NZ712512B2 - 4-amino-6-(4-substituted-phenyl)-picolinates and 6-amino-2-(4-substituted-phenyl)-pyrimidine-4-carboxylates and their use as herbicides - Google Patents

4-amino-6-(4-substituted-phenyl)-picolinates and 6-amino-2-(4-substituted-phenyl)-pyrimidine-4-carboxylates and their use as herbicides Download PDF

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NZ712512B2
NZ712512B2 NZ712512A NZ71251214A NZ712512B2 NZ 712512 B2 NZ712512 B2 NZ 712512B2 NZ 712512 A NZ712512 A NZ 712512A NZ 71251214 A NZ71251214 A NZ 71251214A NZ 712512 B2 NZ712512 B2 NZ 712512B2
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chanmel
annotation
compound
formula
och3
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NZ712512A
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NZ712512A (en
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Joseph D Eckelbarger
Jeffrey B Epp
Lindsey G Fischer
Natalie C Giampietro
Nicholas M Irvine
Jeremy Kister
William C Lo
Christian T Lowe
Jeffrey Petkus
Joshua Roth
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Dow Agrosciences Llc
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Priority claimed from US13/840,233 external-priority patent/US9113629B2/en
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Priority to NZ751548A priority Critical patent/NZ751548B2/en
Publication of NZ712512A publication Critical patent/NZ712512A/en
Publication of NZ712512B2 publication Critical patent/NZ712512B2/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
    • A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
    • A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
    • 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
    • A01N43/54—1,3-Diazines; Hydrogenated 1,3-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
    • A01N43/90—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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/79—Acids; Esters
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32—One oxygen, sulfur or nitrogen atom
    • C07D239/42—One nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine

Abstract

Provided herein are 4-amino-6-(4-substituted-phenyl)-picolinic acids and their derivatives, and 6-amino-2-(4-substituted-phenyl)-pyrimidine-4-carboxylic acids and their derivatives, compositions comprising the acids and their derivatives, and methods of use thereof as herbicides.

Description

-AMINO(4-SUBSTITUTED-PHENYL)—PICOLINATES AND 6-AMINO(4- SUBSTITUTED-PHENYL)—PYRIMIDINECARBOXYLATES AND THEIR USE AS HERBICIDES CROSS REFERENCE TO RELATED APPLICATIONS This application claims the benefit ofUS. Patent ation No. 13/840,233 filed March 15, 2013, the entirety of which is incorporated herein by reference.
BACKGROUND
[0002] The occurrence of undesirable vegetation, e.g., weeds, is a constant problem facing famers in crops, pasture, and other settings. Weeds compete with crops and negatively impact crop yield. The use of al herbicides is an important tool in controlling undesirable vegetation.
There remains a need for new chemical herbicides that offer a broader spectrum ofweed l, selectivity, minimal crop damage, storage stability, ease of handling, higher activity against weeds, and/or a means to address herbicide-tolerance that develops with respect to herbicides tly in use.
