A sulfone thiazole pyridine ketone compound, a preparation method and application thereof

Abstract

The present application provides a kind of compound of formula I, wherein the structure of formula I is as follows: I wherein, R1, R2 and R3 are defined as defined in the specification. The compound of the present application has good control effect on agricultural oomycete diseases and has good application prospect.

Description

Technical Field

[0001] This invention relates to the field of pesticides and fungicides, specifically to the application of a sulfonethiazopyrone compound and its preparation method in the control of oomycete diseases in plants. Background Technology

[0002] Oomycetes are important pathogens causing plant diseases, characterized by their wide parasitic range, high virulence, destructive power, and rapid spread. They pose a significant threat to major economic crops such as potatoes, peppers, tomatoes, tobacco, and grapes. Furthermore, the difficulty in controlling these diseases leads to a significant decline in agricultural productivity and substantial economic losses.

[0003] The main plant pathogens of oomycetes include Phytophthora virulence, Phytophthora lychee, Phytophthora capsicum, and Phytophthora cucumber. Phytophthora virulence is a typical pathogen causing outbreaks of potato blight. Phytophthora capsicum easily causes blight in crops such as peppers, eggplants, and tomatoes, while Phytophthora cucumber causes downy mildew in cucurbits.

[0004] Fluorothiazol pyrone, chemically named 1-(4-[4-[(5RS)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazo-2-yl]-1-piperidinyl)-2-[5-methyl-3-(trifluoromethyl)-IH-pyrazol-1-yl] acetone, is the world's first commercially available piperidinyl thiazole isoxazoline fungicide, exhibiting excellent fungicidal activity against oomycete diseases. The structure of fluorothiazol pyrone is as follows:

[0005] .

[0006] Bayer's fluoxapiprolin, chemically named 2-{(5RS)-3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}-4-piperidinyl)thiazolyl-4-yl]-4,5-dihydroisoxazol-5-yl}-3-chlorophenylmethanesulfonate, has the following structure:

[0007] .

[0008] In addition to the two fungicides already on the market, other pesticide companies are also increasing their R&D efforts to strive for further breakthroughs in terms of higher activity, fungicidal spectrum, and toxicity. For example, Indian agricultural technology company PI Industries Ltd's patent WO2021094904 describes phenyl sulfinylimide or sulfonylimide containing thiazolyl piperidinyl compounds with improved fungicidal activity.

[0009] Huazhong Normal University patent CNl13185509A invented a compound containing an indole ring piperidinyl thiazolyl isoxazoline structure that has excellent control effect on cucumber downy mildew.

[0010] CN117645632A discloses the following compounds with general formulas:

[0011] ,

[0012] It has good bactericidal activity.

[0013] Controlling oomycete diseases is becoming increasingly difficult. Currently, production mainly uses systemic fungicides with single-site action and protective fungicides with multiple sites of action. However, prolonged use of these fungicides has led to severe resistance in many pathogens. Therefore, developing new compounds that are more effective, lower in cost, less toxic, and safer for the environment, or with different sites of action, has become an urgent direction for development in this field. Summary of the Invention

[0014] The purpose of this invention is to provide a new compound with a sulfozypyrone structure, which achieves good control of oomycete diseases at low concentrations.

[0015] A first aspect of the present invention provides a compound of formula I and a salt thereof.

[0016] ,

[0017] I

[0018] in,

[0019] R1 is selected from -SO2R4 or -SONHR4; wherein R4 is a C1-C6 alkyl or C3-C6 cycloalkyl, preferably methyl or cyclopropyl;

[0020] R2 and R3 are each independently selected from hydrogen, halogen, C1-C6 haloalkyl or optionally substituted C3-C8 cycloalkyl.

[0021] The present invention also provides the application of compounds of formula I and their salts in the prevention and control of plant diseases.

[0022] Finally, the present invention also provides a composition containing a compound of formula I and its salt as an active ingredient.

[0023] Beneficial effects of the invention

[0024] 1. The compounds of the present invention have excellent control effects on plant diseases caused by various oomycete pathogens such as Phytophthora indicum, Phytophthora capsici, Pythium oxysporum, Phytophthora indic ... and Phytophthora indicum, and have good market development prospects.

[0025] 2. The compounds provided by this invention can also effectively prevent and control mutant strains that have developed resistance to existing fungicides. Therefore, the compounds of this invention are of great significance for the development of novel oomycete fungicides without cross-resistance. Detailed Implementation

[0026] 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.

[0027] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention. Unless otherwise expressly stated, throughout the specification and claims, the term "comprising" or its variations such as "including" or "comprising of," etc., will be understood to include the stated components or steps, without excluding the presence of other substances or steps.

[0028] Those skilled in the art will understand that the present invention can be practiced even without certain specific details. In some embodiments, materials, methods, and means well known to those skilled in the art are not described in detail in order to highlight the spirit of the invention.

