Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution f129l in the mitochondrial cytochrome b protein conferring resistance to qo inhibitors ii

Abstract

The present invention relates to the use of strobilurin type compounds of formula I and the N-oxides and the salts thereof for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein (also referred to as F129L mutation in the mitochondrial cytochrome b gene) conferring resistance to Qo inhibitors, and to methods for combating such fungi. The invention also relates to novel compounds, processes for preparing these compounds, to compositions comprising at least one such compound, and to seeds coated with at least one such compound.

Description

202209 amended pages 1 PCT / EP 2021 / 059 730 - 04.08.2021 Use of strobilurin type compounds for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors II 5 Description The present invention relates the use of strobilurin type compounds of formula I and the N-oxides and the salts thereof for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein (also referred to as F129L muta- 10 tion in the mitochondrial cytochrome b gene) conferring resistance to Qo inhibitors (Qol), and to methods for combating such fungi. The invention also relates to novel compounds, processes for preparing these compounds, to compositions comprising at least one such compound, to plant health applications, and to seeds coated with at least one such compound. The present invention also relates to a method for controlling soybean rust fungi (Phakopsora pachyrhiz1) 15 with the amino acid substitution F129L in the mitochondrial cytochrome b protein. "Qo inhibitor," as used herein, includes any substance that is capable of diminishing and / or inhibiting respiration by binding to a ubihydroquinone oxidation center of a cytochrome bc1 complex in mitochondria. The oxidation center is typically located on the outer side of the inner mitochrondrial membrane. Many of these compounds are also known as strobilurin-type or 20 strobilurin analogue compounds. The mutation F129L in the mitochondrial cytochrome b (CYTB) gene shall mean any substitution of nucleotides of codon 129 encoding "F" (phenylalanine; e.g. TTT or TTC) that leads to a codon encoding "L'' (leucine; e.g. TTA, TTG, TTG, CTT, CTC, CTA or CTG), for example the substitution of the first nucleotide of codon 129 'T' to 'C' (TTT to CTT), in the CYTB (cytochrome 25 b) gene resulting in a single amino acid substitution in the position 129 from F to Lin the cytochrome b protein. Such F129L mutation is known to confer resistance to Qo inhibitors. Qol fungicides, often referred to as strobilurin-type fungicides (Sauter 2007: Chapter 13.2. Strobilurins and other complex Ill inhibitors. In: Kramer, W.; Schirmer, U. (Ed.) - Modern Crop 30 Protection Compounds. Volume 2. Wiley-VCH Verlag 457-495), are conventionally used to control a number of fungal pathogens in crops. Qo inhibitors typically work by inhibiting respiration by binding to a ubihydroquinone oxidation center of a cytochrome bc1 complex (electron transport complex Ill) in mitochondria. Said oxidation center is located on the outer side of the inner mitochrondrial membrane. A prime example of the use of Qols includes the use of, for 35 example, strobilurins on wheat for the control of Septoria tritici (also known as Mycosphaerel / a graminico / a), which is the cause of wheat leaf blotch. Unfortunately, widespread use of such Qols has resulted in the selection of mutant pathogens which are resistant to such Qols (Gisi et al., Pest Manag Sci 56, 833-841, (2000)). Resistance to Qols has been detected in several phytopathogenic fungi such as Blumeria graminis, Mycosphaerella fijiensis, Pseudoperonspora 40 cubensis or Venturia inaequalis. The major part of resistance to Qols in agricultural uses has been attributed to pathogens containing a single amino acid residue substitution G143A in the cytochrome b gene for their cytochrome bc1 complex, the target protein of Qols which have been found to be controlled by specific Qols (WO 2013 / 092224). Despite several commercial Qol fungicides have also been widely used in soybean rust control, the single amino acid 45 residue substitution G143A in the cytochrome b protein conferring resistance to Qol fungicides was not observed. Instead soybean rust acquired a different genetic mutation in the cytochrome b gene causing CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 2 PCT / EP 2021 / 059 730 - 04.08.2021 a single amino acid substitution F129L which also confers resistance against Qol fungicides. The efficacy of Qol fungicides used against soybean rust conventionally, i.e. pyraclostrobin, azoxystrobin, picoxystrobin, orysastrobin, dimoxystrobin and metominostrobin, has decreased to a level with practical problems for agricultural practice (e.g. Klosowski et al (2016) Pest 5 Manag Sci 72, 1211-1215). Although it seems that trifloxystrobin was less affected by the F129L amino acid substitution to the same degree as other Qol fungicides such as azoxystrobin and pyraclostrobin, trifloxystrobin was never as efficacious on a fungal population bearing the F129L Qol resistance mutation as on a sensitive population (Crop Protection 27, (2008) 427-435). 10 WO 2017 / 157923 discloses the use of the tetrazole compound 1-[2-[[1-(4-chlorophenyl)- pyrazol-3-yl]oxymethyl]-3-methylphenyl]-4-methyltetrazol-5-one for combating phytopathogenic fungi containing said F129L amino acid substitution. Thus, new methods are desirable for controlling pathogen induced diseases in crops comprising plants subjected to pathogens containing a F129L amino acid substitution in the 15 mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. Furthermore, in many cases, in particular at low application rates, the fungicidal activity of the known fungicidal strobilurin compounds is unsatisfactory, especially in case that a high proportion of the fungal pathogens contain a mutation in the mitochondrial cytochrome b gene conferring resistance to Qo inhibitors. Besides there is an ongoing need for new fungicidally active compounds which 20 are more effective, less toxic and / or environmentally safer. Based on this, it was also an object of the present invention to provide compounds having improved activity and / or a broader activity spectrum against phytopathogenic fungi and / or even further reduced toxicity against non target organisms such as vertebrates and invertebrates. The strobilurin-analogue compounds used to combat phytopathogenic fungi containing a 25 F129L amino acid substitution in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors according to the present invention differ from trifloxystrobin inter alia by containing a specific group attached to the central phenyl ring in ortho position to the side chain defined herein as R 3 . 30 Accordingly, the present invention relates to the use of compounds of formula I 35 40 wherein R 1 is selected from O and NH; R 2 is selected from CH and N; I, R 3 is selected from halogen, C 1 -C4-alkyl, C 2 -C4-alkenyl, C 1 -C 2 -monohaloalkyl, C 1 -C 2 -dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C 3 -Cs-cycloalkyl and -O-C1-C4-alkyl; R 4 is selected from C 1 -Cs-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, C 1 -Cs-haloalkyl, C 2 -C4-haloalkenyl, C 2 -C4-haloalkynyl, -C(=O)-C 1 -C4-alkyl, -(C 1 -C 2 -alkyl)-O-(C1-Cz-alkyl), -(C 1 -C2-al- CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 3 PCT / EP 2021 / 059 730 - 04.08.2021 R a is selected from halogen, CN, -NR5R 6 , C1-C4-alkyl, Cz-C4-alkenyl, C2-C4-alkynyl, -O-C1-C4-alkyl, -C(=N-O-C1-C4-alkyl)-C1-C4-alkyl, -C(=O)-C1-C4-alkyl, 5 -O-CH2-C(=N-O-C1-C4-alkyl)-C1-C4-alkyl, C3-C 6 -cycloalkyl, C3-C 6 -cycloalkenyl, -C1-C2-alkyl-C3-C 6 -cycloalkyl, -Q-C3-C 6 -cycloalkyl, phenyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, 0 and S, 10 wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound directly or via an oxygen atom or via a C1-C2-alkylene linker, and wherein the aliphatic and cyclic moieties of R a are unsubstituted or carry 1, 2, 3, 4 or up to the maximum number of identical or different groups R b : R b is selected from halogen, CN, NH2, NO2, C1-C4-alkyl, C1-C4-haloalkyl, -O-C1-C4-alkyl 15 and -O-C1-C4-haloalkyl; R 5 , R 6 are independently of each other selected from the group consisting of H, C1-C 6 -alkyl, C1-C 6 -haloalkyl and C2-C4-alkynyl; 20 n is an integer selected from 0, 1, 2, 3, 4 and 5; and in form or stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof, for combating phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo 25 inhibitors. The mutation F129L in the cytochrome b (cytb, also referred to as cob) gene shall mean any substitution of nucleotides of codon 129 encoding "F" (phenylalanine; e.g. TIT or TTC) that leads to a codon encoding "L" (leucine; e.g. TTA, TTG, TTG, CTT, CTC, CTA or CTG), for 30 example the substitution of the first nucleotide of codon 129 'T' to 'C' (TIT to CTT), in the cytochrome b gene resulting in a single amino acid substitution in the position 129 from F (phenylalanine) to L (leucine) (F129L) in the cytochrome b protein (Cytb). In the present invention, the mutation F129L in the cytochrome b gene shall be understood to be a single amino acid substitution in the position 129 from F (phenylalanine) to L (leucine) (F129L) in the 35 cytochrome b protein. Many other phytopathogenic fungi acquired the F129L mutation in the cytochrome b gene conferring resistance to Qo inhibitors, such as rusts, in particular soybean rust (Phakopsora pachyrhizi and Phakopsora meibromiae) as well as fungi from the genera Alternaria, Pyrenophora and Rhizoctonia. 40 Preferred fungal species are Alternaria solani, Phakopsora pachyrhizi, Phakopsora meibromiae, Pyrenophora teres, Pyrenophora tritici-repentis and Rhizoctonia solani; in particular Phakopsora pachyrhizi. In one aspect, the present invention relates to the method of protecting plants susceptible to and / or under attack by phytopathogenic fungi containing an amino acid substitution F129L in 45 the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors, which method comprises applying to said plants, treating plant propagation material of said plants with, and / or applying to said phytopathogenic fungi, at least one compound of formula I or a composition CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 4 comprising at least one compound of formula I. PCT / EP 2021 / 059 730 - 04.08.2021 According to another embodiment, the method for combating phytopathogenic fungi, comprises: a) identifying the phytopathogenic fungi containing an amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors, or the 5 materials, plants, the soil or seeds that are at risk of being diseased from phytopathogenic fungi as defined herein, and b) treating said fungi or the materials, plants, the soil or plant propagation material with an effective amount of at least one compound of formula I, or a composition comprising it thereof. The term "phytopathogenic fungi an amino acid substitution F129L in the mitochondrial 10 cytochrome b protein conferring resistance to Qo inhibitors" is to be understood that at least 10% of the fungal isolates to be controlled contain a such F129L substitution in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors, preferably at least 30%, more preferably at least 50%, even more preferably at at least 75% of the fungi, most preferably between 90 and 100%; in particular between 95 and 100%. 15 Although the present invention will be described with respect to particular embodiments, this description is not to be construed in a limiting sense. Before describing in detail exemplary embodiments of the present invention, definitions important for understanding the present invention are given. As used in this specification and in 20 the appended claims, the singular forms of "a" and "an" also include the respective plurals unless the context clearly dictates otherwise. In the context of the present invention, the terms "about" and "approximately" denote an interval of accuracy that a person skilled in the art will understand to still ensure the technical effect of the feature in question. The term typically indicates a deviation from the indicated numerical value of ±20 %, preferably ±15 %, more 25 preferably ±1 0 %, and even more preferably ±5 %. It is to be understood that the term "comprising" is not limiting. For the purposes of the present invention the term "consisting of' is considered to be a preferred embodiment of the term "comprising of". Unless otherwise indicated, the following definitions are set forth to illustrate and define the meaning and scope of the various terms used to describe the invention herein and the appen- 30 ded claims. These definitions should not be interpreted in the literal sense as they are not intended to be general definitions and are relevant only for this application. The term "compounds I" refers to compounds of formula I. Likewise, this terminology applies to all sub-formulae, e. g. "compounds 1.2" refers to compounds of formula 1.2 or "compounds V" refers to compounds of formula V, etc .. 35 The term "independently" when used in the context of selection of substituents for a variable, it means that where more than one substituent is selected from a number of possible substituents, those substituents may be the same or different. The organic moieties or groups mentioned in the above definitions of the variables are collective terms for individual listings of the individual group members. The term "C"Cw" indicates the 40 number of carbon atom possible in each case. The term "halogen" refers to fluorine, chlorine, bromine and iodine. The term "C1-C4-alkyl" refers to a straight-chained or branched saturated hydrocarbon group having 1 to 4 carbon atoms, for example, methyl (CH3), ethyl (C2Hs), propyl, 1-methylethyl (isopropyl), butyl, 1-methylpropyl, 2-methylpropyl, 1, 1-dimethylethyl. 45 The term "C2-C4-alkenyl" refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 4 carbon atoms and a double bond in any position such as ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl- CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 5 1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl. PCT / EP 2021 / 059 730 - 04.08.2021 The term "C2-C4-alkynyl" refers to a straight-chain or branched unsaturated hydrocarbon radical having 2 to 4 carbon atoms and containing at least one triple bond such as ethynyl, prop-1-ynyl, prop-2-ynyl, but-1-ynyl, but-2-ynyl, but-3-ynyl, 1-methyl-prop-2-ynyl. 5 The term "C1-C4-haloalkyl" refers to a straight-chained or branched alkyl group having 1 to 4 carbon atoms wherein some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as mentioned above, for example chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-di- 10 fluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2-dichloro- 2-fluoroethyl, 2,2,2-trichloroethyl and pentafluoroethyl, 2-fluoropropyl, 3-fluoropropyl, 2,2-difluoropropyl, 2,3-difluoropropyl, 2-chloropropyl, 3-chloropropyl, 2,3-dichloropropyl, 2-bromopropyl, 3-bromopropyl, 3,3,3-trifluoropropyl, 3,3,3-trichloropropyl, CH2-C2Fs, CF2-C2Fs, CF(CF3)2, 1-(fluoromethyl)-2-fluoroethyl, 1-( chloromethyl)-2-chloroethyl, 1-(bromomethyl)-2-bromoethyl, 15 4-fluorobutyl, 4-chlorobutyl, 4-bromobutyl or nonafluorobutyl. The term "monohalo-ethenyl" refers to an ethenyl wherein one hydrogen atom is replaced by a halogen atom, e.g. 1-chloroethenyl, 1-bromoethenyl, 1-fluoroethenyl, 2-fluoroethenyl. Likewise, dihalo-ethenyl" refers to an ethenyl wherein two hydrogen atoms are replaced by halogen atoms. 20 The term "-O-C1-C4-alkyl" refers to a straight-chain or branched alkyl group having 1 to 4 carbon atoms which is bonded via an oxygen, at any position in the alkyl group, e.g. OCH3, OCH2CH3, O(CH2)2CH3, 1-methylethoxy, O(CH2hCH3, 1-methyl.,propoxy, 2-methylpropoxy or 1, 1-dimethylethoxy. The term "C3-Ce-cycloalkyl" refers to monocyclic saturated hydrocarbon radicals having 3 to 25 6 carbon ring members, such as cyclopropyl (C3Hs), cyclobutyl, cyclopentyl or cyclohexyl. The term "C3-C 6 -cycloalkenyl " refers to monocyclic saturated hydrocarbon radicals having 3 to 6 carbon ring members and one or more double bonds. The term "3- to 6-membered heterocycloalkyl" refers to 3- to 6-membered monocyclic saturated ring system having besides carbon atoms one or more heteroatoms, such as 0, N, S as 30 ring members. The term "C3-Ce-membered heterocycloalkenyl" refers to 3- to 6-membered monocyclic ring system having besides carbon atoms one or more heteroatoms, such as 0, N and S as ring members, and one or more double bonds. The term "-C1-C4-alkyl-C3-Ce-cycloalkyl" refers to alkyl having 1 to 4 carbon atoms (as defined above), wherein one hydrogen atom of the alkyl radical is replaced by a cycloalkyl 35 radical having 3 to 6 carbon atoms. The term "phenyl" refers to CeHs. The term "5- or 6-membered heteroaryl" which contains 1, 2, 3 or 4 heteroatoms from the group consisting of 0, N and S, is to be understood as meaning aromatic heterocycles having 5 or 6 ring atoms. Examples include: 40 5-membered heteroaryl which in addition to carbon atoms, e.g. contain 1, 2 or 3 N atoms and / or one sulfur and / or one oxygen atom: for example 2-thienyl, 3-thienyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl and 1,3,4-triazol-2-yl; 6-membered heteroaryl which, in addition to carbon atoms, e.g. contain 1, 2, 3 or 4 N 45 atoms as ring members, e.g. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl and 2-pyrazinyl. The term "C1-C2-alkylene linker'' means a divalent alkyl group such as -CH2- or -CH2-CHz- CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 6 PCT / EP 2021 / 059 730 - 04.08.2021 that is bound at one end to the core structure of formula I and at the other end to the particular substituent. As used herein, the "compounds", in particular "compounds I" include all the stereoisomeric and tautomeric forms and mixtures thereof in all ratios, prodrugs, isotopic forms, their agricul- 5 turally acceptable salts, N-oxides and S-oxides thereof. The term "stereoisomer" is a general term used for all isomers of individual compounds that differ only in the orientation of their atoms in space. The term stereoisomer includes mirror image isomers (enantiomers), mixtures of mirror image isomers (racemates, racemic mixtures), geometric (cis / trans or E / Z) isomers, and isomers of compounds with more than one chiral 10 center that are not mirror images of one another (diastereoisomers). The term "tautomer'' refers to the coexistence of two (or more) compounds that differ from each other only in the position of one (or more) mobile atoms and in electron distribution, for example, keto-enol tautomers. The term "agriculturally acceptable salts" as used herein, includes salts of the active compounds which are prepared with acids or bases, depending on the particular substituents found on the 15 compounds described herein. "N-oxide" refers to the oxide of the nitrogen atom of a nitrogencontaining heteroaryl or heterocycle. N-oxide can be formed in the presence of an oxidizing agent for example peroxide such as m-chloro-perbenzoic acid or hydrogen peroxide. N-oxide refers to an amine oxide, also known as amine-N-oxide, and is a chemical compound that contains N➔O bond. 20 In respect of the variables, the embodiments of the intermediates correspond to the embodiments of the compounds I. Preference is given to those compounds I and where applicable also to compounds of all sub-formulae provided herein, e. g. formulae 1.1 and 1.2, and to the intermediates such as compounds II, Ill, IV and V, wherein the substituents and variables (such as n, R 1 , R 2 , R 3 , R 4 , 25 R5, R6, R8 , and R b ) have independently of each other or more preferably in combination (any possible combination of 2 or more substituents as defined herein) the following meanings: Preference is also given to the uses, methods, mixtures and compositions, wherein the definitions (such as phytopathogenic fungi, treatments, crops, compounds II, further active ingredients, solvents, solid carriers) have independently of each other or more preferably in 30 combination the following meanings and even more preferably in combination (any possible combination of 2 or more definitions as provided herein) with the preferred meanings of compounds I herein: One embodiment of the invention relates to the abovementioned use and or method of application (herein collectively referred to as "use") of compounds I, wherein R 1 is selected from 35 0 and NH; and R 2 is selected from CH and N, provided that R 2 is N in case R is NH. More preferably R 1 is NH. In particular, R 1 is NH and R 2 is N. Another embodiment relates to the use of compounds I, wherein R 1 is O and R 2 is CH. According to another embodiment, R 3 is selected from halogen, C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 1 -C 2 -monohaloalkyl, C 1 -C 2 -dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C 3 -Cs-cycloalkyl and 40 -O-C -C 4 -alkyl; preferably from halogen, C 1 -C 2 -alkyl, C 1 -Cz-monohaloalkyl, C 1 -C 2 -dihaloalkyl, C 3 -C -cycloalkyl and -O-C 1 -C 2 -alkyl; more preferably from C 1 -C 2 -alkyl, C 1 -Cz-monohaloalkyl, C 1 -C 2 -dihaloalkyl, C 3 -C 4 -cycloalkyl and -O-C1-C 2 -alkyl; even more preferably from halogen, C -C -alkyl, Cz-C -alkenyl, CHF 2 , CFH 2 , -O-C 1 -C -alkyl and cyclopropyl; even more preferably from C 1 -C 2 -alkyl, ethenyl, CHF , CFH , OCH3 and cyclopropyl; particularly preferred from 45 methyl, ethenyl, CHF 2 and CFH 2 ; in particular methyl. According to one embodiment, R 4 is selected from is selected from C1-Cs-alkyl, C 2 -C 4 -alkenyl, -C(=O)-C 1 -C 2 -alkyl, C 1 -Cs-haloalkyl, Cz-C 4 -haloalkenyl, -(C 1 -C 2 -alkyl)-O-(C 1 -C -alkyl) and CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 7 PCT / EP 2021 / 059 730 - 04.08.2021 -CH2-cyclopropyl; more preferably from C1-C4-alkyl, CrC4-alkenyl, -C(=O)-C1-Cralkyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, -(C1-C2-alkyl)-O-(C1-Cralkyl) and -CH2-cyclopropyl; even more preferably from C1-C4-alkyl and C1-C4-haloalkyl, particularly preferably from methyl and C1-haloalkyl; in particular methyl. 