EP4649076A1

EP4649076A1 - Herbicidal pyrazole compounds

Info

Publication number: EP4649076A1
Application number: EP24700848.5A
Authority: EP
Inventors: Suzanna DALE; Philip Michael ELVES; Katharine Mary INGRAM; James Alan Morris; Vikas SIKERVAR; Samuel Vaughan WATKIN
Original assignee: Syngenta Crop Protection AG Switzerland
Current assignee: Syngenta Crop Protection AG Switzerland
Priority date: 2023-01-12
Filing date: 2024-01-05
Publication date: 2025-11-19
Also published as: WO2024149676A1; CN120530101A; UY40599A; AR131574A1; PY2401292A

Abstract

The present invention relates to compounds of Formula (I), or an agronomically acceptable salt of said compounds wherein Q, R1, R2, R3 and m are as defined herein. The invention further relates to herbicidal compositions which comprise a compound 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 processes for their preparation, to herbicidal compositions which comprise the novel compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibiting plant growth.

WO2022/013293, W02022/101270 and WO2023/099354 disclose herbicidal pyrazole compounds featuring a pyrimidine ring.

Thus, according to the present invention there is provided a compound of Formula (I): or an agronomically acceptable salt thereof, wherein

Q is phenyl or a C-linked 6-membered heteroaryl wherein said phenyl or 6- membered heteroaryl is optionally substituted by one or more R⁴;

R¹ is independently selected from the group consisting of halogen, -CN, NO2, Ci-C4alkyl, Ci-C4haloalkyl, Cs-Cecycloalkyl, C2-C4alkenyl, C2-C4alkynyl, - S(O)_pCi-C4alkyl, Ci-C4alkoxy-, -C(O)Ci-C4alkyl, -C(O)OCi-C4alkyl, C1- C4haloalkoxy and Ci-C4alkoxyCi-C3alkyl-;

R² is selected from the group consisting of halogen, -CN, NO2, Ci-C4alkyl, C1- C4haloalkyl, Ci-C4alkoxy, -C(O)Ci-C4alkyl, -C(O)OCi-C4alkyl, C1- C4haloalkoxy, Ci-C4alkoxyCi-C3alkyl-, Ci-C4alkoxyCi-C3alkoxy-, Ci- C4alkoxyCi-C3alkoxyCi-C3alkyl-, -S(O)_pCi-C4alkyl and Cs-Cecycloalkyl;

R³ is selected from the group consisting of hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Ci-C4alkoxyCi-C3alkyl-, C1- C4alkoxyCi-C3alkoxy-, Ci-C4alkoxyCi-C3alkoxyCi-C3alkyl-, -CN, NO2, C2- C4alkenyl, C2-C4alkynyl, -S(O)_pCi-C4alkyl, -S(O)_pCi-C4haloalkyl, -C(O)OCi- C₄alkyl, -C(R⁷)=NOR⁸ and -C(O)NR⁵R⁶;

R⁴ is selected from the group consisting of halogen, C1-C4 alkyl, Ci- 04 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Ci-C4alkoxyCi-C3alkyl-, C1- C4alkoxyCi-C3alkoxy-, Ci-C4alkoxyCi-C3alkoxyCi-C3alkyl-, -CN, NO2, C2- C4alkenyl, C2-C4alkynyl, -S(O)_pCi-C4alkyl, -S(O)_pCi-C4haloalkyl, -C(O)OCi- C₄alkyl and -C(O)NR⁵R⁶;

R⁵ is hydrogen or Ci-C4alkyl;

R⁶ is hydrogen or Ci-C4alkyl;

R⁷ is hydrogen or Ci-C4alkyl;

R⁸ is hydrogen or Ci-C2alkyl; m = 0, 1 or 2; and p = 0, 1 or 2.

Ci-C4alkyl- and Ci-Cealkyl- includes, for example, methyl (Me, CH3), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (/-Pr), n-butyl (n-Bu), isobutyl (/-Bu), sec-butyl and terf-butyl (t-Bu). Ci-C2alkyl is methyl (Me, CH3) or ethyl (Et, C2H5).

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

C2-C4alkynyl- refers to a straight or branched hydrocarbon chain radical group consisting solely of carbon and hydrogen atoms, containing at least one triple bond, having from two to four carbon atoms, and which is attached to the rest of the molecule by a single bond. Examples of C2-C4alkynyl 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 same correspondingly applies to halogen in the context of other definitions, such as haloalkyl.

Ci-C4haloalkyl- 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. Ci-C2haloalkyl 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.

Ci-Cealkoxy includes methoxy and ethoxy.

Ci-C4haloalkoxy- 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.

Ci-C4alkoxyCi-C3alkyl- includes, for example, methoxymethyl-.

Ci-C4alkoxyCi-C3alkoxy- includes, for example, methoxyethoxy-.

Ci-C4alkoxyCi-C3alkoxyCi-C3alkyl- includes, for example, meth- oxyethoxymethyl-.

Cs-Cecycloalkyl includes cyclopropyl, cyclopentyl and cyclohexyl.

Ci-C4alkyl-S- (alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio. Ci-C4alkyl-S(0)- (alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, secbutylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

Ci-C4alkyl-S(O)2- (alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, secbutylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

In one embodiment of the present invention, R³ is hydrogen.

In one embodiment of the present invention, there is provided a compound of Formula (I), wherein m is 1 or 2 and R¹ is independently selected from the group consisting of halogen (e.g F, Cl or Br), -CN, Ci-C4alkyl (e.g Me), Ci-C4haloalkyl (e.g CHF2 or CF3), Ci-C4alkoxy- (e.g MeO-) and Ci-C4haloalkoxy (e.g CF3O-, CHF2O-).

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

In a preferred embodiment of the present invention, m is 1 and R¹ is halogen (e.g chloro).

In another preferred embodiment of the present invention, R² is selected from the group consisting of halogen, Ci-C4haloalkyl- (preferably CF3 or -CF2H), cPr and CN. In a preferred embodiment, R² is Ci-C4haloalkyl (preferably -CF3 or -CF2H).

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

wherein n is 0, 1 or 2. In a preferred embodiment of the present invention, Q is selected from the group consisting of Q-1, Q-3 and Q-4. Thus, in a more preferred embodiment of the present invention the compound of Formula (I) is of Formula (la’), Formula (lb’) or

In another preferred embodiment, n is 1. In this embodiment, R⁴ is preferably selected from the group consisting of cyano, methyl, halogen and -CF3. In a particularly preferred embodiment, Q is 4-CI-phenyl-.

In another embodiment of the present invention, Q is Q-3 and n is 2. Thus, in a more preferred embodiment of the present invention the compound of Formula (I) is a compound of Formula (Iba): wherein R^4a is halogen, preferably fluoro or chloro and R^4b, preferably fluoro or chloro; and wherein R¹, R² and R³ are as defined in Formula (I). In a more preferred embodiment, there is provided a compound of Formula (Iba’) wherein R¹ is chloro, R² is -CF3 or -CF2H and R³ is hydrogen. Compounds of Formula (Iba’) are particularly preferred in the context of the present invention as they typically exhibit improved crop selectivity, particularly in maize.

