Herbicidal imidazole-containing compounds

Abstract

The present invention relates to a compound having the formula (I) or an agronomically acceptable salt of said compound, wherein A, Q, R1, R2, R4 and m are as defined herein. The invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I) for controlling weeds, in particular in crops of useful plants. # imgabs0 #

Description

[0001] The present invention relates to herbicidal compounds, to processes for their preparation, to herbicidal compositions comprising these novel compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.

[0002] WO 2022 / 101270 discloses herbicidal N-heteroaryl pyrazole compounds. WO 2023 / 066783 discloses herbicidal imidazole compounds characterized by a phenyl or 6-membered heteroaryl group at position Q identified below.

[0003] Therefore, according to the present invention, there is provided a compound having the formula (I):

[0004]

[0005] or an agronomically acceptable salt thereof,

[0006] in

[0007] A is for CR 5 or N;

[0008] Q is a 5-membered heteroaryl group, which is optionally substituted by 1 or 2 R 3 Substituent substitution,

[0009] R 1 independently selected from the group consisting of halogen, -CN, C1-C2 alkyl, C1-C2 haloalkyl, C3-C6 cycloalkyl, C1-C2 alkoxy- and C1-C2 haloalkoxy-;

[0010] R 2 Selected from the group consisting of: halogen, -CN, NO2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -C(O)C1-C4 alkyl, -C(O)OC1-C4 alkyl, C1-C4 haloalkoxy, -S(O) p C1-C4 alkyl, -C(R 6 )=NOR 7 and C3-C6 cycloalkyl;

[0011] R 3 independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkoxy C1-C3 alkyl-, C1-C4 alkoxy C1-C3 alkoxy-, C1-C4 alkoxy C1-C3 alkoxy C1-C3 alkyl-, -CN, NO2, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, -S(O) pC1-C4 haloalkyl, -C(O)OC1-C4 alkyl and -C(O)NR 8 R 9 ;

[0012] R 4 independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -CN, NO2, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, -S(O) p C1-C4 haloalkyl, -C(O)OC1-C4 alkyl and -C(O)NR 8 R 9 ;

[0013] R 5 selected from the group consisting of: hydrogen, fluorine, chlorine, and -CN;

[0014] R 6 is hydrogen or C1-C4 alkyl;

[0015] R 7 is hydrogen or C1-C2 alkyl;

[0016] R 8 is hydrogen or C1-C4 alkyl;

[0017] R 9 is hydrogen or C1-C4 alkyl;

[0018] m = 1 or 2; and

[0019] p=0, 1 or 2.

[0020] C1-C4 alkyl- and C1-C6 alkyl- include, for example, methyl (Me, CH3), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu). C1-C2 alkyl is methyl (Me, CH3) or ethyl (Et, C2H5).

[0021] Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The above applies correspondingly to halogen in other defined contexts, such as haloalkyl.

[0022] C1-C6 haloalkyl-includes, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1,1-difluoro-2,2,2-trichloroethyl, 2,2,3,3-tetrafluoropropyl and 2,2,2-trichloroethyl, heptafluoro-n-propyl and perfluoro-n-hexyl. C1-C4 haloalkyl-and C1-C2 haloalkyl include, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, or 1,1-difluoro-2,2,2-trichloroethyl.

[0023] The C1-C4 alkoxy group and the C1-C2 alkoxy group include, for example, a methoxy group and an ethoxy group.

[0024] C1-C6 haloalkoxy- and C1-C4 haloalkoxy- include, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.

[0025] C2-C4alkenyl- includes, for example, -CH=CH2 (vinyl) and -CH2-CH=CH2 (allyl).

[0026] C2-C4 alkynyl - refers to a straight or branched hydrocarbon chain radical consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having two to four carbon atoms, and attached to the remainder of the molecule by a single bond. Examples of C2-C4 alkynyl include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.

[0027] The C1-C4 alkyl-S-(alkylthio) group includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0028] The C1-C4 alkyl-S(O)-(alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0029] The C1-C4 alkyl-S(O)2-(alkylsulfonyl) group includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0030] In one embodiment of the present invention, A is N. In another embodiment of the present invention, m is 1. Therefore, in a preferred embodiment of the present invention, there is provided a compound having formula (Ia),

[0031]

[0032] Among them, Q, R 1 , R 2 and R 4 As defined in claim 1 above.

[0033] In one embodiment of the present invention, R 1 Preferably it is chlorine. In another embodiment of the present invention, R 4 Preferably it is hydrogen. In another embodiment of the present invention, R 2 Preferred is -CF3 or -CF2H.

[0034] In another embodiment of the present invention, Q is preferably selected from the group consisting of:

[0035]

[0036] Where R 3 is hydrogen or as defined in claim 1 above, R 3a is selected from the group consisting of hydrogen, methyl, ethyl, CHF2 and cyclopropyl, and R 3b Selected from the group consisting of hydrogen, fluorine, chlorine and bromine.

[0037] In a more preferred embodiment, Q is selected from the group consisting of: Q-1, Q-2, Q-3, Q-4, Q-13, Q-14, Q-15, Q-16, Q-22, Q-23, Q-24, Q-41, Q-42, and Q-43. In a more preferred embodiment, Q is selected from the group consisting of: Q-1, Q-3, Q-4, Q-13, Q-14, Q-15, Q-16, Q-23, Q-24, Q-41, Q-42, and Q-43. In an even more preferred embodiment, Q is selected from the group consisting of: Q-1, Q-14, Q-22, Q-23, Q-41, and Q-43.

[0038] In one embodiment of the present invention, R 3 It's chlorine.

[0039] The present invention further relates to compounds having the formula VIIIa:

[0040]

[0041] Where R 2 and R 4is as defined above, and X2a is hydrogen or halogen (preferably bromine or iodine). In a preferred embodiment, R 2 is -C(O)OC1-C4 alkyl (e.g., -C(O)OC2H5), C1-C4 haloalkyl (e.g., -CHF2 or -CF3), and R 4 It's hydrogen.

[0042] Compounds of formula (I) may contain asymmetric centers and may exist as single enantiomers, in pairs of enantiomers in any ratio, or, in the case of more than one asymmetric center, in all possible ratios of diastereomers. Typically, one of the enantiomers has an enhanced biological activity compared to the other possibilities.

[0043] The present invention also provides agronomically acceptable salts of compounds of formula (I). Preferably, the compounds of formula (I) can form salts with: amines, including primary amines, secondary amines and tertiary amines (e.g., ammonia, dimethylamine and triethylamine); alkali metal bases and alkaline earth metal bases, transition metal bases or quaternary ammonium bases.

[0044] The compounds of formula (I) according to the invention can be used as herbicides themselves, but they are usually formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents and surfactants (SAAs). Therefore, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the preceding claims and an agriculturally acceptable formulation adjuvant. The composition may be in the form of a concentrate, which is diluted before use, although a ready-to-use composition may also be prepared. The final dilution is usually carried out with water, but may be carried out using, for example, liquid fertilizers, micronutrients, biological organisms, oils or solvents instead of or in addition to water.

[0045] The herbicidal compositions generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of compounds of formula I and 1 to 99.9% by weight of formulation adjuvants which preferably comprise 0 to 25% by weight of surface-active substances.

[0046] The composition can be selected from a number of formulation types. These include emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water dispersible granules (WG), emulsifiable granules (EG), water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersants (OD), oil miscible flowables (OF), oil miscible liquids (OL), soluble concentrates (SL), ultra low volume suspensions (SU), ultra low volume liquids (UL), master batches (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP) and soluble granules (SG). In any case, the formulation type selected will depend on the specific purpose envisaged and the physical, chemical and biological properties of the compound of formula (I).

[0047] Soluble powders (SP) can be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as polysaccharides) and optionally one or more wetting agents, one or more dispersants or mixtures of said agents to improve water dispersibility / water solubility. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water-soluble granules (SG).

[0048] Wettable powders (WP) can be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and preferably one or more dispersants, and optionally one or more suspending agents to facilitate dispersion in a liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water dispersible granules (WG).

[0049] Granules (GR) may be formed by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or by absorbing the compound of formula (I) (or a solution thereof in a suitable agent) into a porous granular material such as pumice, attapulgite clay, Fuller's earth, kieselguhr, diatomaceous earth or corn cob meal, or by adsorbing the compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material such as sand, silicates, mineral carbonates, sulfates or phosphates and drying if necessary from preformed green particles. Agents commonly used to aid absorption or adsorption include solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters and adhesives such as polyvinyl acetate, polyvinyl alcohol, dextrins, sugars and vegetable oils. One or more other additives such as emulsifiers, wetting agents or dispersants may also be included in the granules.

[0050] Dispersible concentrates (DC) can be prepared by dissolving a compound of formula (I) in water or an organic solvent such as a ketone, alcohol or glycol ether. These solutions may contain a surfactant (for example to improve water dilution or to prevent crystallization in a spray tank).

[0051] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) can be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifiers or a mixture of said agents). Suitable organic solvents for use in ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a registered trademark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethylamides of fatty acids (such as C8-C 10 EC products can emulsify spontaneously when added to water, producing an emulsion with sufficient stability to allow spray application by appropriate equipment.

[0052] The preparation of EWs involves obtaining a compound of formula (I) as a liquid (if it is not liquid at room temperature, it can be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in a suitable solvent), and then emulsifying the resulting liquid or solution into water containing one or more SAAs under high shear to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents having low solubility in water.

[0053] Microemulsions (ME) can be prepared by mixing water with a blend of one or more solvents and one or more SAAs to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in water or in a solvent / SAA blend. Suitable solvents for use in MEs include those described above for use in ECs or EWs. MEs can be oil-in-water systems or water-in-oil systems (which system is present can be determined by conductivity measurements) and can be suitable for mixing water-soluble pesticides and oil-soluble pesticides in the same formulation. MEs are suitable for dilution into water, remaining as microemulsions or forming conventional oil-in-water emulsions.