[0029] When the compounds of the present invention can exist in tautomer form, the compounds described above and below should be understood, where applicable, to also include the corresponding tautomer forms, even if such tautomer forms are not explicitly mentioned in each case.

[0030] If the compound of Formula I described in this invention has one or more chiral centers and is therefore present as an enantiomer or diastereomer, then the pure enantiomer, the racemic version, or the diastereomer may be used in the compositions of this invention.

[0031] Any asymmetric atom (e.g., carbon, etc.) in the compounds disclosed in this invention can exist in racemic or enantiomerically enriched forms, such as (R)-, (S)-, or (R,S)- configurations.

[0032] Unless otherwise stated, all technical and technical terms used in this disclosure have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains. All patents and publications referenced in this disclosure are incorporated herein by reference in their entirety.

[0033] Unless otherwise stated, the following definitions shall apply as used herein. For the purposes of this disclosure, chemical elements are consistent with the CAS edition of the periodic table and the Handbook of Chemistry and Physics, 75th edition, 1994. Furthermore, general principles of organic chemistry can be found in "Organic Chemistry," Thomas Sorrell, University Science Books, Sausalito: 1999, and "March's Advanced Organic Chemistry" by Michael B. Smith and Jerry March, John Wiley & Sons, New York: 2007, the entire contents of which are incorporated herein by reference.

[0034] The term "optionally" or "optionally" means that the event or situation described below may, but is not guaranteed to, occur. That is, the description includes both the possibility that the event or situation occurs and the possibility that it does not. For example, "optionally substituted by 1, 2, 3, or 4..." includes the case where the group is substituted by 1, 2, 3, or 4 of the said substituents, and the case where the group is not substituted by the said substituents. Further, when the group is substituted by more than one of the said substituents, the substituents are independent of each other; that is, the more than one substituent can be different or the same.

[0035] As described in this disclosure, the compounds of this disclosure may optionally be substituted by one or more substituents, such as compounds of the formula above, or as specific examples, subclasses, and a class of compounds included in this disclosure. Generally, the term "substitution" means that one or more hydrogen atoms in a given structure are substituted by a specific substituent. Unless otherwise indicated, an optional substituent group may be substituted at each substituted position of the group. When more than one position in a given structural formula can be substituted by one or more substituents selected from a specific group, the substituents may be substituted at the same or different positions. "One or more substituents" means one or more substituents, the number of which is determined by the number of substituted positions of the substituted group. The substituents may include, but are not limited to, hydrogen, oxo (=O), halogen, cyano, nitro, hydroxyl, mercapto, carboxyl, amino, alkyl, alkyloxy, alkylthio, alkenyl, alkynyl, hydroxyalkyl, haloalkyl, etc.; wherein the substituents have the meaning described in this disclosure and may be further substituted by the substituents described in this disclosure, either monosubstituted or polysubstituted in the same or different ways.

[0036] Unless otherwise stated, the numerical ranges described in this specification and claims are equivalent to describing at least each specific integer value therein. For example, the numerical range "1-20" is equivalent to describing each integer value in the numerical range "1-10", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, and each integer value in the numerical range "11-20", namely 11, 12, 13, 14, 15, 16, 17, 18, 19, or 20. As another example, the numerical range "1-10" is equivalent to describing each integer value in the numerical range "1-10", namely 1, 2, 3, 4, 5, 6, 7, 8, 9, 10. Furthermore, when certain numerical ranges are not defined as "integers", they should be understood to include the two endpoints of the range, each integer within the range, and each decimal within the range. For example, "1-99%" should be understood as not only recording each integer of 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, ... 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, but also recording at least the sum of each of these integers with 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, or 0.9%.

[0037] Unless otherwise specified, the percentage content in this invention refers to the percentage content by mass.

[0038] In the context of “one or more”, “multiple” or “multiple types” as described in this article, “multiple” or “multiple types” means two or more types, such as an integer number greater than or equal to 2, such as 2, 3, 4, 5, 6, 7, 8, 9 or 10.

[0039] The terms “at least one” or “at least one” as used in this document mean “one or more” or “one or more types of”.

[0040] In the description of “one, two or more” and “one, two or more” in this article, “more” or “more kinds” means a number greater than 2, such as integers greater than or equal to 3, such as 3, 4, 5, 6, 7, 8, 9 or 10, etc.

[0041] As used in this disclosure, the term "alkyl" means a saturated straight-chain or branched monovalent hydrocarbon group. When the number of carbon atoms is not used when describing "alkyl," it means that the alkyl group has any number of carbon atoms. When the number of carbon atoms is used when describing "alkyl," it means that the alkyl group has the stated number of carbon atoms. For example, an alkyl group is an alkyl group containing 1 to 6 (1, 2, 3, 4, 5, or 6) carbon atoms, i.e., "C1-C6 alkyl."

