BR112020014489B1 - BENZOYL COMPOUNDS REPLACED BY AMIDINE, HERBICIDAL COMPOSITION, METHOD OF CONTROL OF WEEDS IN A LOCUS AND USE OF A COMPOUND - Google Patents

Abstract

The present invention relates to compounds of Formula (I): or an agronomically acceptable salt thereof, wherein Q, X, Z, R2 and R3 are as defined herein. The invention further relates to compositions comprising such compounds, to methods of controlling weeds using such compositions and to the use of Compounds of Formula (I) as a herbicide.

Description

[0001] The present invention relates to new herbicidal compounds, to processes for their preparation, to herbicidal compositions comprising the new compounds, and to their use for controlling weeds, in particular in crops of useful plants, or for inhibition of plant growth.

[0002] N-(tetrazol-5-yl)- and N-(1,3,4-oxadiazol-2-yl) arylcarboxamides are disclosed in, for example, WO2012/028579 and WO2012/126932, respectively. The present invention relates to new amidine-substituted benzoyl compounds.

[0003] Thus, according to the present invention, a compound of Formula (I) is provided: or an agronomically acceptable salt thereof, wherein:- R2 is selected from the group consisting of halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl and -S(O)pC1-C6 alkyl; R3 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl and -S(O)pC1-C6 alkyl; Q is selected from the group consisting of Q1, Q2 and Q3; R1a is C1-C4 alkyl or C1-C3-alkoxy-C1-C3-alkyl; R1b is selected from the group consisting of hydrogen, C1-C4 alkyl and C1-C3 alkoxy-C1-C3 alkyl; A1 is selected from the group consisting of O, C(O) and (CReRf); Ra, Rb, Rc, Rd, Re and Rf are each independently selected from the group consisting of hydrogen and C1-C4 alkyl in which Ra and Rc can together form a C1-C3 alkylene chain. X is -(CH2)n- or -(CH2)nO-(CH2)n-; n is selected independently from between 0, 1 and 2; Z is Z1 or Z2 R4 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl; R5 is selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 haloalkyl; R6 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano and phenyl, wherein phenyl is optionally substituted by 1, 2 or 3 substituents selected from the group consisting of halogen, C1-C6 alkyl, haloalkyl C1-C6 and C1-C6 alkoxy; or R5 and R6 are together -CH2CH2CH2CH2, -CH2CH2CH2CH2CH2- or -CH2CH2OCH2CH2-; and R7 is selected from the group consisting of hydrogen and C1-C6 alkyl; R8 is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl; R9 is selected from the group consisting of hydrogen, cyano, C1-C6 alkyl and C1-C6 alkoxy; ep = 0, 1 or 2.

[0004] C1-C6 alkyl and C1-C4 alkyl groups include, for example, methyl (Me, CH3), ethyl (Et, C2H5), n-propyl (n-Pr), isopropyl (i-Pr), n -butyl (n-Bu), isobutyl (i-Bu), sec-butyl and tert-butyl (t-Bu). C3-C6 cycloalkyl includes cyclopropyl (c-propyl (c-Pr)), cyclobutyl (c-butyl (c-Bu)), cyclopentyl (c-pentyl) and cyclohexyl (c-hexyl).

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

[0006] C1-C6 haloalkyl includes, for example, fluoromethyl-, difluoromethyl-, trifluoromethyl-, chloromethyl-, dichloromethyl-, trichloromethyl-, 2,2,2-trifluoroethyl-, 2-fluoroethyl-, 2-chloroethyl-, pentafluoroethyl -, 1,1-difluoro-2,2,2-trichloroethyl-, 2,2,3,3-tetrafluoroethyl-, 2,2,2-trichloroethyl-, heptafluoro-n-propyl and perfluoro-n-hexyl. C1-C4 haloalkyl includes, for example, fluoromethyl-, difluoromethyl-, trifluoromethyl-, chloromethyl-, dichloromethyl-, trichloromethyl-, 2,2,2-trifluoroethyl-, 2-fluoroethyl-, 2-chloroethyl-, pentafluoroethyl-, 1 ,1-difluoro-2,2,2-trichloroethyl-, 2,2,3,3-tetrafluoroethyl-, 2,2,2-trichloroethyl- and heptafluoro-n-propyl-.

[0007] C1-C6-S-alkyl (alkylthio) is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0008] Alkyl C1-C6-S(O)- (alkylsulfinyl) is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0009] C1-C6-S(O)2-alkyl (alkylsulfonyl) is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0010] In a preferred embodiment of the present invention, R2 is selected from the group consisting of methyl, Cl, -CF3 and -SO2methyl.

[0011] In another preferred embodiment of the present invention, R3 is selected from the group consisting of methyl, Cl, -CF3 and -SO2methyl.

[0012] In another preferred embodiment of the present invention, R1a and R1b are selected from the group consisting of methyl, ethyl and n-propyl.

[0013] In another embodiment of the present invention, Q is Q1 and Z is Z1. In this embodiment, X can be -(CH2)n- and n is 0. In this embodiment, the compound of Formula (I) is a compound of Formula (Ia):

[0014] wherein R1a, R2, R3, R4, R5 and R6 are as defined with respect to a compound of Formula (I).

[0015] In another embodiment of the present invention, Q is Q2 and Z is Z1. In this embodiment, Thus, in another preferred embodiment of the present invention there is provided a compound of Formula (Ib)

[0016] wherein R1b, R2, R3, R4, R5 and R6 are as defined with respect to a compound of Formula (I). In another embodiment of the present invention, Q is Q3 and Z is Z1. In another embodiment of the present invention, Q is Q1 and Z is Z2. In another embodiment of the present invention, Q is Q2 and Z is Z2. In another embodiment of the present invention, Q is Q3 and Z is Z2.

[0017] Compounds of Formula (I) (and certain intermediate compounds used to synthesize the compound of Formula (I)) may contain asymmetric centers and may be present as a single enantiomer, pairs of enantiomers in any proportion or, where present more than one asymmetric center, contain diastereoisomers in all possible ratios. Typically, one of the enantiomers has enhanced biological activity compared to the other possibilities.

[0018] The present invention also includes all possible geometric and tautomeric forms of a compound of formula (I).

[0019] The present invention also includes agronomically acceptable salts that the compounds of Formula (I) can form with amines (for example, ammonia, dimethylamine and triethylamine), alkali metal and alkaline earth metal bases or quaternary ammonium bases. Among the hydroxides, oxides, alkoxides and hydrogen carbonates and carbonates of alkali metals and alkaline earth metals used as salt formers, emphasis should be given to the hydroxides, alkoxides, oxides and carbonates of lithium, sodium, potassium, magnesium and calcium, but especially to those of sodium, magnesium and calcium. The corresponding trimethylsulfonium salt may also be used.

[0020] The compounds of Formula (I) according to the invention can be used as herbicides in their own right, but are generally formulated into herbicidal compositions using formulation adjuvants, such as carriers, solvents and surfactants (SFA). Thus, the present invention further provides a herbicidal composition comprising a compound of the present invention and an agriculturally acceptable formulation adjuvant. The composition may be in the form of concentrates which are diluted before use, although ready-to-use compositions may also be prepared. The final dilution is usually prepared with water, but can be prepared instead of, or in addition to water, with, for example, liquid fertilizers, micronutrients, biological organisms, oil or solvents.

[0021] Herbicidal compositions generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, of compounds of Formula I and from 1 to 99.9% by weight of a formulation adjuvant that preferably includes from 0 to 25% by weight of a surfactant substance.

[0022] Compositions can be chosen from a variety of formulation types, many of which are known from the “Manual on Development and Use of FAO Specifications for Plant Protection Products”, 5th Edition, 1999. These include dustable powders (DP), soluble powders (SP), water-soluble granules (SG), water-dispersible granules (WG), wettable powders (WP), granules (GR) (slow or fast release), soluble concentrates (SL), oil-miscible liquids ( OL), ultra-low volume liquids (UL), emulsifiable concentrates (EC), dispersible concentrates (DC), emulsions (both oil-in-water (EW) and water-in-oil (EO)), microemulsions (ME), suspension concentrates ( SC), aerosols, capsule suspensions (CS) and seed treatment formulations. The type of formulation chosen will in any case depend on the particular purpose intended and the physical, chemical and biological properties of the compound of Formula (I).

[0023] Dustable powders (DP) can be prepared by mixing a compound of Formula (I) with one or more solid diluents (for example natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, diatomite, chalk, diatomaceous earth , calcium phosphates, calcium and magnesium carbonates, sulfur, lime, flours, talc and other organic and inorganic solid carriers) and mechanical grinding of the mixture to a fine powder.

[0024] Soluble powders (SP) can be prepared by mixing a compound of Formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as a polysaccharide) and, optionally, one or more wetting agents, one or more dispersing agents or a mixture of said agents to improve dispersibility/water solubility. The mixture is then crushed to a fine powder. Similar compositions can also be granulated to form water-soluble granules (SG).

[0025] Wettable powders (WP) can be prepared by mixing a compound of Formula (I) with one or more diluents or solid carriers, one or more wetting agents and, preferably, one or more dispersing agents and, optionally, a or more suspending agents to facilitate dispersion in liquids. The mixture is then crushed to a fine powder. Similar compositions can also be granulated to form water-dispersible granules (WG).

[0026] Granules (GR) can be formed by granulating a mixture of a compound of Formula (I) and one or more diluents or solid powder carriers, or from pre-formed blank granules by absorption of 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 earth or crushed corncobs) or by adsorption of a compound of Formula (I) (or a solution thereof, in a suitable agent) in a hard core material (such as sands, silicates, mineral carbonates, sulphates or phosphates) and drying if necessary. Agents that are commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones, and esters) and adhesive agents (such as polyvinyl acetates, polyvinyl alcohols, dextrins, sugars, and oils). vegetables). One or more other additives may also be included in granules (for example an emulsifying agent, wetting agent or dispersing agent).

[0027] Dispersible Concentrates (DC) can be prepared by dissolving a compound of Formula (I) in water or an organic solvent, such as a ketone, alcohol or glycol ether. These solutions may contain a surfactant (for example to improve dilution in water or prevent crystallization in a spray tank).

[0028] Emulsifiable concentrates (EC) or oil-in-water (EW) emulsions can 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 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), fatty acid dimethylamides (such as C8-C10 fatty acid dimethylamide) and chlorinated hydrocarbons. An EC product may emulsify spontaneously upon addition to water, to produce an emulsion with sufficient stability to permit spray application using appropriate equipment.