[0054] Suspension concentrates (SC) may include aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of formula (I). SC may be prepared by ball milling or bead milling a solid compound of formula (I) with one or more dispersants in a suitable medium to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition, and a suspending agent may be included to reduce the rate of particle settling. Alternatively, a compound of formula (I) may be dry-milled and added to water containing the reagents described above to produce a desired final product.

[0055] Aerosol formulations comprise a compound of formula (I) and a suitable propellant (e.g. n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable medium (e.g. water or a water-miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized hand-operated spray pump.

[0056] Capsule suspensions (CS) can be prepared in a similar manner to the preparation of EW formulations, but with an additional polymerization stage, to obtain an aqueous dispersion of oil droplets, each of which is wrapped by a polymer shell and contains a compound of formula (I) and optionally a carrier or diluent for the oil droplet. The polymer shell can be produced by an interfacial polycondensation reaction or by a coacervation procedure. These compositions can provide controlled release of compounds of formula (I) and they can be used for seed treatment. Compounds of formula (I) can also be formulated in a biodegradable polymer matrix to provide slow, controlled release of the compound.

[0057] The composition may include one or more additives to improve the biological performance of the composition, for example by improving wettability, retention or distribution on a surface; rain resistance on a treated surface; or absorption or mobility of a compound of formula (I). Such additives include surfactants (SAAs), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean and rapeseed oils), modified vegetable oils (such as methylated rapeseed oil (MRSO)), and blends of these with other bioenhancement adjuvants (ingredients that can assist or modify the action of a compound of formula (I)).

[0058] The wetting agent, dispersant and emulsifier may be a cationic type, anionic type, amphoteric type or nonionic type SAA.

[0059] Suitable cationic-type SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0060] Suitable anionic SAAs include alkali metal salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (e.g. sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g. sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalenesulfonate and mixtures of sodium di-isopropyl-naphthalenesulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g. sodium laureth-3-sulfate), ether carboxylates (e.g. sodium laureth-3-carboxylate), phosphates (products from the reaction of one or more fatty alcohols with phosphoric acid (mainly monoesters) or with phosphorus pentoxide (mainly diesters), for example the reaction of lauryl alcohol with tetraphosphoric acid; additionally, these products may be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, lignin sulfonates and phosphates / sulfates of tristyrylphenol.

[0061] Suitable amphoteric types of SAA include betaine, propionate and glycinate.

[0062] Suitable SAAs of the nonionic type include condensation products of alkylene oxides (such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long-chain fatty acids or hexitol anhydrides; condensation products of the partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; monoesters (such as fatty acid polyethylene glycol esters); amine oxides (such as lauryl dimethyl amine oxide); lecithin and sorbitan and its esters, alkyl polyglycosides and tristyrylphenol.

[0063] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0064] The compounds of the present invention may also be used in a mixture with one or more additional herbicides and / or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen sodium), bensulfuron, ametryn, amitriptyline, aminopyralid, cypermethrin, atrazine, flubutyric acid-M, quinclorac, bensulfuron-methyl (including bensulfuron-methyl), bentazon, bicyclpyrone, bialaphos, bispyribac-sodium, bixlozone, broclozone, herbicide, bromoxynil, butachlor, fluazifop-butyl, mesotrione (including mesotrione-ethyl), chlorsulfuron (including chlorsulfuron-methyl), chlorsulfuron (including chlorsulfuron-ethyl), green Myluron, chlorsulfuron, cyproconazole, clacyfos, clethodim, clodinafop-butyl (including clodinafop-butyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyprosulfuron, cyhalofop-butyl (including cyhalofop-butyl-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, betaine, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, 2,4-dichloropropionic acid, diethylene glycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), bisclosulam, fluazifop-butyl, fluazifop-butyl, dimethoate, dimethoate-s-propyl, pyridazione (dioxopyritrione), dibromodiquat, diuron, epyrifenacil, ethoflufen, ethoxyfuran, oxadiazine (including oxadiazine-ethyl), fenoxasulfone, fenpyrazone, fenquinotrione, tetrazopyramide, fluazifop-butyl, bispyribac, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop-butyl (including fluorine fluazifop-butyl-butyl), fluchloraminopyr (including fluchloraminopyr) (including fluchloraminopyr) (including fluchloraminopyr). oxalate furfuryl (fluchloramino-tefuryl)), flufenacet, flufenoximacil, fluazifop, fluazifop-butyl, fluazifop-butyl, fluazifop-butyl (including fluazifop-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), flusulfuron, flufenoximacil, foramsulfuron, glufosinate (including L-glufosinate and ammonium salts of both), glyphosate (including its hydrazine, isopropyl ammonium and potassium salts), halauxifen (including halauxifen ester-methyl), haloxalothiocarb (including haloxalothiocarb-methyl), hexazinone,Hydantocidin, icafolin (including icafolin-methyl), imazamox (including R-imazamox), imazapic, imazapic, imazamox, indolepyr (including indolauxipyr-cyanomethyl), iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, iptriazopyrid, isoproturon, isoxathiapiprolin, lancotrione ), MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, isopropylamine, sulfamethoxazole, metribuzin, metsulfuron-methyl, propamide, nicosulfuron, norchlorpyrifos, oxadiazine, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, bendiazole, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, promethazine, propanil, oxadiazine, propyrisulfuron, propyrisulfuron, pyraflufen, promethazine, prosulfuron, bispyribac, pyraflufen (including pyraquinate-ethyl), pyraquinate, pyrasulfuron, pyridazone, pyriflubenzoxim, pyrimisulfan, pyroxosulfuron, pyrasulfuron, quinclorac, clomeclorac, quizalofop-ethyl (including quizalofop-P-tefuryl), rimisoxafen, sulfaquinoxaline, pyriflubenzoxim, sethoxydim, simazine, S-isopropylamine, sulfaquinoxaline, sulfaquinoxaline, butyralid, tetflutrione, temsulfuron, terbuthylazine, terbutaline, tetraflupyramide (tetflup yrolimet), thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, benpyrazone, triazone, triafamone, wild wheat chlorpyrifos, bensulfuron-methyl, bensulfuron-methyl (including bensulfuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifluoxazin, fluralin, flufenacil, triazosulfuron, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester,4-Hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy- 1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, (1RS,5SR)-3-[2-methoxy-4-(prop-1-yn-1-yl)phenyl]-4-oxobicyclo[3.2.1]oct-2-en-2-yl methyl carbonate, ethyl-2-[[3-[[3-chloro-5-fluoro -6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridinyl]oxy]acetate, 2-[2-[2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenoxy]phenoxy]-2-methoxy-acetic acid methyl ester, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, 6-amino-5-chloro-2-(4-chloro -2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid (2-fluorophenyl)methyl ester, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid, and 3-[2-chloro-5-[3,6-dihydro-3-methyl-2,6-dioxo-4-(trifluoromethyl)-1(2H)-pyrimidinyl]-4-fluorophenyl]-3a,4,5,6-tetrahydro-6-methyl-6aH-cyclopenta[d]isoxazole-6a-carboxylic acid methyl ester.

[0065] Mixture partners of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0066] The compounds of formula (I) may also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0067] The mixing ratio of the compound of formula (I) to the mixing partner is preferably 1:100 to 1000:1.

[0068] These mixtures can advantageously be used in the abovementioned formulations (in this case, "active ingredient" relates to the corresponding mixture of the compound of formula (I) with the mixing partner).

[0069] The compounds or mixtures of the present invention can also be used in combination with one or more herbicide safeners. Examples of such safeners include cloquintocet, cloquintocet (including cloquintocet-mexyl), cyclopropylsulfonamide, dichloropropene, oxadiazole (including oxadiazole ethyl), chlorpyrifos, fluazifop, oxadiazole, isoxadiazole (including isoxadiazole-ethyl), mefenpyr (including mefenpyr-butyl), metcamifen and oxadiazole.

[0070] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen-ethyl, clofonet-mexyl and / or sulfamethoxazole.

[0071] The safeners of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, 16th edition (BCPC), 2012. The reference to clofonet-mexyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02 / 34048.

[0072] Preferably, the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, in particular from 20:1 to 1:1.

[0073] The present invention further provides a method for controlling weeds at a site, the method comprising applying a composition comprising a compound of formula (I) to the site in an amount of weed control. In addition, the present invention may further provide a method for selectively controlling weeds at a site including crop plants and weeds, wherein the method comprises applying a composition according to the present invention in an amount of weed control to the site. 'Control' means killing, reducing or delaying growth or preventing or reducing germination. It should be noted that the compounds of the present invention show greatly improved selectivity compared to known structurally similar compounds. Typically, the plants to be controlled are unwanted plants (weeds). 'Site' means the area where the plant is growing or will grow. Application can be applied to the site before and / or after emergence of the crop plant. Some crop plants can inherently tolerate the herbicidal effect of the compound of formula (I). Preferred crop plants include corn, wheat, barley and rice.

[0074] The application rate of the compound of formula I can vary within wide limits and depends on the nature of the soil, the method of application (pre-emergence or post-emergence; seed dressing; application to the seed furrow; no-till application, etc.), the crop plants, one or more weeds to be controlled, the prevailing climatic conditions and other factors governed by the method of application, the time of application and the target crop. The compound of formula I according to the invention is usually applied at a rate of 10 g / ha to 2500 g / ha, in particular 25 g / ha to 1000 g / ha, more particularly 25 g / ha to 250 g / ha.

[0075] Application is usually carried out by spraying the composition, typically by means of a tractor-mounted sprayer for large areas, but other methods such as dusting (for powders), dripping or drenching may also be used.