5 According to a further embodiment, n is 1, 2, 3, 4 or 5; more preferably n is 1, 2 or 3, even more preferably n is 1 or 2; in particular n is 1. According to a further embodiment, n is 0, 1, 2 or 3, more preferably 0, 1 or 2, in particular 0. According to a further embodiment, n is 2 and the two substituents R a are preferably in positions 2,3 (meaning one substituent in position 2, the other in position 3); 2,4; 2,5; 3,4 or 3,5; 10 even more preferably in positions 2,3 or 2,4. According to a further embodiment, n is 3 and the two substituents R a are preferably in positions 2, 3 and 4. According to a further embodiment, R a is selected from CN, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, -O-C1-C4-alkyl, -C(=O)-C1-C4-alkyl,-C(=N-O-C1-C4-alkyl)-C1-C4-alkyl, 15 -O-CH2-(=N-O-C1-C4-alkyl)-C1-C4-alkyl, -C(=N-O-C1-C4-alkyl)-C(=O-NH-C1-C4-alkyl), C3-Ca-cycloalkyl, C3-Ca-cycloalkenyl, -C1-C2-alkyl-C3-Ca-cycloalkyl, -Q-C3-Ca-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl, 3- to 5-membered heterocycloalkenyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl, hetercycloalkenyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, 0 and S, wherein said phenyl, hetero- 20 cycloalkyl, hetercycloalkenyl and heteroaryl are bound directly or via an oxygen atom or via a C1-C2-alkylene linker, and wherein the aliphatic and cyclic moieties of R a are unsubstituted or carry 1, 2, or 3 of identical or different groups R b which independently of one another are selected from halogen, CN, NH2, NO2, C1-C2-alkyl and C1-C2-haloalkyl. More preferably, R a is selected from CN, C1-C4-alkyl, C2-C4-alkenyl, C2-C4-alkynyl, 25 -O-C1-C4-alkyl, -C(=O)-C1-C2-alkyl,-C(=N-O-C1-C2-alkyl)-C1-C2-alkyl, -O-CH2-C(=N-O-C1-C2-alkyl)- C1-C2-alkyl, -C( =N-O-C1 -Cralkyl)-C(=O-N H-C1 -Cralkyl), C3-C4-cycloalkyl, C3-C4-cycloalkenyl, -C1-C2-alkyl-C3-C4-cycloalkyl, -Q-C3-C4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heterocycloalkyl and heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, 0 and S, 30 wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via an oxygen atom or via a methylene linker, and wherein the aliphatic or cyclic moieties of R a are unsubstituted or carry 1, 2, or 3 of identical or different groups R b which independently of one another are selected from halogen, CN, C1-C2-alkyl and C1-C2-haloalkyl. Even more preferably R a is selected from C1-C3-alkyl, C2-C3-alkenyl, C2-C3-alkynyl, 35 -O-C1-C3-alkyl, -C(=O)-C1-C2-alkyl,-C(=N-O-C1-C2-alkyl)-C1-C2-alkyl, C3-C4-cycloalkyl, -C1-C2-alkyl-C3-C4-cycloalkyl, -Q-C3-C4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, 0 and S, wherein said phenyl and heteroaryl are bound directly or via an oxygen atom or via a methylene linker, and wherein the aliphatic 40 and cyclic moieties of R a are unsubstituted or carry 1, 2 or 3 of identical or different groups R b which independently of one another are selected from halogen, CN, methyl and C1-haloalkyl. Particularly preferred R a are selected from halogen, C1-C4-alkyl, C2-C3-alkenyl, C2-C3-alkynyl, -O-C1-C4-alkyl, -C(=N-O-C1-C2-alkyl)-C1-C2-alkyl and phenyl, wherein the aliphatic or cyclic moieties of R a are unsubstituted or carry 1, 2 or 3 of identical or different groups R b which inde- 45 pendently of one another are selected from halogen, CN, methyl and C1-haloalkyl. According to a further embodiment, R 5 , R 6 are independently of each other preferably CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 8 PCT / EP 2021 / 059 730 - 04.08.2021 selected from the group consisting of H, C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl and Cz-C 4 -alkynyl, more preferably from H and C 1 -C4-alkyl. According to a further preferred embodiment, the present invention relates to the use of 5 compounds of formula I wherein: R 1 is selected from O and NH; and R 2 is selected from CH and N, provided that R 2 is N in case R 1 is NH; R 3 is selected from halogen, C 1 -C 4 -alkyl, C2-C 4 -alkenyl, C 1 -C 2 -monohaloalkyl, C 1 -Cz-dihaloalkyl, C 3 -C 4 -cycloalkyl and -O-C 1 -C4-alkyl; 10 R 4 is selected from C 1 -C4-alkyl, C1-C 4 -haloalkyl, -C(=O)-C 1 -C4-alkyl, -(C 1 -C 2 -alkyl)-O-(C1-C 2 -alkyl) and -CH 2 -cyclopropyl; R a is selected from halogen, CN, -NR 5 R 6 , C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C 2 -C 4 -alkynyl, -O-C1-C4-alkyl, -C(=N-O-C 1 -C 4 -alkyl)-C1-C -alkyl, -C(=O)-C 1 -C4-alkyl, -O-CH 2 -C(=N-O-C 1 -C4-alkyl)-C 1 -C4-alkyl, C 3 -Cs-cycloalkyl, C 3 -Cs-cycloalkenyl, -C 1 -C 2 - 15 alkyl-C 3 -Cs-cycloalkyl, -O-C 3 -Cs-cycloalkyl, phenyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1, or 3 heteroatoms selected from N, 0 and S, wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound 20 directly or via an oxygen atom or via a C 1 -C2-alkylene linker, and wherein the aliphatic and cyclic moieties of R a are unsubstituted or carry 1, 2, 3, 4 or up to the maximum number of identical or different groups R b : R b is selected from halogen, CN, NH 2 , NO 2 , C 1 -C 4 -alkyl, C 1 -C 4 -haloalkyl, -O-C 1 -C 4 -alkyl and -O-C1-C 4 -haloalkyl; 25 R 5, R 6 are independently of each other selected from the group consisting of H, C 1 -Cs-alkyl and C 2 -C 4 -alkynyl; n is an integer selected from O, 1, 2 and 3; and in form or stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof, for combating phytopathogenic fungi containing an amino acid sub- 30 stitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. Certain strobilurin type compounds of formula I have been described in EP 370629 and WO 1998 / 23156. However, it is not mentioned that these compounds inhibit fungal pathogens containing a F129L substitution in the mitochondrial cytochrome b protein conferring resistance 35 to Qo inhibitors. The compounds according to the present invention differ from those described in the abovementioned publications that R 3 is an aliphatic or cyclic substituent and R a is a specific substituent as defined herein. 40 Therefore, according to a second aspect, the invention provides novel compounds of formula I which are represented by formula I wherein CA 03171545 2022- 9-- 13 AMENDED SHEET I, 5 202209 R 1 is selected from O and NH; R 2 is selected from CH and N; amended pages 9 PCT / EP 2021 / 059 730 - 04.08.2021 R 3 is selected from C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl, C1-Cz-monohaloalkyl, C 1 -C 2 -dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C 3 -Ca-cycloalkyl and -O-C 1 -C 4 -alkyl; 10 R 4 is selected from C 1 -Ca-alkyl, C 2 -C 4 -alkenyl, C2-C 4 -alkynyl, C 1 -Ca-haloalkyl, C 2 -C 4 -haloalkenyl, C 2 -C 4 -haloalkynyl, -C(=O)-C 1 -C 4 -alkyl, -(C 1 -C 2 -alkyl)-O-(C1-Cz-alkyl), -(C 1 -C 2 -alkyl)- O-(C1-C -haloalkyl) and -C 1 -C4-alkyl-C 3 -Ca-cycloalkyl; R a is selected from halogen, C1-C 4 -haloalkyl, C 2 -C 4 -haloalkenyl, C 2 -C 4 -haloalkynyl, C 3 -Ca- 15 cycloalkyl, C 3 -Ca-cycloalkenyl, -C 1 -C 2 -alkyl-C3-Ca-cycloalkyl, phenyl, 3- to 6-membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1 , 2 or 3 heteroatoms selected from N, 0 and S, wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound 20 directly or via an oxygen atom or via a C 1 -C 2 -alkylene linker, 25 and wherein the cyclic moieties of R a carry 1, 2 or 3 substituents selected from halogen and C 1 -C 4 -haloalkyl, and wherein the aliphatic and cyclic moieties of R a further carry 0, 1, 2 or up to the maximum number of identical or different groups R b : n is an integer selected from 0, 1, 2, 3, 4 and 5; 30 and in form or stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof. One embodiment of the invention relates to preferred compounds I, wherein R 1 is selected from O and NH; and R 2 is selected from CH and N, provided that R 2 is N in case R is NH. More 35 preferably R 1 is NH. In particular, R 1 is NH and R 2 is N. Another embodiment relates to compounds I, wherein R 1 is O and R 2 is CH. According to another embodiment, R 3 is selected from halogen, C 1 -C 4 -alkyl, Cz-C3-alkenyl, C 1 -C 2 -monohaloalkyl, C 1 -C 2 -dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C 3 -Ca-cycloalkyl and -O-C -C 4 -alkyl; preferably from halogen, C 1 -C 2 -alkyl, C 1 -Cz-monohaloalkyl, C 1 -C 2 -dihaloalkyl, 40 C 3 -C -cycloalkyl and -O-C 1 -C 2 -alkyl; preferably selected from C 1 -C 4 -alkyl, Cz-C3-alkenyl, monohalo-methyl, dihalo-methyl, C 3 -C 4 -cycloalkyl and -O-C -C -alkyl; further more preferably selected from C 1 -C 2 -alkyl, CHF 2 , CFH 2 , cyclopropyl and OCH 3 ; particularly preferred from methyl, CHF 2 and CFH 2 ; in particular R 3 is methyl. According to a further embodiment, R 4 is selected from is selected from C 1 -C 4 -alkyl, 45 C 2 -C 4 -alkenyl, -C(=O)-C 1 -C 2 -alkyl, C 1 -C -haloalkyl, C 2 -C 4 -haloalkenyl, -(C -C 2 -alkyl)-O( C 1 -C -alkyl) and -CH 2 -cyclopropyl; more preferably from C 1 -C 4 -alkyl, and C 1 -C 4 -haloalkyl, even more preferably from methyl and C 1 -haloalkyl; in particular methyl. CA 03171545 2022- 9- 13 AMENDED SHEET 202209 amended pages 10 PCT / EP 2021 / 059 730 - 04.08.2021 According to a further embodiment, n is 1, 2, 3, 4 or 5; more preferably n is 1, 2 or 3, even more preferably n is 1 or 2; in particular n is 1. According to a further embodiment, n is 0, 1, 2 or 3, more preferably 0, 1 or 2, in particular 0. 5 According to a further embodiment, n is 2 and the two substituents R a are preferably in 10 positions 2,3 (meaning one substituent in position 2, the other in position 3); 2,4; 2,5; 3,4 or 3,5; even more preferably in positions 2,3 or 2,4. According to a further embodiment, n is 3 and the three substituents R a are preferably in positions 2, 3 and 4. According to a further embodiment, R a is selected from halogen, C 1 -C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C4-cycloalkyl, -C 1 -C2-alkyl-C3-C4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycoalkyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, 0 and S, 15 wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via a C 1 -C2-alkylene linker, and wherein the cyclic moieties of R a carry 1, 2 or 3 substituents selected from halogen and C 1 -C4-haloalkyl. Preferably, R a is selected from halogen, C1-C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C4-cycloalkyl, -CH2-C3-C4-cycloalkyl, phenyl, 3- to 4-membered heterocycloalkyl and 20 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, 0 and S, wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via a C 1 -C2-alkylene linker, and wherein the cyclic moieties of R a carry 1, 2 or 3 substituents selected from halogen and C 1 -C2-haloalkyl. More preferably, R a is selected from halogen, C1-C2-haloalkyl, C2-C4-haloalkenyl, phenyl and 25 5-membered heteroaryl, wherein said heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, 0 and S, wherein said phenyl and heteroaryl are bound directly or via a C 1 -C2-alkylene linker, and wherein the cyclic moieties of R a carry 1, 2 or 3 substituents selected from halogen and C1-C2-haloalkyl. Even more preferably, R a is selected from F, Cl, Br and C1-haloalkyl. 30 According to the abovementioned embodiments for R a , the abovementioned heterocycloalkyl is more preferably a 4-membered heterocycloalkyl, wherein said heterocycloalkyl besides carbon atoms contains 1 heteroatom selected from N, 0 and S, preferably N. According to the abovementioned embodiments for R a , the abovementioned heteroaryl is more preferably a 5-membered heteroaryl, wherein said heteroaryl besides carbon atoms 35 contains 1 or 2 heteroatoms selected from N, 0 and S, preferably from N and 0. According to the abovementioned embodiments for R a , the aliphatic and cyclic moieties of R a further carry 0, 1, 2 or up to the maximum number of identical or different groups R b selected from CN, NH2, NO2, C 1 -C4-alkyl and -O-C1-C4-alkyl; more preferably only the cyclic moieties of R a further carry 0, 1, 2 or up to the maximum number of identical or different groups R b selected 40 from CN, NH2, NO2, C 1 -C4-alkyl and -O-C 1 -C4-alkyl; even more preferably only the phenyl moiety of R a further carries 0, 1 , 2, 3, 4 or 5 identical or different groups R b selected from CN, C 1 -C4-alkyl and -O-C1-C4-alkyl; in particular said phenyl further carries 0, 1, 2 or 3 identical or different groups R b selected from CN, C 1 -C4-alkyl and -O-C 1 -C4-alkyl. 45 According to a further preferred embodiment, the present invention relates to compounds of formula I wherein: R 1 is selected from O and NH ; and CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 1 1 PCT / EP 2021 / 059 730 - 04.08.2021 R 2 is selected from CH and N, provided that R 2 is N in case R 1 is N H; R 3 is selected from halogen, C 1 -C 4 -alkyl, C 2 -C4-alkenyl, C 1 -C2-monohaloalkyl, C 1 -Cz-dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C 3 -C4-cycloalkyl and -O-C1-C 4 -alkyl; R 4 is selected from C1-C 4 -alkyl, C 1 -C 4 -haloalkyl, -C(=O)-C 1 -C 4 -alkyl, 5 -(C 1 -C 2 -alkyl)-O-(C1-C 2 -alkyl) and -CH 2 -cyclopropyl; R a is selected from halogen, C 1 -C 4 -haloalkyl, C 2 -C 4 -haloalkenyl, phenyl, 3- to 5-membered heterocycloalkyl and 5-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contains 1 or 2 heteroatoms selected from N, 0 and S, 10 wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via a C 1 -C 2 -alkylene linker, and wherein the cyclic moieties of R a carry 1 or 2 substituents selected from halogen and C1-C 2 -haloalkyl, and wherein the cyclic moieties of R a further carry 0, 1, 2 or up to the maximum number of 15 identical or different groups R b selected from CN, NH 2 , NO 2 , C 1 -C 4 -alkyl and -O-C 1 -C 4 -al- 20 25 kyl; n is an integer selected from 0, 1, 2 and 3; and in form or stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof. According to a further embodiment, R 1 is O and R 2 is N, which compounds are of formula 1.1: ?" R 4 w·o 􀂍 R 3 : I {R a )n I .:::::,... O 0 H3C' ' 'C H3 0 1.1 . According to a further embodiment, R 1 is O and R 2 is CH, which compounds are of formula 1.2: 1.2. According to a further embodiment, R 1 is NH and R 2 is N, which compounds are of formula 1.3: <•"• "r,(,o;o 􀀆 V H3c' 0 ' N.Jy 'C H3 0 1.3. Preferably, R 3 of compounds I is one of the following radicals 3-1 to 3-6: No. R3 No. R3 No. 3-1 CH 3 3-3 CH F2 3-5 3-2 OCH 3-4 C 3 Hs 3-6 30 Even more preferably R 3 is CH 3 , OCH 3 , CHF2 or C 3 Hs, in particular CH 3 . R3 CH=CH 2 CH 2 CH=C(CH 3 ) 2 CA 03171545 2022- 9-- 13 AMENDED SHEET 5 202209 amended pages 1 2 PCT / EP 2021 / 059 730 - 04.08.2021 Particularly preferred embodiments of the invention relate to compounds I, wherein the R4 is one of the following radicals 4-1 to 4-8: No. R4 No. R4 N o. R4 4-1 CH3 4-4 CH 2 CF3 4-7 C=CH 4-2 C 2 Hs 4-5 CHF 4-8 C=CCH3 4-3 CH OCH3 4-6 CH 2 C3Hs Particularly preferred embodiments of the invention relate to compounds I, wherein the R a is selected of one of the following radicals a-1 to a-7: I No. I R a a-7 C=CCF3 No. R a a-1 F N o. R a a-4 CH F 2 a-2 Cl a-5 CF3 a-3 Br a-6 CH 2 CF3 10 According to a further embodiment, n is 1. More preferably, R a is in ortho-position (2-R a ), 15 which compounds are of formula I .A: I.A wherein even more preferably R 1 is O and R 2 is N. According to a further embodiment, R a is in meta-position (3-R a ), which compounds are of formula I. B: 1.8 wherein even more preferably R 1 is O and R 2 is N. According to a further embodiment, n is 2. More preferably, n is 2 and the two R a substituents are both in meta -position (3,5-R a ), which compounds are of formula I.C: I.C 20 wherein even more preferably R 2 is N. According to a further embodiment, n is 2 and the two R a substituents are both in ortho-position (2,6-R a ), which compounds are of formula I. D: ; a R 4 N""' 0􀄴R 3 : I I O R 1 􀁥 R 8 H 3C" 'R 2 , 'C H3 0 I.D wherein even more preferably R 2 is N. According to a further embodiment, n is 2 and the two R a CA 03171545 2022- 9-- 13 AMENDED SHEET 5 202209 amended pages 1 3 PCT / EP 2021 / 059 730 - 04.08.2021 substituents are in ortho- and meta-position, which compounds are of formula I.E: I.E wherein even more preferably R 2 is N. According to a further embodiment, n is 2 and the two R a substituents are in ortho- and para-position, which compounds are of formula I. F: I.F wherein even more preferably R 2 is N. In an embodiment, compounds I are of formula 1.3 and n, R a , R 3 and R4 are as per any row of per Table A below, which compounds are named 1.3-A-1 to l.3-A-131. 1 O In another embodiment, compounds I are of formula 1.2 and n, R a , R 3 and R4 are as per any row of Table A below, which compounds are named 1.2-A-1 to 1.2-A-131. In an embodiment, compounds I are of formula 1.1 and n, R a , R 3 and R4 are as per any row of Table A below, which compounds are named 1.1-A-1 to l.1-A-131. 