US 20140187776A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0187776 A1 HOLYOKE, JR. et al. (43) Pub. Date: Jul. 3, 2014

(54) MIXTURES OF MESOIONIC PESTICIDES (71) Applicant: E I DUPONT DE NEMOURS AND COMPANY, Wilmington, DE (US) (72) Inventors: CALEB WILLIAM HOLYOKE, JR., NEWARK, DE (US); WENMING ZHANG, NEWARK, DE (US); MY-HANH THITONG, BEAR, DE (US): THOMAS FRANCIS PAHUTSKI, JR., ELKTON, MD (US) (73) Assignee: E I DUPONT DE NEMOURS AND wherein COMPANY, Wilmington, DE (US) R" is phenyl optionally substituted with up to 5 substituents independently selected from R, or pyridinyl optionally (21) Appl. No.: 14/184,778 substituted with up to 4 substituents independently selected from R: (22) Filed: Feb. 20, 2014 R’ is C-C haloalkyl; or thiazolyl pyridinyl or pyrimidi Related U.S. Application Data nyl, each optionally substituted with up to 2 substituents independently selected from the group consisting of (63) Continuation of application No. 13/386,160, filed on halogen and C-C alkyl; Jan. 20, 2012, now Pat. No. 8,697,707, filed as appli each R is independently halogen, cyano, C-C alkyl, cation No. PCT/US2010/044285 on Aug. 3, 2010. C-Chaloalkyl, C-C alkoxy, C-Chaloalkoxy, C(R) (60) Provisional application No. 61/231,483, filed on Aug. —NOR or Q; 5, 2009. each R is independently C-C alkyl: Publication Classification Z is CH=CH or S; and (51) Int. Cl. each Q is independently phenyl or pyridinyl, each option AOIN 43/90 (2006.01) ally substituted with up to 3 substituents independently (52) U.S. Cl. Selected from the group consisting of halogen, cyano, CPC ...... A0IN 43/90 (2013.01) C-C alkyl, C-C haloalkyl, C-C alkoxy and C-C USPC ...... 544/282 haloalkoxy; and (b) at least one invertebrate pest control agent. (57) ABSTRACT Also disclosed are methods for controlling an invertebrate Disclosed are compositions comprising (a) at least one com pest comprising contacting the invertebrate pest or its envi pound selected from compounds of Formula 1, N-oxides, and ronment with a biologically effective amount of a composi salt thereof, tion of the invention. US 2014/O 187776 A1 Jul. 3, 2014

MIXTURES OF MESOONCPESTICIDES

0001. This application is a continuation of application Ser. O No. 13/386,160, filed Jan. 20, 2012, which is a national stage entry of PCT/US2010/44285, filed Aug. 3, 2010. PCT/ R1 US2010/44285 claims priority benefit from Provisional Application 61/231,483, filed Aug. 5, 2009. (COz-s O FIELD OF THE INVENTION 0002 This invention relates to pesticidal mixtures com ls, prising certain pyrimidinium compounds, their N-oxides, and salts, and at least one other invertebrate pest control agent, Suitable for agronomic, nonagronomic and animal health wherein uses, and methods of their use for controlling invertebrate 0008) R' is phenyl optionally substituted with up to 5 pests such as arthropods in both agronomic and nonagro substituents independently selected from R, or pyridi nyl optionally substituted with up to 4 substituents inde nomic environments, and for treatment of parasite infections pendently selected from R: in animals or infestations in the general environment. I0009 R is C-C haloalkyl; or thiazolyl, pyridinyl or BACKGROUND OF THE INVENTION pyrimidinyl, each optionally substituted with up to 2 Substituents independently selected from the group con 0003. The control of invertebrate pests is extremely sisting of halogen and C-C alkyl: important in achieving high crop efficiency. Damage by 0010 each R is independently halogen, cyano, C-C, invertebrate pests to growing and stored agronomic crops can alkyl, C-Chaloalkyl, C-C alkoxy, C-Chaloalkoxy, cause significant reduction in productivity and thereby result in increased costs to the consumer. The control of invertebrate C(R) NOR or Q; pests in forestry, greenhouse crops, ornamentals, nursery I0011 each R is independently C-C alkyl; crops, stored food and fiber products, livestock, household, 0012 Z is CH=CH or S; and turf, wood products, and public health is also important. 0013 each Q is independently phenyl or pyridinyl, each Many products are commercially available for these pur optionally substituted with up to 3 substituents indepen poses, but the need continues for new compounds that are dently selected from the group consisting of halogen, more effective, less costly, less toxic, environmentally safer cyano, C-C alkyl, C-C haloalkyl, C-C alkoxy and or have different sites of action. C-C haloalkoxy; 0004. The control of animal parasites in animal health is 0014 and essential, especially in the areas of food production and com 0.015 (b) at least one invertebrate pest control agent panion animals. Existing methods of treatment and parasite Selected from the group consisting of abamectin, control are being compromised due to growing resistance to acetamiprid, amitraz, avermectin, azadirachtin, bensul many current commercial parasiticides. The discovery of tap, bifenthrin, buprofezin, cartap, chlorantraniliprole, more effective ways to control animal parasites is therefore chlorfenapyr, chlorpyrifos, clothianidin, cyantranilip imperative. role, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cy 0005 U.S. Pat. No. 5,151,427 discloses mesoionic pyri halothrin, lambda-cyhalothrin, cypermethrin, alpha midinium compounds of Formula i as anthelmintics cypermethrin, Zeta-cypermethrin, cyromazine, deltamethrin, dieldrin, dinotefuran, diofenolan, ema mectin, endosulfan, esfenvalerate, ethiprole, fenothio carb, fenoxycarb, fenvalerate, fipronil, flonicamid, R4 flubendiamide, flufenoxuron, hexaflumuron, hydram ethylnon, imidacloprid, indoxacarb, lufenuron, metaflu miZone, methomyl, methoprene, methoxyfenozide, HR nitenpyram, nithiazine, novaluron, oxamyl, phosmet, RN UN N CN pymetrozine, pyrethrin, pyridaben, pyridalyl, lsN H OR3 pyriproxyfen, ryanodine, spinetoram, spinosad, Spirodi H Nt O clofen, spiromesi?en, Spirotetramat, tebufenozide, thia l, cloprid, thiamethoxam, thiodicarb, thiosultap-sodium, tolfenpyrad, tralomethrin, triazamate, triflumuron, Bacillus thuringiensis delta-endotoxins, all strains of wherein, interalia, R' and Rare independently C-C alkyl, Bacillus thuringiensis and all strains of nucleo polyhe R is a heteroaromatic 6-membered ring, and R and Rare drosis viruses. independently hydrogen or C-C alkyl. 0016. This invention is also directed to aforesaid compo 0006. The mixtures of the present invention are not dis sition wherein component (a) is selected from at least one closed in this publication. compound of Formula 1 (including all stereoisomers). 0017. This invention is also directed to the compositions SUMMARY OF THE INVENTION described above, and further herein, provided that (a) when 0007. This invention is directed to a composition compris R" is unsubstituted phenylandR is CF, then Zis S.; (b) when ing (a) at least one compound selected from compounds of R" is 2-fluorophenyl and R is 2-chloro-5-thiazolyl, then Z is Formula 1 (including all stereoisomers), N-oxides, and salts S; and (c) when R' is 2-fluorophenyl or 3-(trifluoromethoxy) thereof, phenyl and R is 6-chloro-3-pyridinyl, then Z is CH=CH. US 2014/O 187776 A1 Jul. 3, 2014

0018. This invention also provides a composition com clofen, spiromesi?en, Spirotetramat, tebufenozide, thia prising any of the compositions described above and at least cloprid, thiamethoxam, thiodicarb, thiosultap-sodium, one additional component selected from the group consisting tolfenpyrad, tralomethrin, triazamate, triflumuron, of Surfactants, Solid diluents and liquid diluents. In one Bacillus thuringiensis delta-endotoxins, all strains of embodiment, this invention also provides a composition for Bacillus thuringiensis and all strains of nucleo polyhe controlling an invertebrate pest comprising the composition drosis viruses; and described above and at least one additional component 0028 (c) at least one fungicide: selected from the group consisting of Surfactants, Solid dilu 0029 provided that when the at least one additional ents and liquid diluents, said composition further comprising biologically active compound or agent is selected from at least one additional biologically active compound or agent. group (b) and (i) when R' is unsubstituted phenylandR 0019. This invention is also directed to a composition is CF, then Z is S.; (ii) when R' is 2-fluorophenyland R' comprising (a) at least one compound selected from com is 2-chloro-5-thiazolyl, then Z is S; and (iii) when R' is pounds of Formula 1, N-oxides, and salts thereof, 2-fluorophenyl or 3-(trifluoromethoxy)phenyland R is 6-chloro-3-pyridinyl, then Z is CH=CH. 0030 This invention further provides a composition for protecting an animal from an invertebrate parasitic pest com O prising any of the compositions described above and at least RI one carrier. 0031. This invention provides a method for controlling an invertebrate pest comprising contacting the invertebrate pest N (DCZ N+ NO or its environment with a biologically effective amount of any of the aforesaid compositions. 0032. This invention also provides a method for control s ling an invertebrate pest comprising contacting the inverte brate pest or its environment with a biologically effective wherein amount of any of the aforesaid compositions wherein the (0020) R' is phenyl optionally substituted with up to 5 environment is a plant. substituents independently selected from R, or pyridi 0033. This invention also provides a method for control nyl optionally substituted with up to 4 substituents inde ling an invertebrate pest comprising contacting the inverte pendently selected from R: brate pest or its environment with a biologically effective I0021 R is C-C haloalkyl; or thiazolyl, pyridinyl or amount of any of the aforesaid compositions wherein the pyrimidinyl, each optionally substituted with up to 2 environment is an animal. Substituents independently selected from the group con 0034. This invention also provides a method for control sisting of halogen and C-C alkyl; ling an invertebrate pest comprising contacting the inverte (0022 each R is independently halogen, cyano, C-C, brate pest or its environment with a biologically effective alkyl, C-Chaloalkyl, C-C alkoxy, C-Chaloalkoxy, amount of any of the aforesaid compositions wherein the C(R) NOR or Q; environment is a seed. I0023 each R is independently C-C alkyl: 0035. This invention also provides a method for control 0024 Z is CH=CH or S; and ling an invertebrate pest comprising contacting the inverte 0025 each Q is independently phenyl or pyridinyl, each brate pest or its environment with a biologically effective optionally substituted with up to 3 substituents indepen amount of any of the aforesaid compositions wherein the dently selected from the group consisting of halogen, environment is a seed coated with the aforesaid compositions cyano, C-C alkyl, C-C haloalkyl, C-C alkoxy and comprising the compound of claim 1 and optionally a film C-C haloalkoxy; former or adhesive agent. 0026 and at least one additional biologically active 0036. This invention also provides a method for protecting compound or agent selected from the group consisting a seed from an invertebrate pest comprising contacting the of seed with any of the compositions described above. This 0027 (b) at least one invertebrate pest control agent invention also relates to the treated seed. Selected from the group consisting of abamectin, 0037. This invention further provides a method for treat acetamiprid, amitraz, avermectin, azadirachtin, bensul ing, preventing, inhibiting and/or killing ecto and/or tap, bifenthrin, buprofezin, cartap, chlorantraniliprole, endoparasites comprising administering to and/or on an ani chlorfenapyr, chlorpyrifos, clothianidin, cyantranilip mal a parasiticidally effective amount of any of the compo role, cyfluthrin, beta-cyfluthrin, cyhalothrin, gamma-cy sitions described above. This invention also relates to such halothrin, lambda-cyhalothrin, cypermethrin, alpha method wherein a parasiticidally effective amount of any of cypermethrin, Zeta-cypermethrin, cyromazine, the compositions described above is administered to an envi deltamethrin, dieldrin, dinotefuran, diofenolan, ema ronment (e.g., a stall or blanket) in which an animal resides. mectin, endosulfan, esfenvalerate, ethiprole, fenothio 0038. This invention is also directed to compounds of carb, fenoxycarb, fenvalerate, fipronil, flonicamid, Formula 1 selected from the group consisting of: flubendiamide, flufenoxuron, hexaflumuron, hydram 0039) 3-(2-chloro-6-fluorophenyl)-1-(6-chloro-3-pyridi ethylnon, imidacloprid, indoxacarb, lufenuron, metaflu nyl)methyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi miZone, methomyl, methoprene, methoxyfenozide, dinium inner salt; nitenpyram, nithiazine, novaluron, oxamyl, phosmet, 0040 1-(2-chloro-5-thiazolyl)methyl-3-(2-ethoxyphe pymetrozine, pyrethrin, pyridaben, pyridalyl, nyl)-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimidinium pyriproxyfen, ryanodine, spinetoram, spinosad, Spirodi inner salt; US 2014/O 187776 A1 Jul. 3, 2014

0041 1-(2-chloro-5-thiazolyl)methyl-2-hydroxy-3-(3- word form of the element or component also includes the methylphenyl)-4-oxo-4H-pyrido 1,2-alpyrimidinium plural unless the number is obviously meant to be singular. inner salt; 0053 As referred to in this disclosure, the term “inverte 0042 3-(3-chloro-2-fluorophenyl)-1-(6-chloro-3-pyridi brate pest” includes arthropods, gastropods and nematodes of nyl)methyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi economic importance as pests. The term “arthropod' includes dinium inner salt; insects, mites, spiders, Scorpions, centipedes, millipedes, pill 0043 2-hydroxy-4-oxo-1-(5-pyrimidinylmethyl)-3-3- bugs and Symphylans. The term 'gastropod' includes Snails, (trifluoromethyl)phenyl]-4H-pyrido 1,2-alpyrimidinium slugs and other Stylommatophora. The term “nematode' inner salt; refers to a living organism of the Phylum Nematoda. The term 0044 1-(2-chloro-5-thiazolyl)methyl-2-hydroxy-4- “helminths' includes roundworms, heartworms, and phy oxo-3-(4-(trifluoromethyl) 1,1'-biphenyl-3-yl)-4H-py tophagous nematodes (Nematoda), flukes (Tematoda), Acan rido 1,2-alpyrimidinium inner salt; thocephala, and tapeworms (Cestoda). 0045 1-(2-chloro-5-thiazolyl)methyl-3-(4-fluoro1,1'- 0054. In the context of this disclosure “invertebrate pest biphenyl-3-yl)-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyri control’ means inhibition of invertebrate pest development midinium inner salt; and (including mortality, feeding reduction, and/or mating dis 0046 3-(5-chloro-2-fluorophenyl)-1-(6-fluoro-3-pyridi ruption), and related expressions are defined analogously. nyl)methyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi 0055. The term “agronomic” refers to the production of dinium inner salt. field crops such as for food and fiber and includes the growth of corn, soybeans and other legumes, rice, cereal (e.g., wheat, oats, barley, rye, rice, maize), leafy vegetables (e.g., lettuce, DETAILS OF THE INVENTION cabbage, and other cole crops), fruiting vegetables (e.g., 0047. As used herein, the terms “comprises”, “compris tomatoes, pepper, eggplant, crucifers and cucurbits), pota ing”, “includes”, “including”, “has”, “having”, “contains”. toes, Sweet potatoes, grapes, cotton, tree fruits (e.g., pome, “containing”, “characterized by or any other variation stone and citrus), small fruit (berries, cherries) and other thereof, are intended to cover a non-exclusive inclusion, Sub specialty crops (e.g., canola, Sunflower, olives). ject to any limitation explicitly indicated. For example, a 0056. The term “nonagronomic’ refers to other than field composition, mixture, process or method that comprises a list crops, such as horticultural crops (e.g., greenhouse, nursery of elements is not necessarily limited to only those elements or ornamental plants not grown in a field), residential, agri but may include other elements not expressly listed or inher cultural, commercial and industrial structures, turf (e.g., sod ent to Such composition, mixture, process or method. farm, pasture, golf course, lawn, sports field, etc.), wood 0048. The transitional phrase “consisting of excludes any products, stored product, agro-forestry and vegetation man element, step or ingredient not specified. If in the claim, Such agement, public health (i.e. human) and animal health (e.g., would close the claim to the inclusion of materials other than domesticated animals such as pets, livestock and poultry, those recited except for impurities ordinarily associated undomesticated animals such as wildlife) applications. therewith. When the phrase “consisting of appears in a 0057. Nonagronomic applications include protecting an clause of the body of a claim, rather than immediately fol animal from an invertebrate parasitic pest by administering a lowing the preamble, it limits only the element set forthin that parasiticidally effective (i.e. biologically effective) amount of clause; other elements are not excluded from the claim as a a compound of the invention, typically in the form of a com whole. position formulated for veterinary use, to the animal to be 0049. The transitional phrase “consisting essentially of is protected. As referred to in the present disclosure and claims, used to define a composition or method that includes materi the terms “parasiticidal' and “parasiticidally” refers to als, steps, features, components or elements, in addition to observable effects on an invertebrate parasite pest to provide those literally disclosed, provided that these additional mate protection of an animal from the pest. Parasiticidal effects rials, steps, features, components or elements do not materi typically relate to diminishing the occurrence or activity of ally affect the basic and novel characteristic(s) of the claimed the target invertebrate parasitic pest. Such effects on the pest invention. The term “consisting essentially of occupies a include necrosis, death, retarded growth, diminished mobility middle ground between "comprising and “consisting of. or lessened ability to remain on or in the host animal, reduced 0050. Where applicants have defined an invention or a feeding and inhibition of reproduction. These effects on portion thereof with an open-ended term such as "compris invertebrate parasite pests provide control (including preven ing, it should be readily understood that (unless otherwise tion, reduction or elimination) of parasitic infestation or stated) the description should be interpreted to also describe infection of the animal. Such an invention using the terms “consisting essentially of 0058. In the above recitations, the term “alkyl, used either or “consisting of. alone or in compound words such as "haloalkyl includes 0051. Further, unless expressly stated to the contrary, 'or' straight-chain or branched alkyl, Such as, methyl, ethyl, refers to an inclusive or and not to an exclusive or. For n-propyl, i-propyl, or the different butyl isomers. example, a condition A or B is satisfied by any one of the 0059. The term “halogen', either alone or in compound following: A is true (or present) and B is false (or not present), words such as “haloalkyl, includes fluorine, chlorine, bro A is false (or not present) and B is true (or present), and both mine or iodine. Further, when used in compound words Such A and B are true (or present). as “haloalkyl, said alkyl may be partially or fully substituted 0052 Also, the indefinite articles “a” and “an preceding with halogen atoms which may be the same or different. an element or component of the invention are intended to be Examples of “haloalkyl include CF, CHCl, CHCF and nonrestrictive regarding the number of instances (i.e. occur CC1CF. rences) of the element or component. Therefore “a” or “an 0060 Alkoxy' includes, for example, methoxy, ethoxy, should be read to include one or at least one, and the singular n-propyloxy, isopropyloxy and the different butoxy isomers. US 2014/O 187776 A1 Jul. 3, 2014

"Haloalkoxy” is defined similarly to “haloalkyl; examples of depicted as a single Valence bond structure herein, this par “haloalkoxy” include OCF, OCHC1, OCHCF and ticular valence bond structure is to be understood as repre OCC1CF. sentative of all six valence bond structures relevant to bond 0061. The R substituent C(R)—NOR represents an ing in molecules of compounds of Formula 1. Therefore Oxime having either of the two regioisomeric structures reference to Formula 1 herein relates to all six applicable shown below. Valence bond structures and other (e.g., molecular orbital theory) structures unless otherwise specified.

0062. The total number of carbon atoms in a substituent group is indicated by the "C-C, prefix where i and j are numbers from 1 to 4. For example, C-C alkyl designates methyl through butyl. 0063. When a radical (e.g., phenyl or pyridinyl in the definition of R') is optionally substituted with listed substitu ents with the number of substituents stated (e.g., “up to 5'). then the radical may be unsubstituted or substituted with a number of Substituents ranging up to the high number stated CCC ODI (e.g., “5”), and the attached substituents are independently selected from the substituents listed. 0064. The term “unsubstituted” in connection with a s s group Such as a ring means the group does not have any Substituents other than its one or more attachments to the remainder of Formula 1. The term “optionally substituted” means that the number of substituents can be zero. Unless otherwise indicated, optionally Substituted groups may be OCC Substituted with as many optional Substituents as can be accommodated by replacing a hydrogen atom with a non ls R2 ls hydrogen Substituent on any available carbon or nitrogen atom. Commonly, the number of optional Substituents (when present) ranges from 1 to 3. 0068 Compounds of Formula 1 can exist as one or more 0065. The number of optional substituents may be Stereoisomers. The various Stereoisomers include enanti restricted by an expressed limitation. For example, the phrase omers, diastereomers, atropisomers and geometric isomers. “optionally substituted with up to 5 substituents’ means that One skilled in the art will appreciate that one stereoisomer 0, 1, 2, 3, 4 or 5 substituents can be present (if the number of may be more active and/or may exhibit beneficial effects potential connection points allows). When a range specified when enriched relative to the other stereoisomer(s) or when for the number of substituents exceeds the number of posi separated from the other stereoisomer(s). Additionally, the tions available for Substituents on a ring, the actual higher end skilled artisan knows how to separate, enrich, and/or to selec of the range is recognized to be the number of available tively prepare said stereoisomers. The compounds of the positions. invention may be present as a mixture of stereoisomers, indi 0066. A wide variety of synthetic methods are known in vidual stereoisomers or as an optically active form. the art to enable preparation of aromatic heterocyclic rings; 0069 Compounds of Formula 1 can exist as one or more for extensive reviews see the eight volume set of Comprehen conformational isomers due to restricted bond rotation sive Heterocyclic Chemistry, A. R. Katritzky and C. W. Rees caused by Steric hinderance. For example, a compound of editors-in-chief, Pergamon Press, Oxford, 1984 and the Formula 1 wherein R is phenyl substituted in the ortho twelve volume set of Comprehensive Heterocyclic Chemistry position with a sterically demanding alkyl group (e.g., iso II. A. R. Katritzky, C. W. Rees and E. F. V. Scriven editors propyl) may exist as two rotamers due to restricted rotation in-chief, Pergamon Press, Oxford, 1996. about the R'-pyrimidinium ring bond. This invention com 0067. The compounds of Formula 1 are mesoionic inner prises mixtures of conformational isomers. In addition, this salts. “Inner salts', also known in the art as "Zwitterions', are invention comprises compounds that are enriched in one con electrically neutral molecules but carry formal positive and former relative to others. negative charges on different atoms in each Valence bond 0070 Compounds selected from Formula 1 (including all structure according to valence bond theory. Furthermore the Stereoisomers, N-oxides, and salts thereof), typically exist in molecular structure of the compounds of Formula 1 can be more than one form, and Formula 1 thus includes all crystal represented by the six valence bond structures shown below, line and non-crystalline forms of the compounds that For each placing the formal positive and negative charges on mula 1 represents. Non-crystalline forms include embodi different atoms. Because of this resonance, the compounds of ments which are solids such as waxes and gums as well as Formula 1 are also described as “mesoionic'. Although for embodiments which are liquids Such as solutions and melts. sake of simplicity, the molecular structure of Formula 1 is Crystalline forms include embodiments which represent US 2014/O 187776 A1 Jul. 3, 2014

essentially a single crystal type and embodiments which rep 0073 Embodiments of the present invention as described resent a mixture of polymorphs (i.e. different crystalline in the Summary of the Invention include those described types). The term “polymorph” refers to a particular crystal below. In the following Embodiments Formula 1 includes line form of a chemical compound that can crystallize in stereoisomers, N-oxides, and salts thereof, and reference to “a different crystalline forms, these forms having different compound of Formula 1 includes the definitions of substitu arrangements and/or conformations of the molecules in the ents specified in the Summary of the Invention unless further crystal lattice. Although polymorphs can have the same defined in the Embodiments. chemical composition, they can also differ in composition due to the presence or absence of co-crystallized water or Embodiment 1 other molecules, which can be weakly or strongly bound in 0074 The composition described in the Summary of the the lattice. Polymorphs can differ in such chemical, physical Invention wherein component (a) is a compound of Formula and biological properties as crystal shape, density, hardness, 1 wherein R' is phenyl optionally substituted with up to 3 color, chemical stability, melting point, hygroscopicity, Sus substituents independently selected from R, or pyridinyl pensibility, dissolution rate and biological availability. One optionally substituted with up to 2 substituents independently skilled in the art will appreciate that a polymorph of a com selected from R. pound represented by Formula 1 can exhibit beneficial effects (e.g., Suitability for preparation of useful formulations, improved biological performance) relative to another poly Embodiment 2 morph or a mixture of polymorphs of the same compound 0075. The composition of Embodiment 1 wherein R' is represented by Formula 1. Preparation and isolation of a phenyl optionally substituted with up to 3 substituents inde particular polymorph of a compound represented by Formula pendently selected from R. 1 can beachieved by methods known to those skilled in the art including, for example, crystallization using selected Sol vents and temperatures. Embodiment 2a 0071. One skilled in the art will appreciate that not all (0076. The composition of Embodiment 2 wherein R' is nitrogen-containing heterocycles can form N-oxides since phenyl substituted with 1, 2 or 3 substituents independently the nitrogen requires an available lone pair for oxidation to the selected from R. oxide; one skilled in the art will recognize those nitrogen containing heterocycles which can form N-oxides. Synthetic Embodiment 2b methods for the preparation of N-oxides of heterocycles are very well known by one skilled in the art including the oxi 0077. The composition of Embodiment 2a wherein R is dation of heterocycles with peroxyacids such asperacetic and phenyl substituted with 1, 2 or 3 substituents independently 3-chloroperbenzoic acid (MCPBA), hydrogen peroxide, selected from Rother than Q. alkyl hydroperoxides such as t-butyl hydroperoxide, sodium perborate, and dioxiranes such as dimethyldioxirane. These Embodiment 2c methods for the preparation of N-oxides have been exten sively described and reviewed in the literature, see for I0078. The composition of Embodiment 2a wherein R is example: T. L. Gilchrist in Comprehensive Organic Synthe phenyl substituted with one substituent selected from Q and sis, vol. 7, pp 748-750, S. V. Ley, Ed., Pergamon Press: M. optionally up to 2 substituents independently selected from Tisler and B. Stanovnik in Comprehensive Heterocyclic Rother than Q. Chemistry, vol. 3, pp 18-20, A. J. Boulton and A. McKillop, Eds. Pergamon Press; M. R. Grimmett and B. R. T. Keene in Advances in Heterocyclic Chemistry, vol.43, pp 149-161, A. Embodiment 2d R. Katritzky, Ed., Academic Press; M. Tisler and B. 007.9 The composition of Embodiment 2c wherein Q is Stanovnik in Advances in Heterocyclic Chemistry, vol. 9, pp phenyl optionally substituted with up to 3 substituents inde 285-291, A. R. Katritzky and A. J. Boulton, Eds. Academic pendently selected from the group consisting of halogen, Press; and G. W. H. Cheeseman and E. S. G. Werstiuk in cyano, C-C alkyl, C-Chaloalkyl, C-C alkoxy and C-C, Advances in Heterocyclic Chemistry, vol. 22, pp. 390-392, A. haloalkoxy. R. Katritzky and A. J. Boulton, Eds. Academic Press. 0072. One skilled in the art recognizes that because in the Embodiment 2e environment and under physiological conditions salts of chemical compounds are in equilibrium with their corre 0080. The composition of Embodiment 2c wherein Q is sponding nonsalt forms, salts share the biological utility of pyridinyl optionally substituted with up to 3 substituents the nonsalt forms. Thus a wide variety of salts of the com independently selected from the group consisting of halogen, pounds of Formula 1 are useful for control of invertebrate cyano, C-C alkyl, C-Chaloalkyl, C-C alkoxy and C-C, pests and animal parasites (i.e. are Suitable for animal health haloalkoxy. use). The salts of the compounds of Formula 1 include acid addition salts with inorganic or organic acids such as hydro Embodiment 2f bromic, hydrochloric, nitric, phosphoric, Sulfuric, acetic, butyric, fumaric, lactic, maleic, malonic, oxalic, propionic, I0081. The composition of Embodiment 2d wherein Q is salicylic, tartaric, 4-toluenesulfonic or Valeric acids. Accord phenyl optionally substituted with up to 3 substituents inde ingly, the present invention comprises compounds selected pendently selected from the group consisting of halogen and from Formula 1, N-oxides and salts thereof. C-C haloalkyl. US 2014/O 187776 A1 Jul. 3, 2014

Embodiment 2g Embodiment 4 0082. The composition of Embodiment 2e wherein Q is 0093. The composition described in the Summary of the pyridinyl optionally substituted with up to 3 substituents Invention or any of Embodiments 1 to 3g wherein each R is independently selected from the group consisting of halogen independently halogen, C-C alkyl, C-C haloalkyl, C-C, and C-Chaloalkyl. alkoxy or C-C haloalkoxy.