[0076] Crop plants are to be understood as also including those crop plants which have been rendered tolerant to other herbicides or classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, HPPD-inhibitors, inhibitor-PDS and ACCase-inhibitors) by conventional methods of breeding or by genetic engineering. Examples of crops which have been rendered tolerant to imidazolinones (e.g. imazamox) by conventional methods of breeding are Summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include, for example, maize varieties resistant to glyphosate and glufosinate, which are marketed under the trade names Roundup and and The compounds of the present invention can also be used in combination with the plants disclosed in WO 2020 / 236790.

[0077] Crop plants are also to be understood as those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to the European corn borer), Bt cotton (resistant to the boll weevil) and also Bt potato (resistant to the Colorado beetle). Examples of Bt maize are Bt 176 corn hybrid (Syngenta Seeds). Bt toxins are proteins naturally produced by the soil bacterium Bacillus thuringiensis. Examples of toxins or transgenic plants capable of synthesizing such toxins are described in EP-A-451 878, EP-A-374 753, WO 93 / 07278, WO 95 / 34656, WO 03 / 052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes encoding insecticide resistance and expressing one or more toxins are (Corn), Yield (corn), (cotton), (cotton), (potato), and Plant crops or their seed material can be both resistant to herbicides and at the same time resistant to insect feeding ("stacked" transgenic events). For example, seeds can have the ability to express an insecticidal Cry3 protein while being tolerant to glyphosate.

[0078] Crop plants are also to be understood as including those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (eg improved storage stability, higher nutritional value and improved flavour).

[0079] These compositions can be used to control unwanted vegetation (collectively referred to as 'weeds'). The weeds to be controlled can be monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, a) and Sorghum, and also dicotyledonous species, such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

[0080] In a further aspect of the invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.

[0081] Process for preparing compounds having formula (I)

[0082] Processes for preparing compounds such as compounds of formula (I) (which may optionally be agrochemically acceptable salts thereof) are now described and form a further aspect of the invention.

[0083] The compound of formula I-3 is a compound of formula I wherein Q is a C-linked 5-membered heterocyclic ring, R 2 , A and R 1 (m) is as defined in Formula I, and wherein R 41 is a C1-C4 alkyl group and can be prepared by a Suzuki reaction involving, for example, reacting a compound of formula I-1,

[0084] Solution 1

[0085]

[0086] Where Q is a C-linked 5-membered heterocyclic ring, R2, A and R 1 (m) is as defined in Formula I, and wherein X 1 is chlorine, bromine or iodine, reacted with a compound of formula II, wherein R 41 is a C1-C4 alkyl group, and wherein Yb1 may be a boron-derived functional group such as, for example, B(OH)2 or B(ORb1)2, wherein Rb1 may be a C1-C4 alkyl group, or two ORb1 groups may form a five-membered ring together with the boron atom, as, for example, pinacol borate. The reaction can be catalyzed by a palladium-based catalyst such as tetrakis(triphenyl-phosphine)palladium(0), (1,1'bis(diphenylphosphino)ferrocene)dichloropalladium-dichloromethane (1:1 complex) or chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (XPhos palladacycle complex) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride in a solvent or solvent mixture such as, for example, cyclopentyl methyl ether, dioxane, acetonitrile, N,N-dimethyl-formamide, a mixture of 1,2-dimethoxyethane and water or a mixture of dioxane / water or a mixture of toluene / water, preferably under an inert atmosphere. The reaction temperature can preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction can be carried out under microwave irradiation. Such Suzuki reactions are well known to those skilled in the art.

[0087] The compound of formula I-4 is a compound of formula I, wherein R 4=CN, and can be prepared from compounds of formula I-1 by reaction with M-CN IIa (cyanidation), wherein M is a metal coordinated to cyanide. Examples of cyaniding agents include NaCN, Zn(CN)2 or potassium ferrocyanide, and the like. The reaction can be catalyzed by a palladium-based catalyst such as tetrakis(triphenylphosphine)palladium(0), (1,1'bis(diphenylphosphino)ferrocene)dichloropalladium-dichloromethane (1:1 complex) or chloro(2-dicyclohexylphosphino-2',4',6'-triisopropyl-1,1'-biphenyl)[2-(2'-amino-1,1'-biphenyl)]palladium(II) (XPhos palladacycle complex) in the presence of a base such as sodium carbonate, tripotassium phosphate or cesium fluoride in a solvent or solvent mixture such as, for example, dioxane, acetonitrile, N,N-dimethyl-formamide, a mixture of 1,2-dimethoxyethane and water or a mixture of dioxane / water or a mixture of toluene / water, preferably under an inert atmosphere. The reaction temperature can preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction can be carried out under microwave irradiation. Such reactions are well known to those skilled in the art.

[0088] Compounds of formula I-1 can be prepared by halogenation reactions involving, for example, reacting a compound of formula I-2 (wherein Q is a C-linked 5-membered heterocycle, R2, A and R 1 (m) is as defined in formula I) with a halogenating agent such as N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS) or N-iodosuccinimide (NIS) optionally in the presence of an additive such as p-toluenesulfonic acid. Alternatively, the halogenation may involve chlorine, bromine or iodine. Such halogenation reactions are carried out in a suitable solvent such as chloroform, carbon tetrachloride, 1,2-dichloroethane, acetic acid, diethyl ether, acetonitrile or N,N-dimethylformamide at a temperature between 20°C and 200°C, preferably at room temperature to 100°C.

[0089] The compound of formula IV, wherein Q is a C-linked 5-membered heterocycle and R2 is as defined in formula I, can be prepared by reacting a compound of formula III, wherein A and R 1 (m)is as defined in formula I, and wherein LG1 is halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group, such as (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate)), in the presence of a base (such as sodium hydride or alkaline earth metal hydride, carbonate (such as sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide), optionally in the presence of potassium iodide, in an inert solvent (such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N-dimethylacetamide or acetonitrile, etc.), at a temperature between 0°C and 120°C, by procedures well known to those skilled in the art to prepare a compound of formula I-2.

[0090] The compound of formula IV may be prepared by the compound of formula VI or a hydrated form thereof (wherein R 2 The compound of formula VI or its hydrated form (wherein R 2 is as defined in formula I) can be obtained by hydrolysis of a compound of formula VII (wherein R 2 is as defined in formula I). ​​Such two-step reactions are well known in the literature.

[0091] Alternatively, a compound of formula I (wherein Q, R 2 , A, R 4 and R 1 (m) is as defined above in Formula I) can be prepared according to Scheme 2.

[0092] Scenario 2:

[0093]

[0094] In Scheme 2, a procedure similar to that described in Scheme 1 for converting a compound of Formula I-1 to a compound of Formula I-3 can be followed by adding a 2-hydroxy-2-(2-hydroxy-1-yl)-2-thiocyanate to a compound of Formula VIII (wherein R 2 , A, R 4 and R 1 (m) is as defined above in formula I and X 2 is a leaving group such as, for example, chlorine, bromine or iodine) and a compound having the formula Yb2-QXV (wherein Q is as defined above in formula I, and Yb2 can be a boron-derived functional group such as, for example, B(OH)2 or B(OR b2 )2, where R b2It can be a C1-C4 alkyl group, or two groups OR b2 Compounds of formula I can be prepared by Suzuki cross-coupling reaction between 2-(4-(2-piperidinol)-2-yl)-2-nitropropene (2-(2-piperidinol)-2-yl)-2-nitropropene (2-piperidinol ...

[0095] Compounds of formula Ia, wherein Q is an N-attached heterocycle, can be prepared from compounds of formula VIII via a CN cross-coupling reaction. Such reactions are well known in the literature and can be carried out in the presence of a metal catalyst, such as using a palladium-based catalyst (such as dichloro-(chloromethylchloroium)-bis[cyclopentyl(diphenyl)phosphinium]palladium(3-)); an iron or copper-based catalyst (such as tetra(acetonitrile)copper(I) tetrafluoroborate), and optionally in the presence of a ligand (such as 8-hydroxyquinoline) and in the presence of a base (such as potassium carbonate or potassium phosphate) and in the presence of a solvent (such as acetonitrile, tetrahydrofuran, dioxane, toluene, xylene) and optionally in the presence of a microwave at a temperature between 40°C and 200°C.

[0096] The compound of formula IX (wherein R 2 , R 4 is as described above in Formula I and X 2 is a leaving group, such as, for example, chlorine, bromine or iodine) and a compound of formula III (wherein A and R 1 (m) wherein LG1 is as described above in formula I and LG1 is halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate), in the presence of a base such as sodium hydride or alkaline earth metal hydride, carbonate (such as sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide), optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N-dimethylacetamide or acetonitrile, at a temperature between 0°C and 120°C, by an alkylation reaction by procedures well known to those skilled in the art to prepare a compound of formula VIII wherein R 2 , R 4 , A and R 1 (m) is as described above in formula I and X2 is a leaving group such as for example chloro, bromo or iodo).

[0097] The compound of formula IX can be prepared by deprotecting the compound of formula X, wherein R2, R4 are as defined in formula I above, and X 2Is a leaving group, such as chlorine, bromine or iodine, and PG1 is an N-protecting group, such as acetyl, trimethylsilylethoxymethyl (SEM), tert-butoxycarbonyl and other amino protecting groups. Such reactions are well known to those skilled in the art and can be carried out, for example, using base catalysis or acid catalysis (such as HCl). Compounds with formula X (wherein X2 is a leaving group, such as chlorine, bromine or iodine and PG1 is an N-protecting group, such as acetyl, trimethylsilylethoxymethyl (SEM), tert-butoxycarbonyl and other amino protecting groups) can be prepared by compounds with formula XI (wherein PG1 is an N-protecting group, such as acetyl, trimethylsilylethoxymethyl (SEM), tert-butoxycarbonyl and other amino protecting groups) using halogenation. Such reactions can be carried out in a two-step procedure involving metalation using a strong base (such as butyl lithium, tert-butyl lithium, tetramethyl piperidine lithium, diisopropyl amide lithium and other bases), and quenching with a suitable desired halogenating agent (such as molecular iodine, bromine or chlorine). Such reactions are well known in the literature and are described, for example, in Journal of Organic Chemistry (1993), 58 (5), 997-8. Compounds of formula XI can be prepared from compounds of formula XII by installing protective groups. Such reactions can be carried out in the presence of a base (such as sodium hydride, potassium carbonate, sodium carbonate) and in the presence of a suitable protective group reagent (such as 2-(trimethylsilyl)ethoxymethyl chloride, acetyl chloride, di-tert-butyl dicarbonate) and in the presence of a solvent (such as tetrahydrofuran, methanol, water, acetonitrile, dimethylformamide). Such reactions are well known in the literature.

