Herbicidal compound

Abstract

The present invention relates to a compound of formula (I) [Formula 1] TIFF2023521170000095.tif37160 (in the formula, Q, R 2 , R 3 , R 4 and R 5 are as described herein) or an agriculturally acceptable salt thereof. The present invention further relates to compositions comprising said compounds, methods of controlling weeds using said compositions and the use of compounds of formula (I) as herbicides.

Description

Technical Field

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

Background Art

[0002] N-(tetrazol-5-yl)- and N-(1,3,4-oxadiazol-2-yl)arylcarboxamides are disclosed, for example, in WO 2012 / 028579 and WO 2012 / 126932 respectively. The present invention relates to novel arylcarboxamides.

Summary of the Invention

Means for Solving the Problems

[0003] Accordingly, the present invention provides a compound of formula (I):

Chemical Formula

Chemical Formula

Mode for Carrying Out the Invention

[0004] Examples of C1-C6 alkyl and C1-C4 alkyl groups include 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).

[0005] Examples of C3-C6 cycloalkyl include cyclopropyl (c-propyl (c-Pr)), cyclobutyl (c-butyl (c-Bu)), cyclopentyl (c-pentyl), and cyclohexyl (c-hexyl).

[0006] Halogen (or halo) includes fluorine, chlorine, bromine, or iodine. The same applies, mutatis mutandis, to halogen related to other definitions such as haloalkyl.

[0007] Examples of C1-C6 haloalkyl include, for example, fluoromethyl-, difluoromethyl-, trifluoromethyl-, chloromethyl-, dichloromethyl-, trichloromethyl-, 2,2,2-trifluoroethyl-, 2,2-difluoroethyl, 1,1-difluoroethyl, 1,1,2,2-tetrafluoroethyl, 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. Examples of C1-C4 haloalkyl include, 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-.

[0008] Examples of C1-C6 alkyl-S-(alkylthio) include methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, or tert-butylthio, preferably methylthio or ethylthio.

[0009] C1-C6 alkyl-S(O)-(alkylsulfinyl) is, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0010] C1-C6 alkyl-S(O)2-(alkylsulfonyl) is, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0011] In a preferred embodiment of the present invention, R 1a and R 1b are selected from the group consisting of methyl, ethyl and n-propyl.

[0012] In another embodiment of the present invention, Q is Q 1 . Therefore, in this embodiment, the compound of formula (I) is of formula (Ia):

Chemical formula

[0013] In another embodiment of the present invention, Q is Q 2 . Therefore, in this particular embodiment of the present invention, formula (Ib)

Chemical formula

[0014] In a preferred embodiment of the present invention, R 2 is selected from the group consisting of methyl, Cl, -CF3 and -SO2methyl, more preferably Cl.

[0015] In another preferred embodiment of the present invention, R 3 is selected from the group consisting of -CH3, -CF3, -CHF2 and -CF2CF2H, more preferably -CF3 or -CHF2.

[0016] In one embodiment of the present invention, R 4 is -C(O)-heteroaryl, where heteroaryl may be optionally substituted as described above, and R 4a , R 4b , R 4c , R 4d , R 4e , R 4f , R 4g and R 4h :

Chemical formula

[0017] In a preferred embodiment of the present invention, heteroaryl may be optionally substituted by one, two or three substituents selected from the group consisting of halogen, C1-C6 alkyl (e.g., methyl), C1-C6 haloalkyl and C1-C6 alkoxy R 4c . In a more preferred embodiment of the present invention, heteroaryl is R 4c which may be optionally substituted by one halogen, preferably fluorine.

[0018] In another embodiment of the present invention, R 4is selected from the group consisting of C1-C6 alkyl-(preferably methyl), C1-C6 alkyl-C(O)-(preferably CH3CH2C(O)-), and C3-C6 cycloalkyl-C(O)-(preferably cPr-C(O)-).

[0019] In another embodiment of the present invention, R 5 is hydrogen or C1-C6 alkyl-(preferably methyl), most preferably hydrogen.

[0020] In one embodiment of the present invention, R 4 is methyl or CH3CH2C(O)-, and R 5 is hydrogen. In another embodiment of the present invention, R 4 is -C(O)-heteroaryl, where heteroaryl is optionally substituted by one halogen, preferably fluorine, and R 4c is, and R 5 is hydrogen.

[0021] In another embodiment of the present invention, R 4 and R 5 together form a 5- or 6-membered saturated heterocycle which may be optionally oxo-substituted, and which is selected from the group consisting of -C(O)-CH2CH2CH2CH2-, -CH2CH2OCH2CH2-, -C(O)CH2CH2CH2-, -CH2CH2CH2CH2CH2-, and -CH2CH2CH2CH2-, preferably -C(O)-CH2CH2CH2CH2-.

[0022] The compounds of formula (I) (and the specific intermediate compounds used to synthesize the compounds of formula (I)) may contain chiral centers and may exist as a single enantiomer, as an enantiomeric pair in any ratio, or, if two or more chiral centers are present, may contain diastereoisomers in any possible ratio. Typically, one of the enantiomers has higher biological activity compared to the other possible ones.

[0023] The present invention also includes all possible geometric and tautomeric forms of the compounds of formula (I).

[0024] The present invention also includes agriculturally acceptable salts that the compounds of formula (I) can form with amines (such as ammonia, dimethylamine and triethylamine), alkali metals and alkaline earth metal bases or quaternary ammonium bases. Among the alkali metal and alkaline earth metal hydroxides, oxides, alkoxides and hydrogen carbonates and carbonates used as salt formers, the hydroxides, alkoxides, oxides and carbonates of lithium, sodium, potassium, magnesium and calcium are important, in particular, the hydroxides, alkoxides, oxides and carbonates of sodium, magnesium and calcium. The corresponding trimethylsulfonium salts can also be used.

[0025] The compounds of formula (I) according to the present invention can be used as herbicides per se, but they are generally formulated into herbicidal compositions using formulation aids such as carriers, solvents and surfactants (SFA). Accordingly, the present invention further provides a herbicidal composition comprising a herbicidal compound according to the present invention and an agriculturally acceptable formulation aid. This composition can be in the form of a concentrate to be diluted before use, but a composition that can be used immediately can also be prepared. The final dilution is usually carried out using water, but it can be carried out using, for example, liquid fertilizers, micronutrients, living organisms, oils or solvents instead of or in addition to water.

[0026] The herbicidal composition generally comprises 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of the compound of formula I and 1 to 99.9% by weight of a formulation aid preferably containing 0 to 25% by weight of a surface active substance.

[0027] This composition can be selected from a number of dosage forms, many of which are known from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. These include dusts (DP), soluble powders (SP), soluble granules (SG), wettable granules (WG), wettable powders (WP), granules (GR) (slow or quick 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. In each case, the dosage form selected will depend on the specific intended purpose and on the physical, chemical and biological properties of the compound of formula (I).

[0028] Dusts (DP) can be prepared by mixing a compound of formula (I) with one or more solid diluents (e.g., natural clays, kaolin, pyrophyllite, bentonite, alumina, montmorillonite, kieselguhr, chalk, diatomaceous earth, calcium phosphate, calcium carbonate and magnesium carbonate, sulfur, lime, wheat flour, talc and other organic and inorganic solid carriers) and mechanically grinding this mixture to a fine powder.

[0029] Soluble powders (SP) can be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium hydrogen carbonate, sodium carbonate or magnesium sulfate) or one or more water-soluble organic solids (such as polysaccharides) and optionally one or more wetting agents, one or more dispersing agents or mixtures of said substances, in order to improve the dispersibility / solubility in water. This mixture is then ground to a fine powder. Also, a similar composition can be granulated to form soluble granules (SG).

[0030] The wettable powder (WP) can be prepared by mixing the 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 promote dispersion in a liquid. Next, this mixture is ground into a fine powder. Also, a similar composition can be granulated to form water-dispersible granules (WG).

[0031] The granule (GR) can be formed either by granulating a mixture of the compound of formula (I) and one or more powdered solid diluents or carriers, or by absorbing the compound of formula (I) (or its solution in a suitable substance) into a porous granular material (such as pumice, attapulgite clay, fuller's earth, kieselguhr, diatomaceous earth or ground corn cob), or by adsorbing the compound of formula (I) (or its solution in a suitable substance) onto a hard core material (such as sand, silicate, inorganic carbonate, sulfate or phosphate) and, if necessary, drying to granulate from pre-formed blank granules. Substances commonly used to assist absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters) and fixing agents (such as polyvinyl acetate, polyvinyl alcohol, dextrin, sugars and vegetable oils). Also, one or more other additives can be included in the granules (for example, emulsifiers, wetting agents or dispersing agents).

[0032] The dispersible concentrate (DC) can be prepared by dissolving the compound of formula (I) in water or an organic solvent such as a ketone, alcohol or glycol ether. These solutions can contain surfactants (for example, to improve water-dilutability or prevent crystallization in the spray tank).

[0033] The emulsifiable concentrate (EC) or the oil-in-water emulsion (EW) can be prepared by dissolving the compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifiers or a mixture of said substances). Suitable organic solvents for use in EC include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes exemplified by SOLVESSO 100, SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a registered trademark), ketones (such as cyclohexanone or methylcyclohexanone) and alcohols (such as benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethylamides of fatty acids (such as dimethylamides of C8-C 10 dimethylamides of fatty acids) and chlorinated hydrocarbons. EC products can form an emulsion with sufficient stability to be spray-applied by a suitable device when added to water.

[0034] The preparation of EW involves obtaining the compound of formula (I) as a liquid (if it is not liquid at room temperature, it can be melted at a suitable temperature, typically below 70 °C) or in solution (by dissolving it in a suitable solvent), and then emulsifying the resulting liquid or solution in water containing one or more SFAs under high shear to form an emulsion. Suitable solvents for use in EW include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes) and other suitable organic solvents with low water solubility.

