2-{[2-(phenoxymethyl)pyridin-5-yl]oxy}ethylamine derivatives and related compounds as, for example, pesticides for protecting plants

Abstract

The present invention relates to compounds of formula (I), in which Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 7 , R 8 and R 9 have the meanings given above, and relates to processes for their preparation and to intermediates for use in their preparation and to their use for controlling animal pests, especially insects.

Description

[0001] The present invention relates to novel heterocyclic compounds, processes for their preparation and intermediates for use in their preparation, and to their use for controlling animal pests, in particular insects.

[0002] Heterocyclic derivatives having fungicidal properties have been described in the literature (for example WO2014 / 179144).

[0003] Heterocyclic derivatives having pharmaceutical properties have been described in the literature (for example WO2005 / 082089, WO2008073929, WO2009 / 145360).

[0004] Modern pesticides must meet many requirements, such as with regard to their efficacy, persistence and spectrum of action and possible uses. Toxicity problems and problems with combination with other active compounds or formulation auxiliaries play a role, as do the costs and complexity involved in synthesizing active compounds. In addition, resistance can occur. For all these reasons alone, the research on new pesticides cannot be considered complete, but there is a continuing need for new compounds which have improved properties at least in some respects compared to known compounds.

[0005] An object of the present invention is to provide compounds which broaden the spectrum of pesticides in several respects.

[0006] This object and other objects which are not explicitly stated but which can be recognized or inferred from the context discussed herein are achieved by the novel compounds of the formula (I) and salts, metal complexes, N-oxides and tautomeric forms of the compounds of the formula (I)

[0007]

[0008] wherein (configuration 1)

[0009] Z represents an optionally substituted naphthyl, dibenzo[b,d]furanyl, dibenzo[b,d]thiophenyl, carbazolyl, indanyl, benzothiophenyl, benzofuranyl, indolyl, fluorenyl, phenanthryl, anthryl or a phenyl of the substructural formula (II)

[0010]

[0011] and the substituted phenyl of the substructural formula (II) may optionally bear two further substituents selected from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C3-C6)-cycloalkyl and (C3-C6)-halocycloalkyl,

[0012] Y represents O, S, -CH2, -NR5 ,

[0013] A 1 represents N or -CR 1 ,

[0014] A 2 represents N or -CR 2 ,

[0015] A 3 represents N or -CR 3 ,

[0016] A 4 represents N or -CR 4 ,

[0017] wherein at least one and at most two of the atoms A1, A2, A3, and A4 in the aromatic ring represent N,

[0018] X represents oxygen, a sulfide group, a sulfinyl group, a sulfonyl group, -CH2, a carbonyl group, -CHOH, or -NR 6 ,

[0019] R 1 、R 2 、R 3 and R 4Each independently of one another represents hydrogen, halogen, nitro, cyano, aminocarbonyl, aminosulfonyl, in each case optionally substituted (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, N-mono-(C1-C4)-alkylamino, N-mono-(C3-C6)-cycloalkylamino, N,N-di-(C1-C4)-alkylamino, N,N-di-(C3-C6)-cycloalkylamino, N,N-(C3-C6)-cycloalkyl-(C1-C4)-alkylamino, N-(C1-C4)-alkanoylamino, N-(C3-C6)-cycloalkanoylamino, N-(C1-C4)-alkanoyl-N-(C1-C4)-alkylamino, N-(C3-C6)-cycloalkanoyl-N-(C1-C4)-alkylamino, N-(C3-C6)-cycloalkanoyl-N-(C3-C6)-cycloalkylamino, N-(C1-C4)-alkanoyl-N-(C3-C6)-cycloalkylamino, (C1-C4)-alkoxycarbonyl, (C3-C6)-cycloalkoxycarbonyl, (C1-C4)-alkanoyl, (C3-C6)-cycloalkanoyl, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, N-(C1-C4)-alkylaminocarbonyl, N-(C3-C6)-cycloalkylaminocarbonyl, N,N-di-(C1-C4)-alkylaminocarbonyl, N,N-di-(C3-C6)-cycloalkylaminocarbonyl, N,N-(C3-C6)-cycloalkyl-(C1-C4)-alkylaminocarbonyl, -CH=N-O-[(C1-C4)-alkyl], -CH=N-O-[(C3-C6)-cycloalkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl], -C[(C3-C6)-cycloalkyl]=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C3-C6)-cycloalkyl], -C[(C3-C6)-cycloalkyl]=N-O-[(C3-C6)-cycloalkyl],

[0020] R 5 represents hydrogen or optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C3)-alkanoyl,

[0021] R 6 represents hydrogen or optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkanoyl or together with R 8A closed ring formed by 1 to 3 CH2 groups

[0022] R 7 represents hydrogen or an optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl or, together with R 8 a closed ring formed by 1 to 3 CH2 groups

[0023] R 8 represents hydrogen or represents an optionally substituted (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C3-C6)-cycloalkyl or, together with R 6 and R 7 is enclosed in a ring formed by 1 to 3 CH2 groups or, together with R 9 is enclosed in a 4- to 6-membered heterocyclic ring which, in the case of a 5- or 6-membered heterocyclic ring, may contain further heteroatoms and which is optionally mono- or polysubstituted by identical or different groups selected from: halogen substituents, cyano or (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy each optionally mono- or polysubstituted by identical or different halogen substituents

[0024] In the case where R 7 represents hydrogen or an optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl or in the case where R 7 together with R 8 forms a 5- or 6-membered ring, R 9 represents in each case an optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylcarbonyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkoxycarbonyl, or

[0025] In the case where R 7 together with R 8 forms a 4-membered ring, R 9represents, in each case optionally substituted, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, or

[0026] R 8 and R 9 represents a 4- to 6-membered heterocyclic closed ring which, in the case of a 5- or 6-membered heterocycle, may contain further heteroatoms and which is optionally mono- or polysubstituted by the same or different groups selected from halogen substituents, cyano or (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, each optionally mono- or polysubstituted by the same or different halogen substituents,

[0027] R 10represents halogen, nitro, cyano, -SF5, or represents phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, (C1-C4)-alkyl, (C1-C4)-alkenyl, (C1-C4)-alkynyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl], which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano, nitro, -SF5, (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C1-C4)-haloalkyl, (C2-C4)-haloalkenyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C2-C4)-alkenyloxy, (C2-C4)-haloalkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C3-C6)-halocycloalkoxy, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-haloalkylsulfonyl, (C1-C4)-haloalkylthio, (C1-C4)-haloalkylsulfinyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, C6-aryl, C 10 -aryl, C 14 -aryl, C6-aryloxy, C 10 -aryloxy, C 14 -aryloxy, benzyl, benzyloxy, benzylthio, C6-arylthio, C 10 -arylthio, C 14 -arylthio, C6-arylamino, C 10 -arylamino, C 14 -arylamino, benzylamino, heterocyclic group and trialkylsilyl,

[0028] R 11represents hydrogen, halogen, cyano or nitro, or represents in each case optionally substituted (C1-C4)-alkyl, (C3-C5)-cycloalkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl],

[0029] and

[0030] with the proviso that the compound 1-[4-(6-{2-[3-(chloromethyl)phenyl]ethyl}pyridin-3-yl)piperazin-1-yl]ethanone is excluded.

[0031] The excluded compound is specifically disclosed in WO2009145360 as an intermediate for the preparation of pharmaceutically active compounds.

[0032] The compounds of the invention are broadly defined by formula (I). The preferred substituents or ranges of the groups given in the formula mentioned in the context are explained below:

[0033] Configuration 2:

[0034] Z preferably represents optionally substituted naphthyl, dibenzo[b,d]furanyl, dibenzo[b,d]thiophenyl, indan-4-yl, benzothiophen-4-yl, benzofuran-4-yl, indol-4-yl or a substituted phenyl of substructure (II), wherein the phenyl of substructure (II) preferably bears no other substituents except R 10 and R 11 thereafter.

[0035] Y preferably represents O, S, -NR 5 ,

[0036] R 1 、R 2 、R 3 and R 4Preferably, each independently represents a substituent selected from hydrogen, halogen, nitro, cyano, or represents (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkoxycarbonyl, (C3-C6)-cycloalkoxycarbonyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, each of which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl,

[0037] R 5 Preferably represents hydrogen, or represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C3)-alkanoyl, which is optionally mono- or polysubstituted by the same or different halogen substituents,

[0038] R 6 Preferably represents hydrogen, or represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C4)-alkanoyl, which is optionally mono- or polysubstituted by the same or different halogen substituents, or together with R 8 forms a closed ring through 1 to 3 CH2 groups,

[0039] R 7 Preferably represents hydrogen, or represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, which is optionally mono- or polysubstituted by the same or different halogen substituents, or together with R 8 forms a closed ring through 1 to 3 CH2 groups,

[0040] R 8 Preferably represents hydrogen, or represents (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C3-C4)-cycloalkyl, which is optionally mono- or polysubstituted by the same or different substituents selected from halogen, nitro, and cyano, or together with R 6 or R 7 forms a closed ring through 1 to 3 CH2 groups together, or together with R 9A 4- to 6-membered heterocyclic closed ring formed together, which in the case of a 5- or 6-membered heterocyclic ring may contain other heteroatoms selected from N and O and which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, (C1-C4)-alkyl, and (C1-C4)-haloalkyl,

[0041] In R 7 represents hydrogen or (C1-C4)-alkyl, (C3-C4)-cycloalkyl, which is optionally mono- or polysubstituted by the same or different halogen substituents, or in the case where R 7 together with R 8 forms a 5- or 6-membered ring, R 9 preferably represents (C1-C4)-alkyl, (C2-C4)-alkenyl, (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylcarbonyl, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkoxycarbonyl, each of which is optionally mono- or polysubstituted by the same or different substituents selected from halogen, cyano, nitro, or (C3-C6)-cycloalkyl, or

[0042] In R 7 together with R 8 forms a 4-membered ring, R 9 preferably represents (C1-C4)-alkyl, (C2-C4)-alkenyl, (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C3-C4)-cycloalkoxy, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, each of which is optionally mono- or polysubstituted by the same or different substituents selected from halogen, cyano, nitro, or (C3-C6)-cycloalkyl, or

[0043] R 8 and R 9 preferably represent a 4- to 6-membered heterocyclic closed ring, which in the case of a 5- or 6-membered heterocyclic ring may contain other heteroatoms selected from N, O and which may be optionally mono- or polysubstituted by the same or different substituents selected from halogen, (C1-C4)-alkyl, and (C1-C4)-haloalkyl,

[0044] R 10Preferably represents halogen, or represents phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, (C1-C4)-alkyl, (C1-C4)-alkenyl, (C1-C4)-alkynyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl], which is optionally mono- or polysubstituted by the same or different substituents selected from: halogen, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl,

[0045] R 11 Preferably represents hydrogen, halogen, cyano or nitro, or represents (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C5)-cycloalkyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl], which is optionally mono- or polysubstituted by the same or different substituents selected from: halogen, cyano, nitro, (C1-C4)-alkoxy and (C3-C6)-cycloalkyl.

[0046] Substituents not mentioned in Configuration 2 are defined as in Configuration 1.

[0047] Configuration 3:

[0048] Z particularly preferably represents naphthyl, dibenzo[b,d]furanyl, dibenzo[b,d]thiophenyl, which is optionally mono- or polysubstituted by the same or different substituents selected from: halogen, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-haloalkylthio, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, (C1-C4)-alkylcarbonyl, (C1-C4)-haloalkylcarbonyl, or represents a substituted phenyl of substructure (II),

[0049] At least one of the atoms A3 or A4 in the aromatic ring particularly preferably represents nitrogen.

[0050] R 1 、R 2 、R 3 and R 4 each independently of one another particularly preferably represent substituents selected from the following: hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C2-C4)-alkenyl, (C2-C4)-haloalkenyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl and (C1-C4)-alkylsulfonyl.

[0051] R 6 particularly preferably represents hydrogen, (C1-C4)-alkyl or a closed ring formed with R 8 via 1 to 3 CH2 groups.

[0052] R 7 particularly preferably represents hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl or a closed ring formed with R 8 via 1 to 3 CH2 groups.

[0053] R 8 particularly preferably represents hydrogen, or represents (C1-C4)-alkyl, (C2-C4)-alkenyl, (C2-C4)-alkynyl, (C3-C4)-cycloalkyl, which is optionally mono- or polysubstituted by the same or different substituents selected from halogen, or a closed ring formed with R 6 or R 7 together via 1 to 3 CH2 groups, or a 4- to 6-membered heterocyclic closed ring formed with R 9 together via 3 to 5 CH2 groups, and the heterocyclic closed ring is optionally mono- or polysubstituted by the same or different substituents selected from halogen, (C1-C4)-alkyl and (C1-C4)-haloalkyl.

[0054] In the case where R 7 represents hydrogen or represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl or in the case where R 7 forms a 5- or 6-membered ring together with R 8 , R 9 particularly preferably represents (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C6)-alkoxy, (C1-C6)-alkylcarbonyl, each of which is optionally mono- or polysubstituted by the same or different substituents selected from halogen, cyano, nitro or (C3-C6)-cycloalkyl, or

[0055] In R 7 and R 8 together form a four-membered ring, R 9 particularly preferably represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, each of which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano, nitro or (C3-C6)-cycloalkyl, or

[0056] R 8 and R 9 particularly preferably represents a 4- to 6-membered heterocyclic closed ring formed by 3 to 5 CH2 groups and which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, (C1-C4)-alkyl and (C1-C4)-haloalkyl,

[0057] R 10 particularly preferably represents halogen or represents phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano, nitro, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C3-C6)-cycloalkyl, (C3-C6)-halocycloalkyl, or represents (C1-C4)-alkyl, (C1-C4)-alkenyl, (C1-C4)-alkynyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C2-C4)-alkenyloxy, (C2-C4)-alkynyloxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C6)-cycloalkylthio, (C3-C6)-cycloalkylsulfinyl, (C3-C6)-cycloalkylsulfonyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl, which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano, nitro,

[0058] R 11 particularly preferably represents hydrogen, halogen, cyano or nitro, or represents (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-alkylthio, (C1-C4)-alkylsulfinyl, (C1-C4)-alkylsulfonyl, (C3-C5)-cycloalkyl, which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen, cyano and (C3-C6)-cycloalkyl.

[0059] Substituents not mentioned in Configuration 3 are as defined in Configuration 1 or Configuration 2.

[0060] Configuration 4:

[0061] Z very particularly preferably represents naphthyl, dibenzo[b,d]furanyl, dibenzo[b,d]thienyl, which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, (C1-C4)-alkylthio, (C1-C4)-haloalkylthio, (C3-C6)-cycloalkyl, or represents a substituted phenyl of the subformula (II),

[0062] Y very particularly preferably represents oxygen,

[0063] X very particularly preferably represents oxygen or -NR 6 .

[0064] Substituents not mentioned in Configuration 4 are as defined in Configuration 1, Configuration 2 or Configuration 3.

[0065] Configuration 5:

[0066] Z particularly preferably represents naphthyl, which is optionally mono- or polysubstituted by identical or different substituents selected from the group consisting of halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, or represents unsubstituted dibenzo[b,d]furanyl or dibenzo[b,d]thienyl or represents a substituted phenyl of the subformula (II),

[0067] R 1 , R 2 , R 3 and R 4 Particularly preferably represents a substituent selected from the group consisting of hydrogen, halogen, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy and (C1-C4)-alkylthio,

[0068] R 6 Particularly preferably represents hydrogen, (C1-C3)-alkyl or 8 The closed ring is formed by 1 to 2 CH2 groups.

[0069] R 7 Particularly preferably represents hydrogen or 8 Through the closed ring formed by 1 to 3 CH2 groups,

[0070] R 8Particularly preferably represents hydrogen, or represents a (C1-C4)-alkyl group which is optionally mono- or polysubstituted by identical or different halogen substituents, or forms a closed ring together with R 6 via 1 or 2 CH2 groups or forms a closed ring together with R 7 via 1 to 3 CH2 groups or forms a closed ring together with R 9 via 3 to 5 CH2 groups to form a 4- to 6-membered heterocyclic closed ring, and the heterocyclic closed ring is optionally mono- or polysubstituted by identical or different substituents selected from the following: halogen, (C1-C4)-alkyl, and (C1-C4)-haloalkyl,

[0071] R 9 Particularly preferably represents a (C1-C6)-alkyl group, a (C3-C6)-cycloalkyl group, or a (C1-C6)-alkoxy group, each of which is optionally mono- or polysubstituted by identical or different substituents selected from the following: halogen, cyano, and (C3-C6)-cycloalkyl, or

[0072] R 8 and R 9 Particularly preferably represents a 4- to 6-membered heterocyclic closed ring formed via 3 to 5 CH2 groups and is optionally mono- or polysubstituted by identical or different substituents selected from the following: halogen, (C1-C4)-alkyl, and (C1-C4)-haloalkyl,

[0073] R 10 Particularly preferably represents halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy, or represents a phenyl group which is optionally mono- or polysubstituted by identical or different substituents selected from the following: halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy, and (C1-C4)-haloalkoxy,

[0074] R 11 Particularly preferably represents hydrogen, halogen, nitro, or cyano, or represents a (C1-C4)-alkyl group, a (C3-C5)-cycloalkyl group, or a (C1-C4)-alkoxy group which is optionally mono- or polysubstituted by identical or different halogen substituents.

[0075] Substituents not mentioned in configuration 5 are defined as in configuration 1, configuration 2, configuration 3, or configuration 4.

[0076] Configuration 6:

[0077] Z preferably represents a naphthyl group of substructural formula (III):

[0078]

[0079] either represents an unsubstituted dibenzo[b,d]furanyl or dibenzo[b,d]thiophenyl group or a substituted phenyl group represented by substructural formula (II).

[0080] R 1 primarily represents hydrogen, halogen, (C1-C4)-alkyl or (C1-C4)-alkoxy,

[0081] R 2 primarily represents hydrogen, halogen or (C1-C4)-haloalkyl,

[0082] R 3 primarily represents hydrogen, halogen, (C1-C4)-alkoxy or (C1-C4)-alkylthio,

[0083] R 4 primarily represents hydrogen or halogen,

[0084] R 6 primarily represents hydrogen, or a piperazine closed ring formed with R 8 formed,

[0085] R 7 primarily represents hydrogen, or a pyrrolidine closed ring formed with R 8 formed,

[0086] R 8 primarily represents hydrogen, (C1-C4)-alkyl or a piperazine closed ring formed with R 6 or a pyrrolidine closed ring formed with R 7 or a piperidine closed ring formed with R 9 formed,

[0087] R 9 primarily represents (C1-C4)-alkyl or (C1-C4)-alkoxy, each of which is optionally mono- or polysubstituted by the same or different substituents selected from the following: halogen and cyano, or

[0088] R 8 and R 9 primarily represents a piperidine closed ring,

[0089] R 10 primarily represents halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy or a phenyl group represented by substructural formula (IV):

[0090]

[0091] R 11 primarily represents hydrogen or halogen or represents (C1-C4)-alkyl or (C1-C4)-alkoxy, which is optionally mono- or polysubstituted by the same or different halogen substituents,

[0092] R 12 , R 13 and R 14 The key points each independently represent hydrogen or halogen,

[0093] R 15 The key represents hydrogen, halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy or (C1-C4)-haloalkoxy.

[0094] Substituents not mentioned in Configuration 6 are as defined in Configuration 1, Configuration 2, Configuration 3, Configuration 4 or Configuration 5.

[0095] In a preferred embodiment, the present invention relates to compounds of formula (I)

[0096] wherein Z has the meaning given in configuration (1), and

[0097] Among them, Y, A 1 , A 2 , A 3 , A 4 ,X,R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 has the meanings given above, in particular the meanings given in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0098] In another preferred embodiment, the present invention relates to compounds of formula (I)

[0099] wherein Z has the meaning given in configuration (2), and

[0100] Among them, Y, A 1 , A 2 , A 3 , A 4 ,X,R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11Having the above meanings, particularly those described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0101] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0102] wherein Z has the meaning described in configuration (3), and

[0103] wherein Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, particularly those described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0104] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0105] wherein Z has the meaning described in configuration (4), and

[0106] wherein Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, particularly those described in configuration (1) or configuration (2) or configuration (3) or configuration (5) or configuration (6).

[0107] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0108] wherein Z has the meaning described in configuration (5), and

[0109] wherein Y, A 1 、A 2 、A3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 have the meanings described above, especially the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0110] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0111] wherein Z has the meaning described in configuration (6), and

[0112] wherein Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 have the meanings described above, especially the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0113] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0114] wherein Y has the meaning described in configuration (1), and

[0115] wherein Z, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11Having the above meanings, especially the meanings described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0116] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0117] wherein Y has the meaning described in configuration (2), and

[0118] wherein Z, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0119] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0120] wherein Y has the meaning described in configuration (4), and

[0121] wherein Z, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (5) or configuration (6).

[0122] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0123] wherein A 3 and A 4 have the meaning described in configuration (1), and

[0124] wherein Z, Y, A1 、A 2 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the meanings described above, especially those described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0125] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0126] wherein A 3 and A 4 have the meanings described in configuration (3), and

[0127] wherein Z, Y, A 1 、A 2 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the meanings described above, especially those described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0128] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0129] wherein R 1 、R 2 、R 3 and R 4 have the meanings described in configuration (1), and

[0130] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11Has the above meanings, especially the meanings described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0131] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0132] wherein R 1 、R 2 、R 3 and R 4 have the meanings described in configuration (2), and

[0133] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0134] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0135] wherein R 1 、R 2 、R 3 and R 4 have the meanings described in configuration (3), and

[0136] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially the meanings described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0137] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0138] wherein R 1 、R 2 、R 3 and R 4 have the meanings described in configuration (5), and

[0139] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0140] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0141] wherein R 1 , R 2 , R 3 and R 4 have the meanings described in configuration (6), and

[0142] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0143] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0144] wherein X has the meaning described in configuration (1), and

[0145] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and R 11Having the above meanings, especially those described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0146] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0147] wherein X has the meaning described in configuration (3), and

[0148] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially those described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0149] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0150] wherein R 6 has the meaning described in configuration (1), and

[0151] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X、R 1 、R 2 、R 3 、R 4 、R 5 、R 7 、R 8 、R 9 、R 10 and R 11 have the above meanings, especially those described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0152] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0153] wherein R 6 has the meaning described in configuration (2), and

[0154] wherein Z, Y, A 1 、A2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 7 、R 8 、R 9 、R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0155] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0156] wherein R 6 has the meaning described in configuration (3), and

[0157] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 7 、R 8 、R 9 、R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0158] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0159] wherein R 6 has the meaning described in configuration (6), and

[0160] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 7 、R 8 、R 9 、R 10 and R 11Has the above meanings, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0161] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0162] wherein R 7 has the meaning described in configuration (1), and

[0163] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 and R 11 has the above meanings, in particular the meanings described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0164] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0165] wherein R 7 has the meaning described in configuration (2), and

[0166] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 8 , R 9 , R 10 and R 11 has the above meanings, in particular the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0167] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0168] wherein R 7 has the meaning described in configuration (3), and

[0169] wherein Z, Y, A 1 , A2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 8 、R 9 、R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0170] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0171] wherein R 7 has the meaning described in configuration (5), and

[0172] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 8 、R 9 、R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0173] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0174] wherein R 7 has the meaning described in configuration (6), and

[0175] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 8 、R 9 、R 10 and R 11Having the above meanings, especially those described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0176] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0177] wherein R 8 has the meaning described in configuration (1), and

[0178] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 and R 11 have the above meanings, especially those described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0179] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0180] wherein R 8 has the meaning described in configuration (2), and

[0181] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 9 、R 10 and R 11 have the above meanings, especially those described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0182] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0183] wherein R 8 has the meaning described in configuration (3), and

[0184] wherein Z, Y, A 1 、A2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0185] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0186] wherein R 8 has the meaning described in configuration (5), and

[0187] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 and R 11 have the meanings described above, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0188] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0189] wherein R 8 has the meaning described in configuration (6), and

[0190] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 9 , R 10 and R 11Has the above meanings, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0191] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0192] Wherein R 9 Has the meaning described in configuration (1), and

[0193] Wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 And R 11 Has the above meanings, in particular the meanings described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0194] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0195] Wherein R 9 Has the meaning described in configuration (2), and

[0196] Wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 And R 11 Has the above meanings, in particular the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0197] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0198] Wherein R 9 Has the meaning described in configuration (3), and

[0199] Wherein Z, Y, A 1 、A2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 and R 11 have the meanings as defined above, particularly the meanings as defined in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0200] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0201] wherein R 9 has the meaning as defined in configuration (5), and

[0202] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 and R 11 have the meanings as defined above, particularly the meanings as defined in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0203] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0204] wherein R 9 has the meaning as defined in configuration (6), and

[0205] wherein Z, Y, A 1 、A 2 、A 3 、A 4 、X, R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、R 7 、R 8 、R 10 and R 11Having the above meanings, in particular the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0206] In a preferred embodiment, the present invention relates to a compound of formula (I)

[0207] wherein R 10 and R 11 have the meanings described in configuration (1), and

[0208] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 have the above meanings, in particular the meanings described in configuration (2) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0209] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0210] wherein R 10 and R 11 have the meanings described in configuration (2), and

[0211] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 have the above meanings, in particular the meanings described in configuration (1) or configuration (3) or configuration (4) or configuration (5) or configuration (6).

[0212] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0213] wherein R 10 and R 11 have the meanings described in configuration (3), and

[0214] wherein Z, Y, A1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 have the above meanings, particularly the meanings described in configuration (1) or configuration (2) or configuration (4) or configuration (5) or configuration (6).

[0215] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0216] wherein R 10 and R 11 have the meanings described in configuration (5), and

[0217] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9 have the above meanings, particularly the meanings described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (6).

[0218] In another preferred embodiment, the present invention relates to a compound of formula (I)

[0219] wherein R 10 and R 11 have the meanings described in configuration (6), and

[0220] wherein Z, Y, A 1 , A 2 , A 3 , A 4 , X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 and R 9Has the above meaning, especially the meaning described in configuration (1) or configuration (2) or configuration (3) or configuration (4) or configuration (5).

[0221] Definition

[0222] Those skilled in the art should be aware that, unless otherwise specified, the expression "a" ("a" or "an") used in this application may, depending on the context, mean "one (1)", "one (1) or more", or "at least one (1)".

[0223] It will be apparent to those skilled in the art that the examples given in this application are not considered restrictive but merely describe some embodiments in more detail.

[0224] For all structures described herein, such as ring systems and groups, adjacent atoms must not be -O-O- or -O-S-.

[0225] Structures with a variable number of possible carbon atoms (C atoms) may be referred to as C 碳原子的下限 -C 碳原子的上限 structure (C LL -C UL structure) in order to make more specific provisions thereby. Example: An alkyl group may consist of 3 to 10 carbon atoms and in this case corresponds to C3-C 10 -alkyl. A ring structure composed of carbon atoms and heteroatoms may be referred to as an "LL- to UL-membered" structure. An example of a 6-membered ring structure is toluene (a 6-membered ring structure substituted with a methyl group).

[0226] If a collective term for substituents (e.g., C LL -C UL -alkyl) is located at the end of a complex substituent (e.g., C LL -C UL -cycloalkyl-C LL -C UL -alkyl), the component (e.g., C LL -C UL -cycloalkyl) located at the beginning of the complex substituent may be independently and identically or differently mono- or polysubstituted by the subsequent substituent (C LL -C UL -alkyl). For all collective terms used in this application for chemical groups, cyclic systems, and cyclic groups, more specific provisions can be made by adding the words "C LL -C UL " or "LL- to UL-membered". Unless otherwise defined, the definition of the collective term also applies to these collective terms in complex substituents. Example: C LL -C UL-The definition of -alkyl also applies to C as part of a compound substituent (e.g., C LL -C UL -cycloalkyl-C LL -C UL -alkyl). LL -C UL -alkyl.

[0227] In the definitions of the symbols given in the above formulas, collective terms are used that generally represent the following substituents:

[0228] Halogen refers to the elements of Group 7, preferably fluorine, chlorine, bromine, and iodine, more preferably fluorine, chlorine, and bromine, and still more preferably fluorine and chlorine.

[0229] Examples of heteroatoms are N, O, S, P, B, Si. Preferably, the term "heteroatom" refers to N, S, and O.

[0230] Unless otherwise defined differently, "alkyl" - by itself or as part of a chemical group - represents a straight-chain or branched hydrocarbon preferably having 1 to 6 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1,1-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,2-dimethylpropyl, 1,3-dimethylbutyl, 1,4-dimethylbutyl, 2,3-dimethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethylbutyl and 2-ethylbutyl. An alkyl having 1 to 4 carbon atoms is also preferred, such as especially methyl, ethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl or tert-butyl. Unless otherwise defined differently, "alkenyl" - by itself or as part of a chemical group - represents a straight-chain or branched hydrocarbon preferably having 2 to 6 carbon atoms and at least one double bond, such as vinyl, 2-propenyl, 2-butenyl, 3-butenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-2-propenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1,3-dimethyl-2-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl and 1-ethyl-2-methyl-2-propenyl. An alkenyl having 2 to 4 carbon atoms is also preferred, such as especially 2-propenyl, 2-butenyl or 1-methyl-2-propenyl.

[0231] Unless otherwise defined differently, "alkynyl" - either by itself or as part of a chemical group - represents a straight-chain or branched-chain hydrocarbon preferably having 2 to 6 carbon atoms and at least one triple bond, such as 2-propynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-methyl-2-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 2-methyl-3-pentynyl, 2-methyl-4-pentynyl, 3-methyl-4-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3-butynyl, 2,2-dimethyl-3-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl, 1-ethyl-1-methyl-2-propynyl, and 2,5-hexadiynyl. An alkynyl having 2 to 4 carbon atoms is also preferred, such as especially ethynyl, 2-propynyl, or 2-butynyl-2-propenyl.

[0232] Unless otherwise defined differently, "cycloalkyl" - either by itself or as part of a chemical group - represents a monocyclic, bicyclic, or tricyclic hydrocarbon preferably having 3 to 10 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl, or adamantyl. A cycloalkyl having 3, 4, 5, 6, or 7 carbon atoms is also preferred, such as especially cyclopropyl or cyclobutyl. Unless otherwise defined differently, "alkylcycloalkyl" represents a monocyclic, bicyclic, or tricyclic alkylcycloalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, such as methylcyclopropyl, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl, and 4-methylcyclohexyl. An alkylcycloalkyl having 4, 5, or 7 carbon atoms is also preferred, such as especially ethylcyclopropyl or 4-methylcyclohexyl.

[0233] Unless otherwise defined differently, "hydroxyalkyl" represents a straight-chain or branched-chain alcohol preferably having 1 to 6 carbon atoms, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, sec-butanol, and tert-butanol. A hydroxyalkyl group having 1 to 4 carbon atoms is also preferred.

[0234] Unless otherwise defined differently, "alkoxy" represents a straight-chain or branched O-alkyl having preferably 1 to 6 carbon atoms, such as methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy and tert-butoxy. An alkoxy group having 1 to 4 carbon atoms is also preferred. Unless otherwise defined differently, "alkylthio" represents a straight-chain or branched S-alkyl having preferably 1 to 6 carbon atoms, such as methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio and tert-butylthio. An alkylthio group having 1 to 4 carbon atoms is also preferred.

[0235] Unless otherwise defined differently, "alkylsulfinyl" represents a straight-chain or branched alkylsulfinyl having preferably 1 to 6 carbon atoms, such as methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, sec-butylsulfinyl and tert-butylsulfinyl. An alkylsulfinyl group having 1 to 4 carbon atoms is also preferred.

[0236] Unless otherwise defined differently, "alkylsulfonyl" represents a straight-chain or branched alkylsulfonyl having preferably 1 to 6 carbon atoms, such as methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl and tert-butylsulfonyl. An alkylsulfonyl group having 1 to 4 carbon atoms is also preferred.

[0237] Unless otherwise defined differently, "alkylcarbonyl" represents a straight-chain or branched alkyl-C(=O) having preferably 2 to 7 carbon atoms, such as methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, sec-butylcarbonyl and tert-butylcarbonyl. An alkylcarbonyl having 1 to 4 carbon atoms is also preferred.

[0238] Unless otherwise defined differently, "alkoxycarbonyl" - by itself or as part of a chemical group - represents a straight-chain or branched alkoxycarbonyl having preferably 1 to 6 carbon atoms in the alkoxy moiety or having 1 to 4 carbon atoms, such as methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl.

[0239] Unless otherwise defined differently, "alkylaminocarbonyl" represents a straight-chain or branched alkylaminocarbonyl having preferably 1 to 6 carbon atoms in the alkyl moiety or having 1 to 4 carbon atoms, such as methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, sec-butylaminocarbonyl and tert-butylaminocarbonyl. The alkylaminocarbonyl according to the present invention may be substituted by one or more identical or different groups.

[0240] Unless otherwise defined differently, "N,N-dialkylaminocarbonyl" represents a straight-chain or branched N,N-dialkylaminocarbonyl preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkyl moiety, such as N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, N,N-di(n-propylamino)carbonyl, N,N-di(isopropylamino)carbonyl, and N,N-di-(sec-butylamino)carbonyl.

[0241] Unless otherwise defined differently, "N,N-dialkylamino" represents a straight-chain or branched N,N-dialkylamino preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkyl moiety, such as N,N-dimethylamino-1, N,N-diethylamino, N,N-di(n-propylamino), N,N-di(isopropylamino), and N,N-di(sec-butylamino). Unless otherwise defined differently, "alkanoyl" or other "alkylcarbonyl" represents a straight-chain or branched alkyl group having 1 to 6 carbon atoms, which carries an oxygen atom connected by a double bond at the 1-position and is connected through the 1-position. Examples include: formyl, acetyl, propionyl, n-butyryl, isobutyryl, pivaloyl, n-hexanoyl.

[0242] Unless otherwise defined differently, "aryl" represents a monocyclic, bicyclic or polycyclic aromatic system preferably having 6 to 14, especially 6 to 10 ring carbon atoms, such as phenyl, naphthyl, anthryl, phenanthryl, preferably phenyl. In addition, aryl also represents a polycyclic system, such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenyl, where the binding site is on the aromatic system.

[0243] Examples of substituted aryl are arylalkyls, which can likewise be substituted by one or more identical or different groups in the C1-C4-alkyl and / or C6-C 14 -aryl moiety. Examples of such arylalkyls include benzyl and 1-phenylethyl.

[0244] Unless otherwise defined differently, "heterocycle", "heterocyclic fused ring" or "heterocyclic system" represent a carbocyclic system having at least one ring, wherein at least one carbon atom is replaced by a heteroatom, preferably a heteroatom selected from N, O, S, P, B, Si, Se, and which is saturated, unsaturated or heteroaromatic, and may be unsubstituted or substituted, wherein the bonding site is on the ring atom. Unless otherwise defined differently, the heterocycle preferably contains 3 to 9 ring atoms, especially 3 to 6 ring atoms, and the heterocycle contains one or more, preferably 1 to 4, especially 1, 2 or 3 heteroatoms preferably selected from N, O and S, provided that two oxygen atoms should not be directly adjacent. The heterocycle usually contains no more than 4 nitrogen atoms and / or no more than 2 oxygen atoms and / or no more than 2 sulfur atoms. If the heterocyclic group or heterocycle is optionally substituted, it may be fused to other carbocycles or heterocycles. In the case of an optionally substituted heterocyclic group, the present invention also includes polycyclic systems, such as 8-azabicyclo[3.2.1]octyl or 1-azabicyclo[2.2.1]heptyl. In the case of an optionally substituted heterocyclic group, the present invention also includes spirocyclic systems, such as 1-oxa-5-azaspiro[2.3]hexyl.

[0245] The heterocyclic groups of the present invention are, for example: piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, dioxanyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, thiazolidinyl, oxazolidinyl, dioxolanyl, m-dioxolylene, pyrazolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, oxiranyl, azetidinyl, aziridinyl, oxazetidinyl, oxaziridinyl, oxazepanyl, oxazinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperazinyl and oxepanyl.