Compounds of Formula (I) may contain asymmetric centres and may be present as a single enantiomer, pairs of enantiomers in any proportion or, where more than one asymmetric centre are present, contain diastereoisomers in all possible ratios. Typically, one of the enantiomers has enhanced biological activity compared to the other possibilities.

The present invention also provides agronomically acceptable salts of compounds of Formula (I). Salts that the compounds of Formula (I) may form with amines, including primary, secondary and tertiary amines (for example ammonia, dimethylamine and triethylamine), alkali metal and alkaline earth metal bases, transition metals or quaternary ammonium bases are preferred.

The compounds of Formula (I) according to the invention can be used as herbicides by themselves, but they are generally formulated into herbicidal compositions using formulation adjuvants, such as carriers, solvents and surfaceactive agents (SAA). Thus, the present invention further provides a herbicidal composition comprising a herbicidal compound according to any one of the previous claims and an agriculturally acceptable formulation adjuvant. The composition can be in the form of concentrates which are diluted prior to use, although ready-to-use compositions can also be made. The final dilution is usually made with water, but can be made instead of, or in addition to, water, with, for example, liquid fertilisers, micronutrients, biological organisms, oil or solvents.

The herbicidal compositions generally comprise from 0.1 to 99 % by weight, especially from 0.1 to 95 % by weight, compounds of Formula I and from 1 to 99.9 % by weight of a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.

The compositions can be chosen from a number of formulation types. These include an emulsion concentrate (EC), a suspension concentrate (SC), a suspo- emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EG), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (Sil), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a soluble powder (SP), a wettable powder (WP) and a soluble granule (SG). The formulation type chosen in any instance will depend upon 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 of 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 a polysaccharide) and, optionally, 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 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 of 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 the dispersion in liquids. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of a compound of Formula (I) and one or more powdered solid diluents or carriers, or from preformed blank granules by absorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) in a porous granular material (such as pumice, attapulgite clays, fuller's earth, kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing a compound of Formula (I) (or a solution thereof, in a suitable agent) on to a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents which are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and sticking agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars and vegetable oils). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

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 surface-active agent (for example to improve water dilution or prevent crystallisation in a spray tank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may be prepared by dissolving a compound of 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 ECs include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark), 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), dimethyl amides of fatty acids (such as Cs-Cio fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may spontaneously emulsify on addition to water, to produce an emulsion with sufficient stability to allow spray application through appropriate equipment.

Preparation of an EW involves obtaining a compound of Formula (I) either as a liquid (if it is not a liquid at room temperature, it may be melted at a reasonable temperature, typically below 70°C) or in solution (by dissolving it in an appropriate solvent) and then emulsifying the resultant liquid or solution into water containing one or more SAAs, under high shear, to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other appropriate organic solvents which have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of one or more solvents with one or more SAAs, to produce spontaneously a thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is present initially in either the water or the solvent/SAA blend. Suitable solvents for use in MEs include those hereinbefore described for use in in ECs or in EWs. An ME may be either an oil-in-water or a water-in-oil system (which system is present may be determined by conductivity measurements) and may be suitable for mixing water- soluble and oil-soluble pesticides in the same formulation. An ME is suitable for dilution into water, either remaining as a microemulsion or forming 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). SCs may be prepared by ball or bead milling the solid compound of Formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition and a suspending agent may be included to reduce the rate at which the particles settle. Alternatively, a compound of Formula (I) may be dry milled and added to water, containing agents hereinbefore described, to produce the desired end product.

Aerosol formulations comprise a compound of Formula (I) and a suitable propellant (for example n-butane). A compound of Formula (I) may also be dissolved or dispersed in a suitable medium (for example water or a water miscible liquid, such as n-propanol) to provide compositions for use in non-pressurised, hand-actuated spray pumps.

Capsule suspensions (CS) may be prepared in a manner similar to the preparation of EW formulations but with an additional polymerisation stage such that an aqueous dispersion of oil droplets is obtained, in which each oil droplet is encapsulated by a polymeric shell and contains a compound of Formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell may be produced by either an interfacial polycondensation reaction or by a coacervation procedure. The compositions may provide for controlled release of the compound of Formula (I) and they may be used for seed treatment. A compound of Formula (I) may also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

The composition may include one or more additives to improve the biological performance of the composition, for example by improving wetting, retention or distribution on surfaces; resistance to rain on treated surfaces; or uptake or mobility of a compound of Formula (I). Such additives include surface active agents (SAAs), spray additives based on oils, for example certain mineral oils or natural plant oils (such as soy bean and rape seed oil), modified plant oils such as methylated rape seed oil (MRSO), and blends of these with other bio-enhancing adjuvants (ingredients which may aid or modify the action of a compound of Formula (I).

Wetting agents, dispersing agents and emulsifying agents may be SAAs of the cationic, anionic, amphoteric or non-ionic type.

Suitable SAAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethyl ammonium bromide), imidazolines and amine salts.

Suitable anionic SAAs include alkali metals salts of fatty acids, salts of aliphatic monoesters of sulphuric acid (for example sodium lauryl sulphate), salts of sulphonated aromatic compounds (for example sodium dodecylbenzenesulphonate, calcium dodecylbenzenesulphonate, butylnaphthalene sulphonate and mixtures of sodium di-/sopropyl- and tri-/sopropyl-naphthalene sulphonates), ether sulphates, alcohol ether sulphates (for example sodium laureth-3-sulphate), ether carboxylates (for example sodium laureth-3-carboxylate), phosphate esters (products from the reaction between one or more fatty alcohols and phosphoric acid (predominately mono-esters) or phosphorus pentoxide (predominately di-esters), for example the reaction between lauryl alcohol and tetraphosphoric acid; additionally these products may be ethoxylated), sulphosuccinamates, paraffin or olefine sulphonates, taurates, lignosulphonates and phosphates I sulphates of tristyrylphenols.

Suitable SAAs of the amphoteric type include betaines, propionates and glycinates.

Suitable SAAs of the non-ionic type include condensation products of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long chain fatty acids or hexitol anhydrides; condensation products of said partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; simple esters (for example fatty acid polyethylene glycol esters); amine oxides (for example lauryl dimethyl amine oxide); lecithins and sorbitans and esters thereof, alkyl polyglycosides and tristyrylphenols.

Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite). The compounds of present invention can also be used in mixture with one or more additional herbicides and/or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), aclonifen, ametryn, amicarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, carfentrazone (including carfentrazone- ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clacyfos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including the choline salt and 2-ethylhexyl ester thereof), 2,4-DB, desmedipham, dicamba (including the aluminium, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts thereof) diclosulam, diflufenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrione, diquat dibromide, diuron, epyrifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, fomesafen, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including L-glufosinate and the ammonium salts of both), glyphosate (including the diammonium, isopropylammonium and potassium salts thereof), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, prometryne, 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-metalochlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrolimet, thiencarbazone, thifensulfuron, tiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, 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]- imidazolidine-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]- imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2- one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-

2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2- one, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, methyl 4-amino-3- chloro-5-fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate, prop-2-ynyl 4-amino-

3-chloro-5-fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate and cyanomethyl 4- amino-3-chloro-5-fluoro-6-(7-fluoro-1 H-indol-6-yl)pyridine-2-carboxylate), 3-ethyl- sulfanyl-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-(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)pyrimidin-1-yl]-2-pyridyl]oxy]acetate,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-ylmethyl2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, 2-[(4-amino- 3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic 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, (2- fluorophenyl)methyl6-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.

