Isoxazolidine derivatives as herbicidal compounds

Abstract

The present invention relates to a compound having formula (I) or an agronomically acceptable salt of said compound, wherein A1, A2, A3, X1, R3, R4, R5, R6 are as defined herein. The invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I) for controlling weeds, in particular in crops of useful plants. # imgabs0 #

Description

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

[0002] The herbicide 3-isoxazolidinone is known from US 4,405,357. The herbicide isoxazolidine-3,5-dione is known from US 4,302,238. The present invention relates to novel 3-isoxazolidinone and isoxazolidine-3,5-dione compounds. Therefore, according to the present invention, there is provided a compound of formula (I):

[0003]

[0004] or an agronomically acceptable salt thereof, wherein:

[0005] A 1 Yes CR 1 R 2 or C(O);A 2 Selected from the group consisting of: CR 7 R 8 、C(O)、O、S(O) p and N(R 11 );A 3 Selected from the group consisting of: CR 9 R 10 、C(O)、O、S(O) p and N(R 11 );X 1 O or S; R 1 Selected from the group consisting of hydrogen, halogen, HO-, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkoxy-, C1-C3 alkyl-C(O)O-, HOC(O)C1-C6 alkoxy-, C1-C6 alkoxy-C(O)-C1-C6 alkoxy-, C1-C3 alkyl-S(O) p - and C1-C3 alkyl-S(O) p C1-C6 alkoxy-; R 2 is hydrogen; R 3 is a C1-C3 alkyl group; R 4 is a C1-C3 alkyl group; R 5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 6 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; provided that R 5 and R 6Not all hydrogen; or R 5 and R 6 Together they are =O or -(CH2) n -; and R 7 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 8 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 7 and R 8 Together is -(CH2) n -; and R 9 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 10 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; R 9 and R 10 Together is -(CH2) n -; R 11 is hydrogen or C1-C3 alkyl; n is independently 2, 3, 4, 5 or 6; and p is independently 0, 1 or 2.

[0006] C1-C6 alkyl - includes, 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). C1-C3 alkyl includes methyl (Me, CH3), ethyl (Et, C2H5) and propyl (Pr, such as isopropyl and n-propyl).

[0007] Halogen (or halo) includes, for example, fluorine, chlorine, bromine or iodine. The above applies correspondingly to halogen in other defined contexts, such as haloalkyl.

[0008] 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-tetrafluoropropyl and 2,2,2-trichloroethyl and heptafluoro-n-propyl. C1-C2 haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, pentafluoroethyl, or 1,1-difluoro-2,2,2-trichloroethyl.

[0009] The C1-C6 alkoxy group includes methoxy, ethoxy and isopropoxy-.

[0010] C1-C6 haloalkoxy - includes, for example, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2-fluoroethoxy, 2-chloroethoxy, 2,2-difluoroethoxy or 2,2,2-trichloroethoxy, preferably difluoromethoxy, 2-chloroethoxy or trifluoromethoxy.

[0011] The C1-C6 alkoxy-C1-C6 alkoxy- includes, for example, methoxymethoxy- and ethoxymethoxy-.

[0012] C1-C3 alkyl-C(O)O- includes methyl-C(O)O- and ethyl-C(O)O-.

[0013] C1-C6 alkoxy-C(O)-C1-C6 alkoxy- includes methoxy-C(O)-methoxy- and ethoxy-C(O)-methoxy-.

[0014] C1-C3 alkyl-S(O) p C1-C6 alkoxy - including methyl - S(O) p Methoxy- and Ethyl-S(O) p Methoxy-.

[0015] The C3-C6 cycloalkyl group includes cyclopropyl, cyclopentyl and cyclohexyl.

[0016] The C1-C4 alkyl-S-(alkylthio) includes, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0017] The C1-C4 alkyl-S(O)-(alkylsulfinyl) includes, for example, methylsulfinyl, ethylsulfinyl, propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl or tert-butylsulfinyl, preferably methylsulfinyl or ethylsulfinyl.

[0018] The C1-C4 alkyl-S(O)2-(alkylsulfonyl) includes, for example, methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfonyl or ethylsulfonyl.

[0019] In one embodiment of the present invention, there is provided a compound having formula (I), wherein X 1 It's O.

[0020] In another embodiment of the present invention, there is provided a compound having formula (I), wherein R3 and R 4 It's methyl.

[0021] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 Yes CR 1 R 2 And R 1 Therefore, in a preferred embodiment of the present invention, there is provided a compound having formula 1a:

[0022]

[0023] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 Yes CR 1 R 2 And R 1 It is a C1-C6 alkoxy group.

[0024] In another embodiment of the present invention, there is provided a compound having formula (I), wherein A 1 is C(O). Therefore, in a preferred embodiment of the present invention, there is provided a compound having formula 1b:

[0025]

[0026] In one embodiment of the present invention, a compound having formula (I), formula (Ia) or formula (Ib) is provided, wherein A 2 Selected from the group consisting of CH2, C(O), O, S and NH, preferably O.

[0027] In another embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein A 3 Selected from the group consisting of CH2, C(O), O, S and NH, preferably O.

[0028] In another embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein (i) A 2 and A 3 is O; (ii)A 2 is NH and A 3 is O; (iii)A 2 is O and A 3 is NH; (iv) A 2 and A 3 is NH; (v) A 2 is CH2 and A 3 is O; (vi) A 2 is O and A 3is CH2; (vii) A 2 is CH2 and A 3 is CH2; (viii) A 2 is O and A 3 is S; or (ix) A 2 is S and A 3 It's O.

[0029] In a preferred embodiment of the present invention, there is provided a compound having formula (I), formula (Ia) or formula (Ib), wherein A 2 and A 3 It's O.

[0030] In another embodiment of the present invention, there is provided a compound having Formula (I), Formula (Ia) or Formula (Ib), wherein R 5 and R 6 In a more preferred embodiment, R 5 and R 6 is independently selected from the group consisting of hydrogen, methyl and fluoro. 5 and R 6 is halogen, preferably fluorine.

[0031] Compounds of formula (I) may contain asymmetric centers and may exist as single enantiomers, in pairs of enantiomers in any ratio, or, in the case of more than one asymmetric center, in all possible ratios of diastereomers. Typically, one of the enantiomers has an enhanced biological activity compared to the other possibilities.

[0032] The present invention also provides agronomically acceptable salts of compounds of formula (I). Preferably, the compounds of formula (I) can form salts with amines, including primary, secondary and tertiary amines (e.g., ammonia, dimethylamine and triethylamine), alkali metal bases and alkaline earth metal bases, transition metal bases or quaternary ammonium bases.

[0033] The compounds of formula (I) according to the invention can be used as herbicides themselves, but they are usually formulated into herbicidal compositions using formulation adjuvants such as carriers, solvents and surfactants (SAAs). Therefore, the present invention further provides herbicidal compositions comprising a herbicidal compound according to any one of the preceding claims and an agriculturally acceptable formulation adjuvant. The compositions may be in the form of concentrates which are diluted before use, although ready-to-use compositions may also be prepared. The final dilution is usually carried out with water, but may be carried out using, for example, liquid fertilizers, micronutrients, biological organisms, oils or solvents instead of or in addition to water.

[0034] The herbicidal compositions generally comprise from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of formula I and from 1 to 99.9% by weight of formulation adjuvants, which preferably include from 0 to 25% by weight of surface-active substances.

[0035] The composition can be selected from a number of formulation types. These include emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water dispersible granules (WG), emulsifiable granules (EG), water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersants (OD), oil suspensions (OF), oil-soluble liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), parent drugs (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP) and soluble granules (SG). In any case, the formulation type selected will depend on the specific purpose envisioned and the physical, chemical and biological properties of the compound of formula (I).

[0036] 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 polysaccharides) and optionally one or more wetting agents, one or more dispersants or a mixture of said agents to improve water dispersibility / water solubility. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water-soluble granules (SG).

[0037] Wettable powders (WP) can be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents and preferably, one or more dispersants, and optionally, one or more suspending agents to facilitate dispersion in a liquid. The mixture is then ground into a fine powder. Similar compositions can also be granulated to form water dispersible granules (WG).

[0038] Granules (GR) may be formed by granulating a mixture of a compound of formula (I) and one or more powdered solid diluents or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) into a porous granular material such as pumice, attapulgite clay, Fuller's earth, kieselguhr, diatomaceous earth or corn cob meal, or from preformed blank particles by adsorbing a compound of formula (I) (or a solution thereof in a suitable agent) onto a hard core material such as sand, silicates, mineral carbonates, sulfates or phosphates and, if necessary, drying. Agents commonly used to aid absorption or adsorption include solvents such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones and esters and adhesives such as polyvinyl acetate, polyvinyl alcohol, dextrins, sugars and vegetable oils. One or more other additives such as emulsifiers, wetting agents or dispersants may also be included in the granules.

