Herbicidal pyrazole compounds

Abstract

The present invention relates to a compound having formula (I) or an agronomically acceptable salt of said compound, wherein Q, R1, R2, R3 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 novel herbicidal compounds, processes for their preparation, herbicidal compositions comprising these novel compounds, and their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.

[0002] WO 2022 / 013293, WO 2022 / 101270 and WO 2023 / 099354 disclose herbicidal pyrazole compounds featuring a pyrimidine ring.

[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] Q is phenyl or C-linked 6-membered heteroaryl, wherein the phenyl or 6-membered heteroaryl is optionally substituted by one or more R 4 replace;

[0008] R 1 independently selected from the group consisting of halogen, -CN, NO2, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, C1-C4 alkoxy-, -C(O)C1-C4 alkyl, -C(O)OC1-C4 alkyl, C1-C4 haloalkoxy and C1-C4 alkoxyC1-C3 alkyl-;

[0009] 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, C1-C4 alkoxyC1-C3 alkyl-, C1-C4 alkoxyC1-C3 alkoxy-, C1-C4 alkoxyC1-C3 alkoxyC1-C3 alkyl-, -S(O) p C1-C4 alkyl and C3-C6 cycloalkyl;

[0010] R 3Selected from the group consisting of hydrogen, 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, -C(R 7 )=NOR 8 and -C(O)NR 5 R 6 ;

[0011] R 4 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 5 R 6 ;

[0012] R 5 is hydrogen or C1-C4 alkyl;

[0013] R 6 is hydrogen or C1-C4 alkyl;

[0014] R 7 is hydrogen or C1-C4 alkyl;

[0015] R 8 is hydrogen or C1-C2 alkyl;

[0016] m = 0, 1, or 2; and

[0017] p=0, 1 or 2.

[0018] 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).

[0019] C2-C4 alkenyl - includes, for example, -CH=CH2 (vinyl) and -CH2-CH=CH2 (allyl).

[0020] 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 groups include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.

[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-C4 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 and heptafluoro-n-propyl. C1-C2 haloalkyl is, 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-C6 alkoxy group includes a methoxy group and an ethoxy group.

[0024] C1-C4 haloalkoxy - includes, 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] C1-C4 alkoxy C1-C3 alkyl- includes, for example, methoxymethyl-.

[0026] C1-C4 alkoxy C1-C3 alkoxy- includes, for example, methoxyethoxy-.

[0027] C1-C4 alkoxy C1-C3 alkoxy C1-C3 alkyl- includes, for example, methoxyethoxymethyl-.

[0028] The C3-C6 cycloalkyl group includes cyclopropyl, cyclopentyl and cyclohexyl.

[0029] C1-C4 alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0030] The C1-C4 alkyl-S(O)-(alkylsulfinyl) group includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0031] 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.

[0032] In one embodiment of the present invention, R 3 It's hydrogen.

[0033] In one embodiment of the present invention, there is provided a compound having formula (I), wherein m is 1 or 2, and R 1 Independently selected from the group consisting of halogen (e.g., F, Cl or Br), -CN, C1-C4 alkyl (e.g., Me), C1-C4 haloalkyl (e.g., CHF2 or CF3), C1-C4 alkoxy- (e.g., MeO-) and C1-C4 haloalkoxy (e.g., CF3O-, CHF2O-).

[0034] In another embodiment of the present invention, m is 1. In another embodiment of the present invention, m is 2.

[0035] In a preferred embodiment of the present invention, m is 1 and R 1 is a halogen (eg, chlorine).

[0036] In another preferred embodiment of the present invention, R 2 is selected from the group consisting of halogen, C1-C4 haloalkyl- (preferably, CF3 or -CF2H), cPr and CN. In a preferred embodiment, R 2 is C1-C4 haloalkyl (preferably, -CF3 or -CF2H).

[0037] In another embodiment of the present invention, Q is selected from the group consisting of:

[0038]

[0039] Where n is 0, 1, or 2.

[0040] In a preferred embodiment of the present invention, Q is selected from the group consisting of: Q-1, Q-3 and Q-4. Therefore, in a more preferred embodiment of the present invention, the compound having formula (I) has formula (Ia'), formula (Ib') or formula (Ic'):

[0041]

[0042] In another preferred embodiment, n is 1. In this embodiment, R 4 Preferably it is selected from the group consisting of cyano, methyl, halogen and -CF3. In a particularly preferred embodiment, Q is 4-Cl-phenyl-.

[0043] In another embodiment of the present invention, Q is Q-3 and n is 2. Therefore, in a more preferred embodiment of the present invention, the compound of formula (I) is a compound of formula (Iba):

[0044]

[0045] where R 4a is halogen, preferably fluorine or chlorine, and R 4b is preferably fluorine or chlorine; and wherein R 1 、R 2 and R 3 is as defined in formula (I). In a more preferred embodiment, there is provided a compound of formula (Iba') wherein R 1 is chlorine, R 2 is -CF3 or -CF2H, and R 3 is hydrogen. Compounds of formula (Iba') are particularly preferred in the context of the present invention, since they typically exhibit improved crop selectivity, in particular in maize.

[0046] 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 enhanced biological activity compared to the other possibility.

[0047] The present invention also provides agronomically acceptable salts of compounds of formula (I). Preferred are salts of compounds of formula (I) that can be formed with amines, including primary, secondary and tertiary amines (e.g., ammonia, dimethylamine and triethylamine); alkali metal bases and alkaline earth metal bases, transition metal bases or quaternary ammonium bases.

[0048] 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). The present invention further provides herbicidal compositions comprising a herbicidal compound according to any one of the preceding claims and an agriculturally acceptable formulation adjuvant. The compositions may be in the form of concentrates that are diluted before use, although ready-to-use compositions can also be prepared. Final dilution is usually carried out with water, but can be carried out using, for example, liquid fertilizers, micronutrients, biological organisms, oils or solvents instead of or in addition to water.

[0049] 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.

[0050] 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), parent drugs (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 envisioned and the physical, chemical and biological properties of the compound of formula (I).

[0051] 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 such 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).

[0052] 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).

[0053] Granules (GR) can 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. 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, dextrin, sugars and vegetable oils). One or more other additives (such as emulsifiers, wetting agents or dispersants) may also be included in the granules.

[0054] 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 (e.g. to improve water dilution or to prevent crystallization in the spray tank).

[0055] 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 spontaneously emulsify when added to water, producing an emulsion with sufficient stability to allow spray application via appropriate equipment.

[0056] 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 suitable 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 with low solubility in water.

[0057] Microemulsions (MEs) 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.

[0058] Suspension concentrates (SC) can include aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound with formula (I). SC can be prepared by ball milling or bead milling a solid compound with formula (I) in a suitable medium with one or more dispersants, to produce a fine particle suspension of the compound. One or more wetting agents can be included in the composition, and a suspending agent can be included to reduce the rate of particle settling. Alternatively, dry grinding can be used to add the compound with formula (I) to the water containing the reagent described above, to produce the desired final product.

[0059] Aerosol formulations comprise a compound of formula (I) and a suitable propellant (e.g., n-butane). The compound of formula (I) can 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.

[0060] Capsule suspensions (CS) can be prepared in a manner similar to that of EW formulations, but with an additional polymerization stage to obtain an aqueous dispersion of oil droplets, each of which is encapsulated by a polymer shell and containing a compound of formula (I) and optionally a carrier or diluent for the droplet. The polymer shell can be produced by an interfacial polycondensation reaction or by a coacervation procedure. These compositions can provide controlled release of the compound of formula (I) and can be used for seed treatment. The compound of formula (I) can also be formulated in a biodegradable polymer matrix to provide slow, controlled release of the compound.

[0061] The composition may contain 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 the 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 the compound of formula (I)).

[0062] The wetting agent, dispersant and emulsifier may be a cationic, anionic, amphoteric or nonionic SAA.

