TREA

ALKYLAMIDE SUBSTITUTED, ANNULATED IMIDAZOLES AND USE THEREOF AS INSECTICIDES

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Information

  • Patent Application
  • 20240254121
  • Publication Number
    20240254121
  • Date Filed
    May 02, 2022
    2 years ago
  • Date Published
    August 01, 2024
    4 months ago
Information
Abstract
The present invention relates to novel alkylamide substituted, annulated imidazole derivatives of the general formula (I), in which the structural elements A1; A2, A3, A4, R1, R2, R3 and R4 have the meaning given in the description, to formulations and compositions comprising such compounds and for their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.
Description

The present invention relates to novel alkylamide substituted, annulated imidazole derivatives, to formulations and compositions comprising such compounds and to their use in the control of animal pests including arthropods and insects in plant protection and to their use for control of ectoparasites on animals.


WO 2002/083143 and WO 2006/004924 disclose numerous benzimidazole compounds which are modulators of the CXCR3 receptor, useful for the treatment and prevention of certain inflammatory and immunoregulatory disorders and diseases. Further, WO 2002/028839 discloses benzimidazoles as CRF receptor modulators. WO 2011/123751 and WO 2012/107465 describe certain alkylamine substituted benzimidazoles and imidazopyridines.


Certain heteroaryl-triazole compounds are disclosed for the use in controlling ectoparasites on animals in WO 2017/192385 and for the use in controlling animal pests including arthropods and insects in the field of plant protection in WO 2019/170626 and WO 2019/215198. Further, the patent applications WO 2019/197468, WO 2019/201835, WO 2019/202077, WO 2019/206799, WO 2021/013719, WO 2021/013720, WO 2021/069575, WO 2021/069567, WO 2021/069569, WO 2021/099303, WO 2021/105091, WO 2021/165195, WO 2021/224323 and WO 2021/259997_disclose certain heteroaryl-triazole or heteroaryl-pyrazine compounds for the use in controlling ectoparasites on animals and for the control of animal pests including arthropods and insects in the field of plant protection. WO 2020/002563, WO 2020/053364, WO 2020/053365, WO 2020/070049, WO 2020/079198, WO 2020/094363, WO 2020/169445, WO 2020/182649, WO 2020/188014, WO 2020/188027, WO 2020/193341, WO 2020/201079, WO 2020/201398, WO 2020/208036, WO 2021/037614, WO 2021/122645 and WO2021/170881 describe azole-amide or pyrazine-amide compounds all of which can be used as insecticides.


Modern plant protection products and veterinary ectoparasiticides have to meet many demands, for example in relation to efficacy, persistence, spectrum and resistance breaking properties. Questions of toxicity, the combinability with other active compounds or formulation auxiliaries play a role, as well as the question of the expense that the synthesis of an active compound requires. Furthermore, resistances may occur. Resistant parasites are an increasing problem both for farm animals as well as for companion animals and also in crop pests. For all these reasons, the search for novel crop protection compositions or veterinary ectoparasiticides cannot be considered to be complete, and there is a constant need for novel compounds having properties which, compared to the known compounds, are improved at least in respect of individual aspects. It is in particular desirable to find new pesticides and parasiticides that overcome resistance.


It was an object of the present invention to provide compounds which widen the spectrum of the pesticides in various aspects.


Therefore, the invention relates to compounds of the general formula (I)




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in which (Configuration 1-1):

    • X is O or S;
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N or CR5;
    • wherein at least one or two of A1, A2, A3, A4 represents a nitrogen (N);
    • R1 is hydrogen; or in each case optionally substituted C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl, C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl;
    • or phenyl-C1-C6 alkyl, in which phenyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —CSNH2, —NO2, —Si(CH3)3, —SF5, —NH2, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycanocycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkylthio, C1-C3 cyanoalkylsulfinyl, and C1-C3 cyanoalkylsulfonyl; or
    • heterocyclyl-C1-C6 alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 3- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —CSNH2, —NO2, —Si(CH3)3, —SF5, —NH2, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycanocycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, C1-C3 alkylthio, C1—C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkylthio, C1-C3 cyanoalkylsulfinyl, and C1-C3 cyanoalkylsulfonyl;
    • R2 is phenyl or a 5- or 6-membered heteroaryl, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
      • halogen, hydroxy, —CN, —COOH, —NO2, —NH2, —SO2NH2, —SF5;
      • and in each case optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C6 cycloalkoxy, C1-C6 haloalkoxy, hydroxy-C1-C6 alkyl, —CO2C1-C6 alkyl, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, S—C1-C6 alkylsulfinimidoyl, S—C3-C6 cycloalkylsulfinimidoyl, S—C2-C6 alkenylsulfinimidoyl, S—C2-C6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C1-C6 alkylsulfonimidoyl, S—C3-C6 cycloalkylsulfonimidoyl, S—C2-C6 alkenylsulfonimidoyl, S—C2-C6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —C(═NOC1-C6 alkyl)H, —C(═NOC1-C6 alkyl)-C1-C6 alkyl, and (C1-C6 alkyl)3-silyl;
      • and the substructures S1-S9, in which the bond to the phenyl or 5- or 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2;




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    • wherein

    • R21 is hydrogen or in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, phenyl, heteroaryl and heterocyclyl;

    • R22 is hydrogen or in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl and C3-C6 cycloalkyl;

    • R23 is independently selected from in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and phenyl;

    • R24 is in each case optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; or

    • R21 and R22 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic optionally substituted 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms;

    • and 3- to 6-membered heterocyclyl or a 5- to 6-membered heteroaryl each containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl or the 5- to 6-membered heteroaryl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —CSNH2, —NO2, —Si(CH3)3, —SF5, —NH2, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycanocycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkylthio, C1-C3 cyanoalkylsulfinyl, and C1-C3 cyanoalkylsulfonyl;

    • R3 is hydrogen, or C1-C6 alkyl optionally substituted with 1 to 3 substituents selected from halogen, —CN, C3-C6-cycloalkyl and C1-C6-alkoxy;

    • R4 is a monocyclic heterocycle selected from the group consisting of a 5-membered heteroaryl and a 6-membered heteroaryl each of which containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, and each of which is optionally substituted by 1, 2, 3 or 4 substituents independently selected from the group consisting of
      • halogen, hydroxy, —CN, —COOH, —NO2, —NH2, —SF5;
      • and in each case optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C6 cycloalkoxy, C1-C6 haloalkoxy, C1-C6 cyanoalkoxy, hydroxy-C1-C6 alkyl, —NH(C1-C6 alkyl), —NH(C1-C6 alkyl-C3-C6 cycloalkyl), —N(C1-C6 alkyl)2, —N(C1-C6 alkyl)(C1-C6 alkyl-C3-C6 cycloalkyl), —CO2C1-C6 alkyl, S—C1-C6 alkylsulfinimidoyl, S—C3-C6 cycloalkylsulfinimidoyl, S—C2-C6 alkenylsulfinimidoyl, S—C2-C6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C1-C6 alkylsulfonimidoyl, S—C3-C6 cycloalkylsulfonimidoyl, S—C2-C6 alkenylsulfonimidoyl, S—C2-C6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —C(═NOC1-C6 alkyl)H, and —C(═NOC1-C6 alkyl)-C1-C6 alkyl;
      • and 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —CSNH2, —NO2, —Si(CH3)3, —SF5, —NH2, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycanocycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkylthio, C1-C3 cyanoalkylsulfinyl, and C1-C3 cyanoalkylsulfonyl;
      • and the following substructures S10-S18, in which the bond to the 5-membered heteroaryl and a 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2:







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    • wherein

    • R41 is hydrogen or in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, phenyl, heteroaryl and heterocyclyl;

    • R42 is hydrogen or in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, or C3-C6 cycloalkyl;

    • R43 is independently selected from in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and phenyl;

    • R44 is in each case optionally substituted C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, phenyl, heteroaryl and heterocyclyl; or

    • R41 and R42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic optionally substituted 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms;

    • R5 is hydrogen, halogen, —CN, —NH2, or in each case optionally substituted C1-C3-alkyl, C1-C3-haloalkyl, C1-C3 cyanoalkyl, C3-C4-cycloalkyl, C3-C4 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, —CO2(C1-C3 alkyl), —CH—(C1-C3 alkoxy)2, —CONH(C1-C4 alkyl), —CON(C1-C4 alkyl)2, —NHCO—C1-C4 alkyl, —N(C1-C4 alkyl)CO—C1-C4 alkyl, —C(═NOC1-C4 alkyl)H, —C(═NOC1-C4 alkyl)-C1-C4 alkyl, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C3-C6 cycloalkylthio, C3-C6 cycloalkylsulfinyl, or C3-C6 cycloalkylsulfonyl;

    • and salts and N-oxides thereof.





The compounds of the formula (I) described anywhere herein likewise encompass any diastereomers or enantiomers and E/Z isomers which exist, and also salts and N-oxides of compounds of the formula (I), and the use thereof for control of animal pests.


The compounds of the formula (I) described anywhere herein may possibly also, depending on the nature of the substituents, be in the form of stereoisomers, i.e. in the form of geometric and/or optical isomers or isomer mixtures of varying composition. This invention provides both the pure stereoisomers and any desired mixtures of these isomers, even though it is generally only compounds of the formula (I) that are discussed here.


However, preference is given in accordance with the invention to using the optically active, stereoisomeric forms of the compounds of the formula (I) and salts thereof.


The invention therefore relates both to the pure enantiomers and diastereomers and to mixtures thereof.


If appropriate, the compounds of the formula (I) may be present in various polymorphic forms or as a mixture of various polymorphic forms. Both the pure polymorphs and the polymorph mixtures are provided by the invention and can be used in accordance with the invention.


Preference (Configuration 2-1) is given to the compounds of the formula (I) in which

    • X is O or S;
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N or CR5;
      • wherein one or two of A1, A2, A3, A4 represents a nitrogen (N);
    • R1 is hydrogen; or
      • C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl, each of which is optionally substituted by a group selected from halogen, —CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl and C1-C3 alkylsulfonyl; or
      • C2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl; or
      • phenyl-C1-C3 alkyl, in which phenyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl; or
      • heterocyclyl-C1-C3 alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 3- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;
    • R2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of
      • halogen, hydroxy, —CN, —COOH, —NO2, —NH2, —SO2NH2, —SF5;
      • C1-C6 alkyl, optionally substituted with —CN, —OH or C3-C6 cycloalkyl; C2-C6 alkenyl, optionally substituted with halogen and —CN; C2-C6 alkynyl, optionally substituted with halogen and —CN; C3-C6 cycloalkyl, optionally substituted with halogen, —CN, C1-C3 alkyl or C1-C3 haloalkyl; C1-C6 haloalkyl, optionally substituted with —CN or C1-C6 alkoxy; C1-C6 alkoxy, optionally substituted with —CN; C3-C6 cycloalkoxy, optionally substituted with halogen or —CN; C1-C6 haloalkoxy, —CO2C1-C6 alkyl, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, S—C1-C6 alkylsulfinimidoyl, S—C3-C6 cycloalkylsulfinimidoyl, S—C2-C6 alkenylsulfinimidoyl, S—C2-C6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C1-C6 alkylsulfonimidoyl, S—C3-C6 cycloalkylsulfonimidoyl, S—C2-C6 alkenylsulfonimidoyl, S—C2-C6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —C(═NOC1-C6 alkyl)H, —C(═NOC1-C6 alkyl)-C1-C6 alkyl, and (C1-C6 alkyl)3-silyl;
      • and the substructures S1-S9, in which the bond to phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2;




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    • wherein

    • R21 is hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cyanocycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, phenyl, heteroaryl, or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;

    • R22 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, or C3-C6 cycloalkyl;

    • R23 is independently selected from in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and phenyl;

    • R24 is C1-C6 alkyl, C1-C6 cyanoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cyanocycloalkyl, phenyl, heteroaryl and heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl; or

    • R21 and R22 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, —CN, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;

    • and 3- to 6-membered heterocyclyl or a 5- to 6-membered heteroaryl each containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein the 3- to 6-membered heterocyclyl or the 5- to 6-membered heteroaryl substituent may optionally carry 1, 2, 3 or 4 substituents independently selected from the group consisting of halogen, hydroxy, —CN, C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycanocycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkyl-C1-C6 alkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkylthio, C1-C3 cyanoalkylsulfinyl, and C1-C3 cyanoalkylsulfonyl;

    • R3 is hydrogen or C1-C6 alkyl optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, —CN, C3-C6-cycloalkyl and C1-C6-alkoxy;

    • R4 is a monocyclic heterocycle selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 or 2 substituents independently selected from the group consisting of
      • halogen, hydroxy, —CN, —COOH, —NO2, —NH2, —SF5;
      • C1-C6 alkyl, C1-C6 cyanoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C3-C6 cyanocycloalkyl, C3-C6 halocycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C6 cycloalkoxy, C1-C6 haloalkoxy, C1-C6 cyanoalkoxy, hydroxy-C1-C6 alkyl, —NH(C1-C6 alkyl), —NH(C1-C6 alkyl-C3-C6 cycloalkyl), —N(C1-C6 alkyl)2, —N(C1-C6 alkyl)(C1-C6 alkyl-C3-C6 cycloalkyl), —CO2C1-C6 alkyl, S—C1-C6 alkylsulfinimidoyl, S—C3-C6 cycloalkylsulfinimidoyl, S—C2-C6 alkenylsulfinimidoyl, S—C2-C6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C1-C6 alkylsulfonimidoyl, S—C3-C6 cycloalkylsulfonimidoyl, S—C2-C6 alkenylsulfonimidoyl, S—C2-C6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, and —C(═NOC1-C6 alkyl)H, —C(═NOC1-C6 alkyl)-C1-C6 alkyl;
      • and the following substructures S10-S18, in which the bond to the 5-membered heteroaryl and a 6-membered heteroaryl is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2:







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    • wherein

    • R41 is hydrogen, C1-C6 alkyl, C1-C6 cyanoalkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cyanocycloalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, phenyl, heteroaryl or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;

    • R42 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 cyanoalkyl, —C1-C6 alkyl-C3-C6 cycloalkyl, or C3-C6 cycloalkyl;

    • R43 is independently selected from in each case optionally substituted C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl and phenyl;

    • R44 is C1-C6 alkyl, C1-C6 cyanoalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 cyanocycloalkyl, phenyl, heteroaryl, or heterocyclyl in which phenyl, heteroaryl and heterocyclyl are optionally substituted with 1 to 3 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl; or

    • R41 and R42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic 3- to 12-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, —CN, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;

    • R5 is hydrogen, halogen, —CN, —NH2, C1-C3-alkyl, C1-C3-haloalkyl, C1-C3 cyanoalkyl, C3-C4-cycloalkyl, C3-C4 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, —NH(C1-C3 alkyl), —N(C1-C3 alkyl)2, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C3-C6 cycloalkylthio, C3-C6 cycloalkylsulfinyl, or C3-C6 cycloalkylsulfonyl;

    • and salts and N-oxides thereof.





Further preferred (Configuration 3-1) are the compounds of the formula (I) in which

    • X is O or S;
    • A1 is N;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N;
    • A3 is N or CR5;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N; or
    • A1 is N;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N;
    • R1 is hydrogen, C1-C6 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C6 cycloalkylC1-C3 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkylthioC1-C3 alkyl, C1-C3 alkylsulfinylC1-C3 alkyl, or C1-C3 alkylsulfonylC1-C3 alkyl;
    • R2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine and pyrazole, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —NO2, —NH2, —SO2NH2, —SF5, C1-C4 alkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl, C3-C6 cycloalkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkoxy, hydroxy-C1-C4 alkyl, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —NHCO—C1-C4 alkyl, NHCO—C3-C6 cycloalkyl, —NHSO2(C1-C4 alkyl), —N(C1-C4 alkyl)CO—C1-C4 alkyl, —N(C1-C4 alkyl)CO—C3-C6 cycloalkyl, —N(C1-C4 alkyl)SO2C1-C4 alkyl, —N(SO2C1-C4 alkyl)2, —CO2C1-C4 alkyl, —CONH(C1-C4 alkyl), —CONH(C3-C6 cycloalkyl), —CONH-phenyl, —CON(C1-C4 alkyl)2, —CON(C1-C4 alkyl)(C3-C6 cycloalkyl), —CON(C1-C4 alkyl)-phenyl, —C(═NOC1-C4 alkyl)H, —C(═NOC1-C4 alkyl)-C1-C4 alkyl, (C1-C4 alkyl)3-silyl, —SO2NH(C1-C4 alkyl), phenylsulfonyl, and 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein phenyl groups of the aforementioned substituents and the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2 or 3 substituents independently selected from the group consisting of halogen, —CN, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy;
    • R3 is hydrogen, C1-C6 alkyl, optionally substituted with 1 to 3 substituents selected from halogen, C3-C6-cycloalkyl, or C1-C6-alkoxy;
    • R4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 or 2 substituents independently selected from the group consisting of halogen, —CN, —COOH, —NO2, —NH2, —SF5, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, and —CO2C1-C6 alkyl, or
    • R4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole,
      • each of which is optionally substituted by 1 substituent selected from the group consisting of halogen, —CN, —COOH, —NO2, —NH2, —SF5, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, and —CO2C1-C6 alkyl;
      • and each of which is furthermore substituted by 1 substituent selected from the group consisting of following substructures S10-S18, in which the bond to the aforementioned pyridine, pyrimidine, pyrazine, pyridazine and thiazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2:




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    • wherein

    • R41 is hydrogen, C1-C4 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, or —C1-C3 alkyl-C3-C6 cycloalkyl;

    • R42 is hydrogen, C1-C4 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, or —C1-C3 alkyl-C3-C6 cycloalkyl;

    • R43 is C1-C4 alkyl, C1-C3 haloalkyl, or C3-C6 cycloalkyl;

    • R44 is C1-C4 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C3 haloalkyl, or C3-C6 cycloalkyl; or

    • R41 and R42 together with the nitrogen atom to which they are attached, represent a monocyclic or polycyclic 5 to 6-membered saturated or unsaturated heterocyclyl which may contain further heteroatoms, and each of the monocyclic or polycyclic to 6-membered saturated or unsaturated heterocyclyl is optionally substituted with 1 to 4 substituents, each independently selected from the group consisting of halogen, —CN, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;

    • R5 is hydrogen, halogen, —CN, C1-C6-alkyl, C1-C3-haloalkyl, C3-C4-cycloalkyl, C1-C3 alkoxy, or C1-C3 haloalkoxy;

    • and salts and N-oxides thereof.





Particularly preferred (Configuration 4-1) are the compounds of the formula (I) in which

    • X is O or S;
    • A1 is N;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N;
    • A3 is N or CR5;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N;
    • A4 is N or CR5; or
    • A1 is N or CR5;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N; or
    • A1 is N;
    • A2 is N or CR5;
    • A3 is N or CR5;
    • A4 is N;
    • R1 is hydrogen, methyl, ethyl, cyclopropylmethyl, methoxymethyl, ethoxymethyl, methoxyethyl, methylthioethyl, methylsulfinylethyl or methylsulfonylethyl;
    • R2 is selected from substructure Q1, Q2 and Q3, in which the bond to the C═X-group is marked with a #:




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    • wherein

    • R25 is hydroxy, —CN, —NH2, —SO2NH2, C1-C4 alkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl, C3-C6 cycloalkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkoxy, hydroxy-C1-C4 alkyl, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —NHCO—C1-C4 alkyl, NHCO—C3-C6 cycloalkyl, —NHSO2(C1-C4 alkyl), —N(C1-C4 alkyl)CO—C1-C4 alkyl, —N(C1-C4 alkyl)CO—C3-C6 cyclolkyl, —N(C1-C4 alkyl)SO2C1-C4 alkyl, —N(SO2C1-C4 alkyl)2, —CO2C1-C4 alkyl, —CONH(C1-C4 alkyl), —CONH(C3-C6 cycloalkyl), —CONH-phenyl, —CON(C1-C4 alkyl)2, —CON(C1-C4 alkyl)(C3-C6 cycloalkyl), —CON(C1-C4 alkyl)-phenyl, —C(═NOC1-C4 alkyl)H, —C(═NOC1-C4 alkyl)-C1-C4 alkyl, (C1-C4 alkyl)3-silyl, —SO2NH(C1-C4 alkyl), phenylsulfonyl, or 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein phenyl groups of the aforementioned substituents and the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2 or 3 substituents independently selected from the group consisting of halogen, —CN, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy; and

    • R26 is hydrogen, halogen, —CN, —COOH, —CONH2, —NO2, C1-C4 alkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl, C3-C6 cycloalkylsulfonyl, C3-C6 cycloalkyl, C1-C3 cyanoalkyl, or C3-C6 cyanocycloalkyl;

    • R27 is hydrogen, or C1-C4 alkyl;

    • R3 is methyl;

    • R4 is selected from the group consisting of pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-3-yl and 1,3-thiazol-2-yl, each of which is optionally substituted by one substituent independently selected from the group consisting of fluorine, chlorine, bromine, —CN, methyl, ethyl, n-propyl, isopropyl, butyl, tert-butyl, cyclopropyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, difluoroethoxy, methoxycarbonyl, and ethoxycarbonyl; or
      • the following substructures S13, in which the bond to the aforementioned pyridin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrazin-3-yl, and 1,3-thiazol-2-yl is marked with a # and Z is CO:







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    • wherein

    • R41 is hydrogen, methyl, ethyl, cyclopropylmethyl, cyanomethyl, cyclopropyl, difluoroethyl, or trifluoroethyl;

    • R42 is hydrogen, methyl, ethyl, cyclopropylmethyl, cyanomethyl, cyclopropyl, difluoroethyl, or trifluoroethyl; or

    • R41 and R42 together with the nitrogen atom to which they are attached, represent a morpholine, optionally substituted by one to four methyl;

    • R5 is hydrogen, fluorine, chlorine, bromine, iodine, —CN, methyl, ethyl, isopropyl, difluoromethyl, trifluoromethyl, cyclopropyl, methoxy, ethoxy, difluoromethoxy, or trifluoromethoxy;

    • and salts and N-oxides thereof.





Very particularly preferred (Configuration 5-1) are the compounds of the formula (I) in which

    • X is O;
    • A1 is N;
    • A2 is CR5;
    • A3 is CR5;
    • A4 is CR5;
    • R1 is hydrogen;
    • R2 is selected from the group consisting of 3-chloro-5-(trifluoromethoxy)phenyl, 3,5-bis-(trifluoromethyl)phenyl, 3,5-bis-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyano-1-methyl-ethyl)phenyl, 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyanocyclopropyl)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, (3-chloro-5-methylsulfonylphenyl), 3-methylsulfonyl-5-(trifluoromethoxy)phenyl and 5-(difluoromethyl)-1-methyl-pyrazol-3-yl;
    • R3 is methyl;
    • R4 is selected from the group consisting of 5-chloro-pyridin-2-yl, 5-cyano-pyridin-2-yl, and 5-methoxycarbonyl-2-pyridyl;
    • R5 is selected from hydrogen and methyl;
    • and salts and N-oxides thereof.


Very particular preference is also given (Configuration 5-2) to the compounds of the formula (I) in which

    • X is O;
    • A1 is N;
    • A2 is CR5;
    • A3 is CR5;
    • A4 is CR5; or
    • A1 is CR5;
    • A2 is CR5;
    • A3 is N;
    • A4 is CR5; or
    • A1 is CR5;
    • A2 is CR5;
    • A3 is CR5;
    • A4 is N;
    • R1 is hydrogen;
    • R2 is selected from the group consisting of 3-chloro-5-(trifluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethyl)phenyl, 3,5-bis-(trifluoromethyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3,5-bis-(trifluoromethoxy)phenyl, 3-(1,1-difluoroethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyano-1-methyl-ethyl)phenyl, 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyanocyclopropyl)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, (3-chloro-5-methylsulfonylphenyl), 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethylsulfonyl)phenyl and 5-(difluoromethyl)-1-methyl-pyrazol-3-yl;
    • R3 is methyl;
    • R4 is selected from the group consisting of pyrimidin-2-yl, 5-chloro-pyridin-2-yl, 5-cyano-pyridin-2-yl, 5-methoxycarbonyl-2-pyridyl, 5-(aminocarbonyl)pyridin-2-yl, 5-(methylcarbamoyl)pyridin-2-yl, and 5-(dimethylaminocarbonyl)pyridin-2-yl;
    • R5 is selected from hydrogen, fluorine and methyl;
    • and salts and N-oxides thereof.


In a further preferred embodiment, the invention relates to compounds of the formula (I-i)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-ii)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-iii)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-iv)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-v)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-vi)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-vii)




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in which the structural elements R1, R2, R3, R4 and R5 have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-a)




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in which the structural elements A1, A2, A3, A4, R1, R2, R3, R4 and X have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


In a further preferred embodiment, the invention relates to compounds of the formula (I-b)




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in which the structural elements A1, A2, A3, A4, R1, R2, R3, R4 and X have the meanings given in Configuration (1-1) or the meanings given in Configuration (2-1) or the meanings given in Configuration (3-1) or the meanings given in Configuration (4-1) or the meanings given in Configuration (5-1) or the meanings given in Configuration (5-2).


Particularly, the invention covers the intermediate compounds INT-1 to INT-7, in case of amines and acids also the salts thereof and in case of amine hydrochlorides or triflates also the free amines (see table 2):

  • INT-1: 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride
  • INT-2: 1-[3-(5-chloro-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethanamine; 2,2,2-trifluoroacetic acid
  • INT-3: 6-[2-(1-aminoethyl)-7-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride
  • INT-4: methyl 6-[2-(1-aminoethyl)imidazo[4,5-b]pyridin-3-yl]pyridine-3-carboxylate hydrochloride
  • INT-5: 6-[2-[1-aminoethyl]-6-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride
  • INT-6: 6-[2-[1-aminoethyl]-5-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride
  • INT-7: 1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine hydrochloride
  • INT-8: 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate


Definitions

The person skilled in the art is aware that, if not stated explicitly, the expressions “a” or “an” as used in the present application may, depending on the situation, mean “one (1)”, “one (1) or more” or “at least one (1)”.


For all the structures described herein, such as ring systems and groups, adjacent atoms must not be —O—O—or —O—S—.


Structures having a variable number of possible carbon atoms (C atoms) may be referred to in the present application as Clower limit of carbon atoms—Cupper limit of carbon atoms structures (CLL-CUL structures), in order thus to be stipulated more specifically. Example: an alkyl group may consist of 3 to 10 carbon atoms and in that case corresponds to C3-C10 alkyl. Ring structures composed of carbon atoms and heteroatoms may be referred to as “LL- to UL-membered” structures. One example of a 6-membered ring structure is toluene (a 6-membered ring structure substituted by a methyl group).


If a collective term for a substituent, for example CLL-CUL alkyl, is at the end of a composite substituent, for example CLL-CUL Cycloalkyl-CLL-CUL alkyl, the constituent at the start of the composite substituent, for example the CLL-CUL Cycloalkyl, may be mono- or polysubstituted identically or differently and independently by the latter substituent, for example CLL-CUL alkyl. All the collective terms used in this application for chemical groups, cyclic systems and cyclic groups can be stipulated more specifically through the addition “CLL-CUL” or “LL- to UL-membered”.


In the definitions of the symbols given in the above formulae, collective terms which are generally representative of the following substituents were used:


Halogen relates to elements of the 7th main group, preferably fluorine, chlorine, bromine and iodine, more preferably fluorine, chlorine and bromine, and even more preferably fluorine and chlorine.


Examples of heteroatom are N, O, S, P, B, Si. Preferably, the term “heteroatom” relates to N, S and O.


According to the invention, “alkyl”—on its own or as part of a chemical group—represents straight-chain or branched hydrocarbons preferably having 1 to 6 carbon atoms, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl, t-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. Preference is also given to alkyls having 1 to 4 carbon atoms such as, inter alia, methyl, ethyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, s-butyl or t-butyl. The inventive alkyls may be substituted by one or more identical or different radicals.


According to the invention, “alkenyl”—on its own or as part of a chemical group—represents straight-chain or branched hydrocarbons preferably having 2 to 6 carbon atoms and at least one double bond, for example 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. Preference is also given to alkenyls having 2 to 4 carbon atoms such as, inter alia, 2-propenyl, 2-butenyl or 1-methyl-2-propenyl. The inventive alkenyls may be substituted by one or more identical or different radicals.


According to the invention, “alkynyl”—on its own or as part of a chemical group—represents straight-chain or branched hydrocarbons preferably having 2 to 6 carbon atoms and at least one triple bond, for example 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. Preference is also given to alkynyls having 2 to 4 carbon atoms such as, inter alia, ethynyl, 2-propynyl or 2-butynyl-2-propenyl. The inventive alkynyls may be substituted by one or more identical or different radicals.


According to the invention, “cycloalkyl”—on its own or as part of a chemical group—represents mono-, bi- or tricyclic hydrocarbons preferably having 3 to 10 carbons, for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl or adamantyl. Preference is also given to cycloalkyls having 3, 4, 5, 6 or 7 carbon atoms such as, inter alia, cyclopropyl or cyclobutyl. The inventive cycloalkyls may be substituted by one or more identical or different radicals.


According to the invention, “alkylcycloalkyl” represents mono-, bi- or tricyclic alkylcycloalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, for example methylcyclopropyl, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl and 4-methylcyclohexyl. Preference is also given to alkylcycloalkyls having 4, 5 or 7 carbon atoms such as, inter alia, ethylcyclopropyl or 4-methylcyclohexyl. The inventive alkylcycloalkyls may be substituted by one or more identical or different radicals.


According to the invention, “cycloalkylalkyl” represents mono-, bi- or tricyclic cycloalkylalkyl preferably having 4 to 10 or 4 to 7 carbon atoms, for example cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, cyclohexylmethyl and cyclopentylethyl. Preference is also given to cycloalkylalkyls having 4, 5 or 7 carbon atoms such as, inter alia, cyclopropylmethyl or cyclobutylmethyl. The inventive cycloalkylalkyls may be substituted by one or more identical or different radicals.


According to the invention, “hydroxyalkyl” represents a straight-chain or branched alcohol preferably having 1 to 6 carbon atoms, for example methanol, ethanol, n-propanol, isopropanol, n-butanol, isobutanol, s-butanol and t-butanol. Preference is also given to hydroxyalkyl groups having 1 to 4 carbon atoms. The inventive hydroxyalkyl groups may be substituted by one or more identical or different radicals.


According to the invention, “alkoxy” represents a straight-chain or branched O-alkyl preferably having 1 to 6 carbon atoms, for example methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, s-butoxy and t-butoxy. Preference is also given to alkoxy groups having 1 to 4 carbon atoms. The inventive alkoxy groups may be substituted by one or more identical or different radicals.


According to the invention, “alkylthio”, or “alkylsulfanyl” represents straight-chain or branched S-alkyl preferably having 1 to 6 carbon atoms, for example methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, s-butylthio and t-butylthio. Preference is also given to alkylthio groups having 1 to 4 carbon atoms. The inventive alkylthio groups may be substituted by one or more identical or different radicals.


According to the invention, “alkylsulfinyl” represents straight-chain or branched alkylsulfinyl preferably having 1 to 6 carbon atoms, for example methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl, n-butylsulfinyl, isobutylsulfinyl, s-butylsulfinyl and t-butylsulfinyl. Preference is also given to alkylsulfinyl groups having 1 to 4 carbon atoms. The inventive alkylsulfinyl groups may be substituted by one or more identical or different radicals and embrace both enantiomers.


According to the invention, “alkylsulfonyl” represents straight-chain or branched alkylsulfonyl preferably having 1 to 6 carbon atoms, for example methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl, n-butylsulfonyl, isobutylsulfonyl, s-butylsulfonyl and t-butylsulfonyl. Preference is also given to alkylsulfonyl groups having 1 to 4 carbon atoms. The inventive alkylsulfonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “cycloalkylthio” or “cycloalkylsulfanyl” represents —S-cycloalkyl preferably having 3 to 6 carbon atoms, for example cyclopropylthio, cyclobutylthio, cyclopentylthio, cyclohexylthio. Preference is also given to cycloalkylthio groups having 3 to 5 carbon atoms. The inventive cycloalkylthio groups may be substituted by one or more identical or different radicals.


According to the invention, “cycloalkylsulfinyl” represents —S(O)-cycloalkyl preferably having 3 to 6 carbon atoms, for example cyclopropylsulfinyl, cyclobutylsulfinyl, cyclopentylsulfinyl, cyclohexylsulfinyl. Preference is also given to cycloalkylsulfinyl groups having 3 to 5 carbon atoms. The inventive cycloalkylsulfinyl groups may be substituted by one or more identical or different radicals and embrace both enantiomers.


According to the invention, “cycloalkylsulfonyl” represents —SO2-cycloalkyl preferably having 3 to 6 carbon atoms, for example cyclopropylsulfonyl, cyclobutylsulfonyl, cyclopentylsulfonyl, cyclohexylsulfonyl. Preference is also given to cycloalkylsulfonyl groups having 3 to 5 carbon atoms. The inventive cycloalkylsulfonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “phenylthio”, or “phenylsulfanyl” represents —S-phenyl, for example phenylthio. The inventive phenylthio groups may be substituted by one or more identical or different radicals.


According to the invention, “phenylsulfinyl” represents —S(O)-phenyl, for example phenylsulfinyl. The inventive phenylsulfinyl groups may be substituted by one or more identical or different radicals and embrace both enantiomers.


According to the invention, “phenylsulfonyl” represents —SO2-phenyl for example phenylsulfonyl. The inventive phenylsulfonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “alkylcarbonyl” represents straight-chain or branched alkyl-C(═O) preferably having 2 to 7 carbon atoms such as methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl, s-butylcarbonyl and t-butylcarbonyl. Preference is also given to alkylcarbonyls having 1 to 4 carbon atoms. The inventive alkylcarbonyls may be substituted by one or more identical or different radicals.


According to the invention, “alkoxycarbonyl”—alone or as a constituent of a chemical group—represents straight-chain or branched alkoxycarbonyl, preferably having 1 to 6 carbon atoms or having 1 to 4 carbon atoms in the alkoxy moiety, for example methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, s-butoxycarbonyl and t-butoxycarbonyl. The inventive alkoxycarbonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “alkylaminocarbonyl” represents straight-chain or branched alkylaminocarbonyl having preferably 1 to 6 carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, for example methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, s-butylaminocarbonyl and t-butylaminocarbonyl. The inventive alkylaminocarbonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “N,N-dialkylaminocarbonyl” represents straight-chain or branched N,N-dialkylaminocarbonyl having preferably 1 to 6 carbon atoms or 1 to 4 carbon atoms in the alkyl moiety, for example N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, N,N-di(n-propylamino)carbonyl, N,N-di(isopropylamino)carbonyl and N,N-di-(s-butylamino)carbonyl. The inventive N,N-dialkylaminocarbonyl groups may be substituted by one or more identical or different radicals.


According to the invention, “aryl” represents a mono-, bi- or polycyclic aromatic system having preferably 6 to 14, especially 6 to 10, ring carbon atoms, for example phenyl, naphthyl, anthryl, phenanthrenyl, preferably phenyl. In addition, aryl also represents fused polycyclic systems such as tetrahydronaphthyl, indenyl, indanyl, fluorenyl, biphenyl, where the bonding site is on the aromatic system. The inventive aryl groups may be substituted by one or more identical or different radicals.


Examples of substituted aryls are the arylalkyls, which may likewise be substituted by one or more identical or different radicals in the C1-C4 alkyl and/or C6-C14 aryl moiety. Examples of such arylalkyls include benzyl and phenyl-1-ethyl.


According to the invention the term “polycyclic” ring refers to fused, bridged and spirocyclic carbocyclic and heterocyclic rings as well as ring systems linked through single or double bonds.


According to the invention, “heterocycle”, “heterocyclic ring” or “heterocyclic ring system” represents a carbocyclic ring system having at least one ring in which at least one carbon atom is replaced by a heteroatom, preferably by a heteroatom from the group consisting of N, O, S, P, B, Si, Se, and which is saturated, unsaturated or heteroaromatic and may be unsubstituted or substituted, where the bonding site is on a ring atom. Unless defined differently, the heterocyclic ring contains preferably 3 to 9 ring atoms, especially 3 to 6 ring atoms, and one or more, preferably 1 to 4, especially 1, 2 or 3, heteroatoms in the heterocyclic ring, preferably from the group consisting of N, O, and S, although no two oxygen atoms should be directly adjacent. The heterocyclic rings usually contain not more than 4 nitrogen atoms and/or not more than 2 oxygen atoms and/or not more than 2 sulphur atoms. In the case of optionally substituted heterocyclyl, the invention also embraces polycyclic ring systems, for example 8-azabicyclo[3.2.1]octanyl, 1-azabicyclo[2.2.1]heptyl, 1-oxa-5-azaspiro[2.3]hexyl or 2,3-dihydro-1H-indole.


Inventive heterocyclyl groups are, for example, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, dihydropyranyl, tetrahydropyranyl, dioxanyl, pyrrolinyl, pyrrolidinyl, imidazolinyl, imidazolidinyl, thiazolidinyl, oxazolidinyl, dioxolanyl, dioxolyl, pyrazolidinyl, tetrahydrofuranyl, dihydrofuranyl, oxetanyl, oxiranyl, azetidinyl, aziridinyl, oxazetidinyl, oxaziridinyl, oxazepanyl, oxazinanyl, azepanyl, oxopyrrolidinyl, dioxopyrrolidinyl, oxomorpholinyl, oxopiperazinyl and oxepanyl.


Of particular significance are heteroaryls, i.e. heteroaromatic systems. According to the invention, the term heteroaryl represents heteroaromatic compounds, i.e. completely unsaturated aromatic heterocyclic compounds which fall under the above definition of heterocycles. Preference is given to 5- to 7-membered rings having 1 to 3, preferably 1 or 2, identical or different heteroatoms from the group above. Inventive heteroaryls are, for example, furyl, thienyl, pyrazolyl, imidazolyl, 1,2,3- and 1,2,4-triazolyl, isoxazolyl, thiazolyl, isothiazolyl, 1,2,3-, 1,3,4-, 1,2,4- and 1,2,5-oxadiazolyl, azepinyl, pyrrolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, 1,3,5-, 1,2,4- and 1,2,3-triazinyl, 1,2,4-, 1,3,2-, 1,3,6- and 1,2,6-oxazinyl, oxepinyl, thiepinyl, 1,2,4-triazolonyl and 1,2,4-diazepinyl. The inventive heteroaryl groups may also be substituted by one or more identical or different radicals.


According to the invention, the substituent ═O (oxo) can replace two hydrogen atoms of a methylene (CH2) group or the lone pairs of a sulfur, nitrogen and phosphorous atom which bears only substituents other than hydrogen. For example the radical C2-alkyl becomes for example —COCH3 through substitution by ═O (oxo) while the heterocycle thietan-3-yl-becomes for example 1-oxothietan-3-yl through substitution by one ═O (oxo) group or 1,1-dioxothietan-3-yl through substitution by two ═O (oxo) groups.


According to the invention, the substituent ═S (thiono) can replace two hydrogen atoms of a methylene (CH2) group. For example the radical C2-alkyl becomes for examples —CSCH3 through substitution by ═S (thiono).


The expression “optionally substituted” as used herein means that the optionally substituted group either is substituted with further substituents or is not substituted with further substituents.


The term “in each case optionally substituted” means that a group/substituent, such as a alkyl, alkenyl, alkynyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, cycloalkyl, aryl, phenyl, benzyl, heterocyclyl and heteroaryl radical, is substituted, meaning, for example, a substituted radical derived from the unsubstituted base structure, where the substituents, for example, one (1) substituent or a plurality of substituents, preferably 1, 2, 3, 4, 5, 6 or 7, are selected from a group consisting of amino, hydroxyl, halogen, nitro, cyano, isocyano, mercapto, isothiocyanato, C1-C4 carboxyl, carbonamide, SF5, aminosulphonyl, C1-C4 alkyl, C1-C4 haloalkyl, 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-C4alkanoylamino, C1-C4 alkoxy, C1-C4 haloalkoxy, C2-C4 alkenyloxy, C2-C4 alkynyloxy, C3-C4 cycloalkoxy, C5-C6 cycloalkenyloxy, C1-C4 alkoxycarbonyl, C2-C4 alkenyloxycarbonyl, C2-C4 alkynyloxycarbonyl, C6-, C10-, C14-aryloxycarbonyl, C1-C4alkanoyl, C2-C4 alkenylcarbonyl, C2-C4 alkynylcarbonyl, C6-, C10-, C14-arylcarbonyl, C1-C4 alkylthio, C1-C4 haloalkylthio, C3-C4 cycloalkylthio, C2-C4 alkenylthio, C5-C6 cycloalkenylthio, C2-C4 alkynylthio, C1-C4 alkylsulfinyl, including both enantiomers of the C1-C4 alkylsulfinyl group, C1-C4 haloalkylsulfinyl, including both enantiomers of the C1-C4 haloalkylsulfinyl group, C1-C4 alkylsulfonyl, C1-C4 haloalkylsulfonyl, N-mono-C1-C4 alkylaminosulfonyl, N,N-di-C1-C4 alkylaminosulfonyl, C1-C4 alkylphosphinyl, C1-C4 alkylphosphonyl, including both enantiomers of C1-C4 alkylphosphinyl and C1-C4 alkylphosphonyl, N—C1-C4 alkylaminocarbonyl, N,N-di-C1-C4 alkylaminocarbonyl, N—C1-C4alkanoylaminocarbonyl, N—C1-C4alkanoyl-N—C1-C4 alkylaminocarbonyl, C6-, C10-, C14-aryl, C6-, C10-, C14-aryloxy, benzyl, benzyloxy, benzylthio, C6-, C10-, C14-arylthio, C6-, C10-, C14-arylamino, benzylamino, heterocyclyl and trialkylsilyl, substituents bonded via a double bond, such as C1-C4 alkylidene (e.g. methylidene or ethylidene), an oxo group, an imino group and a substituted imino group. When two or more radicals form one or more rings, these may be carbocyclic, heterocyclic, saturated, partly saturated, unsaturated, for example including aromatic rings and with further substitution. The substituents mentioned by way of example (“first substituent level”) may, if they contain hydrocarbonaceous components, optionally have further substitution therein (“second substituent level”), for example by one or more of the substituents each independently selected from halogen, hydroxyl, amino, nitro, cyano, isocyano, azido, acylamino, an oxo group and an imino group. The term “(optionally) substituted” group preferably embraces just one or two substituent levels.