Embodiment 3 Embodiment 4a I0083) The composition of Embodiment 1 wherein R' is pyridinyl optionally substituted with up to 2 substituents I0094) The composition of Embodiment 4 wherein each R independently selected from R. is independently halogen or C-C haloalkyl. Embodiment 3a Embodiment 4b I0084. The composition of Embodiment 3 wherein R' is 0.095 The composition of Embodiment 4a wherein each pyridinyl substituted with up to 2 substituents independently R is independently halogen. selected from R. Embodiment 5 Embodiment 3b 0096. The composition described in the Summary of the 0085. The composition of Embodiment 3a wherein R is Invention or any of Embodiments 1 to 4b wherein component pyridinyl substituted with up to 2 substituents independently (a) is a compound of Formula 1 wherein R is C-C, selected from Rother than Q. haloalkyl. Embodiment 3c Embodiment 5a I0086) The composition of Embodiment 3a wherein R' is pyridinyl substituted with one substituent selected from Q 0097. The composition of Embodiment 5 wherein R is and optionally one substituent selected from Rother than Q. C-C haloalkyl. Embodiment 3d Embodiment 5b 0087. The composition of Embodiment 3c wherein Q is 0098 The composition of Embodiment 5a wherein R is phenyl optionally substituted with up to 3 substituents inde CHCF. pendently selected from the group consisting of halogen, cyano, C-C alkyl, C-Chaloalkyl, C-C alkoxy and C-C, Embodiment 6 haloalkoxy. 0099. The composition described in the Summary of the Embodiment 3e Invention or any of Embodiments 1 to 4b wherein component 0088. The composition of Embodiment 3c wherein Q is (a) is a compound of Formula 1 wherein R is thiazolyl, pyridinyl optionally substituted with up to 3 substituents pyridinyl or pyrimidinyl, each optionally substituted with up independently selected from the group consisting of halogen, to 2 substituents independently selected from the group con cyano, C-C alkyl, C-Chaloalkyl, C-C alkoxy and C-C, sisting of halogen and C-C alkyl. haloalkoxy. Embodiment 6a Embodiment 3f 0100. The composition described in the Summary of the 0089. The composition of Embodiment 3d wherein Q is Invention or any of Embodiments 1 to 4b wherein component phenyl optionally substituted with up to 3 substituents inde (a) is a compound of Formula 1 wherein R is thiazolyl pendently selected from the group consisting of halogen or optionally substituted with up to 2 substituents independently C-C haloalkyl. selected from the group consisting of halogen and C-C, alkyl. Embodiment 3g 0090 The composition of Embodiment 3e wherein Q is Embodiment 6b pyridinyl optionally substituted with up to 3 substituents I0101 The composition of Embodiment 6a wherein R is independently selected from the group consisting of halogen thiazolyl optionally substituted with up to 2 substituents inde or C-C haloalkyl. pendently selected from halogen. Embodiment 3h Embodiment 6c 0091. The composition of Embodiment 3 wherein each R is independently halogen, C-C alkyl, C-C haloalkyl, 10102) The composition of Embodiment 6b wherein R is C-C alkoxy, C-C haloalkoxy or Q. thiazolyl optionally substituted with Cl. Embodiment 3i Embodiment 6d 0092. The composition of Embodiment 3h wherein each (0103) The composition of Embodiment 6c wherein R is R is independently halogen or C-C haloalkyl. 2-chloro-5-thiazolyl. US 2014/O 187776 A1 Jul. 3, 2014

Embodiment 7 compounds of Formula 1. In addition, embodiments of this 0104. The composition described in the Summary of the invention, including Embodiments 1-10 above as well as any Invention or any of Embodiments 1 to 4b wherein component other embodiments described herein, and any combination (a) is a compound of Formula 1 wherein R is pyridinyl thereof, pertain to the compositions and methods of the optionally substituted with up to 2 substituents independently present invention. selected from the group consisting of halogen and C-C, 0116 Specific embodiments include the compositions alkyl. described in the Summary of the Invention wherein compo nent (a) is a compound of Formula 1 selected from the group Embodiment 7a consisting of: 0117 1-(2-chloro-5-thiazolyl)methyl-3-(2,6-difluo 0105. The composition of Embodiment 7 wherein R is rophenyl)-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi pyridinyl optionally substituted with up to 2 substituents dinium inner salt; independently selected from halogen. 0118 1-(2-chloro-5-thiazolyl)methyl-3-(2,6-dimethox yphenyl)-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi Embodiment 7b dinium inner salt; I0106) The composition of Embodiment 7a wherein R is 0119) 1-(2-chloro-5-thiazolyl)methyl-2-hydroxy-3-(2- pyridinyl optionally substituted with Cl. methoxyphenyl)-4-oxo-4H-pyrido 1,2-alpyrimidinium inner salt; Embodiment 7c I0120 3-(3,5-dimethoxyphenyl)-1-(6-fluoro-3-pyridinyl) 0107 The composition of Embodiment 7b wherein R is methyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimidinium 6-chloro-3-pyridinyl. inner salt; I0121 1-(6-fluoro-3-pyridinyl)methyl-2-hydroxy-4- Embodiment 8 oxo-3-3-(trifluoromethyl)phenyl]-4H-pyrido 1,2-alpyri 0108. The composition described in the Summary of the midinium inner salt; Invention or any of Embodiments 1 to 4b wherein component 0.122 1-(6-chloro-3-pyridinyl)methyl-3-(2-fluoro-3- (a) is a compound of Formula 1 wherein R is pyrimidinyl methoxyphenyl)-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyri optionally substituted with up to 2 substituents independently midinium inner salt; selected from the group consisting of halogen and C-C, I0123 3-(4-fluorophenyl)-2-hydroxy-1-(2-methyl-5- alkyl. thiazolyl)methyl-4-OXO-4H-pyrido 1,2-alpyrimidinium inner salt; Embodiment 8a 0.124 2-hydroxy-4-oxo-3-phenyl-1-(5-thiazolylmethyl)- 0109 The composition of Embodiment 8 wherein R is 4H-pyrido 1,2-alpyrimidinium inner salt; pyrimidinyl optionally substituted with C-C alkyl. 0.125 3-(2-fluorophenyl)-1-(6-fluoro-3-pyridinyl)me thyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimidinium Embodiment 8b inner salt; 0.126 1-(6-fluoro-3-pyridinyl)methyl-2-hydroxy-4- I0110. The composition of Embodiment 8a wherein R is oxo-3-3-(trifluoromethoxy)phenyl-4H-pyrido 1,2-apy pyrimidinyl optionally substituted with CH. rimidinium inner salt; Embodiment 8c I0127 3-(5-bromo-2-methoxyphenyl)-1-(6-chloro-3-py ridinyl)methyl-2-hydroxy-4-OXO-4H-pyrido 1,2-alpyri I0111. The composition of Embodiment 8b wherein R is midinium inner salt; 2-methyl-5-pyrimidinyl. I0128 1-(6-chloro-3-pyridinyl)methyl-3-2-chloro-5- (trifluoromethyl)phenyl-2-hydroxy-4-oxo-4H-pyrido1, Embodiment 8d 2-alpyrimidinium inner salt; I0112. The composition of Embodiment 8b wherein R is I0129. 1-(6-fluoro-3-pyridinyl)methyl-3-2-fluoro-3- 5-pyrimidinyl. (trifluoromethyl)phenyl-2-hydroxy-4-oxo-4H-pyrido1, 2-alpyrimidinium inner salt; Embodiment 9 0.130 1-(2-chloro-5-thiazolyl)methyl-3-3-(6-fluoro-3- 0113. The composition described in the Summary of the pyridinyl)-5-(trifluoromethoxy)phenyl-2-hydroxy-4- Invention or any of Embodiments 1 to 8d wherein component OXO-4H-pyrido 1,2-alpyrimidinium inner salt; (a) is a compound of Formula 1 wherein Z is CH=CH. I0131 1-(2-chloro-5-thiazolyl)methyl-3-3-chloro-5- (trifluoromethoxy)phenyl-2-hydroxy-4-oxo-4H-pyrido Embodiment 10 1.2-alpyrimidinium inner salt; 0114. The composition described in the Summary of the I0132) 1-(2-chloro-5-thiazolyl)methyl-3-3-chloro-5- Invention or any of Embodiments 1 to 8d wherein component (trifluoromethyl)phenyl-2-hydroxy-4-oxo-4H-pyrido1, (a) is a compound of Formula 1 wherein Z is S. 2-alpyrimidinium inner salt; 0115 Embodiments of this invention, including Embodi 0.133 1-(6-chloro-3-pyridinyl)methyl-2-hydroxy-4- ments 1-10 above as well as any other embodiments oxo-3-(2,3,6-trifluorophenyl)-4H-pyrido 1,2-alpyrimi described herein, can be combined in any manner, and the dinium inner salt; descriptions of variables in the embodiments pertain not only 0.134 3-(3-chloro-2,6-difluorophenyl)-1-(6-chloro-3- to the compounds of Formula 1 but also to the starting com pyridinyl)methyl-2-hydroxy-4-oxo-4H-pyrido 1,2-apy pounds and intermediate compounds useful for preparing the rimidinium inner salt;

US 2014/O 187776 A1 Jul. 3, 2014

0177. Further specific embodiments include the composi ments, one or more food materials, optionally an attractant, tions described in the Summary of the Invention wherein and optionally a humectant. Embodiments of the invention component (a) is a compound of Formula 1 selected from the also include a device for controlling an invertebrate pest group consisting of compound numbers 6, 7, 9, 10, 19, 26, 29. comprising said bait composition and a housing adapted to 34, 38,39, 43,48, 58,74,78, 85, 87, 88,90,94, 111, 117, 122, receive said bait composition, wherein the housing has at least 209, 220, 268, 410, 510, 537, 547 and 548, wherein the one opening sized to permit the invertebrate pest to pass compound number refers to compounds in Index Tables A-C. through the opening so the invertebrate pest can gain access to 0178. Further specific embodiments include the composi said bait composition from a location outside the housing, and tions described in the Summary of the Invention wherein wherein the housing is further adapted to be placed in or near component (a) is a compound of Formula 1 selected from the a locus of potential or known activity for the invertebrate pest. group consisting of compound numbers 541, 542, 576, 583. 0186 Embodiments of the invention also include a 594,654, 657, 669, 670, 682,683, 687, 718, 725, 726, 727, method for protecting a seed from an invertebrate pest com 734, 735, 737, 744, 745, 746, 748, 749, 750, 926 and 930, prising contacting the seed with a biologically effective wherein the compound number refers to compounds in Index amount of a composition of any of the preceding Embodi Tables A-C. mentS. 0179. Of note is that compositions of this invention are 0187 Embodiments of the invention also include methods characterized by favorable metabolic and/or soil residual pat for protecting an animal from an invertebrate parasitic pest terns and exhibit activity controlling a spectrum of agronomic comprising administering to the animal a parasiticidally and nonagronomic invertebrate pests. effective amount of a composition of any of the preceding 0180. Of particular note, for reasons of invertebrate pest Embodiments. control spectrum and economic importance, protection of 0188 Embodiments of the invention also include methods agronomic crops from damage or injury caused by inverte wherein the invertebrate pest or its environment is contacted brate pests by controlling invertebrate pests are embodiments with a biologically effective amount of a composition of any of the invention. Compositions of this invention because of of the preceding Embodiments, and at least one additional their favorable translocation properties or systemicity in component selected from the group consisting of surfactants, plants also protect foliar or other plant parts which are not Solid diluents and liquid diluents, said composition optionally directly contacted with the compositions. further comprising a biologically effective amount of at least 0181 Also noteworthy as embodiments of the present one additional biologically active compound or agent, pro invention are compositions comprising components (a) and vided that the methods are not methods of medical treatment (b) (i.e. in biologically effective amounts) as described in any of a human or animal body by therapy. of the preceding Embodiments, as well as any other embodi 0189 One or more of the following methods and varia ments described herein, and any combinations thereof, fur tions as described in Schemes 1-10 can be used to prepare the ther comprising at least one additional component selected compounds of Formula 1. The definitions of R', Rand Z in from the group consisting of a Surfactant, a Solid diluent and the compounds of Formulae 1-8 below areas defined above in a liquid diluent, said compositions optionally further com the Summary of the Invention unless otherwise noted. For prising at least one additional biologically active compound mulaela and 1b are various Subsets or analogs of Formula 1, or agent (i.e. in a biologically effective amount). and all substituents for Formulae 1a and 1b are as defined 0182 Embodiments of the invention also include a com above for Formula 1 unless otherwise indicated. Ambient or position for protecting an animal comprising components (a) room temperature is defined as about 20-25°C. and (b) (i.e. in parasiticidally effective amounts) of any of the 0.190 Compounds of Formula 1 can be prepared by con preceding Embodiments and a carrier. densation of appropriately Substituted compounds of For 0183 Embodiments of the invention further include meth mula 2 with optionally substituted malonic acids (3a) in the ods for controlling an invertebrate pest comprising contacting presence of condensing agents as shown in Scheme 1. Con the invertebrate pest or its environment with a biologically densing agents can be carbodiimides such as dicyclohexyl effective amount of a composition of any of the preceding carbodiimide (see, for example, Koch, A. et al. Tetrahedron Embodiments. Of particular note is a method for protecting 2004, 60, 10011-10018) or other agents well known in the art an animal comprising administering to the animal a parasiti to form amide bonds with or without activating agents such as cidally effective amount of a composition of any of the pre N-hydroxybenzotriazole as described in Science of Synthesis ceding Embodiments. 2005, 21, 17-25 and Tetrahedron 2005, 61, 10827-10852. 0184 Embodiments of the invention also include a com This reaction is typically carried out in an inert organic Sol position comprising of any of the preceding Embodiments, in vent, such as dichloromethane or 1,2-dichloroethane, attem the form of a soildrench liquid formulation. Embodiments of peratures from about 0 to about 80°C. for a period of 10 min the invention further include methods for controlling an to several days. invertebrate pest comprising contacting the Soil with a liquid composition as a soil drench comprising a biologically effec Scheme 1 tive amount of a composition of any of the preceding Embodi 7 R1 mentS. ls -- condensing 0185 Embodiments of the invention also include a spray Z NH HO OH agent composition for controlling an invertebrate pest comprising a Hs biologically effective amount of a composition of any of the preceding Embodiments and a propellant. Embodiments of ls R2 O O the invention further include a bait composition for control ling an invertebrate pest comprising a biologically effective 2 3a amount of a composition of any of the preceding Embodi US 2014/O 187776 A1 Jul. 3, 2014

-continued -continued O R1 RO OR (CC) O O Z l O 3b(R is C1-C5 alkyl)

0194 Compounds of Formula3b can also be prepared by the method shown in Scheme 2b. Reaction of nitriles of Formula 3g with dialkyl carbonates yields nitrile esters of Formula3h, and Subsequent acidic hydrolysis in the presence 0191 Compounds of Formula 1 can also be prepared by of an alcohol provides the compounds of Formula3b (see, for the condensation of compounds of Formula 2 with malonic example, Helvetica Chimica Acta 1991, 74(2), 309-314). acid esters (3.b) wherein R is a C-C alkyl group, preferably a C-C alkyl group, as shown in Scheme 2. These reactions can be performed neat or in the presence of inert Solvents as Scheme 2b described in Bulletin of the Chemical Society of Japan 1999, R! CN (RO)2CO 72(3), 503-509. Inert solvents include, but are not limited to, N1 RON high boiling hydrocarbons such as mesitylene, tetralin or cymene, or high boiling ethers such as diphenyl ether. Typical 3g R is C1-C5 alkyl temperatures range from 50 to 250° C. Of note are tempera R1 tures from 150 to 200° C., which typically provide rapid reaction times and high yields. These reactions can also be RO id CN 80 performed in microwave reactors within the same tempera ROH 3b ture ranges. Typical reaction times range from 5 minto sev O eral hours. 3.

Scheme 2 0.195 Compounds of Formula 1 can also be prepared by treatment of compounds of Formula 2 with activated esters of Formula 3c wherein LVO is an activated leaving group as shown in Scheme 3. Examples of LV preferred for ease of synthesis or reactivity are phenyl, 4-nitrophenyl or halogen O O Substituted phenyl (e.g., 2,4,6-trichlorophenyl, pentachlo rophenyl or pentafluorophenyl) as described in Archiv der 3b(R is C1-C5 alkyl) Pharmazie (Weinheim, Germany) 1991, 324,863-866. Other activated esters are well known in the art and include, but are not limited to, N-hydroxysuccinimide esters (see, for 0.192 Compounds of Formula 3a can be prepared by a example, J. Am. Chem. Soc. 2002, 124, 6872-6878). Typical variety of methods known in the art, for example by base temperatures range from 50 to 200°C. Of note are tempera hydrolysis of compounds of Formula3b. Compounds of For tures from 50 to 150°C., which typically provide rapid reac mula 3b can be prepared by arylation of malonate esters tion times and high yields. These reactions can be performed catalyzed by palladium (J. Org. Chem. 2002, 67,541-555) or with or without solvent, Such as toluene, and in microwave copper (Org. Lett. 2002, 4, 269-272 and Org. Lett. 2005, 7, reactors within the same temperature ranges. Typical reaction 4693-4695). times range from 5 minto 2 h. 0193 Alternatively, compounds of Formula3b can be pre pared by the method shown in Scheme 2a (see, for example, Scheme 3 J. Med. Chem. 1982, 25(6), 745-747). RI 2 + LvO OLv Rent- 1 Scheme 2a R1 O O R2CO base RO -- O Her 3c (COR)2 O 0.196 Compounds of the Formula 3c can be prepared, for example, from compounds of Formula3a (see, for example, J. Het. Chem. 1980, 17,337). US 2014/O 187776 A1 Jul. 3, 2014

0197) Compounds of Formula 1 can also be prepared by condensation of compounds of Formula 2 with compounds of Scheme 6 Formula 3d or 3e, or by condensation of compounds of For O mula 2 with mixtures of compounds of Formulae 3d and 3e as shown in Scheme 4. These reactions are typically performed Cl, Br or I in an inert Solvent, such as dichloromethane, and optionally in / N the presence of two or more equivalents of an acid acceptor - -- (see, for example, Zeitschrift fir Naturforschung, Teil B. Z Nt O Anorganische Chemie, Organische Chemie 1982, 37B(2), 222-233). Typical acid acceptors include, but are not limited to, triethylamine, N,N-diisopropylethylamine, pyridine and ls, substituted pyridines. 1b Pd(0)source O -e- 1 Scheme 4 M-R pain, 4 and Ligand(s) RI

C C 0200. In a similar manner, compounds of Formula 1 O O wherein a substituent (e.g., R") consists of two directly 2 -- -e- bonded aromatic rings (e.g., a phenyl or pyridinyl ring bonded 3d to a phenyl ring) can be prepared by palladium-catalyzed RI coupling of the two appropriately substituted aromatic rings. 1 and/or C These palladium-catalyzed couplings between an aromatic C Sa chloride, bromide or iodide and an aromatic boronic acid or no ester, or an aromatic tin or Zinc reagent are well known and O have been extensively described in the art. 3e 0201 These coupling reactions are typically carried out in the presence of a palladium catalyst and a base optionally under an inert atmosphere. The palladium catalysts used for 0198 Compounds of Formula 1a (i.e. analogous to For these coupling reactions typically comprises palladium in a mula 1 wherein R' is H), which are useful as starting com formal oxidation state of either 0 (i.e. Pd(0)) or 2 (i.e. Pd(II)). pounds for the methods of Schemes 7 and 8, can be prepared A wide variety of Such palladium-containing compounds and by condensation of compounds of Formula 2 with carbon complexes are useful as catalysts for these reactions. suboxide (3f) (see, for example, J. Org. Chem. 1972, 37(9), Examples of palladium-containing compounds and com 1422-1425) as shown in Scheme 5. The reactions are typically plexes useful as catalysts in the methods include palladium on performed in an inert Solvent such as ether and can include the carbon, PdCl(PPh) (dichlorobis(triphenylphosphine)pal use of a catalyst Such as AlCls. ladium(II)), Pd(PPh) (tetrakis-(triphenylphosphine)palla dium(0)), Pd(C.H.O.). (palladium(II) acetylacetonate), Pd, (dba) (tris(dibenzylideneacetone)dipalladium(0)), and 1,1'- Scheme 5 bis(diphenylphosphino)-ferrocenedichloropalladium(II). 2 -- OCECECEO -- These coupling methods are generally conducted in a liquid phase, and therefore the palladium catalyst preferably has 3f good solubility in the liquid phase. Useful solvents include, O for example, water, ethers such as 1,2-dimethoxyethane, amides Such as N,N-dimethylacetamide, and non-haloge nated aromatic hydrocarbons such as toluene.

N 0202 The coupling methods can be conducted over a wide (DCZ N YO range of temperatures, ranging from about 25 to about 200° C. Of note are temperatures from about 60 to about 150°C., which typically provide fast reaction times and high product ls, yields. The general methods and procedures for Stille, Negishi and Suzuki couplings with aryl iodides, bromides or la chlorides and an aryl tin, aryl Zinc orarylboronic acid respec tively are well known in the literature; see, for example, E. 0199 Compounds of Formula 1 can also be prepared from Negishi, Handbook of Organopalladium Chemistry for compounds of Formula 1b (i.e. Formula 1 wherein R' is Cl, Br Organic Synthesis, Wiley-Interscience, 2002, New York, N.Y. or I, preferably Br or I) and compounds of Formula 4 wherein 0203 Compounds of Formula 1 can also be prepared from Mwith R' forms a boronic acid, boronic acid ester or trifluo compounds of Formula 1a and compounds of Formula 5 roborate salt, or M is trialkylstannyl or zinc as shown in wherein X is Cl, Br or I (preferably Br or I) as shown in Scheme 6. Scheme 7. US 2014/O 187776 A1 Jul. 3, 2014 12

Scheme 7 Scheme 9 Cu or Pd source 1a + RX -e- O and Ligand 5 R1 / N base 1 -ls alkylating agent 0204 These reactions are typically carried out in the pres Z-1SN OH ence of a copper or palladium catalyst optionally under an inert atmosphere. The copper catalysts used for the present 7 method typically comprise copper in metallic form (e.g., as a powder) or copper in a formal oxidation state of 1 (i.e. Cu(I)). Examples of copper-containing compounds useful as cata 0208 Compounds of Formula 7 can be prepared from lysts in the method of Scheme 7 include Cu, CuI, CuBr, CuCl. compounds of Formula 2a by methods analogous to those Examples of palladium-containing compounds useful as shown in Schemes 1 through 5. Compounds of Formula 2a are catalysts in the method of Scheme 7 include, but are not commercially available or can be prepared by general meth limited to, Pd(OAc). Useful solvents for the method of Scheme 7 include, for example, ethers such as 1,4-dioxane, ods well known in the art. amides such as N,N-dimethylacetamide and dimethylsulfox 0209. A particularly useful method for the preparation of ide. compounds of Formula 2 is shown in Scheme 10. In the 0205 The method of Scheme 7 can be conducted over a method of Scheme 10, compounds of Formula 2a are pro wide range of temperatures from 25 to 200° C. Of note are tected with Suitable protecting groups such as, but not limited temperatures from 40 to 150°C. The method of Scheme 7 can to, tert-butoxycarbonyl, acetyl or formyl to form the interme be conducted in the presence of a ligand. A wide variety of diate of Formula 2b wherein PG is a protecting group. The Such copper-binding compounds are useful as ligands for the compound of Formula 2b is then alkylated with an appropri present method. Examples of useful ligands include 1,10 ate reagent of Formula 8 (wherein X is a leaving group Such phenanthroline, N,N-dimethylethylenediamine, L-proline as a halogen) to give an intermediate of Formula 2c. The and 2-picolinic acid. The general methods and procedures for protecting group is removed to provide a compound of For copper-catalyzed Ullmann-type coupling reactions are well mula 2. Conditions for the formation and removal of protect known in the literature; see, for example, Xie, Ma, et al. Org. ing groups on an amine function are known in the literature Lett. 2005, 7, 4693-4695. (see, for example, Greene, T. W.; Wuts, P. G. M. Protective 0206 Compounds of Formula 1b can be prepared from Groups in Organic Synthesis, 2nd ed.: Wiley: New York, compounds of Formula 1a by halogenation using, for 1991). example, liquid bromine or N-haloSuccinimides (6) as shown in Scheme 8. Typically the reaction is performed in an inert 0210 Compounds of Formula 2 can be prepared in a vari Solvent, more typically a halogenated solvent Such as meth ety of ways known in the art; see, for example, Patai, S. The ylene chloride or 1,2-dichloroethane. The reaction is typi Chemistry of Functional Groups. The Chemistry of Amidines cally performed attemperatures from 0 to 80°C., more typi and Imidates; Wiley: Chichester, UK, 1975; The Chemistry of cally at ambient temperature. Amidines and Imidates; Patai, S.; Rappoport, Z., Eds.; Wiley: Chichester, UK, 1991; Vol. 2: Mega, T. et al. Bulletin of the Chemical Society of Japan 1988, 61 (12), 4315-4321: Ife, R. Scheme 8 et al. European Journal of Medicinal Chemistry 1989, 24(3), O 249-257; Wagaw, S.; Buchwald, S.Journal of Organic Chem istry 1996, 61 (21), 7240-7241; Shen, Q. et al. Angewandte Chemie, International Edition 2005, 44(9), 1371-1375; and 1a + N-Cl, Br or I lb Okano, K. et al. Organic Letters 2003, 5(26), 4987-4990.

O Scheme 10

protecting group (PG) attachment 0207 Compounds of Formula 1 can also be prepared by -> alkylation of compounds of Formula 7 using appropriately Substituted alkylating agents and bases such as potassium carbonate as shown in Scheme 9 (see, for example, Kappe, T. et al. Monatschefte fir Chemie 1971, 102, 412-424 and /N base Urban, M. G.; Arnold, W. Helvetica Chimica Acta 1970, 53, X 905-922). Alkylating agents include, but are not limited to, alkyl chlorides, bromides, iodides and sulfonate esters. A Cls wide variety of bases and solvents can be employed in the method of Scheme 9, and these bases and solvents are well 2b known in the art. US 2014/O 187776 A1 Jul. 3, 2014 13

-continued peak observed by mass spectrometry using atmospheric pres ( N protecting group ( N sure chemical ionization (AP). Z -l. - PG - N - Z 1s Synthesis Example 1 Preparation of 2-hydroxy-4-oxo-3-phenyl-1-(2.2.2- s s trifluoroethyl)-4H-pyrido 1.2-c-pyrimidinium inner salt 2c 2 0215. A mixture of diethyl phenylmalonate (0.62 g, 2.7 mmol) and N-(2.2.2-trifluoroethyl)-2-pyridinamine (0.87 g. 0211 Schemes 1 through 10 illustrate methods to prepare 2.7 mmol, prepared by the method of Bissell, E. R.: compounds of Formula 1 having a variety of Substituents Swanslger, R. W.J. Chem. Eng. Data. 1981, 26, 234-235) was noted for R', R and Z. Compounds of Formula 1 having R', heated to 180°C. for 2 h. After cooling, the reaction mixture R° and Z substituents other than those particularly noted for was purified by chromatography on silica gel by elution with Schemes 1 through 10 can be prepared by general methods ethyl acetate to provide the title compound as a yellow solid known in the art of synthetic organic chemistry, including (45 mg). methods analogous to those described for Schemes 1 to 10. 0216) "H NMR (CDC1) & 9.61 (dd. 1H), 8.17 (ddd, 1H), 0212. It is recognized that Some reagents and reaction 7.74 (d. 2H), 7.55 (d. 1H), 7.45 (t, 1H), 7.39 (m, 2H), 7.21 conditions described above for preparing compounds of For 7.25 (m. 1H), 5.10 (brs, 2H). mula 1 may not be compatible with certain functionalities present in the intermediates. In these instances, the incorpo Synthesis Example 2 ration of protection/deprotection sequences or functional group interconversions into the synthesis will aid in obtaining Preparation of 1-(6-chloro-3-pyridinyl)methyl-3- the desired products. The use and choice of the protecting 2-fluoro-5-(trifluoromethoxy)phenyl-2-hydroxy-4- groups will be apparent to one skilled in chemical synthesis OXO-4H-pyrido 1,2-alpyrimidinium inner salt (see, for example, Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 2nd ed.: Wiley: New York, Step A: Preparation of 1991). One skilled in the art will recognize that, in some 6-chloro-N-2-pyridinyl-3-pyridinemethanamine cases, after the introduction of a given reagent as it is depicted in any individual scheme, it may be necessary to perform 0217. A mixture of 2-fluoropyridine (1.4g, 15 mmol) and additional routine synthetic steps not described in detail to 6-chloro-3-pyridinemethanamine (2.55 g, 18 mmol) in complete the synthesis of compounds of Formula 1. One N-methylpyrrolidinone (5 mL) was heated at 230° C. in a skilled in the art will also recognize that it may be necessary microwave reactor for 30 min. This reaction was repeated to perform a combination of the steps illustrated in the above four times using the same amounts of starting materials for schemes in an order other than that implied by the particular each repetition. All five of the reaction mixtures were then sequence presented to prepare the compounds of Formula 1. poured into saturated aqueous sodium bicarbonate Solution and extracted into ethyl acetate. The organic layer was 0213. One skilled in the art will also recognize that com washed with Saturated aqueous Sodium bicarbonate solution, pounds of Formula 1 and the intermediates described herein dried over NaSO, and concentrated under reduced pressure. can be subjected to various electrophilic, nucleophilic, radi The crude product was then purified by chromatography on cal, organometallic, oxidation, and reduction reactions to add silica gel using 10% ethyl acetate in hexanes as the eluent to Substituents or modify existing Substituents. provide the title compound as an oil (5.1 g). 0214 Without further elaboration, it is believed that one 0218 H NMR (CDC1) & 8.38 (s, 1H), 8.1 (m, 1H), 7.67 skilled in the art using the preceding description can utilize (d. 1H), 7.42 (dd. 1H), 7.28 (d. 1H), 6.63 (m, 1H), 6.38 (d. the present invention to its fullest extent. The following Syn 1H), 4.88 (s, 1H), 4.56 (d. 2H). thesis Examples are, therefore, to be construed as merely illustrative, and not limiting of the disclosure in any way Step B: Preparation of 1-(6-chloro-3-pyridinyl)me whatsoever. Steps in the following Synthesis Examples illus thyl-2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimi trate a procedure for each step in an overall synthetic trans dinium inner salt formation, and the starting material for each step may not have necessarily been prepared by a particular preparative run 0219. A solution of dicyclohexylcarbodiimide (4.12g, 20 whose procedure is described in other Examples or Steps. mmol in 10 mL of dichloromethane) was added to a solution Ambient or room temperature is defined as about 20-25°C. of 6-chloro-N-2-pyridinyl-3-pyridinemethanamine (i.e. the Percentages are by weight except for chromatographic Sol product of Step A) (2.19 g, 10 mmol) and malonic acid (1.04 vent mixtures or where otherwise indicated. Parts and per g, 10 mmol) in dichloromethane (10 mL) in a round bottom centages for chromatographic solvent mixtures are by Vol flask. The reaction mixture was stirred at room temperature ume unless otherwise indicated. "HNMR spectra are reported for 16-24 h. The reaction mixture was then filtered, and the in ppm downfield from tetramethylsilane; "s' means singlet, filtration cake was washed with diethyl ether. The filtrate was “d' means doublet, “dd' means doublet of doublets, “ddd concentrated under reduced pressure, and the resulting resi means doublet of doublet of doublets, “t’ means triplet, “m due was washed with methanol to provide the title compound means multiplet, and “brs' means broad singlet. For mass as a pale yellow solid (2.54 g). spectral data, the numerical value reported is the molecular 0220 "H NMR (acetone-d) & 9.32 (d. 1H), 8.52 (s, 1H), weight of the parent molecular ion (M) formed by addition of 8.29 (dd. 1H), 7.79 (m, 2H), 7.52 (t, 1H), 7.42 (d. 1H), 5.63 (s, H" (molecular weight of 1) to the molecule to give a M+1 2H), 5.03 (s, 1H). US 2014/O 187776 A1 Jul. 3, 2014

