OA20499A

OA20499A - Isoxazoline compounds for controlling invertebrate pests

Info

Publication number: OA20499A
Application number: OA1202100106
Authority: OA
Inventors: George Philip Lahm; Ming Xu
Original assignee: Fmc Corporation
Priority date: 2018-09-12
Filing date: 2019-09-11
Publication date: 2022-09-30

Abstract

Disclosed are compounds of Formula 1,

Description

TITLE

ISOXAZOLINE COMPOUNDS FOR CONTROLLING INVERTEBRATE PESTS

FIELD

This disclosure relates to certain isoxazoline compounds and compositions suitable for agronomie and nonagronomic uses, and methods of their use for controlling invertebrate pests such as arthropods in both agronomie and nonagronomic environments,

BACKGROUND

The control of invertebrate pests is extreinely important in achieving high crop efficiency. Damage by invertebrate pests to growing and stored agronomie crops can cause significant réduction in productîvity and thereby resuit in increased costs to the consumer. The control of invertebrate pests in forestry, greenhouse crops, omamentals, nursery crops, stored food and fiber products, household, turf, wood products, and public health is also important. Many products are commercially available for these purposes, but the need continues for new compounds that are more effective, less costly, less toxic, environmentally safer or hâve different sites of action.

SUMMARY

This disclosure is directed to compounds of Formula 1 (including ail stereoisomers, enantiomers, or diastereomers thereof), compositions containing them, and their use for controlling invertebrate pests:

wherein

J is

M J-2 J-3

J-4

J-5

1-7

J-8

J-9

R¹ is H, Cl or CF₃;

R² is H, F or Cl;

R³ is H, Cl or CF₃;

R⁴ is Cj-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₃-C₆ cycloalkenyl, C₄-C₈ alkylcycloalkyl or C₄-C₈ cycloalkylalkyl, each unsubstituted or substituted with substitueras independently selected from halogen, cyano and CO₂R^1S;

R⁵ isHorC,-C₄ alkyl;

R6 is OR14 or S(O)_nR¹⁵;

R⁷ is H or Ci-C₄ alkyl;

R⁸ is H or C[-C₄ alkyl;

R⁹ is H; or Cj-C4 alkyl, unsubstituted or substituted with substituents independently selected from halogen, cyano, OR¹⁶, S(O)nR¹⁷ and CO₂R¹⁸;

R’OisHorC]^ alkyl;

R¹¹ is H or C[-C₄ alkyl;

R¹² îs H; or C]-C4 alkyl, unsubstituted or substituted with substituents independently selected from halogen, cyano, OR¹⁶, S(O)nR¹⁷ and CO₂R¹⁸;

R¹³ is H, C]-C₄ alkyl or Cj-C^ haloalkyl;

R¹⁴ isCj-04 alkyl;

R¹ is H, Cj-C₄ alkyl or C]-C₄ haloalkyl;

each R¹⁶ is independently Cj-C₄ alkyl or haloalkyl;

each R¹⁷ is independently C]-C₄ alkyl or Cj-C₄ haloalkyl;

each R¹⁸ is independently alkyl or C]-C₄ haloalkyl;

Z is pyridinyl, pyrimidinyl, pyrazînyl, pyridazinyi or tetrahydrofuranyl, each unsubstituted or substituted with R¹⁹;

each R¹⁹ is independently halogen, cyano, nitro, C]-C₄ alkyl, Cj-C₄ haloalkyl, Cj-C₄alkoxy, C]-C₄ haloalkoxy, Cj-C₄ alkylthio, C_t-C₄ haloalkylthio, Cj-C₄ alkyl sulfmyl, Cj-C₄ haloalkylsulfmyl, Cj-Cq alkylsulfonyl, haloalkylsulfonyl, C₂-C₅ alkoxycarbonyl, C₂-C₅ alkylaminocarbonyl and C₃-C₅dialkylaminocarbonyl;

R²⁰ is H, C]-C₄ alkyl or Cj-C₄ haloalkyl;

R²¹ is fluoro, C^-C^ alkyl, C[-C₄ haloalkyl, Cj-Cg alkoxy, C]-Cg haloalkoxy, amino or C]— Cg alkylamino;

m is 0, 1 or 2; and each n is independently 0, 1 or 2;

provided that (i) when J is J-l, R¹ is Cl, R² is H and R³ is Cl, then R⁴ is other than -CH₂CH₃,

CH₂CF₃ or -CH₂(cyclopropyl);

(ii) when J is J-3, R¹ is Cl, R² is H, R³ is Cl and R⁷ is FI, then Z is other than 2-pyridinyl; and (iii) when J is J-5, R> is CI, R2 i_s H, R³ is Cl, and Rio _and RH are H, then Ri2 is other than -CH₂CF₃.

(iv) when Ri is H, then R³ is other than H; and when R³ is H, then Ri is other than H.

This disclosure also provides compounds of Formula 1. In one embodiment this disclosure provides a composition comprising a compound of Formula 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In one embodiment, this disclosure also provides a composition for controlling an invertebrate pest comprising a compound of Formula 1 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optîonally further comprising at least one additional biologîcally active compound or agent.

This disclosure provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologîcally effective amount of a compound of Formula 1 and compositions thereof. This disclosure also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologîcally effective amount of a compound of Formula 1, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optîonally further comprising a biologîcally effective amount of at least one additional biologîcally active compound or agent.

This disclosure also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologîcally effective amount of a compound of Formula 1 and compositions comprising a Compound of Formula 1. This disclosure also relates to the treated seed.

This disclosure also provides a method for increasing vigor of a crop plant comprising contacting the crop plant, the seed from which the crop plant is grown or the locus (e.g., growth medium) of the crop plant with a biologîcally effective amount of a compound of Formula 1 or compositions comprising a compound of Formula 1.

DETAILED DESCRIPTION

As used herein, the tenus “comprises,” “comprising,” “includes,” “including,” “has,” “having,” “contains”, “containing,” “characterized by” or any other variation thereof, are intended to cover a non-exclusive inclusion, subject to any limitation explicitly indicated. For example, a composition, mixture, process or method that comprises a list of éléments is not necessarily limited to only those éléments but may include other éléments not expressly listed or inhérent to such composition, mixture, process or method.

The transitional phrase “consisting of’ excludes any element, step, or ingrédient not specîfied. If in the claim, such would close the claim to the inclusion of materials other than those recited except for impurities ordinarily associated therewith. When the phrase “consisting of ’ appears in a clause of the body of a daim, rather than immediateiy folio wing the preamble, it limits only the element set forth in that clause; other éléments are not excluded from the claim as a whole.

The transitional phrase “consisting essentially of’ is used to define a composition or method that includes materials, steps, features, components, or éléments, in addition to those literally disclosed, provided that these additional materials, steps, features, components, or éléments do not materially affect the basic and novel characteristic(s) of the embodiments. The tenn “consisting essentially of ’ occupées a middle ground between “comprising” and “consisting of’.

Where applicants hâve defined an embodiment or a portion thereof with an open-ended terni such as “comprising,” it should be readily understood that (unless otherwise stated) the description should be interpreted to also descrîbe such an embodiment using the tenus “consisting essentially of ’ or “consisting of.”

Further, unless expressly stated to the contrary, “or” refers to an inclusive or and not to an exclusive or. For example, a condition A or B is satisfied by any one of the following: A is true (or présent) and B is false (or not présent), A is false (or not présent) and B is true (or présent), and both A and B are true (or présent).

Also, the indefinite articles “a” and “an” preceding an element or component of the disclosure are intended to be nonrestrictive regarding the number of instances (i.e. occurrences) of the element or component. Therefore “a” or “an” should be read to include one or at least one, and the sîngular word form of the element or component also includes the plural unless the number is obviously meant to be singular.

As referred to in this disclosure, the term “invertebrate pest” includes arthropods, gastropods, nematodes and helminths of économie importance as pests. The term “arthropod” includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs and symphylans. The term “gastropod” includes snails, slugs and other Stylommatophora. The term “nematode” includes members of the phylum Nematoda.

In the context of this disclosure “invertebrate pest control” means inhibition of invertebrate pest development (including mortality, feeding réduction, and/or mating disruption), and related expressions are defined analogously,

The term “agronomie” refers to the production of field crops such as for food and fiber and includes the growth of maize or corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye and rice), leafy vegetables (e.g., lettuce, cabbage, and other cole crops), fruiting vegetables (e.g., tomatoes, pepper, eggplant, crucifers and cucurbits), potatoes, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone and citrus), small fruit (e.g., berries and cherries) and other specialty crops (e.g., canola, sunflower and olives).

The tenu “nonagronomic” refers to other than field crops, such as horticultura] crops (e.g., greenhouse, nursery or omamental plants not grown in a field), residential, agricultural, commercial and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored product, agro-forestry and végétation management, and public health applications.

The term “crop vigor” refers to rate of growth or biomass accumulation of a crop plant. An “increase in vigor” refers to an increase in growth or biomass accumulation in a crop plant relative to an untreated control crop plant. The term “crop yield” refers to the retum on crop material, in terms of both quantîty and quality, obtained after harvesting a crop plant. An “increase in crop yield” refers to an increase in crop yield relative to an untreated control crop plant.

The tenu “biologically effective amount” refers to the amount of a biologically active compound (e.g., a compound of Formula 1) sufficient to produce the desired biological effect when applied to (i.e. contacted with) an invertebrate pest to be control led or its environment, or to a plant, the seed from which the plant is grown, or the locus of the plant (e.g., growth medium) to protect the plant from injury by the invertebrate pest or for other desired effect (e.g., increasing plant vigor).

It also is understood that any numerical range recited hereîn includes ail values from the iower value to the upper value. For example, if a weight ratio range is stated as 1 : 50, it is intended that values such as 2 : 40, 10 : 30, or 1 : 3, etc., are expressly enumerated in this spécification. These are only examples of what is specificalïy intended, and ali possible combinations of numerical values between and including the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.

One skilled in the art can easily détermine through simple expérimentation the biologically effective amounts of active ingrédients necessary for the desired spectrum of biological activity. It will be évident that including these additional components can expand the spectrum of invertebrate pests controlled beyond the spectrum controlled by the compound of Formula 1 alone.

The term “or combinations thereof” as used herein refers to ail permutations and combinations of the listed items preceding the term. For example, “A, B, C, or combinations thereof’ is intended to include at least one of: A, B, C, AB, AC, BC, or ABC, and if order is important in a particular context, also BA, CA, CB, CBA, BCA, ACB, BAC, or CAB. Continuing with this example, expressly included are combinations that contain repeats of one or more item or term, such as BB, AAA, AB, BBC, AAABCCCC, CBBAAA, CABABB, and so forth. The skilled artisan will understand that typically there is no lirait on the number of items or ternis in any combination, unless otherwise apparent from the context.

In the above recitations, the term “alkyl”, used either alone or in compound words such as “alkylthio” or “haloalkyl” includes straight-chain or branched alkyl, such as, methyl, ethyl, n-propyl, i-propyl, or the different butyl, pentyl or hexyl isomers.

“Alkoxy” includes, for example, methoxy, ethoxy, π-propyloxy, isopropyloxy and the different butoxy, pentoxy and hexyloxy isomers. “Alkylthio” includes branched or straight-chain alkylthio moieties such as methylthio, ethylthio, and the different propylthio, butylthîo, pentylthio and hexylthio isomers.

The term “halogen”, either alone or in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” includes fluorine, chlorine, bromine or iodîne. Further, when used in compound words such as “haloalkyl”, or when used in descriptions such as “alkyl substituted with halogen” said alkyl may be parti ally or fully substituted with halogen atoms which may be the same or different. Examples of “haloalkyl” or “alkyl substituted with halogen” include F₃C-, C1CH₂-, CF₃CH₂- and CF₃CC1₂-.

The Chemical abbreviations S (O) and S(=O) as used herein represent a sulfmyl moiety. The Chemical abbreviations SO₂, S(O)₂ and S(=O)₂ as used herein represent a sulfonyl moiety. The Chemical abbreviations C(O) and C(=O) as used herein represent a carbonyl moiety. The Chemical abbreviations CO₂, C(O)O and C(=O)O as used herein represent an oxycarbonyl moiety.

The total number of carbon atoms in a substituent group is indicated by the “Cj-Cj” prefix. For ex ample, Cj-C₄ alkyl désignâtes methyl, ethyl, and the varions propyl and butyl i soin ers.

When a compound is substituted with a substituent bearing a subscript that indicates the number of said substituents can exceed 1, said substituents (when they exceed 1) are independently selected from the group of defined substituents. Further, when the subscript indicates a range, e.g. (R)^, then the number of substituents may be selected from the integers between i and j inclusive. When a group contains a substituent which can be hydrogen, then when this substituent is taken as hydrogen, it is recognized that this is équivalent to said group being unsubstituted. When one or more positions on a group are said to be “not substituted” or unsubstituted , then hydrogen atoms are attached to take up any free valency.

Unless otherwise indicated, heterocyclic rings and ring Systems can be attached through any available carbon or nitrogen by replacement of a hydrogen on said carbon or nitrogen.

When a substituent is a 5- or 6-membered nitrogen-containing heterocyclic ring, it may be attached to the remainder of Formula 1 though any available carbon or nitrogen ring atom, unless otherwise described.

A wide variety of synthetic methods are known in the art to enable préparation of aromatic and nonaromatic heterocyclic rings and ring Systems; for extensive reviews see the eight volume set of Comprehensive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees editors-in-chief, Pergamon Piess, Oxford, 1984 and the twelve volume set of Comprehensive Heterocyclic Chemistry II, A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors-in-chief, Pergamon Press, Oxford, 1996.

Compounds of this disclosure can exist as one or more stereoisomers. Stereoisomers are isomers of identical constitution but differing in the arrangement of their atoms in space and include enantiomers, diastereomers, cis-trans isomers (also known as géométrie isomers) and atropisomers. Atropisomers resuit from restricted rotation about single bonds where the rotational barrier is hîgh enough to permit isolation of the isomeric species. One ski lied in the art will appreciate that one stereoisomer may be more active and/or may exhîbit bénéficia] effects when enriched relative to the other stereoisomer(s) or when separated from the other stereoisomer(s). Additionally, the skilled artisan knows how to separate, enrich, and/or to selectively préparé said stereoisomers. For a comprehensive discussion of ail aspects of stereoisomerism, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

Compounds selected from Formula 1 typically exist in more than one form, and Fonnula 1 thus includes ail crystalline and non-crystalline forms of the compounds that Formula 1 représente. Non-crystalline forms include embodiments which are solids such as waxes and gums as well as embodiments which are liquids such as solutions and melts. Crystalline forms 5 include embodiments which represent essentially a single crystal type and embodiments which represent a mixture of polymorphs (i.e. different crystalline types). The term “polymorph” refers to a particular crystalline form of a Chemical compound that can crystallize in different crystalline forms, these forms having different arrangements and/or conformations of the molécules in the crystal lattice. Although polymorphs can hâve the same Chemical composition, 10 they can also differ in composition due to the presence or absence of co-crystallized water or other molécules, which can be weakly or strongly bound in the lattice. Polymorphs can differ in such Chemical, physical and biological properties as crystal shape, density, hardness, color, Chemical stability, melting point, hygroscopicity, suspensibility, dissolution rate and biological availabîlity, One skilled in the art will appreciate that a polymorph of a compound represented 15 by Fonnula 1 can exhibit bénéficiai effects (e.g., suitability for préparation of useful formulations, improved biological perfonnance) relative to another polymorph or a mixture of polymorphs of the same compound represented by Fonnula 1. Préparation and isolation of a particular polymorph of a compound represented by Formula 1 can be achieved by méthode known to those skilled in the art including, for example, crystallization using selected solvents 20 and températures. Compounds of this disclosure may exist as one or more crystalline polymorphs. This disclosure comprises both individual polymorphs and mixtures of polymorphs, including mixtures enriched in one polymorph relative to others. For a comprehensive discussion of polymorphism see R. Hilfiker, Ed., Polymorphism in the Pharmaceutical Industry, Wiley-VCH, Weinheim, 2006.

Embodiments of the présent disclosure as described in the Summary include those described below. in the following Embodiments, reference to “a compound of Formula 1” includes the définitions of substituents specified in the Summary unless further defined in the Embodiments.

Embodiment la. A compound of Formula 1 wherein R¹ is CF3 or H, R² is F or H, and R³ is 30 HorCF3.

Embodiment Ib. A compound of Fonnula 1 wherein R¹ is Cl or CF₃, R² is H or F, and R³ is Cl.

Embodiment le. A compound of Formula 1 wherein R¹ is Cl or H, R² is F or H, and R³ is CF₃.

Embodiment Id. A compound of Formula 1 wherein R¹ is CF3 or H, R² is F or H, and R³ is H or CF3.

Embodiment le. A compound of Formula 1 wherein R¹ is Cl or CF₃, R² is F, and R³ is Cl.

Embodiment If. A compound of Formula 1 wherein R¹ is CI or H, R2 is F or H, and R³ is CF3.

Embodiment 1g. A compound of Formula 1 wherein R¹ is CI, R² is H, and R³ is Cl.

Embodiment Ih. A compound of Formula 1 wherein R¹ is Cl, R² is F, and R³ is Cl.

Embodiment li. A compound of Formula 1 wherein R¹ is H, R² is F, and R³ is Cl.

Embodiment Ij. A compound of Formula 1 wherein R¹ is FI, R² is F, and R³ is CF₃.

Embodiment 1k. A compound of Formula 1 wherein R¹ is H, R² is H, and R³ is CF₃.

Embodiment IL A compound of Formula 1 wherein R¹ is Cl, R² is H, and R³ is CF₃.

Embodiment 1m. A compound of Formula 1 wherein R¹ is CF₃, R² is H, and R³ is H.

Embodiment In. A compound of Formula 1 wherein R¹ is CF₃, R² is F, and R³ is H.

Embodiment lo. A compound of Formula 1 wherein R¹ is Cl, R² is F, and R³ is CF₃.

Embodiment 2a. A compound of Formula 1 wherein J is J-1.

Embodiment 2b. A compound of Embodiment 2a wherein R⁴ is C^Cg alkyl.

Embodiment 2c. A compound of Embodiment 2a wherein R⁴ is C₂-C₆ alkenyl.

Embodiment 2d. A compound of Embodiment 2a wherein R⁴ is C₂-C₆ alkynyl.

Embodiment 2e. A compound of Embodiment 2a wherein R⁴ is C₃-C6 cycloalkyl.

Embodiment 2f. A compound of Embodiment 2a wherein R⁴ is C^C^ alkylcycloalkyl.

Embodiment 2g. A compound of Embodiment 2f wherein R⁴ is CHz-c-Pr.

Embodiment 2h. A compound of any one of Embodiments 2a-2g wherein R⁴ is substituted with substituents independently selected from halogen, cyano and CO₂R¹⁸.

Embodiment 2i. A compound of Embodiment 2h wherein the substituent is halogen.

Embodiment 2j. A compound of Embodiment 2i wherein the halogen is F.

Embodiment 2k. A compound of Embodiment 2h wherein the substituent is cyano.

Embodiment 21. A compound of Embodiment 2h wherein the substituent is CO9R¹⁸.

Embodiment 2m.A compound of Embodiment 21 wherein R^1S is C!-C₄ alkyl.

Embodiment 3a. A compound of Formula 1 wherein J is J-2.

Embodiment 3b. A compound of Embodiment 3a wherein R⁵ is H or Me.

Embodiment 3c. A compound of Embodiment 3a wherein R⁶ is OMe, SMe, S(O)Me or SO₂Me.

Embodiment 3d. A compound of Embodiment 3a wherein R⁵ is H or Me, and R⁶ is OMe, SMe, S(O)Me or SO₂Me.

Embodiment 4a. A compound of Formula 1 wherein J is J-3.

Embodiment 4b. A compound of Embodiment 4a wherein R⁷ is H or Me.

Embodiment 4c. A compound of Embodiment 4a wherein Z is 2-pyridinyI or 2-pyrimidinyl.

Embodiment 4d. A compound of Embodiment 4a wherein R⁷ is H or Me, and Z is 2pyridinyl or 2-pyrimidinyl.

Embodiment 4e. A compound of Embodiment 4a wherein R⁷ is H or Me, and Z is 2pyrimidinyl.

Embodiment 5a. A compound of Formula 1 wherein J is J-4.

Embodiment 5b. A compound of Embodiment 5a wherein R⁸ is H or Me.

Embodiment 5c. A compound of Embodiment 5a wherein R⁹ is H or C_t-C₃ alkyl.

Embodiment 5d. A compound of Embodiment 5a wherein R⁸ is H or Me, and R⁹ is H or Cj-Ca alkyl.

Embodiment 6a. A compound of Formula 1 wherein J is J-5.

Embodiment 6b. A compound of Embodiment 6a wherein R¹¹ is H.

Embodiment 6c. A compound of Embodiment 6b wherein R¹⁰ is H or Me.

Embodiment 6d. A compound of Embodiment 6b wherein R¹² is H, C!-C₂ alkyl, CH₂CF₃or CH₂CN.

Embodiment 6e. A compound of Embodiment 6b wherein R¹⁰ is H or Me, and R¹² is H,

C!-C₂ alkyl, CH₂CF₃ or CH₂CN.

Embodiment 7a. A compound of Formula 1 wherein J is J-6.

Embodiment 7b. A compound of Embodiment 7a wherein R¹³ is H, C]-C₇ alkyl or CH₂CF₃.

Embodiment 8a. A compound of Formula 1 wherein J is J-7.

Embodiment 8b. A compound of Embodiment 8a wherein R²⁰ is methyl.

Embodiment 9a. A compound of Formula 1 wherein J is J-8.

Embodiment 9b. A compound of Embodiment 9a wherein R²¹ is fluoro, C_rC₃ alkyl, cyclopropyl or dimethylamino.

Embodiment 10a. A compound of Formula 1 wherein J is J-9.

Embodiment 10b. A compound of Embodiment 10a wherein m is !.

Embodiment 11 a. A compound of Formula 1 wherein R¹ is Cl, H, or CF3, R² is H, or F, R³is H, Cl, or CF3 and J is J-l, J-2, or J-3.

Embodiment 11b. A compound of Embodiment lia wherein R¹ is Cl, or H.

Embodiment 1 le. A compound of Embodiment 1 la or 11b wherein R² is H.

Embodiment 1 Id. A compound of any one of Embodiments l la-c wherein R³ is Cl, or CF₃.

Embodiment lie. A compound of any one of Embodiments 1 la-d wherein R³ is Cl.

Embodiment 1 If. A compound of any one of Embodiments I la-e wherein J is J-l, or J-3.

Embodiment 11g. A compound of any one of Embodiments I la-f wherein J is J-l.

Embodiment 1 Ih. A compound of any one of Embodiments 1 la-g wherein J is J-I and J-l is

-C(O)NH(r-Bu), -C(O)NHCH₂CH₃, -C(O)NHCH₂CCH, -C(O)NH(c-Pr), or C(O)NHCH₂(c-Pr),

Embodiment 1 li. A compound of Embodiment 1 Id wherein J-l is C(O)NH(c-Pr), or C(O)NHCH₂(c-Pr).

Embodiments of this disclosure, including Embodiments 1-1 li above as well as any other embodiments described herein, can be combined in any manner, and the descriptions of variables in the embodiments pertain not only to the compounds of Formula 1 but also to the starting compounds and mtermediate compounds useful for preparing the compounds of Formula I. In addition, embodiments of this disclosure, including Embodiments 1-1 li above as well as any other embodiments described herein, and any combination thereof, pertain to the compositions and methods of the present disclosure.

Spécifie embodiments include compounds of Formula 1 selected from the group consisting of compounds 5-[5-(3,5-dichIoro-4~fluorophenyl)-4,5~dihydro-5-(trifluoromethyl)-3-isoxazolyl]N~(l,l-dimethylethyl)-8-isoquinolinecarboxamide (Compound 2), N-(cyclopropylmethyl)-5-[5(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyI)-3-isoxazoIyl]-8isoquinolinecarboxamide (Compound 3), 5-[5-(3>dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)-3-isoxazolyl]-N-(2-pyrimidinyImethyl)-8-isoqLiînolinecarboxamide (Compound 4), N-cyclopropyl-5-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5(trifluoromethyl)-3-isoxazolyl]-8-isoquinoIinecarboxamide (Compound 23), 5-[5-[3-chloro-5(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-(cycIopropylmethyl)8-isoquinolinecarboxamide (Compound 36), N-cyclopropyl-5-[4,5-dihydro-5-(trifluoromethyl)5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8-isoquinolinecarboxamide (Compound 16), N(cyclopropylmethyl )-5-(4,5-dihydro-5-(trifluoromethyl)-5-[3-(trifluorometh yl)phenyl]-3isoxazolyl]-8-isoquinolinecarboxamide (Compound 17), N-(cyclopropylmethyl)-5-[5-[4-fluoro3-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromcthyl)-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 58), 5-[5-[3-chloro-5-(trifluoromethyl)phenyl]-4,5dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-cyclopropyl-8-isoquinolinecarboxamide (Compound 35), 5-[5-[4-fiuoro-3-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-N-2-propyn-l-yI-8-isoquinolinecarboxamide (Compound 74), 5-[5-(3,5-dichloro-4fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazoiyl]-N-ethyl-8-isoqumolinecarboxamide (Compound 46), 5-(5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-N-2-propyn-l-yl-8-isoquinolinecarboxamide (Compound 48), N-cyclopropyl-5-[5(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8-isoquinolinecarboxamide (Compound 70), N-cyclopropyl-5-[5-[4-fluoro-3-(trifluoromethyl)phenyl]-4,5-dihydro-5(trifluoromethyl)-3-isoxazolyl]-8-isoquinolinecarboxamide (Compound 55), S-N-cyclopropyl-5[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazoIyl]-8isoquinolinecarboxamide (Compound 82) and S-N-(cycIopropylmethyI)-5-[4,5-dihydro-5(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8-isoquinolinecarboxamide (Compound 99).