[0246] The term "optionally substituted" group / substituent, such as a substituted alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cycloalkyl, aryl, phenyl, benzyl, heterocyclic group, and heteroaryl group, means, for example, a substituted group derived from an unsubstituted basic structure, where the substituent is, for example, one (1) substituent or multiple substituents, preferably 1, 2, 3, 4, 5, 6, or 7 substituents selected from the following: amino, hydroxy, halogen, nitro, cyano, isocyano, mercapto, isothiocyanato, C1-C4-carboxy, carbamoyl, SF5, aminosulfonyl, C1-C4-alkyl, C3-C4-cycloalkyl, C2-C4-alkenyl, C5-C6-cycloalkenyl, C2-C4-alkynyl, N-mono-C1-C4-alkylamino, N,N-di-C1-C4-alkylamino, N-C1-C4-alkanoylamino, C1-C4-alkoxy, C2-C4-alkenyloxy, C2-C4-alkynyloxy, C3-C4-cycloalkoxy, C5-C6-cycloalkenyloxy, C1-C4-alkoxycarbonyl, C2-C4-alkenyloxycarbonyl, C2-C4-alkynyloxycarbonyl, C6-aryloxycarbonyl, C 10 -aryloxycarbonyl, C 14 -aryloxycarbonyl, C1-C4-alkanoyl, C2-C4-alkenylcarbonyl, C2-C4-alkynylcarbonyl, C6-arylcarbonyl, C 10 -arylcarbonyl, C 14 -arylcarbonyl, C1-C4-alkylthio, C3-C4-cycloalkylthio, C1-C4-alkylsulfenyl, C2-C4-alkenylthio, C5-C6-cycloalkenylthio, C2-C4-alkynylthio, C1-C4-alkylsulfenyl (including the two enantiomers of C1-C4-alkylsulfenyl), C1-C4-alkylsulfonyl, N-mono-C1-C4-alkylaminosulfonyl, N,N-di-C1-C4-alkylaminosulfonyl, C1-C4-alkylphosphinyl, C1-C4-alkylphosphonyl (where for C1-C4-alkylphosphinyl and C1-C4-alkylphosphonyl, including the two enantiomers), N-C1-C4-alkylaminocarbonyl, N,N-di-C1-C4-alkylaminocarbonyl, N-C1-C4-alkanoylaminocarbonyl, N-C1-C4-alkanoyl-N-C1-C4-alkylaminocarbonyl, -CH=N-O-[(C1-C4)-alkyl], -C[(C1-C4)-alkyl]=N-O-[(C1-C4)-alkyl, C6-aryl, C 10 -aryl, C 14 -aryl, C6-aryloxy, C 10 -aryloxy, C 14 -aryloxy, benzyl, benzyloxy, benzylthio, C6-arylthio, C10 -arylthio, C 14 -arylthio, C6-arylamino, C 10 -arylamino, C 14 -arylamino, benzylamino, heterocyclic group and trialkylsilyl, substituents linked by a double bond, such as C1-C4-alkylene (e.g., methylene or ethylene), oxo group, imino group and substituted imino group. If two or more groups form one or more rings, they may be carbocyclic, heterocyclic, saturated, partially saturated, unsaturated, and also e.g., aromatic and further substituted.

[0247] Substituents mentioned by way of example (“first substituent level”) – if they contain a hydrocarbon moiety – optionally have further substitution therein (“second substitution level”), e.g., substituted by one or more substituents each independently selected from: halogen, hydroxy, amino, nitro, cyano, isocyano, azide, amido, oxo group and imino group. The term “optionally substituted” group preferably contains exactly one or two substitution levels.

[0248] Unless otherwise differently defined, a halogen-substituted chemical group (e.g., alkyl, cycloalkyl or alkoxy) is mono- or poly-substituted by halogen until the maximum possible number of substituents. Such groups are also referred to as halogen groups (e.g., haloalkyl). In the case of poly-substitution by halogen, the halogen atoms can be the same or different and can all be bonded to one carbon atom or can all be bonded to multiple carbon atoms. In this text, halogen specifically represents fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine and more preferably fluorine. More specifically, halogen substituents are monohalocycloalkyls such as 1-fluorocyclopropyl, 2-fluorocyclopropyl or 1-fluorocyclobutyl; monohaloalkyls such as 2-chloroethyl, 2-fluoroethyl, 1-chloroethyl, 1-fluoroethyl, chloromethyl or fluoromethyl; perhaloalkyls such as trichloromethyl or trifluoromethyl or CF2CF3; polyhaloalkyls such as difluoromethyl, 2-fluoro-2-chloroethyl, dichloromethyl, 1,1,2,2-tetrafluoroethyl or 2,2,2-trifluoroethyl. Other examples of haloalkyls are trichloromethyl, chlorodifluoromethyl, dichlorofluoromethyl, chloromethyl, bromomethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 2-chloro-2,2-difluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl and pentafluorotert-butyl. Preferred are such haloalkyls that have 1 to 4 carbon atoms and 1 to 9, preferably 1 to 5, identical or different halogen atoms selected from fluorine, chlorine and bromine. Particularly preferred are haloalkyls having 1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms selected from fluorine and chlorine, such as especially difluoromethyl, trifluoromethyl or 2,2-difluoroethyl.Other examples of compounds substituted by halogen are haloalkoxy groups such as OCF3, OCHF2, OCH2F, OCF2CF3, OCH2CF3, OCH2CHF2 and OCH2CH2Cl; haloalkylthio groups such as difluoromethylthio, trifluoromethylthio, trichloromethylthio, chlorodifluoromethylthio, 1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 1,1,2,2-tetrafluoroethylthio, 2,2,2-trifluoroethylthio or 2-chloro-1,1,2-trifluoroethylthio; haloalkylsulfinyl groups such as difluoromethylsulfinyl, trifluoromethylsulfinyl, trichloromethylsulfinyl, chlorodifluoromethylsulfinyl, 1-fluoroethylsulfinyl, 2-fluoroethylsulfinyl, 2,2-difluoroethylsulfinyl, 1,1,2,2-tetrafluoroethylsulfinyl, 2,2,2-trifluoroethylsulfinyl and 2-chloro-1,1,2-trifluoroethylsulfinyl; haloalkylsulfonyl groups such as difluoromethylsulfonyl, trifluoromethylsulfonyl, trichloromethylsulfonyl, chlorodifluoromethylsulfonyl, 1-fluoroethylsulfonyl, 2-fluoroethylsulfonyl, 2,2-difluoroethylsulfonyl, 1,1,2,2-tetrafluoroethylsulfonyl, 2,2,2-trifluoroethylsulfonyl and 2-chloro-1,1,2-trifluoroethylsulfonyl.

[0249] Unless otherwise differently defined, in the case of groups having carbon atoms, those groups having 1 to 4 carbon atoms, especially 1 or 2 carbon atoms, are preferred. Substituents selected from the following are generally preferred: halogen, such as fluorine and chlorine; (C1-C4)alkyl, preferably methyl or ethyl; (C1-C4)haloalkyl, preferably trifluoromethyl; (C1-C4)alkoxy, preferably methoxy or ethoxy; (C1-C4)haloalkoxy; nitro and cyano. The following substituents are particularly preferred herein: methyl, methoxy, fluorine and chlorine.

[0250] Unless otherwise defined differently, a substituted amino group, such as a mono-substituted or di-substituted amino group, is a substituted amino group selected from the following, i.e., the amino group is N-substituted, for example, by one or two identical or different groups selected from: alkyl, hydroxy, amino, alkoxy, acyl, and aryl; preferably N-monoalkylamino and N,N-dialkylamino (such as methylamino, ethylamino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino, or N,N-dibutylamino), N-monoalkoxyalkylamino or N,N-dialkoxyalkylamino groups (such as N-methoxymethylamino, N-methoxyethylamino, N,N-di(methoxymethyl)amino, or N,N-di(methoxyethyl)amino), N-monoarylamino and N,N-diarylamino, such as optionally substituted aniline, acylamino, N,N-diacylamino, N-alkyl-N-arylamino, N-alkyl-N-acylamino, and saturated N-heterocycles; preferably an alkyl group having 1 to 4 carbon atoms; aryl is preferably phenyl or substituted phenyl; acyl is further defined below and is preferably (C1-C4) alkanoyl. This also applies to substituted hydroxyamino or hydrazino groups.

[0251] Substituted amino groups also include quaternary ammonium compounds (salts) having four organic substituents on the nitrogen atom.

[0252] Unless otherwise defined differently, an optionally substituted phenyl group is preferably an unsubstituted or mono-substituted or multi-substituted phenyl group, preferably up to trisubstituted, by the same or different groups selected from: halogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-haloalkyl, C1-C4-haloalkoxy, C1-C4-alkylthio, C1-C4-haloalkylthio, cyano, isocyano, and nitro, such as o-tolyl, m-tolyl, and p-tolyl, dimethylphenyl, 2-chlorophenyl, 3-chlorophenyl, and 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, and 4-fluorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, and 4-trifluoromethylphenyl, and 2-trichloromethylphenyl, 3-trichloromethylphenyl, and 4-trichloromethylphenyl, 2,4-dichlorophenyl, 3,5-dichlorophenyl, 2,5-dichlorophenyl, and 2,3-dichlorophenyl, o-methoxyphenyl, m-methoxyphenyl, and p-methoxyphenyl, 4-heptafluorophenyl.

[0253] Unless otherwise defined differently, an optionally substituted cycloalkyl is preferably an unsubstituted cycloalkyl or a cycloalkyl that is monosubstituted or polysubstituted, preferably up to trisubstituted, by the same or different groups selected from: halogen, cyano, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkoxy, C1-C4-alkoxy-C1-C4-alkyl, C1-C4-haloalkyl, and C1-C4-haloalkoxy, especially substituted by one or two C1-C4-alkyl groups.

[0254] The compounds of the invention can exist in preferred embodiments. The individual embodiments described herein can be combined with one another. Combinations that violate the laws of nature and combinations that the person skilled in the art would exclude on the basis of his / her expert knowledge are excluded. For example, ring structures having three or more adjacent oxygen atoms are excluded.

[0255] Isomers

[0256] Depending on the nature of the substituents, the compounds of formula (I) can be in the form of geometric isomers and / or optically active isomers or corresponding mixtures of isomers with different compositions. These stereoisomers are, for example, enantiomers, diastereomers, atropisomers, or geometric isomers. Accordingly, the invention encompasses the pure stereoisomers and any desired mixtures of these isomers.

[0257] Methods and uses

[0258] The invention further relates to a method for controlling animal pests, wherein a compound of formula (I) is allowed to act on the animal pests and / or their habitat. The control of animal pests is preferably carried out in agriculture and forestry, as well as in material protection. This preferably excludes methods for surgical or therapeutic treatment of the human or animal body and diagnostic methods carried out on the human or animal body.

[0259] The invention further relates to the use of the compounds of formula (I) as pesticides, especially as crop protection compositions.

[0260] In the context of the present application, the term "pesticide" also always includes the term "crop protection composition" in each case.

[0261] The compounds of formula (I) are suitable for the following uses due to their good plant tolerance, favorable warm-blooded animal toxicity, and good environmental compatibility: protecting plants and plant organs against biotic and abiotic stress factors, increasing the harvest yield, improving the quality of the harvested product, and controlling animal pests encountered in agriculture, horticulture, animal husbandry, aquaculture, forestry, gardens and leisure facilities, storage products, and material protection, as well as in the hygiene field, especially insects, arachnids, worms, especially nematodes, and mollusks.

[0262] In the context of the present patent application, the term "hygiene" shall be understood to mean any and all measures, methods and processes aimed at preventing diseases, in particular infectious diseases, and for protecting human and animal health and / or the environment and / or maintaining cleanliness. According to the invention, this particularly includes measures for cleaning, disinfecting and sterilizing, such as textiles or hard surfaces, in particular surfaces made of glass, wood, cement, porcelain, ceramics, plastics or metals, to ensure that they are free from hygienic pests and / or their secretions. In this regard, the scope of protection of the invention preferably excludes surgical or therapeutic treatment methods for the human or animal body and diagnostic methods carried out on the human or animal body.

[0263] The term "hygiene sector" includes all areas, technical fields and industrial applications in which these hygiene measures, methods and processes are important, such as hygiene in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, stables, animal husbandry, etc.

[0264] Thus, the term "hygienic pest" shall be understood to mean one or more such animal pests: the presence of which in the hygiene sector is problematic, in particular for health reasons. Thus, the main aim is to avoid the presence of hygienic pests and / or avoid exposure to these pests in the hygiene sector, or to limit them to a minimum. This can in particular be achieved by using pesticides which can be used both for preventing infections and for treating existing infections. Preparations for preventing or reducing exposure to pests can also be used. For example, hygienic pests include the organisms mentioned below.

[0265] Thus, the term "hygiene protection" encompasses all actions for maintaining and / or improving these hygiene measures, preventive measures and methods.

[0266] The compounds of formula (I) can preferably be used as pesticides. They are active against both normally sensitive and resistant species and against all or particular stages of development. The above-mentioned pests include:

[0267] Pests of the phylum Arthropoda, especially of the class Arachnida, such as mites of the genus Acarus (e.g., Acarus siro, Aceria kuko, Aceria sheldoni), mites of the genus Aculops spp., mites of the genus Aculus spp. (e.g., Aculus fockeui, Aculus schlechtendali), ticks of the genus Amblyomma spp., Amphitetranychus viennensis, ticks of the genus Argas spp., ticks of the genus Boophilus spp., mites of the genus Brevipalpus spp. (e.g., Brevipalpus phoenicis), Bryobia graminum, Bryobia praetiosa, scorpions of the genus Centruroides spp., mites of the genus Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, ticks of the genus Dermacentor spp., mites of the genus Eotetranychus spp. (e.g., Eotetranychus hicoriae), Epitrimerus pyri, mites of the genus Eutetranychus spp. (e.g., Eutetranychus banksi), mites of the genus Eriophyes spp. (e.g., Eriophyes pyri), Glycyphagus domesticus, Halotydeus destructor, mites of the genus Hemitarsonemus spp. (e.g., Hemitarsonemus latus (= Polyphagotarsonemus latus)), ticks of the genus Hyalomma spp., ticks of the genus Ixodes spp., spiders of the genus Latrodectus spp., spiders of the genus Loxosceles spp.)、Neutrombicula autumnalis, genus Nuphersa, genus Oligonychus spp. (such as Oligonychus coffeae, Oligonychus coniferarum, Oligonychus ilicis, Oligonychus indicus, Oligonychus mangiferus, Oligonychus pratensis, Oligonychus punicae, Oligonychus yothersi), genus Ornithodorus spp, genus Ornithonyssus spp., genus Panonychus spp. (such as Panonychus citri (=Metatetranychus citri), Panonychus ulmi (=Metatetranychus ulmi)), Phyllocoptruta oleivora, Platytetranychus multidigituli, Polyphagotarsonemus latus, genus Psoroptes spp., genus Rhipicephalus spp., genus Rhizoglyphus spp., genus Sarcoptes spp., Scorpiomaurus, genus Stenotarsonemus spp., Steneotarsonemus spinki, genus Tarsonemus spp. (such as Tarsonemus confusus, Tarsonemus pallidus), genus Tetranychus spp.(e.g., Tetranychus canadensis, Tetranychus cinnabarinus, Tetranychus turkestani, Tetranychus urticae), Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici;

[0268] Pests of the class Chilopoda, e.g., Geophilus spp., Scutigera spp.;

[0269] Pests of the order or class Collembola, e.g., Onychiurus armatus; Sminthurus viridis;

[0270] Pests of the class Diplopoda, e.g., Blaniulus guttulatus;

[0271] Pests of the class Insecta, e.g., of the order Blattodea, such as Blatta orientalis, Blattella asahinai, Blattella germanica, Leucophaea maderae, Loboptera decipiens, Neostylopyga rhombifolia, Panchlora spp., Parcoblatta spp., Periplaneta spp. (e.g., Periplaneta americana, Periplaneta australasiae), Pycnoscelus surinamensis, Supella longipalpa;

[0272] Pests of the order Coleoptera, such as Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Aethina tumida, Agelastica alni, Agrilus spp. (such as Agrilus planipennis, Agrilus coxalis, Agrilus bilineatus, Agrilus anxius), Agriotes spp. (such as Agriotes linneatus, Agriotes mancus), Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp. (such as Anoplophora glabripennis), Anthonomus spp. (such as Anthonomus grandis), Anthrenus spp., Apion spp., Apogonia spp., Atomaria spp. (such as Atomaria linearis), Attagenus spp., Baris caerulescens, Bruchidius obtectus, Bruchus spp. (such as Bruchus pisorum, Bruchus rufimanus), Cassida spp., Cerotoma trifurcata, Ceuthorrhynchus spp. (such as Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae), Chaetocnema spp.(e.g., Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa), Cleonus mendicus, Conoderus spp., Cosmopolites spp. (e.g., Cosmopolites sordidus), Costelytra zealandica, Ctenicera spp., Curculio spp. (e.g., Curculio caryae, Curculio caryatrypes, Curculio obtusus, Curculio sayi), Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptorhynchus lapathi, Cryptorhynchus mangiferae, Cylindrocopturus spp., Cylindrocopturus adspersus, Cylindrocopturus furnissi, Dendroctonus spp. (e.g., Dendroctonus ponderosae), Dermestes spp., Diabrotica spp. (e.g., Diabrotica balteata, Diabrotica barberi, Diabrotica undecimpunctata howardi, Diabrotica undecimpunctata undecimpunctata, Diabrotica virgifera virgifera, Diabrotica virgifera zeae), Dichocrocis spp., Dicladispa armigera, Diloboderus spp., Epicaerus spp., Epilachna spp.)(e.g., Epilachna borealis, Epilachna varivestis), Epitrix spp. (e.g., Epitrix cucumeris, Epitrix fuscula, Epitrix hirtipennis, Epitrix subcrinita, Epitrix tuberis), Faustinus spp., Gibbium psylloides, Gnathocerus cornutus, Hellula undalis, Heteronychus arator, Heteronyx spp., Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypomeces squamosus, Hypothenemus spp. (e.g., Hypothenemus hampei, Hypothenemus obscurus, Hypothenemus pubescens), Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lema spp., Leptinotarsa decemlineata, Leucoptera spp. (e.g., Leucoptera coffeella), Limonius ectypus, Lissorhoptrus oryzophilus, Listronotus (=Hyperodes) spp., Lixus spp., Luperodes spp., Luperomorpha xanthodera, Lyctus spp., Megacyllene spp. (e.g., Megacyllene robiniae), Megascelis spp., Melanotus spp.)(e.g., Melanotus longulusoregonensis), Meligethes aeneus, Melolontha spp. (e.g., Melolontha melolontha), Migdolus spp., Monochamus spp., Naupactus xanthographus, Necrobia spp., Neogalerucella spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorrhynchus spp. (e.g., Otiorhynchus cribricollis, Otiorhynchus ligustici, Otiorhynchus ovatus, Otiorhynchus rugosostriarus, Otiorhynchus sulcatus), Oulema spp. (e.g., Oulema melanopus, Oulema oryzae), Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllophaga helleri, Phyllotreta spp. (e.g., Phyllotreta armoraciae, Phyllotreta pusilla, Phyllotreta ramosa, Phyllotreta striolata), Popillia japonica, Premnotrypes spp., Prostephanus truncatus, Psylliodes spp. (e.g., Psylliodes affinis, Psylliodes chrysocephala, Psylliodes punctulata), Ptinus spp.)、Rhizobius ventralis, Rhizopertha dominica, Rhynchophorus spp. (such as Rhynchophorus ferrugineus, Rhynchophorus palmarum), Scolytus spp. (such as Scolytus multistriatus), Sinoxylon perforans, Sitophilus spp. (such as Sitophilus granarius, Sitophilus linearis, Sitophilus oryzae, Sitophilus zeamais), Sphenophorus spp., Stegobium paniceum, Sternechus spp. (such as Sternechus paludatus), Symphyletes spp., Tanymecus spp. (such as Tanymecus dilaticollis, Tanymecus indicus, Tanymecus palliatus), Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp. (such as Tribolium audax, Tribolium castaneum, Tribolium confusum), Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp. (such as Zabrus tenebrioides);.

[0273] Pests of the order Dermaptera, such as Anisolabis maritime, Forficula auricularia, Labidura riparia;

[0274] Pests of the order Diptera, such as, Aedes spp. (e.g., Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans), Agromyza spp. (e.g., Agromyza frontella, Agromyza parvicornis), Anastrepha spp., Anopheles spp. (e.g., Anopheles quadrimaculatus, Anopheles gambiae), Asphondylia spp., Bactrocera spp. (e.g., Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae), Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, Chironomus spp., Chrysomya spp., Chrysops spp., Chrysozona pluvialis, Cochliomya spp., Contarinia spp. (e.g., Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora, Contarinia schulzi, Contarinia sorghicola, Contarinia tritici), Cordylobia anthropophaga, Cricotopus sylvestris, Culex spp. (e.g., Culex pipiens, Culex quinquefasciatus), Culicoides spp., Culiseta spp.) Cuterebra spp., Dacus oleae, Dasineura spp. (e.g., Dasineura brassicae), Delia spp. (e.g., Delia antiqua, Delia coarctata, Delia florilega, Delia platura, Delia radicum), Dermatobia hominis, Drosophila spp. (e.g., Drosphila melanogaster, Drosophila suzukii), Echinocnemus spp., Euleia heraclei, Fannia spp., Gastrophilus spp., Glossina spp., Haematopota spp., Hydrellia spp., Hydrellia griseola, Hylemya spp., Hippobosca spp., Hypoderma spp., Liriomyza spp. (e.g., Liriomyza brassicae, Liriomyza huidobrensis, Liriomyza sativae), Lucilia spp. (e.g., Lucilia cuprina), Lutzomyia spp., Mansonia spp., Musca spp. (e.g., Musca domestica, Musca domestica vicina), Oestrus spp., Oscinella frit, Paratanytarsus spp., Paralauterborniella subcincta, Pegomya or Pegomyia spp.)(e.g., Pegomya betae, Pegomya hyoscyami, Pegomya rubivora), Phlebotomus spp., Phorbia spp., Phormia spp., Piophila casei, Platyparea poeciloptera, Prodiplosis spp., Psila rosae, Rhagoletis spp. (e.g., Rhagoletis cingulata, Rhagoletis completa, Rhagoletis fausta, Rhagoletis indifferens, Rhagoletis mendax, Rhagoletis pomonella), Sarcophaga spp., Simulium spp. (e.g., Simulium meridionale), Stomoxys spp., Tabanus spp., Tetanops spp., Tipula spp. (e.g., Tipula paludosa, Tipula simplex), Toxotrypana curvicauda;.

[0275] Pests of the order Hemiptera, such as Acizzia acaciaebaileyanae, Acizziadodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosipon spp. (such as Acyrthosiphon pisum), Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleurocanthus spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp. (such as Amrasca bigutulla, Amrasca devastans), Anuraphis cardui, Aonidiella spp. (such as Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata), Aphanostigma piri, Aphis spp. (such as Aphis citricola, Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis illinoisensis, Aphis middletoni, Aphis nasturtii, Aphis nerii, Aphis pomi, Aphis spiraecola, Aphis viburniphila), Arboridia apicalis, Arytainilla spp., Aspidiella spp., Aspidiotus spp.(e.g., Aspidiotus nerii), Atanus genus, Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysii, Brachycolus spp., Brevicoryne brassicae, Cacopsyllaspp. (e.g., Cacopsylla pyricola), Calligypona marginata, Capulinia genus, Carneocephala fulgida, Ceratovacuna lanigera, Cercopidae, Ceroplastes spp., Chaetosiphon fragaefolii, Chionaspis tegalensis, Chlorita onukii, Chondracris rosea, Chromaphis juglandicola, Chrysomphalus aonidum, Chrysomphalus ficus, Cicadulina mbila, Coccomytilus halli, Coccus spp. (e.g., Coccus hesperidum, Coccus longulus, Coccus pseudomagnoliarum, Coccus viridis), Cryptomyzus ribis, Cryptoneossa genus, Ctenarytaina spp., Dalbulus spp., Dialeurodes chittendeni, Dialeurodes citri, Diaphorina citri, Diaspis spp., Diuraphis genus, Doralis genus, Drosicha spp., Dysaphis spp.(e.g., Dysaphis apiifolia, Dysaphis plantaginea, Dysaphis tulipae), Dysmicoccus spp., Empoasca spp. (e.g., Empoasca abrupta, Empoasca fabae, Empoasca maligna, Empoasca solana, Empoasca stevensi), Eriosoma spp. (e.g., Eriosoma americanum, Eriosoma lanigerum, Eriosoma pyricola), Erythroneura spp., Eucalyptolyma spp., Euphyllura spp., Euscelis bilobatus, Ferrisia spp., Fiorinia spp., Furcaspis oceanica, Geococcus coffeae, Glycaspis spp., Heteropsylla cubana, Heteropsylla spinulosa, Homalodisca coagulata, Hyalopterus arundinis, Hyalopterus pruni, Icerya spp. (e.g., Icerya purchasi), Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp. (e.g., Lecanium corni (= Parthenolecanium corni)), Lepidosaphes spp. (e.g., Lepidosaphes ulmi), Lipaphis erysimi, Lopholeucaspis japonica, Lycorma delicatula, Macrosiphum spp.(e.g., Macrosiphum euphorbiae, Macrosiphum lilii, Macrosiphum rosae), Macrosteles facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metcalfa pruinosa, Metopolophium dirhodum, Monelliacostalis, Monelliopsis pecanis, Myzus spp. (e.g., Myzus ascalonicus, Myzus cerasi, Myzus ligustri, Myzus ornatus, Myzus persicae, Myzus nicotianae), Nasonovia ribisnigri, Neomaskellia spp., Nephotettix spp. (e.g., Nephotettix cincticeps, Nephotettix nigropictus), Nettigoniclla spectra, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp. (e.g., Paratrioza cockerelli), Parlatoria spp., Pemphigus spp. (e.g., Pemphigus bursarius, Pemphigus populivenae), Peregrinus maidis, Perkinsiella spp., Phenacoccus spp. (e.g., Phenacoccus madeirensis), Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp.(e.g., Phylloxera devastatrix, Phylloxera notabilis), Pinnaspis aspidistrae, Planococcus spp. (e.g., Planococcus citri), Prosopidopsylla flava, Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp. (e.g., Pseudococcus calceolariae, Pseudococcus comstocki, Pseudococcus longispinus, Pseudococcus maritimus, Pseudococcus viburni), Psyllopsis spp., Psylla spp. (e.g., Psylla buxi, Psylla mali, Psylla pyri), Pteromalus spp., Pulvinaria spp., Pyrilla spp., Quadraspidiotus spp. (e.g., Quadraspidiotus juglansregiae, Quadraspidiotus ostreaeformis, Quadraspidiotus perniciosus), Quesada gigas, Rastrococcus spp., Rhopalosiphum spp. (e.g., Rhopalosiphum maidis, Rhopalosiphum oxyacanthae, Rhopalosiphum padi, Rhopalosiphum rufiabdominale), Saissetia spp.)(e.g., *Saissetia coffeae*, *Saissetia miranda*, *Saissetia neglecta*, *Saissetia oleae*), *Scaphoideus titanus*, *Schizaphis graminum*, *Selenaspidus articulatus*, *Sipha flava*, *Sitobion avenae*, *Sogata spp.*, *Sogatella furcifera*, *Sogatodes spp.*, *Stictocephala festina*, *Siphoninus phillyreae*, *Tenalaphara malayensis*, *Tetragonocephela* spp., *Tinocallis caryaefoliae*, *Tomaspis* spp., *Toxoptera* spp. (e.g., *Toxoptera aurantii*, *Toxoptera citricidus*), *Trialeurodes vaporariorum*, *Trioza* spp. (e.g., *Trioza diospyri*), *Typhlocyba* spp., *Unaspis* spp., *Viteus vitifolii*, *Zygina* spp.;.

[0276] Pests of the suborder Heteroptera, for example, of the genus Aelia, Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp. (such as Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus), Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp. (such as Euschistus heros, Euschistus servus, Euschistus tristigmus, Euschistus variolarius), Eurydema spp., Eurygaster spp., Halyomorpha halys, Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptocoris varicornis, Leptoglossus occidentalis, Leptoglossus phyllopus, Lygocoris spp. (such as Lygocoris pabulinus), Lygus spp. (such as Lygus elisus, Lygus hesperus, Lygus lineolaris), Macropes excavatus, Megacopta cribraria, Miridae, Monalonion atratum, Nezara spp.(e.g., Nezara viridula), Nysius spp., Oebalus spp., Pentomidae, Piesma quadratum, Piezodorus spp. (e.g., Piezodorus guildinii), Psallus spp., Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp.;

[0277] Pests of Hymenoptera, such as, Acromyrmex spp., Athalia spp. (e.g., Athalia rosae), Atta spp., Camponotus spp., Dolichovespula spp., Diprion spp. (e.g., Diprion similis), Hoplocampa spp. (e.g., Hoplocampa cookei, Hoplocampa testudinea), Lasius spp., Linepithema (Iridiomyrmex) humile, Monomorium pharaonis, Paratrechina spp., Paravespula spp., Plagiolepis spp., Sirex spp. (e.g., Sirex noctilio), Solenopsis invicta, Tapinoma spp., Technomyrmex albipes, Urocerus spp., Vespa spp. (e.g., Vespa crabro), Wasmannia auropunctata, Xeris spp.;

[0278] Pests of the order Isopoda, such as Armadillidium vulgare, Oniscus asellus, Porcellio scaber;

[0279] Pests of the order Isoptera, such as Coptotermes spp. (e.g., Coptotermes formosanus), Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Kalotermes spp., Microtermes obesi, Nasutitermes spp., Odontotermes spp., Porotermes spp., Reticulitermes spp. (e.g., Reticulitermes flavipes, Reticulitermes hesperus);

[0280] Pests of the order Lepidoptera, such as Achroia grisella, Acronicta major, Adoxophyes spp. (e.g., Adoxophyes orana), Aedia leucomelas, Agrotis spp. (e.g., Agrotis segetum, Agrotis ipsilon), Alabama spp. (e.g., Alabama argillacea), Amyelois transitella, Anarsia spp., Anticarsia spp. (e.g., Anticarsia gemmatalis), Argyroploce spp., Autographa spp., Barathra brassicae, Blastodacna atra, Borbo cinnara, Bucculatrix thurberiella, Bupalus piniarius, Busseola spp., Cacoecia spp., Caloptilia theivora, Capua reticulana, Carpocapsa pomonella, Carposina niponensis, Cheimatobia brumata, Chilo spp. (e.g., Chilo plejadellus, Chilo suppressalis), Choreutis pariana, Choristoneura spp., Chrysodeixis chalcites, Clysia ambiguella, Cnaphalocerus spp., Cnaphalocrocis medinalis, Cnephasia spp., Conopomorpha spp., Conotrachelus spp., Copitarsia spp., Cydia spp.)(e.g., Cydia nigricana, Cydia pomonella), Dalaca noctuides, Diaphania spp., Diparopsis spp., Diatraea saccharalis, Dioryctria spp. (e.g., Dioryctria zimmermani), Earias spp., Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp. (e.g., Ephestia elutella, Ephestia kuehniella), Epinotia spp., Epiphyas postvittana, Erannis spp., Erschoviella musculana, Etiella spp., Eudocima spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp. (e.g., Euproctis chrysorrhoea), Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp. (e.g., Grapholita molesta, Grapholita prunivora), Hedylepta spp., Helicoverpa spp. (e.g., Helicoverpa armigera, Helicoverpa zea), Heliothis spp. (e.g., Heliothis virescens), Hofmannophila pseudospretella, Homoeosoma spp., Homona spp.)、Hyponomeuta padella, Kakivoria flavofasciata, Lampides spp., Laphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp. (such as Leucoptera coffeella), Lithocolletis spp. (such as Lithocolletis blancardella), Lithophane antennata, Lobesia spp. (such as Lobesia botrana), Loxagrotis albicosta, Lymantria spp. (such as Lymantria dispar), Lyonetia spp. (such as Lyonetia clerkella), Malacosoma neustria, Maruca testulalis, Mamstra brassicae, Melanitis leda, Mocis spp., Monopis obviella, Mythimna separata, Nemapogon cloacellus, Nymphula spp., Oiketicus spp., Omphisa spp., Operophtera spp., Oria spp., Orthaga spp., Ostrinia spp. (such as Ostrinia nubilalis), Panolis flammea, Parnara spp., Pectinophora spp. (such as Pectinophora gossypiella), Perileucoptera spp., Phthorimaea spp.(e.g., potato tuber moth (Phthorimaea operculella), citrus leafminer (Phyllocnistis citrella), Phyllonorycter spp. (e.g., apple leafminer (Phyllonorycter blancardella), hawthorn leafminer (Phyllonorycter crataegella)), Pieris spp. (e.g., small white (Pieris rapae)), grape berry moth (Platynota stultana), Indianmeal moth (Plodia interpunctella), Plusia spp., diamondback moth (Plutella xylostella) (= Plutella maculipennis), Podesia spp. (e.g., Podesia syringae), Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp. (e.g., true armyworm (Pseudaletia unipuncta)), soybean looper (Pseudoplusia includens), European corn borer (Pyrausta nubilalis), mint looper (Rachiplusia nu), Schoenobius spp. (e.g., yellow rice borer (Schoenobius bipunctifer)), Scirpophaga spp. (e.g., white rice borer (Scirpophaga innotata)), turnip moth (Scotia segetum), Sesamia spp. (e.g., pink rice borer (Sesamia inferens)), Sparganothis spp., Spodoptera spp. (e.g., Spodoptera eradiana, beet armyworm (Spodoptera exigua), fall armyworm (Spodoptera frugiperda), Spodoptera praefica), Stathmopoda spp., Stenoma spp., peanut leafminer (Stomopteryx subsecivella), Synanthedon spp., Andean potato tuber moth (Tecia solanivora), Thaumetopoea spp.)、Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp. (e.g., Trichoplusia ni), Tryporyza incertulas, Tuta absoluta, Virachola spp.;

[0281] Pests of the order Orthoptera or Saltatoria, such as Acheta domesticus, Dichroplus spp., Gryllotalpa spp. (e.g., Gryllotalpa gryllotalpa), Hieroglyphus spp., Locusta spp. (e.g., Locusta migratoria), Melanoplus spp. (e.g., Melanoplus devastator, Paratlanticus ussuriensis), Schistocerca gregaria;

[0282] Pests of the order Phthiraptera, such as Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Ptirus pubis, Trichodectes spp.;

[0283] Pests of the order Psocoptera, such as Lepinatus spp., Liposcelis spp.;

[0284] Pests of the order Siphonaptera, such as Ceratophyllus spp., Ctenocephalides spp. (such as Ctenocephalides canis, Ctenocephalides felis), Pulex irritans, Tunga penetrans, Xenopsylla cheopis;

[0285] Pests of the order Thysanoptera, such as Anaphothrips obscurus, Baliothrips biformis, Chaetanaphothrips leeuweni, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp. (such as Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi), Haplothrips spp., Heliothrips spp., Hercinothrips femoralis, Kakothrips spp., Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamomi, Thrips spp. (such as Thrips palmi, Thrips tabaci);

[0286] Pests of the order Zygentoma (=Thysanura), such as Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus, Thermobia domestica;

[0287] Pests of the class Symphyla, such as the genus Scutigerella spp. (e.g., Scutigerella immaculata);

[0288] Pests of the phylum Mollusca, such as pests of the class Bivalvia, like the genus Dreissena spp.,

[0289] and pests of the class Gastropoda, such as the genus Arion spp. (e.g., Arion ater rufus), the genus Biomphalaria spp., the genus Bulinus spp., the genus Deroceras spp. (e.g., Deroceras laeve), the genus Galba spp., the genus Lymnaea spp., the genus Oncomelania spp., the genus Pomacea spp., the genus Succinea spp.;

[0290] Plant pests of the class Nematoda, i.e., plant-parasitic nematodes, especially those of the genera Aglenchus spp. (e.g., Aglenchus agricola), Anguina spp. (e.g., Anguina tritici), Aphelenchoides spp. (e.g., Aphelenchoides arachidis, Aphelenchoides fragariae), Belonolaimus spp. (e.g., Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni), Bursaphelenchus spp. (e.g., Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus), Cacopaurus spp. (e.g., Cacopaurus pestis), Criconemella spp. (e.g., Criconemella curvata, Criconemella onoensis, Criconemella ornata, Criconemella rusium, Criconemella xenoplax(=Mesocriconema xenoplax)), Criconemoides spp. (e.g., Criconemoides ferniae, Criconemoides onoense, Criconemoides ornatum), Ditylenchus app. (e.g., Ditylenchus dipsaci), Dolichodorus spp., Globodera spp.(e.g., Globodera pallida, Globodera rostochiensis), Helicotylenchus spp. (e.g., Helicotylenchus dihystera), Hemicriconemoides spp., Hemicycliophora spp., Heterodera spp. (e.g., Heterodera avenae, Heterodera glycines, Heterodera schachtii), Hirschmaniella spp., Hoplolaimus spp., Longidorus spp. (e.g., Longidorus africanus), Meloidogyne spp. (e.g., Meloidogyne chitwoodi, Meloidogyne fallax, Meloidogyne hapla, Meloidogyne incognita), Meloinema spp., Nacobbus spp., Neotylenchus spp., Paralongidorus spp., Paraphelenchus spp., Paratrichodorus spp. (e.g., Paratrichodorus minor), Paratylenchus spp., Pratylenchus spp. (e.g., Pratylenchus penetrans), Pseudohalenchus spp., Psilenchus spp., Punctodera spp., Quinisulcius spp., Radopholus spp. (e.g., Radopholus citrophilus, Radopholus similis), Rotylenchulus spp.) Rotylenchus spp., Scutellonema spp., Subanguina spp., Trichodorus spp. (e.g., Trichodorus obtusus, Trichodorus primitivus), Tylenchorhynchus spp. (e.g., Tylenchorhynchus annulatus), Tylenchulus spp. (e.g., Tylenchulus semipenetrans), Xiphinema spp. (e.g., Xiphinema index).