The mixing partners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

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

The mixing ratio of the compound of Formula (I) to the mixing partner is preferably from 1 : 100 to 1000:1.

The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of Formula (I) with the mixing partner).

The compounds or mixtures of the present invention can also be used in combination with one or more herbicide safeners. Examples of such safeners include 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.

Particularly preferred are mixtures of a compound of Formula (I) with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl and/or metcamifen.

The safeners of the compound of Formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 16^th Edition (BCPC), 2012. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048.

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

The present invention still further provides a method of controlling weeds at a locus said method comprising application to the locus of a weed controlling amount of a composition comprising a compound of Formula (I). Moreover, the present invention may further provide a method of selectively controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises application to the locus of a weed controlling amount of a composition according to the present invention. ‘Controlling’ means killing, reducing or retarding growth or preventing or reducing germination. It is noted that the compounds of the present invention show a much-improved selectivity compared to know, structurally similar compounds. Generally the plants to be controlled are unwanted plants (weeds). ‘Locus’ means the area in which the plants are growing or will grow. The application may be applied to the locus pre-emergence and/or postemergence of the crop plant. Some crop plants may be inherently tolerant to herbicidal effects of compounds of Formula (I). Preferred crop plants include maize, wheat, barley soybean and rice.

The rates of application of compounds of Formula I may vary within wide limits and depend on the nature of the soil, the method of application (pre- or postemergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, the weed(s) to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of Formula I according to the invention are generally applied at a rate of from 10 to 2500 g/ha, especially from 25 to 1000 g/ha, more especially from 25 to 250 g/ha.

The application is generally made by spraying the composition, typically by tractor mounted sprayer for large areas, but other methods such as dusting (for powders), drip or drench can also be used.

Crop plants are to be understood as also including those crop plants which have been rendered tolerant to other herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-, HPPD-, -PDS and ACCase-inhibitors) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®. The compounds of the present invention can also be used in conjunction with crops that are tolerant to SDPS-inhibiting herbicides, such as those taught in W02020/236790.

Crop plants are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgenic plants able to synthesise 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 that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding (“stacked” transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

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

The compositions can be used to control unwanted plants (collectively, ‘weeds’). The weeds to be controlled may be both monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachia ria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

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.

Processes for preparation of compounds of Formula (I)

Processes for preparation of compounds, e.g. a compound of Formula (I) (which optionally can be an agrochemically acceptable salt thereof), are now described, and form further aspects of the present invention.

As shown in Scheme 1 , a compound 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.

Compounds of Formula (2) are prepared using a nucleophilic aromatic substitution reaction of compounds of Formula (4) (where LG is represents a suitable leaving group such as halogen or SO2Me) by heating in a suitable solvent, such as sulfolane in the presence of a base such as sodium t-butoxide with a compound of Formula (3). The reaction is typically conducted at 40°C.

Conditions for the formation of pyrazole compounds of Formula (3) are documented in the literature via the condensation of diketones with an arylhydrazines (as documented in Tetrahedron (2013), 69(16), 3459-3464).

Scheme 1

Alternatively compounds of formula I can be prepared via condensation reaction of compounds of formula 3a and compounds of formula 3b. The reaction can be carried out optionally in the presence of an acid catalyst such as acetic acid or trifluoroacetic acid.

Alternatively compounds of formula I can be prepared by following scheme 2.

Scheme 2:

In scheme 2 compounds of formula I can be prepared by reacting compounds of formula VI, with reagents of the formula V, wherein LGi is a halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group, such as a (halo)alkyl or phenyl sulfonate ester, e.g. triflate), in the presence of a base, such as sodium hydride or an alkali 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,N- dimethylformamide DMF, N,N-dimethylacetamide, sulfolane or acetonitrile and the like, at temperatures between 0 and 120°C, by procedures well known to those skilled in the art.

Alternatively compounds of formula I can be prepared by reacting compounds of formula VI with compounds of formula V, wherein LGi is a halogen, preferably iodine, bromine or chlorine (or a pseudo-halogen leaving group, such as a (halo)alkyl or phenyl sulfonate ester, e.g. triflate) in the presence of a metal catalyst such as copper based catalyst for eg Cui or tetrakis(acetonitrile)copper(l) tetrafluoroborate optionally in the presence of a ligand such as trans-1 ,2-bis(methylamino)cyclohexane or its salt (for eg methanesulfonate salt) or 8-hydroxyquinoline amongst similar other ligands. The reaction can be carried out in the presence of a base such as potassium carbonate, cesium carbonate, triethylamine or pyridine and similar others and in the presence of a solvent such as acetonitrile, 1 ,4-dioxane or pyridine and optionally under microwave irradiation at temperature in the range of room temperature and 200 °C. Alternatively compounds of formula I can be prepared by reacting compounds of formula VI and compounds of formula Va under Chan Lam cross-coupling reaction conditions. Such reactions are carried out in the presence of copper-based catalyst such as copper acetate or copper iodide or copper bromide and similar others and in the presence of a base such as pyridine or 2,6-lutidine and similar others. The reaction can be carried out in the presence of a solvent such as dichloromethane, toluene, acetonitrile and in the presence of air or oxygen and at temperature in the range of room temperature and 200 °C.

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

Compounds of formula VII can be prepared from compounds of formula VIII, wherein R¹² is Ci-C4alkyl or phenyl via decarboxylation reaction. The reaction can be carried out using base such as alkaline earth metal hydroxide or alkali metal hydroxide like sodium hydroxide or in the presence of acid such as aqueous hydrochloric acid, sulfuric acid amongst others. The reaction is generally carried out in the presence of a solvent such as water, ethanol, methanol, tetrahydrofuran or dioxane or combination of two or more solvent and at temperature in the range of room temperature to boiling point of solvent.

Compounds of formula VIII, wherein R¹² is Ci-C4alkyl or phenyl can be prepared by reacting compounds of formula X, with reagents of the formula IX, wherein LG2 is a halogen, (or a pseudo-halogen leaving group, such as a (halo)alkyl or phenyl sulfonate ester, e.g. triflate), in the presence of a base, such as sodium tert-butoxide, sodium hydride or an alkali 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 tetra hydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N- dimethylacetamide, dimethyl sulfoxide, sulfolane or acetonitrile and the like, at temperatures between 0 and 200°C, by procedures well known to those skilled in the art. Compounds of formula X can be prepared by the condensation reaction of compounds of formula XII with compounds of formula XI (or its hydrochloric acid salt or trifluoroacetic acid salt), wherein PG is an amino-protecting group for example acetyl, trimethylsilylethoxymethyl (SEM), tert-butyloxycarbonyl, benzyl, p- methoxybenzyl (PMB) amongst others 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.

