Herbicidal pyrazole pyrimidine compounds

Abstract

The present invention relates to a compound represented by formula (I), TIFF2024544633000053.tif46160 (in the formula, Q, R 1 , R 2 and R 4 is as defined herein, or an agriculturally acceptable salt of said compound. The present invention further relates to herbicidal compositions comprising the compounds of formula (I) and to the use of the compounds of formula (I), in particular for the control of weeds in crops of useful plants.

Description

[Technical field]

[0001] The present invention relates to novel herbicidal compounds, processes for their preparation, herbicidal compositions containing the novel compounds, and their use, in particular for controlling weeds or for inhibiting plant growth in crops of useful plants. Summary of the Invention [Means for solving the problem]

[0002] Herbicidal pyrazole compounds are disclosed, for example, in Chinese Patent No. 105037342. The present invention relates to a novel herbicidal pyrazole compound. Thus, according to the present invention, a herbicidal pyrazole compound having the formula (I): [ka] (In the ceremony Q is phenyl, C-linked 6-membered heteroaryl, QA and QB [ka] wherein said phenyl or 6-membered heteroaryl is selected from the group consisting of one or more independent R 3 may be optionally substituted with a substituent; R 1 is halogen, -CN, NO 2 , C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 3 ~C 6 Cycloalkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -S(O) p C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy-, -C(O)C 1 ~C 4 Alkyl, -C(O)OC 1 ~C4 Alkyl, C 1 ~C 4 Haloalkoxy and C 1 ~C 4 Alkoxy C 1 ~C 3 independently selected from the group consisting of alkyl-; R 2 is halogen, -CN, C 1 ~C 2 Alkyl, and C 1 ~C 2 haloalkyl; R 3 is a halogen, C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy, C 1 ~C 4 Haloalkoxy, -CN, NO 2 , C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, -S(O) p C 1 ~C 4 selected from the group consisting of alkyl; R 4 is hydrogen, halogen, -CN, C 1 ~C 2 Alkyl, and C 1 ~C 2 haloalkyl; p=0, 1 or 2) or an agriculturally acceptable salt thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0003] C 1 ~C 4 Alkyl is, for example, methyl (Me, CH 3 ), ethyl (Et, C 2 H 5), n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu). 1 ~C 2 Alkyl is methyl (Me, CH 3 ) or ethyl (Et, C 2 H 5 ).

[0004] C 2 ~C 4 Alkenyl- is, for example, -CH=CH 2 (vinyl) and -CH 2 -CH=CH 2 Contains (allyl).

[0005] C 2 ~C 4 Alkynyl- refers to a straight or branched hydrocarbon chain radical group composed solely of carbon and hydrogen atoms, containing at least one triple bond, having 2 to 4 carbon atoms, which is attached to the rest of the molecule by a single bond. 2 ~C 4 Examples of alkynyl include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.

[0006] 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.

[0007] C 1 ~C 4 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. 1 ~C 2Haloalkyl 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.

[0008] C 1 ~C 4 Alkoxy includes methoxy and ethoxy.

[0009] C 1 ~C 4 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.

[0010] C 3 ~C 6 Cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

[0011] C 1 ~C 4 Alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0012] C 1 ~C 4 Alkyl-S(O)-(alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0013] C 1 ~C 4 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 a preferred embodiment of the present invention, there is provided a compound of formula (I), wherein Q is: [ka] is selected from the group consisting of:

[0015] In another embodiment of the present invention, Q is selected from the group consisting of Q-1, Q-3, and Q-4.

[0016] In a more preferred embodiment of the invention, Q is Q-1 or Q-3.

[0017] In a more preferred embodiment of the invention, Q is Q-1.

[0018] In another preferred embodiment of the invention, Q is Q-3.

[0019] In one embodiment of the present invention, R 3 is a halogen, C 1 ~C 4 Alkyl (e.g., methyl), C 1 ~C 4 Haloalkyl (e.g., -CF 3 or -CHF 2 ), -CN and -S(O) p C 1 ~C 4 Alkyl (e.g., -SO 2 More preferably, R 3 is halogen (preferably fluoro or chloro) or C 1 ~C 4Haloalkyl (e.g., -CF 3 or -CHF 2 ) For example, halogen or -CF 3 It is.

[0020] In another embodiment of the invention, n is 0, 1 or 2, preferably 1 or 2. In one embodiment, n is 1. In another embodiment, n is 2. Compounds with n=2 appear to show improved selectivity (good weed control with little, if any, crop damage).

[0021] In a more preferred embodiment, Q is Q-1 and R 3 is halogen or C 1 ~C 4 haloalkyl and n is 1 (in a preferred embodiment, Q is 4-CF 3 -phenyl-).

[0022] In another preferred embodiment of the invention, Q is Q-1 and R 3 is halogen and n is 2. (In a preferred embodiment, Q is 3,4-dihalophenyl- (e.g., 3-F,4-Cl-phenyl-, 3-Cl,4-F-phenyl-, 3,4-dichlorophenyl-, or 3,4-difluorophenyl-).

[0023] In another preferred embodiment of the invention, Q is Q-3 and R 3 is halogen and n is 2. (In a preferred embodiment, Q is 6,5-dihalo-3-pyridyl-phenyl-(e.g., 6-chloro-5-fluoro-3-pyridyl).

[0024] In another embodiment of the invention, Q is QA or QB: [ka]

[0025] In another embodiment of the present invention, R 1 is halogen, CN, C 1 ~C 4 Alkyl, C1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy and C 1 ~C 4 In a more preferred embodiment, R 1 is selected from the group consisting of methyl, fluoro, chloro, bromo and methoxy-. 1 is chloro.

[0026] In another embodiment of the present invention, R 2 is halogen (e.g., chloro), -CN or C 1 ~C 2 In a preferred embodiment, R 2 -CF 3 or -CF 2 It's H.

[0027] In another embodiment of the present invention, R 4 is hydrogen.

[0028] The 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 compared to the other possible ones.

[0029] The present invention also provides agriculturally acceptable salts of the compounds of formula (I). Salts of the 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 metals, or quaternary ammonium bases being preferred.

[0030] Although the compounds of formula (I) of the present invention can be used as herbicides themselves, they are generally 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 it is also possible to prepare a ready-to-use composition.The final dilution is usually performed with water, but it can also be performed with, for example, liquid fertilizers, trace elements, biological organisms, oils or solvents instead of or in addition to water.

