NZ613659B2 - Pesticidal compositions and processes related thereto - Google Patents

Pesticidal compositions and processes related thereto Download PDF

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Publication number
NZ613659B2
NZ613659B2 NZ613659A NZ61365912A NZ613659B2 NZ 613659 B2 NZ613659 B2 NZ 613659B2 NZ 613659 A NZ613659 A NZ 613659A NZ 61365912 A NZ61365912 A NZ 61365912A NZ 613659 B2 NZ613659 B2 NZ 613659B2
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New Zealand
Prior art keywords
alkyl
haloalkyl
alkenyl
cycloalkyl
phenyl
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NZ613659A
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NZ613659A (en
Inventor
Lawrence C Creemer
Gary D Crouse
William Hunter Dent
Casandra Lee Mcleod
Thomas C Sparks
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Dow Agrosciences Llc
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Priority claimed from PCT/US2012/023932 external-priority patent/WO2012109125A1/en
Publication of NZ613659A publication Critical patent/NZ613659A/en
Publication of NZ613659B2 publication Critical patent/NZ613659B2/en

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    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/64—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with three nitrogen atoms as the only ring hetero atoms
    • A01N43/647—Triazoles; Hydrogenated triazoles
    • A01N43/653—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/78—1,3-Thiazoles; Hydrogenated 1,3-thiazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/28—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N<
    • A01N47/34—Ureas or thioureas containing the groups >N—CO—N< or >N—CS—N< containing the groups, e.g. biuret; Thio analogues thereof; Urea-aldehyde condensation products
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
    • A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/14—Ectoparasiticides, e.g. scabicides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • C07F7/0812—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te comprising a heterocyclic ring

Abstract

The disclosure relates to molecules having the following formulae ("Formula 1", "Formula 2" and "Formula 3"), wherein the variables Ar1, Het, Ar2, R1, R2, R3, R4, and R5 are as described in the specification. Compositions comprising a pesticidally acceptable acid addition salt, a salt derivative, a solvate, or an ester derivative of these compounds are used in a process comprising applying the composition to an area to control a pest, in an amount sufficient to control such pest, wherein said area is an area where apples, com, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted. solvate, or an ester derivative of these compounds are used in a process comprising applying the composition to an area to control a pest, in an amount sufficient to control such pest, wherein said area is an area where apples, com, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, strawberries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted.

Description

_1.docx AUG 2014 PESTICIDAL COlVH’OSITIONS AND PROCESSES RELATED THERETO CROSS REFERENCE TO RELATED ATIONS This Application claims priority from US. provisional application 61/440,003 filed on February 7, 2011. The entire content ofthis ional application is hereby incorporated by reference into this Application.
FIELD OF THE ION The invention disclosed in this nt is related to the field of processes to produce molecules that are useful as pesticides (e.g., acaricides, insecticides, molluscicides, and nematicides), such molecules, and processes of using such molecules to control pests.
BACKGROUND OF THE INVENTION Pests cause millions of human deaths around the world each year. Furthermore, there are more than ten thousand species of pests that cause losses in agriculture. The world-wide agricultural losses amount to ns ofUS dollars each year.
Termites cause damage to all kinds of private and public structures. The world—wide termite damage losses amount to ns of US. dollars each year.
Stored food pests eat and adulterate stored food. The world—wide stored food losses amount to billions ofUS. dollars each year, but more importantly, deprive people of needed food.
There is an acute need for new pesticides. Certain pests are developing resistance to pesticides in current use. Hundreds of pest species are resistant to one or more pesticides. The development of resistance to some of the older pesticides, such as DDT, the ates, and the organophosphates, is well known, but resistance has even developed to some ofthe newer pesticides. ore, for many reasons, including the above reasons, a need exists for new pesticides.
Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment, or any form of suggestion, that this prior art forms part of the common general 1000744116_1.docx 1|: All.“ knowledge in New Zealand or any other jurisdiction or that this prior art could ably be expected to be ained, understood and regarded as relevant by a person skilled in the art.
SUMMARY OF THE INVENTION In one aspect of the invention there is a composition comprising a le ing to Formulas One, Two, or Three R1 $2 Arl/ \ArZAN{bum/8113 Formula 1 R1 R5 pt Flil /““\ A 32 S Het '\ ,N2 \‘s AI'I Arz N1 TJ3/\Fa5 Ar/ \ArZ/KNI \H/ R2: R4 a 2 Formula 3 wherein: (a) Ar] is (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted l, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted l, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3—C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1- C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1—C5 alkyl), S(=O)n(C1-C6 kyl), OSOZ(C1-C6 alkyl), OSOg(C1-C6 haloalkyl), C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1—C5 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 lkyl) C(=O)O(C -C5 cyulOalkyl), C(=O)(C.2-C5 alkenyl), (C2-C5 alkenyl), (C1—C5 alkyl)O(C1—C6 alkyl), (C1-C6 alkyl)S(C1-C6 , C(=O)(C1-C6 alkyl)C(=O)O(C1—C6 alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3~C6 halocycloalkoxy, C1—C6 1000744116_1.docx 1 5 AUG 2014 , C1—C6 koxy, C2-C5 alkenyl, C2—C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOz(C1-C6 alkyl), OSOg(C1-C6 haloalkyl), C(=O)NRXRy, (C1-C6 alky1)NRxR , C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C(, cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl) phenyl, and phenoxy; (b) Het is a 5 membered, heterocyclic ring, selected from the group containing KN/>———Ar2 ’//N Ar2 N NJ1 Ar1/ \ N Ar1/ / Arz T/ / Ar2 N\ N / N AH Ar1/ wherein said heterocyclic ring may also be substituted with one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, 0X0, C1-C6 alkyl, C1—C6 haloalkyl, C3—C6 cycloalkyl, C3-C6 halocycloalkyl, C3—C6 cycloalkoxy, C3—C6 cloalkoxy, C1—C6 alkoxy, C1— C6 haloalkoxy, C2—C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOz(C1-C6 alkyl), 1-C6 kyl), C(=O)NRXRy, (C1—C6 alkyl)NRny, C(ZO)(C1—C6 alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C1—C6 haloalkyl), C(=O)O(C1—C6 haloalkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 , (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1—C6 kyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C5 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), (C1-C(, haloalkyl), 1-C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1- C6 kyl), C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C5 alkenyl), C(=O)O(C2—C6 l), (C1-C6 alkyl)O(C1-C6 alkyl), (C1—C6 alkyl)S(C1-C6 alkyl), C(=O)(C1—C6 alkyl)C(:O)O(C1-C6 alkyl), phenyl, and phenoxy; 4116_1.docx (c) Arz is (1) furanyl, phenyl, pyridazinyl, l, pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted dinyl, or substituted thienyl, wherein said substituted l, substituted phenyl, substituted zinyl, substituted pyridyl, tuted pyrimidinyl, and substituted thienyl, have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C5 cycloalky1,C3-C6 halocycloalkyl, C3-C6 lkoxy, C3-C6 halocycloalkoxy, C1—C6 alkoxy, C1- C5 haloalkoxy, C2-C6 117,1 2C6 alkynyl, S(=O)-n(C1C6 alkyl), S(=O)n(C1=CV6 haloalkyl), 0S02(C1—C6 alkyl), OSOZ(C1-C6 haloalkyl), C(=O)NRXRy, (C1—C6 alkyl)NRXRy, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1—C6 haloalkyl), C(=O)O(C1—C6 haloalkyl) C(=O)(C3-C6 cycloalkyl), C(— ,V1C3-C6 c3cioa 11), C(=O)(C2-C6 alkenyl), c<—o1o<c2c6 a1keny1),(C1C5 alky1)O(C1-C6 alkyl) (C1-C5 alkyl)S( J1—C5 alkyl), C(=O)(C1—C6 alkyl)C(=O)O(C1—C6 alkyl), , phenoxy, tuted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently ed from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 , C1—C6 haloalkoxy, C2—C6 alkenyl, C2-C6 alkynyl, S(:O)H(C1—C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOZ(C1—C6 alkyl), OSOZ(C1—C6 haloalkyl), C(:O)H, C(=O)NRXRy, (C1-C6 NRny, C(:O)(C1—C6 alkyl), C(=O)O(C1-C6 alkyl), C(:O)(C1-C6 haloalkyl), C(=O)O(C1— C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(ZO)O(C3—C6 cycloalkyl), C(=O)(C1-C6 haloalkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1—C6 alky1)O(C1—C6 allq/l), (C1-C6 alky1)S(C1- C6 , C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, and phenoxy; (d) R1 is selected from H, CN, F, Cl, Br, I, C1—C6 alkyl, C3-C6 cycloalkyl, C3-C6 cycloalkoxy, C1—C6 alkoxy, C2-C6 alkenyl, C2—C6 l, S(=O)n(C1-C6 alkyl), OSOg(C1-C6 alkyl), C(=O)NRXRy, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3- C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 l), (C 1- C6 alky1)O(C1-C6 alkyl), (C1-Cc6 a1ky1)S(C1-C6 alkyl), C(=O)(CL1-C6 d1Kyl)L[-O)O(C1-C6 "1k"1), phenyl, or phenoxy, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, and y, are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3—C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1-C6 alkoxy, C1—C6 haloalkoxy, C2-C6 alkenyl, C2- 1000744116_1.docx l THUG 2770M C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOZ(C1—C6 alkyl), OSOz(C1—C6 haloalkyl), C(=O)NRny, (Cl-C(IJ alkyl)NRny, C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), (C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3~C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C(, , (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, and phenoxy; (e) R2 is H, C1-C6 alkyl, C3-C6 cycloalkyl, C2—Cg> alkenyl, C2-C6 l, C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C(, alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C1-C5 alkyl)C(=O)O(C1-C6 alkyl), phenyl, C1-C5 henyl, C1-C6 alkyl-O-phenyl, et-l, Het-l, C1-C6 alkylHet-l, or C1-C6 alkyl-O-Het-l, n each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-l are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, NRny, C1-C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C3—C6 cycloalkoxy, C3-C6 cloalkoxy, C1-C6 alkoxy, C1—C6 haloalkoxy, C2—C6 alkenyl, C3—C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOZ(C1—C6 alkyl), 0802(C1-C5 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1—C(, , C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1—C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C(, cycloalkyl), C(ZO)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 alkyl)O(C1-C6 alkyl), (C1—C6 alkyl)S(C1-C6 alkyl), C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, and Het-l; (f) R3 is C1-C6 alkyl, C3-C6 cycloalkyl, C2—C6 alkenyl, C2—C6 alkynyl, C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alky1)S(C1-C6 alkyl), C1-C6 alkyl)C(=O)O(C1—C6 alkyl), phenyl, C1-C5 alkylphenyl, C1-C6 alkyl—O—phenyl, C(=O)Het-l, Het-l, C1-C6 et-l, C1-C6 alkyl-O-C(=O)C1—C6 alkyl—O—Cl-C6 alkyl, C1—C6 alkyl-O-C(=O)C1-C6 alkyl-O-Cl-C6 alkyl-O— C1-C6 alkyl, C1-C6 O-C(=O)C1- C6 alkyl—O-Cl-C6 haloalkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O-phenyl, C1—C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O-C1-C6 alkylphenyl, C1-C6 alkle(=O)N(Rx)C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1-C6 et-lC(=O)—O-C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1- C6 alkylHet-l, C1-C6 alkle(=O)Het—l, C1—C5 alkle(=O)N(Rx)C1-C6 a1ky1(N(Rx)(Ry))(C(=0)0H), CI'C6 alky1C(=0)N(Rx)C1-C6 alky1N(Rx)(Ry), CI'C6 alkle(=O)N(Rx)C1-C6 alkle(Rx)C(=O)-O—C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1-C6 alky1(N(RX)C(=O)—O—C1—C6 alkyl)(C(=O)OH), C1—C6 alkle(=O)Het~lC(=O)—O—C1—C6 alkyl, C1— 1000744116~11dOCX l SAUG 20111 C6 alkyl—O-C(=O)-O—C1—C6 alkyl, C1—C6 a1kyl—O—C(=O)C1—C6 alkyl, C1-C6 alkyl—O-C(=O)C3—C6 cycloalkyl, C1-C6 alkyl-O-C(=O)Het-1, C1-C6 alkyl-O-C(=O)C1-C6 a1ky1-N(RX)C(=O)—O-C1-C6 alkyl, C1-C6 alkyl-NRny, or C1-C6 alkyl-O-Het—l, wherein each alkyl, cycloalkyl, l, alkynyl, phenyl, and Het-l are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, NRny, C1-C5 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1—C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , (C1-C6 haloalkyl), OSOZ(C1-C6 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRXRy, (C1-C6 a1Hky1)NRny, C(=O)(C1-C6 alkyl), (C1-C6 alkyl), C(=O)(C1—C6 haloalkyl), C(=O)O(C1-C6 kyl), C(=O)(C3-C6 cycloalkyl) C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 n11 1\f\/f“ n ”111\ / auCyUukpl-p6auxy1}, \K/1-»C6 alky1)S(C1-C'K/6 alkyl), C(=v )(Cl-Cé alk‘yi)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, Si(C-C6 alk-1y)3,S=(—O)nNRXRy,and Het— 1; (g) R418 H, C1—C6 alkyl, C3—C6 cycloalkyl, C2—C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(C1—C(, alkyl), C(=O)O(C1—C6 alkyl), C(:0)(C3-C6 cycloalkyl), C(=O)O(C3—C6 lkyl), C(=O)(C2—C6 alkenyl), C(ZO)O(C2—C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1—C6 alkyl)S(C1-C6 alkyl), C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, C1—C6 alkylphenyl, C1—C6 alkyl—O-phenyl, C(=O)Het—1, Het-l, C1—C6 alkylHet—l, or C1-C6 alkyl-O—Het—l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het—l are optionally 2O tuted with one or more tuents independently selected from F, Cl, Br, I, CN, N02, NRny, C1—C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3—C6 halocycloalkyl, C3—C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1—C6 , C1—C6 haloalkoxy, C2—C6 alkenyl, C3-C6 cycloalkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOZ(C1-C6 , 1—C6 kyl), C(=O)H, C(=O)NRny, (C1—C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C1-C6 alkyl)C(=O)O(C1-C6 alkyl), , phenoxy, and Het-l; (h) R5 is a 2 to 4 membered saturated or unsaturated hydrocarbyl linkage where said linkage may also be substituted with F, Cl, Br, 1, CN, N02, oxo, NRXRy, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C5 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1—C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1- C6 alkyl), S(:O)n(C1-C6 haloalkyl), OSOZ(C1—C6 alkyl), 1-C6 haloalkyl), C(=O)H, 1000744116_1,docx 1 SAUG 7mm C(=O)OH, RXRy, (C1—C6 alkyl)NRny, C(=O)(C1—C5 alkyl), C(20)O(C1—C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), (C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), (C2—C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, y, and Het-l, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, l, alkynyl, phenyl, y, and Het-l, are optionally substituted with one or more tuents independently selected from F, Cl, Br, 1, CN, N02, oxo, NRny, C1-C6 alkyl, C1-C5 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2- C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , (C1-C6 haloalkyl), OSOz(C1-C6 , OSO2(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 kyl), C(=O)O(C1- C6 kyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1-C6 alky1)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, halophenyl, phenoxy, and Het-l; (i) 11: 0, l, or 2; (j) RK and Ry are independently selected from H, C1—C6 alkyl, C1—C6 haloalkyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C2—C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1—C6 , S(:O)n(C1— C6 haloalkyl), OSOZ(C1-C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)(C1—C6 alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C1—C6 haloalkyl), (C1-C6 kyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C(> alkyl)S(C1—C6 alkyl), C(=O)(C1—C6 alkyl)C(=O)O(C1—C6 alkyl), and phenyl, wherein each alkyl, cycloalkyl, cycloalkoxy, , alkenyl, alkynyl, phenyl, phenoxy, and Het-l, are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2— C6 l, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOZ(C1-C5 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 , C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, halophenyl, phenoxy, and Het—l, or RK and Ry together can optionally form a 5— to 7—membered saturated or 1000744116_1.d0cx l ‘3 AUG 2011+ unsaturated cyclic group which may contain one or more atoms selected from nitrogen, sulfur, and oxygen, and where said cyclic group can n >C=O or >C=S, and where said cyclic group may be substituted with F, Cl, Br, 1, CN, C1-C6 alkyl, C1-C6 kyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1— C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 , OSOz(C1-C6 haloalkyl), C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1—C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2—C(> alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl\S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1=C5 alkyl), phenyl, substituted phenyl, phenoxy, and Het—l; and (k) Het-l is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, DEFINITIONS The examples given in the definitions are lly non—exhaustive and must not be construed as limiting the invention disclosed in this document. It is understood that a tuent should comply with chemical bonding rules and steric ibility constraints in relation to the particular molecule to which it is attached.
“Acaricide Group” is defined under the g “ACARICIDES”.
“AI Group” is defined after the place in this document where the “Herbicide Group” is defined.
“Alkenyl” means an acyclic, unsaturated (at least one -carbon double bond), branched or unbranched, substituent consisting of carbon and hydrogen, for example, vinyl, allyl, butenyl, pentenyl, and hexenyl.
“Alkenyloxy” means an alkenyl further consisting of a carbon-oxygen single bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy.
“Alkoxy” means an alkyl further consisting of a carbon-oxygen single bond, for example, methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, and tert-butoxy. ” means an acyclic, saturated, branched or unbranched, substituent consisting of carbon and hydrogen, for example, methyl, ethyl, propyl, isopropyl, butyl, and tert-butyl. yl” means an acyclic, unsaturated (at least one carbon—carbon triple bond), branched or unbranched, substituent consisting of carbon and hydrogen, for e, ethynyl, propargyl, butynyl, and yl.
“Alkynyloxy” means an alkynyl r consisting of a carbon—oxygen single bond, for example, pentynyloxy, hexynyloxy, heptynyloxy, and octynyloxy.
“Aryl” means a cyclic, aromatic substituent consisting of hydrogen and carbon, for example, phenyl, naphthyl, and biphenyl.
“Cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at least one carbon— carbon double bond) substituent consisting of carbon and hydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl, norbomenyl, bicyclo[2.2.2]octenyl, ydronaphthyl, hexahydronaphthyl, and octahydronaphthyl.
“Cycloalkenyloxy” means a lkenyl r consisting of a carbon-oxygen single bond, for example, cyclobutenyloxy, cyclopentenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.
“Cycloalkyl” means a monocyclic or polycyclic, saturated substituent consisting of carbon and hydrogen, for e, cyclopropyl, cyclobutyl, cyclopentyl, norbornyl, bicyclo[2.2.2]octyl, and decahydronaphthyl.
“Cycloalkoxy” means a cycloalkyl further consisting of a carbon—oxygen single bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy, norbornyloxy, and bicyclo[2.2.2]octyloxy, “Fungicide Group” is defined under the g “FUNGICIDES.” “Halo” means fluoro, chloro, bromo, and iodo.
PCT/U82012/023932 “Haloalkoxy” means an alkoxy further consisting of, from one to the m le number of cal or different, halos, for example, fluoromethoxy, trifluoromethoxy, 2,2—difluoropropoxy, chloromethoxy, trichloromethoxy, 1,1,22- tetrafluoroethoxy, and pentafluoroethoxy.
“Haloalkyl” means an alkyl further consisting of, from one to the maximum possible number of, identical or different, halos, for example, fluoromethyl, romethyl, 2,2— difluoropropyl, chloromethyl, tn'chloromethyl, and l,1,2,2-tetrafluoroethyl.
“Herbicide Group” is defined under the g “HERBICIDES.” “Heterocyclyl” means a cyclic substituent that may be fully saturated, partially unsaturated, or fully unsaturated, where the cyclic structure contains at least one carbon and at least one heteroatorn, where said heteroatom is nitrogen, sulfur, or oxygen, Examples of aromatic heterocyclyls include, but are not limiaed to, benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, l, olyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, zolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, olyl, thiazolinyl, thiazolyl, thienyl, tn'azinyl, and lyl. Examples of fully saturated heterocyclyls include, but are not limited to, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and ydropyranyl. Examples of partially unsaturated heterocyclyls include, but are not limited to, 1,2,3,4—tetrahydro—quinolinyl, 4,5—dihydro—oxazolyl, 4,5—dihydro-lH-pyrazolyl, 4,5—dihydro-isoxazolyl, and 2,3-dihydro~[l,3,4]—oxadiazolyl.
“Insecticide Group” is defined under the g “INSECTICIDES.” “Nematicide Group” is defined under the heading “NEMATICIDES” “Synergist Group” is defined under the heading “SYNERGISTIC MIXTURES AND ISTS” DETAILED DESCRIPTION OF THE INVENTION This document discloses molecules having the following as (“Formula One” &“Formula Two” and “Formula Three”): (In the following formulas the nitrogens are U)0 numbered 1, 2, and 3, solely for the purpose of identifying them and being able to refer to them throughout this document for clarity purposes) PCT/U82012/023932 R1 1'12 Het\Arz)\N1 \ ,N2 S\ Ar,’ T R3 Formula 1 j: R1 Het N2 3 /R5\ \Ni’ Y \ Het A Arf \Ar N2 5 2 \Arz N] T N3 R5 Arf / N3~ R4 R4 Formula 2 Formula 3 wherein: (a) Arl is (1) l, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) tuted furanyl, substituted phenyl, substituted pyridazinyl, tuted pyridyl, tuted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted l, substituted idinyl, and substituted thienyl, have one or more substituents independently selected from H, F, Cl, Br, I, CN, N02, C1-C5 alkyl, C1-C5 haloalkyl, C3—C5 cycloalkyl, C3-C5 haloeyeloalkyl, C3—C5 eycloalkoxy, C3—C5 halocycloalkoxy, C1-C5 alkoxy, C1-C5 haloalkoxy, C2—C5 alkenyl, C2-C5 alkynyl, S(=O)n(C1— C5 alkyl), S(=O)n(C]-C5 haloalkyl), OSO;(C1—C5 alkyl), OSOZ(C1-C5 haloalkyl), C(=O)NRny, (C1—C5 NRny, C(=O)(C1-C5 alkyl), C(=O)O(C1-C5 alkyl), C(=O)(C1-C5 kyl), C(=O)O(C1-C5 haloalkyl), C(=O)(C3—C5 cycloalkyl), C(=O)O(C3-C5 cycloalkyl), C(=O)(C2-C5 alkenyl), C(=O)O(C2-C5 alkenyl), (C1-C5 alky1)O(C1-C5 alkyl), (C1-C5 a]kyl)S(C1-C5 alkyl), C(=O)(C1-C5 alky])C(=O)O(C1-C5 alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C5 halocycloalkyl, C3-C5 cycloalkoxy, C3-C5 halocycloalkoxy, C1-C5 alkoxy, C1-C5 haloalkoxy, C2-C5 alkenyl, C2-C5 alkynyl, S(=O)n(C1— C5 alkyl), S(=O)5(C1-C5 haloalkyl), 1-C5 alkyl), OSOz(C1-C5 kyl), C(=O)NRny, (C1-C5 NRny, C(=O)(C1-C5 alkyl), C(=O)O(C1'C6 alkyl), C1—C5 haloalkyl), C(=O)O(C1-C5 haloalkyl), C(=O)(C3-C5 cycloalkyl), C(=O)O(C3-C5 cycloalkyl), C(=O)(C2-C5 alkenyl), C(=O)O(C2-C5 alkenyl), (C1-C5 O(C1-C5 alkyl), (C1-C5 PCT/U52012/023932 a1ky1)S(C1-C6 , C(=O)(C1-C6 alkyl)C(=O)O(C1-C5 alkyl) phenyl, and phenoxy; (b) Het is a 5 or 6 membered, ted or unsaturated, cyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur, or , and where Ar] and AI2 are not ortho to each other (but may be meta or para, such as, for a five membered ring they are 1,3 and for a 6 membered ring they are either 1,3 or 1,4), and where said heterocyclic ring may also be tuted with one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, oxo, C1—C6 alkyl, C1-C6 haloalkyl, C3- C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C5 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2—C5 alkynyl, S(=O)n(C1-C5 alkyl), S(=O)n(C1—C6 haloalkyl), OSO2(C1-C6 alkyl), OSOz(C1-C6 haloa]ky1),C(=O)NRny, (C1-C6 alkyl)NRny, (“l-(“KP C, niIrUI\ Cf——O\O(CCénimk‘m m_mm_C6ha]Qalky1) (“{=fl\fl({‘4_(‘, V\—Vl\\/l V0 ”1““ *l! J‘/, V\—V/\Vl VVVVVVVVVVVV haloalkyl), C(=O)(C3~C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 a1kyl)O(C1—C6 alkyl), (C1—C6 alkyl)S(C1-C5 alkyl), C(=O)(C1— C6 alkyl)C(=O)O(C1~C6 alkyl), , phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted y have one or more substituents ndently ed from H, F, Cl, Br, 1, CN, N02, C1—C6 alkyl, C1-C6 kyl, C3-C5 cycloalkyl, C3—C6 halocycloalkyl, C3—C6 lkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1- C6 alkyl), S(=O)n(C1—C6 haloalkyl), OSOZ(C]—C6 alkyl), OSOZ(C1-C5 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C]-C6 haloalkyl), C(=O)O(C1-C5 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C5 alkenyl), (C1-C6 alky1)O(C1-C6 , (C1—C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C5 alkyl), phenyl, and phenoxy; (c) Arz is (1) furanyl, , pyridazinyl,pyridy1,pyrimidinyl, thienyl, or (2) suesti_mted furanyl, substituted phenyl, substitutedpyvriadazinyl. substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted l, substituted pyrimidinyl, and substituted thienyl, have one or more tuents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C5 alkyl, C1-C5 haloalkyl, C3-C5 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C5 alkoxy, C1-C5 haloalkoxy, C2-C5 alkenyl, C2-C6 alkynyl, S(=O)n(C1- W0 2012/109125 PCT/U82012/023932 C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)NRny, (C1—C6 alkyl)NRny, C(=O)(C1'C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C5 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted y have one or more tuents ndently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C5 cycloalkoxy, C3-C6 halocycloalkoxy, C1—C6 alkoxy, C1-C5 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1- C5 alkyl), S(=O)n(C1-C6 haloalkyl), OSOg(C1-C6 , OSOZ(C1-C6 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 NRny, C(=O)(C1—C5 alkyl), C(=O)O(C1-C6 alkyl), C1-C6 haloalkyl), C(=O)O(C1—C6 haloalkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C1-C6 haloalkyl), C2—C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 alkyl)O(C1- C6 alkyl), (C1-C6 alkyl)S(C1—C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 , phenyl, and phenoxy; (d) R1 is selected from H, CN, F, Cl, Br, I, C1-C6 alkyl, C3—C6 lkyl, C3-C6 cycloalkoxy, C1-C6 alkoxy, C2-C6 alkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 alkyl), OSOz(C1—C6 alkyl), C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1—C(, alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C6 lkyl), C(=O)(C2-C(, l), C(=O)O(C2-C6 alkenyl), (C1—C6 O(C1—C6 alkyl), (C1—C6 alkyl)S(C1—C6 alkyl), C(=O)(C1-C6 alky1)C(=O)O(C1-C6 alkyl), phenyl, or phenoxy, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, and phenoxy, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, N02, oxo, C1-C6 alkyl, C1—C6 kyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C5 l, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOg(C1-C6 alkyl), OSOg(C1-C6 haloalkyl), C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C5 lkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C5 l), (C1- C6 alky1)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C5 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, and phenoxy; W0 2012/109125 (6) R2 is H, C1-C5 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=0)(C1-C6 alkyl), (C1-C6 alkyl), C(=O)(C3—C5 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2-C5 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 a1kyl)S(C1-C6 alkyl), C(=O)(C1-C6 alky1)C(=O)O(C1-C6 a1ky1),phenyl, C1-C6 alkylphenyl, C1-C6 alkyl-O-phenyl, C(=O)Het-1, Het-l, C1-C6 alkylHet-l, or C1-C6 alkyl-O- Het-l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-l are ally substituted with one or more substituents ndently selected from F, Cl, Br, 1, CN, N02, NRXRy, C1-C6 alkyl, C1-C5 haloalkyl, C3-C6 cycloalkyl, C3-C6 cloalkyl, C3- C5 cycloalkoxy, C3—C6 halocycloalkoxy, C1—C6 alkoxy, C1-C5 haloalkoxy, C2-C6 alkenyl, C3- C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C(=O)NRny, (Cl-V6 alkyDNRny, C(EOXCl-Ca alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C3- C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), (C2-C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1—C6 alky1)S(C]—C6 alkyl), C(=O)(C1-C6 a1ky1)C(=O)O(C1—C6 alkyl), phenyl, phenoxy, and Het—l; (f) R3 is C1-C6 alkyl, C3—C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkyny], C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3-C5 cycloalkyl), C(=O)O(C3—C6 lkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1—C6 alky1)O(C]-C6 alkyl), (C1—C6 alky1)S(C1-C6 alkyl), C(=O)(C1—C(, alkyl)C(=O)O(C]-C6 alkyl), phenyl, C1-C6 alkylphenyl, C1-C6 a]ky1-O~pheny1, C(=O)Het—1, Het—l, C1-C6 alkylHet-I, C1-C6 alkyl-O— C(=O)C1—C6 alkyI—O—CJ—CG alkyl, C1—C6 alkyl-O—C(=O)C1—C6 alkyl—O-Cl-Cs alkyl-O- C1-C6 alkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl-O-Cl—Cs haloalkyl, C1-C6 alkyl-O-C(=O)C1-C5 alkyl- N(RX)C(=O)-O-pheny1, C1-C6 a1kyl-O-C(=O)C1—C6 N(RX)C(=O)-O-C1—C6 henyl, C1-C6 alkle(=O)N(Rx)C1—C6 alkyl, C1-C6 (=O)N(Rx)C1-C6 et-1C(=O)—O-C]-C6 alkyl, C1-C6 alky1C(=O)N(Rx)C1-C6 alkylHet-l, C1-C6 a]kle(=O)Het-1, C1-C6 alkle(=O)N(RX)C1-C5 alky1(N(Rx)(Ry))(C(=O)OH)9 C1-C6 aka1C(=O)N(Rx)C1-C5 a]kle(Rx)(Ry), C]'C6 alkle(=O)N(Rx)C1-C6 alkle(Rx)C(=O)-O-C1-C5 alkyl, C1-C5 a]ky1C(=O)N(RX_)C1-C6 N(Rx)C(=O)-O-C1-C6 alkyl)(C(=O)OH), C1-C6 (=O)Het— 1C(=O)—O-C1-C6 alkyl, C1-C6 alkyl-O-C(=O)-O-C1-C6 alkyl, C1-C6 alkyl-O-C(=O)C]-C6 alkyl, C1-C6 alkyI-O-C(=O)C3-C5 cycloalkyl, C1-C6 alkyl-O-C(=O)Het-1, C1—C6 alkyl-O- C(=O)C1-C6 alkyl-N(RX)C(=O)—O-C1-C6 alkyl, C1-C6 alkyl—NRny, or C1-C6 alkyl-O-Het-l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-l are PCT/U82012/023932 optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, N02, NRny, C1-C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3-C6 halocycloalkyl, C3— C5 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C3- C6 cycloalkenyl, C2—C6 l, (C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOZ(C1—C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRny, (C1-C6 a]ky1)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 , C(=O)(C1—C6 haloalkyl), C(=O)O(C1—C6 kyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 lkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2—C5 l), (C1-C6 a1ky1)O(C1-C6 alkyl), (C1-C6 a1kyl)S(C1-C6 alkyl), C(=O)(C1- C6 alkyl)C(=O)O(C1-C6 alkyl), , phenoxy, Si(C1-C6 alkyl)3, S(=O)nNRny, and Het-l; (g) R4 is H, C1-C6 alkyl, C3-C6 cycloalkyl, C2—C6 alkenyl, C2-C6 l, C(=O)H, C(=O)(C1'C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C5 a1kyl)O(C1-C6 alkyl), (C1-C6 alky1)S(C1-C6 alkyl), C(=O)(C1-C6 alky1)C(=0)O(C1—C6 , phenyl, C1—C6 alkylphenyl, C1—C6 alkyl—O—phenyl, C(=O)Het—l, Het—l, C1-C6 alkylHet—l, or C1—C6 alkyl-O- Het-l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-l are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, NRny, C1-C6 alkyl, C1-C6 kyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C3— C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1—C6 alkoxy, C1—C6 haloalkoxy, C2-C6 alkenyl, C3— C6 cycloalkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), 0802(C1-C5 alkyl), 0802(C1—C6 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 alky1)NRny, C(=O)(C1—C6 alkyl), C(=O)O(C1—C6 , C(=O)(C1-C5 haloalkyl), C(=O)O(C1—C6 haloalkyl), C(=O)(C3- C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (CI'C6 alkyl)O(C1-C6 , (C1-C6 alky1)S(C1-C6 alkyl), C(=O)(C1"C6 alky1)C(=0)O(C1-C6 alkyl), phenyl, phenoxy, and Het-l; (h) R5 is a 2 to 4 membered saturated or unsaturated hydrocarbyl e where said linkage may also be substituted with F, Cl, Br, 1, CN, N02, oxo, NRXRy, C1-C6 alkyl, C1- C5 haloalkyl, C3-C5 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 cloalkoxy, C1-C6 alkoxy, C1-C5 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , S(=O)n(C1-C6 haloalkyl), OSOZ(C1-C6 alkyl), 0802(C1-C5 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRXRy, (C1-C6 a1ky1)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C5 haloalkyl), C(=O)(C3-C5 PCT/U82012/023932 cycloalkyl), (C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1- C6 alkyl)O(C1—C5 , (C1-C6 S(C1-C5 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), , phenoxy, and Het-l, wherein each alkyl, cycloalkyl, cycloalkoxy, , alkenyl, all<ynyl,pheny1, phenoxy, and Het-l, are optionally substituted with one or more substituents independently selected from F, Cl, Br, I, CN, N02, oxo, NRny, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 cloalkoxy, C1-C6 alkoxy, C1—C5 haloalkoxy, C2-C6 alkenyl, C3-C5 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C5 haloalkyl), OSOZ(C1-C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRny, (Cl'C6 alky1)NRny, C(=O)(C1-C5 alkyl), C(=O)O(Ci-C6 , C(=0)(C1—Ce haloalkyl), C(=O)O(C1-C5 haloalkyl). C(=O)(C3-C5 cycloalkyl,), C(=O)O(C3—C5 cycloalkyl), C(=OXCTC6 311(6111y11,) C(=O)O(C2-C6 alkenyl,,m(p1C6 O(C1—C6 alkyl), (C]-"b6 alkyl)S(C1—C6 a1ky1),CO(=)(Cl-C6 a1ky1)C(=O)O(C1-C6 alkyl), phenyl, halophenyl, phenoxy, and Het—l; (i) 11: 0, 1, or 2; (j) RK and Ry are independently selected from H, C1—C6 alkyl, C1-C6 haloalky], C3—C6 lkyl, C3—C6 halocycloalkyl, C2-C6 alkenyl, C2—C6 alkynyl, (C1-C6 alkyl), S(=O)n(C1-C5 haloalkyl), 0802(C1—C6 alkyl), 0802(C1-C6 kyl), C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1—C(, haloalkyl), (C1-C5 haloalkyl), C(=O)(C3- C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C2—C6 l), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1—C6 alky1)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), and phenyl, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, phenoxy, and Het—l, are optionally substituted with one or more substituents independently ed from F, Cl, Br, I, CN, N02, oxo, C1-C6 a1kyl,C1-C5 haloalkyl, C3-C6 cycloalkyl, C3- C5 halocycloaalkyl, C3-C6cycloalkoxy, C3=C6ualocyc1oalkoxy, C1-C6 alkoxy, C1=C6 haloalkoxy, C2-C6 alkenyl, C3-C6cycloa1kenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , U) C) S(=O)n(C1-Chaloa1ky1),0502(C-C5 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C(=O)OH,1:) C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C5 cycloalkyl), C(=O)O(C3~C6 cycloalkyl), C(=O)(C2-C6 alkenyl), (C2-C5 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 all<y1)S(C1-C6 alkyl), C(=O)(C1- C5 alkyl)C(=O)O(C1-C5 alkyl), phenyl, halophenyl, phenoxy, and Het-l, PCT/U82012/023932 or RK and Ry together can optionally form a 5- to 7-membered saturated or unsaturated cyclic group which may contain one or more heteroatoms selected from en, sulfur, and oxygen, and where said cyclic group can contain >C=O or >C=S, and where said cyclic group may be substituted with F, Cl, Br, 1, CN, C1-C6 alkyl, C1-C6 kyl, C3-C6 cycloalkyl, C3-C6 cloalkyl, C3-C6 cycloalkoxy, C3~C5 halocycloalkoxy, C1-C6 alkoxy, C1—C5 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOZ(C1-C6 alkyl), OSOZ(C1-C6 haloalkyl), C(=O)(C1-C6 alkyl), C(=O)O(C1-C5 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C2—C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1— C5 a1ky1)O(C1-C6 alkyl), (C1-C6 a]kyl)S(C1-C5 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1—C6 alkyl), phenyl, tuted phenyl, phenoxy, and Het-1; and (k) Het—1 is a 5— or 6—membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen.
It is tood that in Formula 1, when R2 is H, the compounds may exist in more than one tautomeric or isomeric form, wherein the hydrogen is attached to either of the nitrogen atoms; further, both E and Z isomers may exist. Any and all isomeric forms of the compounds of this invention are d.
In another embodiment Arl is a substituted phenyl, wherein said substituted phenyl has one or more substituents independently ed from C1-C6 haloalkyl and C1—C6 haloalkoxy.
In another embodiment Arl is a substituted phenyl, wherein said substituted phenyl has one or more substituents independently ed from CF3, OCF3, and OCFzCF3.
In another ment Het is selected from triazolyl, imidazolyl, or pyrazolyl, which can be substituted or unsubstituted.
In another embodiment Het is a 1,2,4-triazolyl PCT/U82012/023932 KyArz/ /N\N AI'1 In r embodiment Het is 1,4-imidazolyl K >——Ar2 N\I/ Ar1/ In another ment Het is 1,3—pyrazoiyi In r embodiment IIet is a substituted 1,3-pyrazoly1.
In another embodiment Het is 1,4—pyrazolyl I Arz N / Ar1/ In another embodiment Arz is a phenyl.
In another embodiment R1 is H or C1-C6 alkyl.
In another embodiment R1 is H or CH3.
In another embodiment R2 is H.
In another embodiment R3 is selected from C1-C6 alkyl. C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 alkylphenyl, C1-C6 alkylHet-l, C1-C6 a]ky1-O-C(=O)C1-C6 alkyl-O-Cl-Cé alkyl, C1-C6 alkyl-O-C(=O)C1~C6 alkyl-O-C1-C6 alkyl-O- C1-C6 alkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl- O-C1-C6 haloalkyl, C1—C6 O-C(=O)C1—C6 alkyl-N(RX)C(=O)—O-phenyl, C1-C6 alkyl-O- C(=O)C1-C6 a1kyl-N(RX)C(=O)-O-C1-C6 alkylphenyl, C1-C6 alkle(=O)N(Rx)C1-C6 alkyl, C1—C6 alkle(=O)N(Rx)C1-C6 alkylHet-1C(=O)-O-C1—C6 alkyl, C1-C6 alkle(=O)N(Rx)C1-C6 alkylHet- l, C1-C6 alkle(=O)Het- l, C1-C6 alkle(=O)N(Rx)C1-C6 alkyl(N(Rx)(Ry))(C(=O)OH), C1-C5 alkle(=O)N(Rx)C1-C6 alkle(Rx)(Ry), C1-C6 alkle(=O)N(Rx)C1-C6 alkle(Rx)C(=O)-O-C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1—C6 alkyl(N(Rx)C(=O)-O—C1—C6 alkyl)(C(=O)OH), C1—C6 alkle(=O)Het—1C(=O)-O-C1—C5 alkyl, C1-C6 alkyl-O-C(=O)-O-C1-C6 alkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl, C1-C6 O- C(=O)C3-C5 lkyl, C1-C6 alkyl-O-C(=O)Het—l, or C1-C6 alkyl-O-C(=O)C1-C6 alkyl— N(RX)C(=O)-O-C1-C6 alkyl, n each alkyl, alkenyl, alkynyl, phenyl, and Het-l are optionally substituted with one or more substituents ndently selected from F, Cl, Br, C1-C6 alkyl, C1—C6 haloalkyl, C1—C6 haloalkoxy, S(=O)n(C1-C6 alkyl), H, C(=O)O(C1— C6 alkyl), phenyl, Si(C1-C6 alky1)3, and S(=O)nNRny.
