CN120530101A - Herbicidal pyrazole compounds - Google Patents

Abstract

The present invention relates to compounds of formula (I) or agronomically acceptable salts thereof, wherein Q, R ¹ , R ² , R ³ and m are as defined herein. The present 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.

Description

Herbicidal pyrazole compounds

The present invention relates to novel herbicidal compounds, to a process for their preparation, to herbicidal compositions comprising these novel compounds, and to their use for controlling weeds, especially in crops of useful plants, or for inhibiting plant growth.

WO 2022/013493, WO 2022/101270 and WO 2023/099354 disclose herbicidal pyrazole compounds featuring pyrimidine rings.

Thus, according to the present invention there is provided a compound having formula (I):

Or an agronomically acceptable salt thereof,

Wherein the method comprises the steps of

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

R ¹ is independently selected from the group consisting of halogen, -CN, NO ₂、C₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₃-C₆ cycloalkyl, C ₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, C ₁-C₄ alkoxy-, -C (O) C ₁-C₄ alkyl, -C (O) OC ₁-C₄ alkyl, C ₁-C₄ haloalkoxy, and C ₁-C₄ alkoxy C ₁-C₃ alkyl-;

r ² is selected from the group consisting of halogen, -CN, NO ₂、C₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, -C (O) C ₁-C₄ alkyl, -C (O) OC ₁-C₄ alkyl, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxyC ₁-C₃ alkyl-, C ₁-C₄ alkoxyC ₁-C₃ alkoxy-, C ₁-C₄ alkoxyC ₁-C₃ alkoxyC ₁-C₃ alkyl-, -S (O) _pC₁-C₄ alkyl, and C ₃-C₆ cycloalkyl;

R ³ is selected from the group consisting of hydrogen, halogen, C ₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxy C ₁-C₃ alkyl-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy C ₁-C₃ alkyl-, -CN, NO ₂、C₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, -S (O) _pC₁-C₄ haloalkyl, -C (O) OC ₁-C₄ alkyl, -C (R ⁷)＝NOR⁸ and-C (O) NR ⁵R⁶;

R ⁴ is selected from the group consisting of halogen, C ₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxy C ₁-C₃ alkyl-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy C ₁-C₃ alkyl-, -CN, NO ₂、C₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, -S (O) _pC₁-C₄ haloalkyl, -C (O) OC ₁-C₄ alkyl, and-C (O) NR ⁵R⁶;

R ⁵ is hydrogen or C ₁-C₄ alkyl;

R ⁶ is hydrogen or C ₁-C₄ alkyl;

R ⁷ is hydrogen or C ₁-C₄ alkyl;

R ⁸ is hydrogen or C ₁-C₂ alkyl;

m=0, 1 or 2, and

P=0, 1 or 2.

C ₁-C₄ alkyl-and C ₁-C₆ alkyl-include, for example, methyl (Me, CH ₃), ethyl (Et, C ₂H₅), n-propyl (n-Pr), isopropyl (i-Pr), n-butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu). C ₁-C₂ alkyl is methyl (Me, CH ₃) or ethyl (Et, C ₂H₅).

C ₂-C₄ alkenyl-includes, for example, -ch=ch ₂ (vinyl) and-CH ₂-CH＝CH₂ (allyl).

C ₂-C₄ alkynyl-refers to a straight or branched hydrocarbon chain group consisting of only 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 single bonds. Examples of C ₂-C₄ alkynyl include, but are not limited to, prop-1-ynyl, propargyl (prop-2-ynyl), and but-1-ynyl.

Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The above correspondingly applies to halogens in the context of other definitions, such as haloalkyl.

C ₁-C₄ haloalkyl includes, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-trifluoroethyl 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, 1-difluoro-2, 2-trichloroethyl, 2, 3-tetrafluoropropyl and 2, 2-trichloroethyl and heptafluoro-n-propyl. C ₁-C₂ haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl or 1, 1-difluoro-2, 2-trichloroethyl.

C ₁-C₆ alkoxy includes methoxy and ethoxy.

C ₁-C₄ haloalkoxy-including, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-trifluoroethoxy 1, 2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2-difluoroethoxy or 2, 2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.

C ₁-C₄ AlkoxyC ₁-C₃ alkyl-includes, for example, methoxymethyl-.

C ₁-C₄ Alkoxy C ₁-C₃ alkoxy-includes, for example, methoxyethoxy-.

C ₁-C₄ Alkoxy C ₁-C₃ Alkoxy C ₁-C₃ alkyl-including, for example, methoxyethoxymethyl-.

C ₃-C₆ cycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

C ₁-C₄ alkyl-S- (alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

C ₁-C₄ alkyl-S (O) - (alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

C ₁-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.

In one embodiment of the invention, R ³ is hydrogen.

In one embodiment of the invention, compounds are provided having formula (I) wherein m is 1 or 2, and R ¹ is independently selected from the group consisting of halogen (e.g., F, cl or Br), -CN, C ₁-C₄ alkyl (e.g., me), C ₁-C₄ haloalkyl (e.g., CHF ₂ or CF ₃)、C₁-C₄ alkoxy- (e.g., meO-) and C ₁-C₄ haloalkoxy (e.g., CF ₃O-、CHF₂ O-).

In another embodiment of the invention, m is 1. In another embodiment of the invention, m is 2.

In a preferred embodiment of the invention, m is 1 and R ¹ is halogen (e.g., chlorine).

In another preferred embodiment of the invention, R ² is selected from the group consisting of halogen, C ₁-C₄ haloalkyl- (preferably CF ₃ or-CF ₂ H), cPr and CN. In a preferred embodiment, R ² is C ₁-C₄ haloalkyl (preferably, -CF ₃ or-CF ₂ H).

In another embodiment of the invention, Q is selected from the group consisting of:

wherein n is 0,1 or 2.

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

In another preferred embodiment, n is 1. In this embodiment, R ⁴ is preferably selected from the group consisting of cyano, methyl, halogen, and-CF ₃. In a particularly preferred embodiment, Q is 4-Cl-phenyl-.

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

Wherein R ^4a is halogen, preferably fluorine or chlorine, and R ^4b is preferably fluorine or chlorine, and wherein R ¹、R² and R ³ are as defined in formula (I). In a more preferred embodiment, compounds of formula (Iba') are provided wherein R ¹ is chloro, R ² is-CF ₃ or-CF ₂ H, and R ³ is hydrogen. Compounds having the formula (Iba') are particularly preferred in the context of the present invention, as they typically exhibit improved crop selectivity, particularly in corn.

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

The invention also provides agronomically acceptable salts of compounds having formula (I). Preferred are salts of the compounds of formula (I) with amines, including primary, secondary and tertiary amines (e.g. ammonia, dimethylamine and triethylamine), alkali and alkaline earth metal bases, transition metal bases or quaternary ammonium bases.

The compounds of formula (I) according to the invention may themselves be used as herbicides, but they are generally formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents and Surfactants (SAA). Accordingly, 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 compositions may be in the form of concentrates which are diluted prior to use, although ready-to-use compositions may also be prepared. The final dilution is usually done with water, but may be done using, for example, liquid fertilizers, micronutrients, biological organisms, oils or solvents instead of or in addition to water.

The herbicidal compositions generally comprise from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of the formula I and from 1 to 99.9% by weight of a formulation auxiliary, which preferably comprises from 0 to 25% by weight of a surface-active substance.