[0029] The 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 can be melted at a reasonable temperature, typically below 70 °C) or in solution ( by dissolving it in an appropriate solvent) and then emulsifying the resulting liquid or solution in water containing one or more SFA, under high shear, to produce an emulsion. Suitable solvents for use in EW include vegetable oils, chlorinated hydrocarbons (such as chlorobenzenes), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other suitable organic solvents that have a low solubility in water.

[0030] Microemulsions (ME) can be prepared by mixing water with a combination of one or more solvents with one or more SFAs, to spontaneously produce a thermodynamically stable isotropic liquid formulation. A compound of Formula (I) is initially present in both water and the solvent/SFA combination. Suitable solvents for use in ME include those previously described herein for use in EC or EW. An ME may be an oil-in-water or water-in-oil system (which system is present can 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 in water, remaining as a microemulsion or forming a conventional oil-in-water emulsion.

[0031] Suspension concentrates (SC) may comprise aqueous or non-aqueous suspensions of finely divided insoluble solid particles of a compound of Formula (I). SCs can be prepared by ball or spherule milling of the solid compound of Formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a suspension of fine particles 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) can be dry milled and added to water containing the agents described above to produce the desired final product.

[0032] Aerosol formulations comprise a compound of Formula (I) and a suitable propellant (for example n-butane). A compound of Formula (I) can 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 manual, non-pressurized spray pumps.

[0033] Capsule suspensions (CS) can be prepared in a similar way to the preparation of EW formulations, but with an additional polymerization step so 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 can be produced either by an interfacial polycondensation reaction or by a coacervation procedure. The compositions can provide controlled release of the compound of Formula (I) and can be used for seed treatment. A compound of Formula (I) can also be formulated in a biodegradable polymeric matrix to provide a slow, controlled release of the compound.

[0034] 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 surfactants (SFAs), oil-based spray additives, for example certain mineral oils or natural vegetable oils (such as soybean and rapeseed oil), and combinations of these with other bio-enhancing adjuvants (ingredients that can assist or modify the action of a compound of Formula (I)).

[0035] Wetting agents, dispersing agents and emulsifying agents can be SFA of the cationic, anionic, amphoteric or non-ionic type.

[0036] Suitable SFAs of the cationic type include quaternary ammonium compounds (for example cetyltrimethylammonium bromide), imidazolines and amine salts.

[0037] Suitable anionic SFAs include alkali metal salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (e.g., sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g., sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, of butylnaphthalene and mixtures of sodium diisopropyl and triisopropylnaphthalenesulfonates), ether sulfates, alcohol ether sulfates (e.g., sodium lauret-3-sulfate), ether carboxylates (e.g., lauret-3- sodium carboxylate), phosphate esters (products of the reaction between one or more fatty alcohols and phosphoric acid (predominantly monoesters) or phosphorus pentoxide (predominantly diesters), e.g. the reaction between lauryl alcohol and tetraphosphoric acid; additionally, these products may be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates and lignosulfonates.

[0038] Suitable SFAs of the amphoteric type include betaines, propionates and glycinates.

[0039] Suitable non-ionic type SFAs 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 (e.g. polyethylene glycol esters of fatty acids); amine oxides (e.g. lauryl dimethylamine oxide); and lecithins.

[0040] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and expandable clays (such as bentonite or attapulgite).

[0041] The present composition may additionally comprise at least one additional pesticide. For example, the compounds according to the invention can also be used in combination with other herbicides or plant growth regulators. In a preferred embodiment the additional pesticide is a herbicide and/or herbicide protectant. Examples of such mixtures are (wherein "I" represents a compound of Formula I). I + acetochlor, I + acifluorfen, I + acifluorfen-sodium, I + aclonifen, I + acrolein, I + alachlor, I + alloxydim, I + ametrine, I + amicarbazone, I + amidosulfuron, I + aminopyralid, I + amitrol, I + anilofos, I + asulam, I + atrazine, I + azafenidine, I + azimsulfuron, I + BCPC, I + beflubutamide, I + benazoline, I + bencarbazone, I + benfluralin, I + benfuresate, I + bensulfurone, I + bensulfuron-methyl, I + bensulide, I + bentazone, I + benzfendizone, I + benzobicyclone, I + benzofenape, I + biciclopyrone, I + bifenox, I + bilanafos, I + bispiribac, I + bispiribac-sodium, I + borax, I + bromacil, I + bromobutide, I + bromoxynil, I + butachlor, I + butamiphos, I + butralin, I + butroxydim, I + butylate, I + cacodylic acid, I + calcium chlorate, I + cafenstrol, I + carbetamide , I + carfentrazone, I + carfentrazone-ethyl, I + chlorflurenol, I + chlorflurenol- methyl, I + chloridazone, I + chlorimurone, I + chlorimurone- ethyl, I + chloroacetic acid, I + chlorotolurone, I + chlorprofam, I + chlorsulfuron, I + chlortal, I + chlorthal-dimethyl, I + cynidone-ethyl, I + cinmethylline, I + cinosulfuron, I + cisanilide, I + clethodim, I + clodinafop, I + clodinafop-propargyl, I + clomazone, I + clomeprope, I + clopyralid, I + cloransulam, I + cloransulam-methyl, I + cyanazine, I + cycloate, I + cyclosulfamurone, I + cycloxidim, I + cyhalofop, I + cyhalofope-butyl, I + 2, 4-D, I + daimurone, I + dalapon, I + dazomet, I + 2,4-DB, I + I + desmedifam, I + dicamba, I + diclobenil, I + dichlorprope, I + dichlorprope-P, I + diclofop, I + diclofop-methyl, I + diclosulam, I + diphenzoquat, I + diphenzoquat methylsulfate, I + diflufenican, I + diflufenzopyr, I + dimefurone, I + dimepiperate, I + dimethachlor, I + dimethamethrin, I + dimethenamid, I + dimethenamid-P, I + dimethipine, I + dimethylarsinic acid, I + dinitramine, I + dinoterb, I + diphenamide, I + dipropetrin, I + diquat, I + diquat dibromide, I + dithiopyr, I + diuron, I + endotal, I + EPTC, I + esprocarb, I + etalfluralin, I + ethametsulfuron, I + etametsulfuron-methyl, I + ethephone, I + ethofumesate, I + ethoxyfen, I + ethoxysulfuron, I + ethobenzanide, I + fenoxaprop-P , I + fenoxaprop-P-ethyl, I + phenquinotrione, I + fentrazamide, I + ferrous sulfate, I + flamprope-M, I + flazasulfuron, I + florasulam, I + fluazifop, I + fluazifop-butyl, I + fluazifope- P, I + fluazifop-P-butyl, I + fluazolate, I + flucarbazone, I + flucarbazone-sodium, I + flucetosulfuron, I + fluchloralin, I + flufenacet, I + flufenpyr, I + flufenpyr-ethyl, I + flumetralin, I + flumetsulam, I + flumiclorac, I + flumiclorac-pentyl, I + flumioxazin, I + flumipropine, I + fluometurone, I + fluoroglycophen, I + fluoroglycophen-ethyl, I + fluoxaprope, I + flupoxam, I + flupropacil, I + flupropanate, I + flupyrsulfuron, I + flupyrsulfuron-methyl- sodium, I + flurenol, I + fluridone, I + flurochloridone, I + fluroxypyr, I + flurtamon, I + flutiacete, I + fluthiacete- methyl, I + falesafen, I + foramsulfuron, I + fosamine, I + glufosinate, I + glufosinate-ammonium, I + glyphosate, I + halauxifene, I + halosulfuron, I + halosulfuron-methyl, I + haloxyfop, I + haloxyfop-P, I + hexazinone, I + imazametabenz, I + imazametabenz-methyl, I + imazamox, I + imazapic, I + imazapyr, I + imazaquine, I + imazethapyr, I + imazosulfuron, I + indanophane, I + indaziflam, I + iodomethane, I + iodosulfuron, I + iodosulfuron-methyl- sodium, I + ioxynil, I + isoproturone, I + isourone, I + isoxaben, I + isoxachlortol, I + isoxaflutole, I + isoxapirifop, I + carbylate, I + lactophen, I + lenacil, I + linurone, I + mecoprope, I + mecoprope-P, I + mefenacet, I + mefluidide, I + mesosulfuron, I + mesosulfuron-methyl, I + mesotrione, I + metam, I + metamifop, I + metamitrone, I + metazaclor, I + metabenzthiazuron, I + methazol, I + methylarsonic acid, I + methyldimrone, I + methyl isothiocyanate, I + metolachlor, I + S-metolachlor, I + metosulam, I + methoxurone, I + metribuzin, I + metsulfuron, I + metsulfuron -methyl, I + molinate, I + monolinuron, I + naproanilide, I + napropamide, I + naptalam, I + neburone, I + nicosulfuron, I + methyl n-glyphosate, I + nonanoic acid, I + norflurazone, I + oleic acid (fatty acids), I + orbencarb, I + orthosulfamurone, I + oryzalin, I + oxadiargyl, I + oxadiazone, I + oxasulfuron, I + oxaziclomephone, I + oxyfluorfen, I + paraquat, I + paraquat dichloride, I + pebulate, I + pendimethalin, I + penoxsulam, I + pentachlorophenol, I + pentanochlor, I + pentoxazone, I + petoxamide, I + phenmedifam, I + picloram, I + picolinaphene, I + pinoxaden, I + piperofos, I + pretilachlor , I + primisulfuron, I + primisulfuron-methyl, I + prodiamine, I + profoxidim, I + prohexadione-calcium, I + promethone, I + promethrin, I + propachlor, I + propanil, I + propaquizafop, I + propazine , I + profam, I + propisochlor, I + propoxycarbazone, I + propoxycarbazone-sodium, I + propyzamide, I + prosulfocarb, I + prosulfurone, I + pyraclonil, I + pyraflufen, I + pyraflufen-ethyl, I + pyrasulfotol, I + pyrazolinate, I + pyrazosulfuron, I + pyrazosulfuron- ethyl, I + pyrazoxifene, I + pyribenzoxim, I + piributicarb, I + pyridafol, I + pyridate, I + pyrifthalide, I + piriminobac, I + piriminobac-methyl, I + pyrimisulfan , I + pyritiobac, I + pyritiobac-sodium, I + pyroxasulfone, I + piroxsulam, I + quinclorac, I + quinmerac, I + quinoclamine, I + quizalofop, I + quizalofop-P, I + rimsulfuron, I + saflufenacil, I + sethoxydim, I + sidurone, I + simazine, I + symethrin, I + sodium chlorate, I + sulcotrione, I + sulfentrazone, I + sulfometurone, I + sulfometurone-methyl, I + sulfosate, I + sulfosulfuron, I + acid sulfuric acid, I + tebuthiurone, I + tefuryltrione, I + tembotrione, I + tepraloxidim, I + terbacil, I + terbumetone, I + terbuthylazine, I + terbutrine, I + tenylchlor, I + thiazopyr, I + thifensulfuron, I + thiencarbazone, I + thifensulfuron-methyl, I + thiobencarb, I + topramezone, I + tralkoxidim, I + tri-allate, I + triasulfuron, I + triaziflam, I + tribenurone, I + tribenurone-methyl, I + triclopyr, I + triethazine, I + trifloxysulfurone, I + trifloxysulfuron-sodium, I + trifluralin, I + triflusulfuron, I + triflusulfuron-methyl, I + trihydroxytriazine, I + trinexapac-ethyl, I + tritosulfurone, I + acid ethyl ester [3- [2-chloro-4-fluoro-5-(1-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy]acetic acid (RN of CAS 353292-31-6), I + 4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, I + 4-hydroxy-1, 5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, I + 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl] imidazolidin-2-one, I + 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, I + 4-hydroxy-1,5-dimethyl-3-[ 1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, I + (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3- methyl-imidazolidin-2-one, I + 3-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione , I + 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione, I + 2-[ 2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl -3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione, I + 6-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo -pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione, I + 2- [2-(3,4-dimethoxyphenyl)-6-methyl-3 -oxo-pyridazine-4-carbonyl]- 5-ethyl-cyclohexane-1,3-dione, I + 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4 -carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1,3-dione, I + 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)- 3-oxo-pyridazine-4 -carbonyl]-5-methyl-cyclohexane-1,3-dione, I + 3-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2 .1]octane-2,4-dione, I + 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane -1,3-dione, I + 6-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane -1,3,5-trione, I + 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione, I + 4-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione and 4- [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione. The compounds of the present invention can also be combined with herbicidal compounds disclosed in WO06/024820 and/or WO07/096576.