In another embodiment R4 is phenyl, C1-C6 alkylphenyl, Het—1, or C1—C6 alkyl-O— phenyl, wherein each alkyl, Het-l, and phenyl are optionally substituted with one or more substituents independently selected from F, Cl, NRny, C1-C6 alkyl, C3-C6 cycloalkyl, Cl—(Tg haloalkoxy, C(=O)O C1-C6 alkyl, or C1-C6 alkoxy.
In another embodiment R5 is substituted with 0x0, C(=O)OH, phenyl, and Het-l, wherein each phenyl and Het—l, may be optionally substituted with one or more substituents independently selected from 0x0, C1—C6 haloalkyl, C1—C6 haloalkoxy, C(=O)OH, and halophenyl.
In another embodiment RK and Ry are independently selected from H and phenyl, wherein said , may be optionally substituted with one or more substituents independently ed from F and C].
In another embodiment: Ar] is a substituted phenyl wherein said substituted , has one or more C1-C6 haloalkoxy; Het is a triazolyl; Arz is a phenyl; W0 2012/109125 PCT/U82012/023932 R1 is H; R2 is H; R3 is C1-C6 alkylHet-l wherein said alkyl and Het-l are optionally substituted with one or more substituents independently selected from F, Cl, Br, C1-C6 alkyl, C1-C6 kyl, C1-C5 haloalkoxy, S(=O)n(C1-C6 , C(=O)OH, C(=O)O(C1-C6 alkyl), phenyl, Si(C1-C6 alkyl)3, and S(=O)nNRny; R4 is phenyl, wherein said phenyl is optionally substituted with one or more substituents independently selected from F, C], NRny, C1—C5 alkyl, or C1-C6 alkoxy; and 11: 0, 1, or 2; RK and Ry are independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F “A (“1- an! allu V1, allu Het-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one or more heteroatoms independently selected from nitrogen, sulfur or oxygen.
In another embodiment Het—1 is selected from benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazoly], hienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, lyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, olinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4—tetrahydro-quinoliny1, 4,5—dihydro— yl, 4,5—dihydro-1H-pyrazoly1, 4,5-dihydro—isoxazolyl, and 2,3—dihydro-[1,3,4]- oxadiazolyl.
In another embodiment Het is selected benzofuranyl, sothiazolyl, benzoisoxazolyl, azolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, inyl, oxazolyl, phthalazinyl, pyraziny1,pyrazolinyl pyrazolyl,pyridaziny1, pyridyl, b.) C) dinyVl, pyrrolyV,01ui__a,__.oli_n_y1, quin _1__ny1,quinoxaliny1,tetrazoly1, linyl thiazolyl, thienyl, tn'azinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-1H-pyrazoly1, 4,5-dihydro-isoxazolyl, and 2,3-dihydro-[1,3,4]-oxadiazolyl.
WO 09125 PCT/U52012/023932 In another embodiment Het-l is selected from benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzothiadizolyl, cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazoly], oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, nyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, inyl, quinoxalinyl, tetrazolyl, thiazolinyl, lyl, thienyl, thienylpyrazolyl, triazinyl, triazolyl, piperazinyl, piperidinyl, morpholinyl, idinyl, ydrofuranyl, tetrahydropyranyl, l,2,3,4-tetrahydro- quinolinyl, 4,5-dihydro-oxazolyl, 4,5—dihydro-1H—pyrazolyl, 4,5-dihydro-isoxazolyl, and 2,3- dihydro-[l,3,4]—oxadiazolyl.
In another embodiment Het-l is selected from benzothiadizolyl, furanyl, oxazolyl, and thienylpyrazolyl.
While these embodiments have been expressed, other embodiments and combinations of these expressed embodiments and other embodiments are possible.
The Molecules of Formulae One, Two and Three will generally have a molecular mass of about 100 s to about 1200 Daltons. However, it is generally preferred if the molecular mass is from about 120 Daltons to about 900 Daltons, and it is even more generally red if the molecular mass is from about 400 Daltons to about 800 Daltons.
PREPARATION OF TRIARYL-INTERMEDMTES Compounds of this invention can be prepared by making a triaryl intermediate, Arl— z, and then linking it to the desired intermediate to form the desired compound. A wide y of triaryl intermediates can be used to prepare nds of this invention, provided that such triaryl intermediates contain a suitable functional group on Ar: to which the rest of the desired intermediate can be attached. Suitable functional groups include an oxoalkyl or a formyl group. These triaryl intermediates can be prepared by methods usly bed in the chemical literature, including Crouse et a1. PCT Int. Appl. Publ. W02009/102736 A1.
PREPARATION OF HYDRAZONE-LINKED COMPOUNDS Hydrazone-linked compounds can be prepared from the corresponding aryl aldehydes or ketones by one of three methods: (1) by reaction with a hydrazine, followed by reaction with an aryl isothiocyanate in tetrahydrofuran (THF), at atures between 0 and 100 °C W0 2012/109 125 2012/023932 (Reaction A); (2) by reaction with methyl hydrazinecarbodithioate, ed by reaction with an aniline in a polar aprotic solvent such as N,N-dimethylformamide (DMF), at temperatures between 25 and 150 °C (Reaction B); or (3) by reaction with an aryl thiosemicarbazide, that is either commercially available or can be prepared by one who is d in the art, in a polar protic solvent such as ethyl alcohol , at temperatures between 0 and 100 °C (Reaction 1. NHZNH-RZ 2. R4-NCS, THF,0-100°C Het leN‘Nks/ ,lHek , \ £52 3&3. '3‘ Ar; \Afi - H Arl A2 N1 T R4 H 2. R4-NH2,DMF, -150°c H2MNi R4 (C) H I.“ EtOH, 0 - 100 °C PREPARATION OF ALKYLATED HYDRAZONE-LINKED COMPOUNDS Alkylated hydrazone-linked compounds can be prepared from the corresponding hydrazone—linked compounds by one of two methods: (1) by reaction with an ting agent in EtOH or acetone, at temperatures between 0 and 100 0C for from 1 to 24 h or (2) by reaction with an alkylating agent in chloroform (CHC13), dichloromethane (CH2C12), or other halocarbon solvent, with or without a base such as sodium bicarbonate, at from 20 to 60 °C. 2012/023932 Alkylating agent, EtOH 0-10000, 1-24h R1 R2 R1 R2 R3 Ht N3 Ar, eszsNiNzm“’\\ R4 2 m2 A“ N N e 2 l W R4 .
Alkylating R5 agent, CHCl3 ’ (E) -60°C, 1-24h Compounds of Formula Two, wherein R5 forms a ring with N3 (see Scheme below) or of Formula Three, wherein R5 forms a ring with N2, can be prepared from a suitable acyclic precursor by using (x—halo acids, acid halides, esters, or ketones (F or G or H). For example, treatment of the thiosemicarbazone with a slight excess of an OL—halo ester, in a protic solvent such as EtOH or methyl alcohol (CH30H) results in S-alkylation and subsequent ring closure exclusively onto N3 (Reaction F; see for example, J. Indian al Society 1966, 43, 275—276, or J.Het’erocycl. Chem. 1978, 15, 335-336). When an aprotic solvent such as CHzClz or dichloroethane (ClCHzCH2Cl) is used at temperatures from 30 0C to 80 ”C, the ation of addition of or halo ketones also favors e onto N3, with subsequent dehydration to form an imino thiazoline (Reaction G). With oc-halo acids or acid halides or esters in a halocarbon solvent such as CH2C12 or CICHZCHQCI, ring closure onto both N2 (Reaction H) and N3 is observed. Though these reactions often proceed in the absence of added base, a base such as sodium bicarbonate, sodium ate or sodium acetate, or an amine base such as pyridine or triethylamine, can be added.
W0 2012/109125 PCT/U82012/023932 BrVCOZH EN R4 ———’ ArH6"”\ NIN\gf0 (F) 13r\/c02cr13 j: E}2 E3 EtOH or MeOH Het\Arz Ar‘ NF 2Tsr 1R4 BQOK JR: I'M r Het\ \ .N N (G) ATI’ AI2 NI 2“( j 131\/cozcr13 R4 -- . R1 ,m “ N: CHZCIZ or zi§ / S in) Het\ ,Nz \ Arl’ AI‘2 NI 1K ClCHZCH2Cl 0 Alternatively, 3-arylidineimino—Z—aryliminothiazolin‘4—ones can be prepared by treating an de 0r ketone, n R1 is as previously described, with a 3-amino— 2- (arylimino)thiazolidin—4—one in acetic acid at from 30 to 70 0C as shown in the following scheme (1). The intermediate l-aminoaryliminothiazolin—S-one, wherein R4 is phenyl, has been described (see for example, J. Org. Chem. 1962, 27, 2878); it was prepared in 80% yield by treatment of 4-pheny1 micarbazide with ethyl 2-chloroacetate and sodium acetate in hot EtOH.
H H LH3 .N N N%S S N.
Ar] AIZ Het/ YR1 (1) R] 5’1 "Het\/J§ ,N _s Ar] Arz N \f Alternatively, compounds of Formula 2 and Formula 3 may be formed by heating a thiosemicarbazone precursor with a di-halo group Hall-RS-Ha12 such as o-Z-chloro ethane, in acetone or 2-butanone or other suitable solvent, using a base such as potassium PCT/U82012/023932 ate or triethylamine, at temperatures between ambient and 100 °C for from 1 to 72 hours. The S—alkylated intermediate undergoes cyclization at N2 or N3 to generate nds of Formula Two or Formula Three (Reaction J). In some cases, addition of KI may be required to accelerate the cyclization of the intermediate lated derivatives to the ring-closed products.
R1 Hal R1 Het H H \R/ Het S /Hal Arl Arz N \[r \R4 Ar1 N2 Y S N'R4 i Kl (I) R] R5 R1 Het I \ Het S / \ \ ,N S Ar/l R‘rz \NN Ar! Ari). N Y \R N' «5 R4 R51 An alternative method of preparing compounds of this invention is by treatment of a thiosemicarbazone precursor with an unsaturated ester or acid chloride (Reaction L). 0 r e Ar]’ Het\Ar2 \N [N2 R] R2 KKCI O (L) | Ill3 /N N R1 ,)\N O Het A N Arl’ ‘Arz N; 2 R4 The es are for illustration purposes and are not to be construed as limiting the invention disclosed in this document to only the embodiments disclosed in these examples.
Starting materials, reagents, and solvents that were obtained from commercial sources were used without further purification. Anhydrous solvents were purchased as Sure/SealTM from Aldrich and were used as received. g points were obtained on a Thomas Hoover W0 2012/109125 PCT/U82012/023932 Unimelt capillary melting point apparatus or an OptiMelt Automated Melting Point System from rd Research Systems and are uncorrected. Molecules are given their known names, named according to naming programs within MDL ISISTM/Draw 2.5, ChemBioDraw Ultra 12.0 or ACD Name Pro. If such programs are unable to name a molecule, the molecule is named using tional naming rules. ]H NMR spectral data are in ppm (8) and were recorded at 300, 400 or 600 MHz, and 13C NMR spectral data are in ppm (8) and were recorded at 75, 100 or 150 MHz, unless otherwise stated.
Example 1: Preparation of (E)-N-(4-dimethylamino)phenyl)(4-(1-(4- 1 0 (trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3—yl)benzylidene)hydrazine-carb0thioamide (Compound 1-1) [Synthesis Method A}. 0 S F7( QNNYQ/ZJNTNQ\ ’ F F V’N If 1 5 Step 1. (E)(4-(Hydrazonomethyl)phenyl)—1-(4-(trifluoromethoxy)phenyl)-1H- 1,2,4-triazole. To a 250 milliliter (mL) round-bottomed flask ning hydrazine hydrate (64% aqueous (aq) solution; 7.27 mL, 15.0 millimoles (mmol)) in EtOH (100 mL) at 80 °C was added 4-trifluoromethoxyphenyl)—lH—[l,2,4]triazol—3—yl]-benzaldehyde (5.00 grams (g), 1.50 mmol) portionwise over 5 minutes (min). The solution was stirred at reflux for an additional 3 hours (h) before being diluted with water (H20; 300 mL) and cooled to 0 °C. The precipitated product was collected by vacuum filtration as a white solid (4.89 g, 93%): mp 222—226 °C; 1H NMR (400 MHz, DMSO-d6) 5 8.59 (s, 1H), 8.22 (d, J = 8.2 Hz, 2H), 7.84-7.79 (m, 3H), 7.66 (d, J = 8.3 Hz, 2H), 7.41 (d, J = 8.2 Hz, 2H), 7.29 (s, 1H), 5.63 (br s, 2H); ESIMS m/z 348 (M+H).
Step 2. To a 25 mL round-bottomed flask containing (E)—3-(4-(hydrazonomethyl)- pheny1)—1—(4-(trifluoromethoxy)phenyl)-1H—1,2,4-triazole (250 mg, 0.720 mmol) in THF (10 mL) was added 4-isothiocyanato-N,N-dimethy1aniline (385 mg, 2.16 mmol). The contents were heated at 65 °C with stirring for 2 h before the solvent was removed under r duced re. The residue was slurried in CH2C12 (10 mL) resulting in precipitation of product b.) C) al. Tne desired t was ed as a yellow solid via vacuum filtration (350 mg, 93%): mp 205—208 °C; 1H NMR (400 MHz, DMSO-d6) 6 11.78 (s, 1H), 10.02 (s, 1H), 9.42 (s, 1H), 8.19-7.99 (m, 6H), 7.64 (d, J: 8.3 Hz, 2H), 7.28 (d, J: 8.3 Hz, 2H), 7.73 (d, J: 8.3 PCT/U82012/023932 Hz, 2H), 2.92 (s, 6H); ESIMS m/z 526 (M+H).
Example 2: Preparation of N-(3-(dimethylamino)phenyl)(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazinecarbothioamide (Compound I-2) [Synthesis Method B].
Step 1. (E)-Methyl 2-(4-(1-(4~(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3— yl)benzylidene)hydrazinecarbodithioate. To a 250 mL round-bottom flask containing hydrazinecarbodithioic acid methyl ester (2.38 g, 1.95 mmol) in EtOH (100 mL) was added 4—[l—(4-t1ifluoromethoxyphenyl)—1H—[1,2,4]triazolyl]-benzaldehyde (5.00 g, 1.50 mmol).
The vessel was heated at 80 °C for 3 h before being diluted with H20 (300 mL) and cooled to 0 0C. The itated t was collected by vacuum filtration as an off—white solid (6.13 g, 93%): mp 204—206 0C; 1H NMR (400 MHz, DMSO-dfi) 5 13.39 (s, 1H), 9.43 (s, 1H), 8.38 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 8.09 (d, J: 8.4 Hz, 2H), 7.88 (d, J = 8.4 HZ, 2H), 7.62 (d, J = 8.3 Hz, 2H), 2.57 (s, 3H); ESIMS m/z 438 (M+H).
Step 2. To a 50 mL round-bottomed flask containing (E)—methyl 2-(4-(1-(4- (trifluoromethoxy)phenyl)- 1H- 1 ,2,4-triazol—3—yl)benzylidene)hydrazinecarbodithioate (250 mg, 0.571 mmol) in DMF (3 mL) was added N1,Nl-dimethylbenzene-1,3-diamine (195 mg, 1.43 mmol). The contents were heated at 150 °C with ng for 5 h before the solution was d to cool overnight. The e was filtered, and the filtrate was purified via RP— HPLC to afford the desired material (235 mg, 78%) as an off-white solid: mp 192—194 °C; 1H NMR (400 MHz, DMSO'd6) 5 11.82 (s, 1H), 10.04 (s, 1H), 9.41 (s, 1H), 8.19 (s, 1H), 8.16— 7.99 (m, 6H), 7.61 (d, J: 8.3 Hz, 2H), 7.16 (t, J=7.2 Hz, 1H), 7.01 (m, 1H), 6.87 (m, 1H), 6.58 (m, 1H), 2.88 (s, 6H); ESIMS m/z 526 ([M+H]+).
Example 3: Preparation of N-benzyl(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4- triazolyl)benzylidene)hydrazinecarbothioamide (Compound I-3) [Synthesis Method C].
EFQo N SyN/‘Q To a 50 mL round-bottomed flask containing 4-[1-[4—(trifluoromethoxy)phenyl]- 1,2,4-triazolyl]benzaldehyde (500 mg, 1.5 mmol) in EtOH (3 mL) was added 4- thiosemicarbazide (650 mg, 3.6 mmol). The reaction mixture was heated at 80 °C overnight. H20 was added upon completion of the reaction, and the crude product material was ed by vacuum filtration. The titl" nd was isolated via RP—HPLC as a white solid (390 mg, 52%): mp 220—224 °C; 1H NMR (400 MHz, CDC13) 8 9.29 (s, 1H), 8.59 (s, 1H), 8.21 (d, J = 8.4 Hz, 2H), 7.85-7.79 (m, 3H), 7.71 (d, J = 8.4 Hz, 2H), 7.46730 (m, 8H), 5.01 (d, J = 5.8 Hz, 2H); ESIMS m/z 497.2 (M+H).
Compounds [-4 through I-31 in Table 1 were sized in accordance with the examples above. Other intermediates used in the preparation of nds of this invention were prepared in accordance with the procedures described in Brown, et al, WO 2011017504, or by other known routes.
Example 4: Preparation of N-(4-dimethylaminophenyl)-S-methyl{4-[1-(4- trifluoromethoxyphenyl)—1H-[1,2,4]-triazolyl]-benzylidene}-hydrazine- carbothioamide (Compound 1C) (Synthesis Method D) F o H . 0 NAg N \ VN EN ,8 A solution ning (E)-N-(4-(dimenhylamino)phenyl)—2u(4=(1s(4=(trifluoromethoxy)= phenyl)—1H-l,2,4-triazolyl)benzylidene)hydrazinecarbothioamide (150 mg, 0 285 mmol) and iodomethane (0.054 mL, 0.856 mmol) in EtOH (5 mL) was heated at 80 °C ror 3 b heroic the solvent was removed under reduced pressure. The residue was purified via normal phase flash chromatography (gradient elution with hexanes/EtOAc) to afford the title compound as an orange foam (93 milligrams (mg), 60%): 1H NMR (400 MHz, DMSO-ds) 5 8.61 (s, 1H), 8.48 (s, 1H), 8.22 (d, J = 8.24 Hz, 2H), 8.17 (s, 1H), 7.89 (d, J: 8.24 Hz, 2H), 7.80 (d, J: PCT/USZ012/023932 8.28 Hz, 2H), 7.41 (d, J = 8.28 Hz, 2H), 7.19 (d, J: 8.24 Hz, 2H), 6.71 (d, J = 8.24 Hz, 2H), 2.99 (s, 6H), 2.42 (s, 3H); EIMS m/z 540 (M+).
Example 5: General procedure for lation of triaryl thiosemicarbazones (Synthesis Method E) A d solution of the thiosemicarbazone and alkylating t in CHzClz or chloroform (CHC13) was heated at from 35 to 50 °C for from 10 to 24 h. The cooled solution was trated under reduced pressure. The residue was generally purified via chromatography using a chloroform/methanol (CHCl3/CH3OH) or EtOAc-hexane solution as the eluent to afford the S-alkylated products.
Example 6: Preparation of (S)-tert-butyl 3-((2-((Z)-(2,6-dimethylphenylimino)-((E)(4- (1-(4—(trifluoromethoxy)phenyl)-lH-l,2,4—triazolyl)benzylidene)hydrazinyl)- methylthio)acetamido)methyl)piperidine-l-carboxylate (Compound 56C) (Synthesis Method E) Arofii).....QNJ‘LSQ MOgrow To a solution of bromoacetyl bromide (26 microliters (uL), 0.299 mmol) in dichloroethane (3 mL) was added dropwise a solution of (S-tert-butyl 3- (aminomethyl)piperidinecarboxylate (63.9 mg, 0.298 mmol) in dichloromethane (1 mL), followed by N-ethyl-N-isopropylpropan-Z-amine (76 mg, 0.588 mmol). This mixture was d at room temperature for 30 min, then (E)—N-(2,6-dimethylphenyl)(4-(1-(4- (trifluoromethoxy)phenyl)- 1H-1,2,4-trilazolyl)benzylidene)hydrazine-carbothioamide (100 mg, 0.196 mmol) was added as a solid and the mixture was heated to 40 °C for 90 min. It was then allowed to cool to room ature and ated under reduced pressure, giving a light yellow glass, which was dissolved in aoetonitrile (2 mL) and allowed to stand at room temperature. The resulting precipitate was isolated by centrifuge and decanting, washing with fresh acetonitn‘le. The solid was dried under a nitrogen stream and then under high vacuum.
The crude product was recrystallized from acetone—isopropyl alcohol. The title compound was isolated as a white solid (36.5 mg, 24%): mp 148—151 “C; 1H NMR (400 MHz, methanol-814)?) 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J: 8.1 Hz, 2H), 8.12 (m, 2H), 8.07 — 8.00 (m, 2H), 7.58 — 7.43 (m, 2H), 7.33 (dd, J = 8.6, 6.5 Hz, 1H), 7.25 (d, J = 7.6 Hz, 2H), 4.02 (m, 2H), 3.97 — 3.75 (m, 2H), 3.21 (d, J = 6.9 Hz, 2H), 2.90 (m, 1H), 2.59 (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 — 1.63 (m, 2H), 1.44 (s, 9H), 1.29 (m, 3H); ESIMS m/z 765 (M+H).
Example 7: Preparation of (1Z,2E)oxo(((R)-piperidinylmethyl)amino)ethyl N- (2,6-dimethylphenyl)—2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol yl)benzylidene)hydrazinecarbimidothioate trifluoroacetic acid (Compound 62C) CF3C02H N 0 oON—RN, .2, N S F ’7< FF / N. *NN A solution of (S)—tert—buty1 ((Z)—(2,6—dimethylpheny1imino)—((E)(4-(1-(4— (trifluoromcthoxy)phenyl)- 1H-1 ,2,4-triazolyl)benzylidene)hydrazinyl)methylthio)- acetamido)methyl)pipe1idine—1—carb0xy1ate (32.0 mg, 0.042 mmol) in TFA (250 pL, 3.24 mmol) was stirred at room ature for 10 min. Eth (10 mL) was then added giving a white precipitate, which was ed by centrifuge and decanting, then rinsing with fresh 320 (5 mL). The solid was dried under nitrogen stream and then under high vacuum giving the title compound as a white solid (19.8 mg, 60%): mp 110—120 °C; 1H NMR (400 MHz, methanol-(1.06 9.18 (s, 1H), 8.56 (m, 1H), 8.26 (m, 2H), 8.16 — 7.84 (m, 4H), 7.52 (m, 2H), 7.27 (m, 1H), 7.22 (m, 2H), 4.00 (s, 2H), 3.28 (m, 3H), 3.06 — 2.83 (m, 1H), 2.75 (t, J: 12.2 Hz, 1H), 2.34 (s, 6H), 2.21 — 1.83 (m, 4H), 1.72 (m, 1H), 1.47 — 1.19 (m, 2H); ESIMS m/z 665 (M+H).
Example 8: Preparation of )-((4-methoxy-2,6-dimethylphenyl)imino)((E)(4-(1- (4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazinyl)methyl)- W0 2012/]09125 PCT/U32012/023932 thio)acetic acid sodium salt (Compound 68C) To a solution of 2-((Z)-(4-methoxy-2,6-dimethylphenylimino)((E)(4-(1-(4- (trifluoromethoxy)phenyl)- 1H- l ,2,4-triazolyl)benzylidene)hydrazinyl)methylthio)acetic acid (77.7 mg, 0.130 mmol) in THF (10 mL) was added slowly sodium olate (0.5 M in ol; 260 uL, 0.130 mol) at room temperature. The mixture immediately turned a darker yellow and was then evaporated at room temperature under vacuum giving a light orange solid. This material was triturated with Eth (2X) and isolated by decanting using a centrifuge and drying under a nitrogen stream and then under high vacuum. The title compound was isolated as a light orange solid (32 mg, 39%). mp 146—154 0C; 1H NMR (400 MHz, methanol—d4) 5 9.11 (s, 1H), 8.64 — 7.68 (m, 7H), 7.51 (m, 2H), 6.70 (s, 2H), 3.85 — 3.70 (m, 411), 3.61 (m, 1H), 2.29 (s, 6H); ESIMS m/z 599 (M+H). e 9: Preparation of (Z)(4-methoxy-2,6—dimethylphenyl)((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)thiazolidin one (Compound 69C) (Synthesis Method F) To a solution of (E)-N-(4-methoxy-2,6-dimethylphenyl)-2—(4-(1-(4- oromethoxy)phenyl)- 1H- 1 ,2,4—triazolyl)benzylidene)hydrazine-carbothioamide (250 mg, 0.462 mmol) in EtOH (5 mL) was added methyl bromoacetate (100 mg, 0.65 mmol), and the mixture was heated to 70 °C for 4 h. The mixture was allowed to cool to room temperature and diluted with water (1 mL). The itate was vacuum filtered, giving the title compound as a white solid (204 mg, 76%): mp 188—190 °C; 1H NMR (400 MHz, CDC13) 8.56 (s, 1H), 8.33 (s, 1H), 8.22 (d, J = 8.1 Hz, 2H), 7.90 — 7.70 (m, 4H), 7.39 (d, J: 8.7 Hz, 2H), 6.72 (s, 2H), 4.01 (s, 2H), 3.87 — 3.73 (s, 3H), 2.18 (s, 6H); ESIMS m/z 581 (M+H).
Example 10: Preparation of 4-((2Z)-3—(2,6-dimethylphenyl)((4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)-2,3- dihydrothiazolyl)—N,N-diethylaniline (Compound 74C) (Synthesis Method G) +2? <7“ or”) waaN EN \ Pz/ \ N‘ s / \ \ To a solution of (E)-N—(2,6-dimcthylphcnyl)—2—(4-(l—(4-(t1ifluoromethoxy)phcnyl)- 1H-l,2,4-triazolyl)benzylidene)hydrazine-carbothioamide (747 mg. 0.144 mmol) in dichloroethane (5 mL), was added (x—bromo—4—diethylamino)acetophenone (53.9 mg, 0.199 mmol), and the mixture was heated to 40 °C for 4 h. The mixture was then cooled to room temperature and evaporated under . The crude al was triturated with acetonitrile and ed (2X). The resulting solid was dried under a stream of nitrogen, giving the title compound as a pale yellow solid (25 mg, 25%): mp 190—193 °C dec; 1H NMR (400 MHZ, methanol—c105 9.20 (s, 1H), 8.38 (s, 1H), 8.31 - 8.24 (m, 2H), 8.08 ~ 8.00 (m, 2H), 7.95 — 7.88 (m, 2H), 7.55 — 7.48 (m, 3H), 7.48 — 7.36 (m, 5H), 7.31 (d, J = 7.7 Hz, 2H), 3.60 (q, J = 7.2 Hz, 4H), 2.20 (s, 6H), 1.07 (t, J = 7.2 Hz, 6H); ESIMS m/z 682 (M+H).
Example 11: Preparation of (Z)(2,6-dimethylphenylimino)((E)(1-(4- (trifluoromethoxy)phenyl)-lH-l,2,4-triazolyl)benzylideneamin0)thiazolidinone (Compound 81C) (Synthesis Method 1) W0 09 125 F0 0 F)? (1 N, TNH, N’N To a solution of l-(2,6-dimethylphenyl)thiourea (1.0 g, 5.55 mmol) in EtOH (10 mL) was added methyl 2-bromoacetate (1.0 g, 6.5 mmol) and sodium acetate (1.0 g, 12.2 mmol).
The solution was stirred and heated to reflux for l h, then it was cooled and the liquid was decanted from a small amount of solid material and the liquid was then diluted with water (10 mL). The precipitate was ed by filtration to give (1.1 g, 83%) of (Z)-3—amino—2—(2,6- dimethylphenylimino)thiazolidinone: mp 149—152 °C; 1H NMR (400 MHZ, CDC13) 6 7.06 (d, J: 7.2 Hz, 2H), 6.98 (m, 1H), 4.75 (s, 2H), 3.80 (s, 2H), 2.12 (s, 6H); ESIMS m/z 236 (M+H).
A portion of this material (0.07 g, 0.3 mmol) was dissolved in glacial acetic acid (3 mL) and treated with 4-(l—(4-(trifluoromethoxy)phenyl)-lH—l,2,4-triazoly1)benzaldehyde (0.10 g, 0.30 mmol), and the solution was heated to 60 0C for 2 h. The solution was then cooled and diluted with water (1 mL), and the resulting solid was filtered and ied to give the title compound (0.12 g, 67%): mp 3 0C; 1H NMR (400 MHZ, CDC13) 8 9.42 (s, 1H), 8.59 (s, 1H), 8.28 (d, J = 8.4 Hz, 2H), 8.01 (d, J: 8.3 Hz, 2H), 7.80 — 7.77 (m, 211), 7.43 7 7.34 (m, 2H), 7.07 (d, J = 7.5 Hz, 2H), 6.98 (dd, J: 8.2, 6.7 Hz, 1H), 3.90 (s, 2H), 2.17 (s, 6H); ESIMS m/z 551 (M+H).
Example 12: Preparation of (2Z,NE)—2-((2-isopropy1phenyl)imino)-N—(4—( l-(4- (trifluoromethyl)phenyl)- 1H~ 1 ,2,4-t1iazolyl)benzy1idene)— 1 ,3 -thiazinan-3 -amine and (Z) (2-isopropylphenyl)((E)—(4-(1-(4-(t1ifluoromethyl)phenyl)-1H-1,2,4-triazol yl)benzylidene)hydrazono)-1,3-thiazinane (Compound 87C and 179C) (Synthesis Method N. I RN N N‘ / F /N\ N F S/j F F N/j /N‘N/J\N F o* A5 W0 2012/109125 PCT/U82012/023932 To (E)-N—(2-isopropylphenyl)(4-(1-(4-(trifluoromethyl)phenyl)—1H-1,2,4-tn'azol yl)benzylidene)hydrazinecarbothioamide (200 mg, 0.393 mmol) and potassium ate (217 mg, 1.57 mmol) in butanone (10 ml) in a 25 mL Vial equipped with a stir bar and vigruex column was added 1—bromo—3—chloropropane (0.047 ml, 0.472 mmol). The on was heated to 60 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with water. The s layer was ted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided two compounds. The minor compound was dried overnight under house vacuum providing the title compound 87C (2Z,NE)—2-((2-isopropylphenyl)imino)-N-(4—(l-(4-(trifluoromethyl)phenyl)-1H-1,2,4-triazol- 3-yl)benzylidene)-1,3-thiazinanamine (28.5 mg, 13%) as a yellow solid: mp 187—189 °C; 1H NMR (400 MHz, CDC13) 5 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J: 8.3 Hz, 2H), 7.92 (d. J = 8.4 Hz, 2H), 7.81 (t, J = 10.2 Hz, 4H), 7.30 - 7.26 (m, 2H), 7.17 — 7.04 (m, 1H), 6.83 (d, J = 6.4 Hz, 1H), 3.96 (t, J: 6.1 Hz, 2H), 3.13 (heptet, J: 6.9 Hz, 1H), 2.97 - 2.90 (m, 2H), 2.47 - 2.38 (m, 2H), 1.25 (d, J = 7.5 Hz, 6H); ESIMS m/z 550 (M+H). The major compound was recrystallized with MeOH. The solid was filtered, washed with MeOH and dried at 50°C under vacuum. The solid was then azeotroped with acetone (3x) and the resultant solid was dried at 50°C under vacuum providing the title nd 179C (Z)(2-isopropy1phenyl) ((E)-(4-(1—(4~(trifluoromethyl)phenyl)—1H-1,2,4-triazol—3-yl)benzylidene)hydrazono)—l,3- thiazinane as a yellow solid (92.3 mg, 0.168 mmol, 43%): mp 212—213 °C; 1H NMR (400 MHz, CDC13)5 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J = 8.5 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.38 (dd, J = 7.8, 1.6 Hz, 1H), 7.33 (td, J = 7.5, 1.4 Hz, 1H), 7.29 — 7.23 (m, 1H), 7.18 (dd, J: 7.8, 1.4 Hz, 1H), 3.78 - 3.72 (m, 1H), 3.59 - 3.48 (m, 1H), 3.18 - 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, 6H); ESIMS m/z 550 (M+H).
Example 13: Preparation of (Z)(2-cyclopropylphenyl)-S-methyl((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)thiazolidin one (Compound 127C) (Synthesis Method F) 2012/023932 :%OOhm/N‘NAN8%.0 To (2-cyclopropylphenyl)(4-(l-(4-(trifluoromethoxy)phenyl)-1H-l,2,4-triazol—3— yl)benzylidene)hydrazinecarbothioamide (100 mg, 0.191 mmol) and sodium acetate (63.0 mg, 0.765 mmol) in EtOH (4 mL) was added methyl 2-bromopropanoate (0.026 mL, 0.230 mmol). The reaction was heated to 60 °C overnight. The reaction was then heated to 85 °C for 72 hours. The reaction mixture was diluted with DCM and washed with water. The aqueous layer was ted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided the title compound as a white solid (32.5 mg, 0.056 mmol, 30%): mp 112—115 0C; 1H NMR (400 MHZ, CDCl3) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (d, J: 8.3 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.43 - 7.32 (m, 4H), 7.26 - 7.24 (m, 2H), 4.23 (q, J = 7.3 Hz, 1H), 1.85 - 1.78 (m, 4H), 0.90 - 0.78 (m, 2H), 0.78 - 0.69 (m, 1H), 0.65 - 0.55 (m, 1H); ESIMS m/z 578 (M+H).
Example 14: Preparation of (Z)-3—(2-is0pr0pylphenyl)—2-((E)-(4-(1-(4- (trifluoromethoxy)phenyl)—1H—1,2,4-triazolyl)benzylidene)hydrazono)thiazolidine (C0mpound 132C) esis Method J) To (E)-N—(2—isopropylphenyl)(4-(1-(4-(trifluoromethoxy)phenyl)- l H— l ,2,4-triazol—3 - zylidene)hydrazinecarbothioamide (214 mg, 0.407 mmol) and potassium carbonate (225 mg, 1.63 mmol) in butanone (4 ml) was added l-bromochloroethane (70.0 mg, 0.489 mmol). The reaction was heated to 90 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was cooled, diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were filtered through a phase separator and concentrated. Separation by flash column chromatography and drying W0 2012/109125 the red solid at 55 °C under vacuum provided the title compound as a white solid (137 mg, 0.249 mmol, 61%): mp 193—196 °C; 1H NMR (400 MHz, CDC13) 5 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.80 (ddd, J = 9.5, 6.9, 4.9 Hz, 4H), 7.43 - 7.33 (m, 4H), 7.31 - 7.21 (m, 2H), 4.05 (td, J = 9.4, 7.1 Hz. 1H), 3.97 - 3.87 (m. 1H), 3.42 - 3.33 (m, 1H), 3.33 — 3.24 (m, 1H), 3.12 (heptet, J = 6.8 Hz, 1H), 1.27 (d, J: 6.8 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H); ESIMS m/z 552 (M+H).
Example 15: ation of (Z)(2-isopropylphenyl)methyl((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)thiazolidine (Compound 155C) (Synthesis Method J) To (E)-N—(2-isopropy1phenyl)—2—(4—(1-(4-(trifluoromethoxy)phenyl)—1H-1,2,4-triazol yl)benzylidene)hydrazinecarbothioamide (300 mg, 0.572 mmol) and potassium carbonate (316 mg, 2.29 mmol) in butanone (4 ml) was added 1,2—dibromopropane (0.072 ml, 0.686 mmol). The reaction was heated to 85 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with water.
The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. cation by flash column chromatography provided a yellow solid. The solid was recrystallized from MeOH. The solid was filtered, washed with MeOH, and dried to provide the title compound as a yellow solid which was dissolved in acetone and concentrated (3x). The light yellow solid was collected and dried under to provide the title compound as a 1:1 mixture of rotational reoisomers (75.1 mg, 0.133 mmol, 23%): mp 4 °C; 1H NMR of mixture (400 MHz, CDC13) 6 8.56 (s, 2H), 8.18 (dd, J = 10.8, 7.4 Hz, 6H), 7.84 - 7.73 (m, 8H), 7.45 - 7.30 (m, 8H), 7.30 - 7.23 (m. 2H). 7.20 (d, J = 6.7 Hz. 1H), 7.12 (dd, J = 7.8, 1.2 Hz, 1H), 4.43 — 4.33 (m, 1H), 4.16 (dd, J = 12.6, 6.3 Hz, 1H), 3.48 (dt, J: 13.3, 6.7 Hz, 1H), 3.37 (dd, J: 10.8, 6.2 Hz, 1H), 3.24 (dt, J = 13.7, 6.9 Hz,1H), 3.08 - 2.92 (m, 3H), 1.33 - 1.16 (m, 18H); ESIMS m/z 566 (M+H).
PCT/U52012/023932 e 16: Preparation of (Z)(2,6-dimethylphenyl)methyl((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazon0)-2,3- dihydrothiazole (Compound 173C) esis Method G) To a solution of (E)-N-(o-tolyl)(4—(1-(4—(trifluoromethoxy)phenyl)-1H—l,2,4-triazol yl)benzylidene)hydrazinecarbothioamide (257 mg, 0.520 mmol) in butanone (5 mL) was added triethylamine (0.14 mL, 1.0 mmol) and chloroacetone (0.06 mL, 0.73 mmol) and refluxed at 75 °C for 15 h. The mixture was allowed to cool to room ature and then transferred to a separatory funnel containing water (5 mL) and extracted twice with dichloromethane. The c layers were filtered through a phase separator, adsorbed onto silica gel, and purified by flash column chromatography to afford the title compound as a yellow solid (229 mg, 83%): mp 87 OC (dec); 1H NMR (400 MHz, CDC13) 8 8.56 (s, 1H), 8.19—8.15 (m, 3H), 7.82 - 7.75 (m, 4H), 7.43 - 7.30 (m, 5H), 7.24 (d, J: 7.3 Hz, 1H), 5.88 (d, J: 1.3 Hz, 1H), 2.21 (s, 3H), 1.80 (d, J=1.2 Hz, 3H); ESIMS m/z 536 (M+H).
Example 17: Preparation of (Z)(2-isopropylphenyl)-S-methyl—2-((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)-1,3-thiazinane (Compound 178C) (Synthesis Method J) :ioO”*&/N~N/J\N87 To (E)-N-(2-isopropylphenyl)(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol yl)benzylidene)hydrazinecarbothioamide (100 mg, 0.191 mmol) and potassium carbonate (105 mg, 0.763 mmol) in butanone (4 H11) was added 1-bromochloromethylpropane (39.0 mg, 0.229 mmol). The reaction was heated to 80 °C overnight. The on mixture was then diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated.