The inventive halogen-substituted chemical groups or halogenated groups (for example alkyl or alkoxy) are mono- or polysubstituted by halogen up to the maximum possible number of substituents. Such groups are also referred to as halo groups (for example haloalkyl). In the case of polysubstitution by halogen, the halogen atoms may be the same or different, and may all be bonded to one carbon atom or may be bonded to a plurality of carbon atoms. Halogen is especially fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine and more preferably fluorine. More particularly, halogen-substituted groups are monohalocycloalkyl such as 1-fluorocyclopropyl, 2-fluorocyclopropyl or 1-fluorocyclobutyl, monohaloalkyl such as 2-chloroethyl, 2-fluoroethyl, 1-chloroethyl, 1-fluoroethyl, chloromethyl, or fluoromethyl; perhaloalkyl such as trichloromethyl or trifluoromethyl or CF2CF3, polyhaloalkyl such as difluoromethyl, 2-fluoro-2-chloroethyl, dichloromethyl, 1,1,2,2-tetrafluoroethyl or 2,2,2-trifluoroethyl. Further 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 pentafluoro-t-butyl. Preference is given to haloalkyls having 1 to 4 carbon atoms and 1 to 9, preferably 1 to 5, identical or different halogen atoms selected from fluorine, chlorine and bromine. Particular preference is given to haloalkyls having 1 or 2 carbon atoms and 1 to 5 identical or different halogen atoms selected from fluorine and chlorine, such as, inter alia, difluoromethyl, trifluoromethyl or 2,2-difluoroethyl. Further examples of halogen-substituted compounds are haloalkoxy such as OCF3, OCHF2, OCH2F, OCF2CF3, OCH2CF3, OCH2CHF2 und OCH2CH2Cl, haloalkylsulfanyls 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, haloalkylsulfinyls 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, haloalkylsulfinyls 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.


In the case of radicals having carbon atoms, preference is given to those having 1 to 4 carbon atoms, especially 1 or 2 carbon atoms. Preference is generally given to substituents from the group of halogen, e.g. 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. Particular preference is given here to the substituents methyl, methoxy, fluorine and chlorine.


Substituted amino such as mono- or disubstituted amino means a radical from the group of the substituted amino radicals which are N-substituted, for example, by one or two identical or different radicals from the group of alkyl, hydroxy, amino, alkoxy, acyl and aryl; preferably N-mono- and N,N-dialkylamino, (for example methylamino, ethylamino, N,N-dimethylamino, N,N-diethylamino, N,N-di-n-propylamino, N,N-diisopropylamino or N,N-dibutylamino), N-mono- or N,N-dialkoxyalkylamino groups (for example N-methoxymethylamino, N-methoxyethylamino, N,N-di(methoxymethyl)amino or N,N-di(methoxyethyl)amino), N-mono- and N,N-diarylamino, such as optionally substituted anilines, acylamino, N,N-diacylamino, N-alkyl-N-arylamino, N-alkyl-N-acylamino and also saturated N-heterocycles; preference is given here to alkyl radicals having 1 to 4 carbon atoms; here, aryl is preferably phenyl or substituted phenyl; for acyl, the definition given further below applies, preferably (C1-C4)-alkanoyl. The same applies to substituted hydroxylamino or hydrazino.


Substituted amino also includes quaternary ammonium compounds (salts) having four organic substituents on the nitrogen atom.


Optionally substituted phenyl is preferably phenyl which is unsubstituted or mono- or polysubstituted, preferably up to trisubstituted, by identical or different radicals from the group of 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, (C1-C4)alkylsulfinyl (C1-C4)haloalkylsulfinyl, (C1-C4)alkylsulfonyl (C1-C4)haloalkylsulfonyl, cyano, isocyano and nitro, for example o-, m- and p-tolyl, dimethylphenyls, 2-, 3- and 4-chlorophenyl, 2-, 3- and 4-fluorophenyl, 2-, 3- and 4-trifluoromethyl- and 4-trichloromethylphenyl, 2,4-, 3,5-, 2,5- and 2,3-dichlorophenyl, o-, m- and p-methoxyphenyl, 4-heptafluorophenyl.


Optionally substituted cycloalkyl is preferably cycloalkyl which is unsubstituted or mono- or polysubstituted, preferably up to trisubstituted, by identical or different radicals from the group of 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 by one or two (C1-C4)alkyl radicals.


Inventive compounds may occur in preferred embodiments. Individual embodiments described herein may be combined with one another. Not included are combinations which contravene the laws of nature and which the person skilled in the art would therefore rule out on the basis of his/her expert knowledge. Ring structures having three or more adjacent oxygen atoms, for example, are excluded.


Isomers

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


Isotopic Variants

The present invention also encompasses all suitable isotopic variants of the compounds of the formula (I). An isotopic variant of such a compound is understood to mean a compound of the formula (I) in which at least one atom is replaced by another atom of the same atomic number, but with a different atomic mass than the atomic mass usually or predominantly occurring in nature. Examples of isotopes that can be incorporated into a compounds of the formula (I) are those of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as 2H (deuterium), 3H (tritium), 13C, 14C, 15N, 17O, 18O, 32P, 33P, 33S, 34S, 35S, 36S, 18F, 36Cl, 82Br, 123J, 124J, 129I and 131I. Certain isotopic variants of a compounds of the formula (I), such as in particular those in which one or more radioactive isotopes are incorporated, can be useful, for example, for investigating the mechanism of action or the active ingredient distribution, for example in the body of a pathogen; for this purpose, compounds labeled with 3H or 14C isotopes are particularly suitable, because their production and detection which is comparatively easy. In addition, the incorporation of isotopes, such as, for example, deuterium, can lead to advantages, for example as a result of greater metabolic stability of the compound, such as, for example, an extension of the half-life or a reduction in the required effective dose. Isotopic modifications of the compounds of the formula (I) can therefore also represent a preferred embodiment of the invention. Isotopic variants of the compounds of the formula (I) can be prepared by methods known to the person skilled in the art, for example by the methods described below and the instructions given in the exemplary embodiments, by using appropriate isotopic modifications of the respective reagents and/or starting compounds (educts).


Methods and Uses

The invention also relates to methods for controlling animal pests, in which compounds of the formula (I) are allowed to act on animal pests and/or their habitat. The control of the animal pests is preferably conducted in agriculture and forestry, and in material protection. Preferably excluded herefrom are methods for the surgical or therapeutic treatment of the human or animal body and diagnostic methods carried out on the human or animal body.


The invention furthermore relates to the use of the compounds of the formula (I) as pesticides, in particular crop protection agents.


In the context of the present application, the term “pesticide” in each case also always comprises the term “crop protection agent”.


The compounds of the formula (I), having good plant tolerance, favourable homeotherm toxicity and good environmental compatibility, are suitable for protecting plants and plant organs against biotic and abiotic stressors, for increasing harvest yields, for improving the quality of the harvested material and for controlling animal pests, especially insects, arachnids, helminths, in particular nematodes, and molluscs, which are encountered in agriculture, in horticulture, in animal husbandry, in aquatic cultures, in forests, in gardens and leisure facilities, in the protection of stored products and of materials, and in the hygiene sector.


Within the context of the present patent application, the term “hygiene” is understood to mean any and all measures, procedures and practices which aim to prevent disease, in particular infectious disease, and which serve to protect the health of humans and animals and/or to protect the environment, and/or which maintain cleanliness. In accordance with the invention, this especially includes measures for cleaning, disinfection and sterilisation of, for example, textiles or hard surfaces, especially surfaces of glass, wood, concrete, porcelain, ceramics, plastic or also of metal(s), and for ensuring that these are kept free of hygiene pests and/or their excretions. Preferably excluded from the scope of the invention in this regard are surgical or therapeutic treatment procedures applicable to the human body or to the bodies of animals and diagnostic procedures which are carried out on the human body or on the bodies of animals.


The term “hygiene sector” thus covers all areas, technical fields and industrial applications in which these hygiene measures, procedures and practices are important, in relation for example to hygiene in kitchens, bakeries, airports, bathrooms, swimming pools, department stores, hotels, hospitals, stables, animal husbandries, etc.


The term “hygiene pest” is therefore understood to mean one or more animal pests whose presence in the hygiene sector is problematic, in particular for health reasons. It is therefore a primary objective to avoid or minimize the presence of hygiene pests, and/or exposure to them, in the hygiene sector. This can be achieved in particular through the application of a pesticide that can be used both to prevent infestation and to tackle an infestation which is already present. Preparations which avoid or reduce exposure to pests can also be used. Hygiene pests include, for example, the organisms mentioned below.


The term “hygiene protection” thus covers all actions to maintain and/or improve these hygiene measures, procedures and practices.


The compounds of the formula (I) can preferably be used as pesticides. They are active against normally sensitive and resistant species and against all or some stages of development. The abovementioned pests include:

    • pests from the phylum of the Arthropoda, in particular from the class of the Arachnida, for example Acarus spp., for example Acarus siro, Aceria kuko, Aceria sheldoni, Aculops spp., Aculus spp., for example Aculus fockeui, Aculus schlechtendali, Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp., for example Brevipalpus phoenicis, Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., for example Eotetranychus hicoriae, Epitrimerus pyri, Eutetranychus spp., for example Eutetranychus banksi, Eriophyes spp., for example Eriophyes pyri, Glycyphagus domesticus, Halotydeus destructor, Hemitarsonemus spp., for example Hemitarsonemus latus (=Polyphagotarsonemus latus), Hyalomma spp., Ixodes spp., Latrodectus spp., Loxosceles spp., Neutrombicula autumnalis, Nuphersa spp., Oligonychus spp., for example Oligonychus coffeae, Oligonychus coniferarum, Oligonychus ilicis, Oligonychus indicus, Oligonychus mangiferus, Oligonychus pratensis, Oligonychus punicae, Oligonychus yothersi, Ornithodorus spp., Ornithonyssus spp., Panonychus spp., for example Panonychus citri (=Metatetranychus citri), Panonychus ulmi (=Metatetranychus ulmi), Phyllocoptruta oleivora, Platytetranychus multidigituli, Polyphagotarsonemus latus, Psoroptes spp., Rhipicephalus spp., Rhizoglyphus spp., Sarcoptes spp., Scorpio maurus, Steneotarsonemus spp., Steneotarsonemus spinki, Tarsonemus spp., for example Tarsonemus confusus, Tarsonemus pallidus, Tetranychus spp., for example Tetranychus canadensis, Tetranychus cinnabarinus, Tetranychus turkestani, Tetranychus urticae, Trombicula alfreddugesi, Vaejovis spp., Vasates lycopersici;
    • from the class of the Chilopoda, for example Geophilus spp., Scutigera spp.;
    • from the order or the class of the Collembola, for example Onychiurus armatus; Sminthurus viridis;
    • from the class of the Diplopodia, for example Blaniulus guttulatus;
    • from the class of the Insecta, for example from the order of the Blattodea, for example Blatta orientalis, Blattella asahinai, Blattella germanica, Leucophaea maderae, Loboptera decipiens, Neostylopyga rhombifolia, Panchlora spp., Parcoblatta spp., Periplaneta spp., for example Periplaneta americana, Periplaneta australasiae, Pycnoscelus surinamensis, Supella longipalpa;
    • from the order of the Coleoptera, for example Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Aethina tumida, Agelastica alni, Agrilus spp., for example Agrilus planipennis, Agrilus coxalis, Agrilus bilineatus, Agrilus anxius, Agriotes spp., for example Agriotes linneatus, Agriotes mancus, Agriotes obscurus, Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anomala dubia, Anoplophora spp., for example Anoplophora glabripennis, Anthonomus spp., for example Anthonomus grandis, Anthrenus spp., Apion spp., Apogonia spp., Athous haemorrhoidales, Atomaria spp., for example Atomaria linearis, Attagenus spp., Baris caerulescens, Bruchidius obtectus, Bruchus spp., for example Bruchus pisorum, Bruchus rufimanus, Cassida spp., Cerotoma trifurcata, Ceutorrhynchus spp., for example Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae, Chaetocnema spp., for example Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa, Cleonus mendicus, Conoderus spp., Cosmopolites spp., for example Cosmopolites sordidus, Costelytra zealandica, Ctenicera spp., Curculio spp., for example Curculio caryae, Curculio caryatrypes, Curculio obtusus, Curculio sayi, Cryptolestes ferrugineus, Cryptolestes pusillus, Cryptorhynchus lapathi, Cryptorhynchus mangiferae, Cylindrocopturus spp., Cylindrocopturus adspersus, Cylindrocopturus furnissi, Dendroctonus spp., for example Dendroctonus ponderosae, Dermestes spp., Diabrotica spp., for example 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., for example Epilachna borealis, Epilachna varivestis, Epitrix spp., for example Epitrix cucumeris, Epitrix fuscula, Epitrix hirtipennis, Epitrix subcrinita, Epitrix tuberis, Faustinus spp., Gibbium psylloides, Gnathocerus cornutus, Hellula undalis, Heteronychus arator, Heteronyx spp., Hoplia argentea, Hylamorpha elegans, Hylotrupes bajulus, Hypera postica, Hypomeces squamosus, Hypothenemus spp., for example Hypothenemus hampei, Hypothenemus obscurus, Hypothenemus pubescens, Lachnosterna consanguinea, Lasioderma serricorne, Latheticus oryzae, Lathridius spp., Lema spp., Leptinotarsa decemlineata, Leucoptera spp., for example Leucoptera coffeella, Limonius ectypus, Lissorhoptrus oryzophilus, Listronotus (=Hyperodes) spp., Lixus spp., Luperodes spp., Luperomorpha xanthodera, Lyctus spp., Megacyllene spp., for example Megacyllene robiniae, Megascelis spp., Melanotus spp., for example Melanotus longulus oregonensis, Meligethes aeneus, Melolontha spp., for example Melolontha melolontha, Migdolus spp., Monochamus spp., Naupactus xanthographus, Necrobia spp., Neogalerucella spp., Niptus hololeucus, Oryctes rhinoceros, Oryzaephilus surinamensis, Oryzaphagus oryzae, Otiorhynchus spp., for example Otiorhynchus cribricollis, Otiorhynchus ligustici, Otiorhynchus ovatus, Otiorhynchus rugosostriarus, Otiorhynchus sulcatus, Oulema spp., for example Oulema melanopus, Oulema oryzae, Oxycetonia jucunda, Phaedon cochleariae, Phyllophaga spp., Phyllophaga helleri, Phyllotreta spp., for example Phyllotreta armoraciae, Phyllotreta pusilla, Phyllotreta ramosa, Phyllotreta striolata, Popillia japonica, Premnotrypes spp., Prostephanus truncatus, Psylliodes spp., for example Psylliodes affinis, Psylliodes chrysocephala, Psylliodes punctulata, Ptinus spp., Rhizobius ventralis, Rhizopertha dominica, Rhynchophorus spp., Rhynchophorus ferrugineus, Rhynchophorus palmarum, Scolytus spp., for example Scolytus multistriatus, Sinoxylon perforans, Sitophilus spp., for example Sitophilus granarius, Sitophilus linearis, Sitophilus oryzae, Sitophilus zeamais, Sphenophorus spp., Stegobium paniceum, Sternechus spp., for example Sternechus paludatus, Symphyletes spp., Tanymecus spp., for example Tanymecus dilaticollis, Tanymecus indicus, Tanymecus palliatus, Tenebrio molitor, Tenebrioides mauretanicus, Tribolium spp., for example Tribolium audax, Tribolium castaneum, Tribolium confusum, Trogoderma spp., Tychius spp., Xylotrechus spp., Zabrus spp., for example Zabrus tenebrioides;
    • from the order of the Dermaptera, for example Anisolabis maritime, Forficula auricularia, Labidura riparia;
    • from the order of the Diptera, for example Aedes spp., for example Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans, Agromyza spp., for example Agromyza frontella, Agromyza parvicornis, Anastrepha spp., Anopheles spp., for example Anopheles quadrimaculatus, Anopheles gambiae, Asphondylia spp., Bactrocera spp., for example 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., for example Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora, Contarinia schulzi, Contarinia sorghicola, Contarinia tritici, Cordylobia anthropophaga, Cricotopus sylvestris, Culex spp., for example Culex pipiens, Culex quinquefasciatus, Culicoides spp., Culiseta spp., Cuterebra spp., Dacus oleae, Dasineura spp., for example Dasineura brassicae, Delia spp., for example Delia antiqua, Delia coarctata, Delia florilega, Delia platura, Delia radicum, Dermatobia hominis, Drosophila spp., for example Drosophila melanogaster, Drosophila suzukii, Echinocnemus spp., Euleia heraclei, Fannia spp., Gasterophilus spp., Glossina spp., Haematopota spp., Hydrellia spp., Hydrellia griseola, Hylemya spp., Hippobosca spp., Hypoderma spp., Liriomyza spp., for example Liriomyza brassicae, Liriomyza huidobrensis, Liriomyza sativae, Lucilia spp., for example Lucilia cuprina, Lutzomyia spp., Mansonia spp., Musca spp., for example Musca domestica, Musca domestica vicina, Oestrus spp., Oscinella frit, Paratanytarsus spp., Paralauterborniella subcincta, Pegomya or Pegomyia spp., for example Pegomya betae, Pegomya hyoscyami, Pegomya rubivora, Phlebotomus spp., Phorbia spp., Phormia spp., Piophila casei, Platyparea poeciloptera, Prodiplosis spp., Psila rosae, Rhagoletis spp., for example Rhagoletis cingulata, Rhagoletis completa, Rhagoletis fausta, Rhagoletis indifferens, Rhagoletis mendax, Rhagoletis pomonella, Sarcophaga spp., Simulium spp., for example Simulium meridionale, Stomoxys spp., Tabanus spp., Tetanops spp., Tipula spp., for example Tipula paludosa, Tipula simplex, Toxotrypana curvicauda;
    • from the order of the Hemiptera, for example Acizzia acaciaebaileyanae, Acizzia dodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosiphon spp., for example Acyrthosiphon pisum, Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleurocanthus spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp., for example Amrasca bigutulla, Amrasca devastans, Anuraphis cardui, Aonidiella spp., for example Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata, Aphanostigma piri, Aphis spp., for example 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., for example Aspidiotus nerii, Atanus spp., Aulacorthum solani, Bemisia tabaci, Blastopsylla occidentalis, Boreioglycaspis melaleucae, Brachycaudus helichrysi, Brachycolus spp., Brevicoryne brassicae, Cacopsylla spp., for example Cacopsylla pyricola, Calligypona marginata, Capulinia spp., 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., for example Coccus hesperidum, Coccus longulus, Coccus pseudomagnoliarum, Coccus viridis, Cryptomyzus ribis, Cryptoneossa spp., Ctenarytaina spp., Dalbulus spp., Dialeurodes chittendeni, Dialeurodes citri, Diaphorina citri, Diaspis spp., Diuraphis spp., Doralis spp., Drosicha spp., Dysaphis spp., for example Dysaphis apiifolia, Dysaphis plantaginea, Dysaphis tulipae, Dysmicoccus spp., Empoasca spp., for example Empoasca abrupta, Empoasca fabae, Empoasca maligna, Empoasca solana, Empoasca stevensi, Eriosoma spp., for example 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., for example Icerya purchasi, Idiocerus spp., Idioscopus spp., Laodelphax striatellus, Lecanium spp., for example Lecanium corni (=Parthenolecanium corni), Lepidosaphes spp., for example Lepidosaphes ulmi, Lipaphis erysimi, Lopholeucaspis japonica, Lycorma delicatula, Macrosiphum spp., for example Macrosiphum euphorbiae, Macrosiphum lilii, Macrosiphum rosae, Macrosteles facifrons, Mahanarva spp., Melanaphis sacchari, Metcalfiella spp., Metcalfa pruinosa, Metopolophium dirhodum, Monellia costalis, Monelliopsis pecanis, Myzus spp., for example Myzus ascalonicus, Myzus cerasi, Myzus ligustri, Myzus ornatus, Myzus persicae, Myzus nicotianae, Nasonovia ribisnigri, Neomaskellia spp., Nephotettix spp., for example Nephotettix cincticeps, Nephotettix nigropictus, Nettigoniclla spectra, Nilaparvata lugens, Oncometopia spp., Orthezia praelonga, Oxya chinensis, Pachypsylla spp., Parabemisia myricae, Paratrioza spp., for example Paratrioza cockerelli, Parlatoria spp., Pemphigus spp., for example Pemphigus bursarius, Pemphigus populivenae, Peregrinus maidis, Perkinsiella spp., Phenacoccus spp., for example Phenacoccus madeirensis, Phloeomyzus passerinii, Phorodon humuli, Phylloxera spp., for example Phylloxera devastatrix, Phylloxera notabilis, Pinnaspis aspidistrae, Planococcus spp., for example Planococcus citri, Prosopidopsylla flava, Protopulvinaria pyriformis, Pseudaulacaspis pentagona, Pseudococcus spp., for example Pseudococcus calceolariae, Pseudococcus comstocki, Pseudococcus longispinus, Pseudococcus maritimus, Pseudococcus viburni, Psyllopsis spp., Psylla spp., for example Psylla buxi, Psylla mali, Psylla pyri, Pteromalus spp., Pulvinaria spp., Pyrilla spp., Quadraspidiotus spp., for example Quadraspidiotus juglansregiae, Quadraspidiotus ostreaeformis, Quadraspidiotus perniciosus, Quesada gigas, Rastrococcus spp., Rhopalosiphum spp., for example Rhopalosiphum maidis, Rhopalosiphum oxyacanthae, Rhopalosiphum padi, Rhopalosiphum rufiabdominale, Saissetia spp., for example 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., for example Toxoptera aurantii, Toxoptera citricidus, Trialeurodes vaporariorum, Trioza spp., for example Trioza diospyri, Typhlocyba spp., Unaspis spp., Viteus vitifolii, Zygina spp.; from the suborder of the Heteroptera, for example Aelia spp., Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp., for example Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus, Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp., for example Euschistus heros, Euschistus servus, Euschistus tristigmus, Euschistus variolarius, Eurydema spp., Eurygaster spp., Halyomorpha halys, Heliopeltis spp., Horcias nobilellus, Leptocorisa spp., Leptocorisa varicornis, Leptoglossus occidentalis, Leptoglossus phyllopus, Lygocoris spp., for example Lygocoris pabulinus, Lygus spp., for example Lygus elisus, Lygus hesperus, Lygus lineolaris, Macropes excavatus, Megacopta cribraria, Miridae, Monalonion atratum, Nezara spp., for example Nezara viridula, Nysius spp., Oebalus spp., Pentomidae, Piesma quadrata, Piezodorus spp., for example Piezodorus guildinii, Psallus spp., Pseudacysta persea, Rhodnius spp., Sahlbergella singularis, Scaptocoris castanea, Scotinophora spp., Stephanitis nashi, Tibraca spp., Triatoma spp.;
    • from the order of the Hymenoptera, for example Acromyrmex spp., Athalia spp., for example Athalia rosae, Atta spp., Camponotus spp., Dolichovespula spp., Diprion spp., for example Diprion similis, Hoplocampa spp., for example Hoplocampa cookei, Hoplocampa testudinea, Lasius spp., Linepithema (Iridiomyrmex) humile, Monomorium pharaonis, Paratrechina spp., Paravespula spp., Plagiolepis spp., Sirex spp., for example Sirex noctilio, Solenopsis invicta, Tapinoma spp., Technomyrmex albipes, Urocerus spp., Vespa spp., for example Vespa crabro, Wasmannia auropunctata, Xeris spp.;
    • from the order of the Isopoda, for example Armadillidium vulgare, Oniscus asellus, Porcellio scaber;
    • from the order of the Isoptera, for example Coptotermes spp., for example Coptotermes formosanus, Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Kalotermes spp., Microtermes obesi, Nasutitermes spp., Odontotermes spp., Porotermes spp., Reticulitermes spp., for example Reticulitermes flavipes, Reticulitermes hesperus;
    • from the order of the Lepidoptera, for example Achroia grisella, Acronicta major, Adoxophyes spp., for example Adoxophyes orana, Aedia leucomelas, Agrotis spp., for example Agrotis segetum, Agrotis ipsilon, Alabama spp., for example Alabama argillacea, Amyelois transitella, Anarsia spp., Anticarsia spp., for example 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., for example 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., for example Cydia nigricana, Cydia pomonella, Dalaca noctuides, Diaphania spp., Diparopsis spp., Diatraea saccharalis, Dioryctria spp., for example Dioryctria zimmermani, Earias spp., Ecdytolopha aurantium, Elasmopalpus lignosellus, Eldana saccharina, Ephestia spp., for example Ephestia elutella, Ephestia kuehniella, Epinotia spp., Epiphyas postvittana, Erannis spp., Erschoviella musculana, Etiella spp., Eudocima spp., Eulia spp., Eupoecilia ambiguella, Euproctis spp., for example Euproctis chrysorrhoea, Euxoa spp., Feltia spp., Galleria mellonella, Gracillaria spp., Grapholitha spp., for example Grapholita molesta, Grapholita prunivora, Hedylepta spp., Helicoverpa spp., for example Helicoverpa armigera, Helicoverpa zea, Heliothis spp., for example Heliothis virescens, Hepialus spp., for example Hepialus humuli, Hofmannophila pseudospretella, Homoeosoma spp., Homona spp., Hyponomeuta padella, Kakivoria flavofasciata, Lampides spp., Laphygma spp., Laspeyresia molesta, Leucinodes orbonalis, Leucoptera spp., for example Leucoptera coffeella, Lithocolletis spp., for example Lithocolletis blancardella, Lithophane antennata, Lobesia spp., for example Lobesia botrana, Loxagrotis albicosta, Lymantria spp., for example Lymantria dispar, Lyonetia spp., for example Lyonetia clerkella, Malacosoma neustria, Maruca testulalis, Mamestra 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., for example Ostrinia nubilalis, Panolis flammea, Parnara spp., Pectinophora spp., for example Pectinophora gossypiella, Perileucoptera spp., Phthorimaea spp., for example Phthorimaea operculella, Phyllocnistis citrella, Phyllonorycter spp., for example Phyllonorycter blancardella, Phyllonorycter crataegella, Pieris spp., for example Pieris rapae, Platynota stultana, Plodia interpunctella, Plusia spp., Plutella xylostella (=Plutella maculipennis), Podesia spp., for example Podesia syringae, Prays spp., Prodenia spp., Protoparce spp., Pseudaletia spp., for example Pseudaletia unipuncta, Pseudoplusia includens, Pyrausta nubilalis, Rachiplusia nu, Schoenobius spp., for example Schoenobius bipunctifer, Scirpophaga spp., for example Scirpophaga innotata, Scotia segetum, Sesamia spp., for example Sesamia inferens, Sparganothis spp., Spodoptera spp., for example Spodoptera eradiana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera praefica, Stathmopoda spp., Stenoma spp., Stomopteryx subsecivella, Synanthedon spp., Tecia solanivora, Thaumetopoea spp., Thermesia gemmatalis, Tinea cloacella, Tinea pellionella, Tineola bisselliella, Tortrix spp., Trichophaga tapetzella, Trichoplusia spp., for example Trichoplusia ni, Tryporyza incertulas, Tuta absoluta, Virachola spp.; from the order of the Orthoptera or Saltatoria, for example Acheta domesticus, Dichroplus spp., Gryllotalpa spp., for example Gryllotalpa gryllotalpa, Hieroglyphus spp., Locusta spp., for example Locusta migratoria, Melanoplus spp., for example Melanoplus devastator, Paratlanticus ussuriensis, Schistocerca gregaria;
    • from the order of the Phthiraptera, for example Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Phthirus pubis, Trichodectes spp.;
    • from the order of the Psocoptera, for example Lepinotus spp., Liposcelis spp.; from the order of the Siphonaptera, for example, Ceratophyllus spp., Ctenocephalides spp., for example Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis; from the order of the Thysanoptera, for example Anaphothrips obscurus, Baliothrips biformis, Chaetanaphothrips leeuweni, Drepanothrips reuteri, Enneothrips flavens, Frankliniella spp., for example 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., for example Thrips palmi, Thrips tabaci;
    • from the order of the Zygentoma (=Thysanura), for example Ctenolepisma spp., Lepisma saccharina, Lepismodes inquilinus, Thermobia domestica;
    • from the class of the Symphyla, for example Scutigerella spp., for example Scutigerella immaculata; pests from the phylum of the Mollusca, for example from the class of the Bivalvia, for example Dreissena spp.,
    • and also from the class of the Gastropoda, for example Arion spp., for example Arion ater rufus, Biomphalaria spp., Bulinus spp., Deroceras spp., for example Deroceras laeve, Galba spp., Lymnaea spp., Oncomelania spp., Pomacea spp., Succinea spp.;
    • plant pests from the phylum of the Nematoda, i.e. phytoparasitic nematodes, in particular Aglenchus spp., for example Aglenchus agricola, Anguina spp., for example Anguina tritici, Aphelenchoides spp., for example Aphelenchoides arachidis, Aphelenchoides fragariae, Belonolaimus spp., for example Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni, Bursaphelenchus spp., for example Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus, Cacopaurus spp., for example Cacopaurus pestis, Criconemella spp., for example Criconemella curvata, Criconemella onoensis, Criconemella ornata, Criconemella rusium, Criconemella xenoplax (=Mesocriconema xenoplax), Criconemoides spp., for example Criconemoides ferniae, Criconemoides onoense, Criconemoides ornatum, Ditylenchus spp., for example Ditylenchus dipsaci, Dolichodorus spp., Globodera spp., for example Globodera pallida, Globodera rostochiensis, Helicotylenchus spp., for example Helicotylenchus dihystera, Hemicriconemoides spp., Hemicycliophora spp., Heterodera spp., for example Heterodera avenae, Heterodera glycines, Heterodera schachtii, Hirschmaniella spp., Hoplolaimus spp., Longidorus spp., for example Longidorus africanus, Meloidogyne spp., for example Meloidogyne chitwoodi, Meloidogyne fallax, Meloidogyne hapla, Meloidogyne incognita, Meloinema spp., Nacobbus spp., Neotylenchus spp., Paralongidorus spp., Paraphelenchus spp., Paratrichodorus spp., for example Paratrichodorus minor, Paratylenchus spp., Pratylenchus spp., for example Pratylenchus penetrans, Pseudohalenchus spp., Psilenchus spp., Punctodera spp., Quinisulcius spp., Radopholus spp., for example Radopholus citrophilus, Radopholus similis, Rotylenchulus spp., Rotylenchus spp., Scutellonema spp., Subanguina spp., Trichodorus spp., for example Trichodorus obtusus, Trichodorus primitivus, Tylenchorhynchus spp., for example Tylenchorhynchus annulatus, Tylenchulus spp., for example Tylenchulus semipenetrans, Xiphinema spp., for example Xiphinema index.


The compounds of the formula (I) can optionally, at certain concentrations or application rates, also be used as herbicides, safeners, growth regulators or agents to improve plant properties, as microbicides or gametocides, for example as fungicides, antimycotics, bactericides, viricides (including agents against viroids) or as agents against MLO (mycoplasma-like organisms) and RLO (rickettsia-like organisms). If appropriate, they can also be used as intermediates or precursors for the synthesis of other active compounds.


Formulations/Use Forms

The present invention further relates to formulations, in particular formulations for controlling unwanted controlling animal pests. The formulation may be applied to the animal pest and/or in their habitat.


The formulation of the invention may be provided to the end user as “ready-for-use” use form, i.e. the formulations may be directly applied to the plants or seeds by a suitable device, such as a spraying or dusting device. Alternatively, the formulations may be provided to the end user in the form of concentrates which have to be diluted, preferably with water, prior to use. Unless otherwise indicated, the wording “formulation” therefore means such concentrate, whereas the wording “use form” means the end user as “ready-for-use” solution, i.e. usually such diluted formulation.


The formulation of the invention can be prepared in conventional manners, for example by mixing the compound of the invention with one or more suitable auxiliaries, such as disclosed herein.


The formulation comprises at least one compound of the invention and at least one agriculturally suitable auxiliary, e.g. carrier(s) and/or surfactant(s).


A carrier is a solid or liquid, natural or synthetic, organic or inorganic substance that is generally inert. The carrier generally improves the application of the compounds, for instance, to plants, plants parts or seeds. Examples of suitable solid carriers include, but are not limited to, ammonium salts, in particular ammonium sulfates, ammonium phosphates and ammonium nitrates, natural rock flours, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth, silica gel and synthetic rock flours, such as finely divided silica, alumina and silicates. Examples of typically useful solid carriers for preparing granules include, but are not limited to crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, synthetic granules of inorganic and organic flours and granules of organic material such as paper, sawdust, coconut shells, maize cobs and tobacco stalks. Examples of suitable liquid carriers include, but are not limited to, water, organic solvents and combinations thereof. Examples of suitable solvents include polar and nonpolar organic chemical liquids, for example from the classes of aromatic and nonaromatic hydrocarbons (such as cyclohexane, paraffins, alkylbenzenes, xylene, toluene, tetrahydronaphthalene, alkylnaphthalenes, chlorinated aromatics or chlorinated aliphatic hydrocarbons such as chlorobenzenes, chloroethylenes or methylene chloride), alcohols and polyols (which may optionally also be substituted, etherified and/or esterified, such as ethanol, propanol, butanol, benzylalcohol, cyclohexanol or glycol), ketones (such as acetone, methyl ethyl ketone, methyl isobutyl ketone, acetophenone, or cyclohexanone), esters (including fats and oils) and (poly)ethers, unsubstituted and substituted amines, amides (such as dimethylformamide or fatty acid amides) and esters thereof, lactams (such as N-alkylpyrrolidones, in particular N-methylpyrrolidone) and lactones, sulfones and sulfoxides (such as dimethyl sulfoxide), oils of vegetable or animal origin, nitriles (alkyl nitriles such as acetonitrile, propionitrile, butyronitrile, or aromatic nitriles, such as benzonitrile), carbonic acid esters (cyclic carbonic acid esters, such as ethylene carbonate, propylene carbonate, butylene carbonate, or dialkyl carbonic acid esters, such as dimethyl carbonate, diethyl carbonate, dipropyl carbonate, dibutyl carbonate, dioctyl carbonate). The carrier may also be a liquefied gaseous extender, i.e. liquid which is gaseous at standard temperature and under standard pressure, for example aerosol propellants such as halohydrocarbons, butane, propane, nitrogen and carbon dioxide.


Preferred solid carriers are selected from clays, talc and silica.


Preferred liquid carriers are selected from water, fatty acid amides and esters thereof, aromatic and nonaromatic hydrocarbons, lactams, lactones, carbonic acid esters, ketones, (poly)ethers.


The amount of carrier typically ranges from 1 to 99.99%, preferably from 5 to 99.9%, more preferably from 10 to 99.5%, and most preferably from 20 to 99% by weight of the formulation.


Liquid carriers are typically present in a range of from 20 to 90%, for example 30 to 80% by weight of the formulation.


Solid carriers are typically present in a range of from 0 to 50%, preferably 5 to 45%, for example 10 to 30% by weight of the formulation.


If the formulation comprises two or more carriers, the outlined ranges refer to the total amount of carriers.


The surfactant can be an ionic (cationic or anionic), amphoteric or non-ionic surfactant, such as ionic or non-ionic emulsifier(s), foam former(s), dispersant(s), wetting agent(s), penetration enhancer(s) and any mixtures thereof. Examples of suitable surfactants include, but are not limited to, salts of polyacrylic acid, ethoxylated polya(alpha-substituted)acrylate derivatives, salts of lignosulfonic acid (such as sodium lignosulfonate), salts of phenolsulfonic acid or naphthalenesulfonic acid, polycondensates of ethylene oxide and/or propylene oxide with or without alcohols, fatty acids or fatty amines (for example, polyoxyethylene fatty acid esters such as castor oil ethoxylate, polyoxyethylene fatty alcohol ethers, for example alkylaryl polyglycol ethers), substituted phenols (preferably alkylphenols or arylphenols), salts of sulfosuccinic esters, taurine derivatives (preferably alkyl taurates), phosphoric esters of polyethoxylated alcohols or phenols, fatty esters of polyols (such a fatty acid esters of glycerol, sorbitol or sucrose), sulfates (such as alkyl sulfates and alkyl ether sulfates), sulfonates (for example, alkylsulfonates, arylsulfonates and alkylbenzene sulfonates), sulfonated polymers of naphthalene/formaldehyde, phosphate esters, protein hydrolysates, lignosulfite waste liquors and methylcellulose. Any reference to salts in this paragraph refers preferably to the respective alkali, alkaline earth and ammonium salts.


Preferred surfactants are selected from ethoxylated polya(alpha-substituted)acrylate derivatives, polycondensates of ethylene oxide and/or propylene oxide with alcohols, polyoxyethylene fatty acid esters, alkylbenzene sulfonates, sulfonated polymers of naphthalene/formaldehyde, polyoxyethylene fatty acid esters such as castor oil ethoxylate, sodium lignosulfonate and arylphenol ethoxylate.


The amount of surfactants typically ranges from 5 to 40%, for example 10 to 20%, by weight of the formulation.


Further examples of suitable auxiliaries include water repellents, siccatives, binders (adhesive, tackifier, fixing agent, such as carboxymethylcellulose, natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, natural phospholipids such as cephalins and lecithins and synthetic phospholipids, polyvinylpyrrolidone and tylose), thickeners and secondary thickeners (such as cellulose ethers, acrylic acid derivatives, xanthan gum, modified clays, e.g. the products available under the name Bentone, and finely divided silica), stabilizers (e.g. cold stabilizers, preservatives (e.g. dichlorophene, benzyl alcohol hemiformal, 1,2-Benzisothiazolin-3-on, 2-methyl-4-isothiazolin-3-one), antioxidants, light stabilizers, in particular UV stabilizers, or other agents which improve chemical and/or physical stability), dyes or pigments (such as inorganic pigments, e.g. iron oxide, titanium oxide and Prussian Blue; organic dyes, e.g. alizarin, azo and metal phthalocyanine dyes), antifoams (e.g. silicone antifoams and magnesium stearate), antifreezes, stickers, gibberellins and processing auxiliaries, mineral and vegetable oils, perfumes, waxes, nutrients (including trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc), protective colloids, thixotropic substances, penetrants, sequestering agents and complex formers.


The choice of the auxiliaries depends on the intended mode of application of the compound of the invention and/or on the physical properties of the compound(s). Furthermore, the auxiliaries may be chosen to impart particular properties (technical, physical and/or biological properties) to the formulations or use forms prepared therefrom. The choice of auxiliaries may allow customizing the formulations to specific needs.


The formulation comprises an insecticidal/acaricidal/nematicidal effective amount of the compound(s) of the invention. The term “effective amount” denotes an amount, which is sufficient for controlling harmful insects/mites/nematodes on cultivated plants or in the protection of materials and which does not result in a substantial damage to the treated plants. Such an amount can vary in a broad range and is dependent on various factors, such as the insect/mite/nematode species to be controlled, the treated cultivated plant or material, the climatic conditions and the specific compound of the invention used. Usually, the formulation according to the invention contains from 0.01 to 99% by weight, preferably from 0.05 to 98% by weight, more preferred from 0.1 to 95% by weight, even more preferably from 0.5 to 90% by weight, most preferably from 1 to 80% by weight of the compound of the invention. It is possible that a formulation comprises two or more compounds of the invention. In such case the outlined ranges refer to the total amount of compounds of the present invention.


The formulation of the invention may be in any customary formulation type, such as solutions (e.g aqueous solutions), emulsions, water- and oil-based suspensions, powders (e.g. wettable powders, soluble powders), dusts, pastes, granules (e.g. soluble granules, granules for broadcasting), suspoemulsion concentrates, natural or synthetic products impregnated with the compound of the invention, fertilizers and also microencapsulations in polymeric substances. The compound of the invention may be present in a suspended, emulsified or dissolved form. Examples of particular suitable formulation types are solutions, watersoluble concentrates (e.g. SL, LS), dispersible concentrates (DC), suspensions and suspension concentrates (e.g. SC, OD, OF, FS), emulsifiable concentrates (e.g. EC), emulsions (e.g. EW, EO, ES, ME, SE), capsules (e.g. CS, ZC), pastes, pastilles, wettable powders or dusts (e.g. WP, SP, WS, DP, DS), pressings (e.g. BR, TB, DT), granules (e.g. WG, SG, GR, FG, GG, MG), insecticidal articles (e.g. LN), as well as gel formulations for the treatment of plant propagation materials such as seeds (e.g. GW, GF). These and further formulations types are defined by the Food and Agriculture Organization of the United Nations (FAO). An overview is given in the “Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6th Ed. May 2008, Croplife International.


Preferably, the formulation of the invention is in form of one of the following types: EC, SC, FS, SE, OD, WG, WP, CS, more preferred EC, SC, OD, WG, CS.


Further details about examples of formulation types and their preparation are given below. If two or more compounds of the invention are present, the outlined amount of compound of the invention refers to the total amount of compounds of the present invention. This applies mutatis mutandis for any further component of the formulation, if two or more representatives of such component, e.g. wetting agent, binder, are present.


i) Water-Soluble Concentrates (SL, LS)

10-60% by weight of at least one compound of the invention and 5-15% by weight surfactant (e.g. polycondensates of ethylene oxide and/or propylene oxide with alcohols) are dissolved in such amount of water and/or water-soluble solvent (e.g. alcohols such as propylene glycol or carbonates such as propylene carbonate) to result in a total amount of 100% by weight. Before application the concentrate is diluted with water.


ii) Dispersible Concentrates (DC)

5-25% by weight of at least one compound of the invention and 1-10% by weight surfactant and/or binder (e.g. polyvinylpyrrolidone) are dissolved in such amount of organic solvent (e.g. cyclohexanone) to result in a total amount of 100% by weight. Dilution with water gives a dispersion.


iii) Emulsifiable Concentrates (EC)


15-70% by weight of at least one compound of the invention and 5-10% by weight surfactant (e.g. a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate) are dissolved in such amount of water-insoluble organic solvent (e.g. aromatic hydrocarbon or fatty acid amide) and if needed additional water-soluble solvent to result in a total amount of 100% by weight. Dilution with water gives an emulsion.


iv) Emulsions (EW, EO, ES)

5-40% by weight of at least one compound of the invention and 1-10% by weight surfactant (e.g. a mixture of calcium dodecylbenzenesulfonate and castor oil ethoxylate, or polycondensates of ethylene oxide and/or propylene oxide with or without alcohols) are dissolved in 20-40% by weight water-insoluble organic solvent (e.g. aromatic hydrocarbon). This mixture is added to such amount of water by means of an emulsifying machine to result in a total amount of 100% by weight. The resulting formulation is a homogeneous emulsion. Before application the emulsion may be further diluted with water.


v) Suspensions and Suspension Concentrates

v-1) Water-Based (SC, FS)


In a suitable grinding equipment, e.g. an agitated ball mill, 20-60% by weight of at least one compound of the invention are comminuted with addition of 2-10% by weight surfactant (e.g. sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1-2% by weight thickener (e.g. xanthan gum) and water to give a fine active substance suspension. The water is added in such amount to result in a total amount of 100% by weight. Dilution with water gives a stable suspension of the active substance. For FS type formulations up to 40% by weight binder (e.g. polyvinylalcohol) is added.


v-2) Oil-Based (OD, OF)


In a suitable grinding equipment, e.g. an agitated ball mill, 20-60% by weight of at least one compound of the invention are comminuted with addition of 2-10% by weight surfactant (e.g. sodium lignosulfonate and polyoxyethylene fatty alcohol ether), 0.1-2% by weight thickener (e.g. modified clay, in particular Bentone, or silica) and an organic carrier to give a fine active substance oil suspension. The organic carrier is added in such amount to result in a total amount of 100% by weight. Dilution with water gives a stable dispersion of the active substance.


vi) Water-Dispersible Granules and Water-Soluble Granules (WG, SG)

1-90% by weight, preferably 20-80%, most preferably 50-80% by weight of at least one compound of the invention are ground finely with addition of surfactant (e.g. sodium lignosulfonate and sodium alkylnaphthylsulfonates) and potentially carrier material and converted to water-dispersible or water-soluble granules by means of typical technical appliances like e. g. extrusion, spray drying, fluidized bed granulation. The surfactant and carrier material is used in such amount to result in a total amount of 100% by weight. Dilution with water gives a stable dispersion or solution of the active substance.


vii) Water-Dispersible Powders and Water-Soluble Powders (WP, SP, WS)


50-80% by weight of at least one compound of the invention are ground in a rotor-stator mill with addition of 1-20% by weight surfactant (e.g. sodium lignosulfonate, sodium alkylnaphthylsulfonates) and such amount of solid carrier, e.g. silica gel, to result in a total amount of 100% by weight. Dilution with water gives a stable dispersion or solution of the active substance.


viii) Gel (GW, GF)


In an agitated ball mill, 5-25% by weight of at least one compound of the invention are comminuted with addition of 3-10% by weight surfactant (e.g. sodium lignosulfonate), 1-5% by weight binder (e.g. carboxymethylcellulose) and such amount of water to result in a total amount of 100% by weight. This results in a fine suspension of the active substance. Dilution with water gives a stable suspension of the active substance.


ix) Microemulsion (ME)

5-20% by weight of at least one compound of the invention are added to 5-30% by weight organic solvent blend (e.g. fatty acid dimethylamide and cyclohexanone), 10-25% by weight surfactant blend (e.g. polyoxyethylene fatty alcohol ether and arylphenol ethoxylate), and such amount of water to result in a total amount of 100% by weight. This mixture is stirred for 1 h to produce spontaneously a thermodynamically stable microemulsion.


x) Microcapsules (CS)

An oil phase comprising 5-50% by weight of at least one compound of the invention, 0-40% by weight water-insoluble organic solvent (e.g. aromatic hydrocarbon), 2-15% by weight acrylic monomers (e.g. methylmethacrylate, methacrylic acid and a di- or triacrylate) are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol). Radical polymerization initiated by a radical initiator results in the formation of poly(meth)acrylate microcapsules. Alternatively, an oil phase comprising 5-50% by weight of at least one compound of the invention, 0-40% by weight water-insoluble organic solvent (e.g. aromatic hydrocarbon), and an isocyanate monomer (e.g. diphenylmethane-4,4′-diisocyanate) are dispersed into an aqueous solution of a protective colloid (e.g. polyvinyl alcohol), this resulting in the formation of polyurea microcapsules. Optionally, the addition of a polyamine (e.g. hexamethylenediamine) is also used to result in the formation of polyurea microcapsules. The monomers amount to 1-10% by weight of the total CS formulation.


xi) Dustable Powders (DP, DS)

1-10% by weight of at least one compound of the invention are ground finely and mixed intimately with such amount of solid carrier, e.g. finely divided kaolin, to result in a total amount of 100% by weight.


xii) Granules (GR, FG)


0.5-30% by weight of at least one compound of the invention are ground finely and associated with such amount of solid carrier (e.g. silicate) to result in a total amount of 100% by weight.


xiii) Ultra-Low Volume Liquids (UL)


1-50% by weight of at least one compound of the invention are dissolved in such amount of organic solvent, e.g. aromatic hydrocarbon, to result in a total amount of 100% by weight.