[0098] Alternatively, a compound of formula I may be prepared by reacting a compound of formula XIII with a compound of formula XVI (wherein X 3 is a halogen, preferably iodine, bromine or chloride) by metal-catalyzed CH activation and arylation (Scheme 3).

[0099] Solution 3:

[0100]

[0101] The reaction can be carried out in the presence of a palladium catalyst such as palladium acetate, bis(acetonitrile)dichloropalladium(II), tris(dibenzylideneacetone)dipalladium(0), palladium chloride(π-cinnamyl) dimer or a copper catalyst such as copper iodide, copper acetate, copper bromide, copper, or a combination of these palladium and copper catalysts. The reaction is usually carried out in the presence of a ligand such as a phosphine-based ligand, for example triphenylphosphine, tricyclohexylphosphine or 1,4-bis(diphenylphosphino)butane and a base such as potassium carbonate, 1,8-diazabicyclo-5.4.0 undec-7-ene, potassium phosphate, potassium acetate or cesium carbonate. The reaction can optionally be carried out under microwave irradiation and at a temperature in the range of 20°C to 200°C and in the presence of a solvent such as xylene, toluene, dioxane, acetic acid or dimethylformamide. Such reactions are described in the literature.

[0102] The compound of formula XIV (wherein R 2 and R 4 is as described in formula I above) with a compound of formula III (wherein LG1 is halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group, such as (halo)alkyl or phenylsulfonate, such as trifluoromethanesulfonate)), in the presence of a base (such as sodium hydride or alkaline earth metal hydride, carbonate (such as sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide), optionally in the presence of potassium iodide, in an inert solvent (such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide, N,N-dimethylacetamide or acetonitrile, etc.), at a temperature between 0°C and 120°C, by procedures well known to those skilled in the art to prepare a compound of formula XIII (wherein R 2 and R 4 is as described in Formula I above).

[0103] The compound of formula I-5 is a compound of formula I, wherein R 2 Yes - CF2H, R 4 Yes -H and Q and R 1 (m) is as defined in Formula I. Compounds of Formula I-5 can be prepared according to Scheme 4. In Scheme 4, the procedure for converting a compound of Formula VIII to a compound of Formula Ia as described in Scheme 4 can be followed by adding a 2-hydroxy-2-(2-oxo-1-yl)-2-thiocyanate to a compound of Formula XXV (wherein X 3 is a leaving group such as, for example, chlorine, bromine or iodine) and a compound having the formula Yb3-QXXVI (wherein Q is as defined above in formula I, and Yb3 can be a boron-derived functional group such as, for example, B(OH)2 or B(OR b3 )2, where R b3 It can be a C1-C4 alkyl group, or two groups OR b3Compounds of formula I-5 can be prepared by a Suzuki cross-coupling reaction between 2-(4-(2-piperidinol)-2-yl)-2-yl pyrrolidone (2-pyrrolidone) and 2-(2-pyrrolidone)-2-yl pyrrolidone (2-pyrrolidone) together with a boron atom to form a five-membered ring, as for example pinacol boronate.

[0104] Compounds of formula XXV can be prepared from compounds of formula XXIV via fluorination using a fluorinating agent such as diethylaminosulfur trifluoride or bis(2-methoxyethyl)aminosulfur trifluoride. Compounds of formula XXIV can be prepared from compounds of formula XXIII via oxidation using an oxidizing agent such as MnO2, SO3, pyridine, pyridinium dichromate or pyridinium chlorochromate.

[0105] Scenario 4:-

[0106]

[0107] Alternatively, compounds of Formula XXIV can be prepared according to Scheme 5.

[0108] Solution 5:

[0109]

[0110] The compound of formula XXIV can be prepared by reacting the compound of formula XXVIII with the compound of formula XXVII in a procedure similar to that described in scheme 1 for converting the compound of formula IV into the compound of formula I-2. The compound of formula XXVIII can be prepared by halogenation, followed by N-deprotection reaction, from the compound of formula XXIX. The halogenation reaction can be carried out in one step under free radical conditions using a halogenating agent (such as N-bromosuccinimide) in the presence of a free radical initiator (such as azobisisobutyronitrile). The deprotection reaction is well known to those skilled in the art and can be carried out, for example, using base catalysis or acid catalysis (such as HCl). The compound of formula XXIX can be prepared by installing a protecting group from a compound of formula XXX. Such reactions can be carried out in the presence of a base (e.g., sodium hydride, potassium carbonate, sodium carbonate), in the presence of a suitable protecting group reagent (e.g., 2-(trimethylsilyl)ethoxymethyl chloride, acetyl chloride, di-tert-butyl dicarbonate), and in the presence of a solvent (e.g., tetrahydrofuran, methanol, water, acetonitrile, dimethylformamide).

[0111] The compound of formula XXIII can be prepared from a compound of formula XXII (wherein R 21is C1-C6 alkyl) via reduction reaction using a reducing agent such as lithium aluminum hydride or diisobutylaluminum hydride. Compounds of formula XXII can be prepared by reacting compounds of formula XX with compounds of formula XXI (wherein LG2 is halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group such as (halo)alkyl or phenylsulfonate, e.g. trifluoromethanesulfonate)) in the presence of a base such as sodium hydride or alkaline earth metal hydride, carbonate such as sodium carbonate, potassium carbonate or cesium carbonate or hydroxide, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, sulfolane, N,N-dimethylacetamide or acetonitrile, etc., at a temperature between 0°C and 120°C by procedures well known to those skilled in the art. Compounds of formula XX can be prepared from compounds of formula XVII in three steps (Scheme 4) following a procedure analogous to the conversion of compounds of formula XII to compounds of formula IX as described in Scheme 2.

[0112] Alternatively, compounds having formula 1-5 can be prepared according to Scheme 6.

[0113] Scenario 6:-

[0114]

[0115] In Scheme 6, compounds of formula I-5 can be prepared from compounds of formula XXXIV via fluorination using a fluorinating agent such as diethylaminosulfur trifluoride or bis(2-methoxyethyl)aminosulfur trifluoride, etc. Compounds of formula XXXIV can be prepared by reacting compounds of formula XXXII with compounds of formula XXXIII, wherein LG3 is a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as (halo)alkyl or phenylsulfonate, such as trifluoromethanesulfonate), in the presence of a base such as sodium hydride or alkaline earth metal hydride, carbonate such as sodium carbonate, potassium carbonate or cesium carbonate, or hydroxide, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, sulfolane, N,N-dimethylacetamide or acetonitrile, etc., at a temperature between 0°C and 120°C, by procedures well known to those skilled in the art. Compounds of formula XXXII can be prepared from compounds of formula XXXI via oxidation using an oxidizing agent such as MnO2, SO3, pyridine, pyridinium dichromate or pyridinium chlorochromate. Compounds of formula XXXI can be prepared according to procedures reported in literature such as J. Med. Chem. 1995, 38, 2251-2255.

[0116] Alternatively, compounds of formula XXXIV can be prepared according to Scheme 7. In Scheme 7, compounds of formula XXXIV can be prepared according to the procedure as described in Scheme 6 by reacting a compound of formula XXXII with a compound of formula XXXIII.

[0117] Solution 7:

[0118]

[0119] Compounds of formula XXXII can be prepared by reacting compounds of formula XXXV with a suitable reducing agent such as diisobutylaluminum hydride. Compounds of formula XXXV can be prepared by reacting compounds of formula XXXVI with ammonium hydroxide or other similar ammonia substitutes to convert trifluoromethyl to cyano. Such reactions are well documented in the literature (see, for example, Matthews, DP; Whitten, JP; McCarthy, JRJ Org. Chem. [Journal of Organic Chemistry] 1986, 51, 3228). The synthesis of imidazole compounds of formula XXXVI is well documented in the literature (see, for example, Journal of Medicinal Chemistry [Journal of Pharmaceutical Chemistry], 2000, 43, 2165 and Synthetic Communications [Synthetic Communications], 2020, 50, 700).

[0120] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention (as mentioned in the table below).

[0121] Example 1: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.001)

[0122]

[0123] Step 1: Preparation of 3,3,3-trifluoro-2-oxo-propanal (I5)

[0124]

[0125] Sodium acetate (1.41 g, 17.05 mmol) and water (5.00 mL) were added to a 100 mL flask. 1,1-dibromo-3,3,3-trifluoroacetone (2.325 g, 8.186 mmol) was added to the above solution to give a turbid solution / suspension. The reaction mixture was then heated to 100 °C for 40 minutes. The reaction mixture was then cooled to room temperature and used as is in the next step.