[0042] Examples of alkyl groups include, but are not limited to, methyl (Me, -CH3), ethyl (Et, -CH2CH3), n-propyl (n-Pr, -CH2CH2CH3), isopropyl (i-Pr, -CH(CH3)2), n-butyl (n-Bu, -CH2CH2CH2CH3), etc.

[0043] The term "halogenated alkyl" refers to a straight-chain or branched alkoxyalkyl group, for example, substituted with one or more halogen atoms that may be the same or different from each other. For example, "halogenated C1-C6 alkyl" refers to a straight-chain or branched alkyl group having 1 to 6 carbon atoms, substituted with one or more halogen atoms that may be the same or different from each other. Examples include 1-fluoromethyl, 1,1-difluoromethyl, trifluoromethyl, pentafluoroethyl, heptafluoro-n-propyl, heptafluoroisopropyl, 2,2-difluoroethyl, 2,2-dichloroethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 2-iodoethyl, 2,2,2-trichloroethyl, 2,2,2-tribromoethyl, 1,3-difluoro-2-propyl, and 1,3-dichloro-2-propyl. 1-Chloro-3-fluoro-2-propyl, 1,1,1-trifluoro-2-propyl, 2,3,3,3-tetrafluoro-n-propyl, 1,1,1,3,3,3-hexafluoro-2-propyl, 1,1,1,3,3,3-hexafluoro-2-chloro-2-propyl, 1,1,1,3,3,3-hexafluoro-2-bromo-2-propyl, 1,1,2,3,3,3-hexafluoro -2-chloropropyl, 1,1,2,3,3,3-hexafluoro-2-bromopropyl, 1,1,2,3,3,3-hexafluoro-1-bromo-2-propyl, 2,2,3,3,3-pentafluoropropyl, 3-fluoropropyl, 3-chloropropyl, 3-bromopropyl, nonafluorobutyl, nonafluoroisobutyl, nonafluorosec-butyl, or nonafluorotert-butyl, etc., but not limited to these.

[0044] The term "halogen" refers to fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

[0045] "Cycloalkyl" refers to a monocyclic monovalent hydrocarbon group with three to eight carbon atoms, which may be saturated or contain a double bond. Cycloalkyl groups may be unsubstituted or substituted with one or two substituents independently selected from alkyl, halogen, alkoxy, hydroxy, or cyano groups, but are not limited thereto. Examples include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, 1-cyanocyclopropyl-1-yl, 1-cyanomethylcyclopropyl-1-yl, 3-fluorocyclohexyl, etc., but are not limited thereto.

[0046] This invention first provides a compound of formula I, a compound of formula I and its salt,

[0047] ,

[0048] I

[0049] in,

[0050] R1 is selected from SO2R4 or SONHR4; wherein R4 is a C1-C6 alkyl or optionally substituted C3-C6 cycloalkyl, preferably methyl or cyclopropyl;

[0051] R2 and R3 are each independently selected from hydrogen, halogen, C1-C6 haloalkyl or optionally substituted C3-C6 cycloalkyl, preferably hydrogen, halogen, 1,1-difluoromethyl, trifluoromethyl or cyclopropyl.

[0052] The compounds particularly preferred in this invention are selected from the following compounds:

[0053] , ,

[0054] , ,

[0055] , ,

[0056] .

[0057] This invention also discloses the application of the compounds of this invention and their salts in the prevention and control of plant diseases. The preferred application is in the prevention and control of oomycete diseases.

[0058] The present invention also provides a composition comprising the compounds described herein and their salts as active ingredients.

[0059] The present invention also discloses a bactericide containing the compound described in the present invention as an active ingredient. 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.

[0060] Preferably, the bactericide of the present invention can be formulated into a suitable preparation, and the dosage form of the preparation is one of emulsifiable concentrate, suspension concentrate, wettable powder, water-dispersible granules, dispersible oil suspension, water emulsion, and microemulsion.

[0061] Preferably, the suitable liquid carrier for preparing pesticide formulations is water and / or organic solvents, specifically plant-derived oils such as soybean oil, corn oil, and rapeseed oil; aromatic solvents such as xylene, tetramethylbenzene, and high-boiling-point aromatic solvents; alcohols such as ethanol and propanol; ketones such as cyclohexanone and acetone; esters such as ethyl acetate and carbonates; and other commonly used solvents such as N-methylpyrrolidone, N,N-dimethylacetamide, and dimethyl sulfoxide.

[0062] Preferably, the suitable solid carrier or filler selected for preparing pesticide formulations includes mineral soils, such as silicates, talc, kaolin, diatomaceous earth, and bentonite; polysaccharides, such as cellulose and starch; and other substances, such as ammonium sulfate, urea, silica, and anhydrous sodium sulfate.