15 Table A: CA 03171545 2022- 9-- 13 No. A-1 A-2 A-3 A-4 A-5 A-6 A-7 A-8 A-9 A-10 A-11 A-12 A-13 A-14 A-15 A-16 A-17 A-18 A-19 A-20 A-21 n 0 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 Ra R3 R4 - CH 3 CH3 2-F CH3 CH3 2-CI CH 3 CH 3 2-Br CH3 CH3 2-CHF 2 CH 3 CH 3 2-CF 3 CH CH 2-CH 2 CF 3 CH 3 CH 3 2-C=CCF3 CH CH3 3-F CH3 CH 3 3-CI CH 3 CH 3-Br CH CH3 3-CHF2 CH 3 CH 3 3-CF 3 CH CH3 3-CH 2 CF 3 CH 3 CH 3 3-C=CCF3 CH CH3 4-F CH 3 CH 3 4-CI CH CH3 4-Br CH 3 CH3 4-CH F2 CH CH3 4-CF 3 CH3 CH 3 4-CH 2 CF 3 CH 3 CH AMENDED SHEET 202209 No. n A-22 1 A-23 0 A-24 1 A-25 1 A-26 1 A-27 1 A-28 1 A-29 1 A-30 1 A-31 1 A-32 1 A-33 1 A-34 1 A-35 1 A-36 1 A-37 1 A-38 1 A-39 1 A-40 1 A-41 1 A-42 1 A-43 1 A-44 1 A-45 0 A-46 1 A-47 1 A-48 1 A-49 1 A-50 1 A-51 1 A-52 1 A-53 1 A-54 1 A-55 1 A-56 1 A-57 1 A-58 1 A-59 1 A-60 1 A-61 1 A-62 1 A-63 1 A-64 1 A-65 1 CA 03171545 2022- 9-- 13 amended pages 1 4 Ra R3 4-C=CCF3 CH3 - CH3 2-F CH3 2-CI CH3 2-Br CH3 2-CH F2 CH3 2-CF3 CH3 2-CH2CF3 CH3 2-C::CCF3 CH3 3-F CH3 3-CI CH3 3-Br CH3 3-CH F2 CH3 3-CF3 CH3 3-CH2CF3 CH3 3-C::CCF3 CH3 4-F CH3 4-CI CH3 4-Br CH3 4-CH F2 CH3 4-CF3 CH3 4-CH2CF3 CH3 4-C::CCF3 CH3 - CH3 2-F CH3 2-CI CH3 2-Br CH3 2-CH F2 CH3 2-CF3 CH3 2-CH2CF3 CH3 2-C=CCF3 CH3 3-F CH3 3-CI CH3 3-Br CH3 3-CH F2 CH3 3-CF3 CH3 3-CH2CF3 CH3 3-C=CCF3 CH3 4-F CH3 4-CI CH3 4-Br CH3 4-CH F2 CH3 4-CF3 CH3 4-CH2CF3 CH3 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 R4 CH3 C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs C2Hs CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 CH2CF3 202209 No. n A-66 1 A-67 0 A-68 1 A-69 1 A-70 1 A-71 1 A-72 1 A-73 1 A-74 1 A-75 1 A-76 1 A-77 1 A-78 1 A-79 1 A-80 1 A-81 1 A-82 1 A-83 1 A-84 1 A-85 1 A-86 1 A-87 1 A-88 1 A-89 0 A-90 1 A-91 1 A-92 1 A-93 1 A-94 1 A-95 1 A-96 1 A-97 1 A-98 1 A-99 1 A-100 1 A-101 1 A-102 1 A-103 1 A-104 1 A-105 1 A-106 1 A-107 1 A-108 1 A-109 1 CA 03171545 2022- 9-- 13 amended pages 15 Ra R3 4-C=CCF3 CH3 - CH3 2-F CH3 2-CI CH3 2-Br CH3 2-CH F2 CH3 2-CF3 CH3 2-CH2CF3 CH3 2-C::CCF3 CH3 3-F CH3 3-CI CH3 3-Br CH3 3-CH F2 CH3 3-CF3 CH3 3-CH2CF3 CH3 3-C::CCF3 CH3 4-F CH3 4-CI CH3 4-Br CH3 4-CH F2 CH3 4-CF3 CH3 4-CH2CF3 CH3 4-C::CCF3 CH3 - CH3 2-F CH3 2-CI CH3 2-Br CH3 2-CH F2 CH3 2-CF3 CH3 2-C=CCF3 CH3 3-F CH3 3-CI CH3 3-Br CH3 3-CH F2 CH3 3-CF3 CH3 3-CH2CF3 CH3 3-C=CCF3 CH3 4-F CH3 4-CI CH3 4-Br CH3 4-CH F2 CH3 4-CF3 CH3 4-CH2CF3 CH3 4-C=CCF3 CH3 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 R4 CH2CF3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH2OCH3 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 CH F2 202209 No. n A-1 10 0 A-1 11 1 A-1 12 1 A-1 13 1 A-1 14 1 A-1 15 1 A-1 16 1 A-1 17 1 A-1 18 1 A-1 19 1 A-120 1 A-121 1 A-122 1 A-123 1 A-124 1 A-125 1 A-126 1 A-127 1 A-128 1 A-129 1 A-130 1 A-131 1 Synthesis amended pages 1 6 Ra R3 - CH3 2-F CH3 2-CI CH3 2-Br CH3 2-CHF2 CH3 2-CF3 CH3 2-CH2CF3 CH3 2-C=CCF3 CH3 3-F CH3 3-CI CH3 3-Br CH3 3-CH F2 CH3 3-CF3 CH3 3-CH2CF3 CH3 3-C=CCF3 CH3 4-F CH3 4-CI CH3 4-Br CH3 4-CH F2 CH3 4-CF3 CH3 4-CH2CF3 CH3 4-C=CCF3 CH3 PCT / EP 2021 / 059 730 - 04.08.2021 R4 CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs CH2C3Hs The compounds can be obtained by various routes in analogy to prior art processes known (e.g EP 463488) and, advantageously, by the synthesis shown in the following schemes 1 to 4 5 and in the experimental part of this application. A suitable method to prepare compounds I is illustrated in Scheme 1 . Scheme 1 : (R"􀂹'V 􀁅 .:::a H H3C' 0 􀃿R 2 -lyN .. c H3 0 l: R 1 = NH It starts with the conversion of a ketone to the corresponding oxime using hydxroxylamine hy- 10 drochloride and a base such as pyridine, sodium hydroxide or sodium acetate in polar solvents such as methanol, methanol-water mixture, or ethanol at reaction temperatures of 60 to 100 °c, CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 1 7 PCT / EP 2021 / 059 730 - 04.08.2021 preferably at about 65 °C. In cases where a EIZ mixture was obtained, the isomers could be separated by purifycation techniques known in art (e.g. column chromatography, crystallization, distillation etc.). Then, coupling with the intermediate IV, wherein X is a leaving group such as halogen, toluene- and methanesulfonates, preferably X is Cl or Br, is carried out under basic 5 conditions using e.g. sodium hydride, cesium carbonate or potassium carbonate as a base and using an organic solvent such as dimethyl formamide (DMF) or acetonitrile, preferably cesium carbonate as base and acetonitrile as solvent at room temperature (RT) of about 24 °C . The ester compound I wherein R1 is O can be converted to the amide of formula I wherein R1 is NH by reaction with methyl amine (preferably 40% aq. solution) using tetrahydrofuran (THF) as 1 0 solvent at RT. Another general method to prepare the compounds I is depicted in Scheme 2. Scheme 2: R3 H2N,.O ! NH2-NH2.H20 VIII O H3C' ,.CH R 3 0 ! + II 1: R1 = 0 MeNH2 (in MeOH)l R3 H N,.O 2 H N .., IX H C C H 3 3 R O l + II I: R1 = NH Intermediate IV is reacted with N-hydroxysuccimide VI, using a base such as triethylamine in 15 DM F. The reaction temperature is usually 50 to 70 °c preferably about 70 °c. Conversion to the correspondding O-benzylhydroxyl amine, intermediate VIII, was achieved through removal of the phthalimide group, preferably using hydrazine hydrate in methanol as solvent at 25 °C. Alternatively, removal of the phthalimide group using methyl amine in methanol as solvent at 25 °C can provide intermediate IX. Intermediate VI I I and intermediate IX, respectively can be 20 condensed with ketones using acetic acid or pyridine in methanol as solvent at temperature of 50 to 65 °C. Alternatively, the condensation could also carried out with titanium (IV) ethoxide (Ti(OEt)4) using THF as solvent at about 70 °C. The desired product is usually accompanied by an undesired isomer, which can be removed e.g by column chromatography, crystallization. A general method for preparation of intermediate IV is shown in Scheme 3. 25 Scheme 3: X XI XII IV R1 = 0, R2 = N Compound XI could be obtained from X by lithium-halogen exchange or by generating Grignard reagent and further reaction with dimethyl oxalate or chloromethyl oxalate in presence of a sol- CA 03171545 2022- 9- 13 AMENDED SHEET 202209 amended pages 18 PCT / EP 2021 / 059 730 - 04.08.2021 vent. The preferred solvent is THF, 2-methyl-THF and the temperature can be between -70 to -78 °C. Conversion of intermediate XI to intermediate XI I can be achieved using N-methylhydroxylamine hydrochloride and a base such as pyridine or sodium acetate in polar solvents such as methanol. The reaction temperature is preferably about 65 °C. An EIZ mixture is usually ob- 5 tained, the isomers can be separated by purification techniques known in art (e.g. column chromatography, crystallization). Bromination of intermediate XI I provides the desired intermediate compounds IV, wherein R 1 is O and R 2 = N. This reaction of intermediate XII with N-bromosuccinimide in solvents such as carbon tetrachloride, chlorobenzene, acetonitrile, using radical initiators such as 1, 1'-azobis (cyclohexanecarbonitrile) or azobisisobutyronitrile and is carried 10 out at temperatures of 70 to 100 °C. The preferred radical initiator is 1, 1 '-azobis (cyclohexanecarbonitrile), preferred solvent chlorobenzene and preferred temperature 80 °C. The synthesis of compounds containing different substituents R 3 follows similar sequence as in Scheme 3, wherein R 3 is bromo. Coupling of intermediate Ill with intermediate IV, wherein R 3 is bromo, provides compounds I as described above. Using standard chemical reactions, such 15 as Suzuki or Stille reaction, the bromo group can be converted e.g. to other R 3 substituents such as cycloalkyl, alkoxy and alkenyl. Additional transformations e.g. of ethenyl provide compounds I with other R 3 substituents such as ethyl, CN and haloalkyl. Most of the ketones of general formula I I were commercially available, however for the ones which were not commercially available, preparation of these was carried out in house using 20 methods known in prior art. Scheme 4 depicts various methods known in literature for the synthesis of these ketones. 25 30 Scheme 4: O H :- ) 􀌰 ' 􀀷 N (R a n􀂺O __(R a )nif II f .,C H3 (R 8 )n 􀂻.10 U 􀀄u XIV XVI The ketone I I can be obtained from the corresponding halogen bearing precursors XIV, wherein X is preferably bromine or iodine. Lithium-halogen exchange (J Org Chem, 1998, 63 (21), 7399- 7 407) in compound XI II using n-butyllithium or synthesis of the corresponding Grignard reagent (Nature Comm, 2017, 8(1), 1-7) using THF as solvent, and subsequent reaction with N-methoxy- N-methylacetamide at about -70 to -78 °C can provide the ketone I I. Alternatively, the coupling reaction of compound XIV and tributyl(1-ethoxyvinyl)stannane in presence of a transition metal catalyst, preferably palladium, with suitable ligands in a solvent such as dioxane and at a reaction temperature of about 100 °C, followed by treatment with 1 N HCI can provide ketone II (Org Lett, 2016, 18(7), 1630-1633, WO 2018 / 115380). Reaction of XIV with 1,4-butanediol vinyl ether in the presence of transition metal catalyst, preferably palladium with suitable ligands and solvent such as 1,2-propane diol and base such as sodium carbonate and reaction temperature 35 of about 120 °C followed by treatment with 1 N HCI can provide ketone I I (Chem A Eur J, 2008, 14(18), 5555-5566). Another method uses acid compounds XV, which can be converted to the corresponding Weinreb amide or carboxylic ester XVI I and subsequent reaction with methyl- CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 1 9 PCT / EP 2021 / 059 730 - 04.08.2021 magnesium bromide (MeMgBr) in solvent such as THF and temperatures of -78 to O °C, preferably O °C, to provide ketone II. Another method uses the reaction of nitrile XVI with MeMgBr which is carried out in solvent such as THF or toluene, preferably THF, and reaction temperature is 25 to 60 °C, preferably 60 °C, followed by treatment with 1 N HCI (Eur J Med Chem, 5 2015, 102, 582-593). The compounds I and the compositions thereof, respectively, are suitable as fungicides effective against a broad spectrum of phytopathogenic fungi, including soil-borne fungi, in particular from the classes of Plasmodiophoromycetes, Peronosporomycetes (syn. Oomycetes), 10 Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, and Deuteromycetes (syn. Fungi imperfecti). They can be used in crop protection as foliar fungicides, fungicides for seed dressing, and soil fungicides. The compounds I and the compositions thereof are preferably useful in the control of phytopathogenic fungi on various cultivated plants, such as cereals, e. g. wheat, rye, barley, 15 triticale, oats, or rice; beet, fruits, leguminous plants such as soybean, oil plants, cucurbits, fiber plants, citrus fruits, vegetables, lauraceous plants, energy and raw material plants, corn; tobacco; nuts; coffee; tea; bananas; vines (table grapes and grape juice grape vines) ; natural rubber plants; or ornamental and forestry plants; on the plant propagation material, such as seeds; and on the crop material of these plants. 20 According to the invention all of the above cultivated plants are understood to comprise all species, subspecies, variants, varieties and / or hybrids which belong to the respective cultivated plants, including but not limited to winter and spring varieties, in particular in cereals such as wheat and barley, as well as oilseed rape, e.g. winter wheat, spring wheat, winter barley etc. Corn is also known as Indian corn or maize (Zea mays) which comprises all kinds of corn 25 such as field corn and sweet corn. According to the invention all soybean cultivars or varieties are comprised, in particular indeterminate and determinate cultivars or varieties. The term "cultivated plants" is to be understood as including plants which have been modified by mutagenesis or genetic engineering to provide a new trait to a plant or to modify an already present trait. 30 The compounds I and compositions thereof, respectively, are particularly suitable for controlling the following causal agents of plant diseases: rusts on soybean and cereals (e.g. Phakopsora pachyrhizi and P. meibomiae on soybean; Puccinia tritici and P. striiformis on wheat); molds on specialty crops, soybean, oil seed rape and sunflowers (e.g. Botrytis cinerea on strawberries and vines, Sclerotinia sclerotiorum, S. minor and S. rolfsii on oil seed rape, 35 sunflowers and soybean); Fusarium diseases on cereals (e.g. Fusarium cu / morum and F. graminearum on wheat); downy mildews on specialty crops (e.g. Plasmopara vitico / a on vines, Phytophthora infestans on potatoes); powdery mildews on specialty crops and cereals (e.g. Uncinula necator on vines, Erysiphe spp. on various specialty crops, Blumeria graminis on cereals); and leaf spots on cereals, soybean and corn (e.g. Septoria tritici and S. nodorum on 40 cereals, S. g / ycines on soybean, Cercospora spp. on corn and soybean). The compounds I and compositions thereof, respectively, are also suitable for controlling harmful microorganisms in the protection of stored products or harvest, and in the protection of materials. The compounds I are employed as such or in form of compositions by treating the fungi, the 45 plants, plant propagation materials, such as seeds; soil, surfaces, materials, or rooms to be protected from fungal attack with a fungicidally effective amount of the active substances. The application can be carried out both before and after the infection of the plants, plant propagation CA 03171545 2022- 9- 13 AMENDED SHEET 202209 amended pages 20 PCT / EP 2021 / 059 730 - 04.08.2021 materials, such as seeds; soil, surfaces, materials or rooms by the fungi. An agrochemical composition comprises a fungicidally effective amount of a compound I. The term "fungicidally effective amount" denotes an amount of the composition or of the compounds I, which is sufficient for controlling harmful fungi on cultivated plants or in the 5 protection of stored products or harvest or of materials and which does not result in a substantial damage to the treated plants, the treated stored products or harvest, or to the treated materials. Such an amount can vary in a broad range and is dependent on various factors, such as the fungal species to be controlled, the treated cultivated plant, stored product, harvest or material, the climatic conditions and the specific compound I used. 10 Plant propagation materials may be treated with compounds I as such or a composition comprising at least one compound I prophylactically either at or before planting or transplanting. The user applies the agrochemical composition usually from a predosage device, a knapsack sprayer, a spray tank, a spray plane, or an irrigation system. Usually, the agrochemical composition is made up with water, buffer, and / or further auxiliaries to the desired application 15 concentration and the ready-to-use spray liquor or the agrochemical composition according to the invention is thus obtained. Usually, 20 to 2000 liters, preferably 50 to 400 liters, of the readyto- use spray liquor are applied per hectare of agricultural useful area. The compounds I, their N-oxides and salts can be converted into customary types of agrochemical compositions, e. g. solutions, emulsions, suspensions, dusts, powders, pastes, granu- 20 les, pressings, capsules, and mixtures thereof. Examples for composition types (see "Catalogue of pesticide formulation types and international coding system", Technical Monograph No. 2, 6 th Ed. May 2008, Croplife International) are suspensions (e. g. SC, OD, FS), emulsifiable concentrates (e. g. EC), emulsions (e. g. EW, EO, ES, M E), 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 25 (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. GF). The compositions are prepared in a known manner, such as described by Mollet and Grubemann, Formulation technology, Wiley VCH, Weinheim, 2001; or by Knowles, New developments in crop protection product formulation, Agrow Reports DS243, T&F lnforma, London, 2005. The invention also 30 relates to agrochemical compositions comprising an auxiliary and at least one compound I. Suitable auxiliaries are solvents, liquid carriers, solid carriers or fillers, surfactants, dispersants, emulsifiers, wetters, adjuvants, solubilizers, penetration enhancers, protective colloids, adhesion agents, thickeners, humectants, repellents, attractants, feeding stimulants, compatibilizers, bactericides, anti-freezing agents, anti-foaming agents, colorants, tackifiers and binders. 35 The agrochemical compositions generally comprise between 0.01 and 95 %, preferably between 0. 1 and 90%, more preferably between 1 and 70 %, and in particular between 10 and 60 %, by weight of active substance (e.g. at least one compound I). Further, the agrochemical compositions generally comprise between 5 and 99.9 %, preferably between 10 and 99.9 %, more preferably between 30 and 99 %, and in particular between 40 and 90 %, by weight of at 40 least one auxiliary. When employed in plant protection, the amounts of active substances applied are, depending on the kind of effect desired, from 0.001 to 2 kg per ha, preferably from 0.005 to 2 kg per ha, more preferably from 0.05 to 0.9 kg per ha, and in particular from 0.1 to 0.75 kg per ha. In treatment of plant propagation materials, such as seeds, e. g. by dusting, coating, or 45 drenching, amounts of active substance of generally from 0.1 to 1000 g, preferably from 1 to 1000 g, more preferably from 1 to 100 g and most preferably from 5 to 100 g, per 100 kg of plant propagation material (preferably seeds) are required. CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 21 PCT / EP 2021 / 059 730 - 04.08.2021 Various types of oils, wetters, adjuvants, fertilizers, or micronutrients, and further pesticides (e. g. fungicides, growth regulators, herbicides, insecticides, safeners) may be added to the compounds I or the compositions thereof as premix, or, not until immediately prior to use (tank mix). These agents can be admixed with the compositions according to the invention in a weight 5 ratio of 1 : 1 00 to 1 00: 1 , preferably 1 : 1 0 to 1 0: 1 . Mixing the compounds I or the compositions comprising them i n the use form as fungicides with other fungicides results in many cases in an expansion of the fungicidal spectrum of activity or in a prevention of fungicide resistance development. Furthermore, in many cases, synergistic 10 effects are obtained (synergistic mixtures). The following list of pesticides II, in conjunction with which the compounds I can be used, is intended to illustrate the possible combinations but does not limit them: A) Respiration inhibitors Inhibitors of complex 1 1 1 at Oo site: azoxystrobin (A. 1 . 1 ), coumethoxystrobin (A. 1 .2), 15 coumoxystrobin (A.1 .3), dimoxystrobin (A. 1 .4), enestroburin (A.1.5), fenaminstrobin (A.1 .6), fenoxystrobin / flufenoxystrobin (A.1 . 7), fluoxastrobin (A. 1 .8), kresoxim-methyl (A.1.9), mandestrobin (A.1 .1 0), metominostrobin (A.1 . 1 1), orysastrobin (A. 1 . 1 2), picoxystrobin (A. 1 . 1 3), pyraclostrobin (A. 1 . 1 4), pyrametostrobin (A. 1 . 1 5), pyraoxystrobin (A.1 . 1 6), trifloxystrobin (A.1 . 1 7), 2-(2-(3-(2,6-dichlorophenyl)-1 -methyl-allylideneaminooxymethyl)-phenyl)- 20 2-methoxyimino-N-methyl-acetamide (A. 1 .1 8), pyribencarb (A. 1 . 1 9), triclopyricarb / chlorodincarb (A. 1 .20), famoxadone (A.1.21), fenamidone (A.1 .21), methyl-N-[2-[(1 ,4-dimethyl- 5-phenyl-pyrazol-3-yl)oxylmethyl]phenyl]-N-methoxy-carbamate (A.1.22), metyltetraprole (A. 1.25), (Z,2E)-5-[1 -(2, 4-dichlorophenyl) pyrazol-3-yl]-oxy-2-methoxyimino-N, 3-di methylpent- 3-enamide (A. 1 .34) , (Z,2E)-5-[1 -(4 -chlorophenyl)pyrazol-3-yl]oxy-2-methoxyimino- 25 N,3-dimethy!-pent-3-enamide (A. 1 .35), pyriminostrobin (A. 1 .36), bifujunzhi (A.1 .37), 2-(ortho-(( 2, 5-dimethylphenyl-oxymethylen)phenyl)-3-methoxy-acrylic acid methylester (A.1 .38); - inhibitors of complex Ill at Qi site: cyazofamid (A.2.1 ), amisulbrom (A. 2.2), [(6 S, 7 R, BR)-8-benzyl-3-{ (3-hydroxy-4-methoxy-pyrid ine-2-carbonyl)amino J-6-methyl-4, 9-dioxo- 1 ,5-dioxonan-7 -yl] 2-methylpropanoate (A.2.3), fenpicoxamid (A.2.4) , f!orylpicoxamid 30 (A.2.5), metarylpicoxamid (A.2.6); - inhibitors of complex I I : benodanil (A.3.1 ), benzovindiflupyr (A.3.2), bixafen (A.3.3), boscalid (A.3.4), carboxin (A.3.5), fenfuram (A.3.6), fluopyram (A.3. 7), flutolanil (A.3. 8), fluxapyroxad (A.3.9), furametpyr (A.3.1 0), isofetamid (A.3.1 1 ), isopyrazam (A.3.1 2), mepronil (A.3.1 3), oxycarboxin (A.3.1 4), penflufen (A.3.1 5), penthiopyrad (A.3.1 6), pydiflumetofen (A.3.1 7), 35 pyraziflumid (A.3.1 8), sedaxane (A.3.1 9), tecloftalam (A.3.20), thifluzamide (A.3. 21), inpyrfluxam (A.3.22), pyrapropoyne (A.3.23), fluindapyr (A.3.28), N-[2-[2-chloro-4-(trifluoromethyl) phenoxy]phenyl]-3-( difl uoromethyl)-5-fluoro-1 -methyl-pyrazole-4-carboxamide (A.3.29), methyl (E)-2-[2-[(5-cyano-2-methyl-phenoxy)methyl]phenyl]-3-methoxy-prop- 2-enoate (A.3.30), isoflucypram (A.3.31 ), 2-(difluoromethyl)-N-(1 , 1 ,3-trimethyl-indan-4-yl)- 40 pyridine-3-carboxamide (A.3.32), 2-(difluoromethyl)-N-[(3R)- 1 , 1 ,3-trimethylindan-4-yl]- pyridi ne-3-carboxam ide (A. 3. 33), 2-( difl uoromethyl)-N-(3-ethyl-1 , 1 -dimethyl-indan-4-yl)pyridi ne-3-carboxam ide (A. 3. 34), 2-( difl uoromethyl)-N-[(3R)-3-ethyl-1 , 1 -di methyl-i ndan-4-yl]pyridi ne-3-carboxam ide (A. 3. 35), 2-( difl uoromethyl)-N-( 1 , 1 -dimethyl-3-propyl-i ndan-4-yl) pyridine- 3-carboxam ide (A.3.36), 2-(difluoromethyl)-N-[(3R)-1 , 1 -dimethyl-3-propyl-indan-4-yl]- 45 pyridine-3-carboxamide (A.3.37), 2-(difluoromethyl)-N-(3-isobutyl-1 , 1 -dimethyl-indan-4-yl)pyridi ne-3-carboxam ide (A. 3. 38), 2-( difl uoromethyl)-N-[(3R)-3-isobutyl-1 , 1 -d imethyl-i ndan- 4-yl]pyri dine-3-carboxam ide (A.3.39) cyclobutrifluram (A.3.24); CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 22 PCT / EP 2021 / 059 730 - 04.08.2021 - other respiration inhibitors: diflumetorim (A.4.1); nitrophenyl derivates: binapacryl (A.4.2), dinobuton (A.4.3), dinocap (A.4.4), fluazinam (A.4.5), meptyldinocap (A.4.6), ferimzone (A.4.7); organometal compounds: fentin salts, e. g. fentin-acetate (A.4.8), fentin chloride (A.4.9) or fentin hydroxide (A.4.10); ametoctradin (A.4.11); silthiofam (A.4.12); 5 B) Sterol biosynthesis inhibitors (SBI fungicides) - C14 demethylase inhibitors: triazoles: azaconazole (B.1.1), bitertanol (B.1.2), bromuconazole (B.1.3), cyproconazole (B.1.4), difenoconazole (B.1.5), diniconazole (B.1.6), diniconazole-M (B.1.7), epoxiconazole (B.1.8), fenbuconazole (B.1.9), fluquinconazole (B.1.10), flusilazole (B.1.11), flutriafol (B.1.12), hexaconazole (B.1.13), imibenconazole 10 (B.1.14), ipconazole (B.1.15), metconazole (B.1.17), myclobutanil (B.1.18), oxpoconazole (B.1.19), paclobutrazole (B.1.20), penconazole (B.1.21), propiconazole (B.1.22), prothioconazole (B.1.23), simeconazole (B.1.24), tebuconazole (B.1.25), tetraconazole (B.1.26), triadimefon (B.1.27), triadimenol (B.1.28), triticonazole (B.1.29), uniconazole (B.1.30), 2-(2,4-d ifluorophenyl)-1, 1-difluoro-3-(tetrazol-1-yl)-1-[5-[4-(2,2,2-trifluoroethoxy) phenyl]- 15 2-pyridyl]propan-2-ol (B.1. 