SUMMARY
[0004] Provided herein are compounds of Formula (I): NR3R4 X I R1 Ar N wherein X is N or CY, wherein Y is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 , C1-C3 haloalkoxy, C1-C3 alkylthio, or C1-C3 kylthio; R1 is ORV, wherein R1/ is H, C1-C8 alkyl, or C7-C10 arylalkyl; R2 is halogen, C1-C4 alkyl, C1-C4 haloalkyl, C2-C4 alkenyl, C2-C4 haloalkenyl, C2-C4 l, C2-C4 haloalkynyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, C1-C4 haloalkylthio, amino, C1-C4 alkylamino, C2-C4 haloalkylamino, formyl, ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel (C1-C3 alkyl)carbonyl, (C1-C3 haloalkyl)carbonyl, cyano, or a group of the formula -CR17=CR18-SiR19R20R21, wherein R17 is hydrogen, F, or Cl; R18 is hydrogen, F, Cl, C1-C4 alkyl, or C1-C4 haloalkyl; and R19, R20, and R21 are each independently C1-C10 alkyl, C3-C6 cycloalkyl, C1-C10 haloalkyl, C3-C6 halocycloalkyl, phenyl, tuted phenyl, C1-C10 alkoxy, or OH; R3 and R4 are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 kenyl, C3-C6 alkynyl, hydroxy, C1-C6 alkoxy, C1-C6 haloalkoxy, formyl, (C1-C3 alkyl)carbonyl, (C1-C3 haloalkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C1-C6 alkyl)carbamyl, C1-C6 alkylsulfonyl, tri(C1-C6 alkyl)silyl, di(C1-C6 alkyl)phosphonyl, or R3 and R4 together with the en atom to which they are attached form a 5- or 6-membered saturated ring, or R3 and R4 taken together represent =CR3/R4/, wherein Ry and R4/ are each independently hydrogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 , or C1-C6 alkylamino, or R3/ and R4/together with the carbon atom to which they are attached form a 5- or 6-membered saturated ring; Ar is Arl, Ar2, Ar3, Ar4, Ar5, or Ar6: NO to am Arl Ar2 Ar3 F F X2 F X3 X2 F F F F Ar4 Ar5 Ar6 wherein X1 is H, F, Br, I, ethynyl, haloethynyl, CF2H, OCFZH, OCF3, CN, CONHZ, COZH, C02CH3, 01' N02; X2 is H, F, Cl, Br, I, ethynyl, haloethynyl, CH3, CFHZ, CF2H, CF3, OCFZH, OCF3, CN, DVHz, COzH, 01' N02; [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel X3 is H, F, Br, I, ethynyl, haloethynyl, CH3, CFH2, CF2H, CF3, OCFZH, OCF3, CN, CONHz, COzH, 01' N02; wherein a) when Ar is X1 then X is N, CH, CF, CCl, or CCH3; with provisos that: i) R2 is not C1 or vinyl, when X is N; ii) X1 is not H, F, OCF3, or CN, when R2 is C1 and X is CH; iii) X1 is not F, 1, CN, or ethynyl, when R2 is OCH3 and X is CF; iv) X1 is not H, when X is CCl; and b) when Ar is F then X is N, CH, CF, CCl, or CCH3; with os that: i) R2 is not C1, when X is N; ii) X2 is not C1, when R2 is OCH3 or vinyl and X is N; iii) X2 is not C1, when R2 is C1 and X is CH; iv) X2 is not Cl, Br, I, or CF3, when R2 is OCH3 and X is CF; and c) when Ar is xg/EZ; then X is N, CH, or CF; with provisos that: i) R2 is not C1, when X is N; ii) X3 is not CH3, when R2 is OCH3 and X is N; iii) X3 is not H, F, or CH3, when R2 is C1 and X is CH; iv) X3 is not Br or I, when R2 is OCH3 and X is CF; and X2' ; F (1) when Ar is F then X is N, CH, or CF; with provisos that: i) R2 is not C1, when X is N; ii) X2 is not C1, when R2 is OCH3 or vinyl and X is N; iii) X2 is not F, when R2 is C1 and X is CH; D iv) X2 is not Cl, Br, I, or CF3, when R2 is OCH3 and X is CF; ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel e) when Ar is F then X is N, CH, or CF; with proviso that: i) X3 is not CH3, when R2 is Cl and X is N; ii) X3 is not Br or I, when X is CF and R2 is OCH3; and X2 F f) when Ar is F then X is N, CH, or CF; or an N-oxide or agriculturally acceptable salt thereof.
Also provided are methods of controlling undesirable vegetation comprising (a) contacting the rable vegetation or area adjacent to the undesirable vegetation, or (b) pre-emergently contacting soil or water, a herbicidally effective amount of at least one compound of Formula (I) or agriculturally acceptable tive (e.g., agriculturally acceptable salts, solvates, hydrates, , , N-oxides, or other derivatives) thereof.
DETAILED DESCRIPTION As used , herbicide and herbicidal active ingredient mean a compound that controls undesirable vegetation when applied in an riate .
As used herein, control of or controlling undesirable vegetation means killing or preventing the vegetation, or causing some other adversely modifying effect to the tion e.g., deviations from natural growth or development, tion, ation, retardation, and the like.