[0063] Preferably, the suitable surfactant selected for preparing pesticide formulations includes emulsifiers, dispersants, or wetting agents. Emulsifiers include alkylphenol polyoxyethylene ethers, fatty alcohol polyoxyethylene ethers, castor oil polyoxyethylene ethers, special phenylethylphenol formaldehyde resin polyoxyethylene ethers, calcium dodecylbenzene sulfonate, etc.; dispersants include sodium lignosulfonate, dispersing agents, calcium lignosulfonate, methylnaphthalene sulfonate formaldehyde condensate, carboxylate dispersants, phosphate ester dispersants, etc.; wetting agents include sodium lauryl sulfate, sodium dodecylbenzene sulfonate, sodium alkylnaphthalene sulfonate, low-foaming wetting agents, etc.

[0064] Preferably, it can be used to control the following diseases: Oomycete diseases, such as downy mildew (cup downy mildew, rapeseed downy mildew, soybean downy mildew, beet downy mildew, sugarcane downy mildew, tobacco downy mildew, pea downy mildew, loofah downy mildew, melon downy mildew, cabbage downy mildew, spinach downy mildew, radish downy mildew, grape downy mildew, onion downy mildew), white rust (rapeseed white rust, cabbage white rust), damping-off (rapeseed damping-off, tobacco damping-off, tomato damping-off, pepper damping-off, eggplant damping-off, cucumber damping-off, cotton seedling damping-off), cottony rot (pepper cottony rot, loofah cottony rot, winter melon cottony rot), blight (blight of broad bean, ... Phytophthora blight of cucumber, pumpkin, winter melon, watermelon, cantaloupe, pepper, leek, garlic, and late blight (potato late blight, tomato late blight), etc.; deuteromycete diseases, such as wilt (sweet potato wilt, cotton wilt, sesame wilt, castor bean wilt, tomato wilt, bean wilt, cucumber wilt, loofah wilt, pumpkin wilt, winter melon wilt, watermelon wilt, cantaloupe wilt, pepper wilt, broad bean wilt, rapeseed wilt, soybean wilt), and root rot (pepper root rot, eggplant root rot, bean root rot, cucumber root rot, bitter gourd root rot, cotton black root rot). Broad bean root rot), damping-off (cotton seedling damping-off, sesame damping-off, pepper damping-off, cucumber damping-off, cabbage damping-off), Verticillium wilt (cotton verticillium wilt, sunflower verticillium wilt, tomato verticillium wilt, pepper verticillium wilt, eggplant verticillium wilt), black spot (zucchini black spot, winter melon black spot, cantaloupe black spot), gray mold (cotton boll gray mold, kenaf gray mold, tomato gray mold, pepper gray mold, bean gray mold, celery gray mold, spinach gray mold, kiwi gray mold), brown spot (cotton brown spot, jute brown spot, beet brown spot, peanut brown spot, pepper brown spot, winter melon brown spot, soybean brown spot, sunflower brown spot, pea brown spot, broad bean brown spot), black spot ( Flax black spot, rapeseed black spot, sesame black spot, sunflower black spot, castor bean black spot, tomato black spot, pepper black spot, eggplant black spot, green bean black spot, cucumber black spot, celery black spot, carrot black rot, carrot black spot, apple black spot, peanut black spot), leaf spot (tomato leaf spot, pepper leaf spot, celery leaf spot), early blight (tomato early blight, pepper early blight, eggplant early blight, potato early blight, celery early blight), ring rot (soybean ring rot, sesame ring rot, green bean ring rot), leaf blight (sesame leaf blight, sunflower leaf blight, watermelon leaf blight, melon leaf blight), stem base rot (tomato stem base rot, green bean stem base rot).Other diseases include (corn leaf spot, kenaf stem breakage, rice blast, chestnut black sheath disease, sugarcane eye spot, cotton boll aspergillosis, peanut crown rot, soybean stem blight, soybean black spot, melon large leaf spot, peanut net spot, tea red leaf spot, pepper white star disease, winter melon leaf spot, celery black rot, spinach heart rot, kenaf leaf mold, kenaf spot, jute stem spot, soybean purple spot, sesame leaf spot, castor bean gray spot, tea brown leaf spot, eggplant brown round star disease, common bean red spot, bitter gourd white spot, watermelon spot, jute wilt rot, sunflower root and stem rot, common bean anthracnose, soybean target spot, eggplant scab leaf spot, cucumber target spot, tomato leaf mold, eggplant leaf mold, broad bean red spot). Basidiomycete diseases; Ascomycete diseases, such as powdery mildew (wheat powdery mildew, rapeseed powdery mildew, sesame powdery mildew, sunflower powdery mildew, beet powdery mildew, eggplant powdery mildew, pea powdery mildew, loofah powdery mildew, pumpkin powdery mildew, zucchini powdery mildew, winter melon powdery mildew, cantaloupe powdery mildew, grape powdery mildew, broad bean powdery mildew), sclerotinia rot (flax sclerotinia rot, rapeseed sclerotinia rot, soybean sclerotinia rot, peanut sclerotinia rot, tobacco sclerotinia rot, pepper sclerotinia rot, eggplant sclerotinia rot, bean sclerotinia rot, pea sclerotinia rot, cucumber sclerotinia rot, bitter gourd sclerotinia rot, winter melon sclerotinia rot, watermelon sclerotinia rot, celery sclerotinia rot), black spot (apple black spot, pear black spot), etc.

