Herbicidal imidazole-containing compounds

Abstract

The present invention relates to a compound of formula (I), 1 , R 2 , R 4 and m is as defined herein), or an agriculturally acceptable salt of said compound. The present invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I), in particular for the control of weeds in crops of useful plants. JPEG2025525367000072.jpg61101

Description

[Technical Field]

[0001] The present invention relates to herbicidal compounds, processes for their preparation, herbicidal compositions containing the novel compounds, and their use, especially for controlling weeds or inhibiting plant growth in crops of useful plants. [Background technology]

[0002] WO 2022 / 101270 discloses herbicidal N-heteroarylpyrazole compounds. WO 2023 / 066783 discloses herbicidal imidazole compounds characterized by a phenyl or 6-membered heteroaryl at position Q as specified below. Summary of the Invention [Means for solving the problem]

[0003] Thus, according to the present invention, a compound of formula (I): [ka] (In the formula, A is CR 5 or N; Q is one or two R 3 a 5-membered heteroaryl optionally substituted with a substituent; R 1 are 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 is 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; R3 is halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkoxyC1-C3 alkyl-, C1-C4 alkoxyC1-C3 alkoxy-, C1-C4 alkoxyC1-C3 alkoxyC1-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 independently selected from the group consisting of: R 4 is 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 independently selected from the group consisting of: R 5 is selected from the group consisting of hydrogen, fluoro, chloro 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; p=0, 1 or 2) or an agriculturally acceptable salt thereof.

[0004] 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).

[0005] Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The same applies correspondingly to halogen in the context of other definitions such as haloalkyl.

[0006] 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, 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.

[0007] C1-C4 alkoxy and C1-C2 alkoxy include, for example, methoxy and ethoxy.

[0008] 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.

[0009] C2-C4 alkenyl- includes, for example, -CH=CH2 (vinyl) and -CH2-CH=CH2 (allyl).

[0010] C2-C4 alkynyl- refers to a straight or branched hydrocarbon chain radical group composed solely of carbon and hydrogen atoms, containing at least one triple bond, and having 2 to 4 carbon atoms, which is attached to the rest 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.

[0011] C1-C4 alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0012] 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.

[0013] C1-C4 alkyl-S(O)2-(alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0014] In one embodiment of the present invention, A is N. In another embodiment of the present invention, m is 1. Thus, in a preferred embodiment of the present invention, a compound of formula (Ia) [ka] (In the formula, Q, R 1 , R 2 and R 4 is as defined in claim 1) The compound of formula (I) is provided.

[0015] In one embodiment of the present invention, R 1 is preferably chloro. In another embodiment of the present invention, R 4 is preferably hydrogen. In another embodiment of the present invention, R 2 is preferably —CF3 or —CF2H.

[0016] In another embodiment of the present invention, Q is preferably [ka] (In the formula, R 3 is hydrogen or as defined in claim 1, and R 3a is selected from the group consisting of hydrogen, methyl, ethyl, CHF2, and cyclopropyl; R 3b is selected from the group consisting of hydrogen, fluoro, chloro and bromo is selected from the group consisting of:

[0017] 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.

[0018] In one embodiment of the present invention, R 3 is chloro.

[0019] The present invention relates to a compound of formula VIIIa: [ka] (In the formula, R 2 and R 4 is as defined above and X2a is hydrogen or halogen (preferably bromo 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 is hydrogen.

[0020] Compounds of formula (I) may contain asymmetric centers and may exist as single enantiomers, pairs of enantiomers in any ratio, or, if two or more asymmetric centers are present, may contain diastereoisomers in all possible ratios. Typically, one of the enantiomers has greater biological activity than the other possible ones.

[0021] The present invention also provides agriculturally acceptable salts of compounds of formula (I). Salts of compounds of formula (I) may be formed with amines, such as primary, secondary, and tertiary amines (e.g., ammonia, dimethylamine, and triethylamine), with alkali metal and alkaline earth metal bases, transition metal, or quaternary ammonium bases being preferred.

[0022] Although the compounds of formula (I) of the present invention can be used as herbicides themselves, they are typically formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents, and surfactants (SAA). 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 that is diluted before use, but ready-to-use compositions can also be prepared. Final dilution is usually with water, but it can also be carried out with, for example, liquid fertilizers, trace elements, biological organisms, oils, or solvents instead of or in addition to water.

[0023] The herbicidal composition usually comprises 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of a compound of formula I and 1 to 99.9% by weight of a formulation adjuvant, which preferably comprises 0 to 25% by weight of a surfactant.

[0024] The compositions can be selected from several formulation types, including emulsifiable 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 (EW) emulsions, microemulsions (ME), oil-based suspensions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical concentrates (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP), and soluble granules (SG). The type of formulation selected in any given case will depend on the specific purpose envisaged and the physical, chemical, and biological properties of the compound of formula (I).

[0025] 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), optionally with one or more wetting agents, one or more dispersing agents, or a mixture of the aforementioned agents to improve water dispersibility / solubility. The mixture is then ground into a fine powder. Similar compositions can also be granulated into water-soluble granules (SG).

[0026] 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, preferably one or more dispersing agents, and optionally one or more suspending agents to promote dispersion in a liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated into water-dispersible granules (WG).

[0027] Granules (GR) can be formed by granulating a mixture of a compound of formula (I) with one or more powdered solid diluents or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) from preformed blank granules into a porous granular material (such as pumice, attapulgite clay, Fuller's earth, Kieselguhr, diatomaceous earth, or crushed corncob), or by adsorbing a compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material (such as sand, silica, carbonate, sulfate, or phosphate minerals), followed by optional drying. Agents commonly used to aid absorption or adsorption include solvents (aliphatic and aromatic petroleum-based solvents, alcohols, ethers, ketones, and esters) and binders (such as polyvinyl acetate, polyvinyl alcohol, dextrin, sugars, and vegetable oils). One or more other additives may also be included in the granules (e.g., emulsifiers, wetting agents, or dispersing agents).

[0028] 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 surfactants (e.g., to improve dilution with water or to prevent crystallization in the spray tank).

[0029] 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 (C8-C9), and the like. 10EC products may emulsify spontaneously when water is added, resulting in emulsions that are stable enough to allow spray application with appropriate equipment.

[0030] The preparation of EWs involves obtaining a compound of formula (I) as a liquid (if not liquid at room temperature, it can be melted at a moderate temperature, typically below 70°C) or as a solution (by dissolving in a suitable solvent), and then emulsifying the resulting liquid or solution in water containing one or more SAAs under high shear to obtain 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 with poor solubility in water.

[0031] Microemulsions (MEs) can be prepared by mixing a blend of one or more solvents and one or more SAA with water to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in water or the solvent / SAA blend. Suitable solvents for use in MEs include those described hereinabove for use in EC or EW. MEs can be oil-in-water or water-in-oil systems (which system is present can be determined by conductivity measurements) and can be suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. MEs can remain as microemulsions or be suitable for dilution with water to form conventional oil-in-water emulsions.

[0032] Suspension concentrates (SCs) may comprise aqueous or non-aqueous suspensions of fine, insoluble solid particles of a compound of formula (I). SCs may be prepared by ball milling or bead milling a solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, 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 at which the particles settle. Alternatively, a compound of formula (I) may be dry-milled and added to water containing the agents described hereinabove to produce the desired final product.

[0033] Aerosol formulations include 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 vehicle (e.g., water or a miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized, manually operated spray pump.

[0034] Capsule suspensions (CS) can be prepared similarly to the preparation of EW formulations, but with an additional polymerization stage to obtain an aqueous dispersion of oil droplets, each of which is encapsulated by a polymeric shell and contains the compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell can be produced by an interfacial polycondensation reaction or a coacervation method. This composition can provide controlled release of the compound of formula (I), and they can be used for seed treatment. The compound of formula (I) can also be formulated in a biodegradable polymer matrix to provide controlled, slow release of the compound.