[0126] Step 2: Preparation of 2-(5-chloro-2-thienyl)-4-(trifluoromethyl)-1H-imidazole (I6)

[0127]

[0128] 5-chlorothiophene-2-carboxaldehyde (1.000g, 6.822mmol), methanol (20.00mL) and 35% ammonia (5.00mL, 44mmol) are added to 3-neck 250mL flasks to give a colorless solution. The reaction mixture of I5 prepared in the above step 1 is slowly added dropwise thereto via a dropping funnel in 30min. After completion of the addition, the reactant is stirred at room temperature for 3 hours. Organic matter is removed under vacuum and residue is distributed between ethyl acetate and water and each phase is separated. The aqueous phase is extracted with ethyl acetate (3x20mL). Organic matter is merged, washed with saturated brine and concentrated onto granular diatomaceous earth. The crude material is subjected to column chromatography using 0-100% ethyl acetate in cyclohexane on silica gel to give 2- (5- chloro-2-thienyl) -4- (trifluoromethyl) -1H- imidazole (I6) (0.952g, 55% yield) as a light yellow solid. 1 H NMR (400MHz, CD3OD) δ = 7.65-7.58 (m, 1H), 7.41-7.36 (m, 1H), 7.09-7.00 (m, 1H)

[0129] Step 3: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.001)

[0130]

[0131] 2-(5-chloro-2-thienyl)-4-(trifluoromethyl)-1H-imidazole I6 (0.100 g, 0.396 mmol) in acetonitrile (1.32 ml) and water (0.06 ml) was added to a 25 ml flask, followed by potassium carbonate (0.164 g, 1.19 mmol), 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (0.0997 g, 0.475 mmol) and potassium iodide (0.0131 g, 0.0792 mmol). The reaction mixture was stirred and heated to 70 ° C. After 1.5 hours, the reaction mixture was cooled to room temperature. The reaction mixture was diluted with water (10 mL) and brine (10 mL) and extracted with ethyl acetate (2x15 mL). The combined organics were passed through a hydrophobic glass frit and evaporated under reduced pressure to give a crude product. This was subjected to column chromatography on silica gel using a gradient of 0-30% ethyl acetate in cyclohexane to give 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.001 (96 mg, 73% yield) as a light yellow gum. 1 H NMR (400MHz, CDCl3) δ = 8.71 (s, 2H), 7.47 (d, 1H), 7.23 (d, 1H), 6.89 (d, 1H), 5.45 (s, 2H)

[0132] Example 2: Preparation of 5-chloro-2-[[2-(3-methylimidazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.013)

[0133]

[0134] Step 1: Preparation of 5-chloro-2-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (I7)

[0135]

[0136] To 4-(trifluoromethyl)-1H-imidazole (204mg, 1.47mmol) in MeCN (4.8mL) and H2O (0.04mL) solution in add K2CO3 (603mg, 4.3629mmol) and 5-chloro-2-(chloromethyl) pyrimidine hydrochloride (365mg, 1.7384mmol).Reaction mixture is heated to 80 ℃ for 22 hours, it is cooled to room temperature, diluted with H2O and extracted with ethyl acetate (x3).The combined organic extracts are adsorbed onto silica gel, and purified by flash chromatography on silica gel using ethyl acetate with a gradient of 0-70% in cyclohexane as eluent, to give 5-chloro-2-[[4-(trifluoromethyl) imidazole-1-yl] methyl] pyrimidine I7 (275mg, 68%) as a yellow solid.1 H NMR (400MHz, DMSO-d6) δ = 8.96 (s, 2H), 7.94 (s, 1H), 7.88 (s, 1H), 5.58 (s, 2H)

[0137] Step 2: Synthesis of 5-chloro-2-[[2-(3-methylimidazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.013)

[0138]

[0139] Under N2 atmosphere, to a solution of 5-chloro-2-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I7 (149 mg, 0.53899 mmol) in toluene (4 mL) was added palladium (II) acetate (7 mg, 0.0296 mmol), 5-bromo-1-methyl-1H-imidazole (140 mg, 0.843473 mmol), cuprous (I) iodide (209 mg, 1.0974 mmol), DBU (0.17 mL, 1.1 mmol) and triphenylphosphine (15 mg, 0.0560 mmol). The reaction mixture was subjected to microwave heating at 150°C for 4 hours, cooled to room temperature, diluted with H2O and extracted with ethyl acetate (x3). The combined organic extracts were adsorbed onto silica gel and purified by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate in cyclohexane as eluent. The product-rich fractions were adsorbed onto silica gel and further purified by reverse phase flash chromatography using a gradient of 40%-70% MeCN in H2O as eluent to give 5-chloro-2-[[2-(3-methylimidazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.013 (3.7 mg, 2%) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ = 8.61 (s, 2H), 7.39 (m, 1H), 6.99 (s, 1H), 6.92 (s, 1H), 6.08 (s, 2H), 4.11 (s, 3H)

[0140] Example 3: Preparation of 5-chloro-2-[[2-(1,5-dimethylpyrazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.012

[0141]

[0142] Step 1 - Preparation of trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (I8):

[0143]

[0144] To 4-(trifluoromethyl)-1H-imidazoles (3.07g, 22.6mmol) and K cO (9.14g, 66.1mmol) in MeCN (45mL) suspension, add 2-(chloromethoxy) ethyl-trimethyl-silane (5.5g, 5.8mL, 33mmol), and by reaction mixture at room temperature under N2, rapid stirring 24h.Extra 2-(chloromethoxy) ethyl-trimethyl-silane (1.8g, 1.9mL) is added drop-wise in reaction mixture, and reactant is at room temperature stirred for 4h.Reaction mixture is quenched with saturated brine (50mL) and ethyl acetate (50mL) is added.Separate each phase, and aqueous phase is extracted with ethyl acetate (3x 50mL).Organic matter is merged, washed with saturated brine and concentrated on granular diatomite. The crude product was purified by flash chromatography on silica gel using a gradient of 0-60% ethyl acetate in cyclohexane as eluent to give trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (I8) (2.74 g, 46%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ = 7.65 (s, 1H), 7.42-7.36 (m, 1H), 5.31 (s, 2H), 3.63-3.34 (m, 2H), 1.02-0.83 (m, 2H), 0.01 (s, 9H)

[0145] Step 2- Preparation of 2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane (I9):

[0146]

[0147] Under N2, a solution of trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (I8) (1.00g, 3.76mmol) in THF (20mL) was cooled to an internal temperature of -70°C. n-BuLi (2.5M in hexane) (2.00mL, 5.0mmol) was added dropwise while maintaining a constant temperature below -60°C. Then, the reaction mixture was stirred for 0.5h at -70°C. I2 (1.25g, 4.92mmol) was added once to the reaction mixture. The reaction mixture was stirred for 1h at -70°C, then warmed to room temperature and stirred overnight. The reaction mixture was quenched with 2M sodium thiosulfate (25mL) and ethyl acetate (25mL) was added. Each phase was separated, and the aqueous phase was extracted with ethyl acetate (3x 25mL). Organic matter was merged and washed with saturated brine (25mL). The organics were concentrated onto granular celite and the crude product was purified by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate in cyclohexane as eluent to give 2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane (I9) (0.91 g, 62%) as a yellow solid. 1 H NMR (400MHz, CDCl3)δ=7.48-7.42(m,1H),5.54-5.13(m,2H),3.66-3.47(m,2H),1.02-0.76(m,2H),0.00(d,9H)

[0148] Step 3 - Preparation of 2-iodo-4-(trifluoromethyl)-1H-imidazole hydrochloride I10:

[0149]

[0150] To a solution of 2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane I9 (0.50 g, 1.27 mmol) in EtOH (6 mL) was added HCl (6M) (2.00 mL, 12.00 mmol) at room temperature and the reaction was heated to 60° C. under N2 for 3.5 h. The reaction mixture was concentrated under vacuum to give 2-iodo-4-(trifluoromethyl)-1H-imidazole; hydrochloride salt I10 (0.348 g, 91% yield) as a white solid. 1 H NMR (400MHz, CD3OD) δ = 7.83 (q, 1H)

[0151] Step 4- Preparation of 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I11:

[0152]

[0153] To a stirred suspension of 2-iodo-4-(trifluoromethyl)-1H-imidazole hydrochloride I10 (0.35 g, 1.17 mmol) and KI (0.037 g, 0.22 mmol) in MeCN (5.25 mL), KCO (0.54 g, 3.88 mmol) and H0 (0.18 mL) were added. 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (0.28 g, 1.33 mmol) was added and the reactants were heated to 80 ° C for 1.5 h. The reactants were cooled to room temperature and concentrated onto granular diatomaceous earth. The crude product was purified by flash chromatography on silica gel using ethyl acetate with a gradient of 0-100% in cyclohexane as eluent to give 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I11 (0.38 g, 84%) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ = 8.69 (s, 2H), 7.51 (d, 1H), 5.34 (s, 2H)

[0154] Step 5 - Preparation of 5-chloro-2-[[2-(1,5-dimethylpyrazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.012):

[0155]

[0156] 5-Chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine II (0.13 g, 0.33 mmol), 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-yl)-1H-pyrazole (0.10 g, 0.46 mmol) and (1,1'-bis(diphenylphosphino)ferrocene)dichloropalladium(II) (13 mg, 0.016 mmol) were added to a 2-5 mL microwave vial. The vessel was placed under an N2 atmosphere and sealed. THF (2.00 mL) and tripotassium phosphate (1.0 M in water) (1.00 mL, 1.00 mmol) were added and heated to 80 °C for 1 h under microwave irradiation. The reactants were cooled to room temperature and water and ethyl acetate were added. The phases were separated and the organics were combined and concentrated onto celite. The crude product was purified by flash chromatography on silica gel using a gradient of 0-100% ethyl acetate in cyclohexane as eluent to give 5-chloro-2-[[2-(1,5-dimethylpyrazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.012 (97 mg, 81%) as an off-white solid. 1H NMR (400MHz, CDCl3) δ = 8.70 (s, 2H), 7.61 (s, 1H), 7.43 (q, 1H), 5.33 (s, 2H), 3.83 (s, 3H), 2.43 (s, 3H)

[0157] Example 4: Preparation of 5-chloro-2-[[2-(5-chloro-3-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.064

[0158]

[0159] Step 1- Preparation of 1-(2-trimethylsilyloxyethyl)imidazole-4-carboxaldehyde (I12):

[0160]

[0161] At 0 ° C, sodium hydride (5.0 g, 125 mmol, 60% in mineral oil) was added to a solution of 1H-imidazole-4-carboxaldehyde (10.0 g, 104 mmol) in tetrahydrofuran (104 mL). The mixture was stirred at 0 ° C for 15 min and 2- (trimethylsilyl) ethoxymethyl chloride (22.5 mL, 114 mmol) was added, and then the mixture was stirred at 25 ° C for 10 h. The reaction mass was cooled to 0 ° C and quenched with saturated ammonium chloride solution. It was extracted with ethyl acetate (3 x 200 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous Na2SO4, filtered and concentrated to obtain 1- (2-trimethylsilyloxyethyl) imidazole-4-carboxaldehyde I12 (23 g, 100%) as a colorless oil. The compound as a mixture of isomers (2: 1) was obtained, and the mixture was used for the next step without further purification. 1 H NMR for the major isomer (400 MHz, CDCl3) δ = 9.91 (s, 1H), 7.74 (s, 1H), 7.69 (s, 1H), 5.34 (s, 2H), 3.46-3.61 (m, 4H), -0.02 (m, 9H).