[0063] Suitable cationic types of SAA include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0064] Suitable anionic SAAs include alkali metal salts of fatty acids, salts of fatty 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 (primarily monoesters) or with phosphorus pentoxide (primarily diesters), such as the reaction of lauryl alcohol with tetraphosphoric acid; alternatively, these products may be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, ligninsulfonates, and phosphates / sulfates of tristyrylphenol.

[0065] Suitable amphoteric types of SAA include betaine, propionate and glycinate.

[0066] 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 said 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.

[0067] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0068] The compounds of the present 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), bennitroprop-butyl, ametryn, amitriptyline, aminopyralid, aminotriazole, atrazine, flubutyric acid-M, quinclorac, bensulfuron-methyl (including bensulfuron-methyl), bentazone, bicyclpyrone, bialaphos, bispyribac-sodium, bixlozone, herbicide, bromoxynil, butachlor, flubutyric acid-butyl, mesotrione (including mesotrione-ethyl), chlorsulfuron (including chlorsulfuron-methyl), chlorsulfuron (including chlorsulfuron-ethyl), chlorotoluron, chlorsulfuron, cyproconazole, chlorpyrifos, chlorpyrifos-butyl, chlorpyrifos-sodium, chlorpyrifos-butyl ... lacyfos), 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, dichloropropane, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), diclosulam, diflufenican, fluazifop-butyl, dimethachlor, dimethofuram-S, dioxopyritrione, diquat dibromide, diquat dichlorvos ... Methiocarb, epyrifenacil, ethoxyfluanid, oxazolidinone (including oxazolidinone-ethyl), fenoxasulfone, fenpyrasulfone, fenquinotrione, tetrazolam, fluazifop-methyl, bispyribac, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop-methyl (including fluazifop-butyl), fluazifop-methyl (including fluazifop-sodium), flufenacet, fluazifop-methyl ... including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including L-glufosinate and its ammonium salts), glyphosate (including its hydrazine, isopropyl ammonium and potassium salts), halauxifen (including halauxifen-methyl), haloxalopropyl (including haloxalopropyl-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapyr, imazapyr, imazethapyr, indazine fluazifop, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium),Iobenzonitrile, isoproturon, isoxaflutol, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methizolin, isopropylamine, sulfamethoxazole, metribuzin, metsulfuron-methyl, propamide, nicosulfuron, norfadazole, oxadiazon, oxasulfuron-methyl, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, benzylpyridinium, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryn, propanil, oxadiazon-butyl, propyrisulfuron, propyrisulfuron, propenylsulfuron, benzylpyridinium chloride, Carbendazim, prosulfuron, pyraflufen, pyraflufen (including pyraflufen-ethyl), pyraflufen, pyridasulfuron, pyridasulfuron, cypermethrin, pyrimisulfan, pyroxasulfone, pyrosulfuron, quinclorac, clomaclorac, quizalofop-P (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, sulfamethoxam, pyrifos, sethoxydim, simazine, metolachlor, sulfentrazone, sulfentrazone, tebuthion, tefurin, tetflupyrolimet , thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, benzylpyrazone, triafamone, triafamone, wild wheat chlorpyrifos, ether bensulfuron-methyl, bensulfuron-methyl (including bensulfuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, trifluralin, trifloxysulfuron, 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 esters, 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,4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate and cyanomethyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazol-2-yl oxazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide Formamide, ethyl 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridinyl]oxy]acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]propanoic acid, tetrahydrofuran-2-ylmethyl 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridinyl)oxy]propanoate -yl methyl ester, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-[(R)-propylsulfinyl]-4-(trifluoromethyl)benzamide, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-propylsulfinyl-4-(trifluoromethyl)benzamide, 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,3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-pyrazole-4-carbonyl)-1,5-dimethyl-quinazoline-2,4-dione and N,N-diethylcarbamic acid [4-[3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-quinazoline-6-carbonyl]-2,5-dimethyl-pyrazol-3-yl] ester.

[0069] Mixing partners of the compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, 16th edition, British Crop Protection Council, 2012.

[0070] The compounds of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0071] The mixing ratio of the compound of formula (I) to the mixing partner is preferably 1:100 to 1000:1.

[0072] These mixtures can advantageously be used in the above-mentioned formulations (in this case, "active ingredient" relates to the corresponding mixture of the compound of formula (I) with the mixing partner).

[0073] The compound of the present invention or mixture can also be used in combination with one or more herbicide safeners. Examples of such safeners include cloquintocet, cloquintocet (including cloquintocet-mexyl), cyclopropylsulfonamide, dichloropropane, oxadiazole (including oxadiazole ethyl), fenclorac, fluazifop, oxadiazole, isoxadiazole (including isoxadiazole-ethyl), mefenpyr (including mefenpyr-butyl), metcamifen and oxadiazole.

[0074] Particularly preferred are mixtures of compounds of formula (I) with cyproconazole, isoxadiazole-ethyl, clofonetyl-mexyl and / or sulfamethoxazole.

[0075] 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. References to cloquintocet-mexyl also apply to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02 / 34048.

[0076] 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.

[0077] The present invention further provides a method for controlling weeds in a place, the method comprising applying a composition comprising a compound of formula (I) to the place in which the amount of weeds to be controlled. In addition, the present invention can further provide a method for selectively controlling weeds in a place including crop plants and weeds, wherein the method comprises applying a composition according to the present invention to the place in which the amount of weeds to be controlled. '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). 'Place' means the area where the plant is growing or will grow. Application can be applied to the place before and / or after emergence of the crop plants. Some crop plants can inherently tolerate the herbicidal effects of the compound with formula (I). Preferred crop plants include corn, wheat, barley, soybeans and rice.

[0078] 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 (before or after emergence; seed dressing; application to the seed furrow; no-till application, etc.), the crop plant, the 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 in particular 25 g / ha to 250 g / ha.

[0079] Application is usually made 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.

[0080] Crop plants are to be understood as also including those crop plants to which tolerance to other herbicides or classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, HPPD-inhibitors, inhibitor-PDS and ACCase-inhibitors) has been rendered by conventional methods of breeding or by genetic engineering. Examples of crops to which tolerance to imidazolinones (e.g. imazamox) has been rendered by conventional methods of breeding are 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 Roundup®. and The compounds of the invention may also be used in conjunction with crops tolerant to SDPS-inhibiting herbicides, such as those taught in WO 2020 / 236790.

[0081] Crop plants are also to be understood as meaning 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.

[0082] 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 flavor).

[0083] These compositions can be used to control unwanted plants (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.

[0084] In a further aspect of the invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.

[0085] Process for preparing compounds of formula (I)

[0086] 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.

[0087] As shown in Scheme 1, compounds of formula (I) can be prepared by decarboxylating compounds of formula (2) under acidic conditions in a suitable solvent such as ethanol at 110°C.

[0088] The compound of formula (2) is prepared by a nucleophilic aromatic substitution reaction of a compound of formula (4) (wherein LG represents a suitable leaving group, such as halogen or SO2Me) with a compound of formula (3) by heating in a suitable solvent (such as sulfolane) in the presence of a base (such as sodium tert-butoxide). The reaction is typically carried out at 40°C.

[0089] Conditions for forming pyrazole compounds of formula (3) by condensation of diketones with arylhydrazines are reported in the literature (e.g., Tetrahedron (2013), 69(16), 3459-3464).

[0090] Solution 1

[0091]

[0092] Alternatively, the compound of formula I can be prepared by condensation reaction of a compound of formula 3a with a compound of formula 3b. The reaction can optionally be carried out in the presence of an acid catalyst such as acetic acid or trifluoroacetic acid.

[0093]

[0094] Alternatively, compounds of Formula I can be prepared by Scheme 2 below.

[0095] Option 2:

[0096]

[0097] In Scheme 2, compounds of formula I can be prepared by reacting a compound of formula VI with a reagent of formula V, wherein LG1 is a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate), in the presence of a base such as sodium hydride or an alkaline earth metal hydride, a carbonate such as 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, sulfolane or acetonitrile, at a temperature between 0°C and 120°C, by procedures well known to those skilled in the art.