Compounds of formula XII can be prepared by reacting compounds of formula XIV, wherein R¹¹ is Ci-C4alkyl or phenyl with compounds of formula XIII in the presence of a base. Such reactions are known by the name of Claisen condensation reaction and well known to those skilled in the art. Reaction can be carried out using base such as lithium diisopropylamide, lithium tetramethylpiperidide, sodium ethoxide, sodium hydride amongst other bases in the presence of solvent such as tetrahydrofuran, ethanol, methanol and at temperature in the range of -80 °C to boiling point of solvent.

Alternatively compounds of formula I can be prepared by following scheme 3.

Scheme 3:

In Scheme 3 compounds of formula-1 are prepared from compounds of formula XV via reduction of alcohol. Reduction of such alcohols are well described in literature and can be carried out using reducing agent such as UAIH4, DIBAL-H, or using triphenyl phosphine in the presence of iodine and imidazole or using triethyl silane in the presence of trifluoroacetic acid. Compounds of formula XV can be prepared by reacting compounds of formula XVI, wherein X¹ is a halogen preferably bromine or iodine with an organometallic reagent such as BuLi or isopropylmagnesium chloride/LiCI complex amongst other metallating reagents to form an intermediate XVIa, wherein M(Ln)^p is a corresponding metal from the organometallic reagent such as lithium or magnesium and (Ln)^p is its optionally substituted group like chloro and then subsequently reacting with compounds of formula XVII.

XVIa

Compounds of formula XVII can be prepared by reacting compounds of formula XVIII with strong bases such as butyl lithium, lithium diisopropylamide and then reacting with DMF. The reaction is generally carried out in the presence of a solvent such as tetrahydrofuran, toluene, heptane and at temperature between -80 °C to boiling point of solvent. Such reactions are well known and described in literature. Compounds of formula XVIII can be prepared by reacting compounds of formula XIX and compounds of formula XX, wherein LG3 is a leaving group like halogen (or a pseudohalogen leaving group, such as a (halo)alkyl or phenyl sulfonate ester, e.g. triflate) in the presence of a base, such as sodium tert-butoxide, sodium hydride or an alkali 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 tetra hydrofuran, dioxane, water, N,N-dimethylformamide DMF, N,N- dimethylacetamide, dimethyl sulfoxide, sulfolane or acetonitrile and the like, at temperatures between 0 °C and boiling point of solvent, by procedures well known to those skilled in the art. Such reactions are known in literature by name of SNAr reaction.

Alternatively compounds of formula XVIII may be prepared by Chan-Lam coupling, which involves for example, reacting compounds of formula XIX, with compounds of formula XXI, wherein Ybi can be a boron-derived functional group, such as for example B(OH)2 or B(ORbi)2 wherein Rbi can be a Ci-C4alkyl group or the two groups ORbi can form together with the boron atom a five membered ring, as for example a pinacol boronic ester. The reaction may be catalyzed by a copper catalyst, for example Cu(OAc)2, Cui, CuBr2, CuCI amongst other copper based catalyst in presence of a base, like pyridine, sodium carbonate, tripotassium phosphate or cesium fluoride, in a solvent or a solvent mixture, like, for example dioxane, dichloromethane, acetonitrile, N,N-dimethyl-formamide, a mixture of 1 ,2- di methoxyethane and water or of dioxane/water, or of toluene/water, under inert atmosphere or under oxygen atmosphere or under air. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture, or the reaction may be performed under microwave irradiation. Such Chan- Lam coupling reactions are well known to those skilled in the art.

Alternatively compounds of formula I wherein R3 is H defined as compounds of formula la and compounds of formula lb can be prepared following scheme 4.

Scheme 4:

In scheme 4 compounds of formula lb can be prepared from compounds of formula XXIII, wherein X is halogen preferably bromide or iodide via cyanation reaction. Reaction can be carried out by reacting compounds of formula XXIII with M-CN XXIId, wherein M is a metal coordinated to the cyanide. Examples of cyanating reagent include NaCN, Zn(CN)2, or potassium ferrocyanide amongst others. The reaction may be catalyzed by a palladium based catalyst, for example tetrakis(triphenylphosphine)palladium(0), (1 ,1'bis(diphenylphosphino)ferrocene) dichloro-palladium-dichloromethane (1 :1 complex) or chloro(2-dicyclohexylphosphin o-2',4',6'-triisopropyl-1 ,T-biphenyl)[2-(2'-amino-1 ,T-biphenyl)]palladium(ll) (XPhos palladacycle), in presence of a base, like sodium carbonate, potassium acetate, tripotassium phosphate or cesium fluoride, in a solvent or a solvent mixture, like, for example dioxane, tetrahydrofuran, acetonitrile, N,N-dimethyl-formamide, a mixture of 1 ,2-dimethoxyethane and water or of dioxane/water, or of toluene/water, preferably under inert atmosphere. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture, or the reaction may be performed under microwave irradiation. Such reactions are well known to those skilled in the art.

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

Compounds of formula la, wherein R2 is Ci-C4alkyl or R2 is Cs-Cscycloalkyl can be prepared by Suzuki reaction which involves reacting compounds of formula XXIII, wherein X is halogen preferably bromide or iodide with compounds of formula R2- Ybs, wherein Yb₃ can be a boron-derived functional group, such as for example B(OH)2 or B(ORbs)2 wherein Rbs can be a Ci-C4alkyl group or the two groups ORbs can form together with the boron atom a five membered ring, as for example a pinacol boronic ester. The reaction may be catalyzed by a palladium based catalyst, for example tetrakis(triphenyl-phosphine)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(ll) (XPhos palladacycle), in presence of a base, like sodium carbonate, tripotassium phosphate or cesium fluoride, in a solvent or a solvent mixture, like, for example dioxane, acetonitrile, N,N-dimethyl-formamide, a mixture of 1 ,2-dimethoxyethane and water or of dioxane/water, or of toluene/water, preferably under inert atmosphere. The reaction temperature can preferentially range from room temperature to the boiling point of the reaction mixture, or the reaction may be performed under microwave irradiation. Such Suzuki reactions are well known to those skilled in the art.

Compounds of formula la within scheme 4, wherein R2 is C1-C4 alkoxy can be prepared by cross-coupling reaction of compounds of formula XXIII, wherein X is halogen preferably bromide or iodide and compounds of formula XXIIc, wherein R2 is C1-C4 alkoxy. Reaction can be carried out in the presence of a metal catalyst such as palladium based catalysts for eg tert-BuBrettPhos-Pd-G3, [(2-Di-tert-butylphosphino- 3,6-dimethoxy-2',4',6'-triisopropyl-1 , 1 '-biphenyl)-2-(2'-amino-1 , 1 '- biphenyl)]palladium(l I) methanesulfonate (tBuBrettPhos Pd G3) amongst others. Reaction is generally carried out in the presence of a solvent such as tetrahydrofuran, 1,4-dioxane amongst others and optionally under microwave irradiation. Such reactions are well known in literature for eg described in Org. Lett. 2013, 15, 15, 3998—4001.

The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to 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 (1-1)

A suspension of 5-(trifluoromethyl)-1 H-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 was heated to 150 °C under microwave irradiation for an hour. The mixture was diluted with brine and extracted with terf-butylmethyl 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 1-1 as a colourless oil 8.04 - 8. 01 (m, 1 H), 7.87 (d, 2H), 7.76 (d, 2H), 6.78 (d, 1 H).