[0162] Step 2- Preparation of 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carbaldehyde (I13):

[0163]

[0164] Azobisisobutyronitrile (0.093 g, 0.55 mmol) was added to a stirred solution of 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxaldehyde I12 (2.5 g, 11 mmol) in carbon tetrachloride (50 mL). N-bromosuccinimide (2.2 g, 12 mmol) was added thereto at room temperature and heated at 90 ° C for 30 h. The reaction mass was quenched with sodium thiosulfate solution and extracted with ethyl acetate (3 x 200 ml). The combined organic layer was washed with saline solution, dried over anhydrous Na2SO4, filtered and concentrated to obtain crude material. The crude product was purified by silica column chromatography using 30% ethyl acetate in cyclohexane to obtain 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxaldehyde I13 (3.0 g, 89%) as an oil. The compound was obtained as a mixture of isomers (2:1) and this mixture was used in the next step without further purification. 1 H NMR for the major isomer (400 MHz, DMSO-d6) δ = 9.66 (s, 1H), 8.38 (s, 1H), 5.38 (s, 2H), 3.57-3.52 (m, 4H), -0.04 (s, 9H).

[0165] Step 3 - Preparation of 2-bromo-1H-imidazole-4-carbaldehyde (I14):

[0166]

[0167] 2-Bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxaldehyde I13 (9.8 g, 32 mmol) was added to a solution of acetonitrile (98 mL) with 2,2,2-trifluoroacetic acid (37 mL, 480 mmol). The reaction mixture was heated to 50 °C for 20 h. The reaction mixture was cooled to room temperature and concentrated in vacuo to give 2-Bromo-1H-imidazole-4-carboxaldehyde I14 (9.3 g, 100%) as a 2,2,2-trifluoroacetate salt. The crude product was used directly in the next step without further purification.

[0168] Step 4 - Preparation of 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carbaldehyde (I15):

[0169]

[0170] To a solution of 2-bromo-1H-imidazole-4-carboxaldehyde I14 (0.4 g, 2.28 mmol) in acetonitrile (9.2 mL) was added potassium carbonate (0.63 g, 4.57 mmol), followed by 5-chloro-2-(chloromethyl)pyrimidine (0.45 g, 2.51 mmol) and potassium iodide (0.038 g, 0.23 mmol). The reaction mass was heated at 60 ° C for 16 h. The reactant was cooled to room temperature, diluted with 100 ml of ice-cold water, and extracted with ethyl acetate (4 x 200 mL). The organic layer was washed with saline solution (100 mL), dried over anhydrous Na2SO4, filtered and concentrated to obtain crude material. The crude product was purified by combi flash using ethyl acetate and cyclohexane. The desired product was eluted with 30% ethyl acetate in cyclohexane. After concentration, 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carbaldehyde 115 (0.455 g, 1.49 mmol, 65%) was obtained as a dark yellow oil. 1 H NMR (400MHz, CDCl3) δ = 9.81 (s, 1H), 8.69 (s, 2H), 7.81 (s, 1H), 5.41 (s, 2H).

[0171] Step 5- Preparation of 2-[[2-bromo-4-(difluoromethyl)imidazol-1-yl]methyl]-5-chloro-pyrimidine (I16):

[0172]

[0173] At 0 ° C, diethylamino sulfur trifluoride (3.32 g, 20.6 mmol) was added to a solution of 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxaldehyde I15 (0.773 g, 2.56 mmol) in dichloromethane (50 mL, 778 mmol), and the reaction mixture was stirred rapidly at 0 ° C under nitrogen and then warmed to room temperature and stirred for 3 h. The reaction mixture was cooled to 0 ° C and quenched by slowly adding saturated NaHCO (100 mL). The reaction mass was extracted with ethyl acetate (3 x 100 ml). The combined organic layers were washed with saline solution, dried over anhydrous Na SO, filtered and concentrated to obtain crude material. The crude product was purified by column chromatography using 20% ​​ethyl acetate in cyclohexane to obtain 2-[[2-bromo-4-(difluoromethyl)imidazole-1-yl]methyl]-5-chloro-pyrimidine I16 (0.44 g, 53%). 1H NMR (400MHz, CDCl3) δ = 8.69 (s, 2H), 7.37 (t, 1H), 6.64 (t, 1H), 5.36 (s, 2H).

[0174] Step 6 - Preparation of 5-chloro-2-[[2-(5-chloro-3-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.064:

[0175]

[0176] In a 30 ml microwave vial, potassium phosphate (0.418 g, 1.93 mmol) was added to 2-[[2-bromo-4-(difluoromethyl)imidazol-1-yl]methyl]-5-chloro-pyrimidine I16 (0.25 g, 0.77 mmol) in cyclopentyl methyl ether (3.75 mL), followed by (5-chloro-3-thienyl)boronic acid (0.25 g, 1.54 mmol). The reaction mixture was purged with nitrogen for 5 min, and then [1,1'-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II). dichloromethane complex (0.031 g, 0.038 mmol) was added thereto. The reaction mixture was heated at 120 °C in a microwave for 2 h. The reaction mixture was cooled to room temperature and slowly poured into an ice-cold sodium bicarbonate solution. The reaction mass was extracted with ethyl acetate (3 x 100 ml). The combined organic layers were washed with brine solution, dried over anhydrous Na2SO4, filtered and concentrated to give the crude material. The crude product was purified by column chromatography using 0-100% ethyl acetate and cyclohexane to give 5-chloro-2-[[2-(5-chloro-3-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.064 (130 mg, 46%). 1 H NMR (400MHz, CDCl3) δ = 8.74 (s, 2H), 7.58 (d, 1H), 7.38 (t, 1H), 7.36 (d, 1H), 6.69 (t, 1H), 5.41 (s, 2H).

[0177] Example 5: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.058

[0178]

[0179] Step 1- Preparation of ethyl 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate (I17):

[0180]

[0181] Sodium hydride (2.20g, 55.0mmol, 60%) and tetrahydrofuran (70mL) were added to a 3-necked 500mL flask equipped with a thermometer. The suspension was cooled to 0°C under nitrogen. Then, 1H-imidazole-4-ethyl formate (6.99g, 49.9mmol) was added thereto in batches at a certain rate so that the internal temperature did not exceed 8°C. When exhaust was complete, a solution of 2-(chloromethoxy)ethyl-trimethyl-silane (10.1mL, 57.8mmol) in tetrahydrofuran (15mL) was added within 30 minutes. Then, the reaction mixture was warmed to room temperature and a white solid was precipitated. The reaction mixture was stirred for 3h at room temperature under nitrogen. The reaction mixture was quenched with saturated brine and water. Then ethyl acetate (150mL) was added, each phase was separated, and the aqueous phase was extracted with ethyl acetate (3x 100mL). Organic matter was merged, washed with saturated brine and concentrated onto granular diatomaceous earth. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to give ethyl 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate 117 (10.4 g, 77%) as a yellow oil. 1 H NMR (400MHz, CDCl3) δ = 7.73 (m, 1H), 7.62 (s, 1H), 5.31 (s, 2H), 4.39 (m, 2H), 3.50 (m, 2H), 1.40 (dt, 3H), 0.92 (m, 2H), 0.00 (br s, 9H).

[0182] Step 2- Preparation of ethyl 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate (I18):

[0183]

[0184] In the 500mL 3-necked flask equipped with condenser and thermometer, add 1-(2-trimethylsilylethoxymethyl)imidazole-4-ethyl formate I17 (9.90g, 36.6mmol) and acetonitrile (100mL), give a faint yellow solution.The solution is degassed 30 minutes with the nitrogen stream bubbling through the solution.Add N-bromosuccinimide (8.64g, 47.6mmol), then add azobisisobutyronitrile (0.307g, 1.83mmol), and the reaction mixture is heated to 65 DEG C under nitrogen for 6h.The reaction is quenched with 100mL 2M sodium thiosulfate, and 100mL ethyl acetate and 100mL salt solution are added.Separate each phase, water layer is extracted with ethyl acetate (3x 200mL), and organic layer is merged, through anhydrous Na2SO4 drying, filter and concentrate under vacuum. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to give ethyl 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate 118 (5.78 g, 45%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ = 7.77 (s, 1H), 5.31 (s, 2H), 4.38 (q, 2H), 3.56 (m, 2H), 1.39 (t, 3H), 0.93 (m, 2H), 0.00 (s, 9H).

[0185] Step 3 - Preparation of ethyl 2-bromo-1H-imidazole-4-carboxylate (I19):

[0186]

[0187] A solution of 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylic acid ethyl ester I18 (5.78 g, 16.5 mmol) in ethanol (145 mL) was added to a 500 mL flask, and HCl (12 M) in deionized water (14 mL, 168 mmol) was added. The reactants were heated to 60 ° C under nitrogen for 1.5 h. The reactants were concentrated under vacuum to give 2-bromo-1H-imidazole-4-carboxylic acid ethyl ester I19 (4.26 g, 96%) as a white solid. 1 H NMR (400MHz, CD3OD) δ = 8.04 (s, 1H), 4.36 (q, 2H), 1.35 (t, 3H).