[0035] The composition may contain one or more additives to improve the biological performance of the composition, for example, by improving the wettability, retention, or dispersibility of the compound of formula (I) on a surface, its resistance to rain on the treated surface, or its uptake or mobility. Such additives include surface active agents (SAA), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean and rapeseed oil), modified vegetable oils such as methylated rapeseed oil (MRSO), and blends of these with other bio-enhancing adjuvants (formulation ingredients that can assist or modify the action of the compound of formula (I)).

[0036] Wetting agents, dispersing agents, and emulsifying agents may be cationic, anionic, amphoteric, or nonionic SAAs.

[0037] Suitable cationic SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0038] 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, butylnaphthalene sulfonate, and mixtures of sodium di-isopropyl-sulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3-sulfate), ether carboxylates (e.g., sodium laureth-3-carboxylate), phosphate esters (products of the reaction of one or more aliphatic alcohols with phosphoric acid (predominantly mono-esters) or phosphorus pentoxide (predominantly di-esters), e.g., the reaction of lauryl alcohol with tetraphosphoric acid; further, these products may be ethoxylated), sulfosuccinates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphate / sulfate salts of tristyrylphenol.

[0039] Suitable amphoteric SAAs include betaines, propionates and glycinates.

[0040] Suitable nonionic SAAs 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 alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of the above partial esters with ethylene oxide; block polymers (including ethylene oxide and propylene oxide); alkanolamides; simple esters (e.g., fatty acid polyethylene glycol esters); amine oxides (e.g., lauryl dimethylamine oxide); lecithin and sorbitan and their esters, alkyl polyglycosides and tristyrylphenols.

[0041] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone, or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0042] The compounds of the invention can also be used in mixtures 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), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, vilanaphos, bipyrazone, bispyribac-sodium, bixlozone, brocorozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chloransulam (including chloransulam-methyl), chloransulam-methyl, ... Rolimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clasiphos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranyl, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, desmedipham, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium, and sodium salts) Diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrion, diquat dibromide, diuron, epirifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), fluchloraminopyr (including fluchloramino-tefuryl), flufenacet, flufenoximacil, flumetsulam, flumioxazin, fluometuron, fomesafenFlupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), flusulfinam, fomesafen, foramsulfuron, glufosinate (including L-glufosinate and both ammonium salts), glyphosate (including its diammonium, isopropylammonium, and potassium salts), halaxifen (including haloxyfop-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, icaforin (including icaforin-methyl), Imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, indoloxypyr (including indoloxypyr-cyanomethyl), iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, iptriazopyride, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor , methiozoline, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryn, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen-ethyl), pyraquine ate, pyrasulfotole, pyridate, pyriftalid, pyriflubenzoxim, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, rimsulfuron, saflufenacil, sethoxydim, simazine, S-metallochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron,Thiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxadine, trifluralin, triflusulfuron, tripyrasulfone, 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 (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-ylmethyl]-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-ylmethyl carbonate, ethyl 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate, methyl 2-[2-[2-bromo-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenoxy]phenoxy]-2-methoxy-acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one,(2-fluorophenyl)methyl 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylate, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid, and methyl 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-cyclopent[d]isoxazole-6a-carboxylate.

[0043] The compound of formula (I) may also be in the form of an ester or salt, as described, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0044] The compounds of formula (I) may also be used in mixtures with other pesticides such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0045] The mixing ratio of the compound of formula (I) to the mixing partner is preferably 1:100 to 1000:1.

[0046] This mixture may be advantageously used in the formulations described above (in which case "active ingredient" relates to the respective mixture of compound of formula (I) and mixing partner).

[0047] The compounds or mixtures of the present invention may also be used in combination with one or more herbicide safeners, examples of which include benoxacor, cloquintocet (including cloquintocet-mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen (including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl), metcamifen, and oxabetrinil.

[0048] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and / or metcamifen.

[0049] The safeners of the compounds of formula (I) can also be used as described, for example, in The Pesticide Manual, 16 th Edition (BCPC), 2012. Reference to cloquintocet-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.

[0050] 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.

[0051] The present invention also provides a method for controlling weeds in a locus, comprising applying a weed-controlling amount of a composition containing a compound of formula (I) to the locus. The present invention may also provide a method for selectively controlling weeds in a locus containing crop plants and weeds, comprising applying a weed-controlling amount of a composition of the present invention to the locus. "Control" means killing, reducing or delaying growth, or preventing or reducing germination. It is noted that the compounds of the present invention exhibit significantly improved selectivity compared to known structurally similar compounds. Generally, the plants to be controlled are undesirable plants (weeds). "Locus" refers to the area where plants are growing or will grow. Application may be made to the locus before and / or after emergence of the crop plants. Several crop plants may be inherently resistant to the herbicidal effects of the compounds of formula (I). Preferred crop plants include corn, wheat, barley, and rice.

[0052] The application rates of the compounds of formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application in the seed furrow; application on non-arable land, etc.), the crop plants, the weeds to be controlled, the prevailing climatic conditions, and other factors governed by the application method, application time, and target crop. The compounds of formula I of the invention are usually applied in amounts of 10 to 2500 g / ha, in particular 25 to 1000 g / ha, and even more particularly 25 to 250 g / ha.

[0053] Application is generally accomplished by spraying the composition, typically with a tractor-mounted large area sprayer, although other methods such as dusting (if powder), dripping or drench can also be used.

[0054] It should be understood that crop plants also include those that have been rendered tolerant to other herbicides or classes of herbicides (e.g., ALS-, GS-, EPSPS-, PPO-, HPPD-, PDS-, and ACCase-inhibitors) by conventional breeding methods or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, such as imazamox, by conventional breeding methods is Clearfield® summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant corn varieties commercially available under the trade names RoundupReady® and LibertyLink®. The compounds of the present invention can be used in combination with plants, for example, as taught in WO 2020 / 236790.

[0055] Crop plants should also be understood as those that have been rendered resistant to harmful insects by genetic engineering, such as Bt corn (resistant to the European corn borer), Bt cotton (resistant to the Mexican boll weevil), and Bt potato (resistant to the Colorado potato beetle). An example of Bt corn is the Bt176 corn hybrid from NK® (Syngenta Seeds). Bt toxins are natural proteins formed by the soil bacterium Bacillus thuringiensis. Examples of toxins or genetically modified plants capable of synthesizing such toxins are described in EP 451 878, EP 374 753, WO 93 / 07278, WO 95 / 34656, WO 03 / 052073, and EP 427 529. Examples of transgenic plants containing one or more genes encoding insecticide resistance and expressing one or more toxins are KnockOut® (corn), Yield Gard® (corn), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potato), NatureGard®, and Protexcta®. Plant crops or their seed material can both be tolerant to herbicides and simultaneously resistant to insect feeding ("stacked" transgenics). For example, seeds can be tolerant to glyphosate and simultaneously capable of expressing the insecticidal Cry3 protein.

[0056] Crop plants should also be understood to include those obtained by conventional breeding methods or by genetic engineering and which contain so-called output traits (such as improved storage stability, higher nutritional value and improved flavor).

[0057] The compositions can be used to control undesirable plants (collectively "weeds"), such as Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, and Sorghum. orghum, as well as dicotyledonous species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola, and Xanthium.

[0058] In a further aspect of the present invention there is provided the use of a compound of formula (I) as defined herein as a herbicide. DETAILED DESCRIPTION OF THE INVENTION

[0059] Process for the preparation of compounds of formula (I) Processes for the preparation of compounds, for example compounds of formula (I), which may optionally be pesticidally acceptable salts thereof, are now described and form further aspects of the invention.