Step 2: Preparation of 5-(trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazole-

3-carbaldehyde (1-2)

To a solution of 3-(trifluoromethyl)-1-[4-(trifluoromethyl)phenyl]pyrazole 1-1 (1.133 g, 3.842 mmol) in tetra hydrofuran (10 mL) was added n-butyllithium (2.5 M in hexanes, 2.2 mL, 5.5 mmol) at -78°C and the resulting mixture was stirred for 30 minutes. To this mixture was then added N,N-dimethylformamide (0.6 mL, 8 mmol) 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 as a light yellow oil (1.014 g, 81%). ¹ H NMR (400 MHz, CDCh) 6 = 9.92 (s, 1H), 7.83 (d, 2H), 7.68 (d, 2H), 7.38 (s, 1 H).

Step 3: Preparation of (3,5-difluoro-2-pyridyl)-[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 (2.5 M in hexanes, 0.50 mL, 1 mmol) at -78°C. The resulting mixture was stirred for 30 minutes before being 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 a further 30 minutes. 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 (3,5-difluoro-2-pyridyl)-[5- (trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]methanol I-3 as a yellow gum (192 mg, 63%). ¹ H NMR (400 MHz, CDCh) 6 = 8.40 (d, 1 H), 7.91 (d, 2H), 7.82 (d, 2H), 7.29 - 7.24 (m, 1 H), 6.18 (s, 1 H), 5.90 (d, 1H), 4.87 (d, 1 H).

Step 4: Preparation of 3,5-difluoro-2-[[5-(trifluoromethyl)-2-[4-

(trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine (1.008)

(1.008)

To a solution of (3,5-difluoro-2-pyridyl)-[5-(trifluoromethyl)-2-[4- (trifluoromethyl)phenyl]pyrazol-3-yl]methanol 1-3 (192 mg, 0.41 mmol) in trifluoroacetic acid (1.4 mL) was added triethylsilane (1.3 mL, 8.1 mmol) and the resulting reaction mixture was stirred at 80°C for 6 hours. The mixture was cooled, diluted with 1 M aqueous sodium hydroxide, 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 3,5-difluoro-2-[[5-(trifluoromethyl)-2-[4- (trifluoromethyl)phenyl]pyrazol-3-yl]methyl]pyridine 1.008 as a white solid (114 mg, 65%). ¹H NMR (400 MHz, CDCh) 6 = 8.28 (d, 1H), 7.78 (d, 2H), 7.70 (d, 2H), 7.21 (ddd, 1 H), 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)

Step 1 : Preparation of ethyl 6,6,6-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 n-butyllithium (2.5 M in hexanes, 9.2 mL, 23 mmol) dropwise at 0°C. The mixture was stirred for 30 minutes, treated dropwise with ethyl acetoacetate (0.97 mL, 7.7 mmol) and was stirred for an hour at 0°C. The reaction mixture was then cooled to -78°C, 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 is 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 , example 2 in acetic acid (15 mL) was added 4-(trifluoromethyl)phenylhydrazine (1.35 g, 7.66 mmol) and the resulting mixture was allowed to stir for 1.5 hours at room temperature. The mixture was diluted with water and extracted with terf-butylmethyl 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 1-5 as an orange solid (1.087 g, 37%). NMR (400 MHz, DMSO-d6) 5 = 7.96 (d, 2H), 7.82 (d, 2H), 6.98 (s, 1 H), 4.08 (s, 2H), 3.95 (q, 2H), 1.00 (t, 3H)

Step 3: Preparation of ethyl 2-(5-chloro-3-fluoro-2-pyridyl)-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, 0.259 mmol) and 5-chloro-2,3-difluoropyridine (135 pL, 1.302 mmol) in sulfolane (1.3 mL) was added sodium tert-butoxide (161 mg, 1.625 mmol) and the resulting mixture was stirred at 40 °C for an hour. The mixture was cooled, diluted with water, and extracted with terf-butylmethyl 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-chloro-3-fluoro-2-pyridyl)-2-[5- (trifluoromethyl)-2-[4-(trifluoromethyl)phenyl]pyrazol-3-yl]acetate I-6 as a yellow oil (84 mg, 52%). ¹H NMR (400 MHz, CDC ) 6 = 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, 1 H), 5.38 (s, 1 H), 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)

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

(1.003)

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

(I-7)

To a mixture of 3-iodo-1 H-pyrazole (1.07 g, 5.52 mmol), (4-fluorophenyl)boronic acid

(1.44 g, 10.3 mmol) and diacetoxycopper (1.50 g, 8.26 mmol) was added dichloromethane (25 mL) and pyridine (0.84 mL, 10.3 mmol). The resulting mixture was stirred at room temperature for 21 hours. The mixture was diluted with aqueous ammonium hydroxide 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 as a white solid (1.38 g, 84%). ¹H NMR (400 MHz, CDCh) 6 = 7.67 (d, 1 H), 7.61 (dd, 2H), 7.14 (t, 2H), 6.62 (d, 1 H).

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

(I-8)

To a solution of 1-(4-fluorophenyl)-3-iodo-pyrazole I-7 (1.35 g, 4.55 mmol) in tetra hydrofuran (17 mL) was added lithium diisopropylamide (2.0 M in THF/heptane/ethylbenzene, 3.5 mL, 7.0 mmol) at -78°C and the mixture was stirred for 30 minutes. To this mixture was added a solution of 5-fluoropyridine-2- carbaldehyde (680 mg, 5.44 mmol) in tetra hydrofuran (5 mL) and the mixture was allowed to stir for 30 minutes before being 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-pyridyl)methanol I-8 as an off-white solid (1.04 g, 55%). ¹H NMR (400 MHz, CDCh) 6 = 8.41 (d, 1 H), 7.61 (m, 2H), 7.41 (m, 1H), 7.14 (d, 3H), 6.17 (s, 1 H), 5.72 (d, 1H), 4.76 (d, 1 H). Step 3: Preparation of 5-fluoro-2-[[2-(4-fluorophenyl)-5-iodo-pyrazol-3- yl]methyl]pyridine (1.011)

(1.011)

To a solution of [2-(4-fluorophenyl)-5-iodo-pyrazol-3-yl]-(5-fluoro-2-pyridyl)methanol I- 8 (1.04 g, 2.52 mmol) in trifluoroacetic acid (8 mL, 103 mmol) was added triethylsilane (4 mL, 25.0 mmol) and the resulting mixture was stirred at 70 °C for 55 hours. The mixture was treated with additional triethylsilane (4 mL, 25.0 mmol) and stirred at 70 °C for a further 19 hours. The mixture was cooled and concentrated. The residues were 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 1.011 as a yellow solid (651 mg, 65%). ¹H NMR (400 MHz, CDCh) 5 = 8.38 (d, 1 H), 7.37 (m, 2H), 7.32 (dt, 1H), 7.12 (m, 2H), 7.04 (dd, 1 H), 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)