Step C: Preparation of 1-(6-chloro-3-pyridinyl)me Step B: Preparation of 1,3-bis(2,4,6-trichlorophenyl) thyl-2-hydroxy-3-iodo-4-oxo-4H-pyrido 1,2-alpyri 2-phenylpropanedioate midinium inner salt 0227. To a slurry of phenylmalonic acid (5.00 g, 27.8 0221 N-iodosuccinimide (1.12g, 5 mmol) was added to a mmol) in dichloromethane (7 mL) at room temperature was solution of 1-(6-chloro-3-pyridinyl)methyl-2-hydroxy-4- added a drop of N,N-dimethylformamide, followed by the OXO-4H-pyrido 1,2-alpyrimidinium inner salt (i.e. the prod dropwise addition of oxalyl chloride (9.09 g, 71.6 mmol) at uct of Step B) (1.4g, 5 mmol) in N,N-dimethylformamide (10 Such a rate to keep gas evolution under control. The reaction mixture was stirred for an additional hour at room tempera mL) and stirred for 5 min. Water was added, and the mixture ture, during which time the reaction mixture clarified. 2.4.6- was extracted with dichloromethane. The combined organic Trichlorophenol (15g, 76 mmol) was added, and the reaction phases were washed repeatedly with water, dried over mixture was stirred at room temperature for 18 h. The reaction Na2SO4, and concentrated under reduced pressure. The mixture was concentrated under vacuum, and methanol (100 resulting crude product (1.8 g) was used in the next step mL) was added to the residue, which resulted in precipitation without further purification. of a large amount of solid. The solid was collected by filtra 0222 "H NMR (CDC1,) & 9.49 (d. 1H), 8.45 (d. 1H), 8.12 tion, rinsed with methanol (80 mL) and air dried to give the (dd. 1H), 7.40 (m, 2H), 7.32 (d. 1H), 5.50 (s. 2H). title product as a white solid (13 g). 0228 H NMR (CDC1) & 7.64-7.62 (m, 2H), 7.46-7.43 Step D: Preparation of 1-(6-chloro-3-pyridinyl)me (m,3H), 7.36 (s, 4H), 5.32 (s, 1H). thyl-3-2-fluoro-5-(trifluoromethoxy)phenyl-2- hydroxy-4-oxo-4H-pyrido 1,2-alpyrimidinium inner Step C: Preparation of 2-hydroxy-4-oxo-3-phenyl-1- salt (2.2.2-trifluoroethyl)-4H-pyrido 1.2-c-pyrimidinium inner salt 0223 1-(6-Chloro-3-pyridinyl)methyl-2-hydroxy-3- 0229. A solution of N-(2.2.2-trifluoroethyl)-2-pyridi iodo-4-oxo-4H-pyrido 1,2-alpyrimidinium inner salt (i.e. the namine (i.e. the product of Step A) (2.00 g, 11.4 mmol) and product of Step C) (206 mg, 0.5 mmol), 2-fluoro-5-(trifluo 1,3-bis(2,4,6-trichlorophenyl) 2-phenylpropanedioate (i.e. romethoxy)benzeneboronic acid (224 mg, 1 mmol) and the product of Step B) (6.40 g, 11.9 mmol) in toluene (40 mL) dichlorobis(triphenyl-phosphine)palladium(II) (35 mg. was refluxed for 1 h. The reaction mixture was cooled in an 0.005 mmol) were dissolved in dioxane (2 mL). Aqueous ice-water bath with stirring for 2 h. The solid that precipitated sodium carbonate solution (2 N, 1 mL) was added, and the was collected by filtration, rinsed with diethyl ether and air reaction mixture was heated in a microwave reactor for 10 dried to give the title compound as a yellow solid (3.44 g). min at 160° C. The cooled reaction mixture was poured 0230 "H NMR (CDS(O)CD,) & 9.37 (d. 1H), 8.42 (m, directly onto a silica gel column and eluted Successively with 1H), 8.11 (d. 1H), 7.66 (d. 2H), 7.61 (m. 1H), 7.32 (t, 2H), hexanes, 30% ethyl acetate in hexanes, 50% ethyl acetate in 7.18 (t, 1H), 5.35 (q, 2H). hexanes, and finally ethyl acetate to yield the title compound as a Solid (20 mg). Synthesis Example 4 0224 'H NMR (CDC1) & 9.53 (d. 1H), 8.49 (s, 1H), 8.11 Preparation of 8-(6-chloro-3-pyridinyl)methyl-7- (dd. 1H), 7.69 (d. 1H), 7.50 (d. 1H), 7.41 (m, 2H), 7.34 (d. hydroxy-5-oxo-6-3-(trifluoromethoxy)phenyl-5H 1H), 7.16 (d. 2H), 7.58 (brs, 2H). thiazolo 3.2-alpyrimidinium inner salt Synthesis Example 3 Step A: Preparation of N-(6-chloro-3-pyridinyl)methylene-2-thiazolamine Preparation of 2-hydroxy-4-oxo-3-phenyl-1-(2.2.2- 0231 2-Aminothiazole (0.75 g, 7.5 mmol) was added to trifluoroethyl)-4H-pyrido 1.2-c-pyrimidinium inner 2-chloropyridine-6-carboxaldehyde (1.0 g, 7.1 mmol) in salt dichloromethane (25 mL) at room temperature. The Suspen sion was stirred an additional 10 min and then concentrated to Step A: Preparation of dryness under vacuum. The resulting residue was heated to N-(2.2.2-trifluoroethyl)-2-pyridinamine 90°C. on a rotary evaporator with a non-returning bump trap to facilitate water removal. After 30 min the resultant yellow 0225. A mixture of 2-fluoropyridine (2.00g, 20.6 mmol) solid was checked by NMR to verify reaction completion (by and 2.2.2-trifluoroethylamine hydrogen chloride (5.00 g, disappearence of the characteristic aldehyde peak at 10.10 36.9 mmol) was heated to 220° C. for 30 min in a microwave ppm (S. 1H)). The title compound was obtained as a yellow reactor. The same reaction was repeated 5 times. The reaction solid (1.55g) and used in the next step without further puri mixtures from all 6 reactions were cooled, combined and fication. diluted with ethyl acetate (150 mL). The organic mixture was 0232 'H NMR (CDC1,) & 9.10 (s, 1H), 8.84 (d. 1H), neutralized by washing with Saturated aqueous Sodium bicar 8.35-8.32 (dd. 1H), 7.72-7.70 (d. 1H), 7.48-746 (d. 1H), bonate, water (30 mL) and brine (30 mL). The organic phase 7.32-7.31 (d. 1H). was dried over NaSO and concentrated, and the resulting residue was purified by chromatography on silica gel using Step B: Preparation of 80% ethyl acetate/hexane as eluant to give the title compound 6-chloro-N-2-thiazolyl-3-pyridinemethanamine as a white solid (17.0 g). 0233 N-(6-chloro-3-pyridinyl)methylene-2-thiazola 0226 H NMR (CDC1) & 8.15 (d. 1H), 7.45 (dd. 1H), 6.69 mine (i.e. the product of Step A) (0.55g, 2.46 mmol) was (dd. 1H), 6.49 (d. 1H), 4.58 (brs, 1H), 4.11 (q, 2H). added portionwise to a stirred excess of sodium borohydride US 2014/O 187776 A1 Jul. 3, 2014

(0.45 g, 11.8 mmol) in methanol (30 mL). Additional portions istry 2000, 65,5834-5836. 2-Phenylmalonic acid monoethyl of sodium borohydride (2x1 equivalent) were added during ester (1.02 g, 5.0 mmol) was dissolved in anhydrous dichlo the addition of the imine to maintain an exothermic reaction. romethane (10 mL), and oxalyl chloride (0.52 mL, 6.0 mmol) After addition was complete, the reaction mixture was was added, followed by one drop of N,N-dimethylforma allowed to stir for 5 min at ambient temperature. The excess mide. The reaction mixture was stirred for 30 min, then con reducing agent was quenched by adding glacial acetic acid centrated, redissolved in anhydrous dichloromethane (5 mL) until gas evolution ceased. The clear reaction mixture was and added to a solution of 6-chloro-N-2-pyridinyl-3-py concentrated, and the resulting residue was partitioned ridinemethanamine (i.e. the product of Example 2, Step A) between Saturated aqueous sodium carbonate and ethyl acetate. The aqueous phase was extracted with ethyl acetate (1.1 g, 5.0 mmol) and triethylamine (0.83 mL, 6.0 mmol) in (3x30 mL), and the combined organic phases were washed anhydrous dichloromethane (5 mL) at 0°C. The stirred reac with brine, dried (MgSO) and concentrated to give the title tion mixture was allowed to warm to room temperature over compound as a tan powder (0.55g). 30 min. The reaction mixture was poured onto a silica gel 0234 H NMR (CDC1) & 8.39 (d. 1H), 7.71-7.68 (dd, cartridge (Bond Elute(R) manufactured by Varian) and purified 1H), 7.30-7.28 (d. 1H), 6.98 (d. 1H), 6.48 (d. 1H), 4.48 (s, using a gradient of 0-50% ethyl acetate/hexanes. A mixture of 2H). desired product and starting amine was isolated (1.3 g of 33 mol % recovered amine/67 mol % desired product). 2-Phe Step C: Preparation of nylmalonic acid monoethyl ester (0.54 g, 2.6 mmol) was 23-(trifluoromethoxy)phenylpropanedioic acid dissolved in anhydrous dichloromethane (3 mL), and oxalyl 0235 Diethyl 3-trifluoromethoxyphenylmalonate (3.00 g, chloride (0.26 mL, 3.0 mmol) was added, followed by one 9.38 mmol) was stirred in an aqueous sodium hydroxide drop of N,N-dimethylformamide. The reaction mixture was solution (15g, 20% by weight) at 65° C. for 10 min. The stirred until gas evolution ceased and then concentrated, reaction mixture was then cooled in an ice bath, and ice (7 g) was added to the reaction mixture, followed by 6 N hydro redissolved in anhydrous dichloromethane (3 mL) and added chloric acid to adjust the pH to about 2. The aqueous mixture to the mixture of recovered amine and desired product iso was saturated with sodium chloride and extracted with ethyl lated previously. The reaction mixture was stirred for 30 min acetate three times. The combined organic phases were dried and then concentrated, and the crude residue was chromato (MgSO4) and concentrated to give a solid, which was tritu graphed as already described to give the title compound as a rated with a mixture of 33% diethyl ether/hexane to give the solid (0.9 g). title compound as a white solid (2.24 g). 0240 "H NMR (CDC1) & 8.50 (m, 1H), 8.18 (s, 1H), 0236 H NMR (CDC(O)CD) 8 11.51 (brs, 2H), 7.54 7.60-7.75 (m, 2H), 7.2-7.3 (m, 5H), 7.13 (m, 2H), 6.87 (s, 7.51 (m, 3H), 7.35-7.30 (m, 1H), 4.91 (s, 1H). 1H), 5.13-4.88 (dd, 2H), 4.86 (s, 1H), 4.16 (m, 2H), 1.22 (t, Step D: Preparation of 8-(6-chloro-3-pyridinyl)me 3H). thyl-7-hydroxy-5-oxo-6-3-(trifluoromethoxy)phe Step B: Preparation of 1-(6-chloro-3-pyridinyl)me nyl-5H-thiazolo 3.2-alpyrimidinium inner salt thyl-2-hydroxy-4-oxo-3-phenyl-4H-pyrido 1,2-a 0237 Oxalyl chloride (1.0 mL, 11 mmol) was added drop pyrimidinium inner salt wise at ambient temperature to a slurry of 2-3-(trifluo 0241 N-(6-chloro-3-pyridinyl)methyl)-2-phenyl-N-(2- romethoxy)phenylpropanedioic acid (i.e. the product of Step pyridinyl)malonamic acid ethyl ester (i.e. the product of Step C) (0.17g, 0.66 mmol) in dichloromethane (0.2 mL) contain A) (200 mg. 0.49 mmol) was added to tetralin (0.5 mL) and ing a catalytic amount of N,N-dimethylformamide. The reac heated at 200°C. for 30 min. The reaction mixture was cooled tion mixture was stirred for an additional 10 min during which and concentrated, and the resulting residue was purified by time gas evolution ceased. The reaction mixture was briefly chromatography on silica gel using 50-100% ethyl acetate/ concentrated under vacuum at ambient temperature. The hexane as eluant to give the title compound as a solid (15 mg). resultant oil was taken up in dichloromethane (2 mL) and added to a solution of 6-chloro-N-2-thiazolyl-3-py 0242 'HNMR (CDC1,) 89.55 (dd. 1H),8.47 (d. 1H),8.04 ridinemethanamine (i.e. the product of Step B) (0.23g, 1.02 (m. 1H), 7.98 (d. 2H), 7.70 (dd. 1H), 7.2-7.4 (m, 6H), 5.58 (s, mmol) and triethylamine (0.40 g, 3.37 mmol) in dichlo 2H). romethane (4 mL) at 0° C. After stirring for 15 min, the Synthesis Example 6 reaction mixture was concentrated, and the resultant residue was purified by chromatography on silica gel using 50-100% Preparation of 1-(2-chloro-5-thiazolyl)methyl-3- ethyl acetate/hexane as eluant to give the title compound as a 2'-chloro-4'-(trifluoromethyl) 1,1'-biphenyl-3-yl)- solid (0.19 g). 2-hydroxy-4-oxo-4H-pyrido 1,2-alpyrimidinium 0238 H NMR (CDC1) & 8.50 (s, 1H), 8.25 (d. 1H), 7.87 inner salt (d. 1H), 7.75 (d. 1H), 7.70 (s, 1H), 741-7.35 (m, 2H), 7.08 (d. 1H), 7.03 (d. 1H), 5.29 (s. 2H). Step A: Preparation of diethyl Synthesis Example 5 2-(3-bromophenyl)propanedioate Preparation of 1-(6-chloro-3-pyridinyl)methyl-2- 0243 Cesium carbonate (15g), Cui (290 mg) and 2-pi hydroxy-4-oxo-3-phenyl-4H-pyrido 1,2-alpyrimi colinic acid (400 mg) were added to a dried flask under a dinium inner salt nitrogen atmosphere, and the flask was again purged with nitrogen. 3-Bromoiodobenzene (8.46 g), diethyl malonate Step A: Preparation of N-(6-chloro-3-pyridinyl) (9.6 mL) and dioxane (50 mL) were then added under a methyl-2-phenyl-N-(2-pyridinyl)malonamic acid nitrogen atmosphere, and the reaction mixture was vigor ethyl ester ously stirred at 50° C. overnight. The reaction mixture was 0239 2-Phenylmalonic acid monoethyl ester was pre then cooled to room temperature, and Saturated aqueous pared following the procedure in Journal of Organic Chem ammonium chloride Solution was added. The reaction mix US 2014/O 187776 A1 Jul. 3, 2014

ture was extracted with ethyl acetate, and the organic phase poured into diethyl ether and filtered to isolate a solid. The was separated, washed with brine, dried over magnesium solid was triturated with diethyl ether, and then heated in sulfate, and concentrated under vacuum to yield 10.5g of the boiling diethyl ether for 1 h. The resulting suspension was title compound containing approximately 25% diethyl mal filtered, and the isolated solid was dried to yield 0.50 g of the onate. "H NMR (CDC1) & 7.47 (s, 1H), 7.33 (d. 1H), 7.24 (d. title compound, a compound of this invention, as a yellow 1H), 7.10 (t, 1H), 4.49 (s, 1H), 4.09 (q, 4H), 1.14 (t, 6H). solid. "H NMR (CDC1) & 9.56 (d. 1H), 8.15 (t, 1H), 7.90 (d. 2H), 7.73 (s, 1H), 7.66 (s, 1H), 7.60 (d. 1H), 7.56 (s. 2H), 7.50 Step B: Preparation of 1,3-diethyl 2-2'-chloro-4'- (t, 1H), 7.41 (t, 1H), 7.39 (d. 1H), 5.60 (brs, 2H). (trifluoromethyl) 1,1'-biphenyl-3-yl)propanedioate 0244 Diethyl 2-(3-bromophenyl)propanedioate (3.75 g), Alternative preparation of 1,3-diethyl 2-2'-chloro-4'- 2-chloro-4-(trifluoromethyl)phenyl boronic acid (4.0 g). (trifluoromethyl) 1,1'-biphenyl-3-ylpropanedioate dioxane (10 mL), 2M aqueous sodium carbonate solution (5 Step A: Preparation of ethyl 2'-chloro-4'-(trifluorom mL) and dichlorobis(triphenylphosphine)palladium(II) (422 ethyl) 1, 1'-biphenyl-3-acetate mg) were added to a vial, and the reaction mixture was heated at 80° C. for 30 minutes. The reaction mixture was then 0248. Ethyl 3-iodophenylacetate (2.90 g), 2-chloro-4-(tri cooled, poured into water, extracted with ethyl acetate, and fluoromethyl)phenyl boronic acid (3.3 g), 2M aqueous the organic phase was separated and concentrated under Sodium carbonate solution (5 mL), dioxane (10 mL) and vacuum in the presence of Celite(R) (diatomaceous earth) to dichloro-bis(triphenylphosphine)palladium(II) (350 mg) yield a crude solid. The crude solid was purified by medium were heated at 80°C. for 30 min with stirring. The reaction pressure liquid chromatography on silica gel eluting with a mixture was then cooled, poured into water, extracted with gradient of ethyl acetate in hexanes to yield 3.2 g of the title ethyl acetate, and the organic layer was separated and con compound. "H NMR (CDC1) & 7.74 (s, 1H), 7.57 (d. 1H), centrated under vacuum in the presence of Celite(R) to a solid 7.37-7.50 (m, 5H), 4.57 (s, 1H), 4.23 (q, 4H), 1.27 (t, 6H). residue. This solid residue was purifed by medium pressure liquid chromatography on silica gel eluting with a gradient of Step C: Preparation of 1,3-bis(2,4,6-trichlorophenyl) ethyl acetate in hexanes to yield 1.7 g of the title compound. 2-2'-chloro-4'-(trifluoromethyl) 1,1'-biphenyl-3-yl) "H NMR (CDC1) & 7.14 (s, 1H), 7.56 (d. 1H) 7.30-7.45 (m, propanedioate 5H), 4.77 (q, 2H), 3.67 (s. 2H), 1.26 (t, 3H). 0245. 1,3-Diethyl 2-2'-chloro-4-(trifluoromethyl)1,1'- Step B: Preparation of 1,3-diethyl 2-2'-chloro-4'- biphenyl-3-ylpropanedioate (3.0 g) was added to 10% aque (trifluoromethyl) 1,1'-biphenyl-3-ylpropanedioate ous sodium hydroxide solution (20 mL) at 50° C., and the reaction mixture was stirred vigorously for 20 min. The reac 0249 NaH (1.2 g. 60% dispersion in mineral oil) was tion mixture was then cooled in an icefacetone bath, and was added to the product of Step A dissolved in diethyl carbonate acidified with concentrated aqueous hydrochloric acid while (10 mL). The reaction mixture was stirred overnight and then keeping the reaction temperature below 10°C. The reaction cautiously quenched by careful addition to saturated aqueous mixture was extracted with diethyl ether, and the separated ammonium chloride solution. The quenched reaction mixture ether phase was dried over magnesium sulfate and concen was extracted with ethyl acetate, and the separated orgranic trated under vacuum to yield a crude product. "H NMR (ac phase was dried and concentrated under vacuum to yield 2.1 etone-d) & 7.89 (s, 1H), 7.79 (d. 1H), 7.67 (d. 2H), 7.60 (m, g of the title compound containing approximately 30% 1H), 7.45-7.55 (m, 2H), 4.88 (s, 1H). diethyl carbonate. "H NMR (CDC1) & 7.74 (s, 1H), 7.57 (d. 0246 The crude product obtained above was dissolved in 1H), 7.35-7.55 (m, 5H), 4.57 (s, 1H)4.19 (q, 4H), 1.29 (t, 6H). anhydrous dichloromethane (50 mL), and N,N-dimethylfor mamide (3 drops) was added, followed by oxalyl chloride Synthesis Example 7 (2.54 mL). The reaction mixture was stirred under nitrogen for 90 min, and then concentrated under vacuum. The result Preparation of 1-(2-chloro-5-thiazolyl)methyl-3-(3. ing oil was redissolved in anhydrous dichloromethane (6 5-dimethoxyphenyl)-2-hydroxy-4-oxo-4H-pyrido1, mL), and 2,4,6-trichlorophenol (3.57 g) was added. The reac 2-alpyrimidinium inner salt tion mixture was stirred overnight, and then the solvent was removed under vacuum to yield a crude solid. The crude solid Step A: Preparation of phenyl was triturated with two 40 mL portions of ice-cold methanol 3,5-dimethoxybenzeneacetate to yield a white solid which was dried under vacuum over 0250. To a slurry of 3,5-dimethoxybenzeneacetic acid night to provide 2.9 g of the title compound as a white solid. (51.5 g) and N,N-dimethylformamide (0.5 mL) in dichlo H NMR (CDC1) & 7.76 (s, 1H), 7.71 (d. 2H), 7.45-7.6 (m, romethane (110 mL) cooled in an ice bath was added drop 4H), 7.37 (s, 4H), 5.38 (s, 1H). wise a solution of oxalyl chloride (41.0 g) in dichloromethane Step D: Preparation of 1-(2-chloro-5-thiazolyl)me (30 mL). The resulting solution was stirred at room tempera thyl-3-2'-chloro-4'-(trifluoromethyl) 1, 1'-biphenyl ture for 5h, and then the solvent was removed under vacuum. 3-yl)-2-hydroxy-4-oxo-4H-pyrido 1.2-cpyrimi A solution of phenol (23.9 g) in dichloromethane (80 mL) dinium inner salt was added, and the reaction mixture was stirred at room temperature for 22h. A saturated aqueous Solution of sodium 0247 bis-trichlorophenyl biphenyl malonate ester (0.72 bicarbonate was added, and the reaction mixture was stirred g), N-(2-chloro-5-thiazolyl)methyl)-2-pyridinamine (0.23 for 0.5 h. The organic layer was separated, dried over anhy g, prepared by the method described in WO 09/099,929) and drous potassium carbonate, and then eluted through a short toluene (1 mL) were heated at 80°C. for 3 h, and then stirred column of silica gel (100 g) with dichloromethane. The first at room temperature overnight. The reaction mixture was then 400 mL of eluent was concentrated under vacuum to yield 65 US 2014/O 187776 A1 Jul. 3, 2014 17 gofthe title compound. 'HNMR (CDC1) & 7.35 (t, 2H), 7.20 namine (34.5 g, prepared by the method described in WO (q, 1H), 7.05 (d. 2H), 6.53 (s. 2H), 6.40 (s, 1H), 3.79 (s, 6H), 09/099,929) and toluene (200 mL) were heated at 100° C. for 3.78 (s. 2H). 22 h, and then cooled and stirred at 0°C. for 3 h. The resulting solid was collected by vacuum filtration and washed with Step B: Preparation of 1,3-diphenyl diethyl ether (500 mL). More solid precipitated upon mixing 2-(3,5-dimethoxyphenyl)propanedioate of the ether washes with the filtrate, and was collected by vacuum filtration and further washed with diethyl ether. The 0251 To a solution of lithium bis(trimethylsilyl)amide two batches of solid were combined and dried under vacuum (400 mL, 1M in tetrahydrofuran obtained commercially from to yield 64 g of the title compound, a compound of this Aldrich Chem. Co.) was added a solution of 3,5-dimethoxy invention, as a yellow solid. "H NMR (DMSO-d) & 9.30 (d. benzeneacetic acid phenyl ester (53.1 g) in tetrahydrofuran 1H), 8.35 (t, 1H), 8.15 (d. 2H), 8.00 (s, 1H), 7.53 (t, 1H), 6.93 (65 mL) dropwise over 20 min while cooling in a dry ice bath (s. 2H), 6.37 (s, 1H), 5.62 (s. 2H), 3.74 (s, 6H). at -70° C. The resulting slurry was stirred at dry ice tempera 0253 By the procedures described herein together with ture for 45 min. Phenyl chloroformate (26 mL) was added all methods known in the art, the following compounds of Tables at once followed by 50 mL of tetrahydrofuran. The resulting 1 to 30 can be prepared. The following abbreviations are used thick slurry was stirred for 2.5 h at 0°C. while cooling in an in Tables 1 to 30 which follow: Me means methyl, Et means ice bath before quenching with diluted aqueous HCl (50 mL ethyl and Primeans propyl. of conc. HCl diluted to 150 mL with water). The bulk of 0254 Tables 1-15 pertain to the structure of Formula T-1 tetrahydrofuran was removed under vacuum and diethyl ether shown below. (550 mL) and water (80 mL) were added. The aqueous layer was separated and extracted with diethyl ether (50 mL). The combined etherlayers were dried over magnesium sulfate and T-1 concentrated under vacuum to yield a crude Solid which was stirred with hexane (250 mL) for 24 h. The solid was then R RC collected by filtration, washed with hexane (100 mL), and O vacuum dried to yield 62 g of the title compound. "H NMR (CDC1) & 7.37 (t, 2H), 7.26 (q, 1H), 7.13 (d. 2H), 6.73 (s, 2H), 6.45 (s, 1H), 5.02 (s, 1H), 3.82 (s, 6H). 21 NN Step C: Preparation of 1-(2-chloro-5-thiazolyl)me S s O thyl-3-(3,5-dimethoxyphenyl)-2-hydroxy-4-oxo-4H pyrido 1,2-alpyrimidinium inner salt 0252) 1,3-diphenyl 2-(3,5-dimethoxyphenyl)propanedio ls, ate (77.7 g), N-(2-chloro-5-thiazolyl)methyl-2-pyridi TABLE 1. R, R, R and R are H: R is 2-chloro-5-thiazolyl

Ra Re Re

OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl 4-cyanophenyl 2-methyl-4-chlorophenyl 4-bromophenyl 2-fluoro-4-(CF)phenyl OCF 6-chloro-3-pyridinyl 2,4-bis(CF)pheny OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl OCHCF, 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl t-Bu C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichloropheny 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF)phenyl R, R, R and R are H; R2 is 2-chloro-5-thiazolyl Rb Rb

OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl O i-Pr 4-bromophenyl 2-fluoro-4-(CF)phenyl OCF 6-chloro-3-pyridinyl 2,4-bis(CF)phenyl cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl

US 2014/O 187776 A1 Jul. 3, 2014 27

TABLE 1-continued R is F: R is Cl; Ran Rare H; R is 2-chloro-5-thiazolyl R Ra Ra Ra H OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl F OEt 4-(CF)phenyl 2-fluoro-4-chloropheny C O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl Br O-i-Pr 4-bromophenyl 2-fluoro-4-(CF)phenyl I OCF, 6-chloro-3-pyridinyl 2.4-bis(CF)phenyl cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromopheny Me OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluoropheny Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)pheny i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)pheny c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chloropheny t-Bu C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chloropheny 3-chlorophenyl 3-(OCF)phenyl 2,4- ichlorophenyl 2,5-dichlorophenyl 3-(CF)phenyl 4-fluorophenyl 2,4- ifluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF)pheny R and Ri are F: Ran Rare H; R is 2-chloro-5-thiazolyl Rb Rb Rb Rb H OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl F OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl C O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl Br O-i-Pr 4-bromophenyl 2-fruoro-4-(CF)phenyl I OCF 6-chloro-3-pyridinyl 2,4-bis(CF)phenyl cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl Me OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl t-Bu C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichlorophenyl 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF)phenyl

Table 2 Table 6 0255 Table 2 is identical to Table 1, except that R is 0259 Table 6 is identical to Table 1, except that R is 6-chloro-3-pyridinyl. For example, the first compound in 5-thiazolyl. For example, the first compound in Table 6 is the Table 2 is the compound of Formula T-1 wherein R. R. R. compound of Formula T-1 wherein R. R. R. R. and Rare R" and Rare H; and R is 6-chloro-3-pyridinyl. H; and R is 5-thiazolyl. Table 3 Table 7 0256 Table 3 is identical to Table 1, except that R is 0260 Table 7 is identical to Table 1, except that R is 6-bromo-3-pyridinyl. For example, the first compound in 2-methyl-5-thiazolyl. For example, the first compound in Table 3 is the compound of Formula T-1 wherein R. R. R. Table 7 is the compound of Formula T-1 wherein R. R. R. R" and Rare H; and R is 6-bromo-3-pyridinyl. R and Rare H; and R is 2-methyl-5-thiazolyl.

Table 4 Table 8 0257 Table 4 is identical to Table 1, except that R is 0261 Table 8 is identical to Table 1, except that R is 6-methyl-3-pyridinyl. For example, the first compound in 6-fluoro-3-pyridinyl. For example, the first compound in Table 4 is the compound of Formula T-1 wherein R. R. R. Table 8 is the compound of Formula T-1 wherein R. R. R. R" and Rare H; and R is 6-methyl-3-pyridinyl. R" and Rare H; and R is 6-fluoro-3-pyridinyl.

Table 5 Table 9 0258 Table 5 is identical to Table 1, except that R is 0262 Table 9 is identical to Table 1, except that R is 3-pyridinyl. For example, the first compound in Table 5 is the 2-bromo-5-thiazolyl. For example, the first compound in compound of Formula T-1 wherein R. R. R. R. and Rare Table 9 is the compound of Formula T-1 wherein R. R. R. H; and R is 3-pyridinyl. R" and Rare H; and R is 2-bromo-5-thiazolyl. US 2014/O 187776 A1 Jul. 3, 2014 28

Table 10 Table 14 0267 Table 14 is identical to Table 1, except that R is 0263 Table 10 is identical to Table 1, except that R is CHCF. For example, the first compound in Table 14 is the 2-fluoro-5-thiazolyl. For example, the first compound in compound of Formula T-1 wherein R. R. R. R. and Rare Table 10 is the compound of Formula T-1 wherein R,R,R, H; and R is CHCF. R and Rare H; and R is 2-fluoro-5-thiazolyl. Table 15 0268 Table 15 is identical to Table 1, except that R is Table 11 CHCFCIF.H. For example, the first compound in Table 15 is 0264. Table 11 is identical to Table 1, except that R is the compound of Formula T-1 wherein R. R. R. RandR 5-pyrimidinyl. For example, the first compound in Table 11 is are H; and R is CHCFCIF.H. the compound of Formula T-1 wherein R. R. R. RandR 0269 Tables 16-30 pertain to the structure of Formula T-2 are H; and R is 5-pyrimidinyl. shown below.

Table 12 0265 Table 12 is identical to Table 1, except that R is 2-methyl-5-pyrimidinyl. For example, the first compound in Table 12 is the compound of Formula T-1 wherein R,R,R, R" and Rare H; and R is 2-methyl-5-pyrimidinyl.

Table 13 0266 Table 13 is identical to Table 1, except that R is CF. For example, the first compound in Table 13 is the compound of Formula T-1 wherein R. R. R. Rand Rare H; and R is CF. TABLE 16 R. R. Rand R are H; R2 is 2-chloro-5-thiazolyl Ra Ra Ra Ra

H OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl F OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl C O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl Br O i-Pr 4-bromophenyl 2-fluoro-4-(CF)phenyl I OCF, 6-chloro-3-pyridinyl 2,4-bis(CF)pheny cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl Me OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichloropheny 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF)phenyl R, R, R and R are H; R2 is 2-chloro-5-thiazolyl R R R OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl O i-Pr 4-bromophenyl 2-fluoro-4-(CF)phenyl OCF 6-chloro-3-pyridinyl 2,4-bis(CF)phenyl cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl Me OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichlorophenyl 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl

US 2014/O 187776 A1 Jul. 3, 2014 38

TABLE 16-continued cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl Me OCHCF, 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl t-Bu C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichlorophenyl 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF3)phenyl RandR are F: Ran Rare H; R is 2-chloro-5-thiazolyl Rb Rb Rb Rb H OMe 4-chlorophenyl 2-fluoro-4-cyanophenyl F OEt 4-(CF)phenyl 2-fluoro-4-chlorophenyl C O—n-Pr 4-cyanophenyl 2-methyl-4-chlorophenyl Br O-i-Pr 4-bromophenyl 2-fruoro-4-(CF)phenyl I OCF 6-chloro-3-pyridinyl 2,4-bis(CF)phenyl cyano OCHF, 6-fluoro-3-pyridinyl 2-fluoro-4-bromophenyl Me OCHCF 6-(CF)-3-pyridinyl 2-chloro-4-fluorophenyl Et CF 4,6-dichloro-3-pyridinyl 2-(CF)-4-fluorophenyl Pr CHF 2-fluoro-6-chloro-3-pyridinyl 2-methyl-4-(CF)phenyl i-Pir CHF, 2,6-dichloro-3-pyridinyl 2-chloro-4-(CF)phenyl c-Pr C(=NOMe)Me 2-bromo-5-chloro-4-pyridinyl 2-(CF)-4-chlorophenyl t-Bu C(=NOEt)Me 3-bromo-5-fluorophenyl 2,5-difluorophenyl phenyl 3-fluorophenyl 3-chloro-5-fluorophenyl 2-fluoro-5-(CF)phenyl 2-fluorophenyl 3-cyanophenyl 3-fluoro-4-chlorophenyl 2-fluoro-5-chlorophenyl 3-chlorophenyl 3-(OCF)phenyl 2,4-dichlorophenyl 2,5-dichlorophenyl 3-(CF)phenyl 4-fluorophenyl 2,4-difluorophenyl 2-fluoro-5-(OCF)phenyl 2-chloro-5-(CF)phenyl

Table 17 Table 22 0270 Table 17 is identical to Table 16, except that R is (0275 Table 22 is identical to Table 16, except that R is 6-chloro-3-pyridinyl. For example, the first compound in 2-methyl-5-thiazolyl. For example, the first compound in Table 17 is the compound of Formula T-2 wherein R,R,R, Table 22 is the compound of Formula T-2 wherein R. R. R. R" and Rare H; and R is 6-chloro-3-pyridinyl. R and Rare H; and R is 2-methyl-5-thiazolyl.