[0065] The examples of diseases mentioned above are only used to illustrate the present invention, but are by no means limiting the present invention.

[0066] In this invention, the excipients can be various excipients conventionally used in the art, such as surfactants, solvents, etc.

[0067] The present invention will be described in detail below through embodiments.

[0068] In the following examples, unless otherwise specified, all raw materials used are commercially available and are chemically pure.

[0069] I. Preparation of intermediate compounds:

[0070] Preparation Example 1: Preparation of intermediate compound 2:

[0071]

[0072] Compound 1 (15 g) and sodium methanethiol (9.3 g) were added to 80 mL of DMF. The mixture was gradually heated to room temperature under ice bath conditions and reacted for 1 hour. The mixture was extracted twice with water and ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography. The mixture was concentrated with petroleum ether (PE): ethyl acetate (EA) = 10:1 to obtain 15 g of light yellow oily intermediate compound 2.

[0073] Preparation Example 2: Preparation of intermediate compound 3:

[0074]

[0075] Potassium tert-butoxide (24.2 g) and methyltriphenylphosphine bromide (58.9 g) were added to 160 mL of ultra-dry tetrahydrofuran (THF) and stirred at 0 °C for 30 min. Then, intermediate compound 2 (18 g) was dissolved in 40 mL of THF and slowly added to the above reaction. The reaction was carried out under nitrogen protection for 1 hour. The starting material disappeared as monitored by LCMS. Water and EA were added for extraction. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography (EA:PE = 20:1). The purified product was concentrated to obtain 9.4 g of colorless oily intermediate compound 3.

[0076] Preparation Example 3: Preparation of intermediate compound 5:

[0077]

[0078] Intermediate compound 3 (9.4 g), compound 4 (9.7 g), and NaHCO3 (9.8 g) were added to 100 mL MeCN and incubated overnight at room temperature in an ice bath. The mixture was then extracted twice with water and ethyl acetate, and the combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography. The PE:EA ratio was 10:1, and the mixture was concentrated to give 5 g of brown oily intermediate compound 5.

[0079] Preparation Example 4: Preparation of intermediate compound 7:

[0080]

[0081] Intermediate compound 5 (5 g) and compound 6 (5.25 g) were added to 50 mL of MeOH and heated under reflux for 6 hours. The reaction was monitored by LCMS until it was complete, and the crude intermediate compound 7 was obtained by concentration.

[0082] Preparation Example 5: Preparation of intermediate compound 8:

[0083] Intermediate compound 7 (9.2 g) was added to 50 ml of 4 M HCl methanol solution, stirred at room temperature for 1 hour, and concentrated to obtain crude intermediate compound 8.

[0084] Preparation Example 6: Preparation of intermediate compound 10:

[0085]

[0086] Intermediate compound 8 (7.2 g) and triethylamine (3.9 g) were added to DCM. Chloroacetyl chloride (4.37 g) was slowly added dropwise under ice bath conditions. The temperature was then raised to room temperature and stirred for 1 hour. Water and dichloromethane were added for extraction twice. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography (PE:EA = 1:2) to obtain 5 g of yellow oily intermediate compound 10.

[0087] Preparation Example 7: Preparation of intermediate compound 11:

[0088]

[0089] Intermediate compound 10 (5g) was added to DCM, and then m-CPBA (4.2g) was slowly added to the above reaction. The mixture was stirred at room temperature for 2 hours, washed with saturated sodium bicarbonate, extracted twice with dichloromethane, and the organic phases were combined. The mixture was purified by column chromatography. The dichloromethane (DCM):MeOH = 10:1 was concentrated to obtain 4g of light yellow oil intermediate compound 11.

[0090] II. Compound Preparation

[0091] Example 1: Synthesis of Compound A

[0092]

[0093] Intermediate compound 11 (0.8 g), K2CO3 (0.459 g), and compound 12 (0.588 g) were added to DMF. The reaction was heated to 90 °C and carried out for 2 hours under LCMS monitoring. Then, 100 ml of water and ethyl acetate were added for extraction twice. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography (DCM:MeoH = 10:1). The purified DCM was concentrated to give 400 mg of compound A as a white solid.