[0031] 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 surface-active substance.

[0032] 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 each case will depend on the specific purpose envisaged, the physical, chemical and biological properties of the compound of formula (I).

[0033] Soluble powders (SP) can be prepared by mixing the 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 said 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).

[0034] Wettable powders (WP) can be prepared by mixing the 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 liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated into water-dispersible granules (WG).

[0035] Granules (GR) can be formed by granulating a mixture of the compound of formula (I) with one or more powdered solid diluents or carriers, or by absorbing the compound of formula (I) (or its solution in a suitable agent) from preformed blank granules into a porous granular material (such as pumice, attapulgite clay, Fuller's earth, Kiesler's earth, diatomaceous earth or ground corn cob), or by adsorbing the compound of formula (I) (or its solution in a suitable agent) into a hard core material (such as sand, silicic acid, carbonate, sulfate or phosphate minerals) and optionally drying. Agents commonly used to aid absorption or adsorption include solvents (such as 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 can also be included in the granules (e.g., emulsifiers, wetting agents or dispersing agents).

[0036] Dispersible Concentrates (DC) may 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 dilution with water or to prevent crystallization in the spray tank).

[0037] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) can be prepared by dissolving the 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). Organic solvents suitable 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 (C 8 ~C 10 fatty acid dimethylamides, etc.) and chlorinated hydrocarbons. EC products can emulsify spontaneously when water is added, resulting in an emulsion that is stable enough to allow spray application with appropriate equipment.

[0038] The preparation of an EW 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. Solvents suitable for use in an EW 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.

[0039] Microemulsions (MEs) can be prepared by mixing a blend of one or more solvents and one or more SAA with water to spontaneously result in a thermodynamically stable isotropic liquid formulation. The compound of formula (I) is initially present in water or a solvent / SAA blend. Solvents suitable 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 are suitable for dilution with water to form a conventional oil-in-water emulsion, or as a microemulsion.

[0040] Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of fine, insoluble solid particles of the 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, the compound of formula (I) may be dry milled and added to water containing the agents described hereinbefore to produce the desired end product.

[0041] 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 medium (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.

[0042] Capsule suspensions (CS) can be prepared similarly to the preparation of EW formulations, but with an additional polymerization stage, such that an aqueous dispersion of oil droplets is obtained, 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 a 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 polymeric matrix to provide a controlled, slow release of the compound.

[0043] 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; the resistance to rain on the treated surface; or the uptake or mobility of the compound of formula (I). 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)).

[0044] Wetting agents, dispersing agents and emulsifying agents may be cationic, anionic, amphoteric or nonionic SAAs.

[0045] Suitable cationic SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines and amine salts.

[0046] 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 reaction of one or more aliphatic alcohols with phosphoric acid (mainly mono-esters) or phosphorus pentoxide (mainly di-esters), e.g., 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.

[0047] Suitable amphoteric SAAs include betaines, propionates and glycinates.

[0048] Suitable SAAs that are non-ionic 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 said 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.

[0049] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone, or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0050] 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), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, vilanaphos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including acetochlor, acetofluorfen ... carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chlorimuron (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, desmedifa , dicumba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrione, diquat dibromide, diuron, epirifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenpyrazone, fenoxaprop-P-ethyl ... Enquinotrion, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-p-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, fomesafen, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron,Glufosinate (including L-glufosinate and both ammonium salts), glyphosate (including its diammonium, isopropylammonium and potassium salts), haloxifen (including haloxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iodosulfuron-sodium-methyl), iofensulfuron (including iofens ... containing mesosulfuron-methyl), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (containing 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), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-p-ethyl and quizalofop-p-tefuryl), rimisoxafen, rimsulfuron, saflufenacil, sethoxydim, simazine, S-metallochloride , sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetlfpyrolimeth, thiencarbazone, thifensulfuron, thiaphenacyl, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazine, 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, 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- 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (and its agriculturally acceptable esters, such as 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-(isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide;3-(isopropylsulfonyl-methyl)-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, ethyl-2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl) 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, tetrahydro-furan-2-ylmethyl (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]-propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, tetrahydrofuran-2-ylmethyl 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]-propanoic acid 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, 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, (2-fluorophenyl)methyl 6-amino-5-chloro-2-(4-chloro-2-fluoro-3 -methoxyphenyl)-pyrimidine-4-carboxylate, 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 [4-[3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-quinazoline-6-carbonyl]-2,5-dimethyl-pyrazol-3-yl]N,N-diethylcarbamate.

[0051] The compound of formula (I) may also be in the form of an ester or salt, for example as described in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0052] 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.

[0053] The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1:100 to 1000:1.

[0054] The mixtures may be advantageously used in the formulations described above (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the mixing partner).

[0055] The compounds or mixtures of the present invention may also be used in combination with one or more herbicide safeners. Examples of such safeners 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.

[0056] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and / or metcamifen.

[0057] The safeners of the compounds of formula (I) may also be described, for example, in The Pesticide Manual, 16 thEdition (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.

[0058] 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.

[0059] The present invention also provides a method for controlling weeds in a locus, comprising applying to said locus a weed-controlling amount of a composition containing a compound of formula (I). The present invention may further provide a method for selectively controlling weeds in a locus containing crop plants and weeds, comprising applying to said locus a weed-controlling amount of a composition of the present invention. "Control" means killing, reducing or retarding growth, or preventing or reducing germination. It is noted that the compounds of the present invention show much improved selectivity compared to known structurally similar compounds. In general, the plants to be controlled are undesirable plants (weeds). "Locus" means the area where the plants are growing or will grow. Application may be applied to the locus before and / or after emergence of the crop plants. Several crop plants may be inherently resistant to the herbicidal effect of the compounds of formula (I). Preferred crop plants include corn, wheat, barley, soybean and rice.

[0060] 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; non-arable application, etc.), the crop plants, the weeds to be controlled, the prevailing climatic conditions, as well as other factors governed by the method of application, the time of application and the 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.

[0061] Application is generally accomplished by spraying the composition, typically with a tractor-mounted large area sprayer, although other methods such as dusting (if a powder), dripping or irrigation can also be used.

[0062] It should be understood that crop plants also include crop plants that have been rendered resistant to another herbicide or class 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 resistant to an imidazolinone, such as imazamox, by conventional breeding methods is Clearfield® summer rapeseed (canola). Examples of crops that have been rendered resistant to herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant corn varieties, for example, commercially available under the trade names RoundupReady® and LibertyLink®. The compounds of the present invention can also be used in combination with crops that are resistant to SDPS-inhibiting herbicides, for example, as taught in WO 2020 / 236790.