(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) was added water (1.1 mL) and tetra hydrofuran (1.1 mL) and the resulting mixture was heated to 110 °C for an hour under microwave irradiation. The mixture was cooled, filtered, and concentrated. The residues were subjected to column chromatography on silica gel using 0-60% ethyl acetate in cyclohexane to give 1-(4- fluorophenyl)-5-[(5-fluoro-2-pyridyl)methyl]pyrazole-3-carbonitrile 1.003 as a yellow solid (110 mg, 93%). ¹H NMR (400 MHz, CDCh) 6 = 8.39 (d, 1 H), 7.42 (m, 2H), 7.35 (dt, 1H), 7.18 (m, 2H), 7.05 (dd, 1 H), 6.60 (s, 1 H), 4.15 (s, 2H). pyridyl]methyl]pyrazol-1 -yl]pyrimidine (1.009)

(1.009)

Step 1 : Preparation of ethyl 6,6,6-trifluoro-3,5-dioxo-hexanoate (I-4)

(I-4)

To an ice-cooled solution of diisopropylamine (22 mL, 157 mmol) in THF (110 mL) in a 250 mL round bottomed flask was added n-butyllithium (2.5 M in hexanes, 65 mL, 160 mmol) over approximately 30 minutes. The mixture was stirred for 30 minutes, treated dropwise with ethyl acetoacetate (6.8 mL, 54 mmol) and was stirred for a further 45 minutes at 0 °C. The reaction mixture was then cooled to -78°C, 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 is in the next step.

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

(I-9) To a solution of the I-4 prepared in step 1 , example 4 in acetic acid (90 mL) in a 100 mL round bottomed flask was added (4-methoxybenzyl)hydrazine hydrochloride (10.56 g, 54.29 mmol) and the resulting mixture was allowed to stir for 1.5 hours at room temperature. The mixture was diluted with terf-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 as a yellow oil (11.97 g, 59% yield). ^{1 H NMR} (⁴⁰⁰ MHz, CDCh) ⁵ = ^{7 10} ' ^{7 04} (^m> ^2H), ^{6 88} ' 6.83 (m, 2H), 6.50 (s, 1 H), 5.35 (s, 2H), 4.12 (q, 2H), 3.79 (s, 3H), 3.54 (s, 2H), 1.24 (t, 3H).

Step 3: Preparation of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5- (trifluoromethyl)pyrazol-3-yl]-2-[6-(trifluoromethyl)-2-pyridyl]acetate (1-10)

(1-10)

To a solution of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3- yl]acetate 1-9 (501 mg, 1.390 mmol) and 2-fluoro-6-(trifluoromethyl)pyridine (820 pL, 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 an hour. The mixture was then diluted with dilute aqueous sodium bicarbonate and extracted with tert- butylmethyl 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-pyridyl]acetate 1-10 as a yellow oil (195 mg, 24%). ¹H NMR (400 MHz, CDC ) 6 = 7.72 (t, 1 H), 7.54 (dd, 1H), 7.24 (dd, 1 H), 7.01 - 6.95 (m, 2H), 6.75 - 6.70 (m, 2H), 6.66 (s, 1 H), 5.37 - 5.24 (m, 3H), 4.23 - 4.14 (m, 2H), 3.75 (s, 3H), 1.22 (t, 3H).

Step 4: Preparation of 2-[[2-[(4-methoxyphenyl)methyl]-5-

(trifluoromethyl)pyrazol-3-yl]methyl]-6-(trifluoromethyl)pyridine (1-11 )

To a solution of ethyl 2-[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]- 2-[6-(trifluoromethyl)-2-pyridyl]acetate 1-10 (195 mg, 0.3401 mmol) in ethanol (2.0 mL) was added aqueous sodium hydroxide (2.0 mL, 2 mol/L) and the resulting mixture was stirred at 50 °C for 30 minutes. The mixture was cooled and acidified with aqueous hydrochloric acid (2.0 mL, 6 mol/L) before being 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 1-11 as a pale yellow oil (148 mg, 84%). ¹H NMR (400 MHz, CDCh) 6 = 7.71 (t, 1H), 7.53 (d, 1 H), 7.09 - 7.01 (m, 3H), 6.80 - 6.75 (m, 2H), 6.39 (s, 1 H), 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 (1-12)

A solution of 2-[[2-[(4-methoxyphenyl)methyl]-5-(trifluoromethyl)pyrazol-3-yl]methyl]- 6-(trifluoromethyl)pyridine 1-11 (148 mg, 0.285 mmol) in 2,2,2-trifluoroacetic acid (0.6 mL, 8 mmol) was stirred at 70°C for 30 minutes. The mixture was cooled, diluted with water, and basified carefully with aqueous sodium bicarbonate until effervescence 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)-1 H- pyrazol-5-yl]methyl]pyridine 1-12 as a brown oil (114 mg). ¹H NMR (400 MHz, CDCh) 5 = 7.89 (t, 1 H), 7.64 (d, 1 H), 7.46 (d, 1 H), 6.48 - 6.44 (m, 1 H), 4.30 (s, 2H).

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

A mixture of 2-(trifluoromethyl)-6-[[3-(trifluoromethyl)-1 H-pyrazol-5-yl]methyl]pyridine 1-12 (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 °C for 2 hours. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The combined organics were concentrated and subjected to reverse-phase column chromatography on C-18 silica gel using 50- 100% acetonitrile in water, both with 0.1% formic acid, to give 5-chloro-2-[3- (trifluoromethyl)-5-[[6-(trifluoromethyl)-2-pyridyl]methyl]pyrazol-1-yl]pyrimidine 1.009 as an off-white solid (66 mg, 53%). ¹ H NMR (400 MHz, CDC ) 6 = 8.70 (s, 2H), 7.79 (t, 1H), 7.55 (d, 1 H), 7.30 (d, 1 H), 6.52 (s, 1H), 4.82 (m, 2H).

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

Step 1 : Preparation of diethyl 2-(3,5-difluoro-2-pyridyl)propanedioate (1-13)

A suspension of sodium hydride (60 mass%) in mineral oil (1.35 g, 33.8 mmol) in tetrahydrofuran (28.2 mL) in a 100 mL round bottomed flask was placed under an atmosphere of nitrogen and treated dropwise with diethyl malonate (5.53 g, 33.8 mmol). The mixture was allowed to stir for 5 minutes before being treated with 2,3,5- trifluoropyridine (1.50 g, 11.3 mmol). The mixture was warmed to 60 °C and was allowed to stir for 3.5 h. The reaction mixture was allowed to cool to room temperature before being diluted with water (50 mL) and extracted with ethyl acetate (2 x 40 mL). The combined organics were concentrated in vacuo. The residues were subjected to silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent. The fractions forming the major peak of interest were combined and concentrated in vacuo, yielding diethyl 2-(3,5-difluoro-2- pyridyl)propanedioate 1-13 (2.40 g, 11%) as colourless oil as a mixture of isomers (4:1). The product contains excess of diethyl malonate as impurity which was used directly for the next step without further purification. ¹H NMR (400 MHz, CDCh) 6 = 8.33 (d, 1 H), 7.26 - 7.20 (m, 1H), 5.03 (d, 1 H), 4.28 (q, 4H), 1.28 (t, 6H).