[0042] 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 presented in The Pesticide Manual.

[0043] The mixing ratio between the compound of Formula I and the mixing partner is preferably 1: 100 to 1000:1.

[0044] Mixtures can be advantageously used in the above-mentioned formulations (in which case the "active ingredient" relates to the respective mixture of the compound of Formula I with the mixing partner).

[0045] The compounds of Formula I according to the invention can also be used in combination with one or more phytoprotectants. Likewise, mixtures of a compound of Formula I according to the invention with one or more additional herbicides can also be used in combination with one or more phytoprotectants. Phytoprotectors can be AD 67 (MON 4660), benoxacor, cloquintocete-mexil, cyprosulfamide (RN of CAS 221667-31-8), dichlormide, fenchlorazol-ethyl, fenclorim, fluxfenim, furilazole and the corresponding R-isomer, isoxadiphene-ethyl, mefenpyr-diethyl, oxabetrinil, N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-344). Other possibilities include phytoprotective compounds disclosed in, for example, EP0365484, for example, N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide. Particularly preferred are mixtures of a compound of Formula I with cyprosulfamide, isoxadiphene-ethyl, cloquintocet-mexyl and/or N-(2-methoxybenzoyl)-4-[(methyl-aminocarbonyl)amino]benzenesulfonamide.

[0046] Phytoprotectors of the compound of Formula I may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, 16th Edition (BCPC), 2012. The reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salt thereof as disclosed in WO 02/34048, and the reference to fenchlorazol-ethyl also applies to fenchlorazole, etc.

[0047] Preferably, the mixing ratio between the compound of Formula I and the phytoprotectant is 100:1 to 1:10, especially 20:1 to 1:1.

[0048] The mixtures can be used advantageously in the formulations mentioned above (in this case "active ingredient" refers to the respective mixture of the compound of Formula I with the protectant).

[0049] The present invention further provides a method for controlling weeds at a location, said method comprising applying to the weed locus a control amount of a composition comprising a compound of Formula (I). Furthermore, the present invention further provides a method of selectively controlling weeds at a locus comprising crop plants and weeds, wherein the method comprises applying to the locus a weed control amount of a composition according to with the present invention. "Control" means killing, reducing or retarding growth or preventing or reducing germination. Generally, the plants to be controlled are unwanted plants (weeds). "Locus" means the area in which plants are growing or will grow. Some crop plants may be inherently tolerant to the herbicidal effects of compounds of Formula (I). However, in some cases tolerance may need to be manipulated in the crop plant, for example through genetic engineering. It is therefore possible for the crop plant to be made tolerant to HPPD inhibitors through genetic engineering. Methods of making crop plants tolerant to HPPD inhibitors are known, for example, from WO0246387. Thus, in an even more preferred embodiment, the crop plant is transgenic with respect to a polynucleotide comprising a DNA sequence encoding an HPPD inhibitor-resistant HPPD enzyme derived from a bacterium, more particularly from Pseudomonas fluorescens or Shewanella colwelliana. , or of a plant, more particularly, derived from a monocotyledonous plant or, even more particularly, from barley, corn, wheat, rice, species of Brachiaria, Cenchrus, Lolium, Festuca, Setaria, Eleusine, Sorghum or Avena. Several HPPD-tolerant transgenic soybean "events" are known, and include, for example, SYHT04R (WO2012/082542), SYHT0H2 (WO2012/082548) and FG72. Other polynucleotide sequences that can be used to provide plants that are tolerant to the compounds of the present invention are disclosed in, for example, WO2010/085705 and WO2011/068567. Crop plants in which the composition according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, rapeseed, sunflower, maize, rice, soya, sugar beet, sugar cane and lawn. .

[0050] Crop plants may also include trees, such as fruit trees, palm trees, coconut trees or other nuts. Also included are vines such as grapes, fruit bushes, fruit plants and vegetables.

[0051] The application rates of compounds of Formula I can vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed treatment; application in the seed furrow; no application of plowing, etc.), the crop plant, the weed(s) to be controlled, the prevailing climatic conditions and other factors controlled by the method of application, the time of application and target culture. The compounds of Formula I according to the invention are generally applied at a rate of 10 to 2000 g/ha, especially 50 to 1000 g/ha.

[0052] Application is generally done by spraying the composition, typically by tractor-mounted sprayer for large areas, but other methods such as dusting (for powders), dripping or watering can also be used.

[0053] Crop plants are to be understood as also including those crop plants that have been made tolerant to herbicides or classes of herbicides (e.g., ALS, GS, EPSPS, PPO, ACCase and HPPD inhibitors) by conventional methods breeding or genetic engineering. An example of a crop that has been made tolerant to imidazolinones, e.g., imazamox by conventional breeding methods is Clearfield® summer rapeseed (canola). Examples of crops that have been made tolerant to herbicides by genetic improvement methods include, for example, glyphosate- and glufosinate-resistant corn varieties commercially available under the trade names RoundupReady® and LibertyLink®.

[0054] Crop plants are also to be understood as being those that have been made resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to the European corn borer), Bt cotton (resistant to the boll weevil). ) and also Bt potatoes (resistant to the Colorado beetle). Examples of Bt corn are the Bt 176 corn hybrids from NK® (Syngenta Seeds). Bt toxin is a protein that is naturally formed by the soil bacteria Bacillus thuringiensis. Examples of toxins, or transgenic plants capable of synthesizing such toxins, are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants that comprise one or more genes encoding insecticide resistance and express one or more toxins are KnockOut® (corn), Yield Gard® (corn), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf ® (potatoes), NatureGard® and Protexcta®. Plant crops or their seed material can be resistant to herbicides and at the same time resistant to insect feeding ("stacked" transgenic events). For example, seeds may have the ability to express an insecticidal Cry3 protein while also being tolerant to glyphosate.

[0055] Crop plants are also to be understood as including those obtained by conventional breeding methods or genetic engineering and contain so-called production traits (e.g., improved storage stability, higher nutritional value and improved flavor).

[0056] Other useful plants include grass, for example on golf courses, lawns, parks and roadsides, or grown commercially for lawns, and ornamental plants such as flowers or shrubs.

[0057] The compositions can be used to control unwanted plants (collectively, "weeds"). The weeds to be controlled may be monocotyledonous species, for example Agrostis, Alopecurus, Avena, Brachiaria, 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. Weeds can also include plants that might be considered crop plants, but that are growing outside of a crop area ("escaped"), or that grow from seeds left over from a previous planting of a different crop ("volunteers"). ). Such volunteers or escapees may be tolerant to certain other herbicides.

[0058] The compounds of the present invention can be prepared according to the following schemes.

[0059] Compounds of formula (I) can be prepared from benzoic acids of formula (II).

[0060] As shown in Scheme 1.1, where Q = Q1, benzoic acid of formula (II) is treated with an amine of formula (III) in the presence of a suitable amide coupling reagent in a suitable solvent. Examples of suitable amide coupling reagents are propylphosphonic anhydride (T3P) and 1,1'-carbonyldiimidazole (CDI). Examples of suitable solvents are dichloromethane and 1,4-dioxane. Scheme 1.1

[0061] As shown in Scheme 1.2, where Q = Q2, benzoic acid of formula (II) is treated with an amine of formula (IV) in the presence of a suitable amide coupling reagent in a suitable solvent to give the compound of formula (I) where Q = Q2. Examples of suitable amide coupling reagents are propylphosphonic anhydride (T3P) and 1,1'-carbonyldiimidazole (CDI). Examples of suitable solvents are dichloromethane and 1,4-dioxane. Scheme 1.2

[0062] As shown in Scheme 1.3, where Q = Q3, benzoic acid of formula (II) is treated with oxalyl chloride and catalytic DMF in dichloromethane. Once chlorination is complete, triethylamine and a 1,3-dione of formula (V) are then added to the reaction mixture. After approximately 1 hour, catalytic acetone cyanohydrin is added to give the compound of formula (I) where Q = Q3. Scheme 1.3

[0063] Benzoic acids of formula (II) can be prepared from esters of formula (VI), as shown in Scheme 2, where “Alk” is defined as a C1-C6 alkyl, for example methyl or ethyl. Scheme 2

[0064] The ester of formula VI is treated with an alkoxide base, for example sodium hydroxide or lithium hydroxide and a suitable solvent. Two examples of a suitable solvent are: a 2:1 mixture of ethanol: water or a 2:1 mixture of tetrahydrofuran: water. Esters of formula (VI) can be prepared from a variety of media depending on the nature of Z. Where Z = Z1, esters of formula (VI) can be prepared from anilines of formula (VII) and Vilsmeier salts of formula (VIII) as shown in Scheme 3: Scheme 3

[0065] Some Vilsmeier salts are commercially available, such as (chloromethylene)dimethyliminium chloride. Following Scheme 3, the amine of formula (VII) is treated with the Vilsmeier salt of formula (VIII) in a suitable solvent, for example tetrahydrofuran.