[0035] Microemulsions (MEs) can be prepared by mixing water with a blend of one or more SFAs and one or more solvents to spontaneously yield a thermodynamically stable isotropic liquid formulation. The compound of formula (I) is initially present in either water or the solvent / SFA blend. Suitable solvents for use in MEs include those described above for use in EC or EW. MEs can be either oil-in-water or water-in-oil systems (which system is present can be determined by conductivity measurements) and may be suitable for mixing water-soluble and oil-soluble pesticidal agents in the same formulation. MEs are suitable for dilution in water and remain as microemulsions or form conventional oil-in-water emulsions.

[0036] Suspension concentrates (SCs) can contain an aqueous or non-aqueous suspension of micronized insoluble solid particles of the compound of formula (I). SCs can be prepared by ball milling or bead milling the solid compound of formula (I) optionally with one or more dispersants in a suitable medium to produce a fine particle suspension of the compound. One or more wetting agents can be included in the composition and a suspending agent can be included to reduce the sedimentation rate of the particles. Alternatively, the compound of formula (I) can be dry milled and added to water containing the substances described above to produce the desired final product.

[0037] Aerosol formulations contain the compound of formula (I) and a suitable propellant (e.g., n-butane). The compound of formula (I) is also dissolved or dispersed in a suitable medium (e.g., a water-miscible liquid such as water or n-propanol) to obtain a composition for use in a non-pressurized, hand-held spray pump.

[0038] The capsule suspension (CS) can be prepared in a manner similar to the preparation of the EW formulation, except that each oil droplet is encapsulated by a polymer shell and an additional polymerization step is involved to obtain an aqueous dispersion of oil droplets containing the compound of formula (I) and optionally a carrier or diluent therefor. The polymer shell can be produced by either an interfacial polycondensation reaction or a coacervation procedure. This composition provides a controlled release of the compound of formula (I) and can be used for seed treatment. The compound of formula (I) can also be formulated in a biodegradable polymer matrix to provide a delayed controlled release of this compound.

[0039] The composition can contain one or more additives to improve the biological performance of the composition, for example, by improving wetting, retention or dispersion on the surface; rainfastness on the treated surface; or uptake or mobility of the compound of formula (I). Such additives include surfactants (SFA), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean oil and rapeseed oil) and blends thereof with other biological enhancement aids (components that can assist or modulate the action of the compound of formula (I)).

[0040] Wetting agents, dispersing agents and emulsifying agents can be cationic, anionic, amphoteric or non-ionic SFA.

[0041] Suitable cationic SFA include quaternary ammonium compounds (e.g., cetyltrimethylammonium bromide), imidazolines and amine salts.

[0042] 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, butylnaphthalene sulfonic acid, and a mixture of sodium di - isopropyl - and tri - isopropyl - naphthalene sulfonates), sulfuric acid ethers, sulfuric acid alcohol ethers (e.g., sodium laureth - 3 - sulfate), carboxylic acid ethers (e.g., sodium laureth - 3 - carboxylate), phosphate esters (products from the reaction of one or more aliphatic alcohols with phosphoric acid (mainly mono - esters) or phosphorus pentoxide (mainly di - esters), e.g., the reaction product of lauryl alcohol and tetraphosphoric acid; further, these products can be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, and lignosulfonates.

[0043] Suitable amphoteric SFAs include betaines, propionates, and glycineates.

[0044] Suitable non - ionic 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 alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long - chain fatty acids or hexitol anhydrides; condensation products of the said partial esters with ethylene oxide; block polymers (including ethylene oxide and propylene oxide); alkanolamides; simple esters (e.g., fatty acid polyethylene glycol esters); amine oxides (e.g., lauryldimethylamine oxide); and lecithin.

[0045] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0046] The herbicidal compounds of the present invention can also be used in mixtures with one or more additional herbicides and / or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), acronifen, ametryn, aminocarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, bilanafos, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butaphenacil, carfentrazone (including carfentrazone-ethyl), chloransulam (including chloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorosulfuron, cinmethylin, clazifos, clethodim, clodinafop (including clodinafop-propargyl), chlormazone, clopyralid, cyclopyranil, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including choline salt and its 2-ethylhexyl ester), 2,4-DB, desmedipham, dicamba (including aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, its potassium and sodium salts), diclosulam, difluhenican, diflufenzoppil, dimethachlor, dimethenamid-P, diquat dibromide, diuron, epirifluorfen, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, flupyradifurone (including flupyradifurone-benzyl), fluazifop (including fluazifop-P-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, flumeturon, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen, foramsulfuron, glufosinate (including its ammonium salt), glyphosate (including its diammonium,(including isopropylammonium and potassium salts), halauxifen (including halauxifen-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox, imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iofensulfuron-sodium), ioxynil, isoproturon, isoxaflutole, rankotriol, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozolin, metachlor, metosulam, metribuzin, metsulfuron, napropamide,nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, fenmedifam, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, promethrin, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen-ethyl), pyrazosulfuron, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxysulam, cinchlorac, cinmethylin, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimsulfuron, sulfofenacil, sethoxydim, simazine, S-metachlor, sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetrafluoropyrimeth, thienacarbazone, thifensulfuron, thiafenacil, topramezone, traloxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), triflumizoxazin, trifluralin, triflusulfuron,Ethyl 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-carboxylate, 4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-t-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, 3-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione, 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, 6-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-ethyl-cyclohexane-1,3-dione, 2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1,3-dione2-[6-Cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione, 3-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione, 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione, 6-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione, 2-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione, 4-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione, 4-[6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including its agrochemically acceptable esters, such as methyl 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylate), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide,3-(Ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide and ethyl 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate may be mentioned.

[0047] The mixing partners of the compounds of formula I can also be in the form of esters or salts, for example as mentioned in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0048] The compounds of formula I can also be used in mixtures with other pesticides such as fungicides, nematicides or insecticides, examples of which are shown in The Pesticide Manual.

[0049] The mixing ratio of the compounds of formula I to the mixing partner is preferably 1:100 to 1000:1.

[0050] The mixtures can advantageously be used in the abovementioned formulations (in which case the "active ingredient" relates to each mixture of the compound of formula I with the mixing partner).

[0051] 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, flurioxyphen, furilazole, isoxadifen (including isoxadifen - ethyl), mefenpyr (including mefenpyr - diethyl), metcamifene and oxabetrinil. Mixtures of the compounds of formula I with cyprosulfamide, isoxadifen - ethyl, cloquintocet - mexyl and / or metcamifene are particularly preferred.

[0052] The toxicity relaxant of the compound of formula I can also be in the form of an ester or a salt, for example, as described in The Pesticide Manual, 16 th Edition (BCPC), 2012. The reference to clocinatset methyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in International Publication No. 02 / 34048. The reference to fenchlorazole-ethyl also applies to fenchlorazole and the like.

[0053] Preferably, the mixing ratio of the compound of formula I to the toxicity relaxant is from 100:1 to 1:10, especially from 20:1 to 1:1.

[0054] The mixture can advantageously be used in the above formulations (in this case, the "active ingredient" relates to each mixture of the compound of formula I and the toxicity relaxant).

[0055] The present invention further provides a method for controlling weeds in a habitat, said method comprising the application to the weed habitat of a composition comprising a controlling amount of a compound of formula (I). The present invention also further provides a method for selectively controlling weeds in a habitat comprising crop plants and weeds, wherein the method comprises the application to the habitat of a composition according to the invention in a weed controlling amount. "Control" means killing, reducing or delaying growth or preventing or reducing germination. Generally, the plants to be controlled are unwanted plants (weeds). "Habitat" means an area where a plant is growing or will grow. Some crop plants may be inherently resistant to the herbicidal effect of the compounds of formula (I). However, in some cases, resistance may need to be artificially introduced into the crop plants, for example, by genetic engineering. Thus, it is possible to confer resistance to HPPD inhibitors on crop plants by genetic engineering. Methods for conferring resistance to HPPD inhibitors on crop plants are known, for example, from WO 02 / 46387. Thus, in a more preferred embodiment, the crop plants are transgenic with respect to a polynucleotide comprising a DNA sequence encoding an HPPD inhibitor-resistant HPPD enzyme from bacteria, more specifically Pseudomonas fluorescens or Shewanella colwelliana, or plants, more specifically monocotyledonous plants or even more specifically wheat, maize, barley, rice, Brachiaria, Cenchrus, Lolium, Festuca, Setaria, Eleusine, Sorghum or Avena species. Numerous HPPD-resistant soybean transgenic "events" are known, including, for example, SYHT04R (WO 2012 / 082542), SYHT0H2 (WO 2012 / 082548) and FG72.Other polynucleotide sequences that can be used to produce plants that are resistant to the compounds of the present invention are disclosed, for example, in WO 2010 / 085705 and WO 2011 / 068567. Thus, crop plants for which the compositions according to the invention can be used include, for example, cereals such as barley and wheat, cotton, rape, sunflower, maize, rice, soybeans, sugar beets, sugar cane and turf grass.

[0056] Crop plants can also include trees such as fruit trees, palm trees, coconut trees or other nuts. Vining plants such as grapes, low-growing fruit trees, fruit plants and vegetables are also included.

[0057] The application rate of the compounds of formula I can vary within wide limits and depends on the nature of the soil, the method of application (pre-emergence or post-emergence; seed dressing; application to furrows; application to non-cultivated land, etc.), the crop, the weeds to be controlled, the general climatic conditions and other factors depending on 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 10 to 2000 g / ha, in particular 50 to 1000 g / ha.

[0058] Application is generally carried out by spraying the composition, typically by means of a sprayer attached to a tractor for large areas, but other methods such as dusting (for powders), dripping or irrigation can also be used.

[0059] It should be understood that crops also include crops that have been given resistance to herbicides or types of herbicides (e.g., ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD inhibitors) by conventional breeding methods or genetic recombination. An example of a crop that has been given resistance to imidazolinones, such as imazamox, by conventional breeding methods is Clearfield® summer canola. Examples of crops that have been given resistance to herbicides by genetic recombination methods include, for example, glyphosate-resistant and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.