Table 18 Table 23 (0271 Table 18 is identical to Table 16, except that R is (0276 Table 23 is identical to Table 16, except that R is 6-bromo-3-pyridinyl. For example, the first compound in 6-fluoro-3-pyridinyl. For example, the first compound in Table 18 is the compound of Formula T-2 wherein R,R,R, Table 23 is the compound of Formula T-2 wherein R,R,R, R" and Rare H; and R is 6-bromo-3-pyridinyl. R" and Rare H; and R is 6-fluoro-3-pyridinyl.

Table 19 Table 24 (0272 Table 19 is identical to Table 16, except that R is (0277 Table 24 is identical to Table 16, except that R is 6-methyl-3-pyridinyl. For example, the first compound in 2-bromo-5-thiazolyl. For example, the first compound in Table 19 is the compound of Formula T-2 wherein R,R,R, Table 24 is the compound of Formula T-2 wherein R. R. R. R" and Rare H; and R is 6-methyl-3-pyridinyl. R" and Rare H; and R is 2-bromo-5-thiazolyl.

Table 20 Table 25 (0273 Table 20 is identical to Table 16, except that R is (0278 Table 25 is identical to Table 16, except that R is 3-pyridinyl. For example, the first compound in Table 20 is 2-fluoro-5-thiazolyl. For example, the first compound in the compound of Formula T-2 wherein R. R. R. RandR Table 25 is the compound of Formula T-2 wherein R,R,R, are H; and R is 3-pyridinyl. R" and Rare H; and R is 2-fluoro-5-thiazolyl.

Table 21 Table 26 0274 Table 21 is identical to Table 16, except that R is (0279 Table 26 is identical to Table 16, except that R is 5-thiazolyl. For example, the first compound in Table 21 is the 5-pyrimidinyl. For example, the first compound in Table 26 is compound of Formula T-2 wherein R. R. R. R. and Rare the compound of Formula T-2 wherein R. R. R. RandR H; and R is 5-thiazolyl. are H; and R is 5-pyrimidinyl.

US 2014/O 187776 A1 Jul. 3, 2014 54

TABLE 36-continued selected from the group consisting of Surfactants, Solid dilu

ents and liquid diluents, which serves as a carrier. The formu lation or composition ingredients are selected to be consistent with the physical properties of the active ingredient, mode of application and environmental factors such as Soil type, mois ture and temperature. 0285) Useful formulations include both liquid and solid compositions. Liquid compositions include Solutions (in cluding emulsifiable concentrates), Suspensions, emulsions (including microemulsions and/or Suspoemulsions) and the like, which optionally can be thickened into gels. The general types of aqueous liquid compositions are soluble concentrate, R’ is 5-thiazolyl Suspension concentrate, capsule Suspension, concentrated emulsion, microemulsion and Suspo-emulsion. The general 4-chloro-2-fluoropheny types of nonaqueous liquid compositions are emulsifiable 2-fluoro-4-(trifluoromethyl)p henyl 4-cyano-2-fluoropheny concentrate, microemulsifiable concentrate, dispersible con 2-chloro-4-cyanopheny centrate and oil dispersion. 2-chloro-4-(trifluoromethyl)phenyl 0286 The general types of solid compositions are dusts, 2-fluoro-5-(trifluoromethyl)phenyl 2-fluoro-5-(trifluoromethoxy)phenyl powders, granules, pellets, prills, pastilles, tablets, filled films 4-chloro-2-methylpheny (including seed coatings) and the like, which can be water R’ is 2-methyl-5-thiazolyl dispersible (“wettable') or water-soluble. Films and coatings formed from film-forming Solutions or flowable Suspensions 4-chloro-2-fluoropheny 2-fluoro-4-(trifluoromethyl)p henyl are particularly useful for seed treatment. Active ingredient 4-cyano-2-fluoropheny can be (micro)encapsulated and furtherformed into a Suspen 2-chloro-4-cyanopheny sion or solid formulation; alternatively the entire formulation 2-chloro-4-(trifluoromethyl)phenyl of active ingredient can be encapsulated (or “overcoated'). 2-fluoro-5-(trifluoromethyl)phenyl 2-fluoro-5-(trifluoromethoxy)phenyl Encapsulation can control or delay release of the active ingre 4-chloro-2-methylpheny dient. An emulsifiable granule combines the advantages of R’ is 2-fluoro-5-thiazoly both an emulsifiable concentrate formulation and a dry granu lar formulation. High-strength compositions are primarily 4-chloro-2-fluoropheny 2-fluoro-4-(trifluoromethyl)p henyl used as intermediates for further formulation. 4-cyano-2-fluoropheny 0287 Sprayable formulations are typically extended in a 2-chloro-4-cyanopheny 2-chloro-4-(trifluoromethyl)phenyl Suitable medium before spraying. Such liquid and Solid for 2-fluoro-5-(trifluoromethyl)phenyl mulations are formulated to be readily diluted in the spray 2-fluoro-5-(trifluoromethoxy)phenyl medium, usually water. Spray Volumes can range from about 4-chloro-2-methylpheny one to several thousand liters per hectare, but more typically R’ is 2-bromo-5-thiazoly are in the range from about ten to several hundred liters per 4-chloro-2-fluoropheny hectare. Sprayable formulations can be tank mixed with water 2-fluoro-4-(trifluorome or another suitable medium for foliar treatment by aerial or 4-cyano-2-fluoropheny ground application, or for application to the growing medium 2-chloro-4-cyanopheny of the plant. Liquid and dry formulations can be metered 2-chloro-4-(trifluorome 2-fluoro-5-(trifluorome directly into drip irrigation systems or metered into the furrow 2-fluoro-5-(trifluorome during planting. Liquid and solid formulations can be applied 4-chloro-2-methy onto seeds of crops and other desirable vegetation as seed R’ is 5-pyrimidi treatments before planting to protect developing roots and 4-chloro-2-fluoropheny other Subterranean plant parts and/or foliage through sys 2-fluoro-4-(trifluorome temic uptake. 4-cyano-2-fluoropheny 2-chloro-4-cyanopheny 0288 The formulations will typically contain effective 2-chloro-4-(trifluorome amounts of active ingredient, diluent and Surfactant within 2-fluoro-5-(trifluorome the following approximate ranges which add up to 100 per 2-fluoro-5-(trifluorome cent by weight. 4-chloro-2-methy R’ is 2-me 4-chloro-2-fluoropheny Weight Percent 2-fluoro-4-(trifluorome 4-cyano-2-fluoropheny Active 2-chloro-4-cyanopheny Ingredient Diluent Surfactant 2-chloro-4-(trifluorome Water-Dispersible and Water- O.OO1-90 O-99.999 O-15 2-fluoro-5-(trifluorome soluble Granules, Tablets and 2-fluoro-5-(trifluorome Powders 4-chloro-2-methy Oil Dispersions, Suspensions, 1-SO 40-99 O-SO Emulsions, Solutions (including Emulsifiable 0284. A composition of this invention will generally be Concentrates) used as a formulation with at least one additional component US 2014/O 187776 A1 Jul. 3, 2014 55

-continued alcohols (which are branched or linear) and prepared from the alcohols and ethylene oxide, propylene oxide, butylene oxide Weight Percent or mixtures thereof, amine ethoxylates, alkanolamides and ethoxylated alkanolamides; alkoxylated triglycerides such as Active ethoxylated Soybean, castor and rapeseed oils; alkylphenol Ingredient Diluent Surfactant alkoxylates such as octylphenol ethoxylates, nonylphenol Dusts 1-2S 70-99 O-5 ethoxylates, dinonyl phenol ethoxylates and dodecyl phenol Granules and Pellets O.OO1-95 S-99.999 O-15 ethoxylates (prepared from the phenols and ethylene oxide, High Strength Compositions 90-99 O-10 O-2 propylene oxide, butylene oxide or mixtures thereof); block polymers prepared from ethylene oxide or propylene oxide 0289 Solid diluents include, for example, clays such as and reverse block polymers where the terminal blocks are bentonite, montmorillonite, attapulgite and kaolin, gypsum, prepared from propylene oxide; ethoxylated fatty acids; cellulose, titanium dioxide, Zinc oxide, starch, dextrin, Sugars ethoxylated fatty esters and oils; ethoxylated methyl esters: (e.g., lactose, Sucrose), silica, talc, mica, diatomaceous earth, ethoxylated tristyrylphenol (including those prepared from urea, calcium carbonate, sodium carbonate and bicarbonate, ethylene oxide, propylene oxide, butylene oxide or mixtures and sodium sulfate. Typical solid diluents are described in thereof); fatty acid esters, glycerol esters, lanolin-based Watkins et al., Handbook of Insecticide Dust Diluents and derivatives, polyethoxylate esters such as polyethoxylated Carriers, 2nd Ed., Dorland Books, Caldwell, N.J. sorbitan fatty acid esters, polyethoxylated sorbitol fatty acid 0290 Liquid diluents include, for example, water, N.N- esters and polyethoxylated glycerol fatty acid esters; other dimethylalkanamides (e.g., N,N-dimethylformamide), Sorbitan derivatives such as Sorbitan esters; polymeric Surfac limonene, dimethyl Sulfoxide, N-alkylpyrrolidones (e.g., tants such as random copolymers, block copolymers, alkyd N-methylpyrrolidinone), ethylene glycol, triethylene glycol, peg (polyethylene glycol) resins, graft or comb polymers and propylene glycol, dipropylene glycol, polypropylene glycol, star polymers; polyethylene glycols (pegs); polyethylene gly propylene carbonate, butylene carbonate, paraffins (e.g., col fatty acid esters; silicone-based Surfactants; and Sugar white mineral oils, normal paraffins, isoparaffins), alkylben derivatives such as Sucrose esters, alkyl polyglycosides and Zenes, alkylnaphthalenes, glycerine, glycerol triacetate, Sor alkyl polysaccharides. bitol, triacetin, aromatic hydrocarbons, dearomatized aliphat 0293 Useful anionic surfactants include, but are not lim ics, alkylbenzenes, alkylnaphthalenes, ketones Such as ited to: alkylaryl sulfonic acids and their salts; carboxylated cyclohexanone, 2-heptanone, isophorone and 4-hydroxy-4- alcohol or alkylphenol ethoxylates; diphenyl sulfonate methyl-2-pentanone, acetates such as isoamyl acetate, hexyl derivatives; lignin and lignin derivatives such as lignoSul acetate, heptyl acetate, octyl acetate, nonyl acetate, tridecyl fonates; maleic or Succinic acids or their anhydrides; olefin acetate and isobornyl acetate, other esters such as alkylated Sulfonates; phosphate esters such as phosphate esters of alco lactate esters, dibasic esters and Y-butyrolactone, and alco hol alkoxylates, phosphate esters of alkylphenol alkoxylates hols, which can be linear, branched, saturated or unsaturated, and phosphate esters of Styryl phenol ethoxylates; protein Such as methanol, ethanol, n-propanol, isopropyl alcohol, based Surfactants; sarcosine derivatives; Styryl phenol ether n-butanol, isobutyl alcohol, n-hexanol, 2-ethylhexanol, n-oc Sulfate; sulfates and Sulfonates of oils and fatty acids; Sulfates tanol, decanol, isodecyl alcohol, isooctadecanol, cetyl alco and sulfonates of ethoxylated alkylphenols; sulfates of alco hol, lauryl alcohol, tridecyl alcohol, oleyl alcohol, cyclohex hols; sulfates of ethoxylated alcohols; sulfonates of amines anol, tetrahydrofurfuryl alcohol, diacetone alcohol and and amides such as N,N-alkyltaurates; Sulfonates of benzene, benzyl alcohol. Liquid diluents also include glycerolesters of cumene, toluene, Xylene, and dodecyl and tridecylbenzenes; saturated and unsaturated fatty acids (typically C-C). Such Sulfonates of condensed naphthalenes; Sulfonates of naphtha as plant seed and fruit oils (e.g., oils of olive, castor, linseed, lene and alkyl naphthalene; Sulfonates of fractionated petro sesame, corn (maize), peanut, Sunflower, grapeseed, saf leum; SulfoSuccinamates; and SulfoSuccinates and their flower, cottonseed, soybean, rapeseed, coconut and palm ker derivatives such as dialkyl SulfoSuccinate salts. nel), animal-sourced fats (e.g., beef tallow, pork tallow, lard, 0294. Useful cationic surfactants include, but are not lim cod liver oil, fish oil), and mixtures thereof. Liquid diluents ited to: amides and ethoxylated amides; amines such as also include alkylated fatty acids (e.g., methylated, ethylated, N-alkyl propanediamines, tripropylenetriamines and dipro butylated) wherein the fatty acids can be obtained by hydroly pylenetetramines, and ethoxylated amines, ethoxylated sis of glycerol esters from plant and animal sources, and can diamines and propoxylated amines (prepared from the be purified by distillation. Typical liquid diluents are amines and ethylene oxide, propylene oxide, butylene oxide described in Marsden, Solvents Guide, 2nd Ed., Interscience, or mixtures thereof); amine salts such as amine acetates and New York, 1950. diamine salts; quaternary ammonium salts such as quaternary 0291. The solid and liquid compositions of the present salts, ethoxylated quaternary salts and diquaternary salts; and invention often include one or more surfactants. When added amine oxides such as alkyldimethylamine oxides and bis-(2- to a liquid, Surfactants (also known as 'surface-active hydroxyethyl)-alkylamine oxides. agents”) generally modify, most often reduce, the Surface 0295 Also useful for the present compositions are mix tension of the liquid. Depending on the nature of the hydro tures of nonionic and anionic Surfactants or mixtures of non philic and lipophilic groups in a surfactant molecule, Surfac ionic and cationic Surfactants. Nonionic, anionic and cationic tants can be useful as wetting agents, dispersants, emulsifiers Surfactants and their recommended uses are disclosed in a or defoaming agents. variety of published references including McCutcheon's 0292 Surfactants can be classified as nonionic, anionic or Emulsifiers and Detergents, annual American and Interna cationic. Nonionic Surfactants useful for the present compo tional Editions published by McCutcheon's Division, The sitions include, but are not limited to: alcohol alkoxylates Manufacturing Confectioner Publishing Co.: Sisely and Such as alcohol alkoxylates based on natural and synthetic Wood, Encyclopedia of Surface Active Agents, Chemical US 2014/O 187776 A1 Jul. 3, 2014 56

Publ. Co., Inc., New York, 1964; and A. S. Davidson and B. through Col. 7, line 62 and Examples 8, 12, 15, 39, 41, 52, 53. Milwidsky, Synthetic Detergents, Seventh Edition, John 58, 132, 138-140, 162-164, 166, 167 and 169-182: U.S. Pat. Wiley and Sons, New York, 1987. No. 2,891,855, Col. 3, line 66 through Col. 5, line 17 and 0296 Compositions of this invention can also contain for Examples 1-4. Klingman, Weed Control as a Science, John mulation auxiliaries and additives, known to those skilled in Wiley and Sons, Inc., New York, 1961, pp 81–96: Hance et al., the art as formulation aids (some of which can be considered Weed Control Handbook, 8th Ed., Blackwell Scientific Pub to also function as solid diluents, liquid diluents or Surfac lications, Oxford, 1989; and Developments in formulation tants). Such formulation auxiliaries and additives can control: technology, PJB Publications, Richmond, UK, 2000. pH (buffers), foaming during processing (antifoams such polyorganosiloxanes), sedimentation of active ingredients 0299. In the following Examples, all formulations are pre (Suspending agents), viscosity (thixotropic thickeners), in pared in conventional ways. “Active ingredients' refers to the container microbial growth (antimicrobials), product freez aggregate of biologically active compounds or agents con ing (antifreezes), color (dyes/pigment dispersions), wash-off sisting of invertebrate pest control agents selected from the (film formers or stickers), evaporation (evaporation retar group (b) and fungicides in combination with the compound dants), and other formulation attributes. Film formers of Formula 1. For example, “active ingredients’ can include a include, for example, polyvinyl acetates, polyvinyl acetate compound of Formula 1 and a further second invertebrate pest copolymers, polyvinylpyrrolidone-vinyl acetate copolymer, control agent selected from the group (b), or a compound of polyvinyl alcohols, polyvinyl alcohol copolymers and waxes. Formula 1, a further second invertebrate pest control agent Examples of formulation auxiliaries and additives include selected from the group (b), and a fungicide. Without further those listed in McCutcheon's Volume 2: Functional Materi elaboration, it is believed that one skilled in the art using the als, annual International and North American editions pub preceding description can utilize the present invention to its lished by McCutcheon's Division, The Manufacturing Con fullest extent. The following Examples are, therefore, to be fectioner Publishing Co.; and PCT Publication WO construed as merely illustrative, and not limiting of the dis 03/024222. closure in any way whatsoever. Percentages are by weight 0297. The compound of Formula 1 and any other active except where otherwise indicated. ingredients are typically incorporated into the present com positions by dissolving the active ingredient in a solvent or by grinding in a liquid or dry diluent. Solutions, including emul Example A sifiable concentrates, can be prepared by simply mixing the ingredients. If the solvent of a liquid composition intended for 0300 use as an emulsifiable concentrate is water-immiscible, an emulsifier is typically added to emulsify the active-containing Solvent upon dilution with water. Active ingredient slurries, High Strength Concentrate with particle diameters of up to 2,000 um can be wet milled using media mills to obtain particles with average diameters active ingredients 98.5% below 3 Lum. Aqueous slurries can be made into finished silica aerogel O.S90 Suspension concentrates (see, for example, U.S. Pat. No. synthetic amorphous fine silica 1.0% 3,060,084) or further processed by spray drying to form water-dispersible granules. Dry formulations usually require dry milling processes, which produce average particle diam eters in the 2 to 10 um range. Dusts and powders can be Example B prepared by blending and usually grinding (such as with a hammer mill or fluid-energy mill). Granules and pellets can 0301 be prepared by spraying the active material upon preformed granular carriers or by agglomeration techniques. See Brown ing, "Agglomeration’, Chemical Engineering, Dec. 4, 1967. Wettable Powder pp 147-48, Perry's Chemical Engineer's Handbook, 4th Ed., active ingredients 65.0% McGraw-Hill, New York, 1963, pages 8-57 and following, dodecylphenol polyethylene glycol ether 2.0% and WO 91/13546. Pellets can be prepared as described in sodium ligninsulfonate 4.0% U.S. Pat. No. 4,172,714. Water-dispersible and water-soluble sodium silicoaluminate 6.0% granules can be prepared as taught in U.S. Pat. No. 4,144,050, montmorillonite (calcined) 23.0% U.S. Pat. No. 3,920,442 and DE 3,246,493. Tablets can be prepared as taught in U.S. Pat. Nos. 5,180,587, 5,232,701 and 5,208,030. Films can be prepared as taught in GB 2,095,558 Example C and U.S. Pat. No. 3,299,566. 0298 For further information regarding the art of formu 0302) lation, see T. S. Woods, “The Formulator's Toolbox Prod uct Forms for Modern Agriculture' in Pesticide Chemistry and Bioscience, The Food-Environment Challenge, T. Brooks Granule and T. R. Roberts, Eds. Proceedings of the 9th International active ingredients 10.0% Congress on Pesticide Chemistry, The Royal Society of attapulgite granules (low volatile matter, 90.0% Chemistry, Cambridge, 1999, pp. 120-133. See also U.S. Pat. 0.71/0.30 mm; U.S.S. No. 25-50 sieves) No. 3,235,361, Col. 6, line 16 through Col. 7, line 19 and Examples 10-41; U.S. Pat. No. 3,309,192, Col. 5, line 43 US 2014/O 187776 A1 Jul. 3, 2014 57

Example D -continued 0303 Fertilizer Stick

kaolin 38.00% Extruded Pellet Water 10.60% active ingredients 25.0% anhydrous Sodium sulfate 10.0% crude calcium ligninsulfonate S.O% Example I Sodium alkylnaphthalenesulfonate 1.0% calcium/magnesium bentonite 59.0% 0308

Example E Suspension Concentrate active ingredients 35% 0304 butyl polyoxyethylene polypropylene block copolymer 4.0% Stearic acid polyethylene glycol copolymer 1.0% styrene acrylic polymer 1.0% Xanthan gum O.1% Emulsifiable Concentrate propylene glycol S.O% silicone based defoamer O.1% active ingredients 10.0% 12-benzisothiazolin-3-one O.1% polyoxyethylene sorbitol hexoleate 20.0% s 0.XO Co-Co fatty acid methyl ester 70.0% Water 53.7%

Example J Example F p 0309 0305

Emulsion in Water Microemulsion active ingredients 10.0% active ingredients S.0% butyl polyoxyethylene polypropylene block copolymer 4.0% polyvinylpyrrollidone-vinyl acetate copolymer 30.0% Stearic acid polyethylene glycol copolymer 1.0% alkylpolyglycoside 30.0% styrene acrylic polymer 1.0% glyceryl monooleate 15.0% Xanthan gum O.1% Water 20.0% propylene glycol S.0% silicone based defoamer O.1% 1,2-benzisothiazolin-3-one O.1% aromatic petroleum based hydrocarbon 2O.O Example G Water 58.7% 0306 Example K Seed Treatment 0310 active ingredients 20.00% polyvinylpyrrollidone-vinyl acetate copolymer S.OO% montan acid wax S.OO% Oil Dispersion calcium ligninsulfonate 1.00% 0. polyoxyethylene polyoxypropylene block copolymers 1.00% active ingredients 25 % stearyl alcohol (POE 20) 2.00% polyoxyethylene sorbitol hexaoleate 15% poly organosilane O.20% organically modified bentonite clay 2.5% colorant red dye O.05% fatty acid methyl ester 57.5% Water 65.75% Example L Example H 0311 0307 Suspoemulsion Fertilizer Stick active ingredients 10.0% flusiazole S.0% active ingredients 2.50% butyl polyoxyethylene polypropylene block copolymer 4.0% pyrrollidone-styrene copolymer 4.80% Stearic acid polyethylene glycol copolymer 1.0% tristyrylphenyl 16-ethoxylate 2.30% styrene acrylic polymer 1.0% talc O.80% Xanthan gum O.1% corn starch S.00% propylene glycol S.0% slow-release fertilizer 36.00% silicone based defoamer O.1% US 2014/0187776 A1 Jul. 3, 2014 58

