Herbicidal pyridone derivatives

Abstract

A compound of formula (I), in which the substituents are as defined in claim 1. The present invention further relates to herbicidal compositions comprising compounds of formula (I) and to the use of compounds of formula (I) for controlling weeds, especially in crops of useful plants. [Formula 1] JPEG2025501721000163.jpg41160

Description

[Technical Field]

[0001] The present invention relates to herbicidal pyridone derivatives, for example as active ingredients having herbicidal activity. The present invention also relates to agrochemical compositions comprising at least one pyridone derivative, processes for the preparation of these compounds, and the use of the pyridone derivatives or compositions in the control of weeds in agriculture or horticulture, especially in crops of useful plants. [Background technology]

[0002] EP 0239391, EP 0127313, EP 0040082, CN108617661, and GB 2182931 describe pyridone derivatives as herbicides. Summary of the Invention [Means for solving the problem]

[0003] According to the present invention, a compound of formula (I): [ka] (In the formula, R 1 is C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl or C1-C6 alkoxyC1-C6 alkyl; R 2 is phenyl or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and each phenyl and heteroaryl moiety is selected from R 7 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 3 is hydrogen or C1-C6 alkyl; R 4 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or phenyl, and each phenyl moiety is R8 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 5 is heteroaryl, wherein the heteroaryl moiety is a 5-membered aromatic monocyclic ring containing 1, 2, or 3 nitrogen atoms, the heteroaryl moiety is attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety is selected from the group consisting of R 9 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 6 is hydrogen, C1-C3 alkyl or C1-C6 alkoxy; R 7 is cyano, nitro, amino, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonamido, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, or N,N-di(C1-C4 alkyl)aminocarbonyl; R 8 is halogen, C1-C3 alkyl or C1-C3 alkoxy; R 9is formyl, acetyl, cyano, amino, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkyl, cyanoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonylC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonamido, hydroxycarbonyl, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl , C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C6 alkoxyiminoC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C4 alkyl)amino, N,N-di(C1-C4 alkyl)aminocarbonyl, phenyl, benzyloxy, or heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties are selected from R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring can be formed by R 11 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 10 is halogen, nitro, C1-C3 alkyl or C1-C3 alkoxy) Alternatively, a salt or N-oxide thereof is provided.

[0004] Surprisingly, it has now been found that the novel compounds of formula (I) have, for practical purposes, a highly advantageous level of herbicidal activity.

[0005] According to a second aspect of the present invention, there is provided an agricultural composition comprising a herbicidally effective amount of a compound of formula (I) according to the present invention, which may further comprise at least one additional active ingredient and / or an agrochemically acceptable diluent or carrier.

[0006] According to a third aspect of the present invention there is provided a method of controlling weeds in a locus, the method comprising the step of applying to the locus a weed-controlling amount of a composition comprising a compound of formula (I).

[0007] According to a fourth aspect of the present invention there is provided the use of a compound of formula (I) as a herbicide. DETAILED DESCRIPTION OF THE INVENTION

[0008] Where a substituent is described as being "optionally substituted", this includes one or more equal or different substituents, for example, one, two, or three R 7 This means that it may or may not have a substituent. For example, C1-C6 alkyl substituted with 1, 2, or 3 halogens may include, but is not limited to, -CH2Cl, -CHCl2, -CCl3, -CH2F, -CHF2, -CF3, -CH2CF3, or -CF2CH3 groups. As another example, C1-C6 alkoxy substituted with 1, 2, or 3 halogens may include, but is not limited to, CH2ClO-, CHCl2O-, CCl3O-, CH2FO-, CHF2O-, CF3O-, CF3CH2O-, or CH3CF2O- groups.

[0009] As used herein, the term "cyano" refers to a -CN group.

[0010] As used herein, the term "hydroxy" or "hydroxyl" refers to an --OH group.

[0011] As used herein, the term "halogen" refers to fluorine (fluoro), chlorine (chloro), bromine (bromo) or iodine (iodo).

[0012] As used herein, the term "nitro" refers to the group --NO.sub.2.

[0013] As used herein, the term "formyl" refers to a -C(O)H group.

[0014] As used herein, the term "acetyl" refers to a -C(O)CH3 group.

[0015] As used herein, the term "C1-C6 alkyl" refers to a straight or branched hydrocarbon chain group consisting solely of carbon and hydrogen atoms, containing no unsaturation, having 1 to 6 carbon atoms, and attached to the remainder of the molecule by a single bond. "C1-C4 alkyl" and "C1-C3 alkyl" should be interpreted similarly. Examples of C1-C6 alkyl include, but are not limited to, methyl, ethyl, n-propyl, and isomers thereof, such as isopropyl. A "C1-C6 alkylene" group refers to the corresponding definition of C1-C6 alkyl, except that such a group is attached to the remainder of the molecule by two single bonds. The term "C1-C2 alkylene" should be interpreted similarly. Examples of C1-C6 alkylene include, but are not limited to, -CH2-, -CH2CH2-, and -(CH2)3-.

[0016] As used herein, the term "C1-C6 haloalkyl" refers to a C1-C6 alkyl group, generally as defined above, substituted with one or more of the same or different halogen atoms. The terms "C1-C4 haloalkyl" and "C1-C3 haloalkyl" should be interpreted similarly. Examples of C1-C6 haloalkyl include, but are not limited to, trifluoromethyl.

[0017] As used herein, the term "C1-C6 alkoxy" refers to a group consisting of R a is a C1-C6 alkyl group as defined above, a The terms "C1-C4 alkoxy" and "C1-C3 alkoxy" should be interpreted similarly. Examples of C1-C6 alkoxy include, but are not limited to, methoxy, ethoxy, 1-methylethoxy (isopropoxy), and propoxy.

[0018] As used herein, the term "C1-C6 haloalkoxy" refers to a C1-C6 alkoxy group generally as defined above, substituted with one or more of the same or different halogen atoms. The terms "C1-C4 haloalkoxy" and "C1-C3 haloalkoxy" should be interpreted similarly. Examples of C1-C6 haloalkoxy include, but are not limited to, trifluoromethoxy.

[0019] As used herein, the term "cyano C1-C6 alkoxy" generally refers to a C1-C6 alkoxy group, as defined above, substituted with one or more cyano groups. The terms "cyano C1-C4 alkoxy" and "cyano C1-C3 alkoxy" should be interpreted similarly. Examples of cyano C1-C6 alkoxy include, but are not limited to, cyanoethoxy.

[0020] As used herein, the term "cyano C1-C6 alkyl" generally refers to a C1-C6 alkyl group, as defined above, substituted with one or more cyano groups. The terms "cyano C1-C4 alkyl," "cyano C1-C3 alkyl," and "cyano C1-C2 alkyl" should be interpreted similarly. Examples of cyano C1-C6 alkyl include, but are not limited to, cyanomethyl.

[0021] As used herein, the term "C2-C6 alkenyl" refers to a straight or branched hydrocarbon chain radical having from 2 to 6 carbon atoms, composed solely of carbon and hydrogen atoms, containing at least one double bond which may be in the (E)- or (Z)-configuration, and attached to the remainder of the molecule by a single bond. The term "C2-C3 alkenyl" should be interpreted similarly. Examples of C2-C6 alkenyl include, but are not limited to, ethenyl (vinyl), prop-1-enyl, prop-2-enyl (allyl), and but-1-enyl.

[0022] As used herein, the term "C2-C6 alkynyl" refers to a straight or branched hydrocarbon chain group composed solely of carbon and hydrogen atoms, containing at least one triple bond, having 2 to 6 carbon atoms, and attached to the rest of the molecule by a single bond. The term "C2-C3 alkynyl" should be interpreted similarly. Examples of C2-C6 alkynyl include, but are not limited to, ethynyl, prop-1-ynyl, and but-1-ynyl.

[0023] As used herein, the term "C2-C6 alkenyloxy" refers to a straight or branched hydrocarbon chain radical group having from 2 to 6 carbon atoms, composed solely of carbon and hydrogen atoms, containing at least one double bond which may be in the (E)- or (Z)-configuration, and attached to the remainder of the molecule with an oxygen linker.

[0024] As used herein, the term "C1-C6 alkoxyC1-C6 alkyl" refers to R b is a C1-C6 alkyl group as generally defined above, and R a is generally a C1-C6 alkylene group as defined above b OR a The term "C1-C4 alkoxyC1-C4 alkyl" should be interpreted similarly.

[0025] As used herein, the term "C1-C6 alkoxyC1-C6 alkoxy" refers to R a and R b are both C1-C6 alkylene groups generally defined above b OR a The term "C1-C4 alkoxy C1-C4 alkoxy" should be interpreted similarly.

[0026] As used herein, the term "C1-C6 alkoxycarbonyl C1-C6 alkoxy" refers to R a and R band R are both C1-C6 alkylene groups as generally defined above. b OC(O)R a Refers to the O- group.

[0027] As used herein, the term "C3-C6 cycloalkyl" refers to a group that is a monocyclic saturated ring system and contains 3 to 6 carbon atoms. The terms "C3-C5 cycloalkyl" and "C3-C4 cycloalkyl" should be interpreted similarly. Examples of C3-C6 cycloalkyl include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0028] As used herein, the term "C3-C6 cycloalkylaminocarbonyl" refers to a C3-C6 cycloalkyl ring attached to the rest of the molecule via a -NHC(O)- linker.

[0029] As used herein, the term "benzyloxy" refers to a benzyl ring attached to the rest of the molecule via an oxygen atom.

[0030] As used herein, the term "heteroaryl" refers to a 5- or 6-membered aromatic monocyclic ring group containing 1, 2, 3, or 4 heteroatoms individually selected from nitrogen, oxygen, and sulfur. In some cases, the heteroaryl moiety may be attached to the remainder of the molecule at a nitrogen atom in the heteroaryl ring. In other cases, the heteroaryl moiety may be attached to the remainder of the molecule at a carbon atom in the heteroaryl ring. Examples of heteroaryl include, but are not limited to, furanyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, triazolyl, tetrazolyl, pyrazinyl, pyridazinyl, pyrimidyl, or pyridyl.

[0031] As used herein, the term "heterocyclyl" refers to a stable 4-, 5-, or 6-membered (and in this case, preferably 5- or 6-membered) non-aromatic monocyclic ring containing one, two, or three heteroatoms, where the heteroatoms are individually selected from nitrogen, oxygen, and sulfur. The heterocyclyl group can be attached to the remainder of the molecule through a carbon atom or a heteroatom. Examples of heterocyclyl include, but are not limited to, aziridinyl, azetidinyl, oxetanyl, thietanyl, tetrahydrofuryl, pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, piperazinyl, morpholinyl, dioxolanyl, dithiolanyl, and thiazolidinyl.

[0032] As used herein, the term "C1-C6 alkylcarbonyl" refers to R a is generally a C1-C6 alkyl group as defined above, a Examples of C1-C6 alkylcarbonyl include, but are not limited to, acetyl.

[0033] As used herein, the term "C1-C6 alkoxycarbonyl" refers to R a is generally a C1-C6 alkyl group as defined above, a Refers to the group of

[0034] As used herein, the term "C1-C6 alkylamino" refers to a group generally defined as above, R a is a C1-C6 alkyl group of formula R a Refers to the group NH-.

[0035] As used herein, the term "C1-C6 alkylaminocarbonyl" refers to R a is generally a C1-C6 alkyl group as defined above, a Refers to the group of

[0036] As used herein, the term "C1-C6 alkylcarbonylamino" refers to a group generally defined as above, R a is a C1-C6 alkyl group of formula R a It refers to the group C(O)NH-.

[0037] As used herein, the term "C1-C6 alkoxyC1-C6 alkylaminocarbonyl" refers to a group generally defined as above, R a is a C1-C6 alkyl group, and R a is a C1-C6 alkylene group a OR b refers to the group NHC(O)-.

[0038] As used herein, the term "C1-C6 alkoxyC1-C6 alkylcarbonylamino" refers to a group generally defined as above, R a is a C1-C6 alkyl group, and R a is a C1-C6 alkylene group a OR b It refers to the group C(O)NH-.

[0039] As used herein, the term "C2-C6 alkenylcarbonylamino" generally refers to a C2-C6 alkenylcarbonylamino group, as defined above, a is a C1-C6 alkylene group a It refers to the group OC(O)NH-.

[0040] As used herein, the term "N,N-di(C1-C4 alkyl)amino" refers to a group generally defined as above, where each R a and R b are each a C1-C4 alkyl group of the formula (R a )(R b )NH— group.

[0041] As used herein, the term "N,N-di(C1-C4 alkyl)aminocarbonyl" refers to R a and Rb are each a C1-C4 alkyl group as individually defined generally above, of the formula —C(O)N(R a )(R b The term "N,N-di(C1-C3 alkyl)aminocarbonyl" should be construed similarly.

[0042] As used herein, the term "C1-C6 alkylsulfanyl" refers to R a is a C1-C6 alkyl group as defined above a The terms "C1-C4 alkylsulfanyl" and "C1-C3 alkylsulfanyl" should be interpreted similarly. Examples of C1-C6 alkylsulfanyl include, but are not limited to, methylsulfanyl.

[0043] As used herein, the term "C1-C6 alkylsulfinyl" refers to R a is generally a C1-C6 alkyl group as defined above, a The terms "C1-C4 alkylsulfinyl" and "C1-C3 alkylsulfinyl" should be interpreted similarly. Examples of C1-C6 alkylsulfinyl include, but are not limited to, methylsulfinyl.

[0044] As used herein, the term "C1-C6 alkylsulfonyl" refers to R a is generally a C1-C6 alkyl group as defined above, a The terms "C1-C4 alkylsulfonyl" and "C1-C3 alkylsulfonyl" should be interpreted similarly. Examples of C1-C6 alkylsolfanyl include, but are not limited to, methylsulfonyl.

[0045] As used herein, the term "C1-C6 alkylsulfonamide" refers to a compound of the formula -NHS(O)Ra R refers to the group a is generally a C1-C6 alkyl group as defined above.

[0046] As used herein, the term "hydroxycarbonyl" or "carboxy" refers to a group of formula -COOH.

[0047] As used herein, the term "C1-C6 alkoxyimino C1-C6 alkyl" refers to a group generally defined as above, R a is a C1-C6 alkoxy group, and R is as generally defined above b is a C1-C6 alkylene group a =NR b - refers to the group.

[0048] The presence of one or more possible stereogenic elements in a compound of formula (I) means that the compound can exist in optically isomeric forms, i.e., enantiomeric or diastereomeric forms. Atropisomers can also arise due to restricted rotation about a single bond. Formula (I) is intended to include all these possible isomeric forms and mixtures thereof. The present invention includes all these possible isomeric forms and mixtures thereof of the compounds of formula (I). Similarly, formula (I) is intended to include all possible tautomeric forms. The present invention includes all possible tautomeric forms of the compounds of formula (I).

[0049] In each case, the compounds of formula (I) according to the invention may be in free form, in oxidized form as N-oxides, or in salt form, for example in agriculturally usable salt form. Preferred are the salts that the compounds of formula (I) can form with amines, including primary, secondary and tertiary amines (e.g., ammonia, dimethylamine and triethylamine), alkali metal and alkaline earth metal bases, transition metal or quaternary ammonium bases.

[0050] N-oxides are oxidized forms of tertiary amines or nitrogen-containing aromatic heterocyclic compounds, as described, for example, in the book "Heterocyclic N-oxides" by A. Albini and S. Pietra, CRC Press, Boca Raton (1991).

[0051] The following list refers to compounds of formula (I) and defines the substituent R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 For any one of these substituents, any definition set forth below may be combined with any definition of any other substituent set forth below or elsewhere in this document.

[0052] R 1 is C1-C6 alkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, or C1-C6 alkoxyC1-C6 alkyl. Preferably, R 1 is C1-C4 alkyl, C1-C4 alkoxy, C2-C4 alkenyl, C2-C4 alkynyl, or C1-C4 alkoxyC1-C4 alkyl. More preferably, R 1 is C1-C3 alkyl, C1-C3 alkoxy, C2-C3 alkenyl, C2-C3 alkynyl, or C1-C3 alkoxyC1-C3 alkyl. Even more preferably, R 1 is methyl, ethyl, n-propyl, methoxy, 2-methoxyethyl, aryl, and prop-2-ynyl. Even more preferably, R 1 is methyl or ethyl. In one series of embodiments, R 1 is ethyl.

[0053] R 2is phenyl or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and each phenyl and heteroaryl moiety is selected from R 7 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by

[0054] Preferably, R 2 is phenyl or heteroaryl (wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S), and each phenyl and heteroaryl moiety is R 7 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0055] More preferably, R 2 is phenyl or heteroaryl (wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms individually selected from N and O), and each phenyl and heteroaryl moiety is 7 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0056] Even more preferably, R 2 is phenyl or heteroaryl (wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms individually selected from N and O), and each phenyl and heteroaryl moiety is 7 It may be optionally substituted with one or two groups, which may be the same or different, represented by:

[0057] Even more preferably, R 2 is R 7 In one set of embodiments, R is phenyl optionally substituted with one or two groups, which may be the same or different, represented by 2In a further set of embodiments, R is 3,4-dichlorophenyl, 4-chloro-3-cyanophenyl, 4-chlorophenyl, 2-chloro-4-methylsulfonylphenyl, or 4-amino-3-chlorophenyl. 2 is 3,4-dichlorophenyl.