[0066] Where Z = Z2, compounds of formula (VI) can be prepared from thioamides of formula (IX) as shown in Scheme 4. Scheme 4

[0067] The thioamide of formula (IX) is treated with the appropriate amine H2N-R6 in the presence of a suitable Lewis acid and a suitable solvent. An example of a suitable Lewis acid is silver tetrafluoroborate. An example of a suitable solvent is tetrahydrofuran. Thioamides of formula (IX) can be prepared from amines of formula (X), as shown in Scheme 5, where “Alk” is a C1 to C6 alkyl, such as methyl or ethyl. Scheme 5

[0068] As shown in Scheme 5, the amine of formula (X) is treated with the appropriate dithioester of formula (XI) and a base in a suitable solvent. An example of a suitable base is triethylamine. An example of a suitable solvent is tetrahydrofuran. Amines of formula (X) can be prepared by alkylation of amines of formula (VII). Such alkylation methods, for example reductive amination, should be familiar to one skilled in the art. Alternatively, amines of formula (X) can be prepared by amination of halides of formula (XII) as shown in Scheme 6, where "Hal" is a halogen atom such as chlorine or bromine. Scheme 6

[0069] The halide of formula (XII) is treated with the appropriate amine H2N-R7 in an appropriate solvent, for example tetrahydrofuran. A base can be used in this reaction. Alkyl halides of formula (XII) can be prepared by several methods. An example of its preparation, where X = -CH2- is the bromination of methyl substituted benzene derivatives of formula (XIII). Scheme 7

[0070] In this example, suitable bromination conditions are N-bromosuccinimide in the presence of a catalytic amount of benzoylperoxide or azobisisobutyronitrile using CCl4 or 1,2-dichloroethane as solvent. The synthesis of many examples of Compound of formula (XIII) is reported. Examples include 2-chloro-3-methyl-4-trifluoromethyl ethyl benzoate and 2-chloro-3-methyl-4-methylsulfonyl ethyl benzoate. The synthesis of compound of formula (VII) can be derived from carboxylic acids of formula (XIV) by an esterification reaction as shown in Scheme 8. Scheme 8

[0071] Compounds of formula (XIV) are heated in the appropriate orthoester to give compounds of formula (VII). For example, where Alk = ethyl, triethylorthoformate is used. The orthoester can be used both as a reagent and as a solvent if it is a liquid. Compounds of formula (XIV) may be known in the literature or may be readily prepared from available starting materials. An example of a compound of formula (XIV) is 3-amino-2-methyl-4-(methylsulfonyl)benzoic acid.

[0072] The following non-limiting examples provide specific synthesis methods for representative compounds of the present invention, as referred to in the Tables provided herein.

Preparative Example 1: Compound 1.025

[0073] Oxalyl dichloride (1.20 g, 9.4 mmol) was added dropwise to a solution of DMF (0.34 g, 4.7 mmol) in DCM (25 mL) at 0 °C. (vigorous effervescence, followed by the formation of a white suspension). The reaction mixture was allowed to stir for 30 minutes at room temperature and was then concentrated to dryness, giving an off-white solid. This was suspended in dichloromethane (25 mL) and then 3-amino-2-methyl-4-methylsulfonyl ethyl benzoate (600 mg, 2.33 mmol) was added as a solution in DCM (2 mL). A few seconds later, a yellow solution formed and was stirred for 10 minutes. The reaction mixture was added dropwise to a stirred solution of saturated NaHCO3 in an ice bath and stirred for 10 minutes (caution: effervescence). The organic layer was separated, extracted with CHCl3:IPA (ratio 7:3, 2 x 10 mL) and then dried and concentrated in vacuo. The material was loaded onto celite and purified by flash chromatography. Column: 40 g of silica. Solvent A: Dichloromethane. Solvent B: Methanol. Gradient: 0 - 5% B in A for 15 min. It began to elute at 2% B in A. The fractions containing the product were combined and concentrated in vacuo to give 3-[(E)-dimethylaminomethyleneamino]-2-methyl-4-methylsulfonyl ethyl benzoate (665 mg, 2. 13 mmol) as a yellow oil. 1H NMR (400MHz, chloroform) δ = 7.88 (d, J=8.3 Hz, 1H), 7.47 (d, J=8.3 Hz, 1H), 7.21 (s, 1H), 4.38 (q, J=7.1 Hz, 2H), 3.20 (s, 3H), 3.06 (d l, J=14.8 Hz, 6H), 2.33 (s, 3H), 1.40 (t, J=7.2 Hz, 3H). To 3-[(E)-dimethylaminomethyleneamino]-2-methyl-4-methylsulfonyl ethyl benzoate (660 mg, 2.11 mmol) in ethanol (12 mL) and water (3.4 mL) was added lithium hydroxide. monohydrate (222 mg, 5.28 mmol). After 2 hours, the mixture was concentrated in vacuo to remove ethanol. The residue was absorbed in water and the aqueous solution was adjusted to pH 10 by adding excess ammonia solution (38% in water). This solution was purified directly by liquid injection for reversed-phase flash chromatography using a 50 g aq C-18 column. Solvent A: Water + 0.1% ammonia. Solvent B: acetonitrile + 0.1% ammonia. Gradient: 0% for 3 column volumes, then 0-50% of B to A over 10 column volumes. Eluted at 0% B in A. Product-containing fractions were combined and concentrated in vacuo, the material was then dissolved in water and lyophilized overnight to give 3-[(E)-dimethylaminomethyleneamino]-2-methyl-4 acid -methylsulfonyl-benzoic acid (496 mg, 1.75 mmol as a white solid). 1H NMR (400MHz, DMSO-d6) δ = 7.49 (d, J=8.1 Hz, 1H), 7.30 (s, 1H), 6.94 (d, J=8.1 Hz, 1H ), 3.16 (s, 3H), 2.97 (s, 6H), 2.15 - 2.04 (m, 3H).

[0074] To a flask containing 3-[(E)-dimethylaminomethyleneamino]-2-methyl-4-methylsulfonyl-benzoic acid (245 mg, 0.862 mmol) was added anhydrous 1,4-dioxane (5 mL) and N,N '-carbonyldiimidazole (210 mg, 1.29 mmol). The mixture was stirred at 100°C for 16 hours and was then cooled to RT. 1-methyltetrazol-5-amine (128 mg, 1.29 mmol) and DBU (0.132 mL, 0.862 mmol) were added and the reaction mixture was stirred at 100°C for 3 days. Another portion of 1-methyltetrazol-5-amine (128 mg, 1.29 mmol) and DBU (0.132 mL, 0.862 mmol) was then added and the reaction mixture was stirred at 100 ° C for 2 h. The reaction was allowed to cool and was then concentrated in vacuo. Water (10 mL) was added to the residue and DCM (10 mL). The mixture was separated and the aqueous phase was extracted with CHCl3:IPA (7:3, 2 x 10 mL). The organic phases were combined, dried over MgSO4, filtered and concentrated in vacuo. The material was loaded onto celite and purified by flash chromatography (0 to 10% MeOH/DCM) to give 3-[(E)-dimethylaminomethyleneamino]-2-methyl-4-methylsulfonyl-N-(1-methyltetrazol-5-yl )benzamide (136 mg, 0.372 mmol) as a white solid. 1H NMR (400MHz, DMSO-d6) δ = 7.71 (d, J=8.2 Hz, 1H), 7.39 (s, 1H), 7.30 (d, J=8.2 Hz, 1H ), 3.88 (s, 3H), 3.24 (s, 3H), 3.00 (s, 6H), 2.18 (s, 3H).

Preparative Example 2: Compound 1.130

[0075] 2-[3-Fluoro-4-(trifluoromethyl)phenyl]-4,4-dimethyl-5H-oxazole (14 g, 51 mmol) was added in 120 mL of dry THF at a 4-neck RBF of 500 mL equipped with a thermometer. The reaction mass was cooled to -74°C and then, dropwise, n-butyl lithium was added as a 2.0 M solution in hexane (36 mL, 71 mmol). The reaction mass was stirred at about -74°C for an additional 1.5 h. To this solution was then added the solution of hexachloroethane (8.8 mL, 77 mmol) in 40.3 mL of dry THF at -70°C. The mixture was stirred at about -70°C for 30 min and allowed to stand for 16 h, during which time TLC did not show any starting material. The mixture was poured into an ice-cold aq. HCl solution. at 6N (40.30 mL) and extracted with EtOAc (750ml X 3). The combined organic phases were then washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was then purified by silica gel column chromatography and the desired product was eluted with 4.0% EtOAc in hexane to give 2-[2-chloro-3-fluoro-4-(trifluoromethyl)phenyl]- 4,4-dimethyl-5H-oxazole (25 g, 28 mmol)

[0076] To the solution of tBuOK (15.4 g) in N,N-dimethylacetamide (96 mL) in an RBF, formamide (14.5 mL) was added dropwise and stirred. After 15 min, a solution of 2-[2-chloro-3-fluoro-4-(trifluoromethyl)phenyl]-4,4-dimethyl-5H-oxazole (16 g) in N,N-dimethylacetamide (38 mL) was added. ). The mixture was then heated to 120°C for 2 h. The reaction mass was then cooled to room temperature and then poured into ice water (160 mL) and extracted with 30% EtOAc solution in MTBE (160 mL X 4). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under high vacuum. Finally, the crude product was triturated with 5% solution of Et2O in Hexane to provide the desired product N-[2-chloro-3-(4,4-dimethyl-5H-oxazol-2-yl)-6-( trifluoromethyl)phenyl]formamide (16.8 g) as an off-white solid.

[0077] N-[2-chloro-3-(4,4-dimethyl-5H-oxazol-2-yl)-6-(trifluoromethyl)phenyl]formamide (12 g, 37 mmol) was absorbed in 52.2 mL of hydrochloric acid in an rbf, and the mixture was heated under reflux. After 4 hours, the mixture was cooled in an ice bath and the resulting solid was removed by filtration and the residue was washed with ice water and then dried under high vacuum to give 3-amino-2-chloro-4-(trifluoromethyl) acid benzoic acid (9.0 g) as a solid. 1H NMR (d6-DMSO): 7.44 (1H, d), 6.92 (1H, d), 5.90 (2H, s l).