-continued phosphorus, potassium, sulfur, calcium, magnesium, iron, copper, boron, manganese, zinc, and molybdenum. Of note Suspoemulsion are compositions comprising at least one fertilizer composi 1,2-benzisothiazolin-3-one 0.1% tion comprising at least one plant nutrient selected from nitro aromatic petroleum based hydrocarbon 20.0% gen, phosphorus, potassium, Sulfur, calcium and magnesium. water 53.7% Compositions of the present invention which further com prise at least one plant nutrient can be in the form of liquids or 0312 Compositions of this invention exhibit activity solids. Of note are solid formulations in the form of granules, against a wide spectrum of invertebrate pests. These pests small sticks or tablets. Solid formulations comprising a fer include invertebrates inhabiting a variety of environments tilizer composition can be prepared by mixing the compound such as, for example, plant foliage, roots, soil, harvested or composition of the present invention with the fertilizer crops or other foodstuffs, building structures or animal composition together with formulating ingredients and then integuments. These pests include, for example, invertebrates preparing the formulation by methods such as granulation or feeding on foliage (including leaves, stems, flowers and extrusion. Alternatively solid formulations can be prepared fruits), seeds, wood, textile fibers or animal blood or tissues, by spraying a solution or suspension of a compound or com and thereby causing injury or damage to, for example, grow position of the present invention in a volatile solvent onto a ing or stored agronomic crops, forests, greenhouse crops, previous prepared fertilizer composition in the form of ornamentals, nursery crops, stored foodstuffs or fiber prod dimensionally stable mixtures, e.g., granules, Small sticks or ucts, or houses or other structures or their contents, or being tablets, and then evaporating the solvent. harmful to animal health or public health. Those skilled in the 0315 Examples of agronomic or nonagronomic inverte art will appreciate that not all compounds are equally effec brate pests include eggs, larvae and adults of the order Lepi tive against all growth stages of all pests. doptera, such as armyworms, cutworms, loopers, and helio 0313. These present compositions are thus useful agro thines in the family Noctuidae (e.g., pink stem borer (Sesamia nomically for protecting field crops from phytophagous inferens Walker), corn stalk borer (Sesamia nonagrioides invertebrate pests, and also nonagronomically for protecting Lefebvre), southern armyworm (Spodoptera eridania otherhorticultural crops and plants from phytophagous inver Cramer), fall armyworm (Spodoptera fugiperda J. E. Smith). tebrate pests. This utility includes protecting crops and other beet armyworm (Spodoptera exigua Hübner), cotton leaf plants (i.e. both agronomic and nonagronomic) that contain worm (Spodoptera littoralis Boisduval), yellowstriped army genetic material introduced by genetic engineering (i.e. trans worm (Spodoptera Ornithogalli Guenée), black cutworm genic) or modified by mutagenesis to provide advantageous (Agrotis ipsilon Hufnagel), Velvetbean caterpillar (Anticarsia traits. Examples of such traits include tolerance to herbicides, gemmatalis Hübner), green fruitworm (Lithophane anten resistance to phytophagous pests (e.g., insects, mites, aphids, nata Walker), cabbage armyworm (Barathra brassicae Lin spiders, nematodes, snails, plant-pathogenic fungi, bacteria naeus), soybean looper (Pseudoplusia includens Walker). and viruses), improved plant growth, increased tolerance of cabbage looper (Trichoplusia ni Hübner), tobacco budworm adverse growing conditions such as high or low temperatures, (Heliothis virescens Fabricius)); borers, casebearers, web low or high soil moisture, and high salinity, increased flow worms, coneworms, cabbageworms and skeletonizers from ering or fruiting, greater harvest yields, more rapid matura the family Pyralidae (e.g., European corn borer (Ostrinia tion, higher quality and/or nutritional value of the harvested nubilalis Hübner), navel orangeworm (Amyelois transitella product, or improved storage or process properties of the Walker), corn root webworm (Crambus caliginosellus Clem harvested products. Transgenic plants can be modified to ens), sod webworms (Pyralidae: Crambinae) such as sod express multiple traits. Examples of plants containing traits worm (Herpetogramma licarsisalis Walker), Sugarcane stem provided by genetic engineering or mutagenesis include vari borer (Chilo infiscatellus Snellen), tomato small borer (Neo eties of corn, cotton, soybean and potato expressing an insec leucinodes elegantalis Guenée), green leafroller (Cnaphalo ticidal Bacillus thuringiensis toxin such as YIELD GARDR, cerus medinalis), grape leaffolder (Desmia funeralis Hüb KNOCKOUTR), STARLINK(R, BOLLGARDR, ner), melon worm (Diaphania initidalis Stoll), cabbage center NuCOTNR) and NEWLEAF(R), and herbicide-tolerant variet grub (Helluala hydralis Guenée), yellow stem borer (Scir ies of corn, cotton, soybean and rapeseed such as ROUNDUP pophaga incertulas Walker), early shoot borer (Scirpophaga READYR), LIBERTY LINKR, IMIR, STS(R) and infiscatellus Snellen), white stem borer (Scirpophaga inno CLEARFIELDR), as well as crops expressing N-acetyltrans tata Walker), top shoot borer (Scirpophaga nivella Fabri ferase (GAT) to provide resistance to glyphosate herbicide, or cius), dark-headed rice borer (Chilo polychrysus Meyrick), crops containing the HRA gene providing resistance to her cabbage cluster caterpillar (Crocidolomia binotalis bicides inhibiting acetolactate synthase (ALS). The present English)); leafrollers, budworms, seed worms, and fruit compositions may interact synergistically with traits intro worms in the family Tortricidae (e.g., codling moth (Cydia duced by genetic engineering or modified by mutagenesis, pomonella Linnaeus), grape berry moth (Endopiza Viteana thus enhancing phenotypic expression or effectiveness of the Clemens), oriental fruit moth (Grapholita molesta Busck), traits or increasing the invertebrate pest control effectiveness citrus false codling moth (Cryptophlebia leucotreta Mey of the present compositions. In particular, the present com rick), citrus borer (Ecdytolopha aurantiana Lima), red positions may interact synergistically with the phenotypic banded leafroller (Argyrotaenia velutinana Walker), oblique expression of proteins or other natural products toxic to inver banded leafroller (Choristoneura rosaceana Harris), light tebrate pests to provide greater-than-additive control of these brown apple moth (Epiphyas postvittana Walker), European pests. grape berry moth (Eupoecilia ambiguella Hübner), apple bud 0314 Compositions of this invention can also optionally moth (Pandemis pyrusana Kearfott), omnivorous leafroller comprise plant nutrients, e.g., a fertilizer composition com (Platynota Stultana Walsingham), barred fruit-tree tortrix prising at least one plant nutrient selected from nitrogen, (Pandemis cerasana Hübner), apple brown tortrix (Pandemis US 2014/O 187776 A1 Jul. 3, 2014 59 heparana Denis & Schiffermüller)); and many other eco idae, phylloxera from the family Phylloxeridae, mealybugs nomically important lepidoptera (e.g., diamondback moth from the family Pseudococcidae, scales from the families (Plutella xylostella Linnaeus), pink bollworm (Pectinophora Coccidae, Diaspididae and Margarodidae, lace bugs from the gossypiella Saunders), gypsy moth (Lymantria dispar Lin family Tingidae, Stink bugs from the family Pentatomidae, naeus), peach fruit borer (Carposina niponensis Walsing chinch bugs (e.g., hairy chinch bug (Blissus leucopterus hir ham), peach twig borer (Anarsia lineatella Zeller), potato tus Montandon) and Southern chinch bug (Blissus insularis tuberworm (Phthorimaea operculella Zeller), spotted teni Barber)) and other seed bugs from the family Lygaeidae, form leafminer (Lithocolletis blancardella Fabricius), Asiatic Spittlebugs from the family Cercopidae squash bugs from the apple leafminer (Lithocolletis ringoniella Matsumura), rice family Coreidae, and red bugs and cotton stainers from the leaffolder (Lerodea eufala Edwards), apple leafminer (Leu family Pyrrhocoridae. coptera scitella Zeller)); eggs, nymphs and adults of the order Blattodea including cockroaches from the families Blattel 0317 Agronomic and nonagronomic pests also include: lidae and Blattidae (e.g., oriental cockroach (Blatta Orientalis eggs, larvae, nymphs and adults of the order Acari (mites) Linnaeus), Asian cockroach (Blatella asahinai Mizukubo), Such as spidermites and red mites in the family Tetranychidae German cockroach (Blattella germanica Linnaeus), brown (e.g., European red mite (Panonychus ulmi Koch), two spot banded cockroach (Supella longipalpa Fabricius), American ted spider mite (Tetranychus urticae Koch), McDaniel mite cockroach (Periplaneta americana Linnaeus), brown cock (Tetranychus mcdanieli McGregor)); flat mites in the family roach (Periplaneta brunnea Burmeister), Madeira cockroach Tenuipalpidae (e.g., citrus flat mite (Brevipalpus lewisi (Leucophaea maderae Fabricius)). Smoky brown cockroach McGregor)); rustandbud mites in the family Eriophyidae and (Periplaneta fuliginosa Service), Australian Cockroach other foliar feeding mites and mites important in human and (Periplaneta australasiae Fabr.), lobster cockroach (Naupho animal health, i.e. dust mites in the family Epidermoptidae, eta cinerea Olivier) and Smooth cockroach (Symplocepallens follicle mites in the family Demodicidae, grain mites in the Stephens)); eggs, foliar feeding, fruit feeding, root feeding, family Glycyphagidae, ticks in the family Ixodidae, com seed feeding and vesicular tissue feeding larvae and adults of monly known as hard ticks (e.g., deer tick (Ixodes scapularis the order Coleoptera including weevils from the families Say), Australian paralysis tick (Ixodes holocyclus Neumann), Anthribidae, Bruchidae, and Curculionidae (e.g., boll weevil American dog tick (Dermacentor variabilis Say), lone star (Anthonomus grandis Boheman), rice water weevil (Lissor tick (Amblyomma americanum Linnaeus)) and ticks in the hoptrus Oryzophilus Kuschel), granary weevil (Sitophilus family Argasidae, commonly known as Soft ticks (e.g., relaps ing fever tick (Ornithodoros turicata), common fowl tick granarius Linnaeus), rice weevil (Sitophilus Oryzae Lin (Argas radiatus)): scab and itch mites in the families Psorop naeus)), annual bluegrass weevil (Listronotus maculicollis tidae, Pyemotidae, and Sarcoptidae; eggs, adults and imma Dietz), bluegrass billbug (Sphenophorus parvulus Gyllen tures of the order Orthoptera including grasshoppers, locusts hal), hunting billbug (Sphenophorus venatus Vestitus), Den and crickets (e.g., migratory grasshoppers (e.g., Melanoplus ver billbug (Sphenophorus cicatristriatus Fahraeus); flea sanguinipes Fabricius, M. differentialis Thomas), American beetles, cucumber beetles, rootworms, leaf beetles, potato grasshoppers (e.g., Schistocerca americana Drury), desert beetles, and leafminers in the family Chrysomelidae (e.g., locust (Schistocerca gregaria Forskal), migratory locust (LO Colorado potato beetle (Leptinotarsa decemlineata Say), custa migratoria Linnaeus), bush locust (Zonocerus spp.), western corn rootworm (Diabrotica virgifera virgifera house cricket (Acheta domesticus Linnaeus), mole crickets LeConte)); chafers and other beetles from the family Scara (e.g., tawny mole cricket (Scapteriscus vicinus Scudder) and baeidae (e.g., Japanese beetle (Popillia japonica Newman), southern mole cricket (Scapteriscus borellii Giglio-Tos)); oriental beetle (Anomala Orientalis Waterhouse, Exomala eggs, adults and immatures of the order Diptera including orientalis (Waterhouse) Baraud), northern masked chafer leafminers (e.g., Liriomyza spp. Such as serpentine vegetable (Cyclocephala borealis Arrow), Southern masked chafer (Cy leafminer (Liriomyza sativae Blanchard)), midges, fruit flies clocephala immaculata Olivier or C. lurida Bland), dung (Tephritidae), frit flies (e.g., Oscinella frit Linnaeus), soil beetle and white grub (Aphodius spp.), black turfgrass atae maggots, house flies (e.g., Musca domestica Linnaeus), lesser nius (Ataenius spretulus Haldeman), green June beetle (Coti house flies (e.g., Fannia canicularis Linnaeus, F, femoralis nis initida Linnaeus), Asiatic garden beetle (Maladera casta Stein), stable flies (e.g., Stomoxys calcitrans Linnaeus), face nea Arrow), May/June beetles (Phyllophaga spp.) and flies, horn flies, blow flies (e.g., Chrysomya spp., Phormia European chafer (Rhizotrogus maialis Razoumowsky)); car spp.), and other muscoid fly pests, horse flies (e.g., Tabanus pet beetles from the family Dermestidae; wireworms from the spp.), bot flies (e.g., Gastrophilus spp., Oestrus spp.), cattle family Elateridae; bark beetles from the family Scolytidae grubs (e.g., Hypoderma spp.), deer flies (e.g., Chrysops spp.), and flour beetles from the family Tenebrionidae. keds (e.g., Mellophagus Ovinus Linnaeus) and other Brachyc 0316. In addition, agronomic and nonagronomic pests era, mosquitoes (e.g., Aedes spp., Anopheles spp., Culex include: eggs, adults and larvae of the order Dermaptera spp.), black flies (e.g., Prosimulium spp., Simulium spp.), including earwigs from the family Forficulidae (e.g., Euro biting midges, sand flies, Sciarids, and other Nematocera; pean earwig (Forficula auricularia Linnaeus), black earwig eggs, adults and immatures of the order Thysanoptera includ (Chelisoches morio Fabricius)); eggs, immatures, adults and ing onion thrips (Thrips tabaci Lindeman), flower thrips nymphs of the orders Hemiptera and Homoptera Such as, (Frankliniella spp.), and other foliar feeding thrips; insect plant bugs from the family Miridae, cicadas from the family pests of the order Hymenoptera including ants of the Family Cicadidae, leafhoppers (e.g. Empoasca spp.) from the family Formicidae including the Florida carpenterant (Camponotus Cicadellidae, bed bugs (e.g., Cimex lectularius Linnaeus) floridanus Buckley), red carpenterant (Camponotus ferrug from the family Cimicidae, planthoppers from the families ineus Fabricius), black carpenterant (Camponotus pennsyl Fulgoroidae and Delphacidae, treehoppers from the family vanicus De Geer), white-footed ant (Technomyrmex albipes Membracidae, psyllids from the family Psyllidae, whiteflies fr. Smith), big headed ants (Pheidole sp.), ghost ant (Tapi from the family Aleyrodidae, aphids from the family Aphid noma melanocephalum Fabricius); Pharaoh ant (Monomo US 2014/O 187776 A1 Jul. 3, 2014 60 rium pharaonis Linnaeus), little fire ant (Wasmannia auro Fabricius (spotted bollworm), Helicoverpa armigera Hübner punctata Roger), fire ant (Solenopsis geminata Fabricius), (American bollworm), Helicoverpa zea Boddie (corn ear red imported fire ant (Solenopsis invicta Buren), Argentine worm), Heliothis virescens Fabricius (tobacco budworm), ant (Iridomyrmex humilis Mayr), crazyant (Paratrechina lon Herpetogramma licarsisalis Walker (sod webworm), Lobe gicornis Latreille), pavement ant (Tetramorium caespitum sia botrana Denis & Schiffermüller (grape berry moth), Pec Linnaeus), cornfield ant (Lasius alienus Förster) and odorous tinophora gossypiella Saunders (pink bollworm), Phyllocnis house ant (Tapinoma sessile Say); bees (including carpenter tis citrella Stainton (citrus leafminer), Pieris brassicae bees), hornets, yellow jackets, wasps, and sawflies (Neodip Linnaeus (large white butterfly), Pieris rapae Linnaeus rion spp.; Cephus spp.); insect pests of the order Isoptera (small white butterfly), Plutella xylostella Linnaeus (dia including termites in the Termitidae (e.g., Macrotermes sp., mondback moth), Spodoptera exigua Hübner (beet army Odontotermes obesus Rambur), Kalotermitidae (e.g., Cryp worm), Spodoptera litura Fabricius (tobacco cutworm, clus totermes sp.), and Rhinotermitidae (e.g., Reticulitermes sp., ter caterpillar), Spodoptera frugiperda J. E. Smith (fall Coptotermes sp., Heterotermes tenuis Hagen) families, the armyworm), Trichoplusia ni Hübner (cabbage looper) and eastern subterranean termite (Reticulitermes flavipes Kollar), Tuta absoluta Meyrick (tomato leafminer)). western Subterranean termite (Reticulitermes hesperus 0320 Compositions of the invention also have significant Banks). Formosan Subterranean termite (Coptotermes formo activity on members from the order Homoptera including: sanus Shiraki), West Indian drywood termite (Incisitermes Acyrthosiphon pisum Harris (pea aphid), Aphis craccivora immigrams Snyder), powder post termite (Cryptotermes Koch (cowpea aphid), Aphis fabae Scopoli (black bean brevis Walker), drywood termite (Incisitermes Snyderi aphid), Aphis gossypii Glover (cotton aphid, melon aphid), Light), Southeastern Subterranean termite (Reticulitermes vir Aphis pomi De Geer (apple aphid), Aphis spiraecola Patch ginicus Banks), western drywood termite (Incisitermes minor (spirea aphid), Aulacorthum Solani Kaltenbach (foxglove Hagen), arboreal termites such as Nasutitermes sp. and other aphid), Chaetosiphon fragaefolii Cockerell (strawberry termites of economic importance; insect pests of the order aphid), Diuraphis noxia Kurdumov/Mordvilko (Russian Thysanura Such as silverfish (Lepisma saccharina Linnaeus) wheat aphid), Dysaphis plantaginea Paaserini (rosy apple and firebrat (Thermobia domestica Packard); insect pests of aphid), Eriosoma lanigerum Hausmann (woolly apple the order Mallophaga and including the headlouse (Pediculus aphid), Hvalopterus pruni Geoffroy (mealy plum aphid), humanus capitis De Geer), body louse (Pediculus humanus Lipaphis erysimi Kaltenbach (turnip aphid), Metopolophium Linnaeus), chicken body louse (Menacanthus stramineus dirrhodium Walker (cereal aphid), Macrosiphum euphorbiae Nitszch), dog biting louse (Trichodectes canis De Geer), fluff Thomas (potato aphid), Myzus persicae Sulzer (peach-potato louse (Goniocotes gallinae De Geer), sheep body louse (Bo aphid, greenpeach aphid), Nasonovia ribisnigri Mosley (let vicola Ovis Schrank), short-nosed cattle louse (Haematopinus tuce aphid), Pemphigus spp. (root aphids and gall aphids), eurysternus Nitzsch), long-nosed cattle louse (Linognathus Rhopalosiphum maidis Fitch (corn leaf aphid), Rhopalosi vituli Linnaeus) and other Sucking and chewing parasitic lice phum padi LinnaeuS (bird cherry-oat aphid), Schizaphis that attack man and animals; insect pests of the order graminum Rondani (greenbug), Sitobion avenae Fabricius Siphonoptera including the oriental rat flea (Xenopsylla cheo (English grain aphid), Therioaphis maculata Buckton (spot pis Rothschild), cat flea (Ctenocephalides felis Bouche), dog ted alfalfa aphid), Toxoptera aurantii Boyer de Fonscolombe flea (Ctenocephalides canis Curtis), hen flea (Ceratophyllus (black citrus aphid), and Toxoptera citricida Kirkaldy (brown gallinae Schrank), Sticktight flea (Echidnophaga gallinacea citrus aphid); Adelges spp. (adelgids); Phylloxera devastatrix Westwood), human flea (Pulex irritans Linnaeus) and other Pergande (pecan phylloxera); Bemisia tabaci Gennadius (to fleas afflicting mammals and birds; spiders in the order Ara bacco whitefly, sweetpotato whitefly), Bemisia argentifolii neae such as the brown recluse spider (Loxosceles reclusa Bellows & Perring (silverleaf whitefly), Dialeurodes citri Gertsch & Mulaik) and the black widow spider (Latrodectus Ashmead (citrus whitefly) and Trialeurodes vaporariorum mactans Fabricius), and centipedes in the order Scutigero Westwood (greenhouse whitefly); Empoasca fabae Harris morpha Such as the house centipede (Scutigera Coleoptrata (potato leafhopper), Laodelphax striatellus Fallen (Smaller Linnaeus). brown planthopper), Macrolestes quadrilineatus Forbes (as 0318. Examples of invertebrate pests of stored grain ter leafhopper), Nephotettix cinticeps Uhler (green leafhop include larger grain borer (Prostephanus truncatus), lesser per), Nephotettix nigropictus Stal (rice leafhopper), Nilapar grain borer (Rhyzopertha dominica), rice weevil (Stiophilus vata lugens Stal (brown planthopper), Peregrinus maidis Oryzae), maize weevil (Stiophilus zeamais), cowpea weevil Ashmead (corn planthopper), Sogatella furcifera Horvath (Callosobruchus maculatus), red flour beetle (Tribolium cas (white-backed planthopper), Sogatodes Orizicola Muir (rice taneum), granary weevil (Stiophilus granarius), Indian meal delphacid), Tiphlocyba pomaria McAtee white apple leaf moth (Plodia interpunctella), Mediterranean flour beetle hopper, Erythroneoura spp. (grape leafhoppers); Magicidada (Ephestia kuhniella) and flat or rusty grain beetle (Cryptoles Septendecim Linnaeus (periodical cicada); Icerya purchasi tis ferrugineus). Maskell (cottony cushion scale), Ouadraspidiotus pernicio 0319 Compositions of the invention show particularly sus Comstock (San Jose scale); Planococcus citri Risso (cit high activity against pests in the order Lepidoptera (e.g., rus mealybug); Pseudococcus spp. (other mealybug com Alabama argillacea Hübner (cotton leaf worm), Archips plex); Cacopsylla pyricola Foerster (pear psylla), Trioza argyrospila Walker (fruit tree leafroller), A. rosana Linnaeus diospyri Ashmead (persimmon psylla). (European leaf roller) and other Archips species, Chilo Sup 0321 Compositions of this invention may also have activ pressalis Walker (rice stem borer), Cnaphalocrosis medinalis ity on members from the order Hemiptera including: Guenée (rice leaf roller), Crambus caliginosellus Clemens Acrosternum hilare Say (green Stink bug), Anasa tristis De (corn root webworm), Crambus teterrellus Zincken (blue Geer (squash bug), Blissus leucopterus leucopterus Say grass webworm), Cydia pomonella Linnaeus (codling moth), (chinch bug), Cimex lectularius Linnaeus (bed bug) Earias insulana Boisduval (spiny bollworm), Earias vittella Corythuca gossypii Fabricius (cotton lace bug), Cyrtopeltis US 2014/O 187776 A1 Jul. 3, 2014

modesta Distant (tomato bug), Dysdercus suturellus Herrich component selected from the group consisting of surfactants, Schäffer (cotton stainer), Euchistus servus Say (brown stink Solid diluents and liquid diluents, and at least one additional bug), Euchistus variolarius Palisot de Beauvois (one-spotted biologically active compound or agent. For compositions of Stink bug), Graptosthetus spp. (complex of seed bugs), Lep the present invention, the other biologically active com toglossus Corculus Say (leaf-footed pine seed bug), Lygus pounds or agents can be formulated together with the present lineolaris Palisot de Beauvois (tarnished plant bug), Nezara compounds, including the compounds of Formula 1, to form viridula Linnaeus (Southern green Stink bug), Oebalus pug a premix, or the other biologically active compounds or nax Fabricius (rice Stink bug). Oncopeltus fasciatus Dallas agents can be formulated separately from the present com (large milkweed bug), Pseudatomoscelis seriatus Reuter pounds, including the compounds of Formula 1, and the two (cotton fleahopper). Other insect orders controlled by com formulations combined together before application (e.g., in a pounds of the invention include Thysanoptera (e.g., Franklin spray tank) or, alternatively, applied in Succession. iella occidentalis Pergande (western flower thrips), Scirtho 0327 Examples of such biologically active compounds or thrips citri Moulton (citrus thrips), Sericothrips variabilis agents with which compounds of this invention can be for Beach (soybean thrips), and Thrips tabaci Lindeman (onion mulated are insecticides such as abamectin, acephate, ace thrips); and the order Coleoptera (e.g., Leptinotarsa decem quinocyl, acetamiprid, acrinathrin, amidoflumet, amitraz, lineata Say (Colorado potato beetle), Epilachna varivestis avermectin, azadirachtin, azinphos-methyl, benSultap, Mulsant (Mexican bean beetle) and wireworms of the genera bifenthrin, bifenazate, bistrifluoron, borate, buprofezin, Agriotes, Althous or Limonius). cadusafos, carbaryl, carbofuran, cartap, carZol, chlorantranil 0322 Compositions of this invention may also have activ iprole, chlorfenapyr, chlorfluaZuron, chlorpyrifos, chlorpyri ity on members of the Classes Nematoda, Cestoda, Trema fos-methyl, chromafenozide, clofentezin, clothianidin, toda, and Acanthocephala including economically important cyantraniliprole, cyflumetofen, cyfluthrin, beta-cyfluthrin, members of the orders Strongylida, Ascaridida, Oxyurida, cyhalothrin, gamma-cyhalothrin, lambda-cyhalothrin, cyper Rhabditida, Spirurida, and Enoplida such as but not limited to methrin, alpha-cypermethrin, Zeta-cypermethrin, cyro economically important agricultural pests (i.e. root knot mazine, deltamethrin, diafenthiuron, diazinon, dieldrin, nematodes in the genus Meloidogyne, lesion nematodes in the diflubenzuron, dimefluthrin, dimehypo, dimethoate, dinote genus Pratylenchus, stubby root nematodes in the genus Tri furan, diofenolan, emamectin, endosulfan, esfenvalerate, chodorus, etc.) and animal and human health pests (i.e. all ethiprole, etofenprox. etoxazole, fenbutatin oxide, fenothio economically important flukes, tapeworms, and roundworms, carb, fenoxycarb, fenpropathrin, fenvalerate, flpronil, floni such as Strongylus vulgaris in horses. Toxocara canis in dogs, camid, flubendiamide, flucythrinate, flufenerim, flufenoxu Haemonchus contortus in sheep, Dirofilaria immitis Leidy in ron, fluvalinate, tau-fluvalinate, fonophos, formetanate, dogs, Anoplocephala perfoliata in horses, Fasciola hepatica fosthiazate, halofenozide, hexaflumuron, hexythiazox, Linnaeus in ruminants, etc.). hydramethylnon, imidacloprid, indoxacarb, insecticidal 0323 Note that some contemporary classification systems Soaps, isofenphos, lufenuron, malathion, meperfluthrin, place Homoptera as a suborder within the order Hemiptera. metaflumizone, metaldehyde, methamidophos, methi 0324 Of note is use of compositions of this invention for dathion, methiodicarb, methomyl, methoprene, methoxy controlling potato leafhopper (Empoasca fabae). Of note is chlor, metofluthrin, monocrotophos, methoxyfenozide, use of compositions of this invention for controlling corn nitenpyram, nithiazine, novaluron, noviflumuron, oxamyl. planthopper (Peregrinus maidis). Of note is use of composi parathion, parathion-methyl, permethrin, phorate, phosalone, tions of this invention for controlling cotton melon aphid phosmet, phosphamidon, pirimicarb, profenofos, profluthrin, (Aphis gossypii). Of note is use of compositions of this inven propargite, protrifenbute, pymetrozine, pyrafluprole, pyre tion for controlling green peach aphid (Myzus persicae). Of thrin, pyridaben, pyridalyl pyrifluquinazon, pyriprole, note is use of compositions of this invention for controlling pyriproxyfen, rotenone, ryanodine, spinetoram, spinosad, diamondback moth (Plutella xylostella). Of note is use of spirodiclofen, Spiromesifen, spirotetramat, Sulprofos, Sul compositions of this invention for controlling fall armyworm foxaflor, tebufenozide, tebufenpyrad, teflubenzuron, (Spodoptera frugiperda). tefluthrin, terbufos, tetrachlorvinphos, tetramethrin, tetram 0325 Of note is use of compositions of this invention for ethylfluthrin, thiacloprid, thiamethoxam, thiodicarb, thiosul controlling Southern green Stink bug (Nezara viridula), west tap-sodium, tolfenpyrad, tralomethrin, triazamate, trichlor ern tarnished plant bug (Lygus hesperus), rice water weevil fon, triflumuron, Bacillus thuringiensis delta-endotoxins, (Lissorhoptrus Oryzophilus), rice brown planthopper entomopathogenic bacteria, entomopathogenic viruses and (Nilaparvata lugens), rice green leafhopper (Nephotettix entomopathogenic fungi. virescens) and striped rice borer (Chilo suppressalis). 0328. Of note are insecticides such as abamectin, acetami 0326 Compositions of this invention can also be mixed prid, acrinathrin, amitraz, avermectin, azadirachtin, bensul with one or more other biologically active compounds or tap, bifenthrin, buprofezin, cadusafos, carbaryl, cartap, chlo agents including insecticides, fungicides, nematocides, bac rantraniliprole, chlorfenapyr, chlorpyrifos, clothianidin, tericides, acaricides, herbicides, herbicide Safeners, growth cyantraniliprole, cyfluthrin, beta-cyfluthrin, cyhalothrin, regulators such as insect molting inhibitors and rooting gamma-cyhalothrin, lambda-cyhalothrin, cypermethrin, stimulants, chemosterilants, semiochemicals, repellents, alpha-cypermethrin, Zeta-cypermethrin, cyromazine, delta attractants, pheromones, feeding stimulants, other biologi methrin, dieldrin, dinotefuran, diofenolan, emamectin, cally active compounds or entomopathogenic bacteria, virus endosulfan, esfenvalerate, ethiprole, etofenproX, etoxazole, or fungi to form a multi-component pesticide giving an even fenothiocarb, fenoxycarb, fenvalerate, fipronil, flonicamid, broader spectrum of agronomic and nonagronomic utility. flubendiamide, flufenoxuron, fluvalinate, formetanate, fos Thus the present invention also pertains to a composition thiazate, hexaflumuron, hydramethylnon, imidacloprid, comprising a biologically effective amount of a compound of indoxacarb, lufenuron, metaflumizone, methiodicarb, meth Formula 1, an N-oxide or salt thereof, at least one additional omyl, methoprene, methoxyfenozide, nitenpyram, nithiaz US 2014/O 187776 A1 Jul. 3, 2014

ine, novaluron, oxamyl, pymetrozine, pyrethrin, pyridaben, lated delta-endotoxins of Bacillus thuringiensis, and other pyridalyl pyriproxyfen, ryanodine, spinetoram, spinosad, naturally occurring or genetically modified insecticidal spirodiclofen, Spiromesi?en, Spirotetramat, tebufenozide, tet viruses. ramethrin, thiacloprid, thiamethoxam, thiodicarb, thiosultap 0331 Further examples of biologically active compounds Sodium, tralomethrin, triazamate, triflumuron, Bacillus thur or agents with which compounds of this invention can be ingiensis delta-endotoxins, all strains of Bacillus formulated are: fungicides such as 1-4-4-5-(2,6-difluo thuringiensis and all strains of nucleo polyhedrosis viruses. rophenyl)-4,5-dihydro-3-isoxazolyl)-2-thiazolyl)-1-pip eridinyl-2-5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl) 0329. One embodiment of biological agents for mixing ethanone, acibenzolar, aldimorph, amisulbrom, azaconazole, with compounds of this invention include entomopathogenic azoxystrobin, benalaxyl, benomyl, benthiavalicarb, benthia bacteria Such as Bacillus thuringiensis, and the encapsulated valicarb-isopropyl, binomial, biphenyl, bitertanol, blastici delta-endotoxins of Bacillus thuringiensis such as MVPR) din-S, Bordeaux mixture (Tribasic copper sulfate), boscalid/ and MVPII(R) bioinsecticides prepared by the CellCap(R) pro nicobifen, bromuconazole, bupirimate, buthiobate, carboxin, cess (CellCap(R), MVPR) and MVPIIR) are trademarks of carpropamid, captafol, captan, carbendazim, chloroneb, Mycogen Corporation, Indianapolis, Ind., USA); ento chlorothalonil, chloZolinate, clotrimazole, copper oxychlo mopathogenic fungi such as green muscardine fungus; and ride, copper salts such as copper Sulfate and copper hydrox entomopathogenic (both naturally occurring and genetically ide, cyaZofamid, cyflunamid, cymoxanil, cyproconazole, modified) viruses including baculovirus, nucleopolyhedro cyprodinil, dichlofluanid, diclocymet, diclomeZine, dicloran, virus (NPV) such as Helicoverpa zea nucleopolyhedrovirus diethofencarb, difenoconazole, dimethomorph, dimox (HZNPV), Anagrapha falcifera nucleopolyhedrovirus yStrobin, diniconazole, diniconazole-M, dinocap, discos (AfNPV); and granulosis virus (GV) such as Cydia trobin, dithianon, dodemorph, dodine, econazole, etacona pomonella granulosis virus (CpGV). Zole, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethridiazole, famoxadone, fenamidone, fenarimol, fen 0330. Of particular note is such a combination where the buconazole, fencaramid, fenfuram, fenhexamide, fenoxaniil, other invertebrate pest control active ingredient belongs to a fenpiclonil, fenpropidin, fempropimorph, fentin acetate, fen different chemical class or has a different site of action than tin hydroxide, ferbam, ferfurazoate, ferimZone, fluaZinam, the compound of Formula 1. In certain instances, a combina fludioxonil, flumetover, fluopicolide, fluoxastrobin, fluguin tion with at least one other invertebrate pest control active conazole, fluguinconazole, flusilaZole, flusulfamide, flutola ingredient having a similar spectrum of control but a different nil, flutriafol, fluxapyroxad, folpet, fosetyl-aluminum, ftha site of action will be particularly advantageous for resistance lide, fuberidazole, furalaxyl, furametpyr, hexaconazole, management. Thus, a composition of the present invention hymexazole, guazatline, imazalil, imibenconazole, iminocta can further comprise a biologically effective amount of at dine, iodicarb, ipconazole, iprobenfos, iprodione, iprovali least one additional invertebrate pest control active ingredient carb, isoconazole, isoprothiolane, isotianil, kasugamycin, having a similar spectrum of control but belonging to a dif kresoxim-methyl, mancoZeb, mandipropamid, maneb, mapa ferent chemical class or having a different site of action. nipyrin, mefenoxam, mepronil, metalaxyl, metconazole, These additional biologically active compounds or agents methasulfocarb, metiram, metominostrobin/fenominos include, but are not limited to, Sodium channel modulators trobin, mepanipyrim, metrafenone, miconazole, myclobuta Such as bifenthrin, cypermethrin, cyhalothrin, lambda-cyha nil, neo-asozin (ferric methanearsonate), nuarimol, octhili lothrin, cyfluthrin, beta-cyfluthrin, deltamethrin, dime none, ofurace, orysastrobin, oxadixyl, oxolinic acid, fluthrin, esfenvalerate, fenvalerate, indoxacarb, metofluthrin, Oxpoconazole, oxycarboxin, paclobutraZol, penconazole, profluthrin, pyrethrin and tralomethrin; cholinesterase inhibi pencycuron, penflufen, penthiopyrad, perfurazoate, phos tors such as chlorpyrifos, methomyl, oxamyl, thiodicarb and phonic acid, picobenzamid, picoxystrobin, polyoxin, triazamate; neonicotinoids such as acetamiprid, clothianidin, probenazole, prochloraz, procymidone, propamocarb, pro dinotefuran, imidacloprid, nitenpyram, nithiazine, thiaclo pamocarb-hydrochloride, propiconazole, propineb, pro prid and thiamethoxam; insecticidal macrocyclic lactones quinazid, prothioconazole, pyraclostrobin, pyrametostrobin, Such as spinetoram, spinosad, abamectin, avermectin and pyraoxystrobin, pryaZophos, pyrifenox, pyrimethanil, emamectin; GABA (y-aminobutyric acid)-gated chloride pyrifenox, pyriofenone, pyronitrine, pyroquilon, quincona channel antagonists such as avermectin or blockers such as Zole, quinoxyfen, quintoZene, silthiofam, Simeconazole, ethiprole and fipronil; chitin synthesis inhibitors such as spiroxamine, streptomycin, Sulfur, tebuconazole, tebuflo buprofezin, cyromazine, flufenoXuron, hexaflumuron, quin, tecloftalam, tecnaZene, tetraconazole, thiabendazole, lufenuron, novaluron, noviflumuron and triflumuron; juve thifluZamide, thiophanate, thiophanate-methyl, thiram, tiadi nile hormone mimics such as diofenolan, fenoxycarb, metho nil, tolclofos-methyl, tolyfluanid, triadimefon, triadimenol, prene and pyriproxyfen; octopamine receptor ligands such as triarimol, triaZOxide, tridemorph, trimorphamide, tricycla amitraZ. molting inhibitors and ecdysone agonists such as Zole, trifloxystrobin, triforine, triticonazole, uniconazole, azadirachtin, methoxyfenozide and tebufenozide, ryanodine validamycin, Valifenalate, VincloZolin, Zineb, Ziram, and receptor ligands Such as ryanodine, anthranilic diamides Such Zoxamide; nematocides Such as aldicarb, imicyafos, oxamyl as chlorantraniliprole, cyantraniliprole and flubendiamide; and fenamiphos; bactericides Such as Streptomycin; acari nereistoxin analogs such as cartap; mitochondrial electron cides such as amitraz, chinomethionat, chlorobenzilate, transport inhibitors such as chlorfeinapyr, hydramethylnon cyhexatin, dicofol, dienochlor, etoxazole, fenazaquin, fenb and pyridaben; lipid biosynthesis inhibitors such as spirodi utatin oxide, fempropathrin, fenpyroximate, hexythiazox, clofen and Spiromesi?en; cyclodiene insecticides such as propargite, pyridaben and tebufenpyrad. dieldrin or endosulfan; pyrethroids; carbamates; insecticidal 0332 Of note are fungicides and compositions compris ureas; and biological agents including nucleopolyhedro ing fungicides such as 1-4-4-5-(2,6-difluorophenyl)-4,5- viruses (NPV), members of Bacillus thuringiensis, encapsu dihydro-3-isoxazolyl-2-thiazolyl)-1-piperidinyl-2-5-me US 2014/O 187776 A1 Jul. 3, 2014 thyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone, lists specific combinations of a compound of Formula 1 with azoxystrobin, copper hydroxide, cymoxanil, cyproconazole, other invertebrate pest control agents illustrative of the mix difenoconazole, famoxadone, fenoxanil, ferimZone, flusila tures, compositions and methods of the present invention and Zole, flutolanil, fthalide, furametpyr, hexaconazole, isopro includes additional embodiments of weight ratio ranges for thiolane, isotianil, kasugamycin, mancoZeb, metominos application rates. trobin, orysastrobin, pency Curon, penthiopyrad, picoxystrobin, probenazole, propiconazole, produinazid, TABLE A pyroquilon, Simeconazole, tiadinil, tricyclazole, triflox yStrobin and validamycin. Invertebrate 0333. In certain instances, combinations of a compound of Pest Control Mode of Action or Typical this invention with other biologically active (particularly Agent Chemical Class Weight Ratio invertebrate pest control) compounds or agents (i.e. active Abamectin macrocyclic lactones SO:1 to 1:SO Acetamiprid neonicotinoids 1SO:1 to 1:200 ingredients) can result in a greater-than-additive (i.e. syner Amitraz Octopamine receptor ligands 2OO:1 to 1:100 gistic) effect. Reducing the quantity of active ingredients Avermectin macrocyclic lactones SO:1 to 1:SO released in the environment while ensuring effective pest Azadirachtin ecclysone agonists 100:1 to 1:120 control is always desirable. When synergism of invertebrate Beta-cyfluthrin Sodium channel modulators 1SO:1 to 1:200 Bifenthrin Sodium channel modulators 100:1 to 1:10 pest control active ingredients occurs at application rates Buprofezin chitin synthesis inhibitors SOO:1 to 1:SO giving agronomically satisfactory levels of invertebrate pest Cartap nereistoxin analogs 100:1 to 1:200 control. Such combinations can be advantageous for reducing Chloran- ryanodine receptor ligands 100:1 to 1:120 crop production cost and decreasing environmental load. traniliprole Chlorfeinapyr mitochondrial electron 3OO:1 to 1:200 0334 Compositions of this invention can be applied to transport inhibitors plants genetically transformed to express proteins toxic to Chlorpyrifos cholinesterase inhibitors SOO:1 to 1:200 invertebrate pests (such as Bacillus thuringiensis delta-endot Clothianidin neonicotinoids OO:1 to 1:400 oxins). Such an application may provide a broader spectrum Cyantraniliprole ryanodine receptor ligands OO:1 to 1:120 Cyfluthrin Sodium channel modulators SO:1 to 1:200 of plant protection and be advantageous for resistance man Cyhalothrin Sodium channel modulators SO:1 to 1:200 agement. The effect of the exogenously applied invertebrate Cypermethrin Sodium channel modulators SO:1 to 1:200 pest control compositions of this invention may be synergistic Cyromazine chitin synthesis inhibitors 400:1 to 1:50 with the expressed toxin proteins. Deltamethrin Sodium channel modulators 50:1 to 1:400 Dieldrin cyclodiene insecticides 2OO:1 to 1:100 0335 General references for these agricultural protectants Dinotefuran neonicotinoids SO:1 to 1:200 (i.e. insecticides, fungicides, nematocides, acaricides, herbi Diofenolan molting inhibitor SO:1 to 1:200 cides and biological agents) include The Pesticide Manual, Emamectin macrocyclic lactones 50:1 to 1:10 Endosulfan cyclodiene insecticides 2OO:1 to 1:100 13th Edition, C. D. S. Tomlin, Ed., British Crop Protection Esfenvalerate Sodium channel modulators OO:1 to 1:400 Council, Farnham, Surrey, U.K., 2003 and The BioPesticide Ethiprole GABA-regulated chloride 2OO:1 to 1:100 Manual, 2" Edition, L. G. Copping, Ed., British Crop Pro channel blockers tection Council, Farnham, Surrey, U.K., 2001. Fenothiocarb SO:1 to 1:200 Fenoxycarb juvenile hormone mimics SOO:1 to 1:100 0336. For embodiments where one or more of these vari Fenvalerate Sodium channel modulators SO:1 to 1:200 ous mixing partners are used, the weight ratio of these various Fipronil GABA-regulated chloride SO:1 to 1:100 mixing partners (in total) to the compound of Formula 1, an channel blockers Flonicamid 2OO:1 to 1:100 N-oxide or salt thereof, is typically between about 1:3000 and Flubendiamide ryanodine receptor ligands OO:1 to 1:120 about 3000:1. Of note are weight ratios between about 1:300 Fufenoxuron chitin synthesis inhibitors 2OO:1 to 1:100 and about 300:1 (for example ratios between about 1:30 and Hexaflumuron chitin synthesis inhibitors 300:1 to 1:SO about 30:1). One skilled in the art can easily determine Hydramethylnon mitochondrial electron SO:1 to 1:250 through simple experimentation the biologically effective transport inhibitors midacloprid neonicotinoids 1OOO:1 to 1:1OOO amounts of active ingredients necessary for the desired spec indoxacarb Sodium channel modulators 2001 to 1:SO trum of biological activity. It will be evident that including Lambda- Sodium channel modulators SO:1 to 1:250 these additional components can expand the spectrum of cyhalothrin invertebrate pests controlled beyond the spectrum controlled Lufenuron chitin synthesis inhibitors SOO:1 to 1:250 by the compound of Formula 1 alone. Metaflumizone 2OO:1 to 1:200 Methomyl cholinesterase inhibitors SOO:1 to 1:100 0337 Table A lists specific combinations of a compound Methoprene juvenile hormone mimics SOO:1 to 1:100 of Formula 1 with other invertebrate pest control agents illus Methoxyfenozide ecclysone agonists SO:1 to 1:SO trative of the mixtures, compositions and methods of the Nitenpyram neonicotinoids 1SO:1 to 1:200 present invention. The first column of Table A lists the spe Nithiazine neonicotinoids 1SO:1 to 1:200 cific invertebrate pest control agents (e.g., "Abamectin’ in the Novaluron chitin synthesis inhibitors SOO:1 to 1:150 Oxamyl cholinesterase inhibitors 2OO:1 to 1:200 first line). The second column of Table A lists the mode of Pymetrozine 2OO:1 to 1:100 action (if known) or chemical class of the invertebrate pest Pyrethrin Sodium channel modulators 100:1 to 1:10 control agents. The third column of Table Alists embodiment Pyridaben mitochondrial electron 2OO:1 to 1:100 (s) of ranges of weight ratios for rates at which a compound of transport inhibitors Formula 1 can be applied relative to an invertebrate pest Pyridalyl 2OO:1 to 1:100 Pyriproxyfen juvenile hormone mimics SOO:1 to 1:100 control agent (e.g., “50:1 to 1:50 of a compound of Formula Ryanodine ryanodine receptor ligands 100:1 to 1:120 1 relative to abamectin by weight). Thus, for example, the first Spinetoram macrocyclic lactones 150:1 to 1:100 line of Table A specifically discloses the combination of a Spinosad macrocyclic lactones SOO:1 to 1:10 compound of Formula 1 with abamectin can be applied in a Spirodiclofen lipid biosynthesis 2OO:1 to 1:200 weight ratio between 50:1 to 1:50. The remaining lines of inhibitors Table A are to be construed similarly. Of further note Table A US 2014/O 187776 A1 Jul. 3, 2014 64