The formulations types i) to xiii) may optionally comprise further auxiliaries, such as 0.1-1% by weight preservatives, 0.1-1% by weight antifoams, 0.1-1% by weight dyes and/or pigments, and 5-10% by weight antifreezes.


Mixtures

The compounds of the formula (I) may also be employed as a mixture with one or more suitable fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbiologicals, beneficial species, herbicides, fertilizers, bird repellents, phytotonics, sterilants, safeners, semiochemicals and/or plant growth regulators, in order thus, for example, to broaden the spectrum of action, to prolong the duration of action, to increase the rate of action, to prevent repulsion or prevent evolution of resistance. In addition, such active compound combinations may improve plant growth and/or tolerance to abiotic factors, for example high or low temperatures, to drought or to elevated water content or soil salinity. It is also possible to improve flowering and fruiting performance, optimize germination capacity and root development, facilitate harvesting and improve yields, influence maturation, improve the quality and/or the nutritional value of the harvested products, prolong storage life and/or improve the processability of the harvested products.


Furthermore, the compounds of the formula (I) can be present in a mixture with other active compounds or semiochemicals such as attractants and/or bird repellants and/or plant activators and/or growth regulators and/or fertilizers. Likewise, the compounds of the formula (I) can be used to improve plant properties such as, for example, growth, yield and quality of the harvested material.


In a particular embodiment according to the invention, the compounds of the formula (I) are present in formulations or the use forms prepared from these formulations in a mixture with further compounds, preferably those as described below.


If one of the compounds mentioned below can occur in different tautomeric forms, these forms are also included even if not explicitly mentioned in each case. Further, all named mixing partners can, if their functional groups enable this, optionally form salts with suitable bases or acids.


Insecticides/Acaricides/Nematicides

The active compounds identified here by their common names are known and are described, for example, in the pesticide handbook (“The Pesticide Manual” 16th Ed., British Crop Protection Council 2012) or can be found on the Internet (e.g. http://www.alanwood.net/pesticides). The classification is based on the current IRAC Mode of Action Classification Scheme at the time of filing of this patent application.


(1) Acetylcholinesterase (AChE) inhibitors, preferably carbamates selected from 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 selected from acephate, azamethiphos, azinphos-ethyl, azinphos-methyl, cadusafos, chlorethoxyfos, chlorfenvinphos, chlormephos, chlorpyrifos-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, trichlorfon and vamidothion.


(2) GABA-gated chloride channel blockers, preferably cyclodiene-organochlorines selected from chlordane and endosulfan, or phenylpyrazoles (fiproles) selected from ethiprole and fipronil.


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


(4) Nicotinic acetylcholine receptor (nAChR) competitive modulators, preferably neonicotinoids selected from acetamiprid, clothianidin, dinotefuran, imidacloprid, nitenpyram, thiacloprid and thiamethoxam, or nicotine, or sulfoximines selected from sulfoxaflor, or butenolids selected from flupyradifurone, or mesoionics selected from triflumezopyrim.


(5) Nicotinic acetylcholine receptor (nAChR) allosteric modulators (Site I), preferably spinosyns selected from spinetoram and spinosad.


(6) Glutamate-gated chloride channel (GluCl) allosteric modulators, preferably avermectins/milbemycins selected from abamectin, emamectin benzoate, lepimectin and milbemectin.


(7) Juvenile hormone mimics, preferably juvenile hormone analogues selected from hydroprene, kinoprene and methoprene, or fenoxycarb or pyriproxyfen.


(8) Miscellaneous non-specific (multi-site) inhibitors, preferably alkyl halides selected from methyl bromide and other alkyl halides, or chloropicrine or sulphuryl fluoride or borax or tartar emetic or methyl isocyanate generators selected from diazomet and metam.


(9) Chordotonal organ TRPV channel modulators, preferably pyridine azomethanes selected from pymetrozine and pyrifluquinazone, or pyropenes selected from afidopyropen.


(10) Mite growth inhibitors affecting CHS1 selected from clofentezine, hexythiazox, diflovidazin and etoxazole.


(11) Microbial disruptors of the insect gut membranes selected from Bacillus thuringiensis subspecies israelensis, Bacillus sphaericus, Bacillus thuringiensis subspecies aizawai, Bacillus thuringiensis subspecies kurstaki, Bacillus thuringiensis subspecies tenebrionis, and B.t. plant proteins selected from Cry1Ab, Cry1Ac, Cry1Fa, Cry1A.105, Cry2Ab, Vip3A, mCry3A, Cry3Ab, Cry3Bb and Cry34Ab1/35Ab1.


(12) Inhibitors of mitochondrial ATP synthase, preferably ATP disruptors selected from diafenthiuron, or organotin compounds selected from azocyclotin, cyhexatin and fenbutatin oxide, or propargite or tetradifon.


(13) Uncouplers of oxidative phosphorylation via disruption of the proton gradient selected from chlorfenapyr, DNOC and sulfluramid.


(14) Nicotinic acetylcholine receptor channel blockers selected from bensultap, cartap hydrochloride, thiocylam and thiosultap-sodium.


(15) Inhibitors of chitin biosynthesis affecting CHS1, preferably benzoylureas selected from bistrifluron, chlorfluazuron, diflubenzuron, flucycloxuron, flufenoxuron, hexaflumuron, lufenuron, novaluron, noviflumuron, teflubenzuron and triflumuron.


(16) Inhibitors of chitin biosynthesis, type 1 selected from buprofezin.


(17) Moulting disruptor (in particular for Diptera, i.e. dipterans) selected from cyromazine.


(18) Ecdysone receptor agonists, preferably diacylhydrazines selected from chromafenozide, halofenozide, methoxyfenozide and tebufenozide.


(19) Octopamine receptor agonists selected from amitraz.


(20) Mitochondrial complex III electron transport inhibitors selected from hydramethylnone, acequinocyl, fluacrypyrim and bifenazate.


(21) Mitochondrial complex I electron transport inhibitors, preferably METI acaricides and insecticides selected from fenazaquin, fenpyroximate, pyrimidifen, pyridaben, tebufenpyrad and tolfenpyrad, or rotenone (Derris).


(22) Voltage-dependent sodium channel blockers, preferably oxadiazines selected from indoxacarb, or semicarbazones selected from metaflumizone.


(23) Inhibitors of acetyl CoA carboxylase, preferably tetronic and tetramic acid derivatives selected from spirodiclofen, spiromesifen, spiropidion and spirotetramat.


(24) Mitochondrial complex IV electron transport inhibitors, preferably phosphides selected from aluminium phosphide, calcium phosphide, phosphine and zinc phosphide, or cyanides selected from calcium cyanide, potassium cyanide and sodium cyanide.


(25) Mitochondrial complex II electron transport inhibitors, preferably beta-ketonitrile derivatives selected from cyenopyrafen and cyflumetofen, or carboxanilides selected from pyflubumide.


(28) Ryanodine receptor modulators, preferably diamides selected from chlorantraniliprole, cyantraniliprole, cyclaniliprole, flubendiamide and tetraniliprole.


(29) Chordotonal organ Modulators (with undefined target site) selected from flonicamid.


(30) GABA-gated chlorid channel allosteric modulators, preferably meta-diamides selected from broflanilide, or isoxazoles selected from fluxametamide.


(31) Baculoviruses, preferably Granuloviruses (GVs) selected from Cydia pomonella GV and Thaumatotibia leucotreta (GV), or Nucleopolyhedroviruses (NPVs) selected from Anticarsia gemmatalis MNPV, Flucypyriprole and Helicoverpa armigera NPV.


(32) Nicotinic acetylcholine receptor allosteric modulators (Site II) selected from GS-omega/kappa HXTX-Hv1a peptide.


(33) further active compounds selected from Acynonapyr, Afoxolaner, Azadirachtin, Benclothiaz, Benzoximate, Benzpyrimoxan, Bromopropylate, Chinomethionat, Chloroprallethrin, Cryolite, Cyclobutrifluram, Cycloxaprid, Cyetpyrafen, Cyhalodiamide, Cyproflanilide (CAS 2375110-88-4), Dicloromezotiaz, Dicofol, Dimpropyridaz, epsilon-Metofluthrin, epsilon-Momfluthrin, Flometoquin, Fluazaindolizine, Flucypyriprole (CAS 1771741-86-6), Fluensulfone, Flufenerim, Flufenoxystrobin, Flufiprole, Fluhexafon, Fluopyram, Flupyrimin, Fluralaner, Fufenozide, Flupentiofenox, Guadipyr, Heptafluthrin, Imidaclothiz, Iprodione, Isocycloseram, kappa-Bifenthrin, kappa-Tefluthrin, Lotilaner, Meperfluthrin, Nicofluprole (CAS 1771741-86-6), Oxazosulfyl, Paichongding, Pyridalyl, Pyrifluquinazon, Pyriminostrobin, Sarolaner, Spidoxamat, Spirobudiclofen, Tetramethylfluthrin, Tetrachlorantraniliprole, Tigolaner, Tioxazafen, Thiofluoximate, Tyclopyrazoflor, Iodomethane; furthermore preparations based on Bacillus firmus (T-1582, Votivo) and azadirachtin (BioNeem), and also the following compounds: 1-{2-fluoro-4-methyl-5-[(2,2,2-trifluoroethyl)sulphinyl]phenyl}-3-(trifluoromethyl)-1H-1,2,4-triazole-5-amine (known from WO2006/043635) (CAS 885026-50-6), 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), PF1364 (known from JP2010/018586) (CAS 1204776-60-2), (3E)-3-[1-[(6-chloro-3-pyridyl)methyl]-2-pyridylidene]-1,1,1-trifluoro-propan-2-one (known from WO2013/144213) (CAS 1461743-15-6), 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-pyridyl)pyrazole-3-carboxamide (known from CN103232431) (CAS 1449220-44-3), 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)thioxomethyl]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 WO 2011/085575 A1) (CAS 1233882-22-8), 4-[3-[2,6-dichloro-4-[(3,3-dichloro-2-propen-1-yl)oxy]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-dichloroethenyl)-2,2-dimethyl-4-(1H-benzimidazol-2-yl)phenyl-cyclopropanecarboxylic acid ester (known from CN 103524422 A) (CAS 1542271-46-4); (4aS)-7-chloro-2,5-dihydro-2-[[(methoxycarbonyl)[4-[(trifluoromethyl)thio]phenyl]amino]carbonyl]-indeno[1,2-e][1,3,4]oxadiazine-4a(3H)-carboxylic acid methyl ester (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-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS 1253850-56-4), (8-anti)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (CAS 933798-27-7), (8-syn)-8-(2-cyclopropylmethoxy-4-trifluoromethyl-phenoxy)-3-(6-trifluoromethyl-pyridazin-3-yl)-3-aza-bicyclo[3.2.1]octane (known from WO 2007040280 A1, WO 2007040282 A1) (CAS 934001-66-8), N-[4-(aminothioxomethyl)-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), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-1,8-diazaspiro[4.5]decane-2,4-dione (known from WO 2014/187846 A1) (CAS 1638765-58-8), 3-(4-chloro-2,6-dimethylphenyl)-8-methoxy-1-methyl-2-oxo-1,8-diazaspiro[4.5]dec-3-en-4-yl-carbonic acid ethyl ester (known from WO 2010/066780 A1, WO 2011151146 A1) (CAS 1229023-00-0), N-[1-(2,6-difluorophenyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO 2014/053450 A1) (CAS 1594624-87-9), N-[2-(2,6-difluorophenyl)-2H-1,2,3-triazol-4-yl]-2-(trifluoromethyl)benzamide (known from WO 2014/053450 A1) (CAS 1594637-65-6), N-[1-(3,5-difluoro-2-pyridinyl)-1H-pyrazol-3-yl]-2-(trifluoromethyl)benzamide (known from WO 2014/053450 A1) (CAS 1594626-19-3), (3R)-3-(2-chloro-5-thiazolyl)-2,3-dihydro-8-methyl-5,7-dioxo-6-phenyl-5H-thiazolo[3,2-a]pyrimidinium inner salt (known from WO 2018/177970 A1) (CAS 2246757-58-2); 3-(2-chloro-5-thiazolyl)-2,3-dihydro-8-methyl-5,7-dioxo-6-phenyl-5H-thiazolo[3,2-a]pyrimidinium inner salt (known from WO 2018/177970 A1) (CAS 2246757-56-0); N-[3-chloro-1-(3-pyridinyl)-1H-pyrazol-4-yl]-2-(methylsulfonyl)-propanamide (known from WO 2019/236274 A1) (CAS 2396747-83-2), N-[2-bromo-4-[1,2,2,2-tetrafluoro-1-(trifluoromethyl)ethyl]-6-(trifluoromethyl)phenyl]-2-fluoro-3-[(4-fluorobenzoyl)amino]-benzamide (known from WO 2019059412 A1) (CAS 1207977-87-4), 3-bromo-1-(3-chloro-2-pyridinyl)-N-[4,6-dichloro-3-fluoro-2-[(methylamino)carbonyl]phenyl]-1H-pyrazole-5-carboxamide (Fluchlorodiamide; known from CN110835330 A, CN106977494 A) (CAS: 2129147-03-9).


Nematicides

The active compounds identified here by their common names are known and are described, for example, in the pesticide handbook (“The Pesticide Manual” 16th Ed., British Crop Protection Council 2012) or can be found on the Internet (e.g. http://www.alanwood.net/pesticides). The classification is based on the current Nematicide IRAC Mode of Action Classification Groups at the time of filing of this patent application.


(Group N-1) Acetylcholinesterase (AChE) inhibitors, preferably (N-1A) carbamates selected from aldicarb, benfuracarb, carbofuran, carbosulfan and thiodicarb, or (N-1B) organophosphates selected from cadusafos, ethoprophos, fenamiphos, fosthiazate, imicyafos, phorate and terbufos.


(Group N-2) Glutamate-gated chloride channel (GluCl) allosteric modulators, preferably avermectins selected from abamectin and emamectin benzoate.


(Group N-3) Mitochondrial complex II electron transport inhibitors, especially inhibitors of succinate-coenzyme Q reductase, preferably pyridinylmethyl-benzamides selected from fluopyram.


(Group N-4) Lipid synthesis/growth regulation modulators, especially inhibitors of acetyl CoA carboxylase, preferably tetronic and tetramic acid derivatives selected from spirotetramat.


(Group N-UN) Compounds of unknown or uncertain mode of action with various chemistries, selected from fluensulfone, fluazaindolizine, furfural, iprodione and tioxazafen.


(Group N-UNX) Compounds of unknown or uncertain mode of action: Presumed multi-site inhibitors, preferably volatile sulphur generators selected from carbon disulphide and dimethyl disulphide (DMDS), or carbon disulphide liberators selected from sodium tetrathiocarbonate, or alkyl halides selected from methyl bromide and methyl iodide (iodomethane), or halogenated hydrocarbons selected from 1,2-dibromo-3-chloropropane (DBCP) and 1,3-dichloropropene, or chloropicrin, or methyl isothiocyanate generators selected from allyl isothiocyanate, diazomet, metam potassium and metam sodium.


(Group N-UNB) Bacterial agents (non-Bt) of unknown or uncertain mode of action, preferably bacterium or bacterium-derived, selected from Burkholderia spp., e.g. rinojensis A396, Bacillus spp., e.g. firmus, licheniformis, amyloliquefaciens or subtilis, Pasteuria spp., e.g. penetrans or nishizawae, Pseudomonas spp., e.g. chlororaphis or fluorescens, and Streptomyces spp., e.g. lydicus, dicklowii or albogriseolus.


(Group N-UNF) Fungal agents of unknown or uncertain mode of action, preferably fungus or fungus-derived, selected from Actinomyces spp., e.g. Streptococcus, Arthrobotrys spp., e.g. oligospora, Aspergillus spp., e.g. niger, Muscodor spp., e.g. albus, Myrothecium spp., e.g. Verrucaria, Paecilomyces spp., e.g. lilacinus (Purpureocillium lilacinum), carneus or fumosoroseus, Pochonia spp., e.g. chlamydosporia, and Trichoderma spp., e.g. harzianum, virens, atroviride or viride.


(Group N-UNE) Botanical or animal derived agents, including synthetic extracts and unrefined oils, with unknown or uncertain mode of action, preferably botanical or animal derived agents selected from azadirachtin, camellia seed cake, essential oils, garlic extract, pongamia oil, terpenes, e.g. carvacrol, and Quillaja saponaria extract.


Fungicides

The active ingredients specified herein by their Common Name are known and described, for example, in The Pesticide Manual (16th Ed. British Crop Protection Council) or can be searched in the internet (e.g. www.alanwood.net/pesticides).


All named fungicidal mixing partners of the classes (1) to (15) can, if their functional groups enable this, optionally form salts with suitable bases or acids. All named mixing partners of the classes (1) to (15) can include tautomeric forms, where applicable.


1) Inhibitors of the ergosterol biosynthesis, for example (1.001) cyproconazole, (1.002) difenoconazole, (1.003) epoxiconazole, (1.004) fenbuconazole, (1.005) fenhexamid, (1.006) fenpropidin, (1.007) fenpropimorph, (1.008) fenpyrazamine, (1.009) fluquinconazole, (1.010) flutriafol, (1.011) hexaconazole, (1.012) imazalil, (1.013) imazalil sulfate, (1.014) ipconazole, (1.015) ipfentrifluconazole, (1.016) mefentrifluconazole, (1.017) metconazole, (1.018) myclobutanil, (1.019) paclobutrazol, (1.020) penconazole, (1.021) prochloraz, (1.022) propiconazole, (1.023) prothioconazole, (1.024) pyrisoxazole, (1.025) spiroxamine, (1.026) tebuconazole, (1.027) tetraconazole, (1.028) triadimenol, (1.029) tridemorph, (1.030) triticonazole, (1.031) (1R,2S,5S)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.032) (1S,2R,5R)-5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclopentanol, (1.033) (2R)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.034) (2R)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.035) (2R)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.036) (2S)-2-(1-chlorocyclopropyl)-4-[(1R)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.037) (2S)-2-(1-chlorocyclopropyl)-4-[(1S)-2,2-dichlorocyclopropyl]-1-(1H-1,2,4-triazol-1-yl)butan-2-ol, (1.038) (2S)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl)phenyl]-1-(1H-1,2,4-triazol-1-yl)propan-2-ol, (1.039) (R)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.040) (S)-[3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.041) [3-(4-chloro-2-fluorophenyl)-5-(2,4-difluorophenyl)-1,2-oxazol-4-yl](pyridin-3-yl)methanol, (1.042) 1-({(2R,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.043) 1-({(2S,4S)-2-[2-chloro-4-(4-chlorophenoxy)phenyl]-4-methyl-1,3-dioxolan-2-yl}methyl)-1H-1,2,4-triazole, (1.044) 1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.045) 1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.046) 1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazol-5-yl thiocyanate, (1.047) 2-[(2R,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethyl-heptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.048) 2-[(2R,4R,5S)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.049) 2-[(2R,4S,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.050) 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, (1.051) 2-[(2S,4R,5R)-1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethyl-heptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.052) 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, (1.053) 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, (1.054) 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, (1.055) 2-[1-(2,4-dichlorophenyl)-5-hydroxy-2,6,6-trimethylheptan-4-yl]-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.056) 2-[6-(4-bromophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, (1.057) 2-[6-(4-chlorophenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol, (1.058) 2-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.059) 2-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.060) 2-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)-oxiran-2-yl]methyl}-2,4-dihydro-3H-1,2,4-triazole-3-thione, (1.061) 3-[2-(1-chlorocyclopropyl)-3-(3-chloro-2-fluoro-phenyl)-2-hydroxy-propyl]imidazole-4-carbonitrile, (1.062) 4-[[6-[rac-(2R)-2-(2,4-difluorophenyl)-1,1-difluoro-2-hydroxy-3-(5-thioxo-4H-1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]-benzonitrile, (1.063) 5-(4-chlorobenzyl)-2-(chloromethyl)-2-methyl-1-(1H-1,2,4-triazol-1-ylmethyl)cyclo-pentanol, (1.064) 5-(allylsulfanyl)-1-{[3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.065) 5-(allylsulfanyl)-1-{[rel(2R,3R)-3-(2-chlorophenyl)-2-(2,4-difluorophenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.066) 5-(allylsulfanyl)-1-{[rel(2R,3S)-3-(2-chlorophenyl)-2-(2,4-difluoro-phenyl)oxiran-2-yl]methyl}-1H-1,2,4-triazole, (1.067) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1H-1,2,4-triazol-1-yl)propanoate, (1.068) N′-(2-chloro-5-methyl-4-phenoxyphenyl)-N-ethyl-N-methylimidoformamide, (1.069) N′-[2-chloro-4-(2-fluorophenoxy)-5-methylphenyl]-N-ethyl-N-methy-limidoformamide, (1.070) N′-[5-bromo-6-(2,3-dihydro-1H-inden-2-yloxy)-2-methylpyridin-3-yl]-N-ethyl-N-methylimidoformamide, (1.071) N′-{4-[(4,5-dichloro-1,3-thiazol-2-yl)oxy]-2,5-dimethylphenyl}-N-ethyl-N-methylimidoformamide, (1.072) N′-{5-bromo-2-methyl-6-[(1-propoxypropan-2-yl)oxy]pyridin-3-yl}-N-ethyl-N-methylimidoformamide, (1.073) N′-{5-bromo-6-[(1R)-1-(3,5-difluorophenyl)ethoxy]-2-methyl-pyridin-3-yl}-N-ethyl-N-methylimidoformamide, (1.074) N′-{5-bromo-6-[(1S)-1-(3,5-difluorophenyl)-ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidoformamide, (1.075) N′-{5-bromo-6-[(cis-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidoformamide, 1.076) N′-{5-bromo-6-[(trans-4-isopropylcyclohexyl)oxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidoformamide, (1.077) N′-{5-bromo-6-[1-(3,5-difluorophenyl)ethoxy]-2-methylpyridin-3-yl}-N-ethyl-N-methylimidoformamide, (1.078)N-isopropyl-N′-[5-methoxy-2-methyl-4-(2,2,2-trifluoro-1-hydroxy-1-phenylethyl)phenyl]-N-methylimidoformamide. 2) Inhibitors of the respiratory chain at complex I or II, for example (2.001) benzovindiflupyr, (2.002) bixafen, (2.003) boscalid, (2.004) carboxin, (2.005) cyclobutrifluram, (2.006) flubeneteram, (2.007) fluindapyr, (2.008) fluopyram, (2.009) flutolanil, (2.010) fluxapyroxad, (2.011) furametpyr, (2.012) inpyrfluxam, (2.013) Isofetamid, (2.014) isoflucypram, (2.015) isopyrazam, (2.016) penflufen, (2.017) penthiopyrad, (2.018) pydiflumetofen, (2.019) pyrapropoyne, (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-[(3S)-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1H-pyrazole-4-carboxamide, (2.029) 3-(difluoromethyl)-N-[(3R)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.030) 3-(difluoromethyl)-N-[(3S)-7-fluoro-1,1,3-trimethyl-2,3-dihydro-1H-inden-4-yl]-1-methyl-1H-pyrazole-4-carboxamide, (2.031) 5,8-difluoro-N-[2-(2-fluoro-4-{[4-(trifluoromethyl)pyridin-2-yl]oxy}phenyl)ethyl]quinazolin-4-amine, (2.032)N-[(1R,4S)-9-(dichloro-methylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.033)N-[(1S,4R)-9-(dichloromethylene)-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.034)N-[1-(2,4-dichlorophenyl)-1-methoxypropan-2-yl]-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide, (2.035)N-[rac-(1S,2S)-2-(2,4-dichlorophenyl)cyclobutyl]-2-(trifluoromethyl)nicotinamide.


3) Inhibitors of the respiratory chain at complex III, for example (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) famoxadone, (3.010) fenamidone, (3.011) fenpicoxamid, (3.012) florylpicoxamid, (3.013) flufenoxystrobin, (3.014) fluoxastrobin, (3.015) kresoxim-methyl, (3.016) mandestrobin, (3.017) metominostrobin, (3.018) metyltetraprole, (3.019) orysastrobin, (3.020) picoxystrobin, (3.021) pyraclostrobin, (3.022) pyrametostrobin, (3.023) pyraoxystrobin, (3.024) trifloxystrobin, (3.025) (2E)-2-{2-[({[(1E)-1-(3-{[(E)-1-fluoro-2-phenylvinyl]oxy}phenyl)ethylidene]amino}oxy)methyl]phenyl}-2-(methoxyimino)-N-methylacetamide, (3.026) (2E,3Z)-5-{[1-(4-chlorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.027) (2R)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.028) (2S)-2-{2-[(2,5-dimethylphenoxy)methyl]phenyl}-2-methoxy-N-methylacetamide, (3.029)N-(3-ethyl-3,5,5-trimethylcyclohexyl)-3-formamido-2-hydroxybenzamide, (3.030) (2E,3Z)-5-{[1-(4-chloro-2-fluorophenyl)-1H-pyrazol-3-yl]oxy}-2-(methoxyimino)-N,3-dimethylpent-3-enamide, (3.031) methyl {5-[3-(2,4-dimethylphenyl)-1H-pyrazol-1-yl]-2-methylbenzyl}carbamate.


4) Inhibitors of the mitosis and cell division, for example (4.001) carbendazim, (4.002) diethofencarb, (4.003) ethaboxam, (4.004) fluopicolide, (4.005) fluopimomide, (4.006) metrafenone, (4.007) pencycuron, (4.008) pyridachlometyl, (4.009) pyriofenone (chlazafenone), (4.010) thiabendazole, (4.011) thiophanate-methyl, (4.012) zoxamide, (4.013) 3-chloro-5-(4-chlorophenyl)-4-(2,6-difluorophenyl)-6-methylpyridazine, (4.014) 3-chloro-5-(6-chloropyridin-3-yl)-6-methyl-4-(2,4,6-trifluorophenyl)pyridazine, (4.015) 4-(2-bromo-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.016) 4-(2-bromo-4-fluorophenyl)-N-(2-bromo-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.017) 4-(2-bromo-4-fluorophenyl)-N-(2-bromophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.018) 4-(2-bromo-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.019) 4-(2-bromo-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.020) 4-(2-bromo-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.021) 4-(2-chloro-4-fluorophenyl)-N-(2,6-difluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.022) 4-(2-chloro-4-fluorophenyl)-N-(2-chloro-6-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.023) 4-(2-chloro-4-fluorophenyl)-N-(2-chlorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.024) 4-(2-chloro-4-fluorophenyl)-N-(2-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.025) 4-(4-chlorophenyl)-5-(2,6-difluorophenyl)-3,6-dimethylpyridazine, (4.026)N-(2-bromo-6-fluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.027)N-(2-bromophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine, (4.028)N-(4-chloro-2,6-difluorophenyl)-4-(2-chloro-4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-5-amine.


5) Compounds capable to have a multisite action, for example (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, (5.011) dodine, (5.012) folpet, (5.013) mancozeb, (5.014) maneb, (5.015) metiram, (5.016) metiram zinc, (5.017) oxine-copper, (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]dithiino[2,3-c][1,2]thiazole-3-carbonitrile.


6) Compounds capable to induce a host defence, for example (6.001) acibenzolar-S-methyl, (6.002) fosetyl-aluminium, (6.003) fosetyl-calcium, (6.004) fosetyl-sodium, (6.005) isotianil, (6.006) phosphorous acid and its salts, (6.007) probenazole, (6.008) tiadinil.


7) Inhibitors of the amino acid and/or protein biosynthesis, for example (7.001) cyprodinil, (7.002) kasugamycin, (7.003) kasugamycin hydrochloride hydrate, (7.004) oxytetracycline, (7.005) pyrimethanil. 8) Inhibitors of the ATP production, for example (8.001) silthiofam.


9) Inhibitors of the cell wall synthesis, for example (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.


10) Inhibitors of the lipid synthesis or transport, or membrane synthesis, for example (10.001) fluoxapiprolin, (10.002) natamycin, (10.003) oxathiapiprolin, (10.004) propamocarb, (10.005) propamocarb hydrochloride, (10.006) propamocarb-fosetylate, (10.007) tolclofos-methyl, (10.008) 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, (10.009) 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, (10.010) 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, (10.011) 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, (10.012) 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, (10.013) 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, (10.014) 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, (10.015) 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, (10.016) 3-[2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-1,5-dihydro-2,4-benzodioxepin-6-yl methanesulfonate, (10.017) 9-fluoro-3-[2-(1-{[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-1,5-dihydro-2,4-benzodioxepin-6-yl methanesulfonate, (10.018) 3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-1,5-dihydro-2,4-benzodioxepin-6-yl methanesulfonate, (10.019) 3-[2-(1-{[3,5-bis(difluoromethyl)-1H-pyrazol-1-yl]acetyl}piperidin-4-yl)-1,3-thiazol-4-yl]-9-fluoro-1,5-dihydro-2,4-benzodioxepin-6-yl methanesulfonate. 11) Inhibitors of the melanin biosynthesis, for example (11.001) tolprocarb, (11.002) tricyclazole. 12) Inhibitors of the nucleic acid synthesis, for example (12.001) benalaxyl, (12.002) benalaxyl-M (kiralaxyl), (12.003) metalaxyl, (12.004) metalaxyl-M (mefenoxam). 13) Inhibitors of the signal transduction, for example (13.001) fludioxonil, (13.002) iprodione, (13.003) procymidone, (13.004) proquinazid, (13.005) quinoxyfen, (13.006) vinclozolin. 14) Compounds capable to act as an uncoupler, for example (14.001) fluazinam, (14.002) meptyldinocap. 15) Further compounds, for example (15.001) abscisic acid, (15.002) aminopyrifen, (15.003) benthiazole, (15.004) bethoxazin, (15.005) capsimycin, (15.006) carvone, (15.007) chinomethionat, (15.008) cufraneb, (15.009) cyflufenamid, (15.010) cymoxanil, (15.011) cyprosulfamide, (15.012) dipymetitrone, (15.013) flutianil, (15.014) ipflufenoquin, (15.015) methyl isothiocyanate, (15.016) mildiomycin, (15.017) nickel dimethyldithiocarbamate, (15.018) nitrothal-isopropyl, (15.019) oxyfenthiin, (15.020) pentachlorophenol and salts, (15.021) picarbutrazox, (15.022) quinofumelin, (15.023) D-tagatose, (15.024) tebufloquin, (15.025) tecloftalam, (15.026) tolnifanide, (15.027) 2-(6-benzylpyridin-2-yl)quinazoline, (15.028) 2-[6-(3-fluoro-4-methoxyphenyl)-5-methylpyridin-2-yl]quinazoline, (15.029) 2-phenylphenol and salts, (15.030) 4-amino-5-fluoropyrimidin-2-ol (tautomeric form: 4-amino-5-fluoropyrimidin-2(1H)-one), (15.031) 4-oxo-4-[(2-phenylethyl)amino]butanoic acid, (15.032) 5-amino-1,3,4-thiadiazole-2-thiol, (15.033) 5-chloro-N′-phenyl-N′-(prop-2-yn-1-yl)thiophene-2-sulfonohydrazide, (15.034) 5-fluoro-2-[(4-fluorobenzyl)oxy]-pyrimidin-4-amine, (15.035) 5-fluoro-2-[(4-methylbenzyl)oxy]pyrimidin-4-amine, (15.036) 5-fluoro-4-imino-3-methyl-1-[(4-methylphenyl)sulfonyl]-3,4-dihydropyrimidin-2(1H)-one, (15.037) but-3-yn-1-yl {6-[({[(Z)-(1-methyl-1H-tetrazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyridin-2-yl}carbamate, (15.038) ethyl (2Z)-3-amino-2-cyano-3-phenylacrylate, (15.039) phenazine-1-carboxylic acid, (15.040) propyl 3,4,5-trihydroxybenzoate, (15.041) quinolin-8-ol, (15.042) quinolin-8-ol sulfate (2:1), (15.043) 1-(4,5-dimethyl-1H-benzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.044) 1-(5-(fluoromethyl)-6-methyl-pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.045) 1-(5,6-dimethylpyridin-3-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.046) 1-(6-(difluoromethyl)-5-methoxy-pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.047) 1-(6-(difluoromethyl)-5-methyl-pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.048) 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinoline, (15.049) 2-{2-fluoro-6-[(8-fluoro-2-methylquinolin-3-yl)oxy]phenyl}propan-2-ol, (15.050) 3-(4,4,5-trifluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)quinoline, (15.051) 3-(4,4-difluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-8-fluoroquinoline, (15.052) 3-(4,4-difluoro-5,5-dimethyl-4,5-dihydrothieno[2,3-c]pyridin-7-yl)quinoline, (15.053) 3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)quinoline, (15.054) 5-bromo-1-(5,6-dimethylpyridin-3-yl)-3,3-dimethyl-3,4-dihydroisoquinoline, (15.055) 8-fluoro-3-(5-fluoro-3,3,4,4-tetramethyl-3,4-dihydroisoquinolin-1-yl)-quinoline, (15.056) 8-fluoro-3-(5-fluoro-3,3-dimethyl-3,4-dihydroisoquinolin-1-yl)-quinoline, (15.057) 8-fluoro-N-(4,4,4-trifluoro-2-methyl-1-phenylbutan-2-yl)quinoline-3-carboxamide, (15.058) 8-fluoro-N-[(2S)-4,4,4-trifluoro-2-methyl-1-phenylbutan-2-yl]quinoline-3-carboxamide, (15.059) 9-fluoro-2,2-dimethyl-5-(quinolin-3-yl)-2,3-dihydro-1,4-benzoxazepine, (15.060)N-(2,4-dimethyl-1-phenylpentan-2-yl)-8-fluoroquinoline-3-carboxamide, (15.061)N-[(2S)-2,4-dimethyl-1-phenylpentan-2-yl]-8-fluoroquinoline-3-carboxamide, (15.062) 1,1-diethyl-3-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.063) 1,3-dimethoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.064) 1-[[3-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl]methyl]azepan-2-one, (15.065) 1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin-2-one, (15.066) 1-methoxy-1-methyl-3-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.067) 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.068) 1-methoxy-3-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.069) 2,2-difluoro-N-methyl-2-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]acetamide, (15.070) 3,3-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]piperidin-2-one, (15.071) 3-ethyl-1-methoxy-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]urea, (15.072) 4,4-dimethyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one, (15.073) 4,4-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.074) 4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl dimethylcarbamate, (15.075) 5,5-dimethyl-2-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]isoxazolidin-3-one, (15.076) 5-methyl-1-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]pyrrolidin-2-one, (15.077) ethyl 1-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}-1H-pyrazole-4-carboxylate, (15.078) methyl {4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl}carbamate, (15.079)N-(1-methylcyclopropyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.080)N-(2,4-difluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.081)N-(2-fluorophenyl)-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.082) N,2-dimethoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.083) N,N-dimethyl-1-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}-1H-1,2,4-triazol-3-amine, (15.084)N—[(E)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.085)N—[(E)-N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.086)N—[(Z)-methoxyiminomethyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.087)N—[(Z)—N-methoxy-C-methyl-carbonimidoyl]-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.088)N-[[2,3-difluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]-3,3,3-trifluoro-propanamide, (15.089)N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.090)N-[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]cyclopropanecarboxamide, (15.091)N-{2,3-difluoro-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}butanamide, (15.092)N-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzyl}cyclopropanecarboxamide, (15.093)N-{4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl}propanamide, (15.094)N-allyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]acetamide, (15.095)N-allyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.096)N-ethyl-2-methyl-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]propanamide, (15.097)N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropanecarboxamide, (15.098)N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide, (15.099)N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide, (15.100)N-methyl-N-phenyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzamide.


Biological Pesticides as Mixing Components

The compounds of the formula (I) can be combined with biological pesticides.


Biological pesticides comprise in particular bacteria, fungi, yeasts, plant extracts and products formed by microorganisms, including proteins and secondary metabolites.


Biological pesticides comprise bacteria such as spore-forming bacteria, root-colonising bacteria and bacteria which act as biological insecticides, fungicides or nematicides.


Examples of such bacteria which are employed or can be used as biological pesticides are: Bacillus amyloliquefaciens, strain FZB42 (DSM 231179), or Bacillus cereus, in particular B. cereus strain CNCM 1-1562 or Bacillus firmus, strain 1-1582 (Accession number CNCM 1-1582) or Bacillus pumilus, in particular strain GB34 (Accession No. ATCC 700814) and strain QST2808 (Accession No. NRRL B-30087), or Bacillus subtilis, in particular strain GB03 (Accession No. ATCC SD-1397), or Bacillus subtilis strain QST713 (Accession No. NRRL B-21661) or Bacillus subtilis strain OST 30002 (Accession No. NRRL B-50421) Bacillus thuringiensis, in particular B. thuringiensis subspecies israelensis (serotype H-14), strain AM65-52 (Accession No. ATCC 1276), or B. thuringiensis subsp. aizawai, in particular strain ABTS-1857 (SD-1372), or B. thuringiensis subsp. kurstaki strain HD-1, or B. 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).


Examples of fungi and yeasts which are employed or can be used as biological pesticides are:



Beauveria bassiana, in particular strain ATCC 74040, Coniothyrium minitans, in particular strain CON/M/91-8 (Accession No. DSM-9660), Lecanicillium spp., in particular strain HRO LEC 12, Lecanicillium lecanii, (formerly known as Verticillium lecanii), in particular strain KV01, Metarhizium anisopliae, in particular strain F52 (DSM3884/ATCC 90448), Metschnikowia fructicola, in particular strain NRRL Y-30752, Paecilomyces fumosoroseus (now: Isaria fumosorosea), in particular strain IFPC 200613, or strain Apopka 97 (Accession No. ATCC 20874), Paecilomyces lilacinus, in particular P. lilacinus strain 251 (AGAL 89/030550), Talaromyces flavus, in particular strain V117b, Trichoderma atroviride, in particular strain SC1 (Accession Number CBS 122089), Trichoderma harzianum, in particular T. harzianum rifai T39. (Accession Number CNCM 1-952).


Examples of viruses which are employed or can be used as biological pesticides are: Adoxophyes orana (summer fruit tortrix) granulosis virus (GV), Cydia pomonella (codling moth) granulosis virus (GV), Helicoverpa armigera (cotton bollworm) nuclear polyhedrosis virus (NPV), Spodoptera exigua (beet armyworm) mNPV, Spodoptera frugiperda (fall armyworm) mNPV, Spodoptera littoralis (African cotton leafworm) NPV.


Also included are bacteria and fungi which are added as ‘inoculant’ to plants or plant parts or plant organs and which, by virtue of their particular properties, promote plant growth and plant health. Examples which may be mentioned are:



Agrobacterium spp., Azorhizobium caulinodans, Azospirillum spp., Azotobacter spp., Bradyrhizobium spp., Burkholderia spp., in particular 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., in particular Rhizobium trifolii, Rhizopogon spp., Scleroderma spp., Suillus spp., Streptomyces spp.


Examples of plant extracts and products formed by microorganisms including proteins and secondary metabolites which are employed or can be used as biological pesticides are:



Allium sativum, Artemisia absinthium, azadirachtin, Biokeeper WP, Cassia nigricans, Celastrus angulatus, Chenopodium anthelminticum, chitin, Armour-Zen, Dryopteris filix-mas, Equisetum arvense, Fortune Aza, Fungastop, Heads Up (Chenopodium quinoa saponin extract), Pyrethrum/Pyrethrins, Quassia amara, Quercus, Quillaja, Regalia, “Requiem™ Insecticide”, rotenone, ryania/ryanodine, Symphytum officinale, Tanacetum vulgare, thymol, Triact 70, TriCon, Tropaeulum majus, Urtica dioica, Veratrin, Viscum album, Brassicaceae extract, in particular oilseed rape powder or mustard powder, as well as bioinsecticidal/acaricidal active substances obtained from olive oil, in particular unsaturated fatty/carboxylic acids having carbon chain lengths C16-C20 as active ingredients, such as, for example, contained in the product with the trade name FLiPPER®.


Safener as Mixing Components

The compounds of the formula (I) can be combined with safeners such as, for example, 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}sulphonyl)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).