[0291] Depending on the circumstances, at a certain concentration or application rate, the compounds of formula (I) can also be used as herbicides, safeners, growth regulators or agents for improving plant characteristics, as microbicides or gametocides, for example as fungicides, antimycotics, bactericides, virucides (including agents against viroids) or as agents against MLO (mycoplasma-like organisms) and RLO (rickettsia-like organisms). Depending on the circumstances, they can also be used as intermediates or precursors for the synthesis of other active compounds.

[0292] Formulations

[0293] The present invention also relates to formulations comprising at least one compound of formula (I) and application forms prepared therefrom as pesticides, such as irrigation, drip irrigation and spraying liquids. Optionally, the application forms comprise other pesticides and / or adjuvants for improving the effect, such as penetrants, such as vegetable oils (such as rapeseed oil, sunflower oil), mineral oils (such as paraffin oil), alkyl esters of plant fatty acids (such as methyl rapeseed oil or methyl soybean oil), or alkanol alkoxylates; and / or spreaders, such as alkyl siloxanes and / or salts (such as organic or inorganic ammonium salts or phosphonium salts, such as ammonium sulfate or diammonium hydrogen phosphate); and / or retention promoters, such as dioctyl sulfosuccinate or hydroxypropyl guar gum polymers; and / or wetting agents, such as glycerol; and / or fertilizers, such as ammonium-containing, potassium-containing or phosphorus-containing fertilizers.

[0294] Conventional formulations are, for example, water-soluble liquid formulations (SL), emulsion concentrates (EC), emulsifiable concentrates (EW), suspension concentrates (SC, SE, FS, OD), water-dispersible granules (WG), granules (GR), and capsule suspensions (CS); these formulations and other possible formulation types are documented, for example, by Crop Life International and described in the following documents: "Pesticide Standards", "Manual on the Development and Use of FAO and WHO Specifications for Pesticides", "FAO Plant Production and Protection Paper - 173" (prepared by the Joint Meeting on Pesticide Specifications of the Food and Agriculture Organization of the United Nations (FAO) / World Health Organization (WHO), 2004, ISBN: 9251048576). In addition to one or more compounds of formula (I), the formulations optionally further contain other agrochemical active compounds.

[0295] Preferred are formulations or application forms comprising the following substances: at least one auxiliary agent, such as a filler, solvent, self-promoter, carrier, emulsifier, dispersant, antifreeze, biocide, thickener; and / or other auxiliary agents, such as adjuvants. In the context of the present invention, an adjuvant is a component that enhances the biological efficacy of the formulation, while the component itself does not have any biological efficacy. Examples of adjuvants are agents that promote retention, spreading, attachment to the leaf surface or penetration.

[0296] These formulations are prepared in a known manner, for example, by mixing a compound of formula (I) with auxiliary agents such as fillers, solvents and / or solid carriers and / or other auxiliary agents such as surfactants. The formulations are prepared in suitable equipment or during or before application.

[0297] The auxiliary agents used can be substances suitable for imparting specific properties (such as certain physical, technical and / or biological properties) to the formulations of the compounds of formula (I) or to the application forms prepared from these formulations (such as ready-to-use pesticides, such as spray liquids or seed dressing products).

[0298] Suitable fillers are, for example, water, polar and non-polar organic chemical liquids, for example selected from: aromatic and non-aromatic hydrocarbons (such as paraffins, alkylbenzenes, alkylnaphthalenes, chlorobenzenes), alcohols and polyols (which may also be substituted, etherified and / or esterified if appropriate), ketones (such as acetone, cyclohexanone), esters (including fats and oils) and (poly)ethers, simple and substituted amines, amides, lactams (such as N-alkylpyrrolidones) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide).

[0299] If the extender used is water, organic solvents such as, for example, can also be used as cosolvents. Useful liquid solvents are mainly: aromatic compounds such as xylene, toluene or alkylnaphthalenes; chlorinated aromatic compounds or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons such as cyclohexane or paraffins such as petroleum fractions, mineral oils and vegetable oils; alcohols such as butanol or ethylene glycol and their ethers and esters; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; strongly polar solvents such as dimethylformamide and dimethyl sulfoxide; and water.

[0300] In principle, all suitable solvents can be used. Examples of suitable solvents are: aromatic hydrocarbons such as xylene, toluene or alkylnaphthalenes; chlorinated aromatic hydrocarbons or chlorinated aliphatic hydrocarbons such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons such as cyclohexane, paraffins, petroleum fractions, mineral oils and vegetable oils; alcohols such as methanol, ethanol, isopropanol, butanol or ethylene glycol and their ethers and esters; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; strongly polar solvents such as dimethyl sulfoxide; and water.

[0301] In principle, all suitable carriers can be used. Suitable carriers include in particular: for example, ammonium salts and finely ground natural rocks such as kaolin, alumina, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth; and finely ground synthetic rocks such as highly disperse silica, alumina and natural or synthetic silicates; resins; waxes; and / or solid fertilizers. Mixtures of these carriers can also be used. Useful carriers for granulates include: for example, crushed and classified natural rocks such as calcite, marble, pumice, sepiolite, dolomite; and synthetic granules of inorganic and organic powders; and granules of organic materials such as sawdust, paper, coconut husk, corn cobs and tobacco stalks.

[0302] Liquefied gas extenders or solvents can also be used. Particularly suitable extenders or carriers are those which are gaseous at standard temperature and atmospheric pressure, for example, aerosol propellants such as halogenated hydrocarbons, and butane, propane, nitrogen and carbon dioxide.

[0303] Examples of emulsifiers and / or foam formers, dispersants or wetting agents having ionic or non-ionic properties, or mixtures of these surface-active substances are: salts of polyacrylic acid; salts of lignosulphonic acid; salts of phenolsulphonic or naphthalenesulphonic acid; polycondensates of ethylene oxide with fatty alcohols or with fatty acids or with fatty amines, with substituted phenols (preferably alkylphenols or arylphenols); salts of sulphonosuccinates; taurine derivatives (preferably alkyl taurates); phosphates of polyethoxylated alcohols or phenols; fatty acid esters of polyols; and derivatives of compounds containing sulphate, sulphonate and phosphate groups, such as alkylaryl polyethylene glycol ethers, alkyl sulphonates, alkyl sulphates, aryl sulphonates, protein hydrolysates, lignosulphite waste liquors and methylcellulose. If one of the compounds of formula (I) and / or one of the inert carriers is insoluble in water and if the application is carried out in water, the presence of a surfactant is advantageous.

[0304] Other auxiliaries which may be present in the formulations and in the application forms obtained therefrom include: dyes, such as inorganic pigments, for example iron oxide, titanium oxide and Prussian blue; and organic dyes, such as alizarin dyes, azo dyes and metal phthalocyanine dyes; and nutrients and micronutrients, such as iron salts, manganese salts, boron salts, copper salts, cobalt salts, molybdenum salts and zinc salts.

[0305] Other components which may be present are stabilizers, such as cryo-stabilizers, preservatives, antioxidants, light stabilizers or other agents which improve chemical and / or physical stability. A foam generator and an anti-foaming agent may also be present.

[0306] In addition, the formulations and the application forms obtained therefrom may also contain the following substances as further auxiliaries: adhesives, such as carboxymethyl cellulose; and natural and synthetic polymers in the form of powders, granules or latexes, such as gum arabic, polyvinyl alcohol and polyvinyl acetate; and natural phospholipids, such as cephalins and lecithins and synthetic phospholipids. Other auxiliaries may be mineral oils and vegetable oils.

[0307] If appropriate, other auxiliaries may also be present in the formulations and in the use forms obtained therefrom. Examples of these additives are fragrances, protective colloids, binders, adhesives, thickeners, thixotropic agents, penetrants, retention promoters, stabilizers, chelating agents, complexing components, wetting agents, spreading agents. In general, the compounds of formula (I) can be combined with any solid or liquid additives customarily used for formulation purposes.

[0308] Useful retention promoters include all those substances which reduce the dynamic surface tension (such as dioctyl sulphosuccinate) or increase the viscoelasticity (such as hydroxypropyl guar gum polymer).

[0309] In the context of the present invention, useful penetrants are all those substances which are customarily used to improve the penetration of agrochemically active compounds into plants. In the context of the present invention, penetrants are defined by their ability to penetrate from the (usually aqueous) application liquid and / or from the spray coating into the epidermis of plants, thereby increasing the mobility of the active compound in the epidermis. The method described in the literature (Baur et al., 1997, Pesticide Science 51, 131 - 152) can be used to determine this property. Examples include: alcohol alkoxylates such as coconut fatty alcohol ethoxylate (10) or isotridecyl ethoxylate (12); fatty acid esters such as rapeseed oil methyl ester or soybean oil methyl ester; fatty amine alkoxylates such as tallow amine ethoxylate (15); or ammonium salts and / or phosphonium salts such as ammonium sulfate or diammonium hydrogen phosphate.

[0310] The preparation preferably comprises from 0.00000001% to 98% by weight of the compound of the formula (I), more preferably from 0.01% to 95% by weight of the compound of the formula (I), most preferably from 0.5% to 90% by weight of the compound of the formula (I), based on the weight of the preparation.

[0311] In the application forms (especially pesticidal) prepared from the preparation, the content of the compound of the formula (I) can vary within a wide range. In the application form, the concentration of the compound of the formula (I) can generally be from 0.00000001% to 95% by weight of the compound of the formula (I), preferably from 0.00001% to 1% by weight, based on the weight of the application form. Application is carried out in a conventional manner adapted to the application form.

[0312] Mixture

[0313] The compound of the formula (I) can also be used in admixture with one or more suitable substances such as fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbials, beneficial organisms, herbicides, fertilizers, bird repellents, phytotonics, reproduction inhibitors, safeners, chemical pheromones and / or plant growth regulators, thus, for example, broadening the spectrum of action, prolonging the action time, increasing the rate of action, preventing repulsion or preventing the development of resistance. In addition, such active compound combinations can improve plant growth and / or the tolerance to abiotic factors such as high or low temperature, drought or high water level or soil salinity. They can also improve the flowering and fruiting performance, optimize the germination ability and root development, promote harvesting and increase the yield, influence ripening, improve the quality and / or nutritional value of the harvested product, extend the storage period and / or improve the processability of the harvested product.

[0314] In addition, the compounds of formula (I) may be present in admixture with other active compounds or chemical pheromones such as attractants and / or bird repellents and / or plant activators and / or growth regulators and / or fertilizers. Similarly, the compounds of formula (I) can be used to improve plant performance, such as the growth, yield and quality of the harvested product.

[0315] In a particular embodiment of the invention, the compounds of formula (I) are present in admixture with other compounds (preferably those described below) in a formulation or in an application form prepared from these formulations.

[0316] If one of the compounds mentioned below can exist in different tautomeric forms, these forms are also included, even if not explicitly mentioned in each case. Depending on the circumstances, if all the mixing components mentioned are capable of forming salts on the basis of their functional groups, they can also form salts with suitable bases or acids.

[0317] Insecticide / acaricide / nematicide

[0318] The active compounds mentioned herein by their common names are known and are described, for example, in "The Pesticide Manual" (16th Edition, British Crop Protection Council 2012), or can be retrieved on the Internet (e.g., http: / / www.alanwood.net / pesticides). This classification is based on the IRAC mode of action classification scheme applicable at the time of filing of this patent application.

[0319] (1) Acetylcholinesterase (AChE) inhibitors, such as carbamates, such as alanycarb, aldicarb, bendiocarb, benfuracarb, butocarboxim, butoxycarboxim, carbaryl, carbofuran, carbosulfan, ethiofencarb, fenobucarb, formetanate, furathiocarb, isoprocarb, methiocarb, methomyl, metolcarb, oxamyl, pirimicarb, propoxur, thiodicarb, thiofanox, triazamate, trimethacarb, XMC, and xylylcarb; or organophosphates, such as acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chloropyrifos-methyl, coumaphos, cyanophos, demeton-S-methyl, diazinon, dichlorvos / DDVP, dicrotophos, dimethoate, dimethylvinphos, disulfoton, EPN, ethion, ethoprophos, famphur, fenamiphos, fenitrothion, fenthion, fosthiazate, heptenophos, imicyafos, isofenphos, isopropyl O-(methoxyaminothiophosphoryl) salicylate, isoxathion,Malathion, mecarbam, methamidophos, methidathion, mevinphos, monocrotophos, naled, omethoate, oxydemeton-methyl, parathion-methyl, phenthoate, phorate, phosalone, phosmet, phosphamidon, phoxim, pirimiphos-methyl, profenofos, propetamphos, prothiofos, pyraclofos, pyridaphenthion, quinalphos, sulfotep, tebupirimfos, temephos, terbufos, tetrachlorvinphos, thiometon, triazophos, triclorfon and vamidothion.

[0320] (2) GABA-gated chloride channel blockers, such as cyclodiene organochlorines, such as chlordane and endosulfan; or phenylpyrazoles (fiproles), such as ethiprole and fipronil.

[0321] (3) Sodium channel modulators, such as pyrethroids, such as acrinathrin, allethrin, d-cis-trans allethrin, d-trans allethrin, bifenthrin, bioallethrin, bioallethrin S-cyclopentenyl isomer, resmethrin, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, lambda-cyhalothrin, gamma-cyhalothrin, cypermethrin, alpha-cypermethrin, beta-cypermethrin, theta-cypermethrin, zeta-cypermethrin, cyphenothrin [(1R)-trans isomers], deltamethrin, empenthrin [(EZ)-(1R) isomers], esfenvalerate, etofenprox, fenpropathrin, fenvalerate, flucythrinate, flumethrin, tau-fluvalinate, halfenprox, imiprothrin, kadethrin, momfluorothrin, permethrin, phenothrin [(1R)-transisomers), prallethrin, pyrethrine, pyrethrum, resmethrin, silafluofen, tefluthrin, tetramethrin, tetramethrin [(1R) isomers], tralomethrin, and transfluthrin; or DDT; or methoxychlor.

[0322] (4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, such as neonicotinoids, such as acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam, or nicotine, or sulfoxaflor, or flupyradifurone.

[0323] (5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators, such as spinosyns, such as spinetoram and spinosad.

[0324] (6) Glutamate-gated chloride channel (GluCl) allosteric modulators, such as avermectins / milbemycins, such as abamectin, emamectin benzoate, lepimectin, and milbemectin.

[0325] (7) Juvenile hormone mimics, such as juvenile hormone analogs such as hydroprene, kinoprene, and methoprene, or fenoxycarb, or pyriproxyfen.

[0326] (8) Other non-specific (multi-site) inhibitors, such as alkyl halides, such as methyl bromide and other alkyl halides; or chloropicrin or sulfuryl fluoride or borax or tartar emetic or methyl isocyanate generators, such as dazomet or metam.

[0327] (9) Chordotonal organ regulators, such as pymetrozine or flonicamide.

[0328] (10) Mite growth inhibitors, such as clofentezine, hexythiazox and diflovidazin or etoxazole.

[0329] (11) Microbial disruptors of the insect midgut, such as Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, Bacillus thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis and B.t. plant proteins: Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, VIP3A, mCry3A, Cry3Ab, Cry3Bb, Cry34Ab1 / 35Ab1.

[0330] (12) Inhibitors of mitochondrial ATP synthase, such as ATP disruptors, such as diafenthiuron or organotin compounds, such as azocyclotin, cyhexatin and fenbutatin oxide or propargite or tetradifon.

[0331] (13) Uncouplers that block oxidative phosphorylation of the proton gradient, such as chlorfenapyr, DNOC and sulphluramid.

[0332] (14) Nicotinic acetylcholine receptor channel blockers, such as bensultap, cartap hydrochloride, thiocyclam, and thiosultap-sodium.

[0333] (15) Chitin biosynthesis inhibitors, type 0, such as bistrifluron, chlofluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron, and triflumuron.

[0334] (16) Chitin biosynthesis inhibitors, type 1, such as buprofezin.

[0335] (17) Molting disruptors (especially for Diptera), such as cyromazine.

[0336] (18) Ecdysone receptor agonists, such as chromafenozide, halofenozide, methoxyfenozide, and tebufenozide.

[0337] (19) Octopamine receptor agonists, such as amitraz.

[0338] (20) Mitochondrial complex III electron transport inhibitors, such as hydramethylnone, or acequinocyl, or fluacrypyrim.

[0339] (21) Mitochondrial complex I electron transport inhibitors, such as METI acaricides, such as fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad, and tolfenpyrad; or rotenone (derris).

[0340] (22) Voltage-dependent sodium channel blockers, such as indoxacarb or metaflumizone.

[0341] (23) Inhibitors of acetyl-CoA carboxylase, such as tetronic acid and tetramic acid derivatives, such as spirodiclofen, spiromesifen, and spirotetramat.

[0342] (24) Mitochondrial complex IV electron transport inhibitors, such as phosphines, such as aluminium phosphide, calcium phosphide, phosphine, and zinc phosphide; or cyanides, such as calcium cyanide, potassium cyanide, and sodium cyanide.

[0343] (25) Mitochondrial complex II electron transport inhibitors, such as β-ketonitrile derivatives, such as cyenopyrafen and cyflumetofen, and formanilides, such as pyflubumide.

[0344] (28) Ryanodine receptor modulators, such as diamides, such as chlorantraniliprole, cyantraniliprole, and flubendiamide;

[0345] Other active compounds, such as afidopyropen, afoxolaner, azadirachtin, benclothiaz, benzoximate, bifenazate, broflanilide, bromopropylate, chinomethionat, chloroprallethrin, cryolite, cyclaniliprole, cycloxaprid, cyhalodiamide, dicloromezotiaz, dicofol, epsilonmetofluthrin, epsilon momfluthrin, flometoquin, fluazaindolizine, fluensulfone, flufenerim, flufenoxystrobin, flufiprole, fluhexafon, fluopyram, fluralaner, fluxametamide, fufenozide, guadipyr, heptafluthrin, imidaclothiz, iprodione, kappabifenthrin, kappa tefluthrin, lotilaner, meperfluthrin, paichongding, pyridalyl, pyrifluquinazon, pyriminostrobin, spirobudiclofen, tetramethylfluthrin, tetraniliprole, tetrachlorantraniliprole, tioxazafen, thiofluoximate, triflumezopyrim and iodomethane; and products based on Bacillus firmus, I-1582, BioNeem, Votivo, and the following compounds: 1-{2-fluoro-4-methyl-5-[(2,2,{2-[(2-Trifluoroethyl)sulfinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazol-5-amine (known from WO2006 / 043635) (CAS 885026-50-6), {1′-[(2E)-3-(4-Chlorophenyl)prop-2-en-1-yl]-5-fluorospiro[indole-3,4′-piperidine]-1(2H)-yl}(2-chloropyridin-4-yl)methanone (known from WO2003 / 106457) (CAS 637360-23-7), 2-Chloro-N-[2-{1-[(2E)-3-(4-chlorophenyl)prop-2-en-1-yl]piperidin-4-yl}-4-(trifluoromethyl)phenyl]isonicotinamide (known from WO2006 / 003494) (CAS 872999-66-1), 3-(4-Chloro-2,6-dimethylphenyl)-4-hydroxy-8-methoxy-1,8-diazaspiro[4.5]dec-3-en-2-one (known from WO 2010052161) (CAS 1225292-17-0), 3-(4-Chloro-2,6-dimethylphenyl)-8-methoxy-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl ethyl carbonate (known from EP2647626) (CAS-1440516-42-6), 4-(But-2-yn-1-yloxy)-6-(3,5-dimethylpiperidin-1-yl)-5-fluoropyrimidine (known from WO2004 / 099160) (CAS 792914-58-0), PF1364 (known from JP2010 / 018586) (CAS registration number 1204776-60-2), N-[(2E)-1-[(6-Chloropyridin-3-yl)methyl]pyridin-2(1H)-ylidene]-2,2,2-trifluoroacetamide (known from WO2012 / 029672) (CAS 1363400-41-2), (3E)-3-[1-[(6-Chloro-3-pyridinyl)methyl]-2-pyridinylidene]-1,1,1-trifluoropropan-2-one (known from WO2013 / 144213) (CAS1461743-15-6), N-[3-(Benzylcarbamoyl)-4-chlorophenyl]-1-methyl-3-(pentafluoroethyl)-4-(trifluoromethyl)-1H-pyrazole-5-carboxamide (known from WO2010 / 051926) (CAS 1226889-14-0), 5-Bromo-4-chloro-N-[4-chloro-2-methyl-6-(methylcarbamoyl)phenyl]-2-(3-chloro-2-pyridinyl)pyrazole-3-carboxamide (known from CN103232431) (CAS1449220-44-3), 4-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)benzamide, 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(trans-1-oxido-3-thietanyl)benzamide, and 4-[(5S)-5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-2-methyl-N-(cis-1-oxido-3-thietanyl)benzamide (known from WO 2013 / 050317 A1) (CAS 1332628-83-7), N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide, (+)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide, and (-)-N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-trifluoropropyl)sulfinyl]propanamide (known from WO 2013 / 162715 A2, WO 2013 / 162716 A2, US 2014 / 0213448 A1) (CAS 1477923-37-7), 5-[[(2E)-3-chloro-2-propen-1-yl]amino]-1-[2,6-dichloro-4-(trifluoromethyl)phenyl]-4-[(trifluoromethyl)sulfinyl]-1H-pyrazole-3-carbonitrile (known from CN 101337937 A) (CAS 1105672-77-2), 3-bromo-N-[4-chloro-2-methyl-6-[(methylamino)thiomethyl]phenyl]-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide, (Liudaibenjiaxuanan, known from CN 103109816 A) (CAS 1232543-85-9); N-[4-chloro-2-[[(1,1-dimethylethyl)amino]carbonyl]-6-methylphenyl]-1-(3-chloro-2-pyridinyl)-3-(fluoromethoxy)-1H-pyrazole-5-carboxamide (known from WO 2012 / 034403 A1) (CAS 1268277-22-0), N-[2-(5-amino-1,3,4-thiadiazol-2-yl)-4-chloro-6-methylphenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (known from WO2011 / 085575 A1) (CAS 1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-(dichloroprop-2-en-1-yloxy)phenoxy]propoxy]-2-methoxy-6-(trifluoromethyl)pyrimidine (known from CN 101337940 A) (CAS 1108184-52-6); (2E)- and 2(Z)-2-[2-(4-cyanophenyl)-1-[3-(trifluoromethyl)phenyl]ethylidene]-N-[4-(difluoromethoxy)phenyl]hydrazinecarboxamide (known from CN 101715774 A) (CAS 1232543-85-9); 3-(2,2-dichlorovinyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl cyclopropanecarboxylate (known from CN 103524422 A) (CAS 1542271-46-4); methyl (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylate (known from CN 102391261 A) (CAS 1370358-69-2); 6-deoxy-3-O-ethyl-2,4-di-O-methyl-1-[N-[4-[1-[4-(1,1,2,2,2-pentafluoroethoxy)phenyl]-1H-1,2,4-triazol-3-yl]phenyl]carbamate]-α-L-mannopyranose (known from US 2014 / 0275503 A1) (CAS 1181213-14-8); 8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (CAS 1253850-56-4), (8-trans)-8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (CAS 933798-27-7), (8-cis)-8-(2-cyclopropylmethoxy-4-trifluoromethylphenoxy)-3-(6-trifluoromethylpyridazin-3-yl)-3-azabicyclo[3.2.1]octane (known from WO 2007040280 A1, WO 2007040282 A1) (CAS 934001-66-8), N-[3-chloro-1-(3-pyridyl)-1H-pyrazol-4-yl]-N-ethyl-3-[(3,3,3-(Trifluoropropyl)thio]propanamide (known from WO 2015 / 058021 A1, WO 2015 / 058028 A1) (CAS 1477919-27-9) and N-[4-(aminothiomethyl)-2-methyl-6-[(methylamino)carbonyl]phenyl]-3-bromo-1-(3-chloro-2-pyridinyl)-1H-pyrazole-5-carboxamide (known from CN 103265527 A) (CAS 1452877-50-7).

[0346] Fungicide

[0347] The active compounds mentioned herein by their common names are known and are described, for example, in the "Pesticide Manual" (16th Edition, British Crop Protection Council) or can be retrieved on the Internet (e.g. http: / / www.alanwood.net / pesticides ).

[0348] All mixed components mentioned in categories (1) to (15) can optionally form salts with suitable bases or acids if they are capable of forming salts based on their functional groups. All fungicidal mixed components mentioned in categories (1) to (15) can optionally include tautomeric forms.

[0349] 1) Ergosterol biosynthesis inhibitors, such as (1.001) cyproconazole, (1.002) difenoconazole, (1.003) epoxiconazole, (1.004) fenhexamide, (1.005) fenpropidin, (1.006) fenpropimorph, (1.007) fenpyrazamine, (1.008) fluquinconazole, (1.009) flutriafol, (1.010) imazalil, (1.011) imazalil sulfate, (1.012) ipconazole, (1.013) metconazole, (1.014) myclobutanil, (1.015) paclobutrazol, (1.016) prochloraz, (1.017) propiconazole, (1.018) prothioconazole, (1.019) pyrisoxazole, (1.020) spiroxamine, (1.021) tebuconazole, (1.022) tetraconazole, (1.023) triadimenol, (1.024) tridemorph, (1.025) triticonazole, (1.026) (1R,2S,5S)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.027) (1S,2R,5R)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.028) (2R)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (1.029) (2R)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.030) (2R)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.(1.031) (2S)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.032) (2S)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.033) (2S)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.034) (R)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.035) (S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.036) [3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.037) 1-({(2R,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.038) 1-({(2S,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.039) 1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.040) 1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.041) 1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.042) 2-[(2R,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.043) 2-[(2R,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.044) 2-[(2R,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylhept-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.045) 2-[(2R,4S,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.046) 2-[(2S,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.047) 2-[(2S,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.048) 2-[(2S,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.049) 2-[(2S,4S,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.050) 2-[1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.051) 2-[2-chloro-4-(2,4-dichlorophenoxy)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.052) 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.053) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.054) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)pentan-2-ol, (1.055) 2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.056) 2-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.057) 2-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.058) 2-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxirane-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.059) 5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.060) 5-(allylthio)-1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl-2-yl]methyl}-1H-1,2,4-triazole, (1.061) 5-(allylthio)-1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl-2-yl]methyl}-1H-1,2,4-triazole, (1.062) 5-(allylthio)-1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiranyl-2-yl]methyl}-1H-1,2,4-triazole, (1.063) N'-(2,5-dimethyl-4-{[3-(1,1,2,2-tetrafluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.064) N'-(2,5-dimethyl-4-{[3-(2,2,2-trifluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.065) N'-(2,5-dimethyl-4-{[3-(2,2,3,3-tetrafluoropropoxy)phenyl]thio}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.066) N'-(2,5-dimethyl-4-{[3-(pentafluoroethoxy)phenyl]thio}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.067) N'-(2,5-dimethyl-4-{3-[(1,1,2,2-tetrafluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.068) N'-(2,5-dimethyl-4-{3-[(2,2,2-trifluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.069) N'-(2,5-dimethyl-4-{3-[(2,2,3,3-tetrafluoropropyl)thio]phenoxy}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.070) N'-(2,5-dimethyl-4-{3-[(pentafluoroethyl)thio]phenoxy}phenyl)-N-ethyl-N-methylcarbamimidamide, (1.071) N'-(2,5-dimethyl-4-phenoxyphenyl)-N-ethyl-N-methylcarbamimidamide, (1.072) N'-(4-{[3-(difluoromethoxy)phenyl]thio}-2,5-dimethylphenyl)-N-ethyl-N-methylcarbamimidamide, (1.073) N'-(4-{3-[(difluoromethyl)thio]phenoxy}-2,5-dimethylphenyl)-N-ethyl-N-methylcarbamimidamide, (1.N'-[5-bromo-6-(2,3-dihydro-1H-inden-2-yloxy)-2-methylpyridin-3-yl]-N-ethyl-N-methylformimidamide, (1.075) N'-{4-[(4,5-dichloro-1,3-thiazol-2-yl)oxy]-2,5-dimethylphenyl}-N-ethyl-N-methylformimidamide, (1.076) N'-{5-bromo-6-[(1R)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformimidamide, (1.077) N'-{5-bromo-6-[(1S)-1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformimidamide, (1.078) N'-{5-bromo-6-[(cis-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformimidamide, (1.079) N'-{5-bromo-6-[(trans-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformimidamide, (1.080) N'-{5-bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylformimidamide, (1.081) mefentrifluconazole, (1.082) ipfentrifluconazole.

[0350] 2) Inhibitors of respiratory chain complex I or II, such as (2.001) benzovindiflupyr, (2.002) bixafen, (2.003) boscalid, (2.004) carboxin, (2.005) fluopyram, (2.006) flutolanil, (2.007) fluxapyroxad, (2.008) furametpyr, (2.009) isofetamid, (2.010) isopyrazam (trans-diastereomeric enantiomer 1R, 4S, 9S), (2.011) isopyrazam (trans-diastereomeric enantiomer 1S, 4R, 9R), (2.012) isopyrazam (trans-diastereomeric racemate 1RS, 4SR, 9SR), (2.013) isopyrazam (mixture of cis-diastereomeric racemate 1RS, 4SR, 9RS and trans-diastereomeric racemate 1RS, 4SR, 9SR), (2.014) isopyrazam (cis-diastereomeric enantiomer 1R, 4S, 9R), (2.015) isopyrazam (cis-diastereomeric enantiomer 1S, 4R, 9S), (2.016) isopyrazam (cis-diastereomeric racemate 1RS, 4SR, 9RS), (2.017) penflufen, (2.018) penthiopyrad, (2.019) pydiflumetofen, (2.020) Pyraziflumid, (2.021) sedaxane, (2.022) 1,3-dimethyl-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)-1H-pyrazole-4-carboxamide, (2.023) 1,3-dimethyl-N-[(3R)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.024) 1,3-dimethyl-N-[(3S)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.025) 1-methyl-3-(trifluoromethyl)-N-[2′-(trifluoromethyl)biphenyl-2-yl]-1H-pyrazole-4-carboxamide, (2.026) 2-fluoro-6-(trifluoromethyl)-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)benzamide, (2.027) 3-(difluoromethyl)-1-methyl-N-(1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)-1H-pyrazole-4-carboxamide, (2.028) 3-(Difluoromethyl)-1-methyl-N-[(3R)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.029) 3-(Difluoromethyl)-1-methyl-N-[(3S)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.030) 3-(Difluoromethyl)-N-(7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl)-1-methyl-1H-pyrazole-4-carboxamide, (2.031) 3-(Difluoromethyl)-N-[(3R)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.032) 3-(Difluoromethyl)-N-[(3S)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.033) 5,8-Difluoro-N-[2-(2-fluoro-4-{[4-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)ethyl]quinazolin-4-amine, (2.034) N-(2-Cyclopentyl-5-fluorobenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.035) N-(2-tert-Butyl-5-methylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.036) N-(2-tert-Butylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.037) N-(5-Chloro-2-ethylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.038) N-(5-Chloro-2-isopropylbenzyl)-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.039) N-[(1R,4S)-9-(Dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.040) N-[(1S,4R)-9-(Dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.041) N-[1-(2,4-Dichlorophenyl)-1-methoxypropan-2-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.042) N-[2-Chloro-6-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.043) N-[3-chloro-2-fluoro-6-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.044) N-[5-chloro-2-(trifluoromethyl)benzyl]-N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.045) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-1-methyl-N-[5-methyl-2-(trifluoromethyl)benzyl]-1H-pyrazole-4-carboxamide, (2.046) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-fluoro-6-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.047) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropyl-5-methylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.048) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-thiocarboxamide, (2.049) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.050) N-cyclopropyl-3-(difluoromethyl)-5-fluoro-N-(5-fluoro-2-isopropylbenzyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.051) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-4,5-dimethylbenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.052) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-5-fluorobenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.053) N-cyclopropyl-3-(difluoromethyl)-N-(2-ethyl-5-methylbenzyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.054) N-cyclopropyl-N-(2-cyclopropyl-5-fluorobenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.055) N-cyclopropyl-N-(2-cyclopropyl-5-methylbenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide, (2.056) N-cyclopropyl-N-(2-cyclopropylbenzyl)-3-(difluoromethyl)-5-fluoro-1-methyl-1H-pyrazole-4-carboxamide.

[0351] 3) Inhibitors of respiratory chain complex III, such as (3.001) ametoctradin, (3.002) amisulbrom, (3.003) azoxystrobin, (3.004) coumethoxystrobin, (3.005) coumoxystrobin, (3.006) cyazofamid, (3.007) dimoxystrobin, (3.008) enoxastrobin, (3.009) famoxadon, (3.010) fenamidon, (3.011) flufenoxystrobin, (3.012) fluoxastrobin, (3.013) kresoxim-methyl, (3.014) metominostrobin, (3.015) orysastrobin, (3.016) picoxystrobin, (3.017) pyraclostrobin, (3.018) pyrametostrobin, (3.019) pyraoxystrobin, (3.020) trifloxystrobin, (3.021) (2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylethenyl]oxy}phenyl)ethylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylacetamide, (3.022) (2E,3Z)-5-{[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.023) (2R)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.024) (2S)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.025) (3S,6S,7R,8R)-8-benzyl-3-[({3-[(isobutyryloxy)methoxy]-4-methoxypyridin-2-yl}carbonyl)amino]-6-methyl-4,9-dioxo-1,5-dioxonan-7-yl 2-methylpropionate, (3.026) 2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.027) N-(3-Ethyl-3,5,5-trimethylcyclohexyl)-3-carbamoyl-2-hydroxybenzamide, (3.028) (2E,3Z)-5-{[1-(4-chloro-2-fluorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.029) methyl {5-[3-(2,4-dimethylphenyl)-1H-pyrazol-1-yl]-2-methylbenzyl}carbamate.

[0352] 4) Mitotic and cell division inhibitors, such as (4.001) carbendazim, (4.002) diethofencarb, (4.003) ethaboxam, (4.004) fluopicolide, (4.005) pencycuron, (4.006) thiabendazole, (4.007) thiophanate-methyl, (4.008) zoxamide, (4.009) 3-chloro-4-(2,6-difluorophenyl)-6-methyl-5-phenylpyridazine, (4.010) 3-chloro-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-6-methylpyridazine, (4.011) 3-chloro-5-(6-chloropyridin-3-yl)-6-methyl-4-(2,4,6-trifluorophenyl)pyridazine, (4.012) 4-(2-bromo-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.013) 4-(2-bromo-4-fluorophenyl)-N-(2-bromo-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.014) 4-(2-bromo-4-fluorophenyl)-N-(2-bromophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.015) 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.016) 4-(2-bromo-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.017) 4-(2-bromo-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.018) 4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.019) 4-(2-chloro-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.020) 4-(2-chloro-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.021) 4-(2-chloro-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.022) 4-(4-chlorophenyl)-5-(2,6-difluorophenyl)-3,6-dimethylpyridazine, (4.023) N-(2-bromo-6-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.024) N-(2-bromophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.025) N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine.

[0353] 5) Compounds capable of having multi-site activity, such as (5.001) Bordeaux mixture, (5.002) captafol, (5.003) captan, (5.004) chlorothalonil, (5.005) copper hydroxide, (5.006) copper naphthenate, (5.007) copper oxide, (5.008) copper oxychloride, (5.009) copper(2+) sulfate, (5.010) dithianon, (5.0l1) dodine, (5.012) folpet, (5.013) mancozeb, (5.014) maneb, (5.015) metiram, (5.016) zincmetiram, (5.017) copper oxine, (5.018) propineb, (5.019) sulfur and sulfur preparations (including calcium polysulfide), (5.020) thiram, (5.021) zineb, (5.022) ziram, (5.023) 6-ethyl-5,7-dioxo-6,7-dihydro-5H-pyrrolo[3’,4’:5,6][1,4]dithieno[2,3-c][1,2]thiazole-3-carbonitrile.

