.24 (t, J = 5.2 Hz), 25.79, 23.33 (d, J = 2.2 Hz). HRMS (MALDI) calculated value C 24 H 27 F2N3NaO3S[M+Na] + :498.1633, measured value 498.1637.

[0295]

[0296] Formula (Ⅱ-95). A light yellow, oily substance. 1H NMR (400MHz, CDCl3) δ7.36–7.27(m,1H),7.00(s,1H),6.96–6.89(m,2H),6.12(dd,J=12.0,9.2Hz, 1H),4.73(d,J=12.8Hz,1H),4.01–3.89(m,3H),3.88–3.82(m,1H),3.68(dd,J=17.4,9.2Hz,1H),3. 42 (td, J = 11.8, 2.0 Hz, 2H), 3.22–3.11 (m, 1H), 3.04 (tt, J = 11.6, 3.6 Hz, 1H), 2.71 (t, J = 10.6 Hz, 1H), 2.28 (d, J = 6.8 Hz, 2H), 2.17–2.05 (m, 3H), 1.72–1.61 (m, 4H), 1.39–1.27 (m, 2H). HRMS (MALDI) calculated value C 24 H 28 F2N3O3S[M+H] + :476.1814, measured value 476.1818.

[0297]

[0298] Formula (Ⅱ-103). White solid; mp = 95-97℃. 1 H NMR (400MHz, CDCl3) δ7.38–7.27(m,2H),7.00–6.89(m,5H),6.16–6.06(m,1H),4.89(dd,J=7.6,3.2H z,1H),4.77–4.63(m,1H),4.19(dd,J=17.2,8.0Hz,1H),3.89–3.57(m,3H),3.53(d,J=3.2Hz,3H),3.0 9 (d, J = 2.0 Hz, 3 H), 3.00–2.80 (m, 1 H), 2.68 (t, J = 13.2 Hz, 1 H), 2.39 (d, J = 2.6 Hz, 3 H), 2.29–2.20 (m, 3 H), 1.98 (d, J = 13.6 Hz, 1 H), 1.81–1.65 (m, 2 H), 1.46–1.35 (m, 1 H), 0.70–0.59 (m, 1 H). HRMS (MALDI) calculated value C 30 H 34 F2N3O4S[M+H] + :570.2233, measured value 570.2238.

[0299]

[0300] Formula (Ⅱ-105). White solid; mp = 97-99℃. 1 H NMR (400MHz, CDCl3) δ7.54–7.47(m,1H),7.36–7.28(m,1H),7.24–7.17(m,1H),6.99–6.86(m,4H),6.74(s,1 H),6.16–6.07(m,1H),5.12–5.06(m,1H),4.74–4.59(m,2H),4.22(t,J=15.6Hz,1H),3.86(s,3H),3.82–3.7 6 (m, 1H), 3.70–3.59 (m, 1H), 3.49 (d, J = 1.8 Hz, 3H), 3.15 (s, 3H), 3.13–3.07 (m, 1H), 3.02–2.86 (m, 1H), 2.71–2.63 (m, 1H), 2.02–1.93 (m, 1H), 1.84–1.75 (m, 1H), 1.42–1.30 (m, 1H), 0.79–0.65 (m, 1H). HRMS (MALDI) calculated value C 29 H 32 F2N3O5S[M+H] + :572.2025, measured value 572.2029.

[0301] Test Example 1: In vivo activity against cucumber downy mildew

[0302] The testing and investigation methods followed SOP-SC-1098, the pot method for cucumber downy mildew, in the fungicide volume of "Standard Operating Procedures for Testing the Biological Activity of Pesticides" compiled by Kang Zhuo and Gu Baogen. Test results are shown in Tables 1, 2, and 3. Items marked with " / " in the tables indicate that no test was conducted (the same applies below). The structural formula of the control agent, fluoxetine (OXA), is as follows:

[0303]

[0304] Explanation of the control efficacy levels in the activity test results: 90%≤A≤100%; 75%≤B<90%; 60%≤C<75%; 45%≤D<60%; 0%≤E<45%.