Purification by flash column chromatography provided the title compound as a light yellow solid as a mixture of rotational diastereoisomers: mp 186—190 °C; 1H NMR (400 MHz, CDCl3) 6 8.55 (d, J = 3.6 Hz, 1H), 8.14 (d, J: 8.4 Hz, 2H), 8.06 (s, 1H), 7.84 - 7.77 (m, 2H), 7.74 (d, J: 8.4 Hz, 2H), 7.38 (d, J = 9.0 Hz, 3H), 7.32 (td, J = 7.5, 1.4 Hz, 1H), 7.26 (s, 1H), 7.17 (t, J: 7.1 Hz, 1H), 3.69 - 3.26 (m, 1H), 3.55 - 3.37 (m, 1H), 3.18 - 2.98 (m, 2H), 2.93 - 2.80 (m, 1H), 2.47 (d, J = 35.9 Hz, 1H), 1.31 — 1.12 (m, 9H); ESIMS m/z 580 (M+H). e 18: Preparation of (Z)(2,6-dimethylphenyl)((E)-(4-(1-(4- (trifluoromethoxy)pheny!)-LEI-1.2,4-triaza!y!)benzylidene)hydralone)-1,3-thiazepane und2 1C) (Syntuesis Met:-ulu 25 F 0”“ 83 To (E)—N—(2,6-dimethylphenyl)(4-(1-(4—(t1ifluoromcthoxy)phenyl)-1H—l,2,4-triazol zylidene)hydrazinecarbothioamide (500 mg, 0.979 mmol) and potassium carbonate (541 mg, 3.92 mmol) in acetone (4 ml) was added 1-br0mochlorobutane (0.135 ml, 1.18 mmol). The reaction was heated to 60 °C overnight. The alkylation was determined to be complete by ultra performance liquid chromatography (“UPLC”). The reaction mixture was diluted with DCM and washed with water. The s layer was extracted with DCM. The c layers were poured through a phase separator and concentrated. Purification by flash column chromatography provided (1Z,N’E)—4—chlorobutyl N—(2,6-dimethylphenyl)—N’-(4-(1- (4-(trifluoromethoxy)phenyl)- 1H-1 riazolyl)benzylidene)carbamohydrazonothioate (427 mg, 0.710 mmol, 73%) as a yellow gum which was used without further purification. To (lZ,1‘v"11")chlorobutyl N-(2,6-dimethylphenyl)—1‘v”-(4-( 1 -(4-(trifiuoromethoxy)phenyl)-1H- 1,2,4—t1iazol-3~yl)benzylidene)—carbamohydrazonothioate (427 mg, 0.710 mmol), potassium iodide (236 mg, 1.42 mmol) and potassium carbonate (393 mg, 2.84 mmol) was added acetone (7 ml). The reaction was heated to 65°C for 72 h. The on was cooled to room temperature, diluted with DCM and washed with water. The aqueous layer was extracted with DCM. The organic layers were poured h a phase separator and concentrated.
Purification by flash column chromatography provided a yellow oil. The yellow oil was recrystallized from MeOH, filtered, washed with MeOH and dried to provide the title nd as a yellow solid (100 mg, 0.177 mmol, 25%): mp 100—106 °C; 1H NMR (400 MHz, CDC13)5 8.55 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.10 (s, 1H), 7.79 (dt, J = 10.4, 5.8 Hz, 4H), 7.38 (d, J = 8.3 Hz, 2H), 7.11 (s, 3H), 3.85 - 3.78 (m, 2H), 3.20 - 3.12 (m, 2H), 2.30 (s, 6H), 2.13 - 2.07 (m, 2H), 1.87 - 1.82 (m, 2H); ESIMS m/z 566 (M+H).
Example 19: Preparation of (Z)(2-isopropylphenyl)((E)-(4-(1-(4- (trifluoromethoxy)phenyl)-1H-1,2,4-triazolyl)benzylidene)hydrazono)-1,3-thiazinan- 4-one (Compound 224C) (Synthesis Method L) To (2—isopropylphenyl)(4-(1-(4-(trifluoromethoxy)phenyl)—1H—1,2,4—triazol—3— yl)benzylidene)hydrazinecarbothioamide (500 mg, 0.953 mmol) in butanone (9.5 ml) was added acryloyl chloride (0.077 ml, 0.953 mmol). The reaction was stirred at ambient temperature for 10 min followed by 50 0C for 2 h. The reaction was cooled to 40 °C overnight. The reaction was determined to be complete by LCMS. The reaction mixture was diluted with DCM and washed with saturated sodium bicarbonate. The s layer was extracted with DCM. The organic layers were poured through a phase separator and concentrated. Purification by flash column tography provided a yellow oil. The oil was tallized with diethyl ether/hexanes to provide the title compound as a light yellow solid (125 mg, 0.217 mmol, 23%): mp 118 °C (dec); 1H NMR (400 MHz, CDC13) 8 8.57 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 - - 7.75 (m, 4H), 7.46 - 7.36 (m, 4H), 7.33 7.26 (m, 1H), 7.10 (d, J = 7.6 Hz, 1H), 3.26 - 3.14 (m, 4H), 2.81 (heptet, J: 6.9 Hz, 1H), 1.21 (t, J = 7.2 Hz, 6H); ESIMS m/z 580 (M+H).
Example 20: Separation of rotationally stable atropisomers from racemic mixtures W0 2012/109125 Separation of constituent isomers from c mixtures can be carried out utilizing one of the following chiral HPLC methods.
Separation Method A: The column used for separation was a Chiral Technologies INC Chiral Pak 1A 5 mm, 4.6 X 250 mm column (Part number 80325). The method consists of a 1.0 mI/min flow rate from O to 30 min with an isocratic hold at 25% B for the duration of the run. The A eluent is n—hexane, the B eluent is iso-propyl alcohol.
Separation Method B: The column used for separation was a Chiral logies INC Chiral Pak 1B 5 pm, 4.6 X 250 mm column (Part number 81325). The method consists of a 1.0 mI/min flow rate from O to 30 min with an isocratic hold at 15% B for the duration of the run 'T'Ima A 1311 rt... u.. V VI at rs nupentane, the B eluent is l alcohol.
Example 21: BIOASSAYS ON BEET ARMYWORM (“BAW”) AND CORN M (“CEW”) BAW has few effective parasites, es, or predators to lower its tion. BAW infests many weeds, trees, grasses, legumes, and field crops. In various places, it is of economic concern upon asparagus, cotton, corn, soybeans, tobacco, alfalfa, sugar beets, peppers, tomatoes, potatoes, onions, peas, sunflowers, and citrus, among other plants. CEW is known to attack corn and tomatoes, but it also attacks artichoke, asparagus, cabbage, cantaloupe, collards, cowpeas, ers, eggplant, lettuce, lima beans, melon, okra, peas, peppers, potatoes, pumpkin, snap beans, spinach, squash, sweet potatoes, and elon, among other plants. CEW is also known to be resistant to n insecticides. Consequently, because of the above factors control of these pests is important. Furthermore, molecules that control these pests are useful in controlling other pests.
Certain molecules disclosed in this document were tested against BAW and CEW using procedures described in the following examples. In the reporting of the results, the “BAW & CEW Rating Table” was used (See Table Section).
BIOASSAYS ON BAW (Spodoptera exigua) Bioassays on BAW were conducted using a 11 diet tray assay. One to five second instar BAW larvae were placed in each well (3 mL) of the diet tray that had been usly filled with 1 mL of artificial diet to which 50 pig/cm2 of the test compound (dissolved in 50 uL of 90:10 acetone-water mixture) had been applied (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 °C, 14:101ight-dark for five to seven days. Percent mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The s are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
BIOASSAYS 0N CEW (Helicoverpa zea) Bioassays on CEW were conducted using a 128—well diet tray assay. One to five second instar CEW larvae were placed in each well (3 mL) of the diet tray that had been previously filled with 1 mL of artificial diet to which 50 rig/cm2 of the test nd lved in 50 uL of 90: 10 acetone—water mixture) had been d (to each of eight wells) and then allowed to dry. Trays were covered with a clear self-adhesive cover and held at 25 CC, 14: 10 light-dark for five to seven days. t mortality was recorded for the larvae in each well; activity in the eight wells was then averaged. The results are indicated in the table entitled “Table 5: Biological Results” (See Table Section).
Example 22: BIOASSAYS ON GREEN PEACH APHID (“GPA”) (Myzus persicae).
GPA is the most significant aphid pest of peach trees, causing decreased growth, shriveling of the leaves, and the death of various tissues. It is also ous because it acts as a vector for the transport of plant Viruses, such as potato virus Y and potato ll virus to members of the nightshade/potato family Solcmaceae, and various mosaic viruses to many other food crops. GPA attacks such plants as broccoli, burdock, cabbage, carrot, cauliflower, daikon, eggplant, green beans, lettuce, macadamia, papaya, peppers, sweet potatoes, tomatoes, watercress, and zucchini, among other plants. GPA also attacks many ornamental crops such as carnation, Chrysanthemum, flowering white cabbage, poinsettia, and roses.
GPA has developed resistance to many pesticides.
Certain les disclosed in this document were tested against GPA using procedures described in the following example. In the reporting of the results, the “GPA Rating Table” was used (See Table Section).
Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) true , were used as test substrate. The seedlings were infested with 20-50 GPA (Wingless adult and nymph stages) one day prior to al application. Four pots with individual seedlings were used for each treatment. Test compounds (2 mg) were dissolved in 2 mL of acetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm test compound. The stock solutions were diluted 5X with 0.025% Tween 20 in H20 to obtain the on at 200 ppm test compound. A hand-held tor-type sprayer was used for spraying a solution to W0 2012/109125 both sides of cabbage leaves until runoff. Reference plants nt check) were sprayed with the diluent only containing 20% by volume of acetone/methanol (1:1) solvent. Treated plants were held in a holding room for three days at approximately 25 °C and ambient ve humidity (RH) prior to grading. Evaluation was conducted by counting the number of live aphids per plant under a microscope. Percent Control was measured by using Abbott’s correction formula (W8. Abbott, “A Method of Computing the Effectiveness of an Insecticide” J. Econ. Entomol. 18 (1925), pp.265-267) as follows.
Corrected % l: 100 * (X - Y) / X where X = No. of live aphids on solvent check plants and Y = No. of live aphids on treated plants The results are indiCated n the t“ble entitled‘‘Table 5: Biological Re“t’s’S(ee Table Section).
PESTICIDALLY ACCEPTABLE ACID ADDITION SALTS, SALT DERIVATIVES, SOLVATES, ESTER DERIVATIVES, POLYMORPHS, ISOTOPES AND RADIONUCLIDES Molecules of Formulas One, Two and Three may be formulated into idally acceptable acid addition salts. By way of a non-limiting example, an amine function can form salts with hydrochloric, hydrobromic, ic, phosphoric, acetic, c, citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric, , ic, ascorbic, maleic, aspartic, benzenesulfonic, methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, and hydroxyethanesulfonic acids. Additionally, by way of a non—limiting example, an acid function can form salts including those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Examples of preferred cations e sodium, ium, and magnesium.
Molecules of Formulas One, Two and Three may be formulated into salt derivatives.
D . . . . . my way of a non-limiting example, a salt env me can be prepared byco a .reebease L») (3 by treating the salt wit‘h a s ' hydroxide (NaOH), potassium carbonate, ammonia, and sodium bicarbonate. As an example, in many cases, a pesticide, such as 2,4—D, is made more water-soluble by ting it to its dimethylamine salt. les of Formulas One, Two and Three may be formulated into stable complexes W0 20] 2/109125 with a solvent, such that the complex remains intact after the non—complexed solvent is removed. These complexes are often referred to as "solvates.” However, it is particularly desirable to form stable hydrates with water as the solvent.
Molecules of Formulas One, Two and Three may be made into ester derivatives.
These ester derivatives can then be applied in the same manner as the invention disclosed in this nt is applied.
Molecules of Formulas One, Two and Three may be made as various crystal polymorphs. Polymorphism is ant in the development of agrochemicals since different crystal polymorphs or structures of the same molecule can have vastly different physical properties and biological performances.
Molecules of Formulas One, Two and Three may be made with different isotopes. Of particular importance are molecules having 2H (also known as deuterium) in place of 1H. les of as One, Two and Three may be made with different radionuclides. Of particular ance are molecules having 14C.
STEREOISOMERS Molecules of Formulas One, Two and Three may exist as one or more stereoisomers.
Thus, n molecules can be produced as c mixtures. It will be appreciated by those skilled in the art that one stereoisomer may be more active than the other isomers.
Individual isomers may be obtained by known selective synthetic procedures, by conventional synthetic procedures using resolved starting materials, or by conventional resolution ures.
INSECTICIDES Molecules of as One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following insecticides — 1,2-dichloropropane, abamectin, acephate, acetamiprid, acethion, acetoprole, acrinathrin, nitrile, alanycarb, aldicarb, aldoxycarb, aldrin, allethrin, allosamidin, carb, alpha-cypermethrin, alpha-ecdysone, alpha-endosulfan, amidithion, aminocarb, amiton, amiton oxalate, amitraz, anabasine, athidathion, achtin, azamethiphos, azinphos-ethyl, azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin, bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta—cypermethrin, bifenthrin, bioallethrin, bioethanomethrin, biopermethrin, bistrifluron, borax, boric acid, bromfenvinfos, W0 2012/109125 PCT/U52012/023932 bromocyclen, bromo-DDT, bromophos, hos-ethyl, bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate, butoxycarboxim, cadusafos, m arsenate, calcium polysulfide, camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbon tetrachloride, carbophenothion, carbosulfan, , carcap hydrochloride, ntraniliprole, chlorbicyclen, Chlordane, chlordecone, chlordimeform, chlordimeform hydrochloride, chlorethoxyfos, chlorfenapyr, chlorfenvinphos, chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim, razophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos, chromafenozide, cinerin I, cinerin II, cinen'ns, cismethrin, cloethocarb, closantel, clothianidin, copper acetoarsenite, copper arsenate, copper naphthenate, copper oleate, coumaphos, coumithoate, crotamiton, crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate, cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin, otl‘dn, cyrnmazine, cythioate, DDT, decarbof an, deltamethrin, demephion, ion—O, ion-S, demeton, demeton—methyl, demeton—O, demeton-O- , demeton—S, demeton-S-methyl, demeton-S—methylsulphon, diafenthiuron, dialifos, diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos, dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor, thrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos, dimetilan, dinex, dinex-diclexine, dinoprop, dinosam, furan, diofenolan, dioxabenzofos, arb, dioxathion, disulfoton, dithicrofos, d— limonene, DNOC, DNOC—ammonium, DNOC-potassiurn, DNOC-sodium, doramectin, ecdysterone, emamectin, emamectin benzoate, EMPC, empenthrin, endosulfan, ion, endrin, EPN, epofenonane, mectin, lléthrine, esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate—methyl, ethoprophos, ethyl formate, ethyl—DDD, ethylene dibromide, ethylene dichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur, fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin, fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin, fenpropathrin, fothion, fenthion, fenthion-ethyl, fenvalerate, fipronil, flometoquin, mid, flubendiamide (additionally resolved isomers thereof), flucofuron, flucycloxuron, rinate, flufenerim, flufenoxuron, HITFDfl‘nfnv “n inate, fonofos, formeemnate, remuetar 11.“Mlpwnumirp wadiiarone 11v, 1.1-4 hydrochloride, formothion, formparanate, formparanate hydrochloride, fosmethilan, fospirate, (a) :3 fosthietan, -Jienozide, -mathiocarb, furethuln, gamma-cyhalothrimgamma-H l—Inhlfennmx--a. --‘_,--, 1'"”’ nozide, HCH, HEOD, hlor, heptenophos, heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide, hydroprene, hyquincarb, loprid, imiprothrin, indoxacarb, iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin, isofenphos, phos-methyl, isoprocarb, isoprothiolane, isothioate, isoxathion, ivermectin, jasmolin I, W0 2012/109125 PCTfU82012/023932 jasmolin II, jodfenphos, juvenile hormone I, juvenile hormone II, juvenile hormone IH, kelevan, kinoprene, lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane, lirimfos, ron, lythidathion, malathion, malonoben, mazidox, mecarbam, mecarphon, menazon, meperfluthrin, mephosfolan, mercurous de, mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion, carb, methocrotophos, methomyl, methoprene, methothrin, methoxychlor, methoxyfenozide, methyl bromide, methyl ocyanate, methylchloroform, methylene chloride, metofluthrin, arb, metoxadiazone, mevinphos, mexacarbate, milbemectin, milbemycin oxime, mipafox, mirex, molosultap, monocrotophos, monomehypo, monosultap, morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine, nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron, noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos, oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl, ron, pentachlorophenol, hrin, phenkapton, hrin, phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor, phosphamidon, phosphine, phoxim, -methyl, pirimetaphos, pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite, potassium thiocyanate, pp‘—DDT, thrin, ene I, precocene II, precocene HI, primidophos, profenofos, profluralin, profluthrin, promacyl, promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos, prothoate, protrifenbute, pymetrozine, pyraclofos, prole, pyrazophos, pyresmethrin, pyrethrin I, pyrethrin II, pyrethrins, pyridaben, pyridalyl, pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole, pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion, rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan, selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride, sodium uorosilicate, sodium thiocyanate, ide, spinetoram, spinosad, spiromesifen, spirotetramat, sulcofuron, sulcofuron-sodium, sulfluramid, sulfotep, sulfoxaflor, yl fluoride, sulprofos, tau-fluvalinate, tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron, tefluthn'n, temephos, TEPP, terallethn'n, terbufos, tetrachloroethane, tetrachlorvinphos, tetramethrin, tetramethylfluthrin, theta-cypermethrin, thiacloprid, thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiocyclam oxalate, thiodicarb, thiofanox, thiometon, thiosultap, thiosultap-disodium, thiosultap-monosodium, thuringiensin, tolfenpyrad, tralomethrin, transfluthrin, transpermethrin, tn'arathene, triazamate, triazophos, trichlorfon, trichlormetaphos-S, trichloronat, trifenofos, triflumuron, trimethacarb, ne, vamidothion, vaniliprole, XMC, xylylcarb, ypermethrin, and zolaprofos ctively these ly named insecticides are defined as the “Insecticide Group”).
W0 09125 PCT/USZ012/023932 ACARICIDES Molecules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following acaricides - nocyl, amidoflumet, arsenous oxide, azobenzene, azocyclotin, benomyl, benoxafos, benzoximate, benzyl benzoate, bifenazate, binapacryl, ropylate, chinomethionat, chlorbenside, chlorfenethol, chlorfenson, chlorfensulphide, chlorobenzilate, mebuform, chloromethiuron, chloropropylate, clofentezine, yrafen, cyflumetofen, cyhexatin, dichlofluanid, dicofol, dienochlor, diflovidazin, dinobuton, dinocap, p-4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenyl sulfone, disulfiram, dofenapyn, etoxazole, fenazaquin, fenbutatin oxide, pyrox' ate, -enso--, -entrifanfl, fluacrypyrim, flu azuron, flubenzimine, fluenetil, flumethrin, fluorbenside, hexythiazox, mesulfen, MNAF, nikkomycins, proclonol, propargite, quintiofos, spirodiclofen, sulfiram, sulfur, ifon, tetranactin, tetrasul, and thioquinox (collectively these commonly named acaricides are defined as the “Acaricide Group”).
NEMATICIDES Molecules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a aneous or sequential application) with one or more of the following nematicides - 1,3-dichloropropene, benclothiaz, t, dazomet-sodium, DBCP, DCIP, diamidafos, fluensulfone, fosthiazate, furfural, imicyafos, isamidofos, isazofos, metam, metam—ammonium, potassium, sodium, phosphocarb, and thionazin (collectively these ly named nematicides are defined as the “Nematicide Group”) FUNGICIDES Molecules of Formulas One, Two and Three may also be used in combination (such as, in a compositional mixture, or a simultaneous or sequential application) with one or more of the following fungicides - (3-ethoxypropyl)mercury bromide, 2-methoxyethylmercury de, 2-phenylphenol, 8-hydroxyquinoline e, 8-phenylmercurioxyquinoline, acibenzolar, acibenzolar-S-methyl, acs, acypetacs-copper, acypetacs-zinc, aldimorph, ally] alcohol, ametoctradin, amisulbrom, ampropylfos, anilazine, auIeofungin, azaconazole, azithiram, azoxystrobin, barium polysulfide, benalaxyl, benalaxyl-M, benodanil, benomyl, benquinox, bentaluron, benthiavalicarb, benthiavalicarb-isopropyl, benzalkonium chloride, WO 09125 PCT/U82012/023932 benzamacn'l, benzamacril-isobutyl, benzamorf, benzohydroxamic acid, bethoxazin, binapacryl, yl, bitertanol, bithionol, bixafen, blasticidin-S, Bordeaux mixture, boscalid, bromuconazole, bupirimate, Burgundy mixture, buthiobate, butylamine, calcium polysulfide, captafol, captan, carbamorph, carbendazim, carboxin, carpropamid, carvone, Cheshunt e, chinomethionat, chlobenthiazone, chloraniformethan, chloranil, chlorfenazole, chlorodinitronaphthalene, chloroneb, chloropicrin, thalonil, chlorquinox, chlozolinate, zole, clotrimazole, copper acetate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper zinc chromate, cresol, cufraneb, cuprobam, cuprous oxide, cyazofamid, cyclafuramid, cycloheximide, cyflufenamid, nil, cypendazole, onazole, cyprodinil, dazomet, dazomet-sodium, DBCP, debacarb, ntin, dehydroacetic acid, dichlofluanid, dichlone, dichlorophen, dichlozoline, diclobutrazol, diclocymet, diclomezine, ezine—sodium, dicloran, diethofencarb, diethyl rbonate, conazole, diflumetorim, dimethirimol, dimethomorph, dimoxystrobin, diniconazole, diniconazole-M, dinobuton, dinocap, dinocap- 4, dinocap-6, dinocton, dinopenton, dinosulfon, dinoterbon, diphenylamine, dipyrithione, disulfiram, ditalimfos, dithianon, DNOC, DNOC—ammonium, DNOC-potassium, DNOC— sodium, dodemorph, dodemorph acetate, dodemorph te, dodicin, dodicin-sodium, dodine, drazoxolon, edifenphos, epoxiconazole, etaconazole, etem, ethaboxam, ethin'mol, ethoxyquin, ethylmercury 2,3—dihydroxypropy1 mercaptide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury phosphate, etridiazole, famoxadone, fenamidone, fenaminosulf, fenapanil, fenan‘mol, fenbuconazole, fenfuram, fenhexamid, fenitropan, fenoxanil, fenpiclonil, fenpropidin, fenpropimorph, fentin, fentin de, fentin hydroxide, ferbam, ferimzone, am, fludioxonil, flumetover, flumorph, fluopicolide, fluopyram, fluoroimide, fluotrimazole, fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutianil, flutolanil, flutriafol, fluxapyroxad, folpet, formaldehyde, fosetyl, fosetyl-alumim'um, fuberidazole, furalaxyl, furametpyr, furcarbanil, furconazole, furconazole-cis, furfural, furmecyclox, furophanate, glyodin, griseofulvin, guazatine, halacrinate, lorobenzene, hexachlorobutadiene, hexaconazole, hexylthiofos, hydrargaphen, hymexazol, imazalil, il nitrate, imazalil sulfate, imibenconazole, iminoctadine, iminoctadine triacetate, iminoctadine trialbesilate, iodomethane, ipconazole, iprobenfos, iprodione, iprovalicarb, isoprothiolane, isopyrazam, nil, isovaledione, kasugamycin, kresoxim-methyl, mancopper, mancozeb, mandipropamid, maneb, mebenil, mecarbinzid, pyrim, mepronil, meptyldinocap, mercuric chloride, mercuric oxide, mercurous chloride, metalaxyl, metalaxyl—M, metam, ammonium, metam-potassium, 2012/023932 metam—sodium, metazoxolon, metconazole, methasulfocarb, methfuroxam, methyl bromide, methyl isothiocyanate, methylmercury benzoate, methylmercury dicyandiamide, mercury pentachlorophenoxide, metiram, metominostrobin, metrafenone, metsulfovax, milneb, myclobutanil, olin, N-(ethylmercury)-p—toluenesulphonanilide, nabam, natamycin, nitrostyrene, nitrothal-isopropyl, nuarimol, OCH, octhilinone, ofurace, orysastrobin, oxadixyl, oxine-copper, oxpoconazole, oxpoconazole fumarate, oxycarboxin, pefurazoate, penconazole, pencycuron, penflufen, pentachlorophenol, opyrad, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury late, phosdiphen, phthalide, picoxystrobin, piperalin, rbamate, polyoxins, polyoxorim, polyoxorim-zinc, potassium azide, potassium polysulfide, potassium thiocyanate, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, proquinazid, prothiocarb, prothiocarb hydrochloride, prothioconazole, pyracarbolid, pyraclostrobin, pyraclostrobin, pyrametoslrobin, pyraoxystrobin, pyrazophos, pyribencarb, pyridinitril, pyrifenox, pyrimethanil, pyriofenone, pyroquilon, pyroxychlor, pyroxyfur, quinacetol, quinacetol e, quinazamid, quinconazole, quinoxyfen, quintozene, rabenzazole, salicylanilide, ne, silthiofam, simeconazole, sodium azide, sodium orthophenylphenoxide, sodium pentachlorophenoxide, sodium polysulfide, spiroxamine, streptomycin, sulfur, pen, TCMTB, tebuconazole, tebufloquin, tecloftalam, tecnazene, tecoram, onazole, thiabendazole, thiadifluor, thicyofen, thifluzamide, thiochlorfenphim, thiomersa], thiophanate, thiophanate-methyl, thioquinox, , tiadinil, tioxymid, tolclofos— methyl, tolylfluanid, tolylmercury acetate, tn'adimefon, triadimenol, tn'amiphos, triarimol, tn'azbutil, xide, tributyltin oxide, tn'chlamide, tricyclazole, tridemorph, tn'floxystrobin, triflumizole, triforine, onazole, uniconazole, uniconazole—P, validamycin, valifenalate, Vinclozolin, zarilamid, zinc naphthenate, zineb, ziram, zoxamide (collectively these commonly named ides are defined as the “Fungicide Group”). anagrams11.141 Molecules of Formulas One, Two and Three may also be used in combination (such DJ CD as, in 13> compos'tional mix are,_. or a simultaneous or sequential application) with one or m __e of the ing herbicides - 2,3,6-TBA, TBA-dimethy1ammonium, 2,3,6-TBA-sodium, 2,4,5-T, 2,4,5-Tbutoxypropyl, 2,4,5-T—2-ethylhexyl, 2,4,5-Tbutoxypr0pyl, 2,4,5—TB, T—butometyl, 2,4,5-T-butotyl, 2,4,5-T-buty1, 2,4,5-T-isobutyl, T-isoctyl, 2,4,5-T- isopropyl, 2,4,5-T-methy], T-pentyl, 2,4,5-T-sodium, 2,4,5-T-triethylammonium, 2,4,5- PCT/U82012/023932 T-trolamine, 2,4-D, 2,4-Dbutoxypropyl, 2,4-Dethylhexyl, 3-butoxypropyl, 2,4- D—ammonium, 2,4—DB, 2,4-DB-butyl, 2,4-DB-dimethylammonium, 2,4—DB-isoctyl, 2,4-DB- potassium, -sodium, 2,4-D-butotyl, 2,4-D-butyl, 2,4-D-diethylammonium, 2,4-D- dimethylammonium, 2,4—D-diolamine, dodecylammonium, 2,4-DEB, 2,4—DEP, 2,4-D- ethyl, 2,4—D-heptylammonium, 2,4-D-isobutyl, 2,4—D-isocty1, 2,4-D-isopropyl, 2,4—D- isopropylammonium, 2,4-D-1ithium, 2,4—D—mepty1, 2,4-D-methyl, 2,4-D-octyl, 2,4—D-pentyl, 2,4-D-potassium, propyl, 2,4-D-sodium, tefury1, 2,4-D-tetradecylammonium, triethy1ammonium, 2,4-D-tris(2-hydroxypropyl)ammonium, 2,4-D-trolamine, 3,4—DA, 3,4-DB, 3,4-DP, 4-CPA, 4-CPB, 4-CPP, acetochlor, acifluorfen, acifluorfen—methyl, acifluorfen—sodium, aclonifen, acrolein, alachlor, allidochlor, alloxydim, alloxydim—sodium, ally] alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminocyclopyrachlor-methyl, aminocyclopyrachlor-potassium, yralid, aminopyralid~potassium, aminopyralid-tris(2—hydroxypropy1)ammonium, amiprofos-methyl, amitrole, um sulfamate, os, on, asulam, asulam- potassium, asulam-sodium, atraton, atrazine, azafenidin, lfuron, aziprotryne, , BCPC, beflubutamid, benazolin, benazolin—dimethylammonium, benazolin—ethyl, bcnazolin— potassium, bencarbazone, alin, benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone, bentazone-sodium, benzadox, benzadox—ammonium, benzfendizone, benzipram, benzobicyclon, benzofenap, benzofluor, benzoylprop, benzoylprop-cthyl, benzthiazuron, bicyclopyrone, bifenox, bilanafos, bilanafos—sodium, bispyribac, bispyribac— sodium, borax, bromacil, bromacil-lithium, bromacil—sodium, bromobonil, bromobutide, bromofenoxim, bromoxynil, bromoxynil butyrate, bromoxynil heptanoate, bromoxynil octanoate, bromoxynil-potassium, brompyrazon, lor, butafenacil, butamifos, butenachlor, buthidazole, buthiuron, butralin, butroxydim, buturon, butylate, cacodylic acid, cafenstrole, calcium chlorate, m ide, cambendichlor, carbasulam, carbetamide, carboxazole, carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlomethoxyfen, chloramben, chloramben-ammonium, chloramben-diolamine, chloramben-methyl, mben-methylammonium, chloramben—sodium, chloranocryl, chlorazifop, chlorazifop- propargyl, chlorazine, chlorbromuron, chlorbufam, chloreturon, chlorfenac, chlorfenac— sodium, chlorfenprop, chlorfenprop-methyl, chlorflurazole, chlorflurenol, chlorflurenol— methyl, chloridazon, chlorimuron, chlorimuron-ethyl, chlornitrofen, chloropon, chlorotoluron, chloroxuron, chloroxynil, rocarb, chlorpropham, chlorsulfuron, chlorthal, chlorthal-dimethyl, chlorthal-monomethyl, chlorthiamid, cinidon-ethyl, cinmethylin, lfuron, cisanilide, clethodim, cliodinate, clodinafop, clodinafop- W0 2012/109125 PCT/U52012/023932 propargyl, clofop, clofop-isobutyl, clomazone, clomeprop, cloprop, cloproxydim, clopyralid, alid-methyl, clopyralid—olamine, clopyralid-potassium, clopyralid-tfis(2— hydroxypropy1)amrnonium, cloransulam, cloransulam-methyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, cumyluron, cyanamide, cyanatryn, ine, cycloate, cyclosulfamuron, cycloxydim, cycluron, cyhalofop, fop—butyl, cyperquat, cyperquat chloride, cyprazine, cyprazole, cypromid, daimuron, dalapon, dalapon-calcium, dalapon— ium, dalapon-sodium, dazomet, t—sodium, delachlor, desmedipham, desmetryn, di—allate, dicamba, dicamba-dimethylammonium, dicamba—diolamine, dicamba— isopropylammonium, dicamba-methyl, dicamba-olamine, dicamba-potassium, dicamba- sodium, dicamba-trolamine, dichlobenil, dichloralurea, dichlormate, dichlorprop, dichlorprop—Z-ethylhexyl, dichlorprop-butotyl, rprop-dimethylammonium, dichlorprop- ethyl mmonium, dichlorp op—isoctyl,._- l3?-_h___ rprop-methyl-9 V- .1--- .,dichlorprop—P, dichlorprop-P- dimethylammonium, dichlorprop-potassium, dichlorprop~sodium, diclofop, diclofop—methyl, diclosulam, diethamquat, diethamquat dichloride, diethatyl, tyl-ethyl, difenopenten, penten-ethyl, difenoxuron, difenzoquat, difenzoquat metilsulfate, diflufenican, diflufenzopyr, diflufenzopyr—sodium, dimefuron, dimepiperate, dimethachlor, dimethametryn, dimethenamid, dimethenamid—P, dimexano, dimidazon, amine, dinofenate, dinoprop, dinosam, dinoseb, dinoseb acetate, b-ammonium, dinoseb- diolamine, dinoseb-sodium, b-trolamine, rb, dinoterb acetate, diphacinone- sodium, diphenamid, dipropetryn, diquat, diquat ide, disul, disul—sodium, dithiopyr, diuron, DMPA, DNOC, DNOC-ammonium, DNOC—potassium, DNOC-sodium, DSMA, EBEP, eglinazine, eglinazine—ethyl, endothal, endothal-diammonium, al—dipotassium, endothal-disodium, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethametsulfuron, ethametsulfuron-methyl, ethidimuron, ethiolate, ethofumesate, ethoxyfen, ethoxyfen-ethyl, ethoxysulfuron, etinofen, etnipromid, etobenzanid, EXD, lam, fenoprop, fenoprop-3— butoxypropyl, fenoprop-butometyl, fenoprop—butotyl, fenoprop-butyl, fenoprop-isoctyl, fenoprop-methyl, fenoprop-potassium, fenoxaprop, fenoxaprop-ethyl, prop-P, fenoxaprop—P-ethyl, fenoxasulfone, fenteracol, fenthiaprop, fenthiaprop-ethyl, fentrazamide, fenuron, fenuron TCA, ferrous sulfate, flamprop, flamprop-isopropyl, flamprop-M, flamprop— methyl, flamprop-M-isopropyl, flamprop—M-methyl, lfuron, florasulam, fluazifop, fluazifop-butyl, fluazifop-methyl, fluazifop-P, fluazifop—P-butyl, fluazolate, flucarbazone, flucarbazone—sodium, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr, flufenpyr-ethyl, flumetsulam, flumezin, flumiclorac, flumiclorac-pentyl, flumioxazin, flumipropyn, turon, fluorodifen, fluoroglycofen, fluoroglycofen-ethyl, fluoromidine, fluoronitrofen, uron, flupoxam, acil, anate, flupropanate-sodium, flupyrsulfuron, flupyrsuifuron—methyl-sodium, fluridone, flurochloridone, fluroxypyr, fluroxypyr-butometyl, fluroxypyr—meptyl, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, fomesafen-sodium, foramsulfuron, fosamine, fosamine-ammonium, xyfen, glufosinate, glufosinate-ammonium, glufosinate-P, inate-P-ammonium, glufosinate-P- sodium, glyphosate, glyphosate-diammonium, glyphosate-dimethylammonium, glyphosate- isopropylammonium, glyphosate-monoammonium, sate-potassium, glyphosate- sesquisodium, sate-trimesium, fen, halosulfuron, halosulfuron-methyl, haloxydine, haloxyfop, haloxyfop-etotyl, haloxyfop-methyl, haloxyfop—P, haloxyfop-P—etotyl, haloxyfop-P-methyl, haloxyfop-sodium, hexachloroacetone, hexaflurate, hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox, imazamox-ammonium, imazapic, imazapic-ammonium, imazapyr, imazapyr-isopropylammonium, imazaquin, imazaquin- um, imazaquin—methyl, imazaquin—sodium, imazethapyr, imazethapyr—ammonium, imazosulfuron, indanofan, flam, iodobonil, iodomethane, iodosulfuron, iodosulfuron- methyl-sodium, l, ioxynil ate, ioxynil—lithium, ioxynil—sodium, ipazine, ipfencarbazone, iprymidam, isocarbamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, isoxaben, isoxachlortole, isoxaflutole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA—Z- ethylhexyl, utotyl, MCPA-butyl, MCPA—dimethylammonium, iolamine, MCPA-ethyl, MCPA-isobutyl, MCPA-isoctyl, MCPA-isopropyl, MCPA-methyl, MCPA- olamine, MCPA—potassium, MCPA-sodium, MCPA—thioethyl, MCPA-trolamine, MCPB, MCPB—ethyl, MCPB—methyl, MCPB-sodium, mecoprop, mecoprop-Z-ethylhexyl, mecoprop- dimethylammonium, mecoprop-diolamine, mecoprop—ethadyl, mecoprop—isoctyl, mecoprop- methyl, mecoprop-P, mecoprop-P-dimethylammonium, mecoprop-P-isobutyl, mecoprop- potassium, mecoprop-P-potassium, mecoprop-sodium, mecoprop-trolamine, medinoterb, medinoterb acetate, mefenacet, mefluidide, mefluidide—diolamine, mefluidide-potassium, mesoprazine, lfuron, mesosulfuron-methyl, 'one, metam, metam-ammonium, metamifop, metamitron, metam-potassium, metam-sodium, metazachlor, metazosulfuron, razon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl isothiocyanate, methyldymron, metobenzuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, metsulfuron-methyl, molinate, monalide, monisouron, monochloroacetic acid, monolinuron, monuron, monuron TCA, morfamquat, morfamquat ride, MSMA, nilide, napropamide, naptalam, naptalam—sodium, neburon, nicosulfuron, nipyraclofen, nitralin, en, nitrofluorfen, norflurazon, noruron, OCH, orbencarb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, azon-dimolamine, oxapyrazon-sodium, oxasulfuron, oxaziclomefone, oxyfluorfen, parafluron, paraquat, paraquat ride, paraquat dimetilsulfate, pebulate, pelargonic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, phenmedipham-ethyl, phenobenzuron, mercury acetate, picloram, picloram-Z-ethylhexyl, picloram-isoctyl, picloram-methyl, picloram-olamine, picloram-potassium, picloram-triethylammonium, picloram-tn's(2- hydroxypropyl)ammonium, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, ium cyanate, pretilachlor, primisulfuron, primisulfuron-methyl, nromazine. omdia I J 7 L etuyi, prL..1 4“,.”16“)”, prohieuyi, propaciilor,.. .. m L... 1‘ panil, propaquizafop, propazme, propuai i, propisochlor, propoxycarbazone, propoxycarbazone-sodium, propyrisulfuron, propyzamide, falin, prosulfocarb, prosulfuron, proxan, proxan—sodium, prynachlor, pydanon, pyraclonil, pyraflufen, pyraflufen-ethyl, pyrasulfotole, lynate, pyrazosulfuron, pyrazosulfuron-ethyl, xyfen, pyribenzoxim, pyributicarb, pyn'clor, ol, pyfidate, pyriftalid, pyriminobac, pyIiminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac—sodium, pyroxasulfone, ulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop—ethyl, quizalofop—P, quizalofop-P-ethyl, ofop-P—tefuxy], rhodethanil, Iimsulfuron, saflufenacil, sebuthylazine, eton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, S-metolachlor, sodium te, sodium azide, sodium chlorate, sulcotIione, sulfallate, sulfentrazone, sulfometuron, eturon—methyl, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, TCA-ammonium, TCA-calcium, TCA-ethadyl, TCA— magnesium, TCA-sodium, tebutam, tebuthiuron,tefury1t1ione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, terbumeton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, pyr, thidiazimin, thidiazuron, thiencarbazone, thiencarbazone-methyl, thifensulfuron, sulfuron-methyl, thiobencarb, tiocarbazil, tioclon’m, topramezone, “no“, maziflam, tnbenuron, mbeuurommetuyl, m (A) (3 trifop, trifop—methyl, trifopsime, trihydroxytn'azine, trimeturon, tripropindan, tritac, nitosulfuron, vemolate, xylachlor, ctively these commonly named herbicides are defined as the “Herbicide Group”).
W0 2012/109125 PCT/U82012/023932 BIOPESTICIDES Molecules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a aneous or sequential application) with one or more biopesticides. The term “biopesticide” is used for microbial biological pest control agents that are d in a similar manner to chemical pesticides. Commonly these are ial, but there are also examples of fungal l agents, including Trichoderma spp. and Ampelomyces quisqualis (a control agent for grape powdery mildew). Bacillus is are used to control plant pathogens. Weeds and s have also been controlled with ial agents. One well-known insecticide example is Bacillus thuringiensis, a bacterial disease of Lepidoptera, Coleoptera, and Diptera. Because it has little effect on other organisms, it is considered more environmentally friendly than synthetic pesticides. Biological icides include products based on: 1. entomopathogenic fungi (e. g. Metarhizium anisopliae); 2. entomopathogenic nematodes (e.g. Steinernema feltiae); and 3. entomopathogenic viruses (e.g. Cydia pomonella granulovirus).
Other examples of entomopathogenic organisms include, but are not limited to, baculoviruses, bacteria and other prokaryotic organisms, fungi, protozoa and Microsproridia.