The composition may 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 Dispersions (OD), oil miscible flowable (OF), oil miscible liquids (OL), soluble concentrates (SL), ultra low volume Suspensions (SU), ultra low volume liquids (UL), masterbatches (TK), dispersible Concentrates (DC), soluble Powders (SP), wettable Powders (WP) and Soluble Granules (SG). In any event, the type of formulation selected will depend on the particular purpose envisaged and the physical, chemical and biological properties of the compound of formula (I).

Soluble Powders (SP) may be prepared by mixing a compound having formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulphate) or one or more water-soluble organic solids (such as polysaccharides) and optionally one or more wetting agents, one or more dispersing agents or mixtures of said agents to improve water dispersibility/water solubility. The mixture was then ground to a fine powder. Similar compositions may also be granulated to form water Soluble Granules (SG).

Wettable Powders (WP) may be prepared by mixing a compound having formula (I) with one or more solid diluents or carriers, one or more wetting agents and preferably one or more dispersing agents, and optionally one or more suspending agents to facilitate dispersion in a liquid. The mixture was then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

The Granules (GR) may be formed by granulating a mixture of a compound of formula (I) with one or more powdered solid diluents or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) into a porous particulate material such as pumice, attapulgite clay, fuller's earth, kieselguhr (kieselguhr), diatomaceous earth (diatomaceous earth) or corncob powder, or by adsorbing a compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material such as sand, silicate, mineral carbonate, sulphate or phosphate 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, dextrins, sugars and vegetable oils). One or more other additives (e.g., emulsifiers, wetting agents, or dispersants) may also be included in the granule.

Dispersible Concentrates (DC) may be prepared by dissolving a compound having formula (I) in water or an organic solvent such as a ketone, alcohol or glycol ether. These solutions may contain surfactants (e.g., to improve water dilution or to prevent crystallization in spray cans).

Emulsifiable Concentrates (EC) or oil-in-water Emulsions (EW) may be prepared by dissolving a compound having formula (I) in an organic solvent, optionally containing one or more wetting agents, one or more emulsifying agents or a mixture of said agents. Suitable organic solvents for use in the EC 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 C ₈-C₁₀ fatty acid dimethylamides), and chlorinated hydrocarbons. The EC product may spontaneously emulsify upon addition to water, thereby producing an emulsion with sufficient stability to allow spray application by appropriate equipment.

The preparation of EW involves obtaining a compound of formula (I) as a liquid (if it is not a liquid at room temperature, it may be melted at a suitable temperature typically below 70 ℃) 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 EW include vegetable oils, chlorinated hydrocarbons (e.g., chlorobenzene), aromatic solvents (e.g., alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents having low solubility in water.

Microemulsions (ME) can be prepared by mixing water with a blend of one or more solvents and one or more SAAs to spontaneously produce thermodynamically stable isotropic liquid formulations. The compound of formula (I) is initially present in water or in a solvent/SAA blend. Suitable solvents for use in ME include those described above for use in EC or in EW. The ME may be an oil-in-water system or a water-in-oil system (which system is present can be determined by conductivity measurements) and may be suitable for mixing a water-soluble pesticide and an oil-soluble pesticide in the same formulation. ME is suitable for dilution into water, either to remain as a microemulsion or to form a conventional oil-in-water emulsion.

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

The aerosol formulation comprises a compound having formula (I) and a suitable propellant (e.g. n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable medium (e.g., water or a water miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized manual spray pump.

The Capsule Suspension (CS) can be prepared in a similar manner to the preparation of the EW formulation, but with an additional polymerization stage, to obtain an aqueous dispersion of oil droplets, each of which is surrounded by a polymeric shell and contains a compound having formula (I) and optionally a carrier or diluent for the oil droplets. The polymer shell may be produced by interfacial polycondensation reactions or by coacervation procedures. These compositions can provide controlled release of compounds having formula (I) and they can be used for seed treatment. The compounds of formula (I) may also be formulated in biodegradable polymer matrices to provide slow, controlled release of the compounds.

The composition may contain one or more additives to improve the biological properties of the composition, for example by improving the wettability, retention or distribution on the surface, the resistance to rain on the treated surface, or the absorption or mobility of the compound of formula (I). Such additives include Surfactants (SAA), oil-based spray additives such as certain mineral or natural vegetable oils (e.g., soy and rapeseed oils), modified vegetable oils (e.g., methylated rapeseed oil (MRSO)), and blends of these with other bio-enhancing adjuvants (ingredients that can assist or alter the action of compounds having formula (I)).

Wetting agents, dispersants and emulsifiers may be SAA of cationic, anionic, amphoteric or nonionic type.

Suitable cationic types of SAAs include quaternary ammonium compounds (e.g., cetyltrimethylammonium bromide), imidazolines, and amine salts.

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 dodecyl benzene sulfonate, calcium dodecyl benzene sulfonate, butylnaphthalene sulfonate and mixtures of sodium di-isopropyl naphthalene sulfonate and sodium tri-isopropyl naphthalene sulfonate), ether sulfates, alcohol ether sulfates (e.g. sodium laureth-3-sulfate), ether carboxylates (e.g. sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (mainly monoesters) or with phosphorus pentoxide (mainly diesters), such as between lauryl alcohol and tetraphosphoric acid; alternatively, these products may be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, lignin sulfonates and phosphate/sulfates of tristyrylphenols.

Suitable amphoteric types of SAAs include betaines, propionates, and glycinates.

Suitable nonionic SAAs include condensation products of alkylene oxides (such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol), partial esters derived from long chain fatty acids or hexitol anhydrides, condensation products of the partial esters with ethylene oxide, block polymers (comprising ethylene oxide and propylene oxide), alkanolamides, monoesters (such as polyethylene glycol esters of fatty acids), amine oxides (such as lauryl dimethyl amine oxide), lecithins and sorbitan and esters thereof, alkylpolyglycosides and tristyrylphenols.

Suitable suspending agents include hydrocolloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