[0305] Screening results of the target compound's indoor in vivo bactericidal activity against cucumber downy mildew.

[0306] Table 1: Indoor fungicidal activity of target compounds against cucumber downy mildew

[0307]

[0308]

[0309] To further explore the relationship between compound structure and activity, this invention conducted a secondary screening experiment at lower concentrations for some compounds that showed efficacy exceeding 75% at the lowest concentration (1.25 mg / L) in the initial indoor in vivo fungicidal activity test for cucumber downy mildew. The experimental results are shown in Table 2.

[0310] Table 2: Re-screening of the in vivo bactericidal activity of target compounds against cucumber downy mildew in indoor environments

[0311]

[0312] The above activity results show that several compounds of the present invention have good control effects against cucumber downy mildew. At three application concentrations from 20 mg / L to 1.25 mg / L, several compounds have control efficacy of 75% to 100%, comparable to the control agent fluthiazopyrone. In the activity re-screening stage, four compounds of the present invention (II-3, II-4, II-18, and II-19) have excellent fungicidal activity, with control efficacy of 90% or more at an application concentration of 0.078 mg / L, comparable to the efficacy of fluthiazopyrone at the same concentration, and superior to the control efficacy of dimethomorph and cyazofamid. Most importantly, compounds II-3 and II-18 of the present invention have control efficacy comparable to the control agent OXA at ​​an application concentration of 0.005 mg / L, and have value for further development.

[0313] Comparison with the closest existing compounds: Activity data for the comparative compounds (Comparatives 1-7) in Table 3 are sourced from: Li, J. Letal. Pestic. Biochem. Phys. 2020, 169, 104673. DOI: doi.org / 10.1016 / j.pestbp.2020.104673. As can be seen from the comparison in Table 3, most of the compounds in this invention exhibit higher efficacy against cucumber downy mildew at a concentration of 0.625 mg / L than the comparative compounds.

[0314] Table 3: Comparative results of the in vivo fungicidal activity of the compounds against cucumber downy mildew in the indoor environment.

[0315]

[0316]

[0317] Note: Prevention efficacy levels: 90% ≤ A ≤ 100%; 75% ≤ B < 90%; 60% ≤ C < 75%; 45% ≤ D < 60%; 0% ≤ E < 45%

[0318] Test Example 2: In vitro activity against the growth of oomycete pathogen hyphae

[0319] The microplate method was used to determine the in vitro bioactivity of the agents. Culture of *Phytophthora capsici*, *Phytophthora sacchari*, *Phytophthora causalis*, and *Phytophthora tumefaciens*: The target bacteria were inoculated into PDB or V8 liquid medium and shaken for 72-96 hours. After filtration, fresh mycelia were collected. Then, 0.1 g of mycelium was weighed and placed in 50 ml of PDB liquid medium. The mycelium was then broken into small mycelial fragments using a tissue homogenizer to prepare a mycelial fragment suspension, which was stored at 4°C for later use.

[0320] Culture of pathogenic *Phytophthora*: *Phytophthora* was inoculated onto V8 agar plates and cultured for 12 days until a large number of sporangia were produced. Sterile water was then added, and the plates were placed in a 4°C refrigerator for 1 hour, followed by transfer to room temperature to induce zoospore release. After sufficient zoospore release, a spore concentration of 10⁻⁶ was prepared. 5 A spore suspension of 1 spore per mL was prepared and stored at 4°C for later use.

[0321] The test reagent was prepared into a 2000 mg / L stock solution using DMSO, and then diluted with sterile water to form a series of gradient concentration solutions, which were then stored at 4°C for later use.