Biologically derived insecticides include, but not limited to, rotenone, veratridine, as well as microbial toxins; insect tolerant or resistant plant varieties; and sms modified by recombinant DNA technology to either produce insecticides or to convey an insect resistant property to the cally modified organism. In one embodiment, the Molecules of a One, Two or Three may be used with one or more biopesticides in the area of seed treatments and soil amendments. The Manual ofBiocontrol Agents gives a review of the available ical insecticide (and other biology-based control) products. Copping L.G. (ed.) (2004).
The Manual of Biocontrol Agents (formerly the Biopesticide Manual) 3rd Edition. British Crop Production Council (BCPC), Farnham, Surrey UK.
OTHER ACTIVE COMPOUNDS Molecules of as One, Two and Three may also be used in combination (such as in a compositional e, or a simultaneous or sequential application) with one or more of the following: 1. 3-(4-chloro-2,6-dimethylphenyl)hydroxyoxaazaspiro[4,5]decen—2-one; 2. 3-(4’ -chloro-2,4—dimethyl[1,1’-bipheny1]yl)hydroxyoxaazaspiro[4,5]dec- 3-enone; W0 2012/109125 PCTm52012/023932 3. 4-[[(6—chloropyridinyl)methyl]methylamino]-2(5H)-furanone; 4. 4-[[(6—chloropyridinyl)methyl]cyclopropylamino]-2(5H)-furanone; . 3-chloro-N2-[(15)-l-methyl(methylsulfonyl)ethyl]-N1-[2—methyl[12,2,2- tetrafluoro-l—(trifluoromethyl)ethyl]phenyl]-1,2-benzenedicarboxamide; 6. 2-cyano-N-ethylfluoromethoxy-benenesulfonamide; 7. 2-cyano-N-ethylmethoxy-benzenesu1fonamide; 8. 2-cyanodifluoromethoxy-N-ethyl-4—fluoro-benzenesulfonamide; 9. 2-cyano-3—fluoromethoxy-N—ethy1—benzenesulfonamide; . 2-cyanofluoromethoxy-N,N-dimethyl-benzenesulfonamide; 11. 2-cyano-N-ethylfluoromethoxy—N—methyl-benzenesulfonamide; 12. 2-cyanodifluoromethoxy-1\J,N-dimethylbenzenesulfon—amide; 13. 3—(difluoromethyl)—N— [2—(3 ,3—dimethylbutyl)phenyl]a 1 :methyl- lH—pyrazole—lt— carboxamide; 14. N-ethyl-2,2-dimethylpropionamide-Z-(Z,6-dichloro—a,a,a-trifluoro—p—tolyl) hydrazone; 15. 1—2,2-dichloro- l lcyclopropane—carboxamide(2,6-dichloro-a,0t,0t- tn'fluorO-p-tolyl) hydrazone ne; 16. O-{ (E—)-[2-(4-chloro-phenyl)-2—cyano—1—(2-trifluoromethylphenyl)~vinyl] } S-methyl rbonate; 17. (E)-N 1 — loro- l ,3-thiazolylmethyl)]—N2—Cyano—N 1 —methylacetamidine; 18. l—(6—chloropyridin—3—ylmethyl)—7—methylnitro—1 2,3,5,6,7—hexahydro-imidazo[1,2— a]pyridin—5-ol; 19. 4—[4-chlorophenyl—(2—buty1idine—hydrazono)methyl)]phenyl mesylate; and . N-Ethyl—2,2—dichloromethylcyclopropanecarboxamide—2—(2,6-dichloro— alpha,alpha,a[pha-trifluoro—p—tolyl)hydrazone.
Molecules of Formulas One, Two and Three may also be used in combination (such as in a compositional mixture, or a simultaneous or sequential application) with one or more compounds in the following groups: algicides, antifeedants, avicides, bactericides, bird 1121142 We ..e,. . repellents, mating disrupters, molluscicides, plant activators, plant growth regulators, U) C) -odentlcides, and/or virucides (collectively these ly named groups are defined as the “AI ). It should be noted that compounds falling within the AI Group, Insecticide Group, Fungicide Group, Herbicide Group, ide Group, or Nematicide Group might be in more than one group, because of multiple activities the compound has. For more information consult the “COMPENDIUM 0F PESTICIDE COMMON NAMES” located at http://www.alanwood.net/pesticides/indexhtml. Also consult “THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright 2006 by British Crop Production Council, or its prior or more recent editions.
SYNERGISTIC MIXTURES AND ISTS Molecules of Formulas One, Two and Three may be used with the compounds in the Insecticide Group to form synergistic mixtures where the mode of action of such compounds compared to the mode of action of the Molecules of Formula One and Two are the same, similar, or ent. es of modes of action include, but are not limited to: acetylcholinesterase inhibitor; sodium channel modulator; chitin biosynthesis tor; GABA-gated chloride channel antagonist; GABA and glutamate-gated chloride channel agonist; acetylcholine receptor agonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nic acetylcholine receptor; Midgut membrane disrupter; oxidative phosphorylation disrupter, and ryanodine or . Additionally, Molecules of Formula One and Two may be used with compounds in the Fungicide Group, Acaricide Group, Herbicide Group, or Nematicide Group to form synergistic mixtures. Furthermore, les of Formulas One, Two and Three may be used with other active compounds, such as the nds under the heading “OTHER ACTIVE COMPOUNDS”, algicides, avicides, bactericides, molluscicides, rodenticides, virucides, herbicide safeners, adjuvants, and/or surfactants to form synergistic mixtures. Generally, weight ratios of the Molecules of Formulas One, Two and Three in a istic mixture with another compound are from about 10:1 to about 1:10, preferably from about 5:1 to about 1:5, and more preferably from about 3:1, and even more preferably about 1: 1. Additionally, the following compounds are known as synergists and may be used with the molecules disclosed in Formula One: piperonyl butoxide, piprotal, propyl isome, x, sesamolin, ide, and tribufos (collectively these synergists are d as the “Synergists Group”).
FORMULATIONS A pesticide is rarely suitable for application in its pure form. It is usually necessary to add other substances so that the pesticide can be used at the required concentration and in an appropriate form, permitting ease of application, handling, transportation, storage, and maximum pesticide activity. Thus, pesticides are formulated into, for example, baits, concentrated emulsions, dusts, emulsifiable concentrates, nts, gels, granules, microencapsulations, seed treatments, sion concentrates, suspoemulsions, tablets, WO 09125 PCT/U52012/023932 water e liquids, water sible granules or dry es, wettable powders, and ultra low volume solutions. For further information on formulation types see “Catalogue of Pesticide Formulation Types and International Coding System” cal Monograph n°2, 5th Edition by CropLife International (2002).
Pesticides are applied most often as aqueous suspensions or emulsions prepared from trated formulations of such pesticides. Such water—soluble, water-suspendable, or emulsifiable formulations are either solids, usually known as wettable s, or water dispersible granules, or liquids usually known as emulsifiable concentrates, or aqueous suspensions. Wettable powders, which may be compacted to form water dispersible granules, comprise an intimate mixture of the pesticide, a carrier, and surfactants. The concentration of the pesticide is usually from about 10% to about 90% by weight. The r is usually chosen from among thCl) 9:Hm. pulgit" clays, the mentmerillonite clays, the diatemaceeus earths, or the purified silicates. ive surfactants, comprising from about 0.5% to about 10% of the wettable powder, are found among sulfonated lignins, condensed naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates, and non-ionic surfactants such as ne oxide adducts of alkyl phenols.
Emulsifiable concentrates of pesticides se a convenient concentration of a pesticide, such as from about 50 to about 500 grams per liter of liquid dissolved in a carrier that is either a water miscible solvent or a mixture of water-immiscible organic solvent and emulsifiers. Useful organic ts include aromatics, especially xylenes and petroleum fractions, especially the oiling naphthalenic and olefinic portions of petroleum such as heavy aromatic naphtha. Other organic ts may also be used, such as the terpenic solvents including rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitable emulsifiers for ifiable concentrates are chosen from conventional anionic and non-ionic surfactants.
Aqueous suspensions comprise suspensions of insoluble pesticides dispersed in an aqueous carrier at a concentration in the range from about 5 % to about 50% by weight.
Suspensrons are prepared by lineiy grinuing the pes 'ci e and vigorously mixing it into a carrier comprised of water and surfactants. Ingredients, such as inorganic salts and synthetic (A (3 r. It is often most effective to grind and mix the pesticide at the same time by preparing the aqueous mixture and homogenizing it in an implement such as a sand mill, ball mill, or piston-type homogenizer.
Pesticides may also be applied as granular compositions that are particularly useful PCT/U82012/023932 for applications to the soil. Granular compositions usually contain from about 0.5% to about % by weight of the pesticide, dispersed in a carrier that comprises clay or a similar substance. Such compositions are usually ed by dissolving the pesticide in a suitable solvent and applying it to a granular carrier which has been pre-formed to the appropriate particle size, in the range of from about 0.5 to about 3 mm. Such compositions may also be formulated by making a dough or paste of the carrier and compound and crushing and drying to obtain the desired granular particle size.
Dusts containing a pesticide are prepared by intimately mixing the pesticide in powdered form with a suitable dusty ltural carrier, such as kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1% to about 10% of the pesticide.
They can be applied as a seed dressing or as a foliage ation with a dust blower machine.
It is equally practical to apply a pesticide in the form of a solution in an appropriate organic solvent, usually petroleum oil, such as the spray oils, which are widely used in agricultural chemistry.
Pesticides can also be applied in the form of an aerosol composition. In such compositions the pesticide is dissolved or dispersed in a carrier, which is a pressure- generating lant mixture. The aerosol composition is packaged in a container from which the mixture is dispensed through an atomizing valve.
Pesticide baits are formed when the pesticide is mixed with food or an attractant or 2O both. When the pests eat the bait they also consume the pesticide. Baits may take the form of es, gels, le powders, liquids, or solids. They can be used in pest harborages.
Fumigants are pesticides that have a relatively high vapor re and hence can exist as a gas in sufficient concentrations to kill pests in soil or enclosed spaces. The toxicity of the fumigant is proportional to its tration and the exposure time. They are characterized by a good capacity for diffusion and act by penetrating the pest’s respiratory system or being absorbed through the pest’s cuticle. Fumigants are d to control stored product pests under gas proof sheets, in gas sealed rooms or buildings or in special chambers. ides can be ncapsulated by suspending the pesticide particles or droplets in plastic polymers of various types. By altering the try of the polymer or by changing factors in the processing, microcapsules can be formed of various sizes, solubility, wall thicknesses, and degrees of ability. These factors govern the speed with which the active ingredient within is released, which in turn, affects the residual performance, speed of action, and odor of the product.
Oil on concentrates are made by dissolving pesticide in a solvent that will hold W0 2012/109125 PCT/U82012/023932 the pesticide in solution. Oil solutions of a pesticide usually provide faster knockdown and kill of pests than other formulations due to the solvents themselves having idal action and the dissolution of the waxy covering of the integument increasing the speed of uptake of the pesticide. Other advantages of oil solutions include better storage stability, better penetration of crevices, and better adhesion to greasy surfaces.
Another embodiment is an oil-in-water emulsion, wherein the emulsion comprises oily globules which are each provided with a lamellar liquid crystal coating and are dispersed in an aqueous phase, wherein each oily globule comprises at least one compound which is agriculturally active, and is dually coated with a monolamellar or oligolamellar layer comprising: (1) at least one non-ionic lipophilic surface-active agent, (2) at least one non- ionic hydrophilic surface-active agent and (3) at least one ionic surface-active agent, wherein the globules having a mean particle diameter of less than 800 nanometers. i r information on the ment is disclosed in U.S. patent publication 20070027034 hed February 1, 2007, having Patent Application serial number 11/495,228. For ease of use, this ment will be ed to as “OIWE”.
For r information consult “Insect Pest Management” 2nd Edition by D. Dent, copyright CAB International (2000). Additionally, for more detailed information consult “Handbook of Pest Control — The Behavior, Life History, and Control of Household Pests” by Arnold Mallis, 9th Edition, copyright 2004 by GIE Media Inc.
OTHER FORMULATION ENTS lly, when the molecules disclosed in Formulas One, Two and Three are used in a formulation, such ation can also contain other components. These components include, but are not limited to, (this is a non—exhaustive and tually exclusive list) wetters, Spreaders, stickers, penetrants, buffers, sequestering agents, drift reduction agents, compatibility agents, anti-foam agents, cleaning agents, and emulsifiers. A few components are described forthwith.
A wetting agent is a s1 bstarce that when added to a 11' penetration power of the liquid by ng the interfacial tension between the liquid and the b) <3 surface on which it is spreading. Weting aocnts are used for two main functions in agrochemical formulations: during processing and manufacture to increase the rate of wetting of powders in water to make concentrates for soluble liquids or sion concentrates; and during mixing of a product with water in a spray tank to reduce the wetting time of wettable s and to improve the penetration of water into dispersible granules. Examples of W0 2012/109125 PCT/U82012/023932 wetting agents used in wettable powder, sion concentrate, and water-dispersible granule ations are: sodium lauryl sulfate; sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphatic alcohol ethoxylates.
A dispersing agent is a substance which adsorbs onto the surface of particles and helps to preserve the state of sion of the particles and prevents them from reaggregating. Dispersing agents are added to agrochemical formulations to facilitate dispersion and suspension during manufacture, and to ensure the particles redisperse into water in a spray tank. They are widely used in wettable powders, suspension concentrates and water-dispersible granules. Surfactants that are used as dispersing agents have the ability to adsorb strongly onto a particle surface and provide a d or steric barrier to reaggregation of particles. The most commonly used surfactants are anionic, non-ionic, or mixtures of the two types. For wettable powder formulations, the most common dispersing agents are sodium lignosulfonates. For suspension concentrates, very good adsorption and stabilization are obtained using polyelectrolytes, such as sodium naphthalene sulfonate formaldehyde condensates. Tristyrylphenol ethoxylate phosphate esters are also used. nics such as alkylarylethylene oxide condensates and EO-PO block copolymers are sometimes combined with anionics as dispersing agents for suspension concentrates. In recent years, new types of very high molecular weight polymeric surfactants have been developed as sing agents.
These have very long hydrophobic ‘backbones’ and a large number of ethylene oxide chains forming the ’ of a ‘comb’ surfactant. These high molecular weight polymers can give very good long—term stability to suspension concentrates because the hydrophobic backbones have many anchoring points onto the particle surfaces. Examples of dispersing agents used in agrochemical formulations are: sodium lignosulfonates; sodium alene sulfonate dehyde condensates; tristyrylphenol late phosphate esters; aliphatic alcohol ethoxylates; alkyl ethoxylates; EO-PO block copolymers; and graft copolymers.
An emulsifying agent is a substance which stabilizes a sion of droplets of one liquid phase in another liquid phase. Without the fying agent the two liquids would separate into two immiscible liquid phases. The most commonly used emulsifier blends n alkylphenol or aliphatic alcohol with twelve or more ne oxide units and the oil- soluble calcium salt of dodecylbenzenesulfonic acid. A range of hydrophile-lipophile balance (“HLB”) values from 8 to 18 will normally provide good stable emulsions. Emulsion stability can sometimes be improved by the addition of a small amount of an EO-PO block copolymer surfactant.
A solubilizing agent is a tant which will form micelles in water at PCT/U82012/023932 concentrations above the critical micelle concentration. The micelles are then able to dissolve or solubilize water-insoluble als inside the hydrophobic part of the e. The types of surfactants usually used for solubilization are non-ionics, sorbitan monooleates, sorbitan monooleate ethoxylates, and methyl oleate esters. tants are sometimes used, either alone or with other ves such as mineral or vegetable oils as adjuvants to spray-tank mixes to improve the biological mance of the pesticide on the target. The types of surfactants used for bioenhancement depend generally on the nature and mode of action of the pesticide. However, they are often non-ionics such as: alkyl ethoxylates; linear aliphatic alcohol ethoxylates; tic amine lates.
A carrier or diluent in an agricultural formulation is a al added to the pesticide to give a product of the required strength. Carriers are usually materials with high absorptive “I 1 vnananifina ll" materials with! w absorptive capacities. Carriers and 11 Vluva, nu; diluents are used in the formulation of dusts, wettable powders, granules and water‘ dispersible granules.
Organic solvents are used mainly in the formulation of emulsifiable concentrates, oil- in-water ons, suspoemulsions, and ultra low volume formulations, and to a lesser extent, granular formulations. Sometimes mixtures of ts are used. The first main groups of solvents are aliphatic paraffinic oils such as kerosene or refined paraffins. The second main group (and the most common) comprises the aromatic solvents such as xylene and higher molecular weight fractions of C9 and C10 aromatic solvents. Chlorinated hydrocarbons are useful as cosolvents to prevent crystallization of pesticides when the formulation is emulsified into water. ls are sometimes used as cosolvents to increase solvent power. Other solvents may include vegetable oils, seed oils, and esters of ble and seed oils.
Thickeners or gelling agents are used mainly in the formulation of suspension concentrates, emulsions and suspoemulsions to modify the rheology or flow properties of the liquid and to prevent separation and settling of the dispersed les or droplets.
Thickening, gelling, and anti-settling agents generally fall into two categories, namely water- insoluble particulates and water-soluble polymers. It is possible to produce suspension concentrate formulations using clays and silicas. Examples of these types of materials, include, but are not limited to, montmorillonite, ite, ium aluminum silicate, and attapulgite. Water-soluble polysaccharides have been used as thickening-gelling agents for many years. The types of polysaccharides most commonly used are natural extracts of seeds and seaweeds or are synthetic derivatives of cellulose. Examples of these types of materials include, but are not limited to, guar gum; locust bean gum; eenam; alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC); hydroxyethyl cellulose (HEC). Other types of anti-settling agents are based on modified starches, polyacrylates, polyvinyl l and hylene oxide. Another good anti-settling agent is xanthan gum.
Microorganisms can cause spoilage of formulated products. Therefore preservation agents are used to eliminate or reduce their effect. Examples of such agents include, but are not limited to: nic acid and its sodium salt; sorbic acid and its sodium or potassium salts; benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt; methyl p- hydroxybenzoate; and 1,2-benzisothiazolinone (BIT), The presence of surfactants often causes water-based ations to foam during mixing operations in production and in application through a spray tank. In order to reduce the cy to foam, anti—foam agents are often added either during the production stage or before filling into bottles. Generally, there are two types of anti—foam agents, namely Silicones and non—Silicones. Silicones are usually aqueous emulsions of dimethyl polysiloxane, while the non-silicone anti-foam agents are water-insoluble oils, such as octanol and nonanol, or . In both cases, the function of the anti—foam agent is to displace the tant from the air—water interface.
“Green” agents (e. g., adjuvants, surfactants, solvents) can reduce the overall environmental footprint of crop protection formulations. Green agents are biodegradable and generally d from natural and/or sustainable sources, 6. g. plant and animal sources.
Specific examples are: vegetable oils, seed oils, and esters thereof, also lated alkyl polyglucosides.
For further information, see “Chemistry and Technology of emical Formulations” edited by DA. Knowles, ght 1998 by Kluwer Academic Publishers.
Also see “Insecticides in lture and Environment — Retrospects and Prospects” by AS.
Perry, I. Yamamoto, I. Ishaaya, and R. Perry, copyright 1998 by Springer-Verlag.
PESTS In general, the Molecules of Formula Formulas One, Two and Three may be used to control pests e. g. beetles, earwigs, cockroaches, flies. aphids, scales, whiteflies, leafhoppers, ants, wasps, termites, moths, butterflies, lice, grasshoppers, locusts, crickets, fleas, thrips, bristletails, mites, ticks, nematodes, and symphylans.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Phyla da and/or Arthropoda.
WO 09125 PCTRISZ012/023932 In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Subphyla Chelicerata, Myriapoda, and/or Hexapoda.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests in the Classes of Arachnida, Symphyla, and/or Insecta.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Anoplura. A haustive list of particular genera includes, but is not limited to, Haematopinus sppi, Hoplopleura spp., Linognathus spp., Pediculus spp., and Polyplax spp. A non-exhaustive list of particular s includes, but is not limited to, Haematopinus asini, Haematopinus suis, Linognathus setosus, Linognazhus ovillus, Pediculus humanus 's, Pediculus s humanus, and s pubis.
In another embodiment, the Molecules of Formulas One, Two and Three may be used tv sensep—I 1‘pCre ip fh. “Av 01-minuv- Cglnnngerg. A_ yvuuu . Avvla . -. A v._- ‘4' but is not limited to, Acanthoscelides spp., Agriotes spp., Anthonomus spp., Apion spp., Apogonia spp., Aulacophora spp., s spp., Cerosterna spp., Cerotoma spp., Ceutorhynchus spp., Chaetocnema spp., Colaspis spp., Ctenicera spp., Curculio spp., Cyclocephala spp., Diabrozica spp., Hypera spp., Ips spp., Lyctus spp., elis spp., Meligethes spp., ynchus spp., orus spp., Phyllophaga spp., treta spp., Rhizotrogus spp., Rhynchites spp., Rhynchophorus spp., Scolytus spp., phorus spp., Sitophilus spp., and Tribolium spp. A non—exhaustive list of particular species includes, but is not limited to, Acanthoscelides obtectus, Agrilus planipennis, Anoplophora glabripennis, Anthonomus grandis, Azaenius spretulus, Atomaria linearis, Bothynoderes punctiventris, Bruchus pisorum, Callosobruchus maculatus, Carpophilus hemipterus, Cassida vittata, Cerotoma trifurcata, Ceutorhynchus assimilis, Ceutorhynchus napi, Conodems scalaris, Conoderus stigmosus, Conotrachelus nenuphar, Cotinis nitida, Crioceris asparagi, Cryptolestesferrugineus, Cryptolestes pusillus, lestes turcicus, Cylindrocopturus adspersus, Deporaus marginatus, Dermestes lardarius, Dermestes maculatus, Epilachna varivestis, Faustinus cubae, Hylobius pales, Hypera postica, enemus hampei, Lasioderma serricorne, Leprinotarsa decemlineata, Liogenysfuscus, ys suturalis, Lissorhoptrus oryzophz’lus, Maecolaspisjoliveti, Melanotus communis, Meligethes aeneus, Melolontha melolontha, Oberea brevis, Oberea linearis, Oryctes rhinoceros, Ortvzaephilus mercator, 0ryzaephilus surinamensis, Oulema melanopus, Oulema oryzae, Phyllophaga na, iajaponica, Prostephanus truncatus, Rhyzopertha d0minica,, Sitona us, Sitophilus ius, ilus oryzae, Sitophilus zeamais, Stegobium paniceum, Tribolium castaneum, Tribolium confusum, Trogoderma variabile, and Zabrus tenebrioides.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Dermaptera.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Blattaria. A non—exhaustive list of particular species es, but is not limited to, Blattella germanica, Blatta alis, Parcoblatta pennsylvanica, Periplaneta americana, Periplaneta australasiae, Periplaneta brunnea, aneta fitliginosa, Pycnoscelus mensis, and Supella longipalpa.
In another embodiment, the Molecules of as One, Two and Three may be used to control pests of the Order Diptera. A non-exhaustive list of particular genera includes, but is not limited to, Aedes spp., Agromyza spp., epha spp., Anopheles spp., Bactrocera spp., Ceratitis spp., Chrysops spp., Cochliomyz'a spp., Contarinia spp., Culex spp., Dasineura spp., Delia spp., Drosophila spp., Fannia spp., ia spp., Liriomyza spp., Musca spp., Phorbia spp., Tabanus spp., and Tipula spp. A non-exhaustive list of particular species includes, but is not d to, Agromyzafrontella, Anastrepha sa, epha ludens, Anastrepha obliqa, cera cucurbitae, Bactrocera dorsalis, Bactroce ra invadens, Bactrocera zonata, Ceratitis capitata, Dasineura cae, Delia platura, Fannia canicularis, Fannia scalaris, Gasterophilus intestinalis, Gracillia perseae, Haematobia irritans, Hypoderma lineamm, Liriomyza brassicae, Melophagus ovinus, Musca autumnalis, Musca domestica, Oestrus ovis, Oscinella frit, Pegomya betae, Psila rosae, Rhagoletis cerasi, Rhagoletis pomonella, Rhagoletis mendax, Sitodiplosis mosellana, and Stomoxys calcitrans.
In r embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Hemiptera. A non-exhaustive list of particular genera includes, but is not limited to, Adelges spp,, Aulacaspis spp., Aphrophora spp., Aphis spp., Bemisia spp., Ceroplastes spp., Chionaspis spp., Chrysomphalus spp., Coccus spp., Empoasca spp., Lepidosaphes spp., Zagynotomus spp., Lygus spp., Macrosiphum spp., Nephotem'x spp., Nezara spp., Philaenus spp., Phytocoris spp., Piezodorus spp., Planococcus spp., coccus spp., Rhopalosiphum spp., Saissetia spp., Therioaphis spp., Toumeyella spp., Toxoptera spp., Trialeurodes spp., Triatoma spp. and Unaspis spp. A non-exhaustive list of particular species includes, but: is not limited to, Acrosternum hilare, Acyrthosiphon pisum, Aleyrodes proletella, Aleurodicus dispersus, Aleurothrixusfloccosus, a biguttula ula, Aonidiella aurantii, Aphis gossypii, Aphis glycines, Aphis pomi, Aulacorthum solam', Bemisia argentifolii, Bemisia tabaci, Blissus leucopterus, Brachycorynella gi, Brevennia rehi, Brevicoryne brassicae, Calocoris norvegicus, Ceroplastes rubens, Cimex W0 09125 PCT/U82012/023932 erus, Cimex lectularius, Dagbertusfasciatus, opsfurcatus, his noxia, Diaphorina citri, Dysaphz’s plantaginea, Dysdercus suturellus, Edessa meditabunda, Eriosoma lam'gerum, Emygaster maura, Euschistus heros, Euschistus servus, Helopeltis antonii, ltis theivora, Icerya purchasi, Idioscopus nitidulus, Laodelphax striatellus, Leptocorisa ius, Leptocorisa varicornis, Lygus hesperus, Maconellicoccus hirsutus, Macrosiphum euphorbiae, Macrosiphum granarium, Macrosiphum rosae, Macrosteles quadrilineatus, Mahanarvafrimbiolata, Metopolophium dirhodum, Mictis longicomis, Myzus persicae, ettix cinctipes, Neurocolpus longirostris, Nezara viridula, Nilaparvata lugens, Parlatoria pergarzdii, Parlatoria ziziphi, Peregrinus maidis, Phylloxera vitifoliaé, Physokermes ,, Phytocoris californicus, Phytocoris relativus, Piezodorus guildinii, ocapsus lineatus, Psallus vaccinicola, Pseudacysta perseae, coccus brevipes, Quudlwpiuzu us pal/ticiasus, “no"alosi"..um muiuis, Rhopalosiphum padi, .ia oleae, Scaptocoris castanea, Schizaphis graminum, Sitobion avenae, Sogatellafurcifera, Trialeurodes vaporariorum, Trialeurodes abutiloneus, Unaspis yanonensis, and Zulia entrerriana.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order ptera. A non-exhaustive list of particular genera es, but is not limited to, Acramyrmex spp., Atta spp., Camponotus spp., Diprion spp., Formica spp., Monomorium spp., rion spp., Pogonomyrmex spp., Polistes spp., Solenopsis spp., Vespula spp., and Xylocopa spp. A non—exhaustive list of particular species includes, but is not limited to, a rosae, Atta texana, Iridomyrmex humilis, Monomorium minimum, Monomorium pharaonis, Solenopsis invicta, Solenopsis za, Solenopsis molesta, Solenopsis richtery, Solenopsis xyloni, and Tapinoma sessile.
In r embodiment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order ra. A non-exhaustive list of particular genera includes, but is not limited to, Coptotermes spp., Cornitermes spp., Cryptotermes sppi, Heterotermes spp., Kalotermes spp., Incisitermes spp., Macrotermes spp., Marginitermes spp., Reiculiermt..rmes spp., echeworhimonte ev spp., and Zootermopsis spp. A non-exhaustive list of particular species includes, but is not limited (A CD ' %Sm(a <5 3OS3...a,thus, Coptozermesfrenchi, Coptotermesformosanus, Heterotermes aureus, Microtermes obesi, Reticulitermes banyulensis, Reticulitermes grassei, Reticulitermesflavipes, Reticulitermes hageni, Reticulitermes hesperus, Reticulitermes santonensis, Reticulitermes speratus, Reticulitermes tibialis, and Reticulitermes virginicus.
In another embodiment, the Molecules of Formulas One, Two and Three may be used PCT/U82012/023932 to control pests of the Order Lepidoptera. A non-exhaustive list of particular genera includes, but is not limited to, Adoxophyes spp., Agrotis spp., taenia sppi, Cacoecia spp., Caloptilia spp., Chilo spp., Chrysodeixis spp., Colias spp., Crambus spp., Diaphania spp., Diatraea spp., Earias spp., Ephestia spp., is spp., Feltia spp., Gortyna spp., Helicoverpa spp., Heliothis sppi, Indarbela spp., olletis spp., Loxagrotis spp., Malacosoma spp., Peridroma spp., Phyllonorycter spp., Pseudaletia spp., Sesamia spp., Spodoptera spp., hedon spp., and Yponomeuta spp. A non-exhaustive list of particular species includes, but is not limited to, Achaea , Adoxophyes orana, Agron‘s n, Alabama argillacea, Amorbia cuneana, Amyelois transitella, ptodes defectaria, Anarsia lineatella, Anomis sabulifera, rsia gemmatalis, Archips argyrospila, Archips rosana, Argyrotaenia citrana, Autographa gamma, Bonagota cranaodes, Borbo cinnara, atrix thurberiella, Capua reticulana, Carposina niponensis, Chlumetia transversa, Choristoneura rosacearza, Cnaphalocrocis medinalis, morpha cramerella, Cossus cossus, Cydia caryana, Cydia funebrana, Cydia molesta, Cydia nigricana, Cydia lla, Darna didacta, ea saccharalis, Diatraea grandiosella, Earias insulana, Earias vittella, Ecdytolopha aurantianum, Elasmopalpus lignosellus, Ephestia cautella, Ephestia elutella, Ephestia kuehniella, Epinotia aporema, Epiphyas postvittana, Erionota thrax, Eupoecilia ella, Euxoa aris, Grapholita molesta, Hedylepta indicata, Helicoverpa armigera, Helicoverpa zea, Heliothis virescens, Hellula undalis, Keiferia lycopersicella, Leucinodes orbonalis, tera coffeella, Leucoptera liella, a botrana, Loxagrotis albicosla, Lymantria dispar, Lyonetia Clerkella, Mahasena corbetti, Mamestra brassicae, Maruca testulalis, Metisa plana, Mythimna unipuncta, Neoleucinodes elegantalis, Nymphula depunctalis, Operophtera brumata, Ostrinia nubilalis, Oxydia vesulia, Pandemis cerasana, Pandemis heparana, Papilio demodocus, Pectinophora iella, Peridroma saucia, Perileucoptera coffeella, Phthorimaea lella, Phyllocnistis citrella, Pieris rapae, Plathypena scabra, Plodia interpunctella, Plutella xylostella, Polychrosis viteana, Prays endocarpa, Prays oleae, Pseudaletia unipuncta, Pseudoplusia includens, Rachiplusia nu, Scirpophaga incertulas, Sesamia inferens, Sesamia nonagrioides, Setora nitens, Sitotroga cerealella, nothis pilleriana, Spodoptera exigua, Spodoptera frugiperda, Spodoptera eridam'a, Theda basilides, Tineola bisselliella, Trichoplusia ni, Tum absoluta, Zeuzera cofieae, and Zeuzera pyrina.
In another ment, the Molecules of Formulas One, Two and Three may be used to control pests of the Order Mallophaga. A non-exhaustive list of particular genera es, but is not limited to, Anaticola spp., Bovicola spp., Chelopistes spp., Goniodes sppi, PCT/U82012/023932 Menacanthus spp., and Trichodectes spp. A non-exhaustive list of particular species includes, but is not limited to, Bovicola bovis, Bovicola caprae, Bovicola ovis, Chelopistes meleagridis, Goniodes dissimilis, Goniodes gigas, Menacanthus neus, Menopon gallinae, and Trichodectes canis.
In another embodiment, the Molecules of as One, Two and Three may be used to control pests of the Order Orthoptera. A non—exhaustive list of particular genera es, but is not d to, Melanoplus spp., and Pterophylla spp. A non-exhaustive list of particular species includes, but is not d to, Anabrus simplex, talpa na, Gryllotalpa australis, Gryllotalpa brachyptera, Gryllotalpa hexadactyla, Locusta oria, Microcentrum retinerve, Schistocerca gregaria, and Scudderia furcata.
In another embodiment, the Molecules of Formulas One, Two and Three may be used Order Siphenaptera. A nen~exhaustive 1‘ includes, but is not limited to, Ceratophyllus gallinae, Ceratophyllus niger, Ctenocephalides canis, Ctenocephalidesfelis, and Pulex ns.
In another embodiment, the Molecules of as One, Two and Three may be used to control pests of the Order Thysanoptera. A non-exhaustive list of particular genera includes, but is not d to, Caliothrips spp., Frankliniella spp., Scirtothrips spp., and Thrips spp. A non-exhaustive list of particular sp. includes, but is not limited to, Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella williamsi, Heliothrips haemorrhoidalis, Rhipiphorothrips cruentatus, Scirtothrips citri, Scirtothrips dorsalis, and Taeniolhrips rhopalantennalis, Thrips hawaiiensis, Thrips nigropilosus, Thrips orientalis, Thrips tabaci.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to l pests of the Order Thysanura. A non-exhaustive list of particular genera includes, but is not limited to, Lepisma spp. and bia spp.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to l pests of the Order Acarina. A non-exhaustive list of particular genera includes, but is not limited to, Acaras spp., Aczwops spp., Boophilus spp., Demadex spp., Derrmcemor spp., Epitrimerus spp., yes spp., Ixodes spp., Oligonychus spp., Panonychus spp., DJ CD Rhizoglyphus spp,, and Tetranychus spp, A non-exhaustive list of particular species includes, but is not limited t0, Acarapis woodi, Acarus siro, Aceria mangiferae, Aculops lycopersici, Aculus pelekassi, Aculus schlechtendali, Amblyomma americanum, alpus obovatus, Brevipalpus phoenicis, Dermacentor variabilis, Dermatophagoides pteronyssinus, anychus carpini, Notoedres cati, Oligonychus cofleae, Oligonychus ilicis, Panonychus citri, Panonychus ulmi, Phyllocoptruta oleivora, Polyphagotarsonemus Zatus, Rhipicephalus sanguineus, Sarcoptes scabiei, Tegolophus perseaflorae, Tetranychus urticae, and Varroa destructor.
In another embodiment, the Molecules of Formulas One, Two and Three may be used to control pest of the Order Symphyla. A non-exhaustive list of particular sp. includes, but is not limited to, Scutigerella immaculata.
In another embodiment, the les of Formulas One, Two and Three may be used to control pests of the Phylum Nematoda. A haustive list of particular genera includes, but is not limited to, Aphelenchoides spp., Belonolaimus spp., Criconemella spp., Ditylenchus spp., Heterodera spp., manniella spp., Hoplolaimus spp., Meloidogyne spp., Pratylenchus spp., and Radopholus spp. A non-exhaustive list of particular sp. includes, but is not limited to, Dirofilaria immitis, dera zeae, Meloidogyne incognita, Meloidogyne javanica, Onchocerca valvulus, Radopholus similz‘s, and Rotylenchulus reniformis.
For additional information consult “HANDBOOK OF PEST CONTROL — THE BEHAVIOR, LIFE HISTORY, AND L OF HOUSEHOLD PESTS” by Arnold Mallis, 9th n, copyright 2004 by GIE Media Inc.
APPLICATIONS Molecules of Formulas One, Two and Three are generally used in amounts from about 0.01 grams per hectare to about 5000 grams per hectare to provide control. Amounts from about 0.1 grams per hectare to about 500 grams per e are generally red, and amounts from about 1 gram per hectare to about 50 grams per hectare are generally more preferred.
The area to which a molecule of Formulas One, Two and Three is applied can be any area inhabited (or maybe inhabited, or traversed by) a pest, for example: where crops, trees, fruits, cereals, fodder species, vines, turf and ornamental plants, are growing; where domesticated animals are residing; the or or or surfaces of ngs (such as places where grains are stored), the materials of construction used in building (such as impregnated wood), and the soil around buildings. Particular crop areas to use a molecule of Formula One include areas where apples, corn, sunflowers, cotton, soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, a, lettuce, strawberries, tomatoes, peppers, ers, pears, tobacco, s, sugar beets, beans and other valuable crops are growing or the seeds thereof are going to be planted. It is also advantageous to use aluminum PCT/U52012/023932 sulfate with a molecule of Formula One when growing s plants.
Controlling pests generally means that pest populations, pest activity, or both, are reduced in an area. This can come about when: pest populations are repulsed from an area; when pests are incapacitated in or around an area; or pests are exterminated, in whole, or in part, in or around an area. Of course, a combination of these results can occur. Generally, pest populations, activity, or both are desirably reduced more than fifty percent, preferably more than 90 percent. Generally, the area is not in or on a human; consequently, the locus is generally a non-human area.
The Molecules of Formulas One, Two and Three may be used in mixtures, d simultaneously or sequentially, alone or with other compounds to enhance plant vigor (e. g. to grow a better root system, to better withstand stressful growing conditions). Such other compounds are, for example, compounds tuat modulate plant ethylene receptors, ...ost notably 1-methylcyclopropene (also known as l-MCP).
The Molecules of as One, Two and Three can be applied to the foliar and fruiting portions of plants to control pests. The molecules will either come in direct t with the pest, or the pest will consume the pesticide when eating leaf, fruit mass, or extracting sap, that contains the pesticide. The Molecules of Formulas One, Two and Three can also be applied to the soil, and when applied in this manner, root and stem g pests can be controlled. The roots can absorb a molecule taking it up into the foliar portions of the plant to control above ground chewing and sap feeding pests.
Generally, with baits, the baits are placed in the ground where, for example, termites can come into contact with, and/or be attracted to, the bait. Baits can also be d to a surface of a building, (horizontal, al, or slant surface) where, for example, ants, termites, cockroaches, and flies, can come into t with, and/or be attracted to, the bait.
Baits can comprise a molecule of Formula One, Two or Three.
The Molecules of Formulas One, Two and Three can be encapsulated inside, or placed on the surface of a e. The size of the capsules can range from nanometer size (aver... 10,900 nanometers in dia.--ete-) to eter size (about 10-900 microns in diameter).
Because of the unique ability of the eggs of some pests to resist certain pesticides, repeated applications of the Formula One, Two or Three may be desirable to l newly emerged larvae. ic movement of pesticides in plants may be utilized to control pests on one portion of the plant by applying (for example by spraying an area) the Molecules of Formula PCT/U82012/023932 One, Two or Three to a different portion of the plant. For example, control of foliar~feeding s can be achieved by drip irrigation or furrow application, by treating the soil with for example pre- or post-planting soil drench, or by treating the seeds of a plant before planting.
Seed treatment can be applied to all types of seeds, including those from which plants genetically modified to express specialized traits will germinate. entative examples include those expressing proteins toxic to invertebrate pests, such as Bacillus thuringiensis or other insecticidal toxins, those expressing herbicide resistance, such as “Roundup Ready” seed, or those with “stacked” n genes expressing insecticidal toxins, herbicide resistance, nutrition-enhancement, drought resistance, or any other beneficial traits.
Furthermore, such seed treatments with the Molecules of Formula One, Two or Three may further enhance the ability of a plant to better withstand stressful growing conditions. This results in a healthier, more Vigorous plant, which can lead to higher yields at harvest time.
Generally, about 1 gram of the Molecules of Formula One, Two or Three to about 500 grams per 0 seeds is expected to provide good s, amounts from about 10 grams to about 100 grams per 100,000 seeds is ed to e better benefits, and amounts from about 25 grams to about 75 grams per 100,000 seeds is expected to provide even better benefits.