In one embodiment, the compound of Formula 1 is selected from N-cyclopropyl-5-[4,5dihydro-5-(trifIuoromethyl)-5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 16), N-(cyclopropylmethyI)-5-[4,5-dihydro-5(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-3-isoxazoly]]-8-isoquinolinecarboxamide (Compound 17), N-cyclopropyl-5-[5-(3,5-dichlorophenyi)-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-8-isoquinolinecarboxamide (Compound 70), N-cyclopropyl-5-[5-[4-fluoro-3(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 55), S-N-cyclopropyl-5-[5-(3,5-dichloro-4-fluorophenyl)4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8-isoquinolinecarboxamide (Compound 82), and

S-N-(cyclopropylmethyl)-5-[4,5-dihydrO5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-3isûxazolyl]-8-isoquinolinecarboxamide (Compound 99).

In one embodiment, the compounds of Formula 1 are those wherein the compound is selected from the compounds in Table 1.

Table 1.

Compound

Chemical name 5-(5-(3,5-dichloro-4fl uorophenyl)-4,5 dihydro-5(trifluoromethyl)-3Îsoxazolyl]-N-(1,1dimethylethyl)-8isoquinolinecarboxami de

N(cyclopropylmethyl)-5[5-(3,5-dichloro-4fluorophenyl)-4,5dihydro-5(trifluoromethyl)-3isoxazolyl]-8isoquinolinecarboxami de

4	F Μ /-n ^ci VYH \ 7 AA/A /A /A i J C. O	5-[5-(3,5-dichloro-4fluorophenyl)-4,5dihydro-5(trifluoromethyl)-3isoxazolyl]-N-(2pyrimidinylmethyl)-8isoquinolinecarboxami de
23	ÇjA Z==A 1 ) c</ J U-·—7k J jj 2 k 1! i' ^Xtu Ü	N-cyclopropyl-5-[5(3,5-dichloro-4fluorophenyI)-4,5dihydro-5(trifluoromethyl)-3isoxazolyl]-8isoquinolinecarboxami de
36	F M p—n Cl·— A U « /V—“F N ^F F	5-[5-[3-chloro-5(tri fl uorom ethyl )phenyl ]-4,5-ddiydro-5(trifluoromethyl)-3 isoxazolyl]-N(cyclopropylmethyl)- 8 isoquinolinecarboxami de
16	F ^F-^</⁰ ξ\ F ___/ \ Μ. ^F /—\ υ F \=V 4 \ ° ^Ά'	N-cyclopropy]-5-[4,5dihydro-5(trifluoromethyl)-5~[3(trifluoromethyl)phenyl ]-3-isoxazoIyl]-8isoquinolinecarboxami de

17	F F-~~À F^Z	F ^F\l P N /Ύ X [j ΊΤ	h / 0	N- (cyclopropylmethyl )- 5 [4,5-dihydro-5- (tri fluoromethyl )-5 -[3(trifluoromethyl)phenyl ]-3-isoxazolyl]-8isoquinolinecarboxami de
58				N-
		F F- 1 P N		(cyclopropylmethyl)-5-
				[5-[4-fluoro-3-
	F F—		7\| h / Il N	(tri fluorom ethyl )ph enyl
	F^Z			]-4,5-dihydro-5-
	/	L J	O	(trifluoromethyl)-3isoxazoiyl]-8isoquinolinecarboxami de
35	F		HN--	5-[5-[3-chloro-
	F--			5-
	F		O	(trifluoromethyl)phenyl
	J Cl—\	/ F		]-4,5-dihydro-5- (tri fluoromethyl )-3-
		J F		isoxazolyl]-N-
				cyclopropyl-8isoquinolinecarboxami de
74				5-[5-[4-fluoro-
		F o—.__		3-
	F	\ 7	π / > N-—/	(trifluoromethyl)phenyl
	F		O	]-4,5-dihydro-5-
	^F /---			(trifluoromethyl)-3-
	F	~J N		isoxazolyl]-N-2-
		F		propyn-l-yl-8-

		isoquinofinecarboxami de
46	F F-^ 1 P—N 7—/ U ^H / /Z Λ 1 ’L / 'x i J ° ^F Ci ^N	5-(5-(3,5dichloro-4fluorophenyl)-4,5dihydro-5- (tri fl uoromethyl)-3 isoxazolyl]-N-ethyl-8isoquinolinecarboxami de (Compound 46)
48	F F-^J p—N Z-—/ U ^H ^c1^ χΑ/Ύ /\ C ⁰ ^F C] N	5-(5-(3,5dichloro-4fluorophenyl)-4,5dihydro-5(trifluoromethyl)-3isoxazolyl]-N-2propyn-i-yl-8isoquinolinecarboxami de
70	^F. 0—N V__FI F / \ \7 ^c,^3 M ° Cl	N-cyclopropyl5-(5-(3,5dichlorophenyl)-4,5dihydro-5(tri fluorom ethyl)-3 isoxazolyl]-8isoquinolinecarboxaini de
55	^F\ ο—N ^F-^KJ \\ >Γ-Λ f / \/ y \\ ^Ν~^—7 'W cv / ^N _{_}_________F_______________________________________________	N-cyclopropyl- 5-[5-[4-fluoro-3- (trifluoroinethyl)phenyl ]-4,5-dihydro-5(trifluoromethyl)-3-

		isoxazolyl]-8isoquinolinecarboxami de
82	F —41111 \ / /7 m ° j] % / / Cl F	S-Ncyclopropyl-5-[5-(3,5dichloro-4fluoroph eny 1)-4,5dihydro-5(trifluoromethyl)-3isoxazolyl]-8isoquinolinecarboxami de (Compound 82)
99	F ο \ 0—N _F 1 A F— / \=/ t ) °	S-N(cyclopropylmethyl)-5[4,5-dihydro-5(trifluoromethyI)-5-[3(trifluoromethyl)phenyl ]-3-isoxazoIyl]-8isoquinolinecarboxami de

controlling an invertebrate pest comprising at least one compound of Formula 1. In some also provides compounds and composition for one embodiments, compounds or compositions disclosed herein fiirther comprise at least one additional component selected from surfactants, solid diluents and liquid diluents. In some embodiments, the compositions disclosed herein optionally further comprise at least one additional biologically active compound or agent.

In one embodiment, this disclosure also provides compounds and compositions for controlling an invertebrate pest comprising a compound of Formula 1, and at least one additional biologically active compound or pest control agent.

In one embodiment, this disclosure provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1. This disclosure also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optîonally further comprising a biologically effective amount of at least one additional biologically active compound or agent.

In one embodiment, this disclosure also relates to such method wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, and at least one additional biologically active compound or pest control agent.

In one embodiment, this disclosure also relates to such method wherein the invertebrate 10 pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1 at least one additional biologically active compound or pest control agent and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents. In some embodiments, the environment is soil or plant foliage.

^one embodiment, this disclosure also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula I.

In one embodiment, this disclosure also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a 20 compound of Formula 1, and at least one additional biologically active compound or pest control agent.

In one embodiment, this disclosure also provides a method for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of Formula 1, at least one additional biologically active compound or pest control 25 agent, and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents.

In one embodiment, this disclosure provides a soil drench formulation comprising the compounds or compositions disclosed herein.

In one embodiment, the compositions as disclosed herein further comprise liquid fertilizer. 30 In some embodiments, the liquid fertilizer is aqueous-based.

In one embodiment, this disclosure provides a spray composition comprising the compounds or compositions disclosed herein. In some embodiments the spray composition further comprises a propellant.

In one embodiment, this disclosure provides a bait composition comprising the compounds or composition disclosed herein. In one embodiment, the bait composition further comprises one or more food materials.

In one embodiment, the bait composition further comprises an attractant. In one embodiment, the bait composition further comprises a humectant.

In one embodiment, the compounds or compositions disclosed herein are solid compositions, such as dusts, powders, granules, pellets, prills, pastilles, tablets, or fil lcd films. In some embodiments, the compositions disclosed herein are solid compositions and are waterdîspersible or water -soluble.

In one embodiment, a liquid or dry formulation comprising the compounds or compositions as disclosed herein for use in a drip irrigation System, furrow during planting, handheld sprayer, backpack sprayer, boom sprayer, ground sprayer, aerial application, unmanned aerial vehicle, or a seed treatment.

In one embodiment, the compounds or compositions as disclosed herein for use in a drip irrigation System, furrow during planting, handheld sprayer, backpack sprayer, boom sprayer, ground sprayer, aerial application, unmanned aerial vehicle, or a seed treatment wherein said formulation is sprayed at an ultra-low volume.

In one embodiment, this disclosure also relates to the treated seed.

Of note is that compounds of this disclosure are characterized by favorable metabolic and/or soil resîdual patterns and exhibit activity controlling a spectrum of agronomie and nonagronomic invertebrate pests.

Of particular note, for reasons of invertebrate pest control spectrum and économie importance, protection of agronomie crops from damage or injury caused by invertebrate pests by controlling invertebrate pests are embodiments of the disclosure. Compounds of this disclosure because of their favorable translocation propertîes or systemîcity in plants also protect foliar or other plant parts which are not directly contacted with a compound of Formula 1 or a composition comprising the compound.

Bioaccumulation of pesticides in non-target organisms is an important safety considération and it is often désirable to limit the systemic exposure and/or accumulation of pesticides and/or their métabolites in non-target organisms. For example, if a compound is to be applied as an insecticide to a crop plant, it is désirable that the compound does not accumulate in the plasma or fat of a vertebrate animal.

Compounds of Formula 1 may show favorable pharmacokinetic properties in vertebrate animais. In particular, compounds of Formula 1 hâve been found to hâve rapid clearance from vertebrate animal plasma/blood and a low distribution into vertebrate animal fat, thus reducing the possibility of unwanted bioaccumulation. Of note is the fluorine atom at the 4-position of the phenyl ring attached to the 5-position of the isoxazoline ring.

The pharmacokinetic properties of compounds of Formula 1 can be measured using a wide variety of assay protocols known in the science of pharmacology. In one illustrative method involvîng a single oral dose, three male and three female rats each receive a single dose of a test substance via oral gavage. Blood is collected via tail vein at 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h, and then every 24 h thereafter until sacrifice. To process the s amples to plasma, blood is collected in tubes containing ethylenediaminetetracetic acid (EDTA) and centrifuged at approximately 3000 rpm to separate plasma from red blood cells. Altematively, blood is collected using microcapillary tubes and dispensed into tubes containing HPLC water (1:1, v/v). Fat is also collected, homogenized and extracted to détermine the concentration of the compound of Formula 1 at sacrifice. The plasma or blood and fat are analyzed for the compound of Formula 1 and/or métabolites, for example, by high-performance lîquid chromatography (HPLC) with tandem mass spectrometry détection (LC/MS/MS) to detennine the concentration of the test substance. The plasma or blood pharmacokinetic data is analyzed using nonlinear modeling software (e.g., Phoenix® WinNonlin®, Pharsight-A Certara™ Company, St. Louis, MO, U.S.A.) to detennine the plasma/blood half-life of the compound of Formula 1, the time after administration when the maximum plasma/blood concentration is reached (T_max), the maximum plasma/blood concentration (C_raax), and the area under the plasma/blood concentration curve (AUC). As analysis of fat requires rat sacrifice, fat data is obtained at single time points (i.e. the time of rat sacrifice). The fat:plasma or fat:blood ratio of the compound of Formula 1 is then determined.

Also noteworthy as embodiments of the présent disclosure are compositions comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional coinponent selected from the group consisting of a surfactant, a solid diluent and a liquid diluent, said compositions optionally further comprising at least one additional bîologically active compound or agent.

Further noteworthy as embodiments of the présent disclosure are compositions for controlling an invertebrate pest comprising a compound of any of the preceding Embodiments, as well as any other embodiments described herein, and any combinations thereof, and at least one additional component selected from the group consisting of a surfactant, a solid diluent and a hquid diluent, said compositions optionally further comprising at least one additional biologically active compound or agent. Embodiments of the disclosure further include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of any of the preceding Embodiments (e.g., as a composition described herein).

Embodiments of the disclosure also include a composition comprising a compound of any of the preceding Embodiments, in the form of a soil drench liquid formulation. Embodiments of the disclosuie further include methods for controlling an invertebrate pest comprising contacting the soil with a liquid composition as a soil drench comprising a biologically effective amount of a compound of any of the preceding Embodiments.

Embodiments of the disclosure also include a spray composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments and a propellant. Embodiments of the disclosure further include a bait composition for controlling an invertebrate pest comprising a biologically effective amount of a compound of any of the preceding Embodiments, one or more food materials, optionally an attractant, and optionally a humectant. Embodiments of the disclosure also include a device for controlling an invertebrate pest comprising said bait composition and a housing adapted to leceive said bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to said bait composition from a location outside the housing, and wherein the housing is further adapted to be placed in or near a locus of potential or known activity for the invertebrate pest.

Embodiments of the disclosure also include methods for protecting a seed from an invertebrate pest comprising contacting the seed with a biologically effective amount of a compound of any of the preceding Embodiments.

Embodiments of the disclosure also include methods for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of Formula 1 (e.g., as a composition described herein), provided that the methods are not methods of medical treatment of a human body by therapy.

This disclosure also relates to such methods wherein the invertebrate pest or its environment is contacted with a composition comprising a biologically effective amount of a compound of Formula 1, and at least one additional component selected from the group 22 consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising a biologically effective amount of at least one additional biologically active compound or agent, provided that the methods are not methods of medical treatment of a human body by therapy.

The compounds of Formula 1 can be prepared by one or more of the following methods and variations as described in Schemes 1-11. The définitions of substituents in the compounds of Formulae 1-20 below are as defmed above in the Summary unless otherwise noted. The following abbreviations may be used: DMF is W-dimethylformamide, and DBU is 1,8diazabicyclo[5.4.0]undec-7-ene.

Compounds of Formula 1 can be prepared from compounds of Formulae 2 or 3 by the general method shown in Scheme 1. In one variation of this method, the compound of Formula 1 is prepared by the coupling of a carboxylic acid chloride of Formula 2 with an appropriate amine compound of Fonnula of 4. The acid chloride of Formula 2 can be prepared by known methods from the carboxylic acid of Formula 3.

Scheme 1

R is C(O)C1

R is C(O)OH

Altematively, the compound of Formula 1 can be prepared directly from the carboxylic acid of Formula 3 by coupling with an appropriate amine of Formula 4. In this method, the coupling is generally done in the presence of a dehydrating coupling reagent. Coupling reagents useful in this method include dicyclohexyl carbodiimide, l-(3-dimethylaminopropyl)-3ethylcarbodiimide and carbonyl diîmidazole. Further coupling reagents useful in this method 25 include 1-propanephosphonic acid cyclic anhydride, 1 -[bis(dimethylamino)methylene]-127-1,2,3triazolo[4,5-ô]pyridinium 3-oxide hexafluorophosphate and A-[(dimethylamino)-1/7-1,2,3tnazoIo-[4,5-ô]pyridin-l -yImethyIene]-jV-methylmethanaminium hexafluorophosphate jV-oxide;

these coupling reagents are generally used in the presence of a base such as triethylamine, pyridine, 4-(dimethylamino)pyridine or W-diisopropylethylamine. Typical reaction conditions include an anhydrous aprotîc solvent such as dichloromethane, tetrahydrofuran or DMF, and a reaction température between room température and 70 °C. The method of Scheme 1 is illustrated in Steps H of Synthesis Example 4.

Compounds of Formula 1 can also be prepared by the method shown in Scheme 2. In this method, an aryl bromide or iodide of Formula 5 is carbonylated and coupled with an appropriate amine compound of Formula of 4.

Scheme 2

H₂N—J

CO gas catalyst

R is Br or f

This aminocarbonylation method typically involves treatment of an aryl bromide of Formula 5 (wherein X is Br or I) with an appropriate amine of Formula 4 in the presence of a palladium catalyst under a CO (carbon monoxide) atmosphère. Palladium catalysts useful in this method typically comprise palladium in a fonnal oxidation State of either 0 (i.e. Pd(0)) or 2 (i.e. Pd(II)). Examples of palladium-containing compounds and complexes useful as catalysts in this method include PdC12(PPh3)2 (bis(triphenylphosphine)palladium (II) dichloride), Pd(PPh3)4 (tetrakis(triphenylphosphine)palladium(O)), Ρά(Ο₅Η₇θ2)2 (palladium(II) acetylacetonate), Pd2(dba)3 (tris(dibenzylideneacetone)dipalladium(O)), and [l,l'-bis(diphenylphosphino)ferrocene]dichloropalladium(II). The method of Scheme 2 is generally conducted in a liquid phase, with the palladium catalyst having good solubility in the liquid phase. Useful liquid phase solvents include ethers such as 1,2-dimethoxyethane, amides such as AÇV-dimethylacetamide, and non-halogenated aromatic hydrocarbons such as toluene.

The method of Scheme 2 can be conducted over a wide range of températures, ranging from about 25 to about 150 °C. Of note are températures from about 60 and about 110 °C, which typically provide faster reaction rates and higher product yields. Literature examples of aminocarbonylation methods include H. Horino et al., Synthesis 1989, 715; and J. J. Li, G. W. Gnbble, edi tors, Palladium in Heterocyclic Chemistry: A Guide for the Synthetic Chemist, 2000. The method of Scheme 2 is illustrated in Step C of Synthesis Example 1.

Compounds of Formula 1 can also be prepared by the method shown in Scheme 3. In this method, a tnfluoromethyl ketone of Formula 6 is condensed with a compound of Formula 7, followed by reaction with hydroxylamine to form the isoxazoline ring of the compound of Formula 1.

Scheme 3

This method involves reaction of the compounds of Formulae 6 and 7 in the presence of a base such as Ca(OH)₂, K₂CO₃ or CsCO₃ in a solvent such as toluene, DMF, MTBE, trifluormethylbenzene, dichloroethane or acetonitriie, or in a mixture of such solvents. The condensation product is subsequently treated with hydroxylamine or a hydroxylamine sait in the presence of base, such as NaOH or LiOH to form the isooxazoline compound of Formula 1. For an example of this method, see G. Annis, WO 2009/126668. The method of Scheme 3 is illustrated in Steps D and E of Synthesis Example 2 and Steps B and C of Synthesis Example 3.

Compounds of Formula 5 can be prepared by the 1,3-dîpoIar cycloaddition of styrenes of Formula 8 with nitrile oxides derived from oximes of Formula 9 as shown in the method of Scheme 4.

Scheme 4

R is Br or [

This method typically involves chlorination of the oxime of Formula 9 and subséquent dehydrochlorination to yield an in situ generated nitrile oxide, which then undergoes 1,3-dipolar cycloaddition with the styrene of Formula 8 to afford the compound of Formula 5. In a typical procedure, a chlorinating reagent such as sodium hypochlorite, TV-chlorosuccinimide, or chloramine-T is combined with the oxime of Formula 9 in the presence of the styrene of Formula 8. Depending on the reaction conditions, an amine base such as pyridine or triethylamine may be necessary to facilitate the dehydrochlorination reaction. Solvents useful in this method include tetrahydrofuran, diethyl ether, methylene chloride, dioxane, and toluene. Reaction températures range from room température to the reflux température of the solvent. For general procedures for the cycloaddition of nitrile oxides and olefins, see Lee, Synthesis, 1982, 6, 508509; Kanemasa et al., Tetrahedron, 2000, 56, 1057-1064; EP 1,538,138 Al, as well as référencés cited within. The préparation of the compound of Formula 9 (wherein R is Br) is known in the art; see Ming Xu et al., Bioorg. Med. Chem. Lett. 2014, 24, 4026.

Compounds of Formula 5 can also be prepared by the method shown in Scheme 5. In this method, a trifluoromethyl ketone of Formula 6 is condensed with a compound of Formula 10, followed by réaction with hydroxylamine to form the isoxazoline ring of the compound of Formula 5.

Scheme 5

This method is analogous to the method described in Scheme 3. The compound of Formula 10 wherein R is Br is commercially available.

Carboxylic acids ot Formula 3 can also be prepared by a method analogous to the method desciibed in Scheme 3. Condensation of the compound of Fonnula 6 with the compound of Formula 11, followed by cyclization with hydroxyl amine provides the corresponding ester as shown in Scheme 6. Subséquent hydrolysis of the corresponding ester can be accomplished by various procedures known in the art. For example, treatment of the ester with aqueous lithium hydroxide in tetrahydrofuran, followed by acidification, yields the corresponding carboxylic acid of Formula 3. The method of Scheme 6 is illustrated in Steps E, F and G of Synthesis Example 4.

Scheme 6

R* îs methyl or ethyl

Carboxylic acids of Formula 3 can also be prepared by acidic hydrolysis of amides of

Formula 12 as shown in Scheme 7.

Scheme 7

In this method, an amide of Formula 12 is converted to the corresponding carboxyiic acid of Formula 3 by procedures known in the art; see, for example, Hoang V. Le, et al. Tetrahedron Lett. 2011, 52(17), 2209. Acids useful for this method include CF₃COOH, H₂SO₄, HOAc, HCI and HBr. Reaction températures range from room température to the reflux température of the solvent. This method is illustrated in Step A of Synthesis Example 3.

Compounds of Formula 11 can be prepared by the method shown in Scheme 8. In this method, an aryl bromide or iodide of Formula 13 is treated with carbon monoxide gas in the présence of a palladium catalyst and coupled with methanol or éthanol to form the compound of Formula of 11 (wherein R^a is methyl or ethyl). This method is sîmilar to the method described in Scheme 2.

Scheme 8

CO gas

Pd catalyst

MeOH or EtOH

X is Br or I

R^a is methyl or ethyl

Compounds of Formula 12 can be prepared by the method shown in Scheme 9. This method is similar to the method described in Scheme 3.

Scheme 9

In this method, a trifluoromethyl ketone of Fonnula 6 is coupled with an amide of Formula 14 and cyclized to provide the compound of Formula 12.

Compounds of Formula 14 can be prepared by the two-step method shown in Scheme 10. In the First step ofthis method, an amine compound of Formula 15 is diazotized and reacted with a r-butylisocyanide to form a compound of Formula 16.

Scheme 10

This method of converting an aniline to a diazonium sait and then quenching with an isocyanide to form an amide is known in the literature; see Zhonghua Xia and Qiang Zhu, Org. Lett. 2013, 15(16), 4110, and U. Basavanag, et al. Angew. Chem. Int. Ed. 2013, 52, 7194. The compound of Formula 15 is commercially available. This First step of the method of Scheme 10 is îllustrated in Step A of Synthesis Example 2.

The second step of the method of Scheme 10, in which an aryl bromîde is converted to a methyl ketone, is well known in the art; see, for example, Youssef, Ei-Ahmad, et al. WO2013/190123; Dan Xu, et al. Tetrahedron Lett. 200S, 49(42), 6104; and Wen Pei, et al. J. Organometallîc Chem. 2005, 690(15), 3546. In this step, a compound of Formula 16 is reacted with a vinyl ether such as n-butyl vinyl ether, tributyl(l-ethoxyvinyl)tin or ethyl vinyl ether, in the presence of a palladium catalyst, such as Pd(OAc)₂/Ph₃P(CH₂)₃PPh₃, PdCl?(PPh₃)₂ or Pd(PPh₃)₄ to provide the coupled product, which is then hydrolyzed with acid to give a compound of Formula 14. The method of Scheme 10 is illustrated in Steps B and C of Synthesis Example 2.

An altemate method for the préparation of the compound of Formula 11 is shown in

Scheme 11. In the first step of this method, 2-broinobenzaldehyde 17 is condensed with 2amino-l,l-dimethoxyethane followed by cyclization with sulfuric acid to yield the bromoisoquinoline of Formula 18. For an example of this Pomerantz-Fritsch reaction, see N, Briet, et al., Tetrahedron, 2002, 58(29), 5761-5766. This procedure may be adapted to préparé 10 other isoquinolines.

Scheme 11

In the second step of this method, the isoquinoline ester of Formula 19 is prepared by treatment of the compound of Formula 18 with carbon monoxide gas in the presence of a palladium catalyst and methanol or éthanol as solvent; see, for example, J. Papillon, et al., J. Med. Chem., 2015, 58(23), 9382-9384. In the third step of this method, the isoquinoline ester of Formula 19 is selectively brominated at the 5-position with JV-bromosuccinimide in sulfuric acid/water or with molecular bromine and aluminum chloride to provide the compound of

Formula 20; see, for example, W. Brown, et al., Synthesis, 2002, 1, 83-86. In the final step of this method, introduction of the acetyl group can be accomplished by a variety of methods, including the cross coupling of the compound of Formula 20 with tributyl(ethoxyethenyl)stannane in the presence of a palladium catalyst followed by hydrolysis of the vinyl ether to afford the compound of Formula 11; see, for example, N. Sato and N. Narita, Synthesis, 2001, 10, 1551-1555. The method of Scheme 11 is ÎHustrated in Steps A, B, C and D of Synthesis Example 4.