[0188] Step 4- Preparation of ethyl 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxylate (I20):

[0189]

[0190] 2-bromo-1H-imidazole-4-carboxylic acid ethyl ester was added to a 100 mL flask; hydrochloride I19 (4.26 g, 15.8 mmol), potassium iodide (0.548 g, 3.30 mmol) and acetonitrile (100 mL). Potassium carbonate (6.57 g, 47.5 mmol) and water (5 mL) were added, followed by a one-time addition of 5-chloro-2-(chloromethyl)pyrimidine (2.84 g, 17.4 mmol). The reaction mixture was then heated to 75 ° C for 1 h under air. The reactant was cooled to room temperature. The reaction was quenched with 200 mL 50% brine and 200 mL ethyl acetate was added. Each phase was separated, the aqueous layer was extracted with ethyl acetate (3 x 200 mL), and the organic layers were combined, dried over anhydrous Na2SO4, filtered and concentrated under vacuum. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to give ethyl 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxylate 120 (4.45 g, 77%). 1 H NMR (400MHz, CDCl3) δ = 8.68 (s, 2H), 7.79 (s, 1H), 5.38 (s, 2H), 4.38 (q, 2H), 1.38 (t, 3H).

[0191] Step 5- Preparation of ethyl 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxylate (I21):

[0192]

[0193] To a microwave vial was added ethyl 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxylate I20 (0.1 g, 0.27 mmol), 5-chlorothiophene-2-boric acid (0.053 g, 0.32 mmol), 2-methyltetrahydrofuran (2.00 mL) and tripotassium phosphate (1.0 M in water) (0.69 mL, 0.69 mmol). The flask was evacuated and backfilled with nitrogen (three times). [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II).dichloromethane complex (0.01 g, 0.012 mmol) was added to the vial and evacuated and backfilled with nitrogen three times. The reactants were heated to 75 °C under nitrogen for 2 h. The reactants were cooled to room temperature and the reaction was quenched with 50 mL of water and the phases were separated. The aqueous layer was extracted with ethyl acetate (3 x 50 mL), and the organic layers were combined, dried over anhydrous Na2SO4, filtered, and concentrated under vacuum. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to obtain ethyl 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxylate I21 (0.056 g, 56%). 1 H NMR (400MHz, CDCl3) δ = 8.70 (s, 2H), 7.81 (s, 1H), 7.21 (d, 1H), 6.88 (d, 1H), 5.47 (s, 2H), 4.39 (q, 2H), 1.39 (t, 3H).

[0194] Step 6 Preparation of 6-[1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazol-4-yl]methanol (I22):

[0195]

[0196] 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxylic acid ethyl ester I21 (0.41 g, 1.07 mmol) and tetrahydrofuran (10 mL) were added to a 3-neck 100 mL flask equipped with a thermometer, a dropping funnel and a nitrogen inlet. The reactant was cooled to 0 ° C under nitrogen, and 1M diisobutylaluminum hydride in hexane (3.3 mL, 3.3 mmol) was added dropwise via a dropping funnel while keeping the temperature less than 15 ° C. After completion of the addition, the reactant was warmed to room temperature and stirred for 24 h. The reaction mixture was diluted with methyl tert-butyl ether (50 mL). The reaction was quenched by adding 0.131 mL of water at 0 ° C, followed by the addition of 0.131 mL of 15% NaOH. Then, 0.33 mL of water was added dropwise thereto. The reaction mixture was warmed to room temperature for 30 minutes, and MgSO was added. The reaction mixture was then filtered through a pad of celite. The filtrate was concentrated under vacuum to give [1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazol-4-yl]methanol 122 (0.208 g, 56%). 1 H NMR (400MHz, CDCl3) δ = 8.70 (s, 2H), 7.15 (d, 1H), 7.08 (s, 1H), 6.86 (d, 1H), 5.42 (s, 2H), 4.64 (br s, 2H), 2.19 (br s, 1H).

[0197] Step 7- Preparation of 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carbaldehyde (I23):

[0198]

[0199] To a 250 mL flask was added [1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazol-4-yl]methanol I22 (0.208 g, 0.61 mmol) and ethyl acetate (10 mL). Manganese (IV) oxide (1.00 g, 11.5 mmol) was added to the reaction mixture and stirred rapidly at room temperature overnight under nitrogen. The reactants were diluted with 150 mL of ethyl acetate and celite was added. The suspension was then filtered through a pad of Cetyl acetate and concentrated in vacuo to give 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carbaldehyde I23 (0.11 g, 54%). 1 H NMR (400MHz, CDCl3) δ = 9.92 (s, 1H), 8.71 (s, 2H), 7.83 (s, 1H), 7.22 (d, 1H), 6.90 (d, 1H), 5.51 (s, 2H).

[0200] Step 8 - Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.058:

[0201]

[0202] 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxaldehyde I23 (0.113 g, 0.33 mmol) and dichloromethane (10 mL) were added to a 250 mL flask. The reactants were cooled to 0 ° C, and diethylaminosulfur trifluoride (0.25 mL, 1.9 mmol) was added, and the reactants were rapidly stirred at 0 ° C under nitrogen for 3 h. The reactants were warmed to room temperature and stirred for 16 h. After this time, the reaction mixture was cooled to 0 ° C and quenched by slowly adding 50 mL of saturated NaHCO 3 . 100 mL of dichloromethane was added, and the biphasic mixture was passed through a phase filter. The filtrate was concentrated to give a crude product. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to give 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.058 (0.086 g, 71%). 1 H NMR (400MHz, CDCl3) δ = 8.72 (s, 2H), 7.38 (t, 1H), 7.21 (d, 1H), 6.89 (d, 1H), 6.70 (t, 1H), 5.46 (s, 2H).

[0203] Example 6: Preparation of 2-chloro-5-[1-[(5-chloropyrimidin-2-yl)methyl]-4-(difluoromethyl)imidazol-2-yl]thiazole 1.071

[0204]

[0205] Step 1-Ethyl 2-chloro-5-[4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole (I24) Preparation:

[0206]

[0207] To a 25mL flask equipped with a reflux condenser and a thermometer, sodium acetate (1.68g, 20.3mmol) and water (6.00mL) were added. 1,1-dibromo-3,3,3-trifluoroacetone (1.40mL, 9.76mmol) was added to give a turbid solution / suspension. The reaction mixture was heated to 90°C for 30 minutes. Then, the reaction mixture was cooled to room temperature to provide a solution of 1,1-dihydroxy-3,3,3-trifluoroacetone. 2-chlorothiazole-5-carboxaldehyde (1.2g, 8.131mmol), methanol (18.00mL) and ammonia (6.00mL, 51mmol) were added to another 3-neck 100mL flask to give an orange solution. In 0.5h, a solution of 1,1-dihydroxy-3,3,3-trifluoroacetone (prepared as above) was added dropwise to the reaction mixture using a dropping funnel while maintaining the internal temperature at 45°C (note: addition is exothermic). After completion of the addition, the reaction mixture was stirred overnight at room temperature under air. The reaction mixture was concentrated under vacuum to remove MeOH and excess NH3. The residue was diluted with water (10ml) and ethyl acetate (30ml). Each phase was separated, and the aqueous phase was extracted with ethyl acetate (30ml). Organics were merged, filtered and concentrated through a hydrophobic filter. The crude product was purified by column chromatography using 0-50% ethyl acetate in cyclohexane to obtain ethyl 2-chloro-5-[4-(trifluoromethyl)-1H-imidazole-2-yl] thiazole I24 (0.66g, 32%). 1 H NMR (400MHz, CD3OD) δ = 8.01 (s, 1H), 7.71 (s, 1H).

[0208] Step 2- Preparation of 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbonitrile (I25):

[0209]

[0210] 2-Chloro-5-[4-(trifluoromethyl)-1H-imidazole-2-yl]thiazole I24 (0.663 g, 2.61 mmol), methanol (3.32 mL) and aqueous ammonia (6.2 mL, 39.2 mmol) were added to a vial. The reaction mixture was stirred overnight at 70 ° C. The reaction mixture was cooled to room temperature and evaporated under reduced pressure to give a brown jelly. The crude product was purified by column chromatography using 0-50% ethyl acetate in cyclohexane to obtain 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbonitrile I25 (0.33 g, 60%). 1 H NMR (400MHz, CD3OD) δ = 8.01 (s, 1H), 8.00 (s, 1H).

[0211] Step 3- Preparation of 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbaldehyde (I26):

[0212]

[0213] In 10 minutes, diisobutylaluminum hydride (1.0M in toluene) (7.60mL, 7.60mmol) was added dropwise to a stirred solution of 2-(2-chlorothiazole-5-yl)-1H-imidazole-4-carbonitrile I25 (0.320g, 1.52mmol) in tetrahydrofuran (4.00mL) cooled to -78°C under nitrogen via a syringe. The reaction mixture was stirred for 1 hour at -78°C, then it was warmed to 0°C and stirred for 1h at 0°C. At 0°C, by adding 0.3mL water and 0.3mL15% NaOH aqueous solution, and finally adding 0.76mL water, the reaction was quenched. The reaction mixture was warmed to room temperature and stirred at room temperature for 15 minutes. Methyl tert-butyl ether (15ml) was added to the reaction mixture, followed by diatomaceous earth and MgSO4. The reaction mixture was filtered and the filter cake was washed with ethyl acetate (3x 20ml). The filtrate was concentrated under vacuum to give 66mg light orange solid. The filter cake is neutralized with 2M HCl and is resuspended in ethyl acetate (50ml) and stirred for 2.5h. The filtrate is concentrated under vacuum to give another 44mg orange solid. The filter cake is acidified with 2M HCl and is resuspended in ethyl acetate (50ml) and stirred for 30min. The filtrate is concentrated under vacuum to give another 12mg orange solid. The combined solid is dried to obtain 2- (2- chlorothiazol-5-yl) -1H- imidazole -4- carbaldehyde I26 (112mg, 34%) as an orange solid. 1 H NMR (400MHz, CD3OD) δ = 9.65 (s, 1H), 7.98 (s, 1H), 7.88 (s, 1H).