Plants and Plant Parts

All plants and plant parts can be treated in accordance with the invention. Here, plants are to be understood to mean all plants and plant parts such as wanted and unwanted wild plants or crop plants (including naturally occurring crop plants), for example cereals (wheat, rice, triticale, barley, rye, oats), maize, soya bean, potato, sugar beet, sugar cane, tomatoes, pepper, cucumber, melon, carrot, watermelon, onion, lettuce, spinach, leek, beans, Brassica oleracea (e.g. cabbage) and other vegetable species, cotton, tobacco, oilseed rape, and also fruit plants (with the fruits apples, pears, citrus fruits and grapevines). Crop plants can be plants which can be obtained by conventional breeding and optimization methods or by biotechnological and genetic engineering methods or combinations of these methods, including the transgenic plants and including the plant varieties which can or cannot be protected by varietal property rights. Plants should be understood to mean all developmental stages, such as seeds, seedlings, young (immature) plants up to mature plants. Plant parts should be understood to mean all parts and organs of the plants above and below ground, such as shoot, leaf, flower and root, examples given being leaves, needles, stalks, stems, flowers, fruit bodies, fruits and seeds, and also tubers, roots and rhizomes. Parts of plants also include harvested plants or harvested plant parts and vegetative and generative propagation material, for example seedlings, tubers, rhizomes, cuttings and seeds.


Treatment according to the invention of the plants and plant parts with the compounds of the formula (I) is carried out directly or by allowing the compounds to act on the surroundings, environment or storage space by the customary treatment methods, for example by immersion, spraying, evaporation, fogging, scattering, painting on, injection and, in the case of propagation material, in particular in the case of seeds, also by applying one or more coats.


As already mentioned above, it is possible to treat all plants and their parts 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 also parts thereof, are treated. In a further preferred embodiment, transgenic plants and plant cultivars obtained by genetic engineering methods, if appropriate in combination with conventional methods (genetically modified organisms), and parts thereof are treated. The term “parts” or “parts of plants” or “plant parts” has been explained above. The invention is used with particular preference to treat plants of the respective commercially customary cultivars or those that are in use. Plant cultivars are to be understood as meaning plants having new properties (“traits”) and which have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.


Transgenic Plant, Seed Treatment and Integration Events

According to the invention, the compounds of formula (I) can be advantageously used to treat transgenic plants, plant cultivars or plant parts that received genetic material which imparts advantageous and/or useful properties (traits) to these plants, plant cultivars or plant parts. Therefore, it is contemplated that the present invention may be combined with one or more recombinant traits or transgenic event(s) or a combination thereof. For the purposes of this application, a transgenic event is created by the insertion of a specific recombinant DNA molecule into a specific position (locus) within the chromosome of the plant genome. The insertion creates a novel DNA sequence referred to as an “event” and is characterized by the inserted recombinant DNA molecule and some amount of genomic DNA immediately adjacent to/flanking both ends of the inserted DNA. Such trait(s) or transgenic event(s) include, but are not limited to, pest resistance, water use efficiency, yield performance, drought tolerance, seed quality, improved nutritional quality, hybrid seed production, and herbicide tolerance, in which the trait is measured with respect to a plant lacking such trait or transgenic event. Concrete examples of such advantageous and/or useful properties (traits) are better plant growth, vigor, stress tolerance, standability, lodging resistance, nutrient uptake, plant nutrition, and/or yield, in particular improved growth, increased tolerance to high or low temperatures, increased tolerance to drought or to levels of water or soil salinity, enhanced flowering performance, easier harvesting, accelerated ripening, higher yields, higher quality and/or a higher nutritional value of the harvested products, better storage life and/or processability of the harvested products, and increased resistance or tolerance against animal and microbial pests, such as against insects, arachnids, nematodes, mites, slugs and snails.


Among DNA sequences encoding proteins which confer properties of resistance or tolerance to such animal and microbial pests, in particular insects, mention will particularly be made of the genetic material from Bacillus thuringiensis encoding the Bt proteins widely described in the literature and well known to those skilled in the art. Mention will also be made of proteins extracted from bacteria such as Photorhabdus (WO97/17432 and WO98/08932). In particular, mention will be made of the Bt Cry or VIP proteins which include the Cry1A, CryIAb, CryIAc, CryIIA, CryIIIA, CryIIIB2, Cry9c Cry2Ab, Cry3Bb and CryIF proteins or toxic fragments thereof and also hybrids or combinations thereof, especially the Cry1F protein or hybrids derived from a Cry1F protein (e.g. hybrid Cry1A-Cry1F proteins or toxic fragments thereof), the Cry1A-type proteins or toxic fragments thereof, preferably the Cry1Ac protein or hybrids derived from the Cry1Ac protein (e.g. hybrid Cry1Ab-Cry1Ac proteins) or the Cry1Ab or Bt2 protein or toxic fragments thereof, the Cry2Ae, Cry2Af or Cry2Ag proteins or toxic fragments thereof, the Cry1A.105 protein or a toxic fragment thereof, the VIP3Aa19 protein, the VIP3Aa20 protein, the VIP3A proteins produced in the COT 202 or COT 203 cotton events, the VIP3Aa protein or a toxic fragment thereof as described in Estruch et al. (1996), Proc Natl Acad Sci US A. 28; 93(11):5389-94, the Cry proteins as described in WO2001/47952, the insecticidal proteins from Xenorhabdus (as described in WO98/50427), Serratia (particularly from S. entomophila) or Photorhabdus species strains, such as Tc-proteins from Photorhabdus as described in WO98/08932. Also any variants or mutants of any one of these proteins differing in some amino acids (1-10, preferably 1-5) from any of the above named sequences, particularly the sequence of their toxic fragment, or which are fused to a transit peptide, such as a plastid transit peptide, or another protein or peptide, is included herein.


Another and particularly emphasized example of such properties is conferred tolerance to one or more herbicides, for example imidazolinones, sulphonylureas, glyphosate or phosphinothricin. Among DNA sequences encoding proteins which confer properties of tolerance to certain herbicides on the transformed plant cells and plants, mention will be particularly be made to the bar or PAT gene or the Streptomyces coelicolor gene described in WO2009/152359 which confers tolerance to glufosinate herbicides, a gene encoding a suitable EPSPS (5-Enolpyruvylshikimat-3-phosphat-synthase) which confers tolerance to herbicides having EPSPS as a target, especially herbicides such as glyphosate and its salts, a gene encoding glyphosate-n-acetyltransferase, or a gene encoding glyphosate oxidoreductase. Further suitable herbicide tolerance traits include at least one ALS (acetolactate synthase) inhibitor (e.g. WO2007/024782), a mutated Arabidopsis ALS/AHAS gene (e.g. U.S. Pat. No. 6,855,533), genes encoding 2,4-D-monooxygenases conferring tolerance to 2,4-D (2,4-dichlorophenoxyacetic acid) and genes encoding Dicamba monooxygenases conferring tolerance to dicamba (3,6-dichloro-2-methoxybenzoic acid).


Further and particularly emphasized examples of such properties are increased resistance against phytopathogenic fungi, bacteria and/or viruses owing, for example, to systemic acquired resistance (SAR), systemin, phytoalexins, elicitors and also resistance genes and correspondingly expressed proteins and toxins.


Particularly useful transgenic events in transgenic plants or plant cultivars which can be treated with preference in accordance with the invention include Event 531/PV-GHBK04 (cotton, insect control, described in WO2002/040677), Event 1143-14A (cotton, insect control, not deposited, described in WO2006/128569); Event 1143-51B (cotton, insect control, not deposited, described in WO2006/128570); Event 1445 (cotton, herbicide tolerance, not deposited, described in US-A 2002-120964 or WO2002/034946); Event 17053 (rice, herbicide tolerance, deposited as PTA-9843, described in WO2010/117737); Event 17314 (rice, herbicide tolerance, deposited as PTA-9844, described in WO2010/117735); Event 281-24-236 (cotton, insect control—herbicide tolerance, deposited as PTA-6233, described in WO2005/103266 or US-A 2005-216969); Event 3006-210-23 (cotton, insect control—herbicide tolerance, deposited as PTA-6233, described in US-A 2007-143876 or WO2005/103266); Event 3272 (corn, quality trait, deposited as PTA-9972, described in WO2006/098952 or US-A 2006-230473); Event 33391 (wheat, herbicide tolerance, deposited as PTA-2347, described in WO2002/027004), Event 40416 (corn, insect control—herbicide tolerance, deposited as ATCC PTA-11508, described in WO 11/075593); Event 43A47 (corn, insect control—herbicide tolerance, deposited as ATCC PTA-11509, described in WO2011/075595); Event 5307 (corn, insect control, deposited as ATCC PTA-9561, described in WO2010/077816); Event ASR-368 (bent grass, herbicide tolerance, deposited as ATCC PTA-4816, described in US-A 2006-162007 or WO2004/053062); Event B16 (corn, herbicide tolerance, not deposited, described in US-A 2003-126634); Event BPS-CV127-9 (soybean, herbicide tolerance, deposited as NCIMB No. 41603, described in WO2010/080829); Event BLR1 (oilseed rape, restoration of male sterility, deposited as NCIMB 41193, described in WO2005/074671), Event CE43-67B (cotton, insect control, deposited as DSM ACC2724, described in US-A 2009-217423 or WO2006/128573); Event CE44-69D (cotton, insect control, not deposited, described in US-A 2010-0024077); Event CE44-69D (cotton, insect control, not deposited, described in WO2006/128571); Event CE46-02A (cotton, insect control, not deposited, described in WO2006/128572); Event COT 102 (cotton, insect control, not deposited, described in US-A 2006-130175 or WO2004/039986); Event COT 202 (cotton, insect control, not deposited, described in US-A 2007-067868 or WO2005/054479); Event COT 203 (cotton, insect control, not deposited, described in WO2005/054480); Event DAS21606-3/1606 (soybean, herbicide tolerance, deposited as PTA-11028, described in WO2012/033794), Event DAS40278 (corn, herbicide tolerance, deposited as ATCC PTA-10244, described in WO2011/022469); Event DAS-44406-6/pDAB8264.44.06.1 (soybean, herbicide tolerance, deposited as PTA-11336, described in WO2012/075426), Event DAS-14536-7/pDAB8291.45.36.2 (soybean, herbicide tolerance, deposited as PTA-11335, described in WO2012/075429), Event DAS-59122-7 (corn, insect control—herbicide tolerance, deposited as ATCC PTA 11384, described in US-A 2006-070139); Event DAS-59132 (corn, insect control—herbicide tolerance, not deposited, described in WO2009/100188); Event DAS68416 (soybean, herbicide tolerance, deposited as ATCC PTA-10442, described in WO2011/066384 or WO2011/066360); Event DP-098140-6 (corn, herbicide tolerance, deposited as ATCC PTA-8296, described in US-A 2009-137395 or WO 08/112019); Event DP-305423-1 (soybean, quality trait, not deposited, described in US-A 2008-312082 or WO2008/054747); Event DP-32138-1 (corn, hybridization system, deposited as ATCC PTA-9158, described in US-A 2009-0210970 or WO2009/103049); Event DP-356043-5 (soybean, herbicide tolerance, deposited as ATCC PTA-8287, described in US-A 2010-0184079 or WO2008/002872); Event EE-I (brinjal, insect control, not deposited, described in WO 07/091277); Event Fil 17 (corn, herbicide tolerance, deposited as ATCC 209031, described in US-A 2006-059581 or WO 98/044140); Event FG72 (soybean, herbicide tolerance, deposited as PTA-11041, described in WO2011/063413), Event GA21 (corn, herbicide tolerance, deposited as ATCC 209033, described in US-A 2005-086719 or WO 98/044140); Event GG25 (corn, herbicide tolerance, deposited as ATCC 209032, described in US-A 2005-188434 or WO98/044140); Event GHB119 (cotton, insect control—herbicide tolerance, deposited as ATCC PTA-8398, described in WO2008/151780); Event GHB614 (cotton, herbicide tolerance, deposited as ATCC PTA-6878, described in US-A 2010-050282 or WO2007/017186); Event GJ11 (corn, herbicide tolerance, deposited as ATCC 209030, described in US-A 2005-188434 or WO98/044140); Event GM RZ13 (sugar beet, virus resistance, deposited as NCIMB-41601, described in WO2010/076212); Event H7-1 (sugar beet, herbicide tolerance, deposited as NCIMB 41158 or NCIMB 41159, described in US-A 2004-172669 or WO 2004/074492); Event JOPLIN1 (wheat, disease tolerance, not deposited, described in US-A 2008-064032); Event LL27 (soybean, herbicide tolerance, deposited as NCIMB41658, described in WO2006/108674 or US-A 2008-320616); Event LL55 (soybean, herbicide tolerance, deposited as NCIMB 41660, described in WO 2006/108675 or US-A 2008-196127); Event LLcotton25 (cotton, herbicide tolerance, deposited as ATCC PTA-3343, described in WO2003/013224 or US-A 2003-097687); Event LLRICE06 (rice, herbicide tolerance, deposited as ATCC 203353, described in U.S. Pat. No. 6,468,747 or WO2000/026345); Event LLRice62 (rice, herbicide tolerance, deposited as ATCC 203352, described in WO2000/026345), Event LLRICE601 (rice, herbicide tolerance, deposited as ATCC PTA-2600, described in US-A 2008-2289060 or WO2000/026356); Event LY038 (corn, quality trait, deposited as ATCC PTA-5623, described in US-A 2007-028322 or WO2005/061720); Event MIR162 (corn, insect control, deposited as PTA-8166, described in US-A 2009-300784 or WO2007/142840); Event MIR604 (corn, insect control, not deposited, described in US-A 2008-167456 or WO2005/103301); Event MON15985 (cotton, insect control, deposited as ATCC PTA-2516, described in US-A 2004-250317 or WO2002/100163); Event MON810 (corn, insect control, not deposited, described in US-A 2002-102582); Event MON863 (corn, insect control, deposited as ATCC PTA-2605, described in WO2004/011601 or US-A 2006-095986); Event MON87427 (corn, pollination control, deposited as ATCC PTA-7899, described in WO2011/062904); Event MON87460 (corn, stress tolerance, deposited as ATCC PTA-8910, described in WO2009/111263 or US-A 2011-0138504); Event MON87701 (soybean, insect control, deposited as ATCC PTA-8194, described in US-A 2009-130071 or WO2009/064652); Event MON87705 (soybean, quality trait—herbicide tolerance, deposited as ATCC PTA-9241, described in US-A 2010-0080887 or WO2010/037016); Event MON87708 (soybean, herbicide tolerance, deposited as ATCC PTA-9670, described in WO2011/034704); Event MON87712 (soybean, yield, deposited as PTA-10296, described in WO2012/051199), Event MON87754 (soybean, quality trait, deposited as ATCC PTA-9385, described in WO2010/024976); Event MON87769 (soybean, quality trait, deposited as ATCC PTA-8911, described in US-A 2011-0067141 or WO2009/102873); Event MON88017 (corn, insect control—herbicide tolerance, deposited as ATCC PTA-5582, described in US-A 2008-028482 or WO2005/059103); Event MON88913 (cotton, herbicide tolerance, deposited as ATCC PTA-4854, described in WO2004/072235 or US-A 2006-059590); Event MON88302 (oilseed rape, herbicide tolerance, deposited as PTA-10955, described in WO2011/153186), Event MON88701 (cotton, herbicide tolerance, deposited as PTA-11754, described in WO2012/134808), Event MON89034 (corn, insect control, deposited as ATCC PTA-7455, described in WO 07/140256 or US-A 2008-260932); Event MON89788 (soybean, herbicide tolerance, deposited as ATCC PTA-6708, described in US-A 2006-282915 or WO2006/130436); Event MS1 1 (oilseed rape, pollination control—herbicide tolerance, deposited as ATCC PTA-850 or PTA-2485, described in WO2001/031042); Event MS8 (oilseed rape, pollination control—herbicide tolerance, deposited as ATCC PTA-730, described in WO2001/041558 or US-A 2003-188347); Event NK603 (corn, herbicide tolerance, deposited as ATCC PTA-2478, described in US-A 2007-292854); Event PE-7 (rice, insect control, not deposited, described in WO2008/114282); Event RF3 (oilseed rape, pollination control—herbicide tolerance, deposited as ATCC PTA-730, described in WO2001/041558 or US-A 2003-188347); Event RT73 (oilseed rape, herbicide tolerance, not deposited, described in WO2002/036831 or US-A 2008-070260); Event SYHT0H2/SYN-000H2-5 (soybean, herbicide tolerance, deposited as PTA-11226, described in WO2012/082548), Event T227-1 (sugar beet, herbicide tolerance, not deposited, described in WO2002/44407 or US-A 2009-265817); Event T25 (corn, herbicide tolerance, not deposited, described in US-A 2001-029014 or WO2001/051654); Event T304-40 (cotton, insect control—herbicide tolerance, deposited as ATCC PTA-8171, described in US-A 2010-077501 or WO2008/122406); Event T342-142 (cotton, insect control, not deposited, described in WO2006/128568); Event TC1507 (corn, insect control—herbicide tolerance, not deposited, described in US-A 2005-039226 or WO2004/099447); Event VIP1034 (corn, insect control—herbicide tolerance, deposited as ATCC PTA-3925, described in WO2003/052073), Event 32316 (corn, insect control-herbicide tolerance, deposited as PTA-11507, described in WO2011/084632), Event 4114 (corn, insect control-herbicide tolerance, deposited as PTA-11506, described in WO2011/084621), event EE-GM3/FG72 (soybean, herbicide tolerance, ATCC Accession N° PTA-11041) optionally stacked with event EE-GM1/LL27 or event EE-GM2/LL55 (WO2011/063413A2), event DAS-68416-4 (soybean, herbicide tolerance, ATCC Accession N° PTA-10442, WO2011/066360A1), event DAS-68416-4 (soybean, herbicide tolerance, ATCC Accession N° PTA-10442, WO2011/066384A1), event DP-040416-8 (corn, insect control, ATCC Accession N° PTA-11508, WO2011/075593A1), event DP-043A47-3 (corn, insect control, ATCC Accession N° PTA-11509, WO2011/075595A1), event DP-004114-3 (corn, insect control, ATCC Accession N° PTA-11506, WO2011/084621A1), event DP-032316-8 (corn, insect control, ATCC Accession N° PTA-11507, WO2011/084632A1), event MON-88302-9 (oilseed rape, herbicide tolerance, ATCC Accession N° PTA-10955, WO2011/153186A1), event DAS-21606-3 (soybean, herbicide tolerance, ATCC Accession No. PTA-11028, WO2012/033794A2), event MON-87712-4 (soybean, quality trait, ATCC Accession N°. PTA-10296, WO2012/051199A2), event DAS-44406-6 (soybean, stacked herbicide tolerance, ATCC Accession N°. PTA-11336, WO2012/075426A1), event DAS-14536-7 (soybean, stacked herbicide tolerance, ATCC Accession N°. PTA-11335, WO2012/075429A1), event SYN-000H2-5 (soybean, herbicide tolerance, ATCC Accession N°. PTA-11226, WO2012/082548A2), event DP-061061-7 (oilseed rape, herbicide tolerance, no deposit N° available, WO2012071039A1), event DP-073496-4 (oilseed rape, herbicide tolerance, no deposit N° available, US2012131692), event 8264.44.06.1 (soybean, stacked herbicide tolerance, Accession N° PTA-11336, WO2012075426A2), event 8291.45.36.2 (soybean, stacked herbicide tolerance, Accession N°. PTA-11335, WO2012075429A2), event SYHT0H2 (soybean, ATCC Accession N°. PTA-11226, WO2012/082548A2), event MON88701 (cotton, ATCC Accession N° PTA-11754, WO2012/134808A1), event KK179-2 (alfalfa, ATCC Accession N° PTA-11833, WO2013/003558A1), event pDAB8264.42.32.1 (soybean, stacked herbicide tolerance, ATCC Accession N° PTA-11993, WO2013/010094A1), event MZDT09Y (corn, ATCC Accession N° PTA-13025, WO2013/012775A1).


Further, a list of such transgenic event(s) is provided by the United States Department of Agriculture's (USDA) Animal and Plant Health Inspection Service (APHIS) and can be found on their website on the world wide web at aphis.usda.gov. For this application, the status of such list as it is/was on the filing date of this application, is relevant.


The genes/events which impart the desired traits in question may also be present in combinations with one another in the transgenic plants. Examples of transgenic plants which may be mentioned are the important crop plants, such as cereals (wheat, rice, triticale, barley, rye, oats), maize, soya beans, potatoes, sugar beet, sugar cane, tomatoes, peas and other types of vegetable, cotton, tobacco, oilseed rape and also fruit plants (with the fruits apples, pears, citrus fruits and grapes), with particular emphasis being given to maize, soya beans, wheat, rice, potatoes, cotton, sugar cane, tobacco and oilseed rape. Traits which are particularly emphasized are the increased resistance of the plants to insects, arachnids, nematodes and slugs and snails, as well as the increased resistance of the plants to one or more herbicides.


Commercially available examples of such plants, plant parts or plant seeds that may be treated with preference in accordance with the invention include commercial products, such as plant seeds, sold or distributed under the GENUITY®, DROUGHTGARD®, SMARTSTAX®, RIB COMPLETE®, ROUNDUP READY®, VT DOUBLE PRO®, VT TRIPLE PRO®, BOLLGARD II®, ROUNDUP READY 2 YIELD®, YIELDGARD®, ROUNDUP READY® 2 XTENDTM, INTACTA RR2 PRO®, VISTIVE GOLD®, and/or XTENDFLEX™ trade names.


Crop Protection—Types of Treatment

The treatment of the plants and plant parts with the compounds of the formula (I) is carried out directly or by action on their surroundings, habitat or storage space using customary treatment methods, for example by dipping, spraying, atomizing, irrigating, evaporating, dusting, fogging, broadcasting, foaming, painting, spreading-on, injecting, watering (drenching), drip irrigating and, in the case of propagation material, in particular in the case of seed, furthermore as a powder for dry seed treatment, a solution for liquid seed treatment, a water-soluble powder for slurry treatment, by incrusting, by coating with one or more coats, etc. It is furthermore possible to apply the compounds of the formula (I) by the ultra-low volume method or to inject the application form or the compound of the formula (I) itself into the soil.


A preferred direct treatment of the plants is foliar application, i.e. the compounds of the formula (I) are applied to the foliage, where treatment frequency and the application rate should be adjusted according to the level of infestation with the pest in question.


In the case of systemically active compounds, the compounds of the formula (I) also access the plants via the root system. The plants are then treated by the action of the compounds of the formula (I) on the habitat of the plant. This may be done, for example, by drenching, or by mixing into the soil or the nutrient solution, i.e. the locus of the plant (e.g. soil or hydroponic systems) is impregnated with a liquid form of the compounds of the formula (I), or by soil application, i.e. the compounds of the formula (I) according to the invention are introduced in solid form (e.g. in the form of granules) into the locus of the plants, or by drip application (often also referred to as “chemigation”), i.e. the liquid application of the compounds of the formula (I) according to the invention from surface or sub-surface driplines over a certain period of time together with varying amounts of water at defined locations in the vicinity of the plants. In the case of paddy rice crops, this can also be done by metering the compound of the formula (I) in a solid application form (for example as granules) into a flooded paddy field.


Digital Technologies

The compounds of the invention can be used in combination with models e.g. embedded in computer programs for site specific crop management, satellite farming, precision farming or precision agriculture. Such models support the site specific management of agricultural sites with data from various sources such as soils, weather, crops (e.g. type, growth stage, plant health), weeds (e.g. type, growth stage), diseases, pests, nutrients, water, moisture, biomass, satellite data, yield etc. with the purpose to optimize profitability, sustainability and protection of the environment. In particular, such models can help to optimize agronomical decisions, control the precision of pesticide applications and record the work performed.


As an example, the compounds of the invention can be applied to a crop plant according to an appropriate dose regime if a model models the development of a pest and calculates that a threshold has been reached for which it is recommendable to apply the compound of the invention to the crop plant.


Commercially available systems which include agronomic models are e.g. FieldScripts™ from The Climate Corporation, Xarvio™ from BASF, AGLogic™ from John Deere, etc.


The compounds of the invention can also be used in combination with smart spraying equipment such as e.g. spot spraying or precision spraying equipment attached to or housed within a farm vehicle such as a tractor, robot, helicopter, airplane, unmanned aerial vehicle (UAV) such as a drone, etc. Such an equipment usually includes input sensors (such as e.g. a camera) and a processing unit configured to analyze the input data and configured to provide a decision based on the analysis of the input data to apply the compound of the invention to the crop plants (respectively the weeds) in a specific and precise manner. The use of such smart spraying equipment usually also requires positions systems (e.g. GPS receivers) to localize recorded data and to guide or to control farm vehicles; geographic information systems (GIS) to represent the information on intelligible maps, and appropriate farm vehicles to perform the required farm action such as the spraying.


In an example, pests can be detected from imagery acquired by a camera. In an example the pests can be identified and/or classified based on that imagery. Such identification and/classification can make use of image processing algorithms. Such image processing algorithms can utilize machine learning algorithms, such as trained neutral networks, decision trees and utilize artificial intelligence algorithms. In this manner, the compounds described herein can be applied only where needed.


Treatment of Seed

The control of animal pests by treating the seed of plants has been known for a long time and is the subject of continuous improvements. However, the treatment of seed entails a series of problems which cannot always be solved in a satisfactory manner. Thus, it is desirable to develop methods for protecting the seed and the germinating plant which dispense with, or at least reduce considerably, the additional application of pesticides during storage, after sowing or after emergence of the plants. It is furthermore desirable to optimize the amount of active compound employed in such a way as to provide optimum protection for the seed and the germinating plant from attack by animal pests, but without damaging the plant itself by the active compound employed. In particular, methods for the treatment of seed should also take into consideration the intrinsic insecticidal or nematicidal properties of pest-resistant or -tolerant transgenic plants in order to achieve optimum protection of the seed and also the germinating plant with a minimum of pesticides being employed.


The present invention therefore in particular also relates to a method for the protection of seed and germinating plants, from attack by pests, by treating the seed with one of the compounds of the formula (I). The method according to the invention for protecting seed and germinating plants against attack by pests furthermore comprises a method where the seed is treated simultaneously in one operation or sequentially with a compound of the formula (I) and a mixing component. It also comprises a method where the seed is treated at different times with a compound of the formula (I) and a mixing component.


The invention likewise relates to the use of the compounds of the formula (I) for the treatment of seed for protecting the seed and the resulting plant from animal pests.


Furthermore, the invention relates to seed which has been treated with a compound of the formula (I) according to the invention so as to afford protection from animal pests. The invention also relates to seed which has been treated simultaneously with a compound of the formula (I) and a mixing component. The invention furthermore relates to seed which has been treated at different times with a compound of the formula (I) and a mixing component. In the case of seed which has been treated at different points in time with a compound of the formula (I) and a mixing component, the individual substances may be present on the seed in different layers. Here, the layers comprising a compound of the formula (I) and mixing components may optionally be separated by an intermediate layer. The invention also relates to seed where a compound of the formula (I) and a mixing component have been applied as component of a coating or as a further layer or further layers in addition to a coating.


Furthermore, the invention relates to seed which, after the treatment with a compound of the formula (I), is subjected to a film-coating process to prevent dust abrasion on the seed.


One of the advantages encountered with a systemically acting compound of the formula (I) is the fact that, by treating the seed, not only the seed itself but also the plants resulting therefrom are, after emergence, protected against animal pests. In this manner, the immediate treatment of the crop at the time of sowing or shortly thereafter can be dispensed with.


It has to be considered a further advantage that by treatment of the seed with a compound of the formula (I), germination and emergence of the treated seed may be enhanced.


It is likewise to be considered advantageous that compounds of the formula (I) can be used in particular also for transgenic seed.


Furthermore, compounds of the formula (I) can be employed in combination with compositions or compounds of signalling technology, leading to better colonization by symbionts such as, for example, rhizobia, mycorrhizae and/or endophytic bacteria or fungi, and/or to optimized nitrogen fixation.


The compounds of the formula (I) are suitable for protection of seed of any plant variety which is used in agriculture, in the greenhouse, in forests or in horticulture. In particular, this takes the form of seed of cereals (for example wheat, barley, rye, millet and oats), corn, cotton, soya beans, rice, potatoes, sunflowers, coffee, tobacco, canola, oilseed rape, beets (for example sugarbeets and fodder beets), peanuts, vegetables (for example tomatoes, cucumbers, bean, cruciferous vegetables, onions and lettuce), fruit plants, lawns and ornamental plants. The treatment of the seed of cereals (such as wheat, barley, rye and oats), maize, soya beans, cotton, canola, oilseed rape, vegetables and rice is of particular importance.


As already mentioned above, the treatment of transgenic seed with a compound of the formula (I) is also of particular importance. This takes the form of seed of plants which, as a rule, comprise at least one heterologous gene which governs the expression of a polypeptide with in particular insecticidal and/or nematicidal properties. The heterologous genes in transgenic seed can originate from microorganisms such as Bacillus, Rhizobium, Pseudomonas, Serratia, Trichoderma, Clavibacter, Glomus or Gliocladium. The present invention is particularly suitable for the treatment of transgenic seed which comprises at least one heterologous gene originating from Bacillus sp. It is particularly preferably a heterologous gene derived from Bacillus thuringiensis.


In the context of the present invention, the compound of the formula (I) is applied to the seed. Preferably, the seed is treated in a state in which it is stable enough to avoid damage during treatment. In general, the seed may be treated at any point in time between harvest and sowing. The seed usually used has been separated from the plant and freed from cobs, shells, stalks, coats, hairs or the flesh of the fruits. For example, it is possible to use seed which has been harvested, cleaned and dried down to a moisture content which allows storage. Alternatively, it is also possible to use seed which, after drying, has been treated with, for example, water and then dried again, for example priming. In the case of rice seed, it is also possible to use seed which has been soaked, for example in water to a certain stage of the rice embryo (‘pigeon breast stage’), stimulating the germination and a more uniform emergence.


When treating the seed, care must generally be taken that the amount of the compound of the formula (I) applied to the seed and/or the amount of further additives is chosen in such a way that the germination of the seed is not adversely affected, or that the resulting plant is not damaged. This must be ensured particularly in the case of active compounds which can exhibit phytotoxic effects at certain application rates.


In general, the compounds of the formula (I) are applied to the seed in a suitable formulation. Suitable formulations and processes for seed treatment are known to the person skilled in the art.


The compounds of the formula (I) can be converted to the customary seed dressing formulations, such as solutions, emulsions, suspensions, powders, foams, slurries or other coating compositions for seed, and also ULV formulations.


These formulations are prepared in a known manner, by mixing the compounds of the formula (I) with customary additives such as, for example, customary extenders and also solvents or diluents, colorants, wetting agents, dispersants, emulsifiers, antifoams, preservatives, secondary thickeners, adhesives, gibberellins and also water.


Colorants which may be present in the seed-dressing formulations which can be used in accordance with the invention are all colorants which are customary for such purposes. It is possible to use either pigments, which are sparingly soluble in water, or dyes, which are soluble in water. Examples include the dyes known by the names Rhodamine B, C.I. Pigment Red 112 and C.I. Solvent Red 1.


Useful wetting agents which may be present in the seed dressing formulations usable in accordance with the invention are all substances which promote wetting and which are conventionally used for the formulation of agrochemically active compounds. Preference is given to using alkylnaphthalenesulphonates, such as diisopropyl- or diisobutylnaphthalenesulphonates.


Useful dispersants and/or emulsifiers which may be present in the seed dressing formulations usable in accordance with the invention are all nonionic, anionic and cationic dispersants conventionally used for the formulation of active agrochemical ingredients. Preference is given to using nonionic or anionic dispersants or mixtures of nonionic or anionic dispersants. Suitable nonionic dispersants include in particular ethylene oxide/propylene oxide block polymers, alkylphenol polyglycol ethers and tristyrylphenol polyglycol ethers, and the phosphated or sulphated derivatives thereof. Suitable anionic dispersants are in particular lignosulphonates, polyacrylic acid salts and arylsulphonate/formaldehyde condensates.


Antifoams which may be present in the seed dressing formulations usable in accordance with the invention are all foam-inhibiting substances conventionally used for the formulation of active agrochemical ingredients. Preference is given to using silicone antifoams and magnesium stearate.


Preservatives which may be present in the seed dressing formulations usable in accordance with the invention are all substances usable for such purposes in agrochemical compositions. Examples include dichlorophene and benzyl alcohol hemiformal.


Secondary thickeners which may be present in the seed dressing formulations usable in accordance with the invention are all substances which can be used for such purposes in agrochemical compositions. Cellulose derivatives, acrylic acid derivatives, xanthan, modified clays and finely divided silica are preferred.


Adhesives which may be present in the seed dressing formulations usable in accordance with the invention are all customary binders usable in seed dressing products. Polyvinylpyrrolidone, polyvinyl acetate, polyvinyl alcohol and tylose may be mentioned as being preferred.


Gibberellins which can be present in the seed-dressing formulations which can be used in accordance with the invention are preferably the gibberellins A1, A3 (=gibberellic acid), A4 and A7; gibberellic acid is especially preferably used. The gibberellins are known (cf. R. Wegler “Chemie der Pflanzenschutz- and Schädlingsbekämpfungsmittel”, vol. 2, Springer Verlag, 1970, pp. 401-412).


The seed dressing formulations usable in accordance with the invention can be used to treat a wide variety of different kinds of seed either directly or after prior dilution with water. For instance, the concentrates or the preparations obtainable therefrom by dilution with water can be used to dress the seed of cereals, such as wheat, barley, rye, oats, and triticale, and also the seed of maize, rice, oilseed rape, peas, beans, cotton, sunflowers, soya beans and beets, or else a wide variety of different vegetable seed. The seed dressing formulations usable in accordance with the invention, or the dilute use forms thereof, can also be used to dress seed of transgenic plants.


For treatment of seed with the seed dressing formulations usable in accordance with the invention, or the use forms prepared therefrom by adding water, all mixing units usable customarily for the seed dressing are useful. Specifically, the procedure in the seed dressing is to place the seed into a mixer, operated batch-wise or continuously, to add the particular desired amount of seed dressing formulations, either as such or after prior dilution with water, and to mix everything until the formulation is distributed homogeneously on the seed. If appropriate, this is followed by a drying operation.


The application rate of the seed dressing formulations usable in accordance with the invention can be varied within a relatively wide range. It is guided by the particular content of the compounds of the formula (I) in the formulations and by the seed. The application rates of the compound of the formula (I) are generally between 0.001 and 50 g per kilogram of seed, preferably between 0.01 and 15 g per kilogram of seed.


Animal Health

In the animal health field, i.e. in the field of veterinary medicine, the compounds of the formula (I) are active against animal parasites, in particular ectoparasites or endoparasites. The term endoparasite includes in particular helminths and protozoae, such as coccidia. Ectoparasites are typically and preferably arthropods, in particular insects or acarids.


In the field of veterinary medicine, the compounds of the formula (I) are suitable, with favourable toxicity in warm blooded animals, for controlling parasites which occur in animal breeding and animal husbandry in livestock, breeding, zoo, laboratory, experimental and domestic animals. They are active against all or specific stages of development of the parasites.


Agricultural livestock include, for example, mammals, such as, sheep, goats, horses, donkeys, camels, buffaloes, rabbits, reindeers, fallow deers, and in particular cattle and pigs; or poultry, such as turkeys, ducks, geese, and in particular chickens; or fish or crustaceans, e.g. in aquaculture; or, as the case may be, insects such as bees.


Domestic animals include, for example, mammals, such as hamsters, guinea pigs, rats, mice, chinchillas, ferrets or in particular dogs, cats; cage birds; reptiles; amphibians or aquarium fish.


According to a particular embodiment, the compounds of the formula (I) are administered to mammals.


According to another particular embodiment, the compounds of the formula (I) are administered to birds, namely cage birds or in particular poultry.


By using the compounds of the formula (I) to control animal parasites, it is intended to reduce or prevent illness, cases of deaths and performance reductions (in the case of meat, milk, wool, hides, eggs, honey and the like), so that more economical and simpler animal keeping is made possible and better animal well-being is achievable.


The term “control” or “controlling”, as used herein with regard to the animal health field, means that the compounds of the formula (I) are effective in reducing the incidence of the respective parasite in an animal infected with such parasites to innocuous levels. More specifically, “controlling”, as used herein, means that the compounds of the formula (I) are effective in killing the respective parasite, inhibiting its growth, or inhibiting its proliferation.


Exemplary arthropods include, without any limitation

    • from the order of the Anoplurida, for example, Haematopinus spp., Linognathus spp., Pediculus spp., Phtirus spp., Solenopotes spp.;
    • from the order of the Mallophagida and the suborders Amblycerina and Ischnocerina, for example Bovicola spp., Damalina spp., Felicola spp., Lepikentron spp., Menopon spp., Trichodectes spp., Trimenopon spp., Trinoton spp., Werneckiella spp.;
    • from the order of the Diptera and the suborders Nematocerina and Brachycerina, for example 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 spp., Phlebotomus spp., Rhinoestrus spp., Sarcophaga spp., Simulium spp., Stomoxys spp., Tabanus spp., Tipula spp., Wilhelmia spp., Wohlfahrtia spp. from the order of the Siphonapterida, for example Ceratophyllus spp.; Ctenocephalides spp., Pulex spp., Tunga spp., Xenopsylla spp.;
    • from the order of the Heteropterida, for example Cimex spp., Panstrongylus spp., Rhodnius spp., Triatoma spp.; as well as nuisance and hygiene pests from the order of the Blattarida.


Further, among the arthropods, the following acari may be mentioned by way of example, without any limitation:

    • from the subclass of the Acari (Acarina) and the order of the Metastigmata, for example, from the family of argasidae like Argas spp., Ornithodorus spp., Otobius spp., from the family of Ixodidae like Amblyomma spp., Dermacentor spp., Haemaphysalis spp., Hyalomma spp., Ixodes spp., Rhipicephalus (Boophilus) spp, Rhipicephalus spp. (the original genus of multi host ticks); from the order of mesostigmata like Dermanyssus spp., Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Sternostoma spp., Tropilaelaps spp., Varroa spp.; from the order of the Actinedida (Prostigmata), for example Acarapis spp., Cheyletiella spp., Demodex spp., Listrophorus spp., Myobia spp., Neotrombicula spp., Ornithocheyletia spp., Psorergates spp., Trombicula spp.; and from the order of the Acaridida (Astigmata), for example 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.


Exemplary parasitic protozoa include, without any limitation:

    • Mastigophora (Flagellata) such as:
    • Metamonada: from the order Diplomonadida, for example, Giardia spp., Spironucleus spp.
    • Parabasala: from the order Trichomonadida, for example, Histomonas spp., Pentatrichomonas spp., Tetratrichomonas spp., Trichomonas spp., Tritrichomonas spp.
    • Euglenozoa: from the order Trypanosomatida, for example, Leishmania spp., Trypanosoma spp Sarcomastigophora (Rhizopoda), such as Entamoebidae, for example, Entamoeba spp., Centramoebidae, for example, Acanthamoeba sp., Euamoebidae, e.g. Hartmanella sp.
    • Alveolata such as Apicomplexa (Sporozoa): e.g. Cryptosporidium spp.; from the order Eimeriida, for example, Besnoitia spp., Cystoisospora spp., Eimeria spp., Hammondia spp., Isospora spp., Neospora spp., Sarcocystis spp., Toxoplasma spp.; from the order Adeleida e.g. Hepatozoon spp., Klossiella spp.; from the order Haemosporida e.g. Leucocytozoon spp., Plasmodium spp.; from the order Piroplasmida e.g. Babesia spp., Ciliophora spp., Echinozoon spp., Theileria spp.; from the order Vesibuliferida e.g.
    • Balantidium spp., Buxtonella spp.
    • Microspora such as Encephalitozoon spp., Enterocytozoon spp., Globidium spp., Nosema spp., and furthermore, e.g. Myxozoa spp.
    • Helminths pathogenic for humans or animals include, for example, Acanthocephala, nematodes, pentastoma and platyhelmintha (e.g. monogenea, cestodes and Trematodes).


Exemplary helminths include, without any limitation:

    • Monogenea: e.g.: Dactylogyrus spp., Gyrodactylus spp., Microbothrium spp., Polystoma spp., Troglocephalus spp.
    • Cestodes: from the order of the Pseudophyllidea, for example: Bothridium spp., Diphyllobothrium spp., Diplogonoporus spp., Ichthyobothrium spp., Ligula spp., Schistocephalus spp., Spirometra spp. from the order of the Cyclophyllida, for example: Andyra spp., Anoplocephala spp., Avitellina spp., Bertiella spp., Cittotaenia spp., Davainea spp., Diorchis spp., Diplopylidium spp., Dipylidium spp., Echinococcus spp., Echinocotyle spp., Echinolepis spp., Hydatigera spp., Hymenolepis spp., Joyeuxiella spp., Mesocestoides spp., Moniezia spp., Paranoplocephala spp., Raillietina spp., Stilesia spp., Taenia spp., Thysaniezia spp., Thysanosoma spp.
    • Trematodes: from the class of the Digenea, for example: 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., Eurytrema spp., Fasciola spp., Fasciolides spp., Fasciolopsis spp., Fischoederius spp., Gastrothylacus spp., Gigantobilharzia spp., Gigantocotyle 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.
    • Nematodes: from the order of the Trichinellida, for example: Capillaria spp., Eucoleus spp., Paracapillaria spp., Trichinella spp., Trichomosoides spp., Trichuris spp. from the order of the Tylenchida, for example: Micronema spp., Parastrongyloides spp., Strongyloides spp. from the order of the Rhabditina, for example: Aelurostrongylus spp., Amidostomum spp., Ancylostoma spp., Angiostrongylus spp., Bronchonema spp., Bunostomum spp., Chabertia spp., Cooperia spp., Cooperioides spp., Crenosoma spp., Cyathostomum spp., Cyclococercus spp., Cyclodontostomum spp., 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 spp., Parafilaroides spp., Parelaphostrongylus spp., Pneumocaulus spp., Pneumostrongylus spp., Poteriostomum spp., Protostrongylus spp., Spicocaulus spp., Stephanurus spp., Strongylus spp., Syngamus spp., Teladorsagia spp., Trichonema spp., Trichostrongylus spp., Triodontophorus spp., Troglostrongylus spp., Uncinaria spp.
    • from the order of the Spirurida, for example: 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.
    • Acantocephala: from the order of the Oligacanthorhynchida, for example: Macracanthorhynchus spp., Prosthenorchis spp.; from the order of the Moniliformida, for example: Moniliformis spp. from the order of the Polymorphida, for example: Filicollis spp.; from the order of the Echinorhynchida, for example: Acanthocephalus spp., Echinorhynchus spp., Leptorhynchoides spp.
    • Pentastoma: from the order of the Porocephalida, for example: Linguatula spp.


In the veterinary field and in animal keeping, the administration of the compounds of the formula (I) is carried out by methods generally known in the art, such as enterally, parenterally, dermally or nasally, in the form of suitable preparations. Administration can be carried out prophylactically, methaphylactically or therapeutically.


Thus, one embodiment of the present invention refers to the compounds of the formula (I) for use as a medicament.


Another aspect refers to the compounds of the formula (I) for use as an antiendoparasitical agent.