[0063] Crop plants are also to be understood as those which have been rendered resistant to harmful insects by genetic engineering methods, such as Bt maize (resistant to the European corn borer), Bt cotton (resistant to the boll weevil) and Bt potato (resistant to the Colorado potato beetle). An example of Bt maize is the Bt176 maize hybrid from NK® (Syngenta Seeds). Bt toxins are natural proteins formed by the Bacillus thuringiensis soil bacterium. Examples of toxins or transgenic 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 that contain 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®. Both plant crops or their seed material can be tolerant to herbicides and at the same time to insect feeding ("stacked" transgenics). For example, seeds can be tolerant to glyphosate and at the same time capable of expressing the insecticidal Cry3 protein.

[0064] 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.

[0065] The compositions can be used to control undesirable plants (collectively "weeds"). Weeds to be controlled include, for example, 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, for example, Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola, and Xanthium.

[0066] 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.

[0067] 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 agriculturally acceptable salts thereof, are now described and form further aspects of the invention.

[0068] As shown in Scheme 1, compounds of formula (I) can be prepared via decarboxylation of compounds of formula (2) by heating at 110° C. under acidic conditions in a suitable solvent such as ethanol.

[0069] Compounds of formula (2) can be converted to compounds of formula (4), where LG is a halogen or SO, by heating with compounds of formula (3) in the presence of a base, such as sodium t-butoxide, in a suitable solvent, such as sulfolane. 2 They are prepared using a nucleophilic aromatic substitution reaction of a compound represented by the formula (I) (which represents a suitable leaving group such as Me). The reaction is typically carried out at 40 °C.

[0070] Conditions for forming pyrazole compounds of formula (3) have been described in the literature by condensation of diketones with arylhydrazines (as described in Tetrahedron (2013), 69(16), 3459-3464).

[0071] Scheme 1 [ka] Alternatively, compounds of formula I may be prepared according to Scheme 2 below.

[0072] Scheme 2: [ka] In scheme 2, a compound of formula I can be prepared by converting a compound of formula VI into a compound of formula V, where LG is a 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), N,N-dimethylacetamide, sulfolane or acetonitrile at a temperature between 0 and 120° C., according to procedures well known to those skilled in the art. 1 can be prepared by reaction with a reagent which is a halogen, preferably iodine, bromine or chlorine (or a pseudo halogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g. a triflate).

[0073] Alternatively, a compound of formula I can be prepared by converting a compound of formula VI into a compound of formula V, where LG is a carboxylic acid, optionally in the presence of a metal catalyst such as a copper-based catalyst, e.g., CuI or tetrakis(acetonitrile)copper(I) tetrafluoroborate, and optionally in the presence of a ligand, e.g., trans-1,2-bis(methylamino)cyclohexane or a salt thereof (e.g., the methanesulfonate salt) or 8-hydroxyquinoline, among other similar ligands. 1 may be prepared by reacting with a compound of a halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group, e.g. a (halo)alkyl or phenylsulfonate ester, e.g. a triflate). The reaction can be carried out in the presence of a base such as potassium carbonate, cesium carbonate, triethylamine or pyridine and similar others, in the presence of a solvent such as acetonitrile, 1,4-dioxane or pyridine, optionally under microwave irradiation, at temperatures ranging from room temperature to 200°C.

[0074] Alternatively, compounds of formula I may be prepared by reacting compounds of formula VI with compounds 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, in the presence of a base, such as pyridine or 2,6-lutidine and similar. The reaction can be carried out in the presence of a solvent, such as dichloromethane, toluene, acetonitrile, in the presence of air or oxygen, at temperatures ranging from room temperature to 200°C.

[0075] Compounds of formula VI can be prepared by a protecting group deprotection reaction from a compound of formula VII, where PG is an amino protecting group, such as acetyl, trimethylsilylethoxymethyl (SEM), tert-butyloxycarbonyl, benzyl, p-methoxybenzyl (PMB), among other amino protecting groups. Such reactions are well known to those skilled in the art and can be carried out, for example, under base catalysis, such as using sodium hydroxide in the case of deprotection of an acetyl group, or under acid catalysis, such as using hydrochloric acid or 2,2,2-trifluoroacetic acid in the case of deprotection of a trimethylsilylethoxymethyl (SEM), tert-butyloxycarbonyl or p-methoxybenzyl (PMB) group.

[0076] Compounds of formula VII can be converted to compounds of formula VIII, 12 is C 1 ~C 4 The reaction can be carried out using a base, for example an alkaline earth metal hydroxide or an alkali metal hydroxide such as sodium hydroxide, or in the presence of an acid such as aqueous hydrochloric acid, sulfuric acid, among others. The reaction is generally carried out in the presence of a solvent such as water, ethanol, methanol, tetrahydrofuran or dioxane, or a combination of two or more solvents, at a temperature ranging from room temperature to the boiling point of the solvent.

[0077] Formula VIII (wherein, R 12 is C 1 ~C 4 Compounds of formula X can be converted to compounds of formula IX (wherein LG is an alkyl or phenyl) by procedures well known to those skilled in the art in the presence of a base such as sodium tert-butoxide, sodium or alkaline earth metal hydride, a carbonate (e.g. 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, dimethylsulfoxide, sulfolane or acetonitrile at temperatures between 0 and 200° C. 2can be prepared by reaction with a reagent which is a halogen, (or a pseudo halogen leaving group, such as a (halo)alkyl or phenylsulfonate ester, e.g. a triflate).

[0078] Compounds of formula X can be prepared by condensation reaction of compounds of formula XII with compounds of formula XI (or their hydrochloride or trifluoroacetate salts), where PG is an amino protecting group, e.g., acetyl, trimethylsilylethoxymethyl (SEM), tert-butyloxycarbonyl, benzyl, p-methoxybenzyl (PMB), among other amino protecting groups. Such reactions are well known in the literature and can be carried out, optionally in the presence of an acid catalyst, such as acetic acid.

[0079] The compound of formula XII can be reacted with the compound of formula XIV, 11 is C 1 ~C 4 The compound of formula XIII may be prepared by reacting a compound of formula XIII (wherein the compound is alkyl or phenyl). Such a reaction is known as Claisen condensation reaction and is well known to those skilled in the art. The reaction can be carried out using bases such as lithium diisopropylamide, lithium tetramethylpiperidine, sodium ethoxide, sodium hydride, among other bases, in the presence of solvents such as tetrahydrofuran, ethanol, methanol, at temperatures ranging from -80°C to the boiling point of the solvent.