It is recognized that some reagents and reaction conditions described above for preparing compounds of Formula 1 may not be compatible with certain functionalities présent in the intermediates. In these instances, the incorporation of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining the desired products. The use and choice of the protecting groups will be apparent to one skilled in Chemical synthesis (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.; Wiley: New York, 1991). One skilled in the art will recognize that, in some cases, after introduction of the reagents depicted in the individual schemes, additional routine synthetic steps not described in detail may be needed to complété the synthesis of compounds of Formula 1. One skilled in the art will also recognize that it may be necessary to perform a combination of the steps illustrated in the above schemes in an order other than that implied by the particular sequence presented to préparé the compounds of Formula 1.

One skilled in the art will also recognize that compounds of Formula 1 and the intermediates described herein can be subjected to various electrophilic, nucleophilic, radical, organometallic, oxidation, and réduction reactions to add substituents or modify existing substituents.

Examples of intermediates useful in the préparation of compounds of this disclosure are shown in Tables 1-1 through 1-5.

TABLE 1-1

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	F	CI
Cl	H	cf₃	H	F	cf₃
Cl	F	CI	H	Cl	Cl
Cl	F	cf₃	H	Cl	cf₃
Cl	Ci	Cl	Cl	H	FI
Cl	Cl	cf₃	cf₃	H	H
cf₃	H	cf₃	Cl	F	H
cf₃	F	cf₃	cf₃	F	H
cf₃	CI	cf₃	Cl	Cl	H
H	H	C!	cf₃	Cl	H
H	H	cf₃

TABLE 1-2

R¹	R²	R³	R¹	R²	R³
Cl	H	CI	H	F	Cl
Cl	H	cf₃	H	F	cf₃
Cl	F	Cl	H	Cl	Cl
CI	F	cf₃	H	Cl	cf₃
Cl	Cl	Cl	Cl	H	H
Cl	Cl	cf₃	CF₃	H	H
cf₃	H	cf₃	Ci	F	H
cf₃	F	cf₃	cf₃	F	H
cf₃	Cl	cf₃	Cl	Cl	H
H	H	Cl	cf₃	Cl	H
H	H	cf₃

TABLE 1-3

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	F	Cl
Cl	H	cf₃	H	F	cf₃
Ci	F	Cl	H	Cl	Cl
Cl	F	cf₃	H	Cl	cf₃
Cl	Cl	Cl	Cl	H	H
Cl	Cl	cf₃	cf₃	H	H
cf₃	H	cf₃	Cl	F	H
cf₃	F	cf₃	cf₃	F	H
cf₃	Cl	cf₃	Cl	Cl	H
H	H	Cl	cf₃	Cl	H
H	H	cf₃	Cl	H	H

TABLE 1-4

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	F	Cl
Cl	H	cf₃	H	F	cf₃
Cl	F	Cl	H	Cl	Cl
Cl	F	cf₃	H	Ci	cf₃
Cl	Cl	Ci	Cl	H	H
Cl	Cl	cf₃	cf₃	H	H

CF3	H	cf₃	Cl	F	H
cf₃	F	cf₃	cf₃	F	H
CF3	Cl	cf₃	CI	Cl	H
H	H	Cl	cf₃	Cl	H
H	H	cf₃

TABLE 1-5

R^x	Ry	R*	RY	R*	RY
Br	C(O)OH	C(0)Me	Br	CHO	Br
Br	CO₂Me	C(0)Me	I	CHO	I
Br	CO₂Et	C(O)Me	C(0)0H	CHO	C(O)OH
Br	C(O)NH(t-Bu)	C(0)Me	C0₂Me	CHO	C0₂Me
I	C(O)OH	C(0)Me	CO₂Et	CHO	CO₂Et
1	C0₂Me	C(O)Me	C(O)NH(t-Bu)	CHO	C(O)NH(t-Bu)
I	CO₂Et
I	C(O)NH(t-Bu)

Without further élaboration, ît is believed that one skilled in the art using the preceding description can utilize the présent disclosure to its fullest extent. The following Synthesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Steps in the following Synthesis Examples illustrate a procedure for 10 each step in an overall synthetic transformation, and the starting material for each step may not hâve necessarily been prepared by a particular préparative run whose procedure is described in other Examples or Steps. Percentages are by weight except for chromatographie solvent mixtures or where otherwise indicated. Parts and percentages for chromatographie solvent mixtures are by volume unless otherwise indicated. NMR spectra are reported in ppm 15 downfield from tetramethylsilane; “s” means singlet, “d” means doublet, “t” means triplet, “q” means quartet, “m” means multiplet, “dd” means doublet of doublets, “dt” means doublet of triplets, br s means broad singlet. DMF means TYA-dimethylformamide. Compound numbers refer to Index Table A.

SYNTHES1S EXAMPLE 1

Préparation of5-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]N-(2-pyrimidinylmethyl)-8-isoquinolinecarboxamide (Compound 4)

Step A: Préparation of l-(8-bromo-5-isoquinolinyI)-3-(3,5-dichloro-4-fIuorophenyl)-4,4.4trifluoro-2-buten-l-one

A mixture of l-(3,5-dichloro-4-fluorophenyl)-2,2,2-trifluoroethanone (1.80 g, 6.39 mmol), l-(8-bromo-5-isoquinolyl)ethanone (1.00 g, 4.00 mmol, CAS Reg. No. 1890438-87-5)) and césium carbonate (2.60 g, 8.00 mmol) in toluene (200 mL) was stirred at reflux for 16 hr. The reaction mixture was then coolcd and filtered to remove insoluble salts. The filtrate was concentrated and the residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the tîtle compound as a brown oil (0.39 g, 20% yield, 0.79 mmol). NMR (CDC1₃): 9.69 (s, 1H), 8.74 (d, 1H), 8.43 (d, 1H), 7.89 (d, 1H), 7.85 (d, 1H), 7.38 (s, IH), 7.19 (s, 1H), 7.17 (s, 1H).

Step B: Préparation of 8-bromo-5-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihvdro-5(trifluoromethyl)-3-isoxazolyl]isoquinoline

To a stirred solution of l-(8-bromo-5-isoquinolinyl)-3-(3,5-dichloro-4-fluorophenyl)-4,4,4tritluoro-2-buten-l-one (350 mg, 0.71 mmol) and n-tetrabutylammonium bromide (46 mg, 0.14 mmol) was added a solution of sodium hydroxide (284 mg, 71 mmol) and hydroxylamine (0.09 mL, 50% aqueous solution, 1.42 mmol) at 0 °C. After stirring at 0 °C for 1 hr, the reaction mixture was partitioned between water and ethyl acetate, the layers were separated, and the aqueous layer was washed again with ethyl acetate. The combined organic layers were washed with water and brine, dried (Na₂SO₄), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the tîtle compound as a yellow solid (290 mg, 80% yield, 0.57 mmol). *H NMR (CDC1₃): 9.69 (s, 1H), 8.80 (d, 1H), 8.74 (d, 1H), 7.87 (d, 1H), 7.63 (s, 1H), 7.62 (s, 1H), 7.54 (d, 1H), 4.27 (d, 1H), 3.90 (d, 1H).

Step C: Préparation of 5-r5-(3,5-dichloro-4-fluorophenvl)-4.5-dihydro-5-(trifluoromethyl)-3isoxazolyI1-A-(2-pyrimidinylmethyl)-8-isoquinolinecarboxamide

A mixture of 8-bromo-5-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)3-isoxazolyl]isoquinoline (180 mg, 0.35 mmol), 2-aminomethylpyrimidîne hydrochloride (154 mg, 1.41 mmol), [l,r-bis(diphenylphosphino)fenOcene]-dichloropailadium(n) (29 mg, 0.04 mmol) and triethylamine (0.49 mL, 3.5 mmol) in toluene (10 mL) was stirred at 80 °C under one atmosphère of carbon monoxide for 6 hr. The reaction mixture was then filtered through a short pad of Celite®, rinsed with ethyl acetate, and the filtrate was concentrated. The resulting residue was purified by silica gel column chromatography using ethyl acetate/methanol as eluent to afford the title compound, a compound of this disclosure, as a yellow solid (88 mg, 45% yield, 0.16 mmol). NMR (DMSO-d₆): 9.83 (s, 1H), 9.46 (t, 1H), 8.86 (d, 2H), 8.71 (s, 2H), 8.17 (d, 1H), 7.92 (d, 1H), 7.90 (s, 1H), 7.88 (s, 1H), 7.47 (t, 1H), 4.78 (d, 2H), 4.62 (d, 1H), 4.58 (d, 1H).

SYNTHESIS EXAMPLE 2

Préparation of 5-[5-(3,5-dichioro-4-fluorophenyl)-4,5-dihydro-5-(tritluoromethyl)-3isoxazolyl]-N-(l ,l-dimethylethyl)-8-isoquinolinecarboxamide (compound 2)

Step A: Préparation of 5-bromo-A-(Ll-dimethvlethyl)-8-isoqumolinecarboxamide

To a stirred suspension of 5-bromo-8-isoquînolinamine (8.0 g, 35.86 mmol) and HBF4 (10.67 mL, 50% in aqueous solution, 58.32 mmol) in water (25 mL) was added slowly a solution of NaNO₂ (2.73 g, 39.56 mmol) in water (15 mL) at 0 °C. The reaction mixture was stirred at 0 °C for 30 min, and then stirred at room température for 1 hr. The brown insoluble solid was collected via filtration and rinsed with a small amount of water. This solid was transferred to another reaction flask and acetone (90 mL) was added, followed by the slow addition of tbutylisocyanide (12.15 mL, 107.49 mmol), then césium carbonate (35 g, 107.49 mmol). After stirring ai room température for 1.5 hr, the reaction mixture was concentrated to remove most of the acetone solvent and excess r-butylisocyanide. The resulting residue was partitioned between water and ethyl acetate. The phases were separated, the organic layer was washed with brine, dried (Na₂SO4), and concentrated under reduced pressure. The residue was purified b y silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the title compound as a brown solid (7.60 g, 69% yîeld, 24.76 mmol). *H NMR (CDC1₃): 9.63 (s, 1H), 8.68 (d, 1H), 8.01 (d, 1H), 7.94 (d, 1H), 7.50 (d, 1 H), 5.90 (br s, 1H), 1.55 (s, 9H).

Step B: Préparation of 79-(1,1-dimethyl ethyl )-5-( 1-ethoxyethenyl)-8-isoquinolinecarboxamide

To a stirred mixture of 5-bromo-A-(l, l-dimethylethyl)-8-isoquinolinecarboxamide (2.95 g,

9.60 mmol) in toluene (50 mL) was added (l-ethoxyethenyl)tributylstannane (4.85 mL, 14.39 mmol) and tetrakis(triphenylphosphine)palladium (0) (1.1 g, 0.96 mmol). The reaction mixture was heated to reflux under a nitrogen atmosphère for 4 hr. The reaction mixture was then concentrated, and the residue purified by silica gel column chromatography using hexanes/ethyl 10 acetate as eluent to afford the title compound as a brown solid (2.44 g, 85% yîeld, 8.17 mmol).

1H NMR (CDC1₃): 9.64 (s, 1 H), 8.58 (d, 1H), 7.99 (d, 1H), 7.704 (d, 1H), 7.60 (d, 1H), 5.80 (br s, 1 H), 4.55 (d, 1H), 4.40(d, 1 H), 4.03 (q, 2H), 1.54 (s, 9H), 1.43 (t, 3H).

Step C: Préparation of 5-acetyl-A^f-(I,l-dimethylethyl)-8-isoquinolinecarboxamide

To a stirred solution of Λ7-(1, l-dimethylethyl)-5-( 1 -ethoxyethenyl)-8isoquinolinecarboxamide (2.44 g, 8.17 mmol) in toluene (50 mL) was added concentrated HCl (10 mL) and water (10 mL). After stîrring at room température for 1 hr, the reaction mixture was partitioned between water and ethyl acetate, the pH of the aqueous layer was adjusted to 8, and the aqueous layer was separated and further extracted with ethyl acetate. The combined organic 20 extracts were washed with brine, dried (Na2SC>4), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the title compound as a yellow solid (1.80 g, 80% yîeld, 6.67 mmol). 'H NMR (CDC1₃): 9.62 (s, 1H), 8.64 (d, IH), 8.58 (d, 1H), 8.12 (d, 1H), 7.65 (d, 1H), 5.89 (s, br. 1H), 2.75 (s, 3H), 1.56 (s, 9H).

Step D: Préparation of 5-[3-(3.5-dîchloro-4-fluorophenyl)-4,4.4-trifluoro-l-oxo-2-buten-I-yl1N-( l, 1 -dimethvlethvl)-8-isoquinoiinecarboxamide

To a stirred solution of 5-acetyl-/9-(l,l-dimethylethyl)-8-isoquinolinecarboxamide (0.20 g, 0.74 mmol) in 1,2-dichloroethane (5 mL) was added l-(3,5-dichloro-4-fluoro-phenyl)-2,2,230 trifluoroethanone (0.39 g, 1.48 mmol), K₂CO₃ (0.13 g, 0.96 mmol) and triethylamine (0.14 mL, 0.96 mmol). The reaction mixture was heated to 100 °C and stirred for 16 hrs under a nitrogen atmosphère. The reaction mixture was then cooled and concentrated. The residue was partitioned between water and ethyl acetate, the iayers were separated, and the aqueous layer was washed again with ethyl acetate. The combined organic Iayers were washed with brine, dried (Na2SÜ4), and concentrâted under reduced pressure. The residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the title compound as a brown oil (0.22 g, 58% yield, 0.43 mmol). ^lH NMR (CDC1₃): 9.51 (s, 1H), 8.58 (d, IH), 8.28 (d, 1H), 7.93 (d, 1H), 7.56 (d, 1H), 7.38 (s, 1H), 7.16 (s, 1H), 7.15 (s, 1H), 6.07 (br s, 1H), 2.75 (s, 3H), 1.54 (s, 9H).

Step E: Préparation of 5-r5-(3,5-dichloro-4-fluorophenyI)-4,5-dihydro-5-(tritluoromethyl)-3isoxazolyl~[-AM 1_Ί1 -dim ethyl ethyl)-8-isoquinoÎinecarboxamide

To a stirred solution of 5-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluoro-l-oxo-2-buten-lyI]-A-(l,l-dimethylethyl)-8-isoquinolmecarboxamide (0.22 g, 0.43 mmol) in 1,2dimethoxyethethane (5 mL) and water (1 mL) was added hydroxylamine hydrochloride (30 mg, 0.86 mmol) and lithium hydroxide monohydrate (72 mg, 1.72 mmol). The reaction mixture was stirred at room température for 1 hr, and then partitioned between water and ethyl acetate. The Iayers were separated, and the aqueous layer was washed again with ethyl acetate. The combined organic Iayers were washed with brine, dried (NagSOq), and concentrated under reduced pressure. The residue was purified by silica gel column chromatography using hexanes/ethyl acetate as eluent to afford the title compound, a compound of this disclosure, as a brown oil (0.22 g, 58% yield, 0.43 mmol). 'H NMR (CDC1₃): 9.58 (s, 1H), 8.71 (d, 1H), 8.63 (d, 1H), 7.64 (m,4H), 6.02 (brs, 1H),4.25 (d, 1H), 3.90 (d, 1H), 1.55 (s, 9H).

SYNTHESIS EXAMPLE 3

Préparation of 5-[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]A-[l-(methylsulfonyl)-3-azetidinyl]-8-isoquinolinecarboxamide (compound 21)

Step A:Préparation of 5-acetyl-7V-ri-(methyÎsulfonvl)-3-azetidinyÎ]-8isoquinolinecarboxamide

A mixture of 5-acetyï-/V-(l,l-dimethylethyl)-8-isoquinolinecarboxamide (0.20 g, 0.74 mmol) in acetic acid (2 mL) and hydrobromic acid (2 mL, 48% aqueous solution) was stirred at 120 °C for 12 hr. The reaction mixture was then cooled to room température and concentered under reduced pressure. The residue was dissolved in DMF (3 mL), and to this solution was added I-methylsulfonylazetidin-3-amine (213 mg, 1.4 mmol), triethylamine (0.4 mL) and HATU (424 mg, 1.11 mmol). The reaction mixture was stirred at room température ovemight, and was then adsorbed onto Celite® and purified by reverse phase chromatography with H₂O/CH₃CN/MeOH as eluent to afford the title compound as a white solid (68 mg, 26% yield, 0.20 mmol). Ή NMR (CDC1₃): 9.55 (s, 1H), 9.51 (d, 1H), 8.66 (d, 1H), 8.49 (d, 1H), 8.47 (d, 1H), 7.89 (d, 1H), 4.81 (m, 1H), 4.21 (dd, 2H), 3.98 (dd, 2H), 3.06 (s, 3H), 2.77 (s, 3H).

Step B: Préparation of 5-f3-(3,5-dichloro-4-fluorophenyl)-4A4-trifluoro-l-oxo-2-buten-lyl]-7V-[l-(niethylsulfonyI)-3-azetidinyI]-8-isoquinolinecarboxamide

The title compound was prepared by a procedure anal o go us to Step D of Synthesîs Example 2 as a yellow oil (40 mg, 47% yield). ’H NMR (CDC1₃): 9.56 (s, 1H), 8.62 (d, III), 8.31 (d, 1H), 7.97 (d, 1H), 7.68 (d, 1H), 7.39 (d, 1H), 7.28 (br s, 1H), 7.18 (s, 1H), 7.17 (s, 1H), 5.00 (m, IH), 4.26 (dd, 2H), 4.07 (dd, 2H), 2.89 (s, 3H).

Step C: Préparation of 5-r5-(3,5-dichloro-4-fluorophenyl)-4,5-dihvdro-5-(trifluoromethyl)3-isoxazoÎyl]-V-[l-(methylsuÎfonyl)-3-azetidinyl1-8-isoquinolinecarboxamide

The title compound, a compound of this disclosure, was prepared by a procedure analogous to Step E of Synthesîs Example 2 as a white solid. *H NMR (CDC1₃): 9.54 (s, 1H), 8.67 (d, 1H), 8.58 (d, 1H), 7.84 (m, 5H), 7.36 (d, IH), 4.97 (m, 1H), 4.26 (d, IH), 4.24 (dd, 2H), 4.08 (dd, 2H), 3.90 (d, 1 H), 2.90 (s, 3H).

SYNTHESIS EXAMPLE 4

Préparation of N-(cyclopropyhnethyI)-5-[4,5-dihydro-5-(trifluoromethyl)-5-[3(trifluoromethyl)phenyl]-3-isoxazolyl]-8-isoquinolinecarboxamide (compound 17)

Step A: Préparation of 8-bromoisoquinoÎine

A solution of 2-bromobenzaldéhyde (50 g, 270.27 mmol, 1 eq) and 2,2dimethoxyethylamine (34.4g, 324.32 mmol, 1.2 eq) in toluene (300 mL) was azeotroped at reflux for 2 hr using a Dean-Stark apparatus. The progress was monitored by TLC. The reaction mixture was concentrated under reduced pressure to obtain a pale brown viscous oil. The crude compound was dissolved in dichloromethane (400 mL) and A1C1₃ (118.6 g, 891.89 mmol, 3.3 eq) was added portionwise at 0 ^ÛC. The reaction was gradually heated to 45 °C and stirred for 16 hr at the same température. The reaction was monitored by TLC. Upon completion, it was poured into cold water (500 mL) and extracted with dichloromethane (2 x 500 mL). The organic layer was washed with brine solution, dried over anhydrous Na₂SO4, and concentrated under reduced pressure to afford a purple-colored solid. The crude compound was purified by silîca gel (605 120) column chromatography and eluted with 50% ethyl acetate in petroleum ether to give a pale yellow solid 8-bromoisoquinoline (40 g, 71.5% yield). ^lH NMR (400 MHz CDC1₃), 9.621 (s, 1H), 8.623-8.609 (d, 1H, 7=5.6), 7.860-7.842 (d, 1H, 7=7.2), 7.803-7.782 (d, 1H. 7=8.4), 7.633-7.619 (d, 1 H, 7=5.6), 7.552-7.513, fi 1H, 7=15.6).

Step B: Préparation of methyl isoquinoline-8-carboxylate

A solution of 8-bromoisoquinoline (13 g, 63.106 mmol, 1 eq, from Step A) in MeOH (130 mL) was charged in a Steel bomb and Et₃N (19.15 g, 189.32 mmol, 3.0 eq) was added. The solution was purged with nitrogen for 10-15 min and PdCl₂(dppf) (4.61 g, 6.310 mmol, 0.1 eq) was added. After which, the reaction mixture was passed with CO gas (150 psi), heated to 100 °C for 16 hr. After TLC indication, the reaction mixture was cooled to room température, passed 15 through a pad of celite, and washed with ethyl acetate (500 mL). The combined organic layers were washed with water (200 mL) then a brine solution, dried over anhydrous Na₂SC>4, and concentrated under reduced pressure. The resulting crude solid was purified by silica gel (60120) column chromatography, eluted with 30% pet ether/ethyl acetate to give a pale yellow solid methyl isoquinoline-8-carboxylate (10.2 g, 86.80% ), ’H NMR (400 MHz, CDC1₃); 10.23 (s, 20 1H), 8.629-8.615 (d, 1H, 7=5.6), 8.286-8.268 (d, 1H, 7=7.2), 8.011-7.991 (d, 1H, 7=8.0), 7.7397.720 (d, 1H, 7=7.6), 7.700-7.686, (d, 1H, 7=5.6), 4.100 (s, 3H).

Step C: Préparation of methyl 5-bromo-isoquinoline-8-carboxvlate

To a solution of methyl isoquinoline-8-carboxylate (22 g, 118.279 mmol, 1 eq, from Step B) in H2SO4 (200 mL) was added 7V-broinosuccinimide (27.36 g, 153.76 mmol, 1.3 eq.) 25 portionwise at 0 °C. The reaction mixture was warmed to room température, stirred for 16 hr, and monitored by TLC. The reaction mixture was poured into ice cold water (2 L) and basifîed (pH 8) with NH4OH solution. The resulting precipitate was collected (l^st crop). The aqueous layer was extracted with ethyl acetate (1 L), and the organic layer was washed with brine solution, dried over anhydrous Na₂SO₄ and concentrated under reduced pressure (2^nd crop). The 30 combined crude crops were triturated with n-pentane to give title compound methyl 5-bromoisoquinoline-8-carboxylate (22 g, 70.31% yield) as a pale brown solid. ^lH NMR (400 MHz,

CDCR); 10.281 (s, 1H), 8.736-8.722 (d, 1H, J=5.6), 8.117-8.098 (d, 1 H, 7=7.6), 8.083-8.068 (d, 1H, J=6.0), 8.033-8.013 (d, 1H, ^=8.0), 4.010 (s, 3H).

Step D: Préparation of methyl 5-acetyl-isoquinoline-8-carboxylate

To a solution of methyl 5-bromo-isoqumoline-8-carboxylate (22 g, 82.706 mmol, 1 eq, from Step C) in toluene (220 mL) was added tributyl(l-ethoxyvinyl)tin (38.8 g, 107.51 mmol, 1.3 eq) and purged with N₂ for 15 min. PdCl₂(PPh₃) (5.8 g, 8.270 mmol, 0.1 eq) was added at room température, and the resulting mixture was stirred at 100 °C for 16 hr. The reaction was monitored by TLC. Upon completion, the mixture was cooled to room température and 1 N HCl (55 mL) was added before stirring at room température for an additional 2 hr. The reaction mixture was neutralized (pH 7) with aq. NaHCO₃ solution (300 mL) and extracted with ethyl acetate (2 L). The combined organic layers were washcd with brine, dried over anhydrous Na₂SO₄ and concentrated. The crude solid was purified by silîca gel (60-120) column chromatography, eluted with 70% ethyl acetate in petroleum ether to provide the title compound (16.5 g, 87%) as a pale-yellow solid. ¹H NMR (400 MHz, CDC1₃); 10.207-10.204 (d, 1H, 7=1.2), 8.707-8.691 (d, 1H, 7=6.4), 8.509-8.492 (d, 1 H, 7=6.8), 8.235-8.215 (d, 1H, 7=8.0), 8.134-8.115 (d, 1H, 7=7.6) 4.079 (s, 3H), 2.779 (s, 3H).

