Substituted pyridazinones as herbicides

Abstract

The present invention relates to herbicidal substituted phenyl-pyridazine-dione and substituted phenyl-pyridazinone derivatives of formula (I), as well as processes and intermediates used for the preparation of such derivatives. The invention further extends to herbicidal compositions containing such derivatives, and the use of such compounds and compositions in the control of undesirable plant growth, particularly in the control of weeds, such as broadleaf dicotyledonous weeds, in crops of useful plants. [Formula 1] TIFF2022540908000091.tif57158

Description

Technical Field

[0001] The present invention relates to herbicidal substituted phenyl-pyridazine-diones and substituted phenyl-pyridinone derivatives of formula (I), and to methods and intermediates used in the preparation of such derivatives. The present invention further relates to herbicidal compositions containing such derivatives, and to the use of such compounds and compositions in the control of unwanted plant growth: in particular, their use in the control of weeds such as broad-leaved dicotyledonous weeds in crops of useful plants.

Background Art

[0002] Herbicidal pyridinones are known from WO 2009 / 086041 pamphlet. Further, herbicidal 5 / 6-membered heterocyclyl-substituted pyridinones are known from WO 2011 / 045271 pamphlet. On the other hand, WO 2013 / 160126 pamphlet describes indolyl-pyridinone derivatives showing herbicidal activity.

Summary of the Invention

Means for Solving the Problems

[0003] The present invention is based on the discovery of substituted phenyl-pyridazine-diones and substituted phenyl-pyridinone derivatives of formula (I) which surprisingly exhibit good herbicidal activity.

[0004] Thus, in a first aspect, a compound of formula (I)

Chemical Formula

Chemical formula

[0005] The compounds of formula (I) may contain asymmetric centers and may exist as a single enantiomer, as a pair of enantiomers in any ratio, or, when two or more asymmetric centers are present, include all possible ratios of diastereoisomers. Typically, one of the enantiomers has enhanced biological activity compared to the other possible enantiomers.

[0006] Similarly, in the case of disubstituted alkenes, these may exist as the E-isomer or the Z-isomer or as a mixture of both in any proportion.

[0007] Furthermore, the compounds of formula (I) may be in equilibrium with another tautomer. For example, the compound of formula (I-i), i.e., the compound of formula (I) (wherein R 2 is hydrogen and G is hydrogen) can be depicted as at least three tautomers:

Chemical formula

[0008] It should be understood that all tautomers (single tautomer or a mixture thereof), racemic mixtures and single isomers are included within the scope of the present invention.

[0009] Each alkyl moiety can be straight-chain or branched, either alone or as part of a larger group (such as alkoxy, alkylthio, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, or dialkylaminocarbonyl, etc.). Typically, alkyl is, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, neopentyl, or n-hexyl. The alkyl group is generally a C1-C6 alkyl group (except when already more narrowly defined), preferably a C1-C4 alkyl or C1-C3 alkyl group, and more preferably a C1-C2 alkyl group (such as methyl).

[0010] Alkenyl and alkynyl moieties can be in linear or branched form, and the alkenyl moiety can, if desired, be of either (E)- or (Z)-configuration. The alkenyl or alkynyl moiety is typically C2-C4 alkenyl or C2-C4 alkynyl, more particularly vinyl, allyl, ethynyl, propargyl or prop-1-ynyl. The alkenyl and alkynyl moieties can contain one or more double and / or triple bonds in any combination; preferably, they contain only one double bond (in the case of alkenyl) or only one triple bond (in the case of alkynyl).

[0011] Preferably, the term cycloalkyl refers to cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

[0012] In the context of this specification, the term "aryl" preferably means phenyl. The term "heteroaryl", as used herein, means a monocyclic or bicyclic aromatic ring system containing at least one ring heteroatom. Preferably, the monocyclic ring system contains one, two or three ring heteroatoms, and the bicyclic ring system contains one, two, three or four ring heteroatoms, each heteroatom being independently selected from nitrogen, oxygen and sulfur.

[0013] Typically, the monocyclic heteroaryl ring is selected from the group consisting of furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, 1,2,3-triazinyl, 1,2,4-triazinyl, or 1,3,5-triazinyl rings.

[0014] Typically, a bicyclic heteroaryl ring system is selected from the group consisting of indolizine, indole, iso-indole, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, purine, 4H-quinolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinoxaline, 1,8-naphthyridine, or pteridine ring systems.

[0015] A heterocyclyl group and a heterocyclic ring (alone or as part of a larger group, e.g., a heterocyclyl-alkyl-) are ring systems containing at least one heteroatom, may be in monocyclic or bicyclic form, and may be partially saturated or fully saturated. Preferably, a heterocyclyl group preferably contains up to 2 heteroatoms selected from nitrogen, oxygen, and sulfur. Examples of heterocyclic groups include oxetanyl, thietanyl, azetidinyl, and 7-oxa-bicyclo[2.2.1]hept-2-yl. A heterocyclyl group containing a single oxygen atom as the heteroatom is most preferred.

[0016] Halogen (or halo) includes fluorine, chlorine, bromine, or iodine. Correspondingly, the same applies to halogen in the context of other definitions such as haloalkyl or halophenyl.

[0017] Haloalkyl groups having a chain length of 1 to 6 carbon atoms are, 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, and 2,2,2-trichloroethyl, heptafluoro-n-propyl, and perfluoro-n-hexyl.

[0018] The alkoxy group preferably has a chain length of 1 to 6 carbon atoms. Alkoxy is, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy or tert-butoxy or pentyloxy or hexyloxy isomers, preferably methoxy and ethoxy. It should also be understood that two alkoxy substituents can be present on the same carbon atom.

[0019] Haloalkoxy is, 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.

[0020] C1-C6 alkyl-S-(alkylthio) is, for example, methylthio, ethylthio, propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio or tert-butylthio, preferably methylthio or ethylthio.

[0021] 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.

[0022] 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.

[0023] Group Q [Chemistry] is referred to herein as the pyridazinedione / pyridazinone moiety, in which B represents the point of attachment to the remainder of the molecule (i.e., the optionally substituted phenyl W-D moiety).

[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 metal and alkaline earth metal bases, or quaternary ammonium bases. Among the hydroxides, oxides, alkoxides, bicarbonates, and carbonates of alkali metals and alkaline earth metals used as salt-forming agents, the hydroxides, alkoxides, oxides, and carbonates of lithium, sodium, potassium, magnesium, and calcium are emphasized, and the hydroxides, alkoxides, oxides, and carbonates of sodium, magnesium, and calcium are particularly emphasized. The corresponding trimethylsulfonium salts can also be used. The compounds of formula (I) according to the present invention also include hydrates that can be formed during salt formation.

Mode for Carrying Out the Invention

[0025] R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 The preferred values of W, D, G, X, Y, Z, and m are as described below, and the compounds of formula (I) according to the present invention can include any combination of the above values. Those skilled in the art will understand that any set of values of any provision of the embodiments can be combined with any other set of values of the embodiments if the combinations are not mutually contradictory.

[0026] Preferably, R 1is selected from the group consisting of methyl, ethyl, propyl (especially n- or c-propyl), propargyl or C1 haloalkyl. More preferably, R 1 is methyl, ethyl, cyclopropyl, propargyl or C1 fluoroalkyl. Even more preferably, R 1 is methyl, ethyl, cyclopropyl or propargyl. Most preferably, R 1 is methyl.

[0027] Preferably, R 2 is selected from the group consisting of hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C3 alkoxy-C1-C3 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl and C2-C6 haloalkynyl. More preferably, R 2 is chloro, fluoro, methyl, ethyl, cyclopropyl, trifluoromethyl and methoxymethyl, even more preferably selected from the group consisting of chloro, cyclopropyl, trifluoromethyl or methyl, most preferably chloro or methyl. In one set of embodiments of the present invention, R 2 is hydrogen. In a further set of embodiments, R 2 is cyclopropyl, in a third set of embodiments, R 2 is methyl, in a fourth set of embodiments, R 2 is trifluoromethyl, and in a fifth set of embodiments, R 2 is chloro. As described herein, G can be hydrogen or -C(O)-R 3 and R 3 is selected from the group consisting of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkyl-S-, C1-C6 alkoxy, -NR 4 R 5 , and phenyl optionally substituted with one or more R 6 . As defined herein, each R 4 and R 5is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkoxy-, and C3-C6 cycloalkyl; or alternatively, these can together form a morpholinyl ring. Preferably, R 4 and R 5 are each independently selected from the group consisting of methyl, ethyl, propyl, methoxy, ethoxy, and propoxy. R 6 is selected from the group consisting of halogen, cyano, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, and C1-C3 haloalkoxy. Preferably, R 6 is selected from the group consisting of halogen, methyl, ethyl, trifluoromethyl, methoxy, and ethoxy.

[0028] Preferably, R 3 is C1-C4 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, C1-C4 alkoxy, or -NR 4 R 5 and R 4 and R 5 together form a morpholinyl ring. More preferably, R 3 is isopropyl, t-butyl, methyl, ethyl, propargyl, methoxy, ethoxy, or tert-butoxy.

[0029] In one set of embodiments, G is hydrogen or -C(O)-R 3 wherein R 3 is C1-C4 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, or -C1-C3 alkoxy. In a further set of embodiments, G is hydrogen or -C(O)-R 3 wherein R 3 is isopropyl, t-butyl, methyl, ethyl, propargyl, or methoxy. However, it is particularly preferred that G is hydrogen or -C(O)-R 3 wherein R 3 is isopropyl.

[0030] X is preferably hydrogen, halogen, or C1 haloalkyl, more preferably hydrogen, fluoro, chloro, bromo, or C1 fluoroalkyl, even more preferably hydrogen, fluoro, chloro or trifluoromethyl. In one set of embodiments, X is preferably ortho (6-position) to the pyridazinone / pyridazine-dione moiety (group Q). It is particularly preferred that X is fluoro, chloro or C1-haloalkyl (especially C1 fluoroalkyl) and is ortho (6-position) to the pyridazinone / pyridazine-dione moiety (group Q). Most preferably, X is fluoro and is ortho (6-position) with respect to the pyridazinone / pyridazine dione moiety.

[0031] Y is preferably hydrogen, C1-C3 alkyl, cyclopropyl, C1-C3 haloalkyl, or halogen. More preferably, Y is hydrogen, chloro, fluoro, or bromo.

[0032] In one set of embodiments, Y is preferably ortho (3-position) to the W-D moiety. In a further set of embodiments, Y is para to the pyridazinone / pyridazine-dione moiety (group Q).

[0033] It is particularly preferred that Y is ortho (3-position) to the W-D moiety and is halogen, especially chloro or fluoro; more preferably chloro.

[0034] In one particularly preferred set of embodiments, X is fluoro and is ortho (6-position) with respect to the pyridazinone / pyridazine dione moiety, Y is chloro and is ortho (3-position) with respect to the -W-D moiety.

[0035] As described herein, D is a substituted or unsubstituted naphthalene ring system, or a substituted or unsubstituted 8- to 10-membered bicyclic saturated, partially saturated or unsaturated heterocyclic ring system containing 1, 2, 3 or 4 heteroatoms independently selected from oxygen, nitrogen and sulfur. When D is substituted, it has R on at least one ring carbon atom8 is replaced with, and / or, when appropriate, R on the ring nitrogen atom 9 is substituted. In one set of preferred embodiments, ring system D is linked to the remainder of the molecule via a ring carbon atom.

[0036] Preferably, D is a substituted or unsubstituted naphthalene ring system or a substituted or unsubstituted 8- to 10-membered bicyclic heterocyclic ring containing one, two, three, or four heteroatoms independently selected from oxygen, nitrogen, and sulfur. More preferably, D is substituted (with at least one R as described herein 8 and / or R 9 as) or unsubstituted naphthalene, indolizine, indole, iso-indole, indoline, isoindoline, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, benzoxazole, benzodioxole, purine, 4H-quinolizine, quinoline, isoquinoline, tetrahydroquinoline, cinnoline, phthalazine, quinoxaline, 1-8-naphthyridine, pteridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrazine, or 1H-benzotriazole ring system.

[0037] Even more preferably, D is substituted (with at least one R as described herein 8 and / or R 9 as) or unsubstituted naphthalene, indolizine, indole, iso-indole, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, benzoxazole, purine, 4H-quinolizine, quinoline, isoquinoline, tetrahydroquinoline, cinnoline, phthalazine, quinoxaline, 1-8-naphthyridine, or pteridine ring system.

[0038] More preferably, in such embodiments, D is a substituted (as described herein) or unsubstituted naphthalene, quinoline, tetrahydroquinoline, indole, or benzoxazole ring.