[0214] Step 4- Preparation of 1-[(5-chloropyrimidin-2-yl)methyl]-2-(2-chlorothiazol-5-yl)imidazole-4-carbaldehyde (I27):

[0215]

[0216] 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carboxaldehyde I26 (0.112 g, 0.524 mmol) in acetonitrile (1.75 mL) and water (0.05 mL) was added to a 50 mL flask. Potassium carbonate (0.217 g, 1.57 mmol), 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (0.132 g, 0.629 mmol) and potassium iodide (0.0174 g, 0.105 mmol) were added to the above reaction mixture to give a brown suspension. The mixture was heated to 70 ° C. After 1 h, another portion of 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (55 mg, 0.26 mmol) and potassium carbonate (36 mg, 0.26 mmol) were added and heated for another 45 minutes. After this time, the reaction mixture was cooled to room temperature. The reaction mixture was diluted with water (4 mL) and brine (4 mL) and extracted with ethyl acetate (2 x 15 mL). The combined organics were passed through a hydrophobic filter paper and concentrated in vacuo to give the crude material as a brown gum (345 mg). The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to give 1-[(5-chloropyrimidin-2-yl)methyl]-2-(2-chlorothiazol-5-yl)imidazole-4-carbaldehyde 127 (0.052 g, 29%). 1 H NMR (400MHz, CDCl3) δ = 9.90 (s, 1H), 8.71 (s, 2H), 7.91 (s, 1H), 7.86 (s, 1H), 5.51 (s, 2H).

[0217] Step 5 - Preparation of 2-chloro-5-[1-[(5-chloropyrimidin-2-yl)methyl]-4-(difluoromethyl)imidazol-2-yl]thiazole 1.071:

[0218]

[0219] 1-[(5-chloropyrimidine-2-yl) methyl]-2-(2-chlorothiazole-5-yl) imidazole-4-carboxaldehyde I27 (0.09g, 0.2646mmol) and dichloromethane (5.3mL) were added to a 50mL 3-necked flask. The reactant was cooled to 0°C in an ice / water bath and stirred under nitrogen. Diethylamino sulfur trifluoride (0.28mL, 2.1mmol) was added to the reaction mixture, and the reaction mixture was rapidly stirred for 3h at 0°C under nitrogen. The reaction mixture was warmed to room temperature and stirred for another 48h at room temperature. After this time, the reaction mixture was cooled to 0°C and quenched by slowly adding saturated NaHCO (3ml). 50mL dichloromethane was added, and the biphasic mixture was passed through a hydrophobic phase filter. The filtrate was concentrated to give an orange jelly (105mg). The crude product was purified by column chromatography using 40% ethyl acetate in cyclohexane to give 2-chloro-5-[1-[(5-chloropyrimidin-2-yl)methyl]-4-(difluoromethyl)imidazol-2-yl]thiazole 1.071 (0.054 g, 56%). 1 H NMR (400MHz, CDCl3) δ = 8.71 (s, 2H), 7.90 (s, 1H), 7.42 (t, 1H), 6.68 (t, 1H), 5.45 (s, 2H).

[0220] Example 7: 5-chloro-2-[[2-(4-chloropyrazol-1-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.065

[0221]

[0222] In a 30 mL microwave vial, 4-chloro-1H-pyrazole (0.26 g, 2.57 mmol) was added to a solution of 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine Ill (prepared in Example 3, Step 4) (0.2 g, 0.51 mmol) in acetonitrile (2 mL), followed by potassium carbonate (0.71 g, 5.14 mmol) and 8-hydroxyquinoline (0.03 g, 0.20 mmol). The reaction mixture was degassed for 5 min by bubbling with nitrogen, then tetra(acetonitrile)copper(I) tetrafluoroborate (0.033 g, 0.10 mmol) was added thereto, and the reaction mixture was heated at 130°C for 1.5 h. The reaction was cooled to room temperature, diluted with 70 ml of water, extracted with ethyl acetate (4 x 80 mL), the organic layer was washed with brine solution (25 mL), dried over anhydrous Na2SO4, filtered and concentrated to give the crude material. The crude product was purified by column chromatography using 10% ethyl acetate in cyclohexane to give 5-chloro-2-[[2-(4-chloropyrazol-1-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.065 (0.091 g, 48%) as a white solid. 1 H NMR (400MHz, CDCl3) δ = 8.61 (s, 2H), 8.21 (d, 1H), 7.49 (d, 1H), 7.30 (q, 1H), 5.78 (s, 2H).

[0223] Table 1. Compounds of the present invention

[0224]

[0225]

[0226]

[0227]

[0228]

[0229]

[0230]

[0231]

[0232]

[0233]

[0234]

[0235]

[0236]

[0237]

[0238]

[0239]

[0240]

[0241]

[0242] Table 2. Intermediate compounds of the present invention.

[0243]

[0244]

[0245] Biological Examples

[0246] Seeds of various test species were sown in standard soil in pots: Amaranthus retoflexus (AMARE), Echinochloa crus-galli (ECHCG), Setaria faberi (SETFA). After one day of cultivation (pre-emergence) or after 8 days of cultivation (post-emergence) under controlled conditions in a greenhouse (24°C / 16°C, day / night; 14 hours of light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from a formulation of the technical grade active ingredient in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5). Unless otherwise stated, the compounds were applied at 250 g / ha. The test plants were then grown in a greenhouse under controlled conditions in a greenhouse (24°C / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice a day. The percentage of damage caused to the plants by the test was evaluated before emergence and 13 days after emergence. The biological activity is shown in the following table on a five-point scale (5 = 81%-100%; 4 = 61%-80%; 3 = 41%-60%; 2 = 21%-40%; 1 = 0-20%).

[0247] Table B1 Post-emergence test

[0248]

[0249]

[0250]

[0251] NT = Not tested Table B2 Pre-emergence test

[0252]

[0253]

[0254] NT = not tested.

Claims

1. A compound having formula (I): or an agronomically acceptable salt thereof, in A is for CR 5 or N; Q is a 5-membered heteroaryl group, which is optionally substituted by 1 or 2 R 3 Substituent substitution, R 1 independently selected from the group consisting of halogen, -CN, C1-C2 alkyl, C1-C2 haloalkyl, C3-C6 cycloalkyl, C1-C2 alkoxy- and C1-C2 haloalkoxy-; R 2 Selected from the group consisting of: halogen, -CN, NO2, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, -C(O)C1-C4 alkyl, -C(O)OC1-C4 alkyl, C1-C4 haloalkoxy, -S(O) p C1-C4 alkyl, -C(R 6 )=NOR 7 and C3-C6 cycloalkyl; R 3 independently selected from the group consisting of halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkoxy C1-C3 alkyl-, C1-C4 alkoxy C1-C3 alkoxy-, C1-C4 alkoxy C1-C3 alkoxy C1-C3 alkyl-, -CN, NO2, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, -S(O) p C1-C4 haloalkyl, -C(O)OC1-C4 alkyl and -C(O)NR 8 R 9 ; R 4 independently selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, -CN, NO2, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, -S(O) p C1-C4 haloalkyl, -C(O)OC1-C4 alkyl and -C(O)NR 8 R 9 ; R 5 selected from the group consisting of: hydrogen, fluorine, chlorine, and -CN; R 6 is hydrogen or C1-C4 alkyl; R 7 is hydrogen or C1-C2 alkyl; R 8 is hydrogen or C1-C4 alkyl; R 9 is hydrogen or C1-C4 alkyl; m = 1 or 2; and p=0, 1 or 2.

2. The compound of claim 1 having formula (I), which has formula (Ia) Among them, Q, R 1 , R 2 and R 4 As defined in claim 1 above.

3. The compound according to claim 1 or claim 2, wherein R 4 It's hydrogen.

4. A compound according to any one of the preceding claims, wherein R 1 It's chlorine.

5. A compound according to any one of the preceding claims, wherein R 2 It is -CF3 or -CF2H.

6. A compound according to any one of the preceding claims, wherein Q is selected from the group consisting of: Where R 3 is hydrogen or as defined in claim 1 above, R 3a is selected from the group consisting of hydrogen, methyl, ethyl, CHF2 and cyclopropyl, and R 3b Selected from the group consisting of hydrogen, fluorine, chlorine and bromine.

7. A compound according to any one of the preceding claims, wherein Q is selected from the group consisting of Q-1, Q-2, Q-3, Q-4, Q-13, Q-14, Q-15, Q-16, Q-22, Q-23, Q-24, Q-41, Q-42 and Q-43.

8. A compound according to any one of the preceding claims, wherein Q is selected from the group consisting of Q-1, Q-14, Q-22, Q-23, Q-41 and Q-43.

9. The compound according to claim 8, wherein R 3 It's chlorine.

10. A herbicidal composition comprising a compound according to any one of the preceding claims and an agriculturally acceptable formulation adjuvant.

11. The herbicidal composition according to claim 10, further comprising at least one additional pesticide.

12. The herbicidal composition according to claim 11, wherein The additional pesticide is a herbicide or a herbicide safener.

13. A method of controlling weeds at a locus comprising applying to the locus a weed controlling amount of a composition according to any one of claims 10 to 12.

14. Use of the compound of formula (I) according to claim 1 as a herbicide.

15. A compound having formula (VIIIa): Where R 2 and R 4 is as defined in claim 1 above and X2a is hydrogen or halogen.

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