[0080] Alternatively, compounds of formula I may be prepared according to Scheme 3 below.

[0081] Scheme 3: [ka] In scheme 3, compounds of formula-I are prepared from compounds of formula XV via reduction of an alcohol. Such reduction of an alcohol is well documented in the literature and can be carried out using LiAlH 4Compounds of formula XV can be prepared by the reaction of the compound of formula XVI, where X is a fluorine atom, ... 1 is a halogen, preferably bromine or iodine) with an organometallic reagent, such as BuLi or isopropylmagnesium chloride / LiCl complex, among other metallating reagents, to give intermediate XVIa, where M(Ln) p corresponds to the metal from the organometallic reagent, such as lithium or magnesium, and (Ln) p is an optionally substituted group thereof, such as chloro), and then reacting with a compound of formula XVII. [ka]

[0082] Compounds of formula XVII can be prepared by reacting compounds of formula XVIII with a strong base, such as butyllithium, lithium diisopropylamide, and then with DMF. The reaction is generally carried out in the presence of a solvent, such as tetrahydrofuran, toluene, heptane, and at temperatures 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 compounds of formula XIX with compounds of formula XX, where LG is a fluorine atom, in an inert solvent, such as tetrahydrofuran, dioxane, water, N,N-dimethylformamide, DMF, N,N-dimethylacetamide, dimethylsulfoxide, sulfolane, or acetonitrile, in the presence of a base, such as sodium tert-butoxide, sodium hydride or alkaline earth metal hydride, a carbonate (e.g. sodium carbonate, potassium carbonate, or cesium carbonate) or hydroxide, or a phosphate, such as potassium phosphate, optionally in the presence of potassium iodide, at temperatures between 0° C. and the boiling point of the solvent, according to procedures well known to those skilled in the art. 3can be prepared by reacting a leaving group such as a halogen (or a pseudohalogen leaving group, e.g., a (halo)alkyl or phenylsulfonate ester, e.g., a triflate). Such reactions are described in the literature as S N This is known as the Ar reaction.

[0083] Alternatively, compounds of formula XVIII may be prepared by Chan-Lam coupling, for example by coupling a compound of formula XIX with a compound of formula XXI, 1 For example, B(OH) 2 ORb 1 ) 2 and Rb 1 is C 1 ~C 4 It may be an alkyl group or two groups ORb 1 may form a five-membered ring together with the boron atom, e.g., pinacolboronic acid ester, with a compound of formula (I) (which may form a five-membered ring together with the boron atom, e.g., pinacolboronic acid ester) in the presence of a base such as pyridine, sodium carbonate, potassium triphosphate, or cesium fluoride, in a solvent or solvent mixture such as dioxane, dichloromethane, acetonitrile, N,N-dimethyl-formamide, 1,2-dimethoxyethane and water, or a mixture of dioxane / water, or toluene / water, under an inert atmosphere or under an oxygen atmosphere or under air, using a copper catalyst, e.g., Cu(OAc) among other copper-based catalysts. 2 , CuI, CuBr 2 , which may be catalyzed by CuCl. The reaction temperature may preferentially range 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.

[0084] The following non-limiting examples provide specific methods of synthesis of representative compounds of the invention referenced in Table 1 below.

[0085] Example 1 Synthesis of 5-chloro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine (compound 1.001) Step 1: Synthesis of ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate [ka] A solution of diisopropylamine (3.2 mL, 23 mmol) in tetrahydrofuran (19 mL) was placed under an atmosphere of nitrogen, cooled on ice, and n-butyllithium (2.5 M in hexanes) (9.2 mL, 23 mmol) was added dropwise. The resulting pale yellow mixture was left stirring at 0° C. for 30 min.

[0086] Ethyl acetoacetate (1.00 mL, 7.91 mmol) was added dropwise to the above mixture. The reaction mixture was stirred at 0° C. for 1 hour, then cooled to −78° C., and then ethyl trifluoroacetate (1.20 mL, 10.1 mmol) was added dropwise. The resulting reaction mixture was stirred for 3 hours, during which it warmed to about 0° C.

[0087] The reaction was quenched with 1M hydrochloric acid, diluted with water, extracted with dichloromethane and concentrated to give ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate, which was used without further purification.

[0088] Step 2: Synthesis of ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate [ka] A solution of ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate in acetic acid (15 mL) was treated with 4-(trifluoromethyl)phenylhydrazine (1.35 g, 7.66 mmol) and stirred at room temperature for 1 h, then diluted with water, extracted with tert-butyl methyl ether, and concentrated. The residue was subjected to flash column chromatography to give ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate as an orange solid (1.708 g, 53%). 1H 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)

[0089] Step 3: Synthesis of ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate [ka] A mixture of ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (109 mg, 0.2827 mmol), 2,5-dichloropyrimidine (210 mg, 1.41 mmol) and sodium tert-butoxide (189 mg, 1.91 mmol) was placed under a nitrogen atmosphere and diluted with sulfolane (1.4 mL). The mixture was warmed to 40° C. and stirred for 2 h.

[0090] The reaction mixture was cooled to room temperature, diluted with water and brine, extracted with tert-butyl methyl ether, concentrated, and the residue was subjected to flash column chromatography to give ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate as a yellow oil (110 mg, 65%). 1 H NMR (400 MHz, CDCl 3 )δ=8.69(s,2H),7.83-7.76(m,2H),7.71-7.66(m,2H),6.86(s,1H),5.40(s,1H),4.26-4.17(m,2H),1.21(t,3H)

[0091] Step 4: Synthesis of 5-chloro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine [ka] A solution of ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (110 mg, 0.184 mmol) in ethanol (0.6 mL) was treated with hydrochloric acid (6 mol / L) in deionized water (1.0 mL) and the resulting mixture was irradiated under microwave radiation at 110° C. for 45 min.