[0058] R 3 is hydrogen or C1-C6 alkyl. Preferably, R 3 is hydrogen or C1-C4 alkyl. More preferably, R 3 is hydrogen, methyl, ethyl or t-butyl. Even more preferably, R 3 is hydrogen, methyl or ethyl.

[0059] R 4 is hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl or phenyl, and each phenyl moiety is R 8 Preferably, R 4 is hydrogen, halogen, C1-C4 alkyl, C1-C4 haloalkyl or phenyl, and the phenyl moiety is R 8 More preferably, R 4 is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl or phenyl, and the phenyl moiety is R 8 Even more preferably, R 4 is hydrogen, halogen, C1-C3 alkyl or phenyl, and the phenyl portion is a single R 8 Even more preferably, R 4 is hydrogen, halogen, methyl or 4-chlorophenyl. Even more preferably, R 4 is hydrogen, bromo, methyl, or 4-chlorophenyl. In one set of embodiments, R 4is hydrogen, bromo, or 4-chlorophenyl. In another set of embodiments, R 4 is hydrogen.

[0060] R 5 is heteroaryl, the heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 1, 2, or 3 nitrogen atoms, and the heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety being R 9 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by

[0061] Preferably, R 5 is heteroaryl, the heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 1, 2, or 3 nitrogen atoms, and the heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety being R 9 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0062] More preferably, R 5 is heteroaryl, the heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 2 or 3 nitrogen atoms, and the heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety being R 9 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0063] Even more preferably, R 5 is pyrazolyl, imidazolyl, or triazolyl, where any of the pyrazolyl, imidazolyl, and triazolyl moieties can each be R 9 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0064] In one set of embodiments, R 5is benzotriazol-2-ylmethyl, indazol-1-yl, indazol-2-yl, 4,5,6,7-tetrahydroindazol-2-yl, imidazo[4,5-b]pyridin-1-yl, 6-chloropyrazolo[4,3-c]pyridin-1-yl, 3-(difluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl, 3-(difluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl, 4,6-dihydrofuro[3,4-c]pyrazol-2-yl or 3-(trifluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl.

[0065] R 6 is hydrogen, C1-C3 alkyl or C1-C6 alkoxy. Preferably, R 6 is hydrogen or C1-C3 alkyl. More preferably, R 6 is hydrogen or methyl. Even more preferably, R 6 is hydrogen.

[0066] R 7 is cyano, nitro, amino, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonamido, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, or N,N-di(C1-C4 alkyl)aminocarbonyl.

[0067] Preferably, R 7is cyano, nitro, amino, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxyC1-C3 alkyl, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkylsulfonamido, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, or N,N-di(C1-C3 alkyl)aminocarbonyl.

[0068] More preferably, R 7 is cyano, nitro, amino, halogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkylsulfanyl, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 alkylsulfonamido, C1-C3 alkylcarbonyl, C1-C3 alkoxycarbonyl, C1-C3 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, or N,N-di(C1-C3 alkyl)aminocarbonyl.

[0069] Even more preferably, R 7 is cyano, nitro, amino, halogen and C1-C3 alkylsulfonyl, and even more preferably, R 7 is cyano, nitro, amino, chloro, fluoro and methylsulfonyl.

[0070] In one set of embodiments, R 7is cyano, nitro, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonamido, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C1-C6 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, or N,N-di(C1-C4 alkyl)aminocarbonyl.

[0071] Preferably, R 7 is cyano, nitro, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C1-C4 alkoxyC1-C3 alkyl, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkylsulfonamido, C1-C4 alkylcarbonyl, C1-C4 alkoxycarbonyl, C1-C4 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl or N,N-di(C1-C3 alkyl)aminocarbonyl.

[0072] More preferably, R 7 is cyano, nitro, halogen, C1-C3 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkylsulfanyl, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 alkylsulfonamido, C1-C3 alkylcarbonyl, C1-C3 alkoxycarbonyl, C1-C3 alkylaminocarbonyl, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl or N,N-di(C1-C3 alkyl)aminocarbonyl.

[0073] Even more preferably, R 7 is cyano, nitro, halogen or C1-C3 alkylsulfonyl, and even more preferably, R7 is cyano, nitro, chloro, fluoro and methylsulfonyl.

[0074] R 8 is halogen, C1-C3 alkyl or C1-C3 alkoxy. Preferably, R 8 is halogen, methyl, ethyl, methoxy or ethoxy. More preferably, R 8 is chloro, bromo, fluoro, methyl or methoxy. Even more preferably, R 8 is chloro.

[0075] R 9 is formyl, acetyl, cyano, amino, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkyl, cyanoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonylC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylsulfonamido, hydroxycarbonyl, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl , C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C6 alkoxyiminoC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C4 alkyl)amino, N,N-di(C1-C4 alkyl)aminocarbonyl, phenyl, benzyloxy, or heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties are selected from R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by

[0076] Preferably, R 9is formyl, acetyl, cyano, amino, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfonyl, hydroxycarbonyl, C1 C1-C6 alkylcarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkoxyiminoC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, phenyl, or heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties are each independently selected from R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

[0077] More preferably, R 9 is acetyl, cyano, nitro, hydroxy, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkenyloxy, cyanoC1-C4 alkyl, C1-C4 alkoxyC1-C4 alkyl, C1-C4 alkoxyC1-C4 alkoxy, C1-C4 alkoxycarbonyl, C1-C4 alkylsulfanyl, C1-C4 alkylsulfonyl, C1-C4 alkylcarbonyl, C1-C4 alkylcarbonylamino, C1-C4 alkoxyiminoC1-C4 alkyl, C1-C4 alkoxyC1-C4 alkylcarbonylamino, C2-C4 alkenylcarbonylamino, C3-C4 cycloalkyl, phenyl, or heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing one or two heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties are each independently selected from R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C5-C6 cycloalkyl ring or a phenyl ring, and the C5-C6 cycloalkyl and phenyl moieties can be R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms individually selected from N, O and S, and the heteroaryl moiety being R10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring can be formed by R 10 It may be optionally substituted with one or two groups, which may be the same or different, represented by:

[0078] Even more preferably, R 9 is acetyl, cyano, nitro, hydroxy, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C3 haloalkyl, C1-C3 haloalkoxy, C2-C3 alkenyloxy, cyanoC1-C2 alkyl, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkoxyC1-C3 alkoxy, C1-C2 alkoxycarbonyl, C1-C2 alkylsulfanyl, C1-C2 alkylsulfonyl, C1-C3 alkylcarbonyl, C1-C3 alkylcarbonylamino, C1-C2 alkoxyiminoC1-C2 alkyl, C2-C3 alkenylcarbonylamino, cyclopropyl, phenyl, or heteroaryl, wherein the heteroaryl moiety is a 5- or 6-membered aromatic ring containing one or two heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties are each independently selected from a single R 10 optionally substituted with a group; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a cyclohexyl or phenyl ring, and the phenyl portion can be R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a heteroaryl ring, the heteroaryl moiety being a six-membered aromatic ring containing a single nitrogen atom, and the heteroaryl moiety being a single R 10optionally substituted with a group; or Any two adjacent R 9 Groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring can be joined by a single R 10 The group may be optionally substituted with a group.

[0079] In one set of embodiments, R 9 is formyl, cyano, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonylC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkyl sulfonamide, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C4 alkyl)amino, N,N-di(C1-C4 alkyl)aminocarbonyl or benzyloxy; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Preferably, R 9 is formyl, cyano, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C4 alkoxy, C1-C4 alkoxyC1-C4 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C4 alkoxycarbonylC1-C4 alkoxy, C1-C6 alkoxycarbonyl, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkyl sulfonamide, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C4 alkoxyC1-C4 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C3 alkyl)amino, N,N-di(C1-C3 alkyl)aminocarbonyl or benzyloxy; or Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by More preferably, R 9is formyl, cyano, nitro, hydroxy, halogen, C1-C4 alkyl, C1-C4 alkoxy, C1-C4 haloalkyl, C1-C4 haloalkoxy, C2-C4 alkenyloxy, cyanoC1-C3 alkoxy, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkoxyC1-C3 alkoxy, C1-C3 alkoxycarbonylC1-C3 alkoxy, C1-C3 alkoxycarbonyl, C1-C3 alkylsulfanyl, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 alkyl sulfonamide, C1-C3 alkylcarbonyl, C1-C3 alkylaminocarbonyl, C1-C3 alkylcarbonylamino, C1-C3 alkylamino, C1-C3 alkoxyC1-C3 alkylaminocarbonyl, C1-C3 alkoxyC1-C3 alkylcarbonylamino, C2-C4 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C3 alkyl)amino, N,N-di(C1-C3 alkyl)aminocarbonyl or benzyloxy; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with one or two groups, which may be the same or different, represented by Even more preferably, R 9 is formyl, cyano, nitro, halogen, C1-C4 alkyl, C1-C3 alkoxy, C1-C3 haloalkyl, C1-C2 haloalkoxy, C2-C3 alkenyloxy, cyano C1-C2 alkoxy, C1-C3 alkoxy C1-C3 alkyl, C1-C3 alkoxy C1-C3 alkoxy, C1-C3 alkoxycarbonyl C1-C3 alkoxy, C1-C3 alkoxycarbonyl, C1-C3 alkylsulfanyl, C1-C3 alkylsulfonyl, C1-C3 alkylcarbonyl, C1-C3 alkylaminocarbonyl, C1-C3 alkylcarbonylamino, C1-C3 alkylamino, C1-C3 alkoxyC1-C3 alkylaminocarbonyl, C1-C2 alkoxyC1-C2 alkylcarbonylamino, C3-C4 alkenylcarbonylamino, C3-C4 cycloalkyl or N,N-di(C1-C3 alkyl)amino; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C5-C6 cycloalkyl ring or a phenyl ring, and the C5-C6 cycloalkyl and phenyl moieties can be a single R 10 optionally substituted with a group; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a six-membered heteroaryl ring, the heteroaryl moiety being a six-membered aromatic ring containing a single nitrogen atom, and the heteroaryl moiety being a six-membered aromatic ring containing a single R 10 optionally substituted with a group; or Any two adjacent R 9Groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring can be joined by a single R 10 The group may be optionally substituted with a group.

[0080] In a particularly preferred set of embodiments, R 9 is acetyl, cyano, nitro, hydroxy, chloro, fluoro, bromo, methyl, ethyl, methoxy, ethoxy, isopropoxy, tertbutoxy, difluoromethyl, trifluoromethyl, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, allyloxy, cyanomethyl, methoxymethyl, ethoxymethyl, methoxymethoxy, methoxyethoxy, methoxycarbonyl, methylsulfanyl, methylsulfonyl, methylcarbonylamino(acetamino), propanoylamino, methoxyiminoethyl, (but-2-enoyl)amino, cyclopropyl, phenyl, pyridyl, thienyl, furanyl, thiazolyl, or pyrazinyl, and the phenyl and heteroaryl moieties are each independently selected from a single R 10 The group may be optionally substituted with a group.

[0081] R 10 is halogen, nitro, C1-C3 alkyl or C1-C3 alkoxy. Preferably, R 10 is halogen, nitro, methyl or methoxy. More preferably, R 10 is halogen or methyl. Even more preferably, R 10 is chloro, fluoro or methyl. Even more preferably, R 10 is chloro or fluoro, and R 10 It is particularly preferred if is chloro.

[0082] In one set of embodiments, R 10 is halogen, C1-C3 alkyl or C1-C3 alkoxy. Preferably, R 10 is halogen, methyl or methoxy. More preferably, R10 is halogen. Even more preferably, R 10 is chloro or fluoro. Even more preferably, R 10 is chloro.

[0083] In the compounds of formula (I) according to the present invention, preferably: R 1 is methyl or ethyl; R 2 is R 7 phenyl optionally substituted with 1 or 2 groups, which may be the same or different, represented by R 3 is hydrogen, methyl or ethyl; R 4 is hydrogen, bromo, methyl or 4-chlorophenyl; R 5 is pyrazolyl, imidazolyl, or triazolyl, where any of the pyrazolyl, imidazolyl, and triazolyl moieties can each be R 9 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by R 5 is benzotriazol-2-ylmethyl, indazol-1-yl, indazol-2-yl, 4,5,6,7-tetrahydroindazol-2-yl, imidazo[4,5-b]pyridin-1-yl, 6-chloropyrazolo[4,3-c]pyridin-1-yl, 3-(difluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl, 3-(difluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-2-yl, 4,6-dihydrofuro[3,4-c]pyrazol-2-yl or 3-(trifluoromethyl)-6,7-dihydro-4H-pyrano[4,3-c]pyrazol-1-yl; R 6 is hydrogen or methyl; R 7 is cyano, nitro, halogen or C1-C3 alkylsulfonyl; and R 9is formyl, cyano, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonylC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkyl arylsulfonamide, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C4 alkyl)amino, N,N-di(C1-C4 alkyl)aminocarbonyl or benzyloxy.

[0084] In one embodiment, the compounds of formula (I) according to the present invention are preferably: R 1 is methyl or ethyl; R 2 is 3,4-dichlorophenyl; R 3 is hydrogen or C1-C4 alkyl; R 4 is hydrogen, bromo or 4-chlorophenyl; R 5 is heteroaryl, the heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 2 or 3 nitrogen atoms, and the heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety being R 9 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by R 6 is hydrogen; R 9is formyl, cyano, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C4 alkoxy, C1-C4 alkoxyC1-C4 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C4 alkoxycarbonylC1-C4 alkoxy, C1-C6 alkoxycarbonyl, C1-C4 alkylsulfanyl, C1-C4 alkylsulfinyl, C1-C4 alkylsulfonyl, C1-C4 alkyl sulfonamide, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C4 alkoxyC1-C4 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C3 alkyl)amino, N,N-di(C1-C3 alkyl)aminocarbonyl or benzyloxy; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by R 10 is a halogen.

[0085] In another embodiment, in the compounds of formula (I) according to the present invention, preferably: R 1 is methyl or ethyl; R 2 is 3,4-dichlorophenyl; R 3 is hydrogen, methyl or ethyl; R 4 is hydrogen, bromo, methyl or 4-chlorophenyl; R 5 is heteroaryl, the heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 1, 2, or 3 nitrogen atoms, and the heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in the heteroaryl ring, and each heteroaryl moiety being R 9 and optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by R 6 is hydrogen or methyl; R 7 is cyano, nitro, halogen or C1-C3 alkylsulfonyl; and R 9is formyl, cyano, nitro, hydroxy, halogen, C1-C6 alkyl, C1-C6 alkoxy, C1-C6 haloalkyl, C1-C6 haloalkoxy, C2-C6 alkenyloxy, cyanoC1-C6 alkoxy, C1-C6 alkoxyC1-C6 alkyl, C1-C6 alkoxyC1-C6 alkoxy, C1-C6 alkoxycarbonylC1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C6 alkylsulfanyl, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkyl sulfonamide, C1-C6 alkylcarbonyl, C1-C6 alkylaminocarbonyl, C1-C6 alkylcarbonylamino, C1-C6 alkylamino, C1-C6 alkoxyC1-C6 alkylaminocarbonyl, C1-C6 alkoxyC1-C6 alkylcarbonylamino, C2-C6 alkenylcarbonylamino, C3-C6 cycloalkyl, C3-C6 cycloalkylaminocarbonyl, N,N-di(C1-C4 alkyl)amino, N,N-di(C1-C4 alkyl)aminocarbonyl or benzyloxy; or Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a C3-C6 cycloalkyl ring or a phenyl ring, and the C3-C6 cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heteroaryl ring, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and the heteroaryl moiety being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9The groups, together with the carbon atoms to which they are attached, can form a 5- or 6-membered heterocyclyl ring, the heterocyclyl portion being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and the heterocyclyl ring is R 10 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 10 is chloro or fluoro.

[0086] The compounds of the present invention can be formed as shown in the following schemes, where, unless otherwise specified, the definition of each variable is as defined above for compounds of formula (I). General methods for producing compounds of formula (I) are described below. Unless otherwise specified in the context, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 is as previously defined herein. The starting materials used in the preparation of the compounds of the present invention can be purchased from ordinary commercial suppliers or prepared by known methods. The starting materials and intermediates can be purified by state-of-the-art techniques such as chromatography, crystallization, distillation and filtration before being used in the next step.

[0087] Compounds of formula (I) according to the present invention can be prepared from compounds of formula (I) as shown below in Scheme 1.

[0088] Scheme 1: [ka] R 3is hydrogen can be prepared by reacting a compound of formula (I) (wherein R 3 is not hydrogen and is any other R defined above 3 When a base is used, the product is obtained after acidification with a suitable acid (such as hydrochloric acid). 4 When is pyridyl or pyridazinyl, the product was obtained as the equivalent salt (such as the hydrochloride salt).

[0089] Or, R 3 Compounds of formula (I) where R is hydrogen can be prepared by the reaction of R in the presence of a water-stable Lewis acid such as scandium(III) trifluoromethanesulfonate in a suitable solvent (such as tetrahydrofuran) in the presence of water. 3 is not hydrogen, but is any other R defined above 3 It can be prepared by hydrolysis of a compound of formula (I) in which

[0090] Compounds of formula (I) may also be prepared by the methods described below.

[0091] Scheme 2: [ka] Compounds of formula (B) (wherein Y=Br, Cl or I) can be converted to compounds of formula (I) (wherein R 4 is hydrogen).

[0092] Alternatively, a compound of formula (B) (wherein Y is Br) can be converted to a compound of formula (I) (wherein R 4 is hydrogen).