TABLE A-continued TABLE A-continued

Invertebrate Invertebrate Pest Control Mode of Action or Typical Pest Control Mode of Action or Typical Agent Chemical Class Weight Ratio Agent Chemical Class Weight Ratio NPV (e.g., biological agents 50:1 to 1:10 Spiromesifen lipid biosynthesis 2OO:1 to 1:200 Gemstar) inhibitors Tebufenozide ecclysone agonists SOO:1 to 1:250 0338. Of note is the composition of the present invention Thiacloprid neonicotinoids 100:1 to 1:200 wherein the at least one additional biologically active com Thiamethoxam neonicotinoids 1250:1 to 1:1000 pound or agent is selected from the Invertebrate Pest Control Thiodicarb cholinesterase inhibitors SOO:1 to 1:400 Agents listed in Table A above. Thiosultap 150:1 to 1:100 0339. The weight ratios of a compound, including a com Sodium pound of Formula 1, an N-oxide or salt thereof, to the addi Trailomethrin Sodium channel modulators 150:1 to 1:200 tional invertebrate pest control agent typically are between Triazamate cholinesterase inhibitors 250:1 to 1:100 1000:1 and 1:1000, with one embodiment being between Trifumuron chitin synthesis inhibitors 2OO:1 to 1:100 500:1 and 1:500, another embodiment being between 250:1 Bacilius biological agents 50:1 to 1:10 and 1:200 and another embodiment being between 100:1 and 1:50. thiringiensis 0340 Listed below in Tables B1 to B77 are embodiments Bacilius biological agents 50:1 to 1:10 of specific compositions comprising a compound of Formula thiringiensis 1 (compound numbers (Cmpd. No.) refer to compounds in delta-endotoxin Index Tables A-C) and an additional invertebrate pest control agent. TABLE B1

Mixture Cmpd. Invertebrate Pest Mixture Cmpd. Invertebrate Pest No. No. 8 Control Agent No. No. 8 Control Agent

Abamectin B1-36 6 8. Imidacloprid Acetamiprid B1-37 6 8 Indoxacarb Amitraz B1-38. 6 8 Lambda-cyhalothrin Avermectin B1-39 6 8 Lufenuron Azadirachtin B1-40 6 8 Metaflumizone Bensultap B1-41 6 8 Methomyl Beta-cyfluthrin B1-42 6 8 Methoprene Bifenthrin B1-43 6 8 Methoxyfenozide Buprofezin B1-44 6 8 Nitenpyram Cartap B1-45 6 8 Nithiazine Chlorantraniliprole B1-46 6 8 Novaluron Chlorfeinapyr B1-47 6 8 Oxamyl Chlorpyrifos B1-48 6 8 Phosmet Clothianidin B1-49 6 8 Pymetrozine Cyantraniliprole B1 -SO 6 8 Pyrethrin Cyfluthrin B1-51 6 8 Pyridaben Cyhalothrin B1-52 6 8 Pyridalyl -1 7 Cypermethrin B1-53 6 8 Pyriproxyfen Cyromazine B1-54 6 8 Ryanodine Deltamethrin B1-SS 6 8 Spinetoram Dieldrin B1-S6 6 8 Spinosad Dinotefuran B1-57 6 8 Spirodiclofen Diofenolan B1-58 6 8 Spiromesifen Emamectin B1-59 6 8 Spirotetramat Endosulfan B1-6O 6 8 Tebufenozide Esfenvalerate B1-61. 6 8 Thiacloprid Ethiprole B1-62 6 8 Thiamethoxam Fenothiocarb B1-63 6 8 Thiodicarb Fenoxycarb B1-64 6 8 Thiosultap-sodium Fenvalerate B1-6S 6 8 Tolfenpyrad Fipronil B1-66 6 8 Trailomethrin Flonicamid B1-67 6 8 Triazamate Flubendiamide B1-68 6 8 Trifumuron Fufenoxuron B1-69 6 8 Bacilius thuringiensis Hexaflumuron B1-7O 6 8 Bacilius thuringiensis delta-endotoxin 8 Hydramethylnon B1-71 6 8 NPV (e.g., Gemstar) US 2014/O 187776 A1 Jul. 3, 2014

Table B2 first mixture in Table B9 is designated B9-1 and is a mixture (0341 Table B2 is identical to Table B 1, except that each of compound 31 and the additional invertebrate pest control reference to compound 6 in the column headed “Cmpd. No.” agent abamectin. is replaced by a reference to compound 7. For example, the first mixture in Table B2 is designated B2-1 and is a mixture Table B10 of compound 7 and the additional invertebrate pest control (0349 Table B10 is identical to Table B1, except that each agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 34. For example, the Table B3 first mixture in Table B 10 is designated B 10-1 and is a (0342 Table B3 is identical to Table B 1, except that each mixture of compound 34 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 8. For example, the first mixture in Table B3 is designated B3-1 and is a mixture Table B11 of compound 8 and the additional invertebrate pest control 0350 Table B11 is identical to Table B1, except that each agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” Table B4 is replaced by a reference to compound 39. For example, the first mixture in Table B11 is designated B1 1-1 and is a mix (0343 Table B4 is identical to Table B 1, except that each ture of compound 39 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 9. For example, the first mixture in Table B4 is designated B4-1 and is a mixture Table B12 of compound 9 and the additional invertebrate pest control agent abamectin. 0351 Table B12 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B5 is replaced by a reference to compound 48. For example, the first mixture in Table B12 is designated B12-1 and is a mix (0344) Table B5 is identical to Table B 1, except that each ture of compound 48 and the additional invertebrate pest reference to compound 6 in the column headed "Cmpd. No.” control agent abamectin. is replaced by a reference to compound 10. For example, the first mixture in Table B5 is designated B5-1 and is a mixture Table B13 of compound 10 and the additional invertebrate pest control agent abamectin. 0352 Table B 13 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B6 is replaced by a reference to compound 54. For example, the (0345 Table B6 is identical to Table B 1, except that each first mixture in Table B13 is designated B13-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 54 and the additional invertebrate pest is replaced by a reference to compound 19. For example, the control agent abamectin. first mixture in Table B6 is designated B6-1 and is a mixture of compound 19 and the additional invertebrate pest control Table B14 agent abamectin. 0353 Table B 14 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B7 is replaced by a reference to compound 55. For example, the (0346 Table B7 is identical to Table B 1, except that each first mixture in Table B14 is designated B1 4-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 55 and the additional invertebrate pest is replaced by a reference to compound 20. For example, the control agent abamectin. first mixture in Table B7 is designated B7-1 and is a mixture of compound 20 and the additional invertebrate pest control Table B15 agent abamectin. 0354) Table B 15 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B8 is replaced by a reference to compound 58. For example, the (0347 Table B8 is identical to Table B1, except that each first mixture in Table B15 is designated B15-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 58 and the additional invertebrate pest is replaced by a reference to compound 29. For example, the control agent abamectin. first mixture in Table B8 is designated B8-1 and is a mixture of compound 29 and the additional invertebrate pest control Table B16 agent abamectin. 0355 Table B 16 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B9 is replaced by a reference to compound 105. For example, the (0348 Table B9 is identical to Table B 1, except that each first mixture in Table B16 is designated B16-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 105 and the additional invertebrate pest is replaced by a reference to compound 31. For example, the control agent abamectin. US 2014/O 187776 A1 Jul. 3, 2014 66

Table B17 first mixture in Table B24 is designated B24-1 and is a mix 0356. Table B 17 is identical to Table B1, except that each ture of compound 113 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 106. For example, the first mixture in Table B17 is designated B17-1 and is a mix Table B25 ture of compound 106 and the additional invertebrate pest 0364 Table B25 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 114. For example, the Table B18 first mixture in Table B25 is designated B25-1 and is a mix 0357 Table B 18 is identical to Table B1, except that each ture of compound 114 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 107. For example, the first mixture in Table B18 is designated B18-1 and is a mix Table B26 ture of compound 107 and the additional invertebrate pest 0365 Table B26 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” Table B19 is replaced by a reference to compound 115. For example, the first mixture in Table B26 is designated B26-1 and is a mix 0358 Table B19 is identical to Table B1, except that each ture of compound 115 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 108. For example, the first mixture in Table B19 is designated B19-1 and is a mix Table B27 ture of compound 108 and the additional invertebrate pest control agent abamectin. 0366 Table B27 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B20 is replaced by a reference to compound 116. For example, the first mixture in Table B27 is designated B27-1 and is a mix 0359 Table B20 is identical to Table B1, except that each ture of compound 116 and the additional invertebrate pest reference to compound 6 in the column headed "Cmpd. No.” control agent abamectin. is replaced by a reference to compound 109. For example, the first mixture in Table B20 is designated B20-1 and is a mix Table B28 ture of compound 109 and the additional invertebrate pest control agent abamectin. 0367 Table B28 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B21 is replaced by a reference to compound 117. For example, the 0360 Table B21 is identical to Table B1, except that each first mixture in Table B28 is designated B28-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 117 and the additional invertebrate pest is replaced by a reference to compound 110. For example, the control agent abamectin. first mixture in Table B21 is designated B21-1 and is a mix ture of compound 110 and the additional invertebrate pest Table B29 control agent abamectin. 0368 Table B29 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B22 is replaced by a reference to compound 118. For example, the 0361 Table B22 is identical to Table B1, except that each first mixture in Table B29 is designated B29-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 118 and the additional invertebrate pest is replaced by a reference to compound III. For example, the control agent abamectin. first mixture in Table B22 is designated B22-1 and is a mix ture of compound III and the additional invertebrate pest Table B30 control agent abamectin. 0369 Table B30 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B23 is replaced by a reference to compound 119. For example, the 0362 Table B23 is identical to Table B1, except that each first mixture in Table B30 is designated B30-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 119 and the additional invertebrate pest is replaced by a reference to compound 112. For example, the control agent abamectin. first mixture in Table B23 is designated B23-1 and is a mix ture of compound 112 and the additional invertebrate pest Table B31 control agent abamectin. 0370 Table B31 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B24 is replaced by a reference to compound 120. For example, the 0363 Table B24 is identical to Table B1, except that each first mixture in Table B31 is designated B31-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 120 and the additional invertebrate pest is replaced by a reference to compound 113. For example, the control agent abamectin. US 2014/O 187776 A1 Jul. 3, 2014 67

Table B32 first mixture in Table B39 is designated B39-1 and is a mix 0371 Table B32 is identical to Table B1, except that each ture of compound 128 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 121. For example, the first mixture in Table B32 is designated B32-1 and is a mix Table B40 ture of compound 121 and the additional invertebrate pest 0379 Table B40 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 129. For example, the Table B33 first mixture in Table B40 is designated B40-1 and is a mix 0372 Table B33 is identical to Table B1, except that each ture of compound 129 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 122. For example, the first mixture in Table B33 is designated B33-1 and is a mix Table B41 ture of compound 122 and the additional invertebrate pest (0380 Table B41 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” Table B34 is replaced by a reference to compound 130. For example, the first mixture in Table B41 is designated B41-1 and is a mix 0373 Table B34 is identical to Table B1, except that each ture of compound 130 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 123. For example, the first mixture in Table B34 is designated B34-1 and is a mix Table B42 ture of compound 123 and the additional invertebrate pest control agent abamectin. (0381 Table B42 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B35 is replaced by a reference to compound 131. For example, the first mixture in Table B42 is designated B42-1 and is a mix 0374 Table B35 is identical to Table B1, except that each ture of compound 131 and the additional invertebrate pest reference to compound 6 in the column headed "Cmpd. No.” control agent abamectin. is replaced by a reference to compound 124. For example, the first mixture in Table B35 is designated B35-1 and is a mix Table B43 ture of compound 124 and the additional invertebrate pest control agent abamectin. (0382 Table B43 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B36 is replaced by a reference to compound 132. For example, the 0375 Table B36 is identical to Table B1, except that each first mixture in Table B43 is designated B43-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 132 and the additional invertebrate pest is replaced by a reference to compound 125. For example, the control agent abamectin. first mixture in Table B36 is designated B36-1 and is a mix ture of compound 125 and the additional invertebrate pest Table B44 control agent abamectin. (0383 Table B44 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B37 is replaced by a reference to compound 133. For example, the 0376 Table B37 is identical to Table B1, except that each first mixture in Table B44 is designated B44-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 133 and the additional invertebrate pest is replaced by a reference to compound 126. For example, the control agent abamectin. first mixture in Table B37 is designated B37-1 and is a mix ture of compound 126 and the additional invertebrate pest Table B45 control agent abamectin. (0384 Table B45 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B38 is replaced by a reference to compound 134. For example, the 0377 Table B38 is identical to Table B1, except that each first mixture in Table B45 is designated B45-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 134 and the additional invertebrate pest is replaced by a reference to compound 127. For example, the control agent abamectin. first mixture in Table B38 is designated B38-1 and is a mix ture of compound 127 and the additional invertebrate pest Table B46 control agent abamectin. (0385 Table B46 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B39 is replaced by a reference to compound 135. For example, the 0378 Table B39 is identical to Table B1, except that each first mixture in Table B46 is designated B46-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 135 and the additional invertebrate pest is replaced by a reference to compound 128. For example, the control agent abamectin. US 2014/O 187776 A1 Jul. 3, 2014

Table B47 first mixture in Table B53 is designated B53-1 and is a mix 0386 Table B47 is identical to Table B1, except that each ture of compound 576 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 136. For example, the first mixture in Table B47 is designated B47-1 and is a mix Table B54 ture of compound 136 and the additional invertebrate pest 0394 Table B54 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 583. For example, the Table B48 first mixture in Table B54 is designated B54-1 and is a mix (0387 Table B48 is identical to Table B1, except that each ture of compound 583 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 137. For example, the first mixture in Table B48 is designated B48-1 and is a mix Table B55 ture of compound 137 and the additional invertebrate pest 0395 Table B55 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” Table B49 is replaced by a reference to compound 594. For example, the first mixture in Table B55 is designated B55-1 and is a mix 0388 Table B49 is identical to Table B1, except that each ture of compound 594 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 138. For example, the first mixture in Table B49 is designated B49-1 and is a mix Table B56 ture of compound 138 and the additional invertebrate pest control agent abamectin. 0396 Table B56 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B50 is replaced by a reference to compound 654. For example, the first mixture in Table B56 is designated B56-1 and is a mix 0389 Table B50 is identical to Table B1, except that each ture of compound 654 and the additional invertebrate pest reference to compound 6 in the column headed "Cmpd. No.” control agent abamectin. is replaced by a reference to compound 139. For example, the first mixture in Table B50 is designated B50-1 and is a mix Table B57 ture of compound 139 and the additional invertebrate pest control agent abamectin. 0397 Table B57 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B51 is replaced by a reference to compound 657. For example, the 0390 Table B51 is identical to Table B1, except that each first mixture in Table B57 is designated B57-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 657 and the additional invertebrate pest is replaced by a reference to compound 140. For example, the control agent abamectin. first mixture in Table B51 is designated B51-1 and is a mix ture of compound 140 and the additional invertebrate pest Table B58 control agent abamectin. 0398 Table B58 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B51 a is replaced by a reference to compound 669. For example, the 0391 Table B51a is identical to Table B1, except that each first mixture in Table B58 is designated B58-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 669 and the additional invertebrate pest is replaced by a reference to compound 541. For example, the control agent abamectin. first mixture in Table B51a is designated B51a-1 and is a mixture of compound 541 and the additional invertebrate pest Table B59 control agent abamectin. 0399. Table B59 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B52 is replaced by a reference to compound 670. For example, the 0392 Table B52 is identical to Table B1, except that each first mixture in Table B59 is designated B59-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 670 and the additional invertebrate pest is replaced by a reference to compound 542. For example, the control agent abamectin. first mixture in Table B52 is designated B52-1 and is a mix ture of compound 542 and the additional invertebrate pest Table B60 control agent abamectin. (0400 Table B60 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B53 is replaced by a reference to compound 682. For example, the 0393 Table B53 is identical to Table B1, except that each first mixture in Table B60 is designated B60-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 682 and the additional invertebrate pest is replaced by a reference to compound 576. For example, the control agent abamectin. US 2014/O 187776 A1 Jul. 3, 2014 69

Table B61 first mixture in Table B68 is designated B68-1 and is a mix 04.01 Table B61 is identical to Table B1, except that each ture of compound 735 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 683. For example, the first mixture in Table B61 is designated B61-1 and is a mix Table B69 ture of compound 683 and the additional invertebrate pest 04.09 Table B69 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 737. For example, the Table B62 first mixture in Table B69 is designated B69-1 and is a mix 0402 Table B62 is identical to Table B1, except that each ture of compound 737 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 687. For example, the first mixture in Table B62 is designated B62-1 and is a mix Table B70 ture of compound 687 and the additional invertebrate pest 0410 Table B70 is identical to Table B1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” Table B63 is replaced by a reference to compound 744. For example, the first mixture in Table B70 is designated B70-1 and is a mix 0403 Table B63 is identical to Table B1, except that each ture of compound 744 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 718. For example, the first mixture in Table B63 is designated B63-1 and is a mix Table B71 ture of compound 718 and the additional invertebrate pest control agent abamectin. 0411 Table B71 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B64 is replaced by a reference to compound 745. For example, the first mixture in Table B71 is designated B71-1 and is a mix 04.04 Table B64 is identical to Table B1, except that each ture of compound 745 and the additional invertebrate pest reference to compound 6 in the column headed "Cmpd. No.” control agent abamectin. is replaced by a reference to compound 725. For example, the first mixture in Table B64 is designated B64-1 and is a mix Table B72 ture of compound 725 and the additional invertebrate pest control agent abamectin. 0412 Table B72 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B65 is replaced by a reference to compound 746. For example, the 04.05 Table B65 is identical to Table B1, except that each first mixture in Table B72 is designated B72-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 746 and the additional invertebrate pest is replaced by a reference to compound 726. For example, the control agent abamectin. first mixture in Table B65 is designated B65-1 and is a mix ture of compound 726 and the additional invertebrate pest Table B73 control agent abamectin. 0413 Table B73 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B66 is replaced by a reference to compound 748. For example, the 04.06 Table B66 is identical to Table B1, except that each first mixture in Table B73 is designated B73-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 748 and the additional invertebrate pest is replaced by a reference to compound 727. For example, the control agent abamectin. first mixture in Table B66 is designated B66-1 and is a mix ture of compound 727 and the additional invertebrate pest Table B74 control agent abamectin. 0414 Table B74 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B67 is replaced by a reference to compound 749. For example, the 04.07 Table B67 is identical to Table B1, except that each first mixture in Table B74 is designated B74-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 749 and the additional invertebrate pest is replaced by a reference to compound 734. For example, the control agent abamectin. first mixture in Table B67 is designated B67-1 and is a mix ture of compound 734 and the additional invertebrate pest Table B75 control agent abamectin. 0415 Table B75 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table B68 is replaced by a reference to compound 750. For example, the 0408 Table B68 is identical to Table B1, except that each first mixture in Table B75 is designated B75-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 750 and the additional invertebrate pest is replaced by a reference to compound 735. For example, the control agent abamectin. US 2014/O 187776 A1 Jul. 3, 2014 70

Table B76 first mixture in Table C4 is designated C4-1 and is a mixture 0416) Table B76 is identical to Table B1, except that each of compound 9 and the additional fungicide probenazole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 926. For example, the Table C5 first mixture in Table B76 is designated B76-1 and is a mix 0423 Table C5 is identical to Table C1, except that each ture of compound 926 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 10. For example, the first mixture in Table C5 is designated C5-1 and is a mixture Table B77 of compound 10 and the additional fungicide probenazole. 0417. Table B77 is identical to Table B1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table C6 is replaced by a reference to compound 930. For example, the 0424 Table C6 is identical to Table C1, except that each first mixture in Table B77 is designated B77-1 and is a mix reference to compound 6 in the column headed “Cmpd. No.” ture of compound 930 and the additional invertebrate pest is replaced by a reference to compound 19. For example, the control agent abamectin. first mixture in Table C6 is designated C6-1 and is a mixture 0418. The specific mixtures listed in Tables B1 to B77 of compound 19 and the additional fungicide probenazole. typically combine a compound of Formula 1 with the other invertebrate pest agent in the ratios specified in Table A. Table C7 0419 Listed below in Tables C1 to C77 are embodiments of specific compositions comprising a compound of Formula 0425 Table C7 is identical to Table C1, except that each 1 (compound numbers (Cmpd. No.) refer to compounds in reference to compound 6 in the column headed “Cmpd. No.” Index Tables A-C) and an additional fungicide. is replaced by a reference to compound 20. For example, the TABLE C1 Mixture Cmpd. Mixture Cmpd. No. No. 8 Fungicide No. No. 8 Fungicide

C1-1 6 8 Probenazole C1-17 6 8 Difenoconazole C1-2 6 8. Tiadinil C1-18 6 8. Cyproconazole C1-3 6 8 Sotianil C1-19 6 8 Propiconazole C1-4 6 8 Pyroquilon C1-2O 6 8 Fenoxanil C1-5 6 8 Metominostrobin C1-21 6 8 Ferimzone C1-6 6 8 Flutolani C1-22 6 8 Fthalide C1-7 6 8 Validamycin C1-23 6 8 Kasugamycin C1-8 6 8 Furametpyr C1-24 6 8 Picoxystrobin C1-9 6 8 Pencycuron C1-2S 6 8 Penthiopyriad C1-10 6 8 Simeconazole C1-26 6 8 Famoxadone C1-11 6 8 Orysastrobin C1-27 6 8 Cymoxanil C1-12 6 8 Trifloxystrobin C1-28 6 8 Proquinazid C1-13 6 8 Soprothiolane C1-29 6 8 Fusillazole C1-14 6 8 Azoxystrobin C1-3O 6 8 Manco Zeb C1-1S 6 8 Tricyclazole C1-31 6 8 Copper hydroxide C1-16 6 8 Hexaconazole C1-32 6 8 (a) (a) 1-4-4-5-(2,6-difluorophenyl)-4,5-dihydro-3-isoxazolyl)-2-thiazolyl)-1-piperidinyl-2-5-methyl 3-(trifluoromethyl)-1H-pyrazol-1-yl)ethanone