[0008] As used herein, a herbicidally effective or vegetation controlling amount is an amount of herbicidal active ingredient the application of which controls the relevant undesirable vegetation.
As used herein, applying a herbicide or herbicidal composition means delivering it dirdy to the targeted vegetation or to the locus thereof or to the area where control of [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel undesired vegetation is desired. Methods of application include, but are not limited to, pre- emergently contacting soil or water, or mergently contacting the rable vegetation or area adjacent to the undesirable tion.
As used herein, plants and vegetation include, but are not d to, dormant seeds, germinant seeds, emerging seedlings, plants emerging from vegetative propagules, immature vegetation, and established vegetation.
As used herein, agriculturally acceptable salts and esters refer to salts and esters that exhibit herbicidal activity, or that are or can be converted in plants, water, or soil to the referenced herbicide. Exemplary agriculturally acceptable esters are those that are or can be hydrolyzed, oxidized, metabolized, or otherwise ted, e.g., in plants, water, or soil, to the corresponding carboxylic acid which, depending on the pH, may be in the dissociated or undissociated form. le salts include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred s include sodium, potassium, magnesium, and aminium cations of the formula: R13R14R15R16N+ wherein R13, R14, R15 and R16 each, independently represents en or C1-C12 alkyl, C3-C12 alkenyl, or C3-C12 alkynyl, each of which is optionally substituted by one or more substituents such as hydroxy, C1-C4 alkoxy, C1-C4 hio, or phenyl groups, provided that R13, R14, R15 and R16 are sterically compatible. Additionally, any two R13, R14, R15 and R16 together may represent an aliphatic difunctional moiety containing one to twelve carbon atoms and up to two oxygen or sulfur atoms. Salts of the compounds of Formula (I) can be ed by treatment of nds of Formula (I) with a metal hydroxide, such as sodium hydroxide, with an amine, such as ammonia, trimethylamine, diethanolamine, 2-methyl- thiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine, or with a tetraalkylammonium hydroxide, such as ethylammonium hydroxide or choline hydroxide. Amine salts of nds of Formula (I) are useful forms or derivatives of compounds of a (I) because they are water-soluble and lend them- selves to the preparation of desirable aqueous based herbicidal compositions.
[0013] Other forms or derivatives of compounds of the Formula (I) include N—oxides of compounds of Formula (I). Pyridine N—oxides can be obtained by ion of the corresponding pyridines. le oxidation methods are described, for example, in [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Houben-Weyl, Methoden der organischen Chemie [Methods in organic chemistry], expanded and subsequent volumes to the 4th edition, volume E 7b, p. 565 f.
As used herein “acyl” includes formyl, (C1-C3 alkyl)carbonyl, and (C1-C3 haloalkyl)carbonyl.
As used herein, “alkyl” refers to saturated, straight-chained or branched hydrocarbon moieties. Unless otherwise specified, C1-C10 alkyl groups are intended.
Examples include, but are not limited to, methyl, ethyl, propyl, l-methyl-ethyl, butyl, l-methyl-propyl, 2-methyl-propyl, l,l-dimethyl-ethyl, pentyl, l-methyl-butyl, 2-methyl- butyl, 3-methyl-butyl, 2,2-dimethyl-propyl, l-ethyl-propyl, hexyl, l,l-dimethyl-propyl, l,2-dimethyl-propyl, yl-pentyl, yl-pentyl, 3-methyl-pentyl, 4-methyl-pentyl, l,l-dimethyl-butyl, l,2-dimethyl-butyl, l,3-dimethyl-butyl, 2,2-dimethyl-butyl, 2,3- dimethyl-butyl, 3,3-dimethyl-butyl, l-ethyl-butyl, 2-ethyl-butyl, l,l,2-trimethyl-propyl, l,2,2-trimethyl-propyl, l-ethyl-l-methyl-propyl, and l-ethylmethyl-propyl.