[0093] In another transformation, a compound of formula (I) 4 is C1-C6 alkyl) can be obtained from the reaction of compounds of formula (B) (where Y is I or Br) with alkylboronic acids (such as methylboronic acid) under Suzuki-Miyaura cross-coupling conditions similar to those in the literature. Typically, the reaction proceeds by reacting R with a suitable catalyst (such as dichlorobis(triphenylphosphine)palladium(II), tetrakis(triphenylphosphine)palladium), tris(dibenzylideneacetone)dipalladium, or dichloro(1,1'-bis(diphenylphosphine)ferrocene)palladium(II) dichloromethane adduct) or palladium diacetate (optionally with a ligand such as 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl) in the presence of a base (such as potassium or cesium carbonate or tripotassium phosphate) in a suitable organic solvent (such as 1,4-dioxane, toluene or tetrahydrofuran), optionally in the presence of water, at elevated temperature. 4 by reaction of a compound of formula (B) with a boronic acid or boroxine.

[0094] In another transformation, a compound of formula (I) 4 is phenyl) can be obtained from the reaction of compounds of formula (B) (where Y is I or Br) with phenylboronic acid or boroxine under Suzuki-Miyaura cross-coupling conditions similar to those in the literature. This is shown in Scheme 2 above.

[0095] Scheme 2a: [ka] In an alternative transformation, compounds of formula (I) 4 and R 6 is hydrogen, and R 3 is hydrogen or any other R defined above 3 group) can be prepared by the reaction of a compound of formula R with a suitable ligand (such as 1,10-phenanthroline) and a suitable base (such as potassium carbonate) in the presence of a stoichiometric amount of copper (such as copper(I) iodide) in an organic solvent (such as N,N-dimethylacetamide) at elevated temperature. 5 -H, where R 5 Compounds of -H can be obtained from the reaction of compounds of formula (BI) (where Y is I or Br) with an azole such as pyrazole, imidazole or triazole. Azoles are commercially available or can be prepared by methods reported in the literature (Tetrahedron 2012, 68, 3165-3171). This is shown in Scheme 2a above.

[0096] Scheme 3: [ka] Compounds of formula (C), where Y is Br, Cl, I, or H and X is Br, can be reacted with a nucleophile R in the presence of a base, such as potassium carbonate or sodium hydride, in a suitable solvent, such as acetonitrile, N,N-dimethylformamide, or tetrahydrofuran, at ambient or elevated temperature. 5 Azoles can be converted to compounds of formula (B) by nucleophilic substitution with -H (such as pyrazole, imidazole, or triazole). Azoles are commercially available or can be prepared by methods known to those skilled in the art. This is shown in Scheme 3 above.

[0097] Scheme 4: [ka] Compounds of formula (C), where Y and X are the same and X is Br, Cl, or I, can be prepared by treatment of compounds of formula (D) with a suitable halogenating agent (such as N-bromo-, N-chloro-, or N-iodo-succinimide) in a suitable solvent (such as acetonitrile), optionally with additional acid (such as trifluoroacetic acid), at ambient or elevated temperature. This is shown in Scheme 4 above.

[0098] Scheme 5: [ka] Compounds of formula (C) can be prepared by reacting compounds of formula (E) with compounds of formula (F), optionally in the presence of a solvent (such as dioxane) at elevated temperatures (e.g., 120°C). Compounds of formula E are commercially available or can be prepared by methods known to those skilled in the art. This is shown in Scheme 5 above.

[0099] Scheme 5a: [ka] In a different transformation, compounds of formula (L) (wherein X is Br) can be prepared by reacting compounds of formula (M) with compounds of formula (F), optionally in the presence of a solvent (such as dioxane), at elevated temperatures (e.g., 120°C). Compounds of formula (M) are commercially available or can be prepared by methods known to those skilled in the art. This is shown in Scheme 5a above.

[0100] Scheme 6: [ka] Compounds of formula (F) can be prepared from the reaction of a β-ketoester of formula (G) with an amine salt. The amine salt can be prepared in situ by acidifying an amine of formula (H) with a suitable acid (such as acetic acid). These amine salts can then be reacted with compounds of formula G in a suitable solvent (such as toluene) in the presence of an acid (such as acetic acid) and a drying agent (such as 4 Å molecular sieves). Compounds of formula (G) are commercially available or can be prepared using the conditions described below. Compounds of formula (H) are commercially available or can be prepared by methods reported in the literature. This is shown in Scheme 6 above.

[0101] Reaction 7: [ka] Compounds of formula (H) may be prepared by treatment of a ketone of formula (K) with a base (such as sodium hydride) in the presence of a dialkyl carbonate of formula (J) (such as dimethyl carbonate).

[0102] Compounds of formula (K) and formula (J) are commercially available or can be prepared by methods known to those skilled in the art, as shown in Scheme 7 above.

[0103] The present invention further provides a method for controlling weeds in a habitat, the method comprising applying to the habitat a weed-controlling amount of a composition comprising a compound of formula (I). Moreover, the present invention may further provide a method for selectively controlling weeds in a habitat containing useful (crop) plants and weeds, the method comprising applying to the habitat a weed-controlling amount of a composition of the present invention. "Control" means eradicating, reducing or preventing growth, or preventing or reducing germination. It should be noted that the compounds of the present invention exhibit significantly improved selectivity compared to known structurally similar compounds. Generally, the plants to be controlled are unwanted plants (weeds). "Habitat" refers to the area where plants are growing or will grow. Application to the habitat can be carried out before and / or after emergence of the crop plants. Some crop plants may be inherently resistant to the herbicidal effects of the compounds of formula (I).

[0104] The application rates of the compounds of formula (I) can vary within wide limits and depend on the nature of the soil, the method of application (pre- or post-emergence; seed dressing; application in the sowing furrow; no-till application, etc.), the crop plant, the weeds to be controlled, the prevailing weather conditions, and other factors governed by the application method, time of application and target crop. The compounds of formula I according to the invention are generally applied in amounts of 10 to 2500 g / ha, in particular 25 to 1000 g / ha, especially 25 to 250 g / ha.

[0105] Application is generally made by spraying the composition, typically with a tractor-mounted large area sprayer, although other methods such as dusting (if powdered), dripping or drench can also be used.

[0106] The term "useful plants" should also be understood to include useful plants that have been rendered tolerant to herbicides such as bromoxynil or to certain classes of herbicides, such as, for example, 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitors, ALS inhibitors such as primisulfuron, prosulfuron and trifloxysulfuron, 5-enol-pyroyl-shikimate-3-phosphate-synthase (EPSPS) inhibitors, glutamine synthetase (GS) inhibitors or protoporphyrinogen oxidase (PPO) inhibitors, by conventional breeding or genetic engineering methods. An example of a crop that has been rendered tolerant to imidazolinones, such as imazamox, by conventional breeding methods (mutagenesis) is Clearfield® summer rapeseed (canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-tolerant corn varieties commercially available under the trade names RoundupReady®, Herculex I®, and LibertyLink®.

[0107] The term "useful plants" should also be understood to include useful plants that have been transformed using recombinant DNA techniques so as to be able to synthesize one or more selectively acting toxins, such as those known from toxin-producing bacteria, especially those of the genus Bacillus.

[0108] Examples of such plants are YieldGard® (a corn variety expressing a CryIA(b) toxin); YieldGard Root-Feeding Nematode® (a corn variety expressing a CryIIIB(b1) toxin); YieldGard Plus® (a corn variety expressing a CryIA(b) and a CryIIIB(b1) toxin); Starlink® (a corn variety expressing a Cry9(c) toxin); Herculex I® (a corn variety expressing a CryIF(a2) toxin and the enzyme phosphinothricin N-acetyltransferase (PAT) to achieve tolerance to the herbicide glufosinate ammonium); NuCOTN 33B® (a cotton variety expressing a CryIA(c) toxin); Bollgard I® (a cotton variety expressing a CryIA(c) toxin); Bollgard II® (a cotton variety expressing CryIA(c) and CryIIA(b) toxins); VIPCOT® (a cotton variety expressing VIP toxin); NewLeaf® (a potato variety expressing CryIIIA toxin); NatureGard® Agrisure® GT Advantage (GA21 glyphosate tolerance trait), Agrisure® CB Advantage (Bt11 corn borer (CB) trait), Agrisure® RW (corn root nematode trait), and Protecta®.

[0109] Plant crops or their seed material can both be tolerant to herbicides and simultaneously resistant to insect feeding ("stacked" transgenic events). For example, seeds can be capable of expressing an insecticidal Cry3 protein while simultaneously being tolerant to glyphosate.

[0110] Crop plants should also be understood to include those obtainable by conventional methods of breeding or genetic engineering and containing so-called output traits (e.g., improved storage stability, higher nutritional value, and improved flavor).

[0111] The compounds of formula (I) (or compositions containing them) can be used to control unwanted plants (collectively "weeds"), such as Agrostis, Alopecurus, Avena, Brachiaria, Bromus, Cenchrus, Cyperus, Digitaria, Echinochloa, Eleusine, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, and Morus. The species may be both monocotyledonous, such as Sorghum, and dicotyledonous, such as Abutilon, Amaranthus, Ambrosia, Chenopodium, Chrysanthemum, Conyza, Galium, Ipomoea, Nasturtium, Sida, Sinapis, Solanum, Stellaria, Veronica, Viola, and Xanthium.

[0112] The compound of formula (I) can be used in its unmodified form, or preferably, can be used with formulation adjuvants such as carriers, solvents, and surfactants (SAA), together with adjuvants conventionally used in the formulation art to provide a herbicidal composition.The present invention therefore further provides a herbicidal composition comprising at least one compound of formula (I), an agriculturally acceptable carrier, and optionally an adjuvant.An agriculturally acceptable carrier is, for example, a carrier suitable for agricultural use.Agricultural carriers are well known in the art.

[0113] The herbicidal compositions generally comprise 0.1 to 99% by weight, in particular 0.1 to 95% by weight, of a compound of formula I and 1 to 99.9% by weight of formulation adjuvants, preferably including 0 to 25% by weight of a surface-active substance.

[0114] The compositions can be selected from a number of formulation types, including emulsion concentrates (EC), suspension concentrates (SC), suspoemulsions (SE), capsule suspensions (CS), water-dispersible granules (WG), emulsifiable granules (EG), water-in-oil emulsions (EO), oil-in-water emulsions (EW), microemulsions (ME), oil dispersions (OD), oil-miscible flowables (OF), oil-miscible liquids (OL), soluble concentrates (SL), ultra-low volume suspensions (SU), ultra-low volume liquids (UL), technical concentrates (TK), dispersible concentrates (DC), soluble powders (SP), wettable powders (WP), and soluble granules (SG). The formulation type selected in any given case will depend on the specific purpose envisaged and the physical, chemical, and biological properties of the compound of formula (I).

[0115] Soluble powders (SP) can be prepared by mixing a compound of formula (I) with one or more water-soluble inorganic salts (such as sodium bicarbonate, sodium carbonate, or magnesium sulfate) or one or more water-soluble organic solids (such as polysaccharides), and optionally one or more wetting agents, one or more dispersing agents, or a mixture of the aforementioned agents to improve dispersibility / solubility in water. The mixture is then ground to a fine powder. Similar compositions can also be granulated to form water-soluble granules (SG).

[0116] Wettable powders (WP) can be prepared by mixing a compound of formula (I) with one or more solid diluents or carriers, one or more wetting agents, and preferably one or more dispersing agents and, optionally, one or more suspending agents to promote dispersibility in a liquid. The mixture is then ground to a fine powder. Similar compositions may also be granulated to form water-dispersible granules (WG).

[0117] Granules (GR) can be formed by granulating a mixture of a compound of formula (I) with one or more powdered solid diluents or carriers, or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) into a porous granular material (such as pumice, attapulgite clay, Fuller's earth, Kieselguhr, diatomaceous earth, or crushed corncob), or by absorbing a compound of formula (I) (or a solution thereof in a suitable agent) into a hard core material (such as sand, silica, carbonate minerals, sulfates, or phosphates), followed by optional drying. Agents commonly used to aid absorption or adsorption include solvents (such as aliphatic and aromatic petroleum solvents, alcohols, ethers, ketones, and esters) and binders (such as polyvinyl acetate, polyvinyl alcohol, dextrin, sugars, and vegetable oils). One or more other additives may also be included in the granules (e.g., emulsifiers, wetting agents, or dispersing agents).

[0118] Dispersible concentrates (DC) can be prepared by dissolving a compound of formula (I) in water or an organic solvent such as a ketone, alcohol, or glycol ether. These solutions may contain surfactants (e.g., to improve dilution with water or to prevent crystallization in the spray tank).

[0119] Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) can be prepared by dissolving a compound of formula (I) in an organic solvent (optionally with one or more wetting agents, one or more emulsifiers, or a mixture of said agents). Organic solvents suitable for use in EC include aromatic hydrocarbons (such as alkylbenzenes or alkylnaphthalenes, as exemplified by SOLVESSO 100, SOLVESSO 150, and SOLVESSO 200 (SOLVESSO is a registered trademark)), ketones (such as cyclohexanone or methylcyclohexanone), alcohols (such as benzyl alcohol, furfuryl alcohol, or butanol), N-alkylpyrrolidones (such as N-methylpyrrolidone or N-octylpyrrolidone), dimethylamides of fatty acids (C8-C9), and the like. 10EC products include fatty acid dimethylamides, etc., and chlorinated hydrocarbons. EC products can emulsify spontaneously when added to water, resulting in emulsions that are stable enough to allow spray application with appropriate equipment.

[0120] In preparing an EW, the compound of formula (I) is obtained as a liquid (if not liquid at room temperature, it may be melted at a suitable temperature, typically below 70°C) or in solution (by dissolving in a suitable solvent), and the resulting liquid or solution is then emulsified under high shear in water containing one or more SAAs to produce an emulsion. Solvents suitable for use in EWs include vegetable oils, chlorinated hydrocarbons (such as chlorobenzene), aromatic solvents (such as alkylbenzenes or alkylnaphthalenes), and other suitable organic solvents with low solubility in water.

[0121] Microemulsions (MEs) can be prepared by mixing a blend of one or more solvents and one or more SAA with water to spontaneously produce a thermodynamically stable, isotropic liquid formulation. The compound of formula (I) is initially present in either water or the solvent / SAA blend. Solvents suitable for use in MEs include those previously described for use in ECs or EWs. MEs can be either oil-in-water or water-in-oil systems (which system is present can be determined by conductivity measurements) and are suitable for mixing water-soluble and oil-soluble pesticides in the same formulation. MEs are suitable for dilution in water, either as microemulsions or to form conventional oil-in-water emulsions.

[0122] Suspension concentrates (SCs) may comprise aqueous or insoluble suspensions of fine, insoluble solid particles of the compound of formula (I). SCs may be prepared by ball milling or bead milling the solid compound of formula (I) in a suitable medium, optionally with one or more dispersing agents, to produce a fine particle suspension of the compound. One or more wetting agents may be included in the composition, and a suspending agent may be included to reduce the settling rate of the particles. Alternatively, the compound of formula (I) may be dry milled and added to water containing the agents described hereinabove to produce the desired final product.

[0123] Aerosol formulations include a compound of formula (I) and a suitable propellant (e.g., n-butane). The compound of formula (I) may also be dissolved or dispersed in a suitable vehicle (e.g., water or a miscible liquid such as n-propanol) to provide a composition for use in a non-pressurized manual spray pump.

[0124] Capsule suspensions (CS) can be prepared similarly to the preparation of EW formulations, but with an additional polymerization stage to obtain an aqueous dispersion of oil droplets, each of which is encapsulated in a polymeric shell and containing the compound of formula (I) and, optionally, a carrier or diluent therefor. The polymeric shell can be produced by either an interfacial polycondensation reaction or a coacervation technique. The composition can provide sustained release of the compound of formula (I) and can be used for seed treatment. The compound of formula (I) can also be formulated in a biodegradable polymeric matrix to provide a slow, sustained release of the compound.

[0125] The composition may contain one or more additives to improve the biological performance of the composition, for example, by improving the wetting, retention, or distribution of the compound of formula (I) on a surface, resistance to rain on the treated surface, or uptake or mobility. Such additives include surface active agents (SAA), oil-based spray additives such as certain mineral oils or natural vegetable oils (such as soybean oil and rapeseed oil), modified vegetable oils such as methylated rapeseed oil (MRSO), and blends of these with other bio-enhancing adjuvants (formulation ingredients that can assist or modify the action of the compound of formula (I)).

[0126] Wetting agents, dispersing agents and emulsifying agents may be cationic, anionic, amphoteric or nonionic SAAs.

[0127] Suitable cationic SAAs include quaternary ammonium compounds (eg, cetyltrimethylammonium bromide), imidazolines, and amine salts.

[0128] Suitable anionic SAAs include alkali metal salts of fatty acids, sulfates of aliphatic monoesters (e.g., sodium lauryl sulfate), salts of sulfonated aromatic compounds (e.g., sodium dodecylbenzenesulfonate, calcium dodecylbenzenesulfonate, butyl naphthalene sulfonate, and mixtures of sodium di- and tri-isopropyl-naphthalenesulfonates), ether sulfates, alcohol ether sulfates (e.g., sodium laureth-3 sulfate), ether carboxylates (e.g., sodium laureth-3 carbonate), phosphate esters (e.g., products from the reaction of one or more aliphatic alcohols with phosphoric acid (primarily monoesters) or phosphorus pentoxide (primarily di-esters), such as the reaction of lauryl alcohol with tetraphosphoric acid; these products may also be ethoxylated), sulfosuccinamates, paraffin or olefin sulfonates, taurates, lignosulfonates, and phosphate / sulfate salts of tristyrylphenol.