[0322] Spore suspension (mycelial fragment suspension) and a series of pre-prepared gradient solutions were added sequentially to each microplate at a rate of 100 μl + 100 μl. The 96-well microplate was then placed in an incubator at 25°C (18°C for Phytophthora infestans) and incubated statically for 3-4 days (7 days for Phytophthora infestans). The OD of each treatment was then measured using a microplate reader. 595 Values. The in vitro toxicity of the agent against the target bacteria was calculated. The results are listed in Table 4.

[0323] Inhibition rate % = (Blank treatment OD) 595 -Pharmaceutical treatment of OD 595 ) / (Blank processing OD 595 -Reference OD 595 )*100

[0324] Table 4: Inhibitory activity of target compounds II-3 and II-18 on the hyphal growth of oomycete pathogens

[0325]

[0326]

[0327] Note: Inhibition activity level: 90%≤A≤100%; 75%≤B<90%; 60%≤C<75%;

[0328] As shown in Table 4, compounds II-3 and II-18 exhibited good inhibitory activity against the mycelial growth of oomycete pathogens. At application concentrations of 5, 0.5, and 0.05 mg / L, their inhibitory activities against Phytophthora capsici, Phytophthora sacchariformis, Phytophthora causalis, and Pythium spp. were comparable to those of the control agent OXA.

[0329] Test Example 3: Field efficacy trial of pesticide for controlling cucumber downy mildew

[0330] This experiment was conducted in accordance with the "Field Application Guidelines for Pesticides (I) Fungicides for the Control of Cucumber Downy Mildew" (GB / T17980.26-2000). The experimental site was the Hushu Vegetable Base in Nanjing, Jiangsu Province. Cucumber downy mildew was the target disease, with fluoxetine and silver-based fungicides used as control agents. The experimental crop was cucumber, variety "Green Core". A randomized block design was used, with each plot approximately 8m². 2 Each treatment was replicated three times. The entire plant was sprayed with the fungicide. The experiment was conducted at the early stage of cucumber downy mildew, with two consecutive applications. The second application was performed five days after the first. The survey method involved setting up one survey point per row of cucumbers in each treatment plot to investigate the degree of downy mildew on all leaves of all cucumber seedlings. The disease index and control efficacy were calculated, and the results are shown in Table 5.

[0331] Table 5. Field control efficacy of target compound II-3 against cucumber downy mildew.

[0332]

[0333] Test results showed that compound II-3 was effective in controlling cucumber downy mildew, effectively protecting new leaves and inhibiting the spread of lesions on already infected leaves. In the field, a dosage of 50 mg / L, applied 2-3 times at 5-7 day intervals, effectively controlled the occurrence of downy mildew. At the experimental dosage of 50 mg / L, its efficacy was superior to the control agents OXA and silver-based fungicides.

[0334] Test Example 4: Field efficacy trial of pesticides for controlling potato late blight

[0335] This experiment was conducted in accordance with the "Guidelines for Field Application of Pesticides (I) Fungicides for the Control of Potato Late Blight" (GB / T17980.34-2000). The experimental site was Qishan, Shaanxi Province. Potato late blight was the target disease, and commercially available Zengwei Yinglv (10% fluoxetine dispersible oil suspension) was used as the control. Potato was the experimental crop. A randomized block design was used, with three replicates per treatment. Whole-plant foliar spraying was employed. The experiment was conducted at the early stage of potato late blight occurrence, with two consecutive applications. The second application was performed 7 days after the first. The survey method involved sampling at five points diagonally across each plot, selecting two plants at each point, and surveying approximately 20 upper and middle leaves per plant. The total number of leaves, the number of diseased leaves, and the disease severity were recorded. The disease index and control efficacy were calculated. The results are shown in Table 6.