31 ), 2-(2,4-difluorophenyl)-1, 1-difluoro-3-(tetrazol-1-yl)-1-[5-[ 4-(trifluoromethoxy) phenyl]-2-pyridyl]propan-2-ol (B.1.32), fluooxytioconazole (B.1.33), ipfentrifluconazole (B.1.37), mefentrifluconazole (B.1.38), (2R)-2-[4-(4-chlorophenoxy)-2-(trifluoromethyl) phenyl]-1-( 1,2,4-triazol-1-yl) propan-2-ol, (2S)-2-[4-( 4-chlorophenoxy)-2-(trifluoromethyl) phenyl]-1-( 1,2 ,4-triazol-1-yl)propan-2-ol, 2-( chloromethyl)-2-methyl-5-(p-tolylmethyl)- 20 1-(1,2,4-triazol-1-ylmethyl)cyclopentanol (B.1. 43); imidazoles: imazalil (B.1.44), pefurazoate (B.1.45), prochloraz (B.1.46), triflumizol (B.1.47); pyrimidines, pyridines, piperazines: fenarimol (B.1.49), pyrifenox (B.1.50), triforine (B.1.51), [3-(4-chloro-2-fluoro-phenyl)-5-(2,4-difluorophenyl) isoxazol-4-yl]-(3-pyridyl)methanol (B.1.52), 4-[[6-[2-(2,4-difluorophenyl)-1, 1-difluoro- 2-hydroxy-3-(1,2,4-triazol-1-yl)propyl]-3-pyridyl]oxy]benzonitrile (B.1.53), 2-[6-(4-bromo- 25 phenoxy)-2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (B.1. 54), 2-[6-(4-chlorophenoxy)- 2-(trifluoromethyl)-3-pyridyl]-1-(1,2,4-triazol-1-yl)propan-2-ol (B. 1.55); Delta14-reductase inhibitors: aldimorph (B.2.1), dodemorph (B.2.2), dodemorph-acetate (B.2.3), fenpropimorph (B.2.4), tridemorph (B.2. 5), fenpropidin (B.2.6), piperalin (B.2.7), spiroxamine (B.2.8); 30 - Inhibitors of 3-keto reductase: fenhexamid (B.3. 1); - Other Sterol biosynthesis inhibitors: chlorphenomizole (B.4.1); C) Nucleic acid synthesis inhibitors - phenylamides or acyl amino acid fungicides: benalaxyl (C.1.1 ), benalaxyl-M (C.1.2), kiralaxyl (C.1.3), metalaxyl (C.1.4), metalaxyl-M (C.1.5), ofurace (C. 1.6), oxadixyl (C.1.7); 35 - other nucleic acid synthesis inhibitors: hymexazole (C.2.1), octhilinone (C.2.2), oxolinic acid (C.2.3), bupirimate (C.2.4), 5-fluorocytosine (C.2.5), 5-fluoro-2-(p-tolylmethoxy)pyrimidin- 4-amine (C.2. 6), 5-fluoro-2-(4-fluorophenylmethoxy)pyrimidin-4-amine (C.2. 7), 5-fluoro- 2-(4-chlorophenylmethoxy)pyrimidin-4 amine (C.2.8); D) Inhibitors of cell division and cytoskeleton 40 - tubulin inhibitors: benomyl (D.1.1), carbendazim (D.1.2), fuberidazole (D1 .3), thiabendazole (D.1.4), thiophanate-methyl (D.1.5), pyridachlometyl (D.1.6), N-ethyl-2-[(3-ethynyl-8-methyl- 6-quinolyl)oxy]butanamide (D.1.8), N-ethyl-2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methylsulfanyl- acetamide (D. 1. 9), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-(2-fluoroethyl)butanamide (D. 1.10), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-(2-fluoroethyl)-2-methoxy-acet- 45 amide (D. 1.11 ), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-N-propyl-butanamide (D.1.12), 2-[(3-ethynyl-8-methyl-6-quinolyl)oxy]-2-methoxy-N-propyl-acetamide (D.1.13), 2-[(3-ethynyl- 8-methyl-6-quinolyl)oxy]-2-methylsulfanyl-N-propyl-acetamide (D.1.14), 2-[(3-ethynyl-8-meth- CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 23 PCT / EP 2021 / 059 730 - 04.08.2021 yl-6-quinolyl)oxy]-N-(2-fluoroethyl)-2-methylsulfanyl-acetamide (D.1.15), 4-(2-bromo-4-fluorophenyl)- N-(2-chloro-6-fluoro-phenyl)-2,5-dimethyl-pyrazol-3-amine (D.1.16); - other cell division inhibitors: diethofencarb (D.2.1), ethaboxam (D.2.2), pencycuron (D.2.3), fluopicolide (D.2.4), zoxamide (D.2.5), metrafenone (D.2.6), pyriofenone (D.2.7), 5 phenamacril (D.2.8); E) Inhibitors of amino acid and protein synthesis - methionine synthesis inhibitors: cyprodinil (E.1.1), mepanipyrim (E.1.2), pyrimethanil (E.1.3); - protein synthesis inhibitors: blasticidin-S (E.2.1), kasugamycin (E.2.2), kasugamycin hydrochloride- hydrate (E.2.3), mildiomycin (E.2.4), streptomycin (E.2.5), oxytetracyclin (E.2.6); 10 F) Signal transduction inhibitors - MAP / histidine kinase inhibitors: fluoroimid (F.1.1), iprodione (F. 1. 2), procymidone (F. 1.3), vinclozolin (F. 1.4), fludioxonil (F.1.5); - G protein inhibitors: quinoxyfen (F.2.1); G) Lipid and membrane synthesis inhibitors 15 - Phospholipid biosynthesis inhibitors: edifenphos (G.1.1), iprobenfos (G.1.2), pyrazophos (G.1.3), isoprothiolane (G.1.4); - lipid peroxidation: dicloran (G.2.1), quintozene (G.2.2), tecnazene (G.2.3), tolclofos-methyl (G.2.4), biphenyl (G.2.5), chloroneb (G.2.6), etridiazole (G.2.7), zinc thiazole (G.2.8); - phospholipid biosynthesis and cell wall deposition: dimethomorph (G.3.1), flumorph (G.3.2), 20 mandipropamid (G.3.3), pyrimorph (G.3.4), benthiavalicarb (G.3. 5), iprovalicarb (G.3.6), valifenalate (G.3.7); - compounds affecting cell membrane permeability and fatty acides: propamocarb (G.4.1); - inhibitors of oxysterol binding protein: oxathiapiprolin (G.5.1), fluoxapiprolin (G.5.3), 4-[1-[2-[3-( difl uoromethyl)-5-methyl-pyrazol-1-yl]acetyl]-4-piperidyl]-N-tetrali n-1-yl-pyridine- 25 2-carboxamide (G. 5.4), 4-[1-[2-[3,5-bis( difluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]-N-tetralin- 1-yl-pyridine-2-carboxamide (G.5.5), 4-[1-[2-[3-(difluoromethyl)-5-(trifluoromethyl)pyrazol- 1-yl]acetyl]-4-piperidyl]-N-tetralin-1-yl-pyrid ine-2-carboxamide (G. 5.6), 4-[1-[2-[5-cyclopropyl- 3-( difluoromethyl) pyrazol-1-yl]acetyl]-4-piperidyl]-N-tetrali n-1-yl-pyrid i ne-2-carboxamide ( G. 5. 7), 4-[1-[2-[5-methyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]-N-tetralin- 30 1-yl-pyridine-2-carboxamide (G.5.8), 4-[1-[2-[5-( difluoromethyl)-3-(trifluoromethyl)pyrazol- 1-yl]acetyl]-4-piperidyl]-N-tetralin-1-yl-pyridine-2-carboxamide (G.5.9), 4-[1-[2-[3,5-bis(trifluoromethyl) pyrazol-1-yl)acetyl]-4-piperidyl]-N-tetralin-1-yl-pyridine-2-carboxamide (G.5.10), (4-[1-[2-[5-cyclopropyl-3-(trifluoromethyl)pyrazol-1-yl]acetyl]-4-piperidyl]-N-tetralin-1-yl-pyridine- 2-carboxamide (G.5.11); 35 H) Inhibitors with Multi Site Action - inorganic active substances: Bordeaux mixture (H.1. 1), copper (H.1.2), copper acetate (H.1.3), copper hydroxide (H.1.4), copper oxychloride (H.1.5), basic copper sulfate (H.1.6), sulfur (H.1.7); - thio- and dithiocarbamates: ferbam (H.2.1), mancozeb (H.2.2), maneb (H.2.3), metam 40 (H.2.4), metiram (H.2.5), propineb (H.2.6), thiram (H.2.7), zineb (H.2.8), ziram (H.2.9); - organochlorine compounds: anilazine (H.3.1), chlorothalonil (H.3.2), captafol (H.3.3), captan (H.3.4), folpet (H.3.5), dichlofluanid (H.3.6), dichlorophen (H.3.7), hexachlorobenzene (H.3.8), pentachlorphenole (H.3.9) and its salts, phthalide (H.3.10), tolylfluanid (H.3.11); - guanidines and others: guanidine (H.4.1), dodine (H.4.2), dodine free base (H.4.3), 45 guazatine (H.4.4), guazatine-acetate (H.4.5), iminoctadine (H.4.6), iminoctadine-triacetate (H.4.7), iminoctadine-tris(albesilate) (H.4. 8), dithianon (H.4.9), 2,6-dimethyl-1H,5H-[1 ,4]dithiino[ 2,3-c:5,6-c'Jdipyrrole-1,3,5,7(2H,6H)-tetraone (H.4.10); CA 03171545 2022· 9- 13 AMENDED SHEET 202209 I) Cell wall synthesis inhibitors amended pages 24 PCT / EP 2021 / 059 730 - 04.08.2021 - inhibitors of glucan synthesis: validamycin (1.1.1 ), polyoxin B (1.1. 2); - melanin synthesis inhibitors: pyroquilon (1.2.1), tricyclazole (1.2.2), carpropamid (1. 2.3), dicyclomet (1.2.4), fenoxanil (1.2.5); 5 J) Plant defence inducers - acibenzolar-S-methyl (J. 1.1), probenazole (J.1.2), isotianil (J.1.3), tiadinil (J. 1.4), prohexadione- calcium (J.1.5); phosphonates: fosetyl (J.1. 6), fosetyl-aluminum (J.1.7), phosphorous acid and its salts (J.1.8), calcium phosphonate (J.1.11), potassium phosphonate (J.1.12), potassium or sodium bicarbonate (J.1.9), 4-cyclopropyl-N-(2,4-dimethoxyphenyl)thiadiazole- 10 5-carboxamide (J.1.10); K) Unknown mode of action - bronopol (K.1.1 ), chinomethionat (K.1.2), cyflufenamid (K.1.3), cymoxanil (K.1.4), dazomet (K.1.5), debacarb (K.1.6), diclocymet (K.1. 7), diclomezine (K.1.8), difenzoquat (K.1.9), difenzoquat- methylsulfate (K.1. 10), diphenylamin (K.1.11), fenitropan (K.1.12), fenpyrazamine 15 (K.1.13), flumetover (K.1.14), flumetylsulforim (K.1.60), flusulfamide (K.1.15), flutianil (K.1.16), harpin (K.1.17), methasulfocarb (K.1.18), nitrapyrin (K.1.19), nitrothal-isopropyl (K.1.20), tolprocarb (K.1.21), oxin-copper (K.1.22), proquinazid (K.1.23), seboctylamine (K.1.61 ), tebufloquin (K.1.24), tecloftalam (K.1.25), triazoxide (K.1.26), N'-(4-(4-chloro-3-trifluoromethyl- phenoxy)-2, 5-dimethyl-phenyl)-N-ethyl-N-methyl formamidine (K.1.27), 20 N'-(4-(4-fluoro-3-trifluoromethyl-phenoxy)-2,5-dimethyl-phenyl)-N-ethyl-N-methyl formamidine (K. 1.28), N'-[4-[[3-[(4-chlorophenyl)methyl)-1, 2,4-thiadiazol-5-yl]oxy]-2,5-dimethyl- phenyl]-N-ethyl-N-methyl-formamidine (K.1.29), N'-(5-bromo-6-indan-2-yloxy-2-methyl- 3-pyridyl)-N-ethyl-N-methyl-formamidine (K.1.30), N'-[5-bromo-6-[1-(3,5-difluorophenyl)ethoxy)- 2-methyl-3-pyridyl)-N-ethyl-N-methyl-formamidine (K.1.31), N'-[5-bromo-6-(4-isopro- 25 pylcyclohexoxy)-2-methyl-3-pyridyl)-N-ethyl-N-methyl-formamidine (K.1.32), N'-[5-bromo- 2-methyl-6-(1-phenylethoxy)-3-pyridyl)-N-ethyl-N-methyl-formamidine (K.1.33), N'-(2-methyl- 5-trifluoromethyl-4-(3-trimethylsilanyl-propoxy)-phenyl)-N-ethyl-N-methyl formamidine (K.1.34), N'-(5-difluoromethyl-2-methyl-4-(3-trimethylsilanyl-propoxy)-phenyl)-N-ethylN- methyl formamidine (K.1.35), 2-(4-chloro-phenyl)-N-[4-(3,4-dimethoxy-phenyl)-isoxazol- 30 5-yl)-2-prop-2-ynyloxy-acetamide (K.1.36), 3-[5-(4-chloro-phenyl)-2,3-dimethyl-isoxazolidin- 3-yl)-pyridine (pyrisoxazole) (K.1.37), 3-[5-(4-methylphenyl)-2,3-dimethyl-isoxazolidin-3-yl)pyridine (K.1.38), 5-chloro-1-(4,6-dimethoxy-pyrimidin-2-yl)-2-methyl-1 H-benzoimidazole (K.1.39), ethyl (Z)-3-amino-2-cyano-3-phenyl-prop-2-enoate (K.1 .40), picarbutrazox (K.1.41), pentyl N-[6-[[(Z)-[( 1-methyltetrazol-5-yl)-phenyl-methylene]amino )oxymethyl)-2-pyridyl)carba- 35 mate (K.1.42), but-3-ynyl N-[6-[[(Z)-[(1-methyltetrazol-5-yl)-phenyl-methylene]amino]oxymethyl]- 2-pyridyl]carbamate (K.1.43), ipflufenoquin (K.1.44), quinofumelin (K.1.47), benzothiazolinone (K.1 .48), bromothalonil (K.1.49), 2-(6-benzyl-2-pyridyl)quinazoline (K.1. 50), 2-[6-(3-fluoro-4-methoxy-phenyl)-5-methyl-2-pyridyl]quinazoline (K.1.51), dichlobentiazox (K.1.52), N'-(2,5-dimethyl-4-phenoxy-phenyl)-N-ethyl-N-methyl-formamidine (K.1.53), 40 aminopyrifen (K.1. 54), fluopimomide (K.1.55), N-[5-bromo-2-methyl-6-(1-methyl-2-propoxyethoxy)- 3-pyridyl]-N-ethyl-N-methyl-formamidine (K.1.56), N'-[4-( 4,5-dichlorothiazol-2-yl)oxy- 2,5-dimethyl-phenyl]-N-ethyl-N-methyl-formamidine (K.1.57), flufenoxadiazam (K.1.58), N-methyl-4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]benzenecarbothioamide (K.1.59), N-methoxy-N-[[4-[5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl]phenyl]methyl]cyclopropane- 45 carboxamide (WO2018 / 177894, WO 2020 / 212513); In the binary mixtures the weight ratio of the component 1) and the component 2) generally CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 25 PCT / EP 2021 / 059 730 - 04.08.2021 depends from the properties of the components used, usually it is in the range of from 1: 10,000 to 10,000:1, often from 1:100 to 100:1, regularly from 1:50 to 50:1, preferably from 1 :20 to 20:1, more preferably from 1: 10 to 10: 1, even more preferably from 1 :4 to 4: 1 and in particular from 1 : 2 to 2:1. According to further embodiments, the weight ratio of the component 1) and the 5 component 2) usually is in the range of from 1000: 1 to 1: 1, often from 100: 1 to 1: 1, regularly from 50: 1 to 1: 1, preferably from 20: 1 to 1 : 1, more preferably from 10: 1 to 1 : 1, even more preferably from 4: 1 to 1: 1 and in particular from 2: 1 to 1: 1. According to further embodiments, the weight ratio of the component 1) and the component 2) usually is in the range of from 20,000:1 to 1:10, often from 10,000:1 to 1:1, regularly from 5,000:1 to 5:1, preferably from 10 5,000:1 to 10:1, more preferably from 2,000:1 to 30:1, even more preferably from 2,000:1 to 100:1 and in particular from 1,000:1 to 100:1. According to further embodiments, the weight ratio of the component 1) and the component 2) usually is in the range of from 1:1 to 1:1000, often from 1:1 to 1:100, regularly from 1:1 to 1:50, preferably from 1:1 to 1:20, more preferably from 1: 1 to 1: 10, even more preferably from 1: 1 to 1 :4 and in particular from 1: 1 to 1 :2. 15 According to further embodiments, the weight ratio of the component 1) and the component 2) usually is in the range of from 10:1 to 1 :20,000, often from 1:1 to 1 :10,000, regularly from 1 :5 to 1:5,000, preferably from 1:10 to 1: 5,000, more preferably from 1:30 to 1:2,000, even more preferably from 1 :100 to 1 :2, 000 to and in particular from 1:100 to 1 :1,000. In the ternary mixtures, i.e. compositions comprising the component 1) and component 2) 20 and a compound Ill (component 3), the weight ratio of component 1) and component 2) depends from the properties of the active substances used, usually it is in the range of from 1: 100 to 100: 1, regularly from 1 :50 to 50: 1, preferably from 1 :20 to 20: 1, more preferably from 1:10 to 10: 1 and in particular from 1:4 to 4:1, and the weight ratio of component 1) and component 3) usually it is in the range of from 1: 100 to 100: 1, regularly from 1: 50 to 50: 1, 25 preferably from 1:20 to 20:1, more preferably from 1:10 to 10:1 and in particular from 1:4 to 4:1. Any further active components are, if desired, added in a ratio of from 20:1 to 1 :20 to the component 1). These ratios are also suitable for mixtures applied by seed treatment. Preference is given to mixtures comprising as component 2) at least one active substance 30 selected from inhibitors of complex 1 1 1 at O o site in group A), more preferably selected from compounds (A.1.1), (A.1.4), (A.1.8), (A.1.9), (A.1.10), (A.1.12), {A.1.13), (A.1.14), (A. 1.17), (A.1.21), (A.1.25), (A.1.34) and (A.1.35); particularly selected from (A.1.1), (A.1.4), (A. 1.8), (A.1.9), (A. 1.13), (A.1.14), (A.1.17), (A. 1.25), (A.1.34) and (A.1.35). Preference is also given to mixtures comprising as component 2) at least one active 35 substance selected from inhibitors of complex I ll at Qi site in group A), more preferably selected from compounds (A.2.1), (A. 2.3), (A.2.4) and (A.2.6); particularly selected from (A.2.3), (A.2.4) and (A.2.6). Preference is also given to mixtures comprising as component 2) at least one active substance selected from inhibitors of complex II in group A), more preferably selected from 40 compounds (A.3. 2), (A.3.3), (A.3.4), (A.3.7), (A.3.9), (A.3.11), (A.3.12), (A.3.15), (A.3.16), (A.3.17), (A.3.18), (A.3.19), (A.3.20), (A.3.21), (A.3.22), (A.3.23), (A.3.24), (A.3. 28), (A.3.31), (A.3.32), (A.3.33), (A.3.34), (A.3.35), (A.3.36), {A.3.37), (A.3.38) and {A.3.39); particularly selected from (A.3.2), (A.3.3), (A.3.4), (A.3.7), (A.3. 9), (A.3.12), (A.3.15), (A.3.17), (A.3.19), (A.3.22), (A.3.23), (A.3.24), (A.3.31), (A.3.32), (A.3.33), (A.3.34), (A.3.35), (A.3.36), (A.3.37), 45 (A.3.38) and (A.3.39). Preference is also given to mixtures comprising as component 2) at least one active substance selected from other respiration inhibitors in group A), more preferably selected from CA 03171545 2022· 9- 13 AMENDED SHEET 202209 amended pages 26 compounds (A.4.5) and (A.4.11); in particular (A.4.11). PCT / EP 2021 / 059 730 - 04.08.2021 Preference is also given to mixtures comprising as component 2) at least one active substance selected from C14 demethylase inhibitors in group B), more preferably selected from compounds (B.1.4), (B.1.5), (B.1.8), (B.1.10), (B.1.11), (B.1.12), (B.1.13), (B. 1.17), (B.1.18), 5 (B.1.21), (B.1.22), (B.1.23), (B.1.25), (B.1.26), (B.1.29), (B.1.33), (B.1.34), (B.1.37), (B.1.38), (B.1.43), (B.1.46), (B.1.53), (B.1.54) and (B.1.55); particularly selected from (B.1.5), (B. 1.8), (B.1.10), (B.1.17), (B.1.22), (B.1.23), (B.1.25), (B.1.33), (B.1.34), (B.1.37), (B.1.38), (B.1.43) and (B.1.46). Preference is also given to mixtures comprising as component 2) at least one active 10 substance selected from Delta14-reductase inhibitors in group B), more preferably selected from compounds (B.2.4), (B.2.5), (B.2.6) and (B.2.8); in particular (B.2.4). Preference is also given to mixtures comprising as component 2) at least one active substance selected from phenylamides and acyl amino acid fungicides in group C), more preferably selected from compounds (C.1.1), (C.1.2), (C.1.4) and (C.1.5); particularly selected 15 from (C.1.1) and (C.1.4). Preference is also given to mixtures comprising as component 2) at least one active substance selected from other nucleic acid synthesis inhibitors in group C), more preferably selected from compounds (C.2.6), (C.2.7) and (C.2.8). Preference is also given to mixtures comprising as component 2) at least one active 20 substance selected from group D), more preferably selected from compounds (D.1.1), (D.1.2), (D.1.5), (D.2.4) and (D.2.6); particularly selected from (D.1.2), (D.1.5) and (D.2.6). Preference is also given to mixtures comprising as component 2) at least one active substance selected from group E), more preferably selected from compounds (E.1.1), (E.1.3), (E.2.2) and (E.2.3); in particular (E.1.3). 25 Preference is also given to mixtures comprising as component 2) at least one active substance selected from group F), more preferably selected from compounds (F.1.2), (F.1.4) and (F.1.5). Preference is also given to mixtures comprising as component 2) at least one active substance selected from group G), more preferably selected from compounds (G.3.1), (G.3.3), 30 (G.3.6), (G.5.1), (G.5.3), (G.5.4), (G.5.5), G.5.6), G.5.7), (G.5.8), (G.5. 9), (G.5.10) and (G.5.11); particularly selected from (G.3.1), (G.5.1) and (G.5.3). Preference is also given to mixtures comprising as component 2) at least one active substance selected from group H), more preferably selected from compounds (H.2.2), (H.2.3), (H. 2.5), (H.2.7), (H.2.8), (H.3. 2), (H.3.4), (H.3. 5), (H.4.9) and (H.4. 10); particularly selected from 35 (H. 2.2), (H. 2.5), (H.3. 2), (H.4.9) and (H.4.10). Preference is also given to mixtures comprising as component 2) at least one active substance selected from group I), more preferably selected from compounds (1.2.2) and (1.2.5). Preference is also given to mixtures comprising as component 2) at least one active substance selected from group J), more preferably selected from compounds (J.1.2), (J.1.5), 40 (J.1.8), (J.1.11) and (J.1.12); in particular (J.1.5). 45 Preference is also given to mixtures comprising as component 2) at least one active substance selected from group K), more preferably selected from compounds (K.1.41), (K.1.42), (K.1.44), (K.1.47), ( K.1.57), (K.1.58) and (K.1.59); particularly selected from (K.1.41), (K.1.44), (K.1.47), (K.1.57), (K.1.58) and (K.1.59). The compositions comprising mixtures of active ingredients can be prepared by usual means, e. g. by the means given for the compositions of compounds I. CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 Examples: Synthetic process amended pages 27 PCT / EP 2021 / 059 730 - 04.08.2021 Example 1: Methyl (2E)-2-[2-[[(E)-3-(2-fluorophenyl)ethylideneamino]oxymethyl]-3-methyl- 5 phenyl]-2-methoxyimino-acetate Step 1: 1-(2-Fluorophenyl)ethanone oxime 1-(2-fluorophenyl)ethenone (10 g, 1. 0 eq) was taken in methanol (300 ml) and hydroxyl amine hydrochloride (7.54 g, 1.8 eq) was added. Pyridine (33.45 g, 2 eq) was added drop wise 10 at 25 "C. Reaction mixture was stirred at 50 "C for 2 hr. Reaction was monitored using LCMS & TLC. Methanol was evaporated under vacuum. Crude mass was diluted with water (200 ml) and it was extracted with ethyl acetate (3 x 100 ml). Combined organic layer was again washed with water and brine. Organic layer was dried over sodium sulphate and concentrated under vacuum. Crude compound was purified by flash column chromatography. Pure compound was 15 eluted with 0% to 20% ethyl acetate (EtOAc) in heptane. Evaporation of solvent afforded 8 g title compound as white solid (Yield 72%). 1H NMR 300 MHz, DMSO-d6: B 11.4 (s , 1 H), 7.46- 7.41 (m, 2 H), 7.27-7.23 (m, 2H), 2.14 (s, 3H). Step 2: Ethyl (2E)-2-[2-[[(E)-1-(2-fluorophenyl)ethylideneamino]oxymethyl]-3-methyl-phenyl]-2- 20 methoxyimino-acetate (Ex. 2) 1-(2-fluorophenyl)ethanone oxime (0.3 g, 3 eq) was taken in dimethyl formamide (DMF, 5 ml) and Cs2CO3 (3.27 g, 2.0 eq) was added. The reaction mixture was stirred for 30 minutes at room temperature ( RT; at about 25 °C) and then added methyl (2E)-2-[2-(bromomethyl)-3- methyl-phenyl]-2-methoxyimino-acetate (0.6 g, 3.02 eq). The reaction mixture was stirred at RT 25 for 32 hr and monitored by TLC and LCMS. Reaction was quenched with water (45 ml) and the product was extracted in ethyl acetate (3 x 35 ml). The combined organic layer was washed with brine (50 ml), dried over sodium sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 35-20% EtOAc in heptane. Evaporation of solvent afforded an off-white solid title compound (0.328 g, 45% yield). 30 1H NMR (300 MHz, DMSO-d6): B 7.56 - 7.36 (m, 2H), 7.33 - 7.32 (m, 4H), 7.03 (dd, J = 6.2, 2.8 Hz, 3H), 5.00 (s, 2H), 3.93 (s, 3H), 3.64 (s, 3H), 2.42 (s, 3H), 2.08 (d, J = 2.5 Hz, 3H). 