[0129] Suitable amphoteric SAAs include betaines, propionates, and glycinates. Suitable nonionic SAAs include condensates of alkylene oxides, such as ethylene oxide, propylene oxide, butylene oxide, or mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetyl alcohol) or alkylphenols (such as octylphenol, nonylphenol, or octylcresol); partial esters derived from long-chain fatty acids or hexitol anhydrides; condensates of the above partial esters with ethylene oxide; block polymers (including ethylene oxide and propylene oxide); alkanolamides; simple esters (e.g., fatty acid polyethylene glycol esters); amine oxides (e.g., lauryl dimethylamine oxide); lecithin and its sorbitan and esters, alkyl polyglycosides, and tristyryl phenols. Suitable suspending agents include hydrophilic colloids (such as polysaccharides, polyvinylpyrrolidone, or sodium carboxymethylcellulose) and swelling clays (such as bentonite or attapulgite).

[0130] The compounds of the present invention can also be used in mixtures with one or more additional herbicides and / or plant growth regulators. Examples of such additional herbicides or plant growth regulators include acetochlor, acifluorfen (including acifluorfen-sodium), aclonifen, ametryn, aminocarbazone, aminopyralid, aminotriazole, atrazine, beflubutamid-M, benquitrione, bensulfuron (including bensulfuron-methyl), bentazone, bicyclopyrone, vilanaphos, bipyrazone, bispyribac-sodium, bixlozone, bromacil, bromoxynil, butachlor, butafenacil, and carfen. Trazone (including carfentrazone-ethyl), cloransulam (including cloransulam-methyl), chlorimuron (including chlorimuron-ethyl), chlorotoluron, chlorsulfuron, cinmethylin, clasifos, clethodim, clodinafop (including clodinafop-propargyl), clomazone, clopyralid, cyclopyranyl, cyclopyrimorate, cyclosulfamuron, cyhalofop (including cyhalofop-butyl), 2,4-D (including its choline salt and 2-ethylhexyl ester), 2,4-DB, dextromethorphan, cyclosulfamuron ... Smedipham, dicamba (including its aluminum, aminopropyl, bis-aminopropylmethyl, choline, dichloroprop, diglycolamine, dimethylamine, dimethylammonium, potassium, and sodium salts), diclosulam, difluhenican, diflufenzopyr, dimethachlor, dimethenamid-P, dioxopyritrion, diquat dibromide, diuron, epirifenacil, ethalfluralin, ethofumesate, fenoxaprop (including fenoxaprop-P-ethyl), fenoxasulfone , fenpyrazone, fenquinotrione, fentrazamide, flazasulfuron, florasulam, florpyrauxifen (including florpyrauxifen-benzyl), fluazifop (including fluazifop-p-butyl), flucarbazone (including flucarbazone-sodium), flufenacet, flumetsulam, flumioxazin, fluometuron, fomesafen, flupyrsulfuron (including flupyrsulfuron-methyl-sodium), fluroxypyr (including fluroxypyr-meptyl), fomesafen,Foramsulfuron, glufosinate (including L-glufosinate and both ammonium salts), glyphosate (including its diammonium, isopropylammonium, and potassium salts), halaxifen (including haloxyfop-methyl), haloxyfop (including haloxyfop-methyl), hexazinone, hydantocidin, imazamox (including R-imazamox), imazapic, imazapyr, imazethapyr, indaziflam, iodosulfuron (including iodosulfuron-methyl-sodium), iofensulfuron (iofensulfuron-methyl-sodium), including mesosulfuron-sodium), ioxynil, isoproturon, isoxaflutole, lancotrione, MCPA, MCPB, mecoprop-P, mesosulfuron (including mesosulfuron-methyl), mesotrione, metamitron, metazachlor, methiozoline, metolachlor, metosulam, metribuzin, metsulfuron, napropamide, nicosulfuron, norflurazon, oxadiazon, oxasulfuron, oxyfluorfen, paraquat dichloride, pendimethalin, penoxsulam, phenmedipham, picloram, pinoxaden, Pretilachlor, primisulfuron-methyl, prometryn, propanil, propaquizafop, propyrisulfuron, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen (including pyraflufen-ethyl), pyrasulfotole, pyridate, pyriftalid, pyrimisulfan, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quizalofop (including quizalofop-P-ethyl and quizalofop-P-tefuryl), rimisoxafen, rimsulfuron, saflufenacil, sethoxydim, simazine, S-metolachlor (S-metalochlor), sulfentrazone, sulfosulfuron, tebuthiuron, tefuryltrione, tembotrione, terbuthylazine, terbutryn, tetflupyrrolimet, thiencarbazone, thifensulfuron, thiafenacil, tolpyralate, topramezone, tralkoxydim, triafamone, triallate, triasulfuron, tribenuron (including tribenuron-methyl), triclopyr, trifloxysulfuron (including trifloxysulfuron-sodium), trifludimoxazine, trifluralin,Triflusulfuron, tripyrasulfone, [(E)-[2-(trifluoromethyl)phenyl]methyleneamino]2,6-bis[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoate, 3-(2-chloro-4-fluoro-5-(3-methyl-2,6-dioxo-4-trifluoromethyl-3,6-dihydropyrimidin-1(2H)-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, 4-hydroxy-1-methoxy-5-methyl-3-[4-( trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 5-ethoxy-4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1-methyl-3-[4-(trifluoromethyl)-2-pyridyl]imidazolidin-2-one, 4-hydroxy-1,5-dimethyl-3-[1-methyl-5-(trifluoromethyl)- (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, (4R)1-(5-tert-butylisoxazol-3-yl)-4-ethoxy-5-hydroxy-3-methyl-imidazolidin-2-one, 4-amino-3-chloro-5-fluoro-6-(7-fluoro-1H-indol-6-yl)pyridine-2-carboxylic acid (including 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-ynyl 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), 3-ethylsulfanyl-N-(1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide,3-(Isopropylsulfanylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(Isopropylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, 3-(Ethylsulfonylmethyl)-N-(5-methyl-1,3,4-oxadiazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide Diazol-2-yl)-5-(trifluoromethyl)-[1,2,4]triazolo[4,3-a]pyridine-8-carboxamide, ethyl-2-[[3-[[3-chloro-5-fluoro-6-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]-2-pyridyl]oxy]acetate, 6-chloro-4-(2,7-dimethyl-1-naphthyl)-5-hydroxy-2-methyl-pyridazin-3-one, tetrahydrofuran-2-ylmethyl(2R)-2-[(4-amino-3 ,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, (2R)-2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, tetrahydrofuran-2-ylmethyl 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoate, 2-[(4-amino-3,5-dichloro-6-fluoro-2-pyridyl)oxy]propanoic acid, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-[(R )-propylsulfinyl]-4-(trifluoromethyl)benzamide, 2-fluoro-N-(5-methyl-1,3,4-oxadiazol-2-yl)-3-propylsulfinyl-4-(trifluoromethyl)benzamide, (2-fluorophenyl)methyl 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylate, 6-amino-5-chloro-2-(4-chloro-2-fluoro-3-methoxy-phenyl)pyrimidine-4-carboxylic acid,3-(3-chlorophenyl)-6-(5-hydroxy-1,3-dimethyl-pyrazole-4-carbonyl)-1,5-dimethyl-quinazoline-2,4-dione and [4-[3-(3-chlorophenyl)-1,5-dimethyl-2,4-dioxo-quinazoline-6-carbonyl]-2,5-dimethyl-pyrazol-3-yl]N,N-diethylcarbamate, methyl 2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropanoate and methyl (2R)-2-[(E)-[2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)pyrimidin-1-yl]phenyl]methyleneamino]oxypropanoate.

[0131] The compound of formula (I) may also be in the form of an ester or salt, as described, for example, in The Pesticide Manual, Sixteenth Edition, British Crop Protection Council, 2012.

[0132] Mixtures can be used to advantage in the above formulations (in which case the "active ingredient" relates to the respective mixture of the compound of formula (I) with the mixing partner).

[0133] The compound or mixture of the present invention can also be used in combination with one or more herbicide safeners. Examples of such safeners include benoxacor, cloquintocet (including cloquintocet-mexyl), cyprosulfamide, dichlormid, fenchlorazole (including fenchlorazole-ethyl), fenclorim, fluxofenim, furilazole, isoxadifen (including isoxadifen-ethyl), mefenpyr (including mefenpyr-diethyl), metcamifen, and oxabetrinil. Particularly preferred is a mixture of the compound of formula I with cyprosulfamide, isoxadifen-ethyl, cloquintocet-mexyl, and / or metcamifen.

[0134] The safeners of the compounds of formula (I) can also be used as anti-toxicants, as described, for example, in The Pesticide Manual, 16 th Edition (BCPC), 2012. Reference to cloquintocet-mexyl also applies to its lithium, sodium, potassium, calcium, magnesium, aluminum, iron, ammonium, quaternary ammonium, sulfonium or phosphonium salts, as disclosed in WO 02 / 34048.

[0135] Preferably, the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, in particular from 20:1 to 1:1.

[0136] The compounds of formula (I) are usually used in the form of pesticide compositions and can be applied to the crop areas or plants to be treated simultaneously or sequentially with additional compounds. These additional compounds can be, for example, fertilizers or trace element donors, or other preparations that affect plant growth. They can also be selective or non-selective herbicides, as well as insecticides, fungicides, bactericides, nematicides, molluscicides, or mixtures of several of these preparations, optionally with additional carriers, surfactants, or application promoters customarily used in the formulation art.

[0137] As used herein, the term "habitat" means the field in which the plant is growing, or the field in which the seeds of the cultivated plant are sown, or the field in which the seeds will be sown in the soil. It includes the soil, the seeds and seedlings, and the established vegetation.

[0138] The term "plant" refers to all physical parts of a plant, including seeds, seedlings, seedlings, roots, tubers, stems, stalks, foliage, and fruits.

[0139] The term "plant propagation material" is understood to refer to reproductive parts of plants, such as seeds, that can be used for their propagation, as well as vegetative bodies, such as cuttings or tubers, e.g., potatoes. For example, seeds (in the strict sense), roots, fruits, tubers, bulbs, rhizomes, and plant parts may be mentioned. Also included are sprouted plants and shoots that will be transplanted after germination or emergence from the soil. These shoots may be protected by a complete or partial treatment by immersion before transplantation. Preferably, "plant propagation material" is understood to refer to seeds.

[0140] Pesticides referred to herein using common names are known, for example, from “The Pesticide Manual”, 15th Ed., British Crop Protection Council 2009.

[0141] The compounds of formula (I) can be used in their unmodified form, or preferably, together with the adjuvants conventionally employed in the formulation field.For this purpose, they can be conveniently formulated in a known manner into emulsifiable concentrates, coating pastes, directly sprayable or dilutable solutions or suspensions, diluted emulsions, wettable powders, soluble powders, dusts, granules, and capsules, for example, in polymeric materials.As well as the type of composition, the application method, such as spraying, misting, dusting, scattering, coating, or pouring, is selected according to the intended purpose and the current situation.The composition can also contain further adjuvants, such as stabilizers, antifoaming agents, viscosity adjusters, binders or adhesives, as well as fertilizers, trace element sources, or other compounds for achieving special effects.

[0142] For example, suitable carriers and adjuvants for use in agriculture can be solid or liquid and are substances useful in formulation technology, such as natural or regenerated mineral substances, solvents, dispersants, wetting agents, adhesives, thickeners, binders or fertilizers. Such carriers are described, for example, in WO 97 / 33890.

[0143] The compounds of formula (I) are usually used in the form of compositions and can be applied to the crop area or plants to be treated simultaneously or sequentially with additional compounds. These additional compounds can be, for example, fertilizers or trace element donors or other preparations that affect plant growth. They can also be selective or non-selective herbicides, as well as insecticides, fungicides, bactericides, nematicides, molluscicides, or mixtures of several of these preparations, optionally with additional carriers, surfactants, or application-promoting adjuvants commonly used in the formulation art.

[0144] The compound of formula (I) may be the sole active ingredient in the composition or, where appropriate, may be mixed with one or more additional active ingredients, such as pesticides, fungicides, synergists, herbicides or plant growth regulators, which may in some cases result in unexpected synergistic activity.

[0145] Typically, the formulations contain 0.01 to 90% by weight of active agent, 0 to 20% by weight of an agriculturally acceptable surfactant, and 10 to 99.99% by weight of solid or liquid inert compounding agents and adjuvants, where the active agent is composed of at least a compound of formula (I) together with components (B) and (C) and, optionally, other active agents, particularly fungicides or preservatives. Concentrated forms of the compositions generally contain about 2 to 80% by weight, preferably about 5 to 70% by weight, of the active agent. Application forms of the formulations may contain, for example, 0.01 to 20% by weight, preferably 0.01 to 5% by weight, of the active agent. While commercial products will preferably be formulated as concentrates, end users will typically utilize diluted formulations.

[0146] The following table shows individual compounds of formula (I) according to the present invention: [ka] An example of this is illustrated below.

[0147] [Table 1-1] [Table 1-2] [Table 1-3]

[0148] Table A-1 provides 54 compounds of formula (I), A-1.001 to A-1.054, where R 3 and R 4 are both hydrogen, and R 1 , R 2 , R 5 and R 6 is as defined in Table 1.

[0149] Formulation example

[0150] [Table 2]

[0151] The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill to give a wettable powder which can be diluted with water to give a suspension of the desired concentration.

[0152] [Table 3]

[0153] The active ingredient is thoroughly mixed with the adjuvant and the mixture is thoroughly ground in a suitable mill to obtain a powder that is ready for use in seed treatment.

[0154] emulsifiable concentrate Active ingredient [compound of formula (I)] 10% Octylphenol polyethylene glycol ether 3% (4-5 mol of ethylene oxide) Calcium dodecylbenzenesulfonate 3% Castor oil polyglycol ether (35 mol ethylene oxide) 4% Cyclohexanone 30% Xylene mixture 50% Emulsions of any required dilution that can be used in plant protection can be obtained from this concentrate by dilution with water.

[0155] [Table 4]

[0156] Ready-to-use dusts are obtained by mixing the active ingredient with a carrier and grinding the mixture in a suitable mill. Such powders can also be used for dry seed dressing.

[0157] Extruded Granules Active ingredient [compound of formula (I)] 15% Sodium lignosulfonate 2% Carboxymethylcellulose 1% Kaolin 82% The active ingredient is mixed and ground with the adjuvants, the mixture is moistened with water, the mixture is extruded and then dried in a current of air.

[0158] Coated Granules Active ingredient [compound of formula (I)] 8% Polyethylene glycol (mol.wt.200) 3% Kaolin 89% The finely ground active ingredient is applied uniformly in a mixer to kaolin moistened with polyethylene glycol, thereby obtaining dust-free coated granules.

[0159] Suspension concentrate Active ingredient [compound of formula (I)] 40% Propylene glycol 10% Nonylphenol polyethylene glycol ether (15 mol ethylene oxide) 6% Sodium lignosulfonate 10% Carboxymethylcellulose 1% Silicone oil (in the form of a 75% emulsion in water) 1% water 32% The finely ground active ingredient is thoroughly mixed with adjuvants to give a suspension concentrate, from which suspensions of any desired dilution can be obtained by dilution with water, which allows living plants and plant propagation material to be treated by spraying, pouring or immersion to protect them from microbial infestation.

[0160] Seed treatment flowable concentrate Active ingredient [compound of formula (I)] 40% Propylene glycol 5% Copolymer butanol PO / EO 2% Tristyrenephenol + 10-20 moles of EO 2% 1,2-Benzisothiazolin-3-one (in the form of a 20% aqueous solution) 0.5% Monoazo pigment calcium salt 5% Silicone oil (in the form of a 75% emulsion in water) 0.2% Water 45.3% The finely ground active ingredient is thoroughly mixed with adjuvants to obtain a suspension concentrate, from which suspensions of any desired dilution can be obtained by dilution with water, which can be used to treat living plants and plant propagation material by spraying, pouring, or immersion to protect them from microbial infestation.

[0161] slow-release capsule suspension 28 parts of a combination of compounds of formula (I) are mixed with 2 parts of an aromatic solvent and 7 parts of a toluene diisocyanate / polymethylene-polyphenylisocyanate mixture (8:1). This mixture is emulsified in a mixture of 1.2 parts of polyvinyl alcohol, 0.05 parts of a defoamer, and 51.6 parts of water until the desired particle size is achieved. To this emulsion, a mixture of 2.8 parts of 1,6-diaminohexane in 5.3 parts of water is added. The mixture is stirred until the polymerization reaction is complete. The resulting capsule suspension is stabilized by adding 0.25 parts of a thickener and 3 parts of a dispersant. This capsule suspension formulation contains 28% active ingredient. The average capsule diameter is 8 to 15 microns. The resulting formulation is applied to seeds as an aqueous suspension in equipment suitable for this purpose. [Example]

[0162] The following non-limiting examples provide specific methods for synthesizing representative compounds of the invention referenced in Table 2 below.

[0163] List of Abbreviations brd = broad doublet, brm = broad multiplet, brs = broad singlet, °C = degrees Celsius, d = doublet, dd = doublet of doublets, DMSO = dimethyl sulfoxide, HPLC = high performance liquid chromatography, LCMS = liquid chromatography mass spectrometry, M = molar amount, m = multiplet, MHz = megahertz, q = quartet, s = singlet, t = triplet.