Step E: Préparation of methyl 4-[(Z)-4.4.4-trifluoro-3-r3-(trifluoromethyl)phenvl]but-2enoyl]naphthalene-l-carboxylate

To a solution of methyl 5-acetyl-isoquinoline-8-carboxyIate (10 g, 43.668 mmol, 1 eq, from Step D) in 2-methyltetrahydrofuran was added molecular sieves (10 g), K₂CO₃ (30 g, 218.340 mmol, 5 eq) and 2,2,2-trifluoro-1-(3-trifluoromethyl)phenyl)ethanone (18 g, 86.60 mmol, 2 eq). The resulting reaction mixture was stirred at 90 °C for 16 hr under a N₂ atmosphère. Upon indication by TLC, the reaction was cooled to room température, passed through a pad of celite, washed with ethyl acetate (IL) and concentrated under reduced pressure. The obtained crude oil was purified by sîlica gel (60-120) column chromatography (5% MeOH/dichloromethane) to provide an off-white solid of the title compound (8 g, 40.48%). ^!H NMR (400 MHz DMS0-D₆); 9.890 (s, 1H), 8.624-8.609 (d, 1H, 7=6.0), 8.344-8.325 (d, 1H, 7=7.6), 8.142-8.117 (m, 2H, 7=10.0), 7.770 (s, IH,) 7.542 (s, 1H) 7.525(s, 1H), 7.480 (s, lH),7.423-7.385(t, 1H, 7=15.2), 4.001 (s, 3H).

Step F:Preparation of methvl 5-[5-(trifluoromethyl)-5-f3-(trifluoromethyl)phenyl]-4Hisoxazol-3-vl]isoquinoIine-8-carboxylate

To a solution of compound methyl 4-[(Z)-4,4,4-trifluoro-3-[3-(trifluoromethyI)phenyl]but2-enoyl]naphthalene-l-carboxylate (8 g, 17.660 mmol, 1 eq, from Step E) in THF (100 mL) was added (NHîOH^TTSCU (1.44 g, 8.830 mmol, 0.5 eq) at 0 ^ÜC followed by the addition of 50% aq. NaOH solution (1.5 g, 38.852 mmol, 2.2 eq). The resulting reaction mixture was stirred at room température for 3 hr. The reaction mixture was concentrated to yield compounds methyl 5[5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyI]-4H-isoxazol-3-yl]isoquinoline-8-carboxylate: 5-[5-(trifluoromethyl)-5-[3-(Îrifluoromethyl)phenyl]-4H-isoxazol-3-yl]isoquinoline-8-carboxylic acid (1:1 mixture) as paie yellow oil (7 g, 84.64%), which was taken directly to the next step.

Step G: Préparation of 5-r5-(trifluoromethyl)-5-r3-(trifluoromethvl)phenyl1-4H-isoxazol-3vllisoquinoline-8-carboxvlic acid

To a solution of compounds methyl 5-[5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]4H-isoxazol-3-yl]isoquinolîne-8-carboxylate: 5-[5-(trifluoromethyl)-5-[3(trifluoromethyl)phenyl]-4H-isoxazoF3-yI]isoquinoline-8-carboxylic acid (1:1, 7 g, 1 eq., from Step F) în THF (20 mL), FI₂O (5 mL) was added LiOH (2.5 g, 59.82 mmol, 4.0 eq.) at 0 °C. Then reaction mixture was stirred at room température for 3 hr. After monitoring by TLC, the reaction mixture was concentrated under vacuum, acidified with 1 N HCl (pH 5), and the resulting precipitated was collected, washed with water (500 mL) and dried under reduced pressure to yield compound 5-[5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-4H-isoxazol-3yl]isoquinoline-8-carboxylic acid as an off-white solid (5 g, 73.63 %). ’H N MR (400 MHz, DMSO-D₆); 10.180 (s, 1H) 8.767-8.725 (m, 2H, >16.8), 8.295-8.230 (m, 2H, >26), 8.0Ί17.991 (d, 1H, >8.0), 7.942-7.923 (m, 2H) 7.845-7.806 (t, 1H, >15.6), 4.726-4.680 (d, 1H, J= 18.4), 4.591 -4.545 (d, 1 H, > 18.4).

Step__H:Preparation of N-(cyclopropylmethyl)-5-[4,5-dihydro-5-(triflnoromethy1)-S-[3(trifluoromethyI)phenyl]-3-isoxazolyl]-8-isoquinoIinecarboxamide

To a solution of 5-[5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-4H-isoxazol-3yl]isoquinoline-8-carboxylic acid (0.8 g, 1.766 mmol, 1 eq, from Step G) in DMF (5 mL) were added HATU (1.0, 2.624 mmol, 1.5 eq), DIPEA (0.68g, 5.286 mmol, 3 eq), cyclopropanemethanamine (0.15g, 2.114 mmol, 1.2 eq) and stirred at RT for 16 hr. The reaction mixture was poured into ice cold water (50 mL). The resulting precipitate was collected, washed with water (20 mL) dried under reduced pressure, and yielded the title product (200 mg, 22.39 %) as racemic mixture. ^!H NMR (400 MHz, DMSO-d6), 9.563 (s, 1H), 8.976-S.948 (t, 1H, ⁷⁼¹1.2), 8.724-8.686 (m, 2H, >15.2), 8.190-8.170 (d, 1H, J=8.0), 8.015-7.995 (d, 1H, J=8.0), 5 7.945-7.923 (d, 2H, J= 8.8), 7.847-7.790 (m, 2H, J= 22.8), 4.714-4.668 (d, IH, J= 18.4), 4.5804.535 (d, 1H, J= 18.0), 3.322-3.253 (t, 2H, J= 27.3), 1.135-1.097 (m, 2H, J= 15.2), 0.527-0.482 (m, 2H, J= 18.0),0.319-0.281 (m, 2H,J= 15.2),

By the procedures described herein together with methods known in the art, the following 10 compounds of Table 2 can be prepared. The following abbreviations are used in the Tables which follow: Me means methyl.

TABLE 2

J is J-l and R⁴ is Me

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	CF3	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-l and R⁴ is Et

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	PI
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-1 and R⁴ is cyclopropyl

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-l and R⁴ is isopropyl

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H

H	H	cf₃	cf₃	Cl	H
II	F	Cl
H	F	cf₃

J is J-l and R⁴ is -CH?(cyclopropyl)

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	FI	cf₃	FI	Cl	cf₃
Cl	F	Cl	Cl	H	H
Ci	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	FI
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-l and R⁴ is -CH₂CHÎCH₃)₂

R¹	R²	R³___	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	CF₃	II	Cl	CF₃
Cl	F	Cl	Cl	H	II
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-2. R⁵ is H, and R⁶ is OMe

R¹	R²	R³		R¹	R²	R³
Cl	H	Cl		H	Cl	Cl

Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	CI	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	II	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-2, R⁵ is H, and R⁶ is SMe

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	CF₃	cf₃	F	H
H	H	Cl	CI	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-2. R⁵ is H, and R⁶ is S(O)Me

R¹	R?	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	1-1	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	CF₃	CF₃	H	H
Cl	Cl	Cl	Cl	F	FI
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl

H

F

cf₃

J is J-2, R⁵ is H, and R⁶ is SO₂Me

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	FI
H	F	Cl
H	F	cf₃

J is J-2. R⁵ is Me, and R⁶ is OMe

R¹	r²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	CI	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
II	H	CI	Cl	Cl	H
H	H	cf₃	CF₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-2. R⁵ is Me, and R⁶ is SMe

R¹	R²	R³	R¹	R²	R³
Cl	H	CI	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
C)	F	Cl	Cl	H	H
Cl	F	cf₃	CF₃	H	H

Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	CF₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	r f	Cl
H	F

J is J-2, R⁵ is Me, and R⁶ is S(O)Me

J is J-2, R⁵ is Me, and R⁶ is SCuMe

R¹	R²	R³	R¹	R²	R³
CI	H	Cl	II	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	II
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-3, R⁷ is H, and Z is 2-pyridinyl

4S

R¹	R²	R³	R¹	R²	R³
Cl	FI	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-3. R⁷ is H. and Z is 2-pvrimidinyl

R¹	R²	R³	R¹	R²___	R³
Cl	H	CI	H	Cl	Cl
Cl	H	cf₃	II	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-3, R⁷ is Me, and Z is 2-pyridinyl

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	CI	Cl	CL	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	FI

H	II	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-3, R⁷ is Me, and Z is 2-pvrimidinyl

J is J-4, R⁸ is H. and R⁹ is H

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	II	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-4, R⁸ is H. and R⁹ is Me

R¹	R²	R³	R¹	R²	R³
Cl	FI	Cl	H	Cl	C1
Cl	H	cf₃	H	Cl	^cf3

Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	FI	Cl	Cl	Cl	Fl
H	H	cf₃	cf₃	Cl	Fl
H	F	Cl
H	F	cf₃

J is J-4, R⁸ is H, and R⁹ is Et

R¹	r£	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	^CF3
Cl	F	Cl	Cl	H	H
Cl	F	CF₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-4, R⁸ is H, and R⁹ is n-Pr

R¹	R²	R³	r‘	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-4, R⁸ is H, and R⁹ is i-Pr

J is J-4, R⁸ is Me, and R⁹ is H

R¹	R²	R³	bL	r²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	CF₃	cf₃	F	H
1-1	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-4, R⁸ is Me, and R⁹ is Me

R¹	r2	R³	R^]	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	FI	cf₃	H	C!	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H

H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	CF3

J is J-4, R⁸ is Me, and R⁹ is Et

J is J-4, R⁸ is Me, and R⁹ is n-Pr

R¹	R²	R³	R¹	R²	R³
CI	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-5, R^!0 is H, R¹¹ is H, and R¹² is H

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	II	H
Cl	Cl	Cl	Cl	F	II
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	II
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-5. R¹⁰ is H, R¹¹ is H, and R¹² is Me

J is J-5, R^îq is H, R¹¹ is H, and R¹² is Et

H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

Jis J-5. R¹⁰is H, R¹¹ is H, and R¹² is CH₂CF_?

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	II	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-5, R¹⁰ is H, R¹¹ is H, and R¹² is CH₂CN

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	CF₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cr₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	Fl	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-5. R¹⁰ is Me, R¹¹ is H, and R¹² is H

R¹	R²	R³		R¹	R²	R³
Cl	H	Cl		FI	Cl	Cl

Cl	H	CF₃	H	Cl	C^f3
Cl	F	Ci	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	^cf3 .	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
II	F	Cl
H	F	C^f3

J is J-5, R¹⁰ îs Me, R^H is H, and R¹² is Me

R¹	___R²	R³	R¹	r²	R³
Cl	H	Cl	H	Cl	Ci
Cl	H	cf₃	H	Cl	^FF3
Cl	F	Cl	Cl	H	H
Cl	F	C^f3	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	II
II	H	Cl	Cl	Cl	H
H	H	cf₃	C^f3	Cl	H
H	F	Cl
H	F	cf₃

J is J-5, R¹⁰ is Me, R¹¹ is H, and R¹² is Et

R¹	R²	R³	R¹	A	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	C^f3
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	C^f3	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	ct₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	C^f3	Cl	H
H	F	Cl

II F CF₃

J is J-5, R¹⁰ is Me. R¹¹ is H, and R¹² is CH₂CF₃

R¹	R²	R³	R^]	R²	r³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	II	Cl	cf₃
Cl	F	Cl	Cl	H	FI
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
FI	II	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-5, R¹⁰ is Me, R¹¹ is H, and R¹² is CH_?CN

R¹	R²	R³	R¹	R²	R³
Cl	II	Cl	II	Cl	Cl
Cl	II	cf₃	II	Cl	cf₃
Cl	F	Cl	Cl	II	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	FI	Cl	Cl	Cl	H
H	II	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-6 and R¹³ is H

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H

Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

J is J-6 and R¹³ is Me

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	H
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
FI	F	cf₃

J is J-6 and R¹³ is Et

R¹	R²	R³	R^;	r!	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	II
Cl	Cl	Cl	Cl	F	H
Cl	Cl	cf₃	cf₃	F	I-I
H	H	Cl	Cl	Cl	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
H	F	cf₃

5S

J is J-6 and R¹³ is CH₂CF₃

R¹	R²	R³	R¹	R²	R³
Cl	H	Cl	H	Cl	Cl
Cl	H	cf₃	H	Cl	cf₃
Cl	F	Cl	Cl	H	H
Cl	F	cf₃	cf₃	H	H
Cl	Cl	Cl	Cl	F	H
Cl	CI	cf₃	cf₃	F	H
H	H	Cl	Cl	CI	H
H	H	cf₃	cf₃	Cl	H
H	F	Cl
II	F	cf₃

Spécifie compounds of Formula 1, prepared by the methods and variations as described în preceding Schemes 1-11 and Synthesis Examples 1-4, are shown in the Index Tables below. The 5 following abbreviations are used in Index Table A: i-Pr means Ao-propyl, α-Pr means «-propyl, c-Pr means cyc/o-propyl, /-Bu means Bo-butyl, c-Bu means cyc/obutyl, s-Bu means seobutyl, tBu means ZerAbutyl, Me means methyl, Et means ethyl and Ph means phenyl. The abbrevîation “Cmpd.” stands for “Compound”, and the abbrevîation “Ex.” stands for “Example” and is followed by a number indicatîng în which example the compound is prepared. For mass spectral 10 data (AP⁺ (M+l)), the numerical value reported is the molecular weight of the parent molecnlar ion (M) formed by addition of EU (molecular weight of 1) to the molécule to give a M+l peak observed by mass spectrometry using atmospheric pressure Chemical ionization (AP⁺). The altemate molecular ion peaks (e.g., M+2 or M+4) that occur with compounds containing multiple halogens are not reported.

INDEX TABLE A

R³

Cmpd. No,	R¹	R²	R³	J	MS data	m.p. (°Ο
1	Cl	II	Cl	O 'y', N. JJ ' Π N—Et o L._oz	567
2	Cl	F	Cl	-C(O)NH(Z-Bu)	528
3	Cl	F	Cl	- C ( O)NH CH 2 (c y c lopro py 1)	526
4	Cl	F	Cl	, h \Z /K /¼ 0	564
5	Cl	F	Cl	O . H \|\| /γ ^^nh₂0 Me	543
6	Cl	F	Cl	0 , H II N4 .Me Y i ^û O Me	558
7	Cl	F	Cl	..Fk , h 11] NC Y /y ^N 0	564
8	Cl	F	Cl	, H ?γ^Νγ^^Μ6 0 Me	560

Cmpd. No.	R¹	R²	R³	J	MS data	m.p. m
9	Cl	F	Cl	, H 0	546
10	Cl	F	Cl	, Fl \/ χ/ ' ]< CN 0	551
11	Cl	F	CI	, H x/ .Me Il li O O	562
12	Cl	F	Cl	, H 'T A	578
13	Cl	F	Cl	, H χ/ N. A A 'il il ^N 0 Me		577
14	Cl	F	Cl	, H x/ ^x^ Me ' 7Γ ΊΓ S Il 1 il 0 Me 0	576
15	Cl	F	Cl	-C(O)NHCH₂CN	511
16	H	FI	cf₃	-C(O)NH(cyclopropyl)	494
17	H	FI	cf₃	-C (O)NHC Η₃ ( c yc lo prop yl )	50S
IS	H	H	cf₃	, H Y^ⁿ 0		546
19	H	H	cf₃	□ /% IZ 1 ^₌Q	560
20	Cl	F	Cl	. H x/ .Me 'Il 1 ⁰ O Me	544

Cmpd. No.	R¹	R²	R³	J	MS data	m.p. (°C)
21	Cl	F	Cl	, FI ^u SO₂Me	605
22	H	H	cf₃	, H 'Il T h 0 Me 0	558
23	Cl	F	Cl	- C( O )NII (c y c lop rop y 1 )	512
24	H	H	cf₃	-C(O)NHCH₂C(O)NH₂	511
25	II	H	cf₃	O , H II \/ N. /y γ nh₂ 0 Me	525
26	Cl	F	Cl	, H / ) V .bk / 0	556
27	Cl	F	Cl	-C(O)NHMe	486
28	CL	F	Cl	-C(O)NHCH(CH₃)₂	514
29	H	H	cf₃	, H •V .bk Me />< S 0	528
30	H	H	cf₃	, FI χ/ Me Il il 0 0	544
31	cf₃	H	H	-C(=O)NH(CH₂)₂S(=O)CH₂CF₃	612
32	Cl	F	Cl	-C(=O)NH-3-furanyl	542
33	Cl	F	Cl	-C(=O)NH-j-Bu	528
34	Cl	H	cf₃	-C(=O)NH(CH₂)₂SCH₃	562
35	Cl	FI	cf₃	-C(=O)NH-c-Pr	528
36	Cl	H	cf₃	-C(=O)NHCH₂-c-Pr	542
37	Cl	H	cf₃	-C(=O)NHCH2-2-pynmidmyl	580
38	Cl	H	cf₃	-C(=O)NH(CH₂)₂S(=O)₂CH₃	594
39	Cl	H	cf₃	-C(=O)NI-ICH₂C(=O)NH₂	545

Ctnpd. No.	R¹	R²	R³	J	MS data	m.p. m
40	Ci	H	cf₃	O ?^H3 y N ^H II 0	559
41	Cl	H	cf₃	-C(=O)NH(CH₂)₂S(=O)CH₃	578
42	cf₃	F	II	-C(=O)NH-i-Bu	528
43	Cl	F	Cl	, H -V N. o	544
44	Cl	F	Cl	-C(=O)NH(CH₂)₂OCH₃	531
45	Cl	F	Cl	-C(=O)NHCH₂CH=CH₂	512
46	Cl	F	Cl	-C(=O)NHCH₂CH₃	500
47	Cl	F	C!	-C(=O)NH’CBu	528
48	Cl	F	Cl	-C(=O)NHCH₂C=CH	510
49	Cl	F	Cl	-C(=O)NHCH(CH₃)CN	525
50	Cl	F	Cl	-C(=O)NHCH(CH₃)CH₂C=N	539
51	Cl	F	Cl	-C(=O)NH(CH₂)₂C=N	525
52	cf₃	H	H	-C(=O)NHCH(CH₃)CsN	507
53	cf₃	H	H	-C(=O)NHCH(c-Pr)C=N	533
54	cf₃	H	H	-C(=O)NHCH(CPr)C=N	535
55	cf₃	F	H	-C(=O)NH-c-Pr	512
56	Cl	F	Cl	O , H II A N. ' IT Tr N cf₃ Il 1 ^H 0 ch₃		150-154
57	Cl	F	Cl	-C(=O)NHCH₂C(=O)NHCH₂CF₃		219-223
58	cf₃	F	H	-C(=O)NHCH₂-c-Pr	526
59	cf₃	F	H	-C(=O)NH-;-Pr	514
60	cf₃	F	H	-C(=O)NHCH₂CH₃	500
61	Cl	F	Cl	-C(=O)NHCH(CH₃ )-c-Pr	540
62	Cl	F	Cl	, H S^^y^S^^CFj o ch₃		126-130

Cmpd. No.	R¹	R²	R³	J	MS data	m.p, (°Ç)
63	Cl	F	Cl	-C(=O)NHCH(CH₃)CFI₂S(=O)₂CH₃	592
64	Cl	F	Cl	, H \/ N- > Tf s cf₃ Il 1 h O ch₃ O		271-275
65	Cl	F	Cl	, H ' ri Ίτ cf₃ Il 1 //^ O ch₃ ° ⁰		147-151
66	cf₃	F	H	-C(=O)NH-M-Pr	514
67	Cl	H	Cl	-C(=O)NHCH₂-2-pyrimidiny!	546
68 *	Cl	F	Cl	-C(=O)NHCH₂-2-pyrimidinyl		133-137
69 *	Cl	F	Cl	-C(=O)NHCH₂-2-pyrimidinyI		114-118
70	Cl	H	Cl	-C(=O)NH-c-Pr	494
71	cf₃	F	H	-C(=O)NH-FBu	528
72	cf₃	F	H	-C(=O)NH(CH₂)₂OCH₃	530
73	cf₃	F	H	-C(=O)NHCH₂CH=CH₂	512
74	cf₃	F	H	-C(=O)NHCH₂C=CH	510
75	Cl	F	cf₃	-C(=O)NHCH₂-2 -pyrimidinyl		101-105
76	cf₃	F	H	-C(=O)NHCH₂-2-pyrimidinyl		109-113
77	Cl	F	cf₃	-C(=O)NI-ICH₂-c-Pr		198-202
78	Cl	H	Cl	-C(=O)NHCH(CH₃)C=N		139.5-160.7
79	cf₃	F	FI	-C(=O)NHCH(CH₃)C=N	525
80	Cl	F	cf₃	-C(=O)NH-c-Pr		147-151
81	C!	F	Cl	-C(=O)NHCH=NOCH₃	529
82 [Note 1]	Cl	F	Cl	-C(=O)NH-c-Pr	512	245-249
83 [Note 2]	Cl	F	Cl	-C(=O)NH-c-Pr	512	244-248
84	Cl	H	cf₃	-C(=O)NHCH₃		204-208
85	Cl	H	cf₃	-C(=O)NH-i-Pr		134-138
86	Cl	H	cf₃	-C(=O)NH-c-Bu		112-116
87	cf₃	H	H	-C(=O)NH-i-Pr		178-182
88	cf₃	H	H	-C(=O)NH-c-Bu		120-124

Cmpd. No.	R¹	R²	r3	J	MS data	m.P. UC)
89	Cl	H	cf₃	-C(=O)NH-mPr		92-96
90	Cl	H	cf₃	-C(=O)NHCH₂CH₃		106-110
91	Cl	H	cf₃	-C(=O)N1ICH₂CH=CH₂		94-98
92	Cl	H	cf₃	-C(=O)NHCH₂C=CH		111-115
93	cf₃	H	H	-C(=O)NHCH₃		125-130
94	cf₃	H	H	-C(=O)NI-ICH₂CH=CH₂		122-126
95	Cl	H	cf₃	-C(=O)NH-NBu		183-187
96	cf₃	H	H	-C(=O)NHCH₂CH₃		200-204
97	cf₃	H	H	-C(=O)NH-w-Pr		120-124
98 [Note 3]	cf₃	H	H	-C(=O)NI-ICH₂-c-Pr		171-175
99 [Note 4]	cf₃	H	H	-C(=O)NHCH₂-c-Pr		171-175
100	cf₃	H	II	-C(=O)NH-t-Bu		94-98
101	cf₃	H	H	-C(=O)NHCH₂C=CH		183-187

Single enantiomer at the 5 position of the isoxazoline ring.

Note 1: Enantiomer (99.70% ee) at the 5 position of the isoxazoline ring [α][)²θ -22.6280° (concentration = 0.5% in chloroform).

Note 2: Enantiomer (99.90% ee) at the 5 position ofthe isoxazoline ring [α]0²θ +15.4840° (concentration = 0.5% in chloroform).

Note 3: Enantiomer (99.75% ee) at the 5 position of the isoxazoline ring [αίρ²³ -6.620° (concentration =

0.1% in chloroform).

Note 4: Enantiomer (97.27% ee) at the 5 position of the isoxazoline ring +20.540° (concentration = 0.1% in chloroform).

A compound of this disclosure will generally be used as an invertebrate pest control active ingrédient in a composition, i.e. formulation, with at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, which serves as a carrier. The formulation or composition ingrédients are selected to be consistent with the physical properties of the active ingrédient, mode of application and environmentai factors such as soil type, moisture and température.

Useful formulations include both liquid and solid compositions. Liquid compositions include solutions (including emulsifiable concentrâtes), suspensions, émulsions (including 65 microemulsions, oil in water émulsions, flowable concentrâtes and/or suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, suspension concentrate, capsule suspension, concentrated émulsion, mîcroemulsion, oil in water émulsion, flowable concentrate and suspoemulsion. The general types of nonaqueous liquid compositions are emulsifiable concentrate, microemulsifiable concentrate, dispersible concentrate and oil dispersion.

The general types of solid compositions are dusts, powders, granules, pellets, prills, pastilles, tablets, fïlled films (including seed coatings) and the like, which can be water-dispersible (“wettable”) or water-soluble. Films and coatings formed from film-forming solutions or flowable suspensions are particularly useful for seed treatment. Active ingrédient can be (micro)encapsulated and further formed into a suspension or solid formulation; alternative!y the entire formdation of active ingrédient can be encapsulated (or “overcoated”). Encapsulation can control or delay release of the active ingrédient. An emulsifiable granule combines the advantages of both an emulsifiable concentrate formulation and a dry granular formulation. High-strength compositions are primarily used as intermediates for further formulation.

Sprayable formulations are typically ex tend ed in a suitable medium before spraying. Such liquid and solid formulations are formai ated to be readily diluted in the spray medium, usually water, but occasionally another suitable medium like an aromatic or paraffmic hydrocarbon or vegetable oil. Spray volumes can range from about one to several thousand liters per hectare, but more typically are in the range from about ten to several hundred liters per hectare. Sprayable formulations can be tank mixed with water or another suitable medium for foliar treatment by aerîal or ground application, or for application to the growing medium of the plant. Liquid and dry formulations can be metered directly into drip irrigation Systems or metered into the furrow during planting. Liquid and solid formulations can be applied onto seeds of crops and other désirable végétation as seed treatments before planting to protect developing roots and other subterranean plant parts and/or foliage through systemic uptake.

The formulations will typically contain effective amounts of active ingrédient, diluent and surfactant within the following approximate ranges which add up to 100 percent by weight.