[0060] Compounds of formula I-3 are compounds of formula I, wherein Q is a C-linked 5-membered heterocycle and R 2 , A and R 1(m) is as defined in Formula I, where R 41 is a C1-C4 alkyl and can be prepared, for example, by a Suzuki reaction comprising reacting a compound of formula I-1

[0061] Scheme 1 [ka] where Q is a C-linked 5-membered heterocycle and R, A and R 1 (m) is as defined in formula I, and X 1 is chlorine, bromine or iodine, and for compounds of formula II, R 41 is a C1-C4 alkyl, where Yb1 may be a boron-derived functional group such as B(OH)2 or B(ORb1)2, Rb1 may be a C1-C4 alkyl group, or two groups ORb1 together with the boron atom may form a five-membered ring, for example, pinacolboronic acid ester. 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), in the presence of a base such as sodium carbonate, tripotassium phosphate, or cesium fluoride, in a solvent or solvent mixture such as cyclopentyl methyl ether, dioxane, acetonitrile, N,N-dimethylformamide, 1,2-dimethoxyethane and water, or a mixture of dioxane / water, or toluene / water, preferably under an inert atmosphere. The reaction temperature can range preferentially 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.

[0062] Compounds of formula I-4 are compounds of formula I, where R 4=CN), which can be prepared from compounds of formula I-1 by reaction with M-CN IIa (cyanation reaction), where M is a metal coordinated to the cyanide. Examples of cyanation reagents include NaCN, Zn(CN), or potassium ferrocyanide, among others. The reaction can be catalyzed by a palladium-based catalyst, such as tetrakis(triphenylphosphine)palladium(0), (1,1'-bis(diphenylphosphino)ferrocene)dichloro-palladium-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), in the presence of a base such as sodium carbonate, tripotassium phosphate, or cesium fluoride, in a solvent or solvent mixture such as dioxane, acetonitrile, N,N-dimethylformamide, 1,2-dimethoxyethane and water, or a mixture of dioxane / water, or toluene / water, preferably under an inert atmosphere. The reaction temperature can range preferentially 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.

[0063] Compounds of formula I-1 can be prepared, optionally in the presence of an additive such as, for example, p-toluenesulfonic acid, by reacting compounds of formula I-2, for example, where Q is a C-linked 5-membered heterocycle and R 2 , A and R 1 (m) can be prepared by a halogenation reaction comprising reacting a compound of Formula I (wherein N is as defined in Formula I) with a halogenating reagent such as N-chlorosuccinimide (NCS), N-bromosuccinimide (NBS), or N-iodosuccinimide (NIS). Alternatively, the halogenation may involve chlorine, bromine, or iodine. Such halogenation reactions are carried out at temperatures between 20 and 200°C, preferably between room temperature and 100°C, in a suitable solvent such as chloroform, carbon tetrachloride, 1,2-dichloroethane, acetic acid, diethyl ether, acetonitrile, or N,N-dimethylformamide.

[0064] Compounds of formula I-2 can be prepared by procedures well known to those skilled in the art from compounds of formula IV, where Q is a C-bonded 5-membered heterocycle and R 2 are as defined in formula I) and a compound of formula III (wherein A and R 1 (m) is as defined in formula I, and LG1 can be prepared by reacting a reagent which is a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g., triflate).

[0065] The compound of formula IV can be reacted with the compound of formula VI or its hydrated form (wherein R 2 is as defined in formula I) with a compound of formula V (wherein Q is a C-bonded 5-membered heterocycle). The reaction can be carried out in the presence of a solvent such as methanol, tetrahydrofuran, ethanol, among others, and at a temperature between 20 and 200°C, preferably between room temperature and 100°C. Compounds of formula VI or their hydrated forms (wherein R 2 is as defined in formula I) can be converted into a compound of formula VII, 2 can be prepared by hydrolysis of a compound of formula I, where I is as defined in formula I. Such two-step reactions are well known in the literature.

[0066] Alternatively, a compound of formula I (wherein Q, R 2 , A, R 4 and R 1 (m) Compounds of formula I (wherein R is as defined above in formula I) can be prepared according to Scheme 2.

[0067] Scheme 2: [ka] In Scheme 2, compounds of formula I can be prepared by converting compounds of formula I-1 to compounds of formula I-3 by a procedure similar to that described in Scheme 1 for the conversion of compounds of formula I-1 to compounds of formula I-3, to compounds of formula VIII (wherein R 2 , A, R 4 and R 1 (m) is as defined in formula I above, and X 2 is a leaving group such as, for example, chlorine, bromine or iodine) with a group of formula Yb2-Q XV, where Q is as defined in formula I above and Yb2 is, for example, B(OH)2 or B(OR b2 )2, and R b2 may be a C1-C4 alkyl group, or two groups OR b2 can be prepared by Suzuki cross-coupling reaction between a compound of formula (which may be taken together with the boron atom to form a five-membered ring, e.g., pinacolboronic acid ester).

[0068] Compounds of formula Ia (wherein Q is an N-linked heterocycle) can be prepared from compounds of formula VIII via a C-N cross-coupling reaction. Such reactions are well known in the literature and can be carried out in the presence of a metal catalyst, for example using a palladium-based catalyst such as dichloro-(chloromethylchloronio)-bis[cyclopentyl(diphenyl)phosphaniumyl]palladium(3-); an iron- or copper-based catalyst such as tetrakis(acetonitrile)copper(I) tetrafluoroborate, 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 microwaves, at temperatures between 40°C and 200°C. Compounds of formula VIII (wherein R 2 , R 4 , A and R 1 (m)is as described in formula I above and X2 is a leaving group such as chlorine, bromine or iodine, can be prepared by procedures well known to those skilled in the art in the presence of a base such as sodium hydride or alkaline earth metal hydride, a carbonate (e.g. sodium carbonate, potassium carbonate or cesium carbonate) or a 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 and 120°C, to give a compound of formula IX (wherein R 2 , R 4 is as described in Formula I above, and X 2 is a leaving group such as chlorine, bromine or iodine) with a compound of formula III (wherein A and R 1 (m) is as described in formula I above, and LG1 can be prepared by alkylation reaction of a compound with a halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g., triflate).

[0069] Compounds of formula IX can be prepared by reacting compounds of formula X, where R, R are as defined in formula I above, and X 2is a leaving group such as chlorine, bromine, or iodine, and PG is an N-protecting group such as acetyl, trimethylsilylethoxymethyl (SEM), or tert-butyloxycarbonyl, among other amino-protecting groups, by a protecting group deprotection reaction from a compound of formula X (wherein X is a leaving group such as chlorine, bromine, or iodine, and PG is an N-protecting group such as acetyl, trimethylsilylethoxymethyl (SEM), or tert-butyloxycarbonyl, among other amino-protecting groups). Such reactions are well known to those skilled in the art and can be carried out, for example, using base-catalyzed or acid-catalyzed HCl. A compound of formula X (wherein X is a leaving group such as chlorine, bromine, or iodine, and PG is an N-protecting group such as acetyl, trimethylsilylethoxymethyl (SEM), or tert-butyloxycarbonyl, among other amino-protecting groups) can be prepared from a compound of formula XI (wherein PG is an N-protecting group such as acetyl, trimethylsilylethoxymethyl (SEM), or tert-butyloxycarbonyl, among other amino-protecting groups) by a halogenation reaction. Such reactions can be carried out in a two-step procedure involving metallation using a strong base such as butyllithium, tert-butyllithium, lithium tetramethylpiperidide, or lithium diisopropylamide, among others, and quenching with the appropriate halogenating reagent, 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 providing a protecting group. Such reactions can be carried out in the presence of a base such as sodium hydride, potassium carbonate, or sodium carbonate, and in the presence of a suitable protecting group reagent such as 2-(trimethylsilyl)ethoxymethyl chloride, acetyl chloride, or di-tert-butyl dicarbonate, and in the presence of a solvent such as tetrahydrofuran, methanol, water, acetonitrile, or dimethylformamide. Such reactions are well known in the literature.