[0354] 6) Compounds capable of triggering host defense, such as (6.001) acibenzolar-S-methyl, (6.002) isotianil, (6.003) probenazole, (6.004) tiadinil.

[0355] 7) Amino acid and / or protein biosynthesis inhibitors, such as (7.001) cyprodinil, (7.002) kasugamycin, (7.003) kasugamycin hydrochloride hydrate, (7.004) oxytetracycline, (7.005) pyrimethanil, (7.006) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline.

[0356] 8) ATP generation inhibitors, such as (8.001) silthiofam.

[0357] 9) Cell wall synthesis inhibitors, such as (9.001) benthiavalicarb, (9.002) dimethomorph, (9.003) flumorph, (9.004) iprovalicarb, (9.005) mandipropamid, (9.006) pyrimorph, (9.007) valifenalate, (9.008) (2E)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one, (9.009) (2Z)-3-(4-tert-butylphenyl)-3-(2-chloropyridin-4-yl)-1-(morpholin-4-yl)prop-2-en-1-one.

[0358] 10) Lipid and membrane synthesis inhibitors, such as (10.001) propamocarb, (10.002) propamocarb hydrochloride, (10.003) tolclofos-methyl.

[0359] 11) Melanin biosynthesis inhibitors, such as (11.001) tricyclazole, (11.002) 2,2,2-trifluoroethyl {3-methyl-1-[(4-methylbenzoyl)amino]butan-2-yl}carbamate.

[0360] 12) Nucleic acid synthesis inhibitors, such as (12.001) benalaxyl, (12.002) benalaxyl-M (kiralaxyl), (12.003) metalaxyl, (12.004) metalaxyl-M (mefenoxam).

[0361] 13) Signal transduction inhibitors, such as (13.001) fludioxonil, (13.002) iprodione, (13.003) procymidone, (13.004) proquinazid, (13.005) quinoxyfen, (13.006) vinclozolin.

[0362] 14) Compounds that can act as uncoupling agents, such as (14.001) fluazinam, (14.002) meptyldinocap.

[0363] 15) Other compounds, such as (15.001) abscisic acid, (15.002) benthiazole, (15.003) bethoxazin, (15.004) capsimycin, (15.005) carvone, (15.006) chinomethionat, (15.007) cufraneb, (15.008) cyflufenamid, (15.009) cymoxanil, (15.010) cyprosulfamide, (15.011) flutianil, (15.012) fosetyl-aluminium, (15.013) fosetyl-calcium, (15.014) fosetyl-sodium, (15.015) methyl isothiocyanate, (15.016) metrafenone, (15.017) mildiomycin, (15.018) natamycin, (15.019) nickel dimethyldithiocarbamate, (15.020) nitrothal-isopropyl, (15.021) oxamocarb, (15.022) oxathiapiprolin, (15.023) oxyfenthiin, (15.024) pentachlorophenol and its salts, (15.025) phosphoric acid and its salts, (15.026) propamocarb-fosetylate, (15.027) pyriofenone (chlazafenone), (15.028) tebufloquin, (15.029) tecloftalam, (15.030) tolnifanide, (15.031) 1-(4-{4-[(5R)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, (15.032) 1-(4-{4-[(5S)-5-(2,6-difluorophenyl)-4,5-dihydro-1,2-oxazol-3-yl]-1,3-thiazol-2-yl}piperidin-1-yl)-2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]ethanone, (15.033) 2-(6-benzylpyridin-2-yl)quinazoline, (15.034) 2,6-dimethyl-1H,5H-[1,4]dithiino[2,3-c:5,6-c']dipyrrole-1,3,5,7(2H,6H)-tetrone, (15.035) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.036) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-chloro-6-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.037) 2-[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]-1-[4-(4-{5-[2-fluoro-6-(prop-2-yn-1-yloxy)phenyl]-4,5-dihydro-1,2-oxazol-3-yl}-1,3-thiazol-2-yl)piperidin-1-yl]ethanone, (15.038) 2-[6-(3-fluoro-4-methoxyphenyl)-5-methylpyridin-2-yl]quinazoline, (15.039) 2-{(5R)-3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenyl methanesulfonate, (15.040) 2-{(5S)-3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenyl methanesulfonate, (15.041) 2-{2-[(7,8-difluoro-2-methylquinolin-3-yl)oxy]-6-fluorophenyl}propan-2-ol, (15.042) 2-{2-fluoro-6-[(8-fluoro-2-methylquinolin-3-yl)oxy]phenyl}propan-2-ol, (15.043) 2-{3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}-3-chlorophenyl methanesulfonate, (15.044) 2-{3-[2-(1-{[3,5-Bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-4,5-dihydro-1,2-oxazol-5-yl}phenyl methanesulfonate, (15.045) 2-phenylphenol and its salts, (15.046) 3-(4,4,5-trifluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)quinoline, (15.047) 3-(4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)quinoline, (15.048) 4-amino-5-fluoropyrimidin-2-ol (tautomeric form: 4-amino-5-fluoropyrimidin-2(1H)-one), (15.049) 4-oxo-4-[(2-phenylethyl)amino]butanoic acid, (15.050) 5-amino-1,3,4-thiadiazole-2-thiol, (15.051) 5-chloro-N′-phenyl-N′-(prop-2-yn-1-yl)thiophene-2-sulfonohydrazide, (15.052) 5-fluoro-2-[(4-fluorobenzyl)oxy]pyrimidin-4-amine, (15.053) 5-fluoro-2-[(4-methylbenzyl)oxy]pyrimidin-4-amine, (15.054) 9-fluoro-2,2-dimethyl-5-(quinolin-3-yl)-2,3-dihydro-1,4-benzoxazepine, (15.055) {6-[({[(Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}but-3-yn-1-yl carbamate, (15.056) (2Z)-ethyl 3-amino-2-cyano-3-phenylacrylate, (15.057) phenazine-1-carboxylic acid, (15.058) propyl 3,4,5-trihydroxybenzoate, (15.059) quinolin-8-ol, (15.060) quinolin-8-ol sulfate (2:1), (15.061) {6-[({[(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}tert-butyl carbamate, (15.062) 5-fluoro-4-imino-3-methyl-1-[(4-methylphenyl)sulfonyl]-3,4-dihydropyrimidin-2(1H)-one.

[0364] Biological pesticides as a mixed component

[0365] The compound of formula (I) can be combined with biological pesticides.

[0366] Biological pesticides especially include bacteria, fungi, yeasts, plant extracts and products formed by microorganisms, including proteins and secondary metabolites.

[0367] Biological pesticides include bacteria such as spore-forming bacteria, root-colonizing bacteria, and bacteria that act as biological insecticides, fungicides, or nematicides.

[0368] Examples of such bacteria that are used or can be used as biological pesticides are:

[0369] Bacillus amyloliquefaciens, strain FZB42 (DSM 231179); or Bacillus cereus, especially Bacillus cereus strain CNCM I-1562; or Bacillus firmus, strain I-1582 (accession number CNCM I-1582); or Bacillus pumilus, especially strains GB34 (accession number ATCC 700814) and QST2808 (accession number NRRL B-30087); or Bacillus subtilis, especially strain GB03 (accession number ATCC SD-1397), or Bacillus subtilis strain QST713 (accession number NRRL B-21661) or Bacillus subtilis strain OST 30002 (accession number NRRL B-50421); Bacillus thuringiensis, especially Bacillus thuringiensis subspecies israelensis (serotype H-14), strain AM65-52 (accession number ATCC 1276), or Bacillus thuringiensis subsp. aizawai, especially strain ABTS-1857 (SD-1372), or Bacillus thuringiensis subsp. kurstaki strain HD-1, or Bacillus thuringiensis subsp. tenebrionis strain NB 176 (SD-5428); Pasteuria penetrans, Pasteuria spp. (Rotylenchulus reniformis nematode)-PR3 (accession number ATCC SD-5834); Streptomyces microflavus strain AQ6121 (=QRD 31.013, NRRL B-50550); Streptomyces galbus strain AQ 6047 (accession number NRRL 30232).

[0370] Examples of fungi and yeasts used or usable as biological pesticides are:

[0371] Beauveria bassiana, especially strain ATCC 74040; Coniothyrium minitans, especially strain CON / M / 91-8 (accession number DSM-9660); Lecanicillium spp., especially strain HRO LEC 12; Lecanicillium lecanii (formerly known as Verticillium lecanii), especially strain KV01; Metarhizium anisopliae, especially strain F52 (DSM3884 / ATCC 90448); Metschnikowia fructicola, especially strain NRRL Y-30752; Paecilomyces fumosoroseus (current name: Isaria fumosorosea), especially strain IFPC 200613, or strain Apopka 97 (accession number ATCC 20874); Paecilomyces lilacinus, especially Paecilomyces lilacinus strain 251 (AGAL 89 / 030550); Talaromyces flavus, especially strain V117b; Trichoderma atroviride, especially strain SC1 (accession number CBS 122089); Trichoderma harzianum, especially Trichoderma harzianum T39 (accession number CNCM I-952).

[0372] Examples of viruses that are used or can be used as biological pesticides are:

[0373] Granulovirus (GV) of Adoxophyes orana (summer fruit tortrix), Granulovirus (GV) of Cydia pomonella (codling moth), Nuclear Polyhedrosis Virus (NPV) of Helicoverpa armigera (cotton bollworm), mNPV of Spodoptera exigua (beet armyworm), mNPV of Spodoptera frugiperda (fall armyworm), NPV of Spodoptera littoralis (African cotton leafworm).

[0374] It also includes bacteria and fungi added as "inoculants" to plants or plant parts or plant organs, which promote plant growth and plant health through their specific properties. Examples include:

[0375] Agrobacterium spp., Azorhizobium caulinodans, Azospirillum spp., Azotobacter spp., Bradyrhizobium spp., Burkholderia spp., especially Burkholderia cepacia (formerly known as Pseudomonas cepacia), Gigaspora spp., or Gigaspora monosporum, Glomus spp., Laccaria spp., Lactobacillus buchneri, Paraglomus spp., Pisolithus tinctorus, Pseudomonas spp., Rhizobium spp., especially Rhizobium trifolii, Rhizopogon spp., Scleroderma spp., Suillus spp., Streptomyces spp.

[0376] Examples of plant extracts and products formed by microorganisms (including proteins and secondary metabolites) that are used or can be used as biological pesticides are:

[0377] Garlic (Allium sativum), wormwood (Artemisia absinthium), azadirachtin, Biokeeper WP, Cassia nigricans, Celastrus angulatus, Chenopodium anthelminticum, chitin, Armour-Zen, Dryopteris filix-mas, Equisetum arvense, Fortune Aza, Fungastop, Heads Up (saponin extract of Chenopodium quinoa), pyrethrum / pyrethroids, Quassia amara, Quercus, Quillaja, Regalia, "Requiem TM Insecticide", rotenone, ryanodine, Symphytum officinale, Tanacetum vulgare, thymol, Triact 70, TriCon, Tropaeulum majus, Urtica dioica, Veratrin, Viscum album, Brassicaceae extracts, especially rapeseed powder or mustard powder.

[0378] Safeners as mixed components

[0379] Compounds of formula (I) can be combined with a safener, such as benoxacor, cloquintocet (-mexyl), cyometrinil, cyprosulfamide, dichlormid, fenchlorazole (-ethyl), fenclorim, flurazole, fluxofenim, furilazole, isoxadifen (-ethyl), mefenpyr (-diethyl), naphthalic anhydride, oxabetrinil, 2-methoxy-N-{4-[(methylcarbamoyl)amino]phenyl}sulfonyl)benzamide (CAS 129531-12-0), 4-(dichloroacetyl)-1-oxa-4-azaspiro[4.5]decane (CAS 71526-07-3), 2,2,5-trimethyl-3-(dichloroacetyl)-1,3-oxazolidine (CAS 52836-31-4).

[0380] Plants and plant parts

[0381] All plants and plant parts can be treated according to the invention. Plants herein are understood to mean all plants and plant populations, such as desired and undesired wild plants or crop plants (including naturally occurring crop plants), such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soybeans, potatoes, sugar beets, sugar cane, tomatoes, sweet peppers, cucumbers, melons, carrots, watermelons, onions, lettuce, spinach, leeks, legumes, brassicas (such as cabbages) and other vegetable varieties, cotton, tobacco, oilseed rape, and fruit plants (the fruits being apples, pears, citrus fruits and grapes). Crop plants can be plants obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including transgenic plants and plant cultivars which may or may not be protected by plant breeders’ rights. Plants are understood to mean all developmental stages, such as seeds, seedlings and young (immature) plants up to and including mature plants. Plant parts are understood to mean all parts and organs above and below ground of the plant, such as shoots, leaves, flowers and roots, examples given being leaves, needles, stems, branches, flowers, fruiting bodies, fruits and seeds, and roots, tubers and rhizomes. Plant parts also include harvested plants or harvested plant parts and asexual and sexual propagation material, such as cuttings, tubers, rhizomes, slips and seeds.

[0382] The treatment of plants and plant parts with the compounds of formula (I) according to the invention is carried out directly by conventional treatment methods or by allowing the compounds to act on their environment, habitat or storage space, for example by dipping, spraying, evaporation, atomization, broadcasting, spreading, painting, injection, and in the case of propagation material, in particular seeds, also by applying one or more coatings.

[0383] As mentioned above, all plants and their parts can be treated according to the invention. In a preferred embodiment, wild plant species and plant cultivars, or those obtained by conventional biological breeding methods such as crossing or protoplast fusion, and their parts are treated. In another preferred embodiment, transgenic plants and plant cultivars (genetically modified organisms) obtained by genetic engineering methods - if appropriate, in combination with conventional methods - and their parts are treated. The terms "part" or "part of a plant" or "plant part" have been explained above. Particular preference is given according to the invention to treating plants of the various commercially available conventional plant cultivars or those in use. Plant cultivars are to be understood as meaning plants having new properties ("traits") and obtained by conventional breeding, by mutagenesis or by recombinant DNA technology. They can be cultivars, varieties, biotypes or genotypes.

[0384] Transgenic plants, seed treatment and integration events

[0385] Preferred transgenic plants or plant cultivars processed according to the invention (those plants obtained by genetic engineering) include all plants that have received, by genetic modification, genetic material that confers upon these plants particularly advantageous useful properties ("traits"). Examples of such properties are: better plant growth, enhanced tolerance to high or low temperatures, enhanced tolerance to drought or to water or soil salinity levels, improved flowering performance, easier harvesting, accelerated ripening, higher harvest yields, higher quality and / or higher nutritional value of the harvested product, better storage capacity and / or processability of the harvested product. Other and particularly emphasized examples of such properties are: enhanced resistance of the plant to animal pests and microbial pests, such as insects, arachnids, nematodes, mites, slugs and snails, which is attributable, for example, to toxins formed in the plant, in particular those toxins formed in the plant by genetic material of Bacillus thuringiensis (such as by genes CryIA(a), CryIA(b), CryIA(c), CryIIA, CryIIIA, CryIIIB2, Cry9c, Cry2Ab, Cry3Bb and CryIF and combinations thereof), and enhanced resistance of the plant to phytopathogenic fungi, bacteria and / or viruses, which is caused, for example, by systemic acquired resistance (SAR), systemin, phytoalexins, elicitors and resistance genes and the correspondingly expressed proteins and toxins, and enhanced tolerance of the plant to certain herbicidally active compounds, such as imidazolinones, sulfonylureas, glyphosate or phosphinothricin (such as the "PAT" gene). The genes conferring the desired properties ("traits") can also be present in the transgenic plants in combination with one another. Examples of the transgenic plants mentioned include important crop plants, such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soybeans, potatoes, sugar beets, sugar cane, tomatoes, peas and other vegetable species, cotton, tobacco, oilseed rape, and fruit plants (the fruits being apples, pears, citrus fruits and grapes), with particular emphasis on maize, soybeans, wheat, rice, potatoes, cotton, sugar cane, tobacco and oilseed rape. A particularly emphasized property ("trait") is the enhanced resistance of the plant to insects, arachnids, nematodes and slugs and snails.

[0386] Plant protection — Type of treatment

[0387] The compounds of formula (I) are used for direct treatment of plants and plant parts using conventional treatment methods or by acting on their environment, habitat or storage space. The conventional treatment methods include, for example, dipping, spraying, atomizing, irrigation, evaporation, dusting, fogging, sowing, foaming, smearing, spreading, injection, watering (irrigation), drip irrigation, and in the case of propagation material, especially seeds, also by dry seed treatment, wet seed treatment, slurry treatment, crusting, treatment by coating with one or more layers, etc. The compounds of formula (I) can also be applied by the ultra-low volume method or injected into the soil in the form of the application form or the compound of formula (I) itself.

[0388] A preferred direct treatment of plants is foliar application, i.e., applying the compound of formula (I) to the leaf surface. In this case, the treatment frequency and application rate should be adjusted according to the infestation level of the pests.

[0389] In the case of systemic active compounds, the compounds of formula (I) also enter the plants via the root system. Thus, the plants are treated by acting on the habitat of the plants. This can be done, for example, by irrigation; or by mixing into the soil or nutrient solution, which means that the growth site of the plants (such as soil or hydroponic system) is impregnated with the compound of formula (I) in liquid form; or by soil application, which means introducing the compound of formula (I) of the present invention in solid form (such as in the form of granules) into the growth site of the plants. In the case of rice crops, this can also be done by metering the compound of formula (I) in solid application form (such as as granules) into the rice paddy.

[0390] Seed treatment

[0391] It has long been known to control animal pests by treating plant seeds and this has been the subject of continuous improvement. However, seed treatment involves a series of problems that cannot always be solved in a satisfactory manner. Therefore, there is a need to develop methods for protecting seeds and germinating plants that do not require or at least significantly reduce the additional application of pesticides during storage, after sowing or after emergence of the plants. In addition, there is a need to optimize the amount of active compound used in order to provide optimal protection for seeds and germinating plants against animal pests without damaging the plants themselves. In particular, the method of treating seeds should also take into account the inherent insecticidal or nematicidal properties of pest-resistant or pest-tolerant transgenic plants in order to achieve optimal protection for seeds and germinating plants with the least amount of pesticides.

[0392] Accordingly, in particular, the present invention also relates to a method for protecting seeds and germinating plants from pests by treating the seeds with one of the compounds of formula (I). The method for protecting seeds and germinating plants from pests according to the present invention also includes a method of treating the seeds with the compound of formula (I) and a mixing component simultaneously or sequentially in one operation. It also includes a method of treating the seeds with the compound of formula (I) and the mixing component at different times.

[0393] The present invention also relates to the use of the compound of formula (I) for treating seeds to protect the seeds and the resulting plants from animal pests.

[0394] The present invention also relates to seeds treated with the compound of formula (I) according to the present invention to protect them from animal pests. The present invention also relates to seeds treated simultaneously with the compound of formula (I) and a mixing component. The present invention also relates to seeds treated with the compound of formula (I) and the mixing component at different times. In the case of seeds treated with the compound of formula (I) and the mixing component at different times, the substances can be present on the seeds in different layers. In this case, the layer containing the compound of formula (I) and the mixing component can optionally be separated by an intermediate layer. The present invention also relates to seeds in which the compound of formula (I) and the mixing component are applied as part of a coating or as another layer or other layers in addition to the coating.

[0395] The present invention also relates to seeds that, after being treated with the compound of formula (I), are subjected to a film coating process to prevent the seeds from being worn by dust.

[0396] When the compound of formula (I) acts systemically, one of the advantages is that the treatment of the seeds not only protects the seeds themselves but also protects the plants obtained therefrom from animal pests after emergence. In this way, it is not necessary to immediately treat the crop at the time of sowing or shortly thereafter.

[0397] Another advantage is that treating the seeds with the compound of formula (I) can promote the germination and emergence of the treated seeds.

[0398] It is also considered advantageous that the compound of formula (I) can also be particularly used for transgenic seeds.

[0399] The compound of formula (I) can also be used in combination with a signaling technology composition, thereby resulting in better colonization of symbionts (such as rhizobia, mycorrhizae, and / or endophytic bacteria or fungi), and / or optimized nitrogen fixation.

[0400] The compounds of formula (I) are suitable for protecting the seeds of any plant variety used in agriculture, greenhouses, forestry or horticulture. More specifically, they are the seeds of the following plants: cereals (e.g. wheat, barley, rye, millet and oats), maize, cotton, soybeans, rice, potatoes, sunflowers, coffee, tobacco, canola, rapeseed, sugar beet (e.g. sugar beet and fodder beet), peanuts, vegetables (e.g. tomatoes, cucumbers, beans, cruciferous vegetables, onions and lettuce), fruit plants, lawn plants and ornamental plants. It is particularly important to treat the seeds of cereals (wheat, barley, rye, oats), maize, soybeans, cotton, canola, rapeseed, vegetables and rice.

[0401] As mentioned above, it is also particularly important to treat transgenic seeds with the compounds of formula (I). This includes the seeds of plants that usually contain at least one heterologous gene that controls the expression of polypeptides having in particular insecticidal and / or nematicidal properties. The heterologous genes in transgenic seeds can be derived from microorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium. The present invention is particularly suitable for treating transgenic seeds containing at least one heterologous gene derived from the genus Bacillus. The heterologous gene is more preferably derived from Bacillus thuringiensis.

[0402] In the context of the present invention, the compounds of formula (I) are applied to the seeds. The seeds are preferably treated in a state such that they are stable enough so that no damage occurs during the treatment. Generally, the seeds can be treated at any time between harvesting and sowing. Seeds that have been separated from the plant and from which the rachis, husk, stem, pod, hair or pulp have been removed are usually used. For example, seeds that have been harvested, cleaned and dried to a moisture content that allows storage can be used. Alternatively, seeds that have been treated with water after drying and then redried (e.g. primed) can also be used. In the case of rice seeds, seeds that have been soaked in water until they reach a certain stage of the rice embryo (the "pigeon breast" stage) can also be used, which results in stimulation of germination and more uniform emergence.

[0403] When treating the seeds, it is generally necessary to ensure that the amount of the compound of formula (I) and / or the amount of other additives applied to the seeds is selected such that it does not have an adverse effect on the germination of the seeds or damage the resulting plants. This must be ensured especially for active compounds that may exhibit phytotoxic effects at certain application rates.

[0404] Generally, the compounds of formula (I) are applied to seeds in a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art.

[0405] The compounds of formula (I) can be converted into conventional seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other seed coating compositions, as well as ULV formulations.

[0406] These formulations are prepared in a known manner by mixing the compounds of formula (I) with conventional additives, such as conventional extenders and solvents or diluents, dyes, wetting agents, dispersants, emulsifiers, defoamers, preservatives, secondary thickeners, adhesives, gibberellins and water.

[0407] Suitable dyes that can be present in the seed dressing formulations that can be used according to the invention are all dyes commonly used for this purpose. Pigments slightly soluble in water or water-soluble dyes can be used. Examples include the dyes known by the names Rhodamine B, C.I. Pigment Red 112 and C.I. Solvent Red 1.

[0408] Useful wetting components that can be present in the seed dressing formulations that can be used according to the invention are all substances that promote wetting and are commonly used for formulating agrochemical active compounds. Alkyl naphthalenesulfonates, such as diisopropyl naphthalenesulfonate or diisobutyl naphthalenesulfonate, are preferably used.

[0409] Suitable dispersants and / or emulsifiers that can be present in the seed dressing formulations that can be used according to the invention are all nonionic, anionic and cationic dispersants commonly used for formulating agrochemical active compounds. Nonionic or anionic dispersants, or mixtures of nonionic or anionic dispersants, can be preferably used. Suitable nonionic dispersants particularly include ethylene oxide / propylene oxide block polymers, alkylphenol polyethylene glycol ethers and triphenylvinylphenol polyethylene glycol ethers, and their phosphorylated or sulfated derivatives. Suitable anionic dispersants are particularly lignosulfonates, polyacrylates and arylsulfonate-formaldehyde condensates.

[0410] Defoamers that can be present in the seed dressing formulations that can be used according to the invention are all substances that inhibit foaming and are conventionally used for formulating agrochemical active compounds. Silicone defoamers and magnesium stearate can be preferably used.

[0411] Preservatives that can be present in the seed dressing formulations that can be used according to the invention are all substances that can be used for this purpose in agrochemical compositions. Examples include dichlorophenol and benzyl alcohol hemiformal.

[0412] Useful secondary thickeners that can be present in the seed dressing preparations that can be used according to the invention are all substances that can be used for this purpose in agrochemical compositions. Preferred examples include cellulose derivatives, acrylic derivatives, xanthan gum, modified clays, and finely divided silica.

[0413] Useful adhesives that can be present in the seed dressing preparations that can be used according to the invention are all conventional adhesives that can be used in seed dressing products. Preferred examples include polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol, and methylcellulose.

[0414] Useful gibberellins that can be present in the seed dressing preparations that can be used according to the invention are preferably gibberellin A1, A3 (= gibberellic acid), A4, and A7; gibberellic acid is particularly preferably used. The gibberellins are known (see R. Wegler "Chemie der Pflanzenschutz-und ", Volume 2, Springer Verlag, 1970, pages 401-412).

[0415] The seed dressing preparations that can be used according to the invention can be used, directly or after prior dilution with water, to treat various different types of seeds. For example, the concentrate or the preparation obtainable therefrom by dilution with water can be used to dress the seeds of the following plants: cereals (such as wheat, barley, rye, oats, and triticale), as well as maize, rice, rape, peas, beans, cotton, sunflowers, soybeans, and sugar beets, or various different vegetables. The seed dressing preparations that can be used according to the invention or their diluted application forms can also be used to dress the seeds of transgenic plants.

[0416] For treating seeds with the seed dressing preparations that can be used according to the invention or the application forms prepared therefrom by adding water, all conventional mixing devices for seed dressing are useful. Specifically, the seed dressing process involves placing the seeds in a mixer operating in batch mode or continuous mode; adding the specifically required amount of the seed dressing preparation (either in itself or after prior dilution with water); and mixing until the preparation is evenly distributed on the seeds. If appropriate, a drying operation is then carried out.

[0417] The application rate of the seed dressing preparations that can be used according to the invention can vary within a wide range. This is determined by the specific content of the compound of formula (I) in the preparation and the seeds. The application rate of the compound of formula (I) is generally 0.001 to 50 g / kg of seeds, preferably 0.01 to 15 g / kg of seeds.

[0418] Animal health

[0419] In the field of animal health, i.e. veterinary medicine, the compounds of formula (I) are active against animal parasites, especially ectoparasites or endoparasites. The term "endoparasite" particularly includes worms and protozoa such as coccidia. Ectoparasites are generally and preferably arthropods, especially insects or mites.

[0420] In the field of veterinary medicine, the compounds of formula (I) with favorable warm-blooded animal toxicity are suitable for controlling parasites that occur in animal breeding and animal husbandry in domestic animals, breeding animals, zoo animals, laboratory animals, experimental animals and domestic pets. They are active against all or specific developmental stages of the parasites.

[0421] Agricultural domestic animals include, for example, mammals such as sheep, goats, horses, donkeys, camels, buffaloes, rabbits, reindeer, fallow deer, especially cattle and pigs; or poultry such as turkeys, ducks, geese, especially chickens; or fish or crustaceans, such as in aquaculture; or, as the case may be, insects such as bees.

[0422] Domestic pets include, for example, mammals such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets, especially dogs, cats, caged birds; reptiles, amphibians or ornamental fish.

[0423] In a specific embodiment, the compounds of formula (I) are administered to mammals.

[0424] In another specific embodiment, the compounds of formula (I) are administered to birds, i.e. caged birds or especially poultry.

[0425] The use of the compounds of formula (I) to control animal parasites aims to reduce or prevent diseases, mortality cases and performance degradation (in the case of meat, milk, hair, skin, eggs, honey, etc.), thereby making animal husbandry more economical and simpler and achieving better animal health.

[0426] In the context of this article, with regard to the field of animal health, the term "control" (control or controlling) means that the compounds of formula (I) effectively reduce the incidence of a specific parasite in an animal infected with the parasite to a harmless level. More specifically, in the context of this article, "control" means that the compounds of formula (I) kill various parasites, inhibit their growth or inhibit their proliferation.

[0427] Arthropods include, but are not limited to, for example:

[0428] Anoplurida, such as Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp. and Solenopotes spp.;

[0429] Mallophagida and Amblycerina and Ischnocerina, such as Bovicola spp., Damalina spp., Felicola spp., Lepikentron spp., Menopon spp., Trichodectes spp., Trimenopon spp., Trinoton spp., Werneckiella spp.;

[0430] Diptera, Nematocerina, Brachycerina, such as Aedes spp., Anopheles spp., Atylotus spp., Braula spp., Calliphora spp., Chrysomyia spp., Chrysops spp., Culex spp., Culicoides spp., Eusimulium spp., Fannia spp., Gasterophilus spp., Glossina spp., Haematobia spp., Haematopota spp., Hippobosca spp., Hybomitra spp., Hydrotaea spp., Hypoderma spp., Lipoptena spp., Lucilia spp., Lutzomyia spp., Melophagus spp., Morellia spp., Musca spp., Odagmia spp., Oestrus spp., Philipomyia, Phlebotomus spp., Rhinoestrus spp., Sarcophaga spp., Simulium spp., Stomoxys spp., Tabanus spp., Tipula spp., Wilhelmia spp., Wohlfahrtia spp.;

[0431] Siphonapterida, such as Ceratophyllus spp., Ctenocephalides spp., Pulex spp., Tunga spp., Xenopsylla spp.;

[0432] Heteropterida, such as Cimex spp., Panstrongylus spp., Rhodnius spp., Triatoma spp.; and nuisance and sanitary pests from Blattarida.

[0433] Furthermore, in the case of arthropods, mention should be made of, for example but not limited to, the following Acari:

[0434] Subclass Acari (order Acarina) and Metastigmata, such as family Argasidae, e.g., genus Argas spp., Ornithodorus spp., Otobius spp.; family Ixodidae, e.g., genus Amblyomma spp., Dermacentor spp., Haemophysalis spp., Hyalomma spp., Ixodes spp., Rhipicephalus (Boophilus) spp., Rhipicephalus spp. (the original genus of multi-host ticks); Mesostigmata, such as genus Dermanyssus spp., Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Sternostoma spp., Tropilaelaps spp., Varroa spp.; Actinedida (Prostigmata), such as genus Acarapis spp., Cheyletiella spp., Demodex spp., Listrophorus, Myobia spp., Neotrombicula spp., Ornithocheyletia spp., Psorergates spp., Trombicula spp.; and Acaridida (Astigmata), such as genus Acarus spp., Caloglyphus spp., Chorioptes spp., Cytodites spp., Hypodectes spp., Knemidocoptes spp., Laminosioptes spp., Notoedres spp., Otodectes spp., Psoroptes spp., Pterolichus spp.) Sarcoptes spp., Trixacarus spp., Tyrophagus spp.

[0435] Examples of parasitic protozoa include, but are not limited to:

[0436] Mastigophora (Flagellata), for example:

[0437] Metamonada: Diplomonadida, such as Giardia spp., Spironucleus spp.

[0438] Parabasala: Trichomonadida, such as Histomonas spp., Pentatrichomonas spp., Tetratrichomonas spp., Trichomonas spp., Tritrichomonas spp.

[0439] Euglenozoa: Trypanosomatida, such as Leishmania spp., Trypanosoma spp.

[0440] Sarcomastigophora (Rhizopoda), for example Entamoebidae, such as Entamoeba spp., Centramoebidae, such as Acanthamoeba sp., Euamoebidae, such as Harmanella sp.

[0441] Alveolata, such as Apicomplexa (Sporozoa): such as Cryptosporidium spp.; Eimeriida, for example Besnoitia spp., Cystoisospora spp., Eimeria spp., Hammondia spp., Isospora spp., Neospora spp., Sarcocystis spp., Toxoplasma spp.; Adeleida, for example Hepatozoon spp., Klossiella spp.; Haemosporida, for example Leucocytozoon spp., Plasmodium spp.; Piroplasmida, for example Babesia spp., Ciliophora spp., Echinozoon genus, Theileria spp.; Vesibuliferida, for example Balantidium spp., Buxtonella spp.

[0442] Microspora, such as Encephalitozoon spp., Enterocytozoon spp., Globidium spp., Nosema spp., and for example Myxozoa spp.

[0443] Worms pathogenic to humans or animals include, for example, Acanthocephala, nematodes, Pentastoma, and Platyhelminthes (such as Monogenea, cestodes, and trematodes).

[0444] Exemplary worms include, but are not limited to:

[0445] Monogenea: e.g., Dactylogyrus spp., Gyrodactylus spp., Microbothrium, Polystoma spp., Troglecephalus;

[0446] Cestoda: Pseudophyllidea, e.g., Bothridium spp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium, Ligula spp., Schistocephalus, Spirometra spp.;

[0447] Cyclophyllidea, e.g., Andyra, Anoplocephala spp., Avitellina spp., Bertiella spp., Cittotaenia spp., Davainea spp., Diorchis spp., Diplopylidium spp., Dipylidium caninum, Echinococcus spp., Echinocotyle spp., Echinolepis spp., Hydatigera spp., Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paranoplocehala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma;

[0448] Trematodes: selected from the class Digenea, such as: Austrobilharzia spp., Brachylaima spp., Calicophoron spp., Catatropis spp., Clonorchis spp., Collyriclum spp., Cotylophoron spp., Cyclocoelum spp., Dicrocoelium spp., Diplostomum spp., Echinochasmus spp., Echinoparyphium spp., Echinostoma spp., Eurytema spp., Fasciola spp., Fascioloides spp., Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp., Gigantoctyle spp., Heterophyes spp., Hypoderaeum spp., Leucochloridium spp., Metagonimus spp., Metorchis spp., Nanophyetus spp., Notocotylus spp., Opisthorchis spp., Ornithobilharzia spp., Paragonimus spp., Paramphistomum spp., Plagiorchis spp., Posthodiplostomum spp., Prosthogonimus spp., Schistosoma spp., Trichobilharzia spp., Troglotrema spp., Typhlocoelum spp.;

[0449] Nematodes: Trichinellida, e.g., Capillaria spp., Trichinella spp., Trichomosoides, Trichuris spp.;

[0450] Tylenchida, e.g., Micronema spp., Parastrangyloides, Strongyloides spp.;

[0451] Order Rhabditida, for example: Aelurostrongylus spp., Amidostomum spp., Ancylostoma spp., Angiostrongylus spp., Bronchonema, Bunostomum spp., Chabertia spp., Cooperia spp., Cooperioides, Crenosoma spp., Cyathostomum spp., Cyclococercus, Cyclodontostomum, Cylicocyclus spp., Cylicostephanus spp., Cylindropharynx spp., Cystocaulus spp., Dictyocaulus spp., Elaphostrongylus spp., Filaroides spp., Globocephalus spp., Graphidium spp., Gyalocephalus spp., Haemonchus spp., Heligmosomoides spp., Hyostrongylus spp., Marshallagia spp., Metastrongylus spp., Muellerius spp., Necator spp., Nematodirus spp., Neostrongylus spp., Nippostrongylus spp., Obeliscoides spp., Oesophagodontus spp., Oesophagostomum spp., Ollulanus spp., Ornithostrongylus spp., Oslerus spp., Ostertagia spp., Paracooperia spp.) Paracrenosoma, Parafilaroides spp., Parelaphostrongylus spp., Pneumocaulus spp., Pneumostrongylus spp., Poteriostomum spp., Protostrongylus spp., Spicocaulus, Stephanurus spp., Strongylus spp., Syngamus spp., Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp., Troglostrongylus spp., Uncinaria spp.;.

[0452] Spirurida, such as: Acanthocheilonema spp., Anisakis spp., Ascaridia spp., Ascaris spp., Ascarops spp., Aspiculuris spp., Baylisascaris spp., Brugia spp., Cercopithifilaria spp., Crassicauda spp., Dipetalonema spp., Dirofilaria spp., Dracunculus spp., Draschia spp., Enterobius spp., Filaria spp., Gnathostoma spp., Gongylonema spp., Habronema spp., Heterakis spp.; Litomosoides spp., Loa spp., Onchocerca spp., Oxyuris spp., Parabronema spp., Parafilaria spp., Parascaris spp., Passalurus spp., Physaloptera spp., Probstmayria spp., Pseudofilaria spp., Setaria spp., Skjrabinema spp., Spirocerca spp., Stephanofilaria spp., Strongyluris spp., Syphacia spp., Thelazia spp., Toxascaris spp., Toxocara spp., Wuchereria spp.;

[0453] Class Acanthocephala: Order Oligacanthorhynchida, such as Macracanthorhynchus spp., Prosthenorchis spp.; Order Moniliformida, such as Moniliformis spp.;

[0454] Order Polymorphida, such as Filicollis spp.; Order Echinorhynchida, such as Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.;

[0455] Phylum Pentastoma: Order Porocephalida, such as Linguatula spp.