35 Example 2: {2E)-2-[2-[[(E)-1-{2-fluorophenyl)ethylideneamino]oxymethyl]-3-methyl-phenyl]-2- methoxyimino-N-methyl-acetamide Methyl {2E)-2-[2-[[(E)-1-(2-fluorophenyl)ethylideneamino]oxymethyl]-3-methyl-phenyl]-2- methoxyimino-acetate (ex. 1; 8 g, 1 eq) was taken in THF (80 ml) and methylamine (40% aqueous) solution (16 ml, 2 vol) was added. The reaction mixture was stirred at 25 "C for 5 hr and monitored by TLC and LCMS. Reaction was quenched with water (200 ml) and the product CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 28 PCT / EP 2021 / 059 730 - 04.08.2021 was extracted in ethyl acetate (3 x 150 ml). The combined organic layer was washed with brine (150 ml), dried over sodium sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 30-40% EtOAc in heptane. Evaporation of solvent afforded white solid title compound (7 g, 87.7% yield). 1 H NMR 5 (500 MHz, DMSO-d6): o 8.20 (q, J = 4. 7 Hz, 1H), 7.44 (ddt, J = 7.8, 5.6, 2.0 Hz, 2H), 7.37 - 7.14 (m, 4H), 6.95 (dd, J = 7.1, 2.0 Hz, 1H), 5.01 (s, 2H), 3.86 (s, 3H), 2.65 (d, J = 4.8 Hz, 3H), 2.42 (s, 3H), 2.09 (d, J = 2.6 Hz, 3H). Example 3: Methyl (2E)-2-[2-[[(E)-1-(3, 5-dich lorophenyl)ethylideneamino ]oxymethyl]-3-methyl- 10 phenyl]-2-methoxyimino-acetate Step 1: 1-(3,5-dichlorophenyl)ethanone oxime 3-(3,5-Dichlorophenyl)ethanone (3.0 g, 3eq) was taken in methanol (30 ml) and NH2OH (0.735 g, 2 eq) followed by pyridine (3.04 g, 2.5 eq) were added. Reaction mixture was heated 15 to 70 °C and stirred for 3 hr. Reaction was monitored using LCMS & TLC. Solvent was evaporated and the residue was diluted with water (50 ml). The product was extracted in with ethyl acetate (3 x 30 ml). The combined organic layer was washed with brine (50 ml), dried over sodium sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 15-20% EtOAc in heptane. Evaporation 20 of solvent afforded white solid compound 1-(3,5-dichlorophenyl)ethanone oxime (1 g, 92.6% yield). Step 2: Methyl (2E)-2-[2-[[(E)-1-(3, 5-dichlorophenyl)ethylideneamino]oxymethyl]-3-methylphenyl]- 2-methoxyimi no-acetate 25 3-(3,5-Dichlorophenyl)ethanone oxime (0.4 g, 1 eq) was taken in acetonitrile (10 ml) and Cs2CO3 (1. 8 g, 2. 5 eq) was added. The reaction mixture was stirred for 30 min at RT and then added methyl (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (0.65 g, 1.05 eq). The reaction mixture was stirred at RT for 3 hr and monitored by TLC and LCMS. Reaction was quenched with water (50 ml) and the product was extracted in ethyl acetate (3 x 30 ml). 30 The combined organic layer was washed with brine (50 ml), dried over sodium sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 20-25% EtOAc in heptane. Evaporation of solvent afforded an off-white solid title compound (0.6 g, 68% yield). 1 H NMR (500 MHz, DMSO-d6): o 7.66 (t, J = 1.9 Hz, 1 H), 7.61 (d, J = 1.9 Hz, 2H), 7.36 - 7.23 (m, 2H), 7.05 - 6.98 (m, 1 H), 5.04 (s, 2H), 35 3.91 (s, 3H), 3.70 (s, 3H), 2.43 (s, 3H), 2.30 (s, 3H). Example 4: {2E)-2-[2-[[(E)-1-{3,5-dichlorophenyl)ethylideneam ino]oxymethyl]-3-methyl-phenyl]- 2-methoxyi mi no-N-methyl-acetam i de CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 29 PCT / EP 2021 / 059 730 - 04.08.2021 Methyl (2E)-2-[2-[[(E)-3-(3,5-dichlorophenyl)ethylideneamino]oxymethyl]-3-methyl-phenyl]-2- methoxyimino-acetate (ex. 3; 0.6 g, 1 eq) was taken in THF (6 ml) and methyl amine (40% aq.) solution (1.2 ml, 2v) was added. The reaction mixture was stirred at RT for 3 hr and monitored by TLC and LCMS. Reaction was quenched with water (25 ml) and the product was extracted in 5 ethyl acetate (3 x 20 ml). The combined organic layer was washed with brine (25 ml), dried over sodium sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 40-45% EtOAc in heptane. Evaporation of solvent afforded white solid title compound (example 2, 0.53 g, 85% yield). 1H NMR (500 MHz, DMSO-d6): o 8. 24 (d, J = 4.8 Hz, 1 H), 7.69 - 7.58 (m, 3H), 7.37 - 7.15 (m, 2H), 6. 95 (dd, 10 J = 7.1, 1. 9 Hz, 1 H), 5.05 (s, 2H), 3.86 (s, 3H), 2.68 (d, J = 4. 7 Hz, 3H), 2.42 (s, 3H), 2.11 (s, 3H). 15 Example 5: Methyl (2E)-2-methoxyimino-2-[3-methyl-2-[[(E)-1-(p-tolyl)ethylideneamino] oxymethyl] phenyl]acetate Step 1: 1-(p-tolyl)ethanone oxime To a solution of 1-(p-tolyl)ethanone (1.0 g, 4.45 mmol, 3 eq.) in methanol (10 ml) was added hydroxylamine hydrochloride (0. 77 g, 11.17 mmol, 1.5 eq) followed by addition of sodium acetate (1. 82 g, 15 mmol, 2 eq.) at RT under nitrogen atmosphere. Reaction mixture was 20 refluxed for 2 hrs. Reaction was monitored by TLC. Reaction mixture was concentrated on rotavapor. To this crude residue was added water (20 ml) and stirred for 0.5 hr. Solid material filtered and dried to obtain pure title compound (1.1 g, yield 98 %) as white solid. MS: [M + H] .. 150. 25 Step 2: Methyl (2E)-2-methoxyimino-2-[3-methyl-1-[[(E)-3-(p-tolyl)ethylideneamino] oxymethyl] phenyl]acetate To a stirred solution of 1-(p-tolyl)ethanone oxime (0.15g, 1. 0 mmol, 1 eq) in acetonitrile (2ml) was added Cs2CO3 (0.66 g, 2.0 mmol, 2 eq). The reaction mixture was stirred at 25 °C for 30 min. Then, methyl (2E)-2-[2-(bromomethyl)-3-methyl-phenyl]-2-methoxyimino-acetate (0.33 g, 30 1.1 mmol, 1.1 eq) was added. The mixture was stirred at 25 °C for 6 h. Reaction was monitored by TLC and LCMS. To this reaction mixture was added water (30 ml) and extracted with EtOAc (3 x 30 ml). Combined organic layer was washed with H2O (2 x 25 ml), followed by brine wash (2 x 20 ml). Organic layer was dried over Na2SO4 and Concentrated to afford crude compound which was further purified by flash column chromatography using 0-20% EtOAc in heptane as 35 the eluent to obtain pure title compound as white solid (0.37 g, Yield 96%). 1H N MR (500 MHz, chloroform-d) : o 7.42 (d, J = 8.2 Hz, 2H), 7.26 - 7.19 (m, 3H), 7.07 (d, J = 8.0 Hz, 2H), 6. 94 (dd, J = 7.2, 1.8 Hz, 2H), 5.03 (s, 2H), 3. 94 (s, 3H), 3.70 (s, 3H), 2.41 (s, 3H), 2.27 (s, 3H), 2.06 (s, 3H). MS: [M + H] + 369. 40 Example 6: (2E)-2-Methoxyimino-N-methyl-2-[3-methyl-2-[[(E)-1-(p-tolyl)ethylideneamino] oxymethyl]phenyl]acetamide CA 03171545 2022- 9- 13 AMENDED SHEET 202209 amended pages 30 PCT / EP 2021 / 059 730 - 04.08.2021 N"' O d3 H 􀌱 C I H3C H3C'O,.N 􀌲"'C H3 0 To a stirred solution of methyl (2E)-2-methoxyimino-2-[3-methyl-1-[[(E)-3-(p-tolyl)ethylideneamino] oxymethyl]phenyl]acetate in TH F (5 ml), methyl amine solution in water (5.0 ml, 40 %) was added at RT. Reaction was continued for 1 hr. Reaction was monitored by TLC. 5 Reaction mixture was evaporated on rotavapor, residue was diluted with EtOAc (20 ml) and washed with 1 N HCI (3 x 20 ml), followed by brine wash (2 x 20 ml). Organic layer was dried over Na2SO4 and Concentrated to afford crude compound which was further purified by flash column chromatography using 0-50% EtOAc in heptane as the eluent to afford pure title compound as white solid (0.200 g, Yield 88%). 1 H NMR (500 MHz, DMSO-d 6): B 8.20 (d, J = 5.0 10 Hz, 1 H), 7.54 - 7.48 (m, 2H), 7.31 - 7.22 (m, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.95 (dd, J = 6.9, 2.1 Hz, 1 H), 4.99 (s, 2H), 3.86 (s, 3H), 2.69 (d, J = 4.7 Hz, 3H), 2.43 (s, 3H), 2.31 (s, 3H), 2.08 (s, 3H). MS: [M + H] + 368. Example 7: (2E)-2-methoxyimino-N-methyl-2-[3-methyl-2-[[(E)-[3,3,3-trifluoro-1-[3-(tri- 15 fluoromethyl)phenyl]propylidene ]amino ]oxym ethyl]phenyl]acetamide F 􀁍 F F F 􀁎 F , I N"' o .f!1P H ,o ..,. N, 0 3,3,3-Trifluoro-1-[3-(trifluoromethyl)phenyl]propan-1-one (0.5 g, 1 eq), prepared in analogy to prior art process (Chem Commun, 2016, 52, 13668-13670), was taken in TH F (10 ml) and (2E)- 2-[2-(aminooxymethyl)-3-methyl-phenyl]-2-methoxyimino-N-methyl-acetamide (0.98 g, 2 eq) 20 followed by Ti(OEt)4 (1.33g, 3 eq) were added. The mixture was heated to 70 ° C and stirred for 12 hr. The reaction was monitored by TLC and LCMS. The reaction was quenched with water (25 ml) followed by EtOAc (25 ml). The emulsion formed was filtered through celite and washed with EtOAc (50 ml). The layers were separated and the aequous layer was extracted in EtOAc (2 x 25ml). The combined organic layer was washed with brine (25 ml), dried over sodium 25 sulphate and concentrated under vacuum. Crude material was purified by flash chromatography. Pure compound was eluted by using 40-45% EtOAc in heptane. Evaporation of solvent followed by crystallization in heptane afforded an off-white solid (0.34g, 35% yield). 1H NMR (500 MHz, DMSO-d6): B 8.27 (q, J = 4.7 Hz, 1H), 8.07 - 8.00 (m, 2H), 7.85 - 7.79 (m, 1H), 7.68 (t, J = 7.8 Hz, 1H), 7.35 - 7.24 (m, 2H), 6.97 (dd, J = 7.3, 1.7 Hz, 1H), 5.12 (s, 2H), 30 4.03-3.96 (q, J = 10 Hz, 2H), 3.86 (s, 3H), 2.67 (d, J = 4.7 Hz, 3H), 2.43 (s, 3H). 35 The following examples in Table S were synthesized as per general Scheme 1 described above (except Ex. 7 and 212 which were synthesized as per scheme 2) and characterized by LCMS as described in Table L. CA 03171545 2022· 9- 13 AMENDED SHEET 5 202209 amended pages 31 PCT / EP 2021 / 059 730 - 04.08.2021 Table L: LCMS Methods LCMS Method A Method details Devi ce details Column: Agilent Eclipse Plus C18 (50 mm LCMS2020 (Shimadzu) x 4.6 mm x 3 μm particles) Ionization source: ESI Mobile Phase: Mass range: 100 - 800 amu A: 10 mM Ammonium formate in water. Polarity: Dual (positive and B: 0.1 % Formic acid in acetonitrile negative simultaneous scan) Gradient: 10 % B to 100 % B in 1.5 min. Mode: Scan Hold 1 min 100 % B. 1 m in 10 % B. Run LC System: Nexera High pressure time: 3.50 or 3.75 min. gradient system, Binary pump Flow: 1.2 ml / min; Detector: PDA Column oven: 30 ° C / 40 ° C Scanning wavelength: 220 nm I max plot LCMS Method B Method details Devi ce details Column: Luna-C18 (30 mm x 2.0 mm x 3 LCMS DELIVER-220 (Shimadzu) μm particles) Ionization source: ESI Mobile Phase: Mass range: 100 - 1000 amu A: 0.037% Trifluoroacetic acid in water. Polarity: Positive B: 0.018% Trifluoroacetic acid in H PLC Mode: Scan grade acetonitrile LC System: Nexera High pressure Gradient: 5-95% B in 3.00 min .5% B in gradient system, Binary pump 0.01 min, 5-95% B (0.01-1.60 min), 95- Detector: DAD 100% B (1.60 - 2.50 min), 100 -5% (2.50 - Scanning wavelength: 220 nm I max plot 2.52 min) with a hold at 5% B for 0.48 min. Flow: 0.8 mUmin; Column oven: 40 ° C LCMS Method C Method details Devi ce details Column: Xbridge Shield RP18 (50 mm x Agilent 2.1 mm, 5 μm particles) Ionization source: ESI Mobile Phase: Mass range: 100 - 1000 amu A: H2O+10 mM NH4HCQ3 Polarity: Positive B: Acetonitrile Mode: Scan Gradient: 5% B in 0.40 m in and 5-95% B LC System: Nexera High pressure at 0.40-3.40 min, hold on 95% B for 0.45 gradient system, Binary pump min, and then 95-5%B in 0.01 min. Detector: DAD Flow: 0.8 ml / min; Scanning wavelength: 220 nm I max plot Column oven: 40 ° C CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 LCMS Method D Method details amended pages 32 Device details PCT / EP 2021 / 059 730 - 04.08.2021 Column: Agilent Eclipse Plus C1 8 (50 mm LCMS 2020 (Shimadzu) x 4.6 mm x 3 μm particles) Ionization source: ESI Mobile Phase: Mass range: 1 00 - 800 amu A: 1 0 mM NH4(HCOO) in water Polarity: Dual (positi ve and negative B: Acetonitrile simultaneous scan) Gradient: 1 0 % B to 1 00 % B in 5 min, Mode: Scan hold on 1 00 % B for 3 min, 2 min 1 0 % B. LC System: Nexera High pressure Run time: 1 0 min. gradient system, Binary pump Flow: 1 .2 ml / min; Detector: PDA Column oven: 40 ° C Scanning wavelength: 220 nm / max plot Used LCMS Method in Table S to be found in Column LCMS. Table S: No. 1 2 3 4 5 6 7 CA 03171545 2022- 9-- 13 Structure crF 􀂷 --.,:, WO u ..,.. o ,N O .... 0 crF 􀀃 '<::I:: WO u ..,.. o ,N N, 0 C l 􀂸 I w o 􀂹: :::,... ..,.. ,N o, C l 0 C l 􀂸 I N' o 􀂺: :::,... ..,.. ,N N C .... l 0 ff 􀁆--.,:, WO u ..,.. o , o, 0 ff 􀁆 '<::::: WO b ..,.. o ,N N, 0 􀂻 F3 C 􀂼 I WO b ..,.. o ,N N, CF 3 0 Rt [min] 2.08 1 .941 2.252 2.1 5 2.144 2.027 2.1 23 AMENDED SHEET Mass LCMS 373.7 A 372 A 422.9 A 421 .9 A 369 A 368 A 490 A 202209 No. 8 9 1 0 1 1 1 2 1 3 1 4 1 5 16 1 7 CA 03171545 2022- 9-- 13 amended pages 33 Structure Rt [mi n] 2 . 1 5 2 . 1 9 2.22 2 . 1 3 1 .95 2 . 1 8 2 . 1 1 2.05 2 . 1 7 1 .99 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass 422.5 423.5 449.2 3 448.4 404 435.3 434.4 425.2 426.2 447. 1 LCMS A A A A A A A A A A 202209 No. 1 8 1 9 20 21 22 23 24 25 26 CA 03171545 2022- 9-- 13 amended pages 34 Structure F3Cdwoa N C :::,,,. I / o, 0 􀂹 F 􀂺 -.::::: F W O A .,...o, o, 0 dF F 􀂻 I WO A Cl .,...o,N O..... 0 d F F 􀂺 I N'O A F .,...o,N o, 0 d F F 􀂼 I W O A Cl .,...o,N N..... 0 F F3C -9' WO I A F 􀂽 d / o'N N, 0 F 􀂾 F3Cd 1 WO I A :::,,,. ,,.o,N O..... 0 F F3cd 1 wo􀂿: :::,,,. ,,.o,N a, 0 F F3 C d l w o􀃀: :::,,,. ,,.0,N N..... 0 Rt [min] 2.09 2.06 2 . 1 55 2.06 2.08 2.04 2.07 2.07 1 .984 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 448.2 A 404 A 425 A 408.5 A 424 A 458.3 A 458.9 A 441 .0 5 A 440 A 202209 No. 27 28 29 30 31 32 33 34 35 36 CA 03171545 2022- 9-- 13 amended pages 35 Structure d F F a I W O -6 F ,..... o, N N, 0 CF30 dl wo ?,Z: ::::,... ...0,N O..... 0 CF30 􀃁I N 'o 􀂺 : 􀃂 ...,.o,N N ...., 0 cfW􀁗􀁘 O 􀃃 ,.....o,N O..... 0 􀀘 􀀙"'.:::::: W O -6 ,.....o , N...... 0 F3C 􀃄I wo 􀃅 : 􀃆 ,.....o,N N...., CF3 0 F3C 􀃇I wo t( : 􀃂 ...,. o,N O ..... Cl 0 F3C 􀃈I wo 􀃉 : 􀃂 ...,. o,N 0..... CF3 0 F􀃊N dl wo 􀃋: ::::,... ...,.o,N 0..... N"'O 􀃍 0 􀃌 CF ;£􀁖 ...,.o,N O ..... 0 Rt [min] 1.97 2.17 2.09 2.058 1.963 2.17 2.25 2.25 2.1 2.101 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 408 A 439 A 438 A 355 A 354 A 490 A 456.9 A 491 A 446.8 A 423 A 202209 No. 37 38 39 40 41 42 43 44 45 46 47 CA 03171545 2022- 9-- 13 amended pages 36 Structure Rt [min] 2. 1 55 1 .999 2.059 2.271 2 . 1 5 1 .94 2.09 1 .99 2 . 1 3 2.01 2.08 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 422.9 A 422 A 422 A 423.7 A 422 A 435.9 A 436 A 445.9 A 397 A 447 A 440 A 202209 No. 48 49 50 51 52 53 54 55 56 57 58 CA 03171545 2022- 9-- 13 amended pages 37 Structure Br􀁆wo:{) U ✓􀁇-􀁈o, Rt [min] 2.1 1 2.18 2.1 1 2.2 2.274 2.094 1 .984 2.02 2.197 2.208 2.091 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 448 A 441 A 440.8 A 441 A 447.8 A 379.8 A 378 A 396 A 435.6 A 446.1 A 432.8 A 202209 No. 59 60 61 62 63 64 65 66 67 68 CA 03171545 2022- 9-- 13 amended pages 38 Structure F3c )Ywo 􀁀 Cl :::,,. I ,,,, o, 0 F3C N'0 0 d 􀀂 '<::l Cl ,,, O ,N N, 0 F3 c d 1 wo 􀁁: :::,,. ,..o,N O..... 0 F3 c d 1 N'o 􀁂: :::,,. ,,,O,N N...., 0 W O ,,;::; 􀁝 􀁞'<::, 0 ,,,0,N O O..... W O ,,;::; 􀁝 􀁟'<::, 0 ,,,o, 0 N..... F3C vl w o􀁃: ::,,:,. ,..o,N o, 0 0-N 􀁄 F3C-{ 􀁅 0 I N ? N' ,,;::; :::,,. I ,..o,N O, 0 F3 C-tvl O􀁆o'<::l N ? N' :::,,. I ,,,0,N N. F3c v1 N'o􀁇: ::,,:,. ,..o,N N.... 0 Rt [min] 2.26 2.15 2.22 2.146 2.099 1 .97 2.24 2.24 2.15 2.14 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 457 A 456 A 437 A 436 A 436 A 435 A 437 A 491 A 490 A 436 A 202209 No. 69 70 71 72 73 74 75 76 77 78 CA 03171545 2022- 9-- 13 amended pages 39 Structure F 3C N' O h' ifF 􀀸 -..::: I ...,o, N .... 0 F 3 :􀄸-N ? I N' o 􀄹: ::::,.. ,..... o ,N o, 0 I O,N 􀂺 F3C􀄵I wo I 􀄶 ::::,.. ,.....o, N, 0 dF F 􀂎 I WO 􀁂 ...,o,N O.... 0 d F F 􀄷 I W O h' ...,o,N .... 0 c1vc1 􀁓"' wo .& ,.....N o , 0 c1 V CI a'<::: w o .& ,.....o,N N. 0 'd' 􀁙'a::: W O ,,::: ...,o,N o, 0 􀀓 􀀔'a::: W O ,,::: ...,O ,N N.... 0 ...,o-d 1 wo 􀀖: 􀀪 ,.....O,N O. 0 Rt [min] 2.059 2. 1 97 2.091 1 .337 1 .256 2.208 2. 1 01 2.22 2. 1 2. 1 33 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 440 A 480 A 479 A 391 A 390 A 463 A 462 A 369 A 368 A 385 A 202209 No. 79 80 81 82 83 84 85 86 87 88 CA 03171545 2022- 9-- 13 amended pages 40 Structure ,,..o􀀽1 wo􀀾: ::::,... .,..o,N .... 0 Fyo '(f 1 w o 􀂏 : F or::,.. ,,0,N O.. 0 Fy o d1 w o 􀂐: F or::,.. ,,0,N N.... 0 N'O .,;:; 􀁠 􀁡'<::, 0 ,,o,N o, 0 N'O .,;:; 􀀚 􀀛 ---:, 0 ,, 0 ,N N... 0 F 􀁢 􀁣 'sl: W O ..& .,..O,N N ..... 0 if 􀁚􀁖 N'O .,,t;:; ..... 0 Fif i N'O 􀂎 : ::::,... .,.. o ,N o, 0 􀀜 􀀝􀀞 F N'O A ,,.. o .N o.... F 0 F3C 􀂑 I 'o􀂒: ::::,... ,,o,N N .... 0 Rt [min] 2.005 2 . 1 3 2.037 2.08 1 .92 2.08 2.03 2 . 1 7 2.08 2.24 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 384 A 421 A 420 A 425 A 424 A 390 A 372 A 373 A 391 A 448 A 202209 No. 89 90 91 92 93 94 95 96 97 98 99 CA 03171545 2022- 9-- 13 amended pages 41 Structure if 􀁛'<::, F3C N'O ,,:;:; ,..0,N O.. 0 dF F 􀁽 F3C WO I A ,..0,N O.... 0 dF F 􀁾 F3C N'o I ,,:;:; ,..0 ,N N.. 0 F3Cif􀁿 WO􀂀: ::::,,,. ,.. o,N O.... 0 F3Cif􀂁 N'O􀂂: ::::,,,. ,..o,N N.. 0 􀂃 􀂄􀂅 wo .& ,, o , N O O.. V 􀀆'<:::, WO 􀃎 ,.. 0,N o, 0 􀀤 8.--:::, WO ,,:::; ,..0,N o, 0 °'(la 's::: wo '° ,..O,N o, 0 °'dN'O 􀀂􀀃􀂆 ,..O,N N.... 0 V 􀀃􀀄 W O 6- ,, o , N O N, Rt [min] 2 . 1 5 2.261 2 . 1 55 2.21 2 . 1 1 2 . 1 87 2.22 2.283 2.208 5.01 2.08 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 449 A 459 A 458 A 451 A 450 A 383 A 397 A 41 1 A 431 A 430 D 382 A 202209 No. 100 101 102 103 104 105 106 107 108 109 CA 03171545 2022- 9-- 13 amended pages 42 Structure 􀁤 􀁥"'ll, W O o .,...o,N N.... 0 V ?Z '<:::: W O .6 .,...o, o, Cl 0 xf 􀁜'<:::: W O .6 Cl .,...o,N o , 0 d ZZ'<:::: WO o F .,...o,N O.... 0 Nc'of 1 wo 􀀸: :::,.... .,...o,N o, 0 􀀸 􀀹'<:::: W O & .,...o,N N, 0 y4 􀁝 "'<:::: W O & .,...o,N N.... Cl 0 :er 􀀑 "'<:::: N'O ..? Cl .,... o,N N.... 0 d 􀀅 W "'<:::: O -& F .,...o ,N N.,, 0 c􀀹'P"' I wo 􀀺: ::::,... .,... o,N N, 0 Rt [min] 2.187 2.22 2.21 2.08 1.995 2.144 2.112 2.123 1.952 2. 123 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 4 10 A 403 A 403 A 373 A 380 A 396 A 402 A 402 A 372 A 402 A 202209 No. 110 111 112 113 114 115 116 117 118 119 CA 03171545 2022- 9-- 13 amended pages 43 Structure 􀄺 a-s::: Cl WO .o ....O,N O Cl 0 . 􀀂 a􀀃 N'o .o ....O,N O.... 0 􀄻 􀄼-s::: NC N' O .& .... O ,N N . 0 off 􀀥 '<::, N' O .&l .... O,N N. d 􀀆 WO 's::::.& Br ,.... o ,N °, cf !.Z's:::: W O .& .... O ,N O . 0 &1- CI 􀄽 WO '-::::.& ,....o,N a, 0 ¢! Cl 􀄾 -..::::, WO .& ,.....o,N o.... Cl 0 ql F a-s::: N' O .o .... O , N o, F 0 (Y Br a -s::: wo .o ,.... o ,N a, 0 Rt [min] 2.25 2.2 1.87 2.11 2.17 2.113 2.101 2.197 2.091 2.12 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 441 A 431 A 379 A 430 A 435 A 369 A 389 A 423 A 391 A 434 A 202209 No. 120 1 2 1 122 123 124 125 126 127 128 129 CA 03171545 2022- 9- - 13 amended pages 44 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Rt [min] Mass LCMS 2.005 433 A 2.2 431 A 2.05 379 A 2.04 385 A 2.11 430 A 1 .93 378 A 1 .931 384 A 1 .984 368 A 1 .984 388 A 2.112 391 A AMENDED SHEET 202209 No. 1 30 1 3 1 1 32 1 33 1 34 1 35 1 36 1 37 1 38 1 39 CA 03171545 2022- 9-- 13 amended pages 45 Structure ql C I 􀂻-.::::: N'O A .,,.O,N N .... Cl 0 􀂼 F 􀂽􀂾 WO A .,,. o ,N N .... F 0 d ?2r '<::: F WO .&r, F .,. o .N N ,.., d 􀀇-.;:;, WO o 9 .,. O .N 0 , CF 3 0 '(YF ?2r'<::: Br WO .&r, .,. 0 ,N o , 0 Br􀂿I N' o ?2r: 􀃀 .,. O . N o , Br 0 d 􀀈-.;:;, WO o 9 .,. 0 ,N N,.., C F3 0 xiWO􀁞 o-.;:, .,. o . o 0 , tr 􀀦-.;:;, Br N' o '° F .,. O .N 0, 0 xiWO􀁞 A􀁟 .,. o .N N ,.., Rt [min] 2.08 1 .984 1 .984 2. 1 87 2. 1 55 2.29 2.08 2 . 1 8 2.261 2. 1 55 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 422 A 390 A 390 A 439 A 453 A 5 1 3 A 438 A 383 A 453 A 382 A 202209 No. 140 141 142 143 144 145 146 147 148 CA 03171545 2022- 9-- 13 amended pages 46 Structure Br 'OCI N'o􀀞: :::,... F .,,0, N 0 , '(fF 􀄿-.a:::: Br N' O .& .,,0,N N ..... 0 Br 􀁉I N'o􀀞: 􀀹 .,,0,N N, Br 0 F3 C yl N' o a: :::,... .,,0,N o, I I 0 F3C -?' I N'oa :::,... / o , I --:::: 0 ,& F 3 C tl N'oa: :::,... ,..o,N o, 0 F3 C v l w o􀀟: 􀀹 .,,0,N o, 0 F3 C v l wo􀀠: :::,... ,.. 0,N o, 􀅀 0 F3 C vl N'o􀀡: :::,... ,..0,N N, I I 0 Rt [min] 2 . 1 44 2.069 2.208 2. 1 97 2.304 2.261 2.261 2.24 2. 1 87 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 450 A 452 A 5 1 2 A 447 A 499 A 463 A 451 A 449 A 446 A 202209 No. 149 1 50 1 5 1 1 52 1 53 1 54 1 55 1 56 1 57 CA 03171545 2022- 9-- 13 amended pages 47 Structure F3C -:?' I w0:£ 11,,.. ,, N.. I 􀀻 0 .& F3C vl N"'o 􀃏 : ::::,,,. ,,0,N N.. 0 F3C zl N"'O 􀃐: :i,,.. ,,0,N N.. 0 F3C vl W O 􀃑: 􀁊 ,,O,N N...., :::::, 0 ql 􀁠--::: WO ,,;; ,......o,N O.... Cl 0 d 􀀈--:;: W O o Cl ,, O,N O.. 0 d 􀀉--:;: W O ,,;; NC ,.. O,N o, 0 tc 􀀒--:;: F3C N'O ,,;; F ,, 0, N 0, 0 􀀟 􀀠--::: WO ,,;; ....,.o,N N .... C l 0 Rt [min] 2.347 2.272 2.261 2.229 2. 1 55 2 . 1 44 1 .995 2. 1 33 2. 1 32 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 498 A 462 A 450 A 448 A 389 A 389 A 380 A 459 A 388 A 202209 No. 1 58 1 59 160 161 162 163 164 165 166 167 CA 03171545 2022- 9-- 13 amended pages 48 Structure WO ,:; d 􀀇 "l::: Cl .,.O,N N.. 0 dN'Q 􀀈A "l::: NC .,.O,N N.. 0 􀀡 􀀢􀀥 N ' O ,;:; 0 ,.. O , N O .. 0 􀀣 􀀤􀀥 N' O ,;:; 0 ,..O ,N N .. 0 '()CF 􀀣 '<.:::: F3C N'O ,:;; F .,. 0 , N N.. 0 cxl,:::,,- 1 wo􀀑: :::::,,,. ,...0,N 0 ..., 0 d 􀀂 "l::: N'O .o 0 .,.0,N N-.., I o 􀀤 􀀥'<::::: wo '° .,. 0, N O N, wo .& yd 􀁇"" 0 ,.. o , O o Cl ,0 ,:;; 􀀦 F 􀀧 '<::::: N .,. 0, N N -.., Cl 0 Rt [min] 2. 1 33 1 .941 2.08 2.091 2.229 1 .995 2. 