The compounds of the invention may also be used in mixtures with one or more further herbicides and/or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), benomyl, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, fluobutamid-M, quinclorac (benquitrione), bensulfuron (including bensulfuron-methyl), bentazone, dicyclopyrone, bialaphos, bispyribac-sodium Luo Zong (bixlozone), triclopyr, bromoxynil, butachlor, flumetsulam, carfentrazone (including carfentrazone-ethyl), clomazone (including clomazone-methyl), chlorimuron-ethyl, chlorsulfuron, clomazone (clacyfos), clethodim, clodinafop-propargyl (including clodinafop-propargyl), clomazone, clopyralid, ciclopirox (cyclopyranil), ciclopirox (cyclopyrimorate), cyclosulfamuron, cyhalofop-butyl (including cyhalofop-butyl), 2,4-D (including choline salts and 2-ethylhexyl esters thereof), 2,4-DB, betalain, dicamba (including aluminum, aminopropyl, bis-aminopropyl methyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), diclosulam, diflufenican, diflufenzopyr, dimethenamine, dimethenamid, dioxopyrithione (dioxopyritrione), dibromodiquat, diuron, epyrazamate (EPYRIFENACIL), ethaboxam, ethofumesafen, fenoxaprop-p-ethyl (including fenoxaprop-ethyl), benoxazamate (fenoxasulfone), fenflurazon, fentanyl Cui Du (fenquinotrione), fentrazamide, flazasulfuron, diflufenican, flurbipyridyl (florpyrauxifen) (including fluroxypyr-benzyl), trifluramate-methyl, Fluazifop-butyl (including fluazifop-butyl), flucarbazone-sodium (including flucarbazone-sodium), flufenacet, flumetsulam, flubenuron, fomesafen, fluflazasulfuron (including fluazifop-methyl-sodium), flubenfop-butyl (including fluazifop-methyl-heptyl ester (fluroxypyr-meptyl)), fomesafen, foramsulfuron, glufosinate (including L-glufosinate and ammonium salts thereof), glyphosate (including the diamine, isopropylammonium and potassium salts thereof), fluclopyralid (halauxifen) (including fluclopyralid-methyl), fluazifop-methyl (including fluazifop-methyl), Cyclozinone, hydantoin (hydantocidin), imazamox (including R-imazethapyr), imazethapyr, indenofloxacin, iodosulfuron (including iodosulfuron-methyl-sodium), iodofensulfuron (iofensulfuron) (including iodofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lan Ke San ketone (lancotrione), MCPA, MCPB, homo2-methyl-4-chloropropionic acid (mecoprop-P), methyldisulfone (including methyldisulfone-methyl), mesotrione, benzodiazepinone, metazachlor, isothiabendazole (metazolin), metolachlor, sulfentrazone, zinone, metsulfuron, dichlormid, nicosulfuron, dactylon, oxadiazon, cyclosulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, bendiuron, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryn, propanil, oxazamate, propyrisulfuron (propyrisulfuron), penoxsulam, prosulfuron, flucarbazone, bispyribac-sodium, pyriftalin (pyraflufen) (including pyribac-ethyl), sulfenpyr-ethyl, pyridate, benfuracarb, Cyclofenacet, flusulfamide (pyrimisulfan), pyrsulfuron-ethyl (pyroxasulfone), pyroxsulam, quinclorac, cloquintocet-mexyl (including quizalofop-ethyl and quizalofop-ethyl (quizalofop-P-tefuryl)), li Misha-fen (rimisoxafen), rimsulfuron, pyribenzoxim, sethoxydim, simazine, primisulfenamine, sulfenuron, buthiuron, terfutrione, cyclosulfamone, terbuthylazine, terbutryn, tetrafluoro-troben (tetflupyrolimet), Thiosulfuron (thiencarbazone), thifensulfuron methyl, flumetsulam (tiafenacil), tolbutate (tolpyralate), topramezone, triclopyr, flucarbazone-sodium (triafamone), dicamba, cinosulfuron, tribenuron-methyl (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifluoperazine (trifludimoxazin), trifluralin, flucarbazone-sodium, triazosulfuron, 3- (2-chloro-4-fluoro-5- (3-methyl-2, 6-dioxo-4-trifluoromethyl-3, 6-dihydropyrimidin-1 (2H) -yl) phenyl) -5-methyl-4, 5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1-methoxy-5-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one, 4-hydroxy-1, 5-dimethyl-3- [4- (trifluoromethyl) -2-pyridinyl ] imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3- [4- (trifluoromethyl) -2-pyridinyl ] 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, propyl 4-amino-3-chloro-5-fluoro-6- (7-fluoro-1H-indol-6-yl) pyridine-2-carboxylate and methyl 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] triazolo [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, 2- [ [3- [ [ 3-chloro-5-fluoro-6- [ 3-methyl-2, 6-dioxo-4- (trifluoromethyl) pyrimidin-1-yl ] -2-pyridinyl ] oxy ] acetic acid ethyl ester, 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 ] propionic acid tetrahydrofuran-2-ylmethyl ester, (2R) -2- [ (4-amino-3, 5-dichloro-6-fluoro-2-pyridinyl) oxy ] propionic acid, tetrahydrofuran-2-ylmethyl ester of 2- [ (4-amino-3, 5-dichloro-6-fluoro-2-pyridinyl) 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.

The mixed compatibility of the compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in THE PESTICIDE Manual, sixteenth edition, british Crop Protection Council, british crop protection committee 2012.

The compounds of formula (I) can also be used in combination with other agrochemicals, such as fungicides, nematicides or insecticides, examples of which are given in THE PESTICIDE Manual.

The mixing ratio of the compound of formula (I) to the mixed compatibilisation is preferably from 1:100 to 1000:1.

These mixtures can be advantageously used in the formulations mentioned above (in which case "active ingredient" refers to the corresponding mixture of a compound of formula (I) with a mixed compatibility).

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 clomazone, clomazone (cloquintocet) (including cloquintocet-mexyl), cyclopropanesulfonamide, dichlorvos, clomazone (including clomazone ethyl), clomazone, trifloxystrobin, clomazone, bisbenzoxazole acid (including bisbenzoxazole acid-ethyl), mefenpyr (mefenpyr) (including mefenpyr), clomazone (metcamifen), and clomazone.

Particularly preferred are mixtures of compounds of formula (I) with cyclopropanesulfonamide, bisbenzoxazole acid-ethyl, cloquintocet-mexyl and/or clomazone.

Safeners of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in THE PESTICIDE Manual, 16 th edition (BCPC), 2012. Reference to cloquintocet-mexyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02/34048.

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

The present invention still further provides a method of controlling weeds at a locus comprising applying to the locus a weed controlling amount of a composition comprising a compound of formula (I). In addition, the present invention may further provide a method of selectively controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises applying to the locus a weed controlling amount of a composition according to the invention. By 'control' is meant killing, reducing or delaying growth or preventing or reducing germination. It should be noted that the compounds of the present invention show a greatly improved selectivity compared to known structurally similar compounds. Typically, the plants to be controlled are unwanted plants (weeds). By 'locus' is meant the area in which plants are growing or will grow. The application may be to the locus pre-emergence and/or post-emergence of the crop plants. Some crop plants may inherently tolerate the herbicidal effect of compounds having formula (I). Preferred crop plants include corn, wheat, barley, soybean and rice.

The application rate of the compounds of the formula I can vary within wide limits and depends on the nature of the soil, the application method (pre-or post-emergence; seed dressing; application to seed furrows; no-tillage application etc.), the crop plant, the weed or weeds to be controlled, the prevailing climatic conditions and other factors governed by the application method, the application time and the target crop. The compounds of the formula I according to the invention are generally applied in a ratio of from 10g/ha to 2500g/ha, in particular from 25g/ha to 1000g/ha, more in particular from 25g/ha to 250 g/ha.

Application is usually carried out by spraying the composition, typically by tractor mounted sprayers for large areas, but other methods such as dusting (for powders), dripping or dipping may also be used.

Crop plants are understood to also include those crop plants which have been rendered tolerant to other herbicides or classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, HPPD-inhibitors, inhibitor-PDS and accase-inhibitors) by conventional breeding methods or by genetic engineering. Examples of crops which have been rendered tolerant to imidazolinones (e.g. imazethapyr) by conventional breeding methods areSummer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include, for example, maize varieties with glyphosate and glufosinate resistance, which are under the trade nameAndAre commercially available. The compounds of the invention may also be used in combination with crops that are tolerant to SDPS inhibiting herbicides, such as those taught in WO 2020/236790.