[0078] To the solution of 3-amino-2-chloro-4-(trifluoromethyl)benzoic acid (16 g, 58 mmol) in 78 mL of DMF in an RBF was added 8.36 potassium carbonate and stirred at room temperature for 15 minutes. To this, 23.4 ml of iodoethane were then added and stirring was carried out at room temperature for 2h. TLC and HPLC were checked and the reaction was completed. The reaction mixture was diluted with 750 mL of cold water and extracted with TBME (250 mL X 2). The combined TBME layers were washed with aqueous Na2S2O3 solution, then brine, dried with Na2SO4, filtered and concentrated to give ethyl 3-amino-2-chloro-4-(trifluoromethyl) benzoate (8 g, 27 mmol) as a black liquid.

[0079] Oxalyl dichloride (0.49 g, 0.34 mL, 3.8 mmol) was added dropwise to a colorless solution of N-methyl-N-(2,2,2-trifluoroethyl)formamide (268 mg, 1.9 mmol) in dichloromethane (12 mL). The reaction mixture was allowed to stir for 30 minutes (giving rise to the formation of a yellow solution) and was then concentrated to dryness, yielding an orange oil. This was dissolved in dichloromethane (5 mL) and then 3-amino-2-chloro-4-(trifluoromethyl) ethyl benzoate (250 mg, 0.934 mmol) was added as a solution in DCM (1 mL). A yellow suspension has formed. The reaction mixture was stirred for 5 minutes and LCMS analysis showed it to be complete. The reaction mixture was added dropwise to a stirred saturated solution of NaHCO3 (10 mL) in an ice bath and stirred for 5 minutes (caution: effervescence). The organic layer was separated and the aqueous layer was extracted a second time with dichloromethane (10 ml). LCMS showed the product in the aqueous layer. Extraction with CHCl3:IPA (7:3, 10 mL) successfully extracted the product from the aqueous layer. The material was purified with flash chromatography (0 to 100% EtOAc/isohexane) to give 2-chloro-3-[(E)-[methyl(2,2,2-trifluoroethyl)amino]methyleneamino]-benzoate 4-(trifluoromethyl)ethyl (330 mg, 0.845 mmol) as a colorless oil. NMR shows two rotamers. 1H NMR (400MHz, chloroform) δ = 7.53 (d l, J=8.1 Hz, 2H), 7.45 - 7.30 (m, 4H), 4.41 (q, J=7.2 Hz , 4H), 4.20 (q, J=8.9 Hz, 2H), 3.77 (q, J=8.4 Hz, 2H), 3.24 - 3.18 (m, 1H), 3 .18 - 3.11 (m, 1H), 3.18 (d l, J=16.1 Hz, 4H), 1.40 (t, J=7.2 Hz, 6H).

[0080] To a stirred solution of 2-chloro-3-[(E)-[methyl(2,2,2-trifluoroethyl)amino] methyleneamino]-4-(trifluoromethyl) ethyl benzoate (320 mg, 0.819 mmol) in ethanol (5 mL) and water (1.5 mL) lithium hydroxide monohydrate (86 mg, 2.05 mmol) was added and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated in vacuo to remove EtOH. The mixture was diluted with DCM (10 mL) and then washed with 10% w/v citric acid in water (10 mL). The aqueous phase was further extracted with CHCl3:IPA (ratio 7:3, 10 mL). LCMS displays only trace amounts of product present in the aqueous phase. The organic layer was dried over MgSO4, filtered and concentrated in vacuo to give 2-chloro-3-[(E)-[methyl(2,2,2-trifluoroethyl)amino]methyleneamino]-4-(trifluoromethyl)benzoic acid ( 250 mg, 0.689 mmol) as a yellow oil. 1H NMR (400MHz, chloroform) δ = 7.56 (d, J=4.2 Hz, 4H), 7.38 (d l, J=5.5 Hz, 2H), 4.21 (q, J=8 .9Hz, 2H), 3.85 - 3.75 (m, 2H), 3.19 (m, 6H).

[0081] To a flask containing 2-chloro-3-[(E)-[methyl(2,2,2-trifluoroethyl)amino]methyleneamino]-4-(trifluoromethyl)benzoic acid (125 mg, 0.345 mmol) was added Anhydrous 1,4-dioxane (3 mL) and CDI (84 mg, 0.52 mmol). The mixture was stirred at 100°C for 45 minutes and then cooled to RT. To the reaction mixture was added 1-methyltetrazol-5-amine (51 mg, 0.52 mmol) and DBU (52 μL, 0.34 mmol). . The reaction mixture was heated at 100 °C for 16 hours. The reaction mixture was concentrated in vacuo. The crude material was diluted with CH2Cl2 (10 mL) and washed with aqueous sodium bicarbonate (10 mL). The aqueous phase was additionally extracted with CHCl3:IPA (10 mL, 7:3). The organic phases were combined and dried over MgSO4, filtered and concentrated in vacuo. The material was loaded onto celite and purified by flash chromatography (0 to 10% MeOH in CH2Cl2). The product-containing fractions were combined and concentrated in vacuo to give 2-chloro-N-(1-methyltetrazol-5-yl)-3-[(E)-[methyl(2,2,2-trifluoroethyl)amino]methylene amino]-4-(trifluoromethyl)benzamide (66 mg, 0.15 mmol) as a glassy solid. 1H NMR (400MHz, chloroform) δ = 11.21 (s l, 1H), 7.65 - 7.56 (m, 2H), 7.36 (d l, J=7.9 Hz, 1H), 4.21 (q, J=9.0 Hz, 0.9H), 4.12 (s, 3H), 3.84 (q, J=8.4 Hz, 1.1H), 3.21 (s, 3H) (note: rotamers present in NMR).

Preparative Example 3: Compound 1.132

[0082] Oxalyl dichloride (0.49 g, 0.34 mL, 3.8 mmol) was added dropwise to a colorless solution of pyrrolidine-1-carbaldehyde (0.18 mL, 1.9 mmol) in dichloromethane (4 mL). The reaction mixture was allowed to stir for 30 minutes (giving rise to the formation of a yellow solution) and was then concentrated to dryness, yielding an orange solid. This was dissolved in dichloromethane (5 mL) and then 3-amino-2-chloro-4-(trifluoromethyl) ethyl benzoate (250 mg, 0.934 mmol) was added as a solution in dichloromethane (1 mL). A yellow suspension has formed. The reaction mixture was stirred for 10 minutes and LCMS analysis showed it to be complete. The reaction mixture was added dropwise to stirred saturated NaHCO3 solution (10 mL) in an ice bath and stirred for 5 minutes. The organic layer was separated and the aqueous layer was extracted a second time with dichloromethane (10 ml) and then with CHCl3:IPA (7:3, 10 ml). The reaction mixture was dried over MgSO4, filtered and concentrated in vacuo. The material was purified by flash chromatography (0 to 20% EtOAc/isohexane) to give 2-chloro-3-[(E)-pyrrolidin-1-ylmethyleneamino]-4-(trifluoromethyl)ethyl benzoate (296 mg , 0.849 mmol) as a colorless oil. 1H NMR (400MHz, chloroform) δ = 7.50 (d, J=8.3 Hz, 2H), 7.29 (dd, J=0.6, 8.1 Hz, 1H), 4.41 (q , J=7.2 Hz, 2H), 3.63 - 3.45 (m, 4H), 1.99 (d ld, J=5.9, 14.1 Hz, 4H), 1.40 (t , J=7.2 Hz, 3H)

[0083] To a stirred solution of 2-chloro-3-[(E)-pyrrolidin-1-ylmethyleneamino]-4-(trifluoromethyl) ethyl benzoate (296 mg, 0.849 mmol) in ethanol (4.8 mL) and water (1.4 mL) lithium hydroxide monohydrate (89 mg, 2.12 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated in vacuo to remove ethanol. The mixture was diluted with water (2 mL) and ammonia solution (38% in water) was added dropwise until the aqueous solution had pH 10. The material was purified by reverse phase chromatography (0 to 12% acetonitrile +0.1% NH3/water+0.1% NH3). The product-containing fractions were combined and concentrated in vacuo to give 2-chloro-3-[(E)-pyrrolidin-1-ylmethyleneamino]-4-(trifluoromethyl)benzoic acid (242 mg, 0.755 mmol) as colorless crystals. 1H NMR (400MHz, DMSO-d6) δ = 7.69 (s, 1H), 7.47 (d, J=8.2 Hz, 1H), 7.06 (d, J=7.9 Hz, 1H ), 3.57 - 3.29 (m, 4H), 2.00 - 1.78 (m, 4H).

[0084] To a flask containing 2-chloro-3-[(E)-pyrrolidin-1-ylmethyleneamino]-4-(trifluoromethyl)benzoic acid (110 mg, 0.343 mmol) was added anhydrous 1,4-dioxane (3 mL ) and CDI (83 mg, 1.5 equiv., 0.515 mmol). The mixture was stirred at 100°C for 1 hour and then cooled to room temperature. To the reaction mixture was added a second batch of CDI (83 mg, 1.5 equiv., 0.515 mmol). The reaction mixture was stirred at 100 °C for 1 hour.

[0085] To the reaction mixture, DBU (52 mL, 1 equiv., 0.343 mmol) and 1-methyltetrazol-5-amine (51 mg, 1.5 equiv., 0.515 mmol) were added and the reaction mixture was stirred at 100°C for 18 hours.