[0039] Preferably, each R 8 is independently oxygen, hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6-cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 haloalkoxy-C1-C3 alkyl-, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl-, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl, C1-C6 hydroxyalkyl-, C1-C6 alkylcarbonyl-, C1-C6 haloalkylcarbonyl-, C3-C6 cycloalkylcarbonyl-, C1-C6 alkyl-S(O) m -, -S(O) m -C1-C6 haloalkyl, -S(O) m -C3-C6 cycloalkyl, -O-S(O)2C1-C3 alkyl, -C1-C3 alkyl-S(O) m -C1-C6 alkyl, -C1-C3 alkyl-S(O) m -C1-C6 haloalkyl, -C1-C3 alkyl-S(O) m -C3-C6 cycloalkyl, cyano-C1-C6-alkyl-, -NR 4 R 5 、-C(C1-C3 alkyl)=N-O-C1-C3 alkyl, -C(S)NH2, C1-C6 alkylaminothiocarbonyl-, di(C1-C6 alkyl)aminothiocarbonyl-, C3-C6-cycloalkylamino-thiocarbonyl-S(O)2NH2, -S(O)2NHC(O)C1-C3 alkyl, C1-C6 alkylaminosulfonyl-, di(C1-C6 alkyl)aminosulfonyl-, C3-C6-cycloalkylamino-sulfonyl-, -C(O)OH, -C(O)OC1-C6 alkyl, -C(O)NHS-(O)2C1-C6 alkyl, -C(O)NR 4 R 5 、-NR 4 C(O)NR 4 R 5, C1-C6 alkylcarbonyl(C1-C6 alkyl)amino-, C1-C6 haloalkylcarbonylamino-, C1-C6 haloalkylcarbonyl(C1-C6 alkyl)amino-, C1-C6 alkoxycarbonylamino-, C1-C6 alkoxycarbonyl(C1-C6 alkyl)amino-, C1-C6 alkylsulfonylamino-, C1-C6 alkylsulfonyl(C1-C6 alkyl)amino-, C1-C6 haloalkylsulfonylamino-, C1-C6 haloalkylsulfonyl(C1-C6 alkyl)amino-, C3-C6 cycloalkylsulfonylamino-, C3-C6 cycloalkylsulfonyl(C1-C6 alkyl)amino-, C1-C6 alkylaminocarbonylamino-, C1-C6 alkylaminocarbonyl(C1-C6 alkyl)amino, di(C1-C6 alkyl)aminocarbonylamino-, C1-C6 haloalkylaminocarbonylamino-, C1-C6 haloalkylamino-carbonyl(C1-C6 alkyl)amino, di(C1-C6 haloalkyl)aminocarbonylamino-, di(C1-C6 haloalkyl)amino-carbonyl(C1-C6 alkyl)amino-, hydroxyamino-, hydroxy(C1-C6 alkyl)amino, C1-C6 alkoxyamino, C1-C6 alkoxy(C1-C6 alkyl)amino, C1-C6 haloalkoxyamino, C1-C6 haloalkoxy(C1-C6 alkyl)amino; More preferably, each R 8 is independently oxygen, hydroxyl, halogen, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C3 haloalkoxy-C1-C3 alkyl-, C1-C6 alkoxy, C1-C3 alkoxy-C1-C3 alkyl, C1-C3 alkoxy-C1-C3 alkoxy-C1-C3 alkyl-, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C1-C6 hydroxyalkyl-, C1-C6 alkylcarbonyl-, C1-C6 alkyl-S(O) m -, amino, C1-C6 alkylamino, C1-C6 dialkylamino, -C(C1-C3 alkyl)=N-O-C1-C3 alkyl or C2-C6 haloalkynyl.

[0040] More preferably, each R 8 is independently hydroxyl, halogen, C1-C6 alkyl, C1-C6 haloalkyl, or C1-C6 alkoxy. Even more preferably, each R 8 is independently C1-C3 alkyl, C1-C3 haloalkyl, chloro, fluoro, hydroxyl, or C1-C3 alkoxy.

[0041] Preferably, each R 9 is independently C1-C4 alkyl, C1-C4 haloalkyl, hydroxyl, C1-C4 alkoxy, or C1-C4 alkylthio. More preferably, each R 9 is independently C1-C4 alkyl, or C1-C4 alkoxy. Even more preferably, each R 9 is independently C1-C4 alkyl. Most preferably, each R 9 is methyl.

[0042] m is an integer of 0, 1, or 2. Preferably, m is 0 or 2.

[0043] W acts as a linker moiety that links the ring system D to the rest of the molecule (i.e., to the phenyl-pyridazinone / phenyl-pyridazinedione moiety). The compound of formula (I) where the linker is W1 and W3 is herbicidal, while the compound of formula (I) where the linker is W2 is not only herbicidal but can also be a useful intermediate in the production of the compound of formula (I) carrying the W1 linker. Thus, in one set of embodiments, W is W1 or W3 (preferably W1), while in a second set of embodiments, W is W2.

[0044] Specific examples of W are -CH2-CH2-, and -CH=CH-, -C≡C-, cis

Chemical formula

Chemical formula

[0045] Preferably, R 10 , R 11 , R 12 and R 13 are each independently selected from hydrogen or C1-C3 alkyl. In one set of embodiments, R 10 , R 11 , R 12 , and R 13 are all hydrogen.

[0046] Preferably, R 14 and R 15 are each independently selected from hydrogen or C1-C3 alkyl. In one set of embodiments, R 14 and R 15 are both hydrogen.

[0047] In one preferred set of embodiments of the compound of formula (I), R 1 is methyl, ethyl, cyclopropyl, propargyl or C1 fluoroalkyl; R 2 is chloro, cyclopropyl, trifluoromethyl or methyl; G is hydrogen or -C(O)-R 3 , and R 3 is isopropyl, t-butyl, methyl, ethyl, propargyl, methoxy, ethoxy, or tert-butoxy; X is fluoro, chloro or C1-haloalkyl and is ortho with respect to the pyridazinone / pyridazinedione moiety; Y is ortho with respect to the -W-D moiety; D is a substituted or unsubstituted naphthalene ring system, or a substituted or unsubstituted 8- to 10-membered bicyclic saturated, partially saturated or unsaturated heterocyclic ring system containing one, two, three or four heteroatoms independently selected from oxygen, nitrogen and sulfur. When D is substituted, it is substituted with R 8 on at least one ring carbon atom and / or with R 9 on at least one ring nitrogen atom; Each R 8 is independently hydroxyl, halogen, C1-C6 alkyl, C1-C6 haloalkyl or C1-C6 alkoxy; Each R 9 is independently C1-C4 alkyl or C1-C4 alkoxy; W is W1; R 10 , R 11 , R 12 and R 13 are all hydrogen.

[0048] In an even more preferred set of embodiments of the compounds of formula (I), R 1 is methyl; R 2 is methyl; G is hydrogen or -C(O)-R 3 where R 3 is isopropyl, t-butyl, methyl, ethyl, propargyl, methoxy, ethoxy or tert-butoxy; X is fluoro and is ortho with respect to the pyridazinone / pyridazinedione moiety; Y is chloro and is ortho with respect to the -W-D moiety; D is a naphthalene, indolizine, indole, iso-indole, indoline, isoindoline, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, benzoxazole, benzodioxole, purine, 4H-quinolizine, quinoline, isoquinoline, tetrahydroquinoline, cinnoline, phthalazine, quinoxaline, 1-8-naphthyridine, pteridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrazine or 1H-benzotriazole ring system, and when D is substituted, it is substituted with R 8 on one or two ring carbon atoms and / or with R 9 on one ring nitrogen atom; each R 8 is independently C1-C3 alkyl, C1-C3 haloalkyl, chloro, fluoro, hydroxyl, or C1-C3 alkoxy; R 9 is C1-C4 alkyl; W is W1; R 10 R 11 R 12 and R 13 are all hydrogen.

[0049] The following Tables 1 to 4 illustrate 2752 specific examples of the compounds of formula (I) of the present invention.

[0050] The numbering system used to explain the positions of X and Y of the herbicidal compounds of the present invention is shown for clarity only.

Chemical formula

[0051] Table 1 provides 688 compounds A-1.001 to A-1.688 of formula (I) as shown above, where G is hydrogen, W is -CH2-CH2-, R 1 R 2, X, Y, and D are as defined for compound numbers 1.001 to 1.688 in Table A below.

[0052]

Table 1-1

Table 1-2

Table 1-3

Table 1-4

Table 1-5

Table 1-6

Table 1-7

Table 1-8

Table 1-9

Table 1-10

Table 1-11

Table 1-12

Table 1-13

Table 1-14

Table 1-15

Table 1-16

Table 1-17

[0053] Table 2 provides compounds A-2.001 to A-2.688 of formula (I) as shown above, where G is hydrogen, W is (E)-CH=CH-, R 1 , R 2 , X, Y, D are as defined for compound numbers 1.001 to 1.688 in Table A above, respectively.

[0054] Table 3 provides compounds A-3.001 to A-3.688 of formula (I) as shown above, where G is -(C=O)iPr, W is -CH2-CH2-, R 1 , R 2 , X, Y, D are as defined for compound numbers 1.001 to 1.288 in Table A above, respectively.

[0055] Table 4 provides compounds A-4.001 to A-4.688 of formula (I) as shown above, where G is -(C=O)iPr, W is (E)-CH=CH-, R 1 , R 2 , X, Y, D are as defined for compound numbers 1.001 to 1.288 in Table A above, respectively.

[0056] The compounds of the present invention can be prepared according to the following scheme, where the substituents R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16, W, D, G, X, Y, Z, and m have the definitions set forth above in this specification (unless otherwise explicitly stated).

[0057] The specific compound (I-ii) of the present invention can be prepared from compound (2) as shown in Reaction Scheme 1. Compound (I-ii) is a compound of formula (I), where W is -CH2-CH2-.

[0058] Reaction Scheme 1

Chemical formula

[0059] Alternatively, compound (I-ii) can also be prepared by the catalytic transfer hydrogenation of compound (2) by treatment with a suitable hydrogen source in a suitable solvent in the presence of a suitable catalyst at a temperature of -10 to 100 °C. Examples of suitable systems are tetrahydroxydiboron in a dichloromethane / water or dichloromethane / methanol mixture in the presence of Pd / C, Pd(OAc)2 or Pd(OH)2 / C (J. Am. Chem. Soc., 2016, 138, 6107-6110), or diethyl 1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate in ethanol in the presence of Pd / C (Tetrahedron Letters, 2009, 50, 1026).

[0060] Alternatively, compound (I-ii) can also be prepared by reduction with diimide generated in situ from a suitable precursor in a suitable solvent at a temperature of -10 to 200 °C. Examples of suitable reagents for the generation of diimide include substituted arylsulfonyl hydrazides, such as 2,4,6-triisopropylbenzenesulfonyl hydrazide, optionally in the presence of a suitable base. Examples of suitable bases include triethylamine, diisopropylethylamine, potassium carbonate and sodium carbonate. Suitable solvents include tetrahydrofuran, 1,4-dioxane, ethyl acetate, acetonitrile and dimethylformamide.

[0061] Compound (2) can be prepared from compounds (3) and (4) as shown in Reaction Scheme 2 by the described Suzuki protocol or Heck protocol. When using the Suzuki protocol, compound (4) is an organoboron compound, such as boric acid, boronic ester or potassium trifluoroborate salt. When using the Heck protocol, compound (4) is styrene.

[0062] Reaction Scheme 2

Chemical Structure

[0063] Those skilled in the art will recognize that the conditions of the Suzuki protocol tend to cleave ester groups, and as a result, reaction scheme 2 can also account for reactions where the starting material (3) contains an ester moiety [such that G is an acyl group], while the product (2) does not contain an ester moiety [such that G is hydrogen].

[0064] Heck protocol Compound (2) can be prepared by treating compound (3) and compound (4) at a temperature of 10 to 150 °C in the presence of a suitable base and a suitable catalyst. An additional solvent may optionally be included. Examples of suitable bases are triethylamine, morpholine, N-methylmorpholine, diisopropylethylamine and pyridine. Examples of suitable catalysts are catalysts formed in situ from a mixture of tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4], palladium(II) acetate and triphenylphosphine, catalyst systems formed in situ from a mixture of tris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphonium tetrafluoroborate, and catalyst systems formed in situ from a paradacycle precatalyst, for example chloro[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II). Examples of any additional solvents are 1,4-dioxane, tetrahydrofuran, acetonitrile and toluene. Many compounds (4) are commercially available [for example, 2-vinylnaphthalene] or can be prepared by known methods. An example of compound (3) having particular utility in the Heck protocol is isobutyryl ester (3-i), where G is isobutyryl.

[0065] Compound (3-i) can be prepared from compound (5) as shown in Reaction Scheme 3.

[0066] Reaction Scheme 3

Chemical formula

[0067] Compound (5) can be prepared from compound (6) as shown in Reaction Scheme 4 by heating compound (6) with a base (e.g., 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium hexamethyldisilazide or lithium hexamethyldisilazide) at a temperature of 50 to 200 °C in a solvent [e.g., acetonitrile, N,N-dimethylformamide or toluene]. Conventional heating or microwave heating can be used.