Table C2 first mixture in Table C7 is designated C7-1 and is a mixture of compound 20 and the additional fungicide probenazole. 0420 Table C2 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” Table C8 is replaced by a reference to compound 7. For example, the 0426 Table C8 is identical to Table C1, except that each first mixture in Table C2 is designated C2-1 and is a mixture reference to compound 6 in the column headed “Cmpd. No.” of compound 7 and the additional fungicide probenazole. is replaced by a reference to compound 29. For example, the first mixture in Table C8 is designated C8-1 and is a mixture Table C3 of compound 29 and the additional fungicide probenazole. 0421 Table C3 is identical to Table C1, except that each Table C9 reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 8. For example, the 0427 Table C9 is identical to Table C1, except that each first mixture in Table C3 is designated C3-1 and is a mixture reference to compound 6 in the column headed “Cmpd. No.” of compound 8 and the additional fungicide probenazole. is replaced by a reference to compound 31. For example, the first mixture in Table C9 is designated C9-1 and is a mixture Table C4 of compound 31 and the additional fungicide probenazole. 0422 Table C4 is identical to Table C1, except that each Table C10 reference to compound 6 in the column headed “Cmpd. No.” 0428 Table C 10 is identical to Table C 1, except that each is replaced by a reference to compound 9. For example, the reference to compound 6 in the column headed “Cmpd. No.” US 2014/O 187776 A1 Jul. 3, 2014

is replaced by a reference to compound 34. For example, the Table C18 first mixture in Table C10 is designated C10-1 and is a mix 0436 Table C18 is identical to Table C 1, except that each ture of compound 34 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 107. For example, the first mixture in Table C18 is designated C18-1 and is a mix Table C11 ture of compound 107 and the additional fungicide probena 0429 Table C11 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 39. For example, the Table C19 first mixture in Table C11 is designated C11-1 and is a mix 0437. Table C19 is identical to Table C 1, except that each ture of compound 39 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 108. For example, the first mixture in Table C19 is designated C19-1 and is a mix Table C12 ture of compound 108 and the additional fungicide probena 0430 Table C12 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 48. For example, the Table C20 first mixture in Table C12 is designated C12-1 and is a mix 0438 Table C20 is identical to Table C1, except that each ture of compound 48 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 109. For example, the first mixture in Table C20 is designated C20-1 and is a mix Table C13 ture of compound 109 and the additional fungicide probena 0431 Table C13 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 54. For example, the Table C21 first mixture in Table C13 is designated C13-1 and is a mix 0439 Table C21 is identical to Table C1, except that each ture of compound 54 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 110. For example, the first mixture in Table C21 is designated C21-1 and is a mix Table C14 ture of compound 110 and the additional fungicide probena 0432 Table C 14 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 55. For example, the Table C22 first mixture in Table C14 is designated C14-1 and is a mix 0440 Table C22 is identical to Table C1, except that each ture of compound 55 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound III. For example, the first mixture in Table C22 is designated C22-1 and is a mix Table C15 ture of compound III and the additional fungicide probena 0433 Table C 15 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 58. For example, the Table C23 first mixture in Table C15 is designated C15-1 and is a mix 0441 Table C23 is identical to Table C1, except that each ture of compound 58 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 112. For example, the first mixture in Table C23 is designated C23-1 and is a mix Table C16 ture of compound 112 and the additional fungicide probena 0434 Table C 16 is identical to Table C 1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 105. For example, the Table C24 first mixture in Table C16 is designated C16-1 and is a mix 0442 Table C24 is identical to Table C1, except that each ture of compound 105 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 113. For example, the first mixture in Table C24 is designated C24-1 and is a mix Table C17 ture of compound 113 and the additional fungicide probena Zole. 0435 Table C 17 is identical to Table C 1, except that each reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 106. For example, the Table C25 first mixture in Table C17 is designated C17-1 and is a mix 0443 Table C25 is identical to Table C1, except that each ture of compound 106 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 114. For example, the US 2014/O 187776 A1 Jul. 3, 2014 72 first mixture in Table C25 is designated C25-1 and is a mix Table C33 ture of compound 114 and the additional fungicide probena 0451 Table C33 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 122. For example, the Table C26 first mixture in Table C33 is designated C33-1 and is a mix 0444 Table C26 is identical to Table C1, except that each ture of compound 122 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 115. For example, the first mixture in Table C26 is designated C26-1 and is a mix Table C34 ture of compound 115 and the additional fungicide probena 0452 Table C34 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 123. For example, the Table C27 first mixture in Table C34 is designated C34-1 and is a mix ture of compound 123 and the additional fungicide probena 0445 Table C27 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 116. For example, the Table C35 first mixture in Table C27 is designated C27-1 and is a mix ture of compound 116 and the additional fungicide probena 0453 Table C35 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 124. For example, the Table C28 first mixture in Table C35 is designated C35-1 and is a mix ture of compound 124 and the additional fungicide probena 0446 Table C28 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 117. For example, the Table C36 first mixture in Table C28 is designated C28-1 and is a mix ture of compound 117 and the additional fungicide probena 0454 Table C36 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 125. For example, the Table C29 first mixture in Table C36 is designated C36-1 and is a mix ture of compound 125 and the additional fungicide probena 0447 Table C29 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 118. For example, the Table C37 first mixture in Table C29 is designated C29-1 and is a mix ture of compound 118 and the additional fungicide probena 0455 Table C37 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 126. For example, the first mixture in Table C37 is designated C37-1 and is a mix Table C30 ture of compound 126 and the additional fungicide probena 0448 Table C30 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 119. For example, the Table C38 first mixture in Table C30 is designated C30-1 and is a mix 0456 Table C38 is identical to Table C1, except that each ture of compound 119 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 127. For example, the first mixture in Table C38 is designated C38-1 and is a mix Table C31 ture of compound 127 and the additional fungicide probena 0449 Table C31 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 120. For example, the Table C39 first mixture in Table C31 is designated C31-1 and is a mix 0457 Table C39 is identical to Table C1, except that each ture of compound 120 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 128. For example, the first mixture in Table C39 is designated C39-1 and is a mix Table C32 ture of compound 128 and the additional fungicide probena Zole. 0450 Table C32 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 121. For example, the Table C40 first mixture in Table C32 is designated C32-1 and is a mix 0458 Table C40 is identical to Table C1, except that each ture of compound 121 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 129. For example, the US 2014/O 187776 A1 Jul. 3, 2014

first mixture in Table C40 is designated C40-1 and is a mix Table C48 ture of compound 129 and the additional fungicide probena 0466 Table C48 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 137. For example, the Table C41 first mixture in Table C48 is designated C48-1 and is a mix 0459 Table C41 is identical to Table C1, except that each ture of compound 137 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 130. For example, the first mixture in Table C41 is designated C41-1 and is a mix Table C49 ture of compound 130 and the additional fungicide probena 0467 Table C49 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 138. For example, the Table C42 first mixture in Table C49 is designated C49-1 and is a mix ture of compound 138 and the additional fungicide probena 0460 Table C42 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 131. For example, the Table C50 first mixture in Table C42 is designated C42-1 and is a mix ture of compound 131 and the additional fungicide probena 0468. Table C50 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 139. For example, the Table C43 first mixture in Table C50 is designated C50-1 and is a mix ture of compound 139 and the additional fungicide probena 0461 Table C43 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 132. For example, the Table C51 first mixture in Table C43 is designated C43-1 and is a mix ture of compound 132 and the additional fungicide probena 0469 Table C51 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 140. For example, the Table C44 first mixture in Table C51 is designated C51-1 and is a mix ture of compound 140 and the additional fungicide probena 0462 Table C44 is identical to Table C1, except that each Zole. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 133. For example, the Table C51 a first mixture in Table C44 is designated C44-1 and is a mix ture of compound 133 and the additional fungicide probena 0470 Table C51a is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 541. For example, the first mixture in Table C51a is designated C51a-1 and is a Table C45 mixture of compound 541 and the additional invertebrate pest 0463 Table C45 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 134. For example, the Table C52 first mixture in Table C45 is designated C45-1 and is a mix 0471 Table C52 is identical to Table C1, except that each ture of compound 134 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 542. For example, the first mixture in Table C52 is designated C52-1 and is a mix Table C46 ture of compound 542 and the additional invertebrate pest 0464 Table C46 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 135. For example, the Table C53 first mixture in Table C46 is designated C46-1 and is a mix 0472 Table C53 is identical to Table C1, except that each ture of compound 135 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 576. For example, the first mixture in Table C53 is designated C53-1 and is a mix Table C47 ture of compound 576 and the additional invertebrate pest control agent abamectin. 0465 Table C47 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 136. For example, the Table C54 first mixture in Table C47 is designated C47-1 and is a mix 0473] Table C54 is identical to Table C1, except that each ture of compound 136 and the additional fungicide probena reference to compound 6 in the column headed “Cmpd. No.” Zole. is replaced by a reference to compound 583. For example, the US 2014/O 187776 A1 Jul. 3, 2014 74 first mixture in Table C54 is designated C54-1 and is a mix Table C62 ture of compound 583 and the additional invertebrate pest 0481 Table C62 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 687. For example, the Table C55 first mixture in Table C62 is designated C62-1 and is a mix 0474 Table C55 is identical to Table C1, except that each ture of compound 687 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 594. For example, the first mixture in Table C55 is designated C55-1 and is a mix Table C63 ture of compound 594 and the additional invertebrate pest 0482 Table C63 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 718. For example, the Table C56 first mixture in Table C63 is designated C63-1 and is a mix 0475 Table C56 is identical to Table C1, except that each ture of compound 718 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 654. For example, the Table C64 first mixture in Table C56 is designated C56-1 and is a mix ture of compound 654 and the additional invertebrate pest 0483 Table C64 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 725. For example, the Table C57 first mixture in Table C64 is designated C64-1 and is a mix ture of compound 725 and the additional invertebrate pest 0476 Table C57 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 657. For example, the Table C65 first mixture in Table C57 is designated C57-1 and is a mix ture of compound 657 and the additional invertebrate pest 0484 Table C65 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 726. For example, the Table C58 first mixture in Table C65 is designated C65-1 and is a mix ture of compound 726 and the additional invertebrate pest 0477 Table C58 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 669. For example, the Table C66 first mixture in Table C58 is designated C58-1 and is a mix 0485 Table C66 is identical to Table C1, except that each ture of compound 669 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 727. For example, the first mixture in Table C66 is designated C66-1 and is a mix Table C59 ture of compound 727 and the additional invertebrate pest 0478 Table C59 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 670. For example, the Table C67 first mixture in Table C59 is designated C59-1 and is a mix 0486 Table C67 is identical to Table C1, except that each ture of compound 670 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 734. For example, the first mixture in Table C67 is designated C67-1 and is a mix Table C60 ture of compound 734 and the additional invertebrate pest 0479. Table C60 is identical to Table C1, except that each control agent abamectin. reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 682. For example, the Table C68 first mixture in Table C60 is designated C60-1 and is a mix 0487. Table C68 is identical to Table C1, except that each ture of compound 682 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 735. For example, the first mixture in Table C68 is designated C68-1 and is a mix Table C61 ture of compound 735 and the additional invertebrate pest control agent abamectin. 0480 Table C61 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 683. For example, the Table C69 first mixture in Table C61 is designated C61-1 and is a mix 0488 Table C69 is identical to Table C1, except that each ture of compound 683 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 737. For example, the US 2014/O 187776 A1 Jul. 3, 2014

first mixture in Table C69 is designated C69-1 and is a mix Table C77 ture of compound 737 and the additional invertebrate pest control agent abamectin. 0496 Table C77 is identical to Table C1, except that each reference to compound 6 in the column headed “Cmpd. No.” is replaced by a reference to compound 930. For example, the Table C70 first mixture in Table C77 is designated C77-1 and is a mix 0489 Table C70 is identical to Table C1, except that each ture of compound 930 and the additional invertebrate pest reference to compound 6 in the column headed “Cmpd. No.” control agent abamectin. is replaced by a reference to compound 744. For example, the 0497 Invertebrate pests are controlled in agronomic and first mixture in Table C70 is designated C70-1 and is a mix nonagronomic applications by applying one or more compo ture of compound 744 and the additional invertebrate pest sitions of this invention, in a biologically effective amount, to control agent abamectin. the environment of the pests, including the agronomic and/or nonagronomic locus of infestation, to the area to be protected, Table C71 or directly on the pests to be controlled. 0498 Thus the present invention comprises a method for 0490 Table C71 is identical to Table C1, except that each controlling an invertebrate pestinagronomic and/or nonagro reference to compound 6 in the column headed “Cmpd. No.” nomic applications, comprising contacting the invertebrate is replaced by a reference to compound 745. For example, the pest or its environment with a biologically effective amount first mixture in Table C71 is designated C71-1 and is a mix of one or more of the compositions of the invention, or with a ture of compound 745 and the additional invertebrate pest composition of the invention further comprising at least one control agent abamectin. additional biologically active compound or agent. Examples of Suitable compositions comprising a composition of the Table C72 invention and a biologically effective amount of at least one 0491 Table C72 is identical to Table C1, except that each additional biologically active compound or agent include reference to compound 6 in the column headed “Cmpd. No.” granular compositions wherein the additional active com is replaced by a reference to compound 746. For example, the pound is present on the same granule as the composition of first mixture in Table C72 is designated C72-1 and is a mix the invention or on granules separate from those of the com ture of compound 746 and the additional invertebrate pest position of the invention. control agent abamectin. 0499 Embodiments of the method of this invention include contacting the environment. Of note is the method Table C73 wherein the environment is a plant. Also of note is the method wherein the environment is an animal. Also of note is the 0492 Table C73 is identical to Table C1, except that each method wherein the environment is a seed. reference to compound 6 in the column headed “Cmpd. No.” 0500. To achieve contact with a composition of the inven is replaced by a reference to compound 748. For example, the tion to protect a field crop from invertebrate pests, the com first mixture in Table C73 is designated C73-1 and is a mix position is typically applied to the seed of the crop before ture of compound 748 and the additional invertebrate pest planting, to the foliage (e.g., leaves, stems, flowers, fruits) of control agent abamectin. crop plants, or to the soil or other growth medium before or after the crop is planted. Table C74 0501 One embodiment of a method of contact is by spray ing. Alternatively, a granular composition comprising a com 0493 Table C74 is identical to Table C1, except that each position of the invention can be applied to the plant foliage or reference to compound 6 in the column headed “Cmpd. No.” the soil. Compositions of this invention can also be effectively is replaced by a reference to compound 749. For example, the delivered through plant uptake by contacting the plant with a first mixture in Table C74 is designated C74-1 and is a mix composition comprising a composition of this invention ture of compound 749 and the additional invertebrate pest applied as a soil drench of a liquid formulation, a granular control agent abamectin. formulation to the soil, a nursery box treatment or a dip of transplants. Of note is a composition of the present invention Table C75 in the form of a soil drench liquid formulation. Also of note is 0494 Table C75 is identical to Table C1, except that each a method for controlling an invertebrate pest comprising con reference to compound 6 in the column headed “Cmpd. No.” tacting the invertebrate pest or its environment with a com is replaced by a reference to compound 750. For example, the position comprising a biologically effective amount of a com first mixture in Table C75 is designated C75-1 and is a mix position of the present invention. Of further note is this ture of compound 750 and the additional invertebrate pest method wherein the environment is soil and the composition control agent abamectin. is applied to the soil as a soil drench formulation. Of further note is that compositions of this invention are also effective by Table C76 localized application to the locus of infestation. Other meth ods of contact include application of a composition of the 0495 Table C76 is identical to Table C1, except that each invention by direct and residual sprays, aerial sprays, gels, reference to compound 6 in the column headed “Cmpd. No.” seed coatings, microencapsulations, systemic uptake, baits, is replaced by a reference to compound 926. For example, the ear tags, boluses, foggers, fumigants, aerosols, dusts and first mixture in Table C76 is designated C76-1 and is a mix many others. One embodiment of a method of contact is a ture of compound 926 and the additional invertebrate pest dimensionally stable fertilizer granule, stick or tablet com control agent abamectin. prising a compound or composition of the invention. The US 2014/O 187776 A1 Jul. 3, 2014 76 compositions of this invention can also be impregnated into doses of active ingredient that are lethal by ingestion rather materials for fabricating invertebrate control devices (e.g., than by direct contact. Some food materials can function both insect netting). as a food source and an attractant. Food materials include 0502 Compositions of this invention are also useful in carbohydrates, proteins and lipids. Examples of food materi seed treatments for protecting seeds from invertebrate pests. als are vegetable flour, Sugar, starches, animal fat, vegetable In the context of the present disclosure and claims, treating a oil, yeast extracts and milk Solids. Examples of attractants are seed means contacting the seed with a biologically effective odorants and flavorants, such as fruit or plant extracts, per amount of a composition of this invention. This seed treat fume, or other animal or plant component, pheromones or ment protects the seed from invertebrate Soil pests and gen other agents known to attract a target invertebrate pest. erally can also protect roots and other plant parts in contact Examples of humectants, i.e. moisture retaining agents, are with the soil of the seedling developing from the germinating glycols and other polyols, glycerine and Sorbitol. Of note is a seed. The seed treatment may also provide protection of foli bait composition (and a method utilizing such a bait compo age by translocation of the compound of Formula 1 or a sition) used to control at least one invertebrate pest selected second active ingredient within the developing plant. Seed from the group consisting of ants, termites and cockroaches. treatments can be applied to all types of seeds, including those A device for controlling an invertebrate pest can comprise the from which plants genetically transformed to express special present bait composition and a housing adapted to receive the ized traits will germinate. Representative examples include bait composition, wherein the housing has at least one open those expressing proteins toxic to invertebrate pests, such as ing sized to permit the invertebrate pest to pass through the Bacillus thuringiensis toxin or those expressing herbicide opening so the invertebrate pest can gain access to the bait resistance such as glyphosate acetyltransferase, which pro composition from a location outside the housing, and wherein vides resistance to glyphosate. the housing is further adapted to be placed in or near a locus 0503. One method of seed treatment is by spraying or of potential or known activity for the invertebrate pest. dusting the seed with a composition of the invention (i.e. as a 0506. The composition of this invention can be applied formulated composition) before sowing the seeds. Composi without other adjuvants, but most often application will be of tions formulated for seed treatment generally comprise a film a formulation comprising one or more active ingredients with former or adhesive agent. Therefore typically a seed coating Suitable carriers, diluents, and Surfactants and possibly in composition of the present invention comprises a biologically combination with a food depending on the contemplated end effective amount of a compound of Formula 1, an N-oxide or use. One method of application involves spraying a water salt thereof, and a film former or adhesive agent. Seed can be dispersion or refined oil solution of a composition of the coated by spraying a flowable Suspension concentrate present invention. Combinations with spray oils, spray oil directly into a tumbling bed of seeds and then drying the concentrations, spreader Stickers, adjuvants, other solvents, seeds. Alternatively, other formulation types such as wetted and synergists such as piperonylbutoxide often enhance com powders, solutions, Suspoemulsions, emulsifiable concen pound efficacy. For nonagronomic uses such sprays can be trates and emulsions in water can be sprayed on the seed. This applied from spray containers such as a can, a bottle or other process is particularly useful for applying film coatings on container, either by means of a pump or by releasing it from seeds. Various coating machines and processes are available a pressurized container, e.g., a pressurized aerosol spray can. to one skilled in the art. Suitable processes include those Such spray compositions can take various forms, for listed in P. Kosters et al., Seed Treatment Progress and Pros example, sprays, mists, foams, fumes or fog. Such spray pects, 1994 BCPC Mongraph No. 57, and references listed compositions thus can further comprise propellants, foaming therein. agents, etc. as needed for application. Of note is a spray 0504 The treated seed typically comprises a composition composition comprising a biologically effective amount of a of the present invention in an amount from about 0.1 g to 1 kg compound or a composition of the present invention and a per 100 kg of seed (i.e. from about 0.0001 to 1% by weight of carrier. One embodiment of Such a spray composition com the seed before treatment). A flowable suspension formulated prises a biologically effective amount of a composition of the for seed treatment typically comprises from about 0.5 to present invention and a propellant. Representative propel about 70% of the active ingredient, from about 0.5 to about lants include, but are not limited to, methane, ethane, pro 30% of a film-forming adhesive, from about 0.5 to about 20% pane, butane, isobutane, butene, pentane, isopentane, neopen of a dispersing agent, from 0 to about 5% of a thickener, from tane, pentene, hydrofluorocarbons, chlorofluorocarbons, 0 to about 5% of a pigment and/or dye, from 0 to about 2% of dimethyl ether, and mixtures of the foregoing. Of note is a an antifoaming agent, from 0 to about 1% of a preservative, spray composition (and a method utilizing such a spray com and from 0 to about 75% of a volatile liquid diluent. position dispensed from a spray container) used to control at 0505. The compositions of this invention can be incorpo least one invertebrate pest selected from the group consisting rated into a bait composition that is consumed by an inverte of mosquitoes, black flies, stable flies, deer flies, horse flies, brate pest or used within a device Such as a trap, bait station, wasps, yellowjackets, hornets, ticks, spiders, ants, gnats, and and the like. Such a bait composition can be in the form of the like, including individually or in combinations. granules which comprise (a) active ingredients, namely a 0507 Nonagronomic uses refer to invertebrate pest con biologically effective amount of a compound of Formula 1 an trol in the areas other than fields of crop plants. Nonagro N-oxide or salt thereof; (b) one or more food materials; nomic uses of the present compositions include control of optionally (c) an attractant, and optionally (d) one or more invertebrate pests in stored grains, beans and other foodstuffs, humectants. Of note are granules or bait compositions which and in textiles Such as clothing and carpets. Nonagronomic comprise between about 0.001-5% active ingredients, about uses of the present compositions also include invertebrate 40-99% food material and/or attractant; and optionally about pest control in ornamental plants, forests, in yards, along 0.05-10% humectants, which are effective in controlling soil roadsides and railroad rights of way, and on turf Such as invertebrate pests at very low application rates, particularly at lawns, golf courses and pastures. Nonagronomic uses of the US 2014/O 187776 A1 Jul. 3, 2014 77 present compositions also include invertebrate pest control in 0513 For purposes of the present invention, the term houses and other buildings which may be occupied by “fish” shall be understood to include without limitation, the humans and/or companion, farm, ranch, Zoo or other animals. Teleosti grouping of fish, i.e., teleosts. Both the Salmoni Nonagronomic uses of the present compositions also include formes order (which includes the Salmonidae family) and the the control of pests Such as termites that can damage wood or Perciformes order (which includes the Centrarchidae family) other structural materials used in buildings. are contained within the Teleosti grouping. Examples of 0508) Nonagronomic uses of the present compositions potential fish recipients include the Salmonidae, Serranidae, also include protecting human and animal health by control Sparidae, Cichlidae, and Centrarchidae, among others. ling invertebrate pests that are parasitic or transmit infectious 0514. Other animals are also contemplated to benefit from diseases. The controlling of animal parasites includes con the inventive methods, including marsupials (Such as kanga trolling external parasites that are parasitic to the Surface of roos), reptiles (such as farmed turtles), and other economi the body of the host animal (e.g., shoulders, armpits, abdo cally important domestic animals for which the inventive men, inner part of the thighs) and internal parasites that are methods are safe and effective in treating or preventing para parasitic to the inside of the body of the host animal (e.g., site infection or infestation. stomach, intestine, lung, veins, under the skin, lymphatic 0515. Examples of invertebrate parasitic pests controlled tissue). External parasitic or disease transmitting pests by administering a parasiticidally effective amount of a com include, for example, chiggers, ticks, lice, mosquitoes, flies, position of this invention to an animal to be protected include mites and fleas. Internal parasites include heartworms, hook ectoparasites (arthropods, acarines, etc) and endoparasites worms and helminths. Compositions of the present invention (helminths, e.g., nematodes, trematodes, cestodes, acantho are particularly suitable for combating external parasitic or cephalans, etc.). disease transmitting pests. Compositions of the present 0516. The disease or group of diseases described generally invention are suitable for systemic and/or non-systemic con as helminthiasis is due to infection of an animal host with trol of infestation or infection by parasites on animals. parasitic worms known as helminths. The term helminths is 0509 Compositions of the present invention are suitable meant to include nematodes, trematodes, cestodes and acan for combating parasites that infest animal Subjects including thocephalans. Helminthiasis is a prevalent and serious eco those in the wild, livestock and agricultural working animals nomic problem with domesticated animals such as Swine, Such as cattle, sheep, goats, horses, pigs, donkeys, camels, sheep, horses, cattle, goats, dogs, cats and poultry. bison, buffalos, rabbits, hens, turkeys, ducks, geese and bees 0517. Among the Helminths, the group of worms (e.g., raised for meat, milk, butter, eggs, fur, leather, feathers described as nematodes causes widespread and at times seri and/or wool). By combating parasites, fatalities and perfor ous infection in various species of animals. Nematodes that mance reduction (in terms of meat, milk, wool, skins, eggs, are contemplated to be treated by the compositions of this honey, etc.) are reduced, so that applying a composition com invention and by the inventive methods include, without limi prising a compound of the present invention allows more tation, the following genera: Acanthocheilonema, Aeluros economic and simple husbandry of animals. trongylus, Ancylostoma, Angiostrongylus, Ascaridia, 0510 Compositions of the present invention are espe Ascaris, Brugia, Bunostomum, Capillaria, Chabertia, Coo cially Suitable for combating parasites that infest companion peria, Crenosoma, Dictyocaulus, Dioctophyme, Dipetal animals and pets (e.g., dogs, cats, pet birds and aquarium onema, Diphyllobothrium, Dirofilaria, Dracunculus, Entero fish), research and experimental animals (e.g., hamsters, bius, Filaroides, Haemonchus, Heterakis, Lagochilascaris, guinea pigs, rats and mice), as well as animals raised for/in Loa, Mansonella, Muellerius, Necator, Nematodirus, Zoos, wild habitats and/or circuses. Oesophagostomum, Ostertagia, Oxyuris, Parafilaria, Paras 0511. In an embodiment of this invention, the animal is caris, Physaloptera, Protostrongylus, Setaria, Spirocerca, preferably a vertebrate, and more preferably a mammal, avian Stephanofilaria, Strongyloides, Strongylus, Thelazia, Toxas or fish. In a particular embodiment, the animal Subject is a caris, Toxocara, Trichinella, Trichonema, TrichoStrongylus, mammal (including great apes, such as humans). Other mam Trichuris, Uncinaria and Wuchereria. malian Subjects include primates (e.g., monkeys), bovine 0518. Of the above, the most common genera of nema (e.g., cattle or dairy cows), porcine (e.g., hogs or pigs), Ovine todes infecting the animals referred to above are Haemon (e.g., goats or sheep), equine (e.g., horses), canine (e.g., chus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, dogs), feline (e.g., house cats), camels, deer, donkeys, bison, Ascaris, Bunostomum, Oesophagostomum, Chabertia, Tri buffalos, antelopes, rabbits, and rodents (e.g., guinea pigs, churis, Strongylus, Trichonema, Dictyocaulus, Capillaria, squirrels, rats, mice, gerbils, and hamsters). Avians include Heterakis, Toxocara, Ascaridia, Oxyuris, Ancylostoma, Anatidae (Swans, ducks and geese), Columbidae (e.g., doves Uncinaria, Toxascaris and Parascaris. Certain of these, Such and pigeons), Phasianidae (e.g., partridges, grouse and tur as Nematodirus, Cooperia and Oesophagostomum attack pri keys). Thesienidae (e.g., domestic chickens), Psittacines marily the intestinal tract while others, such as Haemonchus (e.g., parakeets, macaws, and parrots), game birds, and ratites and Ostertagia, are more prevalent in the stomach while (e.g., ostriches). others such as Dictyocaulus are found in the lungs. Still other 0512 Birds treated or protected by the inventive compo parasites may be located in other tissues such as the heart and sitions can be associated with either commercial or noncom blood vessels, Subcutaneous and lymphatic tissue and the mercial aviculture. These include Anatidae, such as Swans, like. geese, and ducks, Columbidae, such as doves and domestic 0519 Trematodes that are contemplated to be treated by pigeons, Phasianidae, such as partridge, grouse and turkeys, the compositions of this invention and by the inventive meth Thesienidae, such as domestic chickens, and Psittacines, such ods include, without limitation, the following genera: Alaria, as parakeets, macaws, and parrots raised for the pet or col Fasciola, Nanophyetus, Opisthorchis, Paragonimus and lector market, among others. Schistosoma. US 2014/O 187776 A1 Jul. 3, 2014

0520 Cestodes that are contemplated to be treated by the triatomidbugs also known as kissing bugs; for example Rhod compositions of this invention and by the inventive methods nius prolixus and Triatoma spp. include, without limitation, the following genera: Diphyllo 0531 Generally, flies, fleas, lice, mosquitoes, gnats, mites, bothrium, Diplvdium, Spirometra and Taenia. ticks and helminths cause tremendous losses to the livestock 0521. The most common genera of parasites of the gas and companion animal sectors. Arthropod parasites also area trointestinal tract of humans are Ancylostoma, Necator; nuisance to humans and can vector disease-causing organ Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris and isms in humans and animals. Enterobius. Other medically important genera of parasites 0532. Numerous other arthropod pests and ectoparasites which are found in the blood or other tissues and organs are known to the art, and are also contemplated to be treated outside the gastrointestinal tract are the filarial worms such as by the compositions of the invention. These are enumerated in Wuchereria, Brugia, Onchocerca and Loa, as well as Dra great detail in Medical and Veterinary Entomology, D. S. cunculus and extra intestinal stages of the intestinal worms Kettle, John Wiley & Sons, New York and Toronto; Control of Strongyloides and Trichinella. Arthropod Pests of Livestock. A Review of Technology, R. O. 0522) Numerous other Helminth genera and species are Drummand, J. E. George, and S. E. Kunz, CRC Press, Boca known to the art, and are also contemplated to be treated by Raton, Fla. the compositions of the invention. These are enumerated in 0533. The compositions of this invention may also be great detail in Textbook of Veterinary Clinical Parasitology, effective against a number of protozoa endoparasites of ani Volume 1, Helminths, E. J. L. Soulsby, F. A. Davis Co., Philadelphia, Pa.; Helminths, Arthropods and Protozoa, (6" mals, such as those Summarized by Table 1, as follows. Edition of Monnig's Veterinary Helminthology and Entomol TABLE 1 ogy), E. J. L. Soulsby, The Williams and Wilkins Co., Balti more, Md. Exemplary Parasitic Protozoa and Associated Human Diseases 0523. It is also contemplated that the inventive composi Representative Human Disease tions are effective against a number of ectoparasites of ani Phylum Subphylum Genera or Disorder mals, e.g., arthropod ectoparasites of mammals and birds Sarcomastigophora Mastigophora Leishmania Visceral, although it is also recognized that some arthropods can be (with flagella, (Flagella) cutaneous and endoparasites as well. pseudopodia, or mucocutaneous both) Infection 0524 Thus, insect and acarine pests include, e.g., biting Trypansoma Sleeping insects, such as flies and mosquitoes, mites, ticks, lice, fleas, sickness true bugs, parasitic maggots, and the like. Chagas 0525. Adult flies include, e.g., the horn fly or Haematobia disease Giardia Diarrhea irritans, the horse fly or Tabanus spp., the stable fly or Sto Tichomonas Vaginitis moxys calcitrans, the black fly or Simulium spp., the deer fly Sarcodina Entamoeba Dysentery, or Chrysops spp., the louse fly or Mellophagus Ovinus, the (pseudopodia) liver tsetse fly or Glossina spp. Parasitic fly maggots include, e.g., Abscess Dientamoeba Colitis the botfly (Oestrus Ovis and Cuterebra spp.), the blow fly or Naegleria and Central Phaenicia spp., the screwworm or Cochliomyia hominivorax, Acanthamoeba (WOS the cattle grub or Hypoderma spp., the fleeceworm and the system and Gastrophilus of horses. Mosquitoes include, for example, corneal ulcers Culex spp., Anopheles spp., and Aedes spp. Babesia Babesiesis 0526 Mites include Mesostigmata spp. e.g., mesostigma Apicomplexa Plasmodium Malaria tids such as the chicken mite, Dermanyssus gallinae; itch or (apical complex) Isospora Diarrhea scab mites Such as Sarcoptidae spp. for example, Sarcoptes Sarcocystis Diarrhea scabiei; mange mites Such as Psoroptidae spp. including Cryptosporidum Diarrhea Chorioptes bovis and Psoroptes ovis; chiggers e.g., Trom Toxoplasma Toxoplasmosis biculidae spp. for example the North American chigger, Eineria Chicken coccidiosis Trombicula alfreddugesi. Microspora Enterocytozoon Diarrhea 0527 Ticks include, e.g., soft-bodied ticks including Ciliaphora (with Baiantidium Dysentery Argasidae spp. for example Argas spp. and Ornithodoros cilia) spp.; hard-bodied ticks including Ixodidae spp., for example Unclassified Pneumocystis Pneumonia Rhipicephalus sanguineus, Dermacentor variabilis, Derma centor andersoni, Amblyomma americanum, Ixodes Scapu 0534. In particular, the compositions of this invention are laris and Boophilus spp. effective against ectoparasites including fleas Such as Cteno 0528 Lice include, e.g., Sucking lice, e.g., Menopon spp. cephalides felis (cat flea) and Ctenocephalides canis (dog and Bovicola spp., biting lice, e.g., Haematopinus spp., flea). Linognathus spp. and Solenopotes spp. 0535 The compositions of this invention may also be 0529 Fleas include, e.g., Ctenocephalides spp., such as effective against other ectoparasites including flies Such as dog flea (Ctenocephalides canis) and cat flea (Ctenocepha Haematobia (Lyperosia) irritans (horn fly), Stomoxys calci lides fells); Xenopsylla spp. Such as oriental rat flea (Xenop trans (stable fly), Simulium spp. (blackfly), Glossina spp. sylla cheopis); and Pulex spp. Such as human flea (Pulex (tsetse flies), Hydrotaea irritans (head fly), Musca autumna irritans). lis (face fly), Musca domestica (house fly), Morelia simplex 0530 True bugs include, e.g., Cimicidae or e.g., the com (Sweat fly), Tabanus spp. (horse fly), Hypoderma bovis, mon bedbug (Cimex lectularius); Triatominae spp. including Hypoderma lineatum, Lucilia sericata, Lucilia cuprina US 2014/O 187776 A1 Jul. 3, 2014 79