Another particular aspect refers to the compounds of the formula (I) for use as a anthelmintic agent, more particular for use as a nematicidal agent, a platyhelminthicidal agent, an acanthocephalicidal agent, or a pentastomicidal agent.


Another particular aspect refers to the compounds of the formula (I) for use as an antiprotozoal agent.


Another aspect refers to the compounds of the formula (I) for use as an antiectoparasitical agent, in particular an arthropodicidal agent, more particular an insecticidal agent or acaricidal agent.


Further aspects of the invention are veterinary formulations, comprising an effective amount of at least one compound of the formula (I) and at least one of the following: pharmaceutically acceptable excipient (e.g. solid or liquid diluents), pharmaceutically acceptable auxiliary (e.g. surfactants), in particular a pharmaceutically acceptable excipient and/or pharmaceutically acceptable auxiliary which is normally used in veterinary formulations.


A related aspect of the invention is a method for preparing a veterinary formulation as described herein, comprising the step of mixing at least one compound of the formula (I) with pharmaceutically acceptable excipients and/or auxiliaries, in particular with pharmaceutically acceptable excipients and/or auxiliaries which are normally used in veterinary formulations.


Another particular aspect of the invention are veterinary formulations, selected from the group of ectoparasiticidal and endoparasiticidal formulations, more particular selected from the group of anthelmintic, antiprotozoal, and arthropodicidal formulations, even more particular selected from the group of nematicidal, platyhelminthicidal, acanthocephalicidal, pentastomicidal, insecticidal, and acaricidal formulations, in accordance with the mentioned aspects, as well as their methods for preparation.


Another aspect refers to a method for treatment of a parasitic infection, in particular an infection by a parasite selected from the group of ectoparasites and endoparasites mentioned herein, by applying an effective amount of a compound of the formula (I) to an animal, in particular a non-human animal, in need thereof.


Another aspect refers to a method for treatment of a parasitic infection, in particular an infection by a parasite selected from the group of ectoparasites and endoparasites mentioned herein, by applying a veterinary formulation as defined herein to an animal, in particular a non-human animal, in need thereof.


Another aspect refers to the use of the compounds of the formula (I) in the treatment of a parasitic infection, in particular an infection by a parasite selected from the group of ectoparasites and endoparasites mentioned herein, in an animal, in particular a non-human animal.


In the present context of the animal health or veterinary field, the term “treatment” includes prophylactic, methyllactic or therapeutical treatment.


In a particular embodiment, mixtures of at least one compound of the formula (I) with other active ingredients, particularly with endo- and ectoparasiticides, for the veterinary field are provided herewith.


In the field of animal health “mixture” not only means that two (or more) different active ingredients are formulated in a joint formulation and are accordingly applied together but also refers to products which comprise separate formulations for each active compound. Accordingly, if more than two active compounds are to be applied, all active compounds may be formulated in a joint formulation or all active compounds may be formulated in separate formulations; also feasible are mixed forms where some of the active compounds are formulated jointly and some of the active compounds are formulated separately. Separate formulations allow the separate or successive application of the active compounds in question.


The active compounds specified herein by their common names are known and described, for example, in the Pesticide Manual (see above) or can be searched in the internet (e.g. http://www.alanwood.net/pesticides).


Exemplary active ingredients from the group of ectoparasiticides, as mixing partners, include, without limitation insecticides and acaricides listed in detail above. Further active ingredients which may be used are listed below following the aforementioned classification which is 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) Miscellaneous non-specific (multi-site) inhibitors; (9) Modulators of Chordotonal Organs; (10) Mite growth inhibitors; (12) Inhibitors of mitochondrial ATP synthase, such as, ATP disruptors; (13) Uncouplers of oxidative phosphorylation via disruption of the proton gradient; (14) Nicotinic acetylcholine receptor channel blockers; (15) Inhibitors of chitin biosynthesis, type 0; (16) Inhibitors of chitin biosynthesis, type 1; (17) Moulting disruptor (in particular for Diptera, i.e. dipterans); (18) Ecdysone 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) Inhibitors of acetyl CoA carboxylase; (28) Ryanodine receptor modulators; (30) GABA-gated chloride channel allosteric modulators.


Active compounds with unknown or non-specific mode of action, e.g., fentrifanil, fenoxacrim, cycloprene, chlorobenzilate, chlordimeform, flubenzimine, dicyclanil, amidoflumet, quinomethionate, triarathene, clothiazoben, tetrasul, potassium oleate, petroleum, metoxadiazone, gossyplure, flutenzin, bromopropylate, cryolite;


Compounds from other classes:

    • butacarb, dimetilan, cloethocarb, phosphocarb, pirimiphos (-ethyl), parathion (-ethyl), methacrifos, isopropyl o-salicylate, trichlorfon, sulprofos, propaphos, sebufos, pyridathion, prothoate, dichlofenthion, demeton-S-methylsulphone, isazofos, cyanofenphos, dialifos, carbophenothion, autathiofos, aromfenvinfos (-methyl), azinphos (-ethyl), chlorpyrifos (-ethyl), fosmethilan, iodofenphos, dioxabenzofos, formothion, fonofos, flupyrazofos, fensulfothion, etrimfos;
    • organochlorines, e.g. camphechlor, lindane, heptachlor;
    • phenylpyrazoles, e.g. acetoprole, pyrafluprole, pyriprole, vaniliprole, sisapronil;
    • isoxazolines, e.g. afoxolaner, fluralaner, lotilaner, sarolaner;
    • pyrazolyl-arylamides, e.g. nicofluprole, tigolaner;
    • pyrethroids, e.g. (cis-, trans-), metofluthrin, profluthrin, flufenprox, flubrocythrinate, fubfenprox, fenfluthrin, protrifenbute, pyresmethrin, RU15525, terallethrin, cis-resmethrin, heptafluthrin, bioethanomethrin, biopermethrin, fenpyrithrin, cis-cypermethrin, cis-permethrin, clocythrin, cyhalothrin (lambda-), chlovaporthrin, or halogenated carbonhydrogen compounds (HCHs);
    • neonicotinoids, e.g. nithiazine;
    • dicloromezotiaz, triflumezopyrim;
    • macrocyclic lactones, e.g. nemadectin, ivermectin, latidectin, moxidectin, selamectin, eprinomectin, doramectin, emamectin benzoate, milbemycin oxime;
    • triprene, epofenonane, diofenolan;
    • biologicals, hormones or pheromones, for example natural products, e.g. thuringiensin, codlemone or neem components;
    • dinitrophenols, e.g. dinocap, dinobuton, binapacryl;
    • benzoylureas, e.g. fluazuron, penfluron;
    • amidine derivatives, e.g. chlormebuform, cymiazole, demiditraz;
    • beehive varroa acaricides, for example organic acids, e.g. formic acid, oxalic acid.


Exemplary active ingredients from the group of endoparasiticides, as mixing partners, include, without limitation, anthelmintically active compounds and antiprotozoal active compounds.


Anthelmintically active compounds, including, without limitation, the following nematicidally, trematicidally and/or cestocidally active compounds:

    • from the class of macrocyclic lactones, for example: eprinomectin, abamectin, nemadectin, moxidectin, doramectin, selamectin, lepimectin, latidectin, milbemectin, ivermectin, emamectin, milbemycin;
    • from the class of benzimidazoles and probenzimidazoles, for example: oxibendazole, mebendazole, triclabendazole, thiophanate, parbendazole, oxfendazole, netobimin, fenbendazole, febantel, thiabendazole, cyclobendazole, cambendazole, albendazole-sulphoxide, albendazole, flubendazole; from the class of depsipeptides, preferably cyclic depsipetides, in particular 24-membered cyclic depsipeptides, for example: emodepside, PF1022A;
    • from the class of tetrahydropyrimidines, for example: morantel, pyrantel, oxantel;
    • from the class of imidazothiazoles, for example: butamisole, levamisole, tetramisole;
    • from the class of aminophenylamidines, for example: amidantel, deacylated amidantel (dAMD), tribendimidine;
    • from the class of aminoacetonitriles, for example: monepantel;
    • from the class of paraherquamides, for example: paraherquamide, derquantel;
    • from the class of salicylanilides, for example: tribromsalan, bromoxanide, brotianide, clioxanide, closantel, niclosamide, oxyclozanide, rafoxanide;
    • from the class of substituted phenols, for example: nitroxynil, bithionol, disophenol, hexachlorophene, niclofolan, meniclopholan;
    • from the class of organophosphates, for example: trichlorfon, naphthalofos, dichlorvos/DDVP, crufomate, coumaphos, haloxon;
    • from the class of piperazinones/quinolines, for example: praziquantel, epsiprantel; from the class of piperazines, for example: piperazine, hydroxyzine;
    • from the class of tetracyclines, for example: tetracyclin, chlorotetracycline, doxycyclin, oxytetracyclin, rolitetracyclin;
    • from diverse other classes, for example: bunamidine, niridazole, resorantel, omphalotin, oltipraz, nitroscanate, nitroxynile, oxamniquine, mirasan, miracil, lucanthone, hycanthone, hetolin, emetine, diethylcarbamazine, dichlorophen, diamfenetide, clonazepam, bephenium, amoscanate, clorsulon.


Antiprotozoal active compounds, including, without limitation, the following active compounds:

    • from the class of triazines, for example: diclazuril, ponazuril, letrazuril, toltrazuril;
    • from the class of polylether ionophore, for example: monensin, salinomycin, maduramicin, narasin;
    • from the class of macrocyclic lactones, for example: milbemycin, erythromycin;
    • from the class of quinolones, for example: enrofloxacin, pradofloxacin;
    • from the class of quinines, for example: chloroquine;
    • from the class of pyrimidines, for example: pyrimethamine;
    • from the class of sulfonamides, for example: sulfaquinoxaline, trimethoprim, sulfaclozin;
    • from the class of thiamines, for example: amprolium;
    • from the class of lincosamides, for example: clindamycin;
    • from the class of carbanilides, for example: imidocarb;
    • from the class of nitrofuranes, for example: nifurtimox;
    • from the class of quinazolinone alkaloids, for example: halofuginon;
    • from diverse other classes, for example: oxamniquin, paromomycin;
    • from the class of vaccines or antigenes from microorganisms, for example: 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.


All named mixing partners can, if their functional groups enable this, optionally form salts with suitable bases or acids.


Vector Control

The compounds of the formula (I) can also be used in vector control. For the purpose of the present invention, a vector is an arthropod, in particular an insect or arachnid, capable of transmitting pathogens such as, for example, viruses, worms, single-cell organisms and bacteria from a reservoir (plant, animal, human, etc.) to a host. The pathogens can be transmitted either mechanically (for example trachoma by non-stinging flies) to a host, or by injection (for example malaria parasites by mosquitoes) into a host.


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

    • 1) Mosquitoes
      • Anopheles: malaria, filariasis;
      • Culex: Japanese encephalitis, other viral diseases, filariasis, transmission of other worms;
      • Aedes: yellow fever, dengue fever, other viral diseases, filariasis;
      • Simuliidae: transmission of worms, in particular Onchocerca Volvulus;
      • Psychodidae: transmission of leishmaniasis
    • 2) Lice: skin infections, epidemic typhus;
    • 3) Fleas: plague, endemic typhus, cestodes;
    • 4) Flies: sleeping sickness (trypanosomiasis); cholera, other bacterial diseases;
    • 5) Mites: acariosis, epidemic typhus, rickettsialpox, tularaemia, Saint Louis encephalitis, tick-borne encephalitis (TBE), Crimean-Congo haemorrhagic fever, borreliosis;
    • 6) Ticks: borellioses such as Borrelia burgdorferi sensu lato., Borrelia duttoni, tick-borne encephalitis, Q fever (Coxiella burnetii), babesioses (Babesia canis canis), ehrlichiosis.


Examples of vectors in the sense of the present invention are insects, for example aphids, flies, leafhoppers or thrips, which are capable of transmitting plant viruses to plants. Other vectors capable of transmitting plant viruses are spider mites, lice, beetles and nematodes.


Further examples of vectors in the sense of the present invention are insects and arachnids such as mosquitoes, in particular of the genera Aedes, Anopheles, for example A. gambiae, A. arabiensis, A. funestus, A. dirus (malaria) and Culex, psychodids such as Phlebotomus, Lutzomyia, lice, fleas, flies, mites and ticks capable of transmitting pathogens to animals and/or humans.


Vector control is also possible if the compounds of the formula (I) are resistance-breaking.


Compounds of the formula (I) are suitable for use in the prevention of diseases and/or pathogens transmitted by vectors. Thus, a further aspect of the present invention is the use of compounds of the formula (I) for vector control, for example in agriculture, in horticulture, in gardens and in leisure facilities, and also in the protection of materials and stored products.


Protection of Industrial Materials

The compounds of the formula (I) are suitable for protecting industrial materials against attack or destruction by insects, for example from the orders Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psocoptera and Zygentoma.


Industrial materials in the present context are understood to mean inanimate materials, such as preferably plastics, adhesives, sizes, papers and cards, leather, wood, processed wood products and coating compositions. The use of the invention for protecting wood is particularly preferred.


In a further embodiment, the compounds of the formula (I) are used together with at least one further insecticide and/or at least one fungicide.


In a further embodiment, the compounds of the formula (I) are present as a ready-to-use pesticide, i.e. they can be applied to the material in question without further modifications. Suitable further insecticides or fungicides are in particular those mentioned above.


Surprisingly, it has also been found that the compounds of the formula (I) can be employed for protecting objects which come into contact with saltwater or brackish water, in particular hulls, screens, nets, buildings, moorings and signalling systems, against fouling. Likewise, the compounds of the formula (I), alone or in combinations with other active compounds, can be used as antifouling agents.


Control of Animal Pests in the Hygiene Sector

The compounds of the formula (I) are suitable for controlling animal pests in the hygiene sector. In particular, the invention can be applied in the domestic sector, in the hygiene sector and in the protection of stored products, especially for controlling insects, arachnids, ticks and mites encountered in enclosed spaces such as dwellings, factory halls, offices, vehicle cabins, animal husbandries. For controlling animal pests, the compounds of the formula (I) are used alone or in combination with other active compounds and/or auxiliaries. They are preferably used in domestic insecticide products. The compounds of the formula (I) are effective against sensitive and resistant species, and against all developmental stages.


These pests include, for example, pests from the class Arachnida, from the orders Scorpiones, Araneae and Opiliones, from the classes Chilopoda and Diplopoda, from the class Insecta the order Blattodea, from the orders Coleoptera, Dermaptera, Diptera, Heteroptera, Hymenoptera, Isoptera, Lepidoptera, Phthiraptera, Psocoptera, Saltatoria or Orthoptera, Siphonaptera and Zygentoma and from the class Malacostraca the order Isopoda.


They are used, for example, in aerosols, pressure-free spray products, for example pump and atomizer sprays, automatic fogging systems, foggers, foams, gels, evaporator products with evaporator tablets made of cellulose or plastic, liquid evaporators, gel and membrane evaporators, propeller-driven evaporators, energy-free, or passive, evaporation systems, moth papers, moth bags and moth gels, as granules or dusts, in baits for spreading or in bait stations.


ABBREVIATIONS AND SYMBOLS





    • AcOH acetic acid

    • aq. aqueous

    • BINAP 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl

    • br. broad

    • Cs2CO3 cesium carbonate

    • d doublet

    • dppf 1,1′-Bis(diphenylphosphino)ferrocene

    • DCC N,N′-dicyclohexylcarbodiimide

    • DCM dichloromethane

    • DIPEA diisopropylethylamine

    • DIAD diisopropylazodicarboxylate

    • DMA N,N-dimethylacetamide

    • DMF N,N-dimethylformamide

    • DMSO dimethylsulfoxide

    • ee enantiomeric excess

    • eq. equivalent

    • ES electrospray ionization

    • EtOAc ethyl acetate

    • HATU 1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxid hexafluorophosphate

    • H2O water

    • HOBt 1-hydroxybenzotriazole hydrate

    • HPLC high performance liquid chromatography

    • iPrOH isopropanol

    • J coupling constant

    • LCMS liquid chromatography-mass spectrometry

    • m/z mass-to-charge ratio

    • M molarity

    • m multiplet

    • MeCN acetonitrile

    • MeOH methanol

    • MTBE tert-butyl methyl ether

    • NasSO4 sodium sulfate

    • NH4Cl ammonium chloride

    • NMR nuclear magnetic resonance

    • q quartet

    • r. t. room temperature

    • Rt retention time

    • s singlet

    • sat. saturated

    • SnCl2 tin(II) chloride

    • T temperature

    • TMP 2,2,6,6-tetramethylpiperidine

    • t triplet

    • T3P® propylphosphonic anhydride

    • THF tetrahydrofuran

    • wt. weight

    • XantPHOS 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (CAS RN 161265-03-8)

    • δ chemical shift

    • λ wavelength










DESCRIPTION OF THE PROCESSES AND INTERMEDIATES

Compounds of formula (I) may be prepared as illustrated in the following scheme 1 where X is O, R1 is H and A1, A2, A3, A4, R2, R3, R4, R5 are as previously defined, PG is an amino protection group, Hal is fluorine, chlorine, bromine or iodine and Q1, Q2 are hydroxy or chlorine.




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As indicated in Scheme 1 the introduction of the heterocyclic amine group can be carried out by an aromatic nucleophilic substitution of an halogen in nitro-azines (1) by heterocyclic amines (2) in different solvents like acetonitrile, DMF, dioxane or THF in the presence of a base like Cs2CO3 or Pyridine. Alternatively, the heterocyclic amine can be introduced by Buchwald reaction conditions using different palladium catalysts and suitable ligands, e.g. described in US2010/29638 A1 or WO2012/41476 A1. In a subsequent reaction, the reduction of the nitro group can be achieved by different reduction methods using likewise hydrogen/Pd-C, SnCl2 dihydrate or iron/NH4Cl, following methods known in the art. The obtained amine derivatives (4) react further with Boc-protected amino acids or the respective acid chlorides (5 Q1=OH or Cl) to provide the corresponding amides (6) using conventional couplings reagents, like HATU/DIPEA or alternatively, converting first the amino acid (5 Q1=OH) into the corresponding reactive mixed acid anhydride, e.g. with chloroformate and N-methyl morpholine. Intermediates (6) are cyclized under acidic conditions and high temperature, e.g. boiling in acetic acid, to provide annulated imidazole intermediates (7). In case of enantiopure amino acids as starting material, a partially racemization might occur during the cyclization. The Boc protection group can be removed under acidic conditions, e.g. HCl in dioxane or trifluoro acetic acid, to obtain annulated imidazolyl alkylamines or the respective salts (8). Finally, intermediates (8) react further with substituted benzoic acids or with the corresponding acid chlorides to provide final products IA.


Q2=OH: An imidazole compound of formula (8) is reacted with a carboxylic acid of formula (9) (Q2=OH) to form compounds of formula IA. For example, a mixture of an imidazole of formula (8), a carboxylic acid of formula (9) (Q2=OH), a suitable coupling reagent, such as T3P©, HATU or DCC/HOBt, a suitable base such as triethylamine or DIPEA, in a suitable solvent, such as ethyl acetate or DMF are mixed at temperatures ranging from around 0 to 100° C. to provide compounds of formula IA which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.


Q2=Cl: An imidazole compound of formula (8) is reacted with a carboxylic acid chloride of formula (9) (Q2=Cl) to form compounds of formula IA. For example, a mixture of an imidazole of formula (8), a carboxylic acid chloride of formula (9) (Q2=Cl), a suitable base such as triethylamine or DIPEA, in a suitable solvent, such as dichloromethane or THF are mixed at temperatures ranging from around 0 to 100° C. to provide compounds of formula IA which may then be isolated and, if necessary and desired, purified using techniques well known in the art, such as chromatography.


Thioamides of formula (I) (in which X═S) can be obtained by treatment of compounds of formula (IA) with Lawesson's reagent in boiling toluene as described for example in WO 2005009435.


Carboxylic acids of formula (9) (Q2=OH) and carboxylic acid chlorides of formula (9) (Q2=Cl) are commercially available or may be synthesized by methods known to a person skilled in the state of the art.


More specifically, the synthesis of the amine intermediate INT-1 is described in scheme 1a.


As indicated in Scheme 1a, starting material (1a) reacts with 6-aminopyridine-3-carbonitrile in DMA at 80° C. in the presence of Cs2CO3 as a base. The nitro group is reduced in the next step with SnCl2 dihydrate. The formation of amide succeeds from a min (4a) and (S)-Boc-Ala using HATU as a coupling reagent and DIPEA as base. The obtained amide (6a) is cyclized under acidic conditions to provide Boc-protected amine intermediate (7a), subsequently deprotected with HCl 4N in dioxane at room temperature to obtain amine hydrochloride (INT-1) which is further derivatized. In case of partially racemization, chiral separation methods known in the art are applied to isolate the pure (S)-enantiomer of 6a,7a or INT-1.




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Compounds of formula (I) may be prepared as illustrated in the following scheme 2 where X is O, R1 is H and A1, A2, A3, A4, R2, R3, R4, R5 are as previously defined, PG is an amino protection group, Hal is fluorine, chlorine, bromine or iodine and Q1, Q2 are hydroxy or chlorine.




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As indicated in Scheme 2 the introduction of the heterocyclic amine group can be carried out by an aromatic nucleophilic substitution of a halogen in heterocyclic halides (11) by amino-nitro-azines (10) in different solvents like acetonitrile, DMF, dioxane or THF in the presence of a base like Cs2CO3 or pyridine. Alternatively, the heterocyclic amine can be introduced by Buchwald reaction conditions using different palladium catalysts and suitable ligands, e.g. described in US2010/29638 A1 or WO2012/41476 A1. The subsequent transformations to compounds of formula (IA) can be performed as already described in scheme 1.


Optionally, further derivatisations might be possible, e.g. methyl- or ethylester functions in R4 can be converted into amides —CONR41R42 by methods known to the skilled artisan, where R41 and R42 are as previously defined.


Preparation Examples
Intermediates
6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride (INT-1)
Step 1: Synthesis of 6-[(3-nitropyridin-2-yl)amino]nicotinonitrile



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To a stirred solution of 6-aminopyridine-3-carbonitrile (7.11 g, 59.67 mmol) and Cs2CO3 (35.35 g, 108.49 mmol) in 150 ml DMA was added a solution of 2-chloro-3-nitropyridine (8.60 g, 54.24 mmol) in 80 ml DMA dropwise and the reaction mixture was stirred at 80° C. overnight. The mixture was allowed to cool down to room temperature. The reaction was quenched with ice water at room temperature. The resulting mixture was extracted with EtOAc several times. The combined organic layers were washed with H2O and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/EtOAc (2:1) to afford the desired product (5.60 g, 35.7%).



1H-NMR (400.2 MHz, d6-DMSO, peak list): δ=10.6624 (9.4); 8.7054 (7.9); 8.7011 (16.0); 8.6938 (15.8); 8.6896 (8.9); 8.6107 (7.8); 8.6065 (7.6); 8.5900 (8.3); 8.5858 (7.6); 8.5785 (0.5); 8.5558 (0.3); 8.2566 (6.1); 8.2509 (5.9); 8.2430 (0.4); 8.2346 (9.9); 8.2289 (9.8); 8.1653 (12.2); 8.1447 (6.8); 8.1432 (7.5); 7.3306 (8.8); 7.3190 (8.5); 7.3099 (8.4); 7.2983 (8.4); 5.7578 (0.7); 4.0562 (1.1); 4.0384 (3.2); 4.0206 (3.3); 4.0028 (1.1); 3.3300 (57.6); 2.6775 (0.4); 2.6729 (0.6); 2.6684 (0.4); 2.5265 (1.4); 2.5218 (2.0); 2.5130 (28.0); 2.5085 (59.2); 2.5040 (79.6); 2.4995 (56.6); 2.4950 (26.3); 2.3354 (0.4); 2.3308 (0.5); 2.3263 (0.4); 1.9900 (14.4); 1.3971 (3.5); 1.1935 (3.8); 1.1757 (7.7); 1.1579 (3.7); −0.0002 (4.5)


ESI mass [m/z]: 241.9 [M+H]+


Step 2: 6-[(3-aminopyridin-2-yl)amino]nicotinonitrile



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To a stirred solution of 6-[(3-nitropyridin-2-yl)amino]nicotinonitrile (1.25 g, 5.19 mmol) in 20 ml ethyl acetate was added tin chloride dihydrate (5.86 g, 25.90 mmol) and the reaction mixture was stirred at 70° C. for 1 h. When the mixture was cooled down to room temperature the reaction was quenched with water and basified to pH 9-10 with an aqueous solution of sodium carbonate. The mixture was extracted several times with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4. After filtration the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (1.0 g, 72.7% purity, yield: 66%).



1H-NMR (400.2 MHz, d6-DMSO, peak list): δ=9.2833 (0.4); 9.2385 (11.2); 9.0450 (0.6); 8.6368 (0.3); 8.6270 (1.1); 8.6221 (1.2); 8.6090 (0.7); 8.6016 (8.4); 8.5999 (9.5); 8.5960 (9.7); 8.5941 (9.4); 8.5820 (0.3); 8.5689 (0.4); 8.3828 (0.7); 8.1775 (0.5); 8.1430 (0.7); 8.1367 (0.8); 8.1333 (0.6); 8.1252 (0.4); 8.0504 (0.4); 8.0447 (0.5); 8.0280 (0.7); 8.0223 (0.8); 8.0149 (0.3); 7.9948 (7.2); 7.9889 (7.2); 7.9724 (9.3); 7.9665 (9.5); 7.9304 (0.7); 7.9081 (0.6); 7.8491 (12.1); 7.8268 (8.7); 7.6360 (7.7); 7.6323 (8.5); 7.6244 (7.9); 7.6206 (8.4); 7.4959 (0.3); 7.4761 (0.4); 7.2761 (0.6); 7.2722 (0.6); 7.2637 (0.6); 7.2598 (0.6); 7.2342 (0.4); 7.2128 (0.4); 7.0990 (0.4); 7.0762 (7.6); 7.0723 (8.4); 7.0567 (9.6); 7.0528 (9.9); 6.9059 (8.3); 6.8942 (7.9); 6.8864 (6.8); 6.8747 (6.4); 6.6969 (0.5); 6.6930 (0.5); 6.6783 (0.6); 6.6744 (0.6); 6.3806 (0.6); 6.3682 (0.6); 6.3621 (0.6); 6.3496 (0.5); 5.3611 (1.1); 5.3242 (16.0); 5.2441 (0.6); 4.6521 (0.4); 4.0575 (0.6); 4.0397 (1.7); 4.0219 (1.7); 4.0042 (0.6); 3.3470 (14.4); 2.5301 (0.4); 2.5255 (0.6); 2.5165 (7.0); 2.5122 (15.4); 2.5077 (21.3); 2.5033 (15.9); 1.9920 (7.4); 1.3021 (0.4); 1.2595 (0.6); 1.2280 (1.2); 1.1942 (2.5); 1.1764 (4.4); 1.1586 (2.2); −0.0002 (5.4)


ESI mass [m/z]: 212.2 [M+H]+


Step 3: tert-butyl [(2S)-1-({2-[(5-cyanopyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate



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A mixture of (2S)-2-[(tert-butoxycarbonyl)amino]propanoic acid (806.20 mg, 4.26 mmol), N,N-diisopropylethylamine (2.17 ml, 12.78 mmol), HATU (1.94 g, 5.11 mmol) in 3 ml DMF was stirred at room temperature for 10 minutes and then 6-[(3-aminopyridin-2-yl)amino]nicotinonitrile (900.0 mg, 4.26 mmol) was added and the reaction was stirred at room temperature overnight. The mixture was purified directly by preparative HPLC to yield the desired product (1.15 g, 65%).



1H-NMR (400.2 MHz, d6-DMSO, peak list): δ=9.8273 (1.1); 9.4949 (0.8); 8.6284 (2.1); 8.6263 (2.1); 8.1999 (1.2); 8.1886 (1.3); 8.0893 (0.9); 8.0676 (1.1); 7.9605 (1.1); 7.9408 (1.2); 7.8617 (0.8); 7.8398 (0.7); 7.2510 (0.7); 7.2371 (0.7); 7.1922 (0.7); 7.1797 (0.8); 7.1746 (0.8); 7.1610 (0.6); 5.7590 (2.2); 4.1516 (0.5); 4.1352 (0.7); 4.1183 (0.5); 3.6981 (0.6); 2.5057 (34.9); 2.5027 (35.1); 1.3945 (0.9); 1.3699 (16.0); 1.3281 (0.7); 1.2840 (3.8); 1.2664 (3.7); 0.0024 (5.8); −0.0002 (6.5)


ESI mass [m/z]: 383.5 [M+H]+


Step 4: tert-butyl {(1S)-1-[3-(5-cyanopyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate



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To a stirred mixture of tert-butyl [(2S)-1-({2-[(5-cyanopyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate (10.00 g, 26.11 mmol) in dioxane (150.00 mL) was added AcOH (40.00 mL) and the mixture was stirred for 4 days at 100° C. The mixture was basified to pH 8 with saturated NaHCO3 (aq.). The resulting mixture was extracted with EtOAc several times, the combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with petroleum ether/EtOAc (3:1), then purified by prep-HPLC to afford a mixture of both enantiomers. This partially racemate was purified by prep-SFC to afford tert-butyl {(1S)-1-[3-(5-cyanopyridin-2-yl)-3H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate (1.59 g, 4.37 mmol, 16.71%).


ESI mass [m/z]: 365.2 [M+H]+


Step 5: 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile Hydrochloride (INT-1)



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tert-Butyl N-[(1S)-1-[3-(5-cyano-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]carbamate (200 mg, 0.54 mmol) was dissolved in 4 mL dioxane and 4 M HCl in dioxane (1.37 mL) was added. The reaction mixture was stirred at room temperature over night. The solvent was evaporated and the remaining residue was used as such in the next step.


ESI mass [m/z]: 265.2 [amine+H]+


Methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate Hydrochloride (INT-5)
Step 1: methyl 6-[(3-nitropyridin-2-yl)amino]nicotinate



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To a solution of 5.1 g (33.3 mmol) methyl 6-aminonicotinate and 20.5 g (62.8 mmol) cesium carbonate in 80 ml acetonitrile were added 4.1 g (26.1 mmol) of 2-chloro-3-nitropyridine dropwise and the mixture was stirred at 80° C. overnight. After cooling to room temperature, the mixture was treated with ice water and extracted with ethyl acetate several times. The combined organic layers were washed with water, dried over anhydrous Na2SO4 and after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/ethyl acetate to afford 780 mg (10.2%) of the title compound.



1H-NMR (400.2 MHz, CD3CN, peaklist): δ=10.5963 (0.8); 8.8964 (2.0); 8.8913 (2.1); 8.6382 (1.7); 8.6297 (3.8); 8.6074 (3.2); 8.3169 (1.4); 8.3113 (1.4); 8.2948 (1.2); 8.2892 (1.2); 7.1545 (1.4); 7.1430 (1.4); 7.1338 (1.4); 7.1222 (1.4); 3.8870 (16.0); 2.1768 (32.9); 2.1643 (0.5); 1.9547 (2.2); 1.9487 (4.3); 1.9426 (6.2); 1.9365 (4.3); 1.9304 (2.2); −0.0002 (2.8)


ESI mass [m/z]: 275.3 [M+H]+


Step 2: methyl 6-[(3-aminopyridin-2-yl)amino]nicotinate



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728.0 mg (2.66 mmol) methyl 6-[(3-nitropyridin-2-yl)amino]nicotinate were solved in 13 ml ethyl acetate and then 3.0 g (13.3 mmol) tinn chloride dihydrate were added and the reaction mixture was stirred 1.5 h at 70° C. After cooling to room temperature, the mixture was diluted with ethyl acetate and basified to pH 9-10 with sat. Na2CO3 (aq.). The aqueous phase was extracted with ethyl acetate several times and the combined organic layers were washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (645 mg, 94% yield).



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=9.0965 (3.0); 8.7376 (2.6); 8.7332 (2.4); 8.7318 (2.7); 8.1034 (1.4); 8.0976 (1.4); 8.0810 (1.8); 8.0752 (1.8); 7.9141 (3.0); 7.8918 (2.4); 7.6317 (1.9); 7.6294 (1.8); 7.6200 (1.9); 7.6176 (1.8); 7.0557 (1.7); 7.0534 (1.7); 7.0363 (2.1); 7.0339 (2.0); 6.8727 (1.7); 6.8609 (1.7); 6.8533 (1.4); 6.8416 (1.4); 5.3151 (4.0); 4.0378 (0.4); 4.0201 (0.4); 3.8258 (16.0); 3.3346 (10.2); 2.5039 (14.4); 2.5003 (11.0); 1.9899 (1.7); 1.1933 (0.4); 1.1920 (0.5); 1.1754 (0.9); 1.1742 (0.9); 1.1577 (0.4); 1.1564 (0.4); −0.0002 (5.8); −0.0015 (5.7)


ESI mass [m/z]: 245.1[M+H]+


Step 3: methyl 6-[(3-{[N-(tert-butoxycarbonyl)alanyl]amino}pyridin-2-yl)amino]nicotinate



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To a solution of 0.33 g (1.74 mmol)N-(tert-butoxycarbonyl)alanine in 17 ml dichloromethane were added 0.92 mL (5.23 mmol) N,N-diisopropylethylamine (DIPEA, Hünig's Base) and 0.80 g (2.1 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 10 min at room temperature. Then 0.64 g (2.62 mmol) methyl 6-[(3-aminopyridin-2-yl)amino]nicotinate were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was diluted with dichloromethane, washed with a 5% sodium dihydrogen phosphate (aq.), and extracted with dichloromethane several times. The combined organic layers were washed with saturated NaHCO3 (aq.) and brine, dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 497 mg (62.0%) of the title compound.



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=8.7905 (1.4); 8.7856 (1.4); 8.1732 (1.0); 8.1686 (1.1); 8.1515 (0.9); 8.1465 (0.9); 8.0346 (0.6); 7.8287 (0.5); 7.0894 (0.4); 7.0726 (0.5); 7.0608 (0.4); 5.8359 (0.3); 4.1648 (0.5); 4.1481 (0.7); 4.1308 (0.5); 4.0679 (0.9); 4.0501 (0.9); 3.8569 (15.4); 2.1828 (2.7); 1.9728 (4.0); 1.9657 (0.4); 1.9538 (4.1); 1.9476 (7.9); 1.9415 (11.4); 1.9353 (7.8); 1.9292 (4.0); 1.4053 (16.0); 1.3747 (5.8); 1.3567 (5.6); 1.2215 (1.0); 1.2038 (2.0); 1.1859 (1.0); −0.0002 (2.4)


ESI mass [m/z]: 416.3 [M+H]+


Step 5: methyl 6-(2-{1-[(tert-butoxycarbonyl)amino]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate



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To a solution of 490.0 mg (1.18 mmol) methyl 6-[(3-{[N-(tert-butoxycarbonyl)alanyl]amino}pyridin-2-yl)amino]nicotinate in 8 ml dioxane was added 0.7 ml (11.8 mmol) acetic acid and the reaction mixture was stirred at 100° C. overnight. After cooling to room temperature, the mixture was diluted with ethyl acetate, washed with water, basified to pH 8 with saturated NaHCO3 (aq.). The organic phase was washed with brine, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (450 mg, 93% yield).



1H-NMR (400.2 MHz, CD3CN, peaklist): δ=9.1696 (1.2); 9.1645 (1.2); 8.5775 (1.0); 8.5718 (1.0); 8.5565 (1.1); 8.5507 (1.1); 8.3537 (0.9); 8.3503 (1.0); 8.3417 (1.0); 8.3383 (1.0); 8.0907 (1.2); 8.0871 (1.2); 8.0803 (0.6); 8.0706 (1.3); 8.0671 (1.2); 8.0597 (0.5); 7.3741 (1.0); 7.3620 (1.0); 7.3541 (0.9); 7.3421 (0.9); 4.0677 (0.4); 4.0499 (0.4); 3.9547 (11.7); 3.8410 (0.8); 3.6005 (16.0); 2.1979 (1.1); 2.1832 (75.4); 1.9725 (1.7); 1.9658 (0.4); 1.9538 (6.8); 1.9476 (13.1); 1.9414 (18.6); 1.9352 (12.5); 1.9291 (6.3); 1.5206 (1.4); 1.5038 (1.3); 1.2917 (5.9); 1.2216 (0.6); 1.2039 (1.0); 1.1860 (0.6); −0.0002 (4.3)


ESI mass [m/z]: 398.5 [M+H]+


Step 6: methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate Hydrochloride (INT-4)



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To a solution of 409 mg (1.02 mmol) methyl 6-(2-{1-[(tert-butoxycarbonyl)amino]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate in 21 mL dioxane were added 5.15 ml (20.5 mmol) HCl 4N in dioxane. The reaction mixture was stirred at room temperature for three days. The solvent was evaporated, and the remaining residue was used as such in the next step (420 mg, 100% yield).



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=9.1796 (0.8); 9.1741 (0.8); 8.7544 (0.6); 8.7433 (0.6); 8.7018 (0.6); 8.6959 (0.6); 8.6804 (0.7); 8.6746 (0.7); 8.5325 (0.6); 8.5289 (0.7); 8.5205 (0.7); 8.5169 (0.7); 8.4530 (0.9); 8.4318 (0.8); 8.3304 (0.7); 8.3268 (0.7); 8.3103 (0.8); 8.3067 (0.7); 7.5540 (0.6); 7.5421 (0.6); 7.5339 (0.6); 7.5219 (0.6); 3.9584 (5.6); 3.8563 (0.7); 3.7551 (0.4); 3.7107 (0.3); 3.7004 (0.4); 3.6803 (0.5); 3.6707 (0.5); 3.6663 (0.5); 3.6560 (0.5); 3.6503 (0.5); 3.6113 (0.4); 3.5988 (0.4); 3.5820 (0.4); 3.5682 (16.0); 2.5259 (0.8); 2.5211 (1.0); 2.5122 (14.7); 2.5078 (31.5); 2.5033 (42.5); 2.4988 (30.6); 2.4944 (14.6); 1.9097 (0.4); 1.6162 (2.1); 1.5994 (2.1); 1.2341 (0.6); −0.0002 (10.6); −0.0085 (0.3)


ESI mass [m/z]: 298.4 [M+H-HCl]+


1-[1-(5-Chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine Hydrochloride (INT-7)
Step 1: 5-chloro-N-(3-nitro-4-pyridyl)pyridin-2-amine



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To a stirred solution of 5-chloro-2-fluoropyridine (2.27 g, 17.3 mmol) and Cs2CO3 (9.37 g, 28.8 mmol) in 30 ml DMA at 80° C. was added a solution of 3-nitropyridine-4-amine (2.00 g, 14.4 mmol) in 30 ml DMA dropwise and the reaction mixture was stirred at 80° C. overnight. The mixture was allowed to cool down to room temperature. The reaction was quenched with ice water at room temperature. The resulting mixture was extracted with EtOAc several times. The combined organic layers were washed with H2O and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (3.60 g, 88.3% yield).


ESI mass [m/z]: 251.2 [M+H]+


Step 2: N-(5-chloropyridin-2-yl)pyridine-3,4-diamine



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To a stirred solution of 5-chloro-N-(3-nitro-4-pyridyl)pyridin-2-amine (3.60 g, 14.3 mmol) in 72 ml ethyl acetate was added tin chloride dihydrate (16.2 g, 71.7 mmol) and the reaction mixture was stirred at 70° C. for 1 h. When the mixture was cooled down to room temperature the reaction was quenched with water and basified to pH 9-10 with an aqueous solution of sodium carbonate. The mixture was extracted several times with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4. After filtration the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification (2.51 g, 69.8% yield).


ESI mass [m/z]: 221.2 [M+H]+


Step 3: tert-butyl [1-({4-[(5-chloropyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate



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A mixture of N-(tert-butoxycarbonyl)alanine (2.58 g, 13.7 mmol), N,N-diisopropylethylamine (5.94 ml, 34.1 mmol), HATU (5.19 g, 13.7 mmol) in 30 ml DMF was stirred at room temperature for 10 minutes and then N4-(5-chloropyridin-2-yl)pyridine-3,4-diamine (2.51 g, 11.4 mmol) was added and the reaction was stirred at room temperature overnight. Saturated NaHCO3 (aq.) was added and the precipitate was removed by filtration. The filtrate was extracted with EtOAc (3×100 mL), the combined organic layers were dried by the addition of Na2SO4, filtered and evaporated under reduced pressure. The crude product was purified directly by preparative HPLC (eluted with water/acetonitrile) to yield the desired product (472 mg, 10.5% yield).


ESI mass [m/z]: 392.4 [M+H]+


Step 4: tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl]ethyl}carbamate



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To a stirred mixture of tert-butyl [1-({4-[(5-chloropyridin-2-yl)amino]pyridin-3-yl}amino)-1-oxopropan-2-yl]carbamate (815 mg, 2.08 mmol) in dioxane (20.00 mL) was added AcOH (2.38 mL) and the mixture was stirred for 22 h at 100° C. More dioxane (10.00 mL) and AcOH (2.38 mL) were added and the mixture was stirred for 44 h at 100° C. The mixture was basified to pH 8 with saturated NaHCO3 (aq.). The resulting mixture was extracted with EtOAc several times, the combined organic layers were washed with brine and dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by purified by preparative HPLC (eluted with water/acetonitrile) to afford 446 mg (46.5% yield) of the title compound.


ESI mass [m/z]: 374.4 [M+H]+


Step 5:1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine Hydrochloride (INT-7)



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tert-Butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-c]pyridin-2-yl]ethyl}carbamate (446 mg, 1.19 mmol) was dissolved in 8 mL dioxane and 4 M HCl in dioxane (5.97 mL) was added. The reaction mixture was stirred at room temperature over night. The precipitate was collected by filtration (240 mg) and used without further purification in the next step.


ESI mass [m/z]: 274.3 [amine+H]+



1H-NMR: see NMR peaklist (Table 2). 1-[1-(5-Chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate (INT-8)


Step 1: 5-chloro-N-(2-nitropyridin-3-yl)pyridin-2-amine



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12.5 g (95.0 mmol) 5-chloro-2-fluoropyridine and 56.3 g (172.8 mmol) cesium carbonate were suspended in 100 ml DMA and the reaction mixture was stirred at 80° C. Then 12.0 g (86.4 mmol) 2-nitropyridin-3-amine dissolved in 100 ml DMA were added dropwise and the mixture was stirred at 80° C. overnight. After cooling to room temperature, the mixture was treated with ice water and extracted with ethyl acetate several times. The combined organic layers were washed with water, dried over anhydrous Na2SO4 and after filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography, eluted with cyclohexane/EtOAc to afford 13.83 g (72.2%) of the title compound.