[0068] Reaction Scheme 4

Chem.

[0069] Reaction Scheme 5

Chem.

[0070] A specific compound (I-iii) of the present invention can be prepared from compound (11) as shown in Reaction Scheme 6, or from compound (I-iv) as shown in Reaction Scheme 12. Compound (I-iii) is a compound of formula (I), wherein W is -CH2-CH2- and G is hydrogen.

[0071] Reaction Scheme 6

Chem.

[0072] Compound (11) can be prepared from compound (12) as shown in the following Reaction Scheme 7.

[0073] Reaction Scheme 7

Chemical formula

[0074] Reaction Scheme 8

Chemical formula

[0075] Reaction Scheme 9

Chemical formula

[0076] Reaction Scheme 10

Chem.

[0077] Reaction Scheme 11

Chem.

[0078] Reaction Scheme 12

Chem.

[0079] Compound (2) can be prepared from compounds (14) and (15) as shown in Reaction Scheme 13 by the described Suzuki protocol or Heck protocol. When using the Suzuki protocol, compound (14) is an organoboron compound, such as boric acid, boronic ester or potassium trifluoroborate salt, and compound (15) is a halide or pseudohalide compound, such as chloride, bromide, iodide or triflate. When using the Heck protocol, compound (14) is styrene and compound (15) is a halide or pseudohalide compound, such as chloride, bromide, iodide or triflate.

[0080] Reaction Scheme 13 [Chemical Formula] Suzuki protocol Compound (2) can be prepared by treating compounds (14) and (15) in a suitable solvent at a temperature of 10 - 150 °C in the presence of a suitable base and a suitable catalyst. Examples of suitable bases are potassium carbonate, potassium phosphate, sodium carbonate, sodium hydrogen carbonate and potassium fluoride. Examples of suitable catalysts are [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex [PdCl2(dppf)·DCM], tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4], and a catalyst system formed in situ from a mixture of palladium(II) acetate and triphenylphosphine. Examples of suitable solvents are water, 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydrofuran, acetonitrile and toluene. Many compounds (15) are commercially available or can be prepared by known methods. An example of compound (14) having particular utility in the Suzuki protocol is the isobutyryl ester (14-i), where G is isobutyryl.

[0081] The conditions of the Suzuki protocol tend to cleave ester groups, and as a result, Scheme 13 can also describe a reaction where the starting material (14) contains an ester moiety [such that G is an acyl group], while the product (2) does not contain an ester moiety [such that G is hydrogen], which will be recognized by those skilled in the art.

[0082] Heck protocol Compound (2) can be prepared by treating compound (14) with compound (15) in the presence of a suitable base and a suitable catalyst at a temperature of 10 - 150 °C. Optionally, an additional solvent may be included. Examples of suitable bases are triethylamine, morpholine, N - methylmorpholine, diisopropylethylamine, and pyridine. Examples of suitable catalysts are tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4], a catalyst system formed in situ from a mixture of palladium(II) acetate and triphenylphosphine, a catalyst system formed in situ from a mixture of tris(dibenzylideneacetone)dipalladium(0) and tri - tert - butylphosphonium tetrafluoroborate, and a catalyst system formed in situ from a pre - catalyst such as chloro[(tri - tert - butylphosphine)-2-(2 - aminobiphenyl)]palladium(II). Examples of optional additional solvents are 1,4 - dioxane, tetrahydrofuran, acetonitrile, and toluene. Many compounds (15) are commercially available or can be prepared by known methods. An example of a compound (14) having particular utility in the Heck protocol is isobutyryl ester (14 - i), where G is isobutyryl.

[0083] Compound (14 - ii) (where J is an organoboron species, such as a boronic ester) can be prepared from compound (3) and compound (16) as shown in Scheme 14.

[0084] Scheme 14

Chemical formula

[0085] Reaction Scheme 15

Chemical formula

[0086] Compound (14-iii) can be prepared by treating compound (3) and tributyl(vinyl)stannane in a suitable solvent at a temperature of 10 to 150 °C, optionally in the presence of a suitable base and in the presence of a suitable catalyst. Examples of optional bases are triethylamine, morpholine, N-methylmorpholine, diisopropylethylamine and pyridine. Examples of suitable catalysts are [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex [PdCl2(dppf)·DCM], tetrakis(triphenylphosphine)palladium(0) [Pd(PPh3)4], a catalyst system formed in situ from a mixture of palladium(II) acetate and triphenylphosphine, a catalyst system formed in situ from a mixture of tris(dibenzylideneacetone)dipalladium(0) and tri-tert-butylphosphonium tetrafluoroborate, and a catalyst system formed in situ from a paradycle catalyst precursor, for example chloro[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II). Examples of suitable solvents are 1,4-dioxane, tetrahydrofuran, acetonitrile and toluene. An example of compound (3) having specific utility is isobutyryl ester (3-i), where G is isobutyryl.

[0087] Compound (18) can be prepared from compound (3) by a Sonogashira reaction as shown in Reaction Scheme 16.

[0088] Reaction Scheme 16

Chemical Structure

[0089] Those skilled in the art will recognize that the Sonogashira reaction conditions tend to cleave the ester group, and as a result, Scheme 16 can also describe a reaction where the starting material (3) contains an ester moiety [such that G is an acyl group], but the product (18) does not contain an ester moiety [such that G is hydrogen].

[0090] Compound (19) can be prepared from compound (3) and compound (20) as shown in Scheme 17 via a Suzuki reaction, where compound (20) is a suitable organoboron species, for example, a boronic acid, a boronic acid ester, or a potassium trifluoroborate.

[0091] Scheme 17

Chemical Structure

[0092] Reaction Scheme 18

Chemical Structure

[0093] A certain specific compound (I-ii) of the present invention can be prepared from compound (21) as shown in Reaction Scheme 19. Compound (I-ii) is a compound of formula (I), wherein W is -CH2-CH2-.

[0094] Reaction Scheme 19

Chemical formula

[0095] The conditions of the Suzuki protocol tend to cleave ester groups, and as a result, Reaction Scheme 19 can also explain the reaction where the starting material (21) contains an ester moiety [such that G is an acyl group], while the product (I-ii) does not contain an ester moiety [such that G is hydrogen], which is recognized by those skilled in the art.

[0096] Reaction Scheme 20

Chem.

[0097] When [B] is an alkyl boronic acid ester, it can be converted to the corresponding boronic acid by treatment with methylboronic acid [MeB(OH)2] and trifluoroacetic acid in a suitable solvent, such as dichloromethane [DCM], at a temperature of 0 to 40 °C [Org. Lett., 2019, 21, 3048 - 3052]. When [B] is an alkyl boronic acid or ester, it can be converted to the corresponding potassium alkyltrifluoroborate by treatment with potassium hydrogen fluoride in a suitable solvent, such as methanol or acetone, at a temperature of 0 to 40 °C.

[0098] The compounds according to the invention can be used as herbicidal agents in their unmodified form, but they are generally formulated into compositions in various ways using formulation adjuvants such as carriers, solvents and surface-active substances. The formulations can be in various physical forms, such as sprays, gels, wettable powders, water-dispersible granules, water-dispersible tablets, foaming pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil flowables, aqueous dispersions, oily dispersions, suspoemulsions, capsule suspensions, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), in the form of impregnated polymer films, or in other forms known, for example, from the Manual on Development and Use of FAO and WHO Specifications for Pesticides, United Nations, First Edition, Second Revision (2010). Such formulations can be used directly or diluted before use. The dilution can be carried out, for example, with water, liquid fertilizers, micronutrients, living organisms, oils or solvents.

[0099] The complex can be prepared, for example, by mixing the active ingredient with a formulation adjuvant to obtain a composition in the form of a micronized solid, granule, solution, dispersion or emulsion. The active ingredient can also be formulated with other adjuvants such as micronized solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surfactants or combinations thereof.

[0100] The active ingredient can also be contained in fine microcapsules. The microcapsules contain the active ingredient in a porous carrier. This enables the active ingredient to be released into the environment in a controlled amount (e.g., sustained release). Microcapsules typically have a diameter of 0.1 to 500 microns. They contain the active ingredient in an amount of about 25 to 95% by weight of the capsule weight. The active ingredient can be in the form of an integrated solid, in the form of fine particles in a solid or liquid dispersion, or in the form of a suitable solution. The encapsulating membrane can include, for example, natural or synthetic rubber, cellulose, styrene / butadiene copolymer, polyacrylonitrile, polyacrylate, polyester, polyamide, polyureas, polyurethanes or chemically modified polymers and xanthan gum starch or other polymers known to those skilled in the art. Alternatively, fine microcapsules can be formed in which the active ingredient is contained in the form of micronized particles in a solid matrix of the base substance, but the microcapsules themselves are not encapsulated.

[0101] The compounding adjuvants suitable for the preparation of the composition according to the present invention are known per se. As the liquid carrier, water, toluene, xylene, petroleum ether, vegetable oil, acetone, methyl ethyl ketone, cyclohexanone, acid anhydride, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietic acid, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkyl pyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-Trichloroethane, 2-heptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol, propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylene sulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and higher molecular weight alcohols such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone, etc. may be used.,

[0102] Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, porous diatomaceous earth, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, powdered walnut hulls, lignin and similar substances.,

[0103] Most surfactants can be advantageously used in both solid and liquid formulations, especially in those formulations that can be diluted with a carrier before use. The surfactants can be anionic, cationic, nonionic or polymeric, and these can be used as emulsifiers, wetting agents or suspending agents, or for other purposes. Typical surfactants are, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylaryl sulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol / alkylene oxide adducts, such as nonylphenol ethoxylate; alcohol / alkylene oxide adducts, such as tridecyl alcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinates, such as sodium di(2-ethylhexyl) sulfosuccinate; sorbitol esters, such as sorbitol oleate; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono- and dialkyl phosphates; and also include further substances described, for example, in McCutcheon’s Detergents and Emulsifiers Annual, MC Publishing Corp., Ridgewood New Jersey (1981).

[0104] Further adjuvants that can be used in pesticidal formulations include crystallization inhibitors, viscosity regulators, suspending agents, dyes, antioxidants, foaming agents, light absorbers, mixing aids, defoamers, complexing agents, neutralizing or pH-adjusting substances and buffers, corrosion inhibitors, fragrances, wetting agents, absorption enhancers, micronutrients, plasticizers, flow promoters, lubricants, dispersants, thickeners, antifreezes, bactericides, and liquid and solid fertilizers.

[0105] The composition according to the invention can comprise an oil of vegetable or animal origin, a mineral oil, an alkyl ester of such an oil, or a mixture of such oils, and an additive comprising an oil derivative. The amount of the oil additive in the composition according to the invention is generally from 0.01 to 10% based on the mixture to be applied. For example, the oil additive can be added to the spray tank at the desired concentration after preparing the spray mixture. Preferred oil additives include mineral oil or an oil of vegetable origin, such as rapeseed oil, olive oil or sunflower oil, an emulsified vegetable oil, an alkyl ester of an oil of vegetable origin, such as a methyl derivative, or an oil of animal origin, such as fish oil or tallow. Preferred oil additives include alkyl esters of C8 - C 22 fatty acids, in particular, C 12 -C 18 methyl derivatives of fatty acids, such as methyl laurate, methyl palmitate and methyl oleate (methyl laurate, methyl palmitate and methyl oleate respectively). Many oil derivatives are known from Compendium of Herbicide Adjuvants, 10 th Edition, Southern Illinois University, 2010.

[0106] The herbicidal composition generally comprises from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of formula (I) and, preferably, from 0 to 25% by weight of a surfactant, and from 1 to 99.9% by weight of a formulated adjuvant. The composition of the invention generally comprises from 0.1 to 99% by weight, in particular from 0.1 to 95% by weight, of a compound of the invention and, preferably, from 0 to 25% by weight of a surfactant, and from 1 to 99.9% by weight of a formulated adjuvant. Commercially available products can preferably be formulated as concentrates, while the end user usually uses a diluted formulation.

[0107] The application rate varies within wide limits and is determined by the nature of the soil, the method of application, the crop, the pest to be controlled, the general climatic conditions, and other factors depending on the method of application, the time of application and the target crop. As a general guideline, the compound can be applied at a rate of 1 - 2000 l / ha, in particular 10 - 1000 l / ha.