[0092] The mixture was diluted with water, extracted with ethyl acetate, and concentrated, and the residue was subjected to column chromatography to give 5-chloro-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine as a beige solid (51 mg, 65%). 1 H NMR (400 MHz, CDCl 3 )δ=8.64(s,2H),7.80-7.70(m,4H),6.61(s,1H),4.38(s,2H)

[0093] Example 2: Preparation of 5-bromo-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine (1.002) Step 1: Preparation of ethyl 2-(5-bromopyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (I1) [ka] To a solution of ethyl 2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate (352 mg, 0.913 mmol) and 1,8-diazabicyclo[5.4.0]undec-7-ene (420 μL, 2.755 mmol) in sulfolane (2.0 mL), 5-bromo-2-chloropyrimidine (533 mg, 2.756 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. The mixture was treated with additional 1,8-diazabicyclo[5.4.0]undec-7-ene (140 μL, 0.918 mmol) and 5-bromo-2-chloropyrimidine (182 mg, 0.941 mmol) and stirred for an additional 2.5 hours. The mixture was diluted with water, acidified with hydrochloric acid, and extracted with tert-butyl methyl ether. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-20% ethyl acetate in cyclohexane to give ethyl 2-(5-bromopyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I1 (425 mg, 76%). 1 H NMR(400MHz,CDCl3)δ=8.78(s,2H),7.79(d,2H),7.68(d,2H),6.86(s,1H),5.37(s,1H),4.26-4.17(m,2H),1.21(t,3H).

[0094] Step 2: Preparation of 5-bromo-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine (1.002) [ka] To a solution of ethyl 2-(5-bromopyrimidin-2-yl)-2-[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I1 (425 mg, 0.691 mmol) in methanol (3.5 mL) was added aqueous sodium hydroxide (2 M, 3.5 mL, 7.0 mmol) and the reaction mixture was stirred at 50 °C for 1 h. The mixture was cooled, diluted with water, 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 with 0.1% formic acid) to give 5-bromo-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine 1.002 (259 mg, 79%). 1 H NMR (400 MHz, CDCl 3 )δ=8.73(s,2H),7.79-7.70(m,4H),6.61(s,1H),4.35(s,2H).

[0095] Example 3: Preparation of 5-bromo-2-[[4-chloro-5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine (1.034) A solution of 5-bromo-2-[[5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine 1.002 (154 mg, 0.307 mmol) and N-chlorosuccinimide (50 mg, 0.367 mmol) in acetonitrile (1.5 mL) was stirred for 7 hours at 80° C. The mixture was cooled, concentrated, and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 5-bromo-2-[[4-chloro-5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyrimidine 1.034 (103 mg, 66%). 1 H NMR (400 MHz, CDCl 3 )δ=8.80(s,2H),7.76-7.64(m,4H),5.38(s,2H).

[0096] Example 4: Preparation of 5-[(5-chloropyrimidin-2-yl)methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile (1.025) [ka] Step 1: Preparation of 1-(3,4-difluorophenyl)pyrazole-3-carbonitrile (I2) [ka] To a mixture of 1H-pyrazole-3-carbonitrile (519 mg, 5.58 mmol), 3,4-difluorophenylboronic acid (1.79 g, 10.8 mmol) and copper(II) acetate (1.60 g, 8.81 mmol) was added dichloromethane (11 mL) and pyridine (880 μL, 10.8 mmol) and the reaction mixture was rapidly stirred at room temperature under air for 20 h. The mixture was concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 1-(3,4-difluorophenyl)pyrazole-3-carbonitrile I2 (964 g, 80%). 1 H NMR (400 MHz, CDCl 3 )δ=7.93(d,1H),7.65-7.58(m,1H),7.47-7.41(m,1H),7.36-7.27(m,1H),6.88(d,1H).

[0097] Step 2: Preparation of 1-(3,4-difluorophenyl)-5-formyl-pyrazole-3-carbonitrile (I3) [ka] Lithium diisopropylamide (2.0 M in THF / heptane / ethylbenzene, 4.6 mL, 9.2 mmol) was added to a solution of 1-(3,4-difluorophenyl)pyrazole-3-carbonitrile I2 (1.238 g, 5.73 mmol) in tetrahydrofuran (14.0 mL) at -78 °C, and the resulting mixture was stirred for 45 min. N,N-dimethylformamide (0.9 mL, 10 mmol) was then added to the mixture, and the mixture was stirred for 1 h. The mixture was quenched with 1 M hydrochloric acid, diluted with water, and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 1-(3,4-difluorophenyl)-5-formyl-pyrazole-3-carbonitrile I3 (638 mg, 45%). 1 H NMR (400 MHz, CDCl 3 )δ=9.88(s,1H),7.46(s,1H),7.45-7.34(m,2H),7.30-7.27(m,1H).

[0098] Step 3: Preparation of 5-[(5-chloropyrimidin-2-yl)-hydroxy-methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile (I4) [ka] To a solution of 5-chloro-2-iodopyrimidine (387 mg, 1.61 mmol) in toluene (7 mL) was added n-butyllithium (2.5 M in hexanes, 0.55 mL, 1.4 mmol) at −78° C. The resulting mixture was stirred for 15 min and then treated with a solution of 1-(3,4-difluorophenyl)-5-formyl-pyrazole-3-carbonitrile I3 (285 mg, 1.16 mmol) in toluene (4 mL) and stirred for an additional 45 min. The mixture was quenched with 0.5 M hydrochloric acid and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 5-[(5-chloropyrimidin-2-yl)-hydroxy-methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile I4 (232 mg, 52%).1 H NMR (400 MHz, CDCl 3 )δ=8.74(s,2H),7.68(ddd,1H),7.56-7.50(m,1H),7.36-7.29(m,1H),6.46(s,1H),5.85(d,1H),4.62(d,1H).

[0099] Step 4: Preparation of 5-[(5-chloropyrimidin-2-yl)methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile (1.025) [ka] To a solution of 5-[(5-chloropyrimidin-2-yl)-hydroxy-methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile I4 (232 mg, 0.60 mmol), imidazole (70 mg, 1.03 mmol) and triphenylphosphine (404 mg, 1.51 mmol) in tetrahydrofuran (4.6 mL) was added dropwise a solution of iodine (208 mg, 0.82 mmol) in tetrahydrofuran (1.2 mL). The mixture was stirred for 5 min before being quenched with aqueous sodium thiosulfate, diluted with water and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane. The product-rich fractions were concentrated and subjected to reverse phase column chromatography on C-18 silica gel using 50-100% acetonitrile in water (both with 0.1% formic acid) to give 5-[(5-chloropyrimidin-2-yl)methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile 1.025 (148 mg, 71%). 1 H NMR (400 MHz, CDCl 3 )δ=8.64(s,2H),7.53-7.45(m,1H),7.36-7.27(m,2H),6.72(s,1H),4.34(s,2H).