[0456] In the field of veterinary medicine and animal husbandry, the compounds of formula (I) are administered in a suitable formulation by methods generally known in the art (e.g., enterally, parenterally, dermally or nasally). The administration can be prophylactic, metaphylactic or therapeutic.

[0457] Accordingly, one embodiment of the present invention relates to the compounds of formula (I) for use as medicaments.

[0458] Another aspect relates to the compounds of formula (I) for use as anti-endoparasitic agents.

[0459] Another specific aspect of the present invention relates to the compounds of formula (I) for use as anti-helminthics, especially as nematocides, trematocides, acanthocephalocides or pentastomacides.

[0460] Another specific aspect of the present invention relates to the compounds of formula (I) for use as antiprotozoal agents.

[0461] Another aspect relates to the compounds of formula (I) for use as anti-ectoparasitic agents, especially as arthropodicides, very particularly as insecticides or acaricides.

[0462] Other aspects of the invention are veterinary pharmaceutical preparations which comprise an effective amount of at least one compound of formula (I) and at least one of the following: a pharmaceutically acceptable excipient (such as a solid or liquid diluent), a pharmaceutically acceptable adjuvant (such as a surfactant), in particular a pharmaceutically acceptable excipient conventionally used in veterinary pharmaceutical preparations and / or a pharmaceutically acceptable adjuvant conventionally used in veterinary pharmaceutical preparations.

[0463] A related aspect of the invention is a process for preparing a veterinary pharmaceutical preparation as described herein, which comprises the step of mixing at least one compound of formula (I) with a pharmaceutically acceptable excipient and / or adjuvant, in particular with a pharmaceutically acceptable excipient conventionally used in veterinary pharmaceutical preparations and / or a pharmaceutically acceptable adjuvant conventionally used in veterinary pharmaceutical preparations.

[0464] Another specific aspect of the invention is a veterinary pharmaceutical preparation and a process for its preparation, said veterinary pharmaceutical preparation being selected from ectoparasiticide preparations and endoparasiticide preparations, in particular from anthelmintic, antiprotozoal and arthropodicidal preparations of the above aspects, very particularly from nematocidal, trematocidal, acanthocephalocidal, linguatulicidal, insecticidal and acaricidal preparations.

[0465] Another aspect relates to a method for treating a parasitic infection by using an effective amount of a compound of formula (I) in an animal in need, in particular a non-human animal, in particular a method for treating an infection caused by a parasite selected from the ectoparasites and endoparasites mentioned herein.

[0466] Another aspect relates to a method for treating a parasitic infection by using a veterinary pharmaceutical preparation as defined herein in an animal in need, in particular a non-human animal, in particular a method for treating an infection caused by a parasite selected from the ectoparasites and endoparasites mentioned herein.

[0467] Another aspect relates to the use of a compound of formula (I) in the treatment of parasitic infections in animals, in particular non-human animals, in particular infections caused by parasites selected from the ectoparasites and endoparasites mentioned herein.

[0468] In the context of animal health or veterinary medicine of the present invention, the term "treatment" includes prophylactic, palliative or therapeutic treatment.

[0469] In a specific embodiment, in this way, a mixture of at least one compound of formula (I) with other active compounds, in particular with endoparasiticides and ectoparasiticides, is provided for use in the field of veterinary medicine.

[0470] In the field of animal health, a "mixture" refers not only to the formulation of two (or more) different active compounds in a conventional formulation and their corresponding use together, but also to a product comprising separate formulations for each active compound. Thus, when more than two active compounds are used, all the active compounds can be formulated in a conventional formulation or all the active compounds can be formulated in separate formulations; it can also be in a mixed form, in which some active compounds are formulated together and some active compounds are formulated separately. The separate formulations can be used to administer the active compounds either separately or sequentially.

[0471] The active compounds mentioned herein by their common names are known and are described, for example, in the "Pesticide Manual" (see above), or can be retrieved on the Internet (e.g. http: / / www.alanwood.net / pesticides ).

[0472] Exemplary active compounds of ectoparasiticides as mixing components include, but are not limited to any intention, the insecticides and acaricides listed in detail above. Other active compounds that can be used are listed below according to the above classification based on the current IRAC mode of action classification scheme: (1) acetylcholinesterase (AChE) inhibitors; (2) GABA-gated chloride channel blockers; (3) sodium channel modulators; (4) nicotinic acetylcholine receptor (nAChR) competitive modulators; (5) nicotinic acetylcholine receptor (nAChR) allosteric modulators; (6) glutamate-gated chloride channel (GluCl) allosteric modulators; (7) juvenile hormone mimics; (8) other non-specific (multi-site) inhibitors; (9) chordotonal organ modulators; (10) mite growth inhibitors; (12) mitochondrial ATP synthase inhibitors, such as ATP disruptors; (13) uncouplers of oxidative phosphorylation by blocking the proton gradient; (14) nicotinic acetylcholine receptor channel blockers; (15) chitin biosynthesis inhibitors, type 0; (16) chitin biosynthesis inhibitors, type 1; (17) molting disruptors (especially for Diptera); (18) ecdysteroid receptor agonists; (19) octopamine receptor agonists; (21) mitochondrial complex I electron transport inhibitors; (25) mitochondrial complex II electron transport inhibitors; (20) mitochondrial complex III electron transport inhibitors; (22) voltage-dependent sodium channel blockers; (23) acetyl-CoA carboxylase inhibitors; (28) ryanodine receptor modulators;

[0473] Active compounds with unknown or non-specific mechanisms of action, such as fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimin, dicyclanil, amidoflumet, quinomethionat, triarathene, clothiazoben, tetrasul, potassium oleate, petroleum, metoxadiazone, gossyplur, flutenzine, brompropylate, cryolite;

[0474] Other types of compounds, such as butacarb, dimetilan, cloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl), methacrifos, isopropylo-salicylate, trichlorfon, sulprofos, propaphos, sebufos, pyridathion, prothoate, dichlofenthion, demeton-S-methyl sulfone, isazofos, cyanofenphos, dialifos, carbophenothion, autathiofos, aromfenvinfos (-methyl), azinphos (-ethyl), chlorpyrifos (-ethyl), fosmethilan, iodofenphos, dioxabenzofos, formothion, fonofos, flupyrazofos, fensulfothion, etrimfos;

[0475] Organochlorides, such as camphechlor, lindane, heptachlor; or phenylpyrazoles, such as acetoprole, pyrafluprole, pyriprole, vaniliprole, sisapronil; or isoxazolines, such as sarolaner, afoxolaner, lotilaner, fluralaner;

[0476] Pyrethroids, such as (cis-, trans-) metofluthrin, profluthrin, flufenprox, flubrocythrinate, fubfenprox, fenfluthrin, protrifenbut, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin, biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocythrin, cyhalothrin (lambda-), chlovaporthrin, or halogenated hydrocarbon compounds (HCH),

[0477] Neonicotinoids, such as nithiazine;

[0478] dicloromezotiaz, triflumezopyrim;

[0479] Macrolides, such as nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate; milbemycin oxime

[0480] methoprene, epofenonane, diofenolan;

[0481] biological agents, hormones or pheromones, such as natural products, such as thuringiensin, codlemone or neem components

[0482] dinitrophenols, such as dinocap, dinobuton, binapacryl;

[0483] benzoylureas, such as fluazuron, penfluron,

[0484] amidine derivatives, such as chlormebuform, cymiazole, demiditraz

[0485] beehive varroa acaricides, such as organic acids, such as formic acid, oxalic acid.

[0486] Exemplary active compounds of endoparasiticides as mixed components include, but are not limited to, active anthelmintic compounds and active antiprotozoic compounds.

[0487] Active anthelmintic components include, but are not limited to, the following active nematocidal, trematicidal and / or cestocidal components:

[0488] macrolides, such as: eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemectin, ivermectin, emamectin, milbemycin;

[0489] Benzimidazoles and probenzimidazoles, such as: oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole, oxfendazole, netobimin, fenbendazole, febantel, thiabendazole, cyclobendazole, cambendazole, albendazole sulfoxide, albendazole, flubendazole;

[0490] Peptoids, preferably cyclic peptoids, especially 24-membered cyclic peptoids, such as: emodepside, PF1022A;

[0491] Tetrahydropyrimidines, such as: morantel, pyrantel, oxantel;

[0492] Imidazothiazoles, such as: butamisole, levamisole, tetramisole;

[0493] Aminophenylamidines, such as: amidantel, deacylated amidantel (dAMD), tribendimidine;

[0494] Aminoacetonitriles, such as: monepantel;

[0495] Paraherquamide, such as: paraherquamide, derquantel;

[0496] Salicylanilides, such as: tribromsalan, bromoxanide, brotianide, clioxanide, closantel, niclosamide, oxyclozanide, rafoxanide;

[0497] Substituted phenols, such as: nitroxynil, bithionol, disophenol, hexachlorophen, niclofolan, meniclopholan;

[0498] Organophosphates, such as: trichlorfon, naphthalofos, dichlorvos / DDVP, crufomate, coumaphos, haloxon;

[0499] Piperazinone / quinolines, such as: praziquantel, epsiprantel;

[0500] Piperazines, such as: piperazine, hydroxyzine;

[0501] Tetracyclines, such as: tetracycline, chlorotetracycline, doxycycline, oxytetracycline, rolitetracycline;

[0502] Various other types, such as: bunamidine, niridazole, resorantel, omphalotin, oltipraz, nitroscanate, nitroxynil, oxamniquin, mirasan, miracil, lucanthon, hycanthon, hetolin, emetin, diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium, amoscanate, clorsulon.

[0503] Active anti - protozoal compounds include, but are not limited to, the following active compounds:

[0504] Triazines, such as: diclazuril, ponazuril, letrazuril, toltrazuril;

[0505] Polyether ionophores, such as: monensin, salinomycin, maduramicin, narasin;

[0506] Macrolides, such as: milbemycin, erythromycin;

[0507] Quinolones, such as: enrofloxacin, pradofloxacin;

[0508] Quinine, such as: chloroquin;

[0509] Pyrimidines, such as: pyrimethamine;

[0510] Sulfonamides, such as: sulfaquinoxaline, trimethoprim, sulfaclozin;

[0511] Thiamines, such as: amprolium;

[0512] Lincosamides, such as: clindamycin;

[0513] Carbanilides, such as: imidocarb;

[0514] Nitrofurans, such as: nifurtimox;

[0515] Quinazolinone alkaloids, such as: halofuginone;

[0516] Various other types, such as: oxamniquin, paromomycin;

[0517] Vaccines or antigens from microorganisms, such as Babesia canis rossi, Eimeria tenella, Eimeria praecox, Eimeria necatrix, Eimeria mitis, Eimeria maxima, Eimeria brunetti, Eimeria acervulina, Babesia canis vogeli, Leishmania infantum, Babesia canis canis, Dictyocaulus viviparus.

[0518] Optionally, all of the mixed components mentioned may also form salts with suitable bases or acids, if they are capable of forming salts based on their functional groups.

[0519] Vector control

[0520] The compounds of formula (I) can also be used for vector control. In the context of the present invention, vectors are arthropods, especially insects or arachnids, which are capable of transmitting pathogens such as viruses, worms, single-celled organisms and bacteria from reservoirs (plants, animals, humans, etc.) to hosts. Pathogens can be transmitted mechanically to the host (e.g., trachoma is transmitted by non-stinging flies), or can be transmitted to the host after injection (e.g., malaria parasites are transmitted by mosquitoes).

[0521] Examples of vectors and the diseases or pathogens they transmit are:

[0522] 1) Mosquitoes

[0523] - Anopheles: malaria, filariasis;

[0524] - Culex: Japanese encephalitis, filariasis, other viral diseases, other worm transmissions;

[0525] - Aedes: yellow fever, dengue fever, other viral diseases, filariasis;

[0526] - Simuliidae: worm transmission, especially Onchocerca volvulus;

[0527] - Psychodidae: Leishmaniasis transmission;

[0528] 2) Lice: Skin infections, epidemic typhus;

[0529] 3) Fleas: Plague, endemic typhus, tapeworms;

[0530] 4) Flies: Sleeping sickness (trypanosomiasis); Cholera, other bacterial diseases;

[0531] 5) Mites: Tick-borne diseases, epidemic typhus, rickettsialpox, tularemia, Saint Louis encephalitis, tick-borne encephalitis (TBE), Crimean-Congo haemorrhagic fever, borreliosis;

[0532] 6) Ticks: Borrellioses, such as Borrelia bungdorferi sensu lato., Borrelia duttoni, tick-borne encephalitis, Q fever (Coxiella burnetii), babesia (Babesia canis canis), ehrlichiosis.

[0533] In the context of the present invention, examples of vectors are insects, such as aphids, flies, leafhoppers or thrips, which can transmit plant viruses to plants. Other vectors capable of transmitting plant viruses are spider mites, lice, beetles and nematodes.

[0534] In the context of the present invention, other examples of vectors are insects and arachnids, such as mosquitoes, especially of the genera Aedes, Anopheles, such as Anopheles gambiae, Anopheles arabiensis, Anopheles funestus, Anopheles dirus (malaria) and Culex, Psychodidae, such as Phlebotomus, Sergentomyia, lice, fleas, flies, mites and ticks, which can transmit pathogens to animals and / or humans.

[0535] Vector control is also possible if the compound of formula (I) is resistance-breaking.

[0536] The compounds of formula (I) are suitable for preventing vector-borne diseases and / or pathogens. Accordingly, another aspect of the present invention is the use of the compounds of formula (I) for vector control, for example, in agriculture, horticulture, forestry, landscaping and leisure equipment, and in the protection of materials and stored products.

[0537] Protection of industrial materials

[0538] The compounds of formula (I) are suitable for protecting industrial materials against infestation or damage by insects such as those from the Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psocoptera and Zygentoma.

[0539] In the context of the present invention, industrial materials are to be understood to mean inanimate materials, such as, preferably, plastics, adhesives, glues, paper and cardboard, leather, wood, processed wood products and coating compositions. Particular preference is given to the use of the present invention for protecting wood.

[0540] In another embodiment, the compounds of formula (I) are used together with at least one other insecticide and / or at least one fungicide.

[0541] In another embodiment, the compounds of formula (I) are in the form of ready-to-use pesticides, meaning that they do not require further modification before being applied to the materials. Useful other insecticides or fungicides particularly include those mentioned above.

[0542] Surprisingly, it has also been found that the compounds of formula (I) can be used to protect objects in contact with salt water or brackish water against fouling, said objects being in particular ship hulls, partitions, nets, buildings, mooring equipment and signalling systems. The compounds of formula (I) can also be used alone or in combination with other active compounds as antifouling compositions.

[0543] Control of animal pests in the hygiene field

[0544] The compounds of formula (I) are suitable for controlling animal pests in the hygiene field. More specifically, the present invention can be used in the field of indoor protection, hygiene protection and protection of stored products, in particular for controlling insects, arachnids, ticks and mites encountered in enclosed spaces such as, for example, dwellings, factory halls, offices, vehicle cabins, animal breeding facilities. For controlling animal pests, the compounds of formula (I) are used alone or in combination with other active compounds and / or adjuvants. They are preferably used in indoor insecticide products. The compounds of formula (I) are effective against sensitive and resistant species, and all their developmental stages.

[0545] These pests include, for example, the following pests: Arachnida, Scorpiones, Araneae and Opiliones; Chilopoda and Diplopoda; Insecta, Blattodea, Coleoptera, Dermaptera, Diptera, Heteroptera, Hymenoptera, Isoptera, Lepidoptera, Phthiraptera, Psocoptera, Saltatoria or Orthoptera, Siphonaptera and Zygentoma; Malacostraca, Isopoda.

[0546] Application is carried out as follows: for example, in aerosols, non - pressured spray products such as pump sprayers and atomizing sprayers, automatic atomizing systems, atomizers, foams, gels, evaporator products having an evaporator sheet made of cellulose or plastic, liquid evaporators, gel and film evaporators, propeller - driven evaporators, energy - free or passive evaporation systems, moth papers, moth bags, and moth glues, as granulates or powders, for baits or bait stations for broadcasting.

[0547] Preparation method

[0548] The compounds of the present invention can be prepared by conventional methods known to those skilled in the art.

[0549] Reaction Scheme I - Method A

[0550]

[0551] The compounds of formula (I) can be prepared, for example, in one or two steps according to Reaction Scheme I. The groups A 1 、A 2 、A 3 、A 4 、Z, X, R 5 、R 7 、R 8 and R 9 have the above - mentioned meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. Y represents O, S or NR 5 . Hal represents chlorine or bromine.

[0552] For example, using a halogenating agent, the alcohol of formula (A - I) can be converted into the benzyl halide of formula (A - II). Then they react in a second reaction step with the compound of formula (A - III) in a nucleophilic substitution reaction in the presence of a basic reaction auxiliary to obtain the compound of formula (I).

[0553] For the compounds of formula (I) in which Y represents oxygen, the reaction can also be carried out in a one - step method. Here, the benzyl alcohol of formula (A - I) is in - situ activated in the presence of a trialkylphosphine or triarylphosphine and an azodicarboxylate and reacts with the alcohol of formula (A - IV) in a nucleophilic substitution reaction to obtain the compound of formula (I).

[0554] Method A - Step 1: Compounds of formula (A-I) are known (e.g., [6-(4-ethylpiperazin-1-yl)pyridin-3-yl]methanol in WO2010 / 132999, tert-butyl 4-[3-chloro-5-(hydroxymethyl)pyridin-2-yl]piperazine-1-carboxylate in EP2050734, and tert-butyl 3-{[3-fluoro-5-(hydroxymethyl)pyridin-2-yl]amino}pyrrolidine-1-carboxylate in US2006 / 0052599), or can be obtained by known preparation methods. Other preparation methods thereof have been described in the present application, especially for (6-{2-[methoxy(methyl)amino]ethoxy}pyridin-3-yl)methanol and (3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol (see also Schemes II and VI).

[0555] For the halogenation reaction, many reaction conditions have been described. They are known to those skilled in the art. Houben-Weyl, Methoden der Organischen Chemie [Methods of Organic Chemistry], Volume V / 3 (Georg Thieme Verlag Stuttgart), page 760 gives a review for Hal = Cl, and Houben-Weyl, Methoden der Organischen Chemie, Volume V / 4 (Georg Thieme Verlag Stuttgart), page 361 gives a review for Hal = Br. Preferably, benzyl chlorides of formula (A-II) in which Hal represents chlorine are prepared. They can be prepared, for example, from benzyl alcohols of formula (A-I) in the presence of thionyl chloride. The reaction can be carried out in a suitable inert solvent or diluent (such as toluene or dichloromethane) and optionally in the presence of a catalytic amount of N,N-dimethylformamide (see, for example, 5-(chloromethyl)-2-(2,2,3,3-tetrafluoropropoxy)pyridine in WO2013 / 161312).

[0556] Method A - Step 2: Compounds of formula (A-III) are known, commercially available, or can be obtained by known preparation methods (see, for example, 5,6-dichloro-1-naphthol in WO2002017712). Other methods for preparing them have been described in the present application (see, for example, the preparation of 6-fluoro-3'-(trifluoromethoxy)biphenyl-3-ol and 4-chloro-3-methoxyphenol).

[0557] By heating in the presence of a basic reaction auxiliary such as potassium carbonate or cesium carbonate, a nucleophilic substitution reaction is carried out between the halide of formula (A-II) and the compound of formula (A-III) to obtain a compound in which Y represents O, S or NR 5Compound of formula (I). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone and acetonitrile. For Y = O or NR 5 , the reaction is preferably carried out at a temperature of 50 - 120 °C, and for Y = S, the reaction is preferably carried out at room temperature (see WO2015 / 089139 regarding Y = O, WO2013 / 019621 and WO2005 / 049572 regarding Y = NR 5 , and WO2012 / 082566 regarding Y = S).

[0558] Method A - Step 3: Compounds of formula (A-IV) are known, commercially available or obtainable by known preparation methods. Other methods for their preparation are described in this application (see, for example, the preparation of 6-fluoro-3'-(trifluoromethoxy)biphenyl-3-ol or 4-chloro-3-methoxyphenol).

[0559] The benzyl alcohol of formula (A-I) reacts with the alcohol of formula (A-IV) in a nucleophilic substitution reaction in the presence of a trialkylphosphine or triarylphosphine and an azodicarboxylate to give a compound of formula (I) in which Y represents oxygen. This reaction is known to those skilled in the art as the "Mitsunobu reaction". The phosphine used is preferably triphenylphosphine, and the azodicarboxylate used is preferably diethyl azodicarboxylate. The reaction is carried out in the presence of an inert solvent or diluent (such as tetrahydrofuran) (see, for example, WO2016 / 044789).

[0560] Reaction Scheme II - Method B

[0561]

[0562] Compounds of formula (I-B) can be prepared, for example, according to Reaction Scheme II. The groups A 1 、A 2 、A 3 、A 4 、Z、R 5 、R 8 and R 9 have the above meanings (wherein this method does not allow the formation of a ring between R 8 and R 6 or R 7 ), and optionally other meanings related to the preparation method, which are obvious in the context and in the text. Y represents O, S or NR 5 . Hal represents chlorine or bromine. Alk represents (C1-C3)-alkyl.

[0563] For example, the alcohol of formula (B-I) can react with 1,2-dibromoethane in a nucleophilic substitution reaction in the presence of a basic reaction auxiliary to obtain the compound of formula (B-II). In a subsequent step, the alkyl ester functional group in the compound of formula (B-II) can be reduced using a reducing agent to obtain the benzyl alcohol of formula (B-III). Using a halogenating agent, the benzyl alcohol of formula (B-III) can then be converted into the benzyl halide of formula (B-IV). Then, in another reaction step, they can subsequently react with the compound of formula (B-V) in a nucleophilic substitution reaction in the presence of a basic reaction auxiliary to obtain the compound of formula (B-VI). In another nucleophilic substitution reaction, the amine of formula (B-VII) can react with the bromide of formula (B-VI) to obtain the compound of formula (I-B).

[0564] Method B - Step 1:

[0565] The compound of formula (B-I) is known, commercially available or can be obtained by known preparation methods (see, for example, methyl 3-fluoro-5-hydroxypyridine-2-carboxylate in WO2011 / 044181).

[0566] The alcohol of formula (B-I) reacts with 1,2-dibromoethane in a nucleophilic substitution reaction in the presence of a basic auxiliary (such as potassium carbonate or cesium carbonate) and optionally in the presence of a catalytic amount of potassium iodide. The reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone and acetonitrile. The reaction is carried out at an elevated temperature, preferably at 50 °C to 120 °C (for example, where A 1 to A 4 represents -CH, see, for example, WO1998 / 48800).

[0567] Method B - Step 2:

[0568] The ester of formula (B-II) reacts in the presence of a suitable reducing agent (such as sodium borohydride or diisobutylaluminum hydride) to obtain the benzyl alcohol of formula (B-III). If the reaction is carried out in the presence of sodium borohydride, a suitable solvent or diluent is used, such as ethanol or methanol. Here, the reaction is preferably carried out at a temperature of 0 °C to 50 °C. If diisobutylaluminum hydride is used, the reaction is carried out in a suitable inert solvent (such as toluene or dichloromethane). Here, the reaction is preferably carried out at a temperature of -78 °C to +30 °C (see, for example, the synthesis of methyl 5-(2-bromoethoxy)-3-fluoropyridine-2-carboxylate described in this application). If diisobutylaluminum hydride is used, a mixture of the benzyl alcohol of formula (B-III) and a similar benzaldehyde can be obtained. In this case, in the second step, the aldehyde functional group is reduced to obtain the benzyl alcohol of formula (B-III). This reaction can be carried out under the above conditions in the presence of sodium hydride.

[0569] Method B - Step 3:

[0570] For the halogenation reaction, many reaction conditions have been documented. They are known to those skilled in the art and have been described in Step 1 of Method A.

[0571] Method B - Step 4: Compounds of formula (B-V) are known, commercially available, or can be obtained by known preparation methods. Other methods for preparing them are described in this application (see, for example, the preparation of 6-fluoro-3'-(trifluoromethoxy)biphenyl-3-ol or 4-chloro-3-methoxyphenol).

[0572] The compound of formula (B-VI) is obtained by reacting the halide of formula (B-IV) with the compound of formula (B-V) in a nucleophilic substitution reaction when heated in the presence of a basic reaction auxiliary (such as potassium carbonate or cesium carbonate). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone, and acetonitrile. This reaction is preferably carried out at a temperature of 50 °C to 120 °C.

[0573] Method B - Step 5: Compounds of formula (B-VII) are known, commercially available, or can be obtained by known preparation methods (see, for example, 1-(aminooxy)propane in EP0678504). Some are also known as their hydrochloride or hydrobromide salts and are commercially available.

[0574] Upon heating, the bromide of formula (B-VI) reacts with the compound of formula (B-VII) in a nucleophilic substitution reaction to obtain the compound of formula (I-B). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone, acetonitrile, and tetrahydrofuran. This reaction is optionally carried out in the presence of a basic reaction auxiliary (such as potassium carbonate, cesium carbonate, or N,N-diisopropylethylamine). This reaction is preferably carried out at a temperature of 10 °C to 120 °C (without basic reaction auxiliary: WO2006 / 078619, in the presence of K2CO3: WO2010 / 071885, in the presence of N,N-diisopropylethylamine: WO2006 / 105304).

[0575] Method B - Step 6:

[0576] Upon heating, the bromide of formula (B-III) reacts with the compound of formula (B-VII) in a nucleophilic substitution reaction to obtain the compound of formula (B-VIII). The reaction conditions correspond to those described in Step 5. They can be converted to the compound of formula (I-B) using Method A.

[0577] Reaction Scheme III - Method C

[0578]

[0579] The compounds of formula (I-C) can be prepared, for example, according to Reaction Scheme III. The groups A 1 、A 2 、A 3 、A 4 、Z, R 5 、R 7 、R 8 and R 9 have the above meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. Y represents O, S or NR 5 . Hal represents chlorine or bromine. LG represents fluorine or chlorine. Alk represents (C1-C5)-alkyl.

[0580] For example, the compounds of formula (C-I) can react with the compounds of formula (C-II) in a nucleophilic substitution reaction in the presence of a basic reaction auxiliary to obtain the compounds of formula (C-III). In a subsequent step, the compounds of formula (C-III) can be directly converted with the compounds of formula (C-IV) in a nucleophilic aromatic substitution reaction to obtain the compounds of formula (I-C). Alternatively, the compounds of formula (C-III) can react with the compounds of formula (C-V) in a nucleophilic aromatic substitution reaction to obtain the compounds of formula (C-VI). These compounds can be condensed with amines of formula (C-VII) or their hydrochlorides or hydrobromides to obtain the compounds of formula (C-VIII). The compounds of formula (C-VIII) can then be reduced in the first step and reacted with aldehydes of formula (C-IX) in a reductive amination reaction to obtain the compounds of formula (I-C).

[0581] According to another route for preparing the compounds of formula (C-VIII), the benzyl alcohol of formula (C-X) can react with the chloride of formula (C-XI), which first gives the compounds of formula (C-XII). After converting the alcohol to a halogen with a halogenating agent, this halogenated intermediate can react with the compounds of formula (C-II) in a nucleophilic substitution reaction to obtain the compounds of formula (C-VIII).

[0582] Method C - Step 1: The benzyl halides of formula (C-I) are known, commercially available or can be obtained by known preparation methods (see, for example, 2-chloro-5-(chloromethyl)pyridine of EP0366085 or 5-(bromomethyl)-2-chloropyrimidine of WO2014 / 028669).

[0583] The compound of formula (C-III) is obtained by reacting a benzyl halide of formula (C-I) with a compound of formula (C-II) in a nucleophilic substitution reaction by heating in the presence of a basic reaction auxiliary (such as potassium carbonate or cesium carbonate). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone and acetonitrile. This reaction is preferably carried out at a temperature of from 10 °C to 120 °C (see, for example, US 2003 / 0092739).

[0584] Method C - Step 2: The alcohol of formula (C-IV) is known, commercially available or can be obtained by known preparation methods (see, for example, 2-[methoxy(methyl)amino]ethanol in Journal of Organic Chemistry, 1957, 22, 579).

[0585] The compound of formula (I-C) is obtained by reacting the compound of formula (C-III) with the alcohol of formula (C-IV) in a nucleophilic aromatic substitution reaction in the presence of a basic reaction auxiliary (such as sodium hydride). This reaction is carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone and tetrahydrofuran. This reaction is preferably carried out at a temperature of from 0 °C to 120 °C (see, for example, LG = Cl in EP2236507 or LG = F in EP0135894).

[0586] Method C - Step 3: The compound of formula (C-III) is reacted with the compound of formula (C-V) in a nucleophilic aromatic substitution reaction to obtain the acetal of formula (C-VI). This reaction is carried out under the conditions described in Step 2 of Method C.

[0587] Method C - Step 4: The compound of formula (C-VII) is known, commercially available or can be obtained by known preparation methods (see, for example, 1-(aminooxy)propane in EP0678504). Some are also known as their hydrochloride or hydrobromide salts and are commercially available.

[0588] The acetal of formula (C-VI) is optionally reacted with the compound of formula (C-VII) or its hydrochloride or hydrobromide salt in a condensation reaction in the presence of an acid (such as p-toluenesulfonic acid) (see, for example, WO2012 / 038851) or a dehydrating agent (such as magnesium sulfate) (see, for example, WO2010 / 054024) to obtain the compound of formula (C-VIII). This reaction is carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are ethanol, methanol, acetonitrile, tetrahydrofuran and water, and mixtures of these solvents. This reaction is preferably carried out at a temperature of from 10 °C to 80 °C.

[0589] Method C - Step 5: The aldehyde of formula (C-IX) is known, commercially available, or obtainable by known preparation methods.

[0590] The compound of formula (C-VIII) can be converted into the compound of formula (I-C) in a two-step one-pot reaction. In the first step, the compound of formula (C-VIII) is first reacted in the presence of a reducing agent (such as sodium cyanoborohydride) to obtain an intermediate of formula (I-C) wherein R 8 represents hydrogen. This reaction is carried out at a temperature of 10 °C to 80 °C in the presence of a solvent or diluent (such as acetic acid).

[0591] In the second step, this intermediate is reacted with the aldehyde of formula (C-IX) in a reductive alkylation reaction in the presence of a reducing agent to obtain a compound of formula (I-C) wherein R 8 represents (C1-C6)-alkyl (which is optionally substituted on C2 to C6). This reaction is carried out at a temperature of 10 °C to 80 °C in the presence of a solvent or diluent (such as acetic acid).

[0592] Method C - Step 6: The compounds of formula (C-X) and formula (C-XI) are known, commercially available, or obtainable by known preparation methods. Other methods for preparing them are described in this application, for example, the preparation method of 2-fluoro-6-(hydroxymethyl)pyridin-3-ol.

[0593] In the presence of a basic reaction auxiliary (such as potassium carbonate or cesium carbonate), the compound of formula (C-X) reacts with the chloride of formula (C-XI) in a nucleophilic substitution reaction to obtain the compound of formula (C-XII). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone, and acetonitrile. This reaction is preferably carried out at a temperature of 20 °C to 120 °C.

[0594] Method C - Step 7: After converting the alcohol functional group into a halogen, the benzyl alcohol of formula (C-XII) can react with the compound of formula (C-II) in a nucleophilic substitution reaction to obtain the compound of formula (C-VIII). This reaction is carried out under the conditions described in Steps 1 and 2 of Method A.

[0595] Reaction Scheme IV - Method D

[0596]

[0597] The compound of formula (I-D) can be prepared, for example, according to Reaction Scheme IV. The groups A 1 、A 2 、X、Y、Z、R 7 、R 8 and R 9Having the above meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. Hal represents chlorine or fluorine. D represents O or S. Alk represents an optionally substituted (C1-C4)-alkyl group.

[0598] The compounds of formula (I-D') can be obtained by known preparation methods or methods similar to those described in the present application. Thiols and aldehydes (D-I) and their sodium salts are known, commercially available or can be obtained by known preparation methods. In the presence of a basic reaction auxiliary (such as sodium hydride), the compounds of formula (I-D') are reacted with the alcohols and thiols of formula (D-I) in a nucleophilic aromatic substitution reaction to obtain the compounds of formula (I-D). The sodium salts of the alcohols and thiols of formula (D-I) can also be used directly. In this case, the addition of a base is redundant. The reaction is carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-2-pyrrolidone and tetrahydrofuran. The reaction is preferably carried out at a temperature of 0 °C to 80 °C.

[0599] Reaction Scheme V - Method E

[0600]

[0601] The compounds of formula (I-E) can be prepared, for example, according to Reaction Scheme V. The group A 1 , A 2 , A 3 , A 4 , X, Y, R 7 , R 8 , R 9 and R 11 have the above meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. Hal represents bromine or iodine. Ar represents in each case an optionally substituted phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl or thiophen-3-yl.

[0602] In principle, the compounds of formula (I-E') can be obtained by known preparation methods or methods similar to those described in the present application. Boronic esters (E-I) and boronic acids (E-II) are known, commercially available or can be obtained by known preparation methods.

[0603] The compound of formula (I-E‘) reacts with an optionally substituted arylboronic acid (E-II) or arylboronic acid pinacol ester (E-I) in the presence of a suitable coupling catalyst (such as tetrakis(triphenylphosphine)palladium(0) or [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II)) and in the presence of a base (such as potassium carbonate or sodium carbonate) to give a compound of formula (I-E) (see, for example, WO2014 / 201206 or WO2016 / 059097). This reaction is carried out in an inert solvent or diluent. Examples that may be mentioned are 1,4-dioxane, toluene or tetrahydrofuran, optionally in combination with water in each case. This reaction is preferably carried out at a temperature of 40 °C to 120 °C.

[0604] Reaction Scheme VI - Method F

[0605]

[0606] The compounds of formula (F-VIII) and (F-IV) can be prepared, for example, according to Reaction Scheme VI. The groups A 1 、A 2 、A 3 、A 4 、R 6 、R 7 、R 8 and R 9 have the above meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. X represents O, NR 6 or S. LG 1 represents chlorine or fluorine. LG 2 represents chlorine or bromine. Alk represents an optionally substituted (C1-C5)-alkyl. D represents cyano, (C1-C3)-alkoxycarbonyl, formyl or CH2OPG. PG represents a protecting group, such as tert-butyldimethylsilyl. For the protecting groups of alcohols, their introduction and their removal are known to those skilled in the art. For example, a review is given in T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd Edition 1999 (Wiley-Interscience).

[0607] Method F - Step 1: The compounds of formula (F-I) and formula (F-II) are known, commercially available or can be obtained by known preparation methods (see, for example, 2-[methoxy(methyl)amino]ethanol of Journal of Organic Chemistry, 1957, 22, 579).

[0608] In the presence of a basic reaction auxiliary (such as sodium hydride or potassium carbonate), a compound of formula (F-I) is reacted with a compound of formula (F-II) in a nucleophilic aromatic substitution reaction to obtain a compound of formula (F-III). This reaction is carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are N,N-dimethylformamide, N,N-diethylmethylamide, N-methyl-2-pyrrolidone and acetonitrile. This reaction is preferably carried out at a temperature of 0 °C to 100 °C (see, for example, the synthesis of the following substances described in the present application: 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carbonitrile, 6-{2-[methoxy(methyl)amino]ethoxy}nicotinaldehyde, methyl 3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate) and ethyl 5-(4-ethylpiperazin-1-yl)-3-fluoropyridine-2-carboxylate).

[0609] Method F - Step 2: Depending on the substituent D, the compound of formula (F-III) can be converted into a compound of structure (F-IV) by a one-step or optional multi-step method.