[0108] Preferred formulations may have the following compositions (by weight): Emulsifiable concentrate: Active ingredient: 1 - 95%, preferably 60 - 90% Surfactant: 1 - 30%, preferably 5 - 20% Liquid carrier: 1 - 80%, preferably 1 - 35%

[0109] Powder: Active ingredient: 0.1 - 10%, preferably 0.1 - 5% Solid carrier: 99.9 - 90%, preferably 99.9 - 99%

[0110] Suspension concentrate: Active ingredient: 5 - 75%, preferably 10 - 50% Water: 94 - 24%, preferably 88 - 30% Surfactant: 1 - 40%, preferably 2 - 30%

[0111] Wettable powder: Active ingredient: 0.5 - 90%, preferably 1 - 80% Surfactant: 0.5 - 20%, preferably 1 - 15% Solid carrier: 5 - 95%, preferably 15 - 90%

[0112] Granule: Active ingredient: 0.1 - 30%, preferably 0.1 - 15% Solid carrier: 99.5 - 70%, preferably 97 - 85%

[0113] The compositions of the present invention may further comprise at least one additional pesticidal agent. For example, the compounds according to the invention can also be used in combination with other herbicides or plant growth regulators. In a preferred embodiment, the additional pesticidal agent is a herbicide and / or a herbicide safener.

[0114] Thus, the compounds of formula (I) can be used in combination with one or more other herbicides to provide various herbicidal mixtures. Specific examples of such mixtures are (where "I" represents the compound of formula (I)): - I + acetochlor; I + asiflufen; (including asiflufen - sodium); I + acronifen; I + ametryn; I + amicarbazone; I + aminopyralid; I + aminotriazole; I + atrazine; I + beflubutamid - M; I + bentriazone; I + bensulfuron; (including bensulfuron - methyl); I + bentazone; I + bicyclopyrone; I + bilanafos; I + bispyribac - sodium; I + bispyrazon; I + bromacil; I + bromoxynil; I + butachlor; I + butaphenacil; I + carfentrazone; (including carfentrazone - ethyl); I + chloransulam; (including chloransulam - methyl); I + chlorimuron; (including chlorimuron - ethyl); I + chlorotoluron; I + chlorosulfuron; I + cinmethylin; I + clathrifos; I + clethodim; I + clodinafop; (including clodinafop - propargyl); I + chromazone; I + clopyralid; I + cyclopyranil; I + cyclopyrimorate; I + cyclosulfamuron; I + cyhalofop; (including cyhalofop - butyl); I + 2,4 - D; (including its choline salt and 2 - ethylhexyl ester); I + 2,4 - DB; I + desmedipham; I + dicamba; (including its aluminum, aminopropyl, bis - aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium and sodium salts); I + diclosulam; I + diflufenican; I + diflufenzoppil; I + dimethachlor; I + dimethenamid - P; I + diquat dibromide; I + diuron; I + epirifluorfen; I + ethalfluralin; I + ethofumesate; I + fenoxaprop; (including fenoxaprop - P - ethyl); I + fenoxasulfone; I + fenquinotrione; I + fentrazamide; I + flazasulfuron; I + florasulam; I + flupyradifurone; (including flupyradifurone - benzyl); I + fluazifop; (including fluazifop - P - butyl);I + Fullcarbazone (including fullcarbazone-sodium); I + Fullphenacetin; I + Flumetramide; I + Flumioxazin; I + Fluometuron; I + Flupyrsulfuron (including flupyrsulfuron-methyl-sodium); I + Fluoroxypyr (including fluoroxypyr-meptyl); I + Homosafen; I + Horamsulfuron; I + Glufosinate (including its ammonium salt); I + Glyphosate (including its diammonium, isopropylammonium and potassium salts); I + Halauxifen (including halauxifen-methyl); I + Haloxyfop (including haloxyfop-methyl); I + Hexazinone; I + Hydantocidin; I + Imazamox; I + Imazapic; I + Imazapyr; I + Imazethapyr; I + Indaziflam; I + Iodosulfuron (including iodosulfuron-methyl-sodium); I + Iofensulfuron (including iofensulfuron-sodium); I + Ioxynil; I + Isoproturon; I + Isoxazulfutole; I + Rankotrione; I + MCPA; I + MCPB; I + Mecoprop-P; I + Mesosulfuron (including mesosulfuron-methyl); I + Mesotrione; I + Metamitron; I + Metazachlor; I + Methiozolin; I + Metolachlor; I + Metosulam; I + Metribuzin; I + Metsulfuron; I + Napropamide; I +nicosulfuron; I + Norflurazon; I + Oxadiazon; I + Oxasulfuron; I + Oxyfluorfen; I + Paraquat dichloride; I + Pendimethalin; I + Penoxsulam; I + Fenmedifam; I + Picloram; I + Pinoxaden; I + Pretilachlor; I + Primisulfuron-methyl; I + Promethrin; I + Propanil; I + Propyzamide; I + Propisulfuron; I + Propyzamide; I + Prothiofos; I + Protosulfuron; I + Pyraclonil; I + Pyraflufen (including pyraflufen-ethyl); I + Pyrazosulfuron; I + Pyridate; I + Pyribenzoxim; I + Pyrimisulfan; I + Pyroxsulam; I + Pyroxasulfone; I + Quinclorac; I + Quinmerac; I + Quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl); I + Rimsulfuron; I + Sulfofenacil; I + Sethoxydim; I + Simazine;I+S-metachlor; I+sulfentrazone; I+sulfosulfuron; I+tebuthiuron; I+tefuryltrione; I+tenbotrione; I+terbuthylazine; I+terbutryn; I+teflupropim; I+thiencarbazone; I+thifensulfuron; I+thiafenox; I+topramezone; I+tralkoxydim; I+triasulfuron; I+tribenuron (including tribenuron-methyl); I+triclopyr; I+trifloxysulfuron (including trifloxysulfuron-sodium); I+triflumizole; I+trifluralin; I+triflusulfuron; I+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; I+4-hydroxy-1-methoxy-5-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I+4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I+5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I+4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one; I+4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]imidazolidin-2-one; I+(4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one; I+3-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione; I+2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione; I+2-[2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione;I + 2 - [2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione; I + 6 - [2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione; I + 2 - [2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-5-ethyl-cyclohexane-1,3-dione; I + 2 - [2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-4,4,6,6-tetramethyl-cyclohexane-1,3-dione; I + 2 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5-methyl-cyclohexane-1,3-dione; I + 3 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]bicyclo[3.2.1]octane-2,4-dione; I + 2 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-5,5-dimethyl-cyclohexane-1,3-dione; I + 6 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,4,4-tetramethyl-cyclohexane-1,3,5-trione; I + 2 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]cyclohexane-1,3-dione; I + 4 - [2-(3,4-dimethoxyphenyl)-6-methyl-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione; I + 4 - [6-cyclopropyl-2-(3,4-dimethoxyphenyl)-3-oxo-pyridazine-4-carbonyl]-2,2,6,6-tetramethyl-tetrahydropyran-3,5-dione;I + 4 - Amino - 3 - chloro - 5 - fluoro - 6 - (7 - fluoro - 1H - indol - 6 - yl) pyridine - 2 - carboxylic acid (including its agrochemically acceptable esters, for example, methyl 4 - amino - 3 - chloro - 5 - fluoro - 6 - (7 - fluoro - 1H - indol - 6 - yl) pyridine - 2 - carboxylate, prop - 2 - yn - 1 - yl 4 - amino - 3 - chloro - 5 - fluoro - 6 - (7 - fluoro - 1H - indol - 6 - yl) pyridine - 2 - carboxylate, and cyanomethyl 4 - amino - 3 - chloro - 5 - fluoro - 6 - (7 - fluoro - 1H - indol - 6 - yl) pyridine - 2 - carboxylate); I + 3 - ethylsulfanyl - N - (1,3,4 - oxadiazol - 2 - yl) - 5 - (trifluoromethyl) - [1,2,4] triazolo[4,3 - a] pyridine - 8 - carboxamide; I + 3 - (isopropylsulfanylmethyl) - N - (5 - methyl - 1,3,4 - oxadiazol - 2 - yl) - 5 - (trifluoromethyl) - [1,2,4] triazolo[4,3 - a] pyridine - 8 - carboxamide; I + 3 - (isopropylsulfonylmethyl) - N - (5 - methyl - 1,3,4 - oxadiazol - 2 - yl) - 5 - (trifluoromethyl) - [1,2,4] triazolo[4,3 - a] pyridine - 8 - carboxamide; I + 3 - (ethylsulfonylmethyl) - N - (5 - methyl - 1,3,4 - oxadiazol - 2 - yl) - 5 - (trifluoromethyl) - [1,2,4] triazolo[4,3 - a] pyridine - 8 - carboxamide; I + ethyl 2 - [[3 - [[3 - chloro - 5 - fluoro - 6 - [3 - methyl - 2,6 - dioxo - 4 - (trifluoromethyl) pyrimidin - 1 - yl] - 2 - pyridyl] oxy] acetate; I + 6 - chloro - 4 - (2,7 - dimethyl - 1 - naphthyl) - 5 - hydroxy - 2 - methyl - pyridazin - 3 - one;It contains I+1-[2-chloro-6-(5-chloropyrimidin-2-yl)oxy-phenyl]-4,4,4-trifluoro-butan-1-one and I+5-[2-chloro-6-(5-chloropyrimidin-2-yl)oxy-phenyl]-3-(difluoromethyl)isoxazole. The mixing partner of the compound of formula (I) may also be in the form of an ester or a salt, for example, as mentioned in The Pesticide Manual, Fourteenth Edition, British Crop Protection Council, 2006.;

[0115] The compound of formula (I) can also be used in a mixture with other pesticides such as fungicides, nematicides or insecticides, examples of which are shown in The Pesticide Manual.

[0116] The mixing ratio of the compound of formula (I) to the mixing partner is preferably 1:100 to 1000:1.

[0117] The mixture can advantageously be used in the above-mentioned formulations (in which case, the "active ingredient" relates to each mixture of the compound of formula (I) with the mixing partner).

[0118] The compound of formula (I) of the present invention can also be combined with a herbicide safener. Preferred combinations (where "I" represents the compound of formula (I)) include I+benoxacor, I+cloquintocet (including cloquintocet-methyl); I+cyprosulfamide; I+dichlormid; I+fenchlorazole (including fenchlorazole-ethyl); I+fenclorim; I+flurxypyr; I+furilazole I+isoxadifen (including isoxadifen-ethyl); I+mefenpyr (including mefenpyr-diethyl); I+metcamifene; I+N-(2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide and I+oxabetrinil.

[0119] Particularly preferred are mixtures of the compounds of formula (I) with cyprosulfamide, isoxadifen (including isoxadifen-ethyl), clomazone (including clomazone-methyl) and / or N-(2-methoxybenzoyl)-4-[(methyl-aminocarbonyl)amino]benzenesulfonamide.

[0120] The toxicity alleviating agent of the compound of formula (I) may also be in the form of an ester or a salt, for example, as mentioned in The Pesticide Manual, 14 th Edition (BCPC), 2006. The reference to clomazone-methyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02 / 34048 pamphlet. The reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.

[0121] Preferably, the mixing ratio of the compound of formula (I) to the toxicity alleviating agent is from 100:1 to 1:10, especially from 20:1 to 1:1.

[0122] The mixture can advantageously be used in the abovementioned formulations (in this case, the "active ingredient" relates to each mixture of the compound of formula (I) with the toxicity alleviating agent).

[0123] The compound of formula (I) according to the invention is useful as a herbicide. Accordingly, the present invention further includes a method for controlling unwanted plants, which comprises applying an effective amount of the compound of the present invention or a herbicidal composition containing said compound to the plants or their habitats. "Control" means killing, reducing or delaying growth or preventing or reducing germination. Generally, the plants to be controlled are unwanted plants (weeds). "Location" means the area where the plants are growing or the area where they are expected to grow.

[0124] 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; application to furrows; no tillage application, 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 compound of formula (I) according to the invention is generally applied at a rate of 10 to 2000 g / ha, in particular 50 to 1000 g / ha.

[0125] Application is generally made 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), drip or drench can also be used.

[0126] Useful plants on which the compositions according to the invention can be used include crops such as cereals, for example barley and wheat, cotton, rape, sunflower, maize, rice, soybeans, sugar beet, sugar cane and turf.

[0127] Crops can also include trees such as fruit trees, palm trees, coconut trees or other fruit-bearing trees. Vining plants such as grapes, fruit bushes, fruit plants and vegetables are also included.

[0128] It should be understood that the crops also include crops made resistant to herbicides or types of herbicides (for example ALS-, GS-, EPSPS-, PPO-, ACCase- and HPPD inhibitors) by conventional breeding methods or genetic recombination. An example of a crop made resistant to imidazolinones, for example imazamox, by conventional breeding methods is Clearfield® summer rape (canola). Examples of crops made resistant to herbicides by genetic recombination methods include, for example, glyphosate-resistant and glufosinate-resistant maize seeds marketed under the trade names RoundupReady® and LibertyLink®.