[0060] Crops are also to be understood to be crops that have been given resistance to pests by genetic engineering methods, such as Bt corn (resistant to the European corn borer), Bt cotton (resistant to the pink bollworm), and further Bt potatoes (resistant to the Colorado potato beetle). An example of Bt corn is the Bt 176 corn hybrid of NK® (Syngenta Seeds). Bt toxins are proteins that are naturally formed by the soil bacterium Bacillus thuringiensis. Examples of toxins or transgenic plants capable of synthesizing such toxins are described in European Patent Application Publication No. 451878, European Patent Application Publication No. 374753, International Publication No. 93 / 07278, International Publication No. 95 / 34656, International Publication No. 03 / 052073, and European Patent Application Publication No. 427529. Examples of transgenic plants containing one or more genes encoding insecticide resistance and expressing one or more toxins are KnockOut® (corn), Yield Gard® (corn), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potato), NatureGard® and Protexcta®. Any plant crop or its seed material can be resistant to herbicides and at the same time resistant to insect feeding ("multiple" transgenic events). For example, the seeds can have the ability to express the insecticidal Cry3 protein and at the same time be resistant to glyphosate.

[0061] Crops are also to be understood to include crops obtained by conventional breeding methods or genetic engineering, including so-called output traits (e.g., improved storage stability, higher nutritional value, and improved flavor).

[0062] Other useful plants include, for example, turfgrasses and ornamental plants such as flowers or shrubs commercially cultivated for turfgrass or lawns in golf courses, lawns, parks and along roadsides.

[0063] The composition can be used to control unwanted plants (collectively referred to as "weeds"). Weeds to be controlled can be both monocotyledonous plant species such as Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria and Sorghum and dicotyledonous plant species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium. Weeds can be regarded as crops, but can include plants growing outside the area of the crop ("escape") or plants growing from seeds left from a previously planted different crop ("volunteer"). Such volunteers or escapes can be resistant to certain other herbicides.

[0064] The compounds of the present invention can be prepared according to the following scheme.

[0065] The compound of formula (I) can be prepared from the compound of formula (II). [Chemical formula]

[0066] The compound of formula (II) is treated with an amine of formula (III) (wherein, in an embodiment of the present invention, Q = Q1) or an amine of formula (IV) (wherein, in an embodiment of the present invention, Q = Q2), N-formyl saccharin and triethylamine in the presence of N-methylpyrrolidinone as a solvent, palladium(II) acetate catalyst and a xantphos ligand. This reaction can be carried out using a continuous flow reactor.

[0067] Alternatively, the compound of formula (I) can be prepared from benzoic acid of formula (V). [Chemical formula]

[0068] Benzoic acid of formula (V) and an amine of formula (III) (wherein, in an embodiment of the present invention, Q = Q1) or an amine of formula (IV) (wherein, in an embodiment of the present invention, Q = Q 2 is treated with an amide coupling reagent, such as thionyl chloride and N-methylimidazole, in a suitable solvent, such as pyridine.

[0069] The compound of formula (V) can be prepared by hydrolysis of the ester of formula (VI). [Chemical formula]

[0070] The ester of formula (VI) is treated with sodium hydroxide in a suitable solvent, such as a 3:1 mixture of ethanol:water, to obtain the compound of formula (V).

[0071] R 2 is not chloro, the compound of formula (VI) is R 2It can be prepared from the compound of formula (VI) wherein R is chloro.

Chemical formula

[0072] The conversion method will depend on what R is. 2 The method for converting the chloro group to the R group will be known to those skilled in the art. For example, when R 2 is methyl, for example, with a suitable catalyst such as [1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene](3-chloropyridyl)palladium(II) dichloride, trimethylboroxine and a base such as potassium carbonate are used to carry out the Suzuki reaction for treating the compound where R 2 =Cl. 2 =Cl can be prepared from the compound of formula (II) where R

[0073] R 2 =Cl of formula (VI) 2 =Cl.

Chemical formula

[0074] The compound of formula (II) is reacted with a base such as triethylamine and a palladium catalyst such as [1,1'-bis(diphenylphosphino)ferrocene]palladium(II) dichloride in a mixed solvent of methanol and acetonitrile in an autoclave under a carbon monoxide atmosphere.

[0075] R 5 is not hydrogen, the compound of formula (II) where R 2 =Cl can be prepared from the compound of formula (VII) and the compound of formula (VII).

Chemical formula

[0076] In a suitable solvent, a compound of formula (VII) is treated with a compound of formula (VIII) wherein LG is defined as a leaving group. In this reaction, a base may optionally be required. The requirements and selection of the base will be known to those skilled in the art. For example, when R 5 is acetyl, the compound of formula (VIII) is acetyl chloride. For example, when R 5 is methyl, the compound of formula (VIII) is iodomethane and the base is sodium hydride.

[0077] The compound of formula (VII) can be prepared from a compound of formula (IX) and a compound of formula (X).

Chemical formula

[0078] In a suitable solvent, a compound of formula (IX) is treated with a compound of formula (X) wherein LG is defined as a leaving group. In this reaction, a base may optionally be required. The requirements and selection of the base will be known to those skilled in the art. For example, when R4 is acetyl, the compound of formula (X) is acetyl chloride. For example, when R 5 is methyl, the compound of formula (X) is iodomethane and the base is sodium hydride.

[0079] The compound of formula (IX) can be prepared from a compound of formula (XI).

Chemical formula

[0080] A compound of formula (XI) is treated with dichlorodimethylhydantoin in the presence of a catalytic amount of isopropylammonium chloride and toluene as the solvent to obtain a compound of formula (IX).

[0081] Compounds of formula (XI) may be commercially available. Alternatively, these can be prepared from 2-amino-4-bromo-phenol.

Chemical formula

[0082] The conversion method will depend on the properties of R 3 . For example, when R 3 is -CH2CF3, 2-amino-4-bromo-phenol is treated with potassium carbonate and 2,2,2-trifluoroethyl triflate. For example, when R 3 is -CF2H, 2-amino-4-bromo-phenol is treated with sodium bromodifluoroacetate and a base such as cesium carbonate.

[0083] Accordingly, according to the present invention, a compound of formula (II)

Chemical formula

[0084] The present invention further provides a compound of formula (V)

Chemical formula

[0085] The present invention further provides a compound of formula (VIa)

Chemical formula

[0086] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention referred to in the tables provided herein.

Example

[0087] Preparation Example 1: Compound 1.004 Step 1. Toluene (100 mL) and diisopropylammonium chloride (1.08 g, 7.81 mmol) were added to a flask containing 5-bromo-2-(trifluoromethoxy)aniline (10 g, 39.1 mmol). The reaction mixture was covered with foil to shield from light. At 0 °C, 1,3-dichloro-5,5-dimethyl-imidazolidine-2,4-dione (7.70 g, 39.1 mmol) was added, and the reaction mixture was warmed to room temperature and stirred for 3 hours. The reaction mixture was deactivated by the addition of saturated aqueous sodium bisulfite, then diluted with water and ethyl acetate, and the phases were separated. The organic phase was dried and concentrated under reduced pressure. The crude material was purified by normal-phase flash chromatography (0-5% ethyl acetate in cyclohexane) to obtain 3-bromo-2-chloro-6-(trifluoromethoxy)aniline (7.07 g, 21.9 mmol, 56%) as a pale yellow oil. 1 1H NMR (methanol): 7.05 (m, 1H), 6.99 (d, 1H).

[0088] Step 2. Acetonitrile (20 mL) was added to a flask containing 3-bromo-2-chloro-6-(trifluoromethoxy)aniline (1.00 g, 3.40 mmol), and the reaction mixture was placed under a nitrogen atmosphere. 5-Bromopentanoyl chloride (1.10 g, 0.79 mL, 5.90 mmol) was added. The reaction mixture was stirred at 50 °C for 6 hours. The reaction mixture was quenched by the addition of water and concentrated under reduced pressure to remove the acetonitrile solvent. The reaction residue was taken up in ethyl acetate and water, and the phases were separated. The aqueous phase was further extracted with ethyl acetate. The organic phases were combined, dried, and concentrated under reduced pressure. The crude material was purified by normal-phase flash chromatography (0 - 30% ethyl acetate in cyclohexane) to give the product containing impurities as a pale yellow solid. The crude material was taken up in ethyl acetate and washed with 2 M aqueous sodium hydroxide solution. The organic phase was dried and concentrated under reduced pressure to give 5-bromo-N-[3-bromo-2-chloro-6-(trifluoromethoxy)phenyl]pentanamide (1.44 g, 2.92 mmol, 85%) as a pale yellow solid. 1 H NMR (chloroform): 7.62 (d, 1H), 7.16 (m, 1H), 6.90 (br s, 1H), 3.45 (t, 2H), 2.47 (br s, 2H), 2.02 - 1.87 (m, 4H).

[0089] Step 3. To a flask containing N-[3-bromo-2-chloro-6-(trifluoromethoxy)phenyl]acetamide (1.44 g, 2.92 mmol) was added tetrahydrofuran (14 mL). The reaction mixture was stirred at 0 °C under a nitrogen atmosphere for 10 minutes. Sodium hydride (60 mass%, 0.129 g, 3.21 mmol) in paraffin oil was added to the reaction mixture. The reaction mixture was stirred at room temperature for 4.5 hours. Sodium hydride (60 mass%, 0.0818 g, 2.04 mmol) in paraffin oil was further added to this reaction mixture. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was quenched by the addition of water and concentrated under reduced pressure to remove the tetrahydrofuran solvent. The residue was taken up in ethyl acetate and water, and the phases were separated. The aqueous phase was further extracted with ethyl acetate. The organic phases were combined, dried, and concentrated under reduced pressure. The crude material was purified by normal-phase flash chromatography (0 - 25% ethyl acetate in cyclohexane) to give 1-[3-bromo-2-chloro-6-(trifluoromethoxy)phenyl]piperidin-2-one (1.03 g, 2.43 mmol, 83%) as a colorless oil. 1 1H NMR (chloroform): 7.64 (d, 1H), 7.17 (dq, 1H), 3.64 - 3.50 (m, 1H), 3.49 - 3.38 (m, 1H), 2.58 (dt, 2H), 2.07 - 1.88 (m, 4H).