[0086] The reaction mixture was concentrated in vacuo. The crude material was diluted with CH2Cl2 (10 mL) and washed with aqueous sodium bicarbonate (10 mL). The aqueous phase was additionally extracted with CHCl3:IPA (10 mL, 7:3). The organic phases were combined and dried over MgSO4, filtered and concentrated in vacuo. The material was loaded onto celite and purified by flash chromatography (0 to 5% MeOH in CH2Cl2). The product-containing fractions were combined and concentrated in vacuo to give 2-chloro-N-(1-methyltetrazol-5-yl)-3-[(E)-pyrrolidin-1-ylmethyleneamino]-4-(trifluoromethyl)benzamide ( 47 mg, 0.12 mmol) as a white solid. 1H NMR (400MHz, chloroform) δ = 10.46 (s l, 1H), 7.58 (d, J=8.2 Hz, 1H), 7.49 (s, 1H), 7.30 (d, J =7.8 Hz, 1H), 4.09 (s, 3H), 3.63 (s l, 2H), 3.53 (t l, J=6.4 Hz, 2H), 2.11 - 1.94 (m, 4H)

Preparative Example 4: Compound 4,033

[0087] (starting material from Preparative Example 7)

[0088] To a solution of 2-chloro-3-[[ethanethioyl(methyl)amino]methyl]-4-methylsulfonyl ethyl benzoate (100 mg, 0.275 mmol) in acetonitrile (5 mL) was added triethylamine (0.39 mL, 2.7 mmol), cyanamide (58 mg, 1.4 mmol) and silver tetrafluoroborate (270 mg, 1.37 mmol). The reaction mixture was stirred for 16 hours overnight at RT. The solution was filtered and then concentrated in vacuo. The residue was dissolved in EtOAc (20 ml) and washed with potassium carbonate solution (20 ml), brine (20 ml), dried with magnesium sulfate and concentrated in vacuo. The product was purified with flash column chromatography (0 to 100% EtOAc/isohexane) to give 2-chloro-3-[[[N-cyano-C-methyl-carbonimidoyl]-methyl-amino]methyl benzoate ]-4-methylsulfonyl ethyl (77 mg, 0.21 mmol). NMR analysis showed that the desired product exists as a mixture of isomers (~1:7). 1H NMR (500MHz, Chloroform) d = 8.16 (d, J=8.2 Hz, 1H), 7.83 (d, J=8.2 Hz, 1H), 5.29 (s, 2H), 4.46 (q, J=7.2Hz, 2H), 3.20 (s, 2.65H), 3.10 (s, 0.35H), 2.91 (s, 2.65H), 2 .79 (s, 0.35H), 2.66 (s, 0.35H), 2.45 (s, 2.65H), 1.43 (t, J=7.1 Hz, 3H).

[0089] To a solution of 2-chloro-3-[[[N-cyano-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl ethyl benzoate (77 mg, 0.19 mmol), in THF (2 mL) and water (2 mL) lithium hydroxide monohydrate (24 mg, 0.56 mmol) was added. The mixture was stirred at room temperature for 30 minutes. The mixture was acidified with 2N HCl to pH ~2. The mixture was extracted with EtOAc (x3), re-acidifying the aqueous layer each time to maintain pH ~2. The combined organics were dried by passing through a phase separator and then concentrated in vacuo. 2-Chloro-3-[[[N-cyano-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl-benzoic acid (51 mg, 0.14 mmol) as a solid.

[0090] A solution of 2-chloro-3-[[[(Z)-N-cyano-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl-benzoic acid (54 mg, 0.16 mmol), 1-methyl-1H-tetrazol-5-amine (0.20 mmol, 21 mg) and DMAP (0.47 mmol, 58 mg) in CH2Cl2 (1.5 mL) was stirred at RT for 1 h. Propylphosphonic anhydride (50 wt% in ethyl acetate, 0.94 mmol, 0.56 mL) was added to the reaction mixture and transferred to a microwave flask and heated in the microwave at 100 °C for 30 min. . The reaction mixture was concentrated in vacuo to give an orange oil and then dissolved in EtOAc (25 mL). The organic was washed with water (carefully acidified to pH ~4), and the aqueous layer was further extracted with EtOAc (x2). The combined organics were washed with brine, dried with magnesium sulfate and concentrated in vacuo. The residue was purified by prep HPLC. phase to give 2-chloro-3-[[[(Z)-N-cyano-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl-N-(1-methyltetrazol-5-yl )benzamide (8.5 mg, 0.018 mmol) as a colorless oil. NMR analysis showed that the desired product exists as a mixture of isomers (~2:1 unassigned). 1H NMR (400MHz, Methanol) d = 8.29 - 8.22 (m, 1H), 7.99 - 7.88 (m, 1H), 5.37 (s, 2H), 4.06 (s, 3H), 3.93 (s, 1H), 2.95 (s, 2H), 2.83 - 2.78 (m, 1H), 2.68 - 2.65 (m, 1H), 2.47 (s, 2H). NOTE: 2H not observed (masked by residual methanol peak at 3.30 ppm).

Preparative Example 5: Compound 2,049

[0091] Oxalyl dichloride (0.67 g, 0.46 mL, 5.2 mmol) was added dropwise to a solution of N,N-dimethylformamide (0.20 mL, 2.6 mmol) in dichloromethane ( 3.8 mL) at 0 °C. Vigorous effervescence was observed, followed by the formation of a white suspension. The reaction mixture was allowed to stir for 30 minutes at room temperature and was then concentrated to dryness, giving an off-white solid. This solid was suspended in dichloromethane (5 mL) and then 3-amino-2-chloro-4-(trifluoromethyl) ethyl benzoate (350 mg, 1.31 mmol) was added as a solution in dichloromethane (2 mL). A few seconds later, a yellow solution formed, which was stirred for 10 minutes. The reaction mixture was added dropwise to a stirred saturated NaHCO3 solution in an ice bath and stirred for 10 minutes (caution: effervescence). The organic layer was separated, extracted again with dichloromethane (10 mL), then CHCl3:IPA (ratio 7:3, 10 mL) and then the combined organic layers were dried (MgSO4) and concentrated in vacuo. The material is loaded onto celite and purified by flash chromatography. Column: 24 g of silica. Solvent A: isohexane. Solvent B: Ethyl acetate. Gradient: 0 - 50% B in A for 15 min. The product-containing fractions were combined and concentrated in vacuo to give ethyl 2-chloro-3-[(E)-dimethylaminomethyleneamino]-4-(trifluoromethyl)benzoate (319 mg, 0.989 mmol) as a yellow oil. 1H NMR (400MHz, chloroform) δ = 7.50 (d, J=8.2 Hz, 1H), 7.34 - 7.28 (m, 2H), 4.41 (q, J=7.1 Hz , 2H), 3.05 (d l, J=8.8 Hz, 6H), 1.40 (t, J=7.2 Hz, 3H).

[0092] To a stirred solution of ethyl 2-chloro-3-[(E)-dimethylaminomethyleneamino]-4-(trifluoromethyl) benzoate (300 mg, 0.930 mmol), in ethanol (5 mL) and water (1. 5 mL) lithium hydroxide monohydrate (98 mg, 2.3 mmol) was added. After stirring at RT for 2 hours, the mixture was concentrated in vacuo. The material was absorbed in water (10 mL) and the aqueous solution was adjusted to pH 10 by adding excess ammonia solution (38% in water). This was directly purified by reversed phase flash chromatography: Column: C-18 aq (50 g). Solvent A: Water + 0.1% ammonia. Solvent B: acetonitrile + 0.1% ammonia. Gradient: 0% for 3 column volumes, then 0-50% of B to A over 10 column volumes. Eluted at 5% B in A. The desired fractions were concentrated and lyophilized to give 2-chloro-3-[(E)-dimethylaminomethyleneamino]-4-(trifluoromethyl)benzoic acid (280 mg, 274 mmol) as a white solid. 1H NMR (400MHz, DMSO-d6) δ = 7.42 (s, 1H), 7.34 (d, J=8.1 Hz, 1H), 6.85 (d, J=7.9 Hz, 1H ), 3.05 - 2.87 (m, 6H).

[0093] To a flask containing 2-chloro-3-[(E)-dimethylaminomethyleneamino]-4-(trifluoromethyl) benzoic acid (270 mg, 0.916 mmol) was added anhydrous 1,4-dioxane (8 mL) and N, N'-carbonyldiimidazole (223 mg, 1.37 mmol). DBU (0.140 mL, 0.916 mmol) and 5-methyl-1,3,4-oxadiazol-2-amine (136 mg, 1.37 mmol) were added and the mixture was heated at 100 °C for 16 h. The material was cooled to RT and concentrated in vacuo. Saturated sodium bicarbonate (10 mL) and DCM (10 mL) were added and the layers were separated. The aqueous layer was extracted with DCM (10 mL) and CHCl3:IPA (7:3, 10 mL). The combined organic layers were dried over MgSO4, filtered and concentrated in vacuo. The material was loaded onto celite and purified by flash chromatography: 24 g of silica. Solvent A: Dichloromethane. Solvent B: Methanol. Gradient: 0 - 10% B in A for 25 min. The product-containing fractions were combined and concentrated in vacuo to give 2-chloro-3-[(E)-dimethylaminomethyleneamino]-N-(5-methyl-1,3,4-oxadiazol-2-yl)- 4-( trifluoromethyl)benzamide (75 mg, 0.20 mmol) as a white solid. 1H NMR (400MHz, DMSO-d6) δ = 7.60 - 7.50 (m, 2H), 7.18 - 7.11 (m, 1H), 3.02 (s, 3H), 2.98 - 2.90 (m, 3H), 2.46 - 2.33 (m, 3H).

Preparative Example 6: Compound 3.129

[0094] To a dry flask was added ethyl 3-(bromomethyl)-2-chloro-4-methylsulfonyl benzoate (2.7 g, 7.6 mmol), potassium carbonate (1.g g, 9.1 mmol ) and anhydrous acetonitrile (41 mL). The reaction mixture was purged and placed under a nitrogen atmosphere. A suspension of N'-hydroxy-N,N-dimethyl-acetamidine (0.85 g, 8.4 mmol) in anhydrous acetonitrile (20 mL) was added dropwise to the reaction mixture and the reaction mixture was stirred at room temperature for 13 days. Another portion of N'-hydroxy-N,N-dimethylacetamidine (0.16 g, 1.5 mmol) and potassium carbonate (0.21 g, 1.5 mmol) was added and the reaction mixture was restless at T.A. for another day. The reaction mixture was diluted with dichloromethane (50 mL) and water (10 mL) was added to the reaction mixture. The phases were separated and the organic phase was passed through a phase separation cartridge and concentrated in vacuo to give a yellow oil. The crude material was purified by flash chromatography (Solvent A = hexane, Solvent B = ethyl acetate) gradient of 0-50% ethyl acetate to give the desired product 2-chloro-3-[[(Z) benzoate )-1-(dimethylamino)ethylideneamino]oxymethyl]-4-methylsulfonyl ethyl (1.56 g, 4.13 mmol) as a yellow oil. 1H NMR (400MHz, chloroform) δ = 8.11 (d, J=8.3 Hz, 1H), 7.73 (d, J=8.3 Hz, 1H), 5.56 (s, 2H), 4.55 - 4.33 (m, 2H), 3.39 (s, 3H), 2.73 (s, 6H), 1.94 (s, 3H), 1.42 (t, J=7, 2Hz, 3H).