[0039] 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 water dilution or to prevent crystallization in a spray tank).

[0040] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) can be prepared by dissolving a compound of formula (I) in an organic solvent (optionally containing one or more wetting agents, one or more emulsifiers or a mixture of said agents). 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), dimethylamides of fatty acids (such as C8-C 10 EC products can spontaneously emulsify when added to water, producing an emulsion with sufficient stability to allow spray application by appropriate equipment.

[0041] The preparation of EWs involves obtaining a 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 into water containing one or more SAAs under high shear to produce an emulsion. Suitable solvents for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents having low solubility in water.

[0042] Microemulsions (ME) can be prepared by mixing water with a blend of one or more solvents and one or more SAAs to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in water or in a solvent / SAA blend. Suitable solvents for use in MEs include those described above for use in ECs or EWs. MEs can be oil-in-water systems or water-in-oil systems (which system is present can be determined by conductivity measurements) and can be suitable for mixing water-soluble pesticides and oil-soluble pesticides in the same formulation. MEs are suitable for dilution into water, remaining as microemulsions or forming conventional oil-in-water emulsions.

[0043] Suspension concentrates (SC) may include aqueous or non-aqueous suspensions of finely dispersed insoluble solid particles of a compound of formula (I). SC may be prepared by ball milling or bead milling a solid compound of formula (I) with one or more dispersants in a suitable medium to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition, and a suspending agent may be included to reduce the rate of particle settling. Alternatively, a compound of formula (I) may be dry-milled and added to water containing the reagents described above to produce a desired final product.

[0044] Aerosol formulations comprise a compound of formula (I) and a suitable propellant (e.g. n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable medium (e.g. water or a water-miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized hand-operated spray pump.

[0045] Capsule suspensions (CS) can be prepared in a similar manner to the preparation of EW formulations, but with an additional polymerization stage, so that an aqueous dispersion of oil droplets is obtained, wherein each oil droplet is wrapped by a polymer shell and contains a compound with formula (I) and optionally a carrier or diluent for the oil droplet. The polymer shell can be produced by an interfacial polycondensation reaction or by a coacervation procedure. These compositions can provide controlled release of compounds with formula (I) and they can be used for seed treatment. Compounds with formula (I) can also be formulated in a biodegradable polymer matrix to provide slow, controlled release of the compound.

[0046] The composition may include one or more additives to improve the biological performance of the composition, for example by improving wettability, retention or distribution on a surface; rain resistance on the treated surface; or absorption or flow of the compound of formula (I). Such additives include surfactants (SAAs), oil-based spray additives, such as certain mineral oils or natural vegetable oils (such as soybean and rapeseed oils), modified vegetable oils (such as methylated rapeseed oil (MRSO)), and blends of these with other bioenhancement adjuvants (ingredients that can assist or modify the action of the compound of formula (I)).

[0047] The wetting agent, dispersant and emulsifier may be a cationic type, anionic type, amphoteric type or nonionic type SAA.

[0048] Suitable cationic-type SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0049] Suitable anionic SAAs include alkali metal salts of fatty acids, salts of aliphatic monoesters of sulfuric acid (e.g., sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g., sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butylnaphthalenesulfonate, and mixtures of sodium di-isopropyl-naphthalenesulfonate and sodium tri-isopropyl-naphthalenesulfonate), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3-sulfate), ether carboxylates (e.g., sodium laureth-3-carboxylate), phosphates (products from the reaction of one or more fatty alcohols with phosphoric acid (mainly monoesters) or with phosphorus pentoxide (mainly diesters), for example, the reaction of lauryl alcohol with tetraphosphoric acid; these products may additionally be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphates / sulfates of tristyrylphenol.

[0050] Suitable amphoteric types of SAA include betaine, propionate and glycinate.

[0051] Suitable SAAs of the nonionic type include condensation products of alkylene oxides (such as ethylene oxide, propylene oxide, butylene oxide or mixtures thereof) with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or with alkylphenols (such as octylphenol, nonylphenol or octylcresol); partial esters derived from long-chain fatty acids or hexitol anhydrides; condensation products of the partial esters with ethylene oxide; block polymers (comprising ethylene oxide and propylene oxide); alkanolamides; monoesters (such as fatty acid polyethylene glycol esters); amine oxides (such as lauryl dimethyl amine oxide); lecithin and sorbitan and their esters, alkyl polyglycosides and tristyrylphenol.

[0052] Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0053] The compounds of the present invention can also be used in admixture 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), bensulfuron, ametryn, amitriptyline, aminopyralid, cypermethrin, atrazine, flubutyric acid-M, quinclorac, benquitrione, benzylsulfuron-methyl (including benzylsulfuron-methyl), bentazon, bicyclic pyrone, bialaphos, bispyribac-sodium, bixlozone, herbicide, bromoxynil, butachlor, flubutyric acid-butyl, mesotrione (including mesotrione-ethyl), chlorsulfuron (including chlorsulfuron-methyl), chlorsulfuron (including chlorsulfuron-ethyl), chlorotoluron, chlorsulfuron, cyproconazole, chlorpyrifos-butyl ... cyfos), clethodim, clodinafop-butyl (including clodinafop-butyl), clomazone, clopyralid, cyclopyranil, cyclopyrimorate, cyprosulfuron, cyhalofop-butyl (including cyhalofop-butyl-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, betaine, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloropropane, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts), bisclorac, fluazifop-butyl, fluazifop-butyl, dimethoate, dimethoate-s-propyl, dioxopyritrione, diquat dibromide, diquat , epyrifenacil, ethoxyfluralin, oxadiazine (including oxadiazine-ethyl), fenoxasulfone, benzazin, fenquinotrione, tetrazoline, fluazifop-butyl, bispyribac, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop-butyl (including fluazifop-butyl-butyl), fluazifop-butyl (including fluazifop-sodium), flufenacet, fluazifop-butyl ... fluroxypyr-meptyl), fluazifop-butyl, foramsulfuron, glufosinate (including L-glufosinate and ammonium salts of both), glyphosate (including its hydrazine, isopropyl ammonium and potassium salts), halauxifen (including halauxifen-methyl), fluazifop-methyl (including fluazifop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapyr, imazapyr, imazamox, indazine fluazifop-butyl, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (including iodofensulfuron-sodium), ioboxynil, isoproturon,Isotrione, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methizolin, isopropyl metolachlor, sulfamethoxazole, metribuzin, metsulfuron-methyl, propamide, nicosulfuron, norfadine, oxadiazine, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, bendisulfuron, picloram, pinoxaden, pretilachlor, primisulfuron-methyl, promethazine, propanil, oxadiazine, propyrisulfuron, propyrisulfuron, promethazine, procarb, prosulfuron, dimethoate pyraflufen (including pyraflufen-ethyl), pyraflufen, pyraflufen, pyrimisulfan, pyroxasulfone, pyraflufen, quinclorac, quinclorac, quizalofop-P (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, sulfasulfuron, pyraflufen ... hiencarbazone), thifensulfuron-methyl, tiafenacil, tolpyralate, benpyrazone, trimethoprim-butyl, triafamone, wild wheat chlorpyrifos, bensulfuron-methyl, bensulfuron-methyl (including bensulfuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazin, trifluralin, trifloxysulfuron, triazosulfuron, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4- Hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one,4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including agrochemically acceptable esters thereof, for example, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid methyl ester, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid prop-2-ynyl ester and 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid cyanomethyl ester), 3-ethyl-sulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxylic acid methyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(isopropylsulfonyl-methyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 2-[[3-[[3-chloro-5-fluoro-6-[3-methyl -2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]ethyl acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid tetrahydrofuran-2-ylmethyl ester, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid tetrahydrofuran-2-ylmethyl ester, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propionic acid, Fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-[(R)-propylsulfinyl]-4-(trifluoromethyl)benzamide, 2-Fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-propylsulfinyl-4-(trifluoromethyl)benzamide, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxyphenyl)-pyrimidine-4-carboxylic acid (2-fluorophenyl)methyl ester, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid, 3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-pyrazole-4-carbonyl)-1,5-dimethyl-quinazoline-2,4-dione,and [4-[3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-quinazoline-6-carbonyl]-2,5-dimethyl-pyrazol-3-yl]N,N-diethylcarbamate, 2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropionic acid methyl ester, and (2R)-2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropionic acid methyl ester.

[0054] Mixtures of compounds of formula (I) may also be in the form of esters or salts, as mentioned, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0055] The compounds of formula (I) can also be used in mixtures with other agrochemicals such as fungicides, nematicides or insecticides, examples of which are given in The Pesticide Manual.

[0056] The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1:100 to 1000:1.

[0057] These mixtures can advantageously be used in the abovementioned formulations ("active ingredient" in this case relates to the corresponding mixture of the compound of formula (I) with the mixing partner).