[0090] Step 4. 1-[3-Bromo-2-chloro-6-(trifluoromethoxy)phenyl]piperidin-2-one (0.500 g, 1.34 mmol) was placed in a container, and palladium(II) acetate (0.0301 g, 0.134 mmol), Xantphos (0.160 g, 0.268 mmol), N-formyl saccharin (0.638 g, 3.02 mmol), and 1-methyltetrazol-5-amine (1.20 g, 12.1 mmol) were added. 1-Methyl-2-pyrrolidinone was added to the container to make the total volume in the container 20 mL. 1-Methyl-2-pyrrolidinone was added to a second container containing triethylamine (0.611 g, 6.04 mmol, 0.842 mL) to make the total volume in the container 20 mL. These two solutions were injected into a sample loop via a T-piece and then circulated through a 20 mL stainless steel coil heated to 170 °C. The flow rate was set so that the total residence time was 15 minutes. The reaction mixture was concentrated under reduced pressure to remove 1-methyl-2-pyrrolidinone, the solvent. The residue was taken up in dichloromethane and saturated aqueous sodium carbonate, and the phases were separated. The aqueous phase was further extracted with dichloromethane. The aqueous phase was acidified to pH 5 and extracted with ethyl acetate. The organic phases were combined, dried, and concentrated under reduced pressure. The crude material was purified by normal phase flash chromatography (0 - 10% dichloromethane in methanol) to give the product containing impurities as a glassy solid. The crude material was taken up in ethyl acetate and washed with dilute aqueous HCl. The organic phase was dried and concentrated under reduced pressure to give 3-acetamido-2-chloro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(trifluoromethoxy)benzamide (Compound 1.004) (0.0486 g, 0.116 mmol, 9%) as a foamy white solid. 1 H NMR (methanol): 7.82 (d, 1H), 7.58 (m, 1H), 4.06 (s, 3H), 3.69 - 3.60 (m, 1H), 3.59 - 3.50 (m, 1H), 2.57 (m, 2H), 2.10 - 1.93 (dt, 4H)

[0091] Preparation Example 2: Compound 1.006 3-Bromo-2-chloro-6-(trifluoromethoxy)aniline was prepared as described above.

[0092] Step 1 3-Bromo-2-chloro-6-(trifluoromethoxy)aniline (24 g, 76 mmol) was charged into an autoclave. Methanol (144 mL) was added. Triethylamine (23 g, 228 mmol), then allyl palladium(II) chloride dimer (1.13 g, 3.10 mmol) and 2,2'-bis(diphenylphosphino)-1,1'-binaphthyl (2.44 g, 3.92 mmol) were added. The autoclave was flushed three times with nitrogen and then three times with carbon monoxide. The reaction was pressurized to 20 bar of CO and heated at 100 °C for 4 hours. Then, it was cooled to room temperature and the atmosphere was replaced with N2. The contents were taken out into an Erlenmeyer flask, and the reaction mixture was filtered through celite and evaporated. Methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate (16 g, 59 mmol, 78%) was obtained as a white solid by column chromatography.

[0093] Step 2 Acetonitrile (60 mL) and cyclopropanecarbonyl chloride (2.41 g, 23.1 mmol) were added to a flask containing methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate (2.08 g, 7.70 mmol). The reaction mixture was stirred at 60 °C. After the addition, a white solid was formed, but vigorous stirring was required. After stirring for 2 hours, the reaction mixture was cooled and the solvent was evaporated. The resulting solid was stirred in cyclohexane (100 ml), filtered, and then washed with cyclohexane to obtain methyl 2-chloro-3-(cyclopropanecarbonylamino)-4-(trifluoromethoxy)benzoate (2.40 g, 7.12 mmol, 92%) as a white solid.

[0094] Step 3 A solution of methyl 2-chloro-3-(cyclopropanecarbonylamino)-4-(trifluoromethoxy)benzoate (A, 0.35 g, 1.04 mmol) in THF (9 mL) and water (3 mL) was added lithium hydroxide hydrate (87 mg, 2.1 mmol), and the reaction mixture was stirred for 16 h. The reaction was concentrated to remove THF. 2M HCl was added to the solution until a white solid precipitated, and the solid was isolated by filtration to give 2-chloro-3-(cyclopropanecarbonylamino)-4-(trifluoromethoxy)benzoic acid (0.296 g, 0.915 mmol, 88%) as a white solid. 1H NMR (400 MHz, methanol) δ ppm 7.87 (d, 1H) 7.43 (d, 1H) 1.85 - 1.96 (m, 1H) 0.84 - 1.02 (m, 4H).

[0095] Step 4 2-Chloro-3-(cyclopropanecarbonylamino)-4-(trifluoromethoxy)benzoic acid (1.10 g, 3.4 mmol) and 1-methyltetrazol-5-amine (400 mg, 4.1 mmol) in 2-methylpyridine (8 mL) were stirred under a nitrogen atmosphere for 10 min, then 1-methylimidazole (280 mg, 3.4 mmol) was added, followed by triethylamine (520 mg, 5.1 mmol), and the mixture was stirred at room temperature for 10 min. Then the reaction mass was cooled to 0 °C and thionyl chloride (810 mg, 6.8 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 16 h. The reaction was diluted with 2N HCl and stirred for 30 min. The resulting solid was filtered, washed with ethanol and dried to give 2-chloro-3-(cyclopropanecarbonylamino)-N-(1-methyltetrazol-5-yl)-4-(trifluoromethoxy)benzamide as a white solid (820 mg, 2.08 mmol, 61%). 1H NMR (methanol): 7.73 (d, 1H), 7.52 (br d, 1H), 4.06 (s, 3H), 1.91 (m, 1H), 1.01 - 0.88 (m, 4H).

[0096] Preparation Example 3: Compound 1.007 Methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate was prepared as described above.

[0097] Step 1 To a solution of methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate (2.5 g, 9.3 mmol) in acetonitrile (60 mL) was added propanoyl chloride (2.6 g, 28 mmol). The reaction mixture was stirred at 60 °C for 2 hours. After 2 hours, the mixture was cooled to room temperature and the acetonitrile was removed under reduced pressure. The residue was taken up in ethyl acetate and then washed with sodium bicarbonate solution, dried (MgSO4), and concentrated under reduced pressure. Flash chromatography (0 - 30% EtOAc and cyclohexane) gave methyl 2-chloro-3-(propanoylamino)-4-(trifluoromethoxy)benzoate (2.28 g, 7.00 mmol, 76%) as a white solid. 1H NMR (400 MHz, d4-methanol): 7.87 (d, 1H) 7.45 (m, 1H) 3.93 (s, 3H) 2.46 (q, 2H) 1.24 (t, 3H).

[0098] Step 2 To a stirred solution of methyl 2-chloro-3-(propanoylamino)-4-(trifluoromethoxy)benzoate (27.7 g, 85.1 mmol) in tetrahydrofuran (10 mL) and methanol (10 mL) was added lithium hydroxide (6.11 g, 255 mmol) in water (10 mL), and the mixture was stirred at room temperature for 12 hours. The reaction mass was concentrated under reduced pressure and partitioned between 1N HCl and ethyl acetate. The organic layer was dried over sodium sulfate and concentrated to give 2-chloro-3-(propanoylamino)-4-(trifluoromethoxy)benzoic acid (25.7 g, 78.3 mmol, 92%) as a white solid. 1H NMR (400 MHz, d6-DMSO): 13.70 (1H, s), 9.82 (1H, s), 7.79 (1H, d), 7.51 (1H, d), 2.35n (2H, q), 1.11 (H, t).

[0099] Step 3 Pyridine (50 mL) and 2-chloro-3-(propanoylamino)-4-(trifluoromethoxy)benzoic acid (5.00 g, 16.0 mmol) were charged into a flask at room temperature under a N2 atmosphere. Then, 1-methyltetrazol-5-amine (1.79 g, 17.7 mmol) and 1-methylimidazole (1.33 g, 16.0 mmol) were added, and the reaction mixture was cooled to 0 °C. Thionyl chloride (3.94 g, 32.1 mmol) was added dropwise using a syringe pump over 3 hours while maintaining the temperature at 0 - 10 °C. After the addition was complete, the reaction mixture had a pH of 5.7 and a brown precipitate appeared. The ice bath was removed and the reaction was stirred at room temperature. After a further 2 hours, the reaction mixture became a brown solution. After stirring for a further 2 hours, the reaction mixture was cooled to 0 °C using an ice bath, and then 25 mL of water was added with stirring (pH = 5.8 - 5.9). The reaction mixture was acidified to pH = 1.5 - 2 using 2N HCl. A sticky solid precipitated during acidification. The suspension was extracted with ethyl acetate (50 mL × 3). The combined organic layers were washed with cold water (25 mL), dried (Na2SO4), and concentrated under reduced pressure to give a light orange solid. This was purified by chromatography (30 - 40% ethyl acetate in cyclohexane) to give 2-chloro-N-(1-methyltetrazol-5-yl)-3-(propanoylamino)-4-(trifluoromethoxy)benzamide (2.59 g, 6.61 mmol, 41%) as a white solid. 1H NMR (400 MHz, d6-DMSO): 11.92 (1H, s), 9.90 (1H, s), 7.80 (1H, d), 7.61 (1H, d), 4.00 (3H, s), 2.37 (2H, q), 1.12 (3H, t).

[0100] Preparation Example 4: Compound 1.012 Methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate was prepared as described above.