As used herein, “haloalkyl” refers to ht-chained or branched alkyl groups, where in these groups the hydrogen atoms may partially or entirely be substituted with one or more n atom(s). Unless otherwise specified, C1-C8 groups are ed. Examples include, but are not limited to, chloromethyl, ethyl, dichloromethyl, oromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, l-chloroethyl, l-bromoethyl, l-fluoroethyl, 2-fluoroethyl, 2,2- difluoroethyl, 2,2,2-trifluoroethyl, 2-chlorofluoroethyl, 2-chlorodifluoroethyl, 2,2- dichlorofluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and l,l,l-trifluoropropyl.
As used herein, “alkenyl” refers to unsaturated, straight-chained, or branched hydrocarbon moieties containing one or more double bond(s). Unless otherwise specified, C2-C8 alkenyl are intended. Alkenyl groups may contain more than one unsaturated bond. es include, but are not limited to, l, l-propenyl, 2-propenyl, ylethenyl, l -butenyl, 2—butenyl, 3 -butenyl, 1 -methylpropenyl, yl- l -propenyl, l -methyl propenyl, 2-methylpropenyl, l-pentenyl, enyl, enyl, 4-pentenyl, l-methyl-lbutenyl , 2-methyl-l-butenyl, 3-methyl- l -butenyl, l-methylbutenyl, 2-methylbutenyl, 3-methylbutenyl, l-methylbutenyl, 2-methylbutenyl, 3-methylbutenyl, l l -dimethylpropenyl, l ,2-dimethyl- l -propenyl, l ,2-dimethylpropenyl, l -ethyl- l - propenyl, l-ethylpropenyl, l-hexenyl, 2-hexenyl, nyl, nyl, 5-hexenyl, 1 -methylpentenyl, 2-methyl- l -pentenyl, 3 -methylpentenyl, 4-methyl- l -pentenyl, l-meg-Z-pentenyl, 2-methylpentenyl, 3-methylpentenyl, 4-methylpentenyl,l-me y pentenyl, 2-methylpentenyl, 3-methylpentenyl, 4-methylpentenyl, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel l-methylpentenyl, 2-methylpentenyl, 3-methylpentenyl, 4-methylpentenyl, l l -dimethylbutenyl, l l hyl-3 -butenyl, l ,2-dimethyl- l yl, l ,2-dimethyl , , butenyl, l,2-dimethylbutenyl, l,3-dimethyl-l-butenyl, l,3-dimethylbutenyl, l,3-dimethylbutenyl, 2,2-dimethylbutenyl, 2,3-dimethyl-l-butenyl, methyl butenyl, 2,3 -dimethyl-3 -butenyl, 3 ,3 -dimethyl- l -butenyl, 3 ,3 -dimethylbutenyl, l -ethyl- l - l, l-ethylbutenyl, l-ethylbutenyl, 2-ethyl-l-butenyl, 2-ethylbutenyl, 2-ethylbutenyl, l l ,2-trimethylpropenyl, l -ethyl- l -methylpropenyl, l methyl- l - propenyl, and lmethylpropenyl.
As used , “alkynyl” represents ht-chained or branched hydrocarbon moieties containing one or more triple bond(s). Unless otherwise specified, C2-C8 alkynyl groups are intended. Alkynyl groups may contain more than one unsaturated bond.
Examples include, but are not limited to, C2-C6-alkynyl, such as ethynyl, l-propynyl, 2-propynyl (or propargyl), l-butynyl, 2-butynyl, 3-butynyl, l-methylpropynyl, l-pentynyl, 2-pentynyl, 3-pentynyl, ynyl, yl-l-butynyl, l-methylbutynyl, l-methylbutynyl, 2-methylbutynyl, l, l -dimethylpropynyl, l-ethylpropynyl, l-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 3-methyl-l-pentynyl, 4-methyl-l- pentynyl, l-methylpentynyl, ylpentynyl, l-methylpentynyl, 2-methyl pentynyl, l-methylpentynyl, 2-methylpentynyl, 3-methylpentynyl, l,l-dimethyl butynyl, l,l-dimethylbutynyl, l,2-dimethylbutynyl, 2,2-dimethylbutynyl, 3,3-dimethyl- l -butynyl, l-ethylbutynyl, l-ethyl-3 -butynyl, 2-ethylbutynyl, and l -ethyl- l -methylpropynyl.