[0610] If D represents a cyano group, the cyano functional group can be hydrolyzed in the presence of a base (such as sodium hydroxide) to obtain an acid functional group. This reaction is carried out in the presence of an inert solvent or diluent. Examples that may be mentioned are ethanol, methanol, tetrahydrofuran and water, or optionally a mixture of these substances. This reaction is preferably carried out at a temperature of 20 °C to 120 °C (see, for example, the synthesis of (6-methoxypyridin-3-yl)methanol in WO2010 / 043377 or the synthesis of methyl 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carboxylate in the present application). Then, the acid functional group can be converted into a compound of formula (F-III) in which D represents a (C1-C3)-alkoxycarbonyl group in the presence of an inorganic acid (such as sulfuric acid) and an alkanol having a (C1-C3) chain length (see, for example, the synthesis of methyl 3-bromopyridine-2-carboxylate in WO2003 / 084917 or the synthesis of methyl 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carboxylate in the present application). This reaction is preferably carried out in the presence of an excess of (C1-C3)-alkanol as a solvent or diluent, optionally as a mixture with another solvent or diluent. This reaction is preferably carried out at a temperature of 40 °C to 100 °C.

[0611] If D represents (C1-C3)-alkoxycarbonyl, the ester functional group can be reduced in the presence of a suitable reducing agent such as sodium borohydride or diisobutylaluminum hydride to give the benzyl alcohol of formula (F-IV). If the reaction is carried out in the presence of sodium borohydride, a suitable solvent or diluent such as ethanol or methanol is used. Here, the reaction is preferably carried out at a temperature of from 0 °C to 50 °C. If diisobutylaluminum hydride is used, the reaction is carried out in a suitable inert solvent such as toluene or dichloromethane. Here, the reaction is preferably carried out at a temperature of from -78 °C to +30 °C (see, for example, the synthesis of (5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridin-2-yl)methanol) and (3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol as described in the present application).

[0612] If D represents formyl, the formyl group can be reduced in the presence of a suitable reducing agent such as sodium borohydride to give the benzyl alcohol of formula (F-IV). If the reaction is carried out in the presence of sodium borohydride, a suitable solvent or diluent such as ethanol or methanol, optionally as a mixture with tetrahydrofuran, is used. Here, the reaction is preferably carried out at a temperature of from 0 °C to 50 °C.

[0613] If D represents -CH2OPG, the protecting group can be removed under different conditions depending on its nature. The conditions for removing alcohol protecting groups are known to those skilled in the art. A review is given, for example, in T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd Edition, 1999 (Wiley-InterScience).

[0614] Method F - Step 3: The halides of formula (F-VI) are known, commercially available or can be obtained by the preparation methods described in the present application (see, for example, the preparation of 2-bromo-N-methoxy-N-methyl-ethanamine hydrobromide (1:1)). The compounds of formula (F-V) are known, commercially available or can be obtained by known preparation methods (see, for example, the preparation of 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-ol described in the present application).

[0615] In the presence of a basic reaction auxiliary (such as potassium carbonate) and optionally in the presence of sodium iodide, a compound of formula (F-VI) is reacted with an alcohol of formula (F-V) in a nucleophilic substitution reaction to obtain a compound of formula (F-VII). This reaction is carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone, and tetrahydrofuran. This reaction is preferably carried out at a temperature of 0 °C to 100 °C (see, for example, the reaction of 2-bromo-N,N-dimethylethylamine with 5-bromopyridin-3-ol in WO2016 / 040185).

[0616] Method F - Step 4: Depending on the substituent D, the compound of formula (F-VII) can be converted into a compound of structure (F-VIII) in one step or an optional multi-step method. The reaction conditions correspond to the reaction conditions described for the reaction of the compound of formula (F-III) to form the compound of formula (F-IV) in Step 2.

[0617] Method F - Step 5: The compound of formula (F-IX) is known, commercially available, or can be obtained by known preparation methods.

[0618] In the presence of a basic reaction auxiliary (such as potassium carbonate or cesium carbonate), a compound of formula (F-V) is reacted with a chloride of formula (F-IX) in a nucleophilic substitution reaction to obtain a compound of formula (F-X). This reaction is optionally carried out in the presence of an inert solvent or diluent. Examples that can be mentioned are N,N-dimethylformamide, N-methyl-2-pyrrolidone, and acetonitrile. This reaction is preferably carried out at a temperature of 20 °C to 120 °C (see, for example, the synthesis of methyl 3-fluoro-5-[2-(methoxyimino)ethoxy]pyridine-2-carboxylate described in this application).

[0619] Method F - Step 6: The aldehyde of formula (F-XI) is known, commercially available, or can be obtained by known preparation methods.

[0620] The compound of formula (F-X) can be converted into a compound of formula (F-VIII) in a two-step one-pot reaction. In the first step, the compound of formula (F-X) first reacts in the presence of a reducing agent (such as sodium cyanoborohydride) to obtain an intermediate of formula (F-VIII) in which R 8 represents hydrogen. This reaction is carried out at a temperature of 10 °C to 80 °C in the presence of a solvent or diluent (such as acetic acid).

[0621] In the second step, this intermediate reacts with the aldehyde of formula (F-XI) in a reductive alkylation reaction in the presence of a reducing agent to obtain a compound of formula (F-VIII), in which R 8represents a (C1-C6)-alkyl optionally substituted on C2 to C6. The reaction is carried out at a temperature of 10 °C to 80 °C in the presence of a solvent or diluent (such as acetic acid).

[0622] Reaction Scheme VII - Method G

[0623]

[0624] The compound of formula (I-G) can be prepared, for example, according to Reaction Scheme VII. The group A 1 , A 2 , A 3 , A 4 , R 7 , R 8 , X, Y and Z have the above meanings and optionally other meanings related to the preparation method, which are obvious in the text or context. R 6 represents an optionally substituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkanoyl or a closed ring formed with R 8 through 1 to 3 CH2 groups. R 5 represents an optionally substituted (C1-C4)-alkyl. R 9 represents an optionally substituted (C1-C6)-alkyl, (C1-C6)-alkylcarbonyl, (C1-C6)-alkylsulfonyl or (C1-C6)-alkoxycarbonyl. Alk represents an optionally substituted (C1-C6)-alkyl. Alk' represents an optionally substituted (C1-C5)-alkyl. LG represents a leaving group such as a halogen or a sulfonate ester.

[0625] Method G - Step 1: The compound of formula (G-I) can be obtained by the methods shown in Reaction Schemes I and III.

[0626] The tert-butoxycarbonyl of the compound of formula (G-I) can be removed under acidic conditions. The acid used is preferably hydrogen chloride or trifluoroacetic acid. The reaction is optionally carried out in the presence of an inert solvent or diluent or in pure trifluoroacetic acid. Exemplary solvents that may be mentioned are 1,4-dioxane, dichloromethane and water. The reaction is preferably carried out at a temperature of 0 °C to 60 °C. (See, for example, the synthesis of 5-{[(4-chloro-1-naphthyl)oxy]methyl}-2-(pyrrolidin-3-yloxy)pyridine described in this application or US2015 / 238641).

[0627] Method G - Step 2: Depending on the substituent R 9 , the compound of formula (G-II) can be converted into the compound of structure (1-G) in a one-step process.

[0628] a) wherein R 9Compounds of structure (I-G) representing an optionally substituted (C1-C6)-alkyl are obtained by reacting a compound of formula (G-II) with an alkylating agent of general structure (G-III) in the presence of a basic reaction auxiliary (such as potassium carbonate or triethylamine). Preferred leaving groups LG are halogen chlorine, bromine or iodine or sulfonates, such as mesylate or tosylate. The reaction is optionally carried out in the presence of an inert solvent or diluent (such as acetonitrile, dichloromethane or N,N-dimethylformamide). The reaction is preferably carried out at a temperature of 0 °C to 100 °C (see for example WO2014 / 207240 or WO2014 / 116684).

[0629] Alternatively, compounds of formula (I-G) are obtained by reacting a compound of formula (G-II) with an aldehyde of formula (G-IV) in a reductive alkylation reaction in the presence of a reducing agent (such as sodium cyanoborohydride), where R 9 represents a (C1-C6)-alkyl optionally substituted on C2 to C6. The reaction is carried out at a temperature of 10 °C to 80 °C in the presence of a solvent or diluent (such as acetic acid).

[0630] b) Compounds of structure (I-G) where R 9 represents an optionally substituted (C1-C6)-alkylcarbonyl, (C1-C6)-alkylsulfonyl or (C1-C6)-alkoxycarbonyl are obtained by reacting a compound of formula (G-II) with an acyl chloride of general structure (G-V) or with a sulfonyl chloride of general structure (G-VI) or with a chloroformate of general structure (G-VII). The reaction is preferably carried out in the presence of a basic reaction auxiliary (such as triethylamine or diisopropylethylamine) and an inert solvent or diluent (such as dichloromethane, tetrahydrofuran or acetonitrile). The reaction is preferably carried out at a temperature of 0 °C to 100 °C (see for example the reaction with acyl chloride in US2015 / 259317, the reaction with sulfonyl chloride in WO2004 / 041264 or the reaction with chloroformate in WO2004 / 089925).

[0631] Another embodiment of the invention relates to intermediates and includes compounds of the following formula (Va) or (Vb):

[0632]

[0633] where

[0634] A 1 represents N or CH,

[0635] A 2 represents N or CH, where at least A 1 or A 2 represents N and preferably A 1 represents N and A2 represents CH,

[0636] R 16 represents hydrogen, methyl, fluorine or methoxy,

[0637] R 17 represents cyano, hydroxymethyl, methyl carboxyl, ethyl carboxyl or 3 - bromophenoxymethyl,

[0638] R 18 in the compounds of formula (Va) represents the group:

[0639] or bromine,

[0640] provided that the following compounds are excluded:

[0641]

[0642] In a preferred embodiment of the present invention, R 18 represents the group:

[0643]

[0644] In another preferred embodiment of the present invention, the compounds of formula (Vb) represent:

[0645]

[0646] Furthermore, a particularly preferred embodiment of the present invention relates to the compounds of formula (Va - 1 to Va - 14) and formula (Vb - 1):

[0647]

[0648]

[0649]

[0650]

[0651]

[0652]

[0653]

[0654]

[0655]

[0656]

[0657]

[0658]

[0659]

[0660]

[0661]

[0662]

[0663]

[0664]

[0665] Preparation of 2-[(5-fluoro-6-{[(6-fluorobiphenyl-3-yl)oxy]methyl}pyridin-3-yl)oxy]-N-methoxy-N-methyl ethylamine

[0666]

[0667] Under argon, 58 mg (0.42 mmol) of potassium carbonate, 49 mg (42 μmol) of tetrakis(triphenylphosphine)palladium, 1 ml of water and 51 mg (0.42 mmol) of phenylboronic acid were added to a solution of 85 mg (0.21 mmol) of 2-({6-[(3-bromo-4-fluorophenoxy)methyl]-5-fluoropyridin-3-yl}oxy)-N-methoxy-N-methylacetamide in 5 ml of tetrahydrofuran. By passing an argon stream, the reaction mixture was made free of dissolved oxygen, and then the mixture was stirred overnight at 80 °C, then silica gel was added, and subsequently the solvent was removed under reduced pressure. The residue was first chromatographed on silica gel by MPLC (gradient: ethyl acetate / cyclohexane), and then separated again by HPLC (gradient: H2O / acetonitrile). 80 mg of 2-[(5-fluoro-6-{[(6-fluorobiphenyl-3-yl)oxy]methyl}pyridin-3-yl)oxy]-N-methoxy-N-methylacetamide was obtained.

[0668] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2304 (2.2); 8.2263 (2.2); 7.5763 (1.4); 7.5681 (2.6); 7.5640 (1.8); 7.5471 (4.3); 7.4984 (1.9); 7.4804 (3.7); 7.4611 (2.0); 7.4291 (0.8); 7.4259 (1.4); 7.4227 (0.9); 7.4135 (0.5); 7.4076 (1.7); 7.3895 (0.6); 7.2630 (1.2); 7.2404 (1.7); 7.2374 (1.6); 7.2147 (1.5); 7.1731 (1.2); 7.1653 (1.4); 7.1570 (1.3); 7.1492 (1.4); 7.0680 (0.8); 7.0587 (1.3); 7.0503 (0.8); 7.0456 (0.8); 7.0367 (1.0); 7.0280 (0.6); 5.1873 (4.3); 5.1829 (4.6); 4.2340 (1.9); 4.2203 (4.0); 4.2066 (2.1); 3.4025 (19.6); 3.3189 (19.4); 2.9769 (1.8); 2.9633 (3.6); 2.9495 (1.8); 2.6708 (0.4); 2.5643 (16.0); 2.5409 (36.2); 2.5239 (0.9); 2.5104 (22.3); 2.5061 (46.1); 2.5016 (61.5); 2.4971 (45.7); 2.4929 (23.3); 2.3283 (0.4); 0.0079 (1.5); -0.0002 (41.0); -0.0084 (1.9).

[0669] Preparation of 2-[(6-{[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-2-ethoxypyridin-3-yl)oxy]-N-methoxy- N-methyl ethylamine

[0670]

[0671] At room temperature, 9.6 mg (0.14 mmol) of sodium ethoxide was added to a solution of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxy-N-methylacetamide (20 mg, 47 μmol) in 1 ml of dimethylacetamide. The reaction mixture was stirred overnight and then chromatographed by HPLC (gradient: H2O / acetonitrile). 7 mg of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-ethoxypyridin-3-yl)oxy]-N-methoxy-N-methylacetamide was obtained.

[0672] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 9.9594 (0.4); 8.2457 (2.4); 8.2230 (2.6); 7.7922 (1.9); 7.7708 (2.7); 7.6965 (3.2); 7.6791 (1.9); 7.6739 (3.3); 7.6593 (2.4); 7.6384 (1.3); 7.3698 (2.4); 7.3498 (2.8); 7.2878 (2.3); 7.2684 (2.1); 7.1449 (2.7); 7.1251 (2.3); 5.2364 (7.8); 4.5171 (0.3); 4.3665 (1.3); 4.3490 (4.1); 4.3315 (4.2); 4.3139 (1.4); 4.1371 (2.1); 4.1226 (4.5); 4.1080 (2.3); 3.4096 (18.6); 3.4001 (2.0); 3.3204 (31.9); 2.9799 (2.3); 2.9655 (4.6); 2.9511 (2.3); 2.6709 (0.6); 2.5723 (16.0); 2.5558 (1.6); 2.5058 (75.0); 2.5019 (95.4); 2.4980 (72.3); 2.3286 (0.5); 1.3184 (4.2); 1.3009 (8.7); 1.2834 (4.2); 1.2308 (0.6); 0.1457 (0.5); -0.0004 (99.6); -0.1499 (0.5).

[0673] Preparation of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methylpyridin-3-yl}oxy)-N-methoxy N-methyl ethylamine

[0674]

[0675] Step 1: Preparation of 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carbonitrile

[0676] A solution of 1.38 g (13.1 mmol) of 2-[methoxy(methyl)amino]ethanol in 4 ml of N-methyl-2-pyrrolidone was slowly added dropwise to a cold suspension of 686 mg (15.7 mmol) of sodium hydride (55% mineral oil dispersion) in 32 ml of N-methyl-2-pyrrolidone. The reaction mixture was stirred at room temperature for 30 minutes, and then a solution of 2.00 g (13.1 mmol) of 5-chloro-3-methylpyridine-2-carbonitrile in 4 ml of N-methyl-2-pyrrolidone was added dropwise. Stirring was continued overnight at room temperature, and then 20 ml of ethyl acetate was added. After 5 minutes, water was added, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed on RP silica gel and chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). 1.20 g of 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carbonitrile was obtained.

[0677] 1 1H-NMR (400.0 MHz, CDCl3): δ = 8.7253 (0.4); 8.7197 (0.4); 8.2526 (1.8); 8.2459 (1.9); 7.7789 (0.3); 7.7733 (0.3); 7.2654 (4.4); 7.1286 (1.7); 7.1221 (1.7); 4.2396 (1.4); 4.2259 (2.9); 4.2122 (1.6); 3.9097 (0.7); 3.5168 (16.0); 3.0561 (2.1); 3.0424 (4.0); 3.0286 (2.0); 2.7222 (0.6); 2.6748 (14.6); 2.6247 (1.3); 2.5715 (0.4); 2.5393 (11.4); 2.0097 (3.7); 1.6280 (0.5); -0.0002 (3.7).

[0678] Steps 2&3: Preparation of methyl 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carboxylate

[0679] 2.17 g (54.3 mmol) of sodium hydroxide, 2.7 ml of water and 2.7 ml of ethanol were added to a solution of 1.20 g (5.43 mmol) of 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carbonitrile in 5.4 ml of tetrahydrofuran and the mixture was stirred at 70 °C for 12 h. The reaction mixture was then diluted with water, acidified with 1 M hydrochloric acid and extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. A residue of 245 mg was obtained. The aqueous phase was likewise concentrated under reduced pressure and the residue azeotropically dried with CH2Cl2. A residue of 4.28 g was obtained, which was dissolved in 45 ml of methanol and a catalytic amount of sulfuric acid was added. The reaction solution was heated under reflux for 5 days and then the solvent removed under reduced pressure. Saturated NaHCO3 solution was added to the residue and the resulting solution extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and the solvent removed under reduced pressure. 787 mg of methyl 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carboxylate was obtained.

[0680] 1 H-NMR (400.0 MHz, CDCl3): δ = 8.2899 (1.8); 8.2832 (1.8); 7.2673 (4.3); 7.1065 (1.6); 7.1003 (1.6); 5.3010 (0.6); 4.2446 (1.2); 4.2311 (2.5); 4.2174 (1.4); 4.0111 (1.3); 3.9793 (1.3); 3.9549 (15.8); 3.9047 (0.5); 3.5244 (16.0); 3.0596 (1.9); 3.0459 (3.7); 3.0322 (1.9); 2.6789 (14.2); 2.6359 (11.1); 1.6127 (0.4); -0.0002 (2.9).

[0681] Step 4: Preparation of (5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridin-2-yl)methanol

[0682] At -78 °C, 14.8 ml (14.8 mmol) of 1 M diisobutylaluminum hydride solution was added dropwise to a solution of 750 mg (2.95 mmol) of methyl 5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridine-2-carboxylate in 32 ml of toluene. The reaction solution was stirred at -10 °C for 60 minutes, 50 ml of saturated sodium potassium tartrate solution was added, and then the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in 10 ml of methanol, cooled with ice, and 64 mg (1.7 mmol) of sodium borohydride was added. The solution was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure. Water was added to the residue and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. 498 mg of (5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridin-2-yl)methanol was obtained.

[0683] 1 H-NMR (400.0 MHz, CDCl3): δ = 8.1296 (1.7); 8.1232 (1.8); 7.2654 (3.6); 7.1012 (1.6); 7.0955 (1.6); 4.6307 (3.8); 4.5215 (0.5); 4.1966 (1.3); 4.1829 (2.6); 4.1692 (1.4); 3.8572 (0.5); 3.5324 (16.0); 3.0446 (2.0); 3.0308 (3.9); 3.0171 (2.0); 2.6788 (14.8); 2.2275 (0.4); 2.2064 (10.4); 1.6595 (0.9); -0.0002 (2.0).

[0684] Step 5: Preparation of 2-{[6-(chloromethyl)-5-methylpyridin-3-yl]oxy}-N-methoxy-N-methyl ethylamine

[0685] At 0 °C, 0.23 ml (1.3 mmol) of diisopropylethylamine and 34 μl (0.44 mmol) of methanesulfonyl chloride were added to a solution of 100 mg (442 μmol) of (5-{2-[methoxy(methyl)amino]ethoxy}-3-methylpyridin-2-yl)methanol in 3 ml of CH2Cl2. The reaction solution was stirred at room temperature overnight, then diluted with CH2Cl2 and washed with saturated NaHCO3 solution and water. The organic phase was dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. 102 mg of 2-{[6-(chloromethyl)-5-methylpyridin-3-yl]oxy}-N-methoxy-N-methylacetamide was obtained.

[0686] 11H-NMR (400.0 MHz, CDCl3): δ = 8.1510 (1.8); 8.1442 (1.8); 7.2641 (5.4); 7.0808 (1.7); 7.0743 (1.7); 4.7037 (0.5); 4.6904 (9.1); 4.1959 (1.4); 4.1823 (2.7); 4.1686 (1.5); 3.8559 (0.5); 3.5265 (16.0); 3.0400 (2.0); 3.0263 (3.8); 3.0125 (2.0); 2.6738 (14.6); 2.4657 (0.4); 2.4289 (11.1); 1.6500 (0.9); -0.0002 (3.5)

[0687] Step 6: Preparation of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methylpyridin-3-yl}oxy)-N- methoxy-N-methyl ethylamine

[0688] 61 mg (0.33 mmol) of dibenzo[b,d]furan-2-ol and 227 mg (1.64 mmol) of K2CO3 were added to a solution of 100 mg (409 μmol) of 2-{[6-(chloromethyl)-5-methylpyridin-3-yl]oxy}-N-methoxy-N-methylacetamide in 3 ml of N,N-dimethylformamide. The reaction mixture was stirred at 70 °C for 4 hours and then stirred overnight at room temperature. Then water was added and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed by HPLC (gradient: H2O / acetonitrile). 93 mg of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methylpyridin-3-yl}oxy)-N-methoxy-N-methylacetamide was obtained.

[0689] 11H-NMR (400.0 MHz, CDCl3): δ = 8.2065 (2.0); 8.1997 (2.0); 7.9262 (1.5); 7.9069 (1.6); 7.5833 (2.4); 7.5768 (2.5); 7.5423 (1.4); 7.5217 (2.2); 7.4626 (2.3); 7.4559 (1.0); 7.4536 (0.9); 7.4401 (3.2); 7.4172 (0.8); 7.3375 (1.2); 7.3184 (1.8); 7.3000 (0.8); 7.2610 (7.7); 7.1522 (1.4); 7.1457 (1.4); 7.1299 (1.3); 7.1233 (1.4); 7.1162 (1.9); 7.1096 (1.8); 5.2523 (8.4); 4.2062 (1.4); 4.1927 (2.7); 4.1790 (1.5); 3.8629 (0.5); 3.5287 (16.0); 3.0459 (1.9); 3.0323 (3.8); 3.0186 (1.9); 2.6759 (14.0); 2.4599 (11.8); 2.0045 (1.6); 1.6104 (5.7); -0.0002 (5.0).

[0690] Preparation of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methoxypyridin-3-yl}oxy)-N-methoxy N-methyl ethylamine

[0691]

[0692] Step 1: Preparation of methyl 3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate

[0693] A solution of 1.35 g (12.9 mmol) of 2-[methoxy(methyl)amino]ethanol in 10 ml of N,N-dimethylformamide was added dropwise to a suspension of 673 mg (15.4 mmol) of sodium hydride (55% mineral oil dispersion) in 80 ml of N,N-dimethylformamide. The reaction solution was stirred at room temperature for 30 minutes, and then a solution of 2.38 g (12.9 mmol) of methyl 5-fluoro-3-methoxypyridine-2-carboxylate in 10 ml of N,N-dimethylformamide was added dropwise. The reaction mixture was stirred at room temperature overnight, then water was added, and the mixture was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed by HPLC (gradient: H2O / acetonitrile). 2.76 g of the crude product was obtained and further purified by HPLC (gradient: H2O / acetonitrile). 1.43 g of methyl 3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate (purity about 69%) was obtained, which was a mixture with 2-[methoxy(methyl)amino]ethyl 3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate.

[0694] 1 1H-NMR (400.0 MHz, CDCl3): δ = 8.0372 (1.9); 8.0315 (1.9); 8.0009 (0.9); 7.9951 (0.9); 7.2691 (3.6); 6.9242 (1.7); 6.9186 (1.7); 6.8404 (0.8); 6.8346 (0.8); 4.2815 (1.0); 4.2681 (1.9); 4.2547 (1.1); 3.9713 (0.6); 3.9495 (16.0); 3.9380 (6.1); 3.9351 (6.2); 3.9249 (10.7); 3.9142 (0.6); 3.5489 (0.5); 3.5312 (11.7); 3.0632 (1.4); 3.0497 (2.7); 3.0362 (1.4); 2.6847 (10.4); 2.6366 (0.4); 1.6400 (2.2); -0.0002 (3.8).

[0695] Step 2: Preparation of (3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol

[0696] At -78 °C, 3.3 ml (3.3 mmol) of 1 M diisobutylaluminum hydride solution was added dropwise to a solution of 1.43 g (5.29 mmol) of methyl 3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate in 56 ml of toluene. The reaction solution was stirred overnight at 0 °C. At 0 °C, 10.6 ml (10.6 mmol) of 1 M diisobutylaluminum hydride solution was then added. After stirring for 1 hour at 0 °C, 3 ml of methanol was added dropwise, and 56 ml of saturated sodium potassium tartrate solution was added after 5 minutes. The mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in 5 ml of methanol, cooled with ice, and 114 mg (3.02 mmol) of sodium borohydride was added. The solution was stirred at room temperature for 2 hours. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed by HPLC (gradient: H2O / acetonitrile). 949 mg of (3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol was obtained.

[0697] 1 1H-NMR (400.0 MHz, CDCl3): δ = 7.8658 (0.8); 7.2645 (3.4); 6.8295 (2.2); 6.8242 (2.2); 4.6788 (2.4); 4.6682 (2.5); 4.2230 (1.2); 4.2096 (2.3); 4.1962 (1.3); 4.0111 (0.5); 3.9995 (0.9); 3.9882 (0.4); 3.8247 (14.4); 3.5389 (16.0); 3.0482 (1.8); 3.0347 (3.5); 3.0212 (1.9); 2.6855 (14.5); 1.6298 (0.8); -0.0002 (3.3.)

[0698] Step 3: Preparation of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methoxypyridin-3-yl}oxy)- N-methoxy-N-methyl ethylamine

[0699] To 100 mg (413 μmol) of (3-methoxy-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol was added 246 mg (2.06 mmol) of SOCl2 and a catalytic amount of N,N-dimethylformamide. The reaction mixture was stirred at room temperature for 4 h and then concentrated under reduced pressure. The residue was dissolved in 2 ml of N,N-dimethylformamide, and 61 mg (0.33 mmol) of dibenzo[b,d]furan-2-ol and 285 mg (2.06 mmol) of K2CO3 were added. The reaction mixture was stirred at 70 °C for 4 h, stirred at room temperature for 3 days, adsorbed on RP silica gel, and chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). 48 mg of 2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-methoxypyridin-3-yl}oxy)-N-methoxy-N-methylethylamine was obtained.

[0700] 1 H-NMR (400.0 MHz, CDCl3): δ = 7.9991 (2.4); 7.9934 (2.7); 7.9143 (1.4); 7.8951 (1.5); 7.6111 (2.2); 7.6049 (2.5); 7.5409 (1.3); 7.5202 (2.1); 7.4563 (2.1); 7.4506 (1.1); 7.4471 (1.0); 7.4336 (3.0); 7.4295 (2.1); 7.4115 (0.8); 7.4083 (0.8); 7.3311 (1.0); 7.3289 (1.0); 7.3104 (1.6); 7.2936 (0.7); 7.2916 (0.7); 7.2605 (8.3); 7.1897 (1.4); 7.1832 (1.5); 7.1673 (1.2); 7.1609 (1.3); 6.8950 (2.2); 6.8894 (2.5); 5.2982 (2.7); 5.2508 (8.2); 4.2445 (1.3); 4.2311 (2.5); 4.2178 (1.4); 3.8825 (14.1); 3.5365 (16.0); 3.0517 (1.8); 3.0383 (3.5); 3.0248 (1.8); 2.6834 (13.9); 1.5841 (6.1); -0.0002 (7.8).

[0701] Preparation of (5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol

[0702]

[0703] Step 1: Preparation of 5-[2-(methoxyimino)ethoxy]pyridine-2-carbaldehyde

[0704] At room temperature, a solution of 4.42 g (32.0 mmol) of K2CO3 and 2.41 g (22.4 mmol) of 2-chloro-N-methoxyethylamine in 30 ml of acetonitrile was added to a solution of 1.97 g (16.0 mmol) of 5-hydroxypyridine-2-carbaldehyde in 30 ml of acetonitrile. The reaction mixture was heated under reflux for 40 hours and then stirred at room temperature for another 4 days. The precipitate was filtered off, the filtrate was concentrated under reduced pressure, and the residue was dissolved in 15 ml of acetonitrile. The mixture was filtered again, and the filtrate was concentrated under reduced pressure. 1.91 g of 5-[2-(methoxyimino)ethoxy]pyridine-2-carbaldehyde was obtained as a residue.

[0705] 1 1H-NMR (400.0 MHz, CDCl3): δ = 10.0000 (4.9); 8.4785 (2.5); 8.4717 (2.5); 8.4568 (0.8); 8.4500 (0.8); 7.9809 (2.4); 7.9592 (2.5); 7.5613 (1.3); 7.5469 (2.6); 7.5328 (1.4); 7.3812 (1.3); 7.3743 (1.3); 7.3594 (1.2); 7.3530 (1.2); 7.3203 (0.4); 7.3136 (0.4); 7.2985 (0.4); 7.2918 (0.4); 7.2652 (6.8); 6.9597 (0.4); 6.9506 (0.8); 6.9413 (0.4); 4.9494 (1.7); 4.9403 (1.7); 4.7838 (5.2); 4.7695 (5.1); 3.9757 (5.0); 3.9550 (0.3); 3.9161 (16.0); 3.9032 (1.0); 3.8898 (0.4); 1.6375 (3.0); -0.0001 (3.9).

[0706] Step 2: Preparation of (5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol

[0707] At 10 °C, 926 mg (14.7 mmol) of sodium cyanoborohydride was added to a solution of 1.91 g (9.83 mmol) of 5-[2-(methoxyimino)ethoxy]pyridine-2-carbaldehyde in 15 ml of acetic acid, and the mixture was then stirred at room temperature for 2 hours. By cooling, then 12.1 g (147 mmol) of an aqueous formaldehyde solution with a concentration of 36.5% was added at 20 °C. After 10 minutes, 926 mg (14.7 mmol) of sodium cyanoborohydride was added again. The reaction mixture was stirred at room temperature overnight, and then the solvent was removed under reduced pressure. 50 ml of water was added to the residue, the pH was adjusted to 10 with 50% sodium hydroxide solution, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel by MPLC (gradient: ethyl acetate / cyclohexane). 1.08 g of 5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol was obtained.

[0708] 1 1H-NMR (400.0 MHz, CDCl3): δ = 8.2963 (2.0); 8.2894 (2.0); 7.2869 (1.1); 7.2799 (1.0); 7.2697 (2.7); 7.2657 (2.0); 7.2585 (1.7); 7.2065 (2.4); 7.1852 (1.4); 4.9625 (0.5); 4.7643 (0.5); 4.7038 (7.6); 4.2049 (1.5); 4.1912 (2.9); 4.1775 (1.6); 3.5311 (16.0); 3.0514 (2.2); 3.0377 (4.2); 3.0239 (2.1); 2.6800 (15.3); -0.0002 (1.2).

[0709] Preparation of 2-{[6-{[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-2-(methylthio)pyridin-3-yl]oxy}-N-meth oxy-N-methyl ethylamine

[0710]

[0711] 14.6 mg (0.21 mmol) of sodium methanethiolate was added to a solution of 46 mg (0.10 mmol) of 2-[(2-chloro-6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}pyridin-3-yl)oxy]-N-methoxy-N-methylethanamine in dimethylacetamide, and the mixture was stirred overnight at room temperature. Then 7.3 mg (0.10 mmol) of sodium methanethiolate was added. After 2 hours at room temperature, 7.3 mg (0.10 mmol) of sodium methanethiolate was added again, and the reaction mixture was stirred overnight. Water was added to the reaction mixture, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed by HPLC (gradient: H2O / acetonitrile). 3 mg of 2-{[6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-(methylthio)pyridin-3-yl]oxy}-N-methoxy-N-methylethanamine was obtained.

[0712] 1 1H-NMR (601.6 MHz, CDCl3): δ = 8.2606 (1.7); 8.2455 (1.8); 7.8618 (1.6); 7.8475 (1.7); 7.5069 (1.2); 7.5011 (2.6); 7.4936 (1.8); 7.4861 (2.4); 7.4797 (1.2); 7.2589 (26.6); 7.1854 (1.7); 7.1718 (2.0); 7.0330 (2.2); 7.0193 (1.9); 6.9921 (1.7); 6.9793 (1.6); 5.3152 (6.8); 4.2239 (1.9); 4.2140 (4.0); 4.2041 (2.0); 3.5268 (16.0); 3.1054 (2.2); 3.0956 (4.4); 3.0857 (2.1); 2.6824 (14.6); 2.5371 (15.1); 1.5443 (15.4); 1.2554 (1.0); 0.0691 (3.3); 0.0051 (0.6); -0.0002 (16.0); -0.0056 (0.7).

[0713] Preparation of 2-[(5-{[(4-chloro-1-naphthalenyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxy-N-methyl ethylamine's preparation

[0714]

[0715] Step 1: Preparation of 2-chloro-5-{[(4-chloro-1-naphthalenyl)oxy]methyl}pyridine

[0716] 6.22 g (34.8 mmol) of 4-chloro-1-naphthol and 14.4 g (104 mmol) of K2CO3 were added to a solution of 5.64 g (34.8 mmol) of 2-chloro-5-(chloromethyl)pyridine in 40 ml of N,N-dimethylformamide. The reaction mixture was stirred at 70 °C for 16 h and then concentrated under reduced pressure. The residue was dissolved in ethyl acetate and the solution was washed with water and saturated ammonium chloride solution. The organic phase was then extracted with saturated ammonium chloride solution and the combined aqueous phases were extracted repeatedly with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. The residue was adsorbed onto silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 9.72 g of 2-chloro-5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridine was obtained.

[0717] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.6347 (4.5); 8.6289 (4.7); 8.2855 (3.6); 8.2647 (3.9); 8.1440 (3.6); 8.1229 (4.0); 8.0817 (2.7); 8.0759 (2.7); 8.0612 (2.9); 8.0553 (2.9); 7.7505 (1.7); 7.7325 (3.3); 7.7140 (2.2); 7.6592 (2.5); 7.6462 (6.3); 7.6409 (3.8); 7.6256 (6.5); 7.6154 (5.7); 7.5948 (5.0); 7.1313 (5.5); 7.1104 (5.1); 5.3830 (16.0); 3.3373 (32.0); 2.5096 (30.8); 2.5056 (39.6); 2.5016 (30.3); 0.0074 (0.9); -0.0002 (21.8).

[0718] Step 2: Preparation of 5-{[(4-chloro-1-naphthalenyl)oxymethyl}-2-(2,2-diethoxyethoxy)pyridine

[0719] 359 mg (8.22 mmol) of sodium hydride (a 55% mineral oil dispersion) was added to a solution of 882 mg (6.58 mmol) of 2,2 - diethoxyethanol in tetrahydrofuran, and the mixture was stirred at room temperature for 30 minutes. Then, 1.00 g (3.29 mmol) of 2 - chloro - 5 - {[(4 - chloro - 1 - naphthyl)oxy]methyl}pyridine dissolved in 20 ml of tetrahydrofuran was added, and the reaction solution was stirred at 60 °C for 4 hours and then at room temperature for 12 hours. Then, another 359 mg (8.22 mmol) of sodium hydride (a 55% mineral oil dispersion) was added, and the mixture was stirred at 60 °C for 6 hours and then at room temperature overnight. Water and ethyl acetate were added to the reaction mixture, and the phases were separated. The organic phase was washed with water, and the aqueous phase was repeatedly extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride. The organic phase was dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed onto silica gel, and chromatography was performed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 128 mg of 5 - {[(4 - chloro - 1 - naphthyl)oxy]methyl}-2-(2,2 - diethoxyethoxy)pyridine and 891 mg of a contaminated fraction were obtained. The fraction was chromatographed on RP silica gel by MPLC (gradient: acetonitrile / H2O). An additional 652 mg of 5 - {[(4 - chloro - 1 - naphthyl)oxy]methyl}-2-(2,2 - diethoxyethoxy)pyridine was obtained.