	Weight Percent
Active Ingrédient	Diluent	Surfactant
Water-Dispersible and Watersoluble Granules, Tablets and Powders	0.001-90	0-99.999	0-15
Oil Dispersions, Suspensions, Emulsions, Solutions (including Emulsifiable Concentrâtes)	1-50	40-99	0-50
Dusts	1-25	70-99	0-5
Granules and Pellets	0.001-99	5-99.999	0-15
High Strength Compositions	90-99	0-10	0-2

Solid diluents include, for example, clays such as bentonite, montmorillonite, attapulgite and kaolin, gypsum, cellulose, titanium dioxide, zinc oxide, starch, dextrin, sugars (e.g., lactose, sucrose), silica, talc, mica, diatomaceous earth, urea, calcium carbonate, sodium carbonate and bicarbonate, and sodium sulfate. Typical solid diluents are described in Watkins et al., Handbook 5 of Insecticide Dust Diluents and Carriers, 2nd Ed., Dori and Books, Caldwell, New Jersey.

Liquid diluents include, for example, water, ALV-dimethylalkanamides (e.g., A/.Æ-dimethylfomiamide), limonene, dimethyl sulfoxide, TV-alkyl pyrrolido nés (e.g., jV-methylpyrrolidinone), alkyl phosphates (e.g., triethylphosphate), ethylene glycol, triethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, propylene carbonate, 10 butylène carbonate, paraffins (e.g., white minerai oils, normal paraffms, isoparaffins), alkylbenzenes, alkyl naphthalenes, glycérine, glycerol triacetate, sorbitol, aromatic hydrocarbons, dearomatized aliphatics, alkylbenzenes, alkylnaphthalenes, ketones such as cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4-methyl-2-pentanone, acétates such as isoamyl acetate, hexyl acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl acetate and isobornyl acetate, 15 other esters such as alkylated lactate esters, dibasic esters alkyl and aryl benzoates, γbutyrolactone, and alcohols, which can be linear, branched, saturated or unsaturated, such as inethanol, éthanol, n-propanol, isopropyl alcohol, «-butanol, isobutyl alcohol, n-hexanol, 2ethylhexanol, o-octanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alcohol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohexanol, tetrahydrofurfuryl alcohol, diacetone alcohol, cresol and benzyl alcohol. Lîquîd diluents also include glycerol esters of saturated and unsaturated fatty acids (typically

Cg—C22X such as plant seed and fruit oîls (e.g., oîls of olive, castor, linseed, sesame, corn (maize), peanut, sunflower, grapeseed, safflower, cottonseed, soybean, râpes eed, coconut and palm kernel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, cod liver oil, fish oil), and mixtures thereof. Liquid diluents also include alkylated fatty acids (e.g., methylated, ethylated, butylated) wherein the fatty acids may be obtained by hydroiysis of glycerol esters from plant and animal sources, and can be purified by distillation. Typical liquid diluents are described in Marsden, Solvents Guide, 2nd Ed._s Interscience, New York, 1950.

The solid and liquid compositions of the présent disclosure often include one or more surfactants. When added to a liquid, surfactants (also known as “surface-active agents”) generally modify, most often reduce, the surface tension of the liquid. Depending on the nature of the hydrophilic and lipophilie groups in a surfactant molécule, surfactants can be useful as wetting agents, dispersants, emulsifiers or defoaming agents.

Surfactants can be classîfied as nonionic, anionic or cationic. Nonionic surfactants useful for the present compositions include, but are not limited to: alcohol alkoxylates such as alcohol alkoxylates based on natural and synthetic alcohols (which may be branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylène oxide or mixtures thereof; amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycérides such as ethoxylated soybean, castor and rapeseed oils; alkylphénol alkoxylates such as octylphenol ethoxylates, nonylphenol ethoxylates, dinonyl phénol ethoxylates and dodecyl phénol ethoxylates (prepared from the phénols and ethylene oxide, propylene oxide, butylène oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide and reverse block polymers where the terminal blocks are prepared from propylene oxide; ethoxylated fatty acids; ethoxylated fatty esters and oils; ethoxylated methyl esters; ethoxylated tristyrylphenol (including those prepared from ethylene oxide, propylene oxide, butylène oxide or mixtures thereof); fatty acid esters, glycerol esters, lanolin-based dérivatives, polyethoxylate esters such as polyethoxylated sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid esters and polyethoxylated glycerol fatty acid esters; other sorbitan dérivatives such as sorbitan esters; polymeric surfactants such as random copolymers, block copolymers, alkyd peg (polyethylene glycol) resins, graft or comb polymers and star polymers; polyethylene glycols (pegs);

polyethylene glycol fatty acid esters; silicone-based surfactants; and sugar-derivatives such as sucrose esters, alkyl polyglycosides and alkyl polysaccharides.

Useful anionic surfactants include, but are not limited to: alkylaryl sulfonic acids and their salts; carboxylated alcohol or alkylphenol ethoxylates; diphenyl sulfonate dérivatives; lignin and 5 lignin dérivatives such as lignosulfbnates; maleic or succinîc acids or their anhydrides; olefin sulfonates; phosphate esters such as phosphate esters of alcohol alkoxylates, phosphate esters of alkylphenol alkoxylates and phosphate esters of styryl phénol ethoxylates; protein-based surfactants; sarcosine dérivatives; styryl phénol ether sulfate; sulfates and sulfonates of oils and fatty acids; sulfates and sulfonates of ethoxylated alkylphenols; sulfates of alcohols; sulfates of 10 ethoxylated alcohols; sulfonates of amines and amides such as ÀQV-alkyltaurates; sulfonates of benzene, cumene, toluene, xylene, and dodecyl and tridecylbenzenes; sulfonates of condensed naphthalenes; sulfonates of naphthalene and alkyl naphthalene; sulfonates of fractionated Petroleum; sulfosuccinamates; and sulfosuccinates and their dérivatives such as dialkyl sulfosuccinate salts.

Useful cationic surfactants include, but are not limited to: amides and ethoxylated amides;

amines such as /V-alkyl propanediamines, tripropylenetriamines and dipropylenetetramines, and ethoxylated amines, ethoxylated diamines and propoxylated amines (prepared from the amines and ethylene oxide, propylene oxide, butylène oxide or mixtures thereof); amine salts such as amine acétates and diamine salts; quatemary ammonium salts such as quaternary salts, 20 ethoxylated quatemary salts and diquatemary salts; and amine oxides such as alkyldimethylamine oxides and bis-(2-hydroxyethyl)-alkylamine oxides.

Also useful for the présent compositions are mixtures of nonionic and anionic surfactants or mixtures of nonionic and cationic surfactants. Nonionic, anionic and cationic surfactants and their recommended uses are disclosed in a variety of published référencés including 25 McCutcheon ’s Emulsifiers and Détergents, annual American and International Editions published by McCutcheon’s Division, The Manufacturing Confectioner Publishing Co.; Sisely and Wood, Encyclopedia of Surface Active Agents, Chemical Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. Milwidsky, Synthetic Détergents, Seventh Edition, John Wiley and Sons, New York, 1987.

Compositions of this disclosure may also contain formulation auxiliaries and additives, known to those skilled in the art as formulation aids (some of which may be considered to also fonction as solid diluents, liquid diluents or surfactants). Such formulation auxiliaries and additives may control: pH (buffers), foamîng during processing (antifoams such 69 polyorganosiloxanes), sédimentation of active ingrédients (suspending agents), viscosity (thixotropic thickeners), in-container microbial growth (antimicrobiais), product freezing (antifreezes), col or (dyes/pigment dispersions), wash-off (film form ers or stickers), évaporation (évaporation retardants), and other formulation attributes. Film formers include, for example, polyvinyl acétates, polyvinyl acetate copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Examples of formulation auxiliaries and additives include those listed in McCutcheon ’s Volume 2; Functional Materials, annual International and North American éditions published by McCutcheon’s Division, The Manufacturing Confectioner Publishing Co.; and PCT Publication WO 03/024222.

The compound of Formula 1 and any other active ingrédients are typically incorporated into the present compositions by dissolving the active ingrédient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emulsifiable concentrâtes, can be prepared by simply mixing the ingrédients. If the solvent of a liquid composition intended for use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the actîvecontaining solvent upon dilution with water. Active ingrédient slurries, with parti cl e diameters of up to 2,000 pm can be wet milled using media mills to obtain particles with average diameters below 3 pm. Aqueous slurries can be made into finished suspension concentrâtes (see, for example, U.S. 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usualiy require dry milling processes, which produce average particle diameters in the 2 to 10 pm range. Dusts and powders can be prepared by blending and usualiy grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can be prepared by spraying the active material upon preformed granular carriers or by agglomération techniques. See Browning, “Agglomération”, Chemical Engineering, December 4, 1967, pp 147—48, Perry ’s Chemical Engineer's Handbook, 4th Ed., McGraw-Hill, New York, 1963, pages 8-57 and foliowing, and WO 91/13546. Pellets can be prepared as described in U.S. 4,172,714. Water-dispersible and water-soluble granules can be prepared as taught in U.S. 4,144,050, U.S. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. 5,180,587, U.S. 5,232,701 and U.S. 5,208,030. Films can be prepared as taught in GB 2,095,558 and U,S. 3,299,566.

For further information regarding the art of formulation, see T. S. Woods, “The Formulator’s Toolbox - Product Forms for Modem Agriculture” in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks and T. R. Roberts, Eds., Proceedings of the 9th International Congress on Pesticide Chemistry, The Royal Society of Chemistry, 70

Cambridge, 1999, pp. 120-133. See also U.S. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Exainples 10-41; U.S. 3,309,192, Col. 5, line 43 through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53, 58, 132, 138-140, 162-164, 166, 167 and 169-182; U.S. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and Examples 1-4; Klingman, Weed Control as a Science, John 5 Wiley and Sons, Inc., New York, 1961, pp 81-96; Hance étal., Weed Control Handbook, 8th Ed., Blackwell Scientific Publications, Oxford, 1989; and Developments in formulation technology, PJB Publications, Richmond, UK, 2000.

In the following Examples, ail formulations are prepared in conventional ways. Compound numbers refer to compounds in Index Tables A-B. Without further élaboration, it is 10 believed that one skilled in the art using the preceding description can utilize the présent disclosure to its fullest extent. The following Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way whatsoever. Percentages are by weight except where otherwise indicated.

Example A

High Strength Concentrate

Compound 2 98.5% silica aerogel 0.5% synthetic amorphous fine silica 1.0%

Example B Wettable Powder

Compound 3 65.0% dodecylphenol polyethylene glycol ether 2.0% sodium ligninsulfonate 4.0% sodium silicoaluminate 6.0% montmorillonite (calcined) 23.0%

Example C Granule Compound 4 10.0% attapulgite granules (low volatile matter, 0.71/0.30 mm; 90.0%

U.S.S. No. 25-50 sieves)

Example D

Extruded Pellet

Compound 23	25.0%
anhydrous sodium sulfate	10.0%
crude calcium ligninsulfonate	5.0%
sodium alkylnaphthalenesulfonate	1.0%
calcium/magnesium bentonite	59.0%
Example E
Emulsifiable Concentrate
Compound 2	10.0%
polyoxyethylene sorbitol hexoîeate	20.0%
C₆-C]q fatty acid methyl ester	70.0%
Example F
Microemulsîon
Compound 3	5.0%
polyvinylpyiTolidone-vînyl acetate copolymer	30.0%
alkylpolyglycoside	30.0%
glyceryl monooleate	15.0%
water	20.0%
Example G
Seed Treatment
Compound 4	20.00%
polyvînylpyrrolidone-vinyl acetate copolymer	5.00%
montan acid wax	5.00%
calcium ligninsulfonate	1.00%
polyoxyethylene/polyoxypropylene block copolymers	1.00%
stearyl alcohol (POE 20)	2.00%
polyorganosilanc	0.20%
colorant red dye	0.05%
water	65.75%

Example H

Fertilizer Stick

Compound 23 2.5% pyrrolidone-styrene copolymer 4.8% tristyrylphenyl 16-ethoxyIate 2.3% talc 0.8% corn starch 5.0% slow-release fertilizer 36.0% kaolin 38.0% water 10.6%

Exampie 1

Suspension Concentrate compound 2 35% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1%

1,2- benzîsothiazolin-3-one 0.1 % water 53.7%

Example J

Emulsion in Water compound3 10.0% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1 %

1,2- benzisothiazolin-3-one 0.1 % aromatic petroleum based hydrocarbon 20.0 water 58.7%

Example K

Oil Dispersion compound 4 25% polyoxyethylene sorbitol hexaoleate 15% organically modified bentonite clay 2.5% fatty acid methyl ester 57.5%

Example L

Suspoemulsion compound 23 10.0% îmidacloprid 5.0% butyl polyoxyethylene/polypropylene block copolymer 4.0% stearic acid/polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% xanthan gum 0.1% propylene glycol 5.0% silicone based defoamer 0.1 % l,2'benzîsothiazolin-3-one 0.1% aromatic petroleum based hydrocarbon 20.0% water 53.7%

Compounds of this disclosure exhibit activity against a wide spectrum of invertebrate 5 pests. These pests include invertebrates inhabiting a variety of environments such as, for ex ample, plant foliage, roots, soil, harvested crops or other foodstuffs, or building structures. These pests include, for example, invertebrates feeding on foliage (including leaves, stems, flowers and fruits), seeds, wood or textile fibers, and thereby causing injury or damage to, for example, growing or stored agronomie crops, forests, greenhouse crops, omamentals, nursery 10 crops, stored foodstuffs or fiber products, or bouses or other structures or their contents. Those skilled in the art will appreciate that not ail compounds are equally effective against ail growth stages of ail pests.

These présent compounds and compositions are thus useful agronomically for protecting field crops from phytophagous invertebrate pests, and also nonagronomically for protecting other horticultural crops and plants from phytophagous invertebrate pests. This utility includes protecting crops and other plants (i.e. both agronomie and nonagronomic) that contain genetic material introduced by genetic engineering (i.e. transgenic) or modified by mutagenesis to provide advantageous traits. Examples of such traits include tolérance to herbicides, résistance 5 to phytophagous pests (e.g., insects, mites, aphids, spiders, nematodes, snails, plant-pathogenic fungi, bacteria and viruses), improved plant growth, increased tolérance of adverse growing conditions such as high or low températures, low or high soil moisture, and high salinity, increased flowering or fruiting, greater harvest yields, more rapid maturation, higher quality and/or nutritional value of the harvested product, or improved storage or process properties of 10 the harvested products. Transgenic plants can be modified to express multiple traits. Examples of plants containing traits provided by genetic engineering or mutagenesis include varieties of corn, cotton, soybean and potato expressing an insecticidal Bacillus thuringiensis toxin such as YIELD GARD®, KNOCKOUT®, STARLINK®, BOLLGARD®, NuCOTN® and NEWLEAF®, INVICTA RR2 P RO™, and herbicide-tolerant varieties of corn, cotton, soybean and rapeseed such as ROUNDUP READY®, LIBERTY LINK®, IMI®, STS® and CLEARFIELD®, as well as crops expressing jV-acetyltransferase (GAT) to provide résistance to glyphosate herbicide, or crops containing the HRA gene providing résistance to herbicides inhibiting acetolactate synthase (ALS). The présent compounds and compositions may exhibit enhanced effects with traits introduced by genetic engineering or modified by mutagenesis, thus enhancing phenotypic 20 expression or effectiveness of the traits or increasing the invertebrate pest control effectiveness of the présent compounds and compositions. In particular, the présent compounds and compositions may exhibit enhance effects with the phenotypic expression of proteins or other natural products toxic to invertebrate pests to provide greater-than-additive control of these pests.

Compositions of this disclosure can also optionally comprise plant nutrients, e.g., a 25 fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium, magnésium, îron, copper, boron, manganèse, zinc, and molybdenum. Of note are compositions comprising at least one fertilizer composition comprising at least one plant nutrient selected from nitrogen, phosphorus, potassium, sulfur, calcium and magnésium. Compositions of the présent disclosure which further comprise at least one plant nutrient can be 30 in the form of liquids or solids. Of note are solid formulations in the form of granules, small sticks or tablets. Solid formulations comprising a fertilizer composition can be prepared by mixing the compound or composition of the présent disclosure with the fertilizer composition together with formulating ingrédients and then preparing the formulation by methods such as granulation or extrusion. Alternative!y solid formulations can be prepared by spraying a solution or suspension of a compound or composition of tire présent disclosure in a volatile solvent onto a previous prepared fertilizer composition in the form of dimensionally stable mixtures, e.g., granules, small sticks or tablets, and then evaporating the solvent.

Nonagronomic uses refer to invertebrate pest control in the areas other than fields of crop plants. Nonagronomic uses of the présent compounds and compositions include control of invertebrate pests in stored grains, beans and other foodstuffs, and in textiles such as clothing and carpets. Nonagronomic uses of the présent compounds and compositions also include invertebrate pest control in omamental plants, forests, in yards, along roadsides and railroad rights of way, and on turf such as lawns, golf courses and pastures. Nonagronomic uses of the présent compounds and compositions also include invertebrate pest control in houses and other buildings which may be occupied by humans and/or companion, farm, ranch, zoo or other animais. Nonagronomic uses of the présent compounds and compositions also include the control of pests such as termites that can damage wood or other structural materials used in buildings.

Examples of agronomie or nonagronomic invertebrate pests include eggs, larvae and adults of the order Lepidoptera, such as armyworms, cutwonns, loopers, and heliothines in the family Noctuidae (e.g., pink stem borer (Sesamia inferens Walker), corn stalk borer (Sesamia nonagrioides Lefebvre), southem armyworm (Spodoptera eridania Cramer), fall armyworm (Spodoptera frugiperda J. E. Smith), beet armyworm (Spodoptera exigua Hübner), cotton leafworm (Spodoptera littoralis Boisduval), yellowstriped armyworm (Spodoptera ornithogalli Guenée), black cutworm (Agrotis ipsilon Hufnagel), velvetbean Caterpillar (Anticarsia gemmatalis Hübner), green fruitworm (Lithophane antennata Walker), cabbage armyworm (Barathra brassicae Linnaeus), soybean looper (Pseudoplusia includens Walker), cabbage looper (Trichoplusia ni Hübner), tobacco budworm (Heliothis virescens Fabricius)); borers, casebearers, webworms, coneworms, cabbageworms and skeletonizers from the family Pyralidae (e.g., European corn borer (Ostrinia nubilalis Hübner), navel orangeworm (Amyelois transitella Walker), corn root webworm (Crambus caliginosellus Clemens), sod webworms (Pyralidae: Crambinaé) such as sod worm (Herpetogramma licarsisalis Walker), sugarcane stem borer (Chilo infuscatellus Snelien), tomato small borer (Neoleucinodes elegantalis Guenée), green leafroller (Cnaphalocrocis medinalis), grape leaffolder (Desmia funeralis Hübner), melon worm (Diaphania nitidalis Stoll), cabbage center grub (Helluala hydralis Guenée), yellow stem borer 76 {Scirpophaga incertulas Walker), early shoot borer {Scirpophaga infnscatellus Snellen), white stem borer {Scirpophaga innotata Walker), top shoot borer {Scirpophaga nivella Fabricius), dark-headed ri ce borer (Chilo polychrysus Meyrick), striped riceborer {Chilo suppressalis Walker), cabbage cluster Caterpillar {Crocidolomia binotalis English)); leafrollers, budwonns, seed worms, and fruit worms in the family Tortricidae (e.g., codling moth (Cydia pomonella Linnaeus), grape berry moth (Endopiza viteana Clemens), oriental fruit moth {Grapholita molesta Busck), citrus false codling moth {Cryptophlebia leucotreta Meyrick), citrus borer {Ecdytolopha aurantiana Lima), redbanded leafroller {Argyrotaenia velutinana Walker), obliquebanded leafroller {Choristoneura rosaceana Harris), light brown apple moth (Epiphyas postvittana Walker), European grape berry moth (Eupoecilia ambiguella Hübner), apple bud moth {Pandemis pyrusana Kearfott), omnivorous leafroller {Platynota stultana Walsingham), barred fruit-tree tortrix {Pandemis cerasana Hübner), apple brown tortrix {Pandemis heparana Denis & Schiffermüller)); and many other economically important lepidoptera (e.g,, diamondback moth {Plutella xylostella Linnaeus), pink bollwonn {Pectinophora gossypiella Saunders), gypsy moth {Lymantria dispar Linnaeus), peach fruit borer {Carposina niponensis Walsingham), peach twig borer {Anarsia lineatella Zeller), potato tuberworm {Phthorimaea operculella Zeller), spotted teniform leafminer {Lithocolletis blancardella Fabricius), Asiatic apple leafminer {Lithocolletis ringoniella Matsumura), rice leaffolder {Lerodea eufala Edwards), apple leafminer (Leucoptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea including cockroaches from the families Blattellidae and Blattidae (e.g., oriental cockroach {Blatta orientalis Linnaeus), Asian cockroach {Blatella asahinai Mizukubo), German cockroach {Blattella germanica Linnaeus), brownbanded cockroach {Supella longipalpa Fabricius), American cockroach {Periplaneta americana Linnaeus), brown cockroach (Periplaneta brunnea Burmeister), Madeira cockroach {Leucophaea maderae Fabricius)), smoky brown cockroach {Periplaneta fuliginosa Service), Australian Cockroach {Periplaneta australasiae Fabr.), lobster cockroach {Nauphoeta cinerea Olivier) and smooth cockroach (Symploce pallens Stephens)); eggs, foliar feeding, fruit feeding, root feeding, seed feeding and vesicular tissue feeding larvae and adults of the order Coleoptera including weevils from the families Anthribidae, Bruchidae, and Curculionidae (e.g., bol! weevil {Anthonomus grandis Boheman), rice water weevil {Lissorhoptrus oryzophilus Kuschel), granary weevil {Sitophilus granarius Linnaeus), rice weevil {Sitophilus oryzae Linnaeus)), annual bluegrass weevil {Listronotus maculicollis Dietz), bluegrass billbug {Sphenophorus parvulus Gyllenhal), hunting billbug {Sphenophorits venants vestitus), Denver billbug {Sphenophorus cicatristriatus Fahraeus)); flea beetles, cucumber 77 beetles, rootworms, leaf beetles, potato beetles, and leafrniners in the family Chrysomelidae (e.g., Colorado potato beetle (Leptinotarsa decemlineata Say), western com rootworm (Diabrotica virgifera virgifera LeConte)); chafers and other beetles from the family Scarabaeidae (e.g., Japanese beetle (Popillia japonica Newman), oriental beetle (Anomala orientalis Waterhouse, Exomala orientalis (Waterhouse) Baraud), northem masked chafer (Cyclocephala borealis Arrow), southem masked chafer (Cyclocephala immaculata Olivier or C. lurida Bland), dung beetle and white grub (Aphodius spp.), black turfgrass ataenius (Ataenius spretulus Haldeman), green .lune beetle (Cotinis nitida Linnaeus), Asiatic garden beetle (Maladera castanea Arrow), May/June beetles (Phyllophaga spp.) and European chafer (Rhizotrogus majalis Razoumowsky)); carpet beetles from the family Dermestidae; wireworms from the family Elateridae; bark beetles from the family Scolytidae and flour beetles from the family Tenebrionidae.

In addition, agronomie and nonagronomic pests include: eggs, adults and larvae of the order Dermaptera including earwigs from the family Forficulidae (e.g., European earwig {Forficula auricularia Linnaeus), black earwig (Chelisoches mono Fabricius)); eggs, immatures, adults and nymphs of the orders Hemiptera and Homoptera such as, plant bugs from the family Mîridae, cicadas from the family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Cicadellidae, bed bugs (e.g., Cimex lectularius Linnaeus) from the family Cimicidae, planthoppers from the families Fulgoroidae and Delphacidae, treehoppers from the family Membracidae, psyllids from the family Psyllidae, whiteflies from the family Aleyrodidae, aphids from the family Aphididae, phylloxéra from the family Phylloxeridae, mealybugs from the family Pseudococcidae, scales from the families Coccidae, Diaspididae and Margarodidae, lace bugs from the family Tingidae, stink bugs from the family Pentatomidae, chinch bugs (e.g., hairy chinch bug (BUssus leucopterus hirtus Montandon) and southem chinch bug (Blissus insularis Barber)) and other seed bugs from the family Lygaeidae, spîttlebugs from the family Cercopidae squash bugs from the family Coreidae, and red bugs and cotton stainers from the family Pyrrhocoridae.