[0101] Step 1 Methyl 3-amino-2-chloro-4-(trifluoromethoxy)benzoate (2.0 g, 7.4 mmol) and picolinic acid (1.1 g, 8.9 mmol) were dissolved in pyridine (10 mL), and the solution was cooled to 0 °C with ice water. Phosphorus oxychloride (1.70 g, 11.1 mmol) was added dropwise over 4 minutes, then the reaction was warmed to room temperature and stirred for 3 hours, whereupon a white precipitate appeared. The reaction mixture was slowly deactivated in a saturated aqueous sodium bicarbonate solution at low temperature (0 °C). After the addition, vigorous stirring was continued for 30 minutes. The resulting white solid was filtered and washed three times with water to obtain methyl 2-chloro-3-(pyridine-2-carbonylamino)-4-(trifluoromethoxy)benzoate (1.69 g, 4.51 mmol, 61%) as a white solid. 1H NMR (400 MHz, d6-DMSO): 10.69 (1H, s), 8.78 (1H, d), 8.15 - 8.06 (2H, m), 7.91 (1H, d), 7.73 (1H, ddd), 7.62 (1H, d), 3.90 (3H, s).

[0102] Step 2 A solution of lithium hydroxide hydrate (0.54 g, 13 mmol) in water (8.0 mL) was added to a solution of methyl 2-chloro-3-(pyridine-2-carbonylamino)-4-(trifluoromethoxy)benzoate (1.6 g, 4.3 mmol) in tetrahydrofuran (32 mL). The reaction mixture was stirred at room temperature for 16 hours. The reaction was concentrated to remove THF. The aqueous solution was washed with cyclohexane, then cooled to 0 °C and the pH was adjusted to 3 with a 10% aqueous solution of citric acid. The aqueous mixture was extracted three times with ethyl acetate, and the combined organic layers were dried over sodium sulfate and concentrated under reduced pressure to obtain 2-chloro-3-(pyridine-2-carbonylamino)-4-(trifluoromethoxy)benzoic acid (1.6 g, 4.3 mmol, 100%) as a white solid. 1H NMR (400 MHz, d6-DMSO): 10.65 (1H, d), 8.77 (1H, d), 8.13 (1H, d), 8.05 (1H, t), 7.88 (1H, d), 7.69 (1H, m), 7.58 (1H, d).

[0103] Step 3 2-Chloro-3-(pyridine-2-carbonylamino)-4-(trifluoromethoxy)benzoic acid (1.5 g, 4.2 mmol) and 1-methyltetrazol-5-amine (500 mg, 5.0 mmol) in 3-methylpyridine (15 mL) were stirred for 10 minutes under a nitrogen atmosphere. Triethylamine (630 mg, 6.2 mmol) and then 1-methylimidazole (340 mg, 4.2 mmol) were added, and the mixture was stirred at room temperature for 30 minutes. Then, the reaction mass was cooled to 0 °C, and thionyl chloride (990 mg, 8.3 mmol) was added dropwise. After stirring at room temperature for 16 hours, the reaction mixture was deactivated to pH 1-2 with 2N HCl while stirring vigorously at 0 °C for 30 minutes. The aqueous layer was extracted three times with ethyl acetate and then concentrated under reduced pressure. The solid was recrystallized from ethyl acetate / n-pentane to give N-[2-chloro-3-[(1-methyltetrazol-5-yl)carbamoyl]-6-(trifluoromethoxy)phenyl]pyridine-2-carboxamide (1.45 g, 3.17 mmol, 76%) as a white solid. 1H NMR (400 MHz, d6-DMSO): 12.00 (1H, brs), 10.77 (1H, s), 8.78 (1H, d), 8.16 - 8.05 (2H, m), 7.88 (1H, d), 7.72 (1H, ddd), 7.67 (1H, dd), 4.00 (3H, s).

[0104] Preparation Example 5: Compound 1.014 Step 1 To a 15 mL thick-walled pressure vessel were added 2-amino-4-bromophenol (564 mg, 3.00 mmol), KOH (0.218 g, 3.90 mmol), DMSO (10 mL) and 1,2-dibromotetrafluoroethane (1.17 g, 4.50 mmol) at room temperature. The reaction flask was then closed and heated at 80 °C for 18 h. The reaction mixture was cooled to room temperature. The mixture was washed with H2O (200 mL) and extracted with ethyl acetate (100 mL × 3). The layers were separated and dried over sodium sulfate. After evaporation of the solvent, the residue was purified by chromatography (petroleum ether / ethyl acetate = 30:1) to give 5-bromo-2-(2-bromo-1,1,2,2-tetrafluoro-ethoxy)aniline (0.215 g, 0.586 mmol, 19.5%) as a brown oil, and 5-bromo-2-(1,1,2,2-tetrafluoroethoxy)aniline (0.206 g, 0.715 mmol, yield: 23.8%) as a brown oil. 1H NMR (400 MHz, d6-DMSO) of 5-bromo-2-(1,1,2,2-tetrafluoroethoxy)aniline: 6.97 - 6.76 (3H, m), 6.65 - 6.62 (1H, m), 5.54 (2H, brs).

[0105] Step 2 Diisopropylamine (0.973 g, 9.63 mmol) is added to a mixture of ammonium chloride (0.511 g, 9.63 mmol) and ethanol (25 mL). The mixture is heated to reflux for 4 hours. The reaction mixture is cooled and then concentrated to obtain a white solid, which is further washed with ethanol and then dried under reduced pressure. 5-Bromo-2-(1,1,2,2-tetrafluoroethoxy)aniline (18.5 g, 64.2 mmol), toluene (300 mL) and diisopropylammonium; chloride (1.4 g) are added to a three-necked flask under a nitrogen atmosphere. The flask is covered with foil and then cooled to 0 °C. 1,3-Dichloro-5,5-dimethyl-imidazolidine-2,4-dione (11.4 g, 57.8 mmol) is added in several portions and the mixture is stirred at 0 °C for 2 hours. The reaction mixture is deactivated by the addition of a saturated aqueous sodium bisulfite solution and then diluted with water and ethyl acetate. The residue is purified by chromatography (eluent: petroleum ether / ethyl acetate = 30:1) to obtain 3-bromo-2-chloro-6-(1,1,2,2-tetrafluoroethoxy)aniline (9.00 g, 27.9 mmol, 43.5%) as a yellow oil. 1H NMR (400 MHz, d6-DMSO): 7.03 (1H, d), 3.92 (1H, d), 6.85 (1H, tt), 5.83 (2H, brs).

[0106] Step 3 Synthesis was carried out in a Flow syn equipped with a 20 ml stainless steel loop. The following were added to Loop A: palladium(II) acetate (694 mg, 3.10 mmol), Xantphos (3.59 g, 6.20 mmol), N-formyl saccharin (14.7 g, 69.8 mmol) and 3-bromo-2-chloro-6-(1,1,2,2-tetrafluoroethoxy)aniline (10 g, 31.0 mmol) in 1-methyl-2-pyrrolidinone (190 mL). To Loop B, triethylamine (19.4 mL, 139.54 mmol), 1-methyl-2-pyrrolidinone (190 mL), and water (20.1 mL, 1116.3 mmol) were added. The temperature was set at 170 minutes and the time was set at 15 minutes. In a fixed container, water (1000 ml) and 1M HCl (1000 ml) were added to the resulting reaction mixture, followed by ethyl acetate (1000 ml), and the phases were separated. The organic layer was concentrated under reduced pressure. The crude material was purified by reverse phase chromatography: (gradient of 50 - 70% MeCN in H2O + 0.1% formic acid) to obtain 3-amino-2-chloro-4-(1,1,2,2-tetrafluoroethoxy)benzoic acid (5.13 g, 17.8 mmol, 58%) as a white solid. 1H NMR (400 MHz, methanol) δ ppm 6.25 - 6.62 (m, 1H) 7.01 - 7.26 (m, 2H).

[0107] Step 4 A stirred suspension of 3-amino-2-chloro-4-(1,1,2,2-tetrafluoroethoxy)benzoic acid (5.13 g, 17.8 mmol) and 2,3,4,5,6-pentafluorophenol (3.61 g, 19.6 mmol) in dichloromethane (70 mL) was treated at room temperature with 3-(ethyliminomethyleneamino)-N,N-dimethyl-propan-1-amine hydrochloride (4.1 g, 21 mmol). The mixture was stirred at room temperature. Initially heterogeneous, the mixture became a homogeneous solution within 5 minutes of the addition of EDC. The reaction mixture was stirred at room temperature for 16 h. The reaction was quenched by the addition of saturated aqueous NaHCO3 (100 mL). The mixture was stirred at room temperature for a further 5 minutes. The mixture was filtered through a phase separation cartridge and the organics were recovered. The filtrate was adsorbed onto silica and the crude product was purified by flash column chromatography (0 - 10% gradient of EtOAc in cyclohexane). The fractions containing the product were combined and concentrated in vacuo to give (2,3,4,5,6-pentafluorophenyl) 3-amino-2-chloro-4-(1,1,2,2-tetrafluoroethoxy)benzoate (6.36 g, 14.0 mmol, 79%) as a colorless oil which crystallized on standing. LCMS: M+H = 452.1 (in ES).

[0108] Step 5 (2,3,4,5,6-Pentafluorophenyl) 3-amino-2-chloro-4-(1,1,2,2-tetrafluoroethoxy)benzoate (3.18 g, 7.01 mmol) in acetonitrile (50 mL) was placed in a round bottom flask and treated at room temperature with 1-methyltetrazol-5-amine (1.53 g, 15.4 mmol), followed by 2-t-butylimino-N,N-diethyl-1,3-dimethyl-1,3,2λ 5-Diaza phosphinan-2-amine (4.4 g, 4.6 mL, 15 mmol) was added. The mixture was stirred overnight at room temperature. The reaction was quenched by the addition of 2 M aqueous HCl (100 mL). The mixture was stirred for an additional 5 minutes at room temperature. The mixture was transferred to a separatory funnel and diluted with EtOAc (100 mL). The phases were separated. The aqueous phase was extracted with EtOAc (100 mL). The combined organic phases were adsorbed onto C18-silica and purified via reverse-phase column chromatography (gradient of 40 - 80% MeCN in H2O + 0.1% formic acid) to afford 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(1,1,2,2-tetrafluoroethoxy)benzamide (1.88 g, 4.84 mmol, 69%) as a white solid. 1H NMR (400 MHz, methanol) δ ppm 4.05 (s, 3H) 6.28 - 6.62 (m, 1H) 6.91 - 6.99 (m, 1H) 7.22 - 7.30 (m, 1H).