Crop plants are also understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, such as Bt maize (resistant to european corn borer), bt cotton (resistant to boll weevil) and also Bt potato (resistant to corrador beetle). Examples of Bt corn areBt 176 maize hybrid of (first just reaching seed company (SYNGENTA SEEDS)). Bt toxins are proteins naturally formed by Bacillus thuringiensis (Bacillus thuringiensis) soil bacteria. 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 insecticidal resistance and expression of one or more toxins are(Corn), yield(Corn),(Cotton),(Cotton),(Potato),AndThe plant crop or seed material thereof is resistant to both herbicides and insect ingestion (a "stacked" transgenic event). For example, the seed may have the ability to express an insecticidal Cry3 protein while being tolerant to glyphosate.

Crop plants are also understood to include those obtained by conventional methods of breeding or genetic engineering and containing so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).

These compositions may be used to control unwanted vegetation (collectively, 'weeds'). Weeds to be controlled may be either monocotyledonous species such as Agrostis (Agrostis), myrta (Alopecurus), avena (Avena), mesona (Brachiaria), bromus (Bromus), tribulus (Cenchrus), cyperus (Cyperus), crabgrass (DIGITARIA), barnyard (Echinochloa), eleusines (Eleusine), lolium (Lolium), yujiujiu (Monochoria), legionella (Rottboellia), sagittaria (SAGITTARIA), scirpus (Scirpus), setaria (Setaria) and Sorghum (Sorghum), or dicotyledonous species such as Abutilus (Abutilon), amaranthus (Amaranthus), ambrosia (Ambrosia), chenopodium (Chenopodium), june (Chrysanthemum), echinacea (Conyza), lagranola (Galium), sweet potato (Ipomoea), sida (6724), siberia (Viola (8654), taraxacum (Viola (8654) and Taraxacum (Viola).

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

Process for preparing compounds of formula (I)

The process for preparing compounds, such as compounds of formula (I) which may alternatively be agrochemically acceptable salts thereof, is now described and forms a further aspect of the invention.

As shown in scheme 1, compounds having formula (I) can be prepared by decarboxylating compounds having formula (2) under acidic conditions with heating at 110 ℃ in a suitable solvent such as ethanol.

Using a nucleophilic aromatic substitution reaction of a compound of formula (4) wherein LG represents a suitable leaving group, such as halogen or SO ₂ Me, with a compound of formula (3), the reaction is carried out by heating in a suitable solvent, such as sulfolane, in the presence of a base, such as sodium t-butoxide. The reaction is typically carried out at 40 ℃.

Conditions for the formation of pyrazole compounds of formula (3) by condensation of diketones with arylhydrazines are reported in the literature (as reported in Tetrahedron (2013), 69 (16), 3459-3464).

Scheme 1

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

Alternatively, the compound having formula I may be prepared by scheme 2 below.

Scheme 2:

In scheme 2, compounds of formula I can be prepared by reacting a compound of formula VI with a reagent of formula V, wherein LG ₁ is halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group such as a (halo) alkyl or phenyl sulfonate, e.g. triflate), in the presence of a base such as sodium hydride or alkaline earth metal hydride, carbonate (e.g. sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N-dimethylformamide DMF, N-dimethylacetamide, sulfolane or acetonitrile, etc., at a temperature between 0 ℃ and 120 ℃ by procedures well known to those skilled in the art.

Alternatively, compounds of formula I may be prepared by reacting a compound of formula VI with a compound of formula V, wherein LG ₁ is halogen, preferably iodine, bromine or chlorine (or a pseudohalogen leaving group such as (halo) alkyl or phenyl sulfonate, e.g. triflate), in the presence of a metal catalyst such as a copper-based catalyst, e.g. CuI or tetra (acetonitrile) copper (I) tetrafluoroborate, optionally in the presence of a ligand such as trans-1, 2-bis (methylamino) cyclohexane or a salt thereof, e.g. mesylate, or an 8-hydroxyquinoline, and similar other ligands. The reaction may be carried out in the presence of a base such as potassium carbonate, cesium carbonate, triethylamine or pyridine and similar other substances and in the presence of a solvent such as acetonitrile, 1, 4-dioxane or pyridine and optionally under microwave radiation at a temperature in the range of room temperature and 200 ℃.

Alternatively, compounds having formula I may be prepared by reacting a compound having formula VI with a compound having formula Va under Chan Lam cross-coupling reaction conditions. Such reactions are carried out in the presence of copper-based catalysts (such as copper acetate or iodide or bromide and the like) and in the presence of bases (such as pyridine or 2, 6-lutidine and the like). The reaction may be carried out in the presence of a solvent (e.g., methylene chloride, toluene, acetonitrile) and in the presence of air or oxygen and at a temperature in the range of room temperature and 200 ℃.

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

Compounds of formula VII may be prepared from compounds of formula VIII (wherein R ¹² is C ₁-C₄ alkyl or phenyl) via decarboxylation. The reaction may be carried out using a base (e.g., an alkaline earth metal hydroxide or an alkali metal hydroxide such as sodium hydroxide) or in the presence of an acid (e.g., aqueous hydrochloric acid, aqueous sulfuric acid, etc.). The reaction is typically 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 in the range of room temperature to the boiling point of the solvent.

Compounds of formula VIII (wherein R ¹² is C ₁-C₄ alkyl or phenyl) may be prepared by reacting a compound of formula X with a reagent of formula IX (wherein LG ₂ is halogen, (or a pseudohalogen leaving group such as (halo) alkyl or phenyl sulfonate, e.g. triflate), in the presence of a base such as sodium tert-butoxide, sodium hydride or alkaline earth metal hydride, carbonate (e.g. sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide, or phosphate such as potassium phosphate, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N-dimethylformamide DMF, N-dimethylacetamide, dimethylsulfoxide, sulfolane or acetonitrile, etc., at a temperature between 0 ℃ and 200 ℃ by procedures well known to those skilled in the art.

The compound of formula X may be prepared by condensation reaction of a compound of formula XII with a compound of formula XI (or a hydrochloride or trifluoroacetate salt thereof) wherein PG is an amino protecting group, such as an amino protecting group of acetyl, trimethylsilylethoxymethyl (SEM), t-butoxycarbonyl, benzyl, p-methoxybenzyl (PMB), and the like. Such reactions are well known in the literature and may optionally be carried out in the presence of an acid catalyst such as acetic acid.

The compounds of formula XII may be prepared by reacting a compound of formula XIV (wherein R ¹¹ is C ₁-C₄ alkyl or phenyl) with a compound of formula XIII in the presence of a base. Such reactions are known as claisen condensation reactions and are well known to those skilled in the art. The reaction may be carried out using a base (e.g., lithium diisopropylamide, lithium tetramethylpiperidine, sodium ethoxide, sodium hydride, etc.) in the presence of a solvent (e.g., tetrahydrofuran, ethanol, methanol) and at a temperature in the range of-80 ℃ to the boiling point of the solvent.

Alternatively, the compound having formula I may be prepared by scheme 3 below.

Scheme 3:

In scheme 3, the compound having formula I is prepared from the compound having formula XV via alcohol reduction. The reduction of such alcohols is described in detail in the literature and can be carried out using reducing agents (e.g. LiAlH ₄, DIBAL-H) or triphenylphosphine in the presence of iodine and imidazole or triethylsilane in the presence of trifluoroacetic acid. Compounds of formula XV can be prepared by reacting a compound of formula XVI, wherein X ¹ is halogen, preferably bromine or iodine, with an organometallic reagent such as a BuLi or isopropylmagnesium chloride/LiCl complex or the like metalating reagent to form intermediate XVIa, wherein M (Ln) ^p is the corresponding metal from the organometallic reagent such as lithium or magnesium and (Ln) ^p is an optionally substituted group thereof such as chlorine, and then subsequently reacting with a compound of formula XVII.