[0058] 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 fenthiocarb, cloquintocet (including cloquintocet-mexyl), cyclopropylsulfonamide, dichloropropene, fenthiocarb (including fenthiocarb-ethyl), fenthiocarb, fluazifop, fenthiocarb, isoxadiazole (including isoxadiazole-ethyl), mefenpyr (including pyrazole oxalate-diethyl), metcamifen and fenthiocyanate.

[0059] Particularly preferred are mixtures of compounds of formula (I) with cyprosulfamide, isoxadifen, clofometrexate and / or metcamifen.

[0060] The safeners of compounds 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. References to clofonethiol also apply to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts (as disclosed in WO 02 / 34048).

[0061] Preferably, the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, in particular from 20:1 to 1:1.

[0062] The present invention further provides a method for controlling weeds in a place, the method comprising applying a composition comprising a compound of formula (I) to the place in a controlled amount of weeds. In addition, the present invention may further provide a method for selectively controlling weeds at a place including crop plants and weeds, wherein the method comprises applying a composition according to the present invention to the place in a controlled amount of weeds. 'Control' means killing, reducing or delaying growth or preventing or reducing germination. It should be noted that the compounds of the present invention show greatly improved selectivity compared to known structurally similar compounds. Plants to be controlled are usually unwanted plants (weeds). 'Place' means the area where the plant is growing or will grow. Application can be applied to the place before and / or after emergence of crop plants. Some crop plants can inherently tolerate the herbicidal effect of compounds with formula (I). Preferred crop plants include corn, wheat, barley, soybeans and rice.

[0063] The application rate of the compound 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 the seed furrow; no-till application, etc.), the crop plants, the weed or weeds to be controlled, the prevailing climatic conditions and other factors governed by the method of application, the time of application and the target crop. The compound of formula I according to the invention is usually applied at a rate of from 10 g / ha to 2500 g / ha, in particular from 25 g / ha to 1000 g / ha, more particularly from 25 g / ha to 250 g / ha.

[0064] Application is usually carried out by spraying the composition, typically by means of a tractor-mounted sprayer for large areas, but other methods such as dusting (for powders), dripping or drenching may also be used.

[0065] Crop plants are to be understood as also including those crop plants which have been rendered tolerant to other herbicides or classes of herbicides (e.g. ALS-inhibitors, GS-inhibitors, EPSPS-inhibitors, PPO-inhibitors, HPPD-inhibitors, inhibitor-PDS, inhibitor-SDPS and ACCase-inhibitors) by conventional methods of breeding or by genetic engineering. Examples of crops which have been rendered tolerant to imidazolinones (e.g. imazamox) by conventional methods of breeding are Summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include, for example, maize varieties resistant to glyphosate and glufosinate, which are now and It is commercially available under the trademark ANTIQUID®.

[0066] Crop plants are also to be understood as those which have been rendered 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 potato (resistant to the Colorado beetle). Examples of Bt maize are Bt 176 corn hybrid (Syngenta Seeds). Bt toxins are proteins naturally produced by the soil bacterium 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 comprising one or more genes encoding insecticide resistance and expressing one or more toxins are (Corn), Yield (corn), (cotton), (cotton), (potato), as well as Plant crops or their seed material can both be resistant to herbicides and at the same time resistant to insect feeding ("stacked" transgenic events). For example, a seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.

[0067] Crop plants are also to be understood as including those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (for example improved storage stability, higher nutritional value and improved flavor).

[0068] These compositions can be used to control unwanted vegetation (collectively referred to as '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 may also be dicotyledonous species such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.

[0069] In a further aspect of the invention there is provided the use of a compound of formula (I) as defined herein as a herbicide.

[0070] Processes for preparing compounds such as compounds of formula (I) (which optionally may be agrochemically acceptable salts thereof) are now described and form a further aspect of the invention.

[0071] Solution 1

[0072] In which A 1 Yes-C(R 1 )(R 2 )-and X 1 In embodiments where 0 is O, a compound of formula (1) can be prepared from a compound of formula (2) wherein LG represents a suitable leaving group such as Br or Cl and a compound of formula (3). The compound of formula (2) is treated with an isoxazolidinone of formula (3) and a carbonate base such as potassium carbonate in a suitable solvent such as dimethylformamide.

[0073]

[0074] Solution 2

[0075] Compounds of formula (2) can be prepared from benzyl alcohols of formula (4).

[0076]

[0077] For example, where LG is Cl, the benzyl alcohol having formula (4) is treated with a chlorinating agent such as thionyl chloride.

[0078] Solution 3

[0079] Compounds of formula (4) can be prepared from compounds of formula (5) wherein Z is H or O-alkyl.

[0080]

[0081] For example, where Z is H, a compound of formula (5) is treated with a reducing agent such as sodium borohydride in a suitable solvent such as a toluene / isopropanol mixture.

[0082] Solution 4

[0083] The synthetic route used to obtain compounds of formula (5) will depend on Z, A 2 , A 3 , R 5 and R 6 For example, in the case where Z is H, a compound of formula (5) can be prepared from a compound of formula (6).

[0084]

[0085] A compound of formula (6) is reacted under suitable formylation conditions, for example by treatment with titanium tetrachloride and dichloro(methoxy)methane in a suitable solvent such as dichloromethane.

[0086] Solution 5

[0087] In another example, in A 2 It is S, A 3 It's O, R 5 and R 6 When Z is F and Z is H, the compound of formula (5) can be prepared from 2-chloro-5-hydroxy-4-iodo-benzaldehyde (7).

[0088]

[0089] 2-Chloro-5-hydroxy-4-iodo-benzaldehyde (7) is treated with [(bpy)CuSCF3] and a suitable base (eg potassium fluoride) in a suitable solvent (acetonitrile).

[0090] Solution 6

[0091] In an alternative approach, compounds of formula (4) can be prepared from benzyl alcohols of formula (8).

[0092]

[0093] A compound of formula (8) is treated with a chlorinating agent such as 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione in a suitable solvent such as acetonitrile.

[0094] Solution 7

[0095] Compounds of formula (8) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will depend on A 2 , A 3 , R 5 and R 6 In one method, compounds of formula (8) can be prepared from compounds of formula (9).

[0096]

[0097] For example, where Z is H, a compound of formula (9) is treated with a reducing agent such as sodium borohydride in a suitable solvent such as methanol.

[0098] Solution 8

[0099] Compounds of formula (9) may be commercially available. Alternatively, they may be prepared synthetically. The synthetic route will depend on Z, A 2 , A 3 , R 5 and R 6 For example, in A 2 and A 3 Where Z is O and Z is H, compounds of formula (9) can be prepared from 3,4-dihydroxybenzaldehyde (10).

[0100]

[0101] In one approach, 3,4-dihydroxybenzaldehyde (10) is treated with a dibromide of formula (11) and a suitable base (eg, potassium carbonate) in a suitable solvent (eg, acetonitrile).

[0102] Solution 9

[0103] In another alternative method, a compound of formula (1) (wherein A 2 and A 3=O) can be prepared from 2-chloro-6-chloropiperidinol (12) according to the following scheme.

[0104]

[0105] 2-Chloro-6-chloropiperidinol (12) is treated with a suitable oxidative chlorinating agent (e.g., phosphorus pentachloride) in a suitable solvent (e.g., chlorobenzene). 5-Chloro-6-(chloromethyl)-1,3-benzodioxol-2-one (13) is treated with an isoxazolidinone of formula (3) and a carbonate base (e.g., potassium carbonate) in a suitable solvent (e.g., dimethylformamide). A compound of formula (14) is treated with a ketone of formula (15) and an acid catalyst (e.g., p-toluenesulfonic acid) in a suitable solvent (e.g., toluene).

[0106] Solution 10

[0107] In a variation of Scheme 9, a compound of formula (1) wherein A 2 and A 3 =O) can be prepared from a compound having the formula (14) and a compound having the formula (11).

[0108]

[0109] A compound of formula (14) is treated with a dibromide of formula (11) and a suitable base such as potassium carbonate in a suitable solvent such as dimethylformamide.

[0110] Solution 11

[0111] In A 1 In the case of -C(=O)-, compounds of formula (1) can be prepared from compounds of formula (5) (wherein Z is H) according to the following scheme.

[0112]

[0113] The compound of formula (5) is treated with a hydroxylamine source (e.g. hydroxylamine hydrochloride) and a suitable base (e.g. sodium acetate) in a suitable solvent (e.g. ethanol) to give a compound of formula (16). The compound of formula (16) is treated with a suitable reducing agent (e.g. sodium cyanoborohydride) and a suitable acid (e.g. 4M hydrochloric acid in dioxane) in a suitable solvent (e.g. methanol). The compound of formula (17) is treated with 2,2-dimethylmalonyl chloride and a suitable base (e.g. pyridine) in a suitable solvent (e.g. dichloromethane).