[0070] Alternatively, the compound of formula I can be prepared by reacting a compound of formula XIII with a compound of formula XVI, 3can be prepared by metal-catalyzed C—H activation and arylation by reacting a halogen, preferably iodine, bromine or chlorine (Scheme 3).

[0071] Scheme 3: [ka] 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(π-cinnamyl) chloride dimer, or a copper catalyst such as cuprous iodide, copper acetate, copper bromide, or a combination of these palladium and copper catalysts. The reaction is typically carried out in the presence of a ligand, e.g., a phosphine-based ligand such as 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 be carried out, optionally under microwave irradiation, at temperatures ranging from 20°C to 200°C, and in the presence of solvents such as xylene, toluene, dioxane, acetic acid, or dimethylformamide. Such reactions have been described in the literature.

[0072] A compound of formula XIII, wherein R 2 and R 4 is as described in formula I above) can be converted into a compound of formula XIV (wherein R 2 and R 4is as described in Formula I above) with a compound of Formula III (wherein LG1 is a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g., triflate)).

[0073] Compounds of formula I-5 are compounds of formula I, where R 2 is -CF2H, and R 4 is -H, 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, compounds of formula I-5 can be prepared by converting compounds of formula VIII to compounds of formula Ia using a compound of formula XXV (wherein X 3 is a leaving group such as, for example, chlorine, bromine or iodine) with a compound of formula Yb3-Q XXVI, where Q is as defined in formula I above and Yb3 is, for example, B(OH)2 or B(OR b3 )2, and R b3 may be a C1-C4 alkyl group or may be two groups OR b3 can be prepared by Suzuki cross-coupling reaction between a compound of formula (which may be taken together with the boron atom to form a five-membered ring, e.g., pinacolboronic acid ester).

[0074] Compounds of formula XXV can be prepared from compounds of formula XXIV via a fluorination reaction using fluorinating agents such as diethylaminosulfur trifluoride or bis(2-methoxyethyl)aminosulfur trifluoride, among others. Compounds of formula XXIV can be prepared from compounds of formula XXIII via an oxidation reaction using oxidizing agents such as MnO, SO, pyridine, pyridinium dichromate, or pyridinium chlorochromate, among other alcohol oxidizing agents.

[0075] Scheme 4:- [ka] Alternatively, compounds of formula XXIV can be prepared according to Scheme 5.

[0076] Scheme 5: [ka] A compound of Formula XXIV can be prepared by reacting a compound of Formula XXVIII with a compound of Formula XXVII, following a procedure similar to that described in Scheme 1 for the conversion of a compound of Formula IV to a compound of Formula I-2. A compound of Formula XXVIII can be prepared from a compound of Formula XXIX via halogenation followed by an N-deprotection reaction. The halogenation reaction can be carried out in one step under radical conditions using a halogenating reagent such as N-bromosuccinimide in the presence of a radical initiator such as azobisisobutyronitrile. Deprotection reactions are well known to those skilled in the art and can be carried out, for example, using HCl under base or acid catalysts. A compound of Formula XXIX can be prepared from a compound of Formula XXX by providing a protecting group. Such a reaction can be carried out in the presence of a base such as sodium hydride, potassium carbonate, or sodium carbonate, and a suitable protecting group reagent such as 2-(trimethylsilyl)ethoxymethyl chloride, acetyl chloride, or di-tert-butyl dicarbonate, and in the presence of a solvent such as tetrahydrofuran, methanol, water, acetonitrile, or dimethylformamide.

[0077] The compound of formula XXIII can be prepared by the reaction of formula XXII, where R 21Compounds of formula XXII can be prepared from compounds of formula XX with compounds of formula XXI (wherein LG2 is a halogen, preferably iodine, bromine, or chlorine (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g., triflate)) in the presence of a base such as sodium hydride or an alkaline earth metal hydride, a carbonate (e.g., sodium carbonate, potassium carbonate, or cesium carbonate), or a 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, at a temperature between 0 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 procedures similar to those described in Scheme 2 for the conversion of compounds of formula XII to compounds of formula IX.

[0078] Alternatively, compounds of formula I-5 can be prepared according to Scheme 6.

[0079] Scheme 6:- [ka] In Scheme 6, compounds of formula I-5 can be prepared from compounds of formula XXXIV via a fluorination reaction using, among others, fluorinating agents such as diethylaminosulfur trifluoride or bis(2-methoxyethyl)aminosulfur trifluoride. Compounds of formula XXXIV can be prepared by converting compounds of formula XXXII to compounds of formula XXXIII (wherein LG3 is a halogen, preferably iodine, bromine, or chlorine (or pseudohalides)) in the presence of a base such as sodium hydride or alkaline earth metal hydrides, carbonates (e.g., sodium carbonate, potassium carbonate, or cesium carbonate), or hydroxides, 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 at temperatures between 0 and 120°C, according to procedures well known to those skilled in the art. Compounds of formula XXXII can be prepared from compounds of formula XXXI via oxidation using oxidizing agents such as MnO, SO, pyridine, pyridinium dichromate, or pyridinium chlorochromate, among other alcohol-oxidizing agents. Compounds of formula XXXI can be prepared according to procedures reported in the literature, for example, J. Med. Chem. 1995, 38, 2251-2255.

[0080] Alternatively, compounds of formula XXXIV can be prepared according to Scheme 7. In Scheme 7, compounds of formula XXXIV can be prepared by reacting compounds of formula XXXII with compounds of formula XXXIII according to the procedures described in Scheme 6.

[0081] Scheme 7: [ka] The compound of formula XXXII can be prepared by reacting the compound of formula XXXV with a suitable reducing agent such as diisobutylaluminum hydride. The compound of formula XXXV can be prepared by reacting the compound of formula XXXVI with ammonium hydroxide or other similar ammonia substitutes to convert the trifluoromethyl group to a cyano group. Such reactions are well documented in the literature (see, for example, Matthews, DP; Whitten, JP; McCarthy, JR J Org. Chem. 1986, 51, 3228). The synthesis of the imidazole compound of formula XXXVI is well documented in the literature (see, for example, Journal of Medicinal Chemistry, 2000, 43, 2165 and Synthetic Communications, 2020, 50, 700).

[0082] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention, as shown in the table below. [Example]

[0083] Example 1: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.001) [ka] Step 1: Preparation of 3,3,3-trifluoro-2-oxo-propanal (I5) [ka] A 100 mL flask was charged with sodium acetate (1.41 g, 17.05 mmol) and water (5.00 mL). 1,1-Dibromo-3,3,3-trifluoroacetone (2.325 g, 8.186 mmol) was added to the above solution to give a cloudy 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.