[0720] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.3586 (1.9); 8.3534 (2.0); 8.2309 (1.4); 8.2103 (1.5); 8.1313 (1.5); 8.1105 (1.6); 7.9306 (1.2); 7.9246 (1.2); 7.9094 (1.3); 7.9034 (1.3); 7.7362 (0.7); 7.7333 (0.7); 7.7190 (1.1); 7.7158 (1.4); 7.7124 (0.8); 7.6980 (0.9); 7.6950 (0.9); 7.6373 (2.8); 7.6166 (3.5); 7.5971 (0.7); 7.5944 (0.6); 7.1480 (2.2); 7.1271 (2.0); 6.9259 (2.1); 6.9047 (2.0); 5.2679 (5.9); 4.8430 (1.1); 4.8297 (2.5); 4.8165 (1.2); 4.2634 (4.4); 4.2501 (4.2); 3.7038 (0.5); 3.6861 (1.6); 3.6798 (0.9); 3.6684 (1.8); 3.6622 (2.5); 3.6507 (0.7); 3.6445 (2.4); 3.6269 (0.7); 3.5846 (0.7); 3.5670 (2.3); 3.5608 (0.7); 3.5494 (2.4); 3.5430 (1.8); 3.5318 (0.9); 3.5254 (1.6); 3.5078 (0.5); 3.3325 (27.3); 2.5258 (0.6); 2.5122 (12.8); 2.5081 (24.9); 2.5036 (32.0); 2.4991 (23.6); 2.4951 (11.9); 1.1454 (7.9); 1.1278 (16.0); 1.1102 (7.6); 0.0079 (0.8); -0.0002 (20.6); -0.0083 (0.9).

[0721] Step 3: Preparation of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxyethanamine Preparation

[0722] A solution of 125 mg (1.49 mmol) of O-methylhydroxylamine hydrochloride in 3 ml of water was added to a solution of 200 mg (498 μmol) of 5-{[(4-chloro-1-naphthyl)oxy]methyl}-2-(2,2-diethoxyethoxy)pyridine in 20 ml of ethanol. The mixture was stirred overnight at 65 °C. Then the solvent was removed under reduced pressure. Water and CH2Cl2 were added to the reaction mixture and phase separation was carried out. The organic phase was washed with water, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed on silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 160 mg of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxyethylamine was obtained.

[0723] 1 H-NMR (400.0 MHz, d6-DMSO): δ = 8.3813 (2.0); 8.3765 (3.2); 8.2340 (2.3); 8.2131 (2.4); 8.1323 (2.4); 8.1114 (2.7); 7.9720 (0.9); 7.9659 (1.0); 7.9608 (1.3); 7.9546 (1.3); 7.9510 (1.1); 7.9446 (1.1); 7.9395 (1.3); 7.9335 (1.2); 7.7372 (1.2); 7.7344 (1.2); 7.7200 (1.8); 7.7169 (2.3); 7.6990 (1.5); 7.6960 (1.4); 7.6766 (1.2); 7.6628 (2.4); 7.6490 (1.3); 7.6398 (4.3); 7.6193 (5.6); 7.5989 (1.1); 7.5963 (1.0); 7.1515 (3.4); 7.1306 (3.2); 7.0390 (0.8); 7.0298 (1.8); 7.0208 (0.9); 6.9829 (1.5); 6.9616 (1.5); 6.9545 (2.0); 6.9332 (1.9); 5.2769 (9.9); 5.0632 (3.8); 5.0541 (3.8); 4.9043 (4.8); 4.8905 (4.8); 3.8585 (11.2); 3.7910 (16.0); 3.3331 (34.8); 2.5260 (0.9); 2.5083 (35.1); 2.5039 (45.3); 2.4994 (33.8); 1.9903 (1.2); 1.1934 (0.3); 1.1756 (0.6); 0.0078 (1.4); -0.0002 (33.0).

[0724] Step 4: Preparation of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxy-N-methyl ethanamine

[0725] 49 mg (0.79 mmol) of sodium cyanoborohydride was added to a solution of 140 mg (392 μmol) of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxyethanamine in 20 ml of acetic acid, and the mixture was stirred at room temperature for 1 hour. Then another 49 mg (0.79 mmol) of sodium cyanoborohydride was added. After 30 minutes at room temperature, 2.98 ml (39.2 mmol) of an aqueous formaldehyde solution with a concentration of 36.5% was added, and after another 20 minutes, 74 mg (1.2 mmol) of sodium cyanoborohydride was added. The reaction mixture was stirred at room temperature for 2 hours. Then a saturated aqueous solution of NaHCO3 was added, and the reaction mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed on silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 78 mg of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]-N-methoxy-N-methylethanamine was obtained.

[0726] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.3630 (5.1); 8.3579 (5.5); 8.2317 (3.9); 8.2108 (4.1); 8.1311 (4.0); 8.1102 (4.3); 7.9169 (3.2); 7.9109 (3.2); 7.8956 (3.3); 7.8896 (3.3); 7.7361 (1.8); 7.7335 (2.0); 7.7160 (3.8); 7.6980 (2.3); 7.6953 (2.4); 7.6387 (6.2); 7.6180 (8.4); 7.5966 (1.7); 7.5943 (1.8); 7.1509 (5.6); 7.1300 (5.2); 6.9034 (5.4); 6.8821 (5.2); 5.2613 (16.0); 4.8123 (1.3); 4.7872 (1.6); 4.6588 (1.7); 4.4268 (5.1); 4.4124 (10.6); 4.3979 (5.4); 3.4092 (42.0); 3.3340 (86.0); 3.2821 (2.8); 2.9629 (4.6); 2.9486 (9.2); 2.9341 (4.6); 2.6773 (0.4); 2.6731 (0.6); 2.6687 (0.4); 2.5578 (36.3); 2.5082 (62.5); 2.5039 (81.9); 2.4997 (64.1); 2.3307 (0.5); 1.3969 (1.8); 1.2317 (2.8); 0.8527 (0.4); 0.0077 (0.8); -0.0002 (16.2).

[0727] Preparation of {3-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]pyrrolidin-1-yl}acetonitrile

[0728]

[0729] Step 1: Preparation of 5-{[(4-chloro-1-naphthyl)oxy]methyl}-2-(pyrrolidin-3-yloxy)pyridine

[0730] At 0 °C, a solution of 1.54 ml (6.16 mmol) of 4 M hydrochloric acid in 1,4-dioxane was added to a solution of 280 mg (615 μmol) of tert-butyl 3-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]pyrrolidine-1-carboxylate in 6 ml of CH2Cl2. The reaction solution was stirred overnight at room temperature, 5 ml of water was added, and the pH was adjusted to 8 using saturated aqueous NaHCO3. The phases were separated, and the aqueous phase was extracted twice with 5 ml of CH2Cl2. The combined organic phases were washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. 249 mg of 5-{[(4-chloro-1-naphthyl)oxy]methyl}-2-(pyrrolidin-3-yloxy)pyridine was obtained.

[0731] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.3634 (1.8); 8.3580 (1.7); 8.2375 (1.3); 8.2173 (1.4); 8.1393 (1.4); 8.1186 (1.6); 7.9133 (1.1); 7.9073 (1.0); 7.8920 (1.1); 7.8860 (1.1); 7.7434 (0.7); 7.7405 (0.7); 7.7262 (1.0); 7.7229 (1.3); 7.7051 (0.9); 7.7021 (0.8); 7.6448 (2.6); 7.6241 (3.3); 7.6044 (0.6); 7.6018 (0.6); 7.1562 (2.1); 7.1353 (1.9); 6.8639 (1.8); 6.8427 (1.7); 5.4316 (0.5); 5.4174 (0.7); 5.4022 (0.4); 5.2648 (5.3); 3.5757 (16.0); 3.5001 (0.3); 3.4806 (0.4); 3.4702 (0.4); 3.3656 (2.6); 3.1757 (0.6); 3.1619 (0.6); 3.1449 (0.8); 3.1311 (0.7); 2.9862 (0.6); 2.9784 (0.4); 2.9593 (0.8); 2.9406 (0.4); 2.9270 (0.8); 2.9223 (0.8); 2.8958 (1.0); 2.8838 (0.6); 2.8750 (0.5); 2.8635 (0.5); 2.8569 (0.4); 2.5318 (0.8); 2.5183 (17.8); 2.5140 (35.3); 2.5095 (47.3); 2.5050 (34.4); 2.5007 (16.0); 2.0926 (0.4); 2.0759 (0.5); 2.0575 (0.6); 2.0415 (0.5); 1.8551 (0.4); 1.8380 (0.4); 1.8210 (0.4).

[0732] Step 2: Preparation of {3-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]pyrrolidin-1-yl}acetonitrile Preparation

[0733] 35 μl (0.25 mmol) of triethylamine and 18 μl (0.25 mmol) of bromoacetonitrile were added to a solution of 90 mg (0.25 mmol) of 5-{[(4-chloro-1-naphthyl)oxy]methyl}-2-(pyrrolidin-3-yloxy)pyridine in 3 ml of tetrahydrofuran, and the mixture was stirred at 70 °C for 30 minutes. The solvent was then removed under reduced pressure. The residue was adsorbed on silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 75 mg of {3-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}pyridin-2-yl)oxy]pyrrolidin-1-yl}acetonitrile was obtained.

[0734] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.3569 (3.4); 8.3518 (3.4); 8.3142 (4.9); 8.2335 (2.5); 8.2124 (2.7); 8.1313 (2.6); 8.1106 (2.9); 7.9180 (2.2); 7.9119 (2.1); 7.8967 (2.2); 7.8906 (2.2); 7.7358 (1.2); 7.7328 (1.4); 7.7187 (1.8); 7.7154 (2.5); 7.7119 (1.4); 7.6976 (1.6); 7.6945 (1.6); 7.6371 (5.9); 7.6164 (7.2); 7.5985 (1.2); 7.5958 (1.2); 7.1484 (3.9); 7.1275 (3.6); 6.8863 (3.6); 6.8650 (3.5); 5.7544 (3.1); 5.4337 (0.4); 5.4264 (0.9); 5.4188 (1.0); 5.4112 (1.2); 5.4074 (1.3); 5.3999 (1.1); 5.3921 (0.9); 5.3850 (0.5); 5.2594 (10.2); 3.8567 (16.0); 3.3186 (33.8); 3.2947 (1.9); 3.0038 (1.5); 2.9886 (1.6); 2.9775 (2.0); 2.9623 (1.8); 2.8469 (0.6); 2.8263 (1.3); 2.8108 (1.4); 2.7907 (0.8); 2.7530 (1.7); 2.7463 (1.7); 2.7267 (1.4); 2.7201 (1.4); 2.6757 (0.3); 2.6712 (0.5); 2.6667 (0.4); 2.5830 (0.8); 2.5628 (1.6); 2.5464 (1.6); 2.5420 (1.2); 2.5249 (1.9); 2.5111 (25.9); 2.5067 (53.8); 2.5022 (74.6); 2.4977 (57.1); 2.4934 (28.5); 2.3698 (0.4); 2.3506 (0.8); 2.3356 (1.5); 2.3164 (1.4); 2.3016 (0.9); 2.2820 (0.4); 2.0742 (1.4); 1.9166 (0.4); 1.9096 (0.5); 1.8961 (0.7); 1.8821 (0.8); 1.8750 (0.8); 1.8605 (0.6); 1.8472 (0.4); 1.8408 (0.4); -0.0002 (6.6).

[0735] Preparation of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}-6-fluoropyridin-2-yl)oxy]-N-methoxy-N-methyl ethanamine

[0736]

[0737] 43 mg (0.98 mmol) of sodium hydride (55% mineral oil dispersion) was added to a solution of 52 mg (0.49 mmol) of 2-[methoxy(methyl)amino]ethanol in 3 ml of tetrahydrofuran and 0.5 ml of N,N-dimethylformamide. A solution of 100 mg (327 mmol) of 3-{[(4-chloro-1-naphthyl)oxy]methyl}-2,6-difluoropyridine in 3 ml of tetrahydrofuran was added dropwise. The reaction mixture was stirred at room temperature for 2 days, ice was added, and then the mixture was extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed on RP silica gel and chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). 7 mg of 2-[(5-{[(4-chloro-1-naphthyl)oxy]methyl}-6-fluoropyridin-2-yl)oxy]-N-methoxy-N-methyl-ethanamine was obtained.

[0738] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.3185 (0.4); 8.2012 (3.8); 8.1806 (4.1); 8.1441 (2.6); 8.1346 (4.3); 8.1235 (3.5); 8.1186 (3.5); 8.1138 (5.0); 8.0986 (2.6); 7.7379 (2.0); 7.7351 (2.0); 7.7207 (3.0); 7.7176 (3.8); 7.7141 (2.1); 7.6997 (2.6); 7.6967 (2.4); 7.6441 (6.7); 7.6338 (3.0); 7.6312 (3.0); 7.6234 (7.6); 7.6165 (2.7); 7.6133 (4.0); 7.6105 (2.9); 7.5956 (1.9); 7.5930 (1.8); 7.1689 (6.1); 7.1480 (5.6); 6.8636 (4.3); 6.8431 (4.2); 5.2692 (16.0); 5.2479 (0.4); 4.3869 (4.7); 4.3729 (9.7); 4.3588 (5.1); 3.8703 (3.1); 3.4562 (0.4); 3.4080 (45.7); 3.3516 (5.1); 3.3445 (5.1); 3.2886 (0.4); 3.2287 (0.3); 2.9594 (4.3); 2.9454 (8.5); 2.9314 (4.4); 2.6770 (0.7); 2.6724 (0.9); 2.6680 (0.7); 2.5584 (37.8); 2.5257 (2.1); 2.5120 (53.0); 2.5079 (106.6); 2.5034 (139.2); 2.4989 (102.1); 2.4949 (52.0); 2.3874 (0.4); 2.3346 (0.7); 2.3302 (1.0); 2.3256 (0.7); 1.2984 (0.5); 1.2584 (0.8); 1.2318 (2.7); 0.1460 (0.3); 0.0079 (2.7); -0.0002 (78.0); -0.0084 (3.4); -0.1496 (0.4).

[0739] Preparation of (6-{2-[methoxy(methyl)amino]ethoxy}pyridin-3-yl)methanol

[0740]

[0741] Step 1: Preparation of 6-{2-[methoxy(methyl)amino]ethoxy}nicotinaldehyde

[0742] Under stirring at room temperature, 686 mg (15.7 mmol) of sodium hydride (a 55% mineral oil dispersion) was added to a solution of 1.64 g (13.1 mmol) of 6-fluoronicotinaldehyde in 30 ml of acetonitrile. After 10 minutes at room temperature, a solution of 1.38 g (13.1 mmol) of 2-[methoxy(methyl)amino]ethanol in 5 ml of acetonitrile was added dropwise. The reaction mixture was stirred continuously overnight, then ethyl acetate and water were added, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). 50 mg of 6-{2-[methoxy(methyl)amino]ethoxy}nicotinaldehyde was obtained.

[0743] 1 H-NMR (400.0 MHz, d6-DMSO): δ = 9.9600 (16.0); 8.7610 (8.6); 8.7555 (8.3); 8.3457 (1.0); 8.1297 (5.1); 8.1241 (4.9); 8.1081 (5.5); 8.1024 (5.9); 8.0814 (0.6); 8.0752 (0.5); 8.0607 (0.4); 7.6942 (0.5); 7.6887 (0.5); 7.6727 (0.6); 7.6671 (0.5); 7.2136 (0.7); 7.2067 (0.6); 7.1927 (0.6); 7.1859 (0.5); 7.0042 (7.5); 6.9826 (7.2); 6.8655 (0.9); 6.8443 (0.8); 5.3751 (2.9); 5.1906 (0.6); 5.1765 (1.0); 5.1623 (0.5); 4.8916 (0.4); 4.5316 (7.1); 4.5175 (14.4); 4.5033 (7.6); 4.4439 (1.6); 4.4299 (1.5); 3.4326 (0.9); 3.4004 (56.2); 3.3517 (0.7); 3.3210 (24.3); 2.9809 (6.7); 2.9668 (12.9); 2.9526 (6.7); 2.9050 (0.4); 2.6761 (0.5); 2.6720 (0.6); 2.5761 (1.0); 2.5563 (50.5); 2.5068 (89.3); 2.5025 (113.6); 2.4984 (85.1); 2.3338 (0.5); 2.3295 (0.7); 2.0957 (0.8); 2.0391 (1.0); 0.0038 (9.9); -0.0004 (50.2).

[0744] Step 2: Preparation of (6-{2-[methoxy(methyl)amino]ethoxy}pyridin-3-yl)methanol

[0745] A solution of 100 mg (476 μmol) of 6-{2-[methoxy(methyl)amino]ethoxy}nicotinaldehyde in a mixture of 15 ml of methanol and 25 ml of tetrahydrofuran was added with 27 mg (0.71 mmol) of sodium borohydride at 0 °C. The reaction solution was stirred at room temperature for 1 hour. Then water was added, and the organic solvents were removed under reduced pressure. The aqueous phase was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. 90 mg of 6-{2-[methoxy(methyl)amino]ethoxy}pyridin-3-yl)methanol was obtained.

[0746] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 6.7875 (0.4); 6.7660 (0.3); 5.1460 (0.5); 4.4268 (0.7); 4.4128 (0.6); 4.3792 (0.4); 4.3647 (0.8); 4.3501 (0.4); 3.3975 (3.3); 3.3805 (1.3); 3.3196 (12.3); 3.3030 (4.8); 3.2951 (0.5); 3.2853 (3.6); 2.9374 (0.4); 2.9228 (0.7); 2.9083 (0.3); 2.6950 (16.0); 2.5447 (2.8); 2.5236 (0.4); 2.5103 (8.4); 2.5059 (17.3); 2.5014 (23.1); 2.4968 (16.9); 2.4926 (8.6); 2.1965 (1.8); 2.1765 (3.5); 2.1560 (2.4); 1.9887 (1.4); 1.9379 (0.9); 1.9203 (2.2); 1.9174 (1.8); 1.9117 (0.5); 1.9017 (2.5); 1.8914 (0.4); 1.8819 (2.0); 1.8621 (0.6); 1.3551 (0.5); 1.2351 (0.4); 1.1924 (0.4); 1.1746 (0.7); 1.1568 (0.4); -0.0001 (2.2).

[0747] Preparation of 6-fluoro-3'-(trifluoromethoxy)biphenyl-3-ol

[0748]

[0749] By introducing an argon stream, a mixture of 5.0 g (26 mmol) of 3-bromo-4-fluorophenol, 7.00 g (34.0 mmol) of [3-(trifluoromethoxy)phenyl]boronic acid, 7.60 g (55.0 mmol) of potassium carbonate, 35 ml of tetrahydrofuran and 7 ml of water was made free of dissolved oxygen, and then 0.50 g (0.43 mmol) of tetrakis(triphenylphosphine)palladium was added. The reaction mixture was stirred overnight at 80 °C, then concentrated under reduced pressure, and the pH was adjusted to 1 using 1 M hydrochloric acid. Water and ethyl acetate were added, the phases were separated, and the aqueous phase was repeatedly extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographically separated on RP silica gel by MPLC (gradient: H2O / acetonitrile). 4.85 g of 6-fluoro-3'-(trifluoromethoxy)biphenyl-3-ol was obtained.

[0750] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.3185 (1.1); 7.6289 (0.4); 7.6203 (1.7); 7.6006 (4.7); 7.5807 (3.6); 7.5675 (0.4); 7.5484 (2.9); 7.5453 (3.0); 7.5287 (1.6); 7.5257 (1.5); 7.4457 (3.0); 7.4083 (1.8); 7.4056 (1.9); 7.4028 (1.6); 7.3882 (1.5); 7.3855 (1.6); 7.3826 (1.4); 7.1303 (2.2); 7.1081 (2.7); 7.1037 (2.5); 7.0815 (2.6); 6.8504 (2.1); 6.8429 (2.6); 6.8339 (2.1); 6.8264 (2.6); 6.7931 (1.5); 6.7833 (2.0); 6.7755 (1.3); 6.7710 (1.4); 6.7614 (1.6); 6.7535 (1.0); 2.5257 (0.5); 2.5123 (15.4); 2.5079 (32.4); 2.5034 (43.5); 2.4989 (31.4); 2.4945 (15.1); 2.0760 (16.0); 0.0080 (0.7); -0.0002 (21.3); -0.0085 (0.8).

[0751] Preparation of 2-chloro-5-{[(4-chloro-1-naphthyl)oxy]methyl}pyrimidine

[0752]

[0753] Step 1: Preparation of 5-(bromomethyl)-2-chloropyrimidine

[0754] A solution of 200 mg (1.56 mmol) of 2-chloro-5-methylpyrimidine, 277 mg (1.56 mmol) of N-bromosuccinimide and 26 mg (0.16 mmol) of 2,2'-azobis(2-methylpropionitrile) in 17.6 ml of chlorobenzene was heated under reflux for 16 hours. The reaction solution was then washed with an aqueous solution of Na2SO3 and a saturated aqueous solution of NaHCO3, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 76 mg of 5-(bromomethyl)-2-chloropyrimidine was obtained.

[0755] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.9119 (1.1); 8.8913 (15.0); 8.8619 (0.7); 8.8222 (1.3); 8.6390 (1.4); 5.5539 (0.5); 5.3766 (0.9); 4.8528 (2.2); 4.7481 (16.0); 4.7234 (1.3); 3.3281 (67.0); 2.6718 (0.4); 2.5248 (0.8); 2.5114 (23.6); 2.5071 (48.7); 2.5027 (64.9); 2.4983 (46.7); 2.4941 (22.6); 2.3295 (0.4); 2.2725 (2.8); 2.2461 (0.6); 1.4376 (0.4); -0.0002 (0.7).

[0756] Step 2: Preparation of 2-chloro-5-{[(4-chloro-1-naphthyl)oxy]methyl}pyrimidine

[0757] At room temperature, a suspension of 38 mg (0.21 mmol) of 4-chloro-1-naphthol and 60 mg (0.43 mmol) of potassium carbonate in 1 ml of acetonitrile was stirred for 1 hour. The mixture was cooled to 0 °C, and a solution of 76 mg (0.27 mmol) of 5-(bromomethyl)-2-chloropyrimidine in acetonitrile was added dropwise. The reaction mixture was stirred at room temperature overnight, then water and a saturated solution of NaHCO3 were added. The mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with water and a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 70 mg of 2-chloro-5-{[(4-chloro-1-naphthyl)oxy]methyl}pyrimidine was obtained.

[0758] 1H-NMR (400.0 MHz, d6-DMSO): δ = 9.0173 (16.0); 8.9478 (1.4); 8.8875 (0.4); 8.3103 (2.7); 8.2893 (2.8); 8.1476 (2.8); 8.1269 (3.1); 7.7565 (1.4); 7.7534 (1.6); 7.7393 (2.2); 7.7359 (2.9); 7.7323 (1.5); 7.7183 (2.0); 7.7150 (1.9); 7.6608 (6.9); 7.6439 (1.8); 7.6402 (8.3); 7.6231 (1.4); 7.6202 (1.3); 7.1554 (4.4); 7.1485 (0.6); 7.1345 (4.1); 7.1276 (0.5); 5.4057 (11.9); 5.3819 (1.1); 4.8531 (0.5); 3.3215 (34.5); 2.6719 (0.4); 2.5254 (1.0); 2.5206 (1.5); 2.5120 (25.1); 2.5075 (54.3); 2.5029 (73.9); 2.4983 (52.7); 2.4938 (24.5); 2.3297 (0.4); 0.1459 (0.4); 0.0080 (3.4); -0.0002 (106.7); -0.0085 (3.6); -0.1498 (0.4).

[0759] Preparation of 4-chloro-3-methoxyphenol and 2-chloro-5-methoxyphenol

[0760]

[0761] At 0 °C, 342 mg (2.54 mmol) of sulfonyl chloride was added to a solution of 300 mg (2.42 mmol) of 3-methoxyphenol in 2 ml of CH2Cl2. The reaction solution was stirred at 0 °C for 1 hour, then water and CH2Cl2 were added. The phases were separated, and the aqueous phase was repeatedly extracted with CH2Cl2. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was adsorbed on RP silica gel and chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). 125 mg of 4-chloro-3-methoxyphenol and 194 mg of 2-chloro-5-methoxyphenol were obtained.

[0762] 4-chloro-3-methoxyphenol:

[0763] 1H-NMR (400.0 MHz, d6-DMSO): δ = 9.6746 (2.2); 7.1593 (2.9); 7.1379 (3.1); 7.0630 (0.3); 7.0428 (0.5); 6.5162 (2.7); 6.5096 (2.8); 6.3642 (1.8); 6.3576 (1.7); 6.3484 (0.4); 6.3427 (1.7); 6.3362 (1.7); 6.3152 (0.4); 6.3094 (0.4); 3.7876 (0.8); 3.7744 (16.0); 3.7390 (0.5); 3.6885 (0.6); 3.6800 (2.9); 3.3248 (6.3); 2.5240 (0.4); 2.5064 (18.8); 2.5021 (24.2); 2.4978 (17.3); 2.0253 (0.4); 0.0078 (0.5); -0.0002 (11.6); -0.0073 (0.4).

[0764] 2-chloro-5-methoxyphenol:

[0765] 1 H-NMR (400.0 MHz, d6-DMSO): δ = 10.1114 (4.9); 7.2062 (2.6); 7.1843 (2.8); 6.5256 (2.6); 6.5185 (2.9); 6.4149 (1.6); 6.4077 (1.4); 6.3929 (1.5); 6.3857 (1.3); 3.6893 (16.0); 3.3297 (3.7); 2.5112 (4.3); 2.5071 (8.6); 2.5028 (11.2); 2.4984 (7.9).

[0766] Preparation of 5-[2-(diethylamino)ethoxy]pyridine-2-carbaldehyde

[0767]

[0768] At 65 °C, a suspension of 1.0 g (8.1 mmol) of 5-hydroxypyridine-2-carbaldehyde and 3.4 g (25 mmol) of K2CO3 in 25 ml of N,N-dimethylformamide was stirred for 2 hours. At 30 °C, 13 mg (81 μmol) of potassium iodide and 2.43 g (9.14 mmol) of 2-bromo-N,N-diethyl-ethylamine hydrobromide (1:1) were then added and the reaction mixture was stirred at 65 °C for 16 hours. 1.27 g (4.87 mmol) of 2-bromo-N,N-ethyl-ethanolamine hydrobromide (1:1), 1.7 g (12 mmol) of potassium carbonate and 13 mg (81 μmol) of potassium iodide were added and the mixture was stirred at 65 °C for a further 20 hours. The reaction mixture was filtered through diatomaceous earth and the solvent was removed under reduced pressure. The residue was chromatographed on RP silica gel by MPLC (gradient: H2O / acetonitrile). After removal of the solvent under reduced pressure, water was added to the residue and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and the solvent was removed under reduced pressure. 803 mg of 5-[2-(diethylamino)ethoxy]pyridine-2-carbaldehyde were obtained.

[0769] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 9.8858 (4.6); 8.4862 (2.4); 8.4793 (2.5); 7.9378 (2.3); 7.9161 (2.6); 7.6092 (1.2); 7.6024 (1.3); 7.5874 (1.1); 7.5807 (1.1); 4.2358 (2.2); 4.2208 (4.6); 4.2059 (2.3); 3.3230 (10.4); 2.8232 (2.2); 2.8083 (4.5); 2.7933 (2.2); 2.5739 (2.3); 2.5561 (7.3); 2.5383 (7.5); 2.5205 (3.2); 2.5073 (16.8); 2.5030 (22.2); 2.4987 (17.2); 0.9826 (8.0); 0.9649 (16.0); 0.9471 (7.7); -0.0002 (20.2).

[0770] Preparation of ethyl 5-(4-ethylpiperazin-1-yl)-3-fluoropyridine-2-carboxylate

[0771]

[0772] In a microwave reactor, a suspension of 1.98 g (17.4 mmol) of 1-ethylpiperazine, 2.50 g (13.4 mmol) of ethyl 3,5-difluoropyridine-2-carboxylate, and 2.40 g (17.4 mmol) of potassium carbonate in 21 ml of N,N-dimethylacetamide was heated at 70 °C for 2 hours. Then water was added to the reaction mixture, and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate + 1% v / v triethylamine). 1.46 g of ethyl 5-(4-ethylpiperazin-1-yl)-3-fluoropyridine-2-carboxylate was obtained.

[0773] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2421 (2.7); 8.2374 (4.2); 7.2262 (2.2); 7.2203 (2.2); 7.1891 (2.2); 7.1832 (2.2); 4.2963 (2.2); 4.2786 (7.0); 4.2608 (7.1); 4.2431 (2.3); 3.4222 (6.1); 3.4097 (7.9); 3.3967 (6.4); 3.3230 (23.9); 2.9455 (4.4); 2.7859 (3.6); 2.5080 (21.5); 2.5036 (28.6); 2.4992 (21.7); 2.4833 (6.8); 2.4705 (8.4); 2.4579 (6.3); 2.3926 (1.9); 2.3746 (6.1); 2.3566 (6.2); 2.3387 (2.1); 1.9587 (3.8); 1.3048 (7.7); 1.2870 (16.0); 1.2693 (7.5); 1.0464 (6.7); 1.0284 (13.9); 1.0105 (6.4); 0.0079 (0.8); -0.0002 (18.1); -0.0082 (0.8).

[0774] Preparation of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxy-N-meth yl ethanamine

[0775]

[0776] Step 1: Preparation of {6-fluoro-5-[2-(methoxyimino)ethoxy]pyridin-2-yl}methanol

[0777] 334 mg (3.97 mmol) of sodium bicarbonate was added to a solution of 300 mg (2.65 mmol) of 2-fluoropyridin-3-ol in 2.3 ml of water, and the mixture was stirred at room temperature for 15 minutes. After heating to 90 °C, 696 μl (9.28 mmol) of 37% aqueous formaldehyde solution was added little by little, the mixture was stirred at 90 °C for 2.5 hours, and then stirred at room temperature for 16 hours. After adding 2 g of ice, the pH of the mixture was adjusted to 1 with 6N aqueous hydrochloric acid and extracted repeatedly with ethyl acetate. The combined organic extracts were dried over sodium sulfate, filtered, and the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and filtered, and the solvent was removed under reduced pressure. The intermediate 2-fluoro-6-(hydroxymethyl)pyridin-3-ol thus obtained was dissolved in 9 ml of acetonitrile, 579 mg (4.19 mmol) of potassium carbonate and 413 mg (3.07 mmol, purity 80%) of 2-chloro-N-methoxyethylamine were added, and then the mixture was heated under reflux for 4 hours and stirred at room temperature for 16 hours. After filtering off the precipitate, the filtrate was adsorbed on silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). A mixture of (E,z) isomers of 205 mg of {6-fluoro-5-[2-(methoxyimino)ethoxy]pyridin-2-yl}methanol was obtained.

[0778] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 7.7277 (0.9); 7.7073 (1.0); 7.7015 (1.0); 7.6810 (1.0); 7.6596 (1.1); 7.6456 (2.5); 7.6316 (1.2); 7.6227 (0.4); 7.6167 (0.4); 7.5963 (0.4); 7.3251 (1.6); 7.3048 (1.4); 7.1226 (0.4); 7.1133 (0.9); 7.1040 (0.4); 5.4528 (0.7); 5.4500 (1.3); 5.4382 (1.6); 5.4352 (2.8); 5.4235 (0.8); 5.4205 (1.4); 4.9464 (1.8); 4.9371 (1.8); 4.7654 (4.5); 4.7514 (4.4); 4.4156 (4.5); 4.4009 (4.4); 3.8674 (5.9); 3.7989 (16.0); 3.3316 (17.6); 2.5251 (0.4); 2.5112 (9.1); 2.5072 (18.1); 2.5028 (23.6); 2.4983 (17.5); -0.0002 (4.4).

[0779] Step 2: Preparation of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxyethanamine

[0780] 194 μL (2.66 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added to a solution of 190 mg (0.88 mmol) of a mixture of (E,Z)-isomers of {6-fluoro-5-[2-(methoxyimino)ethoxy]pyridin-2-yl}methanol in 6 mL of toluene. The reaction mixture was stirred at room temperature for 3.5 h and then concentrated under reduced pressure. The residue was dissolved in 6 mL of N,N-dimethylformamide and 246 mg (1.15 mmol) of 5,6-dichloro-1-naphthol and 368 mg (2.66 mmol) of potassium carbonate were added. The reaction mixture was stirred at 70 °C for 50 min and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed onto silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). A mixture of (E,Z)-isomers of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxyethanamine (332 mg) was obtained.

[0781] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2461 (1.6); 8.2385 (0.8); 8.2236 (1.8); 8.2158 (0.9); 8.1528 (0.4); 8.1300 (0.4); 7.8100 (1.9); 7.8011 (0.8); 7.7885 (2.7); 7.7808 (1.1); 7.7752 (0.8); 7.7546 (0.9); 7.7077 (3.1); 7.6876 (3.4); 7.6849 (3.5); 7.6688 (4.6); 7.6549 (1.2); 7.6479 (1.4); 7.6134 (0.6); 7.5859 (1.7); 7.5663 (2.1); 7.5548 (0.4); 7.5472 (0.6); 7.5357 (0.4); 7.2592 (2.2); 7.2397 (2.0); 7.1517 (0.5); 7.1424 (1.1); 7.1331 (0.5); 7.0119 (0.3); 5.2828 (7.5); 4.9992 (2.0); 4.9899 (2.0); 4.8222 (4.0); 4.8083 (3.9); 3.8747 (6.9); 3.8067 (16.0); 3.3316 (25.0); 2.6729 (0.3); 2.5260 (0.9); 2.5125 (20.4); 2.5083 (41.0); 2.5038 (53.8); 2.4993 (39.3); 2.4950 (19.3); 2.3305 (0.4); 1.3971 (0.4); 0.0079 (0.6); -0.0002 (16.4); -0.0084 (0.6).

[0782] Step 3: 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methox y-N-methyl ethanamine

[0783] 68 mg (1.08 mmol) of sodium cyanoborohydride was added to a solution of 295 mg (0.72 mmol) of a mixture of (E,z)-isomers of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxyethanamine in 6.2 ml of acetic acid. After 30 minutes at room temperature, 1.08 ml (14.4 mmol) of an aqueous solution of formaldehyde at 37% concentration was added, and after a further 5 minutes, 68 mg (1.08 mmol) of sodium cyanoborohydride was added. The reaction mixture was stirred at room temperature for 30 minutes and concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed onto silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 236 mg of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-2-fluoropyridin-3-yl)oxy]-N-methoxy-N-methylethanamine was obtained.

[0784] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2363 (2.0); 8.2351 (2.0); 8.2136 (2.2); 8.2124 (2.2); 7.8066 (1.6); 7.7851 (3.2); 7.7646 (1.2); 7.7589 (1.0); 7.7384 (1.1); 7.7052 (3.3); 7.6877 (1.6); 7.6825 (3.2); 7.6679 (2.1); 7.6468 (1.3); 7.5581 (2.0); 7.5379 (1.7); 7.2605 (1.9); 7.2413 (1.8); 5.2740 (6.6); 4.2559 (1.9); 4.2421 (4.0); 4.2282 (2.0); 3.4043 (19.9); 3.3348 (27.4); 2.9998 (1.7); 2.9861 (3.5); 2.9722 (1.7); 2.5742 (16.0); 2.5273 (0.4); 2.5139 (10.8); 2.5095 (22.1); 2.5050 (29.0); 2.5005 (21.1); 2.4961 (10.3); 1.3968 (0.4); 0.0079 (0.5); -0.0002 (15.7); -0.0084 (0.5).

[0785] Preparation of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N-methoxy-N-meth yl ethanamine

[0786]

[0787] Step 1: Preparation of methyl 3-fluoro-5-[2-(methoxyimino)ethoxy]pyridine-2-carboxylate

[0788] At room temperature, 18.39 g (133 mmol) of potassium carbonate and 59.1 ml (44.4 mmol) of a 0.75 M solution of 2-chloro-N-methoxyethanamine in acetonitrile were added to a solution of 7.59 g (44.4 mmol) of methyl 3-fluoro-5-hydroxypyridine-2-carboxylate in 253 ml of acetonitrile. The reaction mixture was heated under reflux for 27 hours and then stirred at room temperature for 3 days. After removing the precipitate by filtration, the filtrate was concentrated under reduced pressure. A mixture of (E,Z) isomers of methyl 3-fluoro-5-[2-(methoxyimino)ethoxy]pyridine-2-carboxylate, 5.17 g, was obtained.

[0789] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.3132 (1.5); 8.3107 (1.6); 8.3074 (1.7); 8.3004 (0.7); 8.2977 (0.7); 8.2942 (0.7); 7.6847 (1.0); 7.6710 (3.1); 7.6648 (1.2); 7.6574 (1.1); 7.6391 (1.0); 7.6331 (1.1); 7.6238 (0.4); 7.6178 (0.4); 7.5925 (0.4); 7.5864 (0.4); 7.1439 (0.4); 7.1344 (0.8); 7.1251 (0.4); 5.0357 (1.5); 5.0263 (1.5); 4.8625 (4.0); 4.8488 (3.9); 3.8787 (5.0); 3.8551 (16.0); 3.8083 (14.4); 3.3195 (2.3); 2.5068 (17.8); 2.5024 (23.4); 2.4981 (17.5); 0.0079 (0.6); -0.0002 (18.6); -0.0085 (0.9).