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=9.6748 (13.6); 8.4673 (9.4); 8.4637 (10.7); 8.4464 (10.4); 8.4428 (11.1); 8.3187 (0.3); 8.1982 (11.6); 8.1945 (12.3); 8.1874 (12.9); 8.1837 (12.3); 8.1273 (13.6); 8.1207 (13.9); 7.8018 (12.2); 7.7951 (11.6); 7.7797 (12.9); 7.7731 (12.8); 7.7646 (11.2); 7.7538 (10.5); 7.7438 (10.5); 7.7330 (10.1); 7.0951 (16.0); 7.0841 (0.4); 7.0730 (15.0); 3.3849 (0.4); 3.3524 (223.7); 3.3306 (1.0); 2.6774 (0.7); 2.6729 (1.0); 2.6684 (0.7); 2.6640 (0.3); 2.5264 (2.2); 2.5217 (3.4); 2.5129 (53.2); 2.5085 (115.2); 2.5039 (156.8); 2.4994 (111.7); 2.4949 (51.7); 2.3397 (0.3); 2.3354 (0.7); 2.3308 (1.0); 2.3263 (0.7); 2.3218 (0.3); 2.0769 (0.4); −0.0002 (0.6)


ESI mass [m/z]: 251.1 [M+H]+


Step 2: N3-(5-chloropyridin-2-yl)pyridine-2,3-diamine



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10.7 g (42.8 mmol) 5-chloro-N-(2-nitropyridin-3-yl)pyridin-2-amine were dissolved in 200 ml ethyl acetate and then 48.3 g (214.1 mmol) tinn chloride dihydrate were added and the reaction mixture was stirred 1 h at 70° C. After cooling to room temperature, the mixture was treated with water and basified to pH 9-10 with saturated Na2CO3 (aq.). The resulting mixture was extracted with EtOAc several times, dried over anhydrous Na2SO4. After filtration, the filtrate was concentrated under reduced pressure and the crude was used in the next step without further purification (6.13 g, 65% yield).



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=8.1607 (7.2); 8.0648 (7.2); 8.0583 (7.3); 7.7234 (16.0); 7.7149 (3.7); 7.7107 (7.2); 7.7046 (6.3); 7.7009 (3.1); 7.6080 (5.4); 7.6013 (5.2); 7.5857 (5.7); 7.5790 (5.5); 6.7264 (7.9); 6.7041 (7.6); 6.5794 (5.1); 6.5664 (4.5); 6.5610 (4.7); 6.5480 (4.9); 5.7173 (8.1); 3.3361 (16.7); 2.6718 (0.4); 2.5254 (1.0); 2.5117 (21.7); 2.5074 (45.4); 2.5029 (60.6); 2.4984 (43.0); 2.4940 (19.9); 2.3296 (0.4); 1.9896 (0.8); 1.1748 (0.4); 0.0079 (1.6); −0.0002 (49.2); −0.0085 (1.6)


ESI mass [m/z]: 221.1 [M+H]+


Step 3: tert-butyl [1-({3-[(5-chloropyridin-2-yl)amino]pyridin-2-yl}amino)-1-oxopropan-2-yl]carbamate



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2.68 g (14.2 mmol)N-(tert-butoxycarbonyl)alanine, 7.2 mL (42.5 mmol) N,N-diisopropylethylamine (DIPEA, Hünig's Base) and 6.45 g (17.0 mmol) [0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU) dissolved in 30 mL dichloromethane were stirred for 10 min at room temperature. Then 3.12 g (14.18 mmol) N3-(5-chloropyridin-2-yl)pyridine-2,3-diamine were added and the reaction mixture was stirred at room temperature overnight. After further addition of 3 ml of dimethylformamide the mixture was stirred additionally 4 h at room temperature. Finally, a solution of 1.34 g (7.08 mmol)N-(tert-butoxycarbonyl)alanine, 3.22 g (8.5 mmol) HATU and 3.1 ml DIPEA in dichloromethane stirred previously 10 minutes was added and the mixture was stirred at room temperature overnight. The reaction mixture was treated with water and extracted with dichloromethane several times. The combined organic layers were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The residue was purified first by silica gel column chromatography, eluted with cyclohexane/EtOAc and then then purified by prep-HPLC to afford 978.0 mg (17.0%) of the title compound.



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=10.2788 (1.0); 8.4417 (0.8); 8.4227 (0.8); 8.1456 (1.3); 8.1397 (1.4); 8.0827 (0.9); 8.0743 (0.9); 8.0333 (1.2); 7.6869 (0.9); 7.6804 (0.9); 7.6647 (1.0); 7.6582 (1.0); 7.3070 (1.3); 7.2954 (1.3); 7.2866 (1.4); 7.2750 (1.9); 7.2621 (0.7); 6.9163 (1.0); 6.8941 (1.0); 4.1486 (0.4); 4.1317 (0.6); 4.1154 (0.4); 3.3175 (15.4); 2.5239 (0.4); 2.5192 (0.7); 2.5106 (9.7); 2.5061 (20.5); 2.5015 (27.5); 2.4969 (19.2); 2.4924 (8.8); 1.3919 (16.0); 1.2698 (3.5); 1.2521 (3.4); −0.0002 (4.4)


ESI mass [m/z]: 392.1 [M+H]+


Step 4: tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate



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To a solution of 739 g (1.88 mmol) tert-butyl [1-({3-[(5-chloropyridin-2-yl)amino]pyridin-2-yl}amino)-1-oxopropan-2-yl]carbamate in dioxane was added 1 ml acetic acid and the reaction mixture was stirred for two days at 100° C. After evaporation of the mixture under vacuum the crude was used in the next step without further purification (702 mg, 76% yield, 76.5% purity).



1H-NMR (400.2 MHz, d6-DMSO, peaklist): δ=12.0060 (0.4); 8.7398 (1.3); 8.7341 (1.3); 8.4797 (1.4); 8.4761 (1.6); 8.4679 (1.5); 8.4643 (1.6); 8.2799 (0.8); 8.2737 (0.8); 8.2582 (0.9); 8.2525 (0.8); 8.2456 (0.6); 7.8147 (1.0); 7.8049 (1.6); 7.7967 (1.1); 7.7838 (1.4); 7.3692 (0.7); 7.3488 (0.8); 7.3113 (1.2); 7.2994 (1.2); 7.2911 (1.2); 7.2792 (1.1); 5.2270 (0.5); 5.2204 (0.4); 5.2018 (0.6); 5.1837 (0.4); 4.9090 (1.1); 4.8399 (0.4); 4.3289 (0.8); 4.3252 (0.4); 4.0010 (0.7); 3.8322 (0.4); 3.8024 (0.5); 3.6092 (0.7); 3.6014 (1.1); 3.5951 (0.6); 3.5900 (0.5); 3.5834 (0.4); 3.5727 (0.5); 3.5669 (0.7); 3.5568 (0.5); 3.5508 (0.6); 3.5460 (0.5); 3.5296 (0.7); 3.5213 (0.8); 3.4993 (0.6); 3.4939 (0.9); 3.4317 (0.3); 3.4276 (0.4); 3.4045 (0.4); 3.3090 (3.6); 3.1705 (0.5); 3.1541 (0.5); 3.1427 (0.4); 3.1261 (0.4); 2.9943 (1.0); 2.8135 (0.5); 2.6908 (2.8); 2.5195 (0.4); 2.5108 (7.7); 2.5064 (16.8); 2.5019 (23.4); 2.4974 (17.2); 2.4931 (8.5); 2.0819 (0.3); 2.0512 (0.6); 1.5027 (2.9); 1.4857 (2.8); 1.3748 (0.6); 1.3654 (2.2); 1.3279 (0.8); 1.2527 (16.0); 1.1257 (0.7); 1.1088 (0.6); 1.0466 (0.8); 1.0314 (0.8); −0.0002 (1.8)


ESI mass [m/z]: 374.1 [M+H]+


Step 5: 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine Trifluoroacetate (INT-8)



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To a solution of 700 mg tert-butyl {1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethyl}carbamate in 25 mL dioxane were added 2.88 ml (37.4 mmol) TFA. The reaction mixture was stirred 3 h at room temperature overnight. The solvent was evaporated, and the remaining residue was used as such in the next step (735 mg, 100% yield).



1H-NMR (600.1 MHz, d6-DMSO, peaklist): δ=8.8227 (1.9); 8.8220 (1.9); 8.8184 (2.0); 8.8176 (1.9); 8.7373 (1.4); 8.7313 (1.4); 8.6617 (0.1); 8.6299 (0.1); 8.6251 (0.1); 8.5961 (1.6); 8.5937 (1.7); 8.5883 (1.8); 8.5858 (1.7); 8.4440 (0.1); 8.3713 (1.7); 8.3669 (1.6); 8.3570 (1.8); 8.3526 (1.7); 8.3167 (0.2); 8.2605 (0.2); 8.2498 (0.2); 8.2288 (0.1); 8.2119 (0.1); 8.1415 (0.2); 8.1378 (0.4); 8.1266 (0.2); 8.1222 (0.1); 8.0741 (1.6); 8.0716 (1.7); 8.0604 (1.8); 8.0579 (1.8); 7.9260 (2.2); 7.9252 (2.1); 7.9117 (2.1); 7.9109 (2.0); 7.7110 (0.1); 7.7065 (0.1); 7.6963 (0.1); 7.6917 (0.1); 7.4599 (1.6); 7.4520 (1.6); 7.4462 (1.6); 7.4383 (1.6); 4.9961 (0.2); 4.9873 (0.4); 4.9778 (0.5); 4.9671 (0.4); 4.9570 (0.2); 4.7158 (1.1); 4.5296 (0.1); 4.5224 (0.1); 4.5145 (0.1); 4.3305 (0.1); 4.0693 (0.2); 3.7756 (0.2); 3.7713 (0.1); 3.7681 (0.2); 3.7650 (0.1); 3.7606 (0.1); 3.7139 (0.7); 3.6822 (0.1); 3.6743 (0.1); 3.6664 (0.1); 3.5698 (16.0); 3.3937 (0.1); 3.0159 (1.1); 2.8890 (1.0); 2.6922 (4.5); 2.6205 (0.2); 2.6174 (0.3); 2.6144 (0.2); 2.5564 (0.1); 2.5471 (0.2); 2.5378 (0.2); 2.5264 (0.7); 2.5233 (0.8); 2.5202 (0.8); 2.5115 (14.5); 2.5085 (32.2); 2.5054 (45.2); 2.5023 (32.4); 2.4993 (14.8); 2.3924 (0.2); 2.3893 (0.3); 2.3862 (0.2); 1.9102 (0.3); 1.5564 (5.1); 1.5450 (5.1); 1.5359 (0.5); 1.4161 (0.3); 1.4045 (0.3); 1.3942 (0.2); 1.3822 (0.2); 1.3577 (0.3); 1.3088 (0.5); 1.2973 (0.5); 1.2365 (0.4); 1.1125 (0.2); 1.0446 (0.2); 1.0345 (0.2); 0.0968 (0.3); 0.0054 (2.1); −0.0001 (72.5); −0.0057 (2.3); −0.1003 (0.3)


ESI mass [m/z]: 274.3 [M+H-TFA]+


Examples
N-[(1S)-1-[3-(5-cyano-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]-3-methylsulfonyl-5-(trifluoromethoxy)benzamide (example I-1)



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To a solution of 35.5 mg (0.13 mmol) 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)benzoic acid in 1 mL N,N-dimethylformamide (DMF) were added 0.06 mL (0.33 mmol) N,N-diisopropylethylamine (DIPEA; Hünig's Base) and 86.3 mg (0.22 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU). The mixture was stirred for 10 min at room temperature. Then 39.1 mg (0.13 mmol) 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride were added and the reaction mixture was stirred at room temperature over night. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 29.1 mg (41.4% yield) of the title compound.


ESI mass [m/z]: 520.2 [M+H]+



1H-NMR: see NMR peaklist (Table 1).


Methyl 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate (example I-22)



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To a solution of 485.0 mg (1.45 mmol) methyl 6-[2-(1-aminoethyl)-3H-imidazo[4,5-b]pyridin-3-yl]nicotinate hydrochloride in 10 ml dichloromethane were added 0.61 mL (4.36 mmol) triethylamine and the mixture was stirred 30 minutes at room temperature followed by the addition of 442.0 mg (1.60 mmol) 3,5-bis(trifluoromethyl)benzoyl chloride solved previously in 2 ml of dichloromethane. The reaction mixture was stirred at room temperature overnight. The mixture was washed with 5% sodium dihydrogen phosphate (aq.) and extracted with dichloromethane several times. The combined organic layers were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated under reduced pressure. The crude was suspended in 6 ml of acetonitrile and the corresponding precipitate was filtered and dried while the filtrate was then purified by preparative HPLC (eluted with water/acetonitrile) to afford 288 mg (36.0%) of the title compound.


ESI mass [m/z]: 538.2 [M+H]+



1H-NMR: see NMR peaklist (Table 1).


6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylnicotinamide (example I-26) Step 1: 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinic Acid



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To a solution of 270 mg (0.50 mmol) methyl 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinate (from example I-22) in a mixture of THF/water (6 ml/0.6 ml) were added 42 mg (1.0 mmol) lithium hydroxide and the mixture was stirred at room temperature overnight.


The mixture was diluted with ethyl acetate and acidified with HCl 10%. The aqueous phase was separated and extracted with ethyl acetate several times. The combined organic layers were dried over anhydrous Na2SO4 and after filtration, the filtrate was concentrated under reduced pressure. The crude was used in the next step without further purification to afford 260 mg (82.0%) of the title compound.



1H-NMR (400.2 MHz, CD3CN, peaklist): δ=9.1430 (4.6); 9.1376 (4.8); 8.8535 (0.4); 8.6401 (0.9); 8.5111 (3.1); 8.5054 (3.0); 8.4903 (4.0); 8.4844 (3.4); 8.4396 (0.5); 8.4351 (0.5); 8.4076 (3.3); 8.4045 (3.4); 8.3955 (3.4); 8.3927 (3.5); 8.2350 (1.1); 8.1991 (10.3); 8.1806 (0.7); 8.1666 (0.4); 8.1485 (0.4); 8.1406 (3.3); 8.1374 (3.3); 8.1205 (8.0); 8.0573 (5.6); 8.0364 (5.8); 8.0222 (1.3); 7.9346 (0.7); 7.5910 (0.4); 7.4266 (3.1); 7.4145 (3.1); 7.4065 (3.0); 7.3944 (2.9); 6.9744 (0.8); 6.0060 (0.6); 5.9886 (2.3); 5.9706 (3.4); 5.9526 (2.3); 5.9355 (0.5); 4.0862 (0.5); 4.0679 (1.5); 4.0502 (1.5); 4.0319 (0.5); 3.9236 (0.4); 3.1779 (0.3); 2.9701 (0.3); 2.9638 (0.3); 2.9029 (0.4); 2.8856 (0.4); 2.8600 (0.4); 2.8542 (0.4); 2.8504 (0.4); 2.8003 (0.5); 2.7166 (0.7); 2.6825 (0.8); 2.6260 (1.0); 2.5965 (1.2); 2.5664 (1.4); 2.5415 (1.6); 2.4809 (3.2); 2.4762 (4.2); 2.4717 (5.0); 2.4670 (4.4); 2.4629 (3.7); 2.2422 (43.0); 2.1221 (8.4); 2.1150 (8.3); 2.1089 (8.3); 2.1027 (7.3); 2.0964 (6.3); 2.0526 (4.0); 1.9994 (2.3); 1.9933 (2.2); 1.9728 (8.9); 1.9657 (7.3); 1.9538 (124.1); 1.9477 (207.5); 1.9415 (297.5); 1.9354 (205.2); 1.9292 (106.5); 1.8818 (1.4); 1.8742 (1.4); 1.8369 (1.0); 1.8190 (1.0); 1.8022 (1.1); 1.7826 (1.6); 1.7762 (2.2); 1.7648 (16.0); 1.7476 (15.0); 1.6748 (1.7); 1.6569 (1.6); 1.6204 (0.5); 1.6009 (0.6); 1.5826 (0.6); 1.5701 (0.5); 1.5591 (0.8); 1.5408 (0.8); 1.5038 (1.1); 1.4860 (1.1); 1.4495 (0.4); 1.4322 (0.4); 1.3869 (11.4); 1.3552 (0.5); 1.3402 (1.0); 1.3156 (1.0); 1.2851 (1.8); 1.2699 (5.2); 1.2405 (1.0); 1.2218 (2.4); 1.2164 (2.4); 1.2039 (4.3); 1.2001 (3.4); 1.1863 (2.1); 1.1637 (0.4); 1.1463 (0.4); 1.0830 (0.5); 1.0607 (0.6); 0.8980 (0.5); 0.8818 (1.1); 0.8590 (1.1); 0.8415 (0.8); 0.1462 (1.2); 0.0080 (7.3); −0.0002 (234.6); −0.0078 (9.7); −0.0411 (0.4); −0.1497 (1.1)


ESI mass [m/z]: 524.3 [M+H]+


Step 2: 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)-N,N-dimethylnicotinamide (Example I-26)



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To a solution of 60 mg (0.11 mmol) 6-(2-{1-[3,5-bis(trifluoromethyl)benzamido]ethyl}-3H-imidazo[4,5-b]pyridin-3-yl)nicotinic acid in 2.0 ml dichloromethane were added 0.06 mL (0.32 mmol) N,N-diisopropylethylamine (DIPEA, Hünig's Base) and 52.0 mg (0.14 mmol) [0-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 30 min at room temperature. Then a solution of 0.086 ml (0.17 mmol) dimethylamine 2 M in THF solved previously in 1 ml dichloromethane was added and the reaction mixture was stirred at room temperature overnight. After evaporation of the solvent under pressure the crude was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 40 mg (64.0%) of the title compound.


ESI mass [m/z]: 551.2 [M+H]+



1H-NMR: see NMR peaklist (Table 1).


N-[1-[I-(5-chloro-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethyl]-3-cyclopropyl-5-(trifluoromethoxy) benzamide (Example I-33)



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To a solution of 67.0 mg (0.27 mmol) 3-cyclopropyl-5-(trifluoromethoxy)benzoic acid in 2 ml mL N,N-dimethylformamide were added 0.12 mL (0.70 mmol) N,N-diisopropylethylamine (DIPEA, Hünig's Base) and 180.0 mg (0.47 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU) and the mixture was stirred for 10 min at room temperature. Then 104.7 mg (0.27 mmol) 1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate were added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile). The obtained product was dissolved in DCM and filtered through a basic cartridge. The filtrate was evaporate under vacuo to afford 53 mg (38.0%) of the title compound.


ESI mass [m/z]: 502.2 [M+H]+



1H-NMR: see NMR peaklist (Table 1).


N-[1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethyl]-3,5-bis(trifluoromethyl)benzamide
Example I-39



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To a solution of 50.0 mg (0.194 mmol) 3,5-bis(trifluoromethyl)benzoic acid in 2 mL N,N-dimethylformamide (DMF) were added 0.05 mL (0.27 mmol) N,N-diisopropylethylamine (DIPEA; Hünig's Base) and 88.4 mg (0.23 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU). The mixture was stirred for 30 min at room temperature. Then 79.5 mg (0.29 mmol) rac-1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridine-2-yl]ethanamine hydrochloride (INT-7) were added and the reaction mixture was stirred at room temperature over night. Another 50.0 mg (0.194 mmol) 3,5-bis(trifluoromethyl)benzoic acid in 1 mL N,N-dimethylformamide (DMF) were mixed with 0.05 mL (0.27 mmol) N,N-diisopropylethylamine (DIPEA; Hünig's Base) and 88.4 mg (0.23 mmol) [O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate] (HATU), stirred for 30 min at room temperature and added to the reaction mixture. The mixture was stirred for 3 d at room temperature. The reaction mixture was then directly purified by preparative HPLC (eluted with water/acetonitrile) to afford 6.8 mg (6.1% yield) of the title compound.


ESI mass [m/z]: 514.3 [M+H]+



1H-NMR: see NMR peaklist (Table 1).


Analytical Methods

The analytical methods described below refer to all information in the entire document, unless the procedure of the respective analytical determination is described separately at the respective passage.


Mass Spectrometry

The determination of [M+H]+ or M− by LC-MS under acidic chromatographic conditions was done with 1 ml formic acid per liter acetonitrile and 0.9 ml formic acid per liter Millipore water as eluents. The column Zorbax Eclipse Plus C18 50 mm*2.1 mm was used. The temperature of the column oven was 55° C.


Instruments:

LC-MS3: Waters UPLC with SQD2 mass spectrometer and SampleManager autosampler. Linear gradient 0.0 to 1.70 minutes from 10% acetonitrile to 95% acetonitrile, from 1.70 to 2.40 minutes constant 95% acetonitrile, flow 0.85 ml/min.


LC-MS6 and LC-MS7: Agilent 1290 LC, Agilent MSD, HTS PAL autosampler. Linear gradient 0.0 to 1.80 minutes from 10% acetonitrile to 95% acetonitrile, from 1.80 to 2.50 minutes constant 95% acetonitrile, flow 1.0 ml/min.


The determination of [M+H]+ by LC-MS under neutral chromatographic conditions was done with acetonitrile and Millipore water containing 79 mg/l ammonia carbonate as eluents.


Instruments:

LC-MS4: Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (column Waters Acquity 1.7 μm 50 mm*2.1 mm, oven temperature 45° C.). Linear gradient 0.0 to 2.10 minutes from 10% acetonitrile to 95% acetonitrile, from 2.10 to 3.00 minutes constant 95% acetonitrile, flow 0.7 ml/min.


LC-MS8: Waters IClass Acquity with QDA mass spectrometer and FTN autosampler (column Waters Acquity 1.7 μm 50 mm*2.1 mm, oven temperature 45° C.). Linear gradient 0.0 to 2.10 minutes from 10% acetonitrile to 95% acetonitrile, from 2.10 to 3.00 minutes constant 95% acetonitrile, flow 0.7 ml/min.


Retention time indices were calculated in all cases according to a homologues series of straight chain alkan-2-ones with 3 to 16 carbons where the index of the first alkanone was set to 300, the last to 1600, the ones between correspondingly and using linear interpolation between successive alkanones.


NMR

The determination of 1H-NMR data was done with a Bruker Avance III 400 MHz spectrometer equipped with a 1.7 mm TCI probehead, with tetramethylsilane as reference (0.00 ppm) and the measurements were recorded usually from solutions in the solvents CD3CN, CDCl3 or d6-DMSO. Alternatively, a Bruker Avance III 600 MHz instrument equipped with a 5 mm CPNMP probehead or a Bruker Avance NEO 600 MHz instrument equipped with a 5 mm TCI probehead were used for the measurements. Usually the measurements were carried out with a probehead temperature of 298 K. Other measurement temperatures are explicitly noticed.


The NMR data of selected examples are listed either in conventional form (δ values, multiplet splitting, number of hydrogen atoms) or as NMR peak lists.


NMR Peak Lists Procedure


1H-NMR data of selected examples are written in form of 1H-NMR peak lists. δ-Values in ppm and the signal intensity in round brackets are listed to each signal peak. Semicolons are depicted as delimiters between the δ-value—signal intensity pairs.


Therefore the peak list of an example has the form:








δ
1

(

intensity
1

)

;


δ
2

(

intensity
2

)

;
…
;


δ
i

(

intensity
i

)

;
…
;


δ
n

(

intensity
n

)





The intensity of sharp signals correlates with the height of the signals in a printed view of a 1H-NMR spectrum in cm and shows the real relations of signal intensities. Several peaks from broad signals or the middle of the signal and their relative intensity in comparison to the most intensive signal in the spectrum can be shown.


Tetramethylsilane or the chemical shift of the solvent in cases where the sample does not contain tetramethylsilane is used for a calibration of the chemical shift for 1H spectra. Therefore, the tetramethylsilane peak can occur in 1H-NMR peak lists, but not necessarily.



1H-NMR peak lists are equivalent to classical 1H-NMR prints and contain usually all peaks, which are also listed at classical 1H-NMR-interpretations.


In addition, they can show signals of solvents, stereoisomers of the compounds which are optionally object of the invention, and/or peaks of impurities, like classical 1H-NMR prints.



1H-NMR solvent signals, the tetramethylsilane signal and the water signal in the corresponding solvent are excluded from the relative intensity calibration as they have very high intensity values.


On average, the peaks of stereoisomers of the compounds according to the invention and/or peaks of impurities have usually a lower intensity than the peaks of compounds according to the invention (for example with a purity >90%).


Such stereoisomers and/or impurities can be typical for the specific preparation process. Thus, the corresponding peaks can help to recognize the reproduction of the preparation process via “side-products-fingerprints”.


An expert, who calculates the peaks of the target compounds with known methods (MestreC, ACD-simulation, but also with empirically evaluated expectation values), can assign the peaks of the target compounds as needed, optionally using additional intensity filters. This assignment would be similar to the usual peak picking at classical 1H-NMR interpretations.


The used solvent can be extracted from the JCAMP file with the parameter “solvent”, the spectrometer frequency with “observe frequency” and the spectrometer type with “spectrometer/data system”.



13C-NMR data are displayed analogous to 1H-NMR data as peak lists from broadband decoupled 13C-NMR spectra. 13C-NMR solvent signals and tetramethylsilane are excluded from the relative intensity calibration as these signals can have very high intensities.


Further details of NMR-data description with peak lists are disclosed in the publication “Citation of NMR Peaklist Data within Patent Applications” of the Research Disclosure Database Number 564025.


The compounds according to the invention described in table 1 below are likewise preferred compounds of the formula (I), wherein R1 is hydrogen and X is oxygen and which are obtained according to or analogously to the preparation examples described above.




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TABLE 1








ESI


Ex-


Mass


ample
Structure1)
NMR Peak List2)
(m/z)3)







I-1


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1H-NMR(400.2 MHz, d6-DMSO) δ = 9.2021 (0.9); 9.1837 (0.9); 9.0596 (1.4); 9.0556 (1.4); 9.0540 (1.4); 8.5575 (1.1); 8.5518 (1.0); 8.5364 (1.2); 8.5307 (1.2); 8.3980 (1.0); 8.3944 (1.2); 8.3860 (1.1); 8.3824 (1.2); 8.2440 (1.1); 8.2405 (1.1); 8.2240 (1.2); 8.2204 (1.1); 8.1271 (1.6); 8.1060 (1.4); 7.8347 (1.0); 7.8310 (1.8); 7.8274 (1.2); 7.6461 (1.2); 7.5876 (1.2); 7.4634 (1.1); 7.4514 (1.0); 7.4434 (1.0); 7.4314 (1.1); 5.8701 (0.6); 5.8525 (0.9); 5.8348 (0.6); 3.3452 (13.2); 2.5272 (0.4); 2.5226 (0.6); 2.5137 (8.1); 2.5093 (17.3); 2.5048 (23.4); 2.5003 (16.9); 2.4959 (8.0); 2.0783 (1.5); 1.7467 (1.1); 1.7201 (3.6); 1.7098 (16.0); 1.7034 (4.5); −0.0002 (3.7)
520.2





I-2


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1H-NMR(400.2 MHz, d6-DMSO) δ = 9.0557 (7.1); 9.0516 (6.7); 9.0502 (6.5); 9.0243 (4.3); 9.0059 (4.3); 8.5604 (5.2); 8.5547 (4.9); 8.5393 (5.6); 8.5336 (5.4); 8.3888 (5.0); 8.3853 (5.4); 8.3768 (5.4); 8.3733 (5.3); 8.2321 (5.2); 8.2286 (5.1); 8.2121 (5.8); 8.2085 (5.2); 8.1150 (7.2); 8.0939 (6.6); 7.4555 (5.1); 7.4435 (4.9); 7.4355 (4.8); 7.4235 (4.8); 7.3075 (9.2); 7.3037 (9.6); 7.2546 (5.9); 5.8553 (0.6); 5.8380 (2.8); 5.8204 (4.2); 5.8027 (2.8); 5.7855 (0.6); 3.3319 (95.5); 2.6767 (0.8); 2.6721 (1.1); 2.6676 (0.8); 2.5254 (3.5); 2.5118 (68.2); 2.5076 (134.6); 2.5032 (174.2); 2.4987 (122.4); 2.4944 (56.2); 2.3344 (0.8); 2.3300 (1.1); 2.3256 (0.8); 2.0767 (0.9); 2.0365 (0.8); 2.0240 (1.7); 2.0155 (1.9); 2.0032 (3.4); 1.9907 (2.0); 1.9823 (1.8); 1.9696 (0.9); 1.6958 (16.0); 1.6786 (15.8); 1.0356 (2.0); 1.0245 (5.8); 1.0189 (6.1); 1.0084 (3.2); 1.0036 (5.8); 0.9981 (5.8); 0.9878 (2.2); 0.7627 (2.4); 0.7519 (6.9);
493.5




0.7469 (6.6); 0.7397 (6.3); 0.7347 (7.1); 0.7232





(1.9); 0.1458 (0.9); 0.0078 (7.8); −0.0002





(199.0); −0.0085 (6.2); −0.1497 (0.9)






I-3


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1H-NMR(400.2 MHz, d6-DMSO) δ = 9.1845 (4.6); 9.1659 (4.7); 9.0615 (7.3); 9.0576 (7.1); 9.0560 (7.3); 8.5657 (4.8); 8.5601 (4.8); 8.5446 (5.2); 8.5390 (5.4); 8.3954 (4.5); 8.3922 (5.8); 8.3834 (4.9); 8.3802 (5.9); 8.3186 (0.4); 8.2394 (4.8); 8.2361 (5.8); 8.2195 (5.3); 8.2161 (6.0); 8.1296 (7.6); 8.1085 (7.1); 7.6224 (8.9); 7.5245 (6.5); 7.4608 (4.8); 7.4484 (8.5); 7.4411 (10.5); 7.4288 (4.7); 5.8730 (0.6); 5.8560 (2.7); 5.8383 (4.3); 5.8207 (2.8); 5.8036 (0.6); 3.3310 (188.4); 3.3075 (0.4); 2.6758 (1.3); 2.6717 (1.9); 2.6676 (1.5); 2.5249 (4.4); 2.5070 (216.7); 2.5027 (298.2); 2.4986 (230.6); 2.4608 (0.4); 2.3339 (1.4); 2.3296 (1.9); 2.3254 (1.5); 2.0761 (6.6); 1.8582 (0.3); 1.8396 (2.8); 1.8306 (7.8); 1.8240 (8.8); 1.8140 (3.8); 1.7976 (0.5); 1.7851 (0.4); 1.7081 (16.0); 1.6910 (16.0); 1.6673 (0.7); 1.6391 (1.0); 1.6333 (0.7); 1.6205 (6.8); 1.6151 (4.6); 1.6093 (7.0); 1.5995 (5.0); 1.5960 (4.8); 1.5853 (0.6); 1.5770 (0.8);
518.4




1.2318 (0.4); 1.2229 (0.4); 1.2171 (0.3); 1.2058





(0.3); 0.1458 (1.2); 0.0179 (0.3); 0.0078 (8.2);





−0.0002 (261.2); −0.0082 (10.2); −0.1498 (1.2)






I-4


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1H-NMR(400.2 MHz, d6-DMSO) δ = 9.4356 (4.3); 9.4171 (4.5); 9.0896 (6.6); 9.0881 (7.1); 9.0841 (7.2); 9.0824 (6.8); 8.5834 (5.6); 8.5777 (5.4); 8.5623 (6.2); 8.5566 (6.2); 8.4015 (5.4); 8.3979 (5.8); 8.3895 (5.6); 8.3860 (5.8); 8.3182 (1.4); 8.2797 (5.6); 8.2762 (10.0); 8.2727 (5.9); 8.2403 (5.5); 8.2367 (5.7); 8.2203 (6.2); 8.2167 (5.9); 8.1650 (7.3); 8.1635 (7.5); 8.1439 (6.7); 8.1423 (6.8); 8.0588 (6.0); 7.9932 (0.4); 7.9501 (6.0); 7.4634 (5.5); 7.4514 (5.4); 7.4434 (5.2); 7.4314 (5.4); 5.9003 (0.6); 5.8827 (2.8); 5.8651 (4.4); 5.8473 (2.8); 5.8301 (0.6); 3.4040 (0.3); 3.3732 (2.8); 3.3645 (0.9); 3.3368 (62.9); 3.3303 (610.6); 3.2997 (0.6); 3.2843 (0.3); 2.6758 (3.9); 2.6713 (5.5); 2.6668 (4.1); 2.6622 (1.9); 2.6191 (0.4); 2.6140 (0.4); 2.5248 (13.3); 2.5201 (19.4); 2.5112 (303.9); 2.5069 (643.6); 2.5023 (863.6); 2.4978 (616.5); 2.4934 (289.2); 2.4318 (0.5); 2.4106 (0.4); 2.3337
531.0




(3.8); 2.3291 (5.4); 2.3247 (3.8); 2.3202 (1.8);





1.7181 (16.0); 1.7009 (16.0); 1.2477 (1.8);





1.2346 (2.3); 1.2184 (1.6); 0.1460 (4.1); 0.0411





(0.4); 0.0380 (0.4); 0.0339 (0.5); 0.0292 (0.6);





0.0213 (0.8); 0.0165 (1.1); 0.0080 (30.9);





−0.0002 (1009.5); −0.0085 (32.7); −0.0279 (0.8);





−0.0316 (0.7); −0.0365 (0.4); −0.0432 (0.4);





−0.0681 (0.5); −0.1495 (4.2)






I-5


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.3635 (4.4); 9.3454 (4.5); 9.0988 (7.0); 9.0933 (7.0); 8.7591 (0.3); 8.7519 (0.3); 8.5978 (5.0); 8.5921 (4.8); 8.5766 (5.4); 8.5710 (5.4); 8.3992 (4.7); 8.3958 (5.4); 8.3872 (5.1); 8.3838 (5.4); 8.3186 (0.7); 8.2984 (0.5); 8.2373 (5.0); 8.2339 (5.3); 8.2174 (5.5); 8.2139 (5.4); 8.1806 (0.4); 8.1673 (7.9); 8.1558 (4.8); 8.1522 (10.1); 8.1479 (11.6); 8.1293 (5.5); 8.1249 (9.2); 8.1207 (5.0); 8.0713 (0.4); 8.0402 (5.7); 8.0360 (8.8); 8.0320 (5.4); 7.9088 (0.5); 7.8858 (0.4); 7.4609 (5.0); 7.4489 (4.8); 7.4408 (4.8); 7.4288 (4.8); 5.8843 (0.6); 5.8674 (2.8); 5.8498 (4.4); 5.8322 (2.8); 5.8150 (0.6); 5.7587 (11.8); 3.3954 (0.4); 3.3667 (0.5); 3.3494 (2.1); 3.3307 (323.5); 3.3073 (46.4); 2.6759 (2.2); 2.6714 (3.1); 2.6670 (2.3); 2.5614 (0.4); 2.5565 (0.5); 2.5248 (7.9); 2.5200 (11.3); 2.5110 (173.1); 2.5069 (368.0); 2.5024 (499.5); 2.4980 (365.3);
481.0




2.4680 (1.0); 2.4636 (0.9); 2.3336 (2.3); 2.3293





(3.2); 2.3249 (2.4); 1.7042 (16.0); 1.6870





(15.9); 1.3510 (0.6); 1.2965 (0.3); 1.2579 (0.7);





1.2436 (2.6); 1.2290 (3.2); 1.2125 (1.4); 1.1929





(0.6); 1.1882 (0.6); 1.1199 (0.3); 0.8525 (0.4);





0.1459 (2.7); 0.0272 (0.4); 0.0079 (17.6);





−0.0002 (581.2); −0.0082 (22.2); −0.0207 (0.9);





−0.0257 (0.6); −0.0293 (0.4); −0.0352 (0.4);





−0.0382 (0.5); −0.1496 (2.7)






I-6


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.2286 (3.9); 9.2103 (4.0); 9.0862 (6.7); 9.0821 (6.2); 9.0805 (6.6); 8.5882 (5.0); 8.5825 (4.9); 8.5671 (5.5); 8.5614 (5.5); 8.3991 (4.9); 8.3955 (5.5); 8.3872 (5.4); 8.3835 (5.5); 8.2377 (5.0); 8.2341 (5.2); 8.2177 (5.6); 8.2141 (5.4); 8.1628 (6.8); 8.1615 (7.2); 8.1417 (6.2); 8.1403 (6.8); 8.0493 (5.1); 8.0458 (9.7); 8.0422 (5.8); 7.9280 (4.7); 7.9236 (8.9); 7.9194 (5.8); 7.8910 (6.0); 7.8869 (8.3); 7.8829 (4.8); 7.4614 (5.2); 7.4493 (5.0); 7.4413 (5.0); 7.4293 (5.1); 5.8777 (0.6); 5.8607 (2.7); 5.8431 (4.2); 5.8254 (2.8); 5.8078 (0.6); 3.3316 (84.3); 2.6771 (0.6); 2.6725 (0.8); 2.6680 (0.6); 2.5260 (1.8); 2.5212 (3.0); 2.5125 (44.3); 2.5081 (93.3); 2.5036 (125.3); 2.4990 (88.6); 2.4945 (40.9); 2.4736 (0.5); 2.4688 (0.3); 2.3349 (0.6); 2.3304 (0.8); 2.3259 (0.6); 2.0769 (0.9); 1.8620 (0.4); 1.8466 (2.0); 1.8342 (6.7); 1.8272 (8.3); 1.8236 (6.3);
459.2




1.8158 (2.6); 1.8002 (0.7); 1.7886 (0.4); 1.7043





(15.5); 1.6871 (16.0); 1.6624 (6.5); 1.6588





(4.4); 1.6526 (4.2); 1.6499 (4.2); 1.6389 (5.4);





1.6259 (0.8); 1.6176 (0.8); 1.2441 (1.3); 0.0080





(1.2); −0.0002 (37.4); −0.0085 (1.1)






I-7


embedded image



1H-NMR(400.2 MHz, CDCl3) δ = 8.9623 (2.3); 8.9574 (2.4); 8.5790 (2.2); 8.5577 (2.6); 8.4432 (1.6); 8.4399 (1.8); 8.4312 (1.8); 8.4279 (1.9); 8.2885 (1.9); 8.2828 (1.9); 8.2672 (1.6); 8.2615 (1.7); 8.2005 (1.7); 8.1963 (3.1); 8.1920 (2.0); 8.1259 (1.6); 8.1226 (1.8); 8.1060 (1.8); 8.1025 (1.8); 8.0757 (2.2); 8.0723 (3.6); 8.0688 (2.0); 7.9174 (2.8); 7.7894 (1.0); 7.7707 (1.0); 7.4083 (1.8); 7.3962 (1.7); 7.3883 (1.7); 7.3762 (1.6); 7.2654 (18.6); 6.2133 (1.0); 6.1951 (1.5); 6.1778 (1.0); 2.0111 (3.4); 1.7828 (15.6); 1.7754 (16.0); 1.7649 (8.0); 1.7480 (7.4); 1.6837 (9.8); 0.0080 (0.8); −0.0002 (27.2)
461.3





I-8


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.4137 (4.0); 9.3953 (4.1); 8.6180 (7.2); 8.6116 (7.3); 8.3615 (4.7); 8.3580 (5.4); 8.3496 (5.0); 8.3461 (5.2); 8.3174 (1.3); 8.3006 (6.4); 8.2804 (15.1); 8.2178 (4.9); 8.2143 (5.1); 8.1978 (5.4); 8.1943 (5.2); 8.1464 (4.7); 8.1398 (4.5); 8.1250 (5.4); 8.1183 (5.3); 7.8430 (8.1); 7.8216 (7.1); 7.4260 (5.0); 7.4140 (4.9); 7.4059 (4.7); 7.3940 (4.7); 5.8044 (0.6); 5.7874 (2.7); 5.7699 (4.2); 5.7522 (2.8); 5.7348 (0.6); 3.9018 (2.3); 3.4680 (0.4); 3.4354 (0.4); 3.4140 (0.5); 3.4016 (0.8); 3.3938 (0.7); 3.3867 (0.9); 3.3564 (2.2); 3.3310 (1284.4); 3.3095 (3.9); 3.2887 (0.4); 3.2822 (0.8); 2.6755 (4.2); 2.6712 (5.6); 2.6668 (4.2); 2.6459 (0.4); 2.6070 (0.4); 2.5705 (0.9); 2.5661 (0.9); 2.5605 (1.0); 2.5246 (12.7); 2.5198 (19.4); 2.5109 (297.7); 2.5067 (628.4); 2.5023 (850.2); 2.4978 (615.3); 2.4597 (0.7); 2.3335 (3.7); 2.3291 (5.3); 2.3246 (3.8); 1.7093
514.3




(16.0); 1.6920 (16.0); 1.2342 (0.3); 0.1459





(1.5); 0.0079 (10.4); −0.0002 (333.6); −0.0084





(11.2); −0.0223 (0.7); −0.1498 (1.4)






I-9


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.2496 (4.1); 9.2311 (4.2); 8.6140 (6.9); 8.6080 (7.1); 8.3609 (4.7); 8.3574 (5.4); 8.3489 (5.1); 8.3454 (5.3); 8.3184 (0.4); 8.2146 (4.8); 8.2111 (5.0); 8.1947 (5.4); 8.1911 (5.1); 8.1497 (4.7); 8.1431 (4.5); 8.1283 (5.3); 8.1216 (5.3); 7.8615 (1.5); 7.8447 (8.2); 7.8231 (7.1); 7.7253 (5.0); 7.7047 (13.3); 7.4248 (5.0); 7.4128 (4.8); 7.4048 (4.8); 7.3928 (4.8); 5.7744 (0.6); 5.7572 (2.8); 5.7395 (4.2); 5.7217 (2.8); 5.7046 (0.6); 3.3297 (133.5); 2.6764 (1.2); 2.6720 (1.6); 2.6675 (1.2); 2.5254 (4.0); 2.5206 (5.9); 2.5118 (86.6); 2.5075 (183.5); 2.5030 (247.6); 2.4985 (178.0); 2.4942 (84.1); 2.3387 (0.6); 2.3343 (1.2); 2.3298 (1.6); 2.3253 (1.2); 1.6885 (16.0); 1.6713 (15.9); 0.0080 (1.2); −0.0002 (37.7); −0.0084 (1.2)
546.1





I-10


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.3289 (4.4); 9.3104 (4.4); 8.6669 (0.3); 8.6556 (7.3); 8.6492 (7.4); 8.3615 (4.8); 8.3580 (5.6); 8.3496 (5.2); 8.3461 (5.6); 8.2216 (0.3); 8.2119 (5.1); 8.2085 (5.4); 8.1924 (9.8); 8.1880 (7.0); 8.1868 (7.0); 8.1714 (5.8); 8.1647 (6.4); 8.1616 (5.7); 8.1577 (10.1); 8.1541 (6.8); 8.1264 (5.4); 8.1219 (9.0); 8.1177 (5.2); 8.0256 (5.6); 8.0213 (8.7); 8.0172 (5.5); 7.8679 (8.3); 7.8464 (7.3); 7.4232 (5.3); 7.4112 (5.1); 7.4032 (4.9); 7.3912 (4.9); 5.7750 (0.6); 5.7577 (2.8); 5.7399 (4.3); 5.7222 (2.8); 5.7049 (0.6); 3.3305 (107.4); 3.3056 (46.1); 2.6767 (0.6); 2.6720 (0.8); 2.6676 (0.6); 2.5254 (2.1); 2.5119 (43.8); 2.5076 (92.1); 2.5031 (124.3); 2.4987 (91.1); 2.4945 (44.5); 2.3346 (0.6); 2.3300 (0.8); 2.3256 (0.6); 2.0764 (1.9); 1.6855 (16.0); 1.6683 (15.9); 1.6264 (0.6); 1.6092 (0.6); 1.2295 (0.4); 0.0078 (0.7); −0.0002 (18.8);
490.1