[0084] Step 2: Preparation of 2-(5-chloro-2-thienyl)-4-(trifluoromethyl)-1H-imidazole (I6) [ka] To a three-necked 250 mL flask was added 5-chlorothiophene-2-carbaldehyde (1.000 g, 6.822 mmol), methanol (20.00 mL), and 35% aqueous ammonia (5.00 mL, 44 mmol) to give a colorless solution. To this was added the reaction mixture of I5 prepared in Step 1 above, dropwise, over 30 minutes via an addition funnel. After complete addition, the reaction was stirred at room temperature for 3 hours. The organics were removed in vacuo, and the residue was partitioned between ethyl acetate and water, and the phases were separated. The aqueous phase was extracted with ethyl acetate (3 × 20 mL). The organics were combined, washed with saturated brine, and concentrated onto granulated Celite. The crude material was subjected to column chromatography on silica gel using 0–100% ethyl acetate in cyclohexane to give 2-(5-chloro-2-thienyl)-4-(trifluoromethyl)-1H-imidazole (I6) as a pale yellow solid (0.952 g, 55% yield). 1 H NMR(400MHz,CD3OD)δ=7.65-7.58(m,1H),7.41-7.36(m,1H),7.09-7.00(m,1H)

[0085] Step 3: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.001) [ka] To a 25 mL flask was added 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), 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 h, the reaction mixture was allowed to cool to room temperature. The reaction mixture was diluted with water (10 mL) and brine (10 mL) and extracted with ethyl acetate (2 × 15 mL). The combined organics were passed through a hydrophobic frit and evaporated under reduced pressure to give the 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 as a pale yellow gum (96 mg, 73% yield). 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)

[0086] Example 2: Preparation of 5-chloro-2-[[2-(3-methylimidazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.013) [ka] Step 1: Preparation of 5-chloro-2-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (I7) [ka] To a solution of 4-(trifluoromethyl)-1H-imidazole (204 mg, 1.47 mmol) in MeCN (4.8 mL) and HO (0.04 mL) was added KCO (603 mg, 4.3629 mmol) and 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (365 mg, 1.7384 mmol). The reaction mixture was heated to 80 °C for 22 h, allowed to cool to room temperature, diluted with HO, and extracted with ethyl acetate (×3). The combined organic extracts were absorbed onto silica gel and purified by flash chromatography on silica gel using a gradient of 0 to 70% ethyl acetate in cyclohexane as eluent to afford 5-chloro-2-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I7 (275 mg, 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)

[0087] Step 2: Synthesis of 5-chloro-2-[[2-(3-methylimidazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.013) [ka] To a solution of 5-chloro-2-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I7 (149 mg, 0.53899 mmol) in toluene (4 mL) under an atmosphere of N was added palladium(II) acetate (7 mg, 0.0296 mmol), 5-bromo-1-methyl-1H-imidazole (140 mg, 0.843473 mmol), copper(I) iodine (209 mg, 1.0974 mmol), DBU (0.17 mL, 1.1 mmol), and triphenylphosphine (15 mg, 0.0560 mmol). The reaction mixture was heated in a microwave at 150 °C for 4 h, allowed to cool to room temperature, diluted with HO, and extracted with ethyl acetate (x3). The combined organic extracts were absorbed onto silica gel and purified by flash chromatography on silica gel using a gradient of 0 to 50% ethyl acetate in cyclohexane as eluent. The product-rich fractions were absorbed onto silica gel and further purified by reverse-phase flash chromatography using a gradient of 40-70% MeCN in HO as eluent to afford 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)

[0088] Example 3: Preparation of 5-chloro-2-[[2-(1,5-dimethylpyrazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.012 [ka] Step 1 - Preparation of trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (I8): [ka] To a suspension of 4-(trifluoromethyl)-1H-imidazole (3.07 g, 22.6 mmol) and K2CO3 (9.14 g, 66.1 mmol) in MeCN (45 mL) was added 2-(chloromethoxy)ethyl-trimethyl-silane (5.5 g, 5.8 mL, 33 mmol), and the reaction mixture was rapidly stirred at room temperature under N2 for 24 h. Additional 2-(chloromethoxy)ethyl-trimethyl-silane (1.8 g, 1.9 mL) was added dropwise to the reaction mixture, and the reaction was stirred at room temperature for 4 h. The reaction mixture was quenched with saturated brine (50 mL), and ethyl acetate (50 mL) was added. The phases were separated, and the aqueous phase was extracted with ethyl acetate (3 x 50 mL). The organics were combined, washed with saturated brine, and concentrated onto granulated Celite. The crude product was purified by flash chromatography on silica gel using a gradient of 0 to 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)

[0089] Step 2 - Preparation of 2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl-trimethyl-silane (I9): [ka] A solution of trimethyl-[2-[[4-(trifluoromethyl)imidazol-1-yl]methoxy]ethyl]silane (I8) (1.00 g, 3.76 mmol) in THF (20 mL) was cooled to an internal temperature of −70 °C under N2. n-BuLi (2.5 M in hexanes) (2.00 mL, 5.0 mmol) was added dropwise to maintain a constant temperature below −60 °C. The reaction mixture was then stirred at −70 °C for 0.5 h. To the reaction mixture was added I2 (1.25 g, 4.92 mmol) in one portion. The reaction mixture was stirred at −70 °C for 1 h, then warmed to room temperature and stirred overnight. The reaction mixture was quenched with 2 M sodium thiosulfate (25 mL) and ethyl acetate (25 mL) was added. The phases were separated and the aqueous phase was extracted with ethyl acetate (3 × 25 mL). The organics were combined and washed with saturated brine (25 mL). The organics were concentrated onto granulated Celite, and the crude product was purified by flash chromatography on silica gel using a gradient of 0 to 50% ethyl acetate in cyclohexane as eluent to afford 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)

[0090] Step 3 - Preparation of 2-iodo-4-(trifluoromethyl)-1H-imidazole hydrochloride I10: [ka] 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) at room temperature was added HCl (6 M) (2.00 mL, 12.00 mmol), and the reaction was heated to 60 °C under N for 3.5 h. The reaction mixture was concentrated in vacuo to give 2-iodo-4-(trifluoromethyl)-1H-imidazole hydrochloride I10 (0.348 g, 91% yield) as a white solid. 1H NMR(400MHz,CD3OD)δ=7.83(q,1H)

[0091] Step 4 - Preparation of 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I11: [ka] 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) was added KCO (0.54 g, 3.88 mmol) and HO (0.18 mL). 5-Chloro-2-(chloromethyl)pyrimidine hydrochloride (0.28 g, 1.33 mmol) was added and the reaction was heated to 80 °C for 1.5 h. The reaction was cooled to room temperature and concentrated onto granulated Celite. The crude product was purified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in cyclohexane as eluent to afford 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)

[0092] Step 5 - Preparation of 5-chloro-2-[[2-(1,5-dimethylpyrazol-4-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine (1.012): [ka] A 2-5 mL microwave vial was charged with 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I11 (0.13 g, 0.33 mmol), 1,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.10 g, 0.46 mmol), and (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride (13 mg, 0.016 mmol). The vessel was placed under an atmosphere of N2 and sealed. THF (2.00 mL) and potassium phosphate tribasic (1.0 M in water) (1.00 mL, 1.00 mmol) were added and heated to 80 °C under microwave irradiation for 1 h. The reaction was 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 to 100% ethyl acetate / cyclohexane as eluent to afford 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. 1 H 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)

[0093] Example 4: Preparation of 5-chloro-2-[[2-(5-chloro-3-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.064 [ka] Step 1 - Preparation of 1-(2-trimethylsilyloxyethyl)imidazole-4-carbaldehyde (I12): [ka] To a solution of 1H-imidazole-4-carbaldehyde (10.0 g, 104 mmol) in tetrahydrofuran (104 mL) was added sodium hydride (5.0 g, 125 mmol, 60% in mineral oil) at 0 °C. The mixture was stirred at 0 °C for 15 minutes, 2-(trimethylsilyl)ethoxymethyl chloride (22.5 mL, 114 mmol) was added, and the mixture was then stirred at 25 °C for 10 hours. The reaction mass was cooled to 0 °C and quenched with saturated ammonium chloride solution. It was extracted with ethyl acetate (3 × 200 mL). The combined organic phase was washed with brine (100 mL), dried over anhydrous NaSO, filtered, and concentrated to give 1-(2-trimethylsilyloxyethyl)imidazole-4-carbaldehyde I12 (23 g, 100%) as a colorless oil. The compound was obtained as a mixture of isomers (2:1), which was used in the next step without further purification. 1 H NMR(400MHz,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).