It should be readily apparent that the Molecules of Formulas One, Two and Three may be used on, in, or around plants genetically modified to express specialized traits, such as us thuringiensis or other icidal toxins, or those expressing herbicide ance, ” foreign or those with “stack genes expressing icidal toxins, herbicide resistance, nutrition-enhancement, or any other beneficial traits.
The Molecules of Formulas One, Two and Three may be used for lling endoparasites and ectoparasites in the veterinary medicine sector or in the field of non-human animal keeping. The Molecules of Formulas One, Two and Three are applied, such as by oral administration in the form of, for example, tablets, capsules, drinks, granules, by dermal application in the form of, for example, dipping, spraying, g on, spotting on, and dusting, and by parenteral administration in the form of, for example, an injection.
The Molecules of Formulas One, Two and Three may also be employed advantageously in livestock keeping, for example, cattle, sheep, pigs, chickens, and geese.
They may also be ed advantageously in pets such as, horses, dogs, and cats. Particular pests to control would be fleas and ticks that are bothersome to such animals. Suitable formulations are stered orally to the animals with the drinking water or feed. The dosages and ations that are suitable depend on the species.
WO 09125 PCT/USZ012/023932 The Molecules of Formulas One, Two and Three may also be used for controlling parasitic worms, especially of the intestine, in the animals listed above.
The Molecules of a One, Two, and Three may also be employed in therapeutic methods for human health care. Such methods include, but are limited to, oral administration in the form of, for example, tablets, capsules, drinks, granules, and by dermal application.
Pests around the world have been migrating to new environments (for such pest) and thereafter becoming a new invasive species in such new environment. The Molecules of Formula One and Two may also be used on such new invasive species to control them in such new environment.
The Molecules of Formula One, Two, and Three may also be used in an area where plants, such as crops, are growing (e.g. pre-planting, planting, pre-harvesting) and where there are low levels (even no l presence) of pests that can comme-eially d mage sue plants. The use of such molecules in such area is to t the plants being grown in the area.
Such benefits, may include, but are not limited to, improving the health of a plant, improving the yield of a plant (e.g. increased biomass and/or sed t of valuable ingredients), improving the vigor of a plant (6. g. improved plant growth and/or greener leaves), improving the quality of a plant (ag. improved content or ition of certain ingredients), and improving the tolerance to abiotic and/or biotic stress of the plant.
Before a pesticide can be used or sold cially, such pesticide undergoes lengthy evaluation processes by various mental authorities (local, regional, state, national, and international). Voluminous data requirements are ed by regulatory authorities and must be addressed through data generation and submission by the product registrant or by a third party on the product registrant's behalf, often using a computer with a connection to the World Wide Web. These governmental authorities then review such data and if a determination of safety is concluded, provide the potential user or seller with product registration approval. Thereafter, in that locality where the product registration is granted and ted, such user or seller may use or sell such pesticide.
Three can be tested to determine its _ _ ___oleeu1e according to a One, Two, and efficacy against pests. Furthermore, mode of action studies can be conducted to determine if said molecule has a different mode of action than other pesticides. Thereafter, such acquired data can be inated, such as by the internet, to third parties.
The headings in this document are for convenience only and must not be used to interpret any portion hereof.
TABLE SECTION BAW & CEW Rating Table % Control (or Mortality) ‘50- 100 More than 0 — Less than 50 No ty noticed in this bioassay GPA Rating Table % Control (or Mortality) 80— 100 More than 0 — Less than 80 Not Tested No activity noticed in this bioassay Z012/023932 Table 1: Structures for Compounds WO 09125 PCT/U82012/023932 WO 09125 Structure F F g 1-24 HN “ownN\ )0 l W0 09125 PCT/U52012/023932 PCT/USZ012/023932 Table 2: Analytical Data for Compounds in Table 1.
Synthesis MS mp (°C) 1H NMR (5)1 Method I: 551 209—211 (DMSO-ds) 12.06 (s, 1H), 10.19 (s, 1H), 9.42 (s, 1H), 8.22 (s, 1H), 8.17-8.03 (m, 5H), 7.66-7.57 (m, 4H), 7.42-7.38 (m, 2H) 220—225 ) 9.30 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.81 (m, 4H), 7.41 (d, J = 8.4 Hz, 2H), 7.19 (m, 3H), 2.35 (s, 6H) C 555 206—209 113) 8.90 (s. 1H), 8.80 (s. 1H). 8.6 (s, I I (M+H) I I 1H), 8.28 (d, J = 8.4 Hz, 2H), 8.9-8.7 (m, I l | I 4H), 7.4 (d, J = 8.6 Hz, 2H), 6.7 (s, 2H), 3.80 (s, 3H), 2.39 (s, 3H), 2.32 (s, 6H) I 0 (CDC13) 9.88 (s, 1H), 8.61 (s, 1H), 8.60 (s, 1H), 8.27 (d, J = 8.4 Hz, 2H), 7.9 (s, 1H), 7.9-7.7 (In, 4H), 7.4 (d, J = 8.6 Hz, 2H), 6.7 (s, 2H), 3.81 (s, 3H), 2.33 (s, 6H) 195—199 (CDC13) 10.2 (s, 1H), 8.7 (s, 1H), 8.6 (s, 1H), 8.25 (d, J: 8.4 Hz, 2H), 8.0 (s, 1H), 7.82 (m, 4H), 7.4 (d, J: 8.4 Hz, 2H), 7.0 (s, 2H), 3.82 (s, 3H) 233—236 (CDC13) 9.89 (s, 1H), 8.60 (s, 2H), 8.25 (d, J = 8.5 Hz, 2H), 7.95 (s, 1H), 7.88-7.70 (In, 4H), 7.41 (d, J: 9.0 Hz, 2H), 6.70 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H) 525 230—240 (CDC13) 9.93 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 9.5 Hz, 2H), 7.95 (s, 1H), 7.86-7.75 (m, 4H), 6.69 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H) 56 234~238 (CDCI3) 9.62 (s, 1H), 8.70 (s, 1H), 8.60 (s, 44. 1H\ 82A {A I- 8.4 Ln, aux 7 92/\s, 1H), 111},u u \u, u — '7 11b, all}, I 7.86-7.75 (m, 4H), 7.41 (d, J: 90 Hz, 2H), 7.18 (In, 3H), 2.35 (s, 6H) I I 1-12 I c 577 I197—200 (c0013) 10.2 (s, 1H), 8.90 (s, 1H), 8.62 (s, l ! 1 8.25 (d, J = 8.4 Hz, 2H), 7.98 (s, 1H), , (M+H) , 1H), I 7.9—7.7 (m, 4H), 7.4(111, 3H), 6.8 (m, 2H), 3.82 (s, 3H), 2.37 (s, 3H) PCT/U52012/023932 Synthesis MS mp (°C) 1H NMR (5)1 Method 1-13 B 541 6 ) 9.9 (s, 1H), 8.6 (s, 1H), 8.23 (d, J: (M+H) 8.4 Hz, 2H), 7.9 (s, 1H), 7.8 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.7 (d, J = 7 Hz, 1H), 7.45-7.35 (m, 4H), 6.91 (d, J: 8 Hz, 2H), 5.73 (m, 1H), 3.80 (s, 3H), 1.65 (d, J: 7.2 Hz, 3H) B 559 196—203 (CDC13)9.32(s, 1H), 8.6 (s, 1H), 8.22 (d, J (M+H) = 8.4 Hz, 2H), 7.85-7.7 (m, 5H), 7.6 (d, J = 6 Hz, 1H), 7.4 (d, J = 8.5 Hz, 2H), 7.25—7.15 (m, 2H), 6.93 (m, 1H), 5.7 (m, 1H), 3.89 (s, 3H), 1.67 (d, J = 6 Hz, 3H) B 201—206 (CDC13)9.32(S, 1H), 8.61 (s, 1H), 8.27 (d, J = 8.4 Hz, 2H), 7.9-7.7 (m, 6H), 7.5—7.3 (m, 7H), 5.76 (m, 1H), 1.67 (d, J: 7 Hz, 3H) I-16 218—225 (CDC13) 9.37 (s, 1H), 8.63 (s, 1H), 8.60 (S, 1H), 8.26 (d, J: 8.4 Hz, 2H), 7.89 (S, 1H), 7.85—7.76 (m, 4H), 7.41 (d, J = 8.4 Hz, 2H), 6.97 (s, 2H), 2.32 (S, 3H), 2.30 (s, 6H) I-l7 168—180 (CDC13) 10.2 (s, 1H), 9.07 (s, 1H), 8.63 (S, 1H), 8.25 (d, J: 8.4 Hz, 2H), 8.0 (S, 1H), 7.9—7.7 (m, 4H), 7.65 (d, J = 8 HZ, 1H), 7.4— 7.25 (m, 5H), 3.25 (heptet, J = 7 Hz, 1H), 1.35 (d, J: 7 Hz, 6H) 216—221 (CDC13)6 9.29 (s, 1H), 8.87 (s, 1H), 8.59 (s, 1H), 8.31 — 8.19 (m, 2H), 7.90 — 7.84 (m, 2H), 7.85 .. 7.79 (m, 2H), 7.73 (dd, J = 7.5, [-18 1.7 Hz, 1H), 7.39 (dd, J = 12.6, 5.1 Hz, 3H), 7.35 - 7.27 (m, 2H), 3.37 — 3.04 (m, 1H), 2.40 (s, 3H), 1.29 (d, J = 7.5 Hz, 6H) C 509 223-225 (CDC13) 6 9.74 (s, 1H), 9.06 (s, 1H), 8.69 (M+1) (s, 1H), 8.31— 8.20 (m, 2H), 7.98 — 7.84 (m, I-l9 3H), 7.80 (m, 4H), 7.65 (d, J: 1.4 Hz, 1H), 7.43 — 7.28 (m, 3H), 3.19 (heptet, J = 6.9 Hz, 1H), 1.32 (d, J = 6.9 Hz, 6H) W0 2012/109125 Synthesis MS mp (°C) 1H NMR(5)1 Method 538 220 (dec) (CDC13) 5 952 (s, 1H), 9.31 (s, 1H), 8.66 (d, (M+H) J= 8.,2Hz 1H)8.60(s, 1H)8.25(dJ= 8.4 Hz, 2H), 7.87 (s, 1H), 7.86 - 7.80 (m, 2H), 7.77 (d, J = 8.4 Hz, 2H), 7.41 (d, J = 8.3 Hz, 2H), 7.32 (ddd, J = 139.1 7.2, 4.3 Hz, 1H), 7.24 — 7.15 (m, 2H), 6.27 (s, 1H), 2.03 (d, J: 1.3 Hz, 3H), 1.73 (d, J = 1.1 Hz, 3H) 540 207210; (CDC13) 5 9.48 (s, 1H), 9.14 (s, 1H), 8.60 (s, | 1 (M+H) | 215218 1H), 8.26 (d, J: 8.4 Hz, 2H), 7.92 (s, 1H), 7.87 (d, J : 7.7 Hz, 1H), 7.84 — 7.76 (m, 4H), I-21 ‘C 7.4,=0(dJ 8.3,Hz 2H),7.=30(dt] 82 37 Hz - 723(m 2H) 257(d 1:72 1 1 le, 2H),.193(dq, J:18.,66.7Hz, 1H), I (dJ 6.,6Hz 6H) 210—215 (CDC13)5 9.46 (s, 1H), 9.05 (s, 1H), 8.60 (s, 1H), 8.26 (d, J : 8.4 Hz, 2H), 7.91 (s, 1H), 7.84 — 7.74 (m, 4H), 7.69 (d, J: 7.4 Hz, 1H), 7.40 (d, J: 8.3 Hz, 2H), 7.36 — 7.27 (m, 3H), 2.91 (dt, J: 13.9, 6.9 Hz, 1H), 1.75 — 1.58 (m, 2H), 1.30 (d, J : 6.9 Hz, 3H), 0.92 (t, J: 7.4 Hz, 3H). 213-216 (CDC13)6 9.41 (s, 1H), 9.01 (s, 1H), 8.74 (d, J=7.7 Hz, 1H), 8.60 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 7.86 - 7.78 (m, 2H), 7.69 (s, 1H), 7.57 — 7.44 (m, 6H), 7.42 (d, J : 9.1 Hz, 2H), 7.37 — 7.27 (m, 4H). 200-206; (CDCla) 8 9.65 (d, J = 17.9 Hz, 1H), 9.20 (s, 210-211 1H), 8.60 (S, 1H), 8.27 (dd, J = 8.0, 4.5 Hz, 3H), 7.89 (S, 1H), 7.86 - 7.75 (m, 4H), 7.41 (d, J: 8.3 Hz, 2H), 7.30 - 7.27 (m, 1H), 7.18 (q, J: 7.8 Hz, 2H), 2.00 - 1.90 (m, 1H), 1.09 - 1.01 (m, 2H), 0.81 - 0.73 (m, 2H).
(DMSO-ds) 5 12.13 (s, 1H), 10.07 (s, 1H), | 1 ‘Hz, 2H),8.1-3 806(m, 2H), 8.01- 7.,98(m31—1) 7,63(d 7:84Hz 71—1)738— 726(m9.44 (s, 1H), 8.23 (s, 1H), 8.16 (d, J: 8.4 1-25 ' I3H),71.23(t, JHF= 741Hz, 1H) .27gd(, 7.,=81(dtJ 8.548.8Hz: Hz, 2H), 7.31 (s, 2H), 2.31 (s, Synthesis Method 556 190192 )89.,39(s 1H), 915 (s 1H), 8.61 (s, (M+H) 1H), 8.29(d, J: 8.,4Hz 2H), 8.16 8.,05(m I-27 2H), 7.95 - 7.85 (m, 3H), 7.85 - 7.76 (m, 4H), 7.41 (d, J: 8.3 Hz, 2H), 4.39 (q, J=7.1 Hz, 2H), 1.41 (t, J: 7.1 Hz, 3H) 528 219-221 (300 MHz, CDClg) 8 10.17 (s, 1H), 9.09 (s, (M+H) 1H), 9.03 (t, J = 5.4 Hz, 1H), 8.60 (s, 1H), 8.23 (t, J = 8.9 Hz, 2H), 7.89 - 7.76 (m, 5H), 7.39 (t, J = 7.2 HZ, 2H), 7.17 - 7.07 (m, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.94 (d, J = 6.9 Hz, 1H), 4.18 (q, J: 7.1 Hz, 2H), 1.61 (t, J: 7.0 Hz, 3H) 499 195—200 (DMSO-dé) 5 9.44 (s, 1H), 8.49 (s, 1H), 8.42 (M+ 1) (d, J = 5.2 Hz, 1H), 8.29 — 8.21 (m, 2H), 8.16 (d, J = 8.5 Hz, 2H), 8.10 (d, J = 2.3 Hz, 1H), 8.08 (d, J = 3.0 Hz, 1H), 8.04 (t, J = 6.5 Hz, 2H), 7.63 (d, J = 8.3 Hz, 3H), 2.29 (s, 311). 114-118 (CDC13) 5 8.60 (s, 1H), 8.31 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.16 (d, J = 3.9 Hz, 1H), 7.95 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 9.0 Hz, 2H), 7.55 (d, J = 6.7 Hz, 1H), 7.41 (s, 2H), 6.99 (dd, J = 7.4, 5.1 Hz, 1H), 2.35 (s, 3H). 122—125 (CDC13)6 8.60 (s, 1H), 8.32 (s, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.19 — 8.16 (m, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.84 — 7.81 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.03 (dd, J = 7.5, 5.1 Hz, 1H), 2.67 (s, 2H), 1.35 (t, J = 7.5 Hz, 3H).
H NMR spectral data were acquired using a 400 MHz instrument.
PCT/USZ012/023932 Table 3: ures for Compounds WO 09125 PCT/U82012/023932 Structure WO 09125 PCT/U82012/023932 2012/023932 ID Structure WO 09125 PCT/U82012/023932 Structure WO 09125 ID Saucuue 2012/023932 Structure 2012/023932 Structure 2012/023932 Structure 1 64C OQ'NTNLO ki / o\ .N l <g <2 2012/023932 Structure WO 09125 PCT/U82012/023932 WO 09125 PCT/U82012/023932 ID Structure 82C p o N X [X N \ N \ S ’N N 83C FXO NN\ \g F F \asN / 05’“ \ 5 ,N c1 84C F O N N ‘( F>< N N F EN \ S o N 85C F N\ \( FXF N N W0 09125 PCT/U52012/023932 PCT/U82012/023932 ID Structure FFXO’O/F \/N,N’ F4 Cl 95C /=N SYN F1950 N‘N /N’N F /=N SYN O a: QN-N W F 0 MO ‘ 97c ,=N SYN F F QN'N/ N’N Fx<0 ’ F F 0 FXOONRN 5% 0“ 98C N ,N-NYNQ F F 0 W0 2012/109125 2012/023932 Structure i106C - 0’\,,.,./~ s N >/N ‘ WO 09125 Structure WO 09125 PCT/U52012/023932 Structure 0 >50 125C N_N/ N S O F 0 . 126C “Km )‘N . n \ ‘ 132C FXO’CyNTNw 5131‘ , } WO 09125 PCT/U82012/023932 Structure W0 09125 PCT/U82012/023932 Structure !153C 3 flN’SM 3"} 9”? I WO 09125 PCT/U82012/023932 Structure W0 2012/109125 2012/023932 Structure l ' 167C U’\,,,/ "‘N’ \ SYN / W0 09125 PCT/U82012/023932 Structure W0 09125 PCT/U82012/023932 Structure 2012/023932 Structure WO 09125 PCT/U82012/023932 2012/023932 Structure W0 09125 PCT/USZ012/023932 I. ‘ Fxo MM HYN/ 22“ \ \ —N N F Mt />—CF W0 09125 PCT/U82012/023932 Structure Table 4: Analytical Data for Compounds in Table 3 Synthesis 1H NMR (5)1 Method (DMSO-de) 8.61 (s, 1H), 8.48 (s, 1H), 8.22 (d, J: 8.24 Hz, 2H), 8.17 (s, 1H), 7.89 (d, J = 8.24 Hz, 2H), 7.80 (d, J = 8.28 Hz, 2H), u l 7.41 (d, J: 8.28 Hz, 2H), 7.19 (d, J: 824 Hz, 2H), 6.71 (d, J = 8.24 Hz, 2H), 2.99 (s, 6H), 2.42 (s, 3H) .
(DMSO-dg) 9.42 (s, 1H), 8.18-8.03 (m, 5H), 7.78-7.69 (111, 2H), 7.61 (d, J: 8.26 Hz, 2H), 7.44 (d, J = 8.24 Hz, 2H), 7.18 (In, 1H), 3.09-2.99 (In, 2H), .32 (m, 3H) (DMSO—dg) 9.42 (s, 1H), 8.18—8.04 (1n, 5H), 7.78-7.69 (In, 2H), 7.61 (d, J = 8.26 Hz, 180~182 2H), 7.48 (d, J = 8.24 Hz, 2H), 7.19 (m, 1H), 3.06-3.02 (In, 2H), 1.78-1.64 (m, 2H), 1.04—0.96 (m, 3H) (DMSO—d6) 8.57 (s, 1H), 8.48 (d, J: 5.5 Hz, 1H), 8.22 (d, J = 8.2 Hz, 2H), 7.91-7.75 (m, 5H), 7.38 (d, J = 8.7 HZ, 2H), 7.22-7.07 (m, 3H), 6.50-6.19 (m, 2H), 3.85 (d, J = 7.2 Hz, 1H), 3.75-3.64 (m, 1H), 2.33 (s, 6H) (300 MHZ, CDC13) 8.56 (s, 1H), 8.54 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.89 (d, J: 8.2 Hz, 3H), 7.79 (d, J = 9.0 Hz, 2H), 7.38 (d, J: 8.7 Hz, 2H), 7.23-7.00 (m, 4H), 6.88— 6.74 (m, 2H), 4.44 (s, 2H), 2.33 (s, 6H) (methanol-d4) 9.16 (s, 1H), 8.46 (s, 1H), 6C‘ 645 8.21 (d, J: 8.3 Hz, 2H), 8.03 (m, 6H), 7.52 D 196—198 (M+H) (d, J: 8.3 Hz, 4H), 7.28 ~ 6.91 (m, 3H), 4.39 (s, 2H), 2.08 (s, 6H) W0 2012/109125 flSynthesis MS 0 1 1 mp ( C) H NMR (8) Method (300 MHz, CDC13) 8.56 (m, 2H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 8.3 Hz, 3H), 7.79 (d, J = 9.0 Hz, 2H), 7.55—7.42 (m, 1H), 7.37 (d, J = 9.0 Hz, 2H), 7.20-7.01 (m, 3H), 6.89- 6.68 (m, 2H), 4.30 (s, 2H), 2.28 (s, 6H) (CDC13) 8.57 (s, 1H), 8.52 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.91-7.84 (m, 3H), 7.80 (d, J = 9.1 Hz, 2H), 7.39 (d, J = 8.6 Hz, 4H), 7.18-7.03 (m, 5H), 4.32 (s, 2H), 2.29 (s, 6H) ) 8.57 (s, 1H), 8.47 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (m, 3H), 7.39 (d, J = 8.4 Hz, 2H), .10 (m, 3H), 3.93 (s, 2H), 2.35 (s, 6H), 0.13 (s, (DMSO-d6) 8.57 (s, 1H), 8.54 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.89 (d, J = 8.3 Hz, 2H), 7.87 (s, 1H), 7.80 (d, J = 9.0 Hz, 2H), 7.44— 7.32 (m, 4H), 7.31—7.19 (m, 3H), 7.19—7.00 (m, 3H), 4.34 (s, 2H), 2.31 (s, 6H) (DMSO—dg) 8.57 (s, 1H), 8.55 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.89 (d, J = 8.3 Hz, 2H), 7.86 (s, 1H), 7.83-7.73 (m, 2H), 7.48 (td, J: 7.6, 1.7 Hz, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.23-6.91 (m, 6H), 4.39 (s, 2H), 2.30 (s, 6H) (DMSO—dg) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d, J: 8.3 Hz, 2H), 7.94 (d, J = 8.3 Hz, 2H), 7.88 (d, J: 8.2 Hz, 2H), 7.86 (s, 1H), 7.79 (d, J: 9.0 Hz, 2H), 7.44 (d, J = 8.3 HZ, 2H), 7.38 (d, J: 8.6 Hz, 2H), 7.20-7.05 (m, 3H), 4.35 (s, 2H), 3.88 (s, 3H), 2.28 (s, 6H) (DMSO-da) 8.59 (s, 1H), 8.51 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.93-7.76 (m, 7H), 7.53 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.7 Hz, 2H), 7.20—7.06 (m, 3H), 4.88 (s, 2H), 4.36 (s, 2H), 2.28 (s, 6H) W0 2012/109125 Synthesis Method (CDC13) 8.57 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.91-7.85 (m, 4H), 7.80 (d, J 658 = 9.1 Hz, 2H), 7.73 (d, J: 6.8 Hz, 1H), 7.52 (dd, J: 8.8, 6.9 Hz, 1H), 7.39 (d, J = 9.0 Hz, 2H), 7.13—7.01 (m, 3H), 4.88 (s, 2H), 2.27 (s, 6H) (CDC13) 8.57 (s, 1H), 8.25-8.14 (m, 3H), m 7.94—7.66 (m, 7H), 7.52-7.35 (m, 6H), 7.16- (M+) 7.03 (m, 3H), 4.54 (s, 2H), 2.32 (s, 6H) (CDC13) 857 (s 1H), 8.49 (s,1H), 8.24 (d, J =8H4H70H\788{d T=8A3 H70n\ALL. All I LHD all 658 a v y 17 .77 (m, 3H), 7. 39 (d, J: 8.3 Hz, 2H), l (M+) I 7 197.07 (m, 3H), 6.69—6.65 (m, 1H), 6.39-6 34(m 1H), 4.36 (s, 2H), 2.29 (s, 6H) (CDCl3) 8.58 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.94-7.74 (m, 7H), 7.59 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.20—7.04 (m, 3H), 4.37 (s, 2H), 3.01 (s, 3H), 2.29 (s, 6H) (CDC13) 8.59 (s, 1H), 8.46 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.86 (d, J = 8.4 Hz, 2H), 7.83-7.75 (m, 3H), 7.63 (d, J = 8.4 Hz, 2H), 7.44 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.17-7.05 (m, 3H), 7.03-6.98 (m, 3H), 6.89 (t, J = 8.6 Hz, 2H), 4.30 (s, 2H), 2.24 (s, 6H) (CDC13) 8.59 (s, 2H), 8.26 (d, J: 8.3 Hz, 2H), 7.93 (d, J = 8.3 Hz, 2H), 7.89 (s, 1H), 7.82 (d, J = 9.1 Hz, 2H), 7.40 (d, J: 8.3 Hz, 2H), 7.20-7.05 (m, 3H), 6.86 (s, 1H), 4.49 (s, 2H), 3.98 (s, 3H), 2.31 (s, 6H) (CDC13) 8.58 (s, 1H), 8.38 (s, 1H), 8.23 (d, J I = 8.3 Hz, 2H), 7.86 (d, J: 8.3 Hz, 3H), 7.81 (d, J = 9.1 Hz, 2H), .63 (m, 2H), 7.46- (M+) 7.36 (m, 5H), 7.18-7.05 (m, 3H), 4.24 (s, 2H), 2.47 (s, 3H), 2.29 (s, 6H) aSynthesis MS Method (DMSO-dg) 8.58 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.47-7.35 E (m, 4H), 7.21-6.93 (m, 5H), 3.68 (t, J: 5.4 Hz, 2H), 3.35 (s, 3H), 2.65 (t, J: 6.2 Hz, 2H), 2.29 (s, 6H) dg) 8.59 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.95-7.75 (m, 5H), 7.39 (d, J = 8.4 Hz, 2H), 7.21-7.06 (m, 3H), 5.80 (s, 2H), 4.12 (s, 2H), 3.69-3.50 (m, 2H), 2.31 (s, 6H), 1.35-1.11 (m, 3H) (DMSO-dé) 8.58 (s, 1H), 8.50 (s, 1H), 8.22 (d, J = 8.2 Hz, 2H), 7.93-7.70 (m, 5H), 7.45- 7.28 (m, 8H), 7.23-7.03 (m, 3H), 5.79 (s, 2H), 5.38-5.27 (m, 1H), 5.11 (s, 2H), 4.07- 3.98 (m, 2H), 2.30 (s, 6H) (DMSO-dg) 8.58 (s, 1H), 8.51 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), .73 (m, 5H), 7.39 (d, J = 8.9 Hz, 2H), 7.21-7.07 (m, 3H), 5.76 (s, 2H), 5.05-4.70 (m, 1H), 2.32 (s, 6H), 1.38-1.17 (m, 6H) (DMSO—de) 8.59 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.91-7.79 (m, 5H), 7.40 (d, J = 8.5 Hz, 2H), 7.18-7.06 (m, 3H), 5.73 (s, 2H), 2.70-2.45 (m, 1H), 2.32 (s, 6H), 1.15 (s, 6H) (DMSO—d6) 8.58 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 6.9 Hz, 2H), 7.69 (s, 1H), 7.40 (d, J = 8.8 Hz, 2H), 6.63 (s, 2H), 5.73 (s, 2H), 3.80 (s, 3H), 2.64-2.53 (m, 1H), 2.58 (s, 3H), 2.28 (s, 6H), 1.17 (d, J = 7.0 Hz, 6H) (DMSO-ds) 8.58 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.2 Hz, 2H), 7.88 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 9.0 Hz, 2H), 7.74 (s, 1H), 7.39 (d, J = 8.6 Hz, 2H), 6.63 (s, 2H), 5.71 (s, 2H), 3.79 (s, 3H), 2.74-2.43 (m, 1H), 2.27 (s, 6H), 1.16 (d, J = 7.0 Hz, 6H) Synthesis MS 0 mp ( C) Method (300 MHZ, CDC13) 8.58 (s, 1H), 8.48 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J: 8.4 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.74 E (s, 1H), 7.45-7.28 (m, 7H), 6.63 (s, 2H), (M+) .78 (s, 2H), 5.29 (m, 1H), 5.12 (s, 2H), 4.03 (d, J = 5.6 Hz, 2H), 3.79 (s, 3H), 2.27 (300 MHZ. CDC13) 8.58 (s, 1H), 8.49 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 7.81 (d, J: 9.0 Hz, 2H), 7.72 29C E (M+) 2H), 5.78 (s, 2H), 11. (s, 2H), 3.80 (s, 3H), 3.59 ((1,! = 70 --z. 2H), 2 27 (s 6H), 1.247 (t,J:7.1 Hz, 3H (300 MHZ, CDC13) 8.60 (s, 1H), 8.50 (s, 1H), 8.22 (d, J: 8.3 Hz, 2H), 7.88 (d, J = 8.2 Ilz, 2H), 7.82 (s, 1H), 7.80 (d, J: 9.0 Hz, 2H), 7.38 (d, J = 8.8 Hz, 3H), 7.23-7.02 (In, 3H), 5.78 (s, 2H), 3.96 (s, 2H), 2.31 (s, 611), 1.44 (s, 911) (300 MHz, CDC13)8.58 (s, 1H), 8.52 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 (m, 3H), 7.80 (d, J = 9.0 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 7.14 (m, 3H), 5.72 (s, 2H), 2.32 (s, 6H), 2.09 (s, 3H) (CDClg) (Mixture of atropisomers) [8.61 (s), 8.58 (s), 8.56 (s), 8.51 (s), 8.37 (d, J = 8.3 Hz), 8.23 (d, J = 8.4 Hz), 8.21-8.14 (m), 8.00 (d, J = 8.4 Hz), 7.89 (d, J = 8.2 Hz), 7.84-7.77 (m), .35 (m); 11H], 6.94 (s, 2H), [5.87 (s), 5.80 (s); 2H], [4.12 (s), 4.11 (s); 2H], 3.83 (s, 3H), 3.69-3.44 (m, 2H), 1.38—1.10(m, 3H) (CDC13) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H), U.) U») (3 tr] 7.83-7.77 (m, 3H), 7.39 (d, J = 8.4 Hz, 2H), 6.94 (s, 2H), 5.76 (s, 2H), 4.96—4.77 (m, 1H), 3.82 (s, 3H), 1.30 (d, = 6.3 HZ, 6H) MS 0 1 1 mp ( C) H NMR (5) Method (CDC13) 8.57 (s, 1H), 8.51 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.92—7.76 (m, 5H), 7.39 (d, J 34C E = 8.4 Hz, 2H), 6.93 (s, 2H), 5.73 (s, 2H), (M+) 3.82 (s, 3H), 2.59 (m, 1H), 1.17 (d, J: 7.0 Hz, 6H) (CDC13)8.57 (S, 1H), 8.50 (S, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.92-7.73 (m, 5H), 7.38 (d, J E = 8.3 Hz, 2H), 7.20-6.92 (m, 3H), 5.72 (s, <M+> 2H), 2.94-2.63 (m, 1H), 2.31 (s, 6H), 2.02— 1.38 (m, 8H) (CDClg) 8.56 (s, 1H), 8.49 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.84 36C (S, 1H), 7.79 (d, J = 9.0 Hz, 2H), 7.38 (d, J: 8.4 Hz, 2H), 7.19-7.05 (m, 3H), 5.71 (s, 2H), 2.31 (s, 6H), 1.20 (s, 9H) (CDC13) 8.59 (s, 1H), 8.50 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), .77 (m, 4H), 7.72 (s, 37C 1H), 7.40 (d, J = 9.0 Hz, 2H), 6.63 (s, 2H), .71 (s, 2H), 3.80 (s, 3H), 2.68-2.48 (m, 1H), 2.28 (s, 6H), 1.16 (d, J = 7.0 Hz, 6H) (CDC13) 8.58 (s, 1H), 8.47 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J: 8.3 Hz, 2H), 7.81 (d, J: 9.1 Hz, 2H), 7.71 (s, 1H), 7.39 (d, J: 38C 9.0 Hz, 2H), 6.64 (s, 2H), 5.76 (dd, J = 37.3, 11.0 Hz, 2H), 4.19 (q, J = 6.9 Hz, 1H), 4.14— 3.97 (m, 1H), 3.80 (s, 3H), 3.79-3.68011, 1H), 2.27 (s, 6H), 1.47 (d, J = 6.9 Hz, 3H) (CDClg) 8.58 (s, 1H), 8.48 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.83 (s, 1H), 7.81 (d, J = 9.1 Hz, 2H), 7.39 (d, J: 8.3 Hz, 2H), 7.23-6.99 (m, 3H), 5.77 (dd, J = 36.4, 11.0 Hz, 2H), 4.19 (q, J = 6.9 Hz, 1H), 4.14-3.97 (m, 1H), 3.84—3.65 (m, 1H), 2.31 (s, 6H), 1.47 (d, J = 6.9 Hz, 3H) (CDC13) 8.57 (s, 1H), 8.48 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (d, J: 9.0 Hz, 2H), 7.72 (s, 1H), 7.38 (d, J: 8.4 Hz, 2H), 6.62 (s, 2H), 5.70 (s, 2H), 3.79 (s, 3H), 2.27 (s, 6H), 1.20 (s, 9H) flSynthesis 0 1 1 MS mp ( C) H NMR (5) Method ) 8.58 (s, 1H), 8.49 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.84 (s, 1H), 7.80 (d, J = 9.0 Hz, 2H), 7.38 (d, J: 670 8.4 Hz, 2H), 7.23-6.96 (m, 3H), 5.77 (dd, J 41C E (M+) = 27.4, 10.9 Hz, 2H), 4.07 (q, J = 6.9 Hz, 1H), 3.78-3.70 (m, 1H), 3.66-3.39 (m, 3H), 3.35 (s, 3H), 2.31 (s, 6H), 1.42 (d, J: 6.9 Hz, 3H) (CDClg) 8.58 (s, 1H), 8.48 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.80 (d, J: 9.1 Hz, 2H), 7.71 (s, 1H), 7.39 (d, J: x00 8.3 Hz, 2H), 6.63 (s, 2H), 5.76 (dd, J = 27.8, 1 1 10.9 Hz, 2H), 4.07 (q. J = 6.9 Hz, 1H), 3.79 (s, 3H), 3.79—3.70011, 1H), 3.63-3.45 (m, 3H), 3.35 (s, 3H), 2.27 (s, 6H), 1.42 (d, J: 6.9 Hz, 3H) (CDC13) 8.57 (s, 1H), 8.49 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.3 Hz, 2H), 7.79 (d, J: 9.1Hz,2H), 7.74 (s, 1H), 7.38 (d, J = 8.3112, 2H), 6.62 (s, 2H), 5.71 (s, 2H), 3.79 (s, 3H), 2.85-2.65 (m, 1H), 2.27 (s, 6H), 1.98—1.51(m, 8H) (CDC13) 8.59 (s, 1H), 8.55 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.87 (d, J: 8.3 Hz, 2H), 7.84—7.74 (m, 3H), 7.38 (d, J = 8.4 Hz, 2H), 6.63 (s, 2H), 5.85—5.73 (m, 2H), 4.54-4.47 (m, 1H), 4.03 (dd, J: 14.7, 6.9 Hz, 1H), 3.91 (dd, J = 13.8, 7.4 Hz, 1H), 3.79 (s, 3H), 2.27 (S, 6H), 2.09-1.83 (m, 4H) (CDC13) 8.68 (s, 1H), 8.49 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.93 (d, J = 8.4 Hz, 2H), 7.88 (d, J: 8.3 Hz, 2H), 7.81 (d, J = 8.5 Hz, 2H), 132—137 7.73 (s, 1H), 7.35 (s, 5H), 6.64 (s, 2H), 5.78 (s, 2H), 5.24 (s, 1H), 5.12 (s, 2H), 4.04 (d, J Synthesis Method (acetone-d6) 9.20 (s, 1H), 8.52 (s, 1H), 8.40 — 8.21 (m, 2H), 8.21 — 8.01 (m, 4H), 7.61 (d, 149—151 J: 8.3 Hz, 2H), 7.32 — 6.94 (m, 3H), 3.83 (s, 2H), 2.34 (s, 6H) (acetone-d6) 9.18 (s, 1H), 8.83 (s, 1H), 8.67 — 7.82 (m, 8H), 7.60 (d, J = 8.4 Hz, 2H), 128—137 6.78 (s, 2H), 3.99 — 3.72 (m, 3H), 2.41 — 2.20 (m, 6H) (methanol-d4) 9.23 (s, 1H). 8.62 (s, 1H), 8.29 (m, 2H), 8.17 — 7.98 (m, 4H), 7.60 — 177—185 7.45 (m, 2H), 7.41 — 7.19 (m, 3H), 4.22 (s, 2H), 2.34 (s, 6H) nol—d4) 9.23 (s, 1H), 8.57 (s, 1H), 8.28 (m, 3H), 8.09 ~ 7.98 (111,411), 7.50 (m, 193~196 4H), 4.19 ~ 4.11 (m, 2H), 3.85 (s, 3H), 2.36 (s, 3H) (methanol-(1.09.23 (s, 1H), 8.60 (s, 1H), 8.30 (m, 2H), 8.14 — 8.00 (m, 4H), 7.52 (m, 176—179 2H), 6.81 (s, 2H), 4.22 (s, 2H), 3.84 4 3.81 (m, 3H), 2.33 (s, 6H) nol-d4) 9.21 (s, 1H), 8.44 (s, 1H), 8.27 (d, J: 8.1 Hz, 2H), 8.09 — 7.98 (m, 4H), 7.52 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 168—178 8.7 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 5.40 (S, 1H). 4.37 — 4.13 (m, 2H), 3.79 (s, 3H), 1.79 (m, 3H) (methanol-d4) 9.21 (s, 1H), 8.44 (m, 1H), 8.28 (d, J: 8.2 Hz, 2H), 8.11 — 7.99 (m, 168—170 4H), 7.52 (d, J = 8.4 Hz, 2H), 7.25 (m, 2H), 7.14 (t, J: 8.5 Hz, 1H), 5.42 (m, 1H), 4.25 (m, 2H), 3.88 (s, 3H), 1.75 (m, 3H) (methanol-d4) 9.23 (s, 1H), 8.46 (s, 1H), 8.27 (m, 2H), 8.05 (m, 4H), 7.57 — 7.39 (m, 167—170 7H), 5.41 (m, 1H), 4.24 (m, 2H), 1.79 (m, W0 2012/109125 Synthesis MS mp (°C) Method (methanol-d4) 9.12 (s, 1H), 8.46 (s, 1H), 8.14 (m, 2H), 7.99 (m, 3H), 7.78 (s, 1H), 7.49 (d, J: 8.5 Hz, 2H), 7.12 (m, 3H), 3.69 (s, 2H), 3.22 — 2.80 (m, 2H), 2.25 (s, 6H), 2.03 (s, 2H), 1.93 — 1.66 (m, 1H), 0.92 (m, J = 9.7 Hz, 6H) (methanol-d4) 9.18 (s, 1H), 8.59 (s, 1H), 8.30 (d, J: 8.1 Hz, 2H), 8.12 (m, 2H), 8.07 — 8.00 (m, 2H), 7.58 — 7.43 (m, 2H), 7.33 765 (dd, J: 8.6, 6.5 Hz, 1H), 7.25 (d, J: 7.6 148—151 (NI+H) Hz, 2H), 402 (m, 2H), 3.97 — 3.75 (m, 2H), ’201 (d’]=69Uw 0L“ 200(m1I—I\ ’)<0 .1441 111.1, all/,5 /\J (111, 111/, k-J/ (m, 1H), 2.35 (s, 6H), 1.84 (m, 2H), 1.78 — I 1.63 (m, 2H), 1.44 (s, 9H), 1.29 (m, 3H) (methanol—d4) 9.20 (s, 1H), 8.65 (s, 1H), 8.30 (m, 2H), 8.21 — 7.96 (m, 4H), 7.53 (d, J 737 = 8.4 Hz, 2H), 7.35 (dd, J = 8.5, 6.5 HZ, 57C 3 (M+H) 1H), 7.28 (d, J: 7.5 Hz, 2H), 4.44 (s, 2H), 3.91 — 3.40 (m, 9H), 2.38 (s, 6H), 1.50 (s, (methanol—d4) 9.18 (s, 1H), 8.61 (s, 1H), 8.31 (m, 2H), 8.14 (m, 2H), 8.06 (d, J: 9.0 725 Hz, 2H), 7.53 (d, J = 8.5 Hz, 2H), 7.32 (dt, J 58C 125—127 (M+H) = 26.0, 7.0 Hz, 3H), 4.02 (s, 2H), 3.38 - 3.34 (m, 2H), 3.22 ~ 3.03 (m, 2H), 2.37 (s, 6H), 1.74 (m, 2H), 1.45 (s, 9H) (methanol—d4) 9.18 (s, 1H), 8.62 (s, 1H), 8.38 — 7.97 (m, 6H), 7.51 (d, J = 8.4 Hz, 755 2H), 7.32 (dd, J: 8.5, 6.6 Hz, 1H), 7.25 (d, 59C 147—149 (M+H) J = 7.6 Hz, 2H), 4.40 (s, 1H), 4.06 (m, 2H), 3.91— 3.74 (m, 2H), 3.56 — 3.41 (m, 1H), 2.36 (s, 6H), 1.44 (s, 9H) (methanol-d4) 9.16 (s, 1H), 8.58 (s, 1H), 7.52(p,J= 8.,8Hz 2H), m 2H), 4.04 136—139 m I. Q < u, run 390_373 (an 3H\ 3 <<_ \u,.l —U.J11L,l—ll ll,u11/,JJJ 3.37(m, 2H),.314-2.75(m,3H),(230(s, 6H),1 99- 1.80 (m 2H), 1.43 Synthesis Method (methanol—d4) 9.12 (s, 1H), 8.12 — 8.07 (m, 2H), 8.02 — 7.96 (m, 2H), 7.55 — 7.50 (m, 2H), 7.50 — 7.45 (m, 2H), 7.43 (d, J = 7.7 Hz, 1H), 7.31 (d, J = 7.6 Hz, 2H), 4.03 (s, 2H), 3.25 (dt, J = 15.5, 7.0 Hz, 4H), 2.84 (s, 3H), 2.04 (s, 6H), 1.81 — 1.66 (m, 2H), 1.44 (s, 9H) (methanol-d4) 8 9.18 (s, 1H), 8.56 (m, 1H), 8.26 (m, 2H), 8.16 — 7.84 (m, 4H), 7.52 (m, 2H), 7.27 (m, 1H), 7.22 (m, 2H), 4.00 (s, 0 2H), 3.28 (m, 3H), 3.06 — 2.83 (m, 1H), 2.75 (t, J: 12.2 Hz, 1H), 2.34 (s, 6H), 2.21 — 1.83 (m, 4H), 1.72 (m, 1H), 1.47 — 1.19 (m, (methanol-d4) 9.18 (s, 1H), 8.63 (s, 1H), 8.28 (m, 2H), 8.13 ~ 7.97 (m, 4H), 7.51 (d, J = 8.3 Hz, 2H), 7.31 (dd, J: 8.5, 6.5 Hz, 1H), 7.24 (d, J = 7.6 Hz, 2H), 4.32 — 4.07 (m, 3H), 3.98 4 3.81 (m, 1H), 3.72 (s, 1H), 2.35 (s, 6H) (methanol-d4) 9.19 (s, 1H), 8.58 (s, 1H), 8.28 (m, 2H), 8.14 — 7.97 (m, 4H), 7.51 (m, 2H), 6.78 (s, 2H), 4.00 (m, 2H), 3.81 (s, 3H), 3.10 — 2.93 (m, 4H), 2.30 (s, 6H), 1.91 (m, 2H) (methanol-d4) 9.20 (s, 1H), 8.65 (s, 1H), 8.27 (m 2H), 8.11 — 7.99 (m, 4H), 7.52 (d, J 128 dec = 8.3 HZ, 2H), 6.78 (s, 2H), 4.40 (s, 2H), 3.87 (m, 4H), 3.53 (s, 3H), 2.32 (s, 6H), 1.33 (m, 4H) (methanol-d4) 9.20 (s, 1H), 8.56 (s, 1H), 8.27 (m, 2H), 8.12 — 7.99 (m, 3H), 7.53 (d, J 100—105 = 8.4 Hz, 2H), 7.24 (m, 4H), 3.99 (s, 2H), 3.42 (m, 2H), 3.05 (m, 2H), 2.36 (s, 6H), 1.99 — 1.88 (m, 2H) (methanol-d4) 9.20 (s, 1H), 8.74 (s, 1H), 8.33 — 8.25 (m, 2H), 8.12 — 7.98 (m, 4H), 237—240 7.53 (d, J: 8.3 Hz, 2H), 7.33 (dd, J: 8.5, dec 6.4 Hz, 1H), 7.26 (d, J = 7.5 Hz, 2H), 4.55 (s, 2H), 3.92 (m, 4H), 3.37 (m, 2H), 3.31 (m, 2H), 2.38 (s, 6H) Synthesis Method (CDC13) 8.56 (s, 1H), 8.33 (s, 1H), 8.22 (d, J 581 = 8.1 Hz, 2H), 7.90 — 7.70 (m, 4H), 7.39 (d, 188—190 (M+H) J: 8.7 Hz, 2H), 6.72 (s, 2H), 4.01 (s, 2H), 3.87 —3.73 (s, 3H), 2.18 (s, 6H) (CDC13) 8.65 (s, 1H), 8.31 (s, 1H), 8.23 (d, J 134—138 = 8.3 Hz, 2H), 7.83 (m, 4H), 7.50 (d, J: 8.1 (M+) Hz, 2H), 7.45 — 7.38 (m, 3H), 4.05 (s, 2H) (CDC13)8.62 (s, 1H), 8.32 (s, 1H), 8.23 (d, J = 8.3 HZ, 2H), 7.88 — 7.74 (m, 4H), 7.40 (d, 71C J: 8.3 Hz, 2H), 7.34 — 7.26 (m, 1H), 7.20 d, T: 7.5 Hz 2H), 4.02 (s, 2H), 2.22 (s, (CDC13)8.58 (s, 1H), 8.33 (s, 1H), 8.23 ((1, J1 = 8.3 Hz, 2H), 7.81 (m, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.01 (d, J = 0.4 Hz, 2H), 4.01 (s, 2H), 2.34 (s, 3H), 2.17 (s, 6H) (CDC13) 8.58 (s, 1H), 8.30 (s, 1H), 8.23 (d, J = 8.3 Hz, 1H), 7.81 (m, 2H), 7.49 (d, J = 4.0 Hz, 1H), 7.40 (d, J = 8.4 Hz, 1H), 7.34 (s, 145-150 1H), 7.18 (d, J: 7.8 ,4.01(d, J: 1.4 Hz, 1H), 2.83 (heptet, J = 6.8 Hz, 1H), 1.23 (t, J: 6.6 Hz, 3H). (methanol—d4) 9.20 (S, 1H), 8.38 (s, 1H), 8.31— 8.24 (m, 2H), 8.08 — 8.00 (m, 2H), 682 7.95 ~7.88 (m, 2H), 7.55 — 7.48 (m, 3H), (M+H) 7.48 —7.36 (m, 5H), 7.31 (d, J: 7.7 Hz, 2H), 3.60 (q, J = 7.2 Hz, 4H), 2.20 (s, 6H), 1.07 (t, J: 7.2 Hz, 6H); (CDC13) 8.56 (s, 1H), 8.23 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.84—7.73 (m, 5H), 7.41—7.33 (m, 3H), 7.21 (d, J = 7.2 Hz, 2H), 7.16 (s, 1H), 7.12 (d, J = 3.2 Hz, 1H), 2.20 (s, 6H).