[0098] Alternatively, compounds of formula I can be prepared by reacting a compound of formula VI with a compound of formula V, wherein LG1 is a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate), in the presence of a metal catalyst, such as a copper-based catalyst, for example CuI or tetrakis(acetonitrile)copper(I) tetrafluoroborate, optionally in the presence of a ligand, such as trans-1,2-bis(methylamino)cyclohexane or a salt thereof, such as methanesulfonate, or other similar ligands such as 8-hydroxyquinoline. The reaction can be carried out in the presence of a base, such as potassium carbonate, cesium carbonate, triethylamine or pyridine, and similar other substances, in the presence of a solvent, such as acetonitrile, 1,4-dioxane or pyridine, and optionally under microwave irradiation at a temperature in the range of room temperature to 200°C.

[0099] Alternatively, the compound of formula I can be prepared by reacting a compound of formula VI with a compound of formula Va under Chan Lam cross-coupling reaction conditions. Such reactions are carried out in the presence of a copper-based catalyst (such as copper acetate or copper iodide or copper bromide and similar other substances) and in the presence of a base (such as pyridine or 2,6-lutidine and similar other substances). The reaction can be carried out in the presence of a solvent (such as dichloromethane, toluene, acetonitrile) and in the presence of air or oxygen, and at a temperature in the range of room temperature to 200°C.

[0100] Compounds of formula VI can be prepared from compounds of formula VII (wherein PG is an amino-protecting group, such as an acetyl, trimethylsilylethoxymethyl (SEM), tert-butoxycarbonyl, benzyl, p-methoxybenzyl (PMB) or the like) by a protecting group deprotection reaction. Such reactions are well known to those skilled in the art and can be carried out, for example, under base catalysis, such as sodium hydroxide, for deprotection of the acetyl group, or under acid catalysis, such as hydrochloric acid or 2,2,2-trifluoroacetic acid for deprotection of the trimethylsilylethoxymethyl (SEM), tert-butoxycarbonyl or p-methoxybenzyl (PMB) group.

[0101] The compound of formula VIII (wherein R 12 The compound of formula VII is prepared by decarboxylation of a C1-C4 alkyl or phenyl group. The reaction can be carried out using a base (such as an alkaline earth metal hydroxide or an alkali metal hydroxide such as sodium hydroxide) or in the presence of an acid (such as an aqueous hydrochloric acid solution, an aqueous sulfuric acid solution, etc.). The reaction is usually carried out in the presence of a solvent (such as water, ethanol, methanol, tetrahydrofuran or dioxane) or a combination of two or more solvents and at a temperature within the range of room temperature to the boiling point of the solvent.

[0102] Compounds of formula VIII (wherein R can be prepared by reacting a compound of formula X with a reagent of formula IX (wherein LG2 is a halogen, (or a pseudohalogen leaving group, such as a (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate)) in the presence of a base (such as sodium tert-butoxide, sodium hydride or an alkaline earth metal hydride, a carbonate (such as sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide, or a phosphate such as potassium phosphate), optionally in the presence of potassium iodide, in an inert solvent (such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N-dimethylacetamide, dimethyl sulfoxide, sulfolane or acetonitrile, etc.) at a temperature between 0°C and 200°C by procedures well known to those skilled in the art. 12 is C1-C4 alkyl or phenyl).

[0103] Compounds of formula X can be prepared by condensation reaction of a compound of formula XII with a compound of formula XI (or its hydrochloride or trifluoroacetate) (wherein PG is an amino protecting group, such as acetyl, trimethylsilylethoxymethyl (SEM), tert-butyloxycarbonyl, benzyl, p-methoxybenzyl (PMB), etc.). Such reactions are well known in the literature and can be optionally carried out in the presence of an acid catalyst such as acetic acid.

[0104] The compound of formula XIV (wherein R 11 The compound of formula XII is prepared by reacting a compound of formula XIII with a compound of formula XIII in the presence of a base. This type of reaction is known as a Claisen condensation reaction and is well known to those skilled in the art. The reaction can be carried out using a base (such as lithium diisopropylamide, lithium tetramethylpiperidinium, sodium ethoxide, sodium hydride, etc.) in the presence of a solvent (such as tetrahydrofuran, ethanol, methanol) at a temperature ranging from -80°C to the boiling point of the solvent.

[0105] Alternatively, compounds of Formula I can be prepared by Scheme 3 below.

[0106] Option 3:

[0107]

[0108] In Scheme 3, a compound of formula I is prepared from a compound of formula XV via reduction of an alcohol. The reduction of such alcohols is well described in the literature and can be performed using reducing agents such as LiAlH4, DIBAL-H or using triphenylphosphine in the presence of iodine and imidazole or using triethylsilane in the presence of trifluoroacetic acid. 1 is halogen, preferably bromine or iodine) reacts with an organometallic reagent (such as BuLi or a metallizing reagent such as isopropylmagnesium chloride / LiCl complex) to form intermediate XVIa (wherein M(Ln) p is the corresponding metal from the organometallic reagent (such as lithium or magnesium) and (Ln) p wherein the compound is an optionally substituted group such as chloro), and then subsequently reacted with a compound of formula XVII to prepare a compound of formula XV.

[0109]

[0110] Compounds of formula XVII can be prepared by reacting a compound of formula XVIII with a strong base such as butyllithium, lithium diisopropylamide, and then reacting with DMF. The reaction is typically carried out in the presence of a solvent (such as tetrahydrofuran, toluene, heptane) and at a temperature between -80°C and the boiling point of the solvent. Such reactions are well known and described in the literature. Compounds of formula XVIII can be prepared by reacting a compound of formula XIX with a compound of formula XX wherein LG3 is a leaving group such as a halogen (or a pseudohalogen leaving group such as a (halo)alkyl or phenylsulfonate, for example trifluoromethanesulfonate) in the presence of a base such as sodium tert-butoxide, sodium hydride or an alkaline earth metal hydride, a carbonate such as sodium carbonate, potassium carbonate or cesium carbonate, or a hydroxide, or a phosphate such as potassium phosphate, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N-dimethylacetamide, dimethyl sulfoxide, sulfolane or acetonitrile, at a temperature between 0°C and the boiling point of the solvent, by procedures well known to those skilled in the art. Such reactions are referred to in the literature as S N Ar reaction.

[0111] Alternatively, compounds of formula XVIII can be prepared by Chan-Lam coupling, which involves, for example, reacting a compound of formula XIX with a compound of formula XXI (wherein Yb1 can be a boron-derived functional group such as, for example, B(OH)2 or B(ORb1)2, wherein Rb1 can be a C1-C4 alkyl group, or the two groups ORb1 can form a five-membered ring together with the boron atom, such as, for example, pinacol borate). The reaction can be catalyzed by a copper catalyst (e.g., a copper-based catalyst such as Cu(OAc)2, CuI, CuBr2, CuCl) in the presence of a base such as pyridine, sodium carbonate, tripotassium phosphate, or cesium fluoride in a solvent or solvent mixture such as, for example, dioxane, dichloromethane, acetonitrile, N,N-dimethylformamide, a mixture of 1,2-dimethoxyethane and water, or a mixture of dioxane / water, or a mixture of toluene / water, under an inert atmosphere or under an oxygen atmosphere or under air. The reaction temperature may preferably be in the range of from room temperature to the boiling point of the reaction mixture, or the reaction may be carried out under microwave irradiation.Such Chan-Lam coupling reactions are well known to those skilled in the art.

[0112] Alternatively, compounds of Formula I (wherein R3 is H, defined as compounds of Formula Ia and compounds of Formula Ib) can be prepared according to Scheme 4.