[0094] Step 2 - Preparation of 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carbaldehyde (I13): [ka] To a stirred solution of 1-(2-trimethylsilylethoxymethyl)imidazole-4-carbaldehyde I12 (2.5 g, 11 mmol) in carbon tetrachloride (50 mL) was added azobisisobutyronitrile (0.093 g, 0.55 mmol). N-bromosuccinimide (2.2 g, 12 mmol) was added at room temperature and heated at 90 °C for 30 hours. The reaction mixture was quenched with sodium thiosulfate solution and extracted with ethyl acetate (3 × 200 ml). The combined organic layers were washed with brine solution, dried over anhydrous NaSO, filtered, and concentrated to give the crude material. The crude material was purified by silica column chromatography using 30% ethyl acetate in cyclohexane to give 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carbaldehyde I13 (3.0 g, 89%) as an oil. The compound was obtained as a mixture of isomers (2:1), which was used in the next step without further purification. 1 H NMR(400MHz,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).

[0095] Step 3 - Preparation of 2-bromo-1H-imidazole-4-carbaldehyde (I14): [ka] To a solution of 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carbaldehyde I13 (9.8 g, 32 mmol) in acetonitrile (98 mL) was added 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-carbaldehyde I14 (9.3 g, 100%) as the 2,2,2-trifluoroacetic acid salt. The crude material was used directly in the next step without further purification.

[0096] Step 4 - Preparation of 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carbaldehyde (I15): [ka] To a solution of 2-bromo-1H-imidazole-4-carbaldehyde 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 reaction was cooled to room temperature, diluted with 100 mL of ice-cold water, and extracted with ethyl acetate (4 × 200 mL). The organic layer was washed with brine solution (100 mL), dried over anhydrous NaSO, filtered, and concentrated to give the 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. Upon concentration, 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carbaldehyde I15 (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).

[0097] Step 5 - Preparation of 2-[[2-bromo-4-(difluoromethyl)imidazol-1-yl]methyl]-5-chloro-pyrimidine (I16): [ka] To a solution of 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carbaldehyde I15 (0.773 g, 2.56 mmol) in dichloromethane (50 mL, 778 mmol) was added diethylaminosulfur trifluoride (3.32 g, 20.6 mmol) at 0 °C. The reaction mixture was rapidly stirred at 0 °C under nitrogen, then warmed to room temperature and stirred for 3 h. The reaction mixture was cooled to 0 °C and quenched by the slow addition of saturated NaHCO (100 mL). The reaction mass was extracted with ethyl acetate (3 × 100 ml). The combined organic layers were washed with brine solution, dried over anhydrous NaSO, filtered, and concentrated to give the crude material. The crude product was purified by column chromatography using 20% ethyl acetate in cyclohexane to give 2-[[2-bromo-4-(difluoromethyl)imidazol-1-yl]methyl]-5-chloro-pyrimidine I16 (0.44 g, 53%). 1H NMR (400 MHz, CDCl3) δ = 8.69 (s, 2H), 7.37 (t, 1H), 6.64 (t, 1H), 5.36 (s, 2H).

[0098] Step 6 - Preparation of 5-chloro-2-[[2-(5-chloro-3-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.064: [ka] 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) in a 30 mL microwave vial, tribasic potassium phosphate (0.418 g, 1.93 mmol) was added, followed by (5-chloro-3-thienyl)boronic acid (0.25 g, 1.54 mmol). The reaction mixture was purged with nitrogen for 5 minutes and then with [1,1'-bis-(diphenylphosphino)ferrocene]-dichloropalladium(II). Dichloromethane complex (0.031 g, 0.038 mmol) was added to it. The reaction mixture was heated at 120 °C in a microwave oven for 2 hours. The reaction mixture was cooled to room temperature and slowly poured into an ice-cold solution of sodium bicarbonate. The reaction mass was extracted with ethyl acetate (3 x 100 ml). The combined organic phase was washed with brine solution, dried over anhydrous NaSO, filtered, and concentrated to give crude material. The crude product was purified by column chromatography (0-100%) using 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).

[0099] Example 5: Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.058 [ka] Step 1 - Preparation of ethyl 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate (I17): [ka] A three-necked 500 mL flask equipped with a thermometer was charged with sodium hydride (2.20 g, 55.0 mmol, 60%) and tetrahydrofuran (70 mL). The suspension was cooled to 0 °C under nitrogen. To this was then added ethyl 1H-imidazole-4-carboxylate (6.99 g, 49.9 mmol) in portions at a rate such that the internal temperature did not exceed 8 °C. When gas evolution was complete, 2-(chloromethoxy)ethyl-trimethyl-silane (10.1 mL, 57.8 mmol) was added as a solution in tetrahydrofuran (15 mL) over 30 minutes. The reaction mixture was then allowed to warm to room temperature, and a white solid precipitated. The reaction mixture was stirred at room temperature under nitrogen for 3 hours. The reaction mixture was quenched with saturated brine and water. Ethyl acetate (150 mL) was then added, the phases were separated, and the aqueous phase was extracted with ethyl acetate (3 × 100 mL). The organics were combined, washed with saturated brine, and concentrated onto granulated Celite. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to afford ethyl 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate I17 (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).

[0100] Step 2 - Preparation of ethyl 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate (I18): [ka] Ethyl 1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate I17 (9.90 g, 36.6 mmol) and acetonitrile (100 mL) were added to a 500 mL three-neck flask equipped with a condenser and thermometer, resulting in a pale yellow solution. The solution was degassed for 30 minutes with a stream of nitrogen bubbling through the solution. N-Bromosuccinimide (8.64 g, 47.6 mmol) was added, followed by azobisisobutyronitrile (0.307 g, 1.83 mmol), and the reaction mixture was heated to 65 °C under nitrogen for 6 hours. The reaction was quenched with 100 mL of 2 M sodium thiosulfate, and 100 mL of ethyl acetate and 100 mL of brine were added. The phases were separated, the aqueous layer was extracted with ethyl acetate (3 × 200 mL), and the organics were combined, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The crude product was purified by column chromatography using 0-100% ethyl acetate in cyclohexane to afford ethyl 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate I18 (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).

[0101] Step 3 - Preparation of ethyl 2-bromo-1H-imidazole-4-carboxylate (I19): [ka] A 500 mL flask was charged with ethanol (145 mL) in deionized water (14 mL, 168 mmol) and ethyl 2-bromo-1-(2-trimethylsilylethoxymethyl)imidazole-4-carboxylate I18 (5.78 g, 16.5 mmol) as a solution in HCl (12 M). The reaction was heated to 60 °C under nitrogen for 1.5 h. The reaction was concentrated in vacuo to give ethyl 2-bromo-1H-imidazole-4-carboxylate I19 (4.26 g, 96%) as a white solid. 1H NMR(400MHz,CD3OD)δ=8.04(s,1H),4.36(q,2H),1.35(t,3H).

[0102] Step 4 - Preparation of ethyl 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxylate (I20): [ka] A 100 mL flask was charged with ethyl 2-bromo-1H-imidazole-4-carboxylate hydrochloride salt 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 5-chloro-2-(chloromethyl)pyrimidine (2.84 g, 17.4 mmol) in one portion. The reaction mixture was then heated to 75 °C under air for 1 h. The reaction was cooled to room temperature. The reaction was quenched with 200 mL of 50% brine, and 200 mL of ethyl acetate was added. The phases were separated, the aqueous layer was extracted with ethyl acetate (3 × 200 mL), and the organics were combined, dried over anhydrous NaSO, filtered, and concentrated in vacuo. 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 I20 (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).