[0109] Step 6 To a stirred solution of 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(1,1,2,2-tetrafluoroethoxy)benzamide (0.3 g, 0.81 mmol) in acetonitrile (6 mL) was added propanoyl chloride (0.23 g, 0.22 mL, 2.5 mmol) at room temperature. The stirred mixture was heated to 60 °C overnight. The reaction was cooled to room temperature and quenched by slowly adding water (2 mL). The mixture was stirred for an additional 5 minutes at room temperature. The mixture was transferred to a separatory funnel and diluted with EtOAc (20 mL) and water (20 mL). The phases were separated. The aqueous phase was extracted with EtOAc (20 mL). The combined organic phases were dried (MgSO4) and filtered. The filtrate was adsorbed onto C18-silica and purified via reverse-phase column chromatography (gradient of 30 - 60% MeCN in H2O + 0.1% formic acid) to afford 2-chloro-N-(1-methyltetrazol-5-yl)-3-(propanoylamino)-4-(1,1,2,2-tetrafluoroethoxy)benzamide (280 mg, 0.626 mmol, 77%) as a white solid. 1H NMR (400 MHz, d4-methanol): 1.16 - 1.28 (m, 3H) 2.41 - 2.53 (m, 2H) 4.06 (s, 3H) 6.21 - 6.53 (m, 1H) 7.49 - 7.57 (m, 1H) 7.73 (d, 1H).

[0110] Preparation Example 6: Compound 1.016 Step 1. To a flask containing 3-chloro-4-methyl-2-nitro-phenol (5.33 mmol, 1.00 g) was added acetone (20 mL), water (0.1 mL), potassium carbonate (10.7 mmol, 1.47 g) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (8.00 mmol, 1.86 g). The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to remove the solvent. The residue was dissolved in water and ethyl acetate. The phases were separated and then the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with water and concentrated under reduced pressure to give 2-chloro-1-methyl-3-nitro-4-(2,2,2-trifluoroethoxy)benzene (5.39 mmol, 1.450 g, quant%) as an orange solid, which did not require further purification. 1 1H NMR (chloroform): 7.32 (m, 1H), 6.91 (d, 1H), 4.42 (q, 2H), 2.39 (s, 3H).

[0111] Step 2. To a flask containing 2-chloro-1-methyl-3-nitro-4-(2,2,2-trifluoroethoxy)benzene (10.0 mmol, 2.70 g) was added water (41 mL) and pyridine (41 mL). The reaction mixture was stirred at 100 °C until the reaction mixture became a solution. Potassium permanganate (40.0 mmol, 6.33 g) was added in 4 portions at 1-hour intervals. The reaction mixture was stirred at 100 °C for an additional 1 hour and then left standing at room temperature overnight. The reaction mixture was cooled to room temperature and the solids were filtered off. The solution was washed with ethyl acetate. The aqueous phase was acidified with aqueous 2M HCl and the material was extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure to give 2-chloro-3-nitro-4-(2,2,2-trifluoroethoxy)benzoic acid (4.37 mmol, 1.31 g) as a white solid, which did not require further purification. 1 1H NMR (methanol): 8.13 (d, 1H), 7.40 (d, 1H), 4.84 (m, 2H)

[0112] Step 3 Triethyl orthoformate (60.1 mmol, 8.91 g, 10 mL) was added to a flask containing 2-chloro-3-nitro-4-(2,2,2-trifluoroethoxy)benzoic acid (4.37 mmol, 1.31 g). The reaction mixture was stirred at 140 °C for 1 h. The reaction mixture was concentrated under reduced pressure to remove triethyl orthoformate. The residue was triturated with ethyl acetate and the solid was dried under reduced pressure to give ethyl 2-chloro-3-nitro-4-(2,2,2-trifluoroethoxy)benzoate (4.23 mmol, 1.39 g, 97%) as an orange solid, which did not require further purification. 1 H NMR (chloroform): 8.05 (d, 1H), 7.02 (d, 1H), 4.52 (m, 2H), 4.42 (m, 2H), 1.41 (m, 3H)

[0113] Step 4 Ethanol (8 mL), ammonium chloride (14.7 mmol, 0.784 g), water (8 mL) and iron (7.33 mmol, 0.409 g) were added to a flask containing ethyl 2-chloro-3-nitro-4-(2,2,2-trifluoroethoxy)benzoate (2.44 mmol, 0.800 g). The reaction mixture was stirred at 95 °C for 1 h. The reaction mixture was cooled to room temperature and the solids were filtered through celite and then washed with water and ethyl acetate. The solution was further diluted with water and ethyl acetate. The phases were separated and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with water and then brine, and concentrated under reduced pressure to give ethyl 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoate (2.43 mmol, 0.723 g, 100%) as a pale orange solid, which did not require further purification. 1 H NMR (chloroform): 7.27 (m, 1H), 6.70 (d, 1H), 4.46 - 4.40 (m, 4H), 4.37 (m, 2H), 1.39 (m, 3H)

[0114] Step 5 Ethyl 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoate (2.43 mmol, 0.723 g) was placed in a flask, and ethanol (15 mL), sodium hydroxide (7.29 mmol, 0.291 g), and water (5 mL) were added. The reaction mixture was stirred at room temperature for 6.5 h. The reaction mixture was concentrated under reduced pressure to remove the ethanol solvent. The aqueous phase was acidified to about pH 4 with concentrated HCl and then concentrated under reduced pressure to remove water. The residue was triturated with ethyl acetate, and the resulting solid was dried under reduced pressure to give 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoic acid (estimated to be 2.43 mmol, % of estimated amount), which was used without further purification as the crude product.

[0115] Step 6 To a flask containing 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoic acid (2.43 mmol, 0.655 g) were added 2,3,4,5,6-pentafluorophenol (2.79 mmol, 0.514 g), dichloromethane (33 mL), and 1-3-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.79 mmol, 0.564 g). The reaction mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure to remove the solvent. The reaction residue was dissolved in ethyl acetate and water. The phases were separated, and then the aqueous phase was further extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure to give (2,3,4,5,6-pentafluorophenyl) 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoate (estimated to be 2.43 mmol, % of estimated amount) as a colorless oil, which was used without further purification as the crude product.

[0116] Step 7 A flask containing (2,3,4,5,6-pentafluorophenyl) 3-amino-2-chloro-4-(2,2,2-trifluoroethoxy)benzoate (2.43 mmol, 1.06 g) was added with 1-methyltetrazol-5-amine (2.68 mmol, 0.265 g), acetonitrile (21 mL) and 2-t-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorin (5.35 mmol, 1.51 g, 1.60 mL). The reaction mixture was stirred at room temperature for 1.5 hours. The reaction mixture was deactivated by the addition of aqueous 2M HCl and then extracted with ethyl acetate. The organic phases were combined, washed with water and concentrated under reduced pressure to give an off-white solid. The crude material was triturated with dichloromethane and the resulting solid was dried under reduced pressure to give 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide (1.87 mmol, 0.655 g, 77%) as a white solid. 1 H NMR (methanol): 7.01 (d, 2H), 4.69 (m, 2H), 4.04 (s, 3H)

[0117] Step 8 A flask containing 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide (0.570 mmol, 0.200 g) was added with acetonitrile (4 mL) and 2-fluoropropanoyl chloride (1.43 mmol, 0.158 g). The reaction mixture was stirred at 60 °C for 1.5 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude material was purified by normal-phase flash chromatography (0 - 5% methanol in dichloromethane) to obtain 2-chloro-3-(2-fluoropropanoylamino)-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide (Compound 1.016) (0.313 mmol, 0.133 g, 55%) as a white solid. 1H NMR (methanol): 7.71 (d, 1H), 7.26 (d, 1H), 5.25 (m, 0.5H), 5.13 (m, 0.5H), 4.68 (m, 2H), 4.04 (s, 3H), 1.68 (d, 1.5H), 1.62 (d, 1.5H).

[0118] Preparation Example 7: Compound 1.018 Step 1 Prepare 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide as described above.

[0119] Step 2 A flask containing 3-amino-2-chloro-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide (0.428 mmol, 0.150 g) was added with acetonitrile (6 mL) and acetyl chloride (1.28 mmol, 0.101 g, 0.092 mL). The reaction mixture was stirred at 60 °C for 1.5 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude material was purified by normal-phase flash chromatography (0 - 5% methanol in dichloromethane) to obtain 3-acetamido-2-chloro-N-(1-methyltetrazol-5-yl)-4-(2,2,2-trifluoroethoxy)benzamide (Compound 1.018) (0.357 mmol, 0.140 g, 83%) as a white solid.1 1H NMR (in methanol): 7.67 (d, 1H), 7.25 (d, 1H), 4.67 (m, 2H), 4.04 (s, 3H), 2.18 (s, 3H).

[0120] Preparation Example 8: Compound 1.028 Step 1 Acetone (20 mL) and water (0.1 mL) were added to a flask containing 3-chloro-4-methyl-2-nitro-phenol (5.33 mmol, 1.00 g). Potassium carbonate (8.00 mmol, 1.11 g) and iodomethane (10.7 mmol, 1.51 g, 0.664 mL) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to remove the acetone solvent. The residue was dissolved in water and ethyl acetate. The phases were separated, and then the aqueous phase was further extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure to obtain 3-chloro-1-methoxy-4-methyl-2-nitro-benzene (4.98 mmol, 1.00 g, 93%) as a yellow solid, which did not require further purification. 1 1H NMR (in chloroform): 7.28 (m, 1H), 6.87 (d, 1H), 3.88 (s, 3H), 2.36 (s, 3H).