[0164] Example 1: Synthesis of 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (compound 4) Step 1: Synthesis of methyl 3-(3,4-dichlorophenyl)-3-oxo-propanoate [ka] To a stirred solution of 1-(3,4-dichlorophenyl)ethanone (5.00 g, 26.5 mmol) and dimethyl carbonate (40 mL, 466 mmol) cooled to 0° C. under a nitrogen atmosphere, sodium hydride (3.17 g, 79.5 mmol, 60% by weight) was added in several portions. The reaction mixture was allowed to warm to room temperature and stirred for 16 hours. Overnight, the reaction mixture became a solid paste and was unable to stir. An attempt was made to quench by adding more dimethyl carbonate (10 mL) to form a mobile slurry. The reaction mixture was cooled to 0° C. and quenched by the addition of water (25 mL) under a nitrogen atmosphere. The reaction mixture was acidified to pH 3 by the addition of 2 M aqueous hydrochloric acid and then extracted with ethyl acetate. The organic extract was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0-15% ethyl acetate in isohexane as eluent to give methyl 3-(3,4-dichlorophenyl)-3-oxo-propanoate (mixture of tautomers) as a colorless liquid. Enol: 1 H NMR (400 MHz, chloroform) δ = 12.47 (s, 1H), 7.87 (d, 1H), 7.59 (m, 3H), 7.49 (d, 1H), 5.65 (s, 1H), 3.82 (s, 3H) Keto: 1 H NMR (400 MHz, chloroform) δ = 8.03 (d, 1H), 7.77 (m, 1H), 7.58 (d, 2H), 3.97 (s, 2H), 3.76 (s, 3H).

[0165] Step 2: Synthesis of ethyl (Z)-3-(3,4-dichlorophenyl)-3-(ethylamino)prop-2-enoate [ka] To a stirred solution of ethyl 3-(3,4-dichlorophenyl)-3-oxopropanoate (1.65 g, 6.319 mmol) in toluene (11 mL) was added ethylammonium acetate (19.0 mmol) and acetic acid (6.32 mmol). The orange reaction mixture was heated at reflux for 6 hours. The cooled reaction mixture was diluted with ethyl acetate, filtered, and washed with saturated aqueous sodium bicarbonate. The phases were separated, and the aqueous phase was extracted with ethyl acetate (×3). The organic extract was dried over magnesium sulfate and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0–10% ethyl acetate in cyclohexane as eluent to give ethyl (Z)-3-(3,4-dichlorophenyl)-3-(ethylamino)prop-2-enoate as a colorless oil. 1 H NMR (400 MHz, chloroform) δ = 7.49-7.43 (m, 2H), 7.23-7.15 (m, 1H), 4.58-4.50 (m, 1H), 4.17-4.08 (m, 2H), 3.12-2.91 (m, 2H), 1.31-1.22 (m, 3H), 1.15-1.06 (m, 3H)

[0166] Step 3: Synthesis of methyl 2-(3,4-dichlorophenyl)-1-ethyl-6-methyl-4-oxo-pyridine-3-carboxylate [ka] A stirred mixture of ethyl (Z)-3-(3,4-dichlorophenyl)-3-(ethylamino)prop-2-enoate (0.583 g, 2.02 mmol) and 2,2,6-trimethyl-1,3-dioxin-4-one (4.05 mmol) was heated at 120° C. for 3 hours under a nitrogen atmosphere. The cooled reaction mixture was diluted with ethyl acetate and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 10% methanol in dichloromethane as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-methyl-4-oxo-pyridine-3-carboxylate as a brown solid. 1 H NMR (400 MHz, chloroform) δ = 7.59 (d, 1H), 7.53 (d, 1H), 7.29 (dd, 1H), 6.39 (s, 1H), 4.04-3.95 (m, 2H), 3.77 (q, 2H), 2.44 (s, 3H), 1.14 (t, 3H), 0.97 (t, 3H).

[0167] Step 4: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-methyl-4-oxo-pyridine-3-carboxylate (80 g, 226 mmol) in acetonitrile (800 mL) at 80° C. was added 2,2,2-trifluoroacetic acid (5.2 mL, 67.8 mmol), followed by the dropwise addition of 1-iodopyrrolidine-2,5-dione (224 mmol). The reaction mixture was stirred at room temperature for 3 hours. The cooled reaction mixture was quenched by the addition of saturated aqueous sodium bicarbonate solution and extracted with dichloromethane (3 times). The combined organic extracts were washed with saturated sodium thiosulfate solution, then brine, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 40-45% ethyl acetate in cyclohexane as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate as a white solid. 1 H NMR (400 MHz, chloroform) δ = 7.57 (d, J = 8.3 Hz, 1H), 7.50 (d, J = 2.0 Hz, 1H), 7.24 (dd, J = 2.1, 8.2 Hz, 1H), 4.10-3.97 (m, 2H), 3.89 (q, J = 7.1 Hz, 2H), 2.87 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H), 1.03 (t, J = 7.2 Hz, 3H).

[0168] Step 5: Synthesis of ethyl 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] A mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate (0.200 g, 0.417 mmol), 3-chloro-1H-pyrazole (0.154 g, 1.50 mmol), copper(I) iodide (0.0801 g, 0.417 mmol), 1,10-phenanthroline (0.155 g, 0.833 mmol), and potassium carbonate (0.116 g, 0.833 mmol) was added to a screw-top vial equipped with a pressure relief device. The contents were purged with nitrogen (three times), and then degassed N,N-dimethylacetamide (2.8 mL) was added. The reaction mixture was heated at 120 °C overnight for 18 hours. The cooled reaction mixture was diluted with water and acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid, then extracted with dichloromethane. The crude residue was purified by mass directed reverse phase HPLC to give ethyl 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as an orange gum. 1 H NMR (400 MHz, chloroform) δ = 7.59 (d, 1H), 7.56-7.52 (m, 2H), 7.29 (d, 1H), 6.58 (brs, 1H), 6.36-6.25 (m, 1H), 5.31 (s, 2H), 4.08-3.93 (m, 4H), 1.09 (t, 3H), 0.99 (t, 3H).

[0169] Step 6: Synthesis of 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (compound 4) [ka] To a solution of ethyl 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (0.064 g, 0.14 mmol) in a mixture of methanol (1.15 mL) and water (0.32 mL) was added lithium hydroxide (0.013 g, 0.56 mmol). The resulting solution was heated at reflux for 1 hour. The cooled reaction mixture was diluted with dichloromethane and water, acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid, and then extracted into dichloromethane. The organic extract was evaporated under reduced pressure to give 6-[(3-chloropyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as an orange gum. 1 H NMR (400 MHz, chloroform) δ = 7.61 (d, 1H), 7.56 (d, 1H), 7.42 (d, 1H), 7.17 (dd, 1H), 6.32 (d, 1H), 6.24 (s, 1H), 5.36 (s, 2H), 3.96 (q, 2H), 1.21 (t, 3H)

[0170] Example 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 10) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate and ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate [ka] A mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate (0.200 g, 0.417 mmol), 5-(trifluoromethyl)-1H-imidazole (0.204 g, 1.50 mmol), copper(I) iodide (0.0801 g, 0.417 mmol), 1,10-phenanthroline (0.155 g, 0.833 mmol), and potassium carbonate (0.116 g, 0.833 mmol) was added to a pressure-relief screw-top vial, followed by the addition of N,N-dimethylacetamide (2.8 mL). The reaction mixture was heated at 120 °C overnight for 18 hours. The cooled reaction mixture was poured into saturated aqueous ammonium chloride solution and diluted with ethyl acetate. Water was added to dissolve the solid precipitate in the aqueous phase. The mixture was filtered through diatomaceous earth, and the organic phase was washed sequentially with saturated aqueous ammonium chloride, water, and brine, then dried over magnesium sulfate and concentrated under reduced pressure. The crude residue was purified by mass-directed reverse-phase HPLC to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate (0.017 g, 0.035 mmol, 8%) and ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate. Isomer 1: 1 H NMR (400MHz, chloroform) δ=7.70(brs,1H),7.61(d,1H),7.55(d,1H),7.41(brs,1H),7.29(dd,1H) ,6.24(brs,1H),5.27(brs,2H),4.06-3.94(m,2H),3.77(brd,2H),1.08(brt,3H),0.97(t,3H) Isomer 2: 1 H NMR (400 MHz, chloroform) δ = 8.05 (brm, 1H), 7.63-7.56 (m, 3H), 7.32 (dd, 1H), 6.01 (s, 1H), 5.38 (s, 2H), 4.09-3.98 (m, 2H), 3.79 (q, 2H), 1.26-1.11 (m, 3H), 0.99 (t, 3H).

[0171] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate (0.015 g, 0.031 mmol) in a mixture of methanol (0.27 mL) and water (0.075 mL) was added lithium hydroxide (0.0029 g, 0.12 mmol). The resulting solution was heated at reflux for 1.2 hours. The cooled reaction mixture was diluted with dichloromethane and water, acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid, and then extracted into dichloromethane. The organic extract was concentrated under reduced pressure to give 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[4-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid as a white solid. 1 H NMR (400 MHz, methanol) δ = 8.07-8.00 (m, 1H), 7.89-7.84 (m, 1H), 7.77-7.71 (m, 1H), 7.68-7.65 (m, 1H), 7.39-7.33 (m, 1H), 6.10 (s, 1H), 5.67 (s, 2H), 4.02-3.94 (m, 2H), 1.22 (t, 3H)

[0172] Example 3: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 16) Step 1: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylate (0.023 g, 0.047 mmol) in a mixture of methanol (0.41 mL) and HCl (0.11 mL) was added lithium hydroxide (0.005 g, 0.19 mmol). The resulting solution was heated at reflux for 1.2 hours and then allowed to stand at room temperature for 18 hours. The cooled reaction mixture was diluted with dichloromethane and water, acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid, and then extracted into dichloromethane. The organic extract was concentrated under reduced pressure to give 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[5-(trifluoromethyl)imidazol-1-yl]methyl]pyridine-3-carboxylic acid as a white solid. 1 H NMR (400 MHz, chloroform) δ = 7.78 (s, 1H), 7.66-7.60 (m, 2H), 7.41 (d, 1H), 7.17 (dd, 1H), 5.99 (s, 1H), 5.37 (s, 2H), 3.84 (q, 2H), 1.33-1.17 (m, 3H).

[0173] Example 4: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 2) Step 1: Synthesis of ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a suspension of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-methyl-4-oxo-pyridine-3-carboxylate (10.05 g, 28.37 mmol) in acetonitrile (100 mL) was added N-bromosuccinimide (NBS, 5.56 g, 31.2 mmol) dropwise over 3 minutes. Once the addition was complete, the reaction mixture was heated at 40° C. for 3 hours. After this time, the reaction mixture was diluted with acetonitrile (100 mL) and trifluoroacetic acid (3.93 g, 2.66 mL, 34 mmol) was added, followed by the dropwise addition of NBS (5.05 g, 28.4 mmol) over 5 minutes. The resulting reaction mixture was heated at 80° C. for 4 hours and then allowed to stand at room temperature for 18 hours. The acetonitrile was removed under reduced pressure, and the residue was partitioned between dichloromethane and water. The organic phase was washed with saturated aqueous sodium bicarbonate, then brine, then dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 100% ethyl acetate in cyclohexane as eluent to give ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as an off-white solid. 1 H NMR (500 MHz, chloroform) δ = 7.59 (d, 1H), 7.53 (d, 1H), 7.28 (d, 1H), 4.72 (brs, 2H), 4.10-3.95 (m, 4H), 1.25 (t, 3H), 1.04 (t, 3H)

[0174] Step 2: Synthesis of ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate [ka] To a solution of ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (5.2 g, 10.1 mmol) in acetonitrile (100 mL) was added 3-(trifluoromethyl)-1H-pyrazole (1.52 g, 11.2 mmol), followed by the dropwise addition of potassium carbonate (2.83 g, 20.3 mmol) over 2 minutes. The reaction mixture was stirred at room temperature for 1.7 hours. The acetonitrile was removed under reduced pressure, and the residue was dissolved in a mixture of dichloromethane (100 mL) and water (100 mL). The aqueous phase was extracted with dichloromethane (twice) and the combined organic extracts were washed with brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to give ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate as a white foam. 1 H NMR (400 MHz, chloroform) δ = 7.80 (dd, 1H), 7.58 (d, 1H), 7.50 (d, 1H), 7.23 (dd, 1H), 6.64-6.61 (m, 1H), 5.81 (s, 2H), 4.23 (brd, 2H), 4.11-3.99 (m, 2H), 1.09-1.01 (m, 6H).

[0175] Step 3: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate [ka] A hydrogenation vessel was charged with 5% palladium on carbon (50% wet) (1.3 g), ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (5.0 g, 8.8 mmol), ethanol (130 mL), and acetic acid (25 mL). The mixture was stirred under a hydrogen atmosphere (2 bar) for 5.5 hours. After this time, additional 5% palladium on carbon (50% wet) (0.5 g) was added, and the mixture was stirred under a hydrogen atmosphere (2 bar) for 2.3 hours. The reaction mixture was filtered through diatomaceous earth, washing with dichloromethane, and the filtrate was evaporated under reduced pressure. The crude residue was purified by flash chromatography on C-18 silica gel using a gradient of 40 to 80% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate as a white solid. 1 H NMR (400 MHz, chloroform) δ = 7.65-7.62 (m, 1H), 7.57 (d, 1H), 7.51 (d, 1H), 7.26-7.23 (m, 1H), 6.65 (d, 1H), 6.34 (s, 1H), 5.35 (s, 2H), 4.09-3.97 (m, 2H), 3.87 (q, 2H), 1.04-0.95 (m, 6H).

[0176] Step 4: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (3.08 g, 6.31 mmol) in a mixture of methanol (55 mL) and water (15 mL) was added lithium hydroxide (0.604 g, 25.2 mmol). The resulting solution was heated at reflux for 2 hours. The reaction mixture was cooled to 40° C., then diluted with water (50 mL) and acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid (20 mL), resulting in the precipitation of a white solid. The methanol was removed under reduced pressure, and the resulting aqueous mixture was cooled in an ice bath. The resulting white solid was isolated by filtration, washed with water, and air-dried to give 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid as a white solid. 1 H NMR (400 MHz, chloroform) δ = 7.73-7.68 (m, 1H), 7.61 (d, 1H), 7.43 (d, 1H), 7.17 (dd, J = 2.0, 8.3 Hz, 1H), 6.67 (d, 1H), 6.20 (s, 1H), 5.47 (s, 2H), 4.02-3.91 (m, 2H), 1.20 (t, 3H).

[0177] Example 5: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid (compound 40) Step 1: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylic acid [ka] Ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate (6.0 g, 12.5 mmol) was dissolved in a mixture of methanol (54 mL) and water (24 mL), and lithium hydroxide (1.32 g, 31.5 mmol) was added. The reaction mixture was heated at 80° C. for 2 hours. The cooled reaction mixture was evaporated to dryness under reduced pressure, and the residue was diluted with cold water and acidified by the addition of 2 M aqueous hydrochloric acid. The resulting precipitate was filtered, washed with water, and dried under reduced pressure to give 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1 H NMR (400 MHz, chloroform) δ = 7.60 (d, 1H), 7.35 (d, 1H), 7.11 (dd, 1H), 4.13-3.92 (q, 2H), 3.00 (s, 3H), 1.23 (t, 3H).

[0178] Step 2: Synthesis of tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate [ka] To a suspension of 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylic acid (4.7 g, 10 mmol) in 2-methylpropan-2-ol (3 mL / mmol) was added N,N-dimethylpyridin-4-amine (5.2 mmol) and tert-butoxycarbonyl tert-butyl carbonate (21 mmol) sequentially at room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (three times). The combined extracts were washed once with saturated aqueous sodium bicarbonate and then dried over magnesium sulfate. The residue was purified by flash chromatography on silica gel using ethyl acetate in cyclohexane as the eluent to give tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate. 1 H NMR (400 MHz, chloroform) δ = 7.64-7.45 (m, 1H), 7.56-7.46 (m, 1H), 7.26-7.24 (m, 1H), 3.97-3.85 (q, 2H), 2.87 (s, 3H), 1.25 (s, 9H), 1.20-1.15 (m, 3H).