As used , “alkoxy” refers to a group of the formula R—O—, where R is alkyl as defined above. Unless otherwise specified, alkoxy groups wherein R is a C1-C8 alkyl group are intended. Examples include, but are not limited to, methoxy, ethoxy, propoxy, l-methyl-ethoxy, butoxy, l-methyl-propoxy, 2-methyl-propoxy, l,l-dimethyl-ethoxy, pentoxy, l-methyl-butyloxy, 2-methyl-butoxy, 3-methyl-butoxy, -methyl-propoxy, l-propoxy, hexoxy, l,l-dimethyl-propoxy, l,2-dimethyl-propoxy, l-methyl-pentoxy, 2-methyl-pentoxy, 3-methyl-pentoxy, 4-methyl-penoxy, l,l-dimethyl-butoxy, l,2-dimethyl- , l,3-dimethyl-butoxy, 2,2-dimethyl-butoxy, 2,3-dimethyl-butoxy, 3,3-dimethyl- , l-ethyl-butoxy, 2-ethylbutoxy, l,l,2-trimethyl-propoxy, l,2,2-trimethyl-propoxy, l -ethyl- l -methyl-propoxy, and l -ethylmethyl-propoxy.
As used herein, “haloalkoxy” refers to a group of the formula R—O—, where R is halofi: as defined above. Unless otherwise specified, haloalkoxy groups n R is a C1-C8 a yl group are intended. Examples include, but are not limited to, chloromethoxy, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l bromomethoxy, dichloromethoxy, trichloromethoxy, fiuoromethoxy, difiuoromethoxy, trifiuoromethoxy, chlorofiuoromethoxy, dichlorofiuoromethoxy, chlorodifiuoromethoxy, l-chloroethoxy, l-bromoethoxy, l-fiuoroethoxy, 2-fiuoroethoxy, 2,2-difluoroethoxy, 2,2,2-trifiuoroethoxy, 2-chlorofiuoroethoxy, 2-chloro,2-difiuoroethoxy, chloro fiuoroethoxy, 2,2,2-trichloroethoxy, pentafiuoroethoxy, and l,l,l-trifiuoropropoxy.
As used herein, “alkylthio” refers to a group of the a R—S— where R is alkyl as defined above. Unless otherwise specified, alkylthio groups wherein R is a C1-C8 alkyl group are intended. es e, but are not limited to, methylthio, ethylthio, thio, ylethylthio, butylthio, yl-propylthio, 2-methylpropylthio, l,l-dimethylethylthio, pentylthio, l-methylbutylthio, 2-methylbutylthio, 3-methylbutylthio, 2,2-dimethylpropylthio, l-ethylpropylthio, hexylthio, methylpropylthio, l,2-dimethylpropylthio, l-methylpentylthio, 2-methylpentylthio, 3-methyl-pentylthio, 4-methyl-pentylthio, l,l-dimethyl butylthio, l,2-dimethyl-butylthio, l,3-dimethyl-butylthio, 2,2-dimethyl butylthio, methyl butylthio, 3,3-dimethylbutylthio, l-ethylbutylthio, lbutylthio, l,l,2-trimethyl propylthio, l,2,2-trimethyl propylthio, l-ethyl-l-methyl propylthio, and l-ethylmethylpropylthio.
As used herein, “haloalkylthio” refers to an alkylthio group as defined above wherein the carbon atoms are partially or entirely substituted with one or more halogen atoms. Unless otherwise specified, haloalkylthio groups wherein R is a C1-C8 alkyl group are intended. Examples include, but are not limited to, chloromethylthio, bromomethylthio, dichloromethylthio, trichloromethylthio, fiuoromethylthio, difiuoromethylthio, trifluoromethylthio, chlorofiuoromethylthio, dichlorofluoromethylthio, chlorodifluoromethylthio, l-chloroethylthio, l-bromoethylthio, l-fiuoroethylthio, 2-fiuoroethylthio, 2,2-difiuoroethylthio, 2,2,2-trifiuoroethylthio, 2-chlorofiuoroethylthio, 2-chlorodifiuoroethylthio, chlorofiuoroethylthio, 2,2,2-trichloroethylthio, pentafiuoroethylthio, and l,l,l-trifiuoropropylthio.