The compound of formula XVII may be prepared by reacting a compound of formula XVIII with a strong base such as butyllithium, lithium diisopropylamide, and then with DMF. The reaction is typically carried out in the presence of a solvent (e.g., tetrahydrofuran, toluene, heptane) and at a temperature of from-80 ℃ to the boiling point of the solvent. Such reactions are well known and described in the literature. The compounds of formula XVIII can be prepared by reacting a compound of formula XIX with a compound of formula XX, wherein LG ₃ is a leaving group such as halogen (or a pseudohalogen leaving group such as (halo) alkyl or phenyl sulfonate, e.g. triflate, in the presence of a base such as sodium tert-butoxide, sodium hydride or alkaline earth metal hydride, carbonate (e.g. sodium carbonate, potassium carbonate or cesium carbonate) or hydroxide, or phosphate such as potassium phosphate, optionally in the presence of potassium iodide, in an inert solvent such as tetrahydrofuran, dioxane, water, N-dimethylformamide DMF, N-dimethylacetamide, dimethylsulfoxide, sulfolane or acetonitrile, etc., at a temperature between 0 ℃ and the boiling point of the solvent by procedures well known to those skilled in the art. Such a reaction is referred to in the literature as the S _N Ar reaction.

Alternatively, the compounds of formula XVIII may be prepared by Chan-Lam coupling involving, for example, reacting a compound of formula XIX with a compound of formula XXI (wherein Yb ₁ may be a boron derived functional group such as, for example, B (OH) ₂ or B (ORb ₁)₂ wherein Rb ₁ may be C ₁-C₄ alkyl or both groups ORb ₁ may form a five membered ring with the boron atom such as, for example, pinacol borate) in the presence of a base such as, for example, pyridine, sodium carbonate, tripotassium phosphate or cesium fluoride) in a solvent or solvent mixture such as, for example, dioxane, methylene chloride, acetonitrile, N-dimethyl-formamide, a mixture of 1, 2-dimethoxyethane and water or a mixture of dioxane/water, or toluene/water, either under an inert atmosphere or under an oxygen atmosphere or at a temperature catalytic reaction preferably ranging from room temperature to the boiling point of Lam, as is well known to those skilled in the art.

Alternatively, compounds of formula I (wherein R ₃ is H, defined as compounds of formula Ia and compounds of formula Ib) can be prepared according to scheme 4.

Scheme 4:

In scheme 4, compounds having formula Ib can be prepared from compounds having formula XXIII (wherein X is halogen, preferably bromine or iodine) via a cyanation reaction. The reaction may be carried out by reacting a compound having the formula XXIII with M-CN XXIId (where M is a metal coordinated to cyanide). Examples of cyanating agents include NaCN, zn (CN) ₂, potassium ferrocyanide, or the like. The reaction may be catalyzed by a palladium-based catalyst, such as tetrakis (triphenylphosphine) palladium (0), (1, 1' bis (diphenylphosphino) ferrocene) palladium dichloride-dichloromethane (1:1 complex) or chlorine (2-dicyclohexylphosphino-2 ',4',6' -triisopropyl-1, 1' -biphenyl) [2- (2 ' -amino-1, 1' -biphenyl) ] palladium (II) (XPhos ring palladium complex)) 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-dimethyl-formamide, a mixture of 1, 2-dimethoxyethane and water or a mixture of dioxane/water, or a mixture of toluene/water, preferably under an inert atmosphere. The reaction temperature may preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction may be carried out under microwave radiation. Such reactions are well known to those skilled in the art.

Compounds having formula XXIII can be prepared by the following procedure analogous to scheme 3.

Compounds of formula Ia, wherein R ₂ is C ₁-C₄ alkyl or R ₂ is C ₃-C₅ cycloalkyl, can be prepared by a ringer reaction involving reacting a compound of formula XXIII, wherein X is halogen, preferably bromine or iodine, with a compound of formula R ₂-Yb₃, wherein Yb ₃ may be a boron-derived functional group, such as, for example, B (OH) ₂ or B (ORb ₃)₂, wherein Rb ₃ may be C ₁-C₄ alkyl, or two groups ORb ₃ may form a five-membered ring with the boron atom, such as, for example, pinacol borate, this reaction can be carried out by a palladium-based catalyst, such as, for example, 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 cyclic palladium complex)) in the presence of a base like sodium carbonate, tripotassium phosphate or cesium fluoride in a solvent or solvent mixture like for example dioxane, acetonitrile, N-dimethyl-formamide, a mixture of 1, 2-dimethoxyethane and water or a mixture of dioxane/water or a mixture of toluene/water, preferably under an inert atmosphere the reaction temperature may preferably be in the range from room temperature to the boiling point of the reaction mixture, or the reaction may be carried out under microwave radiation. Such suzuki reactions are well known to those skilled in the art.

Compounds of formula Ia within scheme 4 (wherein R ₂ is C ₁-C₄ alkoxy) can be prepared by cross-coupling a compound of formula XXIII (wherein X is halogen, preferably bromine or iodine) with a compound of formula XXIIc (wherein R ₂ is C ₁-C₄ alkoxy). The reaction may 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) ] methane-sulfonic acid palladium (II) (tBuBrettPhos Pd G3), etc. The reaction is typically carried out in the presence of a solvent (e.g., tetrahydrofuran, 1, 4-dioxane, etc.) and optionally under microwave radiation. Such reactions are well known in the literature, for example, as described in org.lett. [ organic chemistry communication ]2013,15,15,3998-4001.

The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention (as set forth in table 1 below).

EXAMPLE 1 preparation of 3, 5-difluoro-2- [ [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methyl ] pyridine (1.008)

Step 1 preparation of 3- (trifluoromethyl) -1- [4- (trifluoromethyl) phenyl ] pyrazole (I-1)

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℃for one hour under microwave radiation. The mixture was diluted with brine 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 3- (trifluoromethyl) -1- [4- (trifluoromethyl) phenyl ] pyrazole as a colourless oil I-1(1.468g,66％).¹H NMR(400MHz,CDCl₃)δ＝8.04-8.01(m,1H),7.87(d,2H),7.76(d,2H),6.78(d,1H).

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

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-butyllithium (2.5M, 2.2mL,5.5mmol in hexane) at-78℃and the resulting mixture was stirred for 30 min. Then, N-dimethylformamide (0.6 mL,8 mmol) was added to the 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-carbaldehyde I-2 (1.014 g, 81%) as a pale yellow oil. ¹H NMR(400MHz,CDCl₃ ) δ=9.92 (s, 1H), 7.83 (d, 2H), 7.68 (d, 2H), 7.38 (s, 1H).

Step 3 preparation of (3, 5-difluoro-2-pyridinyl) - [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methanol (I-3)

To a solution of 2-bromo-3, 5-difluoropyridine (245 mg,1.26 mmol) in toluene (2 mL) was added n-butyllithium (2.5M in hexane, 0.50mL,1 mmol) at-78 ℃. The resulting mixture was stirred for 30min, then treated with a solution of 5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazole-3-carbaldehyde I-2 (209 mg,0.64 mmol) in toluene (2 mL) and stirred for an additional 30 min. The mixture was quenched with 0.5M 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 (3, 5-difluoro-2-pyridinyl) - [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methanol as a yellow gum I-3(192mg,63％).¹H 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).