[0094] 1H NMR (500 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.90 (dd, J = 7.9, 1.4 Hz,1H), 7.63 (d, J = 7.6 Hz, 1H), 7.54 (t, J = 7.8 Hz, 1H), 7.16 (d, J = 21.6Hz, 1H), 7.05 (d, J = 22.9 Hz, 1H), 6.92 (s, 1H), 6.55 (t, J = 12.1 Hz, 1H), 5.46-5.35 (m, 2H), 3.90 (dd, J = 17.4, 11.9 Hz, 1H), 3.52 (dd, J = 17.3, 12.2Hz, 1H), 3.43-3.39 (m, 1H), 3.35 (s, 3H), 3.31-3.24 (m, 1H), 2.85 (t, J =12.8, 2.8 Hz, 1H), 2.37 (s, 3H), 2.18-2.06 (m, 2H), 1.89-1.77 (m, 1H), 1.65-1.53 ​​(m, 1H).

[0095] Example 2: Synthesis of Compound B

[0096]

[0097] Intermediate compound 11 (0.8 g), K2CO3 (0.459 g), and compound 14 (0.358 g) were added to DMF. The reaction was heated to 90 °C and carried out for 2 hours under LCMS monitoring. Then, 100 ml of water and ethyl acetate were added for extraction twice. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, purified by column chromatography (DCM:MeOH = 10:1), and concentrated to obtain 500 mg of compound B as a white solid.

[0098] 1H NMR (500 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.89 (d, J = 8.0 Hz, 1H), 7.63 (d, J=7.6 Hz, 1H), 7.54 (t, J=7.8 Hz, 1H), 7.48 (s, 1H), 6.54 (t, J=12.0 Hz, 1H), 5.89 (d, J=35.7 Hz, 1H), 5.10-4.95 (m, 2H), 3.89 (dd, J=17.5,11.9 Hz, 1H), 3.51 (dd, J=17.4, 12.1 Hz, 2H), 3.35 (s, 3H),3.26 (d, J=13.1Hz, 1H),2.80 (t, J=12.9 Hz, 1H), 2.36 (s, 3H), 2.08 (d, J=12.9 Hz, 2H), 1.86-1.78 (m, 1H), 1.78-1.65 (m, 1H), 1.62-1.47 (m, 1H), 0.85-0.76 (m, 2H), 0.63-0.49 (m, 2H).

[0099] Example 3: Synthesis of Compound C

[0100]

[0101] Intermediate compound 11 (0.8 g), K2CO3 (0.459 g), and compound 16 (0.498 g) were added to DMF. The reaction was heated to 90 °C and carried out for 2 hours under LCMS monitoring. Then, 100 ml of water and ethyl acetate were added for extraction twice. The combined organic phases were washed with saturated brine, dried over anhydrous sodium sulfate, purified by column chromatography (DCM:MeOH = 10:1), and concentrated to obtain 450 mg of compound C as a white solid.

[0102] 1H NMR (500 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.90 (dd, J = 7.8, 1.4 Hz,1H), 7.63 (d, J=7.6 Hz, 1H), 7.55 (t, J=7.8 Hz, 1H), 6.55 (t, J=12.0 Hz, 1H),6.50 (s, 1H), 5.35-5.24 (m, 2H), 3.90 (dd, J=17.4, 12.0 Hz, 1H), 3.52 (dd, J=17.4, 12.2 Hz, 1H), 3.43-3.39 (m, 1H),3.35 (s, 3H),3.26 (d, J=13.1 Hz, 1H), 2.84 (t, 1H), 2.37 (s, 3H), 2.21 (s, 3H), 2.12 (t, J=15.3 Hz, 2H), 1.88-1.76 (m, 1H), 1.63-1.53 ​​(m, 1H).

[0103] Example 4: Synthesis of Compound D

[0104] Step 1: Compound 14 (3g) and (1-chloromethyl-4-fluoro-1,4-diazabicyclo[2.2.2]octanebistetrafluoroborate (19g) were added to 50mL of acetonitrile and stirred at room temperature for 8 hours. The mixture was monitored by LCMS. The pH was then adjusted to >7 with saturated sodium bicarbonate. The mixture was extracted twice with water and ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain 650mg of compound 19 as a yellow oil.

[0105] Step 2: Add intermediate compound 11 (1g), K2CO3 (0.58g) and compound 19 (0.397g) to DMF, heat the reaction to 90℃ for 2 hours, monitor with LCMS, then add 100ml of water and ethyl acetate to extract twice, combine the organic phases, wash with saturated brine, dry with anhydrous sodium sulfate, purify by column chromatography (DCM:MeOH = 10:1), and concentrate to obtain 300mg of compound D as a white solid.