Agronomie and nonagronomic pests also include : eggs, larvae, nymphs and adults of the order Acari (mites) such as spider mites and red mites in the family Tetranychidae (e.g., European red mite (Panonychus ulmi Koch), two spotted spider mite (Tetranychus urticae Koch), McDaniel mite (Tetranychns mcdctnieli McGregor)); fiat mites in the family Tenuîpalpidae (e.g., citrus fiat mite {Brevipalpus lewisi McGregor)); rust and bud mites in the family Erîophyidae and other foliar feeding mites, dust mites in the family Epidermoptidae, 78 follicle mites in the family Demodicidae, grain mites in the family Glycyphagidae; ticks in the family ixodidae, commonly known as hard ticks (e.g., deer tick (Ixodes scapularis Say), Australian paraiysis tick {Ixodes holocyclus Neumann), American dog tick {Dermacentor variabilis Say), lone star tick (Amblyomma americanum Linnaeus)) and ticks in the family Argasidae, commonly known as soft ticks (e.g., relapsing fever tick (Ornithodoros turicata), common fowl tick (Argas radiatus)); scab and itch mites in the families Psoroptidae, Pyemotidae, and Sarcoptidae; eggs, adults and immatures of the order Orthoptera including grasshoppers, locusts and crickets (e.g., migratory grasshoppers (e.g., Melanoplus sanguinipes Fabricius, M. differentialis Thomas), American grasshoppers (e.g., Schistocerca americana Drury), desert locust {Schistocerca gregaria Forskal), migratory locust {Locusta migratoria Linnaeus), bush locust (Zonocerus spp.), house cricket {Acheta domesticus Linnaeus), mole crickets (e.g., tawny mole cricket {Scapteriscus vicinus Scudder) and Southern mole cricket {Scapteriscus borellii Giglio-Tos)); eggs, adults and immatures of the order Diptera including leafminers (e.g., Liriomyza spp. such as serpentine vegetable leafminer (Liriomyza sativae Blanchard)), midges, fruit Aies (Tephritidae), frit Aies (e.g., Oscinella frit Linnaeus), soi! maggots, house Aies (e.g., Musca domestica Linnaeus), lesser house Aies (e.g., Fannia canicularis Linnaeus, F. femoralis Stein), stable Aies (e.g., Stomoxys calcitrans Linnaeus), face Aies, horn Aies, blow Aies (e.g., Chrysomya spp., Phormia spp.), and other muscoid Ay pests, horse Aies (e.g., Tabanus spp.), bot Aies (e.g., Gastrophilus spp., Oestrus spp.), cattle grubs (e.g., Hypoderma spp.), deer Aies (e.g., Chrysops spp.), keds (e.g., Melophagus ovinus Linnaeus) and other Brachycera, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex spp.), black Aies (e.g., Prosimulium spp., Simulium spp.), biting midges, sand Aies, sciarids, and other Nematocera; eggs, adults and immatures of the order Thysanoptera including onîon thrips {Thrips tabaci Lindeman), fiower thrips {Frankliniella spp.), and other foliar feeding thrips; insect pests of the order Hymenoptera including ants of the Family Formicidae including the Florida carpenter ant (Camponotus floridanus Buckley), red carpenter ant (Camponotus ferrugineux Fabricius), black carpenter ant {Camponotus pennsylvanicus De Geer), white-footed ant (Technomyrmex albipes fr. Smith), big headed ants {Pheidole sp.), ghost ant (Tapinoma melanocephalum Fabricius); Pharaoh ant (Monomorium pharaonis Linnaeus), little fire ant (Wasmannia auropunctata Roger), fire ant (Solenopsis geminata Fabricius), red imported fire ant (Solenopsis invicta Buren), Argentine ant (Iridomyrmex humilis Mayr), crazy ant (Paratrechina longicornis Latreille), pavement ant (Tetramorium caespitum Linnaeus), comfield ant {Lasius alienus Fôrster) and odorous house ant {Tapinoma sessile Say). Other Hymenoptera including bees 79 (including carpenter bees), homets, yellow jackets, wasps, and sawflies (Neodiprion spp.; Cephus spp.); msect pests of the order Isoptera including termites in the Tennitidae (e.g., Macrotermes sp„ Odontotermes obesus Rambur), Kalotennitidae (e.g., Cryptotermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., Coptotermes sp., Heterotermes tenais Hagen) families, the eastem subterranean ténuité (Reticulitermes flavipes Kollar), western subtenanean ténuité (Reticulitermes hesperus Banks), Formosan subtenanean termite (Coptotermes formosanus Shiraki), West Indian drywood ténuité (Incisitermes immigrons Snyder), powder post ténuité (Cryptotermes brevis Walker), drywood tennite (Incisitermes snyderi Light), southeastem subterranean tennite (Reticulitermes virginicus Banks), western drywood tennite (Incisitermes minor Hagen), arboreal ténuités such as Nasutitermes sp. and other termites of économie importance, insect pests of the order Thysanura such as silverfîsh (Lepisma saccharina Linnaeus) and firebrat (Thermobia domestica Packard). Additional arthropod pests covered include. spiders in the order Araneae such as the brown recluse spîder (Loxosceles reclusa Gertsch & Mulaik) and the black widow spider (Latrodectus mactans Fabricius), and centipedes in the order Scutigeromorpha such as the house centipede (Scutigera coleoptrata Linnaeus).

Examples of invertebrate pests of stored grain include larger grain borer (Prostephanus truncatus), lesser grain borer (Rhyzopertha dominica), rice weevil (Stiophilus oryzae), maize weevil (Stiophilus zeamais), cowpea weevil (Callosobruchus maculatus), red flour beetle (Tribolium castaneum), granary weevil (Stiophilus granarius), Indian meal moth (Plodia interpunctelld), Mediterranean flour beetle (Ephestia kuhniella) and fiat or rusty grain beetle (Cryptolestis ferrugineus).

Compounds of the disclosure may hâve activity against pests in the order Lepidoptera (e.g., Alabama argillacea Hübner (cotton leaf wonu), Archips argyrospila Walker (fruit tree leaf roller), A. rosana Linnaeus (European leaf roller) and other Archips species, Chilo suppressalis Walker (rice stem borer), Cnaphalocrosis medinalis Guenée (rice leaf roller), Crambus caliginosellus Clemens (corn root webwonu), Crambus teterrellus Zincken (bluegrass webworm), Cydia pomonella Linnaeus (codling moth), Earias insulana Boisduval (spiny bollworm), Earias vittella Fabricius (spotted bollwonn), Helicoverpa armigera Hübner (American bollwonn), Helicoverpa zea Boddie (corn earworm), Heliothis virescens Fabricius (tobacco budwonn), Herpetogramma licarsisalis Walker (sod webworm), Lobesia botrana Denis & SchiffenuüIIer (grape berry moth), Pectinophora gossypiella Saunders (pink bollworm), Phyllocnistis citrella Stainton (citrus leafminer), Pieris brassicae Linnaeus (large white butterfly), Pieris rapae Linnaeus (small white butterfly), Plutella xylostella Linnaeus SO (diamondback moth), Spodoptera exigua Hübner (beet armyworm), Spodoptera litura Fabricius (tobacco cutwonn, cluster Caterpillar), Spodoptera frugiperda J. E. Smith (fall armyworm), Trichoplusia ni Hübner (cabbage looper) and Tuta absoluta Meyrick (tomato leafminer)).

Compounds ot the disclosure hâve signifïcant activity on members from the order Homoptera including: Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora Koch (cowpea aphid), Aphis fabae S copoli (black bean aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch (spirea aphid), Aulacorthum solani Kaltenbach (foxglove aphid), Chaetosiphon fragaefolii Cockerell (strawberry aphid), Diui aphis noxia Kurdjumov/Mordvîlko (Russian wheat aphid), Dysaphis plantaginea Paaserini (rosy apple aphid), Eriosoma lanigerum Hausmann (woolly apple aphid), Hyalopterus pruni Geoffroy (mealy plum aphid), Lipaphis erysimi Kaltenbach (tumip aphid), Metopolophium dirrhodum Walker (cereal aphid), Macrosiphum euphorbiae Thomas (potato aphid), Myzus persicae Sulzer (peach-potato aphid, green peach aphid), Nasonovia ribisnigri Mosley (lettuce aphid), Pemphigus spp. (root aphids and gall aphids), Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosiphum padi Linnaeus (bird cherry-oat aphid), Schizaphis graminum Rondani (greenbug), Sitobion avenae Fabricius (English grain aphid), Therioaphis maculata Buckton (spotted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe (black citrus aphid), and Toxoptera citricida Kirkaldy (brown citrus aphid); Adelges spp. (adelgids); Phylloxéra devastatrix Pergande (pecan phylloxéra); Bemisia tabaci Gennadius (tobacco whitefly, sweetpotato whitefly), Bemisia argentifolii Bellows & Perring (silverleaf whitefly), Dialeurodes citri Aslimead (citrus whitefly) and Trialeurodes vaporariorum Westwood (greenhouse whitefly); Empoasca fabae Harris (potato leafhopper), Laodelphax striatellus Fallen (smaller brown planthopper), Macrolestes quadrilineatus Forbes (aster leafhopper), Nephotettix cinticeps Uhler (green leafhopper), Nephotettix nigropictus Stâl (rice leafhopper), Nilaparvata lugens Stâl (brown planthopper), Peregrinus maidis Aslimead (corn planthopper), Sogatella furcifera Horvath (white-backed planthopper), Sogatodes orizicola Muir (rice delphacid), Typhlocyba pomaria McAtee white apple leafhopper, Erythroneoura spp. (grape leafhoppers); Magicidada septendecim Linnaeus (periodical ctcada); Icerya purchasi Maskell (cottony cushion scale), Quadraspidiotus perniciosus Comstock (San José scale); Planococcus citri Rîsso (citrus mealybug); Pseudococcus spp. (other mealybug complex); Cacopsylla pyricola Foerster (pear psylla), Trioza diospyri Ashmead (persimmon psylla).

Compounds of this disclosure also hâve activity on members from the order Hemiptera including: Acrosternum hilare Say (green stink bug), Anasa tristis De Geer (squash bug), Blissus 81 leucopterus Say (chinch bug), Cimex lectularius Linnaeus (bed bug) Corythuca gossypii Fabncius (cotton lace bug), Cyrtopeltis modesta Distant (tomato bug), Dysdercus suturellus Herrich-Schaffer (cotton stainer), Euchistus servus Say (brown stink bug), Euchistus variolarius Palisot de Beauvois (one-spotted stink bug), Graptosthetus spp. (complex of seed bugs), Halymorpha hafys Stâl (brown marmorated stink bug), Leptoglossus corculus Say (leaf-footed pine seed bug), Lygus lineolaris Palisot de Beauvois (tamished plant bug), Nezara viridula Linnaeus (southem green stink bug), Oebalus pugnax Fabricius (rice stink bug), Oncopeltus fasciatus Dallas (large milkweed bug), Pseudatomoscelis seriatus Reuter (cotton fleahopper). Other insect orders controlled by compounds of the disclosure include Thysanoptera (e.g., Frankliniella occidentalis Pergande (western flower thrips), Scirihothrips citri Moulton (citrus thrips), Sericothrips variabilis Beach (soybean thrips), and Thrips tabaci Lindeman (onion thrips); and the order Col copiera (e.g., Leptinotarsa decemlineata Say (Colorado potato beetle), Epilachna varivestis Mulsant (Mexican bean beetle) and wireworms of the généra Agriotes, A thons or Limonius).

Note that some contemporary classification Systems place Homoptera as a suborder within the order Hemiptera.

Of note is use of compounds of this disclosure for controlling diamondback moth (Plutella xylostella). Of note is use of compounds of this disclosure for controlling fall armyworm (Spodopterafrugiperda). Of note is use of compounds of this disclosure for controlling western flower thrips (Frankliniella occidentalis). Of note is use of compounds of this disclosure for controlling potato leafhopper (Empoascafabae). Of note is use of compounds of this disclosure for controlling cotton melon aphid (Aphis gossypii). Of note is use of compounds of this disclosure for controlling green peach aphid (Myzus persicae). Of note is use of compounds of this disclosure for controlling sweetpotato whitefly (Bemisia tabaci).

Compounds ot the présent disclosure may also be useful for increasîng vigor of a crop plant. This method comprises contacting the crop plant (e.g., foliage, flowers, fruit or roots) or the seed from which the crop plant is grown with a compound of Formula 1 in amount sufficient to achieve the desired plant vigor effect (i.e. biologically effective amount). Typically the compound of Fonnula 1 is applied in a formulated composition. Although the compound of Formula 1 is often applied directly to the crop plant or its seed, it can also be applied to the locus of the crop plant, i.e. the environment of the crop plant, particularly the portion of the environment in close enough proximity to ailow the compound of Fonnula 1 to migrate to the crop plant. The locus relevant to this method most commonly comprises the growth medium 82 (i.e. medium providing nutricnts to die plant), typically soil in which the plant is grown. Treatment of a crop plant to increase vigor of the crop plant thus comprises contacting the crop plant, the seed from which the crop plant is grown or the locus of the crop plant with a biologically effective amount of a compound of Formula 1.

Increased crop vigor can resuit in one or more of the foliowing observed effects: (a) optimal crop establishment as demonstrated by excellent seed germination, crop emergence and crop stand; (b) enhanced crop growth as demonstrated by rapid and robust leaf growth (e.g., measured by leaf area index), plant height, number of tillers (e.g., for rice), root mass and overall dry weight of végétative mass of the crop; (c) improved crop yields, as demonstrated by time to flowering, duration of flowering, number of flowers, total biomass accumulation (i.e. yield quantity) and/or fruit or grain grade marketabîlity of produce (i.e. yield quality); (d) enhanced ability of the crop to withstand or prevent plant disease infections and arthropod, nematode or mollusk pest infestations; and (e) increased ability of the crop to withstand environmental stresses such as exposure to thermal extremes, suboptimal moisturc or phytotoxic Chemicals,

The compounds of the present disclosure may increase the vigor of treated plants compared to untreated plants by killing or otherwîse preventing feeding of phytophagous invertebrate pests in the environment of the plants. In the absence of such control of phytophagous invertebrate pests, the pests reduce plant vigor by consuming plant tissues or sap, or transmiting plant pathogens such as viruses. Even in the absence of phytophagous invertebrate pests, the compounds of the disclosure may increase plant vigor by modifying metabolism of plants. Generally, the vigor of a crop plant will be most significantly increased by treating the plant with a compound of the disclosure if the plant is grown in a nonideal environment, i.e. an environment comprising one or more aspects adverse to the plant achieving the full genetîc potential ît would exhibit in an idéal environment.

Of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising phytophagous invertebrate pests. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment not comprising phytophagous invertebrate pests. Also of note is a method for increasing vigor of a crop plant wherein the crop plant is grown in an environment comprising an amount of moisture less than idéal for supporting growth of the crop plant. Of note is a method for increasing vigor of a crop plant wherein the crop is rice. Also of note is a method for increasing vigor of a crop plant wherein the crop is maize (corn). Also of note is a method for increasing vigor of a crop plant wherein the crop is soybean.

Compounds of this disclosure can also be mixed with one or more other biologîcally active compounds or agents including insecticides, fungicides, nematocides, bactéricides, acaricides, herbicides, herbicide safeners, growth regulators such as insect molting inhibitors and rootîng stimulants, chemosterilants, semiochemicals, repellents, attractants, pheromones, feeding stimulants, other biologîcally active compounds or entomopathogenic bacteria, virus or fiingi to form a multi-component pesticide giving an even broader spectrum of agronomie and nonagronomic utility. Thus the présent disclosure also pertains to a composition comprising a biologîcally effective amount of a compound of Formula 1, at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, and at least one additional biologîcally active compound or agent. For mixtures of the présent disclosure, the other biologîcally active compounds or agents can be formulated together with the présent compounds, including the compounds of Formula 1, to form a premix, or the other biologîcally active compounds or agents can be formulated separately from the présent compounds, including the compounds of Formula 1, and the two formulations combined together before application (e.g., in a spray tank) or, alternative!y, applied in succession.

Examples of such biologîcally active compounds or agents with which compounds of this disclosure can be formulated are insecticides such as abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, afidopyropen ([(35^, _î4A,4a7?,65'₎6a5,12A,12a5,12bY)-3[(cyclopropylcarbonyl)oxy]-1,3,4,4a,5,6,6a, 12,12a, 12b-decahydro-6,12-dihydroxy-4,6a, 12btrimethyl-11-oxo-9-(3-pyridînyl)-2//,l l//-naphtho[2,l-ô]pyrano[3,4-e]pyran-4-yl]methyl cyclopropanecarboxylate), ami do fl um et, amitraz, avermectin, azadirachtin, azinphos-m ethyl, benfuracarb, bensultap, bifenthrin, bifenazate, bistrifluron, borate, buprofezîn, cadusafos, carbaryl, carbofuran, cartap, carzol, chlorantraniliprole, chlorfenapyr, chlorfluazuron, chlorpyrifos, chlorpyrifos-methyl, chromafenozide, clofentezin, clothianîdin, cyantraniliprole (3bromo-l-(3-chloro-2-pyridinyl)-A^/'-[4-cyano-2-methyl-6-[(methylamino)carbonyI]phenyl]-I77pyrazole-5-carboxamide), cyclaniliprole (3-bromo-W-[2-bromo-4-chloro-6^ cyclopropylethyl)amino]carbonyl]phenyl]-l-(3-chloro-2-pyridinyl)-l/f-pyrazole-5carboxamide), cycloprothrin, cycloxaprid ((55,8^)-l-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8hexahydro-9-nitro-5,8-Epoxy-l/f-imidazo[I,2-a]azepine) cyflumetofen, cyfluthrin, beta-eyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alphacypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthîuron, diazinon, dieldrin, diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinotefuran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenbutatin oxide, fenitrothion, 84 fenothiocarb, fenoxycarb, fenpropathrin, fenvalerate, fipronil, flometoquin (2-ethyl-3,7dimethyl-6-[4-(trifluoromethoxy)phenoxy]-4-quinolinyl methyl carbonate), flonicamid, flubendiainîde, flucythrinate, flufenerim, flufenoxuron, flufenoxystrobin (methyl (a£)-2-[[2chloro-4-(trifluoromethyl)phenoxy] methyl]-a-(methoxymethylene)benzeneacetate), flufensulfone (5-chloro-2-[(3,4,4-trifluoro-3-buten-1 -yl)sulfonyl]thiazole), fluhexafon. fluopyram, flupiprole (l-[2,6-dichloro-4-(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-lyl)ammo]-4-[(trifluoromethyl)sulfmyl]-lÆ-pyrazole-3-carbonitrile), flupyradifurone (4-[[(6chloro-3-pyridinyl)methyl](2,2-difluoroethyI)amino]-2(5H)-furanone), fluvalinate, tau-fluvalinate, fonophos, formetanate, fosthiazate, halofenozide, heptafluthrin ([2,3,5,6tetrafluoro-4-(methoxyinethyl)phenyI] methyl 2,2-dimethyl-3-[(lZ)-3,3,3-trifluoro-l-propen-ly1]cyclopropanecarboxylate), hexaflumuron, hexythiazox, hydramethylnon, imidacloprid, indoxacarb, insecticidal soaps, isofenphos, lufenuron, malathion, meperfluthrin ([2,3,5,6tetrafluoro-4-(methoxymethyl)phenyl]methyl ( 1Λ,3 5)-3-(2,2-dichloroetheny 1)-2,2dimethylcyclopropanecarboxylate), metaflumizone, metaldehyde, methamidophos, methidathion, methiodicarb, methomyl, methoprene, methoxychlor, metofluthrin, methoxyfenozide, metofluthrin, monocrotophos, monofluorothrin ([2,3,5,6-tetrafluoro-4(methoxymethyl)phenyl] methyl 3-(2-cyano-l-propen-l-yl)-2,2dimethyieyclopropanecarboxylate), nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, parathion, parathion-methyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pyflubumide (l_J3,5-trimethyl-A^r-(2methyI-l-oxopropyl)-jV-[3-(2-methylpropyl)-4-[2,2,2-trifluoro-l-metlioxy-I( tri fl uoromethyl )ethyl]phenyI]-177-pyrazole-4-carboxamide), pymetrozine, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyrifluquinazon, pyriminostrobin (methyl (a£)-2-[[[2-[(2,4dichlorophenyl)amino]-6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-a(methoxymethyl ene)benzeneacetate), pyriprole, pyriproxyfen, rotenone, ryanodine, silafluofen, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulprofos, sulfoxaflor (jV[methyloxido[l-[6-(trifluoromethyl)-3-pyridinyl]ethyl]A⁴-suIfanylidene]cyanamide), tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, tetramethylfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyI] methyl 2,2,3,3tetram ethyl cyclopropanecarboxylate), tetranilîprole, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tioxazafen (3-phenyl-5-(2-thienyl)-l,2,4-oxadiazole), tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumezopyrim (2,4-dioxo-l-(5-pyrimidinylmethyl)-3-[3(trifluoromethyl)phenyI]-27/-pyrido[l,2-n]pyrimidinium inner sait), triflumuron, Bacillus 85 thuringiensis deita-endotoxins, entomopathogenîc bacteria, entomopathogénie viruses and entomopathogenîc fiingi.

Of note are insecticides such as abamectin, acetamiprid, acrinathrin, afidopyropen, amîtraz, avenirectin, azadîrachtin, benfuracarb, bensultap, bîfenthrin, buprofezin, cadusafos, carbaryl, cartap, chlorantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyclaniliprole, cycloprothrin, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefiiran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etotenprox, etoxazole, fenitrothion, fenothiocarb, fenoxycarb, fenvalerate, fïpronil, flometoquin, flonicamid, flubendiamide, flufenoxuron, flufenoxystrobin, flufensulfone, flupiprole, flupyradifurone, fluvalinate, formetanate, fosthiazate, heptafluthrin, hexaflumuron, hydramethylnon, imidacloprid, indoxacarb, lufenuron, meperfluthrin, metaflumizone, methiodicarb, methomyl, methoprene, methoxyfenozide, metofluthrin, monofluorothrin, nitenpyram, nithiazine, novaluron, oxamyl, pyflubumide, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriminostrobin, pyrîproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfbxaflor, tebufenozide, tetramethrin, tetramethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triilumezopyrim, triflumuron, Bacillus thuringiensis deita-endotoxins, ail strains of Bacillus thuringiensis and ail strains of nucleo polyhedrosis viruses.

One embodiment of biological agents for mixing with compounds of this disclosure include entomopathogenîc bacteria such as Bacillus thuringiensis, and the encapsulated deitaendotoxins of Bacillus thuringiensis such as MVP® and MVPII® bioinsecticides prepared b y the CellCap® process (CellCap®, MVP® and MVPII® are trademarks of Mycogen Corporation, Indianapolîs, Indiana, USA); entomopathogenîc fungi such as green muscardîne fungus; and entomopathogenîc (both naturally occurring and genetically modified) viruses including baculovirus, nucleopolyhedro virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus (HzNPV), Anagrapha falcifera nucleopolyhedrovirus (AfNPV); and granulosis virus (GV) such as Cydia pomonella granulosis virus (CpGV).

Of particular note is such a combination where the other invertebrate pest control active ingrédient belongs to a different Chemical class or has a different site of action than the compound of Formula 1. In certain instances, a combination with at least one other invertebrate pest control active ingrédient having a similar spectrum of control but a different site of action wil] be particular! y advantageous for résistance management. Thus, a composition of the présent 86 disclosure can further comprise a biologîcally effective amount of at least one additional invertebrate pest control active ingrédient having a similar spectrum of control but belonging to a different Chemical class or having a different site of action. These additional biologîcally active compounds or agents include, but are not limited to, acetylcholinesterase (AChE) inhibîtors such as the carbainates methomyl, oxamyl, thiodicarb, triazamate, and the organophosphates chlorpyrifos; GABA-gated chloride channel antagonîsts such as the cyclodienes dieldrin and endosulfan, and the phenylpyrazoles ethiprole and fipronil; sodium channel modulators such as the pyrcthroids bifenthrin, cyfluthrin, beta-cyfluthrm. cyhalothrin, /r/mMa-cyhalothrin, cypermethrin, deltamethrin, dimefluthrin, esfenvalerate, metofluthrin and profluthrin; nicotinic acetylcholînereceptor (nAChR) agonists such as the neonicotinoids acetamiprid, clothianîdin, dinotefuran, îmidacloprid, nîtenpyram, nithiazine, thiacloprid, and thiamethoxam, and sulfoxaflor; nicotinic acétylcholine receptor (nAChR) allosteric activators such as the spinosyns spinetoram and spinosad; chloride channel activators such as the avermectins abamectin and emamectin; juvénile honnone mimics such as diofenolan, methoprene, fenoxycarb and pyriproxyfen; sélective homopteran feeding blockers such as pymetrozine and flonicamid; mite growth inhibîtors such as etoxazole; inhibîtors of mitochondrial ATP synthase such as propargite; ucouplers of oxidative phosphorylation via disruption of the proton gradient such as chlorfenapyr; nicotinic acétylcholine receptor (nAChR) channel blockers such as the nereistoxin analogs cartap; inhibîtors of chitin biosynthesis such as the benzoylureas flufenoxuron, hexaflumuron, lufenuron, novaluron, novitlumuron and triflumuron, and buprofezin; dipteran moulting disrupters such as cyromazine; ecdysone receptor agonists such as the diacylhydrazines methoxyfenozide and tebufenozîde; octopamine receptor agonists such as amitraz; mitochondrial complex III électron transport inhibîtors such as hydramethylnon; mitochondrial complex I électron transport inhibîtors such as pyridaben; voltage-dependent sodium channel blockers such as indoxacarb; inhibîtors of acetyl CoA carboxylase such as the tetronic and tetramic acids spirodiclofen, spiromesîfen and spirotetramat; mitochondrial complex II électron transport inhibîtors such as the β-ketonîtriles cyenopyrafen and cyflumetofen; ryanidine receptor modulators such as the anthranilic diamides chlorantraniliprole, cyantraniliprole and cyantraniiiprole, diamides such as flubendiamide, and ryanodine receptor ligands such as ryanodine; compounds wherein the target site responsible for biological activity is unknown or uncharacterized such as azadirachtin, bifenazate, pyridalyl, pyrifluquinazon and triflumezopyrim; microbial disrupters of insect midgut membranes such as Bacilius thuringensis and the delta-endotoxins they produce and Bacilius sphaericus', and biological agents including 87 nucleo polyhedro viruses (NPV) and other naturaily occurring or genetically modified insecticîdal viruses.