−0.0084 (0.6)






I-11


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.1514 (4.3); 9.1326 (4.4); 8.6197 (7.4); 8.6132 (7.7); 8.3586 (4.7); 8.3551 (5.4); 8.3467 (5.2); 8.3432 (5.4); 8.3182 (0.4); 8.2132 (5.0); 8.2097 (5.2); 8.1932 (5.6); 8.1897 (5.4); 8.1559 (4.9); 8.1493 (4.7); 8.1345 (5.6); 8.1279 (5.5); 7.8403 (8.5); 7.8189 (7.5); 7.6211 (4.8); 7.6177 (8.7); 7.6142 (5.9); 7.5328 (5.9); 7.4417 (6.2); 7.4233 (5.2); 7.4113 (5.0); 7.4033 (4.9); 7.3913 (4.9); 5.7708 (0.6); 5.7535 (2.7); 5.7357 (4.2); 5.7179 (2.8); 5.7005 (0.6); 3.3298 (152.4); 2.6763 (1.0); 2.6718 (1.4); 2.6674 (1.0); 2.5252 (3.5); 2.5204 (5.0); 2.5116 (74.1); 2.5073 (158.1); 2.5028 (214.5); 2.4984 (155.0); 2.4941 (74.2); 2.3340 (1.0); 2.3297 (1.4); 2.3251 (1.0); 2.0761 (2.3); 1.8605 (0.4); 1.8441 (3.6); 1.8335 (6.9); 1.8270 (8.7); 1.8227 (4.7); 1.8175 (4.4); 1.8012 (0.4); 1.7874 (0.4); 1.6889 (16.0); 1.6717 (16.0); 1.6419 (0.5); 1.6359 (0.9); 1.6304 (0.6); 1.6182 (6.3); 1.6118 (4.4); 1.6067
527.4




(7.0); 1.5974 (4.3); 1.5929 (4.2); 1.5833 (0.6);





1.5755 (0.7); 1.2484 (0.4); 0.0078 (0.5);





−0.0002 (17.1); −0.0083 (0.6)






I-12


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.4034 (4.3); 9.3848 (4.4); 8.6428 (7.3); 8.6368 (7.4); 8.3641 (4.9); 8.3606 (5.6); 8.3522 (5.4); 8.3486 (5.6); 8.3176 (0.5); 8.2876 (5.3); 8.2842 (9.8); 8.2808 (6.0); 8.2148 (5.1); 8.2113 (5.3); 8.1948 (5.6); 8.1913 (5.5); 8.1760 (5.0); 8.1694 (4.8); 8.1546 (5.7); 8.1480 (5.6); 8.0565 (5.9); 7.9464 (6.0); 7.8676 (8.3); 7.8460 (7.2); 7.4261 (5.2); 7.4141 (5.0); 7.4061 (5.0); 7.3941 (5.0); 5.7901 (0.6); 5.7730 (2.8); 5.7553 (4.2); 5.7375 (2.8); 5.7203 (0.6); 3.3737 (0.4); 3.3346 (58.0); 3.3299 (270.6); 2.6761 (1.3); 2.6716 (1.8); 2.6671 (1.3); 2.5524 (0.3); 2.5250 (4.4); 2.5203 (6.4); 2.5114 (97.1); 2.5071 (208.3); 2.5026 (282.9); 2.4981 (204.0); 2.4938 (97.0); 2.3340 (1.3); 2.3295 (1.8); 2.3249 (1.3); 2.0757 (2.8); 1.6977 (16.0); 1.6805 (16.0); 0.0079 (1.3); −0.0002 (45.8); −0.0085 (1.5)
540.1





I-13


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 8.9973 (4.3); 8.9786 (4.4); 8.6172 (6.9); 8.6110 (7.0); 8.3513 (4.6); 8.3478 (5.3); 8.3393 (5.0); 8.3359 (5.3); 8.3181 (0.5); 8.2033 (4.8); 8.1998 (5.0); 8.1833 (5.3); 8.1799 (5.2); 8.1546 (4.6); 8.1480 (4.5); 8.1332 (5.2); 8.1266 (5.2); 7.8289 (7.9); 7.8075 (7.0); 7.4171 (4.9); 7.4051 (4.7); 7.3971 (4.7); 7.3851 (4.6); 7.3243 (5.8); 7.3032 (8.4); 7.2518 (5.9); 5.7503 (0.6); 5.7329 (2.7); 5.7151 (4.1); 5.6973 (2.7); 5.6801 (0.6); 3.3290 (149.6); 2.6760 (1.2); 2.6716 (1.6); 2.6672 (1.2); 2.5249 (4.0); 2.5201 (6.0); 2.5111 (87.0); 2.5070 (183.4); 2.5026 (247.4); 2.4982 (179.9); 2.3338 (1.2); 2.3294 (1.6); 2.3250 (1.2); 2.0377 (0.7); 2.0250 (1.6); 2.0165 (1.8); 2.0042 (3.3); 1.9917 (2.0); 1.9833 (1.7); 1.9706 (0.9); 1.6746 (16.0); 1.6574 (15.9); 1.0356 (1.9); 1.0245 (5.4); 1.0191 (6.0); 1.0086 (3.0); 1.0037 (5.5); 0.9982 (5.8); 0.9879 (2.2); 0.7660
502.2




(2.3); 0.7553 (6.6); 0.7505 (6.7); 0.7432 (6.1);





0.7381 (7.0); 0.7267 (1.9); 0.0079 (1.1);





−0.0002 (36.0); −0.0084 (1.2)






I-14


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.1704 (1.0); 9.1517 (1.0); 8.6165 (1.7); 8.6101 (1.7); 8.3590 (1.1); 8.3555 (1.2); 8.3470 (1.2); 8.3435 (1.2); 8.2145 (1.1); 8.2110 (1.1); 8.1945 (1.2); 8.1910 (1.2); 8.1456 (1.1); 8.1390 (1.0); 8.1242 (1.2); 8.1177 (1.2); 7.8391 (2.0); 7.8273 (2.0); 7.8237 (1.3); 7.8178 (1.8); 7.6380 (1.4); 7.5950 (1.3); 7.4242 (1.1); 7.4122 (1.1); 7.4041 (1.1); 7.3922 (1.1); 5.7645 (0.6); 5.7468 (0.9); 5.7288 (0.6); 3.3291 (158.8); 2.6757 (0.7); 2.6711 (1.0); 2.6667 (0.8); 2.5245 (2.6); 2.5197 (3.7); 2.5109 (54.5); 2.5066 (115.7); 2.5021 (156.6); 2.4977 (112.3); 2.4933 (53.0); 2.3334 (0.7); 2.3289 (1.0); 2.3245 (0.8); 1.7374 (0.7); 1.7089 (16.0); 1.6972 (3.9); 1.6800 (3.6); 0.1458 (0.7); 0.0079 (4.9); −0.0002 (158.6); −0.0084 (5.3); −0.1496 (0.7)
529.2





I-15


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.4531 (4.1); 9.4349 (4.2); 9.0790 (6.9); 9.0734 (6.9); 8.5677 (4.6); 8.5620 (4.6); 8.5466 (5.0); 8.5409 (5.1); 8.4008 (4.6); 8.3974 (5.4); 8.3889 (4.9); 8.3854 (5.4); 8.3188 (0.4); 8.3029 (6.7); 8.2879 (15.7); 8.2428 (4.7); 8.2395 (5.1); 8.2229 (5.2); 8.2194 (5.2); 8.1458 (7.5); 8.1247 (6.8); 7.4641 (4.8); 7.4521 (4.6); 7.4441 (4.6); 7.4321 (4.6); 5.9083 (0.6); 5.8913 (2.8); 5.8736 (4.3); 5.8561 (2.8); 5.8386 (0.6); 3.3362 (150.2); 2.6778 (0.6); 2.6734 (0.9); 2.6689 (0.7); 2.5266 (2.3); 2.5128 (46.4); 2.5087 (97.5); 2.5043 (132.1); 2.4999 (96.9); 2.3355 (0.6); 2.3311 (0.8); 2.3269 (0.6); 2.0775 (0.5); 1.7308 (16.0); 1.7136 (15.9); −0.0002 (1.0)
505.2





I-16


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.2805 (4.2); 9.2622 (4.3); 9.0630 (6.9); 9.0575 (6.8); 8.5638 (5.0); 8.5581 (4.8); 8.5426 (5.4); 8.5370 (5.5); 8.3988 (4.7); 8.3953 (5.5); 8.3868 (5.2); 8.3833 (5.5); 8.3185 (0.4); 8.2411 (5.0); 8.2376 (5.3); 8.2211 (5.5); 8.2175 (5.4); 8.1399 (7.4); 8.1188 (6.8); 7.7307 (5.2); 7.7026 (13.1); 7.4628 (5.1); 7.4508 (4.9); 7.4428 (4.9); 7.4308 (4.9); 5.8801 (0.6); 5.8630 (2.8); 5.8454 (4.3); 5.8278 (2.8); 5.8104 (0.6); 3.3330 (246.1); 2.6772 (0.9); 2.6727 (1.2); 2.6683 (0.9); 2.5260 (2.9); 2.5213 (4.3); 2.5124 (63.4); 2.5081 (135.4); 2.5037 (184.2); 2.4992 (133.5); 2.4950 (63.9); 2.3349 (0.8); 2.3304 (1.1); 2.3260 (0.8); 1.7084 (16.0); 1.6912 (15.9); −0.0002 (1.2)
537.2





I-17


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.1038 (2.8); 9.0997 (2.8); 8.7771 (0.3); 8.7738 (0.3); 8.7627 (0.3); 8.6297 (1.7); 8.6104 (1.8); 8.5986 (2.2); 8.5930 (2.1); 8.5775 (2.3); 8.5718 (2.2); 8.5323 (0.3); 8.5288 (0.3); 8.3861 (2.1); 8.3826 (2.3); 8.3741 (2.3); 8.3706 (2.2); 8.2227 (2.1); 8.2192 (2.1); 8.2028 (2.4); 8.1992 (2.1); 8.1675 (3.0); 8.1662 (3.0); 8.1463 (2.7); 8.1450 (2.7); 7.5378 (0.4); 7.5269 (0.3); 7.5168 (0.4); 7.5058 (0.3); 7.4516 (2.3); 7.4396 (2.1); 7.4317 (3.2); 7.4196 (2.0); 7.3180 (0.6); 7.2983 (2.9); 7.1650 (1.4); 6.9982 (0.6); 6.8572 (3.9); 5.8263 (1.2); 5.8083 (1.7); 5.7902 (1.2); 3.9791 (2.9); 3.9437 (16.0); 3.3342 (47.6); 2.6767 (0.4); 2.6721 (0.5); 2.6675 (0.4); 2.5252 (1.8); 2.5118 (31.1); 2.5076 (61.4); 2.5031 (79.7);
423.2




2.4986 (56.6); 2.4943 (26.8); 2.3345 (0.4);





2.3299 (0.5); 2.3254 (0.4); 1.6178 (7.0); 1.6007





(7.0); 0.0079 (1.1); −0.0002 (26.2); −0.0084





(1.0)






I-18


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.2311 (2.2); 9.2128 (2.2); 9.0676 (3.4); 9.0632 (3.6); 8.5647 (2.1); 8.5594 (2.1); 8.5436 (2.2); 8.5383 (2.3); 8.2444 (3.4); 8.2321 (3.6); 8.1369 (0.5); 8.1064 (3.4); 8.0853 (3.1); 7.7805 (4.3); 7.7558 (3.4); 7.5753 (3.5); 7.2803 (3.0); 7.2680 (2.9); 5.8449 (0.3); 5.8281 (1.3); 5.8108 (2.1); 5.7931 (1.4); 5.7758 (0.4); 3.6338 (0.6); 3.6236 (0.6); 3.6174 (0.8); 3.6073 (0.8); 3.6012 (0.7); 3.5910 (0.6); 3.5749 (0.3); 3.4016 (45.1); 3.1672 (0.3); 3.1491 (0.9); 3.1382 (1.0); 3.1308 (1.0); 3.1200 (0.9); 3.1021 (0.3); 2.6730 (0.7); 2.6344 (16.0); 2.5041 (95.3); 2.3310 (0.6); 2.2069 (0.6); 1.7122 (7.7); 1.6950 (7.7); 1.4995 (0.3); 1.2882 (6.2); 1.2713 (8.0); 1.2670 (8.4); 1.2584 (4.9); 1.2502 (6.8); 1.2401 (2.2); −0.0002 (8.4)
501.2





I-19


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.7377 (0.4); 9.2776 (0.5); 9.2251 (2.2); 9.2068 (2.2); 9.0639 (3.6); 9.0584 (3.5); 8.5720 (2.4); 8.5663 (2.3); 8.5509 (2.6); 8.5452 (2.6); 8.5020 (0.4); 8.4963 (0.4); 8.2403 (3.6); 8.2369 (3.8); 8.1496 (3.8); 8.1284 (3.5); 8.0489 (0.8); 8.0420 (0.7); 8.0337 (3.7); 8.0310 (3.8); 7.9710 (0.3); 7.8398 (0.4); 7.8050 (0.8); 7.7945 (2.5); 7.7904 (4.6); 7.7868 (3.4); 7.7575 (3.0); 7.7034 (0.4); 7.6814 (0.3); 7.5846 (3.2); 5.8698 (0.3); 5.8527 (1.4); 5.8352 (2.2); 5.8175 (1.5); 3.3709 (0.4); 3.3362 (117.2); 2.6776 (0.4); 2.6730 (0.5); 2.6689 (0.4); 2.5263 (1.7); 2.5126 (28.5); 2.5086 (57.8); 2.5041 (77.1); 2.4997 (56.5); 2.4526 (16.0); 2.3354 (0.4); 2.3310 (0.5); 2.3266 (0.4); 2.2852 (2.0); 2.1135 (0.8); 2.0769 (0.4); 2.0563 (0.7); 1.6841 (8.2); 1.6669 (8.2);
501.2




1.4413 (0.9); 1.4232 (0.9); −0.0002 (1.1)






I-20


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.1828 (4.3); 9.1642 (4.4); 9.0572 (6.7); 9.0521 (6.8); 8.5721 (4.7); 8.5665 (4.6); 8.5510 (5.1); 8.5453 (5.1); 8.3178 (0.5); 8.1205 (7.4); 8.0966 (10.2); 8.0758 (8.7); 8.0484 (0.4); 7.7766 (8.8); 7.7731 (6.9); 7.7551 (6.0); 7.5708 (6.3); 7.3062 (7.9); 7.2857 (7.5); 5.8332 (0.7); 5.8160 (2.7); 5.7983 (4.2); 5.7807 (2.8); 5.7583 (3.6); 3.3823 (0.4); 3.3317 (244.0); 2.8915 (1.0); 2.7319 (0.8); 2.6763 (1.1); 2.6721 (1.5); 2.6678 (1.2); 2.5480 (37.9); 2.5255 (4.2); 2.5075 (172.2); 2.5032 (231.4); 2.4989 (172.0); 2.4683 (1.3); 2.3343 (1.1); 2.3300 (1.5); 2.3257 (1.2); 1.6937 (0.5); 1.6703 (16.0); 1.6532 (15.9); 1.2328 (0.6); −0.0002 (1.2)
501.2





I-21


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.4423 (2.2); 9.4238 (2.2); 9.0762 (3.4); 9.0712 (3.8); 8.5748 (2.3); 8.5692 (2.4); 8.5537 (2.4); 8.5482 (2.6); 8.3174 (0.7); 8.2814 (5.0); 8.2427 (4.2); 8.1680 (3.9); 8.1468 (3.5); 8.0552 (3.5); 8.0343 (4.1); 7.9541 (3.6); 7.9248 (0.3); 5.9065 (0.4); 5.8887 (1.4); 5.8714 (2.2); 5.8542 (1.5); 5.8367 (0.4); 3.4125 (0.6); 3.3981 (0.7); 3.3828 (1.6); 3.3295 (357.4); 3.2989 (0.8); 3.2677 (0.4); 3.2536 (0.3); 2.6755 (2.0); 2.6712 (2.8); 2.6671 (2.3); 2.5808 (0.5); 2.5064 (318.7); 2.5023 (432.9); 2.4980 (345.4); 2.4533 (16.0); 2.3810 (0.5); 2.3328 (2.0); 2.3291 (2.8); 2.3249 (2.3); 1.7059 (8.0); 1.6887 (8.0); 1.2577 (0.4); 1.2345 (0.8); 1.1358 (0.4); 1.1221 (0.4); −0.0002 (1.3)
545.3





I-22


embedded image



1H-NMR(400.2 MHz, CD3CN) δ = 9.1139 (3.0); 8.4753 (1.5); 8.4711 (1.7); 8.4543 (1.7); 8.4500 (1.9); 8.3705 (2.1); 8.3587 (2.3); 8.1302 (7.3); 8.1090 (4.7); 8.0883 (2.3); 8.0544 (2.7); 8.0334 (2.4); 7.8368 (1.1); 7.8187 (1.1); 7.3890 (1.5); 7.3773 (1.6); 7.3694 (1.7); 7.3572 (1.5); 5.9895 (1.2); 5.9719 (1.8); 5.9541 (1.2); 3.9174 (16.0); 2.1674 (63.9); 2.1144 (0.6); 2.1085 (0.6); 1.9714 (1.4); 1.9643 (1.3); 1.9519 (18.6); 1.9460 (36.7); 1.9409 (52.1); 1.9350 (41.0); 1.9300 (24.0); 1.7694 (0.4); 1.7644 (0.3); 1.7390 (7.7); 1.7219 (7.8); 1.2682 (1.2); 1.2469 (0.6); 1.2220 (0.5); 1.2040 (0.7); 1.1849 (0.4); 0.8569 (0.3); −0.0002 (49.3); −0.0013 (48.9)
538.2





I-23


embedded image



1H-NMR(400.2 MHz, d6-DMSO) δ = 9.3962 (4.3); 9.3778 (4.4); 9.0677 (6.9); 9.0623 (7.2); 8.5715 (4.6); 8.5659 (4.6); 8.5504 (5.1); 8.5448 (5.2); 8.3171 (2.0); 8.2656 (9.8); 8.1376 (7.4); 8.1163 (6.9); 8.1000 (8.2); 8.0797 (8.8); 8.0520 (6.5); 7.9398 (6.5); 7.3108 (8.0); 7.2903 (7.7); 5.8674 (0.7); 5.8502 (2.8); 5.8328 (4.4); 5.8151 (2.8); 5.7978 (0.6); 5.7577 (0.3); 3.5066 (0.7); 3.4812 (0.4); 3.4313 (0.6); 3.4097 (1.0); 3.3889 (1.0); 3.3746 (1.6); 3.3301 (1361.4); 3.2962 (1.7); 3.2770 (1.1); 3.2685 (0.6); 3.2406 (0.5); 3.2023 (0.4); 3.1600 (0.4); 3.1406 (0.3); 3.1202 (0.4); 2.7289 (0.4); 2.6754 (5.8); 2.6710 (8.0); 2.6666 (6.2); 2.6031 (0.9); 2.5796 (1.6); 2.5504 (39.1); 2.5243 (20.5); 2.5064 (912.1); 2.5021 (1234.2); 2.4977 (927.7); 2.4543 (1.5); 2.3655 (0.5); 2.3332 (5.8); 2.3289 (7.8); 2.3245 (5.9); 2.2948 (0.4);
545.2




1.6927 (15.9); 1.6756 (16.0); 1.2581 (0.4);





1.2328 (1.4); 1.2032 (0.4); 1.1925 (0.4); 1.1644





(0.4); −0.0002 (4.0)






I-24


embedded image


I-24: 1H-NMR(400.2 MHz, CD3CN): δ = 9.1359 (1.8); 9.1316 (1.9); 9.1303 (1.9); 8.5021 (1.4); 8.4963 (1.4); 8.4810 (1.5); 8.4753 (1.5); 8.3731 (1.4); 8.3697 (1.6); 8.3612 (1.5); 8.3577 (1.6); 8.1105 (1.4); 8.1070 (1.5); 8.0902 (1.8); 8.0869 (3.0); 8.0837 (3.1); 8.0802 (2.0); 8.0640 (2.2); 8.0430 (2.0); 7.9215 (0.7); 7.9060 (2.2); 7.8256 (1.8); 7.3905 (1.5); 7.3784 (1.4); 7.3704 (1.4); 7.3584 (1.4); 5.9775 (0.9); 5.9593 (1.4); 5.9415 (1.0); 3.9266 (16.0); 3.6648 (0.4); 3.6483 (0.9); 3.6316 (1.3); 3.6151 (1.0); 3.5986 (0.4); 3.1324 (0.6); 3.1138 (1.7); 3.1032 (15.6); 3.0955 (2.3); 3.0768 (0.6); 2.7281 (5.3); 2.5076 (0.6); 2.2227 (38.6); 2.1219 (0.4); 2.1159 (0.4); 2.1098 (0.4); 2.1035 (0.4); 1.9667 (1.0); 1.9605 (0.7); 1.9548 (9.8); 1.9486 (19.2); 1.9425 (27.7); 1.9363 (19.2); 1.9301 (9.9); 1.7278 (6.6); 1.7105 (6.5); 1.3535 (2.0); 1.3357 (12.5); 1.3196 (10.1); 1.2680 (0.7); 1.1000 (3.2); 1.0848 (3.2); −0.0002 (11.2); −0.0083 (0.5)
564.3





I-25


embedded image


I-25: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.4344 (3.8); 9.4158 (3.9); 8.9704 (6.0); 8.9647 (6.4); 8.7104 (2.8); 8.6987 (2.8); 8.6880 (1.0); 8.3781 (5.8); 8.3744 (8.0); 8.3658 (4.7); 8.3621 (5.5); 8.3534 (4.1); 8.3187 (0.8); 8.2770 (16.0); 8.2229 (4.1); 8.2196 (4.2); 8.2029 (4.5); 8.1996 (4.3); 7.9364 (6.4); 7.9155 (5.9); 7.4346 (4.0); 7.4226 (3.9); 7.4145 (3.9); 7.4026 (3.9); 5.8779 (0.5); 5.8604 (2.4); 5.8428 (3.7); 5.8252 (2.4); 5.8074 (0.5); 3.9436 (0.5); 3.3780 (0.6); 3.3322 (257.4); 3.2785 (0.3); 2.8117 (15.9); 2.8005 (15.9); 2.6762 (2.6); 2.6717 (3.6); 2.6674 (2.7); 2.6027 (0.4); 2.5908 (0.3); 2.5250 (11.3); 2.5072 (431.8); 2.5028 (571.6); 2.4985 (415.9); 2.3339
537.2





I-26


embedded image


I-26: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.4311 (3.7); 9.4122 (3.8); 8.5915 (6.2); 8.5861 (6.3); 8.3795 (4.1); 8.3768 (4.4); 8.3677 (4.3); 8.3650 (4.2); 8.3033 (14.0); 8.2830 (6.1); 8.2378 (4.1); 8.2351 (4.1); 8.2179 (4.3); 8.2150 (4.1); 8.0759 (3.3); 8.0704 (3.3); 8.0553 (4.0); 8.0498 (4.0); 7.8927 (6.3); 7.8722 (5.1); 7.4393 (3.5); 7.4273 (3.5); 7.4193 (3.5); 7.4073 (3.3); 5.9134 (0.6); 5.8967 (2.2); 5.8790 (3.4); 5.8610 (2.2); 5.8441 (0.5); 3.3608 (18.5); 2.9850 (15.2); 2.9404 (0.3); 2.7467 (16.0); 2.6749 (0.6); 2.5728 (0.4); 2.5100 (70.6); 2.5061 (87.9); 2.5023 (66.9); 2.3327 (0.5); 2.0799 (0.5); 1.7179 (12.8); 1.7008 (12.6); 1.2447 (0.4); 1.2336 (0.7); −0.0002 (0.4)
551.2





I-27


embedded image


I-27: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.2769 (2.4); 9.2585 (2.4); 8.9792 (3.8); 8.9741 (3.9); 8.7271 (1.8); 8.7157 (1.8); 8.7053 (0.6); 8.3980 (2.4); 8.3920 (2.4); 8.3761 (4.3); 8.3716 (5.3); 8.3635 (2.9); 8.3600 (3.0); 8.3185 (0.4); 8.2168 (2.6); 8.2134 (2.8); 8.1968 (3.0); 8.1934 (2.9); 7.9403 (3.9); 7.9194 (3.6); 7.6958 (16.0); 7.4321 (2.6); 7.4201 (2.5); 7.4121 (2.5); 7.4001 (2.5); 5.8393 (0.3); 5.8220 (1.5); 5.8044 (2.3); 5.7868 (1.5); 5.7697 (0.3); 3.3311 (121.0); 2.8226 (10.2); 2.8114 (10.2); 2.6763 (1.2); 2.6718 (1.7); 2.6674 (1.2); 2.5252 (4.6); 2.5204 (7.0); 2.5114 (90.0); 2.5073 (189.1); 2.5028 (254.2); 2.4984 (186.3); 2.3342 (1.1); 2.3296 (1.6); 2.3253 (1.2); 1.6939 (8.5); 1.6767 (8.5); −0.0002 (1.9)
569.2





I-28


embedded image


I-28: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.4177 (3.9); 9.3992 (4.1); 8.9819 (6.2); 8.9763 (6.6); 8.7442 (1.1); 8.7340 (3.0); 8.7226 (3.0); 8.7124 (1.1); 8.4015 (3.7); 8.3957 (3.6); 8.3801 (7.5); 8.3757 (7.8); 8.3675 (4.8); 8.3641 (4.6); 8.3184 (0.8); 8.2596 (8.3); 8.2208 (4.4); 8.2175 (4.3); 8.2008 (4.8); 8.1975 (4.4); 8.0322 (5.6); 7.9559 (6.6); 7.9352 (10.9); 7.4348 (4.0); 7.4228 (3.9); 7.4148 (3.8); 7.4028 (3.9); 5.8639 (0.6); 5.8469 (2.4); 5.8291 (3.7); 5.8115 (2.4); 5.7951 (0.6); 3.3792 (0.4); 3.3671 (0.4); 3.3308 (246.2); 2.8228 (16.0); 2.8116 (15.8); 2.6893 (4.0); 2.6758 (2.4); 2.6714 (3.2); 2.6673 (2.4); 2.6156 (0.4); 2.6056 (0.4); 2.5759 (0.5); 2.5247 (9.8); 2.5069 (376.5); 2.5026 (487.2); 2.4983 (350.7); 2.4417 (0.3); 2.3337 (2.3); 2.3294 (3.0); 2.3250 (2.2); 1.7053 (13.3); 1.6881 (13.2); 1.2338 (0.6); −0.0002 (3.7)
563.2





I-29


embedded image


I-29: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.3834 (3.5); 9.3643 (3.6); 8.5939 (5.8); 8.5893 (5.9); 8.3775 (4.0); 8.3740 (4.5); 8.3656 (4.4); 8.3621 (4.5); 8.3186 (0.4); 8.2491 (4.5); 8.2457 (8.1); 8.2424 (5.1); 8.2356 (4.4); 8.2320 (4.4); 8.2155 (4.6); 8.2120 (4.4); 8.1351 (0.4); 8.0737 (3.7); 8.0679 (3.6); 8.0531 (4.6); 8.0474 (4.7); 8.0354 (5.0); 7.9468 (5.0); 7.8863 (6.2); 7.8657 (5.1); 7.4371 (4.1); 7.4251 (4.0); 7.4171 (3.9); 7.4051 (4.0); 6.5916 (0.7); 5.8949 (0.5); 5.8781 (2.2); 5.8601 (3.2); 5.8421 (2.2); 5.8254 (0.5); 3.3735 (0.9); 3.3317 (91.8); 3.0152 (0.5); 2.9846 (15.1); 2.9081 (0.4); 2.7562 (16.0); 2.6765 (1.0); 2.6721 (1.4); 2.6676 (1.0); 2.5254 (4.4); 2.5205 (6.8); 2.5118 (81.6); 2.5075 (168.3); 2.5031 (222.9); 2.4986 (159.9); 2.4944 (76.5); 2.3343 (0.9); 2.3299 (1.3); 2.3254 (0.9); 2.0764 (2.1); 1.7064 (12.6); 1.6893 (12.5); 1.2348 (0.4); −0.0002 (1.6)
577.3





I-30


embedded image


I-30: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.4603 (4.2); 9.4419 (4.4); 9.0219 (6.8); 9.0164 (7.2); 8.4388 (4.0); 8.4330 (4.0); 8.4179 (4.4); 8.4121 (4.4); 8.3795 (4.4); 8.3764 (5.2); 8.3677 (4.8); 8.3644 (5.2); 8.3191 (0.5); 8.2900 (16.0); 8.2708 (6.8); 8.2196 (8.6); 8.2166 (7.5); 8.1994 (5.2); 8.1961 (5.2); 7.9561 (7.1); 7.9352 (6.6); 7.6848 (4.4); 7.4348 (4.3); 7.4228 (4.2); 7.4148 (4.2); 7.4028 (4.2); 5.8784 (0.6); 5.8610 (2.7); 5.8434 (4.2); 5.8257 (2.7); 5.8088 (0.6); 3.3318 (97.8); 2.6771 (1.0); 2.6726 (1.3); 2.6682 (1.0); 2.5257 (3.3); 2.5079 (155.6); 2.5036 (210.7); 2.4994 (159.5); 2.3347 (1.0); 2.3305 (1.3); 2.3262 (1.0); 2.0767 (1.2); 1.7184 (14.9); 1.7012 (15.0); 1.2334 (0.4); 0.8765 (0.6); 0.8597 (0.6); 0.1460 (1.0); 0.0178 (0.4); 0.0078 (7.0); −0.0002 (216.6); −0.1496 (1.0)
523.2





I-31


embedded image


I-31: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.3193 (3.2); 9.3001 (3.3); 8.9765 (15.6); 8.9642 (16.0); 8.3527 (3.7); 8.3492 (4.2); 8.3408 (4.0); 8.3372 (4.2); 8.2121 (4.0); 8.2085 (4.1); 8.1921 (4.5); 8.1885 (4.2); 7.7272 (4.0); 7.6651 (9.6); 7.6028 (4.1); 7.5905 (7.9); 7.5783 (4.0); 7.4190 (4.1); 7.4070 (3.9); 7.3989 (3.9); 7.3870 (3.9); 5.8105 (0.5); 5.7933 (2.1); 5.7752 (3.0); 5.7571 (2.2); 5.7400 (0.5); 3.3381 (115.2); 2.6778 (0.4); 2.6734 (0.7); 2.6691 (0.5); 2.5267 (1.6); 2.5219 (2.4); 2.5131 (36.3); 2.5089 (76.3); 2.5044 (102.1); 2.4999 (73.3); 2.4956 (34.8); 2.3354 (0.4); 2.3313 (0.6); 2.3268 (0.5); 1.6870 (12.7); 1.6698 (12.7); −0.0002 (0.4)
513.2





I-32


embedded image


I-32: 1H-NMR(600.1 MHz, d6-DMSO): δ = 20.2266 (0.1); 9.5279 (3.8); 9.5155 (3.9); 9.1007 (6.0); 9.0995 (6.3); 9.0970 (6.4); 9.0957 (6.1); 8.6023 (5.7); 8.5985 (5.6); 8.5884 (5.9); 8.5846 (6.0); 8.5684 (0.2); 8.5262 (5.8); 8.5237 (6.2); 8.5184 (6.5); 8.5158 (6.4); 8.4876 (0.1); 8.4838 (0.1); 8.3446 (0.1); 8.3136 (0.5); 8.2991 (5.2); 8.2827 (12.5); 8.0334 (6.6); 8.0321 (6.6); 8.0195 (6.5); 8.0182 (6.5); 7.9507 (5.7); 7.9482 (6.0); 7.9371 (6.6); 7.9346 (6.4); 7.3723 (6.0); 7.3645 (5.7); 7.3588 (5.8); 7.3509 (6.1); 6.9511 (0.1); 5.7946 (0.6); 5.7833 (2.8); 5.7714 (4.0); 5.7595 (3.0); 5.7536 (2.5); 5.7480 (0.6); 3.7444 (0.1); 3.3160 (145.1); 2.6205 (0.5); 2.6174 (1.2); 2.6143 (1.7); 2.6112 (1.2); 2.6081 (0.6); 2.5384 (0.2); 2.5233 (4.3); 2.5202 (5.3); 2.5171 (4.8); 2.5084 (81.5); 2.5053 (185.4); 2.5022 (263.3); 2.4991 (188.4); 2.4961 (85.8); 2.3922 (0.5); 2.3892 (1.2); 2.3861 (1.7); 2.3830 (1.2);
505.5




2.3800 (0.6); 1.7374 (15.9); 1.7260 (16.0);





1.6470 (0.1); 1.4429 (0.3); 1.4309 (0.3); 1.3857





(0.1); 1.3523 (0.4); 1.3411 (0.1); 1.3369 (0.1);





1.2595 (0.2); 1.2501 (0.3); 1.2345 (0.7); 1.1111





(0.1); 1.0455 (0.5); 1.0433 (0.8); 1.0331 (0.8);





0.8516 (0.3); 0.8190 (0.3); 0.0968 (1.4); 0.0054





(12.0); −0.0001 (448.0); −0.0057 (13.9); −0.0269





(0.1); −0.1002 (1.4)






I-33


embedded image


I-33: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.0841 (3.9); 9.0652 (4.0); 8.6535 (6.8); 8.6479 (6.9); 8.6470 (6.7); 8.5014 (5.2); 8.4976 (5.7); 8.4895 (5.7); 8.4857 (5.6); 8.1825 (5.3); 8.1759 (5.2); 8.1612 (6.0); 8.1546 (5.9); 7.8541 (5.0); 7.8503 (5.2); 7.8338 (5.9); 7.8300 (5.6); 7.8198 (7.7); 7.7982 (7.0); 7.3354 (10.5); 7.3234 (10.5); 7.3194 (9.4); 7.3153 (9.0); 7.3032 (5.3); 7.2551 (5.4); 5.6892 (0.6); 5.6720 (2.7); 5.6541 (3.9); 5.6361 (2.8); 5.6189 (0.6); 3.3390 (36.4); 2.6764 (0.4); 2.6719 (0.6); 2.6673 (0.5); 2.5253 (1.9); 2.5206 (2.9); 2.5119 (30.5); 2.5074 (62.6); 2.5028 (83.1); 2.4982 (58.7); 2.4937 (27.2); 2.3342 (0.4); 2.3297 (0.6); 2.3251 (0.4); 2.0746 (7.7); 2.0417 (0.8); 2.0291 (1.7); 2.0206 (1.8); 2.0169 (1.3); 2.0082 (3.5); 1.9996 (1.3); 1.9957 (2.0); 1.9873 (1.8); 1.9747 (0.9); 1.6849 (16.0); 1.6677 (15.9);
502.2




1.0375 (2.2); 1.0268 (5.4); 1.0211 (6.0); 1.0168





(3.1); 1.0108 (3.2); 1.0058 (5.5); 1.0002 (5.9);





0.9900 (2.4); 0.7722 (2.6); 0.7617 (6.6); 0.7565





(6.7); 0.7494 (6.2); 0.7441 (7.0); 0.7329 (2.1);





0.0080 (1.4); −0.0002 (40.8); −0.0085 (1.2)






I-34


embedded image


I-34: 1H-NMR(600.1 MHz, d6-DMSO): δ = 9.2241 (4.1); 9.2118 (4.1); 9.0812 (6.4); 9.0775 (6.6); 8.5865 (4.3); 8.5828 (4.2); 8.5725 (4.4); 8.5687 (4.4); 8.4308 (4.6); 8.4281 (5.8); 8.3120 (1.0); 8.2529 (3.6); 8.2487 (3.4); 8.2377 (3.7); 8.2338 (3.2); 8.1165 (6.8); 8.1025 (6.4); 7.7834 (8.0); 7.7575 (5.4); 7.5777 (5.7); 5.7990 (2.8); 5.7874 (4.3); 5.7757 (2.8); 3.3260 (186.8); 3.3229 (343.5); 3.3212 (540.8); 3.3168 (566.6); 2.6139 (5.0); 2.5228 (9.8); 2.5198 (12.6); 2.5167 (12.1); 2.5076 (262.0); 2.5048 (580.9); 2.5018 (826.9); 2.4988 (635.9); 2.3857 (5.4); 1.6874 (15.8); 1.6759 (16.0); 0.0053 (2.0); −0.0001 (80.2)
505.2





I-35


embedded image


I-35: 1H-NMR(600.4 MHz, CD3CN): δ = 8.9221 (3.6); 8.9209 (3.7); 8.9184 (3.9); 8.9171 (3.6); 8.3808 (3.3); 8.3784 (3.5); 8.3729 (3.5); 8.3704 (3.5); 8.3275 (3.1); 8.3237 (3.1); 8.3134 (3.9); 8.3096 (4.0); 8.2207 (4.7); 8.2196 (4.7); 8.2066 (3.6); 8.2055 (3.6); 8.1859 (8.6); 8.1321 (3.5); 8.1031 (3.5); 8.1007 (3.6); 8.0898 (3.7); 8.0873 (3.6); 7.8100 (0.9); 7.7998 (1.0); 7.3955 (4.0); 7.3875 (4.0); 7.3822 (3.9); 7.3742 (3.9); 6.0166 (0.6); 6.0050 (2.1); 5.9930 (3.0); 5.9811 (2.2); 5.9695 (0.6); 5.4458 (10.2); 4.0656 (0.9); 4.0537 (0.9); 2.1373 (79.2); 2.1046 (0.9); 2.0541 (0.4); 2.0500 (0.6); 2.0459 (0.4); 1.9715 (4.4); 1.9635 (5.0); 1.9554 (2.2); 1.9512 (2.8); 1.9474 (34.9); 1.9433 (66.7); 1.9392 (98.1); 1.9351 (67.6); 1.9310 (34.2); 1.9223 (0.7); 1.8284 (0.4); 1.8242 (0.6); 1.8201 (0.4); 1.7373 (15.9); 1.7258 (16.0); 1.3792 (0.8); 1.2698 (0.4); 1.2158 (1.2); 1.2039 (2.4);
505.1




1.1921 (1.2); 1.1067 (0.4); 0.0967 (0.6); 0.0054





(4.5); −0.0001 (161.1); −0.0057 (5.4); −0.0127





(0.4); −0.1001 (0.6)






I-36


embedded image


I-36: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.5733 (1.4); 9.5552 (1.5); 9.0794 (2.1); 9.0777 (2.4); 9.0739 (2.3); 9.0721 (2.3); 8.5712 (1.8); 8.5655 (1.8); 8.5500 (2.0); 8.5444 (2.0); 8.4068 (1.7); 8.4032 (2.0); 8.3948 (1.9); 8.3912 (2.0); 8.3248 (1.7); 8.3214 (3.2); 8.3180 (2.0); 8.2448 (1.8); 8.2412 (1.9); 8.2248 (2.0); 8.2212 (1.9); 8.1964 (2.0); 8.1943 (1.9); 8.1645 (2.4); 8.1628 (2.6); 8.1434 (2.2); 8.1417 (2.4); 8.1042 (2.0); 7.5603 (1.1); 7.4682 (1.9); 7.4561 (1.8); 7.4481 (1.8); 7.4361 (2.0); 7.4306 (2.6); 7.3008 (1.3); 5.8937 (1.0); 5.8761 (1.5); 5.8584 (1.0); 4.0394 (0.4); 4.0216 (0.4); 3.3419 (86.7); 2.5281 (0.9); 2.5234 (1.4); 2.5146 (15.0); 2.5102 (31.4); 2.5057 (41.9); 2.5011 (30.0); 2.4967 (14.2); 1.9913 (1.8); 1.7261 (5.3); 1.7089 (5.3); 1.3966 (16.0); 1.1943 (0.5); 1.1765 (1.0); 1.1587 (0.5); −0.0002 (0.7)
566.1





I-37


embedded image


I-37: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.2760 (3.2); 9.2577 (3.3); 9.0706 (5.2); 9.0651 (5.2); 8.5675 (3.7); 8.5618 (3.6); 8.5464 (4.0); 8.5407 (4.1); 8.3995 (3.5); 8.3961 (4.2); 8.3876 (3.8); 8.3841 (4.2); 8.2421 (3.7); 8.2386 (4.0); 8.2221 (4.1); 8.2186 (4.2); 8.1426 (5.6); 8.1214 (5.1); 7.8876 (5.7); 7.7347 (4.5); 7.7171 (4.5); 7.4630 (3.8); 7.4510 (3.6); 7.4430 (3.6); 7.4310 (3.6); 5.8937 (0.4); 5.8766 (2.1); 5.8590 (3.2); 5.8414 (2.2); 5.8240 (0.5); 5.7621 (10.3); 3.3434 (55.4); 2.5300 (0.7); 2.5253 (1.0); 2.5163 (15.6); 2.5121 (33.6); 2.5076 (45.7); 2.5032 (33.8); 2.0546 (7.1); 2.0071 (16.0); 1.9930 (0.6); 1.9594 (8.1); 1.7209 (12.0); 1.7037 (12.0); 1.3956 (1.2); 1.2476 (0.4); 1.2320 (0.4); −0.0002 (0.8)
516.1





I-38


embedded image


I-38: 1H-NMR(600.1 MHz, d6-DMSO): δ = 9.4527 (0.6); 9.4406 (0.6); 9.0998 (1.0); 9.0985 (1.0); 9.0960 (1.0); 9.0947 (1.0); 8.5971 (0.9); 8.5933 (0.9); 8.5831 (1.0); 8.5793 (1.0); 8.4409 (0.7); 8.4383 (0.8); 8.4365 (0.8); 8.4340 (0.7); 8.2885 (0.8); 8.2860 (1.5); 8.2835 (0.8); 8.2606 (0.7); 8.2562 (0.6); 8.2454 (0.8); 8.2410 (0.6); 8.1445 (1.0); 8.1432 (1.0); 8.1305 (1.0); 8.1292 (1.0); 8.0669 (0.7); 8.0657 (0.6); 7.9587 (0.7); 7.9571 (0.6); 5.8441 (0.4); 5.8323 (0.6); 5.8206 (0.4); 3.5231 (0.3); 3.3458 (6.5); 3.3368 (16.0); 3.2228 (0.2); 2.5298 (0.1); 2.5267 (0.1); 2.5236 (0.1); 2.5149 (2.3); 2.5118 (5.1); 2.5087 (7.2); 2.5056 (5.3); 2.5026 (2.4); 1.7199 (2.2); 1.7084 (2.2); 1.6662 (0.1); 1.6547 (0.1); −0.0001 (1.4)
548.1