[0114] Solution 12

[0115] Compounds of formula (3) may be commercially available. For example, compounds of formula (3) (wherein R3 and R 4 is a methyl group, and R 1 and R 2 is hydrogen) is commercially available (CAS No. 81778-07-6). Alternatively, compounds of formula (3) can be prepared synthetically. For example, in R 1 is C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkoxy-, HOC(O)C1-C6 alkoxy-, C1-C6 alkoxy-C(O)-C1-C6 alkoxy- or C1-C3 alkyl-S(O) p C1-C6 alkoxy-, and R 2 In the case of hydrogen, the compound of formula (3) can be prepared from 3,3-dichloro-2,2-dimethylpropanoic acid (18).

[0116]

[0117] 3,3-Dichloro-2,2-dimethylpropanoic acid (18) is treated with a suitable chlorinating agent such as thionyl chloride to give 3,3-dichloro-2,2-dimethylpropanoyl chloride (19). 3,3-Dichloro-2,2-dimethylpropanoyl chloride (19) is treated with a suitable hydroxylamine source such as hydroxylamine (50% in H2O) to give 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid (20). 3,3-Dichloro-2,2-dimethyl-propane hydroxamic acid (20) is treated with an alcohol and a suitable base such as 1,8-diazabicyclo(5.4.0)undec-7-ene to give compounds of formula (3).

[0118] Solution 13

[0119] Compounds of formula (21) can be prepared from compounds of formula (22).

[0120]

[0121] A compound of formula (22) is treated with a suitable Lewis acid source such as boron trifluoride etherate in a suitable solvent such as toluene.

[0122] Solution 14

[0123] Compounds of formula (23) can be prepared from compounds of formula (24).

[0124]

[0125] A compound of formula (24) is treated with a suitable base (eg potassium carbonate) in a suitable solvent (eg acetone).

[0126] Solution 15

[0127] Compounds of formula (24) can be prepared from compounds of formula (17).

[0128]

[0129] A compound of formula (17) is treated with 3,3-dichloro-2,2-dimethylpropanoyl chloride (19) and a suitable base (eg pyridine) in a suitable solvent (eg dichloromethane) and optionally in the presence of a suitable additive (eg chloro(trimethyl)silane).

[0130] The following non-limiting examples provide specific synthetic methods for representative compounds of the present invention (as mentioned in Table 1 below).

[0131] Preparation Example

[0132] Example P1: Preparation of Compound 1.001

[0133] Step 1: Preparation of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde

[0134] To a solution of 5-chloro-2,2-dimethyl-1,3-benzodioxole (5.00 g, 26.5 mmol) in dichloromethane (50.0 mL) was added dichloro(methoxy)methane (3.74 g, 2.94 mL, 31.8 mmol) followed by titanium tetrachloride (5.59 g, 3.24 mL, 29.2 mmol) at -5 °C. The reaction mixture was stirred at 0 °C for 1.5 h. Ice water was added and the product was extracted with dichloromethane. The organic portion was purified by The mixture was filtered through a phase separator and then concentrated in vacuo. The crude material was purified by flash column chromatography (0-40% ethyl acetate in isohexane). The fractions containing the product were combined and concentrated to give 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carboxaldehyde (1.6 g, 7.5 mmol, 28%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 10.29 (s, 1H), 6.80 (s, 1H), 6.78 (s, 1H), 1.72 (s, 6H).

[0135] Step 2: Preparation of (6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methanol

[0136] At room temperature, under a nitrogen atmosphere, sodium borohydride (0.856 g, 22.6 mmol) was added in batches to a vigorously stirred solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carboxaldehyde (1.60 g, 7.55 mmol) in toluene (5.0 mL) and isopropanol (2.0 mL) within 15 min. The reaction was stirred for 2 h. Ethyl acetate and brine were added to the reaction. The phases were separated and the aqueous portion was extracted with another portion of ethyl acetate. The organic portions were combined, dried over MgSO4, filtered and concentrated in vacuo to obtain (6-chloro-2,2-dimethyl-1,3-benzodioxole-5-yl) methanol (1.45 g, 6.76 mmol, 44%) as a white solid. 1H NMR (400 MHz, chloroform) δ ppm 6.84 (s, 1H), 6.75 (s, 1H), 4.67 (d, 2H), 1.83 (t, 1H), 1.68 (s, 6H).

[0137] Step 3: Preparation of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxole

[0138] (6-Chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methanol (1.45 g, 6.76 mmol) and thionyl chloride (4.9 mL) were stirred at 60 ° C for 1 h. The reaction mixture was concentrated in vacuo and azeotroped with toluene to give 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxol (0.90 g, 3.9 mmol, 57%) as a white solid. 1HNMR (400 MHz, chloroform) δ ppm 6.80 (s, 1H), 6.76 (s, 1H), 4.62 (s, 2H), 1.68 (s, 6H).

[0139] Step 4: Preparation of 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0140] Potassium carbonate (310 mg, 2.21 mmol) and 4,4-dimethylisoxazolidine-3-one (130 mg, 1.13 mmol) were added to a solution of 5-chloro-6-(chloromethyl)-2,2-dimethyl-1,3-benzodioxole (260 mg, 1.12 mmol) in dimethylformamide (2.5 mL). The reaction was stirred at room temperature overnight. The reaction was quenched with water (50 mL) and the resulting precipitate was filtered and washed with water. The crude material was purified by flash column chromatography (0-20% ethyl acetate in cyclohexane). The fractions containing the product were combined and concentrated to give 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidine-3-one (229 mg, 0.73 mmol, 66%) as a colorless oil, which solidified when standing. 1H NMR (400MHz, CDCl3) δppm 6.74 (s, 1H), 6.71 (s, 1H), 4.72 (s, 2H), 4.01 (s, 2H), 1.68 (s, 6H), 1.27 (s, 6H).

[0141] Example P2: Preparation of Compound 1.002

[0142] Step 1: Preparation of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde oxime

[0143] Sodium acetate (0.745g, 8.98mmol) and hydroxylamine hydrochloride (0.624g, 8.97mmol) are added to a solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carboxaldehyde (1.59g, 7.48mmol) in ethanol (16mL) and the reaction mixture is stirred at reflux for 1h. The reaction mixture is cooled to RT and then concentrated in a vacuum. The residue is diluted with water and dichloromethane. Each layer is separated and the organic part is passed through a hydrophobic glass frit, and then concentrated in a vacuum to obtain 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carboxaldehyde oxime (1.66g, 7.29mmol, 98%) as a white solid. 1HNMR (400MHz, CDCl3) δppm8.48(s,1H),7.19(s,1H),6.73(s,1H),1.68(s,6H).

[0144] Step 2: Preparation of N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine

[0145] A solution of sodium cyanoborohydride (1.37 g, 21.7 mmol) in methanol (5.0 mL) and a 4 M hydrochloric acid solution in dioxane (5.6 mL) were simultaneously added dropwise over 30 min to a stirred solution of 6-chloro-2,2-dimethyl-1,3-benzodioxole-5-carbaldehyde oxime (1.65 g, 7.25 mmol) and a trace of methyl orange in methanol (20 mL) at room temperature. During the addition, care was taken to keep the reaction mixture between 19°C and 27°C and the pH below 3. After the addition was complete, the reaction mixture was stirred at room temperature for 30 min, during which time the reaction mixture was kept acidic by adding a small amount of 4 M hydrochloric acid in dioxane. The reaction mixture was cooled to 0°C and the pH was adjusted to 9.4 by dropwise addition of concentrated sodium hydroxide. The reaction mixture was concentrated in vacuo, then ethyl acetate (25 mL) and water (50 mL) were added and the layers were separated. The organic portion was dried over MgSO4, filtered and concentrated in vacuo to give N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol, 100%) as a light yellow solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.78 (s, 1H), 6.74 (s, 1H), 4.04 (s, 2H), 1.67 (s, 6H).

[0146] Step 3: Preparation of 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidinone-3,5-dione

[0147] 2,2-Dimethylmalonyl dichloride (1.22 g, 0.96 mL, 7.23 mmol) in dichloromethane (10 mL) was added dropwise to a solution of N-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.66 g, 7.23 mmol) and pyridine (1.16 g, 1.18 mL, 14.5 mmol) in dichloromethane (10 mL) at 0°C over 15 min. The reaction mixture was stirred at room temperature for 2 h and allowed to stand overnight. The reaction mixture was acidified with 2M hydrochloric acid, passed through a phase separator and the organic portion was concentrated in vacuo. The crude material was absorbed onto silica gel and purified via flash column chromatography (0-10% ethyl acetate in isohexane). The product-containing fractions were concentrated to give 2-[(6-chloro-2,2-dimethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidine-3,5-dione (1.94 g, 5.94 mmol, 82%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.78 (s, 1H), 6.71 (s, 1H), 4.96 (s, 2H), 1.68 (s, 6H), 1.44 (s, 6H).