[0113] Option 4:

[0114]

[0115] In Scheme 4, compounds of formula Ib can be prepared from compounds of formula XXIII (wherein X is a halogen, preferably bromine or iodine) via a cyanidation reaction. The reaction can be carried out by reacting the compound of formula XXIII with M-CN XXIId (wherein M is a metal coordinated to a cyanide). Examples of cyaniding agents include NaCN, Zn(CN)2, or potassium ferrocyanide. 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, potassium acetate, tripotassium phosphate or cesium fluoride in a solvent or solvent mixture such as, for example, dioxane, tetrahydrofuran, acetonitrile, N,N-dimethylformamide, 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 of 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.

[0116] Compounds of formula XXIII can be prepared by following a procedure similar to Scheme 3.

[0117] Compounds of formula Ia, wherein R2 is C1-C4 alkyl or R2 is C3-C5 cycloalkyl, can be prepared by a Suzuki reaction involving reacting a compound of formula XXIII, wherein X is a halogen, preferably bromine or iodine, with a compound of formula R2-Yb3, wherein Yb3 can be a boron-derived functional group, such as, for example, B(OH)2 or B(ORb3)2, wherein Rb3 can be C1-C4 alkyl, or the two groups ORb3 can form a five-membered ring together with the boron atom, such as, for example, pinacol borate. 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, for example, dioxane, acetonitrile, N,N-dimethylformamide, 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 of 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.

[0118] The compound of formula Ia in scheme 4 (wherein R2 is C1-C4 alkoxy) can be prepared by cross-coupling reaction of a compound of formula XXIII (wherein X is halogen, preferably bromine or iodine) with a compound of formula XXIIc (wherein R2 is C1-C4 alkoxy). The reaction can be carried out in the presence of a metal catalyst (such as a palladium-based catalyst, for example tert-BuBrettPhos-Pd-G3, [(2-di-tert-butylphosphino-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl)-2-(2'-amino-1,1'-biphenyl)] methanesulfonate palladium (II) (tBuBrettPhos Pd G3) etc.). The reaction is typically carried out in the presence of a solvent (such as tetrahydrofuran, 1,4-dioxane etc.) and optionally under microwave irradiation. Such reactions are well known in the literature and are described, for example, in Org. Lett. 2013, 15, 15, 3998-4001.

[0119] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention (as referenced in Table 1 below).

[0120] Example 1: Preparation of 3,5-difluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine (1.00g)

[0121]

[0122] Step 1: Preparation of 3-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]pyrazole (I-1)

[0123]

[0124] A suspension of 5-(trifluoromethyl)-1H-pyrazole (1.03 g, 7.57 mmol) and potassium carbonate (2.045 g, 14.80 mmol) in sulfolane (11 mL) was treated with 4-fluorobenzotrifluoride (1.41 mL, 10.9 mmol) and heated to 150 ° C for one hour under microwave irradiation. The mixture was diluted with saline and extracted with tert-butyl methyl ether. The combined organic matter was concentrated and subjected to column chromatography using 0-20% ethyl acetate in cyclohexane on silica gel to give 3-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]pyrazole I-1 (1.468 g, 66%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ = 8.04-8.01 (m, 1H), 7.87 (d, 2H), 7.76 (d, 2H), 6.78 (d, 1H).

[0125] Step 2: Preparation of 5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazole-3-carbaldehyde (I-2)

[0126]

[0127] At -78 ° C, to a solution of 3- (trifluoromethyl) -1- [4- (trifluoromethyl) phenyl] pyrazole I-1 (1.133 g, 3.842 mmol) in tetrahydrofuran (10 mL) was added n-butyl lithium (2.5 M in hexane, 2.2 mL, 5.5 mmol), and the resulting mixture was stirred for 30 minutes. Then, N, N- dimethylformamide (0.6 mL, 8 mmol) was added to this mixture and the mixture was stirred for 30 minutes. The mixture was quenched with aqueous ammonium chloride, diluted with water and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-25% ethyl acetate in cyclohexane to give 5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl] pyrazole-3-carboxaldehyde I-2 (1.014 g, 81%) as a light yellow oil. 1H NMR (400MHz, CDCl3) δ = 9.92 (s, 1H), 7.83 (d, 2H), 7.68 (d, 2H), 7.38 (s, 1H).

[0128] Step 3: Preparation of (3,5-difluoro-2-pyridyl)-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methanol (I-3)

[0129]

[0130] At -78 ° C, n-butyl lithium (2.5M in hexane, 0.50mL, 1mmol) was added to a solution of 2-bromo-3,5-difluoropyridine (245mg, 1.26mmol) in toluene (2mL). The resulting mixture was stirred for 30 minutes and then treated with a solution of 5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazole-3-carboxaldehyde I-2 (209mg, 0.64mmol) in toluene (2mL) and stirred for another 30 minutes. The mixture was quenched with 0.5M hydrochloric acid and extracted with ethyl acetate. The combined organic matter was concentrated and subjected to column chromatography using 0-40% ethyl acetate in cyclohexane on silica gel to give (3,5-difluoro-2-pyridyl)-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methanol I-3 (192mg, 63%) as a yellow gum. 1 H NMR (400MHz, CDCl3) δ = 8.40 (d, 1H), 7.91 (d, 2H), 7.82 (d, 2H), 7.29-7.24 (m, 1H), 6.18 (s, 1H), 5.90 (d, 1H), 4.87 (d, 1H).

[0131] Step 4: Preparation of 3,5-difluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine (1.00g)

[0132]

[0133] To a solution of (3,5-difluoro-2-pyridyl)-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methanol I-3 (192 mg, 0.41 mmol) in trifluoroacetic acid (1.4 mL) was added triethylsilane (1.3 mL, 8.1 mmol), and the resulting reaction mixture was stirred at 80 ° C for 6 hours. The mixture was cooled, diluted with 1M aqueous sodium hydroxide solution, and extracted with ethyl acetate. The combined organics were concentrated and subjected to reverse phase column chromatography on C-18 silica gel using 50%-100% acetonitrile in water (both water and acetonitrile contained 0.1% formic acid) to give 3,5-difluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine 1.008 (114 mg, 65%) as a white solid. 1 H NMR (400MHz, CDCl3) δ = 8.28 (d, 1H), 7.78 (d, 2H), 7.70 (d, 2H), 7.21 (ddd, 1H), 6.47 (s, 1H), 4.24 (d, 2H).

[0134] Example 2: Preparation of 5-chloro-3-fluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine (1.010)

[0135]

[0136] Step 1: Preparation of 6,6,6-trifluoro-3,5-dioxo-hexanoic acid ethyl ester (I-4)

[0137]

[0138] At 0 ℃, n-butyl lithium (2.5M in hexane, 9.2mL, 23mmol) was added dropwise to an ice-cooled solution of diisopropylamine (3.2mL, 23mmol) in THF (15mL). The mixture was stirred for 30 minutes, treated dropwise with ethyl acetoacetate (0.97mL, 7.7mmol) and stirred at 0 ℃ for one hour. The reaction mixture was then cooled to -78 ℃, treated dropwise with ethyl trifluoroacetate (1.2mL, 1mmol) and stirred for 3 hours. The mixture was quenched with hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined organic matter was dried and concentrated. The resulting oily substance I-4 was used in the next step as it is.

[0139] Step 2: Preparation of ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (I-5)

[0140]

[0141] 4-(trifluoromethyl)phenylhydrazine (1.35 g, 7.66 mmol) was added to a solution of I-4 prepared in Example 2 Step 1 in acetic acid (15 mL), and the resulting mixture was stirred at room temperature for 1.5 hours. The mixture was diluted with water and extracted with tert-butyl methyl ether. The organic matter was concentrated and subjected to column chromatography on silica gel using 0-30% ethyl acetate in cyclohexane to give 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]ethyl acetate I-5 (1.087 g, 37%) as an orange solid. 1 H NMR (400MHz, DMSO-d6)δ=7.96(d,2H),7.82(d,2H),6.98(s,1H),4.08(s,2H),3.95(q,2H),1.00(t,3H)

[0142] Step 3: Preparation of ethyl 2-(5-chloro-3-fluoro-2-pyridinyl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (I-6)

[0143]

[0144] To a solution of ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I-5 (100 mg, 0.259 mmol) and 5-chloro-2,3-difluoropyridine (135 μL, 1.302 mmol) in sulfolane (1.3 mL) was added sodium tert-butoxide (161 mg, 1.625 mmol), and the resulting mixture was stirred at 40 ° C for one hour. The mixture was cooled, diluted with water and extracted with tert-butyl methyl ether. The organic matter was concentrated and column chromatography was performed on silica gel using 0-30% ethyl acetate in cyclohexane to give ethyl 2-(5-chloro-3-fluoro-2-pyridyl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I-6 (84 mg, 52%) as a yellow oil. 1 H NMR(400MHz, CDCl3)δ=8.43-8.37(m,1H),7.82-7.77(m,2H),7.63-7.56(m,2 H),7.48(dd,1H),6.74(s,1H),5.38(s,1H),4.24-4.14(m,2H),1.19(t,3H).