I-39


embedded image


I-39: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.8386 (0.7); 9.5603 (0.5); 9.5464 (0.5); 9.4507 (4.0); 9.4317 (4.1); 9.3739 (0.4); 9.3714 (0.4); 9.2852 (0.6); 9.2009 (0.5); 9.1981 (0.5); 9.1617 (0.6); 9.0767 (1.4); 8.6246 (7.7); 8.6183 (7.8); 8.6017 (2.1); 8.5446 (0.9); 8.5131 (0.6); 8.4912 (0.4); 8.4705 (0.5); 8.4062 (1.6); 8.3762 (1.5); 8.3187 (1.4); 8.3050 (7.4); 8.2857 (1.3); 8.2471 (16.0); 8.1752 (4.8); 8.1686 (4.6); 8.1539 (5.3); 8.1473 (5.2); 7.8985 (0.3); 7.8797 (0.4); 7.8231 (7.8); 7.8019 (7.0); 7.7714 (0.4); 7.7654 (0.4); 7.7496 (0.5); 7.7423 (0.5); 7.5398 (0.3); 7.4591 (2.9); 7.4462 (2.8); 7.3238 (0.4); 7.2918 (0.7); 7.2685 (0.6); 7.1851 (0.7); 7.0462 (0.4); 5.7551 (0.6); 5.7382 (2.7); 5.7202 (3.8); 5.7023 (2.7); 5.6854 (0.6); 4.5764 (0.3); 4.5591 (0.3); 4.1115 (0.9); 4.0984 (0.9); 3.9729 (1.9); 3.9601 (4.6); 3.7909 (0.4); 3.5683 (0.4); 3.3884 (1.2); 3.3352 (360.3); 3.2693 (0.4); 3.1740
514.3




(5.2); 3.1627 (4.9); 2.6765 (2.8); 2.6720 (3.8);





2.6677 (3.0); 2.5758 (0.4); 2.5568 (0.6); 2.5254





(12.5); 2.5118 (236.1); 2.5076 (466.0); 2.5031





(601.0); 2.4986 (423.1); 2.4944 (198.1); 2.3344





(2.7); 2.3299 (3.7); 2.3256 (2.6); 2.2332 (0.4);





2.2173 (0.4); 1.9094 (0.4); 1.7108 (15.9);





1.6937 (15.8); 1.6289 (1.0); 1.6122 (0.9);





1.5339 (2.0); 1.5160 (2.1); 1.4874 (0.4); 1.4501





(1.4); 1.4324 (1.3); 1.3791 (0.4); 1.3007 (5.6);





1.2590 (1.2); 1.2432 (2.9); 1.2344 (3.6); 1.2272





(2.6); 1.2185 (2.1); 1.2126 (1.6); 1.2067 (1.2);





1.1959 (1.2); 1.1904 (1.1); 1.1747 (0.5); 1.1574





(0.3); 1.0569 (0.4); 1.0476 (0.4); 0.8547 (0.4);





0.0079 (0.5); −0.0002 (11.3); −0.0086 (0.4)






I-40


embedded image


I-40: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.1132 (3.4); 9.0949 (3.6); 9.0846 (5.9); 9.0803 (5.8); 9.0790 (5.6); 8.5862 (4.2); 8.5806 (4.1); 8.5651 (4.6); 8.5595 (4.6); 8.3967 (4.0); 8.3932 (4.6); 8.3848 (4.4); 8.3812 (4.6); 8.2321 (4.2); 8.2286 (4.4); 8.2121 (4.7); 8.2086 (4.5); 8.1574 (5.9); 8.1373 (5.3); 8.1363 (5.4); 7.5967 (0.4); 7.5529 (0.8); 7.4864 (7.3); 7.4578 (4.4); 7.4458 (4.1); 7.4378 (4.1); 7.4316 (0.6); 7.4258 (4.2); 7.3694 (1.6); 7.3601 (12.7); 7.3547 (13.7); 7.3412 (0.4); 7.3031 (15.1); 7.2090 (3.6); 7.2036 (6.3); 7.1983 (3.3); 7.1858 (0.7); 7.1197 (7.7); 7.0934 (0.5); 7.0257 (0.6); 5.8677 (0.5); 5.8506 (2.3); 5.8330 (3.6); 5.8153 (2.3); 5.7980 (0.5); 5.7586 (16.0); 3.3301 (15.4); 2.8644 (1.8); 2.5285 (0.6); 2.5238 (0.9); 2.5150 (14.5); 2.5106 (30.9); 2.5061 (41.7); 2.5015 (30.6); 2.4971 (15.1); 1.7015 (13.0); 1.6843 (13.0); 1.2326 (0.4); 1.2217 (0.4); 1.2169 (0.4); 1.2059 (0.4); 1.1785 (0.4); 1.1184 (0.5)
500.1





I-41


embedded image


I-41: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.2083 (1.5); 9.1902 (1.6); 9.0732 (2.6); 9.0678 (2.6); 8.5792 (1.9); 8.5735 (1.9); 8.5582 (2.1); 8.5524 (2.1); 8.3939 (1.9); 8.3904 (2.2); 8.3820 (2.1); 8.3784 (2.2); 8.2346 (2.0); 8.2310 (2.0); 8.2145 (2.2); 8.2109 (2.1); 8.1425 (2.8); 8.1214 (2.6); 7.9105 (1.9); 7.9067 (3.6); 7.9031 (2.4); 7.8610 (2.2); 7.6069 (2.2); 7.4579 (2.1); 7.4458 (2.0); 7.4378 (2.0); 7.4258 (2.0); 5.8418 (1.1); 5.8242 (1.7); 5.8065 (1.1); 3.3224 (406.8); 2.6793 (0.8); 2.6750 (1.7); 2.6704 (2.4); 2.6659 (1.8); 2.6617 (0.8); 2.5408 (1.8); 2.5239 (7.0); 2.5192 (10.0); 2.5105 (133.4); 2.5060 (278.8); 2.5015 (374.2); 2.4969 (271.0); 2.4925 (130.9); 2.3374 (0.8); 2.3328 (1.6); 2.3283 (2.3); 2.3238 (1.7); 2.3193 (0.8); 2.0738 (16.0); 1.6925 (6.4); 1.6753 (6.4); 0.1459 (0.7); 0.0080 (4.8); −0.0002 (159.4); −0.0084 (5.3); −0.1497 (0.7)
530.0





I-42


embedded image


I-42: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.2959 (2.8); 9.2776 (2.9); 9.0820 (5.3); 9.0781 (4.9); 9.0764 (5.0); 8.5789 (4.0); 8.5732 (3.8); 8.5578 (4.4); 8.5521 (4.3); 8.3993 (3.8); 8.3956 (4.2); 8.3874 (4.1); 8.3837 (4.1); 8.3149 (0.4); 8.2369 (4.0); 8.2333 (4.0); 8.2168 (6.5); 8.2132 (7.9); 8.2047 (7.2); 8.2011 (8.1); 8.1599 (5.6); 8.1388 (5.1); 7.9208 (4.2); 7.4612 (4.0); 7.4492 (3.8); 7.4411 (3.8); 7.4292 (3.9); 5.8789 (0.5); 5.8615 (2.0); 5.8442 (3.3); 5.8264 (2.2); 5.8095 (0.4); 3.9083 (0.4); 3.4136 (0.4); 3.3858 (0.6); 3.3628 (1.1); 3.3214 (920.5); 3.2659 (0.3); 2.6790 (2.5); 2.6748 (5.1); 2.6702 (7.1); 2.6656 (5.2); 2.6611 (2.4); 2.6288 (0.4); 2.6101 (0.4); 2.6018 (0.5); 2.5942 (0.5); 2.5406 (3.2); 2.5237 (23.0); 2.5189 (35.7); 2.5102 (416.2); 2.5058 (839.8); 2.5012 (1105.7); 2.4967 (789.7); 2.4922 (373.2); 2.4475 (0.6); 2.4209 (0.3); 2.3371 (2.2); 2.3326 (4.9); 2.3281 (6.8); 2.3235 (4.9); 2.3190 (2.3); 2.0737 (16.0);
477.1




1.7019 (12.0); 1.6847 (12.1); 1.2364 (0.4);





0.1458 (2.2); 0.0080 (18.4); −0.0002 (522.6);





−0.0085 (16.8); −0.1498 (2.2)






I-43


embedded image


I-43: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.8445 (1.3); 9.8257 (1.4); 9.0854 (2.3); 9.0799 (2.2); 8.7650 (6.2); 8.7611 (6.4); 8.5800 (1.6); 8.5741 (1.6); 8.5588 (1.8); 8.5532 (1.9); 8.4671 (2.9); 8.4090 (1.6); 8.4054 (1.8); 8.3970 (1.7); 8.3934 (1.8); 8.3156 (0.4); 8.2409 (1.7); 8.2375 (1.8); 8.2210 (1.8); 8.2174 (1.8); 8.1804 (2.4); 8.1585 (2.2); 7.6261 (2.0); 7.4963 (4.6); 7.4685 (1.6); 7.4563 (1.7); 7.4484 (1.6); 7.4364 (1.6); 7.3665 (2.3); 5.9141 (0.9); 5.8966 (1.6); 5.8791 (1.1); 3.6141 (0.4); 3.5141 (0.4); 3.4882 (0.5); 3.4526 (0.5); 3.4475 (0.5); 3.4109 (0.6); 3.3869 (1.0); 3.3650 (1.6); 3.3211 (1387.0); 3.2692 (0.7); 3.2391 (0.4); 3.2209 (0.3); 2.7113 (0.3); 2.6932 (0.6); 2.6747 (7.9); 2.6701 (10.9); 2.6656 (8.2); 2.6610 (4.1); 2.6310 (0.6); 2.5956 (0.7); 2.5910 (0.7); 2.5405 (13.1); 2.5236 (33.6); 2.5189 (48.8); 2.5101 (627.5); 2.5057 (1288.4); 2.5012 (1714.4); 2.4967 (1244.2); 2.4923 (607.5); 2.4181 (0.5); 2.4128 (0.4);
596.1




2.3980 (0.4); 2.3369 (3.4); 2.3327 (7.5); 2.3279





(10.6); 2.3235 (7.8); 2.0857 (0.4); 2.0736





(16.0); 1.7383 (5.2); 1.7212 (5.1); 1.3575 (0.4);





1.3367 (0.4); 1.2368 (0.4); 0.1459 (3.5); 0.0278





(0.5); 0.0079 (24.6); −0.0002 (786.1); −0.0085





(27.4); −0.0219 (1.2); −0.1497 (3.4)






I-44


embedded image


I-44: 1H-NMR(400.2 MHz, d6-DMSO): δ = 9.2979 (3.9); 9.2795 (4.0); 9.0678 (6.9); 9.0637 (6.5); 9.0623 (6.8); 8.5633 (4.9); 8.5577 (4.8); 8.5422 (5.5); 8.5366 (5.5); 8.3923 (4.8); 8.3887 (5.5); 8.3803 (5.2); 8.3767 (5.4); 8.2309 (5.0); 8.2274 (5.3); 8.2110 (5.5); 8.2074 (5.4); 8.1465 (7.3); 8.1254 (6.8); 8.0194 (13.4); 7.9041 (6.0); 7.4554 (5.1); 7.4434 (4.9); 7.4353 (5.0); 7.4233 (5.0); 7.2820 (5.7); 7.1434 (13.2); 7.0049 (6.2); 5.8966 (0.6); 5.8797 (2.8); 5.8621 (4.3); 5.8445 (2.8); 5.8261 (0.6); 3.3651 (1.0); 3.3209 (929.8); 3.2645 (0.4); 2.6747 (5.2); 2.6702 (7.5); 2.6656 (5.4); 2.6612 (2.7); 2.6126 (0.5); 2.5406 (12.1); 2.5237 (22.6); 2.5190 (32.8); 2.5101 (420.1); 2.5057 (871.4); 2.5012 (1168.6); 2.4967 (851.3); 2.4922 (414.9); 2.4396 (0.7); 2.4161 (0.4); 2.3371 (2.4); 2.3325 (5.2); 2.3281 (7.3); 2.3236 (5.4); 2.0738 (7.6);
468.1




1.7042 (16.0); 1.6870 (16.0); 1.3562 (0.3);





0.1458 (2.0); 0.0080 (15.1); −0.0002 (501.7);





−0.0085 (17.0); −0.0226 (0.5); −0.1497 (2.1)






1)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing.



2)‘lowT’ denotes that the measurement was conducted at a temperature of 260 Kelvin.



3)The stated mass corresponds to the peak from the isotope pattern of the [M + H]+ ion with the highest intensity. # denotes that the [M − H]− ion was recorded.













TABLE 2







Intermediates













ESI


Ex-


Mass


ample
Structure1)
NMR Peak List2)
(m/z)3)





INT-1


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1H-NMR(400.2 MHz, d6-DMSO) δ = 9.18-9.17 (dd, 1H), 8.79-8.78 (bd, 2H, NH2), 8.73-8.71 (dd, 1H), 8.53-8.50 (m, 2H), 8.33-8.31 (dd, 1H), 7.56-7.53 (dd, 1H), 5.27-5.18 (m, 1H), 1.62-1.60 (d, 3H).
265.2 [amine + H+]





INT-2


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274.1 [amine + H+]





INT-3


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279.2 [amine + H+]





INT-4


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1H-NMR(400.2 MHz, d6-DMSO): δ = 9.1796 (1.2); 9.1750 (1.3); 8.8275 (0.4); 8.8230 (0.4); 8.7908 (1.2); 8.7008 (0.8); 8.6950 (0.8); 8.6794 (0.9); 8.6737 (0.9); 8.5309 (0.9); 8.5276 (1.0); 8.5190 (0.9); 8.5156 (0.9); 8.4508 (1.3); 8.4296 (1.1); 8.3292 (0.9); 8.3260 (0.9); 8.3092 (1.0); 8.3058 (1.0); 8.2873 (0.3); 7.5529 (0.8); 7.5409 (0.8); 7.5328 (0.8); 7.5208 (0.8); 5.2145 (0.4); 3.9582 (7.5); 3.8679 (2.0); 3.8383 (0.6); 3.8208 (0.7); 3.8039 (0.5); 3.7965 (0.5); 3.7717 (0.5); 3.7562 (0.9); 3.7336 (0.4); 3.7155 (0.4); 3.7119 (0.4); 3.7016 (0.4); 3.6804 (0.4); 3.5683 (16.0); 2.5083 (28.6); 2.5040 (37.1); 2.4997 (28.0); 1.6206 (3.0); 1.6038 (3.0); 1.5085 (0.6); 1.4910 (0.6); 1.2336 (0.7); −0.0002 (3.9)
298.4 [amine + H+]





INT-5


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279.2 [amine + H+]





INT-6


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279.2 [amine + H+]





INT-7


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1H-NMR(400.2 MHz, d6-DMSO): δ = 11.4123 (1.2); 10.8503 (1.4); 9.7021 (1.8); 9.1542 (2.0); 8.8940 (2.9); 8.8877 (3.0); 8.8240 (2.8); 8.8082 (1.7); 8.7846 (1.1); 8.7691 (1.2); 8.5805 (1.4); 8.5738 (1.4); 8.4838 (1.1); 8.4681 (3.8); 8.4620 (3.4); 8.4465 (1.8); 8.4401 (1.9); 8.1636 (1.8); 8.1475 (1.7); 8.0652 (2.7); 8.0437 (2.6); 8.0400 (1.5); 8.0330 (1.0); 8.0175 (1.2); 8.0109 (1.2); 7.8842 (1.6); 7.8620 (1.2); 4.8996 (0.7); 4.4357 (0.4); 4.4219 (0.5); 4.4066 (0.4); 3.1666 (8.4); 2.5294 (0.9); 2.5118 (28.6); 2.5074 (37.6); 2.5030 (28.4); 2.0791 (16.0); 1.5839 (6.0); 1.5665 (7.4); 1.5461 (3.4)
274.3 [amine + H+]





INT-8


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1H-NMR (600.1 MHz, d6-DMSO): δ = 8.8227 (1.9); 8.8220 (1.9); 8.8184 (2.0); 8.8176 (1.9); 8.7373 (1.4); 8.7313 (1.4); 8.6617 (0.1); 8.6299 (0.1); 8.6251 (0.1); 8.5961 (1.6); 8.5937 (1.7); 8.5883 (1.8); 8.5858 (1.7); 8.4440 (0.1); 8.3713 (1.7); 8.3669 (1.6); 8.3570 (1.8); 8.3526 (1.7); 8.3167 (0.2); 8.2605 (0.2); 8.2498 (0.2); 8.2288 (0.1); 8.2119 (0.1); 8.1415 (0.2); 8.1378 (0.4); 8.1266 (0.2); 8.1222 (0.1); 8.0741 (1.6); 8.0716 (1.7); 8.0604 (1.8); 8.0579 (1.8); 7.9260 (2.2); 7.9252 (2.1); 7.9117 (2.1); 7.9109 (2.0); 7.7110 (0.1); 7.7065 (0.1); 7.6963 (0.1); 7.6917 (0.1); 7.4599 (1.6); 7.4520 (1.6); 7.4462 (1.6); 7.4383 (1.6); 4.9961 (0.2); 4.9873 (0.4);
274.3 [amine + H+]




4.9778 (0.5); 4.9671 (0.4); 4.9570 (0.2); 4.7158





(1.1); 4.5296 (0.1); 4.5224 (0.1); 4.5145 (0.1);





4.3305 (0.1); 4.0693 (0.2); 3.7756 (0.2); 3.7713





(0.1); 3.7681 (0.2); 3.7650 (0.1); 3.7606 (0.1);





3.7139 (0.7); 3.6822 (0.1); 3.6743 (0.1); 3.6664





(0.1); 3.5698 (16.0); 3.3937 (0.1); 3.0159 (1.1);





2.8890 (1.0); 2.6922 (4.5); 2.6205 (0.2); 2.6174





(0.3); 2.6144 (0.2); 2.5564 (0.1); 2.5471 (0.2);





2.5378 (0.2); 2.5264 (0.7); 2.5233 (0.8); 2.5202





(0.8); 2.5115 (14.5); 2.5085 (32.2); 2.5054





(45.2); 2.5023 (32.4); 2.4993 (14.8); 2.3924





(0.2); 2.3893 (0.3); 2.3862 (0.2); 1.9102 (0.3);





1.5564 (5.1); 1.5450 (5.1); 1.5359 (0.5); 1.4161





(0.3); 1.4045 (0.3); 1.3942 (0.2); 1.3822 (0.2);





1.3577 (0.3); 1.3088 (0.5); 1.2973 (0.5); 1.2365





(0.4); 1.1125 (0.2); 1.0446 (0.2); 1.0345 (0.2);





0.0968 (0.3); 0.0054 (2.1); −0.0001 (72.5);





−0.0057 (2.3); −0.1003 (0.3)






1)‘abs’ denotes that the compound was obtained in an enantiomerically enriched or pure form with the major stereoisomer having the absolute configuration depicted in the drawing.



2)‘lowT’ denotes that the measurement was conducted at a temperature of 260 Kelvin.



3)The stated mass corresponds to the peak from the isotope pattern of the [M + H]+ ion with the highest intensity. # denotes that the [M − H]− ion was recorded.






Biological Examples

Rhipicephalus (Boophilus) Microplus—In-Vitro Contact Tests Larval Cattle Tick (Strain Parkhurst, Resistant Against Synthetic Pyrethroids)

9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm2 and a homogeneous distribution, a dose of 5 μg/cm2 is achieved.


After the solvent has evaporated, each test tube is filled with 20-50 cattle tick larvae (Rhipicephalus microplus), closed with a perforated lid and incubated in a horizontal position at 85% relative humidity and 27° C. in an incubator. After 48 hours efficacy is determined. The larvae are patted on the ground of the tubes and negative geotactic behavior is recorded. Larvae that climb back to the top of the vial in a manner comparable to untreated control larvae are marked as alive, larvae not climbing back up comparable to untreated control larvae but are moving uncoordinatedly or only twitching their legs are marked as moribund, tick larvae remaining on the bottom and not moving at all are counted as dead.


A compound shows a good efficacy against Rhipicephalus microplus, if at a compound concentration of 5 μg/cm2 an efficacy of at least 80% is monitored. An efficacy of 100% means all larvae are dead or moribund; 0% means no larvae are dead or moribund.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 5 μg/cm2 (=500 g/ha): I-2.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 5 μg/cm2 (=500 g/ha): I-3.


In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 5 μg/cm2 (=500 g/ha): I-1.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 μg/cm2 (=100 g/ha): 1-2, 1-8, 1-14, 1-15, 1-16, 1-31.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 1 μg/cm2 (=100 g/ha): I-1, 1-3, 1-6, 1-7, I-11, I-13.


In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm2 (=100 g/ha): I-9.



Rhipicephalus (Boophilus) Microplus—Injection Test





    • Solvent: Dimethyl Sulfoxide





To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with solvent to the desired concentration.


Five adult engorged female ticks (Rhipicephalus microplus) are injected with 1 μL compound solution into the abdomen. The ticks are transferred into replica plates and incubated in a climate chamber.


After 7 days egg deposition of fertile eggs is monitored. Eggs where fertility is not visible are stored in a climate chamber till hatching after about 42 days. An efficacy of 100% means all eggs are infertile; 0% means all eggs are fertile.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 4 μg/tick: I-1, I-2, I-3.



Ctenocephalides felis—Oral Test

    • Solvent: Dimethyl Sulfoxide


To produce a suitable preparation of active compound, 10 mg of active compound are dissolved in 0.5 mL solvent, and the concentrate is diluted with citrated cattle blood to the desired concentration.


Approximately 20 adult unfed cat fleas (Ctenocephalides felis) are placed in a flea chamber whose top and bottom is covered with gauze. A chamber whose bottom is sealed with parafilm, is filled with the blood-compound solution and placed on top of the flea chamber, so that the fleas can suck the blood. The blood chamber is heated to 37° C. whereas the flea chamber is kept at room temperature.


After 2 days mortality in % is determined. 100% means all the fleas have been killed; 0% means none of the fleas have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-1.



Ctenocephalides felis—In-Vitro Contact Tests Adult Cat Flea


9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm2 and a homogeneous distribution, a dose of 5 μg/cm2 is achieved.


After the solvent has evaporated, each test tube is filled with 5-10 adult cat fleas (Ctenocephalides felis), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity.


After 48 hours efficacy is determined. The fleas are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving fleas, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.


A compound shows a good efficacy against Ctenocephalides felis, if at a compound concentration of 5 μg/cm2 an efficacy of at least 80% is monitored. An efficacy of 100% means all fleas are dead or moribund; 0% means no fleas are dead or moribund.


In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm2 (=100 g/ha): I-15.



Rhipicephalus sanguineus—In-Vitro Contact Tests with Adult Brown Dog Ticks


9 mg compound is solved in 1 mL acetone and diluted with acetone to the desired concentration. 250 μL of the test solution is filled in 25 mL glass test tubes and homogeneously distributed on the inner walls by rotation and tilting on a shaking device (2 h at 30 rpm). With a compound concentration of 900 ppm, an inner surface of 44.7 cm2 and a homogeneous distribution, a dose of 5 μg/cm2 is achieved.


After the solvent has evaporated, each test tube is filled with 5-10 adult brown dog ticks (Rhipicephalus sanguineus), closed with a perforated lid and incubated in a lying position at room temperature and relative humidity. After 48 hours efficacy is determined. The ticks are patted on the ground of the tubes and are incubated on a heating plate at 45-50° C. for at most 5 minutes. Immotile or uncoordinated moving ticks, which are not able to escape the heat by climbing upwards, are marked as dead or moribund.


A compound shows a good efficacy against Rhipicephalus sanguineus, if at a compound concentration of 5 μg/cm2 an efficacy of at least 80% is monitored. An efficacy of 100% means all ticks are dead or moribund; 0% means no ticks are dead or moribund.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 1 μg/cm2 (=100 g/ha): I-17.


In this test, for example, the following compounds from the preparation examples showed good activity of 80% at an application rate of 1 μg/cm2 (=100 g/ha): I-8, I-13, I-15.



Aphis gossypii—Oral Test

    • Solvent: 100 Parts by Weight Acetone


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.


50 μL compound solution is filled in microtiter plates and 150 μL IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 μL per well. Afterwards the plates are sealed with parafilm through which a mixed population of the cotton aphid (Aphis gossypii) can suck on the compound preparation.


After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 ppm: I-4, I-5, I-7, I-9, I-10, I-24, I-27.


Diabrotica Balteata—Spray Test





    • Solvent: 78.0 Parts by Weight of Acetone
      • 1.5 parts by weight of dimethylformamide

    • Emulsifier: Alkylarylpolyglycol Ether





To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.


Soaked wheat seeds (Triticum aestivum) are placed in a multiple well plate filled with agar and some water and are incubated for 1 day to germinate (5 seeds per well). The germinated wheat seeds are sprayed with a test solution containing the desired concentration of the active ingredient. Afterwards each unit is infected with 10-20 larvae of the banded cucumber beetle (Diabrotica balteata).


After 7 days efficacy in % is determined. 100% means all the seedlings have grown up like in the untreated, uninfected control; 0% means none of the seedlings have grown.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha (=32 μg/well): I-1, I-3, I-4, I-8, I-9, I-11, I-12, I-15, I-16, I-31, I-34, I-35, I-36, I-37, I-38, I-39, I-40, I-41.


Meloidogyne Incognita—Test





    • Solvent: 125.0 parts by weight of acetone





To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.


Vessels are filled with sand, a solution of the active ingredient, a suspension containing eggs and larvae of the southern root-knot nematode (Meloidogyne incognita) and lettuce seeds. The lettuce seeds germinate and the seedlings grow. Galls develop in the roots.


After 14 days the nematicidal effect in percent is determined by the formation of galls. 100% means no galls were found and 0% means the number of galls found on the roots of the treated plants was equal to that in untreated control plants.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 20 ppm: I-25, I-27, I-38.



Myzus persicae—Oral Test

    • Solvent: 100 parts by weight acetone


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water to the desired concentration.


50 μL compound solution is filled in microtiter plates and 150 μL IPL41 insect medium (33%+15% sugar) is added to obtain a total volume of 200 μL per well. Afterwards the plates are sealed with parafilm through which a mixed population of the green peach aphid (Myzus persicae) can suck on the compound preparation.


After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 20 ppm: I-4, I-5, I-7, I-9, 1-10, 1-24, I-27.



Myzus persicae—Spray Test

    • Solvent: 78.0 parts by weight acetone
      • 1.5 parts by weight dimethylformamide
    • Emulsifier: alkylarylpolyglycol ether


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.


Chinese cabbage (Brassica pekinensis) leaf disks infected with all instars of the green peach aphid (Myzus persicae), are sprayed with a preparation of the active ingredient of the desired concentration.


After 5 days mortality in % is determined. 100% means all aphids have been killed and 0% means none of the aphids have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-9.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-3, I-35.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 100 g/ha: I-6, I-15, I-26, I-31.



Nezara viridula—Spray Test

    • Solvent: 78.0 parts by weight of acetone
      • 1.5 parts by weight of dimethylformamide
    • Emulsifier: alkylarylpolyglycol ether


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvent, and the concentrate is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.


Barley plants (Hordeum vulgare) are sprayed with a test solution containing the desired concentration of the active ingredient and are infested with larvae of the southern green stink bug (Nezara viridula).


After 4 days mortality in % is determined. 100% means all the stink bugs have been killed; 0% means none of the stink bugs have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-3, I-4, I-5, I-10, I-12, I-25, I-28, I-30, I-31, I-38, I-39.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: I-29.



Nilaparvata lugens—Spray Test

    • Solvent: 78.0 parts by weight of acetone
      • 1.5 parts by weight of dimethylformamide
    • Emulsifier: alkylarylpolyglycol ether


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.


Rice plants (Oryza sativa) are sprayed with a preparation of the active ingredient of the desired concentration and the plants are infested with the brown planthopper (Nilaparvata lugens).


After 4 days mortality in % is determined. 100% means all planthoppers have been killed and 0% means none of the planthoppers have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 500 g/ha: I-1, I-26.


In this test, for example, the following compounds from the preparation examples showed good activity of 90% at an application rate of 500 g/ha: 1-3, 1-4, 1-15, 1-40.



Spodoptera frugiperda—Spray Test

    • Solvent: 78.0 parts by weight acetone
      • 1.5 parts by weight dimethylformamide
    • Emulsifier: alkylarylpolyglycol ether


To produce a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amount of solvents and is diluted with water, containing an emulsifier concentration of 1000 ppm, to the desired concentration. Further test concentrations are prepared by dilution with emulsifier containing water.


Maize (Zea mays) leaf sections are sprayed with a preparation of the active ingredient of the desired concentration. Once dry, the leaf sections are infested with fall armyworm larvae (Spodoptera frugiperda).


After 7 days mortality in % is determined. 100% means all caterpillars have been killed and 0% means none of the caterpillars have been killed.


In this test, for example, the following compounds from the preparation examples showed good activity of 100% at an application rate of 100 g/ha: I-1, I-2, I-3, I-4, I-5, I-6, I-7, I-8, I-9, I-10, I-11, I-12, I-15, I-16, I-20, I-23, I-31, I-32, I-33, I-34, I-35, I-36, I-37, I-38, I-40, I-41, I-42.


In this test, for example, the following compounds from the preparation examples showed good activity of 83% at an application rate of 100 g/ha: I-14, I-44.



Aedes aegypti Test (AEDSAE Surface Treatment & Contact Assay)

    • Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)


In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Aedes aegypti strain MONHEIM are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m2: I-1, I-2, I-3, I-7, I-8, I-10, I-11, I-14, I-15, I-16, I-24, I-26, I-31, I-35, I-40.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m2: I-3, I-4, I-6, I-10, I-15, I-16, I-24, I-27, I-31, I-35, I-40.



Culex quinquefasciatus Test (CULXFA Surface Treatment & Contact Assay)

    • Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)


In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2,000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult mosquitoes of the species Culex quinquefasciatus strain P00 are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m2: I-3, I-15, I-24, I-31, I-35.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m2: I-3, I-10, I-24, I-33.



Musca domestica Test (MUSCDO Surface Treatment & Contact Assay)

    • Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)


In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult flies of the species Musca domestica strain WHO-N are placed onto the dried surface. The exposure time is 30 minutes. Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m2: I-1, I-2, I-3, I-8, I-9, I-11, I-14, I-15, I-16, I-31, I-35, I-40.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 4 mg/m2: I-3, I-11, I-15, I-16, I-31, I-35, I-40.



Blattella germanica Test (BLTTGE Surface Treatment & Contact Assay)

    • Solvent: Aceton+2000 ppm rapeseed oil methyl ester (RME)


In order to produce a sufficient, active ingredient containing solution it is necessary to solve the test compound in the solvent-mix (acetone at 2 mg/ml/RME 2000 ppm). This solution is pipetted onto a glazed tile and after evaporation of the acetone, adult animals of the species Blattella germanica strain PAULINIA are placed onto the dried surface. The exposure time is 30 minutes.


Mortality in percent (%) is determined 24 hours after contact of the insects to the treated surface. 100% mortality means that all tested insects are dead, whereas 0% means that no insect died.


The following examples showed in this test efficacy of 80-100% at a surface concentration of 20 mg/m2: I-31.

Claims
  • 1. A compound of general formula (I)
  • 2. The compound according to claim 1, in which X is O or S;A1 is N or CR5;A2 is N or CR5;A3 is N or CR5;A4 is N or CR5; wherein one or two of A1, A2, A3, A4 represents a nitrogen (N);R1 is hydrogen; or C1-C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkylC1-C6 alkyl, each of which is optionally substituted by a group selected from halogen, —CN, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, C1-C3 alkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl and C1-C3 alkylsulfonyl; orC2-C6 alkenyl, C2-C6 haloalkenyl, C2-C6 alkynyl, C2-C6 haloalkynyl; orphenyl-C1-C3 alkyl, in which phenyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl; orheterocyclyl-C1-C3 alkyl, wherein the heterocyclyl is selected from the group consisting of saturated and partially unsaturated 3- to 10-membered heterocyclyl, 5-membered heteroaryl, 6-membered heteroaryl, 9-membered heteroaryl and 10-membered heteroaryl and the heterocyclyl is optionally substituted with 1 to 5 substituents, each independently selected from the group consisting of halogen, —CN, —NO2, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, and C1-C3 haloalkylsulfonyl;R2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole, each of which is optionally substituted with 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —NO2, —NH2, —SO2NH2, —SF5;C1-C6 alkyl, optionally substituted with —CN, —OH or C3-C6 cycloalkyl; C2-C6 alkenyl, optionally substituted with halogen and —CN; C2-C6 alkynyl, optionally substituted with halogen and —CN; C3-C6 cycloalkyl, optionally substituted with halogen, —CN, C1-C3 alkyl or C1-C3 haloalkyl; C1-C6 haloalkyl, optionally substituted with —CN or C1-C6 alkoxy; C1-C6 alkoxy, optionally substituted with —CN; C3-C6 cycloalkoxy, optionally substituted with halogen or —CN; C1-C6 haloalkoxy, —CO2C1-C6 alkyl, —NH(C1-C6 alkyl), —N(C1-C6 alkyl)2, S—C1-C6 alkylsulfinimidoyl, S—C3-C6 cycloalkylsulfinimidoyl, S—C2-C6 alkenylsulfinimidoyl, S—C2-C6 alkinylsulfinimidoyl, S-phenylsulfinimidoyl, S-heterocyclylsulfinimidoyl, S-heteroarylsulfinimidoyl, S—C1-C6 alkylsulfonimidoyl, S—C3-C6 cycloalkylsulfonimidoyl, S—C2-C6 alkenylsulfonimidoyl, S—C2-C6 alkinylsulfonimidoyl, S-phenylsulfonimidoyl, S-heterocyclylsulfonimidoyl, S-heteroarylsulfonimidoyl, —C(═NOC1-C6 alkyl)H, —C(═NOC1-C6 alkyl)-C1-C6 alkyl, and (C1-C6 alkyl)3-silyl;and the substructures S1-S9, in which the bond to phenyl, pyridine, pyrimidine, pyrazine, pyridazine, thiophene and pyrazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2;
  • 3. The compound according to claim 1, in which X is O or S;A1 is N;A2 is N or CR5;A3 is N or CR5;A4 is N or CR5; orA1 is N or CR5;A2 is N;A3 is N or CR5;A4 is N or CR5; orA1 is N or CR5;A2 is N or CR5;A3 is N;A4 is N or CR5; orA1 is N or CR5;A2 is N or CR5;A3 is N or CR5;A4 is N; orA1 is N;A2 is N or CR5;A3 is N or CR5;A4 is N;R1 is hydrogen, C1-C6 alkyl, C1-C3 cyanoalkyl, C1-C3 haloalkyl, C3-C6 cycloalkylC1-C3 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C3 alkoxyC1-C3 alkyl, C1-C3 alkylthioC1-C3 alkyl, C1-C3 alkylsulfinylC1-C3 alkyl, or C1-C3 alkylsulfonylC1-C3 alkyl;R2 is selected from the group consisting of phenyl, pyridine, pyrimidine, pyrazine, pyridazine and pyrazole, each of which is optionally substituted by 1, 2 or 3 substituents independently selected from the group consisting of halogen, hydroxy, —CN, —COOH, —CONH2, —NO2, —NH2, —SO2NH2, —SF5, C1-C4 alkyl, C1-C3 haloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C3 alkylthio, C1-C3 alkylsulfinyl, C1-C3 alkylsulfonyl, C3-C6 cycloalkylsulfanyl, C3-C6 cycloalkylsulfinyl, C3-C6 cycloalkylsulfonyl, C1-C3 haloalkylthio, C1-C3 haloalkylsulfinyl, C1-C3 haloalkylsulfonyl, C1-C3 cyanoalkoxy, hydroxy-C1-C4 alkyl, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —NHCO—C1-C4 alkyl, NHCO—C3-C6 cycloalkyl, —NHSO2(C1-C4 alkyl), —N(C1-C4 alkyl)CO—C1-C4 alkyl, —N(C1-C4 alkyl)CO—C3-C6 cyclolkyl, —N(C1-C4 alkyl)SO2C1-C4 alkyl, —N(SO2C1-C4 alkyl)2, —CO2C1-C4 alkyl, —CONH(C1-C4 alkyl), —CONH(C3-C6 cycloalkyl), —CONH-phenyl, —CON(C1-C4 alkyl)2, —CON(C1-C4 alkyl)(C3-C6 cycloalkyl), —CON(C1-C4 alkyl)-phenyl, —C(═NOC1-C4 alkyl)H, —C(═NOC1-C4 alkyl)-C1-C4 alkyl, (C1-C4 alkyl)3-silyl, —SO2NH(C1-C4 alkyl), phenylsulfonyl, and 3- to 6-membered heterocyclyl containing 1 or 2 heteroatoms selected from the group consisting of N, O, and S, wherein phenyl groups of the aforementioned substituents and the 3- to 6-membered heterocyclyl substituent may optionally carry 1, 2 or 3 substituents independently selected from the group consisting of halogen, —CN, C1-C4 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy and C1-C3 haloalkoxy;R3 is hydrogen, C1-C6 alkyl, optionally substituted with 1 to 3 substituents selected from halogen, C3-C6-cycloalkyl, or C1-C6-alkoxy;R4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 or 2 substituents independently selected from the group consisting of halogen, —CN, —COOH, —NO2, —NH2, —SF5, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, and —CO2C1-C6 alkyl, orR4 is selected from the group consisting of pyridine, pyrimidine, pyrazine, pyridazine and thiazole, each of which is optionally substituted by 1 substituent selected from the group consisting of halogen, —CN, —COOH, —NO2, —NH2, —SF5, C1-C6 alkyl, C3-C6 cycloalkyl, C1-C4 alkyl-C3-C6 cycloalkyl, C1-C3 haloalkyl, C1-C3 cyanoalkyl, C3-C6 halocycloalkyl, C3-C6 cyanocycloalkyl, C1-C4 alkoxy, C1-C3 haloalkoxy, C1-C3 cyanoalkoxy, and —CO2C1-C6 alkyl;and each of which is furthermore substituted by 1 substituent selected from the group consisting of following substructures S10-S18, in which the bond to the aforementioned pyridine, pyrimidine, pyrazine, pyridazine and thiazole is marked with a # and Z is CO or CS and Y is independently selected from CO and SO2:
  • 4. The compound according to claim 1, in which X is O or S;A1 is N;A2 is N or CR5;A3 is N or CR5;A4 is N or CR5; orA1 is N or CR5;A2 is N;A3 is N or CR5;A4 is N or CR5; orA1 is N or CR5;A2 is N or CR5;A3 is N;A4 is N or CR5; orA1 is N or CR5;A2 is N or CR5;A3 is N or CR5;A4 is N; orA1 is N;A2 is N or CR5;A3 is N or CR5;A4 is N;R1 is hydrogen, methyl, ethyl, cyclopropylmethyl, methoxymethyl, ethoxymethyl, methoxyethyl, methylthioethyl, methylsulfinylethyl or methylsulfonylethyl;R2 is selected from substructure Q1, Q2 and Q3, in which the bond to the C═X-group is marked with a #:
  • 5. The compound according to claim 1, in which X is O;A1 is N;A2 is CR5;A3 is CR5;A4 is CR5; orA1 is CR5;A2 is CR5;A3 is N;A4 is CR5; orA1 is CR5;A2 is CR5;A3 is CR5;A4 is N;R1 is hydrogen;R2 is selected from the group consisting of 3-chloro-5-(trifluoromethoxy)phenyl, 3-bromo-5-(trifluoromethoxy)phenyl, 3-cyano-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethyl)phenyl, 3,5-bis-(trifluoromethyl)phenyl, 3,5-bis(difluoromethoxy)phenyl, 3,5-bis-(trifluoromethoxy)phenyl, 3-(1,1-difluoroethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyano-1-methyl-ethyl)phenyl, 3-(1-cyano-1-methyl-ethyl)-5-(trifluoromethoxy)phenyl, 3-cyclopropyl-5-(trifluoromethoxy)phenyl, 3-cyano-5-(1-cyanocyclopropyl)phenyl, 3-(1-cyanocyclopropyl)-5-(trifluoromethoxy)phenyl, (3-chloro-5-methylsulfonylphenyl), 3-methylsulfonyl-5-(trifluoromethoxy)phenyl, 3-(difluoromethylsulfonyl)-5-(trifluoromethoxy)phenyl, 3,5-bis(difluoromethylsulfonyl)phenyl and 5-(difluoromethyl)-1-methyl-pyrazol-3-yl;R3 is methyl;R4 is selected from the group consisting of pyrimidin-2-yl, 5-chloro-pyridin-2-yl, 5-cyano-pyridin-2-yl, 5-methoxycarbonyl-2-pyridyl, 5-(aminocarbonyl)pyridin-2-yl, 5-(methylcarbamoyl)pyridin-2-yl, and 5-(dimethylaminocarbonyl)pyridin-2-yl;R5 is selected from hydrogen, fluorine and methyl;and salts and N-oxides thereof.
  • 6. The compound according to claim 1, wherein the compound has a structure according to formula (I-a)
  • 7. The compound according to claim 1, wherein the compound has a structure according to formula (I-b)
  • 8. The compound of claim 1 selected from the group consisting of: 6-[2-[(1S)-1-aminoethyl]imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride,1-[3-(5-chloro-2-pyridyl)imidazo[4,5-b]pyridin-2-yl]ethanamine; 2,2,2-trifluoroacetic acid,6-[2-(1-aminoethyl)-7-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride,methyl 6-[2-(1-aminoethyl)imidazo[4,5-b]pyridin-3-yl]pyridine-3-carboxylate hydrochloride,6-[2-[1-aminoethyl]-6-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride,6-[2-[1-aminoethyl]-5-methyl-imidazo[4,5-b]pyridin-3-yl]pyridine-3-carbonitrile hydrochloride,1-[1-(5-chloro-2-pyridyl)imidazo[4,5-c]pyridin-2-yl]ethanamine hydrochloride, and1-[1-(5-chloropyridin-2-yl)-1H-imidazo[4,5-b]pyridin-2-yl]ethanamine trifluoroacetate.
  • 9. A formulation comprising at least one compound of the formula (I) according to claim 1.
  • 10. The formulation according to claim 9, further comprising at least one extender and/or at least one surface-active substance.
  • 11. The formulation according to claim 9, characterized in that the compound of the formula (I) is in a mixture with at least one further active compound.
  • 12. A method for controlling pests especially-animal-pests to an animal, characterized in that a compound of the formula (I) according to claim 1 is allowed to act on the pests and/or their habitat, wherein methods for treatment of a body of the animal by surgery or therapy and diagnostic methods practised on the animal body are excluded.
  • 13. The method according to claim 12, characterized in that the animal pest comprises an insect, an arachnid or a nematode, or in that the animal pest is an insect, an arachnid or a nematode.
  • 14-18. (canceled)
  • 19. A method for protecting at least one crop plant from pests, the method comprising contacting the at least one crop plant with a compound of the formula (I) according to claim 1.
  • 20. (canceled)
  • 21. The method of claim 19, wherein protecting the at least one crop plant comprises contacting a seed or germinating plant with a compound of the formula (I) according to claim 1.
  • 22. The method of claim 19, wherein the pests are pests to animals.
  • 23. The method of claim 22, wherein the animal pest comprises an insect, an arachnid or a nematode, or in that the animal pest is an insect, an arachnid or a nematode.
  • 24. A seed obtained by the method according to claim 21.
  • 25. A method of controlling a disease vector, the method comprising use of a compound of the formula (I) according to claim 1, or salt thereof.
Priority Claims (1)
Number Date Country Kind
21172570.0 May 2021 EP regional
PCT Information
Filing Document Filing Date Country Kind
PCT/EP2022/061692 5/2/2022 WO