[0106] 1H NMR (500 MHz, DMSO-d6) δ 8.06 (s, 1H), 7.89 (d, 1H), 7.66 – 7.60 (m, 2H), 7.54 (t, J=7.8 Hz, 1H), 6.54 (t, J=12.1 Hz, 1H), 5.03-4.90 (m, 2H),3.90 (dd, J= 17.4, 12.0 Hz, 1H), 3.51 (dd, J=17.4, 12.2 Hz, 1H), 3.43-3.39(m, 1H),3.35 (s, 3H),3.20 (t, J=12.7 Hz, 1H), 2.79 (t, J=12.3 Hz, 1H), 2.36(s, 3H), 2.14-2.04 (m, 2H), 1.83-1.77 (m, 1H), 1.73 (d, J=12.2 Hz, 1H), 1.56(t, J=12.4 Hz, 1H), 0.88-0.82 (m, 2H), 0.73-0.67 (m, 2H).

[0107] Example 5: Synthesis of Compound E

[0108]

[0109] Step 1: Add intermediate compound 10 (1.5 g), K2CO3 (0.691 g) and compound 12 (0.666 g) to 15 mL of DMF, heat the reaction to 90 °C for 2 hours, monitor with LCMS, then add 100 mL of water and ethyl acetate to extract twice, combine the organic phases, wash with saturated brine, dry with anhydrous sodium sulfate, and concentrate to obtain 1.5 g of compound 20 as a yellow oil.

[0110] Step 2: Compound 20 (1.5 g) and ammonium carbamate (0.4 g) were added to 20 ml of MeOH. Then, iodophenyl diacetic acid (1.67 g) was slowly added to the above reaction. The mixture was stirred at room temperature for 2 hours. After washing with saturated sodium bicarbonate, the mixture was extracted twice with ethyl acetate. The organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography (DCM:MeOH = 10:1). The purified mixture was concentrated to obtain 1.2 g of compound E as a white solid.

[0111] 1H NMR(500 MHz, DMSO-d6) δ 8.05(d, J=5.8 Hz, 1H), 7.98-7.93(m, 1H),7.55-7.51 (m, 1H), 7.50-7.46 (m, 1H), 7.30-7.01 (m, 2H), 6.93-6.85 (m, 2H), 5.38 (dd, 2H), 4.36 (d, J=13.2 Hz, 1H), 3.97 (d, J=13.7 Hz, 1H), 3.91-3.81(m, 1H), 3.53-3.44 (m, 1H), 3.44-3.36 (m, 1H), 3.31-3.23 (m, 2H), 3.19 (t, J=1.1 Hz, 3H), 2.85 (t, J= 12.4 Hz, 1H), 2.35 (d, J = 1.8 Hz, 3H), 2.13 (t, J=17.2, 15.1 Hz, 2H), 1.88-1.77 (m, 1H), 1.65-1.53 ​​(m, 1H).

[0112] Example 6: Synthesis of Compound F

[0113] Step 1: Add intermediate compound 10 (1.5 g), K2CO3 (0.691 g) and compound 14 (0.428 g) to 15 mL of DMF. Heat the reaction to 90 °C for 2 hours and monitor with LCMS. Then add 100 mL of water and ethyl acetate to extract twice. Combine the organic phases, wash with saturated brine, dry with anhydrous sodium sulfate for purification, and concentrate to obtain 1.3 g of compound 21 as a yellow oil.

[0114] Step 2: Compound 21 (1.3g) and ammonium carbamate (0.39g) were added to 20ml MeOH, and then iodophenyl diacetic acid (1.61g) was slowly added to the above reaction. The mixture was stirred at room temperature for 2 hours, washed with saturated sodium bicarbonate, extracted twice with ethyl acetate, the organic phases were combined, washed with saturated brine, dried over anhydrous sodium sulfate, and purified by column chromatography (DCM:MeOH=10:1). The solution was concentrated to obtain 1g of compound F as a white solid.

[0115] 1H NMR (500 MHz, DMSO-d6) δ 8.04 (d, J = 5.3 Hz, 1H), 7.95 (dd, J =8.6, 3.6 Hz, 1H), 7.55 (t, J=6.2 Hz, 1H), 7.50 (dd, J=7.8, 3.2 Hz, 1H), 7.49-7.46 (m, 1H), 6.90-6.80 (m, 1H), 5.89 (d, J=36.0, 2.1 Hz, 1H), 5.09-4.95 (m,2H), 4.38 (d, J = 13.1 Hz, 1H), 3.99 (d, J=13.8 Hz, 1H), 3.89-3.82 (m, 1H),3.49-3.43 (m, 2H), 3.41-3.33 (m, 2H), 3.25(s, 3H)2.80 (t, J=12.6 Hz, 1H),2.35 (s, 3H), 2.08 (d, J=12.8 Hz, 2H), 1.85-1.79 (m, 1H), 1.79-1.65(m, 1H), 1.63-1.49 (m, 1H), 0.85-0.77 (m, 2H), 0.66-0.54 (m, 2H).