[0129] Crops may also be crops that have been given pest resistance by genetic engineering methods, such as Bt corn (resistant to the European corn borer), Bt cotton (resistant to the pink bollworm), and also Bt potato (resistant to the Colorado potato beetle). Examples of Bt corn are the Bt 176 corn hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is naturally formed by the soil bacterium Bacillus thuringiensis. Examples of toxins, or transgenic plants that can synthesize such toxins, are described in European Patent Application Publication No. A-451878, European Patent Application Publication No. A-374753, International Publication No. 93 / 07278 Pamphlet, International Publication No. 95 / 34656 Pamphlet, International Publication No. 03 / 052073 Pamphlet, and European Patent Application Publication No. A-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 ("stacked transgenic events"). For example, the seeds can be resistant to glyphosate while having the ability to express the insecticidal Cry3 protein.

[0130] Crops may also include crops obtained by conventional breeding methods or genetic engineering, including so-called output traits (such as improved storage stability, higher nutritional value, and improved flavor).

[0131] Other useful plants include, for example, turf grass in golf courses, lawns, parks and along roadsides, or turf grass commercially cultivated for lawns, and ornamental plants such as flowers or shrubs.

[0132] The compounds and compositions of formula (I) of the present invention can typically be used to control a wide variety of monocotyledonous and dicotyledonous weed species. Examples of monocotyledonous species that can typically be controlled include Alopecurus myosuroides, Avena fatua, Brachiaria plantaginea, Bromus tectorum, Cyperus esculentus, Digitaria sanguinalis, Echinochloa crus-galli, Lolium perenne, Lolium multiflorum, Panicum miliaceum, Poa annua, Setaria viridis, Setaria faberi, and Sorghum bicolor. Examples of dicotyledonous species that can be controlled include Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Euphorbia heterophylla, Galium aparine, Ipomoea hederacea, Kochia scoparia, Polygonum Convolvulus, Sida spinosa, Sinapis arvensis, Solanum nigrum, Stellaria media, Veronica persica, and Xanthium strumarium. Weeds can also include plants that can be considered crops but grow outside the area of the crop ("escape"), or plants that grow from seeds left from a previously planted different crop ("volunteer").Such volunteers or escapes may be resistant to certain other herbicides.

[0133] Here, various aspects and embodiments of the present invention are illustrated in more detail by way of example. It will be understood that modifications in details can be made without departing from the scope of the present invention. Another aspect of the present invention may be as follows. 〔1〕A compound of formula (I)

Chemical formula

Chem.

[10] . 〔12〕Each R 9 is independently C 1 ~C 4 alkyl, C 1 ~C 4 haloalkyl, hydroxyl, C 1 ~C 4 alkoxy, or C 1 ~C 4 The compound according to any one of [1] to

[11] which is alkylthio. 〔13〕where W is W1, R 10 、R 11 、R 12 , and each of R 13 is hydrogen, the compound according to any one of [1] to

[12] above. 〔14〕where W is W2, R 14 and each of R 15 is hydrogen, the compound according to any one of [1] to

[12] above. 〔15〕where W is cis

Chem.

Chem.

[12] above. 〔16〕A herbicidal composition comprising the herbicidal compound according to any one of [1] to

[15] and an agriculturally acceptable formulation adjuvant. 〔17〕The herbicidal composition according to

[16] above, further comprising at least one additional pest control agent. 〔18〕The herbicidal composition according to

[17] above, wherein the additional pest control agent is a herbicide or a herbicide mitigator. 〔19〕A method for controlling unwanted plant growth, comprising applying the compound of formula (I) according to any one of [1] to

[15] above, or the herbicidal composition according to any one of

[16] to

[18] above, to the unwanted plant or its location. 〔20〕Use of the compound of formula (I) according to any one of [1] to

[15] above as a herbicide.

Example

[0134] Example 1 [5-[3-Chloro-6-fluoro-2-[2-(2-methyl-6-quinolyl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl]2-methylpropanoate (A-3.034) Preparation

Chem.

Chemical formula

[0135] 1.2 2-(2-Bromo-3-chloro-6-fluoro-phenyl)acetic acid A solution of 3-allyl-2-bromo-1-chloro-4-fluoro-benzene (15.0 g, 60.1 mmol) in dichloromethane (200 mL) in a two-necked flask was cooled to -78 °C. One side arm was connected to a trap containing an aqueous solution of KI. Ozone was bubbled through the solution until the starting material was completely consumed (5 hours). Air was bubbled through the solution for 10 minutes to remove excess ozone. Dimethyl sulfide (44 ml, 601 mmol) was added and the mixture was warmed to room temperature. The reaction was continued at room temperature for 16 hours.

[0136] The mixture was washed with brine (2 × 100 mL), and the organic layer was retained. The organic matter was dried over Na2SO4, filtered, concentrated under reduced pressure to obtain crude 2-(2-bromo-3-chloro-6-fluoro-phenyl)acetaldehyde (15.3 g), which was used for the next step without further purification.

[0137] Crude 2-(2-bromo-3-chloro-6-fluoro-phenyl)acetaldehyde (15.3 g, 60.8 mmol) was dissolved in a mixture of tert-butanol (92 mL) and water (46 mL), and then cooled to 0 °C. 2-Methylbut-2-ene (64.5 mL, 608 mmol), sodium dihydrogen phosphate (34.6 g, 243 mmol) and sodium chlorite (16.5 g, 163 mmol) were added. The mixture was stirred for 2 h and then diluted with brine (150 mL) and 2 M hydrochloric acid (150 mL). The mixture was extracted with ethyl acetate (3 × 100 mL). The combined organic extracts were washed with a saturated aqueous solution of sodium metabisulfite (100 mL), then dried over Na2SO4, filtered, concentrated under reduced pressure to give a pale yellow solid. The crude solid was dissolved in a mixture of water (100 mL) and 2.0 M NaOH (30 mL). The aqueous solution was washed with ethyl acetate (100 mL), and the organic matter was discarded. The aqueous layer was acidified by adding concentrated hydrochloric acid (20 mL), resulting in the formation of a white suspension. The mixture was extracted with ethyl acetate (3 × 200 mL). The combined organic matter was washed with brine, dried over Na2SO4, filtered, evaporated to give 2-(2-bromo-3-chloro-6-fluoro-phenyl)acetic acid (8.0 g, 49%) as a white solid.

Chemical formula

[0138] 1.3 2-(2-Bromo-3-chloro-6-fluoro-phenyl)-N-methyl-acetohydrazide To a stirred solution of 2-(2-bromo-3-chloro-6-fluoro-phenyl)acetic acid (2.0 g, 7.5 mmol) in dichloromethane (20 ml) at 0 °C was added N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride [EDC·HCl] (1.4 g, 9.0 mmol), followed by dropwise addition of methylhydrazine (0.4 ml, 7.5 mmol). The temperature of the reaction mixture was maintained at 0 °C for 3 h. The reaction was then quenched with water and extracted into dichloromethane. The organic layer was separated, washed with brine and dried over Na2SO4. Concentration under reduced pressure gave crude 2-(2-bromo-3-chloro-6-fluoro-phenyl)-N-methyl-acetohydrazide (1.8 g, 81%), which was used in the next step without further purification.

Chemical formula

[0139] 1.4 Ethyl 2-{[2-(2-bromo-3-chloro-6-fluoro-phenyl)-acetyl]-methyl-hydrazono}-propionate To a stirred solution of 2-(2-bromo-3-chloro-6-fluoro-phenyl)-N-methyl-acetohydrazide (1.8 g, 6.09 mmol) in ethanol (5 ml) was added dropwise ethyl pyruvate (0.7 ml, 6.7 mmol). The reaction was heated at 80 °C for 4 h. The reaction mixture was then cooled to room temperature and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent, gradient of ethyl acetate / hexane) to give the desired compound ethyl 2-{[2-(2-bromo-3-chloro-6-fluoro-phenyl)-acetyl]-methyl-hydrazono}-propionate (1.8 g, 75%) as an off-white solid.

Chemical formula

[0140] 1.5 4-(2-Bromo-3-chloro-6-fluoro-phenyl)-5-hydroxy-2,6-dimethyl-pyridazin-3-one Ethyl 2-{[2-(2-bromo-3-chloro-6-fluoro-phenyl)-acetyl]-methyl-hydrazono}-propionate (500 mg, 1.27 mmol) was dissolved in acetonitrile (2.5 ml) and treated with 1,8-diazabicyclo[5.4.0]undec-7-ene [DBU] (0.47 ml, 3.2 mmol). The mixture was heated to 125 °C using microwave irradiation for 1 hour. The reaction mixture was then evaporated under reduced pressure. The residue was dissolved in water and acidified to pH 1 with 2N hydrochloric acid. The mixture was extracted with DCM, the organic layer was separated and washed with brine solution. The organic solution was dried over Na2SO4 and concentrated under reduced pressure to give the crude product. The crude was purified by column chromatography on silica gel (eluent, gradient of ethyl acetate / hexane) to give 4-(2-bromo-3-chloro-6-fluoro-phenyl)-5-hydroxy-2,6-dimethyl-pyridazin-3-one (340 mg, 77.1%) as an off-white solid.

Chemical Structure

[0141] 1.6 [5-(2-Bromo-3-chloro-6-fluoro-phenyl)-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate To a stirred solution of 4-(2-bromo-3-chloro-6-fluoro-phenyl)-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.4 g, 4.02 mmol) in dichloromethane (32 ml) were added triethylamine (1.1 ml, 8.06 mmol), 4-(dimethylamino)pyridine [DMAP] (49 mg, 0.40 mmol) and isobutyryl chloride (0.6 ml, 4.83 mmol) at room temperature.

[0142] When judged to be complete, the reaction mixture was diluted with dichloromethane and water. The organic layer was separated, dried over Na2SO4 and concentrated under reduced pressure to give the crude product. The crude product was purified by column chromatography on silica gel (eluent, gradient of ethyl acetate / hexane) to give [5-(2-bromo-3-chloro-6-fluoro-phenyl)-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (1.47 g, 87%).

Chemical formula

[0143] 1.7 2-Methyl-6-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl]quinoline 4,4,5,5-Tetramethyl-2-vinyl-1,3,2-dioxaborolane (0.73 mL, 4.32 mmol) and N,N-diisopropylethylamine (1.25 mL, 7.20 mmol) were added to a stirred solution of 6-bromo-2-methylquinoline (800 mg, 3.6 mmol) and chloro[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) (92 mg, 0.18 mmol) in toluene (14 mL). The reaction mixture was heated to 95 °C under nitrogen for 4 h.

[0144] Upon completion, the reaction mixture was cooled to room temperature and then filtered through Celite® (eluting with DCM). The filtrate was concentrated in vacuo and then purified by flash column chromatography (silica, eluent, gradient of ethyl acetate / i - hexane) to afford 2-methyl-6-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl]quinoline (886 mg, 83% yield).

Chemical Structure

[0145] 1.8 [5-[3-Chloro-6-fluoro-2-[(E)-2-(2-methyl-6-quinolyl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl]2-methylpropanoate (A - 4.034) A solution of [[5-(2-bromo-3-chloro-6-fluoro-phenyl)-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (1.03 g, 2.47 mmol), Cs2CO3 (2.43 g, 7.40 mmol), 2-methyl-6-[(E)-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl]quinoline (0.874 g, 2.96 mmol), and Pd(dppf)Cl2.DCM (0.101 g, 0.123 mmol) in 1,4-dioxane (21 mL) and water (6 mL) was heated to reflux.

[0146] After 16 hours, the reaction mixture was concentrated in vacuo to remove most of the dioxane, then diluted with water and EtOAc. The organic layer was separated and the aqueous phase was extracted with portions of EtOAc (2×). The pH of the aqueous phase was then adjusted to pH 2 with 2 M HCl (aqueous solution), and then extracted with further portions of EtOAc.

[0147] The crude product was purified by flash column chromatography (silica, eluent, gradient of ethyl acetate / iso-hexane) to give [[5-[3-chloro-6-fluoro-2-[(E)-2-(2-methyl-6-quinolyl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (86 mg, 7% yield, A-4.034) and 4-[3-chloro-6-fluoro-2-[(E)-2-(2-methyl-6-quinolyl)vinyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (51 mg, 5% yield, A-2.034). [Chemical formula] 11H NMR (400 MHz, CDCl3) δ ppm 1.11 (app t, J = 7.1 Hz, 6H) 2.23 (s, 3H) 2.63 - 2.71 (m, 1H) 2.74 (s, 3H) 3.69 (s, 3H) 6.81 (d, J = 16.4 Hz, 1H) 7.04 (t, J = 8.7 Hz, 1H) 7.15 (d, J = 16.5 Hz, 1H) 7.27 (s, 1H) 7.45 (dd, J = 8.9, 5.07 Hz, 1H) 7.63 (d, J = 1.7 Hz, 1H) 7.75 - 7.81 (m, 1H) 7.94 (d, J = 8.8 Hz, 1H) 8.01 (d, J = 8.3 Hz, 1H) . [Chemical formula] 1 1H NMR (400 MHz, CDCl3) δ ppm 2.24 (s, 3H) 2.66 (s, 3H) 3.66 (s, 3H) 6.72 (d, J = 16.4 Hz, 1H) 6.93 - 7.07 (m, 2H) 7.26 (s, 1H) 7.38 (dd, J = 8.9, 5.14 Hz, 1H) 7.55 (d, J = 1.7 Hz, 1H) 7.66 (dd, J = 8.8, 2.0 Hz, 1H) 7.84 (d, J = 8.8 Hz, 1H) 7.99 (d, J = 8.4 Hz, 1H)

[0148] 1.9 [5-[3-chloro-6-fluoro-2-[2-(2-methyl-6-quinolyl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (A-3.034) [5-[3-chloro-6-fluoro-2-[(E)-2-(2-methyl-6-quinolyl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (56 mg, 0.12 mmol, 4.034) was subjected to catalytic hydrogenation in tetrahydrofuran (0.3 mL) over 5% Pd / C catalyst (24 mg) with 3 bar of H2.