' . (CDC13) 8.56 (s, 1H), 8.25 (s, 1H), 8.20 (d, J 711 g 8.4 Hz, 2H), 7.80 (dd, J = 8.7, 5.6 Hz, ' |76Cl G r (M+) l 4H), 7.48-7.34 (m, 8H), 7.26 (d, J = 7.7 Hz, 2H), 7.08 (s, 1H), 2.20 (s, 6H) PCT/U52012/023932 flS1y/1ethodnthesis MS mp(C)0 1HNMRGS)1 (methanol-d4) 9.14 (s, 1H), 8.21 — 8.13 (m, 3H), 8.06 — 7.99 (m, 2H), 7.86 — 7.75 (m, 261—263 4H), 7.50 (d, J: 8.3 Hz, 2H), 7.28 — 7.18 (m, 3H), 7.14 (d, J = 7.9 Hz, 2H), 6.72 (s, 1H), 0.09 — -0.09 (m, 6H) (CDC13) 8.55 (s, 1H), 8.22 (s, 1H), 8.18 (d, J = 8.3 Hz, 2H), 7.79 (dd, J: 8.7, 5.1 Hz, 4H), 7.37 (d, J = 9.0 Hz, 2H), 7.23-6.94 (m, 7H), 6.26 (s, 1H), 2.17 (s, 6H) (CDC13) 8.55 (s, 1H), 8.23 (s, 1H), 8.19 (d, J = 8.3 Hz, 2H), 7.79 (d, J = 8.7 Hz, 4H), 7.43 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.9 Hz, 2H), 7.23-7.16 (m, 3H), 7.08 (d, J = 7.4 Hz, 2H), 6.35 (s, 1H), 2.18 (s, 6H) (methanol-d4) 9.23 (s, 1H), 8.40 (s, 1H), 8.26 (m, 2H), 8.22 (s, 1H), 8.07 — 8.00 (m, 215—219 3H), 7.91 (d, J: 8.4 Hz, 2H), 7.51 (d, J = 8.3 Hz, 2H), 6.90 (s, 1H), 3.88 (s, 3H), 2.13 (s, 6H) ) 9.42 (s, 1H), 8.59 (s, 1H), 8.28 (d, J = 8.4 Hz, 2H), 8.01 (d, J = 8.3 Hz, 2H), 7.80 209-213 — 7.77 (m, 2H), 7.43 — 7.34 (m, 2H), 7.07 (d, J: 7.5 Hz, 2H), 6.98 (dd, J = 8.2, 6.7 Hz, 1H), 3.90 (s, 2H), 2.17 (s, 6H) (CDC13) 9.46 (s, 1H), 8.60 (s, 1H), 8.29 (d, J = 8.4 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H), 7.89 225-232 — 7.76 (m, 2H), 7.40 (d, J = 8.3 Hz, 2H), 6.88 (s, 2H), 3.90 (s, 2H), 2.28 (s, 3H), 2.13 (s, 6H). ) 9.44 (s, 1H), 8.60 (s, 1H), 8.30 (d, J = 8.4 Hz, 2H), 8.02 (d, J = 8.4 Hz, 2H), 7.82 211-215 (d, J: 9.1 Hz, 2H), 7.40 (d, J: 8.3 Hz, 2H), 6.63 (s, 2H), 3.90 (s, 2H), 3.78 (s, 3H), 2.15 (s, 6H) (CDClg) 9.42 (s, 1H), 8.40 (s, 1H), 8.18 (d, J = 8.24 Hz, 2H), 8.07 (d, J = 8.28 Hz, 2H), 7.89 (d, J = 8.24 Hz, 2H), 7.76 (d, J = 8.28 Hz, 2H), 7.64-7.58 (m, 3H), 4.42 (s, 2H) Synthesis MS mp (°C) Method (CDC13) 6 9.36 (s, 1H), 8.60 (s, 1H), 8.30 (d, J: 8.4 Hz, 2H), 8.01 (d, J = 8.4 Hz, 2H), 7.86 — 7.77 (m, 2H), 7.40 (d, J = 8.3 Hz, 146-149 2H), 7.32 (dd, J = 6.9, 2.3 Hz, 1H), 7.24 — (M+H) 7.12 (m, 2H), 6.91 (dd, J: 7.1, 2.0 Hz, 1H), 3.93 (s, 2H), 3.15 — 2.97 (m, 1H), 1.21 (d, J = 6.9 Hz, 6H) (CDC13) 5 8.81 (bs, 1H), 8.57 (s, 1H), 8.20 (d, J: 8.3 Hz, 2H), 7.87 — 7.75 (m, 4H), 7.,39(d J= 8.,3Hz 2H), 7.32- 7.25(m, 1H),7.10(2dt,J=7.4,1.,5Hz 2H), 6.,83(d 163-169 J: 6.5 Hz, 1H), 3.96 (t,’J = 6. 1 Hz, 211“, 3.13 et, J = 6.9 Hz, 1H), 2,9 - 2.88 I (m, 2H), 2.49 — 2.36 m, 2H), 1.29 — 1.21(m, (CDC13) 5 8.81 (s, 1H), 8.66 (s, 1H), 8.21 (d, J: 8.3 HZ, 2H), 7.92 (d, J = 8.4112, 2H), 7.81 (t, J: 10.2 Hz, 4H), 7.30 - 7.26 (m, 2H), 7.17 — 7.04 (m, 1H), 6.83 (d, J = 6.4 187-189 Hz, 1171), 3.96 (t, J = 6.1 1), 3.13 (hcptet, J = 6.9 Hz, 1H), 2.97 — 2.90 (m, 2H), 2.47 - 2.38 (m, 2H), 1.25 (d, J: 7.5 Hz, 6H).
(CDC13) 6 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J: 8.3 Hz, 2H), 7.82 (dd, J = 8.7, 7.2 Hz, 4H), 7.48 (dd, J = 4.1, 1.3 Hz, 2H), 7.40 (d, J: 8.3 Hz, 2H), 7.37 — 7.30 (m, 1H), 178-182 7.17 (m, 1H), 4.23 (dq, J: 14.5, 7.2 Hz, 1H), 2.83 (dd, J: 14.6, 6.9 Hz, 1H), 1.79 (d, J: 7.2Hz, 3H), 1.22 (ddd, J = 12.1, 6.9, 1.9 Hz, 6H).
(CDC13) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.90 — 7.75 (m, 4H), 205—206 7.52 - 7.44 (m, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.10 (dd, J = 8.6, 7.4 Hz, 2H), 4.04 (s, 2H).
(CDC13)3858 (51H), 8.31 (s, 1H), 8.23 (d, J: 8.,23HZ 7.82 (t,J=8.5 HZ, 4H), 7.-46 731 (m, 3h),7.2-5 7.18’(m, 2H), ' 4.02 (s, 2H), 2.53 (q, J = 7.6 Hz, 2H), 2.21 (s, 3H), 1.26 - 1.16 (m, 3H).
PCTfUS2012/023932 Synthesis (CDC13) 8 8.58 (s, 1H), 8.36 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.88 - 7.76 (m, 4H), 7.49 — 7.35 (m, 3H), 7.01 (dd, J = 8.5, 2.5 227-235 Hz, 1H), 6.96 (dd, J = 7.8, 1.0 Hz, 1H), 6.91 (t, J = 2.2 Hz, 1H), 3.98 (s, 2H), 3.85 (s, 3H).
(CDC13) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.86 - 7.77 (m, 4H), 7.50 - 7.43 (m, 1H), 7.40 (d, J = 8.3 Hz, 104— 108 2H), 7.32 - 7.27 (m, 1H), 7.14 — 7.04 (m, 2H), 4.01 (d, J = 17.2 Hz, 1H), 3.94 (d, J: 17.3 Hz, 1H). 3.84 (s, 3H).
(CDC13)3 8.58 (s, 1H), 8.31 (S, 1H), 8.27 - 8.18 (111. 2H), 7.88 - 7.77 (In, 4H), 7.43 - 6 7.37 (111, 3H), 7.34 (t, J: 7.8 Hz, 1H), 7.30 - 7.26 (In, 1H), 4.07 (d, J: 17.4 Hz, 1H), 4.00 (d, J: 17.4112, 111), 2.29 (s, 3H).
(CDC13) 8 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.86 - 7.78 (m, 4H), 134—136 7.49 — 7.32 (m, 5H), 7.24 - 7.18 (m, 1H), 4.06 — 3.94 (m, 2H), 2.56 (q, J = 7.6 Hz, 2H), 1.26 — 1.18 (m, 3H).
(CDC13) 8 8.59 (d, J = 4.8 Hz, 1H), 8.26 (m, 3H), 7.89 — 7.74 (m, 4H), 7.52 ~ 7.31 (m, 195-201 4H), 7.24 — 7.13 (m, 1H), 4.05 (d, J = 0.9 Hz, 2H). (300 MHz, CDC13) 8 8.58 (s, 1H), 8.33 (d, J = 7.9 Hz, 1H), 8.24 (s, 1H), 8.21 (s, 1H), 182-185 7.86 — 7.76 (m, 4H), 7.53 (t, J = 5.9 Hz, 3H), 7.44 - 7.29 (m, 8H), 3.80 - 3.73 (m, 1H), 3.59 - 3.51 (m, 1H).
(CDC13) 8 8.57 (s, 1H), 8.37 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.89 - 7.73 (m, 4H), 234—236 7.45 — 7.29 (m, 3H), 6.79 (dd, J = 8.2, 2.2 Hz, 1H), 6.70 (d, 1H), 6.57 (s, 1H), 3.96 (s, 2H), 2.98 (s, 6H) aSynthesis MS Method ) 6 8.55 (s, 1H), 8.29 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 7.86 - 7.71 (m, 4H), 225-226 7.42 — 7.23 (m, 3H), 6.63 (d, J = 8.5 Hz, 2H), 4.07 (q, J = 7.0 Hz, 4H), 3.94 (s, 2H), 1.31 (t, J: 7.0 Hz, 6H) (CDC13) 3 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, J: 8.4Hz, 2H), 7.89- 7.77 (m, 4H), d J: 8.1 Hz,2H), 740 ((1 J=8.3Hz, 2H), 72-9 720 (m 1H) 404 (s, 2H) (CDC13)3 8. 58 (s, 1H), 8.30 (S 1H), 8.22 1,: 1H0 "In”: "ml AU\ \U,J =o.4n"2 run 4n), 1.75—77U \ul, I111}, ":1 7.39(d1=9_0 77H)77R(t1H)719 I \v’ ., ....4 (d, J: 7.7Hz, 21), 401 (s 2H), 2.21(s, RIJW U11]- (CDC13) 6 8.60 (s, 1H), 8.32 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.89 - 7.74 (m, 4H), 106— 107 7.39 (d, J: 8.3 Hz, 2H), 6.56 (s, 1H), 4.01 (s, 2H), 3.94 (8, 3H), 2.32 (s, 3H), 2.16 (s, (CDC13) 5 8.27 (s, 1H), 7.95 - 7.71 (In, 5H), 123— 126 7.60 (d, J = 1.3 Hz, 1H), 7.53 — 7.43 (m, 4H), 7.45 — 7.32 (m, 3H), 4.04 (s, 2H) (CDCI3) 5 8.28 (s, 1H), 7.93 (dd, J: 5.4, 4.1 Hz, 3H), 7.78 (m, 4H), 7.36 - 7.23 (m, 3H), 194-196 7.19 (d, J: 7.6 Hz, 2H), 6.81 (d, J = 2.5 Hz, 1H), 4.00 (s, 2H), 2.21 (s, 6H) (CDC13)6 8.27 (s, 1H), 8.16 (s, 1H), 8.03 (s, 1H), 7.80 - 7.71 (m, 4H), 7.57 (d, J: 8.3 100-102 Hz, 2H), 7.30 (dd, J = 28.7, 5.8 Hz, 3H), 7.19 (d, J: 7.6 Hz, 2H), 4.01 (s, 2H), 2.21 l 105C 1 ‘31)?) 8. 58 (s, 1H), 8. 31 (s, 1H), 8.23 =7.,8Hz 2H), 7.82(m, 4H), 7.39(d, J F 209-211 \ ’11,” 1018 am 401(5 omL/ \u, 5“], u, 4.41;, , PCT/U82012/023932 Synthesis Method ) 8 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (d, J : 8.2 Hz, 2H), 7.81 (m, 4H), 7.58 (dd, 180-182 J = 6.0, 3.3 Hz, 1H), 7.43 (ddd, J: 23.4, 11.3, 5.5 Hz, 5H), 4.02 (dd, J : 29.9, 17.4 Hz, 2H) (CDC13) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.22 (dd, J: 10.0, 8.6 Hz, 4H), 7.82 (m, 4H), 107C 227-232 7.49 (d, J : 8.5 Hz, 2H), 7.40 (d, J : 8.6 Hz, 2H), 4.42 (q, J : 7.1 Hz, 2H), 4.00 (s, 2H), 1.41 (t, J: 7.1 Hz, 3H) (CDC13) 8 8.58 (s, 1H), 8.28 (d, J = 15.0 Hz, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 - 7.76 (m, 4H), 7.53 - 7.30 (m, 5H), 7.18 (ddd, J: 167—171 7.8, 4.2, 1.2 Hz, 1H), 4.03 — 3.98 (m, 2H), 2.53 (dd, J : 14.1, 7.0 Hz, 1H), 1.77 — 1.56 (m, 2H), 1.26 — 1.16 (m, 3H), 0.78 (td, J: 7.4, 2.3 Hz, 3H).
(CDC13)8 8.25 (s, 1H), 7.73 (d, J: 7.4 Hz, 4H), 7.55 - 7.43 (In, 2H), 7.43 — 7.36 (m, 105-111 1H), 7.10 (t, J = 11.6 Hz, 4H), 4.90 - 4.79 (m, 1H), 4.04 (s, 2H), 3.76 (s, 3H), 3.73 — 3.62 (m, 1H), 3.52 - 3.35 (m, 1H) (CDC13) 8 8.25 (s, 1H), 7.82 - 7.64 (m, 4H), 7.30 (1, 1H), 7.22 — 6.99 (m, 6H), 4.83 (dd, J : 12.8, 6.5 Hz, 1H), 4.00 (s, 2H), 3.89 — 3.59 (m, 4H), 3.44 (dd, J : 17.2, 6.5 Hz, 1H), 2.20 (s, 6H).
(CDC13) 8 8.58 (s, 1H), 8.30 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.86 — 7.77 (m, 4H), 7.39 (t, J : 7.8 Hz, 3H), 7.34 — 7.27 (m, 1H), 209-210 7.20 (d, J: 7.4 Hz, 1H), 4.03 (s, 2H), 2.86 - 2.71 (m, 1H), 2.21 (s, 3H), 1.21 (2d, J: 6.7 Hz, 6H).
(CDC13) 8 8.58 (s, 1H), 8.32 (s, 1H), 8.23 (d, J : 8.4 Hz, 2H), 7.87 - 7.75 (m, 4H), 7.43 - 7.33 (m, 4H), 7.26 — 7.19 (m, 2H), 154-158 4.02 (s, 2H), 1.86 - 1.77 (m, 1H), 0.90 - 0.83 (m, 2H), 0.77 - 0.68 (m, 1H), 0.67 - 0.59 (m, 1H).
PCT/U52012/023932 Synthesis MS Method (Acetone~D6) 8 9.20 (s, 1H), 8.28 (d, J: 8.2 Hz, 3H), 8.13 (d, J = 9.0 Hz, 2H), 7.94 (d, J 111-116; = 8.2 Hz, 2H), 7.60 (d, J: 8.8 Hz, 2H), 7.39 210-212 (t, J: 17.1 Hz, 4H), 4.15 (q, J: 17.3 Hz, 2H), 2.23 (s, 3H) (CDC13) 8 8.58 (s, 1H), 8.33 (s, 1H), 8.22 (d, J: 8.3 Hz, 2H), 7.88 - 7.67 (m, 4H), 203-205 7.38 (d, J: 8.4 Hz, 2H), 7.14 (d, J = 8.3 Hz, 1H), 6.87 (d, J = 8.9 Hz, 2H), 3.98 (s, 2H), 3.83 (s, 3H), 2.20 (s, 3H) I .DJ= 8.,2Hz 2H),.(782m,4)(313)8858s, 1.1; 8. 1 ’Tl , (M+H) 8.Z6H,2H)7.,30(d 2H)7.,03(Q: 0'0 2 2H) 397 (5,211) 386 (s, 3H) (CDC13) 5 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.88 — 7.72 (m, 4H), 7.48 — 7.32 (m, 3H), 7.31 — 7.20 (m, 1H), 7.13 — 6.97 (m, 2H), 4.09 (q, J = 7.0 Hz, 2H), 3.95 (t, J = 11.7 Hz, 2H), 1.33 (t, J = 7.0 Hz, 3H).
(CDC13) 8 8.59 (s, 1H), 8.54 (dd, J = 4.8, 1.3 Hz, 1H), 8.28 (s, 1H), 8.22 (d, J = 8.4 Hz, 127—132 2H), 7.84 - 7.77 (In, 411), 7.77 - 7.72 (m, 1H), 7.38 (dd, J = 7.7, 5.0 Hz, 3H), 4.02 (d, J: 1.2 Hz, 2H), 2.30 (s, 3H) (CDC13) 8 8.67 (s, 1H), 8.59 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 7.99 (d, J = 8.4 Hz, 1H), 7.84 (dd, J = 8.3, 3.8 Hz, 4H), 7.80 (s, 1H), 7.42 — 7.39 (m, 3H), 4.03 (d, J = 1.3 Hz, 2H), 2.26 (s, 3H). ) 8 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.88 - 7.77 (In, 4H), 1 119C I I48 7.34 (m, 5H), 7.23 - 7.18 (m, 1H), F 124-138 4.0-6 39,3(111 2H), 2.40(qd, J: 14.2 7.3 n7 4- 121(m, 1H),089(d J: 1:14, by“, 6.6Hz, 6H).
PCTfUS2012/023932 Synthesis Method ) 6 8.67 (s, 1H), 8.30 (s, 1H), 8.24 (d, J = 8.3 Hz, 2H), 7.92 (d, J = 8.5 Hz, 2H), 153-159 7.82 (m, 3H), 4.01 (d,J=1.5 Hz, 2H), 3.80 — 3.64 (m, 2H), 2.91 — 2.76 (m, 2H), 1.30 — 1.14 (m, 6H) (CDC13) 8 8.57 (d, J = 7.4 Hz, 1H), 8.30 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 - 7.78 143-147; 121C (m, 4H), 7.49 - 7.33 (m, 5H), 7.29 - 7.26 (m, 148-151 1H), 6.03 (s, 1H), 3.95 (s, 2H), 1.84 (d, J: 1.3 Hz, 3H), 1.71 (d, J: 1.2 Hz, 3H).
(CDC13) 6 8.58 (s, 1H), 8.24 — 8.18 (m, 2H), 7.99— 7.94 (m, 2H), 7.84 — 7.78 (m, 2H), 7.47 (dd, J = 5.0, 1.1 Hz, 2H),7.40 (d, J: 8.3 Hz, 2H), 7.34 (ddd, J: 7.9, 5.1, 3.7 Hz, 169—171 1H), 7.18 (d, J = 7.6 Hz, 1H), 4.00 (d, J = 1.5 Hz, 2H), 3.72 (dd, J = 7.0, 5.1Hz, 2H), 2.94 — 2.80 (m, 1H), 2.22 (s, 3H), 1.23 (m, 9H).
(CDC13) 5 8.62 (s, 1H), 8.54 (d, J: 3.2 Hz, 1H), 8.28 - 8.19 (m, 3H), 7.82 (d, J: 8.8 130—135 Hz, 5H), 7.43 — 7.37 (m, 3H), 4.02 (s, 2H), 2.63 (d, J: 7.6 Hz, 2H), 1.22 (s, 3H) (CDC13) 5 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.89 - 7.75 (m, 4H), 140— 145 7.58 - 7.51 (m, 1H), 7.49 - 7.36 (In, 5H), 4.04 (d, J: 17.4 HZ, 1H), 3.97 (d, J = 17.4 Hz, 1H).
(CDC13) 6 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.86 - 7.78 (m, 4H), 7.65 (dd, J: 8.1, 1.4 Hz, 1H), 7.49 - 7.42 130—140 (m, 1H), 7.40 (d, J = 8.3 Hz, 2H), 7.35 (dt, J = 7.6, 1.5 Hz, 1H), 7.05 (dd, J = 78,15 Hz, 1H), 3.95 (s, 2H), 1.38 (s, 9H).
(CDC13) 6 8.58 (s, 1H), 8.29 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.87 - 7.77 (m, 4H), 175-177 7.52 (ddd, J: 8.1, 6.0, 3.4 Hz, 1H), 7.44 - 7.34 (m, 5H), 6.46 (t, JHF = 73.5 Hz, 1H), 4.05 - 3.95 (m, 2H).
W0 2012/109125 PCT/U52012/023932 Synthesis 0 1 1 MS mp ( C) H NMR (8) Method (CDC13) 6 8.58 (s, 1H), 8.32 (s, 1H), 8.22 ((1, J: 8.3 HZ, 2H), 7.87 - 7.75 (m, 4H), 578 7.43 — 7.32 (m, 4H), 7.26 — 7.24 (m, 2H), 127C F 112-115 (M+H) 4.23 (q, J: 7.3 Hz, 1H), 1.85 - 1.78 (m, 4H), 0.90 - 0.78 (m, 2H), 0.78 - 0.69 (m, 1H), 0.65 - 0.55 (m, 1H).
(CDC13) 8 8.58 (s, 1H), 8.29 (d, J = 7.8 Hz. 1H), 8.22 (d, J = 8.3 Hz, 2H), 7.88 — 7.74 580 (m, 4H), 7.48 - 7.30 (m, 5H), 7.20 (t, J: 128C F 164-171 (M+H) 11.1 Hz, 1H), 4.26 - 4.14 (m, 1H), 2.50 — 2.46 (m, 2H), 1.79 (d, J = 7.3 Hz, 3H), 1.69 1:;r nnxnna/ 1_’7’}Un on - 1..)u (11 — 1..) 11 , 4n), v.7.) (1,.1 , .111). 1 1 I (CDC13)8 8.58 (s, 1H). 8.30 (s, 1H), 8.22 m I: 8.4 Hz, 2H), 7.87 — 7.76 (m, 4H), ‘ 140—142 7.53 — 7.47 (In, 2H), 7.44 - 7.35 (In, 3H), 4.27 (q, J: 7.3 Hz, 1H), 1.82 (d, J: 7.3 Hz, 3H). ) 3 8.58 (s, 1H), 8.31 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H), 7.88 - 7.76 (In, 4H), 93—97; 7.48 - 7.34 (In, 4H), 7.20 (tt, J = 12.4, 6.1 191—194 , 4.35 — 4.18 (In, 1H), 1.81 (2d, J = 7.3 Hz, 3H).
(CDC13)3 8.58 (s, 1H), 8.32 (s, 1H), 8.26 — 8.20 (In, 2H), 7.86 — 7.78 (In, 4H), 7.53 — 93—98; 7.42 (In, 1H), 7.40 (d, J = 8.3 HZ, 2H), 7.09 185-186 (t, J: 8.1 Hz, 2H), 4.26 (q, J = 7.3 HZ, 1H), 1.80 (d, J: 7.3 Hz, 3H).
(CDC13) 6 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J: 8.4 Hz, 2H), 7.80 (ddd, J = 9.5, 6.9, 4.9 Hz, 4H), 7.43 - 7.33 (m, 4H), 7.31 - 7.21 552 (m, 2H), 4.05 (td, J = 9.4, 7.1 Hz, 1H), 3.97 J 193-196 (1V1+H) - 3.87 (m, 1H), 3.42 - 3.33 (m, 1H), 3.33 - 3.24 (m, 1H), 3.12 (heptet, J = 6.8 Hz, 1H), 1.27 (d, J: 6.8 HZ, 3H), 1.22 (d, J = 6.9 Hz, 3H).
‘ ‘ (CDC13) 8 8.55 (d, J: 7.1 Hz, 1H), 8.23 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.80 (dt, J: I I 538 | . WC . . 11.4, 6.2 Hz, 4H), 7.43 ' - 7.23 (m, 6H), 4.00 (s, 2H), 3.32 (s, 2H), 2.67 (q, J = 7.6 Hz, 2H), 1.25 (dd, J = 9.6.5.5 Hz, 3H).
PCTfUS2012/023932 Synthesis Method (CDC13) 5 8.65 (s, 1H), 8.22 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.94 - 7.88 (m, 2H), 7.81- 7.78 (m, 4H), 7.41 (dd, J = 7.8, 1.5 Hz, 1H), 7.39 - 7.33 (m, 1H), 7.30 - 7.24 (m, 217-220; 1H), 7.23 (dd, J = 7.8, 1.5 Hz, 1H), 4.09 - 230-232 4.02 (m, 1H), 3.98 — 3.88 (m, 1H), 3.43 - 3.24 (m, 2H), 3.12 t, J = 6.9 Hz, 1H), 1.27 (d, J = 6.8 Hz, 3H), 1.22 (d, J = 6.9 Hz, 3H).
(CDC13) 3 8.56 (s, 1H), 8.19 (dd, J: 12.7, 9.0 Hz, 3H), 7.84 - 7.74 (m, 4H), 7.37 (dd, J = 14.9, 6.1 Hz, 4H), 7.26 (s, 1H), 7.21 (d, J 167—169 = 7.6 Hz, 1H), 4.17 — 3.85 (m, 2H), 3.42 — 3.22 (m, 2H), 2.82 (d, J = 23.6 Hz, 1H), 1.80 — 1.55 (m, 2H), 1.23 (2d, J = 6.9 Hz, 3H), 0.82 (21, J = 7.4 Hz, 3H).
(CDC13)8 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.84 — 7.74 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 7.5 Hz, 143— 147 1H), 7.19 (d, J = 6.4 Hz, 1H), 7.15 (d, J: 7.3 Hz, 1H), 3.92 (qt, J = 10.1, 7.3 Hz, 2H), 3.43 — 3.28 (m, 2H), 2.72 — 2.51 (m, 2H), 2.27 (s, 3H), 1.25 (t, J = 7.6 Hz, 3H).
(CDC13)3 8.56 (d, J = 5.3 Hz, 1H), 8.26 (s, 1H), 8.17 (d, J: 8.4 Hz, 2H), 7.84 — 7.74 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.18 (d, J 183-186 = 8.5 Hz, 1H), 6.81 (dt, J = 8.4.2.9 Hz, 2H), 3.96 (t, J: 6.6 Hz, 2H), 3.81 (s, 3H), 3.30 (t, J = 6.9 Hz, 2H), 2.28 (s, 3H).
(CDC13) 6 8.56 (d, J = 5.4 Hz, 1H), 8.25 (s, 1H), 8.17 (d, J = 8.4 Hz, 2H), 7.84 - 7.72 231-233 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 6.67 (s, 2H), 3.92 - 3.85 (m, 2H), 3.79 (s, 3H), 3.34 (t, J: 7.1 Hz, 2H), 2.25 (s, 6H).
(CDC13)3 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J: 8.3 Hz, 2H), 7.83 - 7.73 (m, 4H), 195-197 7.39 (d, J: 8.3 Hz, 2H), 6.95 (s, 2H), 3.90 (t, J=7.1 Hz, 2H), 3.35 (t, J: 7.1Hz,2H), 2.30 (s, 3H), 2.23 (s, 6H).
W0 2012/109 125 aSynthesis MS mp( C)0 1 HNMR(5) 1 Method (CDCI3) 8 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J: 8.3 Hz, 2H), 7.84 - 7.75 (m, 4H), 7.43 — 7.36 (m, 3H), 7.30 (ddd, J = 12.6, 6.9, 181-184 3.1 Hz, 1H), 7.06 - 6.97 (m, 2H), 4.04 (t, J: 7.0 Hz, 2H), 3.86 (s, 3H), 3.29 (t, J = 7.0 Hz, 2H).
(CDC13) 8 8.56 (s, 1H), 8.25 (s, 1H), 8.18 (d, J: 8.4 Hz, 2H), 7.83 - 7.75 (m, 4H), 141C J (121:1) 173-176 7.39 (d, J = 8.3 Hz, 2H), 7.34 - 7.23 (m, 4H), 4.01 (t, J = 6.9 Hz, 2H), 3.32 (t, J = 6.9 Hz, 2H), 2.31 (s, 3H).
I I I I (CDC13)8 8.56 (s, 1H), 8.23 (s, 1H), 8.17 I I (d, J: 8.4 Hz, 2H), 7.84 - 7.74 (m, 4H), 14W”)(“ J 210 213 —— - 73901.1- 8.3 0,722 7.10 (m, (Mm) 3H), 3.92 (t, J = 7.1 Hz, 2H), 3.36 (t, J: 7.1 HZ, 2H), 2.28 (s, 6H).
(CDC13) 8 8.56 (s, 1H), 8.23 (s, 1H), 8.18 (d, J = 8.4 Hz, 2H), 7.83 - 7.74 (m, 4H), 7.38 (d, J: 8.3 Hz, 2H), 7.30 (dt, J: 7.4, 221-224 4.8 Hz, 2H), 7.15 - 7.09 (In, 1H), 4.05 (ddd, J: 9.4, 7.3, 5.2 Hz, 1H), 4.00 - 3.89 (1n, 1H), 3.46 - 3.30 (m, 2H). (300 MHz, CDC13) 5 8.56 (d, J = 4.3 Hz, 1H), 8.34 (s, 1H), 8.21 (s, 1H), 8.18 (s, 1H), 117—123; 7.81 (dd, J = 8.9, 2.3 Hz, 4H), 7.52 (d, J = 134—138 6.7 Hz, 1H), 7.50 — 7.31 (m, 10H), 3.53 - 3.49 (m, 2H), 2.95 — 2.90 (d, J = 6.8 Hz, 2H).
(CDC13) 5 8.56 (s, 1H), 8.26 (s, 1H), 8.18 (d, J = 8.3 Hz, 2H), 7.84 - 7.74 (m, 4H), 7.39 (d, J: 8.3 Hz, 2H), 7.32 - 7.21 (m, 9 3H), 7.01 (dd, J = 8.9, 2.5 Hz, 1H), 4.12 - (M+H) 4.04 (s, 2H), 3.34 (t, J = 6.9 Hz, 2H), 2.09 - 1.98 (m, 1H), 0.95 (dd, J: 8.5, 1.7 Hz, 2H), 0.72 (bs, 2H).
(CDClg) 8 8.56 (d, J :n5.2 Hz, 1H), 8.24 (s, 1H), 8.17 (d, J = 8.3 D z, 2H), 7.80 (dt, J: 554 ' 8.2, 4.6 Hz, 4H), 7.45 - 7.36 (m, 3H), 7.30 — 141—144 7.24 (m, 1H), 7.05 - 6.95 (m, 2H), 4.13 - 4.02 (In, 4H), 3.28 (t, J = 7.0 Hz, 2H), 1.44 - 1.35 (m, 3H).
PCT/U52012/023932 Synthesis Method (CDC13)6 8.57 (s, 1H), 8.37 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 7.87 — 7.76 (m, 4H), 7.40 (d, J: 8.4 Hz, 2H), 7.29 (dd, J = 14.2, 168-170 6.0 Hz, 1H), 7.24 (d, J = 2.3 Hz, 1H), 7.09 — 7.02 (m, 1H), 6.72 (dd, J = 8.0, 2.1 Hz, 1H), 4.20 (t, J = 6.9 Hz, 2H), 3.83 (d, J = 8.7 Hz, 3H), 3.24 (t, J = 6.9 Hz, 2H).
(CDC13) 8 8.56 (s, 1H), 8.24 (s, 1H), 8.18 (d, J = 8.3 Hz, 2H), 7.80 (dt, J = 4.0, 2.5 Hz, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.30 (ddd, J: 148C 213-216 8.5, 7.4, 4.2 Hz, 1H), 7.05 - 6.97 (m, 2H), 4.02 (t, J = 6.9 Hz, 2H), 3.36 (1, J = 6.9 Hz, 2H).
(CDC13) 8 8.56 (s, 1H), 8.18 (d, J = 2.6 Hz, 2H), 8.16 (s, 1H), 7.80 (d1, J: 8.3, 4.7 Hz, 4H), 7.71 (t, J = 8.6 Hz, 2H), 7.47 (t, J: 7.7 149C 200-203 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 4.18 — 4.07 (1H, 1H), 3.93 — 3.84 (m, 1H), 3.46 (td, J: 10.7, 7.3 Hz, 1H), 3.35 — 3.25 (m, 1H).