(green blowfly), Calliphora spp. (blowfly), Protophormia than 20%. 22.23-dihydroavermectin B. Ivermectin is dis spp., Oestrus Ovis (nasal botfly), Culicoides spp. (midges), closed in U.S. Pat. No. 4,199,569. Hippobosca equine, Gastrophilus instestinalis, Gastrophilus 0541. Abamectin is an avermectin that is disclosed as haemorrhoidalis and Gastrophilus nasilis; lice such as Bovi Avermectin B/B, in U.S. Pat. No. 4.310,519. Abamectin cola (Damalinia) bovis, Bovicola equi, Haematopinus asini, contains at least 80% of avermectin B, and not more than Felicola subrostratus, Heterodoxus spiniger; Lignonathus 20% of avermectin B. setosus and Trichodectes canis; keds such as Mellophagus 0542. Another notable avermectin is Doramectin, also ovinus; mites Such as Psoroptes spp., Sarcoptes scabei, known as 25-cyclohexyl-avermectin B. The structure and Chorioptes bovis, Demodex equi, Cheyletiella spp., preparation of Doramectin is disclosed in U.S. Pat. No. 5,089, Notoedres cati, Trombicula spp. and Otodectes cyanotis (ear 480. mites); and ticks such as Ixodes spp., Boophilus spp., Rhipi 0543. Another notable avermectin is Moxidectin. Mox cephalus spp., Amblyomma spp., Dermacentor spp., idectin, also known as LL-F28249 alpha, is known from U.S. Hyalomma spp. and Haemaphysalis spp. Pat. No. 4,916,154. 0536 Biologically active compounds or agents useful in 0544. Another notable avermectin is Selamectin. Sel the compositions of the present invention include the organo amectin is 25-cyclohexyl-25-de(1-methylpropyl)-5-deoxy phosphate pesticides. This class of pesticides has very broad 22.23-dihydro-5-(hydroxyimino)-avermectin B monosac activity as insecticides and, in certain instances, anthelminitic charide. activity. Organophosphate pesticides include, e.g., dicroto 0545 Milbemycin, or B41, is a substance which is isolated phos, terbufos, dimethoate, diazinon, disulfoton, trichlorfon, from the fermentation broth of a Milbemycin producing azinphos-methyl, chlorpyrifos, malathion, Oxydemeton-me strain of Streptomyces. The microorganism, the fermentation thyl, methamidophos, acephate, ethyl parathion, methyl par conditions and the isolation procedures are more fully athion, mevinphos, phorate, carbofenthion and phosalone. It described in U.S. Pat. No. 3,950,360 and U.S. Pat. No. 3,984, is also contemplated to include combinations of the inventive 564. methods and compounds with carbamate type pesticides, 0546 Emamectin (4"-deoxy-4"-epi-methylaminoaver including, e.g., carbaryl, carbofuran, aldicarb, molinate, mectin B), which can be prepared as described in U.S. Pat. methomyl, carbofuran, etc., as well as combinations with the No. 5,288,710 or U.S. Pat. No. 5,399,717, is a mixture of two organochlorine type pesticides. It is further contemplated to homologues, 4'-deoxy-4'-epi-methylaminoavermectin B, include combinations with biological pesticides, including and 4'-deoxy-4"-epi-methylaminoavermectin B. Prefer repellents, the pyrethrins (as well as synthetic variations ably, a salt of Emamectin is used. Non-limiting examples of thereof, e.g., allethrin, resmethrin, permethrin, tralomethrin), salts of Emamectin which can be used in the present invention and nicotine, that is often employed as an acaricide. Other include the salts described in U.S. Pat. No. 5,288,710, e.g., contemplated combinations are with miscellaneous pesti salts derived from benzoic acid, substituted benzoic acid, cides including: bacillus thuringensis, chlorobenzilate, for benzenesulfonic acid, citric acid, phosphoric acid, tartaric mamidines (e.g., amitraZ), copper compounds (e.g., copper acid, maleic acid, and the like. Most preferably, the Emamec hydroxide and cupric oxychloride Sulfate), cyfluthrin, cyper tin Salt used in the present invention is Emamectin benzoate. methrin, dicofol, endosulfan, esenfenvalerate, fenvalerate, 0547 Eprinomectin is chemically known as 4"-epi-acety lambda-cyhalothrin, methoxychlor and sulfur. lamino-4'-deoxy-avermectin B. Eprinomectin was specifi 0537 Of note are additional biologically active com cally developed to be used in all cattle classes and age groups. pounds or agents selected from art-known anthelmintics, It was the first avermectin to show broad-spectrum activity Such as, for example, avermectins (e.g., ivermectin, moxidec against both endo- and ectoparasites while also leaving mini tin, milbemycin), benzimidazoles (e.g., albendazole, tricla mal residues in meat and milk. It has the additional advantage bendazole), Salicylanilides (e.g., closantel, oxyclozanide), of being highly potent when delivered topically. Substituted phenols (e.g., nitroxynil), pyrimidines (e.g., pyr 0548. The composition of the present invention optionally antel), imidazothiazoles (e.g., levamisole) and praziquantel. comprises combinations of one or more of the following antiparasite compounds: imidazo 1.2-bipyridazine com 0538. Other biologically active compounds or agents use pounds as described by U.S. application Ser. No. 11/019,597. ful in the compositions of the present invention can be filed on Dec. 22, 2004: 1-(4-mono and di-halomethylsulpho selected from Insect Growth Regulators (IGRs) and Juvenile nylphenyl)-2-acylamino-3-fluoropropanol compounds, as Hormone Analogues (JHAs) such as diflubenZuron, triflumu described by U.S. application Ser. No. 11/018,156, filed on ron, fluaZuron, cyromazine, methoprene, etc., thereby provid Dec. 21, 2004; trifluoromethanesulfonanilide oxime ether ing both initial and Sustained control of parasites (at all stages derivatives, as described by U.S. application Ser. No. 1 1/231, of insect development, including eggs) on the animal Subject, 423, filed on Sep. 21, 2005; and n-(phenyloxy)phenyl)-1,1, as well as within the environment of the animal subject. 1-trifluoromethanesulfonamide and n-(phenylsulfanyl)phe 0539. Of note are biologically active compounds or agents nyl)-1,1,1-trifluoromethanesulfonamide derivatives, as useful in the compositions of the present invention selected described by U.S. Provisional Application Ser. No. 60/688, from the antiparasitic class of avermectin compounds. As 898, filed on Jun. 9, 2005. stated above, the avermectin family of compounds is a series 0549. The compositions of the present invention can also of very potent antiparasitic agents known to be useful against further comprise a flukicide. Suitable flukicides include, for abroad spectrum of endoparasites and ectoparasites in mam example, triclabendazole, fenbendazole, albendazole, Clor mals. Sulon and oxibendazole. It will be appreciated that the above 0540. A notable compound for use within the scope of the combinations can further include combinations of antibiotic, present invention is ivermectin. Ivermectin is a semi-syn antiparasitic and anti-fluke active compounds. thetic derivative of avermectin and is generally produced as a 0550. In addition to the above combinations, it is also mixture of at least 80%. 22.23-dihydroavermectin Bandless contemplated to provide combinations of the inventive meth US 2014/O 187776 A1 Jul. 3, 2014

ods and compositions, as described herein, with other animal antibiotics may include B-lactams such as penicillins, e.g., health remedies Such as trace elements, anti-inflammatories, penicillin, ampicillin, amoxicillin, or a combination of amox anti-infectives, hormones, dermatological preparations, icillin with clavulanic acid or other beta lactamase inhibitors. including antiseptics and disinfectants, and immunobiologi 0559 Nonagronomic applications in the veterinary sector cals such as vaccines and antisera for the prevention of dis are by conventional means such as by enteral administration CaSC. in the form of for example, tablets, capsules, drinks, drench 0551 For example, such antinfectives include one or more ing preparations, granulates, pastes, boli, feed-through pro antibiotics that are optionally co-administered during treat cedures, or suppositories; or by parenteral administration, ment using the inventive compositions or methods, e.g., in a Such as by injection (including intramuscular, Subcutaneous, combined composition and/or in separate dosage forms. Art intravenous, intraperitoneal) or implants; by nasal adminis known antibiotics suitable for this purpose include, for tration; by topical administration, for example, in the form of example, those listed herein below. immersion or dipping, spraying, washing, coating with pow 0552. One useful antibiotic is Florfenicol, also known as der, or application to a small area of the animal, and through D-(threo)-1-(4-methylsulfonylphenyl)-2-dichloroaceta articles Such as neck collars, eartags, tail bands, limb bands or mido-3-fluoro-1-propanol. Another notable antibiotic com halters which comprise compositions of the present inven pound is D-(threo)-1-(4-methylsulfonyphenyl)-2-difluoroac tion. etamido-3-fluoro-1-propanol. Another useful antibiotic is 0560 Any of the compositions of the present invention, or Thiamphenicol. Processes for the manufacture of these anti a Suitable combination of Such compositions, may be admin biotic compounds, and intermediates useful in Such pro istered directly to the animal subject and/or indirectly by cesses, are described in U.S. Pat. No. 4,311.857: U.S. Pat. No. applying it to the local environment in which the animal 4,582,918; U.S. Pat. No. 4,973,750; U.S. Pat. No. 4,876,352: dwells (such as bedding, enclosures, or the like). Direct U.S. Pat. No. 5,227,494; U.S. Pat. No. 4,743,700; U.S. Pat. administration includes contacting the skin, fur or feathers of No. 5,567,844; U.S. Pat. No. 5,105,009; U.S. Pat. No. 5,382, a Subject animal with the compositions, or by feeding or 673; U.S. Pat. No. 5,352,832; and U.S. Pat. No. 5,663,361. injecting the compositions into the animal. Other florfenicol analogs and/or prodrugs have been dis 0561. The compositions of the present invention may be closed and Such analogs also can be used in the compositions administered in a controlled release form, e.g., in a Subcuta and methods of the present invention (see e.g., U.S. Patent neous slow release formulation, or in the form of a controlled Application Publication No: 2004/0082553, and U.S. patent release device affixed to an animal such as a fleacollar. Collars application Ser. No. 11/016,794). for the controlled release of an insecticide agent for long term 0553 Another useful antibiotic compound is Tilmicosin. protection against flea infestation in a companion animal are Tilmicosin is a macrollide antibiotic that is chemically defined art-known, and are described, for example, by U.S. Pat. No. as 20-dihydro-20-deoxy-20-(cis-3,5-dimethylpiperidin-1- 3,852,416, U.S. Pat. No. 4,224,901, U.S. Pat. No. 5,555,848 yl)-desmycosin and which is reportedly disclosed in U.S. Pat. and U.S. Pat. No. 5,184,573. No. 4,820,695. 0562 Typically a parasiticidal composition according to 0554 Another useful antibiotic for use in the present the present invention comprises a mixture of a compound of invention is tulathromycin. Tulathromycin is also identified Formula 1, an N-oxide or salt thereof, with one or more as (2R,3S,4R,5R, 8R,10R,11R,12S,13S,14R) 13-(2,6- pharmaceutically or veterinarily acceptable carriers compris dideoxy-3-C-methyl-3-O-methyl-4-C-(propylamino)me ing excipients and auxiliaries selected with regard to the thyl-alpha-L-ribo-hexopyranosyl-oxy-2-ethyl-3,4,10-tri intended route of administration (e.g., oral, topical or hydroxy-3,5,8,10,12,14-hexamethyl-11-3,4,6-trideoxy-3- parenteral administration Such as injection) and in accor (dimethyl-amino)-beta-D-Xylo-hexopyranosylloxy-1-Oxa dance with standard practice. In addition, a suitable carrier is 6-azacyclopentadecan-15-one. Tulathromycin can be selected on the basis of compatibility with the one or more prepared in accordance with the procedures set forth in U.S. active ingredients in the composition, including Such consid Patent Publication No. 2003/0064939 A1. erations as stability relative to pH and moisture content. 0555. Further antibiotics for use in the present invention Therefore of note is a composition for protecting an animal include the cephalosporins such as, for example, ceftiofur, from an invertebrate parasitic pest comprising a parasitically cefauinome, etc. The concentration of the cephalosporin in effective amount of a compound of the invention and at least the formulation of the present invention optionally varies one carrier. between about 1 mg/mL to 500 mg/mL. 0563 For parenteral administration including intrave 0556. Another useful antibiotic includes the fluoroquino nous, intramuscular and Subcutaneous injection, a composi lones, such as, for example, enrofloxacin, danofloxacin, tion of the present invention can be formulated in Suspension, difloxacin, orbifloxacin and marbofloxacin. Enrofloxacin is Solution or emulsion in oily or aqueous vehicles, and may typically administered in a concentration of about 100 contain adjuncts such as Suspending, stabilizing and/or dis mg/mL. Danofloxacin is typically administered at a concen persing agents. The compositions of the present invention tration of about 180 mg/mL. may also be formulated for bolus injection or continuous 0557. Other useful macrollide antibiotics include com infusion. Pharmaceutical compositions for injection include pounds from the class of ketolides, or, more specifically, the aqueous solutions of water-soluble forms of active ingredi azalides. Such compounds are described in, for example, U.S. ents (e.g., a salt of an active compound), preferably in physi Pat. No. 6,514,945, U.S. Pat. No. 6,472,371, U.S. Pat. No. ologically compatible buffers containing other excipients or 6,270,768, U.S. Pat. No. 6,437,151, U.S. Pat. No. 6,271,255, auxiliaries as are known in the art of pharmaceutical formu U.S. Pat. No. 6,239,112, U.S. Pat. No. 5,958,888, U.S. Pat. lation. Additionally, Suspensions of the active compounds No. 6,339,063 and U.S. Pat. No. 6,054,434. may be prepared in a lipophilic vehicle. Suitable lipophilic 0558 Other useful antibiotics include the tetracyclines, vehicles include fatty oils such as sesame oil, synthetic fatty particularly chlortetracycline and oxytetracycline. Other acid esters such as ethyl oleate and triglycerides, or materials US 2014/O 187776 A1 Jul. 3, 2014

Such as liposomes. Aqueous injection Suspensions may con 0568 If the parasiticidal compositions are in the form of tain Substances that increase the Viscosity of the Suspension, feed concentrates, the carrier is typically selected from high Such as Sodium carboxymethylcellulose, Sorbitol, or dextran. performance feed, feed cereals or protein concentrates. Such Formulations for injection may be presented in unit dosage feed concentrate-containing compositions can, in addition to form, e.g., in ampoules or in multi-dose containers. Alterna the parasiticidal active ingredients, comprise additives pro tively, the active ingredient may be in powder form for con moting animal health or growth, improving quality of meat stitution with a Suitable vehicle, e.g., Sterile, pyrogen-free from animals for slaughter or otherwise useful to animal water, before use. husbandry. These additives can include, for example, Vita 0564. In addition to the formulations described supra, the mins, antibiotics, chemotherapeutics, bacteriostats, fung compositions of the present invention may also be formulated istats, coccidiostats and hormones. as a depot preparation. Such long acting formulations may be 0569. The compounds of Formula 1 may also be formu administered by implantation (for example, Subcutaneously lated in rectal compositions such as Suppositories or retention or intramuscularly) or by intramuscular or Subcutaneous enemas, using, e.g., conventional Suppository bases such as injection. The compositions of the present invention may be cocoa butter or other glycerides. formulated for this route of administration with suitable poly 0570 Formulations for topical administration are typi meric or hydrophobic materials (for instance, in an emulsion cally in the form of a powder, cream, Suspension, spray, with a pharmacologically acceptable oil), with ion exchange emulsion, foam, paste, aerosol, ointment, salve or gel. More resins, or as a sparingly soluble derivative such as, without typically a topical formulation is a water-soluble solution, limitation, a sparingly soluble salt. which can be in the form of a concentrate that is diluted before 0565 For administration by inhalation, the compositions use. Parasiticidal compositions suitable for topical adminis of the present invention can be delivered in the form of an tration typically comprise a compound of the present inven aerosol spray using a pressurized pack or a nebulizer and a tion and one or more topically suitable carriers. In applica Suitable propellant, e.g., without limitation, dichlorodifluo tions of aparasiticidal composition topically to the exterior of romethane, trichlorofluoromethane, dichlorotetrafluoroet an animal as a line or spot (i.e. 'spot-on' treatment), the active hane or carbon dioxide. In the case of a pressurized aerosol, ingredient migrates over the Surface of the animal to cover the dosage unit may be controlled by providing a valve to most or all of its external Surface area. As a result, the treated deliver a metered amount. Capsules and cartridges of, for animal is particularly protected from invertebrate pests that example, gelatin for use in an inhaler or insufflator may be feed off the epidermis of the animal such as ticks, fleas and formulated containing a powder mix of the composition and lice. Therefore formulations for topical localized administra a suitable powder base such as lactose or starch. tion often comprise at least one organic solvent to facilitate 0566 Compositions of the present invention have been transport of the active ingredient over the skin and/or penetra discovered to have favorable pharmacokinetic and pharma tion into the epidermis of the animal. Carriers in such formu codynamic properties providing systemic availability from lations include propylene glycol, paraffins, aromatics, esters oral administration and ingestion. Therefore after ingestion Such as isopropyl myristate, glycol ethers, alcohols such as by the animal to be protected, parasiticidally effective con ethanol, n-propanol, 2-octyl dodecanol or oleylalcohol; Solu centrations of compounds of the invention in the bloodstream tions in esters of monocarboxylic acids, such as isopropyl protect the treated animal from blood-sucking pests such as myristate, isopropyl palmitate, lauric acid oxalic ester, oleic fleas, ticks and lice. Therefore of note is a composition for acid oleyl ester, oleic acid decyl ester, hexyl laurate, oleyl protecting an animal from an invertebrate parasite pest in a oleate, decyl oleate, caproic acid esters of Saturated fatty form for oral administration (i.e. comprising, in addition to a alcohols of chain length C-Cs; Solutions of esters of dicar parasiticidally effective amount of a compound of the inven boxylic acids, such as dibutyl phthalate, diisopropyl isoph tion, one or more carriers selected from binders and fillers thalate, adipic acid diisopropyl ester, di-n-butyl adipate or Suitable for oral administration and feed concentrate carri Solutions of esters of aliphatic acids, e.g., glycols. It may be ers). advantageous for a crystallization inhibitor or a dispersant 0567 For oral administration in the form of solutions (the known from the pharmaceutical or cosmetic industry also to most readily available form for absorption), emulsions, Sus be present. pensions, pastes, gels, capsules, tablets, boluses, powders, 0571 A pour-on formulation may also be prepared for granules, rumen-retention and feed/water/lick blocks, a com control of parasites in an animal of agricultural worth. The position of the present invention can beformulated with bind pour-on formulations of this invention can be in the form of a ers/fillers known in the art to be suitable for oral administra liquid, powder, emulsion, foam, paste, aerosol, ointment, tion compositions, such as Sugars and Sugar derivatives (e.g., salve or gel. Typically, the pour-on formulation is liquid. lactose, Sucrose, mannitol, Sorbitol), starch (e.g., maize These pour-on formulations can be effectively applied to starch, wheat starch, rice starch, potato starch), cellulose and sheep, cattle, goats, other ruminants, camelids, pigs and derivatives (e.g., methylcellulose, carboxymethylcellulose, horses. The pour-on formulation is typically applied by pour ethylhydroxycellulose), protein derivatives (e.g., Zein, gela ing in one or several lines or in a spot-on the dorsal midline tin), and synthetic polymers (e.g., polyvinyl alcohol, polyvi (back) or shoulder of an animal. More typically, the formu nylpyrrolidone). If desired, lubricants (e.g., magnesium Stear lation is applied by pouring it along the back of the animal, ate), disintegrating agents (e.g., cross-linked following the spine. The formulation can also be applied to polyvinylpyrrolidinone, agar, alginic acid) and dyes or pig the animal by other conventional methods, including wiping ments can be added. Pastes and gels often also contain adhe an impregnated material over at least a small area of the sives (e.g., acacia, alginic acid, bentonite, cellulose, Xanthan animal, or applying it using a commercially available appli gum, colloidal magnesium aluminum silicate) to aid in keep cator, by means of a Syringe, by spraying or by using a spray ing the composition in contact with the oral cavity and not race. The pour-on formulations include a carrier and can also being easily ejected. include one or more additional ingredients. Examples of Suit US 2014/O 187776 A1 Jul. 3, 2014

able additional ingredients are stabilizers such as antioxi dips and sprays typically contain from about 0.5 ppm to about dants, spreading agents, preservatives, adhesion promoters, 5000 ppm, more typically from about 1 ppm to about 3000 active solubilisers such as oleic acid, viscosity modifiers, UV ppm, of a compound of the present invention. blockers or absorbers, and colourants. Surface active agents, including anionic, cationic, non-ionic and ampholytic Surface 0577 Representative compounds of Formula 1 useful in active agents, can also be included in these formulations. the compositions of this invention are shown in Index Tables 0572 The formulations of this invention typically include A-C. See Index Table D for "H NMR data. For mass spectral an antioxidant, such as BHT (butylated hydroxytoluene). The data (AP" (M+1)), the numerical value reported is the antioxidant is generally present in amounts of at 0.1-5% molecular weight of the parent molecular ion (M) formed by (wt/vol). Some of the formulations require a solubilizer, such addition of H' (molecular weight of 1) to the molecule to give as oleic acid, to dissolve the active agent, particularly if spi a M--1 peak observed by mass spectrometry using atmo nosad is used. Common spreading agents used in these pour spheric pressure chemical ionization (AP). The alternate on formulations are: IPM, IPP caprylic/capric acid esters of molecular ion peaks (e.g., M+2 or M+4) that occur with saturated C-C fatty alcohols, oleic acid, oleyl ester, ethyl compounds containing multiple halogens are not reported. oleate, triglycerides, silicone oils and DPM. The pour-on The variable “RA in Index Table A represents one or a formulations of this invention are prepared according to combination of substituents as listed in Index Table A. known techniques. Where the pour-on is a solution, the para siticide/insecticide is mixed with the carrier or vehicle, using 0578. The following additional abbreviations are used in heat and stirring where required. Auxiliary or additional the Index Tables which follow: Cmpd means Compound. CN ingredients can be added to the mixture of active agent and is cyano. A '-' entry in Table A indicates no substitution. carrier, or they can be mixed with the active agent prior to the (0579. Fragments X-1 through X-27 shown below are addition of the carrier. If the pour-on is an emulsion or Sus referred to in the Index Tables. The wavy line denotes the pension, these formulations are similarly prepared using attachment point of the fragment to the remainder of the known techniques. molecule. 0573. Other delivery systems for relatively hydrophobic pharmaceutical compounds may be employed. Liposomes and emulsions are well-known examples of delivery vehicles X-1 or carriers for hydrophobic drugs. In addition, organic Sol vents such as dimethylsulfoxide may be used, if needed. 0574 For agronomic applications, the rate of application required for effective control (i.e. “biologically effective S amount') will depend on Such factors as the species of inver X-Cl tebrate to be controlled, the pest’s life cycle, life stage, its N size, location, time of year, host crop or animal, feeding X-2 behavior, mating behavior, ambient moisture, temperature, and the like. Under normal circumstances, application rates of about 0.01 to 2 kg of active ingredients per hectare are Sufficient to control pests in agronomic ecosystems, but as S little as 0.0001 kg/hectare may be sufficient or as much as 8 kg/hectare may be required. For nonagronomic applications, X-B, effective use rates will range from about 1.0 to 50 mg/square N meter but as little as 0.1 mg/square meter may be sufficient or X-3 as much as 150 mg/square meter may be required. One skilled in the art can easily determine the biologically effective amount necessary for the desired level of invertebrate pest control. S 0575. In general for veterinary use, a composition of this X-CH invention is administered in a parasiticidally effective amount N to an animal to be protected from invertebrate parasite pests. X-4 A parasiticidally effective amount is the amount of active ingredient needed to achieve an observable effect diminish ing the occurrence or activity of the target invertebrate para site pest. One skilled in the art will appreciate that the para S sitically effective dose can vary for the various compounds X and compositions of the present invention, the desired para N sitical effect and duration, the target invertebrate pest species, X-5 the animal to be protected, the mode of application and the like, and the amount needed to achieve a particular result can be determined through simple experimentation. 0576 For oral administration to homeothermic animals, the daily dosage of a composition of the present invention NN typically ranges from about 0.01 mg/kg to about 100 mg/kg, more typically from about 0.5 mg/kg to about 100 mg/kg, of 21 C animal body weight. For topical (e.g., dermal) administration, US 2014/O 187776 A1 Jul. 3, 2014 83

-continued -continued

X-14

to2 F

X-15

als2 toN CH

C

X-16

22 toN N1SCulN1NN X-17 2 CH 3 to X-10

X-18 21 Br to X-11

S C C C C X-19 X-12 C

S C X C HC X-21 X-13

C H3 to C NX

US 2014/O 187776 A1 Jul. 3, 2014 99

INDEX TABLE D-continued Cmpd No. "H NMR Data 470 & 9.55 (d. 1H), 8.48 (s, 1H), 8.10 (m, 3H), 7.67 (d. 1H), 7.48 (s, 1H), 7.42 (m, 2H), 7.36 (d. 1H), 5.59 (brs, 2H). 474 & 9.58 (dd. 1H), 8.12 (m, 1H), 7.82 (d. 1H), 7.78 (s, 1H), 7.49 (d. 1H), 7.42 (m, 2H), 7.26 (m, 2H), 7.12 (d. 1H), 5.67 (brs, 2H). 476 89.53 (d. 1H), 8.49 (s, 1H), 8.12 (dd, 1H), 7.90 (d. 1H), 7.69 (dd, 1H), 7.65 (m, 1H), 7.2- 7.45 (m, 4H), 5.59 (brs, 2H). 480 89.55 (m, 1H), 8.15 (m, 1H), 7.75 (m, 2H), 7.67 (s, 1H), 7.6 (dd, 1H), 7.42 (m, 1H), 7.1 (m, 2H), 5.58 (brs, 2H). 481 89.5 (m, 1H), 8.15 (m, 1H), 7.65 (s, 1H), 7.6 (dd, 1H), 7.5 (m, 1H), 7.4 (m, 1H), 6.9 (m, 2H), 5.55 (brs, 2H). 487 89.53 (d. 1H), 8.48 (s, 1H), 8.14 (t, 1H), 7.75 (t, 1H), 7.68 (dd, 1H), 7.51 (d. 1H), 7.4 (m, 3H), 7.34 (d. 1H), 5.58 (brs, 2H). 512 ö (acetone-d) 9.43 (d. 1H), 8.41 (t, 1H), 8.18 (d. 1H), 7.96 (s, 1H), 7.75 (d. 1H), 7.59 (t, 1H), 7.50-7.56 (m, 1H), 7.05 (dd, 1H), 5.77 (s. 2H), 3.88 (s, 3H). 521 8 (acetone-d) 9.41 (d. 1H), 8.45 (t, 1H), 8.20 (d. 1H), 7.95-8.05 (m, 2H), 7.88 (d. 1H), 7.59 7.65 (m, 2H), 5.75 (brs, 2H). 524 89.51 (d. 1H), 8.21 (t, 1H), 7.67 (s, 1H), 7.62 (d. 1H), 7.42 (t, 1H), 6.75 (t, 2H), 5.59 (s. 2H). 641 8 (acetone-d) 9.45 (d. 1H), 9.21 (s, 1H), 8.60 (s, 1H), 8.5.0-8.40 (m, 2H), 8.22 (d. 1H), 7.97 (s, 1H), 7.62 (t, 1H), 5.79 (s. 2H). 736 8 (acetone-de) 9.43 (dd. 1), 8.92 (s, 1), 8.47 (m, 1), 8.21 (d. 1), 8. O (dd. 1), 7.95 (m. 2), 7.62 (t, 1), 5.76 (s. 2). 752 ö (acetone-d) 9.46 (dd. 1), 8.71 (d. 1), 8.40-8.44 (m, 1), 8.17-8.2 (m. 2), 7.97 (s, 1), 7.60 (t, 1), 6.74 (d. 1), 5.77 (s, 2), 3.90 (s.3). 800 & 8.30 (d. 1H), 7.46 (m, 1H), 7.16 (d. 1H), 6.8-6.9 (m, 2H), 4.8 (brs, 2H). 801 & 8.32 (d. 1H), 7.72 (d. 2H), 7.38 (dd, 2H), 7.23 (dd. 1H), 7.13 (d. 1H), 4.81 (q, 2H). 802 & 8.32 (d. 1H), 7.73 (d. 1H), 7.69 (s, 1H), 7.37 (t, 1H), 7.15 (d. 1H ), 7.08 (d. 1H), 4.81 (q, 2H). 803 88.52 (d. 1H), 8.28 (d. 1H), 7.91 (dd, 1H), 7.72 (d. 2H), 7.35-7.4 (m, 3H), 7.25 (m, 1 H, partially obscured by solvent peak), 7.03 (d. 1H), 5.31 (s, 2H). 804 8 (acetone-d) 8.61 (d. 1H), 8.20 (d. 1H), 7.98 (d. 1H), 7.89 (m, 2H), 7.55 (dd, 1H), 7.47 (m, 1H), 7.03 (dd, 2H), 5.46 (s. 2H). 805 88.29 (d. 1H), 7.67-7.72 (m, 3H), 7.25 (m, 1H, partially obscured by solvent peak), 7.09 (d. 1H), 5.34 (s. 2H). 806 88.28 (d. 1H), 7.67-7.73 (m, 3H), 7.04-7.11 (m, 3H), 5.33 (s. 2H). 807 88.25 (s, 1H), 7.65-7.75 (m, 3H), 7.38 (dd. 1H), 7.08 (d. 1H), 5.32 (d. 1H). 810 8 8.27 (d. 1H), 7.67 (s, 1H), 7.31 (m, 3H), 7.07 (d. 1H), 6.80 (m, 1H), 5.33 (s, 2H), 3.82 (s, 3H). 815 8 8.27 (d. 1H), 7.82 (m, 1H), 7.69 (s, 1H), 7.56 (m, 1H), 7.23 (m, 1H), 7.14 (d. 1H), 5.35 (s, 2H). 822 8 (acetone-d) 8.17 (d. 1H), 7.88 (s, 1 H), 7.59 (d. 1H), 7.21-7.29 (m, 2H), 6.99 (d. 1H), 6.88 (t, 1H), 5.45 (d. 2H), 3.76 (s.3 H). 825 8 (acetone-d) 8.45 (d. 1H), 8.19 (m, 1H), 8.10 (m, 1H), 8.00 (m, 2H), 7.53 (m, 1H), 7.38 (m, 1H), 7.10-7.00 (m, 2H), 5.45 (s. 2H). 828 8 (acetone-d) 8.45 (s, 1H), 8.10 (m, 2H), 7.50 (m, 1H), 7.30 (m, 1H), 7.20 (m, 1H), 7.15 (m, 1H), 6.95 (m, 1H), 6.90 (m, 1H), 5.50-5.30 (dd, 2H), 3.76 (s, 3H). 937 89.52 (dd. 1H), 8.10 (tod, 1H), 8.03 s, 1H), 7.75 (d. 1H), 7.65 (s, 1H), 7.55 (d. 2H), 7.38 (q, 2H), 5.55 (brs, 2H), 3.98 (s.3H), 2.24 (s, 3H). H NMR data are in ppm downfield from tetramethylsilane. CDCl3 solution unless indicated otherwise. Couplings are designated by (s)—singlet, (d)—doublet, (t)—triplet, (m)—multiplet, (dd)—doublet of doublets, (ddd)—doublet of doublet of doublets, (dt)—doublet of triplets, (td)—triplet of doublets, (br)—broad.

0580 Synergism manifested by mixtures of two active 0582. Using the method of Colby, the presence of a syn ingredients may allow a Substantial reduction in the applica ergistic interaction between two active ingredients is estab tion rates of one or both of these active ingredients, while lished by first calculating the predicted activity, p, of the mixture based on activities of the two components applied maintaining good biological efficacy. The greater than alone. In the equation above, A is the biological activity in expected effect may persist for days after application, facili percentage control of one component applied alone at rate X. tating rapid knockdown and mortality. Decreasing applica The B term is the biological activity in percentage control of tion rates reduces treatment cost to the farmer and also eases the second component applied at ratey. The equation calcu the burden on the environment both from manufacturing lates p, the predicted biological activity of the mixture of A at waste and crop protection chemical residues. rate X with Bat rate y if their effects are strictly additive and 0581. The presence of a synergistic effect between two no interaction has occurred. If the experimentally established active ingredients can be established with the aid of the Colby effect of the mixture is greater than the predicted activity, p. equation (see Colby, S. R., "Calculating Synergistic and synergism is present. To use the Colby equation the active ingredients of the mixture are applied in a test separately as Antagonistic Responses of Herbicide Combinations'. Weeds well as in combination. 1967, 15, 20-22): 0583. The following Tests demonstrate the control effi cacy of compositions of this invention on specific pests. “Control efficacy” represents inhibition of invertebrate pest AXB development (including mortality) that causes significantly p = A + B 100 reduced feeding. The pest control protection afforded by the compounds is not limited, however, to these species. See Index Tables A-C for compound descriptions.