[0149] Upon completion, the reaction mixture was filtered through a pad of Celite® eluting with DCM. The filtrate was concentrated in vacuo to afford the crude residue.

[0150] The residue was adsorbed onto silica and purified by flash column chromatography (silica, eluent, ethyl acetate / i - hexane) to obtain [5 - [3 - chloro - 6 - fluoro - 2 - [2 - (2 - methyl - 6 - quinolinyl)ethyl]phenyl]-1,3 - dimethyl - 6 - oxo - pyridazin - 4 - yl]2 - methylpropanoate (15 mg, 27% yield, A - 3.034). The mixture of the further reduced products was further purified by reversed - phase preparative HPLC based on mass to obtain [5 - [3 - chloro - 6 - fluoro - 2 - [2 - (2 - methyl - 1,2,3,4 - tetrahydroquinolin - 6 - yl)ethyl]phenyl]-1,3 - dimethyl - 6 - oxo - pyridazin - 4 - yl]2 - methylpropanoate (6 mg, 11% yield, A - 3.030). [Chemical formula] 1 H NMR (400 MHz, CDCl3) δ ppm 0.97 (dd, J = 7.0, 4.4 Hz, 6H) 2.24 (s, 3H) 2.47 - 2.57 (m, 1H) 2.73 (s, 3H) 2.79 - 3.09 (m, 4H) 3.84 (s, 3H) 7.00 (t, J = 8.6 Hz, 1H) 7.25 (d, J = 8.3 Hz, 1H) 7.49 (app d, J = 1.1 Hz, 3H) 7.90 (d, J = 8.4 Hz, 1H) 7.96 (d, J = 8.3 Hz, 1H). [Chemical formula] 1 H NMR (400 MHz, CDCl3) δ ppm 0.96 (dd, J = 7.03, 2.02 Hz, 6H) 1.25 (d, J = 6.24 Hz, 3H) 1.58 - 1.69 (m, 1H) 1.90 - 1.98 (m, 1H) 2.24 (s, 3H) 2.54 (dt, J = 13.94, 6.97 Hz, 1H) 2.63 - 2.84 (m, 6H) 3.39 (td, J = 6.51, 3.12 Hz, 1H) 3.83 (s, 3H) 6.52 (br d, J = 6.48 Hz, 1H) 6.72 - 6.79 (m, 2H) 6.96 (t, J = 8.62 Hz, 1H) 7.40 (dd, J = 8.80, 5.14 Hz, 1H).

[0151] Example 2 Preparation of 4-[3-chloro-6-fluoro-2-[2-(1H-indol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (A-1.021) [Chemical formula] 2.1 5-Benzyloxy-4-(2-bromo-3-chloro-6-fluoro-phenyl)-2,6-dimethyl-pyridazin-3-one Benzyl bromide (0.19 mL, 1.58 mmol) was added to a suspension of 4-(2-bromo-3-chloro-6-fluoro-phenyl)-5-hydroxy-2,6-dimethyl-pyridazin-3-one (500 mg, 1.44 mmol) and K2CO3 (0.22 g, 1.58 mmol) in acetone (2.9 mL), and the mixture was heated to reflux for 2 hours.

[0152] Upon completion, the reaction mixture was cooled to RT and then filtered (eluting with acetone). The filtrate was concentrated in vacuo and then purified by flash column chromatography (silica, eluent, gradient of ethyl acetate / iso-hexane) to give 5-benzyloxy-4-(2-bromo-3-chloro-6-fluoro-phenyl)-2,6-dimethyl-pyridazin-3-one (560 mg, 89% yield). [Chemical formula] 1 H NMR (400 MHz, CDCl3) δ ppm 2.29 (s, 3H) 3.77 (s, 3H) 4.59 - 4.76 (m, 2H) 7.09 (dd, J = 8.93, 7.95 Hz, 1H) 7.13 - 7.20 (m, 2H) 7.29 - 7.36 (m, 3H) 7.52 (dd, J = 8.93, 5.38 Hz, 1H).

[0153] 2.2 2-[(E)-2-[2-(5-Benzyloxy-2,6-dimethyl-3-oxo-pyridazin-4-yl)-6-chloro-3-fluoro-phenyl]vinyl]-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione A solution of stirred 5-benzyloxy-4-(2-bromo-3-chloro-6-fluoro-phenyl)-2,6-dimethyl-pyridazin-3-one (1.00 g, 2.28 mmol), chloro[(tri-tert-butylphosphine)-2-(2-aminobiphenyl)]palladium(II) (59 mg, 0.11 mmol), N,N-diisopropylethylamine (0.80 mL, 4.57 mmol) and 6-methyl-2-vinyl-1,3,6,2-dioxazaborocane-4,8-dione (0.50 g, 2.74 mmol) in THF (23 mL) was heated at 90 °C for 5 h and then at 70 °C for a further 16 h.

[0154] The reaction mixture was cooled to room temperature, then diluted with DCM, filtered through Celite® and eluted with a further portion of DCM. The filtrate was concentrated in vacuo and then purified by flash column chromatography (silica, eluent, gradient of ethyl acetate / methanol) to give 5-benzyloxy-4-(2-bromo-3-chloro-6-fluoro-phenyl)-2,6-dimethyl-pyridazin-3-one; 2-[(E)-2-[2-(5-benzyloxy-2,6-dimethyl-3-oxo-pyridazin-4-yl)-6-chloro-3-fluoro-phenyl]vinyl]-6-methyl-1,3,6,2-dioxazaborocane-4,8-dione (904 mg, 74% yield).

Chemical formula

[0155] 2.3 5 - Benzyloxy - 4 - [3 - chloro - 6 - fluoro - 2 - [(E) - 2 - (1H - indol - 5 - yl)vinyl]phenyl] - 2,6 - dimethyl - pyridazin - 3 - one Into a microwave vial were added 2 - [(E) - 2 - [2 - (5 - benzyloxy - 2,6 - dimethyl - 3 - oxo - pyridazin - 4 - yl) - 6 - chloro - 3 - fluorophenyl]vinyl] - 6 - methyl - 1,3,6,2 - dioxazaborocane - 4,8 - dione (300 mg, 0.56 mmol), 5 - bromo - 1H - indole (163 mg, 0.84 mmol), Pd(dppf)Cl2.DCM (23 mg, 0.028 mmol), and K3PO4.H2O (512 mg, 2.22 mmol). Then, the vial was capped, purged with N2, and then THF (5.6 mL) and water (0.2 mL) were added. Subsequently, the reaction mixture was heated to 90 °C for 30 minutes under microwave irradiation.

[0156] The reaction mixture was cooled to room temperature and then partitioned between water (20 mL) and EtOAc (20 mL). The organic layer was separated, and the aqueous layer was extracted with EtOAc (2 × 20 mL). The combined organics were collected, dried (MgSO4), filtered, and concentrated in vacuo to afford the crude product.

[0157] The crude product was purified by mass - based reverse - phase preparative HPLC to give 5 - benzyloxy - 4 - [3 - chloro - 6 - fluoro - 2 - [(E) - 2 - (1H - indol - 5 - yl)vinyl]phenyl] - 2,6 - dimethyl - pyridazin - 3 - one (45 mg, 16% yield). [Chemical formula] 11H NMR (400 MHz, CDCl3) δ ppm 2.20 (s, 3H) 3.76 (s, 3H) 4.70 (d, J = 5.3 Hz, 2H) 6.53 (t, J = 2.1 Hz, 1H) 6.78 - 6.86 (m, 1H) 6.88 - 6.94 (m, 1H) 7.01 (t, J = 8.6 Hz, 1H) 7.12 - 7.17 (m, 2H) 7.19 (t, J = 2.8 Hz, 1H) 7.21 - 7.25 (m, 1H) 7.29 - 7.35 (m, 4H) 7.47 (dd, J = 8.9, 5.3 Hz, 1H) 7.55 (s, 1H) 8.25 - 8.44 (m, 1H).

[0158] 2.4 4-[3-Chloro-6-fluoro-2-[2-(1H-indol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (A-1.021) 5-Benzyloxy-4-[3-chloro-6-fluoro-2-[(E)-2-(1H-indol-5-yl)vinyl]phenyl]-2,6-dimethyl-pyridazin-3-one (45 mg, 0.09 mmol) was subjected to catalytic hydrogenation in tetrahydrofuran (0.23 mL) over 5% Pd / C catalyst (38 mg × 2) with 3 bar of H2.

[0159] Upon completion, the reaction mixture was filtered through a pad of Celite® eluting with DCM. The filtrate was concentrated in vacuo to afford the crude residue.

[0160] The residue was adsorbed onto silica and purified by flash column chromatography (silica, eluent, ethyl acetate / i - hexane) to afford 4-[3-chloro-6-fluoro-2-[2-(1H-indol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (24 mg, 65% yield, A-1.021).

Chemical Structure

[0161] Example 3 Preparation of 4-[3-chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.343)

Chemical Structure

[0162] The reaction mixture was cooled to room temperature, then diluted in DCM, filtered through Celite®, and washed with a further portion of DCM. The eluent was then concentrated to dryness.

[0163] The crude product was purified by flash column chromatography to afford [5-[3-chloro-6-fluoro-2-[(E)-2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (5.91 g, 11.4 mmol, 95% yield) as an off-white solid.

Chemical formula

[0164] 3.2 [5-[3-chloro-6-fluoro-2-[(E)-2-(3-methylbenzotriazol-5-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (4.343) [5-[3-Chloro-6-fluoro-2-[(E)-2-(6-methyl-4,8-dioxo-1,3,6,2-dioxazaborocan-2-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (700 mg, 1.35 mmol), [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium(II) dichloromethane complex [PdCl2(dppf).DCM] (55 mg, 0.067 mmol), 6-bromo-1-methyl-benzotriazole (371 mg, 1.75 mmol) and potassium phosphate (1.17 g, 5.39 mmol) were added to a 10 - 20 ml microwave vial. 2-Methyltetrahydrofuran (10 ml) and water (0.5 ml) were added, and then the reaction mixture was degassed by evacuation and refilled with nitrogen (×3). The reaction mixture was heated to 120 °C for 60 minutes under microwave irradiation.

[0165] The reaction mixture was filtered through a plug of celite (registered trademark) and washed with EtOAc and EtOH. The filtrate was concentrated under reduced pressure to give a brown gum (853 mg). The crude material was purified by automated flash chromatography on silica gel eluting with a gradient of cyclohexane / ethyl acetate to give [5-[3-chloro-6-fluoro-2-[(E)-2-(3-methylbenzotriazol-5-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (4.343) as an orange gum (622 mg, 87% yield).

[0166] The purified material was dissolved in acetonitrile (10 mL) and treated with SiliCycle SiliaMetS® thiol (SH) metal scavenger resin (622 mg) at room temperature. The suspension was stirred at room temperature for 1.5 h, then filtered to remove the resin and washed with additional acetonitrile. The filtrate was concentrated in vacuo to give [5-[3-chloro-6-fluoro-2-[(E)-2-(3-methylbenzotriazol-5-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (4.343) as a white solid (583 mg, 87% yield). [Chemical formula] 1 H NMR (400 MHz, chloroform) δ 7.96 (d, J = 9.0 Hz, 1H), 7.39 - 7.49 (m, 3H), 7.15 (d, J = 16.3 Hz, 1H), 7.05 (t, J = 8.7 Hz, 1H), 6.81 (d, J = 16.3 Hz, 1H), 4.29 (s, 3H), 3.68 (s, 3H), 2.67 (spt, J = 7.0 Hz, 1H), 2.23 (s, 3H), 1.13 (d, J = 7.0 Hz, 3H), 1.09 (d, J = 7.0 Hz, 3H)

[0167] 3.3 [5-[3-Chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate [5-[3-Chloro-6-fluoro-2-[(E)-2-(3-methylbenzotriazol-5-yl)vinyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (496 mg, 1.00 mmol) was subjected to catalytic hydrogenation in EtOAc (10 mL) over 5% Pd / C (50% wet) catalyst (0.21 g) with 3 bar of H2 for 18 h at room temperature.