[0100] Example 5: Preparation of 4-[5-[(5-chloropyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-1-yl]benzonitrile (1.007) [ka] Step 1: Preparation of ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate (I5) [ka] To an ice-cold solution of diisopropylamine (22 mL, 157 mmol) in THF (110 mL) in a 250 mL round bottom flask was added n-butyllithium (2.5 M in hexanes, 65 mL, 160 mmol) over approximately 30 min. The mixture was stirred for 30 min, treated dropwise with ethyl acetoacetate (6.8 mL, 54 mmol), and stirred at 0° C. for an additional 45 min. The reaction mixture was then cooled to −78° C., treated dropwise with ethyl trifluoroacetate (8.3 mL, 70 mmol), and stirred for 3 h. The mixture was quenched with hydrochloric acid, diluted with water, and extracted with ethyl acetate. The combined organics were dried and concentrated to give I5 as an oil, which was used as such in the next step.

[0101] Step 2: Preparation of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate (I6) [ka] To a solution of I5 prepared in step 1 in acetic acid (90 mL) in a 100 mL round bottom flask, (4-methoxybenzyl)hydrazine hydrochloride (10.56 g, 54.29 mmol) was added and the resulting mixture was left stirring at room temperature for 1.5 h. The mixture was diluted with tert-butyl methyl ether and washed with water and brine. The organics were concentrated and subjected to column chromatography on silica gel using 0-30% ethyl acetate in cyclohexane to give ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate I6 (11.97 g, 59% yield). 1 H NMR (400 MHz, CDCl 3)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).

[0102] Step 3: Preparation of ethyl 2-(5-chloropyrimidin-2-yl)-2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate (I7) [ka] To a solution of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate I6 (4.22 g, 11.71 mmol) in DMSO (40 mL) in a 250 mL round bottom flask, 2,5-dichloropyrimidine (3.71 g, 24.9 mmol) and potassium phosphate tribasic (7.86 g, 36.3 mmol) were added and the reaction mixture was stirred at 60° C. for 3.5 h. The mixture was allowed to stand at room temperature overnight and then stirred at 60° C. for an additional hour. The mixture was cooled to room temperature, diluted with water and extracted with tert-butyl methyl ether. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give ethyl 2-(5-chloropyrimidin-2-yl)-2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate I7 ​​(5.19 g, 73% yield). 1 H NMR (400 MHz, CDCl 3 )δ=8.55(s,2H),6.98-6.92(m,2H),6.79-6.74(m,2H),6.69(s,1H),5.45-5.31(m,3H),4.20-4.11(m,2H),3.77(s,3H),1.21-1.16(m,3H).

[0103] Step 4: Preparation of 5-chloro-2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine (I8) [ka] To a solution of ethyl 2-(5-chloropyrimidin-2-yl)-2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]acetate I7 ​​(5.19 g, 8.56 mmol) in methanol (40 mL) in a 250 mL round bottom flask, 2 M sodium hydroxide (40 mL) was added and the reaction mixture was stirred at 60° C. for 1.5 h. The mixture was cooled to room temperature and concentrated to half the volume. The residue was then acidified with hydrochloric acid and extracted with ethyl acetate. The combined organics were dried and concentrated to give 5-chloro-2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine I8 (3.92 g, quantitative yield). 1 H NMR (400 MHz, CDCl 3 )δ=8.55(s,2H),7.05-6.95(m,2H),6.84-6.75(m,2H),6.47(s,1H),5.40(s,2H),4.22(s,2H),3.78(s,3H).

[0104] Step 5: Preparation of 5-chloro-2-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyrimidine (I9) [ka] A solution of 5-chloro-2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine I8 (3.92 g, 8.56 mmol) in 2,2,2-trifluoroacetic acid (14 mL) in a 100 mL round bottom flask was stirred at 90 °C for 1 h. The mixture was cooled to room temperature and slowly transferred to aqueous sodium bicarbonate, then extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-60% ethyl acetate in cyclohexane to give 5-chloro-2-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyrimidine I9 (2.365 g, 98% yield). 1 H NMR (400 MHz, CDCl 3)δ=8.70(s,2H),6.49(s,1H),4.41(s,2H).

[0105] Step 6: Preparation of 4-[5-[(5-chloropyrimidin-2-yl)methyl]-3-(trifluoromethyl)pyrazol-1-yl]benzonitrile (1.007) To a mixture of 5-chloro-2-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyrimidine I9 (101 mg, 0.346 mmol), (4-cyanophenyl)boronic acid (126 mg, 0.857 mmol) and copper(II) acetate (101 mg, 0.556 mmol) were added 4 Å molecular sieves, dichloromethane (2.3 mL) and pyridine (55 μL, 0.676 mmol) and the reaction mixture was stirred rapidly at room temperature under air for 24 h. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane. The product-rich fractions were concentrated and subjected to reverse-phase column chromatography on C-18 silica gel using 40-100% acetonitrile in water (both with 0.1% formic acid) to give 5-[(5-chloropyrimidin-2-yl)methyl]-1-(3,4-difluorophenyl)pyrazole-3-carbonitrile 1.007 (11 mg, 8%). 1H NMR (400 MHz, CDCl 3 )δ=8.64(s,2H),7.83-7.75(m,4H),6.63(s,1H),4.39(s,2H).

[0106] Example 6: Preparation of 5-chloro-2-[[2-(p-tolyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine (1.037) A suspension of 5-chloro-2-[[3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl]pyrimidine I9 (46 mg, 0.158 mmol), 4-iodotoluene (76 mg, 0.349 mmol), copper(I) iodide (4 mg, 0.021 mmol), trans-N,N'-dimethyl-1,2-cyclohexanediamine bis-(methanesulfonic acid) (25 mg, 0.075 mmol) and potassium carbonate (71 mg, 0.514 mmol) in 1,4-dioxane (0.6 mL) was irradiated under microwave irradiation to 150 °C for 5 h. The mixture was diluted with water and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane. The product-rich fractions were concentrated and subjected to reverse-phase column chromatography on C-18 silica gel using 40-100% acetonitrile in water (both with 0.1% formic acid) to give 5-chloro-2-[[2-(p-tolyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine 1.037 (9 mg, 15%). 1 H NMR (400 MHz, CDCl 3 )δ=8.62(s,2H),7.39-7.34(m,2H),7.28-7.23(m,2H),6.53(s,1H),4.32(s,2H),2.41(s,3H).