[0148] Example P3: Preparation of Compound 1.005

[0149] Step 1: Preparation of 5-chloro-6-(chloromethyl)-1,3-benzodioxol-2-one

[0150] A solution of chloropiperidinol (10.0g, 53.6mmol) in chlorobenzene (50mL) was slowly added to a solution of phosphorus pentachloride (45.6g, 214mmol) in chlorobenzene (50mL) in 10min. The reaction was heated to reflux for 5h and then cooled to RT. Under stirring, the reaction mixture was added dropwise to water and then extracted with dichloromethane (x2). The organic parts were merged, passed through a phase separator and concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% ethyl acetate in isohexane). The fractions containing the product were merged and concentrated to obtain 5-chloro-6-(chloromethyl)-1,3-benzodioxole-2-one (10.8g, 49.4mmol, 92%) as a brown oil. 1H NMR (400MHz, CDCl3) δppm 7.42 (s, 1H), 7.35 (s, 1H), 4.70 (s, 2H).

[0151] Step 2: Preparation of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0152] To a solution of 5-chloro-6-(chloromethyl)-1,3-benzodioxole-2-one (10.8g, 49.4mmol) in dimethylformamide (111mL) was added potassium carbonate (20.7g, 150mmol) and 4,4-dimethylisoxazolidine-3-one (5.69g, 49.4mmol). The reaction was stirred at room temperature for 65h. The reaction was acidified to pH 2 with 2M hydrochloric acid and extracted with diethyl ether (x4). The organic parts were combined, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (20%-100% ethyl acetate in isohexane). The fractions containing the product were combined and concentrated to give 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidine-3-one (9.95g, 36.6mmol, 74%) as an off-white solid. 1H NMR (400MHz, d6-DMSO) δppm 9.43 (br.s, 1H), 9.31 (br.s, 1H), 6.76 (s, 1H), 6.74 (s, 1H), 4.55 (s, 2H), 4.00 (s, 2H), 1.12 (s, 6H).

[0153] Step 3: Preparation of 2-[(6-chloro-2,2-diethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0154] Pentan-3-one (1.2 g, 1.5 mL, 14 mmol) was added dropwise to a solution of 2-[(2-chloro-4,5-dihydroxy-phenyl)methyl]-4,4-dimethyl-isoxazolidin-3-one (150 mg, 0.552 mmol) and p-toluenesulfonic acid (27.0 mg, 0.149 mmol) in toluene (3 mL) in a sealed microwave vial. The solution was heated at 160 ° C for 2 h by microwave irradiation. The reaction mixture was concentrated to The product was added to 4-nitropropene and purified via flash column chromatography (0-10% ethyl acetate in isohexane). The fractions containing product were combined and concentrated to give 2-[(6-chloro-2,2-diethyl-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (9.0 mg, 0.03 mmol, 5%) as a brown gum. 1H NMR (400 MHz, CDCl3) δ ppm 6.73 (s, 1H), 6.69 (s, 1H), 4.72 (s, 2H), 4.02 (s, 2H), 1.91 (q, 4H), 1.26 (s, 6H), 0.96 (t, 6H).

[0155] Example P4: Preparation of Compound 1.014

[0156] Step 1: Preparation of (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol

[0157] A solution of (2,2-difluoro-1,3-benzodioxol-5-yl)methanol (7.66 g, 40.7 mmol) and 1,3,5-trichloro-1,3,5-triazine-2,4,6-trione (13.2 g, 57.0 mmol) in acetonitrile (100 mL) was stirred overnight at room temperature. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0-50% ethyl acetate in isohexane). The fractions containing the product were combined and concentrated to give (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol (2.30 g, 10.3 mmol, 25%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.29 (s, 1H), 7.10 (s, 1H), 4.74 (s, 2H), 1.98 (s, 1H).

[0158] Step 2: Preparation of 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole

[0159] To a solution of (6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methanol (1.50 g, 6.76 mmol) in dichloromethane (13.0 mL) was added carbon tetrabromide (2.69 g, 8.11 mmol) and the solution was cooled to 0° C. in an ice bath. Triphenylphosphine (2.66 g, 10.1 mmol) was added and the reaction was allowed to warm to room temperature and stirred for 3 h. The reaction mixture was concentrated to 40° C. The product was concentrated to give 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole (1.94 g, 6.76 mmol, 100%) as a colorless gum. 1H NMR (400 MHz, CDCl3) δ ppm 7.18 (s, 1H), 7.13 (s, 1H), 4.57 (s, 2H).

[0160] Step 3: Preparation of 3,3-dichloro-2,2-dimethyl-propionyl chloride

[0161] 3,3-dichloro-2,2-dimethyl-propionic acid (88.0 g, 514 mmol) was added to a stirred solution of thionyl chloride (148 mL) at room temperature. The mixture was heated to 70 ° C for 5 h. Excess thionyl chloride was removed by crude distillation (75 ° C). The residue was then purified by distillation (40 ° C at 5 mbar) to obtain 3,3-dichloro-2,2-dimethyl-propionyl chloride (87.0 g, 459 mmol, 89%) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ ppm 6.17 (s, 1H), 1.50 (s, 6H).

[0162] Step 4: Preparation of 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid

[0163] 3,3-dichloro-2,2-dimethyl-propanoyl chloride (3.00 g, 15.8 mmol) was added dropwise to an aqueous solution (8.09 g, 7.5 mL, 122 mmol) of hydroxylamine (50% by mass). The reaction mixture was stirred at room temperature for 10 min. The reaction mixture was extracted with dichloromethane, passed through a phase separator and concentrated in vacuo to give 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid (1.94 g, 10.4 mmol, 66%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 6.40 (br.s, 1H), 6.12 (s, 1H), 1.40 (s, 6H).

[0164] Step 5: Preparation of 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one

[0165] A solution of 1,8-diazabicyclo (5.4.0) undec-7-ene (0.835 g, 0.82 mL, 5.38 mmol) and 3,3-dichloro-2,2-dimethyl-propane hydroxamic acid (0.500 g, 2.69 mmol) in 2-trimethylsilylethanol (5.0 mL) was heated at 75 ° C overnight. The reaction mixture was diluted with EtOAc and washed with 2M hydrochloric acid (x2) and brine. The organic portion was concentrated to give 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.308 g, 1.33 mmol, 50%) as a light orange gum. This material was used crude in the next reaction without further purification.

[0166] Step 6: Preparation of 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one

[0167] To a solution of 5-(bromomethyl)-6-chloro-2,2-difluoro-1,3-benzodioxole (0.300 g, 1.05 mmol) in acetone (9.0 mL) was added potassium carbonate (0.295 g, 2.10 mmol) and 4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.292 g, 1.26 mmol). The reaction was stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate and filtered through a column of HPLC. Filter and concentrate On the flask, and purified via flash column chromatography (0-40% ethyl acetate in cyclohexane). Product containing fractions were concentrated to give 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-5-(2-trimethylsilylethoxy)isoxazolidin-3-one (0.157 g, 0.360 mmol, 34%) as a colorless gum. 1H NMR (400MHz, CDCl3) δppm 7.18(s,1H),7.13(s,1H),4.95(d,1H),4.92(s,1H),4.71(d,1H),3.75(ddd,1 H),3.50(ddd,1H),1.32(s,3H),1.23(s,3H),0.95-0.87(m,2H),0.00(s,9H).

[0168] Step 7: Preparation of 2-[6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-5-hydroxy-4,4-dimethyl-isoxazolidin-3-one

[0169] At 0 ° C, to 2- [(6- chloro-2,2-difluoro-1,3-benzodioxol-5-yl) methyl] -4,4-dimethyl -5- (2-trimethylsilylethoxy) isoxazolidin-3-one (0.157g, 0.360mmol) in toluene (3.6mL) solution was added dropwise boron trifluoride etherate (0.358g, 0.32mL, 2.52mmol). The reaction mixture was stirred at room temperature under nitrogen for 48h. Additional boron trifluoride etherate (0.358g, 0.32mL, 2.52mmol) was added and the reaction mixture was stirred at room temperature under nitrogen for another 24h. The reaction was quenched with saturated aqueous NaHCO3 and extracted with ethyl acetate (x3). The organic parts were combined, dried over MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash column chromatography (0-50% ethyl acetate in cyclohexane). The fractions containing the product were combined and concentrated to give 2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-5-hydroxy-4,4-dimethyl-isoxazolidin-3-one (60.0 mg, 0.179 mmol, 50%) as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.16 (s, 1H), 7.12 (s, 1H), 5.30 (d, 1H), 4.92-4.88 (m, 1H), 4.79-4.75 (m, 1H), 3.20 (d, 1H), 1.30 (s, 3H), 1.26 (s, 3H).