[0116] Example 7: Synthesis of Compound J

[0117] Step 1: Add intermediate compound 10 (1.5 g), K2CO3 (0.691 g) and compound 19 (0.5 g) to 15 mL of DMF. Heat the reaction to 90 °C for 2 hours and monitor with LCMS. Then add 100 mL of water and ethyl acetate to extract twice. Combine the organic phases, wash with saturated brine, dry with anhydrous sodium sulfate for purification, and concentrate to obtain 1 g of compound 22 as a yellow oil.

[0118] Step 2: Add compound 22 (1g) and ammonium carbamate (0.39g) to 20ml MeOH, then slowly add iodophenyl diacetic acid (1.29g) to the above reaction, stir at room temperature for 2 hours, wash with saturated sodium bicarbonate, extract twice with ethyl acetate, combine the organic phases, wash with saturated brine, dry with anhydrous sodium sulfate, and purify by column chromatography (DCM:MeOH=10:1) to obtain compound J as a white solid (0.5g).

[0119] 1H NMR (500 MHz, DMSO-d6) δ 8.04 (dd, J = 5.8, 1.9 Hz, 1H), 7.98-7.91(m, 1H), 7.64 (d, J= 4.7 Hz, 1H), 7.56-7.51 (m, 1H), 7.51-7.45 (m, 1H), 6.88(t, J = 12.2 Hz, 1H), 5.04-4.90 (m, 2H), 4.37 (d, J = 12.8 Hz, 1H), 3.97-3.92(m, 1H), 3.89-3.79 (m, 1H), 3.52-3.43 (m, 2H), 3.42-3.35 (m, 2H), 3.19 (s,4H), 2.79 (t, J = 12.5 Hz, 1H), 2.34 (d, J = 1.8 Hz, 3H), 2.14-2.04 (m, 2H),1.83-1.77 (m, 1H), 1.77-1.68 (m, 1H), 1.61-.49 (m, 1H), 0.92- 0.80 (m, 2H), 0.77- 0.66 (m, 2H).

[0120] II. Life Test

[0121] 1. Test target

[0122] Live specimens of Phytophthora soybata, live specimens of Peronospora spp., and live specimens of Phytophthora spp. var. ...

[0123] 2. Preparation method of the medicine

[0124] Weigh 0.05g of the test compound of this invention and the control reagent and dissolve them in 1ml of LDM. After complete dissolution, add water to prepare three concentration gradients of 12.5ppm, 6.25ppm and 3.125ppm (if the original drug has poor solubility during the preparation process, an appropriate amount of organic solvent can be added to aid dissolution).

[0125] 3. Preparation of PDA culture medium

[0126] The preparation process for the PDA culture medium required in the experiment is as follows: Weigh 40.1g of PDA culture medium powder and dissolve it completely in 1L of sterile water. After complete dissolution, dispense 200mL of culture medium into Erlenmeyer flasks, then sterilize them in an autoclave before use. Prepare the corresponding amount of culture medium according to the experimental dosage.

[0127] 4. Testing Methods

[0128] Take 1 ml of each of the prepared drug solutions and add it to 50 ml of sterile PDA medium. Mix well and then pour the mixture evenly into three φ=8.5cm petri dishes and inoculate with mycelium.

[0129] 5. Survey, recording, and measurement methods

[0130] Seven days after the first application of the fungicide and inoculation, the colony diameter was measured using the cross-sectional method. The average diameter of each treated colony was calculated, and the inhibition rate was calculated using the following formula:

[0131] Relative inhibition rate (%) = (Control colony diameter - Treated colony diameter) / (Control colony diameter - Bacterial disc diameter) × 100%

[0132] Note: The diameter of the mushroom dish is usually 1 cm.

[0133] In the list below, A represents 90-100% control efficacy, B represents 80-89% control efficacy, C represents 60-79% control efficacy, D represents 30-59% control efficacy, and E represents 0-29% control efficacy.

[0134] Control drug 1: Fluthiazopyrone has the following structure:

[0135] ,

[0136] Control reagent 2: Compound JB-013 in CN117645632A:

[0137] ,

[0138] Control reagent 3: Compound 3 in WO2021094904

[0139] .

[0140] Table 1. Indoor activity test efficacy against Phytophthora soybeanis (7 days)

[0141]

[0142] Table 2. Indoor activity test efficacy against *Peronospora gracilis* (7 days)

[0143]

[0144] Table 3. Indoor activity test efficacy against potato late blight pathogen (7 days)

[0145]

[0146] 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 and its salt, characterized in that, Selected from the following compounds, ， ， ， ， ， ， 。 2. The use of the compound of claim 1 and its salt in the prevention and control of plant diseases.

3. The application according to claim 2, characterized in that, The application described is for the treatment of oomycete diseases in plants.

4. A composition, characterized in that, It contains the compound of claim 1 and its salt as active ingredients.

5. A bactericide containing the compound of claim 1 and its salt as an active ingredient, wherein the content of the active ingredient is 1-99.9%.

6. The bactericide according to claim 5, characterized in that, The content of the active ingredient is 5-95%.

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