[0145] Step 4: Preparation of 5-chloro-3-fluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine (1.010)

[0146]

[0147] A solution of ethyl 2-(5-chloro-3-fluoro-2-pyridinyl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I-6 (84 mg, 0.136 mmol) in ethanol (1.0 mL) was treated with aqueous hydrochloric acid (6 mol / L, 1.0 mL), and the resulting mixture was stirred at 100° C. for 3 hours. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-30% ethyl acetate in cyclohexane. The product-rich fractions were concentrated and subjected to reverse phase column chromatography on C-18 silica gel using 60%-100% acetonitrile in water (both water and acetonitrile contained 0.1% formic acid) to give 5-chloro-3-fluoro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine 1.010 (40 mg, 63%) as a colorless oil. 1 H NMR (400MHz, CDCl3) δ=8.36-8.32(m,1H),7.78(d,2H),7.70(d,2H),7.45(dd,1H),6.48(s,1H),4.23(d,2H).

[0148] Example 3: Preparation of 1-(4-fluorophenyl)-5-[(5-fluoro-2-pyridyl)methyl]pyrazole-3-carbonitrile (1.003)

[0149]

[0150] Step 1: Preparation of 1-(4-fluorophenyl)-3-iodo-pyrazole (I-7)

[0151]

[0152] To a mixture of 3-iodo-1H-pyrazole (1.07 g, 5.52 mmol), (4-fluorophenyl) boronic acid (1.44 g, 10.3 mmol) and diacetoxycopper (1.50 g, 8.26 mmol) was added dichloromethane (25 mL) and pyridine (0.84 mL, 10.3 mmol). The resulting mixture was stirred at room temperature for 21 hours. The mixture was diluted with aqueous ammonium hydroxide solution and extracted with dichloromethane. The combined organic matter was concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 1- (4-fluorophenyl) -3-iodo-pyrazole I-7 (1.38 g, 84%) as a white solid. 1H NMR (400MHz, CDCl3) δ = 7.67 (d, 1H), 7.61 (dd, 2H), 7.14 (t, 2H), 6.62 (d, 1H).

[0153] Step 2: Preparation of [2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]-(5-fluoro-2-pyridinyl)methanol (I-8)

[0154]

[0155] At -78 ℃, to a solution of 1- (4- fluorophenyl) -3- iodo- pyrazole I-7 (1.35g, 4.55mmol) in tetrahydrofuran (17mL), lithium diisopropylamide (2.0M in THF / heptane / ethylbenzene, 3.5mL, 7.0mmol) is added, and the mixture is stirred for 30 minutes. To this mixture, a solution of 5- fluoropyridine -2- carboxaldehyde (680mg, 5.44mmol) in tetrahydrofuran (5mL) is added, and the mixture is stirred for 30 minutes, which is then warmed to room temperature. The mixture is diluted with aqueous ammonium chloride solution and extracted with ethyl acetate. The combined organic matter is concentrated and subjected to column chromatography using 0-100% ethyl acetate in cyclohexane on silica gel to give [2- (4- fluorophenyl) -5- iodo- pyrazole -3- bases] -(5- fluoro-2- pyridyl) methanol I-8 (1.04g, 55%) as a pale white solid. 1 H NMR (400MHz, CDCl3) δ = 8.41 (d, 1H), 7.61 (m, 2H), 7.41 (m, 1H), 7.14 (d, 3H), 6.17 (s, 1H), 5.72 (d, 1H), 4.76 (d, 1H).

[0156] Step 3: Preparation of 5-fluoro-2-[[2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]methyl]pyridine (1.011)

[0157]

[0158] To a solution of [2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]-(5-fluoro-2-pyridyl)methanol I-8 (1.04 g, 2.52 mmol) in trifluoroacetic acid (8 mL, 103 mmol) was added triethylsilane (4 mL, 25.0 mmol), and the resulting mixture was stirred at 70 ° C for 55 hours. The mixture was treated with additional triethylsilane (4 mL, 25.0 mmol) and stirred at 70 ° C for another 19 hours. The mixture was cooled and concentrated. The residue was subjected to column chromatography using 0-40% ethyl acetate in cyclohexane on silica gel to give 5-fluoro-2-[[2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]methyl]pyridine 1.011 (651 mg, 65%) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ = 8.38 (d, 1H), 7.37 (m, 2H), 7.32 (dt, 1H), 7.12 (m, 2H), 7.04 (dd, 1H), 6.33 (s, 1H), 4.12 (s, 2H).

[0159] Step 4: Preparation of 1-(4-fluorophenyl)-5-[(5-fluoro-2-pyridyl)methyl]pyrazole-3-carbonitrile (1.003)

[0160]

[0161] To a mixture of 5-fluoro-2-[[2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]methyl]pyridine 1.011 (151 mg, 0.380 mmol), potassium ferrocyanide trihydrate (163 mg, 0.378 mmol), potassium acetate (38 mg, 0.379 mmol) and XPhosPd G3 (16 mg, 0.019 mmol) was added water (1.1 mL) and tetrahydrofuran (1.1 mL), and the resulting mixture was heated to 110 ° C. under microwave irradiation for one hour. The mixture was cooled, filtered and concentrated. The residue was subjected to column chromatography on silica gel using 0-60% ethyl acetate in cyclohexane to give 1-(4-fluorophenyl)-5-[(5-fluoro-2-pyridyl)methyl]pyrazole-3-carbonitrile 1.003 (110 mg, 93%) as a yellow solid. 1 H NMR (400MHz, CDCl3) δ = 8.39 (d, 1H), 7.42 (m, 2H), 7.35 (dt, 1H), 7.18 (m, 2H), 7.05 (dd, 1H), 6.60 (s, 1H), 4.15 (s, 2H).

[0162] Example 4: 5-chloro-2-[3-(trifluoromethyl)-5-[[6-(trifluoromethyl)-2-pyridinyl]methyl]pyrazol-1-yl]pyrimidine (1.009)

[0163]

[0164] Step 1: Preparation of 6,6,6-trifluoro-3,5-dioxo-hexanoic acid ethyl ester (I-4)

[0165]

[0166] In about 30 minutes, n-butyl lithium (2.5M in hexane, 65mL, 160mmol) was added to an ice-cooled solution of diisopropylamine (22mL, 157mmol) in THF (110mL) in a 250mL round-bottom flask. The mixture was stirred for 30 minutes, dropwise treated with ethyl acetoacetate (6.8mL, 54mmol) and stirred for another 45 minutes at 0°C. The reaction mixture was then cooled to -78°C, dropwise treated with ethyl trifluoroacetate (8.3mL, 70mmol) and stirred for 3 hours. The mixture was quenched with hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined organic matter was dried and concentrated. The gained oily substance I-4 was used in the next step as it is.