Further examples of biologically active compounds or agents with which compounds of this disclosure can be fonnulated are: fungicides such as acibenzolar-S-methyl, aldimorph, ametoctradin, amisulbrom, anilazine, azaconazole, azoxystrobin, benalaxyl (including benalaxylM), benodanil, benomyl, benthîavalicarb (including benthiavalicarb-isopropyl), benzovindiflupyr, bethoxazin, binapacryl, biphenyl, bitertanol, bixafen, blasticidin-S, boscalid, bromuconazole, bupirimate, buthîobate, carboxin, carpropamid, captafol, captan, carbendazim, chloroneb, chlorothalonil, chlozolînate, copper hydroxide, copper oxychloride, copper sulfate, coumoxystrobin, cyazofamid, cyflufenamid, cymoxanil, cyproconazole, cyprodinil, dichlofluanid, diclocymet, diclomezine, dicloran, diethofencarb, difenoconazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole (including dinîconazole-M), dinocap, dithianon, dithiolanes, dodemorph, dodine, econazole, etaconazole, edifenphos, enoxastrobin (also known as enestroburin), epoxiconazole, ethaboxam, ethirimol, etridiazole, famoxadone, fenamidone, fenaminstrobin, fenarimol, fenbuconazole, fenfuram, fenhexamide, fenoxanil, fenpiclonîl, fenpropidin, fenpropimorph, fenpyrazamine, fentin acetate, fentin hydroxide, ferbam, ferimzone, llometoquin, fluazinam, fludioxonil, flufenoxystrobin, flumorph, fluopicolide, fluopyram, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutîanil, flutolanil, flutriafol, fluxapyroxad, folpet, fthalide (also known as phthalide), fuberidazole, furalaxyl, furametpyr, hexaconazole, hymexazole, guazatine, imazalil, imibenconazole, iminoctadine albesilate, iminoctadine triacetate, iodicarb, ipconazole, isofetamid, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, isotianil, kasugamycin, kresoxim-methyl, mancozeb, mandipropamid, mandestrobin, maneb, mapanipyrin, mepronil, meptyldinocap, metalaxyl (including métal axyl-M/mefenoxam), metconazole, methasulfocarb, metiram, metominostrobin, metrafenone, myclobutanil, naftitine, neo-asozin (ferrie methanearsonate), nuarimol, octhilinone, ofurace, orysastrobin, oxadixyl, oxathiapiprolin, oxolinic acid, oxpoconazole, oxycarboxin, oxytetracycline, penconazole, pencycuron, penflufen, penthiopyrad, perfurazoate, phosphorous acid (including saits thereof, e.g., fosetyl-aluminm), picoxystrobin, piperalin, polyoxin, probenazote, prochloraz, procymidone, propamocarb, propiconazole, propineb, proquinazid, prothiocarb, prothioconazole, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyributacarb, pyrifenox, pyriofenone, perisoxazole, pyrimethanil, pyrifenox, pyrrolnitrin, pyroquilon, quinconazole, quinmethionate, quinoxyfen, quintozene, silthiofam, sedaxane, simeconazole, spiroxamine, streptomycin, sulfur, tebuconazole, tebufloquin, teclofthalam, tecloftalam, tecnazene, terbinafine, tetraconazole, thiabendazole, thifluzamide, thiophanate, thiophanate-methyl, thiram, tiadinil, tolclofos-m ethyl, tolprocarb, tolyfluanid, triadimefon, trîadimenol, triarimol, triazoxide, tribasic copper sulfate, triclopyricarb, tridemorph, trifloxystrobin, triflumizole, trimoprhamide tricyclazole, trifloxystrobin, triforine, triticonazole, unîconazoie, validamycin, valifenalate (also known as valifenal), vinclozolin, zineb, zîram, zoxamide and 1-[4-[4-(5-(2,6-difluorophenyl)-4,5-dihydro3-isoxazolyl] -2-thiazolyl ] -1 -piperidinyl] -2 - [5-methyl-3 -(trifluoromethy 1 )-1 H-pyrazol-1 yl]ethanone; nematocides such as fluopyram, spirotetramat, thiodicarb, fosthiazate, abamectîn, iprodione, fluensulfone, dim ethyl disulfïde, tioxazafen, 1,3-dichloropropene (1,3-D), metam (sodium and potassium), dazomet, chloropicrin, fenamiphos, ethoprophos, cadusaphos, terbufos, imicyafos, oxamyl, carbofuran, tioxazafen, Bacillus firmus and Pasteuria nishizawae; bactéricides such as streptomycin; acaricides such as amitraz, chinomethionat, chlorobenzilate, cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenbutatin oxide, fenpropatlirin, fcnpyroximate, hexythiazox, propargite, pyridaben and tebufenpyrad.

In certain instances, combinations of a compound of this disclosure with other biologically active (particularly invertebrate pest control) compounds or agents (i.e. active ingrédients) can resuit in an enhanced effect. Reducing the quantity of active ingrédients released in the environment while ensuring effective pest control is always désirable. When enhanced invertebrate pest control occurs at application rates giving agronomically satisfactory levels of invertebrate pest control, such combinations can be advantageous for reducing crop production cost and decreasing environmenta] load.

Compounds of this disclosure and compositions thereof can be applied to plants genetically transfonned to express proteins toxic to invertebrate pests (such as Bacillus thuringiensis deltaendotoxins). Such an application may provide a broader spectrum of plant protection and be advantageous for résistance management. The exogenously applied invertebrate pest control compounds of this disclosure in combination with the expressed toxin proteins may provide an enhanced effect.

General référencés for these agricultural protectants (i.e. insecticides, fongicides, nematocides, acaricides, herbicides and biologicai agents) include The Pesticide Manual, I3th Edition, C. D. S. Tomlîn, Ed., British Crop Protection Councii, Famham, Suney, U.K., 2003 and The BioPesticide Manual, 2^nd Edition, L. G. Copping, Ed., British Crop Protection Councii, Famham, Surrey, U.K., 2001.

Invertebrate pests are controlled in agronomie and nonagronomic applications by applying one or more compounds of this disclosure, typically in the form of a composition, in a biologically effective amount, to the environment of the pests, including the agronomie and/or nonagronomic locus of infestation, to the area to be protected, or directly on the pests to be controlled.

Thus the present disclosure comprises a method for controlling an invertebrate pest in agronomie and/or nonagronomic applications, comprising contacting the invertebrate pest or its environment with a biologically effective amount of one or more of the compounds of the disclosure, or with a composition comprising at least one such compound or a composition comprising at least one such compound and a biologically effective amount of at least one additional biologically active compound or agent. Examples of suitable compositions comprising a compound of the disclosure and a biologically effective amount of at least one additional biologically active compound or agent include granular compositions wherein the additional active compound is present on the same granule as the compound of the disclosure or on granules separate from those of the compound of the disclosure.

To achieve contact with a compound or composition of the disclosure to protect a field crop from invertebrate pests, the compound or composition is typically applied to the seed of the crop before planting, to the foliage (e.g., leaves, stems, flowers, fruits) of crop plants, or to the soil or other growth medium before or aller the crop is planted.

One embodiment of a method of contact is by spraying. Altematively, a granular composition comprising a compound of the disclosure can be applied to the plant foliage or the soil. Compounds of this disclosure can also be effectively delivered through plant uptake b y contacting the plant with a composition comprising a compound of this disclosure applied as a soil drench of a liquid formulation, a granular formulation to the soil, a nursery box treatment or a dip of transplants. Of note is a composition of the present disclosure in the form of a soil drench liquid formulation. Also of note is a method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound of the present disclosure or with a composition comprising a biologically effective amount of a compound of the present disclosure. Of further note is this method wherein the environment is soil and the composition is applied to the soil as a soil drench formulation. Of further note is that compounds of this disclosure are also effective by localized application to the locus of infestation. Other methods of contact include application of a compound or a composition of the disclosure by direct and residual sprays, aerial sprays, gels, 90 seed coati ngs, microencapsulations, systemic uptake, baits, ear tags, boluses, foggers, fumigants, aérosols, dusts and many others. One embodiment of a method of contact is a dimensionally stable fertilizer granule, stick or tablet comprising a compound or composition of the disclosure. The compounds of this disclosure eau also be impregnated into materials for fabricating invertebrate control devices (e.g., insect netting).

Compounds of the disclosure are useful in treating ail plants, plant parts and seeds. Plant and seed varieties and cultivars can be obtained by conventional propagation and breeding methods or by genetic engineering methods. Genetically modified plants or seeds (transgenic plants or seeds) are those in which a heterologous gene (transgene) has been stably integrated into the plant's or seed's genome. A transgene that is defined by its particular location in the plant genome is called a transformation or transgenic event.

Genetically modified plant and seed cultivars which can be treated according to the disclosure include those that are résistant against one or more biotic stresses (pests such as nematodes, însects, mites, fungi, etc.) or abiotic stresses (drought, cold température, soi! salinity, etc.), or that contaîn other désirable characteristics. Plants and seeds can be genetically modified to exhîbit traits of, for example, herbicide tolérance, insect-resistance, modified oil profiles or drought tolérance.

Treatment of genetically modified plants and seeds with compounds of the disclosure may resuit in super-additive or enhanced effects. For example, réduction in application rates, broadening of the activity spectrum, increased tolérance to biotic/abiotic stresses or enhanced storage stability may be greater than expected from just simple additive effects of the application of compounds of the disclosure on genetically modified plants and seeds.

Compounds of this disclosure are also useful in seed treatments for protecting seeds from invertebrate pests. In the context of the présent disclosure and daims, treating a seed means contacting the seed with a biologically effective amount of a compound of this disclosure, which is typically fonnulated as a composition of the disclosure. This seed treatment protects the seed from invertebrate soil pests and generaliy can also protect roots and other plant parts in contact with the soil of the seedling developing from the germinating seed. The seed treatment may also provide protection of foliage by translocation of the compound of this disclosure or a second active ingrédient within the developing plant. Seed treatments can be applied to ail types of seeds, including those from which plants genetically transformed to express specîalized traits will germinate. Représentative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis toxîn or those expressing herbicide résistance such as 91 glyphosate acetyltransferase, which provides résistance to glyphosate. Seed treatments with compounds of this disclosure can also increase vigor of plants growing from the seed.

One method of seed treatment is by spraying or dusting the seed with a compound of the disclosure (i.e. as a formulated composition) before sowing the seeds. Compositions formulated for seed treatment generally comprise a film former or adhesive agent. Therefore typically a seed coating composition of the présent disclosure comprises a biologically effective amount of a compound of Formula 1, and a film former or adhesive agent. Seed can be coated by spraying a flowable suspension concentrate directly into a tumbling bed of seeds and then drying the seeds. Altematively, other formulation types such as wetted powders, solutions, suspoemulsions, emulsifiable concentrâtes and émulsions in water can be sprayed on the seed. This process is particularly useful for applying film coatings on seeds. Varions coating machines and processes are available to one skilled in the art. Suitable processes include those listed in P. Kosters et al., Seed Treatment: Progress and Prospects, 1994 BCPC Mongraph No. 57, and référencés listed thereîn.

Compounds of Formula 1 and their compositions, both alone and in combination with other insecticides, nematicides, and fongicides, are particularly useful in seed treatment for crops including, but not limited to, maize or corn, soybeans, cotton, cereal (e.g., wheat, oats, barley, rye and rice), potatoes, vegetables and oilseed râpe.

Other insecticides with which compounds of Formula 1 can be formulated to provide mixtures useful in seed treatment include abamectin, acetamiprid, acrinathrin, amitraz, avermeetîn, azadirachtin, bensultap, bifenthrin, buprofezin, cadusafos, carbaryl, carbofuran, cartap, chlorantranilîprole, chlorfenapyr, chlorpyrifos, clothianidin, cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, alphacypennethrin, zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefùran, diofenolan, emamectin, endosulfan, esfenvalerate, ethiprole, etofenprox, etoxazole, fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, flubendiamide, flufenoxuron, fluvalinate, formetanate, fosthiazate, hexaflumuron, hydramethylnon, imidactoprid, indoxacarb, lufenuron, metaflumizone, methiocarb, methomyl, methoprene, methoxyfenozide, nitenpyram, nithiazîne, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, pyridalyl, pyriproxyfen, ryanodine, spinetoram, spinosad, spirodiclofen, spiromesifen, spirotetramat, sulfoxaflor, tebufenozide, tetramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, ail strains of Bacillus thuringiensis and ail strains of nucleo polyhedrosis viruses.

Fungicides with which compounds of Formula I can be formulated to provide mixtures useful in seed treatment include amisulbrom, azoxystrobin, boscalid, carbendazim, carboxin, cymoxanil, cyproconazole, difenoconazole, dimethoinorph, fiuazinam, fludioxonil, fluquinconazole, fluopicolide, fluoxastrobin, flutriafol, fluxapyroxad, îpconazole, iprodione, metalaxyl, mefenoxam, metconazole, myclobutanil, paclobutrazole, penflufen, picoxystrobîn, prothioconazole, pyraclostrobin, sedaxane, silthiofam, tebuconazole, thiabendazole, thiophanatemethyl, thiram, trifloxystrobin and triticonazole.

Compositions comprising compounds of Formula 1 useful for seed treatment can further comprise bacteria and fungi that hâve the ability to provide protection from the hannful effects of plant pathogénie fungi or bacteria and/or soil bom animais such as nematodes. Bacteria exhibiting nematîcîdal properties may include but are not limited to Bacillus firmus, Bacillus cereus. Bacillius subtiliis and Pasteuria penetrans. A suitable Bacillus firmus strain is strain CNCM 1-1582 (GB-126) which is commercially available as BioNem™. A suitable Bacillus cereus strain is strain NCMM 1-1592. Both Bacillus strains are disclosed in US 6,406,690. Other suitable bacteria exhibiting nematicidal activity are B. amyloliquefaciens IN937a and B. subtilis strain GB03. Bacteria exhibiting fungicidal properties may include but are not limited to B. pumilus strain GB34. Fungal species exhibiting nematicidal properties may include but are not limited to Myrothecium verrucaria, Paecilomyces lilacinus and Purpureocillium lilacinum.

Seed treatments can also include one or more nematicidal agents of natural origin such as the elicitor protein called harpin which is isolated from certain bacterial plant pathogens such as Erwinia amylovora. An example is the Harpîn-N-Tek seed treatment technology available as NHibit™ Gold CST.

Seed treatments can also include one or more species of legume-root noduïating bacteria such as the microsymbiotic nitrogen-fïxing bacteria B rady rhizobium japonicum. These inocculants can optionally include one or more lipo-chitooligosaccharides (LCOs), which are nodulation (Nod) factors produced b y rhizobia bacteria during the initiation of nodule formation on the roots of legumes. For exampie, the Optimize® brand seed treatment technology incorporâtes LCO Promoter Technology^{3 M} in combination with an inocculant.

Seed treatments can also include one or more isoflavones which can increase the leveî of root colonization by mycorrhîzal fungi. Mycorrhizal fungi improve plant growth by enhancîng the root uptake of nutrients such as water, sulfates, nitrates, phosphates and metals. Examples of isoflavones include, but are not limited to, genistein, biochanîn

A, formononetin, daidzein, glycitein, hesperetin, naringenin and pratensein. Formononetin is available as an active ingrédient in mycorrhizal inocculant products such as PHC Colonize® AG.

Seed treatments can also include one or more plant activators that induce systemîc acquired résistance in plants following contact by a pathogen. An example of a plant activai or which induces such protective mechanisms is acibenzolar-5-methyl.

The treated seed typically comprises a compound of the present disclosure in an amount from about 0.1 g to 1 kg per 100 kg of seed (Le. from about 0.0001 to 1% by weight of the seed before treatment). A flowable suspension tbrmulated for seed treatment typically comprises from about 0.5 to about 70% of the active ingrédient, from about 0.5 to about 30% of a filmforming adhesive, from about 0.5 to about 20% of a dispersing agent, from 0 to about 5% of a thickener, from 0 to about 5% of a pigment and/or dye, from 0 to about 2% of an antifoaming agent, from 0 to about 1% of a preservative, and from 0 to about 75% of a volatile liquid diluent.

The compounds of this disclosure can be incorporated into a bait composition that is consumed by an invertebrate pest or used within a device such as a trap, bait station, and the like. Such a bait composition can be in the form of granules which comprise (a) active ingrédients, namely a biologically effective amount of a compound of Formula 1; (b) one or more food materials; optionally (c) an attractant, and optionally (d) one or more humectants. Of note are granules or bait compositions which comprise between about 0.001-5% active ingrédients, about 40-99% food material and/or attractant; and optionally about 0.05-10% humectants, which are effective in controlling soil invertebrate pests at very low application rates, particularly at doses of active ingrédient that are léthal by ingestion rather than by direct contact. Some food materials can function both as a food source and an attractant. Food materials include carbohydrates, proteins and lipids. Examples of food materials are vegetable flour, sugar, starches, animal fat, vegetable oil, yeast extracts and milk solids. Examples of attractants are odorants and flavorants, such as fruit or plant extracts, perfume, or other animal or plant component, pheromones or other agents known to attract a target invertebrate pest. Examples of humectants, i.e. moisture retaining agents, are glycols and other polyols, glycérine and sorbitol. Of note is a bait composition (and a method utilîzîng such a bait composition) used to control at least one invertebrate pest selected from the group consisting of ants, termites and cockroaches. A device for controlling an invertebrate pest can comprise the present bait composition and a housing adapted to receive the bait composition, wherein the housing has at least one opening sized to permit the invertebrate pest to pass through the opening so the invertebrate pest can gain access to the bait composition from a location outside the housing, and wherein the housing is 94 further adapted to be placed in or near a locus of potentîal or known activity for the invertebrate pest.

One embodiment of the présent disclosure relates to a method for controlling invertebrate pests, comprising diluting the pesticidal composition of the présent disclosure (a compound of Formula 1 formulated with surfactants, solid diluents and liquid diluents or a formulated mixture of a compound of Formula 1 and at least one other pesticide) with water, and optionally adding an adjuvant to form a diluted composition, and contacting the invertebrate pest or its environment with an effective amount of said diluted composition.

Although a spray composition formed by diluting with water a sufficient concentration of the présent pesticidal composition can provide sufficient efficacy for controlling invertebrate pests, separately formulated adjuvant products can also be added to spray tank mixtures. These additional adjuvants are commonly known as “spray adjuvants” or “tank-mix adjuvants”, and include any substance mixed in a spray tank to improve the performance of a pesticide or alter the physical properties of the spray mixture. Adjuvants can be surfactants, emulsîfying agents, Petroleum-based crop oils, crop-derived seed oils, acidifiers, buffers, thickeners or defoaming agents. Adjuvants are used to enhancîng efficacy (e.g., biological availability, adhesion, pénétration, uniformity of coverage and durability of protection), or minimizing or eliminating spray application problems associated with incompatibîlity, foaming, drift, évaporation, volatilîzation and dégradation. To obtain optimal performance, adjuvants are selected with regard to the properties of the active ingrédient, formulation and target (e.g., crops, insect pests).

Among the spray adjuvants, oils including crop oils, crop oil concentrâtes, vegetable oil concentrâtes and methylated seed oil concentrâtes are most commonly used to improve the efficacy of pesticides, possibly by means of promoting more even and uniform spray deposits. In situations where phytotoxicity potentîally caused by oils or other water-immîscible liquids are of concem, spray compositions prepared from the composition of the présent disclosure will generally not contain oil-based spray adjuvants. However, in situations where phytotoxicity caused by oil-based spray adjuvants is commercially însignificant, spray compositions prepared from the composition of the présent composition can also contain oil-based spray adjuvants, which can potentîally further increase control of invertebrate pests, as well as rainfastness.

Products identified as “crop oil” typically contain 95 to 98% paraffin or naphtha-based Petroleum oil and î to 2% of one or more surfactants functioning as emulsifiers. Products identified as “crop oil concentrâtes” typically consîst of 80 to 85% of emulsifiable petroleumbased oil and 15 to 20% of nonionic surfactants. Products correctly identified as “vegetable oil 95 concentrâtes” typically consîst of 80 to 85% of vegetable oil (i.e. seed or fruit oil, most commonly from cotton, linseed, soybean or sunflower) and 15 to 20% of nonionic surfactants. Adjuvant performance can be improved by replacing the vegetable oil with methyl esters of fatty acids that are typically derived from vegetable oîls. Examples of methylated seed oil concentrâtes include MSO® Concentrate (UAP-Loveland Products, Inc.) and Premium MS O Methylated Spray Oil (Helena Chemical Company).

The amount of adjuvants added to spray mixtures generally does not exceed about 2.5% by volume, and more typically the amount is from about 0.1 to about 1% by volume. The application rates of adjuvants added to spray mixtures are typically between about 1 to 5 L per hectare. Représentative examples of spray adjuvants include: Adigor® (Syngenta) 47% methylated rapeseed oil in liquid hydrocarbons, Sîlwet® (Helena Chemical Company) polyalkyleneoxide modified heptamethyltrisiloxane and Assist® (BASF) 17% surfactant blend in 83% paraffin based minerai oil.

The compounds of this disclosure can be applied without other adjuvants, but most often application will be of a formulation comprising one or more active ingrédients with suitable carriers, diluents, and surfactants and possibly in combination with a food depending on the contemplated end use. One method of application involves spraying a water dispersion or refined oil solution of a compound of the présent disclosure. Combinations with spray oîls, spray oil concentrations, spreader stickers, adjuvants, other solvents, and piperonyl butoxide often enhance compound efficacy. For nonagronomic uses such sprays can be applied from spray containers such as a can, a bottle or other container, either by means of a pump or by releasing it from a pressurized container, e.g., a pressurized aérosol spray can. Such spray compositions can take various forms, for example, sprays, mists, foams, fumes or fog. Such spray compositions thus can further comprise propellants, foaming agents, etc. as the case may be. Of note is a spray composition comprising a biologically effective amount of a compound or a composition of the présent disclosure and a carrier. One embodiment of such a spray composition comprises a biologically effective amount of a compound or a composition of the présent disclosure and a propellant. Représentative propellants include, but are not limited to, methane, ethane, propane, butane, isobutane, butene, pentane, îsopentane, neopentane, pentene, hydrofluorocarbons, chlorofluorocarbons, dimethyl ether, and mixtures of the fore go mg. Of note is a spray composition (and a method utilizing such a spray composition dispensed from a spray container) used to control at least one invertebrate pest selected from the group consisting of mosquitoes, black Aies, stable Aies, deer Aies, horse Aies, wasps, yellow jackets, homets, ticks, spiders, ants, gnats, and the like, including individually or in combinations.

The following Tests demonstrate the control efficacy of compounds of this disclosure on spécifie pests. “Control efficacy” represents inhibition of invertebrate pest development (including mortality) that causes significantly reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. See Index Table A for compound descriptions.

BIOLOGICAL EXAMPLES OF THE INVENTION

Formulation and Spray Methodology for Tests A-H

Test compounds were fonnulated using a solution containing 10% acetone, 90% water and 300 ppm Activator 90® non-ionic surfactant (Loveland Products, Loveland, Colorado, USA). The fonnulated compounds were applied in 1 mL of liquid through an atomizer nozzle posîtioned 1.27 cm (0.5 inches) above the top of each test unit. Test compounds were sprayed at the rates indicated, and each test was replicated three times.

Test A

For evaluating control of diamondback moth (Plutella xylostella (L.)) the test unit consi sted of a small open container with a 12—14-day-old mustard plant inside. This was preinfested with -50 neonate larvae that were dispensed into the test unit via corn cob grits using an inoculator. The larvae moved onto the test plant after being dispensed into the test unit.

Test compounds were fonnulated and sprayed at 250, 50, 10, 2, and 0.4 ppm. After spraying of the fonnulated test compound, each test unit was allowed to dry for 1 hour and then a black, screened cap was placed on top. The test unîts were held for 6 days in a growth chamber at 25 °C and 70% relative humidity. Plant feeding damage was then visually assessed based on foliage consunied, and larvae were assessed for mortality.

Of the compounds of Fonnula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1 and 2.

Of the compounds of Fonnula 1 tested at 50 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1 and 2.

Of the compounds of Formula 1 tested at 10 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): I, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 59, 70, 71, and 74.

Of the compounds of Formula 1 tested at 2 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1, 2, 3,

4, 5, 6, 7, 8,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 23, 26, 27, 28, 29, 30, 32, 33, 34, 35,

36, 37, 38, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51,52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62,

64, 65, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91,

92,93,94, 95, and 96.

Of the compounds of Formula 1 tested at 0.4 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 3, 10,

H, 13, 15, 16, 17, 18, 20, 23, 26,27,28, 30, 32, 33,35, 36, 37,42,43,44,45,46,47,48, 49, 50,

51,52, 53, 54, 55, 56, 58, 59, 60, 61, 66, 67, 68, 70, 71,72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82,

84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 95, and 96.

Test B

For evaluating control of fall armyworm (Spodoptera frugiperda (J.E. Smith)) the test unit consisted of a small open container with a 4—5-day-old corn (maize) plant insîde. This was pre-infested with 10-15 1-day-old larvae on a piece of insect diet.