[0179] Step 3: Synthesis of tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate [ka] To a mixture of tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate (1.0 g, 1.97 mmol), methyl 1H-pyrazole-4-carboxylate (0.89 g, 7.1 mmol), copper(I) iodide (0.379 g, 1.97 mmol), 1,10-phenanthroline (0.731 g, 3.94 mmol), and potassium carbonate (0.55 g, 3.94 mmol) was added degassed N,N-dimethylacetamide (13 mL) under a nitrogen atmosphere. The mixture was heated under microwave irradiation at 120 °C for 2 hours with stirring. The cooled reaction mixture was poured into saturated aqueous ammonium chloride solution, and ethyl acetate and water were added. The mixture was filtered through diatomaceous earth, and the organic phase was washed sequentially with saturated aqueous ammonium chloride, water, and brine, and then dried over magnesium sulfate. The crude residue was purified by HPLC to give tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate as a white solid. 1H NMR (400MHz, chloroform) δ = 8.16-8.12 (m, 1H), 7.99-7.97 (m, 1H), 7.64-7.59 (m, 1H), 7.58-7.55 (m, 1H), 7.33-7.29 (m, 1H), 6.85-6.44 (m, 1H), 5.56-5.27 (m, 2H), 4.01-3.93 (m, 2H), 3.89-3.86 (m, 3H), 1.26-1.20 (m, 9H), 1.14-1.05 (m, 3H)

[0180] Step 4: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a solution of tert-butyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate (100 mg, 0.20 mmol) in trifluoromethylbenzene (10 mL / g) was added 2,2,2-trifluoroacetic acid (15 equivalents, 2.962 mmol) at 0° C. The reaction mixture was warmed to room temperature and stirred for 24 hours. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was washed. It was then stirred at room temperature for 24 hours. The reaction was monitored by LCMS. The reaction was shown to be complete. The reaction mixture was then concentrated under reduced pressure, and the residue was washed with methyl tert-butyl ether to give 2-(3,4-dichlorophenyl)-1-ethyl-6-[(4-methoxycarbonylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid. 1H NMR(400MHz,DMSO-d6)δ=8.66(s,1H),8.07(s,1H),7.86-7.73(m,2H),7.44(d d,1H),6.18(s,1H),5.73(s,2H),3.94-3.89(m,2H),3.78(s,3H),1.05(t,3H)

[0181] Example 6: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-methoxy-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid (compound 44) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-nitro-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate [ka] To a mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-iodo-6-methyl-4-oxo-pyridine-3-carboxylate (1.00 g, 2.08 mmol), 3-nitro-1H-1,2,4-triazole (0.855 g, 7.50 mmol), copper(I) iodide (0.401 g, 2.08 mmol), 1,10-phenanthroline (0.774 g, 4.17 mmol), and potassium carbonate (0.582 g, 4.17 mmol) was added degassed N,N-dimethylacetamide (14 mL) under a nitrogen atmosphere. The reaction mixture was heated under microwave irradiation at 150 °C with stirring for 1 hour. The cooled reaction mixture was poured into saturated aqueous ammonium chloride solution, and ethyl acetate and water were added. The mixture was filtered through diatomaceous earth, and the organic phase was washed sequentially with saturated aqueous ammonium chloride, water, and brine, and then dried over magnesium sulfate. The crude residue was purified by HPLC to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-nitro-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate. 1H NMR(400MHz,DMSO-d6)δ=9.10(s,1H),7.85(d,1H),7.82(d,1H),7.49(dd, 1H),6.17(s,1H),5.78(s,2H),3.91-3.76(m,4H),1.03(t,3H),0.82(t,3H)

[0182] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-methoxy-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-nitro-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate (40 mg, 0.086 mmol) in methanol (10 mL) was added a suspension of lithium hydroxide (0.014 g, 0.34 mmol) in water (0.04 mL). The reaction mixture was stirred at 80° C. for 1 hour. The cooled reaction mixture was acidified by the addition of 2 M aqueous hydrochloric acid, diluted with additional water (10 mL), and then extracted into ethyl acetate (2×10 mL). The combined organic extracts were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was triturated with tert-butyl methyl ether, filtered, and the solid filtrate was dried under reduced pressure to give 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-methoxy-1,2,4-triazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid. 1H NMR(400MHz,DMSO-d6)δ=8.48(s,1H),7.84-7.80(m,1H),7.78(d,1H),7.44(dd,1H),6.27(s,1H),5.62(s,2H),3.92-3.86(m,5H),1.07(t,3H)

[0183] Example 7: Synthesis of 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 177) Step 1: Synthesis of 6-(bromomethyl)-2,2-dimethyl-1,3-dioxin-4-one [ka] A stirred solution of 2,2,6-trimethyl-1,3-dioxin-4-one (4.88 g, 34.3 mmol) and N-bromosuccinimide (7.94 g, 44.6 mmol) in dichloromethane (120 mL) was irradiated with 450 nm light for 12 h at room temperature. The orange reaction mixture was washed with a 50:50 mixture of saturated aqueous sodium bicarbonate and saturated aqueous sodium thiosulfate. The organic phase was dried over magnesium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on C-18 silica gel using a gradient of 30–60% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 6-(bromomethyl)-2,2-dimethyl-1,3-dioxin-4-one as a yellow oil. 1 H NMR (400 MHz, chloroform) δ = 5.54 (s, 1H), 3.90 (s, 2H), 1.73 (s, 6H)

[0184] Step 2: Synthesis of ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl (Z)-3-(3,4-dichlorophenyl)-3-(ethylamino)prop-2-enoate (2.00 g, 6.94 mmol) in xylene (20.0 mL) was added 6-(bromomethyl)-2,2-dimethyl-1,3-dioxin-4-one (2.30 g, 10.4 mmol). The resulting reaction mixture was heated with stirring at 140° C. for 5 minutes. The cooled reaction mixture was diluted with ethyl acetate, and the organic solution was washed with brine, dried over magnesium sulfate, filtered, and evaporated to dryness under reduced pressure to give 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as a brown solid. 1H NMR (400MHz, DMSO-d6) δ=7.89(s,1H),7.79(d,1H),7.49(d,1H),6.59(s,1H),4.72(s,2H),3.82-3.77(q,4H),1.11(t,3H),0.84(t,3H).

[0185] Step 3: Synthesis of ethyl 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a solution of ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (0.500 g, 1.15 mmol) in acetonitrile (10 mL) was added 3-bromo-1H-pyrazole (0.19 g, 1.27 mmol), followed by the addition of potassium carbonate (0.32 g, 2.31 mmol) in portions over 2 minutes. The reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water and ethyl acetate, and the phases were separated. The organic extract was dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 20 to 80% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give ethyl 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as a white solid foam. 1H NMR (400MHz, chloroform) δ = 7.56 (d, 1H), 7.50 (d, 1H), 7.42 (d, 1H), 7.24 (d, 1H), 6.40 (d, 1H), 6.38 (s, 1H), 5.25 (s, 2H), 4.09-3.97 (m, 2H), 3.86 (q, 2H), 1.04 (t, 3H), 0.98 (t, 3H)

[0186] Step 4: Synthesis of 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid [ka] To a solution of ethyl 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (0.139 g, 0.278 mmol) in a mixture of methanol (1.25 mL) and water (0.35 mL) was added lithium hydroxide (0.048 g, 1.11 mmol). The resulting reaction mixture was heated at 80° C. for 3 hours. The cooled reaction mixture was diluted with dichloromethane and water and acidified to pH 1 by the addition of 2 M aqueous hydrochloric acid. The phases were separated and the organic phase was evaporated to dryness under reduced pressure to give 6-[(3-bromopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid foam. 1H NMR (400MHz, chloroform) δ = 7.61 (d, 1H), 7.49 (d, 1H), 7.39 (d, 1H), 7.14 (dd, 1H), 6.43 (d, 1H), 6.34 (s, 1H), 5.37 (s, 2H), 3.96 (q, 2H), 1.20 (t, 3H)

[0187] Example 8: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 206) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-6-methyl-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-methyl-4-oxo-pyridine-3-carboxylate (2.50 g, 7.06 mmol) in ethanol (100 mL) at room temperature was added 1-(chloromethyl)-4-fluoro-1,4-diazoniabicyclo[2.2.2]octane; ditetrafluoroborate (7.50 g, 21.2 mmol). The resulting reaction mixture was heated with stirring at 80 °C for 48 hours. The cooled reaction mixture was diluted with water (100 mL) and extracted into dichloromethane (2 × 100 mL). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 0 to 65% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-6-methyl-4-oxo-pyridine-3-carboxylate as a white solid.

[0188] Step 2: Synthesis of ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-6-methyl-4-oxo-pyridine-3-carboxylate (500 mg, 1.01 mmol) in acetonitrile (25 mL) at room temperature was added 1-bromopyrrolidine-2,5-dione (0.269 g, 1.51 mmol) and trifluoroacetic acid (0.293 g, 1.21 mmol). The resulting reaction mixture was heated with stirring at 80° C. for 2 hours. The cooled reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (twice). The combined organic extracts were washed with brine (20 mL), dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 10 to 50% ethyl acetate in hexanes as the eluent to give ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-pyridine-3-carboxylate as a white solid. 1H NMR(400MHz,DMSO-d6)δ=7.92-7.81(m,2H),7.56-7.43(m,1H),3.90-3.81(m,4H),2.70(s,2H),1.11(t,3H),0.93(t,3H)

[0189] Step 3: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate [ka] To a stirred solution of ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-pyridine-3-carboxylate (400 mg, 0.84 mmol) in acetonitrile (10 mL) was added 3-(trifluoromethyl)-1H-pyrazole (126 mg, 0.93 mmol) and potassium carbonate (232 mg, 1.68 mmol). The resulting reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The residue was purified by flash chromatography on silica gel using a gradient of 10-50% ethyl acetate in hexanes as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate as a white solid.

[0190] Step 4: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (190 mg, 0.38 mmol) in a mixture of acetonitrile (7.5 mL) and water (2.5 mL) at room temperature, lithium hydroxide hydrate (0.063 g, 1.5 mmol) was added at ambient temperature. The resulting reaction mixture was heated with stirring at 80° C. for 4 hours. The cooled reaction mixture was diluted with water (20 mL) and neutralized by the addition of 2 M aqueous hydrogen chloride solution. The precipitated solid was filtered and dried by evaporation of the solvent under reduced pressure to give 2-(3,4-dichlorophenyl)-1-ethyl-5-fluoro-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid as a light brown solid. 1H NMR(400MHz,DMSO-d6)δ=8.24(d,1H),7.81(dd,2H),7.46(dd,1H),6.86(d,1H),5.80(d,2H),3.96(q,2H),0.59(t,3H)

[0191] Example 9: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 20) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate [ka] To a degassed mixture of acetonitrile (8 mL) and water (2 mL) under a nitrogen atmosphere was added ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (200 mg, 0.35 mmol), methylboronic acid (40 mg, 0.67 mmol), and bis(triphenylphosphine)palladium(II)) dichloride (60 mg, 0.083 mmol), followed by potassium carbonate (200 mg, 1.4 mmol). The resulting suspension was heated under a nitrogen atmosphere at 100° C. under microwave irradiation for 0.5 h. The cooled reaction mixture was filtered through diatomaceous earth and washed with dichloromethane. The filtrate was washed with brine, then dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in cyclohexane as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (170 mg, 0.34 mmol) as a cream-colored solid. 1H NMR (400MHz, chloroform) δ = 7.56 (d, 1H), 7.48 (d, 1H), 7.45 (d, 1H), 7.22 (dd, 1H), 6.63 (d, 1H), 5.51 (s, 2H), 4.11-3.98 (m, 2H), 3.92 (q, 2H), 2.31 (s, 3H), 1.06-0.98 (m, 6H)

[0192] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (170 mg, 0.34 mmol) in methanol (5.0 mL) was added a solution of lithium hydroxide hydrate (75 mg, 1.8 mmol) in water (1 mL). The resulting reaction mixture was heated with stirring at 80° C. for 1.5 hours. The cooled reaction mixture was poured into water, acidified with 2 M aqueous hydrogen chloride solution, and extracted into dichloromethane. The crude material was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-5-methyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid as a cream-colored solid. 1H NMR (400MHz, methanol) δ = 7.64 (d, 1H), 7.61 (d, 1H), 7.40 (d, 1H), 7.14 (dd, 1H), 6.65 (d, 1H), 5.61 (s, 2H), 4.19-4.08 (m, 2H), 2.36 (s, 3H), 1.14 (t, 3H)

[0193] Example 10: Synthesis of 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 21) Step 1: Synthesis of ethyl 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate [ka] To a degassed mixture of acetonitrile (8 mL) and water (2 mL) was added ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (200 mg, 0.35 mmol), (4-chlorophenyl)boronic acid (70 mg, 0.45 mmol), and bis(triphenylphosphine)palladium(II) dichloride (50 mg, 0.069 mmol), followed by potassium carbonate (150 mg, 1.1 mmol). The resulting suspension was heated under a nitrogen atmosphere at 100° C. under microwave irradiation for 0.5 h. The cooled reaction mixture was filtered through diatomaceous earth and washed with dichloromethane. The filtrate was washed with brine, then dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of ethyl acetate in cyclohexane as the eluent to give ethyl 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate as a colorless gum. 1H NMR (500MHz, chloroform) δ=7.59(d,1H),7.56(d,1H),7.43(d,2H),7.29(dd,1H),7.15( d,2H),7.10(d,1H),6.54(d,1H),5.29(s,2H),4.14-4.00(m,4H),1.11-1.00(m,6H)

[0194] Step 2: Synthesis of 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a solution of ethyl 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylate (160 mg, 0.27 mmol) in a mixture of methanol (10 mL) and water (1 mL) was added lithium hydroxide hydrate (35 mg, 0.83 mmol). The resulting reaction mixture was heated with stirring at 80° C. for 4 hours. The cooled reaction mixture was poured into a 2 M aqueous solution of hydrogen chloride and extracted into dichloromethane. The organic extract was evaporated to dryness under reduced pressure to give 5-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(trifluoromethyl)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid as a cream-colored solid. 1H NMR (400 MHz, chloroform) δ = 7.61 (d, 1H), 7.48 (brd, 2H), 7.44-7.38 (m, 1H), 7.18 (dd, 1H), 7.12 (brd, 2H), 7.07 (d, 1H), 6.54 (d, 1H), 5.33 (s, 2H), 4.27-4.15 (m, 2H), 1.17 (t, 2H)

[0195] Example 11: Synthesis of 6-[[3,5-bis(ethoxycarbonyl)pyrazol-1-yl]methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 112) Step 1: Synthesis of 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid [ka] To a solution of ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (5.00 g, 9.77 mmol) in a mixture of tetrahydrofuran (50 mL) and water (10 mL) was added scandium(III) trifluoromethanesulfonate (6.25 g, 12.7 mmol) in several portions. The reaction mixture was heated with stirring at 50° C. for 12 hours. The cooled reaction mixture was diluted with ethyl acetate (30 mL), washed successively with water and brine, then dried over anhydrous magnesium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using dichloromethane as the eluent to give 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR (500MHz, chloroform) δ = 7.60 (d, 1H), 7.36 (d, 1H), 7.12 (dd, 1H), 4.96 (s, 2H), 4.18-4.09 (m, 2H), 1.22 (t, 3H)

[0196] Step 2: Synthesis of 6-((3,5-bis(ethoxycarbonyl)-1H-pyrazol-1-yl)methyl)-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid [ka] To a solution of diethyl 1H-pyrazole-3,5-dicarboxylate (158 mg, 0.74 mmol) in anhydrous tetrahydrofuran (3 mL) was added sodium hydride (50 mg) under a nitrogen atmosphere. After 5 minutes, a solution of 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid (300 mg, 0.62 mmol) in anhydrous tetrahydrofuran (3 mL) was added dropwise. The resulting reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was quenched by the addition of water and extracted with ethyl acetate (3 times). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0-5% methanol in dichloromethane as the eluent to give 6-((3,5-bis(ethoxycarbonyl)-1H-pyrazol-1-yl)methyl)-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=14.06(s,1H),7.84(d,1H),7.77(d,1H),7.45(dd,1H),7.36(s,1H) ,6.23(s,2H),4.39(q,2H),4.28(q,2H),3.95(dd,2H),1.35(t,3H),1.29(t,3H),1.03(t,3H)

[0197] Step 3: Synthesis of 6-[[3,5-bis(ethoxycarbonyl)pyrazol-1-yl]methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid [ka] To a solution of 6-((3,5-bis(ethoxycarbonyl)-1H-pyrazol-1-yl)methyl)-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid 9 (250 mg, 0.41 mmol) in methanol (10 mL) was added 10% palladium on carbon (100 mg) at room temperature, and the mixture was stirred under a hydrogen atmosphere for 12 hours. The reaction mixture was concentrated with diatomaceous earth, and the filtrate was evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to give 6-[[3,5-bis(ethoxycarbonyl)pyrazol-1-yl]methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=16.22(s,1H),7.83-7.79(m,2H),7.45(m,2H),6.10(s, 2H),5.52(s,1H),4.33-4.29(m,4H),3.86(q,2H),1.32-1.28(m,6H),1.17(t,3H)

[0198] Example 12: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid (Compound 147) Step 1: Synthesis of ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-(hydrazinomethyl)-4-oxo-pyridine-3-carboxylate [ka] To a solution of hydrazine monohydrate (0.211 g, 4.3 mmol) in acetonitrile (20 mL) at room temperature was added ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (2.0 g, 3.9 mmol). The reaction mixture was stirred at room temperature for 2 hours. Upon completion, the reaction mixture was evaporated to dryness under reduced pressure to give ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-(hydrazinomethyl)-4-oxo-pyridine-3-carboxylate as a bright yellow solid.

[0199] Step 2: Synthesis of ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-(hydrazinomethyl)-4-oxo-pyridine-3-carboxylate (1.4 g, 3.02 mmol) in toluene (3 mL) was added methyl 4,4,4-trifluoro-3-oxo-butanoate (0.514 g, 3.02 mmol) and p-toluenesulfonic acid monohydrate (29 mg, 0.15 mmol). The reaction mixture was heated at reflux with stirring for 8 hours. The cooled reaction mixture was filtered and washed with dichloromethane to give ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-((5-hydroxy-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylate as a white solid.

[0200] Step 3: Synthesis of 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred mixture of ethyl 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-((5-hydroxy-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylate (200 mg, 0.34 mmol) in a mixture of tetrahydrofuran (1 mL) and water (1 mL) was added lithium hydroxide (25 mg, 1.03 mmol). The reaction mixture was heated with stirring at 65° C. for 18 hours. The cooled reaction mixture was evaporated to dryness under reduced pressure, and the residue was suspended in water, which was acidified by the addition of 2 M aqueous hydrogen chloride solution. The product was extracted into ethyl acetate and evaporated to dryness under reduced pressure to give 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid as a bright yellow solid.