As used herein, “aryl,” as well as derivative terms such as “aryloxy,” refers to a phenyl, indanyl, or naphthyl group. In some embodiments, phenyl is preferred. The term “heteroaryl,” as well as derivative terms such as “heteroaryloxy,” refers to a 5- or 6- membered aromatic ring containing one or more atoms, e.g., N, O or S; these aromatic rings may be filsed to other aromatic systems. The aryl or heteroaryl substituents may be unsubstituted or substituted with one or more substituents selected from, e.g.,C1-Cgoxy,gen, hydroxy, nitro, cyano, formyl, C1-C6 alkyl, C2-C6 l, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 haloalkoxy, C1-C6 acyl, C1-C6 alkylthio, C1-C6 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel alkylsulfinyl, C1-C6 alkylsulfonyl, (C1-C6 alkoxy)carbonyl, C1-C6 carbamoyl, hydroxycarbonyl, (C1-C6 alkyl)carbonyl, aminocarbonyl, (C1-C6 alkylamino)carbonyl, (di(C1-C6 alkyl)amino)carbonyl, provided that the substituents are ally compatible and the rules of chemical bonding and strain energy are satisfied. In some embodiments, preferred substituents include, for example, halogen, C1-C2 alkyl, and C1-C2 haloalkyl.
As used herein, “alkoxycarbonyl” refers to a group of the formula XOR wherein R is alkyl.
As used herein, “alkylamino” or “dialkylamino” refers to an amino group substituted with one or two alkyl groups, which may be the same or different.
[0026] As used herein, “alkylcarbamyl” refers to a yl group substituted on the nitrogen with an alkyl group.
As used herein, “alkylsulfonyl” refers to —SOZR, wherein R is alkyl (e.g., C1-C10 alkyl).
As used herein, “carbamyl” (also referred to as carbamoyl or aminocarbonyl) refers to a group of the formula HZNJK_ As used herein, lkylamino” refers to an alkylamino group wherein the alkyl carbon atoms are lly or ly substituted with one or more halogen atoms.
As used herein, “Me” refers to a methyl group.
As used herein, the term “halogen,” including derivative terms such as “halo,” refers to fluorine, chlorine, bromine, or iodine (or fluoride, chloride, bromide, or ).
As used herein, plants and tion include, but are not limited to, germinant seeds, emerging seedlings, plants ng from tive propagules, immature vegetation, and established vegetation.
COMPOUNDS
[0033] Provided herein are compounds of Formula (I) as defined herein (e.g., in the Summary above) and N—oxides and agriculturally acceptable salts thereof In some embodiments, the compound is the carboxylic acid or an agriculturally acceptable ester or salt thereof In some embodiments, the compound is the carboxylic acid or its methyl ester.
D [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel ation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In some embodiments: Ar is selected from the group ting of Arl, Ar2, Ar3, Ar4, Ar5, and Ar6; R1 is ORI’, wherein R1, is H or C1-C8 alkyl; R2 is halogen, C2-C4 alkenyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, or C1-C4 kylthio; R3 and R4 are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, formyl, (C1-C3 alkyl)carbonyl, (C1-C3 haloalkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C1-C6 alkyl)carbamyl, tri(C1-C6 alkyl)silyl, or R3 and R4 taken together represent =CR3/R4/, wherein R3/ and R4/ are each independently en, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 alkoxy, or C1-C6 alkylamino; X is N or CY, where Y is hydrogen, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkoxy, C1-C3 hio, or C1-C3 haloalkylthio.
In one embodiment, X is N. In one embodiment, X is CY.