[0790] Step 2: Preparation of methyl 3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate

[0791] 2.01 g (32.0 mmol) of sodium cyanoborohydride was added to a solution of 5.17 g of a mixture of (E,z)-isomers of methyl 3-fluoro-5-[2-(methoxyimino)ethoxy]pyridine-2-carboxylate in 180 ml of acetic acid. After 1 h at room temperature, 32.0 ml (427 mmol) of 37% aqueous formaldehyde solution was added and, after a further 15 min, 2.01 g (32.0 mmol) of sodium cyanoborohydride was added. The reaction mixture was stirred at room temperature for 1 h and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed on silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 4.61 g of methyl 3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate was obtained.

[0792] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2901 (1.6); 8.2874 (2.2); 8.2844 (2.2); 8.2817 (2.1); 7.6473 (1.3); 7.6414 (1.4); 7.6153 (1.3); 7.6094 (1.4); 4.2890 (2.2); 4.2754 (4.2); 4.2617 (2.2); 3.8498 (16.0); 3.4048 (19.4); 3.3192 (5.5); 2.9915 (1.8); 2.9779 (3.7); 2.9643 (1.9); 2.5678 (16.0); 2.5202 (0.5); 2.5112 (8.5); 2.5070 (18.4); 2.5025 (25.4); 2.4981 (19.5); 1.9893 (0.4); 1.9092 (6.7); 0.0079 (0.6); -0.0002 (18.8); -0.0083 (0.9).

[0793] Step 3: Preparation of (3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol

[0794] At 10 °C, 2.78 g (73.6 mmol) of sodium borohydride was added to a solution of 7.84 g (30.4 mmol) of methyl 3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridine-2-carboxylate in 78 ml of ethanol, and the reaction mixture was stirred at 10 °C for 1 hour and then at room temperature for an additional 16 hours. After adding 100 ml of ice-cooled water, the mixture was stirred at room temperature for 20 minutes. Subsequently, most of the ethanol was removed under reduced pressure, and the residue was repeatedly extracted with ethyl acetate. The combined organic phases were washed with a saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. 5.31 g of (3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol was obtained.

[0795] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.1383 (2.4); 8.1339 (2.4); 7.4605 (1.4); 7.4548 (1.4); 7.4312 (1.4); 7.4254 (1.4); 5.1829 (1.2); 5.1683 (2.5); 5.1537 (1.2); 4.5150 (2.9); 4.5095 (3.0); 4.5004 (2.9); 4.4950 (2.8); 4.2006 (2.3); 4.1868 (4.6); 4.1730 (2.4); 3.4028 (18.6); 3.3203 (16.8); 2.9662 (2.1); 2.9525 (4.1); 2.9386 (2.1); 2.5626 (16.0); 2.5058 (38.8); 2.5016 (49.8); 2.4974 (37.0); -0.0002 (8.2).

[0796] Step 4: Preparation of 2-[(6-[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N-methoxy N-methylacetamide

[0797] 20 mL (273 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added to 1.0 g (4.34 mmol) of (3-fluoro-5-{2-[methoxy(methyl)amino]ethoxy}pyridin-2-yl)methanol. The reaction mixture was stirred at room temperature for 80 minutes and then concentrated under reduced pressure. The residue was dissolved in 26 mL of N,N-dimethylformamide, and 787 mg (3.69 mmol) of 5,6-dichloro-1-naphthol and 2.55 g (18.5 mmol) of potassium carbonate were added. The reaction mixture was stirred at 70 °C for 4 hours and 20 minutes, stirred at room temperature for an additional 15 hours, and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed onto silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 1.16 g of 2-[(6-[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N-methoxy-N-methylacetamide was obtained.

[0798] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2575 (2.3); 8.2531 (2.4); 8.0842 (2.2); 8.0615 (2.5); 7.8056 (1.7); 7.7842 (2.6); 7.7031 (1.6); 7.6833 (2.3); 7.6593 (3.7); 7.6365 (3.1); 7.6107 (1.4); 7.6047 (1.3); 7.5811 (1.4); 7.5752 (1.4); 7.3719 (2.2); 7.3525 (1.9); 5.3891 (4.6); 5.3853 (4.7); 4.2479 (2.0); 4.2342 (4.2); 4.2204 (2.1); 3.4116 (19.6); 3.3190 (60.2); 2.9871 (1.9); 2.9735 (3.7); 2.9597 (1.9); 2.6759 (0.5); 2.6712 (0.7); 2.6670 (0.5); 2.5718 (16.0); 2.5244 (2.2); 2.5108 (43.8); 2.5066 (86.7); 2.5022 (117.2); 2.4978 (89.0); 2.3336 (0.5); 2.3291 (0.7); 2.3247 (0.5); 1.9000 (0.4); 0.0079 (1.3); -0.0001 (31.9); -0.0081 (1.4).

[0799] Preparation of {[2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-fluoropyridin-3-yl}oxy)ethyl](methyl amino}acetonitrile

[0800]

[0801] Step 1: Preparation of methyl 5-(2-bromoethoxy)-3-fluoropyridine-2-carboxylate

[0802] At room temperature, 7.07 g (51.1 mmol) of potassium carbonate and 8.9 mL (103 mmol) of 1,2-dibromoethane were added to a solution of 3.50 g (20.5 mmol) of methyl 3-fluoro-5-hydroxypyridine-2-carboxylate in 100 mL of acetonitrile. The reaction mixture was stirred overnight at 80 °C, then adsorbed on silica gel and chromatographically separated on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 1.96 g of methyl 5-(2-bromoethoxy)-3-fluoropyridine-2-carboxylate was obtained.

[0803] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.3079 (1.6); 8.3054 (1.8); 8.3021 (1.8); 7.6591 (1.2); 7.6532 (1.2); 7.6275 (1.2); 7.6215 (1.2); 4.5409 (2.1); 4.5277 (2.7); 4.5142 (2.3); 3.8715 (2.4); 3.8545 (16.0); 3.8449 (2.6); 3.3192 (14.1); 2.5107 (13.3); 2.5064 (27.3); 2.5019 (37.7); 2.4975 (28.6); 2.4932 (14.4); 1.3979 (0.8); 0.0080 (0.4); -0.0002 (10.4); -0.0083 (0.5).

[0804] Step 2: Preparation of [5-(2-bromoethoxy)-3-fluoropyridin-2-yl]methanol

[0805] Under ice-cooling, 3.19 g (84.4 mmol) of sodium borohydride was added to a solution of 9.39 g (33.8 mmol) of methyl 5-(2-bromoethoxy)-3-fluoropyridine-2-carboxylate in 300 mL of ethanol, and the reaction mixture was stirred for 1 hour under ice-cooling and then stirred overnight at room temperature. After adding 250 mL of ice-cooled water, the mixture was stirred at room temperature for 40 minutes, most of the ethanol was removed under reduced pressure, and the residue was repeatedly extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated under reduced pressure. 5.96 g of [5-(2-bromoethoxy)-3-fluoropyridin-2-yl]methanol (purity 88%) was obtained.

[0806] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.1532 (11.0); 8.1489 (10.9); 8.1037 (0.9); 8.0999 (0.9); 7.4823 (6.6); 7.4763 (6.8); 7.4532 (6.7); 7.4473 (6.8); 7.3980 (0.6); 7.3921 (0.6); 7.3686 (0.6); 7.3625 (0.6); 6.5251 (0.4); 5.2083 (5.5); 5.1936 (11.9); 5.1789 (6.3); 5.1624 (1.1); 5.1480 (0.5); 4.5215 (12.7); 4.5161 (14.0); 4.5069 (13.8); 4.5016 (13.5); 4.4908 (1.7); 4.4486 (11.6); 4.4354 (15.8); 4.4218 (12.8); 4.3831 (0.6); 4.3710 (0.8); 4.3578 (0.7); 4.1452 (0.6); 4.1279 (1.7); 4.1104 (1.7); 4.0930 (0.6); 3.9835 (0.7); 3.9703 (0.8); 3.9581 (0.6); 3.8396 (13.2); 3.8260 (16.0); 3.8128 (12.1); 3.3216 (53.4); 2.6750 (0.7); 2.6709 (0.9); 2.5061 (112.3); 2.5017 (151.1); 2.4974 (118.2); 2.3326 (0.6); 2.3286 (0.8); 1.3559 (1.8); 1.3385 (3.6); 1.3210 (1.7); 0.1459 (0.6); 0.0079 (5.5); -0.0002 (130.8); -0.1497 (0.6).

[0807] Step 3: Preparation of 5-(2-bromoethoxy)-2-[(dibenzo[b,d]furan-2-yloxy)methyl]-3-fluoropyridine Step 4: {[2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-fluoropyridin-3-yl}oxy)ethyl](methyl)amino}acetonitrile

[0808] 11.1 mL (152 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added to 516 mg (2.06 mmol) of [5-(2-bromoethoxy)-3-fluoropyridin-2-yl]methanol. The reaction mixture was stirred at room temperature for 80 minutes and then concentrated under reduced pressure. The residue was dissolved in 14 mL of N,N-dimethylformamide and 388 mg (2.10 mmol) of dibenzo[b,d]furan-2-ol and 1.43 g (10.3 mmol) of potassium carbonate were added. The reaction mixture was stirred at 70 °C for 2 hours and 40 minutes and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed onto silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 120 mg of 5-(2-bromoethoxy)-2-[(dibenzo[b,d]furan-2-yloxy)methyl]-3-fluoropyridine was obtained.

[0809] 11H-NMR (400.0 MHz, d6-DMSO): δ = 8.2654 (7.9); 8.2602 (7.8); 8.1324 (5.7); 8.1134 (6.2); 7.8764 (9.5); 7.8698 (9.6); 7.6849 (6.7); 7.6643 (8.7); 7.6304 (10.0); 7.6131 (5.3); 7.6079 (15.2); 7.5841 (4.8); 7.5781 (4.6); 7.5414 (3.2); 7.5384 (3.2); 7.5205 (6.1); 7.5025 (3.4); 7.5000 (3.2); 7.4159 (4.5); 7.3969 (7.2); 7.3785 (3.2); 7.1949 (5.8); 7.1900 (5.6); 7.1726 (5.2); 7.1659 (5.1); 5.2553 (15.8); 5.2507 (16.0); 4.4973 (7.8); 4.4843 (10.2); 4.4706 (8.4); 4.4321 (0.5); 4.4200 (0.6); 4.4066 (0.5); 4.0096 (0.6); 3.9968 (0.7); 3.9842 (0.5); 3.8650 (8.7); 3.8513 (10.3); 3.8383 (7.9); 3.5441 (0.3); 3.5294 (0.4); 3.3607 (1876.4); 2.6834 (1.1); 2.6791 (1.5); 2.6747 (1.1); 2.5321 (3.9); 2.5187 (89.6); 2.5143 (185.4); 2.5099 (255.8); 2.5055 (190.1); 2.5013 (91.8); 2.3411 (1.0); 2.3368 (1.4); 2.3327 (1.0); 1.4029 (0.4); 1.2389 (0.3).

[0810] Preparation of 2-[(6-{[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N,N-diethylacetamide Step 1: Preparation of {5-[2-(diethylamino)ethoxy]-3-fluoropyridin-2-yl}methanol

[0811] 99 mg (1.41 mmol) of (methylamino)acetonitrile was added to a solution of 117 mg (0.28 mmol) of 5-(2-bromoethoxy)-2-[(dibenzo[b,d]furan-2-yloxy)methyl]-3-fluoropyridine in 2 ml of dimethylformamide, and the mixture was stirred at 80 °C for 4 hours. The reaction mixture was then adsorbed onto silica gel and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 95 mg of {[2-({6-[(dibenzo[b,d]furan-2-yloxy)methyl]-5-fluoropyridin-3-yl}oxy)ethyl](methyl)amino}acetonitrile was obtained.

[0812] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2459 (2.6); 8.2408 (2.7); 8.0776 (2.6); 8.0549 (2.9); 7.8046 (1.9); 7.7832 (2.9); 7.7018 (1.8); 7.6818 (2.6); 7.6614 (5.2); 7.6389 (3.4); 7.5845 (1.5); 7.5786 (1.5); 7.5550 (1.5); 7.5491 (1.5); 7.3692 (2.5); 7.3496 (2.2); 5.3903 (5.1); 5.3868 (5.2); 4.2442 (2.3); 4.2307 (4.4); 4.2171 (2.3); 3.8084 (10.6); 3.3201 (14.6); 2.8214 (2.3); 2.8079 (4.2); 2.7943 (2.2); 2.6761 (0.4); 2.6717 (0.6); 2.6678 (0.4); 2.5247 (1.3); 2.5069 (68.8); 2.5026 (94.4); 2.4983 (71.4); 2.3426 (16.0); 2.3298 (0.8); 0.0078 (1.2); -0.0002 (33.8); -0.0077 (1.4).

[0813] Step 2: Preparation of 2-[(6-{[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N,N-di ethylacetamide

[0814]

[0815] Preparation of N-{2-[(6-{[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]ethyl}-N,2-

[0816] 918 μl (8.88 mmol) of diethylamine was added to a solution of 740 mg (2.96 mmol) of [5-(2-bromoethoxy)-3-fluoropyridin-2-yl]methanol in 2 ml of dimethylformamide, and the mixture was stirred at 75 °C for 5 hours. The reaction mixture was chromatographically separated on RP silica gel by MPLC (gradient: water / acetonitrile). 613 mg of {5-[2-(diethylamino)ethoxy]-3-fluoropyridin-2-yl}methanol was obtained.

[0817] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.1056 (2.0); 8.1019 (2.0); 7.4256 (1.2); 7.4196 (1.2); 7.3961 (1.2); 7.3901 (1.3); 5.1802 (0.5); 5.1657 (0.9); 5.1512 (0.5); 4.5038 (2.1); 4.4959 (2.1); 4.1224 (2.1); 4.1074 (4.6); 4.0923 (2.2); 3.3237 (7.8); 2.7819 (2.2); 2.7669 (4.4); 2.7518 (2.0); 2.5614 (2.3); 2.5436 (7.3); 2.5258 (7.9); 2.5064 (26.0); 2.5019 (33.3); 2.4974 (24.8); 1.9039 (1.0); 0.9769 (7.9); 0.9592 (16.0); 0.9414 (7.5); 0.0079 (1.1); -0.0002 (28.0); -0.0083 (1.3).

[0818] dimethylpropan-2-aminium chloride and N-{2-[(6-[(5,6-dichloro-1-naphthalenyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy ethyl}-N,2-dimethylpropan-2-amine

[0819] 1.0 mL (13.7 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added to a solution of 634 mg (2.62 mmol) of {5-[2-(diethylamino)ethoxy]-3-fluoropyridin-2-yl}methanol in 30 mL of dichloromethane. The mixture was stirred at room temperature for 90 minutes. After adding 30 mL of toluene, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 12 mL of N,N-dimethylformamide, and one-sixth of this solution was added to 79 mg (0.37 mmol) of 5,6-dichloro-1-naphthol and 428 mg (1.31 mmol) of cesium carbonate. The reaction mixture was stirred at 80 °C overnight and then chromatographed on RP silica gel by MPLC (gradient: water / acetonitrile). 144 mg of 2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]-N,N-diethylethylamine was obtained.

[0820] 1 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2239 (2.2); 8.2196 (2.2); 8.0771 (2.1); 8.0544 (2.3); 7.8029 (1.6); 7.7815 (2.3); 7.7006 (1.5); 7.6807 (2.1); 7.6591 (4.2); 7.6363 (2.8); 7.5745 (1.2); 7.5687 (1.3); 7.5449 (1.2); 7.5391 (1.2); 7.3669 (2.0); 7.3476 (1.8); 5.3842 (4.2); 5.3808 (4.4); 4.1683 (1.9); 4.1533 (4.1); 4.1383 (2.0); 3.3230 (39.8); 2.8013 (1.8); 2.7865 (3.8); 2.7714 (1.8); 2.6720 (0.4); 2.6675 (0.3); 2.5675 (2.1); 2.5497 (6.7); 2.5319 (7.2); 2.5071 (57.4); 2.5027 (75.6); 2.4983 (56.7); 2.3294 (0.4); 2.3249 (0.3); 0.9792 (7.8); 0.9615 (16.0); 0.9437 (7.5); 0.0078 (2.3); -0.0002 (54.0); -0.0081 (2.7).

[0821] Preparation of 2-[(2-{[(4-chloro-1-naphthalenyl)oxy]methyl}pyrimidin-5-yl)oxy]-N-methoxy-N-methylacetamide Step 1: 5-(Benzyloxy)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidine Step 2: Preparation of 2-{[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-yl]oxy}-N-meth

[0822]

[0823] 1.0 mL (13.7 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added to a solution of 596 mg (2.33 mmol) of (5-{2-[tert-butyl(methyl)amino]ethoxy}-3-fluoropyridin-2-yl)methanol in 20 mL of dichloromethane. The mixture was stirred at room temperature for 90 minutes. After adding 30 mL of toluene, the reaction mixture was concentrated under reduced pressure. The residue was dissolved in 12 mL of N,N-dimethylformamide, and one-sixth of this solution was added to 70 mg (0.33 mmol) of 5,6-dichloro-1-naphthol and 378 mg (1.16 mmol) of cesium carbonate. The reaction mixture was stirred at 80 °C overnight and then chromatographed on RP silica gel by MPLC (gradient: water / acetonitrile). During the injection of the reaction mixture liquid into the MPLC, the solid that precipitated in the syringe after adding ethanol and water was redissolved by adding acetonitrile and 1 N aqueous hydrochloric acid. 99 mg of N-{2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]ethyl}-N,2-dimethylpropan-2-aminium chloride (purity 78%) and 29 mg of N-{2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]ethyl}-N,2-dimethylpropan-2-amine were obtained.

[0824] N-{2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]ethyl}-N,2-dimethylpropan-2-aminium chloride (purity 78%):

[0825] 1H-NMR (400.0 MHz, d6-DMSO): δ = 9.6357 (0.4); 8.3034 (1.2); 8.2990 (1.2); 8.0670 (1.2); 8.0443 (1.3); 7.8101 (1.0); 7.7885 (1.4); 7.7061 (0.8); 7.6863 (1.3); 7.6764 (1.9); 7.6653 (0.8); 7.6537 (2.2); 7.6362 (0.5); 7.6235 (1.3); 7.3742 (1.2); 7.3549 (1.0); 5.7570 (0.8); 5.4187 (2.5); 5.2320 (0.6); 4.5213 (1.4); 4.5096 (1.0); 3.8081 (0.4); 3.7953 (0.4); 3.7817 (0.4); 3.7708 (0.4); 3.3260 (52.0); 2.8122 (2.7); 2.8002 (2.9); 2.6758 (0.3); 2.6716 (0.4); 2.5068 (60.7); 2.5024 (79.5); 2.4980 (60.3); 2.3292 (0.4); 2.3249 (0.4); 1.3720 (16.0); 0.1460 (0.3); 0.0077 (3.4); -0.0002 (73.8); -0.0083 (4.0); -0.1498 (0.3).

[0826] N-{2-[(6-{[(5,6-dichloro-1-naphthyl)oxy]methyl}-5-fluoropyridin-3-yl)oxy]ethyl}-N,2-dimethylpropan-2-amine:

[0827] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.2188 (1.1); 8.2144 (1.1); 8.0759 (1.0); 8.0532 (1.2); 7.8031 (0.8); 7.7816 (1.2); 7.7000 (0.8); 7.6800 (1.1); 7.6602 (2.0); 7.6378 (1.4); 7.5625 (0.6); 7.5566 (0.6); 7.5326 (0.6); 7.5268 (0.6); 7.3651 (1.0); 7.3459 (0.9); 5.3811 (2.2); 4.1263 (0.8); 4.1109 (1.6); 4.0956 (0.8); 3.3230 (51.0); 2.7359 (0.7); 2.7206 (1.4); 2.7050 (0.7); 2.6712 (0.4); 2.5064 (54.4); 2.5021 (71.6); 2.4977 (54.5); 2.3288 (0.4); 2.2272 (4.9); 1.0083 (16.0); 0.0077 (2.8); -0.0003 (64.9).

[0828] oxy-N-methylacetamide Step 3: Preparation of 2-[(2-{[(4-chloro-1-naphthalenyl)oxy]methyl}pyrimidin-5-yl)oxy]-N-methoxy-N-methyl

[0829]

[0830] acetamide

[0831] 616 mg (4.10 mmol) of tert-butyldimethylsilyl chloride was added to a solution of 744 mg (3.44 mmol) of [5-(benzyloxy)pyrimidin-2-yl]methanol (D. Bensen et al., WO2014 / 043272) and 341 mg (5.0 mmol) of imidazole in 3.5 ml of N,N-dimethylformamide. The mixture was stirred at room temperature for 30 minutes. After addition of ethyl acetate, the mixture was washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed on silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 0.83 g of 5-(benzyloxy)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidine was obtained.

[0832] 11H-NMR (400.0 MHz, CDCl3): δ = 8.3222 (3.5); 7.2949 (1.8); 7.2883 (1.2); 7.2807 (1.3); 7.1373 (2.4); 5.0288 (2.9); 4.7408 (3.4); 1.4579 (1.2); 0.8133 (0.7); 0.8061 (16.0); 0.7990 (0.9); 0.0076 (0.4); -0.0002 (11.7); -0.0079 (0.5); -0.1235 (2.7).

[0833] Preparation of 2-bromo-N-methoxy-N-methylacetamide hydrobromide (1:1) In vitro contact test of Ctenocephalides felis - with adult cat fleas

[0834] In a hydrogenation reactor, a solution of 470 mg (1.42 mmol) of 5-(benzyloxy)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidine in 40 ml of methanol was hydrogenated over 10% Pd / C at 1 bar with a flow rate of 2 ml / min. The reaction solution was then concentrated under reduced pressure. 328 mg of unpurified 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-ol was obtained as an intermediate. 224 mg (1.62 mmol) of potassium carbonate and 202 mg (0.81 mmol) of 2-bromo-N-methoxy-N-methylacetamide hydrobromide (1:1) were added to a solution of 150 mg of the unpurified intermediate 2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-ol in 1.5 ml of N,N-dimethylformamide, and the mixture was stirred at 50 °C for 15 h. After addition of a further 62 mg (0.25 mmol) of 2-bromo-N-methoxy-N-methylacetamide hydrobromide (1:1), the reaction mixture was stirred at 50 °C for a further 3 h and then concentrated under reduced pressure. Water was added to the residue and the mixture was extracted repeatedly with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The crude product was chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 43 mg of 2-{[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-yl]oxy}-N-methoxy-N-methylacetamide was obtained.

[0835] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.5493 (3.9); 4.7338 (3.3); 4.2697 (0.7); 4.2559 (1.5); 4.2421 (0.8); 3.3996 (6.2); 3.3184 (2.0); 2.9778 (0.7); 2.9640 (1.3); 2.9502 (0.7); 2.5641 (5.3); 2.5066 (8.9); 2.5021 (12.5); 2.4978 (9.6); 0.8740 (16.0); 0.8639 (1.7); 0.0677 (0.5); 0.0602 (11.7); 0.0439 (1.0); -0.0002 (8.8); -0.0080 (0.4).

[0836] In vitro contact test of Rhipicephalus sanguineus - with adult dog ticks Immersion test of Boophilus microplus

[0837] 250 μl (0.25 mmol) of a solution of 1 M tetrabutylammonium fluoride in tetrahydrofuran was added to a solution of 40 mg (0.12 mmol) of (2-{[2-({[tert-butyl(dimethyl)silyl]oxy}methyl)pyrimidin-5-yl]oxy}-N-methoxy-N-methylacetamide) in 0.7 ml of tetrahydrofuran, and the mixture was stirred at room temperature for 30 minutes. After addition of saturated aqueous ammonium chloride solution, the mixture was extracted repeatedly with ethyl acetate, and the combined organic phases were dried over magnesium sulfate, filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in 1 ml of toluene, and 25 μl (0.34 mmol) of thionyl chloride and a catalytic amount of N,N-dimethylformamide were added. The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure. The residue was dissolved in 1 ml of N,N-dimethylformamide, and 27 mg (0.15 mmol) of 4-chloro-1-naphthol and 47 mg (0.34 mmol) of potassium carbonate were added. The reaction mixture was stirred at 70 °C for 2 hours and then concentrated under reduced pressure. The residue was dissolved in dichloromethane, adsorbed onto silica gel, and chromatographed on silica gel by MPLC (gradient: cyclohexane / ethyl acetate). 28 mg of 2-[(2-{[(4-chloro-1-naphthyl)oxy]methyl}pyrimidin-5-yl)oxy]-N-methoxy-N-methylacetamide was obtained.

[0838] 1H-NMR (400.0 MHz, d6-DMSO): δ = 8.6301 (12.6); 8.3049 (1.5); 8.2842 (1.6); 8.1276 (1.6); 8.1072 (1.8); 7....

Claims

1. Compounds of formula (I), as well as salts and tautomeric forms of the compounds of formula (I) wherein Z represents naphthyl, dibenzo[b,d]furanyl, dibenzo[b,d]thiophenyl, which is unsubstituted or mono- or polysubstituted by halogen, or represents a substituted phenyl of sub-formula (II) and the substituted phenyl of sub-formula (II) is either not further substituted or bears at most two further substituents selected from: halogen, OCH3, OCH2CH3 and (C1-C4)-haloalkoxy, Y represents O, A 1 represents N or -CR 1 , A 2 represents N or -CR 2 , A 3 represents N or -CR 3 , A 4 represents N or -CR 4 , wherein at least one and at most two of the atoms A1, A2, A3 and A4 in the aromatic ring represent N, X represents oxygen or -NR 6 , R 1 、R 2 、R 3 and R 4 each independently of one another is selected from hydrogen, F, Cl, CH3, halogen-substituted (C1-C4) alkyl, OCH3, OCH2CH3 and SCH3, R 6 represents a (C1-C4)-alkyl or a closed ring formed with R 8 by 1 to 3 CH2 groups R 7 represents a (C1-C4)-alkyl or a closed ring formed with R 8 by 1 to 3 CH2 groups R 8 represents (C1-C4)-alkyl, (C3-C6)-cycloalkyl or, together with R 6 or R 7 is enclosed in a ring formed by 1 to 3 CH2 groups or, together with R 9 is enclosed in a 4- to 6-membered heterocyclic ring which, in the case of a 5- to 6-membered heterocyclic ring, is unsubstituted or mono- or polysubstituted by the same or different groups selected from: cyano or (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, each of which is unsubstituted or mono- or polysubstituted by the same or different halogen substituents At R 7 Together with R 8 In the case of forming a 5- or 6-membered ring, R 9 In each case represents unsubstituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, cyano-substituted (C1-C4)-alkyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylcarbonyl, or In the case where R 7 represents a (C1-C4)-alkyl, R 9 in each case represents an unsubstituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, or a (C1-C4)-alkyl substituted by a cyano group, or At R 7 Together with R 8 When forming a four-membered ring together, R 9 In each case represents unsubstituted or cyano-substituted (C1-C4)-alkyl, unsubstituted (C3-C6)-cycloalkyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, or R 8 and R 9 represent a 4- to 6-membered heterocyclic closed ring, which in the case of a 5- to 6-membered heterocyclic ring is unsubstituted or mono- or polysubstituted by the same or different groups selected from: halogen substituents, cyano groups or (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy groups, each of which is unsubstituted or mono- or polysubstituted by the same or different halogen substituents, R 10 represents a halogen, nitro, cyano group, or represents a phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, (C3-C6)-cycloalkylthio group, where the above groups are unsubstituted, or R 10 is a (C1-C4)-alkyl group substituted by a halogen, a phenyl group substituted by a halogen, or a (C1-C4)-alkoxy group substituted by a halogen, R 11 represents hydrogen or a halogen, with the proviso that the compound 1-[4-(6-{2-[3-(chloromethyl)phenyl]ethyl}pyridin-3-yl)piperazin-1-yl]ethanone is excluded.

2. The compound of formula (I) according to claim 1, wherein R 1 、R 2 、R 3 and R 4 each independently of one another is selected from hydrogen, F, Cl, CH3, halogen-substituted (C1-C4) alkyl, OCH3, OCH2CH3, and SCH3, R 6 represents a (C1-C4)-alkyl group, or a closed ring formed with R 8 by 1 to 3 CH2 groups R 7 represents (C1-C4)-alkyl, or a closed ring formed with R 8 by 1 to 3 CH2 groups R 8 represents a (C1-C4)-alkyl, (C3-C4)-cycloalkyl, or a closed ring formed with R 6 or R 7 together by 1 to 3 CH2 groups, or a 4- to 6-membered heterocyclic closed ring together with R 9 wherein the heterocyclic closed ring is unsubstituted or mono- or polysubstituted by the same or different substituents selected from the following in the case of a 5- to 6-membered heterocycle: (C1-C4)-alkyl and (C1-C4)-haloalkyl, At R 7 With R 8 When forming a 5- or 6-membered ring, R 9 represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylcarbonyl, or In the case where R 7 represents a (C1-C4)-alkyl, R 9 in each case represents an unsubstituted (C1-C4)-alkyl, (C3-C6)-cycloalkyl, N-mono-(C1-C4)-alkylamino, N,N-di-(C1-C4)-alkylamino, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, or a (C1-C4)-alkyl substituted by a cyano group, or At R 7 With R 8 When forming a four-membered ring together, R 9 represents unsubstituted or cyano-substituted (C1-C4)-alkyl, unsubstituted (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C3-C4)-cycloalkoxy, or R 8 and R 9 represent a 4- to 6-membered heterocyclic ring which, in the case of a 5- to 6-membered heterocyclic ring, is unsubstituted or mono- or polysubstituted by identical or different substituents selected from halogen, (C1-C4)-alkyl and (C1-C4)-haloalkyl, R 10 represents halogen, or represents phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, (C3-C6)-cycloalkylthio, wherein the above groups are unsubstituted, or R 10 is (C1-C4)-alkyl substituted by halogen, phenyl substituted by halogen or (C1-C4)-alkoxy substituted by halogen, R 11 represents hydrogen or a halogen.

3. The compound of formula (I) according to claim 1 or 2, wherein at least one of the atoms A3 or A4 in the aromatic ring represents nitrogen, R 1 、R 2 、R 3 and R 4 are each independently selected from: hydrogen, F, Cl, CH3, halogen-substituted (C1-C4) alkyl, OCH3, OCH2CH3, and SCH3, R 6 represents a (C1-C4)-alkyl or a closed ring formed with R 8 via 1 to 3 CH2 groups R 7 represents (C1-C4)-alkyl or a closed ring formed with R 8 by 1 to 3 CH2 groups R 8 represents (C1-C4)-alkyl, (C3-C4)-cycloalkyl, or a closed ring formed with R 6 or R 7 together by 1 to 3 CH2 groups, or a 4- to 6-membered heterocyclic closed ring formed with R 9 together by 3 to 5 CH2 groups, and the heterocyclic closed ring is unsubstituted or mono- or polysubstituted with the same or different substituents selected from: (C1-C4)-alkyl and (C1-C4)-haloalkyl, In R 7 Together with R 8 When forming a 5- or 6-membered ring together, R 9 represents (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C1-C4)-alkylcarbonyl, or In the case where R 7 represents a (C1-C4)-alkyl, R 9 represents a (C1-C4)-alkyl, a (C3-C6)-cycloalkyl or a (C1-C4)-alkoxy, or At R 7 Together with R 8 In the case of forming a four-membered ring together, R 9 Represents unsubstituted or cyano-substituted (C1-C4)-alkyl, unsubstituted (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, or R 8 and R 9 represents a 4- to 6-membered heterocyclic closed ring formed by 3 to 5 CH2 groups and is unsubstituted or mono- or polysubstituted by the same or different substituents selected from the group consisting of halogen, (C1-C4)-alkyl, and (C1-C4)-haloalkyl, R 10 represents halogen or represents phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, thiophen-2-yl, thiophen-3-yl, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, (C1-C4)-alkoxy, (C3-C6)-cycloalkoxy, (C1-C4)-alkylthio, R 11 represents hydrogen or a halogen.

4. The compound of formula (I) according to claim 1, wherein Z represents naphthyl, which is unsubstituted or mono- or polysubstituted by halogen, or represents a substituted phenyl of sub-formula (II), R 1 、R 2 、R 3 and R 4 represent substituents selected from the following: hydrogen, F, Cl, CH3, (C1-C4) alkyl substituted with halogen, OCH3, OCH2CH3, and SCH3, R 6 represents hydrogen, (C1-C3)-alkyl or a closed ring formed by 1 to 2 CH2 groups with R 8 ​ R 7 represents a closed ring formed with R 8 by 1 to 3 CH2 groups R 8 represents a (C1-C4)-alkyl group, or a closed ring formed with R via 1 to 2 CH2 groups or with R 6 a closed ring formed via 1 to 3 CH2 groups or with R 7 a closed ring formed via 1 to 3 CH2 groups or with R 9 a 4- to 6-membered heterocyclic closed ring formed together with R via 3 to 5 CH2 groups, and the heterocyclic closed ring is unsubstituted or mono- or polysubstituted with the same or different substituents selected from: (C1-C4)-alkyl and (C1-C4)-haloalkyl, R 9 represents (C1-C4)-alkyl, (C3-C6)-cycloalkyl or (C1-C4)-alkoxy, or R 8 and R 9 represents a 4- to 6-membered heterocyclic closed ring formed by 3 to 5 CH2 groups and is unsubstituted or mono- or polysubstituted by identical or different substituents selected from the following: halogen, (C1-C4)-alkyl, R 10 represents halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, or represents phenyl, which is unsubstituted or mono- or polysubstituted by the same or different substituents selected from the following: halogen, R 11 represents hydrogen or a halogen.

5. The compound of formula (I) according to claim 1, wherein Z represents a naphthyl of sub-formula (III): or represents unsubstituted dibenzo[b,d]furanyl or dibenzo[b,d]thiophenyl or represents a substituted phenyl of sub-formula (II), R 1 represents hydrogen, F, Cl, CH3, halogen-substituted (C1-C4) alkyl, OCH3 or OCH2CH3, R 2 represents hydrogen, F, Cl or a halogen-substituted (C1-C4) alkyl group, R 3 represents hydrogen, F, Cl, SCH3, OCH3 or OCH2CH3, R 4 represents hydrogen, F or Cl, R 6 represents the piperazine closed ring formed with R 8 and R 8 represents a piperazine closed ring formed with R 6 together, R 10 represents halogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, (C1-C4)-haloalkoxy or phenyl of the substructural formula (IV): R 11 represents hydrogen or a halogen, R 12 、R 13 and R 14 each independently represents hydrogen or halogen, R 15 represents hydrogen, halogen, cyano, (C1-C4)-alkyl, (C1-C4)-haloalkyl, (C1-C4)-alkoxy or (C1-C4)-haloalkoxy.

6. A formulation comprising 0.00000001% to 98% by weight of the compound of formula (I) according to claim 1 and at least one auxiliary 7. The formulation according to claim 6, which additionally comprises another agrochemical active substance.

8. Compounds of formula (Va) or (Vb-1): wherein A 1 represents N or CH, A 2 represents N or CH, where at least A 1 or A 2 represents N, R 16 represents hydrogen, methyl, fluorine or methoxy, R 17 represents cyano, hydroxymethyl, methyl carboxyl, ethyl carboxyl or 3-bromophenoxymethyl, R 18 represents the following groups in the compound of formula (Va): or bromine, provided that the following compounds are excluded:

9. A compound of formula (Va) or (Vb-1) according to claim 8, wherein A 1 represents N and A 2 represents CH.

10. A method for controlling animal pests, characterized in that, The compound of formula (I) according to claim 1 or the formulation according to claim 6 is applied to animal pests and / or their habitats, excluding surgical, therapeutic and diagnostic treatment of the human or animal body.

11. Use of the compound of formula (I) according to claim 1 or the formulation according to claim 6 for controlling animal pests, excluding surgical, therapeutic and diagnostic treatment of the human or animal body.

12. The use according to claim 11, wherein the animal pest is a mosquito.

13. Use of the compound of formula (I) according to claim 1 or the formulation according to claim 6 for controlling ectoparasites on an animal body.

14. A method for controlling animal pests, characterized in that, The compound of formula (I) according to claim 1 or the formulation according to claim 6 is applied to animal pests and / or their habitats, excluding surgical, therapeutic and diagnostic treatment of the human or animal body.

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