Step 4 preparation of 3, 5-difluoro-2- [ [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methyl ] pyridine (1.008)

To a solution of (3, 5-difluoro-2-pyridinyl) - [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 ℃ 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 containing 0.1% formic acid) to give 3, 5-difluoro-2- [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methyl ] pyridine as a white solid 1.008(114mg,65％).¹H 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).

EXAMPLE 2 preparation of 5-chloro-3-fluoro-2- [ [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methyl ] pyridine (1.010)

Step1 preparation of ethyl 6, 6-trifluoro-3, 5-dioxo-hexanoate (I-4)

To an ice-cooled solution of diisopropylamine (3.2 mL,23 mmol) in THF (15 mL) was added dropwise n-butyllithium (2.5M in hexane, 9.2mL,23 mmol) at 0deg.C. The mixture was stirred for 30 min, treated dropwise with ethyl acetoacetate (0.97 ml,7.7 mmol) and stirred at 0 ℃ for one hour. The reaction mixture was then cooled to-78 ℃, treated dropwise with ethyl trifluoroacetate (1.2 ml,1 mmol) and stirred for 3 hours. The mixture was quenched with hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined organics were dried and concentrated. The resulting oil I-4 was used as such in the next step.

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

To a solution of I-4 prepared in step 1 of example 2 in acetic acid (15 mL) was added 4- (trifluoromethyl) phenylhydrazine (1.35 g,7.66 mmol) 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 organics were concentrated and subjected to column chromatography on silica gel using 0-30% ethyl acetate in cyclohexane to give ethyl 2- [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] acetate as an orange solid I-5(1.087g,37％).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)

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)

To a solution of ethyl 2- [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] acetate I-5 (100 mg, 0.299 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 ℃ for one hour. The mixture was cooled, diluted with water and extracted with tert-butyl methyl ether. The organics were concentrated and column chromatographed on silica gel using 0-30% ethyl acetate in cyclohexane to give ethyl 2- (5-chloro-3-fluoro-2-pyridinyl) -2- [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] acetate as a yellow oil I-6(84mg,52％).¹H NMR(400MHz,CDCl₃)δ＝8.43-8.37(m,1H),7.82-7.77(m,2H),7.63-7.56(m,2H),7.48(dd,1H),6.74(s,1H),5.38(s,1H),4.24-4.14(m,2H),1.19(t,3H).

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

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℃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-enriched fraction was concentrated and subjected to reverse phase column chromatography on C-18 silica gel using 60% -100% acetonitrile in water (both water and acetonitrile containing 0.1% formic acid) to give 5-chloro-3-fluoro-2- [ [5- (trifluoromethyl) -2- [4- (trifluoromethyl) phenyl ] pyrazol-3-yl ] methyl ] pyridine as a colorless oil 1.010(40mg,63％).¹H 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).

EXAMPLE 3 preparation of 1- (4-fluorophenyl) -5- [ (5-fluoro-2-pyridyl) methyl ] pyrazole-3-carbonitrile (1.003)

Step 1 preparation of 1- (4-fluorophenyl) -3-iodo-pyrazole (I-7)

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 copper diacetoxy (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 and extracted with dichloromethane. The combined organics were 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).

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

Lithium diisopropylamide (2.0M in THF/heptane/ethylbenzene, 3.5mL,7.0 mmol) was added to a solution of 1- (4-fluorophenyl) -3-iodo-pyrazole I-7 (1.35 g,4.55 mmol) in tetrahydrofuran (17 mL) at-78℃and the mixture was stirred for 30 min. To this mixture was added a solution of 5-fluoropyridine-2-carbaldehyde (680 mg,5.44 mmol) in tetrahydrofuran (5 mL), and the mixture was stirred for 30 minutes, then allowed to warm to room temperature. The mixture was diluted with aqueous ammonium chloride and extracted with ethyl acetate. The combined organics were concentrated and subjected to column chromatography on silica gel using 0-100% ethyl acetate in cyclohexane to give [2- (4-fluorophenyl) -5-iodo-pyrazol-3-yl ] - (5-fluoro-2-pyridinyl) methanol as an off-white solid I-8(1.04g,55％).¹H 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).

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

To a solution of [2- (4-fluorophenyl) -5-iodo-pyrazol-3-yl ] - (5-fluoro-2-pyridinyl) 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 ℃ for 55 hours. The mixture was treated with additional triethylsilane (4 mL,25.0 mmol) and stirred at 70℃for an additional 19 hours. The mixture was cooled and concentrated. The residue was subjected to column chromatography on silica gel using 0-40% ethyl acetate in cyclohexane to give 5-fluoro-2- [ [2- (4-fluorophenyl) -5-iodo-pyrazol-3-yl ] methyl ] pyridine as a yellow solid 1.011(651mg,65％).¹H 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).

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

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 XPhos Pd G3 (16 mg,0.019 mmol) were added water (1.1 mL) and tetrahydrofuran (1.1 mL), and the resulting mixture was heated to 110℃under microwave radiation 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-pyridinyl) methyl ] pyrazole-3-carbonitrile as a yellow solid 1.003(110mg,93％).¹H 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).

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

Step1 preparation of ethyl 6, 6-trifluoro-3, 5-dioxo-hexanoate (I-4)

To an ice-cooled solution of diisopropylamine (22 mL,157 mmol) in THF (110 mL) in a 250mL round-bottom flask was added n-butyllithium (2.5M in hexane, 65mL,160 mmol) over about 30 minutes. The mixture was stirred for 30min, treated dropwise with ethyl acetoacetate (6.8 mL,54 mmol) and stirred at 0℃for an additional 45 min. The reaction mixture was then cooled to-78 ℃, treated dropwise with ethyl trifluoroacetate (8.3 ml,70 mmol) and stirred for 3 hours. The mixture was quenched with hydrochloric acid, diluted with water and extracted with ethyl acetate. The combined organics were dried and concentrated. The resulting oil I-4 was used as such in the next step.

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

To a solution of I-4 prepared in example 4 step 1 in acetic acid (90 mL) in a 100mL round bottom flask was added (4-methoxybenzyl) hydrazine hydrochloride (10.56 g,54.29 mmol) and the resulting mixture was stirred at room temperature for 1.5 hours. The mixture was diluted with t-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 I-9 (11.97 g,59% yield) as a yellow oil ).¹H 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).

Step3 preparation of ethyl 2- [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] -2- [6- (trifluoromethyl) -2-pyridinyl ] acetate (I-10)

To a solution of ethyl 2- [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] acetate I-9 (501 mg,1.390 mmol) and 2-fluoro-6- (trifluoromethyl) pyridine (820 μl,7.0 mmol) in sulfolane (3 mL) was added sodium tert-butoxide (659 mg,6.65 mmol), and the resulting mixture was stirred at room temperature for one hour. The mixture was then diluted with dilute aqueous sodium bicarbonate 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- [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] -2- [6- (trifluoromethyl) -2-pyridinyl ] acetate as a yellow oil I-10(195mg,24％).¹H 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).