[0107] Example 7: Preparation of 5-chloro-2-[[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine 1.026. Step 1: Preparation of tert-butyl N-(6-chloro-5-fluoro-3-pyridyl)carbamate I10-a. [ka] To a mixture of 5-bromo-2-chloro-3-fluoropyridine (1.06 g, 5.04 mmol), tert-butyl carbamate (768 mg, 6.56 mmol), palladium(II) acetate (40 mg, 0.173 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (182 mg, 0.305 mmol) and potassium carbonate (1.33 g, 9.62 mmol) was added 1,4-dioxane (12 mL) and the mixture was stirred at 110 °C for 7 h. 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 0-40% ethyl acetate in cyclohexane to give tert-butyl N-(6-chloro-5-fluoro-3-pyridyl)carbamate I10-a (1.062 g, 77% yield). 1 H NMR (400 MHz, CDCl 3 )δ=8.06(br d,1H),7.98(d,1H),6.64(br s,1H),1.53(s,9H).

[0108] Step 2: Preparation of 6-chloro-5-fluoro-pyridin-3-amine trifluoroacetate I10-b. [ka] To a solution of tert-butyl N-(6-chloro-5-fluoro-3-pyridyl)carbamate I10-a (1.062 g, 3.875 mmol) in dichloromethane (8 mL) was added trifluoroacetic acid (3.0 mL, 39 mmol) and the resulting mixture was stirred at room temperature for 1 h. After completion, the mixture was concentrated to give 6-chloro-5-fluoro-pyridin-3-amine trifluoroacetate I10-b as a gum, which was used as such in the next step.

[0109] Step 3: Preparation of (6-chloro-5-fluoro-3-pyridyl)hydrazine; hydrochloride salt I10-c. [ka] To a solution of I10-b prepared in step 2 in aqueous hydrochloric acid (6.5 mL, 6 M) was added a solution of sodium nitrite (284 mg, 4.116 mmol) in water (2 mL) at 0° C. The resulting mixture was stirred for 15 min and treated with a solution of tin chloride (1.96 g, 10.3 mmol) in aqueous hydrochloric acid (6.5 mL, 6 M). The resulting mixture was stirred at 0° C. for 15 min. After completion, the mixture was basified with aqueous sodium hydroxide and extracted with ethyl acetate. The combined organics were dried and concentrated. The residue was redissolved in tert-butyl methyl ether and treated with hydrochloric acid (1.25 M in EtOH, 3.5 mL, 4.4 mmol). The mixture was stirred for 1 h and the precipitate was collected by filtration to give (6-chloro-5-fluoro-3-pyridyl)hydrazine hydrochloride salt I10-c (558 mg, 69% yield). 1 H NMR(400MHz,DMSO-d6)δ=10.83(br s,3H),8.96(br s,1H),7.99-7.94(m,1H),7.58-7.47(m,1H).

[0110] Step 4: Preparation of ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]acetate I11. [ka] To a solution of (6-chloro-5-fluoro-3-pyridyl)hydrazine hydrochloride I10-c (242 mg, 1.161 mmol) in aqueous hydrochloric acid (6 mL, 6 M) was added a solution of ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate I5 (688 mg, 1.947 mmol) in ethanol (6 mL) and the mixture was stirred at room temperature for 1 h. The mixture was 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 to give ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]acetate I11 (233 mg, 34% yield, 60% purity). 1H NMR (400 MHz, chloroform) δ = 8.42 (d, 1H), 7.80 (dd, 1H), 6.72 (s, 1H), 4.18 (q, 2H), 3.75 (s, 2H), 1.26 (t, 3H).

[0111] Step 5: Preparation of ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]-2-(5-chloropyrimidin-2-yl)acetate I12. [ka] To a solution of ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]acetate I11 (370 mg, 0.631 mmol) and 2,5-dichloropyrimidine (366 mg, 2.457 mmol) in dimethylsulfoxide (2.0 mL) was added tribasic potassium phosphate (693 mg, 3.20 mmol) and the mixture was stirred at 80° C. for 1 h. The mixture was cooled, diluted with 0.5 M hydrochloric acid, and extracted with tert-butyl methyl ether. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-25% ethyl acetate in cyclohexane to give ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]-2-(5-chloropyrimidin-2-yl)acetate I12 (174 mg, 47% yield). 1 H NMR (400 MHz, chloroform) δ = 8.70 (s, 2H), 8.50 (d, 1H), 7.86 (dd, 1H), 6.91 (s, 1H), 5.35 (s, 1H), 4.30-4.17 (m, 2H), 1.23 (t, 3H).

[0112] Step 6: Preparation of 5-chloro-2-[[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine 1.026. [ka] To a solution of ethyl 2-[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]-2-(5-chloropyrimidin-2-yl)acetate I12 (309 mg, 0.585 mmol) in tetrahydrofuran (2.5 mL) was added aqueous hydrochloric acid (6 M, 2.5 mL, 15 mmol) and the mixture was heated at 150 °C under microwave irradiation for 40 min. The reaction mixture was diluted with water 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 with 0.1% formic acid). The product-rich fractions were concentrated and subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 5-chloro-2-[[2-(6-chloro-5-fluoro-3-pyridyl)-5-(trifluoromethyl)pyrazol-3-yl]methyl]pyrimidine 1.026 (180 mg, 74.61% yield). 1 H NMR (400 MHz, chloroform) δ = 8.65 (s, 2H), 8.60 (d, 1H), 7.95 (dd, 1H), 6.65 (s, 1H), 4.38 (s, 2H).

[0113] Example 8: Preparation of 5-chloro-2-[[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]methyl]pyrimidine 1.032 Step 1: Preparation of ethyl 6,6-difluoro-3,5-dioxo-hexanoate I13-a. [ka] To an ice-cold solution of lithium diisopropylamine (2.0 M in THF / heptane / ethylbenzene, 45 mL, 90 mmol) in THF (50 mL) was added ethyl acetoacetate (3.9 mL, 31 mmol) dropwise and the mixture was stirred at 0° C. for 30 min. The reaction mixture was then cooled to −78° C. and treated dropwise with ethyl difluoroacetate (4.2 mL, 40 mmol) and stirred for 2 h. The mixture was quenched with hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined organics were dried and concentrated to give I13-a as an oil, which was used as such in the next step assuming quantitative conversion.