[0170] Example P5: Preparation of Compound 1.019

[0171] Step 1: Preparation of 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol

[0172] In 20min, methyl 2-(4-chloro-2-fluoro-phenyl) acetate (10.0g, 49.4mmol) was added dropwise to a stirred solution of anhydrous THF (250ml) with methyl magnesium chloride (3M solution in THF, 49.4mL, 148mmol). The reaction mixture was stirred at room temperature, then quenched with saturated aqueous NH4Cl, and extracted with EtOAc (x2). The combined organic portion was washed with brine, dried over sodium sulfate and concentrated. Purified by flash column chromatography, 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (5.0g, 24.7mmol, 50%) was obtained. 1H NMR (400MHz, CDCl3) δppm 7.20-7.16 (m, 1H), 7.08-7.06 (m, 2H), 2.77 (s, 2H), 1.23 (s, 6H).

[0173] Step 2: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran

[0174] To a stirred solution of 1-(4-chloro-2-fluoro-phenyl)-2-methyl-propan-2-ol (7.20 g, 35.5 mmol) in THF (80 mL) was added potassium tert-butoxide (1 M solution in THF, 88.8 mL, 88.8 mmol). The reaction was stirred at 65 ° C for 18 h, then quenched with 1 M hydrochloric acid and extracted with EtOAc. The organic phase was dried over sodium sulfate and concentrated. Purification by flash column chromatography (ethyl acetate / hexane) gave 6-chloro-2,2-dimethyl-3H-benzofuran (4.5 g, 24.6 mmol, 69%). 1H NMR (400 MHz, CDCl3) δ ppm 7.01 (d, 1H), 6.77 (d, 1H), 6.70 (s, 1H), 2.95 (s, 2H), 1.46 (s, 6H).

[0175] Step 3: Preparation of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carbaldehyde

[0176] At 0 ° C, under stirring, dimethylformamide (0.93mL, 12.0mmol) was added dropwise to phosphoryl chloride (2.73g, 1.63mL, 17.8mmol). At 0 ° C, the mixture was stirred for 15min, and then 6-chloro-2,2-dimethyl-3H-benzofuran (1.0g, 5.48mmol) was slowly added. The reaction was stirred at room temperature for 30min, and then stirred at 80 ° C overnight. The reaction mixture was cooled to 0 ° C and quenched by adding cold water. The mixture was extracted with EtOAc (x2) and the combined organic parts were concentrated. 6-chloro-2,2-dimethyl-3H-benzofuran-5-carboxaldehyde (0.170g, 0.81mmol, 15%) was obtained by flash column chromatography. 1HNMR (400MHz, CDCl3): δppm 10.29 (s, 1H), 7.73 (s, 1H), 6.74 (s, 1H), 2.99 (s, 2H), 1.49 (s, 6H).

[0177] Step 4: Preparation of (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methanol

[0178] At room temperature, under nitrogen atmosphere, sodium borohydride (0.057g, 1.44mmol) was added to a stirred solution of 6-chloro-2,2-dimethyl-3H-benzofuran-5-carboxaldehyde (0.101g, 0.48mmol) in toluene (0.48mL), isopropanol (0.096mL) and water (0.096mL) in batches over 15min. The reaction was stirred for 1h, and then ethyl acetate and brine were added. The phases were separated and the aqueous phase was extracted with another portion of ethyl acetate. The organic portions were combined, dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (0-10% ethyl acetate in cyclohexane) gave (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl) methanol (0.045g, 0.21mmol, 44%). 1H NMR (400MHz, CDCl3) δppm 7.19 (s, 1H), 6.74 (s, 1H), 4.67 (d, 2H), 2.97 (s, 2H), 2.00 (t, 1H) 1.46 (s, 6H).

[0179] Step 5: Preparation of 2-[(6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0180] Thionyl chloride (0.25g, 0.15mL, 2.1mmol) and (6-chloro-2,2-dimethyl-3H-benzofuran-5-yl) methanol (0.045g, 0.21mmol) are combined and stirred at 60 ° C for 1h. The reaction mixture is concentrated, then dissolved in toluene and concentrated (x3) repeatedly. The resulting residue is combined with 4,4-dimethylisoxazolidin-3-one (0.031g, 0.27mmol), dimethylformamide (0.26mL) and potassium carbonate (0.062g, 0.45mmol), and the mixture is stirred at room temperature overnight. Water and methyl tert-butyl ether are added and the phases are separated. The water layer is extracted with another portion of methyl tert-butyl ether (x2), and the combined organic portion is then washed with saturated aqueous NaHCO3 and brine (x2). The organic layer is dried over MgSO4, filtered and concentrated. Purification by flash column chromatography (0-25% ethyl acetate in cyclohexane) gave 2-[(6-chloro-2,2-dimethyl-3H-benzofuran-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.041 g, 0.13 mmol, 59%). 1H NMR (400 MHz, CDCl3) δ ppm 7.10 (s, 1H), 6.74 (s, 1H), 4.75 (s, 2H), 4.00 (s, 2H), 2.96 (s, 2H), 1.46 (s, 6H), 1.25 (s, 6H).

[0181] Example P6: Preparation of Compound 1.028

[0182] Preparation of ethyl 5-chloro-6-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-1,3-benzodioxole-2-carboxylate

[0183] To 2-[(2-chloro-4,5-dihydroxy-phenyl) methyl]-4,4-dimethyl-isoxazolidine-3-one (0.497g, 1.83mmol) in dimethylformamide (4.94mL) solution of potassium carbonate (0.532g, 3.66mmol) and ethyl dibromoacetate (0.90g, 0.47mL, 3.66mmol). The reaction mixture was heated to 70 ° C for 3h, then diluted with water and extracted with EtOAc (x2). The combined organic portion was washed with water and concentrated. Ethyl 5-chloro-6-[(4,4-dimethyl-3-oxo-isoxazolidine-2-yl) methyl]-1,3-benzodioxole-2-carboxylate (0.296g, 0.832mmol, 46%) was obtained by flash column chromatography (0-30% acetone in cyclohexane). 1H NMR (400MHz, CDCl3) δppm 6.91 (s, 1H), 6.88 (s, 1H), 6.33 (s, 1H), 4.80-4.69 (m, 2H), 4.32 (q, 2H), 4.02 (s, 2H), 1.34 (t, 3H), 1.26 (s, 6H).

[0184] Example P7: Preparation of Compound 1.029

[0185] Step 1: Preparation of methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate

[0186] To a solution of methyl 5-amino-2-chloro-4-hydroxybenzoate (2.105 g, 10.44 mmol) in acetonitrile (41.8 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (3.35 g, 3.284 mL, 20.88 mmol) and 1,1'-carbonyldiimidazole (1.89 g, 11.5 mmol). The reaction mixture was stirred at room temperature for 1 h, then diluted with saturated aqueous NH4Cl and extracted with EtOAc (x2). The combined organic fractions were concentrated to The product was purified by reverse phase flash column chromatography to give impure methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate (2.675 g), which was used in the subsequent step without further purification. 1H NMR (400 MHz, d6-DMSO) δ ppm 7.62 (s, 1H), 7.45 (s, 1H), 3.85 (s, 3H).

[0187] Step 2: Preparation of 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one

[0188] Diisobutylaluminum hydride (1M solution in hexanes, 27.1 mL, 27.1 mmol) was added dropwise to a solution of methyl 6-chloro-2-oxo-3H-1,3-benzoxazole-5-carboxylate (1.77 g, 7.76 mmol) in 2-methyltetrahydrofuran (22 mL) at 0°C under a nitrogen atmosphere. The reaction mixture was stirred at 0°C for 30 min and then at room temperature for 90 min. Additional diisobutylaluminum hydride (1M solution in hexanes, 7.76 mL, 7.76 mmol) was added at 0°C and the reaction was stirred at room temperature for 18 h. The last portion of diisobutylaluminum hydride (1M solution in hexanes, 7.76 mL, 7.76 mmol) was then added at 0°C and the reaction was stirred at room temperature for 2 h. The reaction mixture was quenched at 0°C by the dropwise addition of EtOAc. Saturated aqueous potassium sodium tartrate was added and the mixture was stirred vigorously at room temperature for 1.5h, then extracted with EtOAc (x3). The combined organic portion was washed with brine, dried over MgSO4 and concentrated. Purification by reverse phase flash column chromatography gave 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one (0.517g, 2.59mmol, 33%). 1H NMR (400MHz, d6-DMSO) δppm7.43 (s, 1H), 7.21 (s, 1H), 4.53 (s, 2H).