Step 2: Preparation of 2-(3,5-difluoro-2-pyridyl)acetic acid (1-14)

A solution of diethyl 2-(3,5-difluoro-2-pyridyl)propanedioate 1-13 (2.40 g, 8.78 mmol) in methanol (22.0 mL) in a 100 mL round bottomed flask was treated with 2M sodium hydroxide (22.0 mL, 43.9 mmol) and was allowed to stir at 70°C for 1h. Another portion of 2 M sodium hydroxide (13.2 mL, 26.4 mmol) was added, and the reaction was heated at 70 °C for a further 30 min. The reaction mixture was allowed to cool to room temperature before being diluted with water (20 mL). The mixture was adjusted to pH~4 with hydrochloric acid and was extracted with ethyl acetate (2 x 40 mL). The combined organics were passed through a hydrophobic frit and concentrated in vacuo, yielding 2-(3,5-difluoro-2-pyridyl)acetic acid 1-14 (0.686 g, 43%) as a white solid. ¹H NMR (400 MHz, CDCh) 6 = 8.32 (d, 1 H), 7.29 (m, 1 H), 4.01 - 3.89 (m, 2H).

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

A suspension of 2-(3,5-difluoro-2-pyridyl)acetic acid 1-14 (0.686 g, 3.96 mmol) in acetic anhydride (2.06 g, 19.8 mmol) in a 25 mL round bottomed flask was placed under an atmosphere of nitrogen and was treated with 1 -methylimidazole (0.246 g, 2.97 mmol). The reaction mixture was allowed to stir at room temperature overnight. This was quenched by the slow addition of water (15 mL) at 0 °C and stirred for 5 minutes, 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 residues were purified by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane as eluent. Upon concentration, 1-(3,5-difluoro-2- pyridyl)propan-2-one 1-15 (0.13 g, 19%) was obtained as gummy oil. ¹H NMR (400 MHz, CDC ) 6 = 8.30 (d, 1 H), 7.21 (m, 1 H), 3.99 (d, 2H), 2.27 (s, 3H).

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

(1-16)

A solution of 1-(3,5-difluoro-2-pyridyl)propan-2-one 1-15 (0.13 g, 0.76 mmol) in tetrahydrofuran (2 mL) in a 10 mL round bottomed flask was cooled to 0 °C under an atmosphere of nitrogen and treated with potassium tert-butoxide (12 mass%) in tetra hydrofuran, (1.89 mL, 1.89 mmol) and ethyl 2,2-difluoroacetate (0.32 g, 2.65 mmol). The reaction mixture was allowed to stir at room temperature overnight. The reaction mixture was quenched with 2M HCI and extracted with of ethyl acetate (2 X 30 mL). The combined organics were dried over magnesium sulphate and concentrated in vacuo. The crude material was used directly for the next step.

Step 5: Preparation of tert-butyl N-(tert-butoxycarbonylamino)-N-(6-chloro-5- fluoro-3-pyridyl)-carbamate (1-17)

A solution of 5-bromo-2-chloro-3-fluoropyridine (1.498 g, 7.12 mmol) in tetrahydrofuran (14 mL) in a 100 mL round bottomed flask was placed under an atmosphere of nitrogen, cooled over ice and treated with 1.3 M isopropylmagnesium chloride lithium chloride complex solution (6.0 mL, 7.8 mmol). The mixture was allowed to stir for 15 minutes at 0 °C before being treated dropwise with a solution of di-tert-butyl azodicarboxylate (1.83 g, 7.95 mmol) in tetra hydrofuran (4 mL) in a manner that the internal temperature did not exceed 15 °C. The mixture was allowed to stir for 30 minutes. The reaction mixture was quenched with water (100 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organics were washed with brine (50 mL) and concentrated in vacuo. The crude was purified by silica gel column chromatography using 0-30% ethyl acetate in cyclohexane as eluent yielding tertbutyl N-(tert-butoxycarbonylamino)-N-(6-chloro-5-fluoro-3-pyridyl)-carbamate 1-17 (1.79 g, 66%) as an oil that crystallized on standing to a white solid. ¹H NMR (400 MHz, CDCh) 6 = 8.36 (s, 1 H), 7.92 - 7.64 (m, 1H), 6.73 (br s, 1 H), 1.55 - 1.46 (m, 18H).

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

(1.014)

A solution of tert-butyl N-(tert-butoxycarbonylamino)-N-(6-chloro-5-fluoro-3- pyridyl)carbamate 1-17 (0.27 g, 0.76 mmol) in trifluoroacetic acid (0.88 g, 7.6 mmol) in a 100 mL round bottomed flask was stirred at room temperature for 30 minutes. The reaction mixture was treated with a solution of 5-(3,5-difluoro-2-pyridyl)-1 , 1 -difluoro- pentane-2, 4-dione 1-16 (0.19 g, 0.76 mmol) in acetic acid (1.5 mL) and was 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 sulphate and concentrated onto silica. Purification by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane to provide the product along with impurities. The product was repurified by reverse phase chromatography using 40-100% acetonitrile in water with 0.1% formic acid. A final silica gel purification using 20% ethyl acetate in cyclohexane provided 2-chloro-5-[3-(difluoromethyl)-5-[(3,5-difluoro-2- pyridyl)methyl]pyrazol-1-yl]-3-fluoro-pyridine 1.014. ¹H NMR (400 MHz, CDCh) 6 = 8.55 (d, 1 H), 8.28 (d, 1 H), 7.90 (dd, 1 H), 7.25 - 7.21 (m, 1 H), 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 (1-18)

(1-18)

A solution of lithium diisopropylamide (2.0 mol/L) in tetrahydrofuran (28 mL, 56 mmol) in tetrahydrofuran (28 mL) in a 250 mL round bottomed flask was placed under an atmosphere of nitrogen and cooled over ice before being treated slowly with ethyl acetoacetate (2.0 mL, 16 mmol) over approximately 10 minutes. Addition was controlled such that the internal temperature did not exceed 10 °C. On complete addition, the mixture was allowed to stir for 30 minutes. The mixture was cooled to - 78 °C and treated dropwise with ethyl difluoroacetate (2.2 mL, 21 mmol). The resulting reaction mixture was allowed to stir for 3 hours before being removed from the dry ice bath and stirred at room temperature for a further 30 minutes. On completion, the mixture was quenched with 1 M hydrochloric acid (100 mL), diluted with water (40 mL) and extracted with ethyl acetate (2 x 100 mL). The combined organics were dried over anhydrous magnesium sulphate and concentrated in vacuo, yielding ethyl 6,6-difluoro-3,5-dioxo-hexanoate 1-18 (3.3 g, 100% yield) as a dark orange oil which was used directly without any purification.

Step 2: Preparation of ethyl 2-[5-(difluoromethyl)-2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]acetate (1-19)

A solution of ethyl 6,6-difluoro-3,5-dioxo-hexanoate 1-18 (6.24 g, 30 mmol) in acetic acid (60 mL) in a 250 mL round bottomed flask was treated with trifluoroacetic acid (6.91 g, 60 mmol) and (4-methoxyphenyl)methylhydrazine;hydrochloride (5.65 g., 30 mmol) and was allowed to stir at room temperature for overnight. 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 MgSC , filtered, and concentrated. This was purified by silica gel column chromatography using a gradient from 0-40% ethyl acetate in cyclohexane. Upon concentration of the pure fraction, the product ethyl 2-[5-(difluoromethyl)-2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]acetate 1-19 (2.71 g, 28%) was obtained. ¹H NMR (400 MHz, CDC ) 6 = 7.05 (d, 2 H), 6.55 - 6.88 (m, 3 H), 6.48 (s, 1 H), 5.32 (s, 2 H), 4.12 (m, 2 H), 3.78 (s, 3 H), 3.57 (s, 2 H), 1.24 (t, 3 H).