[0336] Table 6: Field control efficacy of target compound II-3 against potato late blight

[0337]

[0338] The results showed that 5 wt% II-3 EC was effective in controlling potato late blight, effectively protecting new leaves and inhibiting the spread of lesions on already infected leaves. In the field, a dosage of 30–40 ml / mu, applied 2–3 times at 5–7 day intervals, effectively controlled the occurrence of potato late blight, and its efficacy was superior to that of commercially available Zengwei Yinglv at a dosage of 15–20 ml / mu. In other words, at the same active ingredient dosage, 5 wt% II-3 EC was more effective than Zengwei Yinglv.

[0339] The preferred embodiments of the present invention have been described in detail above; however, the present invention is not limited thereto. Within the scope of the inventive concept, various simple modifications can be made to the technical solutions of the present invention, including combinations of various technical features in any other suitable manner. These simple modifications and combinations should also be considered as the content disclosed in the present invention and are all within the protection scope of the present invention.

Claims

1. A compound containing a chain-like carboxylic acid amide structure or an agriculturally chemically acceptable salt thereof, the compound having the formula ( The structure shown in the figure is as follows. Mode( ) in, In equation (I), One of X1 and X2 is S, and the other is CH; R represents the structure shown in equation (Q1) or the structure shown in equation (Q2); Formula (Q1), Formula (Q2) In equation (Q1), R 1 Selected from H, methyl, ethyl, n-propyl, isopropyl, halogen, phenyl, phenyl substituted with at least one group from combination A, cyano; R 2 R 3 Selected from H, methyl, methoxy, and ethoxy; A is N or CH; and when A is N, R 2 and R 3 One of them does not exist; In equation (Q2), R 1 Selected from H, methyl, ethyl, n-propyl, n-butyl, phenyl, and phenyl groups substituted with at least one group from combination A; R 2 R 3 R 4 Selected from H, methyl, methoxy, ethoxy, n-propoxy, ethoxy substituted with at least one halogen, methoxy substituted with phenyl, and R 1 R 2 R 3 R 4 At least one of them is methoxy, ethoxy, or propoxy; or, R 2 and R 3 Together they cyclize to form an unsubstituted or substituted group of at least one group in combination A containing at least one O atom as a cyclizing atom; Combination A consists of methyl, halogen, and methoxy groups.

2. The compound according to claim 1, wherein, The compounds with the structure shown in formula (I) are selected from any of the following: 。 3. The compound according to claim 1, wherein, The compounds with the structure shown in formula (I) are selected from any of the following: 。 4. A method for preparing the compound containing a chain-like carboxylic acid amide structure as described in any one of claims 1-3, or an agriculturally chemically acceptable salt thereof, characterized in that, The method includes: reacting a compound of formula (II) with a compound of formula (III) under condensation reaction conditions. Formula (I ), Formula (III) Furthermore, the definitions of substituents in the compounds shown in formula (II) and formula (III) are the same as those defined in any one of claims 1-3.

5. The use of the compound containing a chain carboxylic acid amide structure as described in any one of claims 1-3, or its agriculturally chemically acceptable salt, in the control of oomycete diseases in plants.

6. The application according to claim 5, wherein, The plant oomycete diseases mentioned are selected from at least one of cucumber downy mildew, potato late blight, and pepper blight.

7. The use of the compound containing a chain carboxylic acid amide structure as described in any one of claims 1-3, or its agriculturally chemically acceptable salt, as an agricultural fungicide.

8. A bactericide, characterized in that, The fungicide is composed of an active ingredient and excipients, wherein the active ingredient includes the compound containing a chain carboxylic acid amide structure as described in any one of claims 1-3, or an agriculturally chemically acceptable salt thereof.

9. The bactericide according to claim 8, wherein, The content of the active ingredient is 1-99.9% by weight.

10. The bactericide according to claim 9, wherein, The formulation of the bactericide is selected from at least one of emulsifiable concentrate, suspension concentrate, powder, granule, aqueous solution, and poison bait.

11. The bactericide according to claim 9, wherein, The formulation of the bactericide is selected from at least one of wettable powder, mother liquor, and masterbatch.

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