[0168] The reaction mixture was filtered through a pad of Celite® and washed with ethyl acetate. The filtrate was concentrated in vacuo to afford a crude residue (503 mg), which was purified by mass-based reverse-phase HPLC to give [5-[3-chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate as a colorless gum (332 mg, 67% yield). [Chemical formula] 1 H NMR (400 MHz, chloroform) δ = 7.92 (d, J = 8.6 Hz, 1H), 7.43 (dd, J = 5.1, 8.7 Hz, 1H), 7.24 (br s, 1H), 7.17 (dd, J = 1.3, 8.6 Hz, 1H), 7.01 (t, J = 8.7 Hz, 1H), 4.26 (s, 3H), 3.81 (s, 3H), 3.11 - 2.91 (m, 3H), 2.86 - 2.72 (m, 1H), 2.54 (spt, J = 7.0 Hz, 1H), 2.25 (s, 3H), 0.98 (d, J = 7.1 Hz, 3H), 0.96 (d, J = 7.0 Hz, 3H)

[0169] 3.4 Preparation of 4-[3-chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridin-3-one (1.343) [5-[3-chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (332 mg, 0.67 mmol) was stirred in ethanol (5 ml) at room temperature. A solution of lithium hydroxide monohydrate (85 mg, 2.00 mmol) in water (2 ml) was added dropwise and the reaction was stirred at room temperature for 21 h.

[0170] The ethanol solvent was removed under reduced pressure, and then the residue was diluted with water (20 ml). The aqueous phase was acidified to about pH 3 - 4 by adding 2 M HCl (aqueous solution), and then extracted with EtOAc (3 × 10 ml). The combined organic extracts were concentrated under reduced pressure to give a white solid (240 mg). The crude residue was purified by automated flash chromatography on silica eluting with a cyclohexane / ethyl acetate gradient to give 4-[3-chloro-6-fluoro-2-[2-(3-methylbenzotriazol-5-yl)ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.343) as a white solid (196 mg, 69%).

Chemical formula

[0171] Example 4 Preparation of 4-[2-[2-(1,3-benzothiazol-5-yl)ethyl]-3-chloro-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.350)

Chemical formula

[0172] The reaction mixture was concentrated to dryness. The residue was treated with water (10 ml) and the aqueous phase was acidified to pH 4 by addition of 1 M HCl (aqueous solution). DCM (20 ml) was added and the layers were separated. The aqueous phase was further extracted with DCM / MeOH (8:1) (2 × 10 ml) and then the combined organic extracts were dried, concentrated to give a brown oil. The crude material was purified by automated flash chromatography on silica gel eluting with a gradient of cyclohexane / ethyl acetate to give 4-[2-[(E)-2-(1,3-benzothiazol-5-yl)vinyl]-3-chloro-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one as a white solid (302 mg, 73% yield).

[0173] The product obtained was dissolved in a 3:2 mixture of methanol / ethyl acetate (25 ml). The solution was treated with activated carbon (100 mg) and then stirred at room temperature for 1 hour. The mixture was filtered through celite® and then washed with a further 3:2 MeOH / EtOAc (10 ml). The filtrate was treated with SiliCycle SiliaMetS® thiol (SH) metal scavenger resin (300 mg) and then stirred at room temperature for 16 hours. The mixture was filtered to remove the resin and then the filtrate was concentrated in vacuo to give an off-white solid (286 mg). [Chemical formula] 1 H NMR (400 MHz, DMSO-d6) δ = 10.84 (br s, 1H), 9.41 (s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.00 (d, J = 1.5 Hz, 1H), 7.62 (dd, J = 5.1, 8.7 Hz, 1H), 7.54 (dd, J = 1.5, 8.4 Hz, 1H), 7.29 (t, J = 8.7 Hz, 1H), 7.09 (d, J = 16.5 Hz, 1H), 6.74 (d, J = 16.5 Hz, 1H), 3.54 (s, 3H), 2.18 (s, 3H)

[0174] 4.2 4-[2-[2-(1,3-Benzothiazol-5-yl)ethyl]-3-chloro-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.350) To a solution of 4-[2-[(E)-2-(1,3-benzothiazol-5-yl)vinyl]-3-chloro-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (835 mg, 1.95 mmol) in tetrahydrofuran (30 ml) was added N,N-diisopropylethylamine (2.70 ml, 16.0 mmol) under a nitrogen atmosphere. The stirred reaction mixture was heated to 70 °C, and 2,4,6-triisopropylbenzenesulfonyl hydrazide (5.17 g, 15.6 mmol) was added portionwise over 4 hours, and then the mixture was heated to reflux for 16 hours. A further amount of N,N-diisopropylethylamine (1.70 ml, 9.80 mmol) was added to the reaction mixture, followed by 2,4,6-triisopropylbenzenesulfonyl hydrazide (3.24 g, 9.77 mmol), and the mixture was heated to reflux for an additional 6 hours.

[0175] The reaction mixture was cooled to room temperature and then concentrated directly onto silica. The crude material was partially purified by automated flash chromatography on silica gel eluting with a gradient of cyclohexane / ethyl acetate. The resulting material was further purified by reverse-phase HPLC based on mass to give 4-[3-chloro-6-fluoro-2-[2-[4-(methylsulfanylmethyl)phenyl]ethyl]phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.350) as a pale yellow solid (227 mg, 27% yield).

Chem.

[0176] Example 5 Preparation of [3-chloro-2-[2-(2,2-dimethyl-1,3-benzodioxol-5-yl)ethyl]-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.361)

Chem.

[0177] After 24 hours, the reaction mixture was cooled to room temperature and then concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with a gradient of cyclohexane / ethyl acetate to give [5-[3-chloro-6-fluoro-2-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl]2-methylpropanoate (4.50 g, 51% yield) as a yellow solid.

Chemical Structure

[0178] 5.2 [3-Chloro-2-[2-(2,2-dimethyl-1,3-benzodioxol-5-yl)ethyl]-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.361) 5-Bromo-2,2-dimethyl-1,3-benzodioxole (70 mg, 0.30 mmol) was charged into a 2 - 5 ml microwave vial. [5-[3-Chloro-6-fluoro-2-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)ethyl]phenyl]-1,3-dimethyl-6-oxo-pyridazin-4-yl] 2-methylpropanoate (100 mg, 0.20 mmol) was added as a solution in 1,4-dioxane (2 ml), followed by the addition of chloro(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1’-biphenyl)[2-(2’-amino-1,1’-biphenyl)]palladium(II) (RuPhos Pd-G2) (26 mg, 0.03 mmol) as a solution in 1,4-dioxane (2 ml). A 2 M aqueous solution of potassium carbonate (0.30 ml, 0.61 mmol) was added and the mixture was heated to 140 °C for 80 minutes under microwave irradiation.

[0179] The reaction mixture was cooled to room temperature and then filtered through a pre-wetted 0.5 g silica-TMT cartridge and washed with acetonitrile (2 × 2 ml). The filtrate was concentrated to dryness and then purified by mass-based reverse-phase HPLC to give [3-Chloro-2-[2-(2,2-dimethyl-1,3-benzodioxol-5-yl)ethyl]-6-fluoro-phenyl]-5-hydroxy-2,6-dimethyl-pyridazin-3-one (1.361) as a white solid (15 mg, 17% yield).

Chemical Structure

[0180] Compounds 1.019, 1.021, 1.027, 1.028, 1.036, 2.034, 3.030, 3.034, 4.034, 1.339, 1.340, 1.341, 1.342, 1.344, 1.345, 1.346, 1.347, 1.348, 1.349, 1.351, 1.352, 1.353, 1.354, 1.355, 1.356, 1.044, 1.053, 1.357, 1.358, 1.359, 1.360, 2.362, 2.363, and 4.342 were prepared using the general method as described above. Table 5 below shows the structures and NMR characterization data of these compounds.

[0181]

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

[0182] Biological Examples Effectiveness after B1 germination - Test 1 Seeds of various test species are sown in standard soil in pots: - Black nightshade (Solanum nigrum) (SOLNI), Redroot amaranth (Amaranthus retoflexus) (AMARE), Giant foxtail (Setaria faberi) (SETFA), Barnyard grass (Echinochloa crus-galli) (ECHCG), Ivy-leaved morning glory (Ipomoea hederacea) (IPOHE), Perennial ryegrass (Lolium perenne) (LOLPE). Eight days after cultivation (after germination) under controlled conditions in the greenhouse (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity), a spray aqueous solution derived 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) is sprayed onto the plants. The compound is applied at 250 g / ha. Next, the test plants are grown in the greenhouse under controlled conditions in the greenhouse (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity) and watered twice a day. After 13 days, the test is evaluated for the percentage of damage caused to the plants. The biological activity is evaluated on a 5-point scale (5 = 80 - 100%; 4 = 60 - 79%; 3 = 40 - 59%; 2 = 20 - 39%; 1 = 0 - 19%). The empty test values in the table indicate that the compound was not tested for the corresponding species.

[0183]

Table 3

[0184] Effectiveness after B2 germination - Test 2 Seeds of various test species are sown in standard soil in pots: - Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE), Zea mays (ZEAMX), Abutilon theophrasti (ABUTH). After 8 days of cultivation (after germination) in a greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity), a spray aqueous solution derived from a formulation of the industrial active ingredient in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5) is sprayed onto the plants. The compound is applied at 250 g / ha. The test plants are then grown in the greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity) in the greenhouse and watered twice a day. After 13 days, the test is evaluated for the percentage of damage inflicted on the plants. The biological activity is assessed on a 5-point scale (5 = 80 - 100%; 4 = 60 - 79%; 3 = 40 - 59%; 2 = 20 - 39%; 1 = 0 - 19%). The blank values in the table indicate that the compound was not tested for that species.

[0185]

Table 4

[0186] B3 Pre-emergence efficacy - Test 1 Seeds of various test species were sown in standard soil in pots: black nightshade (Solanum nigrum) (SOLNI), redroot pigweed (Amaranthus retroflexus) (AMARE), giant foxtail (Setaria faberi) (SETFA), barnyard grass (Echinochloa crus-galli) (ECHCG), ivy-leaved morning glory (Ipomoea hederacea) (IPOHE), perennial ryegrass (Lolium perenne) (LOLPE). After one day of cultivation (before germination) in a greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity), the plants were sprayed with an aqueous spray solution derived from a formulation of industrial active ingredients in an acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5). The compound was applied at 250 g / ha. The test plants were then grown in the greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity) and watered twice a day. After 13 days, the test was evaluated for the percentage of damage inflicted on the plants. The biological activity was assessed on a 5-point scale (5 = 80 - 100%; 4 = 60 - 79%; 3 = 40 - 59%; 2 = 20 - 39%; 1 = 0 - 19%). The blank values in the table indicate that the compound was not tested on that species.

[0187]

Table 5

[0188] B4 Efficacy before germination - Test 2 Seeds of various test species were sown in standard soil in pots: Amaranthus retoflexus (AMARE), Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Ipomoea hederacea (IPOHE), Zea mays (ZEAMX), Abutilon theophrasti (ABUTH). After one day of cultivation (before germination) in a greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity), the plants were sprayed with an aqueous spray solution derived 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). The compound was applied at 250 g / ha. The test plants were then grown in the greenhouse under controlled conditions (24 / 16 °C, day / night; 14 hours of lighting; 65% humidity) and watered twice a day. After 13 days, the test was evaluated for the percentage of damage inflicted on the plants. The biological activity was assessed on a 5-point scale (5 = 80 - 100%; 4 = 60 - 79%; 3 = 40 - 59%; 2 = 20 - 39%; 1 = 0 - 19%). The blank values in the table indicate that the compound was not tested for that species.