[0189] Step 3: Preparation of 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one

[0190] Carbon tetrabromide (0.821 g, 0.34 mL, 2.48 mmol) and triphenylphosphine (0.812 g, 3.10 mmol) were added to a solution of 6-chloro-5-(hydroxymethyl)-3H-1,3-benzoxazol-2-one (0.412 mg, 2.06 mmol) in dichloromethane (6.88 mL). The reaction mixture was stirred at room temperature for 30 min and then concentrated. 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one (0.428 g, 1.63 mmol, 79.0%) was obtained by flash column chromatography (0-50% acetone in cyclohexane). 1H NMR (400 MHz, d6-DMSO) δ ppm 7.54 (s, 1H), 7.36 (s, 1H), 4.78 (s, 2H).

[0191] Step 4: Preparation of 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H-1,3-benzoxazol-2-one

[0192] Potassium carbonate (0.261 g, 1.79 mmol) was added to a solution of 4,4-dimethylisoxazolidin-3-one (0.939 g, 8.15 mmol) in acetone (6.4 mL) at room temperature with stirring. A solution of 5-(bromomethyl)-6-chloro-3H-1,3-benzoxazol-2-one (0.428 g, 1.63 mmol) in acetone (6.4 mL) was then added dropwise over 15 min. The reaction mixture was concentrated to 4% by volume. The mixture was purified by flash column chromatography (0-70% acetone in cyclohexane) and then repurified by reverse phase flash column chromatography to give 6-chloro-5-[(4,4-dimethyl-3-oxo-isoxazolidin-2-yl)methyl]-3H-1,3-benzoxazol-2-one (0.269 g, 0.907 mmol, 56%). 1H NMR (400 MHz, CDCl3) δ ppm 7.25 (s, 1H), 7.12 (s, 1H), 4.85 (s, 2H), 4.05 (s, 2H), 1.27 (s, 6H).

[0193] Example P8: Preparation of Compound 1.031

[0194] Step 1: Preparation of 2-chloro-5-hydroxy-4-iodo-benzaldehyde

[0195] To the stirring solution of 2-chloro-5-hydroxy-benzaldehyde (4.00g, 25.6mmol) in DCM (100mL) and MeOH (100mL), NIS (6.34g, 28.1mmol) is added and the reaction mixture is stirred at room temperature for 2h. The reaction mixture is diluted with water and extracted with DCM (x3), then the organic layer combined is washed with brine, dried over Na2SO4 and concentrated. Purification by flash column chromatography (0-100% EtOAc in hexane) gives 2-chloro-5-hydroxy-4-iodo-benzaldehyde (3.50g, 12.4mmol, 48%). 1H NMR (400MHz, d6-DMSO) δppm 11.1 (s, 1H), 10.2 (s, 1H), 7.98 (s, 1H), 7.35 (s, 1H).

[0196] Step 2: Preparation of 5-chloro-2,2-difluoro-1,3-benzoxathiophene-6-carbaldehyde

[0197] Under nitrogen atmosphere, potassium fluoride (0.069g, 1.22mmol) and [(bpy)CuSCF3] (0.469g, 1.44mmol) are added to a solution of 2-chloro-5-hydroxy-4-iodo-benzaldehyde (0.333g, 1.18mmol) in acetonitrile (10mL). By microwave irradiation, the reaction mixture is heated at 100 ° C for 1h, then diluted with water and extracted with EtOAc (x3). The combined organic layer is washed with brine, dried over Na2SO4 and concentrated. Purification by flash column chromatography (0-100% EtOAc in hexane) gives 5-chloro-2,2-difluoro-1,3-benzothiophene-6-carboxaldehyde (0.265g, 1.12mmol, 95%). 1H NMR (400MHz, d6-DMSO) δppm 10.23 (s, 1H), 8.00 (s, 1H), 7.69 (s, 1H).

[0198] Step 3: Preparation of (5-chloro-2,2-difluoro-1,3-benzoxathiophen-6-yl)methanol

[0199] At 0 ° C, under a nitrogen atmosphere, sodium borohydride (0.040g, 1.05mmol) was added to a solution of 5-chloro-2,2-difluoro-1,3-benzoxathiophene-6-carboxaldehyde (0.250g, 1.05mmol) in MeOH (15mL). The reaction mixture was stirred at room temperature for 2h, then diluted with saturated aqueous NH4Cl and extracted with dichloromethane (x2). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give (5-chloro-2,2-difluoro-1,3-benzoxathiophene-6-yl) methanol (0.120g, 0.50mmol, 48%). 1H NMR (400MHz, d6-DMSO) δppm 7.55 (s, 1H), 7.35 (s, 1H), 5.58 (t, 1H), 5.53 (d, 2H).

[0200] Step 4: Preparation of 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiophene

[0201] At 0 ° C, under a nitrogen atmosphere, phosphorus tribromide (2.88g, 1mL, 10.6mmol) was added to a solution of (5-chloro-2,2-difluoro-1,3-benzoxathiophene-6-yl) methanol (0.20g, 0.84mmol) and DCM (30mL). The reaction mixture was stirred at room temperature for 2h, then diluted with water and extracted with dichloromethane (x2). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to give 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiophene (0.150g, 0.50mmol, 60%). 1H NMR (400MHz, d6-DMSO) δppm7.85 (s, 1H), 7.65 (s, 1H), 4.72 (s, 2H).

[0202] Step 5: Preparation of 2-[(5-chloro-2,2-difluoro-1,3-benzoxathiophen-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0203] Potassium carbonate (0.172g, 1.24mmol) was added to a solution of 6-(bromomethyl)-5-chloro-2,2-difluoro-1,3-benzoxathiophene (0.250g, 0.82mmol) and 4,4-dimethylisoxazolidin-3-one (0.115g, 0.99mmol) in tetrahydrofuran (20mL). The reaction mixture was stirred at 60 ° C for 3h, then diluted with water and then extracted with dichloromethane. The organic portion was washed with brine, dried over Na2SO4 and concentrated. 2-[(5-chloro-2,2-difluoro-1,3-benzoxathiophene-6-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.060g, 0.18mmol, 21%) was obtained by reverse phase flash column chromatography. 1H-NMR (400MHz, d6-DMSO) δppm 7.83 (s, 1H), 7.32 (s, 1H), 4.71 (s, 2H), 4.06 (s, 2H), 1.13 (s, 6H).

[0204] Example P9: Preparation of Compound 1.032

[0205] Step 1: Preparation of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde

[0206] A solution of (2,2-difluoro-1,3-benzodioxol-5-yl)methanol (0.99 g, 5.3 mmol) and N-chlorosuccinimide (1.7 g, 13 mmol) in acetonitrile (5 mL) was stirred overnight at room temperature. The reaction mixture was concentrated onto silica gel and purified by flash column chromatography (0-50% EtOAc in isohexane) to give 6-chloro-2,2-difluoro-1,3-benzodioxol-5-carbaldehyde (0.380 g, 1.72 mmol, 33%). 1H NMR (400 MHz, CDCl3) δ ppm 10.31 (s, 1H), 7.62 (s, 1H), 7.19 (s, 1H).

[0207] Step 2: Preparation of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde oxime

[0208] Pyridine (0.065mL, 0.80mmol) and hydroxylamine hydrochloride (0.057g, 0.82mmol) are added to a solution of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carboxaldehyde (0.160g, 0.73mmol) in ethanol (5mL) and the mixture is heated to reflux for 4h. The reaction mixture is concentrated, then diluted in dichloromethane and washed with 1M hydrochloric acid, water and brine. The organic portion is dried over MgSO4 and concentrated to obtain 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carboxaldehyde oxime (0.150g, 0.64mmol, 88%). 1H NMR (400MHz, CDCl3) δppm 8.50 (s, 1H), 7.58 (s, 1H), 7.10 (s, 1H).

[0209] Step 3: Preparation of N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine

[0210] A solution of sodium cyanoborohydride (0.801 g, 12.7 mmol) in methanol (7 mL) and a 4 M hydrochloric acid solution in dioxane (3.19 mL, 12.7 mmol) were added dropwise simultaneously over 15 min to a stirred solution of 6-chloro-2,2-difluoro-1,3-benzodioxole-5-carbaldehyde oxime (2.31 g, 9.81 mmol) and a trace of methyl orange in methanol (50 mL) at room temperature. During the addition, care was taken to keep the reaction mixture between 19° C. and 27° C. and pH below 3. The reaction mixture was stirred at room temperature for 2 h, during which time the reaction mixture was kept acidic by adding a small amount of 4 M hydrochloric acid in dioxane. The reaction mixture was concentrated and the resulting residue was washed with diethyl ether. The residue was then diluted in dichloromethane and water and the aqueous phase was adjusted to pH 9 by adding aqueous potassium carbonate. The layers were separated and the aqueous phase was extracted with another portion of dichloromethane. The combined organic fractions were washed with brine (x2), dried over MgSO4 and concentrated to give N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine (2.30 g, 9.68 mmol, 99%). 1H NMR (400 MHz, CDCl3) δ ppm 7.16 (s, 1H), 7.12 (s, 1H), 4.12 (s, 2H).