(CDC13)8 8.56 (s, 1H), 8.22 (s, 1H), 8.17 (d, J: 8.4 Hz, 2H), 7.80 (dt, J = 11.5, 6.2 Hz, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.31 — 169-172 7.27 (m, 3H), 7.26 — 7.24 (m, 1H), 4.10 — 3.89 (m, 2H), 3.38 — 3.32 (m, 2H), 2.48 (s, 2H), 2.01 — 1.84 (m, 1H), 0.91 (d, J: 6.2 Hz, 6H).
(CDC13) 8 8.57 (s, 1H), 8.25 (s, 1H), 8.18 (d, J: 8.3 Hz, 2H), 7.99 (s, 1H), 7.81 (dt, J = 8.3, 4.5 Hz, 4H), 7.39 (dd, J = 6.1, 3.5 Hz, 149-153 3H), 7.33 - 7.27 (m, 2H), 6.21 (s, 1H), 3.92 (t, J = 6.9 Hz, 2H), 3.26 (t, J = 6.8 Hz, 2H), 1.89 (d, J: 1.1 Hz, 3H), 1.79 (d, J: 1.1 Hz, 3H). ) 8 8.57 (s, 1H), 8.23 - 8.16 (m, 3H), 7.83 - 7.77 (m, 4H), 7.48 (dd, J = 7.5, 2.0 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 7.33 (dt, J 152C 161-163 = 7.2, 2.1 Hz, 2H), 7.28 (dd, J = 9.8, 1.9 Hz, 1H), 6.52 (1;, JHF = 74.1 Hz, 1H), 4.06 (t, J = 6.9 Hz, 2H), 3.33 (t, J = 6.9 Hz, 2H). wo 2012/109125 PCTfUS2012/023932 aSynthesis MS ml“ C)0 Method (CDC13) 8 8.57 (s, 1H), 8.25 (s, 1H), 8.19 (d, J = 8.4 Hz, 2H), 7.81 (dt, J = 4.1, 2.6 Hz, 153C J (131311) 195197 4H), 7.58 — 7.52 (m, 1H), 7.42 — 7.33 (m, 5H), 4.05 (1, J = 6.9 Hz, 2H), 3.31 (1, J: 6.9 Hz, 2H).
CDC13) 8 8.56 (s, 1H), 8.23 (d, J = 9.8 Hz, 1H), 8.17 (d, J = 8.3 Hz, 2H), 7.84 — 7.74 (m, 4H), 7.39 (d, J: 8.3 Hz, 2H), 7.35 - 154C J 164-167 7.27 (m, 3H), 7.19 (s, 1H), 3.54 - 3.31 (m, (M+H) 1H), 3.07 - 2.93 (m, 1H), 2.31 (d, J: 9.0 Hz, 3H), 1.62 - 1.56 (m, 1H), 1.31 - 1.19 (In, OY‘I\ on). 1 Tonsomers ) 8 8.56 (s, 2H), 8.18(dd, J: 10.8, 7.4 Hz, 6H), 7.84 — 7.73 (1n, ‘ 8H), 7.45 — 7.23 (m, — 7.30 (m, 8H), 7.30 2H), 7.20 (d, J = 6.7 Hz, 1H), 7.12 (dd, J: 201-204 7.8, 1.2 Hz, 1H), 4.43 — 4.33 (m, 1H), 4.16 (M+H) (dd, J: 12.6, 6.3 Hz, 1H), 3.48 (dt, J: 13.3, 6.7 Hz, 1H), 3.37 (dd, J = 10.8, 6.2 Hz, 1H), 3.24 (dt, J: 13.7, 6.9 Hz, 1H), 3.08 — 2.92 (m,3H), 1.33 - 1.16 (m, 18H).
(CDC13) 8 8.56 (S, 1H), 8.20 (d, J = 3.4 Hz, 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.84 - 7.73 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 7.25 — 566 105—110 7.09 (In, 3H), 4.39 — 4.23 (m, 1H), 3.53 — (M+H) 3.35 (m, 1H), 3.04 — 3.00 (m, 1H), 2.78 - 2.49 (m, 2H), 2.28 (28, 3H), 1.34 - 1.08 (m, 6H).
(CDC13) 8 8.56 (d, J = 0.6 Hz, 1H), 8.21 (s, 1H), 8.17 (d, J = 8.2 Hz, 2H), 7.82 - 7.77 592 (m, 4H), 7.49 - 7.35 (m, 4H), 7.30 - 7.28 (m, 175-176 (M+H) 1H), 4.64 - 4.57 (m, 1H), 3.44 (dd, J: 10.2, 6.3 Hz, 1H), 3.16 - 3.01 (m, 1H), 1.27 (d, J = 6.3 Hz, 3H). sis 0 1 1 Two Isomers (CDC13) 5 8.56 (s, 2H), 8.20 (s, 2H), 8.19 - 8.12 (m, 4H), 7.84 - 7.73 (m, 8H), 7.39 (d, J = 8.3 Hz, 4H), 7.36 - 7.29 (m, 2H), 7.25 - 7.17 (m, 4H), 4.78 - 4.55 (m, 1H), 4.35 (dt, 1 = 9.4, 6.3 Hz, 1H), 3.48 (dd, J: 10.7, 6.5 Hz, 1H), 3.38 (dd, J: 10.7, 6.2 Hz, 1H), 3.11 (dd, J: 10.7, 9.4 Hz,1H), 3.01 (dd, J: 10.7, 8.3 Hz, 1H), 2.35 (s, 3H), 2.30 (s, 3H), 1.26 (d, J = 6.3 Hz, 3H), 1.21 (d, J = 6.4 Hz, 3H) (CDC13) 8 8.56 (s, 1H), 8.18 (dd, J: 11.9, .3 Hz, 3H), 7.79 (dd, J = 87,65 Hz, 4H), 7.47 (dd, J = 7.8, 2.3 Hz, 1H), 7.42 — 7.32 (m, 5H), 4.48 ~ 4.29 (m, 1H), 3.45 (dd, J = .7, 6.4 Hz, 1H), 2.98 (dd, J = 10.7, 7.1 Hz, 1H), 1.26 (d, J = 6.3 Hz, 3H) Two Isomers (CDC13) 8 8.56 (s, 2H), 8.19 — 8.12 (m, 6H), 7.84 - 7.73 (m, 10H), 7.71 (d, J = 8.2 Hz, 2H), 7.47 (t, J = 8.0 HZ, 2H), 7.39 (d, J = 8.3 Hz, 4H), 4.76 - 4.64 (m, 1H), 4.48 (dd, J = 14.6, 6.3 Hz, 1H), 3.43 (dd, J: 10.6, 6.2 Hz, 1H), 3.29 (dd, J = .5, 5.5 HZ, 1H), 3.16 - 3.00 (m, 2H), 1.27 (d, J: 6.4 Hz, 3H), 1.17 (d, J = 6.4 Hz, 3H) (CDC13) 8 8.56 (s, 1H), 8.22 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.83 — 7.70 (m, 4H), 7.39 (d, J: 8.3 Hz, 2H), 6.94 (d, J: 9.3 Hz, 2H), 4.43 — 4.22 (m, 1H), 3.42 (dd, J: 10.8, 6.5 Hz, 1H), 3.00 (dd, J: 10.8, 8.5 Hz, 1H), 2.30 (s, 3H), 2.25 (s, 3H), 2.21 (s, 3H), 1.20 (d, J: 6.3 Hz, 3H) (CDC13) 8 8.56 (s, 1H), 8.24 (s, 1H), 8.17 (d, J: 8.4 Hz, 2H), 7.83 — 7.73 (m, 4H), 7.39 (d, J: 8.3 Hz, 2H), 7.18 — 7.09 (m, 1H), 6.86 - 6.76 (m, 2H), 4.33 - 4.19 (m, 1H), 3.82 (s, 3H), 3.47 — 3.38 (m, 1H), 3.00 - 2.99 (m, 1H), 2.29 - 2.27 (m, 3H), 1.33 — 1.15 (m, 3H) W0 2012/109125 PCT/U52012/023932 nSynthesis 1 1 MS H NMR (5) Method (CDC13) 6 8.56 (s, 2H), 8.18 (dd, J: 10.7, .3 Hz, 6H), 7.84 - 7.74 (m, 8H), 7.42 - 7.30 (m, 8H), 7.23 — 7.10 (m, 2H), 4.37 (dd, J: 19.5,13.6 Hz, 1H), 4.16 (dd, J = 13.1, 6.6 Hz,1H), 3.56 - 3.42 (m, 1H), 3.34 (dd, J: .8, 6.0 Hz, 1H), 3.08 - 2.87 (m, 3H), 2.70 (dd, J: 16.0, 7.0 Hz, 1H), 1.71 - 1.56 (m, 4H), 1.34 - 1.25 (m, 6H), 1.24 - 1.14 (m, 6H), 0.93 - 0.73 (m, 6H) (CDC13) 3 8.56 (s, 1H), 8.22- 8. 14 (m, 3H), 7.84- 7.,76(m 4H), 7.-42 727(m, 6H),?“ u. 98 I 1 11(t,JHF—/ 7 __"l/1 F) TTH 11T\ U J 11-h.) 112,111}, 80 (dec) . .
/\E"r\g l 1H) -..,, Two Isomers (CDC13) 5 8.56 (s, 2H), 8.22 (s, 1H), 8.20 (s, 1H), 8.16 (d, J = 8.3 Hz, 4H), 7.84 - 7.74 (m, 8H), 7.58 (ddd, J = 9.7, 8.0, 1.7 Hz, 2H), 7.39 (d, J: 8.4 Hz, 4H), 580 143 7.36 - 7.27 (m, 4H), 7.15 (dd, J = 7.7, 1.6 165C J (M+H) (dec) Hz, 1H), 7.09 (dd, J = 7.6, 1.7 Hz, 1H), 4.38 - 4.22 (m, 2H), 3.61 (dd, J = 10.8, 7.0 Hz, 1H), 3.24 (dd, J = 10.7, 5.6 Hz, 1H), 3.07 - 2.94 (m, 1H), 2.91 (dd, J: 10.8, 1.5 Hz, 1H), 1.47 4 1.38 (m, 24H) (CDC13) 5 8.56 (s, 1H), 8.21 (s, 1H), 8.16 (d, J: 8.4 Hz, 2H), 7.84 — 7.73 (m, 4H), 7.39 (d. J = 8.3 Hz, 2H), 7.32 — 7.28 (m, 166C J 93 (dec) 3H), 7.20 (s, 1H), 4.20 - 4.06 (m, 1H), 3.41 (s, 1H), 3.05 (dd, J: 10.8, 8.2 Hz, 1H), 2.31 - 0.88 — 32.30 (m, 3H), 1.66 (s, 2H), 0.90 (m, 3H) Two s (CDC13) 8 8.56 (s, 2H), 8.20 (s, 2H), 8.16 (d, J = 8.3 Hz, 4H), 7.83 - 7.74 (m, 8H), 7.43 - 7.28 (m, 6H), 7.21 (dd, J: .4, 3.3 Hz, 4H), 4.49 - 4.36 (m, 1H), 4.17 - 586 105 l p_.\ O\\J ('3 '—-1 ' IIH) 340(dd,1=10.7,6.3 Hz. 1H), 3.10(dd, J=‘Lu.7, 9.4 Hz, 1H), 3.04 (dd, J =4.05 (m, 1H), 3.49 (dd, J: 10.7, 6.6 Hz, (M+H) (dec) l ' 10. 8, 8.2 Hz, 1H), 2.34 (s, 3H), 2.30 (s, 3H), 1.73 - 1.48 (m, 4H), 0.91 (m, 6H) WO 09125 Synthesis Method (CDC13) 5 8.56 (s, 1H), 8.18 (m,, 2H), 7.79 (m, 4H), 7.47 (dd, J = 7.8, 2.3 Hz, 1H), 7.42 199-200 - 7.32 (m, 5H), 4.48 - 4.29 (m, 1H), 3.45 (dd, J: 10.7, 6.4 Hz, 1H), 2.98 (dd, J: .7, 7.1 Hz, 1H), 1.26 (d, J: 6.3 Hz, 3H) (CDC13) a 10.45 (s, 1H), 8.59 (s, 1H), 8.25 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.9 Hz, 2H), 7.61 (1, J = 7.5 Hz, 2H), 7.40 (d, J = 8.7 Hz, 2H), 7.11 (t, J = 169C 8.0 Hz, 1H), 5.71 (d, J: 1.1 Hz, 1H), 2.35 (s, 3H) ”P NMR (376 MHz, CDC13) 8 58.02, - 62.31 (CDC13) 5 8.56 (s, 1H), 8.19 — 8.14 (m, 3H), 7.79 (m, 4H), 7.56 — 7.46 (m, 2H), 7.46 — 170C 157-159 7.43 (m, 2H), 7.39 (d, J = 8.3 Hz, 2H), 5.88 (d,J=1.3 Hz, 1H), 1.86 (d, J :12 Hz, 3H) (CDC13) 8 8.56 (s, 1H), 8.19 (d, J = 5.9 Hz, 2H), 8.16 (s, 1H), 7.83 - 7.76 (m, 4H), 7.45 171C 236-237 (tt, J: 8.4, 6.1 HZ, 1H), 7.39 (d, J: 8.3 HZ, 2H), 7.10 (dd, J = 8.5, 7.3 Hz, 2H), 5.90 (d, J: 1.3 Hz, 1H), 1.92 (s, 3H) (00013) 8 8.56 (d, J = 3.7 Hz, 1H), 8.21 (s, 1H), 8.16 (d, J = 8.4 Hz, 2H), 7.84 — 7.72 172C 103-108 (m, 4H), 7.39 (d, J = 8.3 Hz, 2H), 6.72 (s, 2H), 5.89 (d, J =13 Hz, 1H), 3.82 (s, 3H), 2.14 (s, 6H), 1.75 (d, J = 1.2 Hz, 3H).
(CDC13) 8 8.56 (s, 1H), 8.19-8.15 (m, 3H), 7.82 — 7.75 (m, 4H), 7.43 - 7.30 (m, 5H), 7.24 (d, J: 7.3 Hz, 1H), 5.88 (s,1H), 2.21 (s, 3H), 1.80 (d, J: 1.2 Hz, 3H) (CDC13) 8 8.56 (s, 1H), 8.20 - 8.12 (m, 3H), 7.83 - 7.74 (m, 4H), 7.43 - 7.36 (m, 3H), 7.32 (t, J: 7.7 Hz, 1H), 7.29-7.27 (m, 1H), .92 (d, J: 1.3 Hz, 1H), 2.26 (s, 3H), 1.81 (d, J: 1.2 Hz, 3H) flSynthesis 0 1 1 MS mp ( C) H NMR (8) Method (CDC13) 8 8.56 (d, J = 5.0 Hz, 1H), 8.21 - 8.13 (m, 3H), 7.83 - 7.74 (m, 4H), 7.39 (d, J 175C G 132—136 = 8.2 Hz, 2H), 7.29 - 7.23 (m, 1H), 7.19 (d, (M+H) J: 7.7 Hz, 2H), 5.92 (d, J: 1.3 Hz,1H), 2.18 (s, 6H), 1.75 (d, J: 1.2 Hz, 3H). ) 6 8.56 (s, 1H), 8.19 - 8.14 (m, 3H), 7.83 - 7.75 (m, 4H), 7.49 - 7.43 (m, 2H), 7.39 (d, J: 8.3 Hz, 2H), 7.33 (ddd, J: 7.8, 176C G 123—138 5.9, 3.0 Hz, 1H), 7.19 — 7.17 (m, 1H), 5.88 (M+H) (d, J: 1.3 Hz, 1H), 2.96 - 2.76 (m, 1H), 1.81 (d, J: 1.2 Hz, 3H), 1.24 (t, J: 6.4 Hz, (CDC13) 6 8.55 (s, 1H), 8.14 (d, J: 8.4 Hz, 2H), 8.05 (S, 1H), 7.84 - 7.77 (In, 2H), 7.74 ‘ (d, J: 8.3 HZ, 2H), 7.42 - 7.35 (m, 3H), 7.32 (dd, J = 10.6, 4.3 Hz, 1H), 7.28 — 7.24 185—187 (m, 1H), 7.18 (dd, J = 7.8, 1.4 Hz, 111), 3.80 - 3.48 (m, 1H), 3.11 - 3.69 (m, 1H), 3.59 (dd, J: 13.2, 6.8 Hz, 3H), 2.41 - 2.27 (m, 2H), 1.22 (t, J = 5.6 HZ, 6H).
(CDC13) 8 8.55 (d, J = 3.6 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.84 — 7.77 (m, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 9.0 Hz, 3H), 7.32 (td, J = 7.5, 1.4 Hz, 1H), 7.26 (s, 1H), 7.17 (t, J: 7.1 Hz, 1H), 3.69 — 3.26 (m, 1H), 3.55 ~ 3.37 (m, 1H), 3.18 — 2.98 (m, 2H), 2.93 — 2.80 (m, 1H), 2.47 (d, J = 35.9 Hz, 1H), 1.31 - 1.12 (m, 9H).
(CDC13) 8 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J: 8.5 Hz, 2H), 7.79 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.38 (dd, J = 7.8, 1.6 Hz, 1H), 7.33 (td, 212-213 J: 7.5, 1.4 Hz, 1H), 7.29 — 7.23 (m, 1H), 7.18 (dd, J = 7.8, 1.4 Hz, 1H), 3.78 - 3.72 (m, 1H), 3.59 - 3.48 (m, 1H), 3.18 — 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, I l on).’1'" Synthesis Method (300 MHz, CDC13) 5 8.55 (s, 1H), 8.13 (d, J = 8.3 Hz, 2H), 8.05 (s, 1H), 7.76 (dd, J = 17.0, 8.7 Hz, 4H), 7.37 (t, J = 8.4 Hz, 2H), 127-133 7.18 (dd, J: 12.7, 9.6 Hz, 3H), 3.54 — 3.49 (m, 2H), 3.12 - 3.08 (m, 2H), 2.70 - 2.55 (m, 2H), 2.39 - 2.31 (m, 2H), 2.28 (s, 3H), 1.25 (t, J: 7.6 Hz, 3H).
(CDC13)5 8.55 (s, 1H), 8.14 (d, J = 8.3 Hz, 2H), 8.08 (s, 1H), 7.84 - 7.76 (m, 2H), 7.74 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 170—174 6.65 (s, 2H), 3.79 (s, 3H), 3.52 — 3.45 (m, 2H), 3.10 - 3.07 (m, 2H), 2.38 — 2.31 (d, J: .7 Hz, 2H), 2.25 (s, 6H). (300 MHz, CDC13) 5 8.55 (d, J = 1.0 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.05 (s, 1H), ; 7.83 — 7.76 (m, 2H), 7.74 (d, J: 8.4 Hz, 182C 166-168 2H), 7.38 (d, J = 9.0 Hz, 2H), 7.14 — 7.09 (m, 3H), 3.51 (dd, J = 9.1, 3.5 Hz, 2H), 3.15 — 3.03 (m, 2H), 2.36 (s, 2H), 2.28 (s, 6H).
(CDC13)8 8.55 (d, J = 3.7 Hz, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 19.3 Hz, 1H), 7.84 — 7.77 (m, 2H), 7.74 (d, J: 8.4 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 3.8 Hz, 2H), 7.25 (d, J = 6.6 Hz, 1H), 7.19 183C 159—162 (1, J = 8.0 Hz, 1H), 3.76 (ddd, J = 24.2, 12.0, .9 Hz, 1H), 3.58 - 3.46 (m, 1H), 3.11 (dd, J = 15.3, 6.1 Hz, 2H), 2.82 (dd, J: 146,72 Hz, 1H), 2.41 — 2.29 (m, 2H), 1.71-1.55 (m, 2H), 1.20 (d, J = 6.8 Hz, 3H), 0.87 — 0.76 (m, 3H).
(CDC13) 5 8.55 (s, 1H), 8.14 (d, J: 8.4 HZ, 2H), 8.07 (s, 1H), 7.83 - 7.76 (m, 2H), 7.74 (d, J: 8.4 Hz, 2H), 7.40 (t, J = 10.1 Hz, 194-198 2H), 6.93 (s, 2H), 3.53 - 3.47 (m, 2H), 3.12 - 3.05 (m, 2H), 2.34 (dt, J: 11.7, 5.8 Hz, 2H), 2.30 (s, 3H), 2.23 (s, 6H).
PCTfU$2012/023932 Synthesis Method (CDC13) 3 8.55 (s, 1H), 8.14 (d, J: 8.4 Hz, 2H), 8.06 (s, 1H), 7.83 - 7.77 (m, 2H), 7.74 (d, J: 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 157-160 7.36 - 7.27 (m, 3H), 7.23 - 7.19 (m, 1H), 3.74 (m, 1H), 3.50 (m, 1H), 3.10 (d, J: 5.9 Hz, 2H), 2.64 (q, J = 7.6 Hz, 2H), 2.40 - 2.29 (m, 2H), 1.28 - 1.21 (m, 3H).
(CDC13) 5 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.09 (s, 1H). 7.83 — 7.77 (m, 2H), 7.81 - 7.77 (m, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.24 186C J 173-177 - - 7.22 (m, 3H), 7.05 - 6.95 (m, 1H), 3.77 (M+H) 3.63 (m, 2H), 3.14 - 3.07 (111,211), 2.45 — oooz ‘09_1.92(m 11—“ mm. I A.A/ \u AAA, All], v.1 I 0.82 (m, 3H), 0.53 (bs, 1H). (300 MHZ, CDC13) 5 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.05 (d, J = 4.9 Hz, 1H), 7.77 (dd, J: 11.4, 8.6 Hz, 4H), 7.39 (t, J = 8.1 180—182 Hz, 4H), 7.21 (dd, J = 13.2, 5.6 Hz, 1H), 3.65 - 3.58 (In, 2H), 3.09 (t, J = 5.5 Hz, 2H), 2.45 — 2.35 (m, 2H).
(CDC13) 5 8.56 (s, 1H), 8.15 (d, J: 8.4112, 2H), 8.07 (s, 1H), 7.79 (ddd, J: 15.8, 7.8, .8 Hz, 4H), 7.38 (d, J = 8.3 Hz, 2H), 7.31 — 209—212 7.21 (In, 2H), 7.10 (ddd, J = 9.7, 7.8, 2.0 Hz, 1H), 3.64 (t, J = 5.4 Hz, 2H), 3.11 (t, J: 6.0 Hz, 2H), 2.46 — 2.33 (m, 2H).
(CDC13)6 8.56 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.08 (s, 1H), 7.83 - 7.74 (m, 4H). 7.38 217-219 (d, J: 8.3 Hz, 2H), 7.31 - 7.21 (m, 1H), 7.03 - 6.94 (m, 2H), 3.72 - 3.62 (m, 2H), 3.15 - 2.34 (m, 2H). - 3.07 (m, 2H), 2.40 (CDC13) 6 8.55 (s, 1H), 8.14 (d, J = 8.3 Hz, 2H), 8.00 (s, 1H), 7.83 - 7.73 (m, 4H), 7.71 626 (d, J: 8.1 HZ, 1H), 7.67 (d, J = 7.7 Hz, 1H), 190-193 (M+H) 7.40 (dd, J = 15.8, 8.2 Hz, 3H), 3.79 - 3.69 (m, 1H), 3.55 \ ‘ 2H), 2.47 — 3.49011, 1H), 3.16 - 3.04 (m, - 2.31 (m, 2H).
Synthesis Method (CDC13) 8 8.54 (d, J = 4.3 Hz, 1H), 8.13 (d, J: 8.3 Hz, 2H), 8.05 (d, J = 6.3 Hz, 1H), 7.77 (dd, J = 15.4, 8.7 Hz, 4H), 7.38 (d, J: 150—155 8.3 Hz, 2H), 7.29 (dd, J = 8.0, 4.8 Hz, 2H), 7.04 — 6.93 (m, 2H), 3.85 (s, 3H), 3.65 — 3.61 (m, 2H), 3.10 — 3.06 (m, 2H), 2.36 — 2.28 (s, 2H).
(CDC13) 8 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.09 (s, 1H), 7.82 — 7.77 (m, 2H), 7.74 (d, J = 6.7 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 164-167; 192C 7.13 (d, J: 8.3 Hz, 1H), 6.79 (dd, J: 11.9, 168-173 3.3 Hz, 2H), 3.81 (s, 3H), 3.74 — 3.66 (m, 1H), 3.57 - 3.48 (m, 1H), 3.12 — 3.04 (m, 2H), 2.36 - 2.30 (m, 2H), 2.25 (s, 3H).
(CDC13)6 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.04 (s, 1H), 7.83 — 7.77 (m, 2H), 7.74 (d, J: 8.4 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 7.31 — 7.24 (m, 3H), 7.23 - 7.20 (m, 1H), 155—158 3.82 — 3.71 (m, 1H), 3.56 — 3.47 (m, 1H), 3.17 — 3.02 (m, 2H), 2.46 (t, J = 6.7112, 211), 2.39 — 2.27 (m, 2H), 1.99 t, J = 6.8 Hz, 1H), 0.95 — 0.92 (m, 6H).
(CDC13) 8 8.56 (s, 1H), 8.17 (m 3H), 7.80 (m, 4H), 7.52 - 7.47 (m, 2H), 7.47 — 7.31 (m, 102-108 9H), 3.42 — 3.05 (m, 2H), 2.86 (bs, 2H), 2.04 — 1.71 (m, 2H).
(CDC13) 6 8.55 (s, 1H), 8.14 (d, J = 8.3 Hz, 2H), 8.08 (s, 1H), 7.84 — 7.77 (m, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 159-162 7.31— 7.19 (m, 4H), 3.81 - 3.47 (m, 2H), 3.20 - 3.00 (m, 2H), 2.35 (dt, J: 11.7, 5.8 Hz, 2H), 2.28 (s, 3H).
(CDC13) 6 8.55 (s, 1H), 8.14 (d, J: 8.1 Hz, 2H), 8.05 (s, 1H), 7.80 (d, J: 8.9 Hz, 2H), 7.75 (d, J: 8.2 HZ, 2H), 7.38 (d, J: 8.8 Hz, 140-143 2H), 7.33 (dd, J: 6.1, 3.4 Hz,1H), 7.21 - 7.15 (m, 2H), 3.72 - 3.66 (m, 1H), 3.55 — 3.41 (m, 1H), 3.16 - 3.05 (m, 2H), 2.48 — 2.34 (m, 2H), 2.32 (s, 3H).
W0 2012/109125 sis 0 1 1 MS mp ( C) H NMR (5) Method (CDC13) 8 8.55 (s, 1H), 8.14 (d, J = 8.2 Hz, 2H), 8.06 (s, 1H), 7.80 (d, J = 8.9 Hz, 2H), 7.75 (d, J: 8.2 Hz, 2H), 7.38 (d, J: 8.8 Hz, 197C J 151-155 2H), 7.29 (dd, J = 10.7, 4.6 Hz, 4H), 6.20 (s, (M+H) 1H), 3.59 - 3.48 (m, 2H), 3.10 - 3.01 (m, 2H), 2.34 - 2.20 (m, 2H), 1.90 (s, 3H), 1.78 (s, 3H).
(CDC13) 8 8.56 (s, 1H), 8.36 (dd, J = 4.8, 1.3 Hz, 1H), 8.15 (d, J = 8.3 Hz, 2H), 8.09 (s, 1H), 7.78 (m, 4H), 7.54 (dd, J = 7.5, 0.9 Hz, 186-189 1H), 7.37 (d, J = 8.5 Hz, 2H), 7.13 (dd, J: I I I 7.4, 4.8 Hz, 1H), 3.87 (‘1, J = 5.7 "2, 2H), 3.12 H 3.03 (m, 2H), 2.40 — 2.32 (m, 2H), I 2.24 (s, 3H).
(CDC13) 5 8.55 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 8.05 (s, 1H), 7.83 — 7.78 (m, 2H), 7.76 207-208 ((1, J: 8.4 Hz, 2H), 7.43 - 7.36 (m, 3H), 7.34 (t, J: 4.7 Hz, 3H), 3.71 - 3.64 (m, 2H), 3.12 — 3.06 (m, 2H), 2.39 — 2.30 (m, 2H).
(CDC13)5 8.56 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 8.03 (s, 1H), 7.83 - 7.77 (m, 2H), 7.76 170—172 (d, J: 8.3 Hz, 2H), 7.42 - 7.27 (m, 6H), 6.74 - 6.29 (m, 1H), 3.70 - 3.64 (In, 2H), 3.13 - 3.06 (m, 2H), 2.40 - 2.31 (m, 2H).
(CDC13) 5 8.55 (s, 1H), 8.14 (d, J: 8.3 Hz, 2H), 8.00 (s, 1H), 7.83 — 7.73 (m, 4H), 7.71 (d, J: 8.1 Hz, 1H), 7.67 (d, J = 7.7 Hz, 1H), 190-193 7.40 (dd, J = 15.8, 8.2 Hz, 3H), 3.79 - 3.69 (m, 1H), 3.55 - 3.49 (m, 1H), 3.16 - 3.04 (m, 2H), 2.47 - 2.31 (m, 2H).
(CDC13) 5 8.56 (s, 1H), 8.19 - 8.08 (m, 3H), 7.84 - 7.72 (m, 4H), 7.39 (d, J = 8.4 Hz, 231—234 , . \ 2H), 7.25 - 7.20 (m, 2H), 6.96 - 6.88 (111, um“) 2H), 3.83 (s, 3H), 3.76 - — 3.68 (m, 2H), 3.13 3.03 (In, 2H), 2.39 - 2.27 (m, 2H).
(CDC13) 6 8.56 (s, 1H), 8.15 (d, J = 8.2 Hz, 2H), 8.06 (s, 1H), 7.83 = 7.77 (m, 2H), 7.75 I , (d, J: 8.2 Hz, 2H), 7.39 (d, J = 8.5 Hz, 2H), ' 200—201 7.28 - 7.25 (m, 2H), 3.51 - 3.42 (m, 2H), 3.14 - 3.05 (m, 2H), 2.35 (s, 2H), 2.25 (s, 6H). nShydethodnthesis MS mp(C)o 1HNMR(8)1 ) 8 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.09 (s, 1H), 7.84 - 7.77 (m, 2H), 7.75 568 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 204C J 193496 (M+H) 7.08 (t, J : 4.0 Hz, 2H), 6.88 (d, J : 8.6 Hz, 1H), 3.82 (s, 3H), 3.66 — 3.58 (m, 2H), 3.11 - 3.03 (m, 2H), 2.36 — 2.27 (m, 5H).
(CDC13) 8 8.55 (s, 1H), 8.45 (dd, J : 4.8, 1.6 Hz,1H), 8.18 - 8.12 (m, 2H), 8.06 (s, 1H), 539 . 7.82 - 7.72 (m, 4H), 7.53 (dd, J : 7.9, 1.6 205C J 011 (M+H) Hz, 1H), 7.40 - 7.33 (m, 2H), 7.24 — 7.18 (m, 1H), 3.63 (br s, 2H), 3.18 - 3.03 (m, 2H), 2.51 (s 3H), 2.35 (dt, J: 11.7, 5.7 Hz, 2H) (CDC13) 8 8.56 (s, 1H), 8.16 (d, J: 8.9 Hz, 3H), 7.84 - 7.73 (m, 4H), 7.39 (d, J: 8.8 554 Hz, 2H), 7.30 (t, J : 8.1 Hz, 1H), 6.95 — 6.85 206C J 177-178 (M+H) (m, 2H), 6.78 (dt, J :11.1, 5.5 Hz, 1H), 3.81 (s, 3H), 3.79 — 3.73 (m, 2H), 3.12 — 3.04 (m, 2H), 2.38 — 2.28 (m, 2H).
(CDC13)8 8.57 (s, 1H), 8.23 - 8.13 (m, 3H), 8.06 (d, J: 8.5 Hz, 2H), 7.80 (dd, J : 8.5, 596 4.5 Hz, 4H), 7.39 (d, J : 8.5 Hz, 4H), 4.38 207C J 171—173 (M+H) (q, J = 7.2 Hz, 2H), 3.82 (t, J : 6.0 Hz, 2H), 3.14 — 3.03 (m, 2H), 2.37 (s, 2H), 1.40 (t, J: 7.1 Hz, 3H).
(CD013) 8 8.55 (s, 1H), 8.14 (d, J : 8.3 Hz, 2H), 8.07 (s, 1H), 7.84 - 7.77 (m, 2H), 7.75 (d, J : 8.3 Hz, 2H), 7.38 (d, J : 8.3 Hz, 2H), 7.32 - 7.23 (m, 2H), 6.99 (ddd, J = 8.3, 5.5, 208C 171-173 1.4 Hz, 2H), 4.08 (q, J : 7.0 Hz, 2H), 3.69 - 3.57 (m, 2H), 3.16 - 3.02 (m, 2H), 2.32 (dt, J: 11.7, 5.9 Hz, 2H), 1.39 (t, J : 7.0 Hz, 3H).
(CDCl3) 5 8.64 (s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.06 (s, 1H), 7.91 (d, J: 8.5 Hz, 2H), 7.79 (d, J: 8.6 Hz, 2H), 7.75 (d, J: 8.4 Hz, 2H), 7.38 (dd, J: 7.8, 1.6 Hz,1H), 7.33 (td, 209C 212-213 J= 7.5,1.4 Hz, 1H), 7.29 — 7.23 (m, 1H), 7.18 (dd, 1: 78,14 Hz, 1H), 3.78 — 3.72 (m, 1H), 3.59 - 3.48 (m, 1H), 3.18 - 3.04 (m, 3H), 2.40 - 2.30 (m, 2H), 1.26 - 1.20 (m, 6H).
W0 2012/109125 aSynthesis MS 0 1 1 mp ( C) H NMR (5) Method (CDCI3) 8 8.55 (s, 1H), 8.14 (d, J: 8.4 Hz, 2H), 8.07 (s, 1H), 7.83 — 7.77 (m, 2H), 7.75 (d, J: 8.4 Hz, 2H), 7.55 - 7.49 (m, 1H), 7.38 (d, J: 8.3 Hz, 2H), 7.32 — 7.26 (m, J 9 2H), 7.19 - 7.13 (m, 1H), 3.72 (ddd, J: (M+H) 12.9, 9.3, 3.8 HZ, 1H), 3.60 - 3.51 (m,1H), 3.15 (ddd, J: 13.3, 9.4, 4.0 Hz, 1H), 3.10 - 3.01 (m, 1H), 2.51 - 2.36 (m, 1H), 2.36 - 2.22 (m, 1H), 1.43 (s, 9H).
(CDC13) 3 8.55 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 8.10 (s, 1H), 7.79 (dt, J: 10.4, 5.8 Hz, 100-106 i4H), 7.38 (d, J: 8.3 Hz, 2H), 7.11 (s, 3H),3.85 - 3.78 (m, 2H), 3.20 - 3.12 (m, 2H), I I 2.30 (s, 6H), 2.13 - 2.07 (m, 2H), 1.87 — 1.82(m 7H) \u-, _- ‘l' (CDC13)5 8.55 (s, 1H), 8.19 — 8.10 (In, 3H), 7.79 (dt, J = 10.7, 5.9 Hz, 4H), 7.38 (dd, J: 8.5, 2.6 Hz, 3H), 7.30 (td, J: 7.5, 1.4 Hz, 186-188 1H), 7.23 (td, J = 7.5, 1.7 Hz, 1H), 7.13 (dd, J: 7.8, 1.4 Hz, 1H), 3.94 (bs, 2H), 3.24 — 3.02 (In, 3H), 2.13 - 2.05 (In, 2H), 1.84 — 1.73 (In, 2H), 1.24 (t, J = 10.5 Hz, 6H).
(CDC13) 5 8.55 (s, 1H), 8.13 (d, J = 8.4 Hz, 2H), 8.03 (d, J = 4.4 Hz, 1H), 7.83 — 7.76 (m, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.24 — 7.15 (m, 2H), 7.12 (dd, 123—127 J: 11.9, 4.6 Hz, 1H), 3.82 - 3.71 (m, 1H), 3.30 — 3.18 (m, 1H), 3.07 - 2.94 (m, 1H), 2.72 - 2.40 (m, 3H), 2.30 - 2.16 (m, 4H), 1.30 — 1.12 (m, 6H).
(CDC13) 5 8.55 (s, 1H), 8.15 (d, J: 8.4 Hz, 2H), 8.06 (s, 1H), 7.83 - 7.72 (m, 4H), 7.38 (m, 3H), 7.34 (dd, J = 2.9, 1.5 Hz, 3H), 3.58 160-162 (ddd,J=12.3, 3.9, 1.4 Hz, 1H), 3.39 (dd, J I = 12.2, 9.2 Hz, 1H), 3.04 (ddd, J: 12.2, 3.9,1.4 Hz, 1H), 2.84 (dd, J = 12.2, 9.5 Hz, 1H),051 n ,m /m 111x 110 [A 1_ (#11,. own I l 4.U1 - AH; (111, 111}, 1.10 (u, J ; U.I 1 L1, J11} Synthesis Method (CDC13) 6 8.55 (s, 1H), 8.14 (dd, J: 8.3, 1.5 Hz, 2H), 8.00 (d, J = 4.0 Hz, 1H), 7.84 - 7.72 (m, 4H), 7.72 - 7.63 (m, 2H), 7.45 — 7.32 (m, 3H), 3.60 - 3.44 (m, 1H), 3.37 — 3.27 (m, 1H), 3.03 - 2.92 (m, 1H), 2.92 - 2.82 (m, 1H), 2.69 - 2.54 (m, 1H), 1.19 - 1.12 (m, 3H) (CDC13) 8 8.55 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.02 (s, 1H), 7.82 - 7.71 (m, 4H), 7.44 - 7.30 (m, 6H), 3.87 (d, J: 6.3 HZ, 1H), 3.23 216C 132-135 (td, J: 11.9, 3.8 Hz, 1H), 3.07 - 2.94 (m, 1H), 2.54 — 2.43 (m, 1H), 2.19 (ddd, J = 13.9, 9.0, 5.0 Hz, 1H), 1.31 (d, J = 6.6 Hz, Two isomers (CDC13) 6 8.55 (s, 2H), 8.14 (dd, J: 8.4, 2.7 Hz, 4H), 7.98 (d, J: 4.2 Hz, 2H), 7.83 — 7.72 (m, 811), 7.67 (dt, J: 12.9, 7.4 Hz, 4H), 7.40 (dd, J = 15.3, 8.1 Hz, 6H), 4.17 (s, 1H), 3.96 (td, J = 6.6, 3.1 Hz, 1H), 3.24 — 3.12 (m, 2H), 3.12 — 3.01 (m, 2H), 2.41 (dddd, J = 10.8, 10.0, 8.9, 4.2 Hz, 2H), 2.30 - 2.15 (m, 2H), 1.24 (d, J: 6.7 Hz, 3H), 1.04 (d, J = 6.7 Hz, 3H) )5 8.55 (s, 1H), 8.18 - 8.10 (m, 2H), 8.05 (s, 1H), 7.83 — 7.76 (m, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.41 — 7.37 (m, 2H), 6.93 (d, J = 9.4 Hz, 2H), 3.76 (dd, J = 10.8, 4.6 Hz. 1H), 3.29 - 3.16 (m, 1H), 2.99 (ddd, J: 12.2, 5.9, 3.9 Hz, 1H), 2.54 - 2.37 (m, 1H), 2.31 (s, 3H), 2.22 (d, J = 6.4 Hz, 7H), 1.19 (d, J = 6.7 Hz, 3H) (CDC13) 6 8.55 (s, 1H), 8.14 - 8.06 (m, 3H), 7.91 - 7.65 (m, 4H), 7.44 - 7.37 (m, 2H), 7.16 - 7.09 (m, 1H), 6.93 - 6.77 (m, 2H), 4.06 - 3.64 (m, 4H), 3.31 - 3.16(m,1H), 3.02 - 2.92 (m, 1H), 2.51 - 2.40 (m, 1H), 2.25 - 2.17 (m, 4H), 1.41 - 1.14 (m, 3H) WO 09125 Synthesis MS 0 mp ( C) Method Two isomers: (CDC13) 5 8.55 (s, 1H), 8.16 - 8.09 (m, 2H), 8.01 (m, 1H), 7.86 - 7.76 (m, 2H), 7.76 - 7.70 (m, 2H), 7.64 - 7.28 (m, 4H), 7.24 - 7.14 (m, 2H), 4.08 - 3.65 (m, 1H), 3.37 - 3.15 (m, 1H), 3.09 - 2.92 (m, 1H), 2.80 (td, J: 14.2, 6.8 Hz, 1H), 2.45 m, 1H), 2.35 - 2.09 (m, 1H), 1.76 - 1.58 (m, 1H),1.48 - 1.35 (m, 2H), 1.27 - 1.19 (m, 2H),1.19 - 1.13 (m, 2H), 1.06 - 0.92 (m, 1H), 0.92 - 0.72 (m, 3H) (400 MHz, CDC13) a 8.56 (s, 1H), 8.20 — 8.10 (m, 2H), 8.00 (s, 1H), 7.83 — 7.77 (m, l 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.42 — 7.28 | 603 113 (m, 6H), 6.72 — 6.25 (m, 1H), 3.90 (d, J: (M+H) (dec) 6.4 Hz, 1H), 3.24 (td, J = 12.0, 3.6 Hz, 1H), 3.05 . 2.93 (m, 1H), 2.49 (1m = 11.7, 4.0 Hz, 1H), 2.21 (td, J = 8.7, 4.4 Hz, 1H), 1.29 (d, J: 6.6 Hz, 3H) (CDC13) 3 8.55 (s, 1H), 8.14 (dd, J = 8.4, 2.1 Hz, 2H), 8.05 (d, J: 2.8 Hz, 111), 7.87 — 7.72 (In, 4H), 7.61 — 7.49 (m, 1H), 7.38 (d, J = 8.3 Hz, 2H), 7.33 — 7.21 (m, 2H), 7.15 — 7.05 (m, 1H), 3.79 — 3.68 (m, 1H), 3.51 — 3.29 (In, 1H), 3.12 - 2.93 (m, 1H), 2.66 — 2.52 (m, 1H), 2.18 — 2.12 (m, 1H), 1.43 (m, 12H) (CDC13) 6 8.58 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 — 7.77 (m, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.23 (dd, J = 8.4, 6.6 Hz,1H), 7.15 (d, J: 7.5 Hz, 2H), 3.24 - 3.14 (m, 4H), 2.18 (s, 6H).