Step4 preparation of 2- [ [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] methyl ] -6- (trifluoromethyl) pyridine (I-11)

To a solution of ethyl 2- [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] -2- [6- (trifluoromethyl) -2-pyridinyl ] 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℃for 30 minutes. The mixture was cooled and acidified with aqueous hydrochloric acid (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 as a pale yellow oil I-11(148mg,84％).¹H 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).

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

A solution of 2- [ [2- [ (4-methoxyphenyl) methyl ] -5- (trifluoromethyl) pyrazol-3-yl ] methyl ] -6- (trifluoromethyl) pyridine I-11 (148 mg, 0.284 mmol) in 2, 2-trifluoroacetic acid (0.6 mL,8 mmol) was stirred at 70℃for 30 minutes. The mixture was cooled, diluted with water, and carefully basified with aqueous sodium bicarbonate until bubbling ceased. 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 as a brown oil I-12(114mg).¹H 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).

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

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 the mixture was stirred at 80℃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 on C-18 silica gel using 50% -100% acetonitrile in water (both water and acetonitrile contain 0.1% formic acid) to give 5-chloro-2- [3- (trifluoromethyl) -5- [ [6- (trifluoromethyl) -2-pyridinyl ] methyl ] pyrazol-1-yl ] pyrimidine as an off-white solid 1.009(66mg,53％).¹H 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).

EXAMPLE 5 2-chloro-5- [3- (difluoromethyl) -5- [ (3, 5-difluoro-2-pyridinyl) methyl ] pyrazol-1-yl ] -3-fluoro-pyridine (1.014)

Step 1 preparation of diethyl 2- (3, 5-difluoro-2-pyridinyl) malonate (I-13)

A suspension of sodium hydride (60 mass%) in mineral oil (1.35 g,33.8 mmol) in tetrahydrofuran (28.2 mL) in a 100mL round bottom flask was placed under nitrogen and treated dropwise with diethyl malonate (5.53 g,33.8 mmol). The mixture was stirred for 5 minutes and then treated with 2,3, 5-trifluoropyridine (1.50 g,11.3 mmol). The mixture was warmed to 60 ℃ and allowed to stir for 3.5h. The reaction mixture was cooled to room temperature, then diluted with water (50 mL) and extracted with ethyl acetate (2×40 mL). The combined organics were concentrated in vacuo. The residue was subjected to silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent. The fractions forming the main peak of interest were combined and concentrated in vacuo to give diethyl 2- (3, 5-difluoro-2-pyridinyl) malonate I-13 (2.40 g, 11%) as a colorless oil as a mixture of isomers (4:1). The product contained an excess of diethyl malonate as impurity, which was used in the next step without further purification. ¹HNMR(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).

Step 2 preparation of 2- (3, 5-difluoro-2-pyridinyl) acetic acid (I-14)

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

Step 3 preparation of 1- (3, 5-difluoro-2-pyridinyl) propan-2-one (I-15)

A suspension of 2- (3, 5-difluoro-2-pyridinyl) acetic acid I-14 (0.686 g,3.96 mmol) in acetic anhydride (2.06 g,19.8 mmol) in a 25mL round bottom flask was placed under nitrogen and treated with 1-methylimidazole (0.246 g,2.97 mmol). The reaction mixture was allowed to stir at room temperature overnight. It was quenched by slow addition of water (15 mL) at 0 ℃ and stirred for 5 min, then extracted with ethyl acetate (2 x 30 mL). The combined organics were washed with aqueous sodium bicarbonate (2 x 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-pyridinyl) propan-2-one I-15 (0.13 g, 19%) was obtained as a gummy oil. ¹H NMR(400MHz,CDCl₃ ) δ=8.30 (d, 1H), 7.21 (m, 1H), 3.99 (d, 2H), 2.27 (s, 3H).

Step 4 preparation of 5- (3, 5-difluoro-2-pyridinyl) -1, 1-difluoro-pentane-2, 4-dione (I-16)

A solution of 1- (3, 5-difluoro-2-pyridinyl) propan-2-one I-15 (0.13 g,0.76 mmol) in tetrahydrofuran (2 mL) in a 10mL round bottom flask was cooled to 0℃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 allowed to stir at room temperature overnight. The reaction mixture was quenched with 2M HCl and extracted with ethyl acetate (2 x 30 ml). The combined organics were dried over magnesium sulfate and concentrated in vacuo. The crude material was used directly in the next step.

Step 5 preparation of tert-butyl N- (tert-butoxycarbonylamino) -N- (6-chloro-5-fluoro-3-pyridinyl) -carbamate (I-17)

A solution of 5-bromo-2-chloro-3-fluoropyridine (1.498 g,7.12 mmol) in tetrahydrofuran (14 mL) in a 100mL round bottom flask was placed under nitrogen atmosphere, ice-cooled and treated with 1.3M isopropyl magnesium chloride lithium chloride complex solution (6.0 mL,7.8 mmol). The mixture was stirred at 0 ℃ for 15 minutes and then treated dropwise with a solution of di-tert-butyl azodicarbonate (1.83 g,7.95 mmol) in tetrahydrofuran (4 mL) at an internal temperature of no more than 15 ℃. The mixture was stirred for 30 minutes. The reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (2X 50 mL). The combined organics were washed with brine (50 mL) and concentrated in vacuo. The crude product was purified by silica gel column chromatography using 0-30% ethyl acetate in cyclohexane as eluent to give tert-butyl N- (tert-butoxycarbonylamino) -N- (6-chloro-5-fluoro-3-pyridinyl) -carbamate I-17 (1.79 g, 66%) as an oil which crystallized upon standing as a white solid. ¹H 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).

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

A solution of tert-butyl N- (tert-butoxycarbonylamino) -N- (6-chloro-5-fluoro-3-pyridinyl) carbamate I-17 (0.27 g,0.76 mmol) in trifluoroacetic acid (0.88 g,7.6 mmol) in a 100mL round bottom flask was stirred at room temperature for 30 min. The reaction mixture was treated with a solution of 5- (3, 5-difluoro-2-pyridinyl) -1, 1-difluoro-pentane-2, 4-dione I-16 (0.19 g,0.76 mmol) in acetic acid (1.5 mL) and allowed to stir at room temperature for 1h. The reaction was partitioned between water (50 mL) and ethyl acetate (60 mL) and the organics were dried over magnesium sulfate and concentrated onto silica. Purification by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane provided the product as well as impurities. The product was repurified by reverse phase chromatography using 40% -100% acetonitrile in water containing 0.1% formic acid. Final silica gel purification using 20% ethyl acetate in cyclohexane provided 2-chloro-5- [3- (difluoromethyl) -5- [ (3, 5-difluoro-2-pyridinyl) methyl ] pyrazol-1-yl ] -3-fluoro-pyridine 1.014.¹H 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).