[0095] To a stirred solution of 2-chloro-3- [[(Z)-1-(dimethylamino)ethylideneamino]oxymethyl]-4-methylsulfonyl ethyl benzoate (1.5 g, 4.0 mmol) in ethanol ( 23 mL) and water (6.4 mL) lithium hydroxide monohydrate (0.42 g, 9.9 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo to remove ethanol. The crude material was acidified with 2N HCl to pH 3 and then aqueous ammonia was added until the pH reached pH 10. The mixture was loaded onto a reverse phase (high pH) column that had been equilibrated with a solution of 0.1% ammonia in water and acetonitrile. The sample was loaded as a liquid onto the equilibrated column and was eluted using 0% acetonitrile in water (0.1% NH3) until the solvent front exited, followed by a gradient of 0% - 50% acetonitrile in water ( 0.1% NH3) until the product elutes (approx. 30%). The material was absorbed in a minimal amount of water and a small amount of acetonitrile and was freeze-dried overnight. The product 2-chloro-3-[[(Z)-1-(dimethylamino)ethylideneamino]oxymethyl]-4-methylsulfonyl-benzoic acid (1.31 g, 3.76 mmol) was obtained as an off-white solid. 1H NMR (400MHz, DMSO-d6) δ = 7.84 (d, J=8.1 Hz, 1H), 7.43 (d, J=8.1 Hz, 1H), 7.36 - 7.21 (m, 1H), 5.35 (s, 2H), 3.37 (s, 3H), 2.69 (s, 6H), 1.88 (s, 3H).

[0096] To a solution of 2-chloro-3-[[(Z)-1- (dimethylamino)ethylideneamino]oxymethyl]-4-methylsulfonyl-benzoic acid (500 mg, 1.43 mmol), in dichloromethane (7 .5 mL) DMF (0.011 mL, 0.14 mmol) was added. The reaction mixture was purged and placed under a nitrogen atmosphere. Oxalyl chloride (0.24 mL, 0.96 mmol) was added dropwise; Additional effervescence occurred, and a solid red precipitate appeared. The reaction mixture was stirred at room temperature for 1 h and became a pinkish-red suspension. The reaction mixture was concentrated in vacuo to give a pinkish spongy solid, and the residue was dissolved in dichloromethane (7.5 mL). The reaction mixture was cooled to 0 °C under nitrogen atmosphere and after 5 minutes, triethylamine (0.81 mL, 0.734 mmol) was added dropwise, followed by cyclohexane-1,3-dione (161 mg, 1.43 mmol) in a single serving. The reaction mixture was allowed to warm to RT for 1 hour. Acetone cyanohydrin (0.33 mL, 0.36 mmol) was added to the reaction mixture. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated in vacuo and then the crude material was loaded onto celite and purified by flash chromatography using a solvent system of 10:4:2:2:0.5 toluene/1,4-dioxane/ethanol/triethylamine/water. . The crude material (dark green oil) was diluted with dichloromethane (10 mL) and washed with 10% w/v citric acid solution (10 mL). The organic phase was dried with MgSO4, filtered and concentrated in vacuo to give N'-[[2-chloro-3-(2,6-dioxocyclohexanecarbonyl)-6-methylsulfonyl-phenyl]methoxy]-N,N -dimethyl-acetamidine (114 mg, 0.527 mmol) as a yellow oil (114 mg). 1H NMR (CDCl3): 8.12 (d, J=8.1 Hz, 1H), 5.54 (s, 2H), 3.37 (s, 3H), 2.81 (t, J=6, 4 Hz, 2H), 2.73 (s, 6H), 2.44 (t, J=6.4 Hz, 2H), 2.13 - 2.02 (m, 2H), 1.92 (s, 3H).

Preparative Example 7: Compound 4,016

[0097] To a solution of methylamine (2 M in THF, 55 mL, 109 mmol) was added dropwise 3-(bromomethyl)-2-chloro-4-methylsulfonyl ethyl benzoate (2.43 g, 6.83 mmol) in acetonitrile (13.7 mL). The reaction was stirred at room temperature for 10 minutes. LCMS analysis showed product formation without any starting material remaining. The reaction was concentrated in vacuo and then diluted with DCM (250 mL). The organic was washed with saturated K2CO3 solution (100 mL), brine (100 mL), and concentrated in vacuo to give 2-chloro-3-(methylaminomethyl)-4-methylsulfonyl ethyl benzoate (2.08 g, 6.46 mmol) as a colorless oil. 1H NMR (400 MHz, chloroform) δ = 8.10 (d, J=8.2 Hz, 1H), 7.71 (d, J=8.3 Hz, 1H), 4.44 (q, J= 7.1 Hz, 2H), 4.33 (s, 2H), 3.37 (s, 3H), 2.55 (s, 3H), 1.42 (t, J=7.1 Hz, 3H) .

[0098] To a solution of 2-chloro-3-(methylaminomethyl)-4-methylsulfonyl ethyl benzoate (500 mg, 1.55 mmol), 4-dimethylaminopyridine (19.4 mg, 0.155 mmol) and triethylamine (318 mg , 0.437 mL, 3.11 mmol) in tetrahydrofuran (13.8 g, 15.5 mL) was added dropwise ethyl dithioacetate (381 mg, 0.364 mL, 3.11 mmol). The reaction was equipped with a reflux condenser, stirred and heated to 50 °C for 10 days. LCMS analysis showed product formation but also remaining starting material. The reaction was cooled to room temperature and then concentrated in vacuo to remove THF. The mixture was diluted with EtOAc (50 mL) and washed with water (50 mL x 2), brine (50 mL) and concentrated in vacuo. The product was purified with flash column chromatography (0 to 60% EtOAc/isohexane) to give 2-chloro-3-[[ethanethioyl(methyl)amino]methyl]-4-methylsulfonyl ethyl benzoate (217 mg, 0.596 mmol) as a brown gum. 1H NMR (400 MHz, chloroform) δ = 8.23 - 8.14 (m, 1H), 7.89 - 7.80 (m, 1H), 5.79 (s l, 2H), 4.46 (q , J=7.2 Hz, 2H), 3.20 (s, 2.6H), 3.15 (s, 0.4H), 3.10 (s, 0.4H), 2.99 (s, 2.6H), 2.94 - 2.91 (m, 0.4H), 2.71 (s, 2.6H), 1.42 (t, J=7.2 Hz, 3H).

[0099] To a solution of 2-chloro-3-[[ethanethioyl(methyl)amino]methyl]-4-methylsulfonyl ethyl benzoate (120 mg, 0.330 mmol) in acetonitrile (3.89 g, 4.95 mL, 94.2 mmol) triethylamine (337 mg, 0.464 mL, 3.30 mmol), o-methylhydroxylamine hydrochloride (141 mg, 1.65 mmol) and silver tetrafluoroborate (0.3242 g, 1.65 mmol) were added. mmol). The reaction mixture was stirred overnight at room temperature. LCMS analysis showed product formation without any starting material remaining. The solution was filtered through a silica plug to remove the silver precipitate, and washed with MeCN (20 mL). The mixture was concentrated in vacuo to remove MeCN. The residue was dissolved in EtOAc (20 ml) and washed with water (20 ml), brine (20 ml), dried with magnesium sulfate and concentrated in vacuo. The product was purified with flash column chromatography (0 to 50% EtOAc/isohexane) to give 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl benzoate ]-4-methylsulfonyl ethyl (90 mg, 0.239 mmol) as a brown gum. 1H NMR (400 MHz, chloroform) δ = 8.13 (d, J=8.2 Hz, 1H), 7.70 (d, J=8.2 Hz, 1H), 4.94 (s, 2H) , 4.45 (q, J=7.2 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.61 (s, 3H), 2.05 (s, 3H), 1.42 (t, J=7.2 Hz, 3H).

[0100] To a solution of 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl ethyl benzoate (95 mg, 0.252 mmol), in tetrahydrofuran (1.69 g, 1.90 mL, 23.4 mmol) and water (1.9 g, 1.9 mL, 0.106 mmol) lithium hydroxide (53.9 mg, 2.25 mmol) was added. The reaction was stirred at room temperature for 30 minutes. LCMS analysis showed product formation. The mixture was partially concentrated in vacuo to remove tetrahydrofuran. The resulting aqueous solution was diluted with water (1 mL) and acidified with a few drops of 2 M HCl to pH ~2. The mixture was then basified with aqueous NH3 to pH ~9. The resulting solution was loaded onto a reversed-phase column and purified using reversed-phase chromatography (0-20% MeCN in H2O containing 0.1% NH3). The product-containing column fractions were combined and concentrated using a freeze dryer over the weekend to give 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]- 4-methylsulfonyl-benzoic acid (84 mg, 0.229 mmol) as a yellow gum.

[0101] A solution of 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl-benzoic acid (65 mg, 0.186 mmol), 1-methyl -1H-tetrazol-5-amine (25.3 mg, 0.242 mmol) and 4-dimethylaminopyridine (69.0 mg, 0.559 mmol) in DCM (2.47 g, 1.86 mL, 29.0 mmol) was stirred at room temperature for 1 h. 1-Propanephosphonic anhydride (0.712 g, 0.666 mL, 1.12 mmol) was added to the reaction mixture and transferred to a microwave flask and heated in the microwave at 100 °C for 30 min. LCMS analysis showed product formation. The reaction mixture was concentrated in vacuo to give an orange oil. The solution was diluted with water (5 mL) and basified with conc. of NH3 until pH ~9/10. The product was purified by reversed-phase column chromatography (0-50% MeCN in H2O containing 0.1% NH3). The product containing fractions was concentrated using the freeze dryer to give 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-methylsulfonyl-N-(1-methyltetrazol -5-yl)benzamide (8.3 mg, 0.019 mmol) as a colorless gum. 1H NMR (400 MHz, methanol) δ = 8.20 (d, J=8.2 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 4.95 (s, 2H) , 4.06 (s, 3H), 3.68 (s, 3H), 3.27 (s, 3H), 2.60 (s, 3H), 2.06 (s, 3H).