[0201] Step 4: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a solution of 5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid (140 mg, 0.252 mmol) in acetonitrile (3 mL) was added ammonium formate (79.5 mg, 1.26 mmol) and bis(triphenylphosphine)palladium(II) chloride (17.7 mg, 0.025 mmol). The reaction mixture was heated at 120° C. under microwave irradiation for 1 hour. The cooled reaction mixture was diluted with acetonitrile, filtered through diatomaceous earth, and washed with dichloromethane. The filtrate was evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 5 to 95% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid as a white powder. 1H NMR(400MHz,DMSO-d6)δ=12.53(s,1H),7.82(d,1H),7.79(d,1H),7.45(d,1H),5.94-5.89(m,2H),5.48(s,2H),3.88(q,2H),1.06(t,3H)

[0202] Example 13: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid (Compound 144) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate (200 mg, 0.40 mmol) in N,N-dimethylformamide (2 mL) was added 1-iodo-2-methoxyethane (0.148 g, 0.793 mmol) and potassium carbonate (0.164 g, 1.19 mmol). The reaction mixture was heated with stirring at 50° C. for 1 hour. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic phases were washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated to dryness under reduced pressure to give crude ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate, which was used directly in the next step without further purification.

[0203] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate (200 mg, 0.356 mmol) in a mixture of tetrahydrofuran (1 mL) and water (1 mL) was added lithium hydroxide monohydrate (0.045 g, 1.07 mmol) at room temperature. The reaction mixture was heated with stirring at 50° C. for 12 hours. The cooled reaction mixture was diluted with dichloromethane and water and acidified to pH 3 by the addition of 1 M aqueous hydrogen chloride solution. The phases were separated, and the organic phase was dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to afford 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-(2-methoxyethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=7.87-7.70(m,2H),7.44(dd,1H),6.48(s,1H),6.01(s,1H),5. 51(s,2H),4.46-4.30(m,2H),3.88(q,2H),3.68-3.61(m,2H),3.25(s,3H),1.05(t,3H)

[0204] Example 14: Synthesis of 2-(3,4-dichlorophenyl)-6-[[5-(difluoromethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 151) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-6-[[5-(difluoromethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a stirred mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[5-hydroxy-3-(trifluoromethyl)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate (200 mg, 0.397 mmol) and sodium 2-chloro-2,2-difluoroacetate (181 mg, 1.2 mmol) in N,N-dimethylformamide (5 mL) was added cesium carbonate (388 mg, 1.2 mmol). The reaction mixture was stirred at room temperature for 12 hours. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was diluted with water and extracted with ethyl acetate (twice). The combined organic extracts were evaporated to dryness under reduced pressure, and the resulting residue was purified by flash chromatography on silica gel using a gradient of 0-3% methanol in dichloromethane as eluent to give ethyl 2-(3,4-dichlorophenyl)-6-[[5-(difluoromethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate as a white solid.

[0205] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-6-[[5-(difluoromethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-6-[[5-(difluoromethoxy)-3-(trifluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate (82 mg, 0.148 mmol) in a mixture of tetrahydrofuran (5 mL) and water (1 mL) was added scandium(III) trifluoromethanesulfonate (109 mg, 0.22 mmol) in one portion. The reaction mixture was heated with stirring at 50° C. under a nitrogen atmosphere for 24 hours. The cooled reaction mixture was evaporated to remove tetrahydrofuran, and the residue was extracted with ethyl acetate (three times). The combined organic extracts were evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to afford 2-(3,4-dichlorophenyl)-6-((5-(difluoromethoxy)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=16.12(s,1H),7.80(m,2H),7.62-7.26(m,1H),7.47- 7.41(m,1H),6.84(s,1H),5.92(s,1H),5.69(s,2H),3.87(d,2H),1.06(t,3H)

[0206] Example 15: Synthesis of 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 154) Step 1: Synthesis of ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of N-(1H-pyrazol-3-yl)acetamide (1.47 g, 11.7 mmol) in anhydrous tetrahydrofuran (50 mL) at 0° C., sodium hydride (0.508 g, 12.7 mmol) was added in portions over 5 minutes. The reaction mixture was stirred at this temperature for 0.5 hours. A solution of ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (5.0 g, 9.8 mmol) in tetrahydrofuran was added dropwise over 5 minutes. The reaction was stirred at 0° C. for 0.5 hours, then warmed to room temperature and stirred for an additional 0.5 hours. The reaction mixture was diluted with water (100 mL) at 0° C. and extracted into dichloromethane (3 times). The combined organic extracts were washed successively with water (three times) and brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a 10-50% ethyl acetate in petroleum ether gradient as the eluent to give ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate. 1H NMR(400MHz,DMSO)δ=10.46(s,1H),7.89-7.75(m,3H),7.46(dd,1H),6.56(d,1H),5.67(s,2H),4.04-3.78(m,4H),1.97(s,3H),0.98-0.80(m,6H)

[0207] Step 2: Synthesis of ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a solution of ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (3.00 g, 5.4 mmol) in a mixture of methanol (25 mL) and acetonitrile (25 mL) was added 10% palladium on carbon (0.50 g), and the reaction mixture was stirred under balloon pressure hydrogen at room temperature for 12 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 5 to 95% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as a bright yellow solid.

[0208] Step 3: Synthesis of 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (200 mg, 0.42 mmol) in a mixture of tetrahydrofuran (1.5 mL) and water (1.5 mL) at room temperature was added sodium hydroxide (0.067 g, 1.68 mmol). The reaction mixture was heated with stirring at 50° C. for 2 hours. The cooled reaction mixture was acidified to pH 4 by the addition of 1 M aqueous hydrogen chloride solution and extracted into dichloromethane (3 times). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to give 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=10.50(s,1H),7.85(d,1H),7.81-7.74(m,2H),7.42(dd, 1H),6.63(d,1H),6.12(s,1H),5.56(s,2H),3.88(d,2H),2.00(s,3H),1.03(t,3H)

[0209] Example 16: Synthesis of 6-[(3-aminopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 156) [ka] To a stirred solution of ethyl 6-[(3-acetamidopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (0.200 g, 0.42 mmol) in a mixture of tetrahydrofuran (1.5 mL) and water (1.5 mL) was added sodium hydroxide (0.067 g, 1.68 mmol). The reaction mixture was heated with stirring at 80 °C for 2 hours. The cooled reaction mixture was acidified to pH 4 by the addition of 1 M aqueous hydrogen chloride solution and extracted into dichloromethane (3 times). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to give 6-[(3-aminopyrazol-1-yl)methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=7.82-7.74(m,2H),7.57(d,1H),7.42(dd,1H),6. 05(s,1H),5.57(d,1H),5.37(s,2H),4.82(s,2H),3.87(d,2H),1.06(t,3H)

[0210] Example 17: Synthesis of 6-[[3-[[(E)-but-2-enoyl]amino]pyrazol-1-yl]methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid (Compound 155) [ka] To a stirred mixture of (E)-but-2-enoic acid (63 mg, 0.74 mmol) in anhydrous N,N-dimethylformamide (5 mL) was added [dimethylamino(triazolo[4,5-b]pyridin-3-yloxy)methylene]-dimethyl-ammonium hexafluorophosphate (HATU, 280 mg, 0.74 mmol), and triethylamine (150 mg, 1.5 mmol). The reaction mixture was stirred at room temperature for 0.5 hours, after which 6-((3-amino-1H-pyrazol-1-yl)methyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid (200 mg, 0.49 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours, after which it was quenched in water and extracted with ethyl acetate (three times). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by preparative HPLC to afford 6-[[3-[[(E)-but-2-enoyl]amino]pyrazol-1-yl]methyl]-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=10.57(d,1H),7.87(s,1H),7.80-7.76(m,2H),7.42(d,1H),6.86- 6.73(m,1H),6.71(s,1H),6.16(d,2H),5.57(s,2H),3.89(d,2H),1.84(d,3H),1.02(t,3H)

[0211] Example 18: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-hydroxypyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid (Compound 167) Step 1: Synthesis of ethyl 6-((3-(benzyloxy)-1H-pyrazol-1-yl)methyl)-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylate [ka] To a solution of 1-[3-(benzyloxy)-1H-pyrazol-1-yl]ethanone (680 mg, 3.90 mmol) in anhydrous tetrahydrofuran (10 mL) was added sodium hydride (230 mg, 10 mmol) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 0.5 hours, followed by the dropwise addition of a solution of ethyl 5-bromo-6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (2.0 g, 3.9 mmol) in anhydrous tetrahydrofuran (10 mL). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was diluted with water (10 mL) and extracted with ethyl acetate (three times). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to give ethyl 6-[(3-benzyloxypyrazol-1-yl)methyl]-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as a white solid.

[0212] Step 2: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-((3-hydroxy-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylate [ka] To a stirred solution of ethyl 6-((3-(benzyloxy)-1H-pyrazol-1-yl)methyl)-5-bromo-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-1,4-dihydropyridine-3-carboxylate (1.0 g, 1.65 mmol) in tetrahydrofuran (10 mL) was added 10% palladium on carbon (1 g). The reaction mixture was stirred under balloon pressure hydrogen at room temperature for 6 hours. The reaction mixture was filtered through diatomaceous earth, and the filtrate was evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 5% methanol in dichloromethane as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-((3-hydroxy-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylate as a white powder.

[0213] Step 3: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-hydroxypyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-((3-hydroxy-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylate (230 mg, 0.527 mmol) in a mixture of tetrahydrofuran (2.5 mL), methanol (2.5 mL), and water (2.5 mL) was added lithium hydroxide (50 mg, 2.09 mmol) in one portion. The reaction mixture was heated with stirring at 50° C. for 18 hours. The cooled reaction mixture was evaporated to dryness under reduced pressure, then diluted with water (5 mL) and acidified to pH 1 by the addition of 2 M aqueous hydrogen chloride solution. The precipitated solid was filtered, washed with water, and then purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 5 to 100% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-6-((3-hydroxy-1H-pyrazol-1-yl)methyl)-4-oxo-1,4-dihydropyridine-3-carboxylic acid as a white powder. 1H NMR(400MHz,DMSO-d6)δ=9.94(s,1H),7.82-7.73(m,2H),7.66(d,1H),7.45- 7.40(m,1H),6.08(d,1H),5.64(d,1H),5.41(s,2H),3.88(q,2H),1.05(t,3H)

[0214] Example 19: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid (Compound 161) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate [ka] To a stirred mixture of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-hydroxypyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate (150 mg, 0.344 mmol) and 1-iodo-2-methoxy-ethane (192 mg, 1.03 mmol) in N,N-dimethylformamide (3 mL) was added potassium carbonate (190 mg, 1.38 mmol). The reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was evaporated to dryness under reduced pressure, and the residue was diluted with water and extracted with ethyl acetate (3 times). The combined organic extracts were evaporated to dryness under reduced pressure and the crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 3% methanol in dichloromethane as eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate as a white solid.

[0215] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate (120 mg, 0.243 mmol) in a mixture of tetrahydrofuran (2 mL) and water (2 mL) was added lithium hydroxide (23 mg, 0.97 mmol) in one portion. The reaction mixture was stirred at room temperature for 24 hours. The tetrahydrofuran was removed under reduced pressure, and the aqueous residue was washed with ethyl acetate (twice). The aqueous phase was acidified to pH 2 by the addition of 1 M aqueous hydrogen chloride solution and then extracted with ethyl acetate (three times). The combined organic extracts were evaporated to dryness under reduced pressure and the crude residue was purified by preparative HPLC to give 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-(2-methoxyethoxy)pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=7.87-7.68(m,3H),7.43(dd,1H),5.95(s,1H),5.88(d,1H),5. 50(s,2H),4.23-4.12(m,2H),3.88(q,2H),3.67-3.54(m,2H),3.29(s,3H),1.08(t,3H)

[0216] Example 20: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[1-[3-(trifluoromethyl)pyrazol-1-yl]ethyl]pyridine-3-carboxylic acid (Compound 172) Step 1: Synthesis of 5-(1-hydroxypropylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione [ka] To a stirred solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (10.0 g, 69.4 mmol) in dichloromethane (100 mL) at 0° C. was added pyridine (11.2 mL, 139 mmol) and propanoyl chloride (6.42 g, 69.4 mmol). The reaction mixture was stirred at 0° C. for 1 hour and then at room temperature for 1 hour. The reaction mixture was poured into ice water, acidified by the addition of 2 M aqueous hydrogen chloride solution, and extracted into dichloromethane (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to give 5-(1-hydroxypropylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione as a yellow solid. 1H NMR (400MHz, chloroform) δ = 15.4 (brs, 1H), 3.11 (q, 2H), 1.74 (s, 6H), 1.26 (t, 3H)

[0217] Step 2: Synthesis of 6-ethyl-2,2-dimethyl-1,3-dioxin-4-one [ka] To a stirred solution of 5-(1-hydroxypropylidene)-2,2-dimethyl-1,3-dioxane-4,6-dione (1.0 g, 5.0 mmol) in toluene (10 mL) at room temperature, acetone (0.145 g, 2.5 mmol) was added. The reaction mixture was heated with stirring at 120 °C for 1 h. The cooled reaction mixture was poured onto ice and extracted with ethyl acetate (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0 to 50% ethyl acetate in hexane as the eluent to give 6-ethyl-2,2-dimethyl-1,3-dioxin-4-one as a colorless liquid. 1H NMR (400MHz, chloroform) δ = 5.22 (s, 1H), 2.25 (q, 2H), 1.68 (s, 6H), 1.13 (t, 3H)

[0218] Step 3: Synthesis of 6-(1-bromoethyl)-2,2-dimethyl-1,3-dioxin-4-one [ka] To a stirred solution of 6-ethyl-2,2-dimethyl-1,3-dioxin-4-one (2.0 g, 11.5 mmol) in dichloromethane (20 mL) was added 1-bromopyrrolidine-2,5-dione (2.26 g, 12.7 mmol) and 2-[(E)-(1-cyano-1-methyl-ethyl)azo]-2-methyl-propanenitrile (0.189 g, 1.15 mmol) at room temperature. The reaction mixture was irradiated in a Penn reactor (λ = 420 nm) with stirring at room temperature for 16 hours. The reaction mixture was diluted with dichloromethane and a saturated aqueous solution of sodium thiosulfate was added. The phases were separated, and the aqueous phase was extracted with dichloromethane (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate in hexanes as eluent to give 6-(1-bromoethyl)-2,2-dimethyl-1,3-dioxin-4-one as a colorless liquid. 1H NMR (400 MHz, chloroform) δ = 5.48 (s, 1H), 4.49 (q, 1H), 1.84 (d, 3H), 1.72 (d, 6H).

[0219] Step 4: Synthesis of ethyl 6-(1-bromoethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] A stirred solution of ethyl (Z)-3-(3,4-dichlorophenyl)-3-(ethylamino)prop-2-enoate (4.0 g, 14 mmol) and 6-(1-bromoethyl)-2,2-dimethyl-1,3-dioxin-4-one (4.9 g, 21 mmol) in xylene (40 mL) was heated with stirring at 120° C. for 0.5 h. The cooled reaction mixture was evaporated to dryness under reduced pressure, and the residue was washed with methyl tert-butyl ether to give ethyl 6-(1-bromoethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate as a bright yellow solid. 1H NMR(400MHz,DMSO-d6)δ=7.94(d,0.5H)7.85(d,0.5H),7.82(d,1H),7.55-7.47(m,1H),6 .90(d,1H),5.61-5.54(m,1H),3.99-3.82(m,4H),2.03(q,3H),1.13(t,3H),0.83(t,3H)

[0220] Step 5: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[1-[3-(trifluoromethyl)pyrazol-1-yl]ethyl]pyridine-3-carboxylate [ka] To a stirred solution of ethyl 6-(1-bromoethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (100 mg, 0.223 mmol) in N,N-dimethylformamide (10 mL) was added 3-(trifluoromethyl)-1H-pyrazole (28 mg, 0.27 mmol) and potassium carbonate (93 mg, 0.67 mmol). The reaction mixture was stirred at room temperature for 6 hours. The reaction mixture was diluted with water (50 mL) and extracted with ethyl acetate (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 10 to 50% ethyl acetate in hexanes as the eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-(1-(3-(trifluoromethyl)-1H-pyrazol-1-yl)ethyl)-1,4-dihydropyridine-3-carboxylate as a white solid.

[0221] Step 6: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[1-[3-(trifluoromethyl)pyrazol-1-yl]ethyl]pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[1-[3-(trifluoromethyl)pyrazol-1-yl]ethyl]pyridine-3-carboxylate (180 mg, 0.358 mmol) in a mixture of tetrahydrofuran (8 mL) and water (2 mL) was added lithium hydroxide hydrate (30 mg, 0.72 mmol) at room temperature. The reaction mixture was heated with stirring at 80° C. for 6 hours. The cooled reaction mixture was acidified by the addition of 2 M aqueous hydrogen chloride solution and extracted into ethyl acetate. The combined organic extracts were evaporated to dryness under reduced pressure, and the crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 0 to 100% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[1-[3-(trifluoromethyl)pyrazol-1-yl]ethyl]pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=8.38(s,1H),7.87-7.75(m,2H),7.52-7.44(m,1H),6.93(s,1H),6. 63(s,0.5H),6.54(s,0.5H),6.18-6.13(m,1H),4.00-3.85(m,2H),1.93(d,3H),1.14(t,3H)

[0222] Example 21: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid (Compound 204) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-formylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 6-(bromomethyl)-2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-pyridine-3-carboxylate (380 mg, 0.83 mmol) in acetonitrile (15 mL) at room temperature was added 1H-pyrazole-3-carbaldehyde (88 mg, 0.92 mmol) and potassium carbonate (230 mg, 1.67 mmol). The reaction mixture was stirred at room temperature for 24 hours. The reaction mixture was diluted with water and extracted with ethyl acetate (twice). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure to give crude ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-formylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate, which was used in the subsequent step without any purification.