[0211] Step 4: Preparation of 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propionamide

[0212] At -10 ° C, under a nitrogen atmosphere, chloro(trimethyl)silane (0.46 g, 4.2 mmol) was added dropwise to a solution of N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]hydroxylamine (1.0 g, 4.2 mmol) and pyridine (1.2 mL, 15 mmol) in dichloromethane (20 mL). The reaction was stirred at -10 ° C for 30 min, and then at 0 ° C, within 10 min, a solution of 3,3-dichloro-2,2-dimethyl-propionyl chloride (0.80 g, 4.2 mmol) in dichloromethane (20 mL) was added dropwise. The reaction mixture was stirred at room temperature for 18 h, then diluted in dichloromethane and washed with water, brine, and a 1:1 mixture of brine and 2M hydrochloric acid (x2). The organic portion was washed with the last portion of brine, then dried over MgSO4 and concentrated. Purification by flash column chromatography (0-10% EtOAc in isohexane) gave 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propionamide (1.21 g, 3.11 mmol, 74%). 1H NMR (400 MHz, CDCl3) δ ppm 7.15 (s, 2H), 6.66 (s, 1H), 6.49 (br s, 1H), 4.95 (s, 2H), 1.49 (s, 6H).

[0213] Step 5: Preparation of 5-chloro-2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one

[0214] Potassium carbonate (0.862 g, 6.24 mmol) was added to a solution of 3,3-dichloro-N-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-N-hydroxy-2,2-dimethyl-propionamide (1.22 g, 3.12 mmol) in acetone (14 mL). The reaction mixture was stirred at room temperature for 3 h, then diluted in dichloromethane and washed with water. The organic portion was concentrated to give 5-chloro-2-[(6-chloro-2,2-difluoro-1,3-benzodioxol-5-yl)methyl]-4,4-dimethyl-isoxazolidin-3-one (0.923 g, 2.61 mmol, 84%). 1H NMR (400MHz, CDCl3) δppm 7.19 (s, 1H), 7.13 (s, 1H), 6.07 (s, 1H), 4.95 (d, 1H), 4.81 (d, 1H), 1.39 (s, 3H), 1.38 (s, 3H).

[0215] Further compounds of the invention are shown in Table 1 below, which were prepared in a manner analogous to those described above in Examples P1 to P9.

[0216] Table 1 Compounds of the present invention

[0217]

[0218]

[0219]

[0220]

[0221]

[0222]

[0223]

[0224] Biological Examples

[0225] Test B1

[0226] Seeds of various test species (Amaranthus retoflexus (AMARE), Setariafaberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE)) were sown in standard soil in pots. After one day of cultivation (pre-emergence) or after 8 days of cultivation (post-emergence) in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14 h light; 65% humidity), the plants were sprayed with an aqueous spray solution obtained as follows: i) the technical active ingredient was formulated in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5), or ii) the technical active ingredient was dissolved in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether) and then diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. Unless otherwise stated, the compound is applied at 250 g / ha. The test plants are then grown in a greenhouse under controlled conditions in a greenhouse (24°C / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice a day. Before and 13 days after emergence, the percentage of damage caused to the plant is evaluated. The following table shows biological activity on a five-point scale (5 = 81%-100%; 4 = 61%-80%; 3 = 41%-60%; 2 = 21%-40%; 1 = 0-20%).

[0227] Table B1. Post-emergence tests

[0228]

[0229]

[0230] *Applied at 170 g / ha Table B2. Pre-emergence test

[0231]

[0232]

[0233] *Applied at 170g / ha

[0234] Test B2

[0235] Seeds of various test species (Leptochloa chinesis (LEFCH), barnyard grass (ECHCG) and Cyperus esculentus (CYPES)) were sown in standard soil in pots. After one day of cultivation (pre-emergence) or 13 days of cultivation (post-emergence) in a greenhouse under controlled conditions (at 30°C / 20°C, day / night; 18 hours of light; 75% humidity), the plants were sprayed with an aqueous spray solution obtained as follows: the technical grade active ingredient was dissolved in a small amount of acetone and a special solvent and emulsifier mixture called IF50 (11.12% Emulsogen EL360 TM + 44.44% N-methylpyrrolidone + 44.44% Dowanol DPM glycol ether), and then diluted to the desired concentration using 0.2% Genapol XO80 (CAS No. 9043-30-5) in water as a diluent. The compound was applied at 500 g / ha. These test plants were then grown in a greenhouse under controlled conditions in a greenhouse (at 30°C / 20°C, day / night; 18 hours of light; 75% humidity) and watered twice a day. Before emergence and 13 days after emergence, the percentage of damage caused to the plants by the test was evaluated. The biological activity is shown in the following table on a five-point scale (5 = 81%-100%; 4 = 61%-80%; 3 = 41%-60%; 2 = 21%-40%; 1 = 0-20%).

[0236] Table B3. Post-emergence testing

[0237]

[0238] Table B4. Pre-emergence test

[0239]

[0240] Test B3: Comparative test (before emergence)

[0241] Seeds of the test species (barnyard grass, ECHCG) were sown in standard soil in pots. After one day of cultivation in a greenhouse under controlled conditions (at 24°C / 16°C, day / night; 14 hours of light; 65% humidity), the plants were sprayed with an aqueous spray solution obtained as follows: the technical grade active ingredient was prepared in 0.6 ml of acetone and 45 ml of a formulation solution containing 10.6% Emulsogen EL (registration number 61791-12-6), 42.2% N-methylpyrrolidone, 42.2% dipropylene glycol monomethyl ether (CASRN 34590-94-8) and 0.2% X-77 (CAS RN 11097-66-8).

[0242] These test plants are then grown under controlled conditions in a greenhouse (at 24°C / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice daily. After 14 days, the test is evaluated (100 = complete damage to the plant; 0 = no damage to the plant).

[0243] Table B5 Comparative pre-emergence data

[0244]

[0245]

[0246] C1 is a known compound disclosed in US 4,405,357. 5 / R 6 The substituents provide unexpected improvements in observed weed control.

Claims

1. A compound having formula (I), in A 1 Yes CR 1 R 2 or C(O); A 2 Selected from the group consisting of: CR 7 R 8 、C(O)、O、S(O) p and N(R 11 ); A 3 Selected from the group consisting of: CR 9 R 10 、C(O)、O、S(O) p and N(R 11 ); X 1 is O or S; R 1 Selected from the group consisting of hydrogen, halogen, HO-, C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkoxy-, C1-C3 alkyl-C(O)O-, HOC(O)C1-C6 alkoxy-, C1-C6 alkoxy-C(O)-C1-C6 alkoxy-, C1-C3 alkyl-S(O) p - and C1-C3 alkyl-S(O) p C1-C6 alkoxy-; R 2 It is hydrogen; R 3 is a C1-C3 alkyl group; R 4 is a C1-C3 alkyl group; R 5 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; and R 6 independently selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; provided that R 5 and R 6 Not all hydrogen; or R 5 and R 6 Together they are =O or -(CH2) n -; R 7 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; and R 8 Selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 7 and R 8 Together is -(CH2) n -; R 9 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; and R 10 Selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and C1-C6 alkoxy-; or R 9 and R 10 Together is -(CH2) n -; R 11 is hydrogen or C1-C3 alkyl; n is independently 2, 3, 4, 5 or 6; and p is independently 0, 1 or 2.

2. The compound of claim 1 having formula (I), wherein X 1 It's O.

3. A compound of formula (I) according to claim 1 or claim 2, wherein R 3 and R 4 It's methyl.

4. A compound according to any one of the preceding claims having formula (I), wherein A 1 Yes CR 1 R 2 , and R 1 It's hydrogen.

5. A compound of formula (I) according to any one of claims 1 to 3, wherein A 1 Yes CR 1 R 2 , and R 1 It is a C1-C6 alkoxy group.

6. A compound of formula (I) according to any one of claims 1 to 3, wherein A 1 It is C(O).

7. A compound according to any one of the preceding claims, wherein A 2 and A 3 It's O.

8. A compound according to any one of the preceding claims, wherein R 5 and R 6 Independently selected from the group consisting of hydrogen, methyl and fluoro.

9. A compound according to any one of the preceding claims, wherein R 5 and R 6 They are all methyl.

10. A compound according to any one of claims 1 to 8, wherein R 5 and R 6 It’s all fluorine.

11. A herbicidal composition comprising a compound of formula (I) according to any one of the preceding claims, and an agriculturally acceptable formulation adjuvant.

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

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

14. A method of controlling weeds at a locus, the method comprising applying to the locus a weed controlling amount of a composition according to any one of claims 11 to 13.

15. Use of a compound of formula (I) according to any one of claims 1 to 10 as a herbicide.

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