1 87 2.048 2.2 1 9 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 388 A 379 A 425 A 458 A 403 A 384 A 382 A 397 A 440 A 202209 No. 168 169 1 70 1 7 1 1 72 1 73 1 74 1 75 1 76 CA 03171545 2022- 9-- 13 amended pages 49 Structure d 􀀄􀀅 N'O A Br .,,.o,N N..., 0 HF 􀁛 -.::::, N'O A F F ....O,N O. H F 􀀸 􀀺 N'O A F F / O'N N..., 0 ace, 􀀊--:::: N"'O A Cl .,,.o,N O..., 0 P 􀀂 '<:::: W O A ,¢, ,....o,N 0..., 0 ace, N'O 􀀋A--:::: Cl .,,. o , N N ..., 0 CCN"'O 􀁡""-:::A ,..... o, N o, 0 (f 􀁢--:::: N"'O A .,,.O,N 0..., 0 2f 􀀧􀀨 N'O A .,,.o,N N. 0 Rt [min] 2. 1 33 2. 1 12 1 .984 2.29 2 . 1 65 2.069 2.24 2.261 2 . 1 45 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 434 A 409 A 408 A 423 A 379 A 422 A 383 A 383 A 382 A 202209 No. 1 77 1 78 1 79 1 80 181 1 82 1 83 1 84 1 85 1 86 CA 03171545 2022- 9-- 13 amended pages 50 Structure 􀂼 F 􀂽'<::::: F N' O A ,.... o ,N 0 ... 0 􀂾 F 􀂿􀃀 F W O o ,..O,N N ..., 0 􀁦 􀁧'<::::, W O o 0 ,.. 0 ,N O N..., 􀃁 F 􀃂--:::: F W O .o ,.... o ,N 0 ..., CF3 0 􀁨 􀁩'<::::, W O ,,;:; ' o'N .,..o, N o o, 􀀩W:£-.:::: O .& ,􀃃N / 􀃄N O N, 􀃅 􀃆'<::::: WO A ,.. 0 , N O 0 .... I ? W O o F3 C ,O 􀀎 ✓O ' N N-. 0 􀀦 􀀧􀀞 W O .& ,, O ,N N, CF3 0 􀀛 o N'O􀀜 A ,,0, N N , C F3 0 Rt [min] 2 . 1 65 2.037 1 .888 2.273 2.261 2 . 1 44 2.251 2 . 1 23 2.23 2. 1 12 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 391 A 390 A 396 A 459 A 426 A 425 A 383 A 438 A 462 A 452 A 202209 No. 1 87 1 88 1 89 1 90 1 9 1 1 92 1 93 1 94 1 95 CA 03171545 2022- 9-- 13 amended pages 51 Structure '-o􀀼 N 2Y 􀀽 9' I N'o ,-.:; 􀀾 I .,...o,N o, 0 􀀨 􀀩􀀪 wo '° .,...o,N N , CF3 0 􀀫 􀀬􀀪 wo '° .,...o,N N , 0 ql CI 􀅁 􀀺 wo ,-.:; .,...o,N N .... CF3 0 􀀟o 􀀠 I WO ,,-.:; ,...o,N O .... C F3 0 I ?"' WO .& F3C, 0 􀃇 er / O ' N o, 0 Y 􀀂 "Z::: 􀀡 wo 􀀢 .,...o,N N.... 0 􀀭 􀀮􀀪 N'O .o .,...o,N a, CF3 0 6: 􀁣􀁖 wo n .,...o,N N , 0 Rt [min] 2.027 2.24 2 . 1 44 2. 1 87 2.229 2.24 2. 1 01 2.42 1 2 . 1 44 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 426 A 437 A 436 A 456 A 453 A 439 A 402 A 465 A 382 A 202209 No. 1 96 1 97 1 98 1 99 200 201 202 203 204 CA 03171545 2022- 9-- 13 amended pages 52 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Rt [min] Mass LCMS 1 .931 378 A 2. 1 76 458 A 2.204 441 A 2 . 1 44 440 A 2.31 5 457 A 2. 1 33 439 A 2.016 438 A 2.283 383 A 2.31 5 437 A AMENDED SHEET 202209 No. 205 206 207 208 209 210 211 212 213 214 CA 03171545 2022- 9-- 13 amended pages 53 Structure F3 C-<􀁫- 􀁬 􀁭 O 􀁮 .-,:;-s::, N ,::;,- N' I ::,,,. ..,-0,N N, W O b' 􀀯 􀀮"-::: .... O ,N O .... CF3 N'o b' 0 􀀰 􀀱"-::: .... O ,N ..., C F 3 0 wo & CC 􀀪"-:: C F 3 .... 0 ,N 0.... 0 CC 􀀓-.:::: W O b- C F 3 .... O 􀃁 N',N N, O h' 􀀲 􀀳"-::: ::::,.. I ....o .. N o, 0 􀀂 wo Q 􀀲 􀀳 '-::: 􀀝 I ,.....o .. N N .... 0 '-o􀀱 N 􀀲 􀀳 I P W O & i::,... I ....o, N N, wOCo b' F --;:::: F .... O , N 0.... 0 OCF wo & F .... 0 , N N, 0 Rt [min] 2.15 2.336 2.229 2.219 2.187 2.219 2.091 1.952 2.123 1.947 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 490 A 451 A 450 A 452 A 450 A 381 A 380 A 425 A 391 A 391 A 202209 No. 215 216 217 218 219 220 221 222 223 CA 03171545 2022- 9-- 13 amended pages 54 Structure F3C􀀻 I N'o􀀼: 􀀹 ,.- 0 ,N o, 0 ,d 􀁉􀁊 W O .& 0 ,....o,N O.... I o 􀀴 􀀵􀀶 N'O A ,... o ,N O .... 0 2yL 􀁈 '<:::, W O o ....0,N o, 0 &4 􀀫 N' '<:::, O .... .& O ,N N, 0 􀀷 􀀸􀀪 w o .& ,....o,0 􀃒 􀃓'<:::, N'O A ,.- 0 ,N N .... 0 F3C 􀀽 􀀾 -9' N'O A 􀀃 I ,...o, N o , 0 F3C 21 􀀬 I -::,, N'O A 􀀃 I ,...o,N N .... 0 Rt [min] 2.357 2.048 2.208 2.261 2.101 2.155 2.251 2. 165 2.048 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 463 A 385 A 395 A 397 A 394 A 396 A 410 A 437 A 436 A 202209 No. 224 225 226 227 228 229 230 231 232 233 CA 03171545 2022- 9-- 13 amended pages 55 Structure 􀃄CN 􀃅'<::::: WO ,,-::; .,.,o .. N O .... 0 cr C N 􀃆N" '<::::: O ,,-::; .,.,o .. N N .... 0 ,,,,o,NJ,..,,,,o lf 1 wo􀁔; ::,,.. ,,,,o, ... 0 ,,,,o,NJolf 1 wo􀁕; i::,,. ,,,,o,N 0... C l vl N ' o 􀃇: ::::,... .,., o ,N .. CF3 0 4 􀀂 N' '<::::: O .,., ,,-::; o .. N O .... CF3 0 􀃈􀃉'<::::: WO ,,-::; .,.,o .. N N .... CF3 0 yr 􀀭--.:::::: WO ,,-::; .,.,o ,,-::; o, CF 3 0 yrw o􀀿: .,.,o ,,-::; N .... CF3 0 F 3C 'CC1 W O I ,&; '-N 􀀨 􀃊 F .,., o .. N .... Rt [min] 1 .963 1 .853 2.069 2. 1 87 2.25 2.24 2. 1 55 2 . 1 6 2 . 1 65 2.21 AM E N D E D S H E ET PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Mass LCMS 380 A 379 A 455 A 456 A 456 A 437 A 436.3 A 422 A 421 A 469 A 202209 No. 234 235 236 237 238 239 240 241 242 CA 03171545 2022- 9-- 13 amended pages 56 Structure F3 C 􀅂 I w o 􀁛 : ::::,,.. ,..... o ,N N -..., F3 C 􀅃 I w o 􀅄: ::::,... ,.....o,N N -..., orO CF 􀅅 --:::: wo .& I ,......o,N o, 􀀔 :£􀀕 WO .& ,..... o ,N 0 -..., C F3 0 I F ,::;;, WO ,.:;, 'N 􀀗 A􀁏N N, CF3 0 􀁪 􀁫"'I;: WO,..... ,.:;, o ,N o, 􀁬 􀁭"'I;: F WO ,.:;, ,.....o,N o, Br 0 􀅆 F 􀅇 􀀺 F N' O A ,..... o ,N N, Br 0 rF 􀀺 "l:l F WO ,.:;, ,.....o,N o, 0 Rt [min] 2.251 2.251 2.24 2.325 2 . 1 65 2.31 5 2.31 5 2.208 2.2 1 9 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 462 A 465 A 439 A 463 A 469 A 437 A 469 A 468 A 4 1 5 A 202209 No. 243 244 245 246 247 248 249 250 251 CA 03171545 2022- 9-- 13 amended pages 57 Structure VF F N'􀅈-.:::: O .,.. ll 0 ,N N ..... 0 c1C F3 􀅉 ".:::: N' O A ,.,.. o .& o ..... 0 qlC F3 a'a:::: WO., .& 0 ,N N ... Cl 0 􀀹 􀀺--::: Cl N' O .& F .,.. o ,N o ..... Cl 0 􀀻 􀀼-.:::: Cl N' O ll F .,.. 0 ,N N ..... Cl 0 qlB r a'a:::: WO., .& 0 ,N N ... F 0 qlC F3 a'a:::: WO.,.. o,N .& o ..... F 0 􀅊 F3 C 􀅋 I W O .& .,..o,N o ..... C F3 0 􀅌 C F WO.,.. 􀅍--:::.& o ,N 0 ..... Cl 0 Rt [min] 2. 1 1 2 2 . 1 8 2 . 1 76 2.4 2.283 2.048 2 . 1 33 2.251 2 . 1 97 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 4 1 4 A 422 A 456 A 441 A 440 A 452 A 441 A 491 A 457 A 202209 No. 252 253 254 255 256 257 258 259 260 261 CA 03171545 2022- 9-- 13 amended pages 58 Structure Rt [min] 1 .963 208 2. 1 76 2.229 2. 1 55 2.251 2. 1 55 2.251 2.059 2 . 1 65 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 420 A 421 A 453 A 490 A 407 A 503 A 502 A 453 A 440 A 452 A 202209 No. 262 263 264 265 266 267 268 269 270 CA 03171545 2022- 9-- 13 amended pages 59 Structure Rt [min] 2.034 2 . 1 44 2 . 1 44 2.229 2.069 390 2.283 2.229 2 . 1 44 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 406 A 441 A 5 1 3 A 5 1 4 A 391 A 2.005 A 473 A 457 A 456 A 202209 No. 271 272 273 274 275 276 277 278 279 280 CA 03171545 2022- 9-- 13 amended pages 60 Structure N􀃕 O ..& N C I 􀃔 -..::::, CF30 . O ,N 0 N.... qlC F 􀅎--:::: wo & .,...o.N N...... CF3 0 ql 􀁤􀁖 WO & 􀃖CCFF3 .,...􀃗o,N --::::::0 N..... WO & .0,N O .... CF3 F3c wo I .& -6?- F 3 C .􀃘0,N 0 ..., ql 􀁥 's:::, wo ..& .O, N O.. CF3 0 0 20 􀀻 I -:,,, WO n :::.. I ,.o , N N ..... 0 sf 􀀮-..::, WO & . 0 ,N O N.. Y 􀀖 "'=I: wo .0,N .& 0 ..., o 􀀫 􀀬 I -:,,, WO ..& :::.. I ..,.o .N o, 0 Rt [min] 2 . 1 76 2 . 1 23 2 . 1 23 2.2 1 9 2 . 1 65 2.2 1 9 1 .952 2. 1 55 2.347 2.06 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 472 A 490 A 436 A 491 A 491 A 437 A 398 A 382 A 41 1 A 399 A 202209 No. 281 282 283 284 285 286 287 288 289 CA 03171545 2022- 9-- 13 amended pages 61 Structure F 􀂓 􀂔"-<::: P- wo .,,:::; :::,... I .,..o, N o, F tN dl N' o􀂕: :::,,.. ,..0, N... 0 .,. o 􀁛 OC F 􀀘I Cl N .,....o, N o.. 0 ..,o :::::,.... 6c 􀀯I Cl N ..,....o , N N ... 0 6:F 􀀙I wo 􀀇 .,....o ... N 0 .. o 􀀚 I ff 􀁦 F w· .,.... o ,. N N ,. 0 o 􀀛 I F 􀀯 􀀰 N .,. ...... o, N O .. 0 F o 􀁛 I 􀀱 􀀲 N .,. ......O, N N,. 0 .,..0 􀀼 6:;ci 􀀜I : .,.... o, N O,. F 0 Rt [min] 2. 1 76 1 .99 2.12 2.0 2.16 2.02 2 . 1 4 2.02 2.20 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 431 A 445.9 A 407 A 406 A 387 A 396 A 397 A 430 A 457 A 202209 No. 290 291 292 293 294 295 296 297 298 299 CA 03171545 2022- 9-- 13 amended pages 62 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Cl 􀁀 I N' O : .,..... 􀄗 o ,N N.... F 0 Rt [min] Mass LCMS 2. 1 456 A 1 . 95 394 A 2.25 395 A 2.02 386 A 2.05 369 A 1 .94 384 A 2 . 1 8 408 A 2.20 395 A 1 .98 404 A 2 . 1 4 394 A AMENDED SHEET 202209 No. 300 30 1 302 303 304 305 306 307 308 CA 03171545 2022- 9-- 13 amended pages 63 Structure Rt [min] ()CCI 􀀝I N' O :::,. Br ,, o , N °-..... 0 ,o :::,... ()CCI 􀀝I Br N ,, o , N N ....., 0 2.22 2.1 2.16 2 . 04 1.416 1.95 1.96 1.99 1.64 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 469 A 468 A 419 A 4 1 8 A 456.8 A 447 B 465 B 427 B 412 B 202209 No. 309 31 0 31 1 312 31 3 31 4 31 5 316 CA 03171545 2022- 9-- 13 amended pages 64 Structure Rt [min] 0lf l O 􀂝 o I -:?' N,. .:::,... .:::,... I .,..,o .... N a, 1 . 9 1 . 9 1 .74 1 .76 1 .88 1 .69 1 .82 464 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 4 1 3 B 426 B 4 1 3 B 398 B 411 B 4 1 4 B 412 B 1 . 86 B 202209 No. 317 318 319 320 321 322 323 324 CA 03171545 2022- 9-- 13 amended pages 65 Structure Rt [min] F 􀄀 o :::i,... I 0 N .., ,.... o , N N....., I o 1.86 1.83 1.93 1.86 1.87 1.8 1 .386 1 .79 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 399 B 412 B 413 B 453 B 446 B 4 1 5 B 456.7 A 452 B 202209 No. 325 326 327 328 329 330 33 1 332 CA 03171545 2022- 9-- 13 amended pages 66 Structure Rt [min] 1 .64 1.77 1 .83 1 .88 1.78 , 't' l,,o􀀈 'CJ"' ..,, o , N 􀁐 o , 1.86 1.77 1 .93 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 456 B 440 B 436 B 453 B 4 1 0 B 441 B 452 B 437 B 202209 No. 333 334 335 336 337 338 339 340 CA 03171545 2022- 9-- 13 amended pages 67 Structure Rt [min] 2.25 1 . 9 1 .53 1 . 458 1 .67 2 1 .85 1 . 7 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCM S 503 A 457 B 549 A 548. 1 A 468 B 473 B 426 B 452 B 202209 No. 341 342 343 344 345 346 347 CA 03171545 2022- 9-- 13 amended pages 68 Structure Rt [min] 1 .65 1.88 1 .95 1.68 1.6 1 .82 1 .92 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 437 B 505 B 506 B 474 B 440 B 474 B 355 B 202209 No. 348 349 350 351 352 353 354 355 CA 03171545 2022- 9-- 13 amended pages 69 Structure Rt [min] F lf F 􀂖 o I 􀄁 N ,, :::::,, :::::,,. I .,,, o ... N o, 1 .97 3.04 1 .99 1.92 1 .84 1 .86 1.82 2.97 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 453 B 522 C 507 B 457 B 488 B 4 1 9 B 456 B 535 C 202209 No. 356 357 358 359 360 361 362 363 CA 03171545 2022- 9-- 13 amended pages 70 Structure Rt [min] 3.13 1.62 2.93 1.95 1.73 1.76 1.93 1.89 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 536 C 458 B 519 C 459 B 459 B 475 B 455 B 506 B 202209 No. 364 365 366 367 368 369 370 371 CA 03171545 2022- 9-- 13 amended pages 71 Structure Rt [min] F F F 􀄂 w.. o 􀁖 I Br F .,.... o ... N o, 1 .74 1 .7 1 .9 1 .84 3.09 1 .87 1 .94 3.79 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 438 A 441 B 475 B 354 B 520 C 458 B 489 B 523 C 202209 No. 372 373 374 375 376 377 378 379 CA 03171545 2022- 9-- 13 amended pages 72 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Rt [min] Mass LCMS F4 « F o 􀁁 I P N' o II::,. F II::,. I .,...o.. N, 1.76 1.94 1.91 2.07 1.95 1.67 2.2 AMENDED SHEET 418 B 427 B 472 B 403 A 402 A 456 B 457 A 202209 No. 380 38 1 382 383 384 385 386 387 CA 03171545 2022- 9-- 13 amended pages 73 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Rt [min] Mass LCMS (¢F F 􀁂 I wo 􀂇 F ,....o,N N .... F 0 2 . 04 2 . 1 3 2.2 2 .07 1 .67 1 .78 2 .24 2 .25 AMENDED SHEET 422 A 423 A 4 1 7 A 4 1 6 A 472 B 473 B 383 A 383 A 202209 No. 388 389 390 39 1 392 393 394 395 396 CA 03171545 2022- 9-- 13 amended pages 74 Structure 􀀆 􀀇 I N"'O 􀁋 ,o .. N N...... 0 oX 􀀰I N"'O ,o .. N N...... 0 F & F 􀁌 F I P N"'o 􀁋 􀀈 I F ,.....o 􀁍 o, 0 F ql 􀁗 F I P N"' o 􀁋 􀀃 I ,.....o .. N o, F 0 F & 􀀃I N"'O 􀁋 ,o.,N O .... 0 F & 􀀄I N"'o 􀁋 ,.....o .. N N...... 0 F 􀀉 􀀊I P N"'o 􀁋 F 􀀋 I ,..... o.. N.... 0 cfN,o 􀁎 r I ...... o, 0 􀀏r cfN..,O ,..... N...... 0 Rt [min] 2 . 1 4 2 . 1 1 2 . 1 8 2 . 1 5 2 . 1 6 2 . 03 2 . 08 2 . 1 9 2 . 05 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 382 A 382 A 440 A 437 A 437 A 436 A 454 A 421 A 420 A 202209 No. 397 398 399 400 401 402 403 404 405 CA 03171545 2022-9-- 13 amended pages 75 Structure d- 􀁧I N'O :::.::.,,.. ..,...o,.N o, 0 d-N, O􀂦 / o, 0 d- 􀁨I N'O ;:::,... .,,,o ... N N, 0 cfN,O􀂧 / N, 0 'crF 􀁃 􀂨 I N'O ;:::,... .,,,o .. N N, 0 F􀂗 F ;?£1 P N'O 􀂩 F 􀂩 I ,..o .. N o, 0 F F 􀂪 􀂫 I P N'o ;:::,... ill:,,. I ,..o.. N, 0 F F 􀂬 ;?£1 p N'O ill:,,. F 􀂩 I ,..o .. N o, F 0 F F 􀂭 􀂮 ? N'o ;:::,... I F ;:::,... I ,..o A o, F 0 Rt [min] 2.23 2 . 1 8 2.03 1 .99 2.03 2. 1 97 1 .25 2 . 1 67 2.22 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 381 A 367 A 380 A 366 A 396 A 455 A 436 A 473 A 472 A 202209 No. 406 407 408 409 41 0 41 1 412 41 3 CA 03171545 2022- 9-- 13 amended pages 76 Structure F F 􀂘 􀂙 1" N' I O i:i,,.. F i:i,,.. I .,..o .. N N, F 0 F F F P l N' O 􀂚 Ill,,.. .,.. N, 1 -..:::: 0 6 F F F P l .. o􀀅 Ill,,.. .... o, I -..:::: 0 6 􀂛 F F 􀀌I N' O lib. F .,.. o .. O .... F 0 􀂜 F F wo􀀊 ::::.,.. I F .,.. o .. N, 0 F 􀂝 3!1 F P N' O c1 lb. I .,.. o .. N o, 0 F F 􀂞 􀂟 F 1" I N' O lib. Cl ::::.,.. I .,.. o .. N, 0 JIF F N'􀂠I O 􀂡 .,.. o .. O N, Rt [min] 2 . 1 2 2.26 2.29 2.21 2.04 2.24 2 . 1 3 2.25 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 472 A 5 1 2 A 5 1 3 A 459 A 458 A 489 A 488 A 498 A 202209 No. 41 4 41 5 416 41 7 41 8 41 9 420 421 CA 03171545 2022- 9-- 13 amended pages 77 Structure o , I F F 􀃙 .,. ...O,. N...., N .., 0 0 Rt [min] 2.34 2 . 1 8 2.27 2.24 2.28 2. 1 06 2.02 2 . 1 8 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 499 A 509 A 529 A 494 A 5 1 0 A 528 A 493 A 457 A 202209 No. 422 423 424 425 426 427 428 429 430 CA 03171545 2022- 9-- 13 amended pages 78 Structure Rt [min] Cl􀂢:􀂣 N '03! ? I 􀂡 ,...o .. N N..... 0 W O ::::,... »F F 􀀞I N¢- .,,.. o,N O... 0 »F F 􀁄 I W O ::::,... N¢- .,,..o,N 􀂤 .... 0 F YFF 􀂈 I WO :::,,. .,,o,N O... wo ""'- .,,o,N 􀂞 .... F ✓FF 􀂉 I 􀂥Io 􀂦 I ,:::;,- W O ::::,... c,-0: / o'N o , 0 :to 􀀄I -::?' W O ::::,... c, --CX: / o'N 􀂧, 0 􀅏 F F 􀀟I Cl W O ::::,... Cl .,,..o,N O... 0 Cl􀂨: 􀂩 N' 0 􀂪 ,:::;,- 1 Cl ::::,.... .,,..o .& O... 0 2 . 1 2 2.03 1 .898 2.26 2 . 1 5 1 .86 1 .75 2.27 2.3 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 456 A 448 A 447 A 5 1 7 A 516 A 507 B 506 B 491 A 490 A 202209 No. 431 432 433 434 435 436 437 438 CA 03171545 2022- 9-- 13 amended pages 79 Structure Rt [min] AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 490 A 516 A 5 1 4 A 5 1 5 A 5 1 4 A 506 B 436 B 491 B 202209 No. 439 440 441 442 443 444 445 446 CA 03171545 2022- 9-- 13 amended pages 80 Structure Rt [min] ffF F 􀃈 I WO ::::,.... ,....o .& O, 0 1 .82 1 .66 1 .71 1 .77 1 .72 1 .83 2.23 2.1 2 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 507 B 490 B 506 B 490 B 489 B 506 B 500 A 436 A 202209 No. 447 448 449 450 45 1 452 453 454 CA 03171545 2022- 9-- 13 amended pages 81 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Rt [min] Mass LCMS 1 .87 475 B 1 .75 488 B 1 . 8 490 B 1 .89 474 B 1 .78 474 B 1 .9 1 490 B 1 .85 488 B 1 .83 489 B AMENDED SHEET 202209 No. 455 456 457 458 459 460 461 462 463 CA 03171545 2022- 9-- 13 amended pages 82 Structure Rt [min] e􀂟 􀂠,, O ¼ H u ,, o , N)yN , 0 N... o ::::,.. CI 􀁅 I F3C, o N ,, o 􀃉 o , 0 1.9 1.81 1.72 2.04 2.16 2.64 2.00 2.21 2.31 AMENDED SHEET PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 491 B 488 B 488 B 408 A 409 A 465 A 438 A 438 A 472 A 5 202209 No. 464 Biological studies amended pages 83 Structure Rt [min] g cF 􀁆 I N" O ::::,... , 0 ,..,.. o ,,,;::; o , 0 2.10 Green H ouse and detached leaf tests PCT / EP 2021 / 059 730 - 04.08.2021 Mass LCMS 452 A The compound was dissolved in a mixture of acetone and / or dimethylsulfoxide and the wetting agent / emulsifier Wettol, which is based on ethoxylated alkylphenoles, in a ratio (volume) solvent-emulsifier of 99 to 1 to give a total volume of 5 ml. Subsequently, water was added to total volume of 100 ml. This stock solution was then diluted with the described solvent- 10 emulsifier-water mixture to the final concentration given in the table below. Use example 1. Curative control of soybean rust on soybeans caused by Phakopsora pachyrhizi (PHAKPA K4) Leaves of potted soybean seedlings were inoculated with spores of Phakopsora pachyrhizi. 15 The strain used contains the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. To ensure the success of the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95% and 20 to 24 °C for 24 hr. The next day the plants were cultivated for 3 days in a greenhouse chamber at 23 to 27 °C and a relative humidity between 60 and 80 %. Then the plants were sprayed to run- 20 off with the previously described spray solution, containing the concentration of active ingredient or their mixture as described below. The plants were allowed to air-dry. Then the trial plants were cultivated for up to 14 days in a greenhouse chamber at 23 to 27 °C and a relative 25 humidity between 60 and 80 %. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area, the disease level of untreated controls was usually higher than 85 %. Use example 2. Protective control of soybean rust on soybeans caused by Phakopsora pachyrhizi (PHAKPA P2) Leaves of potted soybean seedlings were sprayed to run-off with the previously described spray solution, containing the concentration of active ingredient or their mixture as described 30 below. The plants were allowed to air-dry. The trial plants were cultivated for 2 days in a greenhouse chamber at 23-27 °C and a relative humidity between 60 and 80 %. Then the plants were inoculated with spores of Phakopsora pachyrhizi. The strain used contains the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. To ensure the success the artificial inoculation, the plants were transferred to a humid 35 chamber with a relative humidity of about 95 % and 20 to 24 °C for 24 hr. The trial plants were cultivated for up to 14 days in a greenhouse chamber at 23 to 27 °C and a relative humidity between 60 and 80 %. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area, the disease level of untreated controls was usually higher than 85 %. 40 Use example 3. Protective control of soybean rust on soybeans caused by Phakopsora pachyrhizi (PHAKPA P6) Leaves of potted soybean seedlings were sprayed to run-off with the previously described CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 amended pages 84 PCT / EP 2021 / 059 730 - 04.08.2021 spray solution, containing the concentration of active ingredient as described below. The plants were allowed to air-dry. The trial plants were cultivated for six days in a greenhouse chamber at 23-27 ° C and a relative humidity between 60 and 80 %. Then the plants were inoculated with spores of Phakopsora pachyrhizi. The strain used contains the amino acid substitution F129L in 5 the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. To ensure the success the artificial inoculation, the plants were transferred to a humid chamber with a relative humidity of about 95 % and 23 to 27 °C for 24 hr. The trial plants were cultivated for up to 14 days in a greenhouse chamber at 23 to 27 °C and a relative humidity between 60 and 80 %. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area, the 10 disease level of untreated controls was usually higher than 85 %. Use example 4. Protective control of soybean rust on detached soybean leaves caused by Phakopsora pachyrhizi (PHAKPA P1 DL) Leaves of potted soybean seedlings were sprayed to run-off with the previously described 15 spray solution, containing the concentration of active ingredient as described below. The plants were left for drying in a green house chamber at 20 °C and 14 hours lightning over night. The next day, leaves were harvested and placed on water agar plates. Subsequently, the leaves were inoculated with spores of Phakopsora pachyrhizi. Two different isolates were used: one being sensitive to Qo inhibitors (wt); and one which contains the amino acid substitution 20 F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors (F129L). Inoculated leaves were incubated for 16 to 24 h at room temperature in a dark dust chamber, followed by incubation for 2 to 3 weeks in an incubator at 20 ° C and 12 hours light / day. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area. 25 Micro titer plate tests The active compounds were formulated separately as a stock solution having a concentration of 10,000 ppm in dimethyl sulfoxide. The stock solutions were mixed according to the ratio, pipetted onto a micro titer plate (MTP) and diluted with water to the stated 30 concentrations. After addition of the respective spore suspension as indicated in the different use examples below, plates were placed in a water vapor-saturated chamber at a temperature of 18 ° C. Using an absorption photometer, the MTPs were measured at 405 nm 7 days after the inoculation. The measured parameters were compared to the growth of the active compound-free control 35 variant (100%) and the fungus-free blank value to determine the relative growth in % of the pathogens in the respective active compounds. Use example 5. Activity against Pyricularia oryzae causing rice blast (PYRIOR) A spore suspension of Pyricularia oryzae in an aqueous biomalt or yeast-bactopeptone- 40 glycerine or DOB solution was used. 45 Use example 6. Activity against Septoria tritici causing leaf blotch on wheat (SEPTTR) A spore suspension of Septoria tritici in an aqueous biomalt or yeast-bactopeptone-glycerine or DOB solution was used. Use example 7. Activity against Colletotrichum orbicu / are causing anthracnose (COLLLA) A spore suspension of Colletotrichum orbicu / are in an aqueous 2% malt solution was used. CA 03171545 2022- 9-- 13 AMENDED SHEET 5 202209 amended pages 85 PCT / EP 2021 / 059 730 - 04.08.2021 Use example 8. Activity against Leptosphaeria nodorum causing wheat leaf spots (LEPTNO) A spore suspension of Leptosphaeria nodorum in an aqueous biomalt or yeastbactopeptone- glycerine or DOB solution was used. Use example 9. Activity against Alternaria so / ani causing early blight (ALTESO, wt and F129L) Two different spore suspensions of Altemaria so / ani in an aqueous biomalt or yeast-bactopeptone- glycerine or DOB solution were used: a sensitive wild-type isolate (wt) and a Qo inhibitor-resistant isolate containing the amino acid substitution F129L in the mitochondrial 10 cytochrome b protein conferring resistance to Qo inhibitors (F129L). Use example 10. Activity against Pyrenophora teres causing net blotch on barley (PYRNTE, wt and F129L) Two different spore suspensions of Pyrenophora teres in an aqueous biomalt or yeast-bacto- 15 peptone-glycerine or DOB solution were used: a sensitive wild-type isolate (wt) and a Qo inhibitor-resistant isolate containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors (F129L). Use example 11. Activity against Cercospora sojina causing frogeye leaf spot of soybeans 20 (CERCSO) A spore suspension of Cercospora sojina in an aqueous biomalt or yeast-bactopeptoneglycerine or DOB solution was then added. Use example 12. Activity against Microdochium nivale causing snow mould (MONGNI) 25 A spore suspension of Microdochium nivale in an aqueous biomalt or yeast-bactopeptoneglycerine or DOB solution was used. The results of the abovementioned use examples are given in the following Tables. 30 The test results in Tables 1 and C1 to C4 below are given for the control of phytopathogenic 35 fungi containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors. Table 1: No. 1 2 Treatment with compound Structure 2r 􀁋"" N' O Al ,.,o,N o, 0 􀀽 􀀾 wo "" .& ,.,o,N N, 0 % PHAKPA (F1 29L) Disease level P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 80 27 90 56 5 0 26 1 CA 03171545 2022- 9-- 13 AMENDED SHEET 202209 No. 3 4 5 6 8 9 1 0 1 1 1 2 1 3 1 4 1 5 CA 03171545 2022- 9-- 13 amended pages 86 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure Cl v l N'o 􀂡: .,., ,... o,N O,, Cl 0 Cl v l N'O 􀂡,;t; "'- ,... o,N N,, Cl 0 ffwo􀀋 "'.& ,...o,N O,, 0 ffwo􀀋 .&"' ,...o,N N.,, 0 F3cd1 wo ;.£: .,., ,...o,N N,, 0 F3Cdwo􀀔:: ...O,N o, 0 F3Cd l wo􀀕:: "'- ,.0,N o, 0 F3Cdwo􀀕:: "'- ,.0,N N, 0 F WO ,,,; tr ;X.... ...O,N N, 0 F3cd1 wo 􀂢 I:: :::,,. ,... o,N o, 0 F3c d1 wo 􀂢 I:: :::,,. ,...o,N N.,, 0 o v 􀂣 wo I ,,,; I .,o,N N, 0 P2 at 4 ppm 30 2 28 1 4 35 22 23 25 28 6 4 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 3 40 6 0 1 3 1 1 50 4 0 1 9 1 0 5 0 23 41 4 2 45 3 1 20 0 1 37 9 0 25 0 0 1 1 1 0 24 1 202209 CA 03171545 2022- 9- 13 amended pages 87 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 17 70 50 63 57 19 87 0 87 1 20 73 29 97 18 21 1 00 77 97 88 22 1 00 90 1 00 93 23 12 1 20 1 24 F􀄘 F 􀄙 F3 C 􀄚N' O I ,&; u ,,,.o, o, 36 60 4 28 25 16 3 50 2 26 12 0 19 1 27 5 0 32 0 28 0 0 AMENDED SHEET 202209 No. 29 30 31 32 33 34 36 37 38 39 40 41 CA 03171545 2022- 9- 13 amended pages 88 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure CFaO 􀃾I N'o 􀃿 .. ,.. ,.-0,N N.. 0 􀀿 􀁀... WO A ,,.-0 ,N O.. 􀁁 􀁂... N' O AJ ,,.-0,N N, F3C 􀄀 N'o 􀄁 :: ..0,N N... F3 0 F3C 􀄂 N'o 􀄃 : ,0,N O... Cl 0 F3C V1 w0 􀄄 ....O.,N o...., F3 0 W O J 􀄅 CF3 􀄆'<:! ,0,N O.. d 􀀅... N'O A FaC ...O,N O... 0 􀄇 CF3 N 􀄈'<:! 'O AJ ,,.-0 ,N N , 0 d 􀀆... W O AJ F3 C ...O,N N, 0 Cl dN'􀀊... O Cl ..,.o .. N O..... Cl dN'O􀀋 A... Cl ..O,N N.. 0 P2 at 4 ppm 53 0 80 50 1 00 1 00 40 37 30 40 1 5 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 0 0 1 77 2 0 4 0 50 73 43 33 60 75 90 90 83 42 1 00 43 3 40 2 4 47 1 4 1 5 2 1 8 63 22 9 36 1 4 202209 No. 42 43 44 46 47 48 49 50 51 52 53 54 CA 03171545 2022- 9- 13 amended pages 89 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 􀀂N'oa ,......o .. N N..... I O I 0-N 􀂉 􀂊 N ' ,..o, N O.. 0 F􀂋N 􀂌 I N' ◊ a: ..O,N N. 0 N V 􀂍 .,,, wo I .,..o. N N. Fa 0 wo F 􀁃 ...􀁄 ..., 0,N N. CF3 0 P W O .& N 􀂎 􀂏 -.. I ,...o. N o. CF3 0 w o .& F,st .,.􀁌o,N .... O... 3 0 F N'O .& V 􀀊..... ,...o,N N..., 3 0 F N' O .& V 􀀃""' ...O,N O ... 3 0 iili!.... o I .& "d N ' ..,o, O.. F3C 􀂐 0 rP ,0 .& V􀀋.... I ,..o. N o, 0 V.,, 1 w 0 􀂑 : .,.o,N N.. 0 P2 at 4 ppm 60 1 00 77 63 1 3 1 00 60 2 28 63 63 0 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 23 60 20 1 00 97 87 1 7 77 2 1 50 90 57 0 1 2 0 80 1 00 67 1 8 60 7 1 6 0 2 1 5 0 28 90 43 1 7 1 00 47 1 20 0 202209 No. 55 56 57 58 59 60 61 62 63 64 65 66 CA 03171545 2022- 9-- 13 amended pages 90 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure N' O A Y􀀊""' .,.- 0 ,N N., 0 Brdl N' O 􀄉 A ""- ,, o ,N o, ,P' N' O FaC 'd 􀄊 .., I ..o,N N, 0 Br N' O d 􀀊""' .,.. o ,N N, d􀀈...., F3C N' O A Cl ... O , N o, F3 C N' O A d􀀃"" Cl ... O ,N N, 0 F3 cd1 w o 􀁌; ""- ,, 0 ,N o, 0 F3 cd1 w o 􀁌; .., ... O ,N N, 0 N'O A 􀁅 􀁆"" 0 ,, o , N o , 0 􀁅 􀁆"" N' O A 0 ,, 0 , 0 N , F3C ¢I N' O 􀄋 ; ,,0, N o, 0 FaC-<􀄌- v r o 􀄍 ,,, N ,P' I N' ""- .,.. o ,N o, 0 P2 at 4 ppm 3 43 25 2 67 23 70 43 90 87 93 1 00 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 1 3 5 24 67 1 9 8 43 1 5 0 4 0 20 63 1 1 1 53 2 1 5 90 1 8 0 60 3 77 93 77 73 80 43 77 1 00 87 70 93 87 202209 No. 67 69 70 71 72 73 74 75 76 77 78 79 CA 03171545 2022- 9-- 13 amended pages 91 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure F,c-<􀄎 􀄏v, I , o 􀄐 .,....o.,, N, 0 F3C N'O ,,, 􀁇 􀁈 ... ,.O,N N.,_ 0 O,N F,cV a I N'o I ,,, .., ,o,N O. 0 O,N 􀁍 F,cV I N'o I ,,, .... ,,.0, N., 0 wo I F F CY' 􀀗 ,-0,N O. 0 dF F 􀂅 wo .,0,N N. c1yc1 􀀔"" w o ,....o .. N o, Cl 􀂆 CI 􀂇.. o ,....o... N..., 0 􀁍 ;:£"' W O ,....o .. N O.... 0 􀁉 􀁊... w o ,,,,, ..O,N N... 0 ,, o 􀄑1 _ o 􀁍 : , o,N O. 0 .,.. o d l w o 􀄒: ,.-0,N N., 0 P2 at 4 ppm 67 2 30 2 1 00 0 27 8 30 67 40 21 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 2 80 30 0 1 3 0 0 1 0 1 0 6 0 87 93 80 1 9 6 1 6 3 0 1 3 1 3 9 0 4 40 3 1 30 1 2 44 4 202209 No. 80 81 82 83 84 85 86 87 93 94 95 96 CA 03171545 2022- 9-- 13 amended pages 92 PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 Treatment with compound % PHAKPA (F1 29L) Disease level Structure Fy o d 1 w o 􀁜:'.; F "'- ,.0, 0 ., 0 Fy o lfw o F ,,..􀁜: o ,N N .., 0 N'o .& nlf 􀀌"" 0 ,.,.o,N o, N'o .& nlf 􀀍"" 0 ,.,.o,N N..., F N' O .& 􀁋 􀁌""' ,.,.o.N N..., 0 Fd l wo􀀴:: .,,o,N N., d􀀌""' F N' O ,.O,N O., yr 􀁎-.. F N' O d ,. 0 ,N 0 -. 0 F3Cif l N' O 􀅐: 􀀘 ,....o .. N N..... V􀀃 ..... N' O J ..,- 0 ,N O 0-. Va"" WO ..O,N O . 􀁍 􀁎W ""' O J ,,.. o ,N o , P2 at 4 ppm 50 6 87 97 0 1 1 2 8 83 22 1 1 6 AM E N D E D S H E ET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 0 30 3 0 2 0 57 73 0 0 0 0 0 0 3 23 3 0 7 0 32 43 37 5 35 2 0 33 4 1 3 0 202209 No. 97 98 99 1 00 1 01 1 02 1 03 1 04 1 05 1 06 1 07 1 08 CA 03171545 2022- 9-- 13 amended pages 93 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure °'cl E, N'O Al ,..o,N o, 0 􀁏 􀁐 N'O ..,Al ,..o,N N., 0 V 􀀆.., N'O A ,,.o,N O N, vN'Oa A ..0,N N , 0 􀁑 􀁒N'O ..,A ,..o,N o, Cl 0 xf 􀁇.., N'O A Cl , O,N o, 0 d 􀀉.., N' O ,,:; F ,0,N 0, 0 N ed i w o 􀁀: "'- ,...o,N o, 0 V 􀀄.., W O A ..0,N N, 0 '(f a.., N'o ,,,, .,.o,N N, Cl 0 :d 􀁏.., N'o ,,,, Cl ,..o,N N.. d 􀀍.., wo ,,,, F ..O,N N, 0 P2 at 4 ppm 4 3 43 1 8 70 60 40 22 1 8 5 1 1 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 1 0 0 1 0 1 2 87 33 0 25 4 37 60 1 7 1 1 90 43 3 35 4 1 5 1 9 1 1 1 39 1 3 1 32 9 0 1 5 1 0 1 0 202209 No. 1 09 1 1 0 1 1 1 1 1 2 1 1 3 1 1 4 1 1 5 1 1 6 1 1 7 1 1 8 1 1 9 1 20 CA 03171545 2022- 9-- 13 amended pages 94 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure xrcp , N' o 􀁦: :,,,.. ,.O,N N-., 0 « 􀀈"' Cl N'O -tP ..O,N o, Cl 0 off 􀀈"" WO -tP ,,.o, o, N edi w o 􀁩: :,,,.. ,.O,N N-., 0 off a"" WO -tP ..O, N.., 0 dw􀀌"" o Br ..,o .. N °, 0 clN"O 􀁐d"" ,. O ,N 0 .., 0 (I CI a-s:, WO ,,o. o, qlC I 􀁧-.. WO ..:; ,..o. o, Cl 0 ¢0 F 􀄛-.. wo ,,,,, ,.O,N o, 0 􀁨 B r w􀁩 -.. o ,,,,. ... O ,N o, 0 crBr ,,, wo ,,,,. ... O ,N N ..., P2 at 4 ppm 8 20 28 1 3 25 38 83 85 85 1 0 93 43 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 1 2 0 3 30 1 8 46 1 0 3 30 9 26 41 25 5 52 1 5 63 92 75 57 85 67 1 0 88 1 2 0 32 0 63 92 63 4 90 8 202209 CA 03171545 2022- 9-- 13 amended pages 95 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 121 1 22 1 23 1 24 1 25 1 26 127 1 28 129 1 30 1 31 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 1 00 98 98 92 1 00 73 93 90 1 00 82 90 78 98 87 92 75 72 9 90 44 87 34 95 70 90 44 93 62 32 2 77 2 28 1 24 2 20 1 40 1 0 0 2 0 AMENDED SHEET 202209 No. 1 32 1 33 1 34 1 35 1 36 1 37 1 38 1 39 1 40 141 1 42 CA 03171545 2022- 9- 13 amended pages 96 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure Fd 􀀆""" N'O A F ..,.o,N N, 0 dN'O􀁫 A""" 9 ..,.o,N o, CF3 0 '(YF 􀃌 """ Br N'o .& ..,.o,N o, 0 Br 􀃊I N'o 􀃋 : :i:,.. ..,.o,N O .. Br 0 d 􀀇""" N'O A 9 ..,.O, N N, CF3 0 xf 􀁪 '<::i N'O A ..,.o,N O.. 0 tr 􀁩 '<::i Br N'o o F ..,.o, N o, 0 xiN'O 􀁪A""" ,..o,N N, 0 « a '<::i Br N'o o F ..,.o, N N, 0 '(YF 􀃌'<::: Br N'o o ..,.o,N N, 0 Br 􀃍I N'o 􀃎 : :i:,.. ..,.o,N N, Br 0 P2 at 4 ppm 1 1 37 1 5 1 1 9 47 47 8 2 1 9 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 0 6 0 0 2 0 1 0 22 7 1 1 6 2 0 3 2 2 50 5 2 35 1 2 72 24 0 1 3 4 0 2 0 5 26 5 202209 No. 1 43 1 44 1 45 1 46 1 47 1 48 1 49 1 50 1 51 1 52 1 53 CA 03171545 2022- 9- 13 amended pages 97 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure Fa C il N' o 􀃋: ""' .,.. o , o I I 0 F3 C tl N' o 􀃌: ""- ,..O,N o ... 0 , I .& 􀃐 ,, er: 0 o, F3 c v 1 N' o 􀃍: :::,,. .,..o, 0 F3 c v1 N' o 􀃎: ;:,,,. ,..O,N o, 􀃏 0 F3 C il N' o 􀃐: :::,,. ,..o, N, I I Fa C tl N' o 􀃑: ;:,,,. ,..0, N, ... 0 I .& F 3C vl N' o 􀃒: :::,,. ,..O,N .. 0 F3 c v 1 N' o 􀃓: :,,,.. ,..O,N N, 0 F 3c v 1 N' o 􀃋: :,,,.. ,..0, N, 􀀕 0 ql 􀁑􀁒 N'o ,,::, O,N O.. Cl 0 P2 at 4 ppm 4 87 28 73 73 9 83 56 37 24 1 2 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 0 1 5 0 80 92 90 8 37 1 6 1 2 77 48 1 8 95 1 8 2 1 3 7 45 87 31 8 70 29 3 53 6 1 38 7 3 22 1 202209 No. 1 54 1 55 1 56 1 57 1 58 1 59 1 60 161 1 62 1 63 1 64 CA 03171545 2022- 9- 13 amended pages 98 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure dw􀁬'<::, o b Cl ..,.. o .N o, 0 dN'o􀁭 '<::,,&; NC ..,.. o ,N o, 0 -6c 􀁫'<::, F3C N'O o F ..,..o, o, ql 􀁓 "<::::: w o .& ,.,-0,N N-,,, Cl 0 dwo􀁮 .&'<::, Cl ..,.. o ,N N-,,, 0 d 􀀊""' W O n NC ..,..o,N N-,,, 􀀃Wa O 0 .,...o .,,N O.... 0 􀀃Wa O 0 ..O, N... 0 􀂤 F F3C N'􀂥-.:, O A F ..,..o.N N-,,, cxrrP I N'o 􀂦: ""'- .O,N o, dN'o􀁯 '<::,o 0 ..,..o,N N, I o P2 at 4 ppm 30 97 27 1 0 28 1 00 1 00 0 20 5 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 3 63 9 30 93 20 0 47 3 0 1 0 0 2 0 2 28 1 97 87 90 1 00 1 00 90 0 1 0 1 47 9 0 27 0 202209 No. 1 65 1 66 1 67 1 68 1 69 1 70 1 71 1 72 1 73 1 74 1 75 CA 03171545 2022- 9- 13 amended pages 99 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 􀁓 􀁔""' N' o .& ,..- 0 ,N O N..., yd 􀁔-.. N'O .& 0 ..0,N O O. 􀃚F 􀃛""' Cl N' O .& ,..- 0 ,N N ..., Cl 0 d 􀀋...., W O ..& Br ,... o ,N N..., 0 H F wa'«:: o ..& F F .. o .N o, 0 H F 􀃜'«:: wo .& F F .. O ,N 0 N..., cc. C l N'a'«:: O .& Cl .. O ,N O 0 . P 􀀆.... N'O .& ?' ,.,o,N o , & I N'a'<::, o .& Cl ,..- O ,N N, 0 6: a""' N'O d ,..- 0 ,N O , 0 􀁕 􀁖wo ""' ..& ,..-0,N O ..., 0 P2 at 4 ppm 0 1 00 2 2 77 9 1 00 35 1 00 1 00 1 00 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 0 1 7 0 83 90 43 0 9 0 0 5 0 0 77 0 0 4 0 1 00 80 50 1 83 1 2 53 97 1 7 1 00 80 70 97 1 00 93 202209 CA 03171545 2022- 9-- 13 amended pages 1 00 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 1 76 1 77 1 78 1 79 1 80 181 1 82 1 83 1 84 1 85 1 86 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 1 00 1 00 1 00 90 1 00 2 1 87 47 6 0 2 0 1 00 47 90 28 40 7 5 0 22 1 1 33 5 6 0 1 3 0 1 6 0 38 2 42 4 1 6 1 1 00 67 90 77 1 0 2 0 AMENDED SHEET 202209 No. 1 87 1 88 1 89 1 90 1 91 1 93 1 96 1 97 1 98 1 99 200 CA 03171545 2022- 9- 13 amended pages 1 01 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 'o' if 􀄓 ?' ,o ,6 ,., I ...o ,N o... 0 ql 􀁰􀁱 wo & ... O,N N,... CF3 0 􀄔 􀄕􀄖 W O .& .,...o,N N.... 0 􀁯 C l 􀁰 W 􀁵 O -& .,...o.N N,... CF3 0 􀀭 o W􀀮 O & ...O,N o, CF3 0 y 􀀂 N'o & ,0,N N... 0 P 􀀇"" w o & 1P ,0, N N, 0 􀁱 F 􀁲 -., F N'O .6 ...O,N N, CF3 0 stF -., wo & ,0,N O... 3 0 􀁳 F :£ "" WO .& ,.O,N N,... CF3 0 qlCI w􀁴 􀁵 o & .,...o,N O .... CF3 0 P2 at 4 ppm 1 00 1 82 20 77 1 5 1 0 4 0 93 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 00 90 90 0 1 1 0 28 97 37 0 45 3 2 83 22 0 1 4 0 0 1 1 5 0 2 0 1 0 0 0 0 0 73 1 00 77 202209 CA 03171545 2022- 9-- 13 amended pages 1 02 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 202 203 204 206 207 21 1 2 1 3 214 215 216 2 1 7 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 90 22 1 00 47 87 32 93 32 50 4 80 5 1 00 67 1 00 90 40 1 1 83 5 1 00 43 1 00 77 50 3 40 1 1 1 4 0 28 4 87 37 87 33 77 1 3 80 29 97 53 93 1 00 AMENDED SHEET 202209 No. 2 1 8 2 1 9 220 221 222 223 224 225 226 227 228 CA 03171545 2022- 9-- 13 amended pages 1 03 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure N'O A & ..,􀀉 ""' o,N O ... 0 N'O A 􀁗 􀁘...0,N ""' N., 0 wo & & 􀀊""' ..,0,N N., 0 N'O A 􀁙 􀁚""' ..,0,N N., 0 I ,:;,- N'O A F3C lf 􀁶 􀁷 I ...,o,N o, 0 I ,:;,- N'O A F3C lf 􀁶 􀁷 I ,...o,N N... 0 lfCN 􀁸 ""' wo & ....0,N O... 0 clCN 􀁹 ""' W O o .... O, N N.... 0 .,.o. N .,,l,,o dl N ' o a 􀀖 ..,...o ... N N...., 0 ,,o. N .,,l,,o dl N ' o a 􀃝 .,...o ... N 0 .... 0 Cl 􀁺 I N 'o􀁻 : 􀁷 ....0,.., CF3 0 P2 at 4 ppm 1 00 60 90 1 00 1 00 4 97 83 28 1 00 5 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 87 1 00 1 00 8 87 43 30 1 00 77 63 1 00 1 00 57 1 00 93 0 28 0 1 00 1 00 1 00 27 1 00 97 3 57 7 47 1 00 57 0 22 2 202209 No. 229 230 231 232 233 234 235 236 238 240 241 CA 03171545 2022- 9-- 13 amended pages 104 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 4 ?2r"" wo ,.. .& o ,N 0 ., C F3 4 ?2r N' o .& ,.. o ,N N .,, CF3 0 􀁛 􀁜"" N' O .& o o, CF3 0 􀁝 􀁞wo "" ,..o .& N .,, CF3 0 Fa c 'oc l wo 'N I .& ?2r ""- F ,.. o vl􀁲,N "" 0 N.,, F3C 0 ,..o,N N ., 0 F3 C 􀄜 I N' o "'- ,:&:r: 0 ,N N ., 0 or O C F 3 􀁕 "" wo ,..o,N .& O .,, 0 I F 􀄞 N' O 'N 􀄝.& 􀀠 A, ,, CF3 0 􀄟 F 􀄠"" F N' O ,.... .& o ,N 0 .,, Br 􀀁 F ?2r F N' O .& ,.. o ,N N .,, Br 0 P2 at 4 ppm 27 22 0 1 00 1 00 53 1 00 97 1 00 70 3 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 2 77 6 1 73 4 0 2 0 73 1 00 83 57 87 27 1 8 53 1 5 73 87 77 77 97 1 00 53 1 00 77 8 73 3 0 33 1 2 202209 No. 242 243 244 245 246 247 248 249 250 251 252 CA 03171545 2022- 9-- 13 amended pages 1 05 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure VF 􀃜 F N' "'° O .o ,...o,N o, 0 VF F N'􀃞"'° O ,...o,N .o0 N, crC F 􀃟"'° N' O ,... ,o O .o O 0 , lf CF 􀃡"'° WO,... .o o Cl ,N 0 N. 􀁟 􀁠"" Cl WO A F ,... o ,N 0, 0 􀁟 􀁠"" C l N' O A F ,... o ,N N . Cl 0 􀃠r 􀃡 "" N' O ,...O,N A N . F lf CF3 􀃢 "'° WO,... O,N 4- O , F 0 ql F3 C N'􀃣 O CF ,..0,N .o o, 3 0 qL 􀃜 Cl WO,... o,N .o"" o, F I ).O p N'􀃤 O 􀃥 ,, .o o ,N N, P2 at 4 ppm 87 4 1 4 28 40 1 6 33 87 90 80 50 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 1 0 87 20 0 37 1 0 1 5 2 8 1 3 2 1 5 77 7 2 33 8 2 30 2 37 90 43 90 90 80 80 80 80 3 87 32 202209 CA 03171545 2022- 9-- 13 amended pages 1 06 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 253 254 255 256 257 258 259 260 261 262 263 266 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 1 00 87 1 00 57 1 00 77 1 00 1 00 97 83 1 00 87 50 1 8 70 20 93 35 1 00 57 32 7 73 8 80 1 7 93 40 22 0 22 0 70 9 87 32 63 1 47 4 80 1 5 73 22 67 1 8 90 43 AMENDED SHEET 202209 No. 267 268 269 270 271 272 273 277 278 282 283 CA 03171545 2022-9- 13 amended pages 1 07 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure NF 􀁕,-,,, N' O .,,;:; F ,. 0 ,N N --., 0 w o ,,:; Lf CI 􀁖 -s:, CFa O ,. O , 0 O... N' o ,,:; ll 􀁕"" CF3 0 ,. O ,N O ... w o ,,,; 􀄡 0 􀁖 "" CF30 ,. 0 , 0 N.., wo ,,,; ll ;£-.. CF30 .. O , N N.., 0 ql C F 3 N'􀄢 "" O ,. .,,;:; 0 ,N N --., CF3 0 􀄣N'􀄤 O ,. ,,,; 0 ,N N ... CF3 0 o lf 􀁘 I P' N' O .,,;:; 􀂊 I .,.o ,N N --., 0 􀄥 􀄦 "" WO ,,:p .. 0 ,N o N--., F 􀄧Nd l N' o ""- 􀄨 : 0 , N ... 0 OC􀁇 I N' O Cl / 0 'N:::,, 0 --., P2 at 4 ppm 2 63 5 3 5 60 60 1 00 90 83 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 0 1 0 4 6 60 1 7 0 1 8 0 0 0 1 1 8 3 60 1 00 1 00 60 90 93 1 5 1 8 30 87 22 202209 No. 284 285 286 288 290 294 295 296 297 298 299 CA 03171545 2022- 9-- 13 amended pages PCT / EP 2021 / 059 730 - 04.08.2021 1 08 Treatment with compound % PHAKPA (F1 29L) Disease level Structure .,o :::,,.. (CF 􀁇 I Cl N .,...o, N N -...., ct 0 2£1 N'o :::,,.. .,...o,N O, a ::,,.. I }f 􀁖 F N ,. .,,.o , N N, 0 a ::,,.. I 􀂈 􀂉 N " .,,.o, N N, 0 .,o ::,,.. c¢ci 􀂊 I : .,,.o, N N, F 0 a ::,,.. I a' 􀁳 N ' .,,.o, N N, 0 a ::,,.. I 􀂋 o 􀂌 N " .,,.o, N N, 0 o ::,,.. I 􀂍 􀂎 N " .,,. o , N N, 0 􀂐 N ' : 0, 􀂏 0 F cr F 􀂎 I ?' ,.0 ""'- ::,,.. I N .,,.o, N N , 0 􀂐 N ": N, 􀂏 0 P2 at 4 ppm 63 87 67 87 92 1 2 1 00 90 63 53 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 44 62 34 50 90 35 1 5 97 27 30 97 20 1 4 83 2 1 1 2 0 0 1 1 0 40 1 00 83 37 87 37 7 97 37 1 3 53 22 202209 CA 03171545 2022- 9-- 13 amended pages 1 09 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 302 303 304 312 314 3 1 5 321 324 325 326 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 47 4 47 3 2 0 1 2 0 53 28 1 00 37 1 00 53 1 00 40 1 00 60 1 00 40 2 1 1 2 0 24 4 22 1 25 0 30 1 AMENDED SHEET 202209 CA 03171545 202-9--13 amended pages 1 1 0 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 327 328 329 330 335 336 337 340 344 Ao 􀀝 I p ,o ;:,, lfN / O'N N '- F F+ F l N􀄩oX) u􀀂 / O 'N)y o, 0 23 33 1 00 83 77 63 9 23 6 AMENDED SHEET 3 48 4 8 23 5 53 1 00 73 24 93 1 7 53 80 25 20 50 1 7 0 1 3 1 4 42 7 0 1 6 0 202209 CA 03171545 2022- 9-- 13 amended pages 111 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 345 346 349 354 355 357 358 359 360 361 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 22 1 32 1 4 0 5 0 97 50 97 35 17 2 21 4 34 7 48 4 1 3 1 1 8 0 77 1 7 83 1 8 1 00 37 1 00 43 53 9 80 5 80 1 8 88 31 AMENDED SHEET 202209 CA 03171545 2022- 9-- 13 amended pages 1 1 2 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 363 365 366 367 368 372 373 375 378 380 6:F F 􀄪P' I P' ,. o :::,,.. :::,,.. I F N ,..... o, N o, 29 77 53 63 83 85 77 47 1 8 53 AMENDED SHEET 1 25 2 1 5 97 43 1 3 83 1 2 9 93 30 47 90 73 26 85 1 6 27 1 00 38 8 40 6 1 1 7 1 5 60 1 2 202209 CA 03171545 2022- 9-- 13 amended pages 1 1 3 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 387 388 389 390 393 394 395 396 399 400 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 60 30 80 47 1 0 3 0 28 4 43 3 22 0 18 2 93 55 93 42 9 3 1 2 2 43 4 67 18 3 0 4 0 67 8 90 1 5 2 0 8 0 AMENDED SHEET 202209 No. 401 405 406 407 408 409 4 1 0 4 1 2 4 1 3 414 CA 03171545 2022- 9-- 13 amended pages 1 14 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 􀄃 F 􀀱I N'O ..,...o,N N, 0 F􀄄 F 􀄅 N'O F I ..,...o ,di, o, F 0 F F 􀄆 􀄇 N'O F ""- I ..,...o,N N, F 0 f F F 􀀲I N'O ..,...o,N N. 0 f F F 􀁡I W O ..,...o,N O o, ,di, 􀄫 F F 􀄬 I N'O F ..,...o,N 0, 0 z;F F WO􀄈 F ..,...o, N. F 0 F􀄉 F F 'IP 􀄊 N'O c1 I ..,...o, N N, 0 oif,, -:􀀱,, 0 o« F F 􀀲I N'O ..,...o, o, 0 P2 at 4 ppm 1 7 97 97 1 2 30 77 9 47 40 53 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 5 32 4 27 70 27 30 67 23 6 1 7 4 1 2 33 1 3 40 83 73 0 35 1 6 40 6 1 5 33 1 5 9 53 1 5 202209 No. 4 1 5 4 1 6 4 1 7 418 4 1 9 420 421 422 423 424 CA 03171545 2022- 9- 13 amended pages 1 1 5 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level Structure 􀀁 J wo􀀂 .,... o ,N N ., N,? 0 I 􀀅Io 􀀆 t r'°􀀳o_,􀀴 o o, #·:?.xo, N,y 0 􀀁 i :.£ wo ... O ,N 0 ., N,O I Off i F wo ... O, N ., 􀄭 0 F ,O,..􀄮 o N N ., N,? 0 Cl«: 􀄯 ,-o􀀢I ... O ,N 0 ., 􀃒c:, 􀃓 w o ,...