[0223] Step 2: Synthesis of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-formylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate (140 mg, 0.312 mmol) in a mixture of methanol (5 mL) and water (1.5 mL) at 0° C. was added sodium acetate (0.038 g, 0.47 mmol) and O-methylhydroxylamine hydrochloride (0.052 g, 0.63 mmol). The reaction mixture was stirred at room temperature for 5 minutes and then heated with stirring at 80° C. for 6 hours. The reaction mixture was quenched by the addition of water and extracted with ethyl acetate (three times). The combined organic extracts were washed successively with water and brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on silica gel using a gradient of 0-50% ethyl acetate in hexanes as the eluent to give ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate as a colorless liquid.

[0224] Step 3: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylate (110 mg, 0.22 mmol) in a mixture of tetrahydrofuran (8 mL) and water (2 mL) was added lithium hydroxide (28 mg, 0.66 mmol) at room temperature. The reaction mixture was heated with stirring at 80° C. for 16 hours. The reaction mixture was diluted with 1 M aqueous hydrogen chloride solution and extracted into ethyl acetate. The combined organic extracts were washed successively with water and brine, dried over anhydrous sodium sulfate, filtered, and evaporated to dryness under reduced pressure. The crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using water as the eluent to give 2-(3,4-dichlorophenyl)-1-ethyl-6-[[3-[(E)-methoxyiminomethyl]pyrazol-1-yl]methyl]-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=8.16(s,1H),8.03(d,1H),7.79(d,1H),7.77(d,1H),7.42(dd, 1H),6.68(d,1H),6.00(s,1H),5.71(s,2H),3.91-3.88(m,2H),3.88(s,3H),1.03(t,3H)

[0225] Example 22: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(2,2,2-trifluoroethoxy)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid (Compound 186) Step 1: Synthesis of ethyl 2-(3,4-dichlorophenyl)-6-[[3-(difluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-1-ethyl-6-[(3-formylpyrazol-1-yl)methyl]-4-oxo-pyridine-3-carboxylate (250 mg, 0.50 mmol) in dichloromethane (15 mL) at −20° C. was added N-ethyl-N-(trifluoro-λ 4 (3,4-Dichlorophenyl)-6-[[3-(difluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate] was added as a bright yellow solid. 1H NMR(400MHz,DMSO-d6)δ=8.09(s,1H),7.84-7.79(m,2H),7.48(d,1H),7.18-6.91(s,1H) ),6.77(s,1H),5.67(s,1H),5.60(s,2H),3.86-3.76(m,4H),0.97(t,3H),0.82(t,3H).

[0226] Step 2: Synthesis of 2-(3,4-dichlorophenyl)-1-ethyl-4-oxo-6-[[3-(2,2,2-trifluoroethoxy)pyrazol-1-yl]methyl]pyridine-3-carboxylic acid [ka] To a stirred solution of ethyl 2-(3,4-dichlorophenyl)-6-[[3-(difluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylate (160 mg, 0.34 mmol) in a mixture of tetrahydrofuran (5 mL) and water (2 mL) was added lithium hydroxide hydrate (29 mg, 0.68 mmol) at room temperature. The reaction mixture was heated with stirring at 80° C. for 16 hours. The cooled reaction mixture was acidified by the addition of 2 M aqueous hydrogen chloride solution and extracted into ethyl acetate. The combined organic extracts were evaporated to dryness under reduced pressure, and the crude residue was purified by flash chromatography on reverse-phase C-18 silica gel using a gradient of 0 to 100% acetonitrile (+0.1% formic acid) in water (+0.1% formic acid) as eluent to give 2-(3,4-dichlorophenyl)-6-[[3-(difluoromethyl)pyrazol-1-yl]methyl]-1-ethyl-4-oxo-pyridine-3-carboxylic acid as a white solid. 1H NMR(400MHz,DMSO-d6)δ=8.12(d,1H),7.79(t,2H),7.43(dd,1H),7.19-6.92( m,1H),6.71(s,1H),5.99(s,1H),5.75(s,2H),3.91-3.86(m,2H),1.03(t,3H)

[0227] Throughout this specification, temperatures are given in degrees Celsius (°C) and "mp" means melting point. LC / MS means liquid chromatography mass spectrometry, and a description of the equipment and methods follows. Method A: Spectra were recorded on a Waters Aquity UPLC-MS mass spectrometer using a Sample Organizer + Sample Manager FTN, H-class QSM, Column Manager, 2x Column Manager Aux, Light Emitting Diode Array, ELSD, and a QDA SQD 2. SQD mass spectrometer - Ionization method: electrospray (ESI), polarity: positive ion, capillary (kV) 3.00, cone (V) 30.00, extractor (V) 2.00, source temperature (°C) 150, desolvation temperature (°C) 350, cone gas flow (L / Hr) 0, desolvation gas flow (L / Hr) 650. The instrument was equipped with a Waters HSS T3 C18 column (column length 50 mm, column inner diameter 2.3 mm, particle size 1.8 microns). Gradient elution: 5 to 100% MeCN in water (0.6 ml / min) over 3.3 min. Both MeCN and water contained 0.05% v / v TFA.

[0228] Method B: Spectra were recorded on a Waters mass spectrometer (QDa single quadrupole) equipped with an electrospray source (polarity: positive and negative, probe temperature: 600 °C, cone: 15 V, source temperature: 120 °C, ESI capillary: 0.8 kV, mass range: anode 130–700 Da, cathode 130–700 Da, data: centroid) and a Waters Acquity UPLC, using a 2777 Sample Manager, an H-class BSM, a Column Manager UBM, a Photodiode Array Detector UPD, and a Corona Veo RS Charged Aerosol Detector. Column: Phenomenex Kinetex 2.6 μm C18 100 Å 50 × 4.6 mm PN00B-4462-E0. Temperature: 40°C, DAD wavelength range: 205–310 nm, solvent gradient: Solvent A: HO + 0.1% formic acid, Solvent B: CHCN + 0.1% formic acid, gradient: 0 min 30% B, 70% A; 1.2 min 90% B, 10% A; 1.7 min 90% B, 10% A; 1.8 min 30% B, 70% A; 2.0 min 30% B, 70% A. Flow rate: 2.0 ml / min. Injection volume: 2 μl. Total run time: 2.0 min.

[0229] [Table 5-1] [Table 5-2] [Table 5-3] [Table 5-4] [Table 5-5] [Table 5-6] [Table 5-7]

Table 5-8

Table 5-9

Table 5-10

Table 5-11

Table 5-12

Table 5-13

Table 5-14

Table 5-15

Table 5-16

Table 5-17

Table 5-18

Table 5-19

Table 5-20

Table 5-21

Table 5-22

Table 5-23

Table 5-24

Table 5-25

Table 5-26

Table 5-27

Table 5-28

Table 5-29

Table 5-30

Table 5-31

Table 5-32

Table 5-33

Table 5-34

Table 5-35

Table 5-36

Table 5-37

Table 5-38

Table 5-39

Table 5-40

Table 5-41

Table 5-42

Table 5-43

Table 5-44

Table 5-45

Table 5-46

Table 5-47

Table 5-48

Table 5-49

Table 5-50

Table 5-51

Table 5-52

Table 5-53

Table 5-54

Table 5-55

Table 5-56

Table 5-57

Table 5-58

Table 5-59

Table 5-60

Table 5-61

Table 5-62

Table 5-63

Table 5-64

Table 5-65

[0230] examples of biology Seeds of various test species (Setaria faberi (SETFA), Echinochloa crus-galli (ECHCG), Zea mays (ZEAMX), Ipomoea hederacea (IPOHE), Amaranthus palmeri (AMAPA), and Amaranthus retoflexus (AMARE)) were sown in standard soil in pots. After 8 days of cultivation in a greenhouse under controlled conditions (24°C / 16°C, day / night; 14 hours of light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from a formulation of technical active ingredients in a 50:50 acetone / water solution containing 0.5% Tween 20 (polyoxyethylene sorbitan monolaurate, CAS RN 9005-64-5). Unless otherwise specified, compounds are applied at 1000 g / ha. Test plants are then grown under controlled conditions in a greenhouse (24°C / 16°C, day / night; 14 hours of light; 65% humidity) and watered twice daily. After 13 days, the tests are evaluated for the percentage of plant damage. Biological activity is shown in the table below on a 5-point scale (5 = 81-100%; 4 = 61-80%; 3 = 41-60%; 2 = 21-40%; 1 = 0-20%; - = not tested).

[0231] [Table 6-1] [Table 6-2] [Table 6-3] [Table 6-4] [Table 6-5] [Table 6-6]

[0232]

Table 7-1

Table 7-2

Table 7-3

Table 7-4

Table 7-5

Table 7-6

Table 7-7

Table 7-8

Table 7-9

Claims

1. Compounds of formula (I): 【Chemistry 1】 (In the formula, R 1 is C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy, C 2 ~C 6 Alkenyl, C 2 ~C 6 Alkynyl or C 1 ~C 6 Alkoxy C 1 ~C 6 is alkyl; R 2 is phenyl or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and each phenyl and heteroaryl moiety is R 7 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 3 is hydrogen or C 1 ~C 6 is alkyl; R 4 is hydrogen, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 haloalkyl or phenyl, and each of said phenyl moieties is R 8 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 5 is heteroaryl, said heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 1, 2 or 3 nitrogen atoms, said heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in said heteroaryl ring, each heteroaryl moiety being 9 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 6 is hydrogen, C 1 ~C 3 Alkyl or C 1 ~C 6 is alkoxy; R 7 is cyano, nitro, amino, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Haloalkoxy, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkyl, C 1 ~C 6 Alkylsulfanyl, C 1 ~C 6 Alkylsulfinyl, C 1 ~C 6 Alkylsulfonyl, C 1 ~C 6 Alkyl sulfonamides, C 1 ~C 6 Alkylcarbonyl, C 1 ~C 6 Alkoxycarbonyl, C 1 ~C 6 Alkylaminocarbonyl, C 3 ~C 6 Cycloalkyl, C 3 ~C 6 Cycloalkylaminocarbonyl, or N,N-di(C 1 ~C 4 alkyl)aminocarbonyl; R 8 is halogen, C 1 ~C 3 Alkyl or C 1 ~C 3 is alkoxy; R 9 is formyl, acetyl, cyano, amino, nitro, hydroxy, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Haloalkoxy, C 2 ~C 6 Alkenyloxy, Cyano C 1 ~C 6 Alkyl, Cyano C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxycarbonyl C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxycarbonyl, C 1 ~C 6 Alkylsulfanyl, C 1 ~C 6 Alkylsulfinyl, C 1 ~C 6 Alkylsulfonyl, C 1 ~C 6 Alkyl sulfonamide, hydroxycarbonyl, C 1 ~C 6 Alkylcarbonyl, C 1 ~C 6 Alkylaminocarbonyl, C 1 ~C 6 Alkylcarbonylamino, C 1 ~C 6 Alkylamino, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkylaminocarbonyl, C 1 ~C 6 Alkoxyimino C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkylcarbonylamino, C 2 ~C 6 Alkenylcarbonylamino, C 3 ~C 6 Cycloalkyl, C 3 ~C 6 Cycloalkylaminocarbonyl, N,N-di(C 1 ~C 4 alkyl)amino, N,N-di(C 1 ~C 4 alkyl)aminocarbonyl, phenyl, benzyloxy or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2 or 3 heteroatoms independently selected from N, O and S, and the phenyl and heteroaryl moieties being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atom to which they are attached, are C 3 ~C 6 A cycloalkyl ring or a phenyl ring may be formed, 3 ~C 6 The cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heteroaryl ring, said heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, 3, or 4 heteroatoms individually selected from N, O, and S, and said heteroaryl moiety being R 10 or optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heterocyclyl ring, said heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and said heterocyclyl ring being selected from R 10 and optionally substituted with 1, 2, 3 or 4 groups, which may be the same or different, represented by R 10 is halogen, nitro, C 1 ~C 3 Alkyl or C 1 ~C 3 Alkoxy) Or a salt or N-oxide thereof.

2. R 2 is phenyl or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms individually selected from N and O, and each phenyl and heteroaryl moiety is selected from R 7 2. The compound of claim 1, optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

3. R 2 is R 7 3. The compound according to claim 1 or claim 2, which is phenyl optionally substituted with one or two groups which may be the same or different and are represented by:

4. R 3 is hydrogen or C 1 ~C 4 The compound according to any one of claims 1 to 3, which is alkyl.

5. R 4 is hydrogen, halogen, C 1 ~C 3 alkyl or phenyl, and the phenyl moiety is a single R 8 The compound according to any one of claims 1 to 4, optionally substituted with a group.

6. R 5 is heteroaryl, said heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 1, 2 or 3 nitrogen atoms, and said heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in said heteroaryl ring, and each heteroaryl moiety is selected from the group consisting of R 9 The compound according to any one of claims 1 to 5, optionally substituted with 1, 2 or 3 groups which may be the same or different and are represented by

7. R 5 is heteroaryl, said heteroaryl moiety being a 5-membered aromatic monocyclic ring containing 2 or 3 nitrogen atoms, said heteroaryl moiety being attached to the remainder of the molecule through a nitrogen atom in said heteroaryl ring, each heteroaryl moiety being 9 The compound according to any one of claims 1 to 6, optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

8. R 9 is formyl, acetyl, cyano, amino, nitro, hydroxy, halogen, C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy, C 1 ~C 6 Haloalkyl, C 1 ~C 6 Haloalkoxy, C 2 ~C 6 Alkenyloxy, Cyano C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkoxy, C 1 ~C 6 Alkoxycarbonyl, C 1 ~C 6 Alkylsulfanyl, C 1 ~C 6 Alkyl sulfonyl, hydroxycarbonyl, C 1 ~C 6 Alkylcarbonyl, C 1 ~C 6 Alkylcarbonylamino, C 1 ~C 6 Alkoxyimino C 1 ~C 6 Alkyl, C 1 ~C 6 Alkoxy C 1 ~C 6 Alkylcarbonylamino, C 2 ~C 6 Alkenylcarbonylamino, C 3 ~C 6 cycloalkyl, phenyl, or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and the phenyl and heteroaryl moieties being R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atom to which they are attached, are C 3 ~C 6 A cycloalkyl ring or a phenyl ring may be formed, 3 ~C 6 The cycloalkyl and phenyl moieties are R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heteroaryl ring, said heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1, 2, or 3 heteroatoms individually selected from N, O, and S, and said heteroaryl moiety being R 10 or optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heterocyclyl ring, said heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and said heterocyclyl ring being selected from R 10 The compound according to any one of claims 1 to 7, optionally substituted with 1, 2 or 3 groups, which may be the same or different, represented by

9. R 9 is acetyl, cyano, nitro, hydroxy, halogen, C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy, C 1 ~C 4 Haloalkyl, C 1 ~C 4 Haloalkoxy, C 2 ~C 4 Alkenyloxy, Cyano C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy C 1 ~C 4 Alkoxy, C 1 ~C 4 Alkoxycarbonyl, C 1 ~C 4 Alkylsulfanyl, C 1 ~C 4 Alkylsulfonyl, C 1 ~C 4 Alkylcarbonyl, C 1 ~C 4 Alkylcarbonylamino, C 1 ~C 4 Alkoxyimino C 1 ~C 4 Alkyl, C 1 ~C 4 Alkoxy C 1 ~C 4 Alkylcarbonylamino, C 2 ~C 4 Alkenylcarbonylamino, C 3 ~C 4 cycloalkyl, phenyl, or heteroaryl, the heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms independently selected from N, O, and S, and the phenyl and heteroaryl moieties being R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 The groups, together with the carbon atom to which they are attached, are C 5 ~C 6 A cycloalkyl ring or a phenyl ring may be formed, 5 ~C 6 The cycloalkyl and phenyl moieties are R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heteroaryl ring, said heteroaryl moiety being a 5- or 6-membered aromatic ring containing 1 or 2 heteroatoms individually selected from N, O and S, and said heteroaryl moiety being R 10 or optionally substituted with one or two groups, which may be the same or different, represented by Any two adjacent R 9 Groups, together with the carbon atom to which they are attached, can form a 5- or 6-membered heterocyclyl ring, said heterocyclyl moiety being 5- or 6-membered containing 1 or 2 heteroatoms selected from O and N, and said heterocyclyl ring being selected from R 10 The compound according to any one of claims 1 to 7, optionally substituted with one or two groups, which may be the same or different, represented by

10. R 10 The compound according to any one of claims 1 to 9, wherein is a halogen.

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

12. 12. The herbicidal composition of claim 11 further comprising at least one additional pesticide.

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

14. A method for controlling the growth of unwanted plants, comprising the step of applying a compound of formula (I) as defined in any one of claims 1 to 10 or a herbicidal composition as defined in any one of claims 11 to 13 to said unwanted plants or their habitat.

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

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