[0167] Step 2: Preparation of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate (I-9)

[0168]

[0169] To the solution of I-4 prepared in Example 4 Step 1 in 100mL round-bottom flask in acetic acid (90mL) was added (4-methoxybenzyl) hydrazine hydrochloride (10.56g, 54.29mmol), and the resulting mixture was stirred at room temperature for 1.5 hours. The mixture was diluted with tert-butyl methyl ether and washed with water and brine. Organic matter was concentrated and subjected to column chromatography using 0-30% ethyl acetate in cyclohexane on silica gel to give 2- [2- [(4-methoxyphenyl) methyl] -5- (trifluoromethyl) pyrazole-3-yl] ethyl acetate I-9 (11.97g, 59% yield) as a yellow oil. 1 H NMR (400MHz, CDCl3) δ=7.10-7.04(m,2H),6.88-6.83(m,2H),6.50(s,1H),5.35(s,2H),4.12(q,2H),3.79(s,3H),3.54(s,2H),1.24(t,3H).

[0170] Step 3: Preparation of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]-2-[6-(trifluoromethyl)-2-pyridyl]acetate (I-10)

[0171]

[0172] To a solution of 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]ethyl acetate I-9 (501mg, 1.390mmol) and 2-fluoro-6-(trifluoromethyl)pyridine (820 μL, 7.0mmol) in sulfolane (3mL) was added sodium tert-butoxide (659mg, 6.65mmol), and the resulting mixture was stirred at room temperature for one hour. The mixture was then diluted with a dilute aqueous sodium bicarbonate solution and extracted with tert-butyl methyl ether. The combined organic matter was concentrated and subjected to column chromatography using 0-40% ethyl acetate in cyclohexane on silica gel to give 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]-2-[6-(trifluoromethyl)-2-pyridyl]ethyl acetate I-10 (195mg, 24%) as a yellow oil. 1 H NMR(400MHz, CDCl3)δ=7.72(t,1H),7.54(dd,1H),7.24(dd,1H),7.01-6.95(m,2H),6.75- 6.70(m,2H),6.66(s,1H),5.37-5.24(m,3H),4.23-4.14(m,2H),3.75(s,3H),1.22(t,3H).

[0173] Step 4: Preparation of 2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]-6-(trifluoromethyl)pyridine (I-11)

[0174]

[0175] To a solution of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]-2-[6-(trifluoromethyl)-2-pyridyl]ethyl acetate I-10 (195 mg, 0.3401 mmol) in ethanol (2.0 mL) was added aqueous sodium hydroxide solution (2.0 mL, 2 mol / L), and the resulting mixture was stirred at 50 ° C for 30 minutes. The mixture was cooled and acidified with aqueous hydrochloric acid solution (2.0 mL, 6 mol / L), and then stirred overnight. The mixture was diluted with water and extracted with ethyl acetate. The combined organics were dried to give 2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]-6-(trifluoromethyl)pyridine I-11 (148 mg, 84%) as a light yellow oil. 1 H NMR (400MHz, CDCl3) δ=7.71(t,1H),7.53(d,1H),7.09-7.01(m,3H),6.80-6.75(m,2H),6.39(s,1H),5.35(s,2H),4.16(s,2H),3.77(s,3H).

[0176] Step 5: Preparation of 2-(trifluoromethyl)-6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyridine (I-12)

[0177]

[0178] A solution of 2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]-6-(trifluoromethyl)pyridine I-11 (148 mg, 0.285 mmol) in 2,2,2-trifluoroacetic acid (0.6 mL, 8 mmol) was stirred at 70 ° C for 30 minutes. The mixture was cooled, diluted with water, and carefully basified with aqueous sodium bicarbonate solution until bubbling stopped. The mixture was extracted with ethyl acetate and the combined organics were concentrated and subjected to column chromatography on silica gel using 0-70% ethyl acetate in cyclohexane to give 2-(trifluoromethyl)-6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyridine I-12 (114 mg) as a brown oil. 1 H NMR (400MHz, CDCl3) δ = 7.89 (t, 1H), 7.64 (d, 1H), 7.46 (d, 1H), 6.48-6.44 (m, 1H), 4.30 (s, 2H).

[0179] Step 6: Preparation of 5-chloro-2-[3-(trifluoromethyl)-5-[[6-(trifluoromethyl)-2-pyridinyl]methyl]pyrazol-1-yl]pyrimidine (1.009)

[0180]

[0181] A mixture of 2-(trifluoromethyl)-6-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyridine I-12 (114 mg, 0.290 mmol), 2,5-dichloropyrimidine (71 mg, 0.477 mmol) and potassium carbonate (83 mg, 0.601 mmol) was treated with acetonitrile (1.0 mL) and stirred at 80 ° C for 2 hours. The mixture was cooled, diluted with water and extracted with ethyl acetate. The combined organics were concentrated and subjected to reverse phase column chromatography using 50%-100% acetonitrile in water (both water and acetonitrile contained 0.1% formic acid) on C-18 silica gel to give 5-chloro-2-[3-(trifluoromethyl)-5-[[6-(trifluoromethyl)-2-pyridyl]methyl]pyrazol-1-yl]pyrimidine 1.009 (66 mg, 53%) as an off-white solid. 1 H NMR (400MHz, CDCl3) δ = 8.70 (s, 2H), 7.79 (t, 1H), 7.55 (d, 1H), 7.30 (d, 1H), 6.52 (s, 1H), 4.82 (m, 2H).

[0182] Example 5: 2-Chloro-5-[3-(difluoromethyl)-5-[(3,5-difluoro-2-pyridinyl)methyl]pyrazol-1-yl]-3-fluoro-pyridine (1.014)

[0183]

[0184] Step 1: Preparation of diethyl 2-(3,5-difluoro-2-pyridyl)malonate (I-13)

[0185]

[0186] A suspension of sodium hydride (60% by mass) in tetrahydrofuran (28.2 mL) in mineral oil (1.35 g, 33.8 mmol) in a 100 mL round-bottom flask is placed under a nitrogen atmosphere and treated dropwise with diethyl malonate (5.53 g, 33.8 mmol). The mixture is stirred for 5 minutes and then treated with 2,3,5-trifluoropyridine (1.50 g, 11.3 mmol). The mixture is warmed to 60 ° C and stirred for 3.5 h. The reaction mixture is cooled to room temperature, then diluted with water (50 mL) and extracted with ethyl acetate (2 × 40 mL). The combined organic matter is concentrated in vacuo. The residue is subjected to silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent. The fractions forming the desired main peak were combined and concentrated in vacuo to yield diethyl 2-(3,5-difluoro-2-pyridyl)malonate I-13 (2.40 g, 11%) as a colorless oil as a mixture of isomers (4:1). The product contained excess diethyl malonate as an impurity and was used directly in the next step without further purification. 1 HNMR (400MHz, CDCl3) δ = 8.33 (d, 1H), 7.26-7.20 (m, 1H), 5.03 (d, 1H), 4.28 (q, 4H), 1.28 (t, 6H).

[0187] Step 2: Preparation of 2-(3,5-difluoro-2-pyridyl)acetic acid (I-14)

[0188]

[0189] A solution of diethyl 2-(3,5-difluoro-2-pyridyl)malonate I-13 (2.40 g, 8.78 mmol) in methanol (22.0 mL) in a 100 mL round-bottom flask was treated with 2 M sodium hydroxide (22.0 mL, 43.9 mmol) and stirred at 70 ° C for 1 h. Another portion of 2 M sodium hydroxide (13.2 mL, 26.4 mmol) was added, and the reactants were heated at 70 ° C for another 30 min. The reaction mixture was cooled to room temperature and then diluted with water (20 mL). The mixture was adjusted to pH 4 with hydrochloric acid and extracted with ethyl acetate (2 × 40 mL). The combined organics were passed through a hydrophobic glass frit and concentrated in vacuo to produce 2-(3,5-difluoro-2-pyridyl)acetic acid I-14 (0.686 g, 43%) as a white solid. 1 H NMR (400MHz, CDCl3) δ = 8.32 (d, 1H), 7.29 (m, 1H), 4.01-3.89 (m, 2H).