Test compounds were formulated and sprayed at 250, 50, 10, 2, and 0.4 ppm. After spraying of the formulated test compound, the test uaits were maintained in a growth chamber for 6 days at 25 °C and 70% relative humidity. Plant feeding damage was then visually assessed based on foliage consumed, and larvae were assessed for mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1 and 2.

Of the compounds of Formula 1 tested at 50 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 1 and 2.

Of the compounds of Fonnula 1 tested at 10 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 2, 3, 4,

6, 7, 8, 9, 10, 11, 13, 15, 16, 17, 18, 19, 20, 23, 26, 27, 28, 29, 32, 33, 34, 35, 36, 37, 38, 42, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 59, 70, 71, and 74.

Of the compounds of Formula 1 tested at 2 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 2, 3, 4, 10, 13, 16, 17, 18, 20, 23, 28, 32, 33, 35, 36, 37, 44, 45, 46, 47, 48, 53, 55, 58, 59, 60, 61, 66, 67, 68, 70, 71, 72, 73, 74, 75, 77, 78, 80, 81, 82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 94, 95, 96, and 101.

Of the compounds of Formula 1 tested at 0.4 ppm, the following provided very good to excellent levels of control efficacy (40% or less feeding damage and/or 100% mortality): 3, 13, 16, 17, 23, 28, 35, 36, 37, 47, 48, 58, 59, 60, 61, 66, 68, 70, 73, 74, 77, 81, 82, 84, 85, 88, 89, 90, 91, and 92.

Teste

For evaluating control of corn planthopper (Peregrinus maidis (Ashmead)) through contact and/or systemic means, the test unit consisted of a small open container with a 3-4-day-old corn (inaize) plant inside. White sand was added to the top of the soil prior to application of the test compound.

Test compounds were fomiulated and sprayed at 50 and 10 ppm. After spraying of the formulated test compound, the test units were allowed to dry for 1 h before they were postinfested with -15-20 nymphs (18-to-2l-day-old). A black, screened cap was placed on the top of each test unit, and the test units were held for 6 days in a growth chamber at 22-24 °C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 50 ppm, the following rcsulted in at least 80% mortality: 4, 6, 18, 29, 35, 37, 48, 55, 58, 66, 68, 72, 73, 74, 75, 76, 80, 81, 86, 88, 90, and 92.

Of the compounds of Fonnula 1 tested at 10 ppm, the following resulted in at least 80% mortality: 76.

Test D

For evaluating control of potato leafhopper (Empoasca fabae (Harris)) through contact and/or systemic means, the test unit consisted of a small open container with a 5-6-day-old Soleil bean plant (primary leaves emerged) inside. White sand was added to the top of the soil, and one of the primary leaves was excised prior to application of the test compound.

Test compounds were formulated and sprayed at 250, 50 and 10 ppm. After spraying of the formulated test compound, the test units were allowed to dry for 1 hour before they were post-infested with 5 potato leafhoppers (18-to-21-day-old adults). A black, screened cap was placed on the top of the test unit, and the test unîts were held for 6 days in a growth chamber at 20 °C and 70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% 5 mortality: 2,

Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 2, 4, 6, 7, 10, il, 13, 14, 20, 21,23, 28, 32, 35, 36, 37, 43,45, 48, 49, 53, 55, 58, 61, 62, 66, 68, 70, 71, 74, 76, 77, 80, 81, 82, 86, and 92.

Of the compounds of Formula 1 tested at 10 ppm, tire following resulted in at least 80% 10 mortality: 11,13,35, 36, 61, and 81.

Test E

For evaluatîng control of green peach aphid (Myzus persicae (Sulzer)) through contact and/or systemic means, the test unit consisted of a small opcn container with a 12-15-day-old radish plant inside. This was pre-infested by piacing on a leaf of the test plant 30^40 aphids on a 15 piece of leaf excised from a culture plant (cut-leaf method). The aphids moved onto the test plant as the leaf piece desiccated. After pre-infestation, the soil of the test unit was covered with a layer of sand.

Test compounds were formulated and sprayed at 250, 50 and 10 ppm. After spraying of the formulated test compound, each test unit was allowed to dry for 1 hour and then a black, 20 screened cap was placed on top. The test units were held for 6 days in a growth chamber at 1921 °C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 80% mortality: 1 and 2.

Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 2,3,4, 6, 7, 10, 11, 13, 16, 17, 18,20,23,27,28,29, 32, 34, 35, 36,37,38,45,48, 53, 55, 56, 58, 60, 61, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 80, 81, 82, 85, 86, 87, 88, 89, 90, 91, and 92.

Of the compounds of Fonnula 1 tested at 10 ppm, the following resulted in at least 80% 30 mortality: 3, 6, 13, 17, 18, 20, 23, 28, 35, 36, 45, 58, 61, 66, 68, 81, 82, 86, 89, and 90.

100

Test F

For evaluating control of cotton melon aphid (Aphis gossypii (Glover)) through contact and/or systemic means, the test unit consi sied of a small open container with a 5-day-old okra plant inside. This was pre-infested with 30—40 insects on a piece of leaf according to the cut-leaf method, and the soil of the test unit was covered with a layer of sand.

Test compounds were formulated and sprayed at 250, 50 and 10 ppm. Aller spraying, the test units were maintained in a growth chamber for 6 days at 19 °C and 70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Fonnula 1 tested at 50 ppm, the following resulted in at least 80% mortality: 1, 2, 3,4, 6, 7, 8, 10, 11, 12, 13, 15, 17, 18, 19, 20, 21,23, 25, 26, 27, 28, 29, 30, 32, 35, 36, 37, 40, 43, 44, 45, 46, 48, 53, 55, 56, 58, 59, 60, 61, 62, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, ΊΊ, 79, 80, 81, 82, 84, 85, 86, 87, 89, 90, 91, 92, 94, 96, and 101.

Of the compounds of Formula 1 tested at 10 ppm, the following resulted in at least 80% mortality: 2, 3, 4, 6, 13, 17, 20, 23, 28, 35, 36, 37,46, 55, 58, 61, 66, 67, 68, 70, 72, 73, 76, 80, 81,82, 85, 86, 89, and 90.

Test G

For evaluating control of the sweetpotato whitefly (Bemisia tabaci (Gennadius)) through contact and/or systemic means, the test unit consisted of a small open container with a 12-14day-old cotton plant inside. Prier to the spray application, both cotylédons were removed from the plant, leaving one true leaf for the assay. Adult whiteflies were allowed to lay eggs on the plant and then were removed from the test unit. Cotton plants infested with at least 15 eggs were submitted to the test for spraying.

Test compounds were formulated and sprayed at 250, 50 and 10 ppm. Aller spraying, the test units were allowed to dry for 1 hour. The cylinders were then removed, and the units were taken to a growth chamber and held for 13 days at 28 °C and 50-70% relative humidity. Each test unit was then visually assessed for insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following resulted in at least 50% mortality: 1 and 2.

101

Of the compounds of Formula 1 tested at 50 ppm, the following resulted in at least 50% mortality: 1, 2, 3, 4, 6, 7, 10, 13, 19, 20, 21, 26, 28, 32, 35, 36, 37, 44, 47, 53, 55, 56, 58, 61, 62, 66, 68, 71, 72, 74, 75, 76, 77, 79, and 80.

Of the compounds of Formula 1 tested at 10 ppm, the following resulted in at least 50% mortality: 2, 3, 4, 10, 13, 20, 28, 32, 35, 36, 37, 44, 47, 53, 55, 61, 71, and 80.

Test H

For evaluating control of the Western Flower Thrips (Frankliniellla occidentalis (Pergande)) through contact and/or systemic means, the test unit consisted of a small open container with a 8-9-day-old Soleil bean plant insîde.

Test compounds were formulated and sprayed at 250, 50, 10 and 2 ppm. After spraying, the test units were aliowed to dry for 1 hour, and then -60 thrips (adults and nymphs) were added to each unit. A black, screened cap was placed on top, and the test units were held for 6 days at 25 °C and 45-55% relative humidity. Each test unit was then visually assessed for plant damage and insect mortality.

Of the compounds of Formula 1 tested at 250 ppm, the following provided very good to excellent levels of control effîcacy (30% or less plant damage and/or 100% mortality): 1 and 2.

Of the compounds of Formula 1 tested at 50 ppm, the following provided very good to excellent levels of control effîcacy (30% or less plant damage and/or 100% mortality): 1.

Of the compounds of Formula 1 tested at 10 ppm, the following provided very good to excellent levels of control effîcacy (30% or less plant damage and/or 100% mortality): 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 22, 23, 24, 25, 26, 27, 29, 30, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 59, 71, and 74.

Of the compounds of Formula 1 tested at 2 ppm, the following provided very good to excellent levels of control effîcacy (30% or less plant damage and/or 100% mortality): 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 15, 16, 17, 18, 19, 20, 23,26, 27, 28, 29, 30, 32, 33, 34, 35, 36, 37, 38, 41, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 55, 58, 59, 60, 61, 66, 67, 68, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81,82, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, and 101.

Of the compounds of Formula I tested at 0.4 ppm, the following provided very good to excellent levels of control effîcacy (30% or less plant damage and/or 100% mortality): 2, 3, 4, 13, 16, 17, 23, 28, 35, 36, 37, 44, 45, 46, 47, 48, 53, 55, 58, 60, 61, 67, 68, 70, 74, 75, 76, 77, 78, 79, 80, 81, 82, 84, 85, 88, 89, 90, 91, 92, 93, 94, 95, 96, and 101.

102

Claims

1,3,4,4a, 5,6,6a, 12,12 a, 12b-decahydro-6,12-dihydroxy-4,6a, 12b-trimethyl-l 1 -oxo-9(3-pyridinyl)~2/7,l lÆ-naphtho[2,l-b]pyrano[3,4-e]pyran-4-yl]methyl cyclopropanecarboxylate), amidoflumet, amitraz, avermectin, azadirachtin, azinphos-methyl, benforacarb, bensultap, benzpyrimoxan, bifenthrîn, kappabifenthrin, bifenazate, bistrifluron, borate, broflanilide, buprofezin, cadusafos, carbaryl, carboforan, cartap, carzol, chlorantramliprole, chlorfenapyr, chlorfluazuron, chloroprallethrin, chlorpyrifos, chlorpyrifos-e, chlorpyrifos-methyl, chromafenozide, clofentezin, chloroprallethrin, clothianidin, cyantraniliprole (3bromo-l-(3-chloro-2-pyridinyl)-W-[4-cyano-2-methyl-6[(methylamino)carbonyl]phenyl]-l//-pyrazole-5-carboxamide), cyclaniliprole (3bromo-jV-[2-bromo-4-chloro-6-[[( 1 -cyclopropylethyl)amino]carbonyl]phenylj-1 -(3chloro-2-pyridinyl)-17/-pyrazole-5-carboxamîde), cycloprothrin, cycloxaprid ((55,8R)-l-[(6-chloro-3-pyridinyl)methyl]-2,3,5,6,7,8-hexahydro-9-nitro-5,8-Epoxyl/7-imidazo[l,2-a]azepine), cyenopyrafen, cyflumetofen, cyfluthrin, beta-cyfluthrîn, cyhalodiamide, cyhalothrin, gamina-cyhalothrin, lambda-cyhalothrin, cypermethrin, alpha-cypermethrin, zeta-cypermethrin, cyromazine, deltamethrin, diafenthiuron, diazinon, dicloromezotiaz, dieldrin, dîflubenzuron, dimefluthrin, dimehypo, dimethoate, dimpropyridaz, dinoteforan, diofenolan, emamectin, emamectin benzoate, endosulfan, esfenvalerate, ethiprole, etofenprox, epsilon-metofluthrin, etoxazole, fenbutatin oxide, fenitrothion, fenothiocarb, fenoxycarb, fenpropathrin,

107 fenvalerate, fïpronil, ilometoquin (2-ethyI-3,7-dimethyl-6-[4(trifluoromethoxy)phenoxy]-4-quinolinyl methyl carbonate), flonicamid, fluazaindolizine, flubendîamide, flucythrinate, flufenerim, flufenoxuron, flufenoxystrobin (methyl (a£)-2-[[2-chloro-4<trifluoromethyl)phenoxy]methyl]-a(methoxymethylene)benzeneacetate), fluensulfone (5-chloro-2-[(3,4,4-trifluoro-3buten-l-yl)sulfonyl]thiazole), fluhexafon, fluopyram, flupiprole (l-[2,6-dichloro-4(trifluoromethyl)phenyl]-5-[(2-methyl-2-propen-l-yl)amino]-4[(trifluoroinethyl)sulfïnyl]-l/7-pyrazole-3-carbonitrile), flupyradîfiirone (4-[[(6chloro-3-pyridinyl)methyl](2,2-difluoroethyl)amino]-2(5//)-furanone), flupyrimin, fluvalinate, tau-fluvalinate, fluxametamide, fonophos, formetanate, fosthiazate, gamma-cyhalothrin, halofenozide, heptafluthrin ([2,3,5,6-tetrafluoro-4(methoxymethyl)phenyl] methyl 2,2-dimethyl-3-[( 12)-3,3,3-trifluoro-l -propen-1yl] cyclopropan ecarboxylate), hexaflumuron, hexythîazox, hydramethylnon, îmîdacloprid, indoxacarb, insecticidal soaps, isofenphos, isocycloseram, kappatefluthrîn, lambda-cyhalothrin, lufenuron, malathion, meperfluthrin ([2,3,5,6tetrafluoro-4-(methoxymethyl)phenyl]methyl (IA,3S)-3-(2,2-dichloroethenyl)-2,2dimethylcyclopropanecarboxylate), metaflumizone, metaldehyde, methamidophos, methidathion, methiocarb, methomyl, methoprene, methoxychlor, metofluthrin, methoxyfenozide, epsîlon-metofluthrin, epsilon-momfluorothrin, monocrotophos, monofluorothrin ([2,3,5,6-tetratluoro-4-(methoxymethyl)phenyI]methyl 3-(2-cyano1-propen-l -yl )-2,2-dim ethyl cyclopropanecarboxylate), nicotine, nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl, oxazosulfyl, parathion, parathion-m ethyl, permethrin, phorate, phosalone, phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, propargite, protrifenbute, pyflubumide (1,3,5trimethyl-7V-(2-inethyl-l-oxopropyl)-A^/'-[3-(2-methylpropy[)-4-[2,2,2-trifluoro-lmethoxy-l-(trifluoromethyl)ethyl]phenyl]-l//-pyrazole-4-carboxamide), pymetrozîne, pyrafluprole, pyrethrin, pyridaben, pyridalyl, pyriflnquinazon, pyriminostrobin (methyl (a£)-2-[[[2-[(2,4-dichlorophenyl)amino]-6(trifluoiOmethyl)-4-pyrimidinyl]oxy] methyl]-a-(methoxymethylene)benzeneacetate), pydîflumetofen, pyriprole, pyriproxyfen, rotenone, ryanodine, silafluofen, spinetoram, spinosad, spirodiclofen, spiromesifen, spiropîdion, spirotetramat, sulprofos, sulfoxaflor (JV-[methyloxido[ I -[6-(trifluoromethyl)-3-pyridinyl]ethyl]-λ⁴sulfanylidene]cyanamide), tebufenozide, tebufenpyrad, teflubenzuron, tefluthrin,

108 kappa-tefluthrîn, terbufos, tetrachlorantraniliprole, tetrachlorvinphos, tetramethrin, tetramethylfluthrin ([2,3,5,6-tetrafluoro-4-(methoxymethyl)phenyl]methyl 2,2,3,3tetramethylcyclopropanecarboxylate), tetraniliprole, thiacloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tioxazafen (3-phenyI-5-(2-thienyl)-l,2,4-oxadiazole), tolfenpyrad, tralomethrin, triazamate, trichlorfon, triflumezopyrim (2,4-dioxo-l-(5pyrimidinylmethyl)-3-[3-(trifluoromethyl)phenyl]-2Æ-pyrido[l,2-a]pyrimidinium înner sait), triflumuron, tyclopyrazoflor, zeta-cypermethrin, Bacillus thuringiensis delta-endotoxins, entomopathogenic bacteria, entomopathogenic viruses, and entomopathogenic fungi.

1. A compound selected from Formula 1,

103

RfosH, Cl or CF₃;

R² is H, F or Cl;

R³ is H, Cl or CF₃;

R⁴ is C]-C₆ alkyl, C₂-C₆ alkenyl, C₂-Cg alkynyl, C₃-C₆ cycloalkyl, C₃—Cg cycloalkenyl, C₄-C₈ alkylcycloalkyl or C₄-Cg cycloalkylalkyl, each unsubstituted or substituted with substituents independently selected from halogen, cyano and CO₂R¹⁸;

R⁵ is H or Cj-C₄ alkyl;

R⁶ is OR¹⁴ or S(O)_nR¹⁵;

R⁷ is H or Cj-C₄ alkyl;

R⁸isHorCi~C₄ alkyl;

R⁹ is H; or C^-C4 alkyl, unsubstituted or substituted with substituents independently selected from halogen, cyano, OR¹ A S(O)nR¹⁷ and CO_?R^l$;

R¹⁰ is H or C;-C₄ alkyl;

Rⁿ isHorC₁-C₄ alkyl;

R¹² is H; or Cj-C4 alkyl, unsubstituted or substituted with substituents independently selected from halogen, cyano, OR¹⁶, S(O)nR¹⁷ and CO₂R¹⁸;

R¹³ ts H, C]—C₄ alkyl or C]-C₄ haloalkyl;

R¹⁴isC!-C₄ alkyl;

R¹⁵ is H, Cj-C₄ alkyl or C₁-C₄ haloalkyl;

each R¹⁶ is independently Cj-C₄ alkyl or C!-C₄ haloalkyl;

each R¹⁷ is independently Cj-C₄ alkyl or C^^ haloalkyl;

each R¹⁸ is independently Cj-C₄ alkyl or C]-C₄ haloalkyl;

Z is pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl or tetrahydrofuranyl, each unsubstituted or substituted with R¹⁹;

each R¹⁹ is independently halogen, cyano, nitro, Cj-C₄ alkyl, C_t-C₄ haloalkyl, C]-C₄alkoxy, Cj-C₄ haloalkoxy, Cj-C4 alkylthio, Cj-C₄ haloalkylthio, C]-C₄aîkylsulfmyl, C]-C₄ haloalkylsulfinyl, C]-C₄ alkylsulfonyl, C₁~C₄

104 haloalkylsulfonyl, C2-C5 alkoxycarbonyl, C2-C5 alkylaminocarbonyl and C₃-C₅dialkylaminocarbonyl;

R²⁰ is H, C[—C₄ alkyl or C1-C4 haloalkyl;

R²¹ is fluoro, €^04 alkyl, C4-C4 haloalkyl, Cj-C₆ alkoxy, C^Cg haloalkoxy, amino or Cj-Cg alkylamino;

m is 0, 1 or 2; and each n is indepcndently 0, 1 or 2;

provided that (i) when J is J-l, R¹ is Cl, R² is H and R³ is Cl, then R⁴ is other than -CH₂CH₃, CH2CF3 or -CH₂(cyciopropyl);

(ii) when J is J-3, R¹ is Cl, R² is H, R³ is Cl and R⁷ is H, then Z is other than 2-pyridinyl; and (üi) when J is J-5, R' is Cl, R² is H, R³ is Cl, and R¹⁰ and R¹¹ are H, then R¹² is other than -CH₂CF₃.

(iv) when R¹ is H, then R³ is other than H; and when R³ is H, then R¹ is other than H.

2-pyrimidinyl.

2. The Compound of ciaîm 1 wherein R¹ is H, Cl or CF3, R² is H or F, and R³ is Cl or CF3.

3. The Compound of claim 1 or 2 wherein R¹ is H or Cl, R² is H or F, and R³ is Cl or CF3.

4. The Compound of any one of daims 1 to 3 wherein R¹ is H or Cl, R² is H or F, and R³ is CF3.

5, The Compound of any one of daims 1 to 4 wherein J is J-l, J-2 or J-3.

6. The Compound of any one of daims 1 to 5 wherein J is J-l.

7. The Compound of any one of daims I to 6 wherein R⁴ is C]-C₆ alkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkyl, C₃-C₆ cycloalkenyl, C₄-C_galkyl cydoalkyl.

8. The Compound of daim 7 wherein R⁴ is c-Pr or CH₂-c-Pr.

9. The Compound of daim 7 or 8 wherein R⁴ is substituted with substituents independently selected from halogen, cyano and CO₂R^1S.

10. The Compound of any one of daims 1 to 5 wherein J is J-3.

105

11. The Compound of any one of daims 1 to 5, and 10 wherein R⁷ is H or Me.

12. The compound of any one of daims 1 to 5, and 10 to 11 wherein Z is 2-pyridinyl or

13. The Compound of daim l wherein the Compound is at least one selected from 5-[5(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyI]-N-(l ,1dimethylethyl)-8-isoquinoIinecarboxamide (Compound 2), N-(cyclopropylmethyl)-5[5-(3,5-dichloro-4-fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 3), 5-[5-(3,5-dichloro-4-fluorophenyl)-4,5dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-(2-pyrimidinylmethyl)-8isoquinolinecarboxamide (Compound 4), N-cyclopropyl-5-[5-(3,5-dîchloro-4fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 23), 5-[5-[3-chloro-5- (trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N(cyclopropylmethyl)-8-isoquinolinecarboxamide (Compound 36), N-cyclopropyl-5[4,5-dihydro-5-(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 16), N-(cyclopropylmethyl)-5-[4,5-dihydro-5(trifluoromethyl)-5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 17), N-(cyclopropylmcthyl)-5-[5-[4-fluoro-3(tri fl uoromethyl)phenyl] -4,5-dihydro -5-(tri fluoromethyl)-3 -isoxazolyl] - 8 isoquinolinecarboxamide (Compound 58), 5-[5-[3-chloro-5(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)~3-isoxazolyl]-Ncyclopropyl-8-isoquinolinecarboxamide (Compound 35), 5-[5-[4-fluoro-3(tri fluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl ]-N-2-propyn1 -yl-8-isoquinolinecarboxamide (Compound 74), 5-[5-(3,5-dichloro-4-fluorophenyl)4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-ethyl-8-isoquinolinecarboxamide (Compound 46), 5-[5-(3,5-dichloro-4-fluorophenyI)-4,5-dihydro-5-(trifluoromethyl)3-isoxazolyl]-N-2-propyn-l-yl-8-isoquinolinecarboxamide (Compound 48), NcyclopropyI-5-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3isoxazolyl]-8-isoquinolinecarboxamîde (Compound 70), N-cyclopropyl-5-[5-[4fluoro-3-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 55), S-N-cyclopropyl-5-[5-(3,5-dichloro-4fluorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3 -isoxazolyl]-8isoquînolinecarboxamide (Compound 82), and S-N-(cyclopropylmethyl)-5-[4,5106 dihydro-5-(trifluoromethyI)-5-[3-(trifluoromethyl)phenyl]-3-isoxazolyl]-8isoquinolinecarboxamide (Compound 99).

14. A composition comprising a compound of any one of claims 1-13 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, said composition optionally further comprising at least one additional biologically active compound or agent.

15. The composition of Claim 14 wherein the at least one additional biologically active compound or agent is selected from insecticides, fongicides, bactéricides, nematocides, and herbicides.

16. The composition of Claim 14 or 15 wherein the at least one additional biologically active compound or agent is selected from abamectin, acephate, acequinocyl, acetamiprid, acrinathrin, acynonapyr, afidopyropen ([ (3 5,4R,4aÆ,65,6a5,12R, 12a5,12b5)-3-[(cyclopropyl carbon yl)oxy]-

17, The composition of Claim 3 wherein the at least one additional biologically active compound or agent is selected from cyantraniliprole, acetamiprid, îmidacloprid, spirotetramat, chlorantraniliprole, bifenthrin, indoxacarb, avermectin, Bacillus spp. and any active crystal proteins, buprofezin, carbofuran, chlorfenapyr, chlorpyrîfos, clothianidin, cyromazine, diafenthiuron, dinotefiiran, emamectin benzoate, fîpronil, flonicamid, fluhexafon, flupyradîfurone, methomyl, methoxyfenozîde, novaluron, permethrin, pyriproxifen, sulfoxaflor, thiamethoxam, γ-cyhalothrin, or Çcypermethrin, brofianilide, dimpropyridaz, isocycloseram, tetrachlorantraniliprole, oxazosulfyl, tyclopyrazoflor, flupyrimm, spiropidion, acynonapyr, benzpyrimoxan, chloroprallethrin, epsîlon-metofluthrin, kappa-bifenthrîn, dicloromezotiaz, and kappa-tefluthrin.

18. A liquid or dry formulation comprising the compound or composition of any one of claims 1-17 for use in a drip irrigation system, furrow during pîantîng, handheld sprayer, backpack sprayer, boom sprayer, ground sprayer, aerial application, unmanncd aerial vehicle, or a seed treatment.

19. A method for controlling an invertebrate pest comprising contacting the invertebrate pest or its environment with a biologically effective amount of a compound, composition or formulation of any one of claims 1- 18.

20. A treated seed comprising a compound of Claim 1 in an amount of from about 0.0001 to 1 % by weight of the seed before treatment.