Step 3: Preparation of ethyl 2-(5-chloro-3-fluoro-2-pyridyl)-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 1-19 (2.71 g, 8.36 mmol), 5-chloro-2,3-difluoro-pyridine (3.75 g, 25.1 mmol) and potassium phosphate tribasic (10.9 g, 50.1 mmol) in a 250 mL round bottomed flask was placed under an atmosphere of nitrogen and treated with dimethylsulfoxide (27 mL). The mixture was warmed to 80 °C and was allowed to stir for 1 hour. The reaction mixture was heated for a further 30 minutes then allowed to cool to room temperature before being diluted with water (50 mL), acidified with 2 M hydrochloric acid, and extracted with tert-butylmethyl 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 provide ethyl 2-(5-chloro-3-fluoro-2-pyridyl)-2-[5-(difluoromethyl)-2-[(4- methoxyphenyl)methyl]pyrazol-3-yl]acetate I-20 (1.59 g, 42%) as mixture (1 :1) of isomers. The isomeric mixture was taken for 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 (1-21)

(1-21)

A solution of ethyl 2-(5-chloro-3-fluoro-2-pyridyl)-2-[5-(difluoromethyl)-2-[(4- methoxyphenyl)-methyl]pyrazol-3-yl]acetate I-20 (1.59 g, 3.50 mmol) in methanol (17.5 mL) in a 250 mL round bottomed flask was treated with 2M sodium hydroxide (17.5 mL, 35.0 mmol). The mixture was allowed to stir at 65 °C for 1.5 h. The mixture was acidified with hydrochloric acid, diluted with water (15 mL) and extracted with ethyl acetate (2 x 50 mL). The combined organics were dried over magnesium sulphate and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0-40% ethyl acetate in cyclohexane. Upon concentration, 5- chloro-2-[[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3-yl]methyl]-3- fluoro-pyridine 1-21 (0.68 g, 49%) was obtained as off-white solid. ¹H NMR (400 MHz, CDCh) 6 = 8.30 (s, 1 H) 7.37 (dd, 1 H) 6.95 - 7.06 (m, 2H) 6.80 - 6.83 (m, 2H) 6.69 (t, 1 H), 6.32 (s, 1 H), 5.37 (s, 2H) 4.09 (s, 2H) 3.78 (s, 3H).

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

(I-22)

A solution of 5-chloro-2-[[5-(difluoromethyl)-2-[(4-methoxyphenyl)methyl]pyrazol-3- yl]methyl]-3-fluoro-pyridine 1-21 (0.685 g, 1.79 mmol) in 2,2,2-trifluoroacetic acid (4.13 g, 35.83 mmol) in a 25 mL round bottomed flask was warmed to 70 °C and was allowed to stir for 2 h. The reaction mixture was allowed to cool to room temperature before being added to water (~50 mL), causing a precipitate to form. The aqueous was basified with saturated aqueous bicarbonate and ethyl acetate (100 mL) was added. The phases were separated and the organics were dried over magnesium sulphate and concentrated in vacuo. The orange gum obtained was purified by silica gel column chromatography using 0-100% ethyl acetate in cyclohexane to afford 5- chloro-2-[[3-(difluoromethyl)-1 H-pyrazol-5-yl]methyl]-3-fluoro-pyndine I-22 (0.36 g, 73%). ¹H NMR (400 MHz, CDCI3) 5 = 11.37 - 11.83 (m, 1 H), 8.39 (d, 1 H), 7.49 (dd, 1 H), 6.51 - 6.87 (m, 1 H), 6.42 (s, 1 H), 4.26 (d, 2 H).

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

(1.017)

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

TABLE 1

Biological Examples

Seeds of a variety of test species are sown in standard soil in pots Amaranthus palmeri (AMAPA), Amaranthus retroflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE)). After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity), the plants are sprayed with an aqueous spray solution derived from the dissolution of the test compound in acetone and IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether) which was then diluted to the required concentration using 0.2% Genapol XO80 (CAS No.9043-30-5) in water as the diluent. Test compounds are applied at the rates stated. The test plants are then grown in a glasshouse under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days for pre- and post-emergence, the test is evaluated for the percentage damage caused to the plant.

TABLE B1. Post-emergence Test

NT = Not tested

TABLE B2. Pre-emergence Test

NT = Not tested

Claims

1 . A compound of Formula (I): or an agronomically acceptable salt thereof, wherein

R² is selected from the group consisting of halogen, -CN, NO2, Ci-C4alkyl, C1- C4haloalkyl, Ci-C4alkoxy, -C(O)Ci-C4alkyl, -C(O)OCi-C4alkyl, C1- C4haloalkoxy, Ci-C4alkoxyCi-C3alkyl-, Ci-C4alkoxyCi-C3alkoxy-, C1- C4alkoxyCi-C3alkoxyCi-C3alkyl-, -S(O)_pCi-C4alkyl and Cs-Cecycloalkyl;

R⁴ is selected from the group consisting of halogen, C1-C4 alkyl, C1- C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy, Ci-C4alkoxyCi-C3alkyl-, Ci- C4alkoxyCi-C3alkoxy-, Ci-C4alkoxyCi-C3alkoxyCi-C3alkyl-, -CN, NO2, C2- C4alkenyl, C2-C4alkynyl, -S(O)_pCi-C4alkyl, -S(O)_pCi-C4haloalkyl, -C(O)OCi- C₄alkyl and -C(O)NR⁵R⁶;

R⁵ is hydrogen or Ci-C4alkyl;

R⁶ is hydrogen or Ci-C4alkyl;

R⁷ is hydrogen or Ci-C4alkyl;

R⁸ is hydrogen or Ci-C2alkyl; m = 0, 1 or 2; and p = 0, 1 or 2.

2. A compound according to claim 1, wherein R³ is hydrogen.

3. A compound of Formula (I) according to claim 1 or claim 2, wherein m is one or two and R¹ is independently selected from the group consisting of halogen, -CN, Ci-C4alkyl, Ci-C4haloalkyl, Ci-C4alkoxy- and Ci-C4haloalkoxy.

4. A compound according to claim 3, wherein m is one and R¹ is chloro.

5. A compound according to any one of the previous claims, wherein R² is selected from the group consisting of halogen, Ci-C4haloalkyl-, cPr and CN.

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

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

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

9. A compound according to claim 8, wherein R⁴ is independently selected from the group consisting of cyano, methyl, halogen and -CF3.

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

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

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

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

14. A method of controlling weeds at a locus comprising application to the locus of a weed controlling amount of a composition according to any one of claims

11 to 13.

15. Use of a compound of Formula (I) as defined in claim 1 as a herbicide.