[0189]

Table 6

Claims

1. A compound of the following formula (I) 【Chemical 1】 or an agriculturally acceptable salt or N-oxide thereof [In the formula,[[]]END] R 1 is C 1 to C 4 alkyl, C 3 to C 6 cycloalkyl, C 3 to C 6 alkoxy, C 1 to C 2 alkoxy-C 1 to C 2 alkyl-, C 2 to C 4 alkenyl, C 1 to C 4 haloalkyl, cyano-C 1 to C 4 alkyl, C 2 to C 4 haloalkenyl, C 2 to C 4 alkynyl and C 2 to C 4 selected from the group consisting of haloalkynyl; R 2 is hydrogen, halogen, cyano, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 1 to C 6 haloalkoxy, C 1 to C 3 haloalkoxy-C 1 to C 3 alkyl-, C 1 to C 6 alkoxy, C 1 to C 3 alkoxy-C 1 to C 3 alkyl-, C 1 to C 3 alkoxy-C 1 to C 3 alkoxy-C 1 to C 3 alkyl-, C 3~C 6 Cycloalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Haloalkenyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Hydroxyalkyl-, C 1 ~C 6 Alkylcarbonyl-, -S(O) m C 1 ~C 6 Alkyl, amino, C 1 ~C 6 Alkylamino, C 1 ~C 6 Dialkylamino, -C(C 1 ~C 3 Alkyl)=N-O-C 1 ~C 3 Alkyl and C 2 ~C 6 Selected from the group consisting of haloalkynyl; G is hydrogen, or C(O)R 3 wherein; R 3 is C 1 ~C 6 Alkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Alkynyl, C 1 ~C 6 Alkyl-S-, C 1 ~C 6 Alkoxy, -NR 4 R 5 and one or more R 6 Optionally substituted phenyl selected from the group consisting of; Each R 4 and R 5 is independently selected from the group consisting of hydrogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy, and C 3 ~C 6 Cycloalkyl, or R 4 and R 5 can together form a morpholinyl ring; R 6 is selected from the group consisting of halogen, cyano, nitro, C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, C 1 -C 3 alkoxy and C 1 -C 3 haloalkoxy; X and Y are each independently hydrogen, C 1 -C 3 alkyl, cyclopropyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, or halogen; D is a substituted or unsubstituted naphthalene ring system, or a substituted or unsubstituted 8- to 10-membered bicyclic saturated, partially saturated or unsaturated heterocyclic ring system containing 1, 2, 3 or 4 heteroatoms independently selected from oxygen, nitrogen and sulfur, and when D is substituted, it is substituted with R 8 on at least one ring carbon atom and / or substituted with R 9 on at least one ring nitrogen atom; Each R 8 is independently oxo, hydroxyl, halogen, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 haloalkoxy, C 1 -C 3 alkoxy-C 1 -C 3 alkyl, C 1 -C 3 haloalkoxy-C 1 ~C 3 alkyl-, C 1 ~C 3 alkoxy-C 1 ~C 3 alkoxy-C 1 ~C 3 alkyl-, C 2 ~C 6 alkenyl, C 2 ~C 6 haloalkenyl, C 2 ~C 6 alkynyl, C 2 ~C 6 haloalkynyl, C 1 ~C 6 hydroxyalkyl-, C 1 ~C 6 alkylcarbonyl-, C 1 ~C 6 haloalkylcarbonyl-, C 3 ~C 6 cycloalkylcarbonyl-, C 1 ~C 6 alkyl-S(O) m -, -S(O) m -C 1 ~C 6 haloalkyl, -S(O) m -C 3 ~C 6 cycloalkyl, -O-S(O) 2 C 1 ~C 3 alkyl, -C 1 ~C 3 alkyl-S(O) m -C 1 ~C 6 alkyl, -C 1 ~C 3 alkyl-S(O) m -C 1 ~C 6 haloalkyl, -C 1 ~C 3 alkyl-S(O) m -C 3 ~C 6 cycloalkyl, cyano-C 1 ~C 6 -alkyl-, -NR 4 R 5, -C(C 1 ~C 3 alkyl)=N-O-C 1 ~C 3 alkyl, -C(S)NH 2 C 1 ~C 6 alkylaminothiocarbonyl-, di(C 1 ~C 6 alkyl)aminothiocarbonyl-, C 3 ~C 6 -cycloalkylamino-thiocarbonyl-S(O) 2 NH 2 , -S(O) 2 NH C(O)C 1 ~C 3 alkyl, C 1 ~C 6 alkylaminosulfonyl-, di(C 1 ~C 6 alkyl)aminosulfonyl-, C 3 ~C 6 -cycloalkylamino-sulfonyl-, -C(O)OH, -C(O)OC 1 ~C 6 alkyl, -C(O)NH S-(O) 2 C 1 ~C 6 alkyl, -C(O)NR 4 R 5 , -NR 4 C(O)NR 4 R 5 C 1 ~C 6 alkylcarbonyl(C 1 ~C 6 alkyl)amino-, C 1 ~C 6 haloalkylcarbonylamino-, C 1 ~C 6 haloalkylcarbonyl(C 1 ~C 6 alkyl)amino-, C 1 ~C 6 alkoxycarbonylamino-, C 1 ~C 6 alkoxycarbonyl(C 1 ~C 6 alkyl)amino-, C 1~C 6 alkylsulfonylamino-, C 1 ~C 6 alkylsulfonyl(C 1 ~C 6 alkyl)amino-, C 1 ~C 6 haloalkylsulfonylamino-, C 1 ~C 6 haloalkylsulfonyl(C 1 ~C 6 alkyl)amino-, C 3 ~C 6 cycloalkylsulfonylamino-, C 3 ~C 6 cycloalkylsulfonyl(C 1 ~C 6 alkyl)amino-, C 1 ~C 6 alkylaminocarbonylamino-, C 1 ~C 6 alkylaminocarbonyl(C 1 ~C 6 alkyl)amino, di(C 1 ~C 6 alkyl)aminocarbonylamino-, C 1 ~C 6 haloalkylaminocarbonylamino-, C 1 ~C 6 haloalkylamino-carbonyl(C 1 ~C 6 alkyl)amino, di(C 1 ~C 6 haloalkyl)aminocarbonylamino-, di(C 1 ~C 6 haloalkyl)amino-carbonyl(C 1 ~C 6 alkyl)amino-, hydroxyamino-, hydroxy(C 1 ~C 6 alkyl)amino, C 1 ~C 6 alkoxyamino, C 1 ~C 6 alkoxy(C 1 ~C 6 alkyl)amino, C 1 ~C 6Haloalkoxyamino, C 1 -C 6 haloalkoxy(C 1 -C 6 alkyl)amino; or a ring system selected from the group consisting of a phenyl ring, a 5- to 6-membered heteroaryl ring, and a 3- to 6-membered heterocyclic ring, wherein the ring system is substituted with 0 to 5 R 16 s, provided that when D is a naphthalene ring system or an 8- to 10-membered bicyclic unsaturated heterocyclic ring, R 8 is not oxo; m is an integer of 0, 1, or 2; Each R 9 is independently C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, hydroxyl, C 1 -C 4 alkoxy, C 1 -C 4 alkylthio, C 3 -C 6 -cycloalkyl, C 1 -C 3 alkoxy-C 1 -C 3 alkyl, C 1 -C 3 haloalkoxy-C 1 -C 3 alkyl-, C 1 -C 3 alkoxy-C 1 -C 3 alkoxy-C 1 -C 3 alkyl-, C 1 -C 6 hydroxyalkyl-, -C 1 -C 3 alkyl-S(O) m -C 1 -C 6 alkyl, -C 1 -C 3 alkyl-S(O) m -C 1 -C 6 haloalkyl, -C 1 -C 3 alkyl-S(O) m -C 3 to C 6 cycloalkyl, cyano-C 1 to C 6 -alkyl-, or a ring system selected from the group consisting of a phenyl ring, a 5- to 6-membered heteroaryl ring, and a 3- to 6-membered heterocyclic ring, wherein the ring system is substituted with 0 to 5 R 16 ; Each R 16 is, independently, halogen, cyano, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 1 to C 6 alkoxy or C 1 to C 6 haloalkoxy; W is a group selected from the group of the following formula [Chemical Formula 2 wherein, "a" indicates the attachment point to the phenyl-pyridazinone / phenyl-pyridazinedione moiety, "b" indicates the attachment point to ring D, R 10 , R 12 , R 14 and R 15 are each independently hydrogen, C 1 to C 3 alkyl, or C 1 to C 3 haloalkyl; or R 10 and R 12 together with the carbon atom to which they are attached form a C 3 to C 6 carbocyclic ring; R 11 and R 13 are each independently hydrogen, halogen, C 1 to C 3 alkyl, or C 1 to C 3 haloalkyl, provided that one of R 11 or R 13 is halogen, C 1 to C 3 alkyl or C 1~C 3 when it is haloalkyl, the other is hydrogen].

2. G is hydrogen or C(O)R 3 where R 3 is isopropyl, t-butyl, methyl, ethyl, propargyl, methoxy, ethoxy, or tert-butoxy, the compound according to claim 1.

3. X is hydrogen, halogen, or C 1 haloalkyl, the compound according to any one of claims 1 to 2.

4. Y is hydrogen, C 1 ~C 3 alkyl, cyclopropyl, C 1 ~C 3 haloalkyl, or halogen, the compound according to any one of claims 1 to 3.

5. X is ortho with respect to the pyridazinone / pyridazinedione moiety, the compound according to any one of claims 1 to 4.

6. Y is ortho with respect to the -W-D moiety, the compound according to any one of claims 1 to 5.

7. R 1 is methyl, ethyl, n-propyl, cyclopropyl, propargyl, or C 1 haloalkyl, the compound according to any one of claims 1 to 6.

8. R 2 is hydrogen, halogen, C 1 ~C 6 alkyl, C 1 ~C 6 haloalkyl, C 1 ~C 6 alkoxy, C 1 ~C 3 alkoxy-C 1 ~C 3 alkyl, C 3 ~C 6 cycloalkyl, C 2 ~C 6 Alkenyl, C 2 ~C 6 Haloalkenyl, C 2 ~C 6 Alkynyl and C 2 ~C 6 The compound according to any one of claims 1 to 7, selected from the group consisting of haloalkynyl.

9. D is a substituted or unsubstituted naphthalene, indolizine, indole, iso-indole, indoline, isoindoline, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, benzoxazole, benzodioxole, purine, 4H-quinolizine, quinoline, isoquinoline, tetrahydroquinoline, cinnoline, phthalazine, quinoxaline, 1-8-naphthyridine, pteridine, 1H-pyrrolo[2,3-b]pyridine, imidazo[1,2-a]pyrazine or 1H-benzotriazole ring system, and when D is substituted, it is substituted with R 8 on at least one ring carbon atom and / or substituted with R 9 on at least one ring nitrogen atom, the compound according to any one of claims 1 to 8.

10. D is a substituted or unsubstituted naphthalene, indolizine, indole, iso-indole, 3-H-indole, benzofuran, benzothiophene, 1H-indazole, benzimidazole, benzothiazole, benzoxazole, purine, 4H-quinolizine, quinoline, isoquinoline, tetrahydroquinoline, cinnoline, phthalazine, quinoxaline, 1-8-naphthyridine, or pteridine ring system, and when D is substituted, it is substituted with R 8 on at least one ring carbon atom and / or substituted with R 9 on at least one ring nitrogen atom, the compound according to any one of claims 1 to 9.

11. Each R 8 is independently oxo, hydroxyl, halogen, cyano, C 1 to C 6 alkyl, C 1 to C 6 haloalkyl, C 1 to C 6 haloalkoxy, C 1 to C 3 haloalkoxy-C 1 to C 3 alkyl-, C 1 to C 6 alkoxy, C 1 to C 3 alkoxy-C 1 to C 3 alkyl, C 1 to C 3 alkoxy-C 1 to C 3 alkoxy-C 1 to C 3 alkyl-, C 3 to C 6 cycloalkyl, C 2 to C 6 alkenyl, C 2 to C 6 haloalkenyl, C 2 to C 6 alkynyl, C 1 to C 6 hydroxyalkyl-, C 1 to C 6 alkylcarbonyl-, C 1 to C 6 alkyl-S(O) m -, amino, C 1 to C 6 alkylamino, C 1 to C 6 dialkylamino, -C(C 1 to C 3 alkyl)=N-O-C 1 to C 3 alkyl or C 2 to C 6 haloalkynyl, provided that when D is a naphthalene ring system or an 8- to 10-membered bicyclic unsaturated heterocyclic ring system, R 8 is not oxo, the compound according to any one of claims 1 to 10.

12. Each R 9 is, independently, C 1 -C 4 alkyl, C 1 -C 4 haloalkyl, hydroxyl, C 1 -C 4 alkoxy, or C 1 -C 4 alkylthio, and the compound according to any one of claims 1 to 11.

13. W is W1, and R 10 , R 11 , R 12 , and R 13 each of which is hydrogen, and the compound according to any one of claims 1 to 12.

14. W is W2, and R 14 and R 15 each of which is hydrogen, and the compound according to any one of claims 1 to 12.

15. A herbicidal composition comprising the herbicidal compound according to any one of claims 1 to 14 and an agriculturally acceptable formulation adjuvant.

16. The herbicidal composition according to claim 15, further comprising at least one additional pest control agent.

17. The herbicidal composition according to claim 16, wherein the additional pest control agent is a herbicide or a herbicide mitigator.

18. A method for controlling unwanted plant growth, comprising applying the compound of formula (I) according to any one of claims 1 to 14 or the herbicidal composition according to any one of claims 15 to 17 to the unwanted plant or its location.

19. Use of the compound of formula (I) according to any one of claims 1 to 14 as a herbicide.

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