EXAMPLE 6 5-chloro-2- [ [5- (difluoromethyl) -2- (3, 4-difluorophenyl) pyrazol-3-yl ] methyl ] -3-fluoro-pyridine (1.017)

Step 1 preparation of ethyl 6, 6-difluoro-3, 5-dioxo-hexanoate (I-18)

A solution of lithium diisopropylamide (2.0 mol/L) in tetrahydrofuran (28 mL) in a 250mL round bottom flask was placed under a nitrogen atmosphere and cooled on ice, then slowly treated with ethyl acetoacetate (2.0 mL,16 mmol) for approximately 10 minutes. The addition was controlled so that the internal temperature did not exceed 10 ℃. After the addition was completed, the mixture was stirred for 30 minutes. The mixture was cooled to-78 ℃ and treated dropwise with ethyl difluoroacetate (2.2 ml,21 mmol). The resulting reaction mixture was stirred for 3 hours, then removed from the dry ice bath and stirred at room temperature for an additional 30 minutes. After completion, the mixture was quenched with 1M hydrochloric acid (100 mL), diluted with water (40 mL) and extracted with ethyl acetate (2×100 mL). The combined organics were dried over anhydrous magnesium sulfate and concentrated in vacuo to give ethyl 6, 6-difluoro-3, 5-dioxo-hexanoate I-18 (3.3 g,100% yield) as a dark orange oil, which was used without any purification.

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

A solution of ethyl 6, 6-difluoro-3, 5-dioxo-hexanoate I-18 (6.24 g,30 mmol) in acetic acid (60 mL) in a 250mL round bottom flask was treated with trifluoroacetic acid (6.91 g,60 mmol) and (4-methoxyphenyl) methylhydrazine; hydrochloride (5.65 g,30 mmol) and allowed to stir overnight at room temperature. The reaction mixture was diluted with water (100 mL) and then extracted with ethyl acetate (3 x 100 mL). The organics were combined, washed with brine, dried over MgSO ₄, 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 fraction, the product 2- [5- (difluoromethyl) -2- [ (4-methoxyphenyl) methyl ] pyrazol-3-yl ] acetic acid ethyl ester was obtained I-19(2.71g,28％).¹H 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).

Step3 preparation of ethyl 2- (5-chloro-3-fluoro-2-pyridinyl) -2- [5- (difluoromethyl) -2- [ (4-methoxyphenyl) methyl ] pyrazol-3-yl ] acetate (I-20)

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 250mL round bottom flask was placed under a nitrogen atmosphere and treated with dimethyl sulfoxide (27 mL). The mixture was warmed to 80 ℃ and allowed to stir for 1 hour. The reaction mixture was heated for an additional 30 minutes, then allowed to cool to room temperature, then diluted with water (50 mL), acidified with 2M hydrochloric acid, and extracted with tert-butyl methyl ether (2 x 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 afford 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 isomer mixture was used in the next step without further purification.

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

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 250mL round bottom flask was treated with 2M sodium hydroxide (17.5 mL,35.0 mmol). The mixture was stirred at 65 ℃ for 1.5h. 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 was obtained as an off-white solid I-21(0.68g,49％).¹H 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).

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

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-trifluoroacetic acid (4.13 g,35.83 mmol) in a 25mL round bottom flask was warmed to 70℃and allowed to stir for 2h. 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 I-22(0.36g,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).

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

Oven dried 10-20mL microwave vials 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), tetra (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) were evacuated and backfilled with nitrogen five times. The mixture was treated with acetonitrile (3.8 mL) and irradiated to 120 ℃ for 1h under microwave radiation. 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).

TABLE 1

Biological example

Seeds of various test species (amaranthus longifolius (Amaranthus palmeri) (AMAPA), amaranthus retroflexus (Amaranthus retoflexus) (AMARE), setaria faberi (SETFA), barnyard grass (Echinochloa crus-galli) (ECHCG), gomphrena (Ipomoea hederacea) (IPOHE)) were sown in standard soil in pots. These plants were sprayed under controlled conditions in a greenhouse (24 ℃ C./16 ℃ C.; day/night; 14 hours of light; 65% humidity) after one day of cultivation (pre-emergence) or after 8 days of cultivation (post-emergence), with a spray aqueous solution derived from the test compound dissolved in acetone and IF50 (11.12%Emulsogen EL360 TM+44.44% N-methylpyrrolidone+44.44% Dowanol DPM glycol ether) and then diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as diluent. Test compounds are administered at the stated ratio. These test plants were then grown in a greenhouse under controlled conditions in the greenhouse (at 24/16 ℃, day/night; 14 hours light; 65% humidity) and watered twice daily. The percent damage to the plants by the test was evaluated both pre-emergence and 13 days post-emergence.

TABLE B1 post-emergence test

Nt=untested table b2. Pre-emergence test

NT = untested

Claims (15)

1. A compound having the formula (I):

Or an agronomically acceptable salt thereof,

Wherein the method comprises the steps of

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

R ¹ is independently selected from the group consisting of halogen, -CN, NO ₂、C₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₃-C₆ cycloalkyl, C ₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, C ₁-C₄ alkoxy-, -C (O) C ₁-C₄ alkyl, -C (O) OC ₁-C₄ alkyl, C ₁-C₄ haloalkoxy, and C ₁-C₄ alkoxy C ₁-C₃ alkyl-;

r ² is selected from the group consisting of halogen, -CN, NO ₂、C₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, -C (O) C ₁-C₄ alkyl, -C (O) OC ₁-C₄ alkyl, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxyC ₁-C₃ alkyl-, C ₁-C₄ alkoxyC ₁-C₃ alkoxy-, C ₁-C₄ alkoxyC ₁-C₃ alkoxyC ₁-C₃ alkyl-, -S (O) _pC₁-C₄ alkyl, and C ₃-C₆ cycloalkyl;

R ³ is selected from the group consisting of hydrogen, halogen, C ₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxy C ₁-C₃ alkyl-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy C ₁-C₃ alkyl-, -CN, NO ₂、C₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, -S (O) _pC₁-C₄ haloalkyl, -C (O) OC ₁-C₄ alkyl, -C (R ⁷)＝NOR⁸ and-C (O) NR ⁵R⁶;

R ⁴ is selected from the group consisting of halogen, C ₁-C₄ alkyl, C ₁-C₄ haloalkyl, C ₁-C₄ alkoxy, C ₁-C₄ haloalkoxy, C ₁-C₄ alkoxy C ₁-C₃ alkyl-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy-, C ₁-C₄ alkoxy C ₁-C₃ alkoxy C ₁-C₃ alkyl-, -CN, NO ₂、C₂-C₄ alkenyl, C ₂-C₄ alkynyl, -S (O) _pC₁-C₄ alkyl, -S (O) _pC₁-C₄ haloalkyl, -C (O) OC ₁-C₄ alkyl, and-C (O) NR ⁵R⁶;

R ⁵ is hydrogen or C ₁-C₄ alkyl;

R ⁶ is hydrogen or C ₁-C₄ alkyl;

R ⁷ is hydrogen or C ₁-C₄ alkyl;

R ⁸ is hydrogen or C ₁-C₂ alkyl;

m=0, 1 or 2, and

P=0, 1 or 2.

2. The compound of claim 1, wherein R ³ is hydrogen.

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

4. A compound according to claim 3, wherein m is 1 and R ¹ is chloro.

5. The compound of any of the preceding claims, wherein R ² is selected from the group consisting of halogen, C ₁-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:

wherein n is 0,1 or 2.

7. The compound of any of the preceding claims, wherein Q is selected from the group consisting of Q-1, Q-3 and Q-4.

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

9. The compound of claim 8, wherein R ⁴ is independently selected from the group consisting of cyano, methyl, halogen, and-CF ₃.

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 of claim 11 further comprising at least one additional pesticide.

13. The herbicidal composition of claim 12 wherein the additional pesticide is a herbicide or 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 a compound of formula (I) according to claim 1 as herbicide.