[0190] Step 3: Preparation of 1-(3,5-difluoro-2-pyridyl)propan-2-one (I-15)

[0191]

[0192] A suspension of 2-(3,5-difluoro-2-pyridyl)acetic acid I-14 (0.686 g, 3.96 mmol) in acetic anhydride (2.06 g, 19.8 mmol) in a 25 mL round-bottom flask was placed under a nitrogen atmosphere and treated with 1-methylimidazole (0.246 g, 2.97 mmol). The reaction mixture was stirred at room temperature overnight. It was quenched by slowly adding water (15 mL) at 0 ° C and stirred for 5 minutes, then extracted with ethyl acetate (2 × 30 mL). The combined organics were washed with sodium bicarbonate aqueous solution (2 × 50 mL) and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent. After concentration, 1-(3,5-difluoro-2-pyridyl)propan-2-one I-15 (0.13 g, 19%) was obtained as a gummy oil. 1 H NMR (400MHz, CDCl3) δ = 8.30 (d, 1H), 7.21 (m, 1H), 3.99 (d, 2H), 2.27 (s, 3H).

[0193] Step 4: Preparation of 5-(3,5-difluoro-2-pyridyl)-1,1-difluoro-pentane-2,4-dione (I-16)

[0194]

[0195] The solution of 1- (3,5-difluoro-2-pyridyl) propan-2-one I-15 (0.13 g, 0.76 mmol) in tetrahydrofuran (2 mL) in a 10 mL round-bottom flask was cooled to 0 ° C under a nitrogen atmosphere and treated with potassium tert-butoxide (12 mass %) and ethyl 2,2-difluoroacetate (0.32 g, 2.65 mmol) in tetrahydrofuran (1.89 mL, 1.89 mmol). The reaction mixture was stirred at room temperature overnight. The reaction mixture was quenched with 2M HCl and extracted with ethyl acetate (2 × 30 mL). The combined organics were dried over magnesium sulfate and concentrated in vacuo. The crude material was used directly in the next step.

[0196] Step 5: Preparation of N-(tert-butoxycarbonylamino)-N-(6-chloro-5-fluoro-3-pyridyl)-carbamic acid tert-butyl ester (I-17)

[0197]

[0198] A solution of 5-bromo-2-chloro-3-fluoropyridine (1.498 g, 7.12 mmol) in tetrahydrofuran (14 mL) in a 100 mL round-bottom flask is placed under a nitrogen atmosphere, ice-cooled and treated with 1.3 M isopropylmagnesium chloride lithium chloride complex solution (6.0 mL, 7.8 mmol). The mixture is stirred at 0 ° C for 15 minutes, then dropwise treated with a solution of di-tert-butyl azodicarboxylate (1.83 g, 7.95 mmol) in tetrahydrofuran (4 mL) in a manner such that the internal temperature is no more than 15 ° C. The mixture is stirred for 30 minutes. The reaction mixture is quenched with water (100 mL) and extracted with ethyl acetate (2 × 50 mL). The combined organic matter is washed with brine (50 mL) and concentrated in vacuo. The crude product is purified by silica gel column chromatography using 0-30% ethyl acetate in cyclohexane as eluent to yield tert-butyl N-(tert-butoxycarbonylamino)-N-(6-chloro-5-fluoro-3-pyridinyl)-carbamate 1-17 (1.79 g, 66%) as an oil which crystallizes on standing to a white solid. 1 H NMR (400MHz, CDCl3) δ = 8.36 (s, 1H), 7.92-7.64 (m, 1H), 6.73 (br s, 1H), 1.55-1.46 (m, 18H).

[0199] Step 6: Preparation of 2-chloro-5-[3-(difluoromethyl)-5-[(3,5-difluoro-2-pyridinyl)methyl]pyrazol-1-yl]-3-fluoro-pyridine (1.014)

[0200]

[0201] By N-(tert-butoxycarbonylamino)-N-(6-chloro-5-fluoro-3-pyridyl) t-butyl carbamate I-17 (0.27g, 0.76mmol) in 100mL round-bottom flask in trifluoroacetic acid (0.88g, 7.6mmol) solution at room temperature stirred 30 minutes.Reactant mixture is treated with 5-(3,5-difluoro-2-pyridyl)-1,1-difluoro-pentane-2,4-dione I-16 (0.19g, 0.76mmol) solution in acetic acid (1.5mL) and is made to stir at room temperature 1h.Reaction is distributed between water (50mL) and ethyl acetate (60mL), and organic matter is dried over magnesium sulfate and concentrated onto silica.The purification carried out using 0-40% ethyl acetate in cyclohexane by silica gel column chromatography provides product and impurity. The product was repurified by reverse phase chromatography using 40%-100% acetonitrile in water containing 0.1% formic acid. A final silica gel purification using 20% ​​ethyl acetate in cyclohexane afforded 2-chloro-5-[3-(difluoromethyl)-5-[(3,5-difluoro-2-pyridinyl)methyl]pyrazol-1-yl]-3-fluoro-pyridine 1.014. 1 H NMR (400MHz, CDCl3) δ = 8.55 (d, 1H), 8.28 (d, 1H), 7.90 (dd, 1H), 7.25-7.21 (m, 1H), 6.86-6.52 (m, 1H), 6.49 (s, 1H), 4.25 (d, 2H).

[0202] Example 6: 5-Chloro-2-[[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]methyl]-3-fluoro-pyridine (1.017)

[0203]

[0204] Step 1: Preparation of 6,6-difluoro-3,5-dioxo-hexanoic acid ethyl ester (I-18)

[0205]

[0206] The solution of lithium diisopropylamide (2.0mol / L) in tetrahydrofuran (28mL) in tetrahydrofuran (28mL) in a 250mL round-bottom flask is placed under a nitrogen atmosphere and through ice cooling, then slowly processed about 10 minutes with ethyl acetoacetate (2.0mL, 16mmol). Controlled addition makes internal temperature no more than 10 ℃. After addition is complete, the mixture is stirred for 30 minutes. The mixture is cooled to-78 ℃ and dropwise processed with ethyl difluoroacetate (2.2mL, 21mmol). The gained reaction mixture is stirred for 3 hours, then removed from dry ice bath and at room temperature stirred for 30 minutes in addition. After completion, the mixture is quenched with 1M hydrochloric acid (100mL), diluted with water (40mL) and extracted with ethyl acetate (2 × 100mL). The combined organics were dried over anhydrous magnesium sulfate and concentrated in vacuo to give 6,6-difluoro-3,5-dioxo-hexanoic acid ethyl ester I-18 (3.3 g, 100% yield) as a dark orange oil, which was used directly without any purification.

[0207] Step 2: Preparation of ethyl 2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]acetate (I-19)

[0208]

[0209] A solution of 6,6-difluoro-3,5-dioxo-ethyl hexanoate I-18 (6.24 g, 30 mmol) in acetic acid (60 mL) in a 250 mL round-bottom flask was treated with trifluoroacetic acid (6.91 g, 60 mmol) and (4-methoxyphenyl) methylhydrazine; hydrochloride (5.65 g, 30 mmol) was treated and allowed to stir at room temperature overnight. The reaction mixture was diluted with water (100 mL) and then extracted with ethyl acetate (3 × 100 mL). The organic matter was combined, washed with brine, dried over MgSO4, filtered and concentrated. It was purified by silica gel column chromatography using a gradient of 0-40% ethyl acetate in cyclohexane. After concentrating the pure fractions, product 2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]ethyl acetate I-19 (2.71 g, 28%) was obtained. 1 H NMR (400MHz, CDCl3) δ = 7.05 (d, 2H), 6.55-6.88 (m, 3H), 6.48 (s, 1H), 5.32 (s, 2H), 4.12 (m, 2H), 3.78 (s, 3H), 3.57 (s, 2H), 1.24 (t, 3H).