(CDC13) 3 8.57 (s, 1H), 8.21 (d, J = 8.4 Hz, 2H), 8.16 (s, 1H), 7.85 - 7.75 (m, 4H), 7.46 - 7.36 (m, 4H), 7.33 - 7.26 (m, 1H), 7.10 (d, J kaec) ‘ = 7.6 Hz, 1H), 3.26 - 3.14 (H1, 411'), 2.81(sept, J = 6.9 Hz, 1H), 1.21 (t, J = 7.2 Hz,6H) --_,3 Synthesis Method (CDC13) 3 8.57 (s, 1H), 8.21 (d, ]= 8.4 Hz, 2H), 8.15 (s, 1H), 7.86 - 7.76 (m, 4H), 7.39 (d, J: 8.3 Hz, 2H), 7.29 (t, J = 7.6 HZ, 1H), 7.21- 7.15 (m, 2H), 3.27 - 3.10 (m, 4H), 2.50 (q, J: 7.5 Hz, 2H), 2.18 (s, 3H), 1.20 (t, J: 7.6 HZ, 3H).
(CDC13) 8 8.57 (s, 1H), 8.24 - 8.16 (m, 3H), 226C 196-200 7.85 - 7.76 (m, 4H), 7.43 — 7.34 (m, 3H), 7.03 (dd, J = 8.5, 7.4 Hz, 2H), 3.21 (s, 4H) (CDC13) 6 8.57 (S, 1H), 8.21 (d, J: 8.3 Hz, 2H), 8.15 (s, 1H), 7.81 (t, J: 9.1 Hz, 4H), 227C 7.43 - 7.31 (m, 3H), 7.28 - 7.21 (m, 2H), 3.36 - 3.07 (m, 4H), 2.24 (s, 3H); ”P NMR (376 MHz, CDClg) 5 -58.02 ) 8 8.57 (s, 1H), 8.21 (d, J: 8.3 Hz, 2H), 8.11 (s, 1H), 7.81 (dd, J: 11.5, 4.7 Hz, 228C 4H), 7.72 (dd, J = 17.3, 8.0 Hz, 2H), 7.51 (dd, J: 10.0, 5.4 Hz, 1H), 7.39 (d, J = 8.3 Hz, 2H), 3.36 — 3.03 (m, 4H) (CDC13) 8 8.57 (S, 1H), 8.21 (d, J: 8.4 HZ, 2H), 8.13 (S, 1H), 7.80 (dt, J: 5.5, 4.9 Hz, 229C 4H), 7.44 - 7.34 (In, 6H), 3.29 - 3.10 (In, (CDC13)6 8.57 (s, 1H), 8.21 (d, J = 8.3 Hz, 2H), 8.14 (d, J = 15.4 Hz, 1H), 7.83 — 7.76 (m, 4H), 7.43 - 7.37 (m, 4H), 7.32 — 7.26 (m, 1H), 7.16 — 7.09 (m, 1H), 3.24 — 3.12 (m, 4H), 2.61 - 2.44 (m, 1H), 1.75 — 1.50 (m, 2H), 1.17 (dd, J = 6.9, 3.3 Hz, 3H), 0.87 - 0.73 (m, 3H) (CDC13) 6 8.58 (s, 1H), 8.22 (s, 1H), 8.19 (d, J = 5.0 Hz, 2H), 7.81 (dd, J = 8.7, 5.5 231C Hz, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.05 (d, J = 8.3 Hz, 1H), 6.90 - 6.76 (m, 2H), 3.83 (s, 3H), 3.22 - 3.11 (m, 4H), 2.16 (s, 3H) PCT/U52012/023932 aSynthesis MS 1““ C)0 Method (CDC13) 6 8.57 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 8.16 (s, 1H), 7.81 (dd, J = 8.7, 5.3 Hz, 4H), 7.58 (dd, J: 8.1, 1.5 Hz, 1H), 7.38 (dd, J: 13.2, 5.1 Hz, 3H), 7.33 - 7.27 (m, 1H), 7.02 - 6.96 (m, 1H), 3.37 - 3.01 (m, 4H), 1.36 (s, 9H) (CDC13)5 8.58 (s, 1H), 8.21 (d, J: 8.4 Hz, 2H), 8.14 (s, 1H), 7.86 - 7.72 (m, 4H), 7.48 — 7.28 (m, 6H), 6.40 (t, JHF = 74.3 Hz, 1H), 3.25 - 3.11 (m, 4H) NMR spectral data were ed using a 400 MHz instrument except where noted.
Table 4A: Analytical Data for Optically Active Compounds in Table 3 Chiral Separation Purity 1H NMR (6)1 Method (CDC13)8 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.87 - 7.78 (m, 4H), 7.41 (t, J = 6.3 Hz, 3H), 7.37 — 7.31 (m, 1H), 7.28 (d, J: 7.0 Hz, 1H), 4.09 - 3.98 (m, 2H), 2.29 (s, 3H) (CDC13) 6 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J = 8.3 Hz, 2H), 7.87 - 7.78 (m, 4H), 7.41 (dd, J = 7.0, 5.6 Hz, 3H), 7.34 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 6.0 Hz, 1H), 4.09 - 3.98 (m, 2H), 2.29 (s, 3H) (CDCI3) 5 8.58 (s, 1H), 8.31 (s, 1H), 8.23 (d, J: 8.4 Hz, 2H), 7.81 (dd, J: 11.7, 5.1 Hz, 4H), 7.40 (d, J = 8.4 Hz, 2H), 7.35 (t, J: 7.7 Hz, 1H), 7.24 - 7.18 (m, 2H), 4.02 (s, 2H), 2.53 (q, J: 7.5 HZ, 2H), 2.21 (s, 3H), 1.21 (t, J: 7.6 Hz, 3H) (’CDCl3) 6 8.58 (s, 1H), 8.31 (s, 1H, ((:1 , J = 8.4 Hz, 2H), 7.81 (dd, J = 11.7, 565 Hz, 4H), 7.40 (d, J = 8.3 Hz, 2H), 7.” \O110 1L») b.) (dd, J = 10.4, 4.9 Hz, 1H), 7.24 — 7.20 (m, 2H), 4.02 (s, 2H), 2.59 - 2.45 (m, 2H), 2.21 (s, 3H), 1.21 (t, J = 7.6 Hz, 3H) tion Method (CDC13) 5 8.58 (s, 1H), 8.29 (d, J: 3.9 Hz, 1H), 8.23 (d, J = 8.4 Hz, 2H), 7.82 (t, J = 8.8 Hz, 4H), 7.40 (d, J = 8.3 Hz, 3H), 7.31 (d, J = 6.9 Hz, 1H), 7.19 (dd, J: 7.6, .2 Hz, 1H), 4.03 (s, 2H), 2.83 - 2.73 (m, 1H), 2.21 (s, 3H), 1.25 - 1.18 (m, 6H) (CDC13) 8 8.58 (s, 1H), 8.30 (s, 1H), 8.22 (t, J = 8.7 Hz, 2H), 7.82 (t, J = 8.7 Hz, 4H), 7.40 (d, J = 8.2 Hz, 3H), 7.31 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 7.3 Hz, 1H), 4.03 (s, 2H), 2.83 - 2.73 (In, 1H),2.21(s,3H), 1.25 - 1.18 (m, 6H) NMR spectral data were acquired using a 400 MHz instrument except where noted.
Table 5: Biological Results . % % % Mortallty Compound Mortality Mortality Number GPA 200 PCT/U82012/023932 % % % ity Compound Mortality Mortality GPA 200 I A 20C A I A D 21C C C D 23C A A D 24C A A B 25C A A D 26C C C D me A B 31C A B wNC) O B w b.) Cl a) >O> w w .1;0 lII PCT/U82012/023932 Compound %CI\£I:(‘){Itggty ity Moerity Number GPA 200 H‘s/01112 [Lg/cm2 41C A A D 42C A A D 43C A A B 44C A A D 46C A A D 47C A A B 48C A A C 49C A A B W0 2012/109125 % % % Mortality nd Mortality Mortality CEW 5° Number BAW 50 GPA 200 > > \l 00 ('1 > > wcu \‘I \C) Cr > T? (I! oooO II PCT/U82012/023932 nd %Ché%;tggty Moz’ality Morality Number BAW 520 GPA 200 uglcmz ug/cm 87C C C B 88C A A B 89C A A D I 90C A A B 92C A A B 93C A A D 94C A A D 95C A A B W0 2012/109125 PCT/U82012/023932 nd %Ché%;tggty Mozoality Moriaality Number BAW 520 GPA 200 uglcmz ug/cm ppm 107C D D C 109C A A C 110C i A i A } C 1 111C A A B 112C > 115C UHD> 0003: 116C > ('1 117C >>>>Udl>> > U ao >IIII:l> OOCUOUU > >>D> O . ’ :3Ox0 II O WO 09125 PCT/U82012/023932 Compound Mortality Number GPA200 133C A A B 134C A A C 135C A A D 136C A A D 138C A A B 139C A A B 140C A A B 141C A A D PCT/U52012/023932 % % % Mortality Mortality ity CEW 50 GPA 200 ._. O\ \o O 11> SOO > > OOUOOOOO :3>—A C) > > ('1 StoO II WO 09125 Compound %C1\l"ljt‘);t:gty Mozoality Morality Number BAW 520 GPA 200 uglcmz ug/cm ppm 173C A A D 174C A A B 179C A A D 180C A A B 181C A A B 182C A A B 184C A A D 185C A A D 186C A A B 187C A A D W0 09125 PCT/USZ012/023932 Mortality GPA 200 .I>>>UI>> Ix.)GO > > N r—I <3“O > > A l\) r—A \] ('1 > 3» ('3 [\Da0 HI 0 PCT/U52012/023932 Compound %C1\é(‘);ltggty ity Morality Number BAW 520 GPA 200 uglcmz [Lg/cm 225C A A C 226C A A C ‘ 227C A A C 228C A A C 230C A A C 231C A A C 232C A A C 233C A A C 1ooo74411s_1,docx 1 5AUG 2014

Claims (35)

    WE CLAIM:
  1. l. A ition comprising a molecule according to Formulas One, Two, or Three Arl/ \ i\ ,N2 S\ Ar2 N1 71/ R3 Formula 1 R1 R5 Het A N2 S / \ / \ \ 1 H61 ,N2 s Ar] Ar2 Nl Y\ \ \ Arl/ N1 \H/ R21 ‘R4 Formula 2 a 3 wherein: 5 (a) An is (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substituted l, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted 10 l, substituted pyrimidinyl, and substituted thienyl, have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1—C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 lkoxy, C3—C6 halocycloalkoxy, C1-C6 , C1- C6 haloalkoxy, C2—C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1~C6 kyl), OSOZ(C1-C6 alkyl), OSOz(C1-C6 haloalkyl), Rny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 15 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 O(C1—C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, substituted phenyl, and substituted phenoxy, wherein such substituted phenyl and substituted phenoxy have one or more 20 substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C5 halocycloalkoxy, C1—C6 , C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOZ(C1-C6 alkyl), OSOZ(C1-C6 haloalkyl), C(=O)NRXRy, (C1—C6 alkyl)NRxR , C(=O)(C1—C6 alkyl), (C1—C6 alkyl), C(=O)(C1—C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), 1000744116~1.docx C(=O)(C3-C6 cycloalkyl), C(=O)O(C3—C6 lkyl), C(=O)(C2—C6 l), C(==O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 C(=O)O(C1-C6 alkyl) phenyl, and phenoxy; 5 (b) Het is a 5 membered, heterocyclic ring, selected from the group containing N N / Arz / Arz N N \ / Ar1/ N @— Ar1/ A / I/ N / I Arz N //>iAr2 N\/// Ar1/ \N Ar1/ wherein said heterocyclic ring may also be tuted with one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, 0X0, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 10 cycloalkyl, C3-C6 halocycloalkyl, C3—C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1—C6 alkoxy, C1- C6 haloalkoxy, C2—C6 alkenyl, C2—C6 alkynyl, S(=O)n(C1—C5 alkyl), S(=O)n(C1—C6 haloalkyl), 0802(C1—C6 alkyl), OSOZ(C1—C6 haloalkyl), RXRy, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C1-C6 haloalkyl), (C1-C6 haloalkyl), C(:O)(C3—C6 lkylL C(=O)O(C3—C6 cycloalkyl), C(ZO)(C2-C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 15 alkyl)O(C1—C6 alkyl), (C1-C6 alkyl)S(C1—C6 , C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, substituted phenyl and substituted phenoxy, n such substituted phenyl and substituted phenoxy have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 k '1, C3-C6 cycloalkyl, C3-C5 cloalkyl, C3—C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 20 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, (C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), 0802(C1-C5 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C{=O)NRny, (C1-C5 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1- C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 alkyl)O(C1—C6 alkyl), (C1-C6 alkyl)S(C1—C6 alkyl), C(=O)(C1—C6 25 alkyl)C(=O)O(C1-C6 alkyl), phenyl, and phenoxy; 1000744116_1.d0cx l SAUG 2014 (c) Arz is (l) furanyl, phenyl, pyridazinyl, l, pyrimidinyl, thienyl, or (2) substituted furanyl, tuted , substituted pyridazinyl, substituted pyridyl, substituted dinyl, or substituted thienyl, wherein said substituted furanyl, substituted phenyl, substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl, and substituted thienyl, have one or more substituents independently ed from H, F, Cl, Br, 1, CN, N02, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1- 10 C6 haloalkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , S(=O)n(C1—C6 haloalkyl), OSOZ(C1-C(, alkyl), OSOZ(C1-C6 haloalkyl), C(=O)NRXRy, (C1—C6 alkyl)NRny, C(=O)(C1—C6 alkyl), C(=O)O(C1-C6 , C(ZO)(C1—C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3—C(, lkyl), C(=O)O(C3-C6 lkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 , (C1-C6 alkyl)S(C1—C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), 15 phenyl, phenoxy, substituted phenyl and substituted phenoxy, wherein such substituted phenyl and substituted y have one or more substituents independently selected from H, F, Cl, Br, 1, CN, N02, C1—C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C3-C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1—C6 alkoxy, C1—C6 haloalkoxy, C2—C6 alkenyl, C2—C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1-C6 2O haloalkyl), OSOZ(C1—C6 alkyl), OSOZ(C1—C6 haloalkyl), C(=O)H, C(=O)NRXRy, (C1—C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1— C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), (C3-C6 cycloalkyl), C(=O)(C1-C6 kyl), C(=O)(C2-C6 alkenyl), (C2-C6 alkenyl), (C1—C6 alkyl)O(C1-C6 alkyl), (C1—C6 alkyl)S(C1- C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, and phenoxy; ((1) R1 is selected from H, CN, F, Cl, Br, I, C1-C6 alkyl, C3-C6 cycloalkyl, C3—C6 cycloalkoxy, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), OSOZ(C1-C6 alkyl), C(=O)NRXRy, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C3- C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1- 30 C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1—C6 alkyl), C(IO)(C1—C6 alkyl)C(=O)O(C1—C6 alkyl), 1000744116_1.d0cx l SAUSZ1:) ’l {LN phenyl, or y, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, and phenoxy, are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3-C6 halocycloalkyl, 5 C3-C5 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C2- C6 alkynyl, S(=O)n(C1—C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 , OSOz(C1—C6 haloalkyl), Rny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), (C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 lkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C5 alkyl)O(C1-C6 alkyl), (C1-C6 10 S(C1-C6 , C(=O)(C1-C6 alkyl)C(=O)O(C1—C6 alkyl), phenyl, and phenoxy; (e) R2 is H, C1-C6 alkyl, C3—C6 cycloalkyl, C2—C6 alkenyl, C2—C6 alkynyl, C(=O)H, C(=O)(C1-C6 alkyl), C(ZO)O(C1-C6 , C(=O)(C3—C6 cycloalkyl), (C3—C6 cycloalkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C 1—C6 l5 alkyl)S(C1-C6 alkyl), C(=O)(C1—C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, C1-C6 alkylphenyl, C1-C6 alkyl—O-phenyl, C(=0)Het—l, Het—l, C1-C6 alkylHet—l, or C1-C6 alkyl—O-Het-l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het—l are optionally substituted with one or more substituents ndently selected from F, Cl, Br, 1, CN, N02, NRXRy, C1-C6 alkyl, C1-C6 haloalkyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C3-C6 20 cycloalkoxy, C3—C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2—C6 l, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 alkyl), OSOZ(C1-C6 haloalkyl), C(=O)H, C(=O)NRny, (C1~C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C5 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1—C6 25 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), , phenoxy, and Het-l; (1) R3 is C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2—C6 alkynyl, C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1—C6 , C3-C6 cycloalkyl), (C3-C6 30 cycloalkyl), C(=O)(C2—C6 alkenyl), C(ZO)O(C2—C6 l), (C1—C6 alkyl)O(C1—C6 alkyl), (C 1—C6 1000744116__1.docx l SAUG 281A alkyl)S(C1—C6 alkyl), C(=O)(C1—C6 alky1)C(=O)O(C1-C6 alkyl), , C1—C6 alkylphenyl, C1—C6 alkyl-O-phenyl, C(=O)Het-l, Het-l, C1-C6 alkylHet-l, C1-C6 alkyl-O-C(=O)C1-C6 O-C1wC6 alkyl, C1-C6 alkyl-O-C(=O)C1—C6 alkyl-O-Cl-C6 alkyl-O- C1—C6 alkyl, C1-C6 alkyl-O-C(=O)C1— C6 alkyl-O-Cl—C6 haloalkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O-phenyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O-C1-C6 alkylphenyl, C1-C6 alky1C(=O)N(RX)C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1-C6 alkylHet-1C(=O)—O-C1-C6 alkyl, C1-C5 alkle(=O)N(Rx)C1— C6 alkylHet-l, C1-C6 =O)Het-l, C1-C6 alkle(=O)N(Rx)C1-C6 a1ky1(N(Rx)(Ry))(C(=O)OH), CI'C6 (=O)N(Rx)C1-Cs a1ky1N(Rx)(Ry), CI'CG alky1C(=O)N(Rx)C1-C6 alkle(Rx)C(=O)—O-C1-C6 alkyl, C1-C6 alkle(=O)N(Rx)C1-C6 10 alkyl(N(Rx)C(=O)-O-C1-C6 alky1)(C(=O)OH), C1-C6 alkle(=O)Het-lC(=O)-O-C1-C6 alkyl, C1- C6 alkyl-O-C(=O)-O-C1-C6 alkyl, C1-C6 alkyl-O-C(=O)C1-C6 alkyl, C1-C6 alkyl—O—C(=O)C3-C6 cycloalkyl, C1-C6 alkyl-O-C(=O)Het-l, C1-C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O-C1—C6 alkyl, C1-C6 alkyl-NRXRy, or C1—C6 alkyl—O-Het-l, wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het—l are optionally 15 substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, NRny, C1-C6 alkyl, C1—C6 haloalkyl, C3—C6 cycloalkyl, C3—C6 halocycloalkyl, C3-C6 lkoxy, C3—C6 halocycloalkoxy, C1-C6 alkoxy, C1—C6 koxy, C2—C6 alkenyl, C3—C6 cycloalkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOZ(C1-C6 alkyl), OSOg(Cl-C6 haloalkyl), , C(=O)OH, Rny, (C1-C6 alkyl)NRny, C(=O)(C1—C6 20 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3—C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2~C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, y, Si(C1-C6 alkyl)3, S(=O)nNRny, and Het-l; 25 (g) R4 is H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C(=O)H, C(=O)(C1-C6 alkyl), (C1-C6 alkyl), C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, C1-C6 alkylphenyl, C1-C6 alkyl-O—phenyl, C(=O)Het-l, Het-l, C1—C6 alkylHet-l, or C1-C6 alkyl-O-Het-l, 30 wherein each alkyl, cycloalkyl, alkenyl, alkynyl, phenyl, and Het-l are optionally substituted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, 4116_1.docx NRny, C1-C6 alkyl, C1—C6 haloalkyl, C3-C6 cycloalkyl, C3—C6 halocycloalkyl, C3—C6 cycloalkoxy, C3—C6 halocycloalkoxy, C1-C6 alkoxy, C1—C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1-C6 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C(=O)NRny, (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1—C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C5 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, phenoxy, and Het-l; 10 (h) R5 is a 2 to 4 membered saturated or rated hydrocarbyl linkage where said e may also be substituted with F, Cl, Br D—d C)r—i haloalkyl, C3—C6 cycloalkyl, C3-C/ C1-C6 , C1-C6 haloalkoxy, C2—C6 alkenyl, C3—C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1- C6 alkyl), S(=O)n(C1-C6 haloalkyl), OSOz(C1—C6 alkyl), 1-C6 haloalkyl), , 15 C(=O)OH, C(=O)NRXRy, (C1—C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(ZO)O(C1-C6 alkyl), C(=O)(Cl-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2—C6 alkenyl), C(=O)O(C2—C6 alkenyl), (C1-C6 alkyl)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 , C(=O)(C1—C6 C(:O)O(C1—C6 alkyl), phenyl, phenoxy, and Het—l, wherein each alkyl, cycloalkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, phenyl, 20 phenoxy, and Het—l, are optionally tuted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, 0X0, NRny, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1-C6 alkoxy, C1-C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 l, S(=O)n(C1-C6 alkyl), S(=O)n(C1- C6 haloalkyl), OSOz(C1-C6 alkyl), OSOz(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)NRXRy, [\J VI (C1-C6 alkyl)NRny, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C5 kyl), C(=O)(C3-C6 lkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 alkenyl), C(=O)O(C2-C6 alkenyl), (C1-C6 O(C1-C6 alkyl), (C1-C6 S(C]-C6 alkyl), C(=O)(C1-C6 alkyl)C(=U)U<L1-95 alkyl), phenyl, halophenyl, phenexy, and Het-l; 30 (i) n= 0, l, or 2; 1000744116_1.docx l 5 AUG 2014 (j) RX and Ry are independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 alkyl), S(=O)n(C1— C6 haloalkyl), OSOz(C1-C6 alkyl), OSOZ(C1-C6 haloalkyl), C(=O)H, C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), (C1-C6 haloalkyl), C(=O)(C3—C6 cycloalkyl), C(=O)O(C3-C6 cycloalkyl), C(=O)(C2-C6 l), C(=O)O(C2-C6 alkenyl), (C1-C6 alkyl)O(C1—C6 alkyl), (C1-C6 a1ky1)S(C1-C5 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), and phenyl, wherein each alkyl, lkyl, cycloalkoxy, alkoxy, alkenyl, alkynyl, , 10 phenoxy, and Het-l, are optionally tuted with one or more substituents independently selected from F, Cl, Br, 1, CN, N02, 0x0, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3—C6 cycloalkoxy, C3-C6 halocycloalkoxy, C1—C6 alkoxy, C1-C6 haloalkoxy, C2- C6 alkenyl, C3-C6 cycloalkenyl, C2—C6 alkynyl, S(=O)n(C1-C6 , (C1-C6 haloalkyl), OSOZ(C1—C6 alkyl), 0802(C1-C6 haloalkyl), C(=O)H, C(=O)OH, C(=O)(C1-C6 alkyl), 15 C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C(, haloalkyl), C(=O)(C3-C6 cycloalkyl), C(ZO)O(C3—C6 cycloalkyl), C(=O)(C2—C6 alkenyl), C(:O)O(C2—C(, l), (C1—C6 alkyl)O(C1—C6 alkyl), (C1—C6 alkyl)S(C1-C6 alkyl), C(=O)(C1—C6 alkyl)C(=O)O(C1—C6 alkyl), phenyl, halophenyl, phenoxy, and Het—l, or RK and Ry together can optionally form a 5— to 7—membered saturated or 20 unsaturated cyclic group which may contain one or more heteroatoms selected from en, sulfur, and oxygen, and where said cyclic group can contain >C=O or >C=S, and where said cyclic group may be substituted with F, Cl, Br, 1, CN, C1—C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C3-C6 halocycloalkyl, C3-C6 cycloalkoxy, C3-C6 cloalkoxy, C1-C6 alkoxy, C1- C6 haloalkoxy, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 alkynyl, S(=O)n(C1-C6 , 25 (C1—C6 haloalkyl), OSOz(C1—C6 alkyl), 0S02(C1-C6 haloalkyl), C(=O)(C1-C6 alkyl), C(=O)O(C1-C6 alkyl), C(=O)(C1-C6 haloalkyl), C(=O)O(C1-C6 haloalkyl), C(=O)(C3-C6 cycloalkyl), (C3-C6 cycloalkyl), C2—C6 alkenyl), (C2-C6 alkenyl), (C1-C6 alky1)O(C1-C6 alkyl), (C1-C6 alkyl)S(C1-C6 alkyl), C(=O)(C1-C6 alkyl)C(=O)O(C1-C6 alkyl), phenyl, substituted , phenoxy, and Het-l; and (k) Het-l is a 5- or 6—membered, saturated or unsaturated, heterocyclic ring, 1000744116_1idocx l 5 AUG 201k containing one or more heteroatoms independently ed from nitrogen, sulfur or oxygen.
  2. 2. A composition according to claim 1, wherein the molecule is a molecule according to Formula 1 or Formula 2.
  3. 3. A composition according to claim 1 or 2, wherein Arl is a substituted phenyl wherein 5 said substituted phenyl has one or more substituents independently selected from C1—C6 haloalkyl and C1-C6 haloalkoxy.
  4. 4. A composition according to claim 1 or 2, wherein Arl is a substituted phenyl wherein said substituted , has one or more substituents independently selected from CF3, OCF3, and OCF2CF3. 10
  5. 5. A composition according to any one of claims 1 to 4 wherein Het is a 1,2,4—triazoly1 I? / Arz Ar1/ N
  6. 6. A composition according to any one of claims 1 to 4 wherein Het is a 1,4—imidazolyl N / Ar1/
  7. 7 A composition ing to any one of claims 1 to 4 wherein Het is a 1,3-pyrazoly1 N //I i - A,,/ \N 13 '" -.
  8. 8. A ccrnpcsitinn according t0 any one of claims 1 to 4 wherein Het is a substi‘u‘ed 1,3= pyrazolyl.
  9. 9. A composition according to any one of claims 1 to 4 n Het is a 1,4—pyrazolyl 1000744116_11d0cx z 5 AUG 2011., T// Arz
  10. 10. A composition according to any one ofthe preceding claims wherein AI; is a phenyl.
  11. 11. A composition according to any one of the preceding claims wherein R1 is H or C1-C6 alkyl.
  12. 12. A composition according to claim 11, wherein R1 is H or CH3.
  13. 13. A composition according to any one ofthe preceding claims wherein R2 is H.
  14. 14. A composition according to any one ofthe preceding claims wherein R3 is C1-C6 alkyl, C2-C6 alkenyl, C2—C6 alkynyl, C1-C6 alkylphenyl, C1-C6 alkylHet-l , C1-C6 alkyl—O-C(=O)C1-C6 alkyl-O-Cl-C6 alkyl, C1—C6 alkyl-O—C(=O)C1—C6 alkyl—O—Cl-C6 alkyl-O- C1-C6 alkyl, C1—C6 10 alkyl-O-C(=O)C1—C6 alkyl-O-C1-C6 haloalkyl, C1-C6 alkyl-O-C(=O)C1-C6 N(RX)C(=O)—O— phenyl, C1—C6 alkyl—O—C(:O)C1-C6 alkyl—N(RX)C(=O)—O-C 1-C6 alkylphenyl, C1-C6 =O)N(Rx)C1-C6 alkyl, C1—C6 alkle(=O)N(Rx)C1—C6 alkylHet—lC(=O)—O-C1—C6 alkyl, C1— C6 alkle(=O)N(Rx)C1-C6 alkylHet—l, C1-C6 alkle(=O)Het-l , C1—C6 alkle(:O)N(Rx)C1-C6 alky1(N(Rx)(Ry))(C(=0)0H), C1-C6 (=0)N(Rx)C1—C6 a1ky1N(Rx)(Ry), C1-C6 15 alkle(=O)N(RX)C1-C6 alkle(Rx)C(=O)—O—C1—C6 alkyl, C1-C6 =O)N(RX)C1-C6 alkyl(N(RX)C(=O)—O—C1—C6 alkyl)(C(=O)OH), C1-C6 alkle(=O)Het—1C(=O)—O—C1—C6 alkyl, C1- C6 alkyl—O—C(=O)—O—C1-C6 alkyl, C1—C6 O—C(=O)C1—C6 alkyl, C1—C6 alkyl-O—C(=O)C3—C6 cycloalkyl, C1-C6 alkyl-O-C(=O)Het-1, or C1-C6 alkyl-O-C(=O)C1-C6 alkyl-N(RX)C(=O)-O—C1— C6 alkyl 20 wherein each alkyl, alkenyl, alkynyl, phenyl, and Het-l are optionally tuted with one or more substituents independently ed from F, Cl, Br, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, S(=O)n(C1-C6 alkyl), C(=O)OH, C(=O)O(C1-C6 alkyl), phenyl, Si(C1-C6 alkyl)3, and S(=O)nNRny.
  15. 15. A composition according to any one of the preceding claims n R4 is phenyl, C1-C6 25 alkylphenyl, or C1-C6 alkyl-O-phenyl, wherein each alkyl and phenyl are optionally substituted with one or more substituents independently selected from F, Cl, NRny, C1-C6 alkyl, or C1-C6 alkoxy. 1000744116~1.docx l 5 AUG 2111i
  16. 16. A composition according to any one of the preceding claims wherein R5 is substituted with oxo, C(=O)OH, phenyl, and Het-l, wherein each phenyl and Het-l, may be optionally tuted with one or more substituents independently selected from 0X0, C1-C6 haloalkyl, C1— C6 koxy, C(=O)OH, and halophenyl.
  17. 17. A composition according to any one of the preceding claims wherein RX and Ry are independently selected from H and phenyl, wherein said phenyl, may be optionally substituted with one or more substituents independently selected from F and Cl.
  18. 18. A composition ing to claim 1 or 2, wherein: Arl is a substituted phenyl wherein said substituted phenyl, has one or more C1-C6 10 haloalkoxy; Arz is a phenyl; R1 is H; R2 is H; 15 R3 is C1—C6 alkylHet-l wherein said alkyl and Het—l are optionally substituted with one or more substituents independently selected from F, Cl, Br, C1—C6 alkyl, C1-C6 haloalkyl, C1—C6 haloalkoxy, S(=O)n(C1—C6 , C(=O)OH, (C1—C6 alkyl), phenyl, Si(C1-C(, alkyl)3, and S(=0)nNRny; R4 is phenyl, wherein said phenyl is ally substituted with one or more substituents 20 independently selected from F, C1, NRny, C1—C6 alkyl, or C1-C6 alkoxy; and n= 0,1, or 2; RK and Ry are independently selected from H and phenyl, n said phenyl, may be optionally substituted with one or more substituents ndently selected from F and C1; and Het-l is a 5- or 6-membered, saturated or unsaturated, heterocyclic ring, containing one 25 or more heteroatoms ndently selected from nitrogen, sulfur or oxygen.
  19. 19. A composition according to any one of the preceding claims wherein Het—l is selected 1000744116_1.d0cx l 5 AUG 201A from benzofilranyl, benzoisothiazolyl, bemoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl cinnolinyl, furanyl, lyl, indolyl, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, azinyl, pyrazinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, triazinyl, lyl, zinyl, piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, 1,2,3,4-tetrahydro-quinolinyl, 4,5-dihydro-oxazolyl, 4,5-dihydro-lH—pyrazolyl, 4,5-dihydro-isoxazolyl, and hydro- [1,3,4]-oxadiazolyl.
  20. 20. A composition according to any one of claims 1 to 18, wherein Het-l is ed from 10 benzofuranyl, benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl, benzothiazolyl, benzothiadizolyl, cinnolinyl, furanyl, indazolyl, l, imidazolyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, lyl, zinyl, pyridyl, dinyl, pyrrolyl, olinyl, quinolinyl, quinoxalinyl, tetrazolyl, thiazolinyl, thiazolyl, thienyl, thienylpyrazolyl, triazinyl, triazolyl, piperazinyl, 15 piperidinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, tetrahydropyranyl, l,2,3,4—tetrahydro- quinolinyl, 4,5—dihydro—oxazolyl, 4,5—dihydro-lH—pyrazolyl, 4,5—dihydro-isoxazolyl, and 2,3— dihydro-[l ,3 ,4]—oxadiazolyl.
  21. 21. A composition according to claim 20 wherein Het-l is selected from benzothiadizolyl, furanyl, oxazolyl, and thienylpyrazolyl. 20
  22. 22. A composition according to claim 1 wherein said molecule is selected from 10007441 16_1.docx
  23. 23. A ition according to claim 1, wherein the molecule is selected from the group consisting of: 4116_1.docx 1 5 AUG 2014 4116_1.docx ‘1 5 A05 .2014 4116_1.docx ! 5 AUG 2014 [ ID I Structure 4116_1Vdocx 1 5 AUG 2014 ‘ \N I—28 ' F F HN A X I \ /©/\ fl ’ 0 ‘ . I 4116_1.docx 1 SAUG 201A ID Structure 1-30 1-31 4116_1.docx Structure 4116_1.docx * 5 AUG 2014 4116_1.docx 4116_1.docx 1 5 AUG 2014 Structure 4116~1.d0cx 4116_1.docx ‘ 5 AUG 2014 Structure 4116_1.dOCX 7 H AUG 2014 4116_1.docx 1 SAUG 2014 4116_1.d0cx 1 5 AUG 2014 Structure 4116_1.docx 5 5 “US 2014 ID Structure 4116~1.docx Structure 4116_11d0cx 1 SAU‘G 201.4. Structure 4116_1‘d0cx 4116_18docx 'l SAUG 2014 ID Structure 4116 1.docx Smctum 4116_10docx ’1 5AUG 2.0M ID Structure FX<F 100C F oO’N-N/ 3% F F 0 0 {W\ #6 101C 0 NJm SYN / ,N N O F F 0 FX N/\N\ fl C1 102C 0 2aS N /N—N F F 0 F OQNN/X 103C sifi x \ F N 104C O / 8% /N-N 4116_1.docx Structure 4116_1.docx 1 5 AUG 2014 ID Structure I 114C 115C 116C 117C 118C 119C 120C 121C 4116_1.docx Structure 4116_1.d0cx 6 5 AUG 2014 Structure 4116_1.docx Structure 4116_1.dOCX ll SAUG 20M 4116_1.docx “I 5 AUG 2011, V‘ SAUG 2014 4116_1.docx 4116_1.docx 1 5AUG 2014 ID Structure 180C 181C 182C 183C 184C 185C 186C 4116‘1.docx 15 AUG 2014 4116_1.docx 1 SAUG 20M 4116_1.docx 1’ 5 1306 2011+ 41 16_1 .dOCX 4116_1.docx 1 5 AUG 2014 4116_1.docx 1 SAUG 2014 Structure 4116_1.docx 1 SAUG 2014 Structure 1000744116_1,docx l MUG 201i
  24. 24. A composition according to any one of the ing claims comprising a pesticidally able acid addition salt, a salt derivative, a e, or an ester derivative, of the molecule.
  25. 25. A composition according to any one of claims 1 to 23 comprising a rph ofthe molecule.
  26. 26. A composition according to any one of claims 1 to 23 wherein the molecule includes at least one H that is 2H or at least one C that is 14C.
  27. 27. A composition sing a molecule according to any one of claims 1 to 23 and at least one other compound selected from the Insecticide Group, Acaricide Group, Nematicide Group, 10 Fungicide Group, Herbicide Group, AI Group, or Synergist Group.
  28. 28. A composition according to any one of claims 1 to 23 further comprising a seed.
  29. 29. A composition according to claim 28 wherein said seed has been genetically modified to s one or more specialized traits.
  30. 30. A composition according to any one of claims 1 to 23 and at least one compound that has 15 a mode of action selected from cholinesterase inhibitor, sodium channel modulator, chitin biosynthesis inhibitor, GABA-gated chloride channel antagonist, GABA and glutamate—gated chloride channel agonist, acetylcholine or agonist, MET 1 inhibitor, Mg-stimulated ATPase inhibitor, nicotinic acetylcholine receptor, Midgut membrane disrupter, ive phosphorylation disrupter, and ryanodine receptor (RyRs). 20
  31. 31. A process according to any one of the preceding claims comprising applying the composition to an area to control a pest, in an amount sufficient to control such pest.
  32. 32. A process according to claim 31 wherein said molecule is selected from 1000744116_1.docx 1,5 AUG 2014 and said pest is BAW, CEW, or GPA.
  33. 33. A process according to claim 31 wherein said area is an area where apples, corn, cotton, 5 soybeans, canola, wheat, rice, sorghum, barley, oats, potatoes, oranges, alfalfa, lettuce, erries, tomatoes, peppers, crucifers, pears, tobacco, almonds, sugar beets, or beans, are growing, or the seeds thereof are going to be planted
  34. 34. A process comprising applying a composition according to any one of claims 1 to 23 to a cally modified plant that has been genetically modified to s one or more specialized 10 traits.
  35. 35. A process comprising: orally administering; or topically applying; a composition according to any one of claims 1 to 23, to a non-human animal, to l endoparasites, ectoparasites, or both.
NZ613659A 2011-02-07 2012-02-06 Pesticidal compositions and processes related thereto NZ613659B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201161440003P 2011-02-07 2011-02-07
US61/440,003 2011-02-07
PCT/US2012/023932 WO2012109125A1 (en) 2011-02-07 2012-02-06 Pesticidal compositions and processes related thereto

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NZ613659A NZ613659A (en) 2014-09-26
NZ613659B2 true NZ613659B2 (en) 2015-01-06

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