[0114] Step 2: Preparation of ethyl 2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I13-b. [ka] A solution of ethyl 6,6-difluoro-3,5-dioxo-hexanoate I13-a (1.6 g, 7.75 mmol) in acetic acid (12.5 mL) in a 50 mL round-bottom flask was treated with 3,4-difluorophenylhydrazine hydrochloride (1.44 g, 7.97 mmol) and left stirring at room temperature for 20 h. The reaction mixture was concentrated and subjected to column chromatography (0-40% ethyl acetate in cyclohexane). The product-containing fractions were combined and concentrated under vacuum to give ethyl 2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I13-b (1.299 g, 70% purity, 37.1% yield). 1 H NMR (400 MHz, chloroform) δ = 7.44-7.20 (m, 3H), 6.70 (t, 1H), 6.63 (s, 1H), 4.16 (q, 2H), 3.70 (s, 2H), 1.25 (t, 3H).

[0115] Step 3: Preparation of ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I14. [ka] To a solution of ethyl 2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I13-b (318 mg, 0.704 mmol) and 2,5-dichloropyrimidine (251 mg, 1.685 mmol) in dimethylsulfoxide (2.0 mL) was added tribasic potassium phosphate (572 mg, 2.641 mmol) and the mixture was stirred at 80 °C for 1.5 h. The mixture was cooled, acidified with hydrochloric acid, diluted with water and extracted with tert-butyl methyl ether. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-30% ethyl acetate in cyclohexane to give ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I14 (260 mg, 60% yield). 1 H NMR (400 MHz, chloroform) δ = 8.68 (s, 2H), 7.45-7.26 (m, 3H), 6.76 (s, 1H), 6.70 (t, 1H), 5.35 (s, 1H), 4.26-4.18 (m, 2H), 1.22 (t, 3H).

[0116] Step 4: Preparation of 5-chloro-2-[[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]methyl]pyrimidine 1.032. [ka] To a solution of ethyl 2-(5-chloropyrimidin-2-yl)-2-[5-(difluoromethyl)-2-(3,4-difluorophenyl)pyrazol-3-yl]acetate I14 (304 mg, 0.496 mmol) in methanol (3 mL) was added aqueous sodium hydroxide (2 M, 3 mL) and the mixture was stirred at room temperature for 17 h. The mixture was acidified with hydrochloric acid, diluted with water, 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 with 0.1% formic acid) to give 5-chloro-2-[[5-(difluoromethyl)-2-(4-fluorophenyl)pyrazol-3-yl]methyl]pyrimidine 1.032 (135 mg, 72% yield). 1 H NMR (400 MHz, chloroform) δ = 8.64 (s, 2H), 7.53-7.46 (m, 1H), 7.36-7.22 (m, 2H), 6.69 (t, 1H), 6.53 (s, 1H), 4.34 (s, 2H).

[0117] [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]

[0118] Biological Examples Seeds of the various test species: Amaranthus palmeri (AMAPA), Amaranthus retroflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE) are sown in pots in standard soil. After 1 day of incubation (pre-germination) or 8 days of incubation (post-germination) under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours light; 65% humidity), the plants are sprayed with an aqueous spray solution obtained from a combination of the technical active ingredients 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 are then grown in a greenhouse under controlled conditions in a greenhouse (24 / 16°C, day / night; 14 hours light; 65% humidity) and watered twice a day. After 13 days for pre- and post-emergence, the tests are evaluated for the percentage of damage caused to the plants. The 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%).

[0119] [Table 2]

[0120] [Table 3]

Claims

1. Formula (I): 【Chemistry 1】 (In the ceremony Q is phenyl, C-linked 6-membered heteroaryl, QA and QB 【Chemistry 2】 wherein said phenyl or 6-membered heteroaryl is selected from the group consisting of one or more independent R 3 may be optionally substituted with a substituent; R 1 is halogen, -CN, NO 2 , C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 3 ~C 6 Cycloalkyl, C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, —S(O) p C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy-, —C(O)C 1 ~C 4 Alkyl, —C(O)OC 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkoxy and C 1 ~C 4 Alkoxy C 1 ~C 3 independently selected from the group consisting of alkyl-; R 2 is halogen, -CN, C 1 ~C 2 Alkyl and C 1 ~C 2 haloalkyl; R 3 is a halogen, C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy, C 1 ~C 4 Haloalkoxy, -CN, NO 2 , C 2 ~C 4 Alkenyl, C 2 ~C 4 Alkynyl, —S(O) p C 1 ~C 4 selected from the group consisting of alkyl; R 4 is hydrogen, halogen, -CN, C 1 ~C 2 Alkyl and C 1 ~C 2 haloalkyl; p=0, 1 or 2) or an agriculturally acceptable salt thereof.

2. Q: 【Transformation 3】 2. The compound of formula (I) according to claim 1, selected from the group consisting of:

3. The compound according to claim 2, wherein Q is Q-1 or Q-3.

4. 3. The compound of claim 2, wherein n is 1.

5. R 3 is halogen or -CF 3 5. The compound of claim 4, wherein:

6. Q is 4-CF 3 The compound of claim 1, wherein the aryl group is -phenyl-.

7. R 1 But halogen, CN, C 1 ~C 4 Alkyl, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Alkoxy and C 1 ~C 4 2. The compound of claim 1 selected from the group consisting of haloalkoxy.

8. R 1 The compound of claim 7, wherein is selected from the group consisting of methyl, fluoro, chloro, bromo, and methoxy-.

9. R 1 The compound of claim 8 , wherein is chloro.

10. R 2 Ga-CF 3 or -CF 2 2. The compound of claim 1, wherein R is H.

11. R 4 The compound of claim 1 , wherein is hydrogen.

12. A herbicidal composition comprising a compound according to any one of claims 1 to 11 and an agriculturally acceptable formulation adjuvant.

13. 13. The herbicidal composition of claim 12, further comprising at least one additional pesticide.

14. 14. The herbicidal composition of claim 13, wherein the additional pesticide is a herbicide or a herbicide safener.

15. 13. A method of controlling weeds in a locus, comprising applying to said locus a weed-controlling amount of the composition of claim 12.

16. 10. Use of a compound of formula (I) as defined in claim 1 as a herbicide.

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