􀄰I o , 0 N., » F F 3:rl wo ""' 􀁝 .,... o , N o, 0 » F F 􀁢I N'o ""' 􀁝 .,... o ,N 􀅑--- 0 P2 at 4 ppm 47 57 35 70 40 8 1 00 30 1 00 1 00 AMENDED SHEET P2 at P6 at P6 at 1 6 ppm 4ppm 1 6 ppm 5 67 1 1 27 67 25 1 8 63 22 33 73 57 1 8 60 1 2 0 1 2 1 33 87 57 0 32 2 57 93 53 27 97 50 202209 CA 03171545 2022- 9-- 13 amended pages 1 1 6 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure 425 426 427 428 429 430 431 432 433 435 436 P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 27 28 53 40 7 1 27 1 0 1 00 90 60 47 70 11 83 20 83 50 67 43 22 6 37 1 7 32 7 40 1 2 1 2 0 1 3 3 83 67 80 57 93 57 87 60 70 1 5 73 27 AMENDED SHEET 202209 CA 03171545 2022- 9-- 13 amended pages 117 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound % PHAKPA (F1 29L) Disease level No. Structure P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 437 440 441 442 444 445 446 447 449 450 HF F wo􀀑 I ""- Br ,,., o ,;,::; o , ffF F 􀁁 wo I ""' ,,.,o ,;,I) o, 2 93 100 100 100 1 5 2 7 33 3 AMENDED SHEET 0 8 0 23 73 23 43 97 50 93 80 77 47 83 53 1 30 2 0 6 0 0 33 1 10 57 9 1 4 1 5 202209 amended pages 1 1 8 PCT / EP 2021 / 059 730 - 04.08.2021 Treatment with compound No. Structure 451 452 458 461 462 463 464 􀁮􀁯,- 0 -X)" u / O ' N􀄗N, a 0 􀌳 I N'o 􀁂 F3C, 0 / 0 ,& o, &F ,o 􀌵 􀌴 I 'o N ,,.O -,:; O .. Comparative trials Table C1: Compound Trifloxystrobin as comparative example Structure F3Cd l wo􀀟: o:,,.. / O'N o, % PHAKPA (F1 29L) Disease level P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 1 0 2 0 60 6 70 1 4 93 57 83 50 26 2 52 6 37 6 55 1 0 6 0 3 0 1 0 8 0 PHAKPA (F1 29L) Disease level (%) P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 71 17 79 33 CA 03171545 2022- 9- 13 AMENDED SHEET 202209 Compound Ex. 9 Table C2: Compound Comparative example Ex. 231 Comparative example Ex. 58 Comparative example Ex. 6 Comparative example Ex. 1 58 CA 03171545 2022- 9-- 13 amended pages 1 1 9 PCT / EP 2021 / 059 730 - 04.08.2021 Structure Fa cd 1 w o 􀀯: ,:,.. ,...o,N 0-..,. 0 Structure F3cd 1 N' o 􀁑: :::,,,. ..,.o ,& o, 0 F3 C dl w o 􀁒: :::,... ..,.o ,& o, 0 Brd l wof.Z: :::,... ,....O,N N, 0 Brd l w o 􀃏: :i:,.., ,.,....o ,N N , 0 ff 􀁴 "<:::: W O .& ,.,....o,N N, 0 ff 􀁗--:::: W O .& .....O,N N, 0 d :£ "<:::: N'O .& Cl ,.,.... o ,N N, 0 d 􀀇 "<:::: W O .& Cl ,.... o ,N N, 0 PHAKPA (F1 29L) Disease level (%) P2 at P2 at P6 at P6 at 4 ppm 1 6 ppm 4 ppm 1 6 ppm 35 23 41 4 PHAKPA (F1 29L) Disease level (%) P2 at 4 ppm P6 at 4 ppm 6 30 0 2 27 70 0 4 1 00 1 00 0 23 40 80 1 AMENDED SHEET 202209 Compound Comparative example Ex. 1 57 Comparative example Ex. 4 Comparative example Ex. 3 1 Comparative example Ex. 8 Comparative example Ex. 41 CA 03171545 2022- 9-- 13 amended pages 120 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) Structure c 1d 1 w o 􀁜: ::::,,.. ,,.. O, N N..., 0 c 1d 1 N"' o 􀄋: :::,,... ,,.. O,N N..., 0 Cl 􀁝I N"'o 􀁜: ::::,,.. ,,.. O,N N.... Cl 0 Cl 􀁝I N "'o 􀄌 : :::,,... ,,.. o,N N..., Cl 0 d' 􀁵􀁖 WO .& ,,.. o , N N..., 0 􀌶 􀌷􀌸 W O .& ,,.. O , N N ..., 0 F3c d 1 w o 􀄍: :::,., ,,0, N, 0 F3C d l w o 􀄎: :::,., ,,O,N N, 0 d 􀀌􀀍 Cl W O n Cl ,, O ,N N..., 0 d 􀀎􀀍 Cl W O n Cl ,,.. O ,N N, 0 P2 at 4 ppm 43 0 1 00 2 87 0 1 2 1 43 4 AMENDED SHEET P6 at 4 ppm 80 2 97 1 7 1 00 1 2 38 1 3 77 35 202209 Compound Comparative example Ex. 1 65 Comparative example Ex. 1 30 Comparative example Ex. 1 88 Comparative example Ex. 73 Untreated Table C3· Compound Comparative example CA 03171545 2022- 9- 13 amended pages 1 2 1 PCT / EP 2021 / 059 730 - 04.08.2021 Structure 􀃐 􀃑 􀃒 W O .& ..,..o ,N O N , 􀃓 􀃔 􀃒 N"O o ..,.. o, N O N, 􀂫 C l 􀂬 W -s::i O o ,..0,N N.., C l 0 􀀎 I 􀂭-s::i W O o ,..0,N N.., Cl 0 F3c'((' 1 wo 􀃕 : a::,. ,..0,N N, 0 F3c'((' 1 wo 􀃖 : a::,. ,..o,N N.., I wo & 0 dF F ,..􀃗 O,N N.., 0 dF F 􀃘 I W O o ,..0,N N.., 0 Structure 􀃙 Br 􀃚 􀃒 W O & .,..o,N N, 0 PHAKPA (F1 29L) Disease level (%) P2 at 4 ppm P6 at 4 ppm 35 83 0 27 87 97 33 67 60 70 2 30 43 90 1 37 1 00 99 PHAKPA (F1 29L) Disease level (%) P2 at 1 6 ppm P6 at 16 ppm 23 28 AMENDED SHEET 202209 Compound Ex. 1 20 Comparative example Ex. 1 26 Comparative example Ex. 1 1 3 Comparative example Ex. 1 59 Comparative example Ex. 60 Comparative example Ex. 1 2 CA 03171545 2022- 9-- 13 amended pages 122 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) Structure N'O A (0Br 􀃛--:::, ,..-0,N N... 0 I P N'o .,;:; 'o 􀄏 􀃔 / O'N N, 0 I ? N'O A 'o 􀄐 􀃕 / O'N N , 0 offw oa ""',,;:; ,.. o ,N N. 0 offwo􀀲 '<:, ,-:r; ,..O,N N. 0 d a􀀏 W O A NC ,. O, N N.. 0 d 􀀐 '<::: W O A NC ,. O ,N N.. 0 F3C dN 'o 􀄑 : I O N Cl ::,,... ,. ' N '- 0 F3C d 􀀈"""" W O n Cl ,.O ,N N.. 0 F VN'o an"""' ,.o ,N N.. 0 􀃜 F 􀃖 􀃝 F N'O &'- ,.o ,N N.. 0 P2 at 1 6 ppm 6 87 32 37 1 7 37 0 1 1 0 1 6 3 AMENDED SHEET P6 at 1 6 ppm 1 5 80 60 28 6 63 0 4 0 35 9 202209 Compound Comparative example Ex. 27 Comparative example Ex. 282 Comparative example Ex. 205 Untreated Table C4: Compound Comparative example Ex. 3 CA 03171545 2022- 9- 13 amended pages 123 PCT / EP 2021 / 059 730 - 04.08.2021 Structure dF F a I wo .& F ,,0, N N--., 0 dF F 􀂯 I wo .4- F ,,0,N N--., 0 FtNd l wo􀂰: 􀂱 ,,0, N--., 0 FtN d l wo􀂲: :,,,,.. ,,0,N N--., 0 F3C-4v O I J 0-N :.£ N ? I N' ""- ... O ,N N .. F3 C 􀄱-v\ o􀂳:: N ?..., I N' ...O,N N .. Structure Cl qll N 'Oa: 􀂱 ,,0,N 0.. Cl 0 Cl qll N'O􀂴: :,,,,.. ,,0,N o, Cl 0 PHAKPA (F1 29L) Disease level (%) P2 at 1 6 ppm P6 at 16 ppm 1 5 1 5 0 0 70 53 1 5 1 8 23 32 1 1 1 00 87 PHAKPA (F1 29L) Disease level (%) P2 at 1 6 ppm P6 at 16 ppm 27 1 7 2 1 AMENDED SHEET 202209 Compound Comparative example Ex. 56 Comparative example Ex. 36 Comparative example Ex. 5 Comparative example Ex. 216 Comparative example Ex. 1 Comparative example CA 03171545 2022- 9-- 13 amended pages 124 PCT / EP 2 0 2 1 / 0 59 7 3 0 - 04 . 08 . 2 0 2 1 PHAKPA (F1 29L) Disease level (%) Structure Br-di w o 􀌹: :::,.,. ,.,... ,N O. 0 Br-di w o 􀌺: :::,,. ...0,N O. 0 W O ,,,:; (J('CF 􀃞...0,N 􀃒 O. 0 wo & (J('CF 􀃟 ... 􀃒 O ,N 0 . 0 ff 􀁘 '<:::: W O & ...0,N 0. 0 ff 􀁙􀁚 N' O & ,.,... o ,N 0. 0 d 􀀈 '<:::: N' O & 0 ,.,... ,N 0, I o d 􀀉 '<:::: W& 0 ... o ,N o, I o cfF 'a:::: W O ,,,:; ,.....o,N O. 0 cfF 'a:::: W O A ,.....o,N o, 0 d 􀀌􀀍 N' O & F3 C ,.,... o ,N O . 0 P2 at 1 6 ppm 80 32 87 47 25 1 67 20 83 28 43 AM E N D E D S H E ET PS at 1 6 ppm 87 15 90 57 10 4 33 15 77 47 13 202209 Compound Ex. 37 Comparative example Ex. 30 Comparative example Ex. 1 81 Comparative example Ex. 1 55 Comparative example Ex. 2.Qg Comparative example Ex. 1 54 CA 03171545 2022- 9- 13 amended pages 125 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) Structure dW􀀄'<::, O J F3C .,... o ,N O.... 0 erwo 􀀗􀀳'-:::, .,...o , o, 0 W O -A er 􀀘􀀙 .,...o,N O.... 0 yd a""" N'O & , 0,N .,... o, 0 O . yd 􀀊""' N'O ,&; .0,N .,... o, O O . d 􀀅􀀆 N 'O J NC .,... o , N O .... 0 d 􀀑 '<::: W O n NC .,... o ,N O.... 0 d F F 􀃠 I W O J Cl .,...o, N O .... 0 d F F 􀄒 I N 'Q A Cl .,...o,N O.... 0 d- f.Z􀀨 W O J Cl .,...O, N o, 0 d- 􀁶􀁖 N 'O J Cl ,.... o , N O.... 0 P2 at 1 6 ppm 0 87 2 57 1 2 87 23 1 00 30 63 25 AMENDED SHEET PS at 1 6 ppm 0 43 1 60 5 53 1 8 90 1 8 43 1 7 202209 Compound Comparative example Ex. 76 Comparative example Ex. 86 Comparative example Ex. 153 Comparative example Ex. 104 Comparative example Ex. 244 Comparative example CA 03171545 2022- 9-- 13 amended pages 126 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) Structure 'd 􀁸 "<:::, N􀃖O A ,.....o, N 0..., 0 'd 􀁹 "<:::, N'O A ,.....o, N 0..., 0 'd 􀁺"II:: F N'O A ,.....o,N 0..., 0 'cf 􀁷 '<::, F N'O A ,.....o, N 0..., 0 Cl -d i N 'O 􀃗 : :::,,.. ,.....o,N O ..., 0 c,d1 wo 􀃘 : :::,,.. ,.....o, N 0 ..., 0 􀁲 􀁳"<:::, NC N'O A ,.....o,N 0..., n NC 'dl N 'o 􀃙 : ::::,,. ,.....o,N O... 0 􀃚 CF a---:::, WO A ,.....O A 0... 0 􀃛 C F 3 W􀃜 ---:::, O A ,.....o A 0..., 0 qlF a---:::, WO ,,:;; ,.....o,N N ..., F 0 P2 at 1 6 ppm 93 1 90 6 73 5 80 37 11 0 1 AMENDED SHEET PS at 1 6 ppm 83 80 70 1 43 28 9 2 22 202209 Compound Ex. 131 Untreated amended pages 127 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) Structure P2 at 1 6 ppm PS at 16 ppm ¢rF 􀀽 w '-::: o 􀀡 ,.,. o ,N N, 0 0 F 0 >90 >85 The results in Tables C1 to C4 show that the specific substituent at position R 3 improves the fungicidal activity against phytopathogenic fungi containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo inhibitors compared to 5 compounds where the position R 3 is unsubstituted. 10 Table CS: Concentration applied (ppm) Compound Structure Comparative N 􀀒oJ?: example from N WO 2017 / 157923 O Cl 􀃦If yo N-Ex. 158 Table C6a· Compound Comparative example from WO 17 / 157923 Ex. 158 Table C6b: wo ,,;::. d 􀁻""" Cl ,.. 0 , N -.. Structure 􀂒 Q-o::Q 􀂓 􀂔- N Cl , 􀂕o N-\ 􀀐, O 􀀑 Cl ..,. o ,N N, 0 0 93 CA 03171545 2022- 9-- 13 Fungal g rowth (%) 0.0 1 6 0.01 6 0.01 6 0.0 1 6 PYRIOR ALTESO ALTESO MONGNI wt F 1 29L 87 98 100 97 38 66 79 71 PHAKPA P1 DL Disease level (%) Qo I-sensitive wt isolate (0 % F 1 29L) Test concentration (ppm) 0.3 1 3 1 0 30 1 00 300 78 80 77 48 30 18 5 38 7 2 1 4 5 4 AMENDED SHEET 202209 amended pages 128 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA P1 DL Disease level (%) Qo I-resistant F1 29L isolate ( 1 00 % F1 29L) Compound Comparative example from WO 1 7 / 1 57923 Ex. 1 58 Structure 􀁓 N?-o:rQ Cl 't N )'='o N-N. 􀀄,oa.,,,, Cl .,.... O .. N N, 0 0.3 88 93 87 Test concentration (ppm) 1 3 1 0 30 1 00 300 90 95 92 90 65 52 57 8 2 4 4 5 The results in Tables CS to C6b show that the compounds to the present invention significantly improve the fungicidal activity against phytopathogenic fungi containing the amino acid substitution F129L in the mitochondrial cytochrome b protein conferring resistance to Qo 5 inhibitors compared to the use of a compound disclosed in WO 2017 / 1 57923. Table C7a: Concentration applied (ppm) 0.01 6 Compound Structure PYRIOR Comparative example from WO 98 / 231 56 F3c- 0lf1 w 0 􀁔: :::,,... .,,. o ,N o, 1 00 Ex. 9 10 Table C7b: CA 03171545 2022- 9-- 13 0 F3􀁕 I N' o 􀁖: "'- ,, o, o, 38 Compound Comparative example from WO 98 / 231 56 Ex. 9 Untreated 0 Structure F3c- 0lf1 w 0 􀁗: :::,,... , o ,N a, 0 F3C d l N' o 􀁗: :::,,... .,,. o,N o, AMENDED SHEET Fungal growth (%) 0.01 6 0.025 ALTESO PYRNTE wt wt 94 84 73 44 PHAKPA (F1 29L) Disease level (%) P2 at 4 ppm 17 6 92 4 CERCSO 33 1 1 202209 amended pages 1 29 Table C8a: Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 84 5 Table C8b· Structure F3c- Olf1 w O 􀂧: ::,,,. ,.. O ,N O ... 0 ,...odN'o 􀁘 : H3 C ::,,,. I ,.. O,N O ... 0 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 84 Structure F3c- Olf1 w O 􀂨: ::,,,. ,..o,N O... 0 ,,odN'o􀁙:: H3 C I ::,,,. ,.O, N 0.. 0 0.0 1 6 PYRIOR 100 48 0.25 PYRNTE wt 87 39 PCT / EP 2021 / 059 730 - 04.08.2021 Fungal g rowth (%) 0.063 0.01 6 4 COLLLA ALTESO ALTESO wt F 1 29L 77 94 87 33 43 39 Fungal growth (%) 0.25 0.063 0.0 1 6 PYRNTE LEPTNO MONGNI F1 29L 84 79 86 49 60 32 The results in Table C7a to C8b show that the specific substituent R a of the terminal phenyl improves the fungicidal activity against phytopathogenic fungi compared to compounds from the prior art. 10 CA 03171545 2022- 9- 13 AMENDED SHEET 202209 Table C9: amended pages 130 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 9 5 CA 03171545 2022- 9- 13 Structure ' o 􀁚 F3Cd1 N'o I &J :::::,,. ,.....o,N o, F3 c lf 1 w o 􀁓: ""'- ,.... ,N O ,,,, PCT / EP 2021 / 059 730 - 04.08.2021 Fungal growth (%) 0.01 6 0.063 4 PYRIOR LEPTNO CERCSO 58 100 56 38 67 1 1 AMENDED SHEET 202209 amended pages 131 PCT / EP 2021 / 059 730 - 04.08.2021 Table C10: Fungal growth (%) Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 8 5 Table C11a: Structure 's 􀅒 Fa c d l N' o I J "'- ,.. 0 ,N N.., F3 C lf l N' O ,....a: o ,N N .., 0.016 0.063 0.016 4 PYRIOR LEPTNO ALTESO CERCSO F129L 49 93 85 66 13 70 55 27 Fungal growth (%) Concentration applied (ppm) 0.016 0.25 0.063 0.016 Compound Structure PYRIOR SEPTTR LEPTNO ALTESO wt 1 0 Comparative example from F3 c d' N' o "'- ,...􀄲: o ,N N .., 39 77 WO 98 / 23156 0 Ex. a Table C11b: F3 C 􀄳N' O "'- ,.a0, :: N .., 13 57 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 8 Structure 'o a F3Cdl wo I ,A ::,,,. ,.O,N N. F3 c d1 N' o 􀄴: "'- ,. O ,N N .., CA 03171545 2022- 9-- 13 AMENDED SHEET 95 100 70 56 Fungal growth (%) 4 0.016 CERCSO MONGNI 60 80 27 54 0.016 MONGNI 84 54 0.016 ALTESO F129L 87 52 202209 Table C12: Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 76 5 Table C13: Structure I P wo ,,:; 's 􀀡 􀄵 ,,,, o ,N O ..... 0 v1􀁼􀁽 N" O ,,,, ,,:; o , o , 0 􀇺 􀇻􀇼 N' O A .O,N O.. 0 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 76 CA 03171545 2022- 9-- 13 Structure I P wo ,,:; 's 􀀡 􀁘 ,, O,N 0-. 0 I P N'o ,,:; 'o 􀀡 􀀠 ,,,.o, o, 0 v1 􀁾􀁽 N' O ,.,; .o, o, 0 􀇺 􀇻􀇼 WO .O, N O .. 0 amended pages 132 PCT / EP 2021 / 059 730 - 04.08.2021 Fungal g rowth (%) 0.01 6 0.25 0.063 0.0 1 6 0.25 PYRI OR SEPTTR COLLLA MONGNI PYRTNE F1 29L 87 61 81 69 82 89 93 84 87 43 0 39 35 66 Fungal g rowth (%) 0.063 0.01 6 0.01 6 0.25 4 LEPTNO ALTESO ALTESO PYRNTE CERCSO wt F 1 29L wt 85 67 66 59 71 65 93 81 53 67 100 100 87 78 87 39 55 37 39 28 AMENDED SHEET 202209 Table C14: Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 77 5 Table C15a: Structure I ;? W O '1f' 'o 􀄘 􀄙 ,..o ,N N, 0 v1 􀁿 wo ,., ,,0, N, 'er 􀁛"" W O .. O ,N N, 0 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 153 CA 03171545 2022- 9-- 13 Structure c1lf 1 ' N' o 􀅓,., "" ,,o, o, 0 Cld l N' o a: "" ,.. o , o, 0 c1d 1 N' o 0Z:: :,,.. ,0,N o, amended pages 133 PCT / EP 2021 / 059 730 - 04.08.2021 Fungal growth (%) 0.01 6 0.25 0.063 0.01 6 0.0 1 6 PYRIOR SEPTTR COLLLA ALTESO ALTESO wt F 1 29L 80 100 81 93 95 81 87 93 89 93 20 49 39 73 69 Fungal growth (%) 0.01 6 0.25 0.063 0.01 6 0.01 6 PYRIOR SEPTTR COLLLA ALTESO ALTESO wt F 1 29L 88 39 82 94 100 83 39 89 81 89 50 0 55 71 68 AMENDED SHEET 202209 Table C15b· amended pages 1 34 Concentration applied (ppm) 0.063 Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 153 Table C16a· Structure 's 􀃔 c1 d1 N' o 1 -,:; :::,,. ,o,N 0.. 0 c1d l N' o 􀄓: :::,,. ,o,N o, 0 c1d1 N' o 􀄔: :::,,. , o ,N O.. LEPTNO 88 55 PCT / EP 2021 / 059 730 - 04.08.2021 Fungal growth (%) 0.25 4 0.01 6 PYRNTE wt CERCSO MONGNI 57 62 95 69 61 31 26 75 Fungal growth (%) 5 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 157 Structure c,if 1 ' N'o 􀁫: ,.. o ,N N.,, 0 Cl dN'O􀀎 "" ,.... o ,N N.,, 0 0.016 PYRIOR 100 1 5 Table C16b· CA 03171545 2022- 9-- 13 Concentration applied (ppm) Compound Comparative example from WO 98 / 23156 Ex. 157 Structure ' s 􀁚 c1 d1 N'o I-,:; :::,,. , o , N N.. c1d 1 w o 􀂽: :::.,.. ,o ,N N. 0 0.25 SEPTTR 59 20 0.25 PYRNTE wt 76 54 AMENDED SHEET 0.063 0.25 0.016 COLLLA ALTESO ALTESO wt F 1 29L 82 43 90 63 27 57 Fungal growth (%) 0.25 4 0.01 6 PYRNTE CERCSO MONGNI F129L 80 78 100 58 36 56 202209 Table C17: Compound Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 76 Comparative example from WO 98 / 23156 Comparative example from WO 98 / 23156 Ex. 77 Comparative example from WO 98 / 23156 Ex. 9 Comparative example from WO 98 / 23156 Ex. 157 CA 03171545 2022- 9- 13 Structure amended pages 135 ,:,,- N' I O & 'o 􀀣 􀀤 ..,o, o, 0 v1 􀂀""' N' O & ..,o, o, 0 I ,:,,- N' O & 's 􀀣 􀀤 .., o, o, 0 'if a"" W O n ,,o,N o, 0 I ,,,,- W O n 'o a 􀁙 ,,O, N N, 0 u1 a""' W O n ,,o, N... 0 􀁣 􀁤""' W O n ,,0,N N... 0 ' o 􀄶 F3 c d1 N' o I & :::,.. ,,O,N O. 0 F3 c '(f1 w o 􀄷: :::,.. ...O .N 0. 0 's a c 1lf l w o I & :::,.. ,, O.N N... 0 Cld l N' o a : :::,, ,,O,N N... 0 PCT / EP 2021 / 059 730 - 04.08.2021 PHAKPA (F1 29L) Disease level (%) P2 at 4 ppm P6 at 1 6 ppm 83 57 80 37 60 30 35 4 45 67 67 37 20 23 1 20 9 1 1 AMENDED SHEET 136 Comparative example from WO 98 / 23156 83 87 Comparative example from WO 98 / 23156 47 18 Ex. 153 19 5 Untreated 92 75 Table C18: PHAKPA (F129L) Disease level (%) Compound Structure P2 at 1 ppm P6 at 4 ppm Comparative example from WO 98 / 23156 32 43 Ex. 8 6 1 Untreated 92 75 5 The result in Tables C9 to C18 show that the specific substituent R4 improves the fungicidal activity against phytopathogenic fungi compared to compounds from the prior art. *** According to certain aspects, embodiments of the present invention as 10 described herein include the following items: 1. A compound of formula I I, 15 wherein CA 3171545 Date reçue / Received date 2024-10-04 137 R1 is selected from O and NH; R2 is selected from CH and N; R3 is selected from C1-C4-alkyl, C2-C4-alkenyl, C1-C2-monohaloalkyl, 5 C1-C2-dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C3-C6-cycloalkyl and -O-C1-C4-alkyl; R4 is selected from C1-C4-alkyl, C2-C4-alkenyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, -(C1-C2-alkyl)-O-(C1-C2-alkyl) and -(C1-C2-alkyl)-O-(C1-C2-haloalkyl); 10 Ra is selected from halogen, C1-C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C6-cycloalkyl, C3-C6-cycloalkenyl, -C1-C2-alkyl-C3-C6-cycloalkyl, phenyl, 3- to 6- membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6- membered heteroaryl, 15 wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, O and S, wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound directly or via an oxygen atom or via a C1-C2-alkylene linker, and wherein the cyclic moieties of Ra carry 1, 2 or 3 substituents selected from 20 halogen and C1-C4-haloalkyl, and wherein the aliphatic and cyclic moieties of Ra further carry 0, 1, 2 or up to the maximum number of identical or different groups Rb: Rb is selected from CN, NH2, NO2, C1-C4-alkyl and -O-C1-C4-alkyl; 25 n is an integer selected from 1, 2, 3, 4 and 5; and in form of stereoisomers and tautomers thereof, and the N-oxides and the agriculturally acceptable salts thereof. 30 2. The compound according to item 1, wherein R1 is selected from O and NH; and R2 is selected from CH and N, provided that R2 is N in case R1 is NH. 3. The compound according to item 2, wherein R1 is O and R2 is CH. 35 4. The compound according to any one of items 1 to 3 wherein R3 is selected from C1-C2- alkyl, C1-C2-monohaloalkyl, C1-C2-dihaloalkyl, C3-C4-cycloalkyl and -O-C1-C2-alkyl. 5. The compound according to any one of items 1 to 4, wherein R4 is selected from C1-C4- 40 alkyl, C1-C4-haloalkyl and -(C1-C2-alkyl)-O-(C1-C2-alkyl). 6. The compound according to any one of items 1 to 5, wherein n is 1, 2 or 3. 7. The compound according to any one of items 1 to 6, wherein Ra is selected from halogen, 45 C1-C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C4-cycloalkyl, -CH2-C3-C4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1 CA 3171545 Date reçue / Received date 2024-10-04 138 or 2 heteroatoms selected from N, O and S, wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via a methylene linker, and wherein the cyclic moieties of Ra carry 1, 2, or 3 substituents selected from halogen and C1-C2-haloalkyl, and wherein cyclic moieties of Ra further carry 0, 1, 2 or 3 identical or different groups Rb selected from CN, NH2, NO2, C1-C4-5 alkyl and -O-C1-C4-alkyl. CA 3171545 Date reçue / Received date 2024-10-04

Claims

139 Claims 1. A compound of formula I I, 5 wherein R1 is selected from O and NH; R2 is selected from CH and N; 10 R3 is selected from C1-C4-alkyl, C2-C4-alkenyl, C1-C2-monohaloalkyl, C1-C2-dihaloalkyl, monohalo-ethenyl, dihalo-ethenyl, C3-C6-cycloalkyl and -O-C1-C4-alkyl; R4 is selected from C1-C4-alkyl, C2-C4-alkenyl, C1-C4-haloalkyl, C2-C4-haloalkenyl, 15 -(C1-C2-alkyl)-O-(C1-C2-alkyl) and -(C1-C2-alkyl)-O-(C1-C2-haloalkyl); Ra is selected from halogen, C1-C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C6-cycloalkyl, C3-C6-cycloalkenyl, -C1-C2-alkyl-C3-C6-cycloalkyl, phenyl, 3- to 6- membered heterocycloalkyl, 3- to 6-membered heterocycloalkenyl and 5- or 6- 20 membered heteroaryl, wherein said heterocycloalkyl, heterocycloalkenyl and heteroaryl besides carbon atoms contain 1, 2 or 3 heteroatoms selected from N, O and S, wherein said phenyl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are bound directly or via an oxygen atom or via a C1-C2-alkylene linker, 25 and wherein the cyclic moieties of Ra carry 1, 2 or 3 substituents selected from halogen and C1-C4-haloalkyl, and wherein the aliphatic and cyclic moieties of Ra further carry 0, 1, 2 or up to the maximum number of identical or different groups Rb: 30 Rb is selected from CN, NH2, NO2, C1-C4-alkyl and -O-C1-C4-alkyl; n is an integer selected from 1, 2, 3, 4 and 5; and in form of stereoisomers and tautomers thereof, and the N-oxides and the 35 agriculturally acceptable salts thereof.

2. The compound according to claim 1, wherein R1 is selected from O and NH; and R2 is selected from CH and N, provided that R2 is N in case R1 is NH. 40 3. The compound according to claim 2, wherein R1 is O and R2 is CH. CA 3171545 Date reçue / Received date 2024-10-04 140 4. The compound according to any one of claims 1 to 3 wherein R3 is selected from C1-C2- alkyl, C1-C2-monohaloalkyl, C1-C2-dihaloalkyl, C3-C4-cycloalkyl and -O-C1-C2-alkyl.

5. The compound according to any one of claims 1 to 4, wherein R4 is selected from C1-C4- alkyl, C1-C4-haloalkyl and -(C1-C2-alkyl)-5 O-(C1-C2-alkyl).

6. The compound according to any one of claims 1 to 5, wherein n is 1, 2 or 3.

7. The compound according to any one of claims 1 to 6, wherein Ra is selected from 10 halogen, C1-C4-haloalkyl, C2-C4-haloalkenyl, C2-C4-haloalkynyl, C3-C4-cycloalkyl, -CH2-C3-C4-cycloalkyl, phenyl, 3- to 5-membered heterocycloalkyl and 5- or 6-membered heteroaryl, wherein said heterocycloalkyl and heteroaryl besides carbon atoms contain 1 or 2 heteroatoms selected from N, O and S, wherein said phenyl, heterocycloalkyl and heteroaryl are bound directly or via a methylene linker, and wherein the cyclic moieties of 15 Ra carry 1, 2, or 3 substituents selected from halogen and C1-C2-haloalkyl, and wherein cyclic moieties of Ra further carry 0, 1, 2 or 3 identical or different groups Rb selected from CN, NH2, NO2, C1-C4-alkyl and -O-C1-C4-alkyl. CA 3171545 Date reçue / Received date 2024-10-04