[0121] Step 2 Water (16 mL) and pyridine (16 mL) were added to a flask containing 3-chloro-1-methoxy-4-methyl-2-nitro-benzene (3.97 mmol, 0.800 g). The reaction mixture was stirred at 100 °C until the reaction mixture became a solution. Potassium permanganate (11.9 mmol, 1.88 g) was added in three portions at 1-hour intervals. The reaction mixture was stirred at 100 °C overnight. The reaction mixture was cooled to room temperature, and the solids were filtered off. The solution was washed with TBME. The aqueous phase was acidified with aqueous 2M HCl, and the material was extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure to obtain 2-chloro-4-methoxy-3-nitro-benzoic acid (2.20 mmol, 0.509 g, 55%) as a white solid, which did not require further purification. 11H NMR (methanol): δ 8.11 (d, 1H), 7.29 (d, 1H), 4.00 (s, 3H).

[0122] Step 3 Triethyl orthoformate (120 mmol, 17.8 g, 20 mL) was added to a flask containing 2-chloro-4-methoxy-3-nitro-benzoic acid (8.77 mmol, 2.03 g). The reaction mixture was stirred at 140 °C for 3 h. The reaction mixture was concentrated under reduced pressure to remove triethyl orthoformate. The residue was triturated with ethyl acetate and the solid was dried under reduced pressure to give ethyl 2-chloro-4-methoxy-3-nitro-benzoate (8.77 mmol, 2.28 g, amount %) as an orange solid, which did not require further purification.

[0123] Step 4 Ethanol (10 mL), ammonium chloride (23.1 mmol, 1.24 g), water (10 mL) and iron (11.6 mmol, 0.645 g) were added to a flask containing ethyl 2-chloro-4-methoxy-3-nitro-benzoate (3.85 mmol, 1.00 g). The reaction mixture was stirred at 95 °C for 1 h. The reaction mixture was cooled to room temperature and the solids were filtered through celite and then washed with water and ethyl acetate. The solution was further diluted with water and ethyl acetate. The phases were separated and the aqueous phase was further extracted with ethyl acetate. The organic phases were combined, washed with water and then brine and concentrated under reduced pressure to give ethyl 3-amino-2-chloro-4-methoxy-benzoate (3.76 mmol, 0.864 g, 98%) as an off-white solid, which did not require further purification.

[0124] Step 5 To a flask containing ethyl 3-amino-2-chloro-4-methoxy-benzoate (3.76 mmol, 0.864 g) was added ethanol (15 mL), sodium hydroxide (11.3 mmol, 0.451 g) and water (5 mL). The reaction mixture was stirred overnight at room temperature. The reaction mixture was concentrated under reduced pressure to remove the ethanol solvent. The aqueous phase was acidified to about pH 4 with concentrated HCl and then concentrated under reduced pressure to remove water. The residue was dissolved in water and ethyl acetate and the phases were separated. The organic phase was concentrated under reduced pressure to give 3-amino-2-chloro-4-methoxy-benzoic acid (3.67 mmol, 0.740 g, 98%) as an off-white solid, which did not require further purification.

[0125] Step 6 To a flask containing 3-amino-2-chloro-4-methoxy-benzoic acid (3.70 mmol, 0.740 g) was added 2,3,4,5,6-pentafluorophenol (4.20 mmol, 0.780 g), dichloromethane (37 mL) and 1-3-(dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (4.20 mmol, 0.850 g). The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure to remove the solvent. The reaction residue was dissolved in ethyl acetate and water. The phases were separated and then the aqueous phase was further extracted with ethyl acetate. The organic phases were combined and concentrated under reduced pressure to give (2,3,4,5,6-pentafluorophenyl) 3-amino-2-chloro-4-methoxy-benzoate (estimated 3.70 mmol, estimated yield %) as an orange oil, which was used without further purification as the crude product.

[0126] Step 7 A flask containing (2,3,4,5,6-pentafluorophenyl) 3-amino-2-chloro-4-methoxy-benzoate (3.70 mmol, 1.36 g) was charged with 1-methyltetrazol-5-amine (4.07 mmol, 0.403 g), acetonitrile (27 mL), and 2-t-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (8.14 mmol, 2.30 g, 2.43 mL). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by the addition of aqueous 2M HCl and then extracted with ethyl acetate. The organic phases were combined, washed with water, and concentrated under reduced pressure to give an orange oil. The crude material was purified by normal-phase flash chromatography (0 - 10% methanol in dichloromethane) to give 3-amino-2-chloro-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide (2.21 mmol, 0.624 g, 60%) as a pale orange solid. 1 H NMR (methanol): 7.04 (d, 1H), 6.91 (d, 1H), 4.03 (s, 3H), 3.94 (s, 3H).

[0127] Step 8 Thionyl chloride (23.5 mmol, 2.80 g, 1.68 mL) was added to a flask containing 2-fluoropropanoic acid (10.9 mmol, 1.00 g). The reaction mixture was stirred at 60 °C for 4 hours. The product was filtered off to give 2-fluoropropanoyl chloride (6.81 mmol, 0.753 g, 63%) as a colorless oil. 1 H NMR (chloroform): 5.21 (m, 0.5H), 5.08 (m, 0.5H), 1.74 (d, 1.5H), 1.68 (d, 1.5H)

[0128] Step 9 To a flask containing 3-amino-2-chloro-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide (0.707 mmol, 0.200 g) was added acetonitrile (8 mL) and 2-fluoropropanoyl chloride (1.41 mmol, 0.209 g). The reaction mixture was heated at 60 °C for 4 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude material was purified by normal-phase flash chromatography (0 - 10% methanol in dichloromethane) to give 2-chloro-3-(2-fluoropropanoylamino)-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide (Compound 1.031) (0.555 mmol, 0.198 g, 79%) as a yellow solid. 1 H NMR (methanol): 7.69 (d, 1H), 7.17 (d, 1H), 5.25 (m, 0.5H), 5.13 (m, 0.5H), 4.03 (s, 3H), 3.92 (s, 3H), 1.68 (d, 1.5H), 1.61 (d, 1.5H).

[0129] Preparation Example 10: Compound 1.030 Step 1 Prepare 3-amino-2-chloro-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide as described above.

[0130] Step 2 To a flask containing 3-amino-2-chloro-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide (0.531 mmol, 0.150 g) was added acetonitrile (6 mL) and acetyl chloride (1.06 mmol, 0.0833 g). The reaction mixture was stirred at 60 °C for 2 hours. The reaction mixture was concentrated under reduced pressure to remove the solvent. The crude material was triturated with ethyl acetate and the solid was dried under reduced pressure to give 3-acetamido-2-chloro-4-methoxy-N-(1-methyltetrazol-5-yl)benzamide (Compound 1.033) (0.490 mmol, 0.159 g, 92%) as a white solid. 1 H NMR (methanol): 7.66 (d, 1H), 7.16 (d, 1H), 4.04 (s, 3H), 3.92 (s, 3H), 2.17 (s, 3H).

[0131] Preparation Example 11: Compound 2.001 Step 1 Prepare 3-bromo-2-chloro-6-(trifluoromethoxy)aniline as described above.

[0132] Step 2 To a flask containing 3-bromo-2-chloro-6-(trifluoromethoxy)aniline (2.00 g, 6.89 mmol) was added tetrahydrofuran (30 mL). The reaction mixture was placed under a nitrogen atmosphere and stirred at -78 °C for 30 minutes. n-Butyllithium (2.5 M in hexane, 7.57 mmol, 3.00 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at -78 °C for 1 hour. Iodomethane (2.93 g, 20.7 mmol, 1.29 mL) was added to the reaction mixture. The reaction mixture was warmed to 0 °C and stirred for 3 hours. The reaction mixture was carefully quenched by slowly adding it to a saturated aqueous ammonium chloride solution. The mixture was stirred at room temperature for 15 minutes and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, dried, and concentrated under reduced pressure. The crude material was purified by normal-phase flash chromatography (0 - 5% ethyl acetate in cyclohexane) to give a product containing impurities. The crude material was purified by reverse-phase flash chromatography (60 - 100% (acetonitrile + 0.1% formic acid) in (water + 0.1% formic acid)) to give 3-bromo-2-chloro-N-methyl-6-(trifluoromethoxy)aniline (0.587 g, 1.93 mmol, 28%) as a brown oil. 1 1H NMR (chloroform): 7.03 - 6.99 (m, 1H), 6.99 - 6.94 (m, 1H), 3.08 (s, 3H).

[0133] Step 3 Tetrahydrofuran (41 mL) was added to a flask containing 3-bromo-2-chloro-N-methyl-6-(trifluoromethoxy)aniline (1.36 g, 4.47 mmol). The reaction mixture was placed under a nitrogen atmosphere and stirred at -78 °C for 1 hour. n-Butyllithium (2.5 M in hexane, 4.91 mmol, 2.00 mL) was added dropwise to the reaction mixture. The reaction mixture was stirred at -78 °C for 45 minutes. Iodomethane (1.90 g, 13.4 mmol, 0.834 mL) was added to the reaction mixture. The reaction mixture was warmed to 0 °C and stirred for 3.5 hours. The reaction mixture was carefully quenched by slowly adding it to an ice-cold saturated aqueous ammonium chloride solution. The mixture was stirred at 0 °C for 15 minutes and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, dried, and concentrated under reduced pressure. The crude material was purified by normal-phase flash chromatography (0 - 1% ethyl acetate in cyclohexane) to afford 3-bromo-2-chloro-N,N-dimethyl-6-(trifluoromethoxy)aniline (0.520 g, 1.63 mmol, 37%). 1 1H NMR (chloroform): 7.35 (d, J = 8.9 Hz, 1H), 7.01 (m, 1H), 2.87 (s, 6H).