[0103] Step 5 - Preparation of ethyl 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxylate (I21): [ka] A microwave vial was charged with ethyl 2-bromo-1-[(5-chloropyrimidin-2-yl)methyl]imidazole-4-carboxylate I20 (0.1 g, 0.27 mmol), 5-chlorothiophene-2-boronic acid (0.053 g, 0.32 mmol), 2-methyltetrahydrofuran (2.00 mL), and potassium phosphate tribasic (1.0 M in water) (0.69 mL, 0.69 mmol). The flask was evacuated and back-filled with nitrogen three times. [1,1'-Bis(diphenylphosphino)ferrocene]dichloropalladium(II).dichloromethane complex (0.01 g, 0.012 mmol) was added to the vial, which was then evacuated and back-filled with nitrogen three times. The reaction was heated to 75 °C under nitrogen for 2 hours. The reaction was cooled to room temperature, quenched with 50 mL of water, and the phases were separated. The aqueous layer was extracted with ethyl acetate (3 × 50 mL), and the organics were combined, dried over anhydrous NaSO, filtered, and concentrated in vacuo. The crude product was purified by column chromatography using 0–100% ethyl acetate in cyclohexane to give 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).

[0104] Step 6 - Preparation of [1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazol-4-yl]methanol (I22): [ka] Ethyl 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carboxylate I21 (0.41 g, 1.07 mmol) and tetrahydrofuran (10 mL) were added to a three-necked 100 mL flask equipped with a thermometer, a dropping funnel, and a nitrogen inlet. The reaction was cooled to 0 °C under nitrogen, and 1 M diisobutylaluminum hydride in hexane (3.3 mL, 3.3 mmol) was added dropwise via the dropping funnel, maintaining the temperature below 15 °C. After complete addition, the reaction was then 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 at 0 °C by the dropwise addition of 0.131 mL of water, followed by 0.131 mL of 15% NaOH. To this was then added 0.33 mL of water dropwise. The reaction mixture was allowed to warm to room temperature for 30 min, and MgSO4 was added. The reaction mixture was then filtered through a pad of Celite, and the filtrate was concentrated in vacuo to give [1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazol-4-yl]methanol I22 (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).

[0105] Step 7 - Preparation of 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carbaldehyde (I23): [ka] A 250 mL flask was charged with [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, which was then rapidly stirred at room temperature under nitrogen overnight. The reaction was diluted with 150 mL of ethyl acetate and Celite was added. The suspension was then filtered through a pad 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).

[0106] Step 8 - Preparation of 5-chloro-2-[[2-(5-chloro-2-thienyl)-4-(difluoromethyl)imidazol-1-yl]methyl]pyrimidine 1.058: [ka] A 250 mL flask was charged with 1-[(5-chloropyrimidin-2-yl)methyl]-2-(5-chloro-2-thienyl)imidazole-4-carbaldehyde I23 (0.113 g, 0.33 mmol) and dichloromethane (10 mL). The reaction was cooled to 0 °C, diethylaminosulfur trifluoride (0.25 mL, 1.9 mmol) was added, and the reaction was rapidly stirred at 0 °C under nitrogen for 3 h. The reaction was allowed to warm to room temperature and left stirring for 16 h. After this time, the reaction mixture was cooled to 0 °C and quenched by the slow addition of 50 mL of saturated NaHCO3. 100 mL of dichloromethane was added, and the biphasic mixture was passed through a phase filter. The filtrate was concentrated to give the 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).

[0107] Example 6: Preparation of 2-chloro-5-[1-[(5-chloropyrimidin-2-yl)methyl]-4-(difluoromethyl)imidazol-2-yl]thiazole 1.071 [ka] Step 1 - Preparation of ethyl 2-chloro-5-[4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole (I24): [ka] To a 25 mL flask equipped with a reflux condenser and thermometer was added sodium acetate (1.68 g, 20.3 mmol) and water (6.00 mL). 1,1-Dibromo-3,3,3-trifluoroacetone (1.40 mL, 9.76 mmol) was added to give a cloudy solution / suspension. The reaction mixture was heated to 90°C for 30 minutes. The reaction mixture was then cooled to room temperature to give a solution of 1,1-dihydroxy-3,3,3-trifluoroacetone. To a separate 3-neck 100 mL flask was added 2-chlorothiazole-5-carbaldehyde (1.2 g, 8.131 mmol), methanol (18.00 mL), and aqueous ammonia (6.00 mL, 51 mmol) to give an orange solution. To this reaction mixture, the solution of 1,1-dihydroxy-3,3,3-trifluoroacetone (prepared above) was added dropwise over 0.5 h, maintaining the internal temperature at 45 °C using a dropping funnel (Note: the addition is exothermic). After complete addition, the reaction mixture was stirred overnight at room temperature under air. The reaction mixture was concentrated in vacuo to remove MeOH and excess NH3. The residue was diluted with water (10 ml) and ethyl acetate (30 ml). The phases were separated, and the aqueous phase was extracted with ethyl acetate (30 ml). The organics were combined, filtered through a hydrophobic filter, and concentrated. The crude product was purified by column chromatography using 0-50% ethyl acetate in cyclohexane to give ethyl 2-chloro-5-[4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole I24 (0.66 g, 32%). 1 H NMR(400MHz,CD3OD)δ=8.01(s,1H),7.71(s,1H).

[0108] Step 2 - Preparation of 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbonitrile (I25): [ka] To a vial was added 2-chloro-5-[4-(trifluoromethyl)-1H-imidazol-2-yl]thiazole I24 (0.663 g, 2.61 mmol), methanol (3.32 mL), and aqueous ammonia (6.2 mL, 39.2 mmol). The reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and evaporated under reduced pressure to give a brown gum. The crude product was purified by column chromatography using 0-50% ethyl acetate in cyclohexane to give 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).

[0109] Step 3 - Preparation of 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbaldehyde (I26): [ka] To a stirred solution of 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbonitrile I25 (0.320 g, 1.52 mmol) in tetrahydrofuran (4.00 mL) cooled to −78 °C under nitrogen, diisobutylaluminum hydride (1.0 M in toluene) (7.60 mL, 7.60 mmol) was added dropwise via syringe over 10 minutes. The reaction mixture was stirred at −78 °C for 1 hour, then allowed to warm to 0 °C and stirred at 0 °C for an additional hour. The reaction was quenched at 0 °C by adding 0.3 mL of water and 0.3 mL of 15% aqueous NaOH, and finally 0.76 mL of water. The reaction mixture was warmed to room temperature and stirred at room temperature for 15 minutes. Methyl tert-butyl ether (15 mL) was added to the reaction mixture, followed by Celite and MgSO4. The reaction mixture was filtered, and the filter cake was washed with ethyl acetate (3 x 20 ml). The filtrate was concentrated in vacuo to give 66 mg of a pale orange solid. The filter cake was neutralized with 2 M HCl, resuspended in ethyl acetate (50 ml), and stirred for 2.5 hours. The filtrate was concentrated in vacuo to give an additional 44 mg of an orange solid. The filter cake was acidified with 2 M HCl, resuspended in ethyl acetate (50 ml), and stirred for 30 minutes. The filtrate was concentrated in vacuo to give an additional 12 mg of an orange solid. The combined solids were dried to give 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbaldehyde I26 (112 mg, 34%) as an orange solid. 1 H NMR(400MHz,CD3OD)δ=9.65(s,1H),7.98(s,1H),7.88(s,1H).

[0110] Step 4 - Preparation of 1-[(5-chloropyrimidin-2-yl)methyl]-2-(2-chlorothiazol-5-yl)imidazole-4-carbaldehyde (I27): [ka] A 50 mL flask was charged with 2-(2-chlorothiazol-5-yl)-1H-imidazole-4-carbaldehyde I26 (0.112 g, 0.524 mmol) in acetonitrile (1.75 mL) and water (0.05 mL). 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. This mixture was heated to 70 °C. After 1 h, another 5-chloro-2-(chloromethyl)pyrimidine hydrochloride (55 mg, 0.26 mmol) and potassium carbonate (36 mg, 0.26 mmol) were added and heated for an additional 45 min. 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 × 15 mL). The combined organics were passed through a hydrophobic filter 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 to 100% ethyl acetate in cyclohexane to give 1-[(5-chloropyrimidin-2-yl)methyl]-2-(2-chlorothiazol-5-yl)imidazole-4-carbaldehyde I27 (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).