[0210] Step 3: Preparation of ethyl 2-(5-chloro-3-fluoro-2-pyridinyl)-2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]acetate (I-20)

[0211]

[0212] A mixture of ethyl 2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]acetate I-19 (2.71 g, 8.36 mmol), 5-chloro-2,3-difluoro-pyridine (3.75 g, 25.1 mmol) and tripotassium phosphate (10.9 g, 50.1 mmol) in a 250 mL round-bottom flask was placed under a nitrogen atmosphere and treated with dimethyl sulfoxide (27 mL). The mixture was warmed to 80° C. and allowed to stir for 1 hour. The reaction mixture was heated for an additional 30 minutes and then allowed to cool to room temperature before being diluted with water (50 mL), acidified with 2M hydrochloric acid, and extracted with tert-butyl methyl ether (2×100 mL). The combined organics were concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent to provide ethyl 2-(5-chloro-3-fluoro-2-pyridinyl)-2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]acetate I-20 (1.59 g, 42%) as a mixture of isomers (1:1). The isomeric mixture was used in the next step without further purification.

[0213] Step 4: Preparation of 5-chloro-2-[[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]-pyrazol-3-yl]methyl]-3-fluoro-pyridine (I-21)

[0214]

[0215] A solution of ethyl 2-(5-chloro-3-fluoro-2-pyridinyl)-2-[5-(difluoromethyl)-2-[(4-methoxyphenyl)-methyl]pyrazol-3-yl]acetate I-20 (1.59 g, 3.50 mmol) in methanol (17.5 mL) in a 250 mL round-bottom flask was treated with 2M sodium hydroxide (17.5 mL, 35.0 mmol). The mixture was stirred at 65° C. for 1.5 h. The mixture was acidified with hydrochloric acid, diluted with water (15 mL) and extracted with ethyl acetate (2×50 mL). The combined organics were dried over magnesium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane. After concentration, 5-chloro-2-[[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]methyl]-3-fluoro-pyridine 1-21 was obtained as an off-white solid (0.68 g, 49%). 1 H NMR (400MHz, CDCl3) δ = 8.30 (s, 1H) 7.37 (dd, 1H) 6.95-7.06 (m, 2H) 6.80-6.83 (m, 2H) 6.69 (t, 1H), 6.32 (s, 1H), 5.37 (s, 2H) 4.09 (s, 2H) 3.78 (s, 3H).

[0216] Step 5: Preparation of 5-chloro-2-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-3-fluoro-pyridine (I-22)

[0217]

[0218] A solution of 5-chloro-2-[[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]methyl]-3-fluoro-pyridine I-21 (0.685 g, 1.79 mmol) in 2,2,2-trifluoroacetic acid (4.13 g, 35.83 mmol) in a 25 mL round-bottom flask was warmed to 70 ° C and allowed to stir for 2 h. The reaction mixture was cooled to room temperature and then added to water (about 50 mL), resulting in the formation of a precipitate. The aqueous phase was basified with saturated aqueous bicarbonate solution and ethyl acetate (100 mL) was added. The phases were separated and the organics were dried over magnesium sulfate and concentrated in vacuo. The orange gum obtained was purified by silica gel column chromatography using 0-100% ethyl acetate in cyclohexane to give 5-chloro-2-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-3-fluoro-pyridine 1-22 (0.36 g, 73%). 1H NMR (400MHz, CDCl3) δ=11.37-11.83(m,1H),8.39(d,1H),7.49(dd,1H),6.51-6.87(m,1H),6.42(s,1H),4.26(d,2H).

[0219] Step 6: Preparation of 5-chloro-2-[[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]methyl]-3-fluoro-pyridine (1.017)

[0220]

[0221] The oven-dried 10-20 mL microwave vial containing a mixture of 5-chloro-2-[[3-(difluoromethyl)-1H-pyrazol-5-yl]methyl]-3-fluoro-pyridine I-22 (0.2 g, 0.76 mmol), 8-hydroxyquinoline (0.033 g, 0.23 mmol), tetrakis(acetonitrile)copper(i)tetrafluoroborate (0.037 g, 0.11 mmol), 1,2-difluoro-4-iodo-benzene (0.37 g, 1.52 mmol) and potassium carbonate (0.32 g, 2.29 mmol) was evacuated and backfilled with nitrogen five times. The mixture was treated with acetonitrile (3.8 mL) and irradiated to 120 ° C for 1 h under microwave irradiation. The reaction mixture was filtered through celite and concentrated in vacuo. The residue was loaded onto silica and subjected to silica gel column chromatography using 15% ethyl acetate in cyclohexane to give 5-chloro-2-[[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]methyl]-3-fluoro-pyridine 1.017. 1 H NMR (400 MHz, chloroform) δ = 8.34 (d, 1H), 7.39-7.50 (m, 2H), 7.27-7.32 (m, 2H), 6.48-6.84 (m, 1H), 6.41 (s, 1H), 4.19 (d, 2H).

[0222] Table 1

[0223]

[0224]

[0225]

[0226]

[0227]

[0228]

[0229] Biological Examples

[0230] Seeds of various test species (Amaranthus palmeri (AMAPA), Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE)) were sown in standard soil in pots. After one day of cultivation (pre-emergence) or eight days (post-emergence) in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14-hour photoperiod; 65% humidity), the plants were sprayed with a spray solution consisting of the test compound dissolved in acetone and IF50 (11.12% Emulsogen EL360™ + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether) and diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The test compound was applied at the stated rate. The test plants were then grown in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14-hour photoperiod; 65% humidity) and watered twice daily. The percentage of damage to the plants was assessed pre-emergence and 13 days post-emergence.

[0231] Table B1. Post-emergence testing

[0232]

[0233]

[0234] NT = Not Tested Table B2. Pre-emergence Test

[0235]

[0236] NT = Not Tested

Claims

1. A compound having formula (I): or an agronomically acceptable salt thereof, in Q is phenyl or C-linked 6-membered heteroaryl, wherein the phenyl or 6-membered heteroaryl is optionally substituted by one or more R 4 replace; R 1 independently selected from the group consisting of halogen, -CN, NO2, C1-C4 alkyl, C1-C4 haloalkyl, C3-C6 cycloalkyl, C2-C4 alkenyl, C2-C4 alkynyl, -S(O) p C1-C4 alkyl, C1-C4 alkoxy-, -C(O)C1-C4 alkyl, -C(O)OC1-C4 alkyl, C1-C4 haloalkoxy and C1-C4 alkoxyC1-C3 alkyl-; 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, C1-C4 alkoxyC1-C3 alkyl-, C1-C4 alkoxyC1-C3 alkoxy-, C1-C4 alkoxyC1-C3 alkoxyC1-C3 alkyl-, -S(O) p C1-C4 alkyl and C3-C6 cycloalkyl; R 3 Selected from the group consisting of hydrogen, 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, -C(R 7 )=NOR 8 and -C(O)NR 5 R 6 ; R 4 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 5 R 6 ; R 5 is hydrogen or C1-C4 alkyl; R 6 is hydrogen or C1-C4 alkyl; R 7 is hydrogen or C1-C4 alkyl; R 8 is hydrogen or C1-C2 alkyl; m = 0, 1, or 2; and p=0, 1 or 2.

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

3. A compound of formula (I) according to claim 1 or claim 2, wherein m is 1 or 2, and R 1 independently selected from the group consisting of halogen, -CN, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy- and C1-C4 haloalkoxy.

4. The compound according to claim 3, wherein m is 1, and R 1 It's chlorine.

5. A compound according to any one of the preceding claims, wherein R 2 Selected from the group consisting of halogen, C1-C4 haloalkyl-, cPr and CN.

6. A compound according to any one of the preceding claims, wherein Q is selected from the group consisting of: Where n is 0, 1, or 2.

7. A compound according to any one of the preceding claims, wherein Q is selected from the group consisting of: Q-1, Q-3, and Q-4.

8. The compound according to claim 7, wherein n is 1 or 2.

9. The compound according to claim 8, wherein R 4 Independently selected from the group consisting of cyano, methyl, halogen and -CF3.

10. A compound according to any one of the preceding claims, wherein Q is 4-Cl-phenyl-.

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

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

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

14. A method of controlling weeds at a locus, the method comprising applying to the locus a weed-controlling amount of a composition according to any one of claims 11 to 13.

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

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