[0134] Step 4 3-Bromo-2-chloro-N,N-dimethyl-6-(trifluoromethoxy)aniline (0.520 g, 1.63 mmol) was placed in a container, and palladium(II) acetate (0.0367 g, 0.163 mmol), Xantphos (0.195 g, 0.327 mmol), N-formylsaccharin (0.776 g, 3.67 mmol), and 5-methyl-1,3,4-oxadiazol-2-amine (1.46 g, 14.7 mmol) were added. 1-Methyl-2-pyrrolidinone was added to the container to make the total volume in the container 20 mL. 1-Methyl-2-pyrrolidinone was added to a second container containing triethylamine (0.743 g, 7.35 mmol, 1.02 mL) to make the total volume in the container 20 mL. This reaction was carried out in a Uniqsis FlowSyn. These two solutions were injected into a sample loop via a T-piece and then circulated through a 20 mL stainless steel coil heated to 170 °C. The flow rate was set so that the total residence time was 20 minutes. The reaction mixture was concentrated under reduced pressure to remove the solvent 1-methyl-2-pyrrolidinone. The residue was purified by reverse phase HPLC to obtain a product containing impurities. The crude material was purified by normal phase flash chromatography (10 - 80% ethyl acetate in cyclohexane) to obtain 2-chloro-3-(dimethylamino)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-4-(trifluoromethoxy)benzamide (Compound 2.001) (0.174 g, 0.478 mmol, 29%) as a pale yellow solid. 1 H NMR (methanol): 7.37 - 7.34 (m, 2H), 2.90 (s, 6H), 2.51 (s, 3H).

[0135] Table 1 - Examples of herbicidal compounds of the present invention. The compound is characterized using NMR as described or LCMS using the following conditions. Waters Aquity UPLC-MS equipped with Sample Manager FTN, H-class QSM, Column Manager, 2×Column Manager Aux, light-emitting diode array, ELSD, and Sample Organizer, and Waters HSS C18 column (column length 50 mm, column inner diameter 2.3 mm, particle size 1.8 microns) in QDA SQD 2. The analysis was carried out using a runtime of 4 minutes according to the following gradient table.

[0136]

Table 1

[0137]

Table 2-1

Table 2-2

Table 2-3

Table 2-4

Table 2-5

Table 2-6

Table 2-7

Table 2-8

Table 2-9

Table 2-10

Table 2-11

Table 2-12

Table 2-13

Table 2-14

Table 2-15

Table 2-16

Table 2-17

Table 2-18

Table 2-19

Table 2-20

Table 2-21

Table 2-22

Table 2-23

Table 2-24

Table 2-25

Table 2-26

Table 2-27

Table 2-28

Table 2-29

Table 2-30

Table 2-31

Table 2-32

Table 2-33

Table 2-34

Table 2-35

Table 2-36

Table 2-37

Table 2-38

Table 2-39

Table 2-40

Table 2-41

Table 2-42

Table 2-43

Table 2-44

Table 2-45

Table 2-46

Table 2-47

Table 2-48

Table 2-49

Table 2-50

Table 2-51

Table 2-52

Table 2-53

Table 2-54

Table 2-55

Table 2-56

Table 2-57

Table 2-58

Table 2-59

Table 2-60

Table 2-61

Table 2-62

Table 2-63

Table 2-64

[0138]

Table 3

[0139] Biological Examples Seeds of various test species are sown in standard soil in pots (Lolium perenne (LOLPE), Amaranthus retoflexus (AMARE), Abutilon theophrasti (ABUTH), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE)). After cultivation for 1 day (before germination) or 8 days (after germination) under controlled conditions in a greenhouse (24 / 16 °C, day / night; 14 hours of light; 65% humidity), these plants are sprayed with an aqueous spray solution obtained from a formulation of the technical active ingredient in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5). Unless otherwise specified, the compound is applied at 500 g / h. The test plants are then cultivated in the greenhouse under controlled greenhouse conditions (24 / 16 °C, day / night; 14 hours of light; 65% humidity) with watering twice a day. After 13 days, for before and after germination, the damage rate occurring to the plants is evaluated. The biological activity is shown in the following table on a 5-point scale (5 = 80 - 100%; 4 = 60 - 79%; 3 = 40 - 59%; 2 = 20 - 39%; 1 = 0 - 19%).

[0140]

Table 4-1

Table 4-2

Table 4-3

[0141] Table B2 - Comparative Test Seeds of the test species were sown in standard soil in pots. After cultivation for 1 day under controlled conditions (24 / 16 °C, day / night; 14 hours of light; 65% humidity) in a greenhouse, these plants were sprayed with an aqueous spray solution obtained from a formulation of the active ingredient in acetone (0.6 ml) and a formulation solution (45 ml) containing 10.6% of Emulsogen EL (registration number 61791-12-6), 42.2% of N-methylpyrrolidone, 42.2% of dipropylene glycol monomethyl ether (CAS RN 34590-94-8), and 0.2% of X-77 (CAS RN 11097-66-8).

[0142] Subsequently, the test plants were cultivated by watering twice a day under controlled conditions (24 / 16 °C, day / night; 14 hours of light; 65% humidity) in a greenhouse. After 14 days, the test was evaluated (100 = total damage to the plants; 0 = no damage to the plants).

[0143] Test species: ABUTH (Abutilon theophrasti); BROTE (Bromus tectorum); ECHCG (Echinochloa crus-galli); SINAR (Sinapis arvensis).

[0144]

Table 5-1

Table 5-2

[0145] C1 is compound 4-659 disclosed in International Publication No. 2012 / 028579. As can be understood, unexpected improvement in weed control was observed due to the substitution of the 4-chloro substituent in the phenyl ring according to the present invention with a haloalkoxy group.

Claims

1. Formula (I): 【Chemical 1】 (wherein Q is Q 1 or Q 2 【Chemical 2】 is; R 1a is selected from the group consisting of C 1 -C 4 alkyl-, C 1 -C 4 haloalkyl-, C 1 -C 4 alkoxy-C 1 -C 4 alkyl- and C 1 -C 4 haloalkoxy-C 1 -C 4 alkyl-; R 1b is selected from the group consisting of C 1 -C 4 alkyl-, C 1 -C 4 haloalkyl-, C 1 -C 4 alkoxy-C 1 -C 4 alkyl- and C 1 -C 4 haloalkoxy-C 1 -C 4 alkyl-; R 2 is selected from the group consisting of halogen, C 1 to C 6 alkyl-, C 1 to C 3 alkoxy-, C 1 to C 6 haloalkyl-, C 1 to C 3 haloalkoxy- and -S(O) p C 1 to C 6 alkyl; R 3 is C 1 to C 6 haloalkyl; R 4 is C 1 to C 6 alkyl-, C 1 to C 6 haloalkyl-, C 1 to C 6 alkyl-C(O)-, C 1 to C 6 haloalkyl-C(O)-, C 3 to C 6 cycloalkyl-, C 3 to C 6 cycloalkyl-C 1 to C 3 alkyl-, C 3 to C 6 cycloalkyl-C(O)-, C 1 to C 3 alkoxy-C 1 to C 3 alkyl-, C 1 to C 3 alkoxy-C 1 to C 3 alkyl-C(O)-, -C(O)-phenyl and -C(O)-heteroaryl, and wherein the phenyl, heteroaryl or C 3 to C 6 cycloalkyl may be optionally substituted by one, two or three substituents selected from the group consisting of halogen, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl and C 1 to C 6 alkoxy; R 5 is selected from the group consisting of hydrogen, C 1 -C 6 alkyl-, C 1 -C 6 haloalkyl and C 1 -C 6 cycloalkyl; or R 4 and R 5 together with the nitrogen atom to which they are attached form a 5- or 6-membered saturated heterocycle which may optionally be oxo-substituted; and p is 0, 1 or 2) a compound or an agriculturally acceptable salt thereof.

2. R 1a or R 1b is a compound according to claim 1 selected from the group consisting of methyl, ethyl and n-propyl.

3. Q is Q 1 and R 1a is methyl, the compound according to claim 1 or 2

4. Q is Q 2 and R 1b is methyl, the compound according to claim 1 or 2

5. R 2 is methyl, Cl, -CF 3 and -SO 2 methyl, and is a compound according to any one of claims 1 to 4, selected from the group consisting of.

6. R 2 The compound according to claim 5, wherein R is Cl.

7. R 3 is -CF 3 or -CHF 2 and is the compound according to any one of claims 1 to 6.

8. R 4 is selected from the group consisting of C 1 -C 6 alkyl-, C 1 -C 6 alkyl-C(O)-, and C 3 -C 6 cycloalkyl-; the compound according to any one of claims 1 to 7

9. R 4 is -C(O)-heteroaryl, where said heteroaryl is optionally substituted by one, two or three substituents selected from the group consisting of halogen, C 1 ~C 6 alkyl, C 1 ~C 6 haloalkyl and C 1 ~C 6 alkoxy, and is a compound according to any one of claims 1 to 7.

10. R 5 is hydrogen or C 1 -C 6 -alkyl, a compound according to any one of claims 1 to 9.

11. A herbicidal composition comprising the compound according to any one of Claims 1 to 10 and an agriculturally acceptable formulation adjuvant.

12. The herbicidal composition according to Claim 11, further comprising at least one additional pesticidal agent.

13. The herbicidal composition according to Claim 12, wherein the additional pesticidal agent is a herbicide or a herbicide safener.

14. A method for controlling weeds in a breeding ground, the method comprising the step of applying to the breeding ground the composition according to any one of Claims 11 to 13 in an amount effective for weed control.

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

16. Compound of formula (II) 【Chemical Formula 3】 (wherein, R 2 , R 3 , R 4 and R 5 are as defined in the compound of formula (I) according to any one of claims 1 to 10 above)

17. Compound of formula (V) 【Chemical Formula 4】 (wherein, R 2 , R 3 , R 4 and R 5 are as defined in the compound of formula (I) according to any one of claims 1 to 10 above)

18. Compound of formula (VIa) [Chemical Formula 5] (wherein, "Alk" is C 1 to C 6 alkyl, and R 2 , R 3 , R 4 and R 5 are as defined in the compound of formula (I) according to any one of claims 1 to 10 above). ​

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