[0111] Step 5 - Preparation of 2-chloro-5-[1-[(5-chloropyrimidin-2-yl)methyl]-4-(difluoromethyl)imidazol-2-yl]thiazole 1.071: [ka] To a 50 mL three-neck flask was added 1-[(5-chloropyrimidin-2-yl)methyl]-2-(2-chlorothiazol-5-yl)imidazole-4-carbaldehyde I27 (0.09 g, 0.2646 mmol) and dichloromethane (5.3 mL). The reaction was cooled to 0 °C in an ice / water bath and stirred under nitrogen. Diethylaminosulfur trifluoride (0.28 mL, 2.1 mmol) was added to the reaction mixture, and the reaction mixture was rapidly stirred at 0 °C under nitrogen for 3 h. The reaction mixture was allowed to warm to room temperature and stirred at room temperature for an additional 48 h. After this time, the reaction mixture was cooled to 0 °C and quenched by the slow addition of saturated NaHCO3 (3 mL). 50 mL of dichloromethane was added, and the biphasic mixture was passed through a hydrophobic filter. The filtrate was concentrated to give an orange gum (105 mg). 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).

[0112] Example 7: 5-chloro-2-[[2-(4-chloropyrazol-1-yl)-4-(trifluoromethyl)imidazol-1-yl]methyl]-pyrimidine 1.065 [ka] To a solution of 5-chloro-2-[[2-iodo-4-(trifluoromethyl)imidazol-1-yl]methyl]pyrimidine I11 (prepared in Example 3, Step 4) (0.2 g, 0.51 mmol) in acetonitrile (2 mL) in a 30 mL microwave vial was added 4-chloro-1H-pyrazole (0.26 g, 2.57 mmol), followed by potassium carbonate (0.71 g, 5.14 mmol) and 8-hydroxyquinoline (0.03 g, 0.20 mmol). The reaction mixture was degassed by bubbling nitrogen through it for 5 minutes, and then tetrakis(acetonitrile)copper(I) tetrafluoroborate (0.033 g, 0.10 mmol) was added to it, and the reaction mixture was heated at 130 °C for 1.5 hours. The reaction was cooled to room temperature, diluted with 70 mL of water, and extracted with ethyl acetate (4 × 80 mL). The organic layer was washed with brine solution (25 mL), dried over anhydrous NaSO, filtered, and concentrated to give 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).

[0113] [Table 1-1] [Table 1-2] [Table 1-3] [Table 1-4] [Table 1-5] [Table 1-6]

Table 1-7

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

Table 1-14

[0114]

Table 2

[0115] examples of biology Seeds of various test species: Amaranthus retroflexus (AMARE), barnyardgrass (Echinochloa crus-galli) (ECHCG), and foxtail (Setaria faberi) (SETFA) are sown in pots in standard soil. After 1 day of incubation (pre-emergence) or 8 days of incubation (post-emergence) under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours of light; 65% humidity), the plants are sprayed with an aqueous spray solution obtained from a formulation of the technical 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 are applied at 250 g / ha. The test plants were then grown in a greenhouse under controlled conditions (24 / 16°C day / night; 14 hours light; 65% humidity) and watered twice daily. After 13 days for pre- and post-emergence, the tests were evaluated for the percentage of damage caused to the plants. Biological activity is shown in the table below on a 5-point scale (5 = 81-100%; 4 = 61-80%; 3 = 41-60%; 2 = 21-40%; 1 = 0-20%).

[0116] [Table 3-1] [Table 3-2]

[0117] [Table 4-1] [Table 4-2]

Claims

1. Equation (I): 【Chemistry 1】 (In the formula, A is CR 5 or N; Q is one or two R 3 It is a five-membered heteroaryl compound which may be optionally substituted with substituents. R 1 is independently selected from the group consisting of halogen, -CN, C 1 to C 2 alkyl, C 1 to C 2 haloalkyl, C 3 to C 6 cycloalkyl, C 1 to C 2 alkoxy- and C 1 to C 2 haloalkoxy-; R 2 These are halogen, -CN, NO 2 , C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy, -C(O)C 1 ~C 4 Alkyl, -C(O)OC 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkoxy, -S(O) p C 1 ~C 4 Alkyl, -C(R) 6 ) = NOR 7 and C 3 ~C 6 Selected from the group consisting of cycloalkyl groups; R 3 is halogen, C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy, C 1 ~C 4 Haloalkoxy, C 1 ~C 4 Alkoxy C 1 ~C 3 Alkyl-, C 1 ~C 4 Alkoxy C 1 ~C 3 Alkoxy-, C 1 ~C 4 Alkoxy C 1 ~C 3 Alkoxy C 1 ~C 3 Alkyl-, -CN, NO 2 , C 2 ~C 4 Alkenil, C 2 ~C 4 Alkinyl, -S(O) p C 1 ~C 4 Alkyl, -S(O) p C 1 ~C 4 Haloalkyl, -C(O)OC 1 ~C 4 Alkyl and -C(O)NR 8 R 9 Independently selected from the group consisting of; R 4 is independently selected from the group consisting of hydrogen, halogen, C 1 to C 4 alkyl, C 1 to C 4 haloalkyl, C 1 to C 4 alkoxy, C 1 to C 4 haloalkoxy, -CN, NO 2 , C 2 to C 4 alkenyl, C 2 to C 4 alkynyl, -S(O) p C 1 to C 4 alkyl, -S(O) p C 1 to C 4 haloalkyl, -C(O)OC 1 to C 4 alkyl and -C(O)NR 8 R 9 ; and R 5 is selected from the group consisting of hydrogen, fluoro, chloro and -CN; R 6 is hydrogen or C 1 ~C 4 It is alkyl; R 7 is hydrogen or C 1 ~C 2 It is alkyl; R 8 is hydrogen or C 1 ~C 4 It is alkyl; R 9 is hydrogen or C 1 ~C 4 It is alkyl; m = 1 or 2; p = 0, 1, or 2) Compounds thereof, or agronomically acceptable salts thereof.

2. Equation (Ia) 【Chemistry 2】 (In the formula, Q, R 1 , R 2 and R 4 (This is as defined in claim 1.) The compound of formula (I) as described in claim 1.

3. R 4 The compound according to claim 1, wherein the compound is hydrogen.

4. R 1 The compound according to claim 1, wherein is chloro.

5. R 2 ga-CF 3 or -CF 2 The compound according to claim 1, wherein H.

6. Q: 【Transformation 3】 (In the formula, R 3 is hydrogen or as defined in claim 1, R 3a is hydrogen, methyl, ethyl, CHF 2 Selected from the group consisting of and cyclopropyl, R 3b (Selected from the group consisting of hydrogen, fluoro, chloro, and bromo.) A compound according to claim 1, selected from the group consisting of the following.

7. The compound according to claim 1, 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. The compound according to claim 1, wherein Q is selected from the group consisting of Q-1, Q-14, Q-22, Q-23, Q-41, and Q-43.

9. R 3 The compound according to claim 8, wherein is chloro.

10. A herbicide composition comprising the compound described in any one of claims 1 to 9 and an agriculturally acceptable formulation aid.

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

12. The herbicide composition according to claim 11, wherein the additional pesticide is a herbicide or a herbicide phytotoxicity reducer.

13. A method for controlling weeds in a certain location, comprising applying a composition according to claim 10 to the location in an amount sufficient to control the weeds.

14. Use of the compound of formula (I) as defined in claim 1 as a herbicide.

15. Compound of formula (VIIIa): 【Chemistry 4】 (In the formula, R 2 and R 4 (wherein X2a is hydrogen or halogen, as defined in claim 1).

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