Preparative Example 8: Compound 5,014

[0102] To a solution of methylamine (2 M in THF, 40 g, 46 mL, 92.6 mmol) was added dropwise 3-(bromomethyl)-2-chloro-4-(trifluoromethyl) ethyl benzoate (2 .0 g, 5.79 mmol) in acetonitrile (11.6 mL). The reaction was stirred at room temperature for 10 minutes. LCMS analysis showed product formation without any starting material remaining. The reaction was concentrated in vacuo, then diluted with EtOAc (200 mL) and washed with saturated K2CO3 solution (100 mL), brine (100 mL) and concentrated in vacuo to give 2-chloro-3-(methylaminomethyl) benzoate )-4-(trifluoromethyl) ethyl (1.80 g, 5.78 mmol) as a yellow oil. NMR analysis showed the desired product. 1H NMR (400 MHz, chloroform) δ = 7.73 - 7.53 (m, 2H), 4.43 (q, J=7.1 Hz, 2H), 4.01 (d, J=0.7 Hz, 2H), 2.51 (s, 3H), 1.41 (t, J=7.1 Hz, 3H) (N-H not observed). 19F NMR (376MHz, chloroform) δ = -58.9

[0103] To a solution of 2-chloro-3-(methylaminomethyl)-4-(trifluoromethyl) ethyl benzoate (500 mg, 1.69 mmol), 4-dimethylaminopyridine (21.1 mg, 0.169 mmol) and triethylamine ( 346 mg, 0.476 mL, 3.38 mmol) in tetrahydrofuran (15.0 g, 16.9 mL) ethyl dithioacetate (415 mg, 0.396 mL, 3.38 mmol) was added dropwise. The reaction was equipped with a reflux condenser, stirred and heated to 60 °C for 10 days. LCMS analysis showed product formation but also remaining starting material. The reaction was cooled to room temperature and then concentrated in vacuo to remove tetrahydrofuran. The mixture was diluted with DCM (50 mL) and water (50 mL). The water was extracted with DCM (50 mL x2), and then the organics were washed with brine (50 mL), and concentrated in vacuo. The product was purified with flash column chromatography (0 to 30% EtOAc/isohexane) to give 2-chloro-3-[[ethanethioyl(methyl)amino]methyl]-4-(trifluoromethyl) ethyl benzoate (370 mg, 0.941 mmol) as a brown gum. NMR shows two rotamers. 1H NMR (400MHz, chloroform) δ = 7.87 - 7.71 (m, 2H), 5.54 (s l, 1.5H), 5.09 (s, 0.5H), 4.50 - 4, 39 (m, 2H), 3.09 (s, 0.75H), 2.89 (s, 3H), 2.72 (s, 2.25H), 1.46 - 1.37 (m, 3H) .

[0104] To a solution of 2-chloro-3- [[ethanethioyl(methyl)amino]methyl]-4-(trifluoro methyl) ethyl benzoate (370 mg, 1.05 mmol) in acetonitrile (12.3 g, 15.7 mL) triethylamine (1.07 g, 1.47 mL, 10.46 mmol), O-methylhydroxylamine hydrochloride (446 mg, 5.23 mmol) and silver tetrafluoroborate (1.03 g) were added. , 5.23 mmol). The reaction mixture was stirred for 5 days at room temperature. LCMS analysis showed product formation without any starting material remaining. The solution was filtered through a silica plug to remove the silver precipitate, and washed with MeCN (20 mL). The mixture was concentrated in vacuo to remove MeCN. The residue was dissolved in EtOAc (20 ml) and washed with water (20 ml), brine (20 ml), dried with magnesium sulfate and concentrated in vacuo. The product was purified with flash column chromatography (0 to 20% EtOAc/isohexane) to give 2-chloro-3-[[[(Z)-N-methoxy-C-methyl-carbonimidoyl]-methyl benzoate -amino]methyl]-4-(trifluoromethyl) ethyl (254 mg, 0.692 mmol) as a brown gum. 1H NMR (400MHz, chloroform) δ = 7.67 (s, 2H), 4.66 (d, J=0.9 Hz, 2H), 4.44 (q, J=7.2 Hz, 2H), 3.74 (s, 3H), 2.48 (s, 3H), 2.04 (s, 3H), 1.41 (t, J=7.2 Hz, 3H). 19F NMR (376MHz, chloroform) d = - 58.33 (s, 1F).

[0105] To a solution of 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-(trifluoromethyl) ethyl benzoate (250 mg, 0.682 mmol), in tetrahydrofuran (4.45 g, 5.0 mL, 61.6 mmol) and water (5.0 g, 5.0 mL, 277 mmol) lithium hydroxide (87.4 mg, 2.05 mmol) was added. . The reaction was stirred at room temperature for 3 hours. LCMS analysis showed product formation. The resulting aqueous solution was diluted with water (1 mL) and acidified with a few drops of 2 M HCl to pH ~2. The mixture was concentrated in vacuo to remove THF and most of the water. The mixture was then diluted with water (2 mL total) and basified with aqueous NH3 to pH ~9. The resulting solution was loaded onto a reversed-phase column and purified using reversed-phase chromatography (0.20% MeCN in H2O containing 0.1% NH3). The product containing fractions was concentrated using a freeze dryer overnight to give 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-(trifluoromethyl)benzoic acid (207 mg, 0.580 mmol).

[0106] A solution of 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-4-(trifluoromethyl)benzoic acid (75 mg, 0.221 mmol), 5- methyl-1,3,4-oxadiazol-2-amine (29.4 mg, 0.287 mmol) and 4-dimethylaminopyridine (82.0 mg, 0.665 mmol) in DCM (2.93 g, 2.21 mL, 34. 5 mmol) was stirred at room temperature for 1 h. 1-Propanephosphonic anhydride (846 mg, 0.791 mL, 1.33 mmol) was added to the reaction mixture and transferred to a microwave flask and heated in the microwave at 80 °C for 1 hour. LCMS analysis showed product formation. The reaction mixture was concentrated in vacuo to give an orange oil. The mixture was dissolved in DCM (20 mL) and partitioned with diluted NaHCO3 (20 mL). The aqueous layer was washed with DCM (20 mL x 5). The combined organics were washed with brine (20 mL) and concentrated in vacuo. The product was purified to give 2-chloro-3-[[[N-methoxy-C-methyl-carbonimidoyl]-methyl-amino]methyl]-N-(5-methyl-1,3,4-oxadiazol- 2-yl)-4-(trifluoromethyl)benzamide (4.0 mg, 9.53 μmol) as a colorless gum. 1H NMR (400MHz, Methanol) δ = 7.83 (d, J=8.1 Hz, 1H), 7.68 (d, J=8.1 Hz, 1H), 4.65 (s, 2H), 3.68 (s, 3H), 2.55 - 2.44 (m, 6H), 2.04 (s, 3H). TABLE 1 – Examples of herbicidal compounds of the present invention. TABLE 2 – Examples of herbicidal compounds of the present invention. TABLE 3 – Examples of herbicidal compounds of the present invention. TABLE 4 – Examples of herbicidal compounds of the present invention. TABLE 5 – Examples of herbicidal compounds of the present invention. TABLE 6 – Examples of herbicidal compounds of the present invention. TABLE 7 – Examples of herbicidal compounds of the present invention.

Biological Examples

[0107] Seeds of a variety of test species are sown in standard soil in pots (Lolium perenne (LOLPE), Amaranthus retoflexus (AMARE), Abutilon theophrasti (ABUTH), Setaria faberi (SETFA), Echinochloa crus-galli (ECCHG) , Ipomoea hederacea (IPOHE)). After cultivation for one day (pre-emergence) or after 8 days of cultivation (post-emergence) under controlled conditions in a greenhouse (at 24/16 oC, day/night; 14 hours of light; 65% humidity), the plants are sprayed with an aqueous spray solution derived from the technical active ingredient formulation in acetone/water solution (50:50) containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, RN of CAS 9005-64-5) . Compounds are applied at 500 g/h unless otherwise specified. The test plants are then grown in a greenhouse under controlled greenhouse conditions (at 24/16°C, day/night; 14 hours of light; 65% humidity) and watered twice a day. After 13 days for pre- and post-emergence, the test is evaluated for the percentage of damage caused to the plant. Biological activities are shown in the following table on a five-point scale (5 = 80-100%; 4 = 60-79%; 3 = 40-59%; 2 = 20-39%; 1 = 0-19%) . TABLE B1 (-) = No Data. *Applied at 250 g/ha. ** Applied at 125 g/ha. TABLE B2

[0108] A comparative experiment is conducted to show the advantage provided by the compounds of the present invention. Thus, the biological performance of compound 1049 of the present invention is compared with Compound C1, which is an aniline compound of the type referred to in WO2012/028579. The results are given in (%) of observed phytotoxicity. The result demonstrates that compounds of the present invention provide greatly improved control of problematic weed species, exemplified using Echinochloa crus-galli (ECHCG) and Setaria faberi (SETFA), at similar application rates.

Claims (9)

1. Compound of Formula (I): or an agronomically acceptable salt thereof, characterized by the fact that: R2 is selected from the group consisting of halogen, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C6 haloalkyl and -S(O)pC1-C6 alkyl; R3 is selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl and -S(O)pC1-C6 alkyl; Q is Q1; R1a is C1-C4 alkyl or C1-C3-alkoxy-C1-C3-alkyl; X is -(CH2)n- and n is 0; Z is Z1 R is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl and C3-C6 cycloalkyl; R is selected from the group consisting of hydrogen, C1-C6 alkyl and C1-C6 haloalkyl; R is selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, cyano and phenyl, wherein phenyl is optionally substituted by 1, 2 or 3 substituents selected from the group consisting of halogen, C1-C6 alkyl, haloalkyl C1-C6 and C1-C6 alkoxy; or R5 and R6 are together -CH2CH2CH2CH2, -CH2CH2CH2CH2CH2- or -CH2CH2OCH2CH2-; ep = 0, 1 or 2. 2. Compound according to claim 1, characterized by the fact that R2 is selected from the group consisting of methyl, Cl, -CF3 and -SO2methyl. 3. Compound according to claim 1, characterized by the fact that R3 is selected from the group consisting of methyl, Cl, -CF3 and -SO2methyl. 4. Compound according to any one of claims 1 to 4, characterized in that R1a is selected from the group consisting of methyl, ethyl and n-propyl. 5. Herbicidal composition characterized by the fact that it comprises a compound, as defined in any one of claims 1 to 4, and an adjuvant of an agriculturally acceptable formulation. 6. Herbicidal composition according to claim 5, characterized in that it further comprises at least one additional pesticide. 7. Herbicidal composition according to claim 6, characterized by the fact that the additional pesticide is a herbicide or herbicidal phytoprotectant. 8. Method of controlling weeds at a locus, characterized by the fact that it comprises applying to the locus a weed control amount of a composition as defined in any one of claims 5 to 7. 9. Use of a compound of Formula (I), as defined in claim 1, characterized by the fact that it is as a herbicide.