[0037] In one embodiment, Y is hydrogen. In one embodiment, Y is halogen (e.g., F, Cl, Br, I). In one embodiment, Y is C1-C3 alkyl (e.g., , ethyl, n-propyl, i-propyl). In one embodiment, Y is C1-C3 haloalkyl (e.g., CFH2, CF2H, CF3, CF2CF3). In one embodiment, Y is C1-C3 alkoxy (e.g., OCH3, OCH2CH3). In one embodiment, Y is C1-C3 haloalkoxy (e.g., OCFHZ, OCFZH, OCF3, 3). In one embodiment, Y is C1-C3 alkylthio (e.g., SCH3, SCH2CH3). In one embodiment, Y is C1-C3 haloalkylthio (e.g., SCFHZ, SCFZH, SCF3, SCF2CF3).
In some embodiments, X is N or CY, wherein Y is en, halogen, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 koxy, C1-C3 alkoxy, C1-C3 alkylthio, or C1-C3 haloalkylthio.
[0039] In some embodiments, X is N or CY, wherein Y is H, halo, or C1-C3 alkyl. In some embodiments, X is N or CY, wherein Y is H or halo. In some embodiments, X is N or CY, wherein Y is H, F, Cl, or Br. In some embodiments, X is N or CY, wherein Y is H, F, or Cl. In some embodiments, X is N or CY, wherein Y is H or C1-C3 alkyl. In some embodiments, X is N or CY, wherein Y is H or CH3. In some embodiments, X is N or CY, wherein Y is H. In some embodiments, X is N or CY, wherein Y is H, F, Cl, Br, or CH3. In some embodiments, X is N or CY, wherein Y is H, F, C1, or CH3. In some embodiments, X is N or CY, wherein Y is H or F. In some embodiments, X is N or CY, wherein Y is Br. In som bodiments, X is N or CY, wherein Y is H. In some ments, Y is H. In some embo 1ments, Y is F. In some embodiments, Y is Cl. In some embodiments, Y is Br. In [Annotation] l None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by l some embodiments, Y is CH3. In some embodiments, Y is H, halo, or C1-C3 alkyl. In some embodiments, Y is H or halo. In some embodiments, Y is H, F, Cl, or Br. In some embodiments, Y is H, F, or Cl. In some embodiments, Y is H or C1-C3 alkyl. In some embodiments, Y is H or CH3. In some embodiments, Y is H, F, Cl, Br, or CH3. In some embodiments, Y is H, F, Cl, or CH3. In some embodiments, Y is H or F. In some embodiments, Y is halo.
In one embodiment, R1 is ORV.
In one embodiment, R1/ is H. In one embodiment, R1/ is C1-C8 alkyl (e.g., methyl, ethyl, n-propyl, i-propyl). In one embodiment, R1/ is C7-C10 kyl (e.g., benzyl).
[0042] In some embodiments, R1 is ORV, wherein R1/ is H or C1-C8 alkyl. In some embodiments, R1 is ORV, wherein R1/ is H or C7-C10 arylalkyl.
In some embodiments, R1 is ORV, wherein R1/ is H, methyl, ethyl, or benzyl. In some embodiments, R1 is ORV, wherein R1/ is H, methyl, or ethyl. In some embodiments, R1 is ORV, wherein R1/ is H or methyl. In some embodiments, R1 is ORV, wherein R1/ is H or benzyl.
In one embodiment, R2 is halogen (e.g., F, Cl, Br, I). In one embodiment, R2 is C1-C4 alkyl (e.g., methyl, ethyl, propyl, . In one embodiment, R2 is C1-C4 kyl (e.g., CFH2, CF2H, CF3, CF2CF3). In one embodiment, R2 is C2-C4 alkenyl (e.g., Vinyl or ethenyl, propenyl, butenyl). In one embodiment, R2 is C2-C4 haloalkenyl. In one embodiment, R2 is C2-C4 l. In one embodiment, R2 is C2-C4 haloalkynyl. In one embodiment, R2 is C1-C4 alkoxy (e.g., OCH3, OCH2CH3). In one embodiment, R2 is C1-C4 haloalkoxy (e.g, OCFH2, OCFZH, OCF3, OCF2CF3). In one embodiment, R2 is C1-C4 alkylthio (e.g., SCH3, SCH2CH3). In one embodiment, R2 is C1-C4 haloalkylthio (e.g., SCFHz, SCFzH, SCF3, SCF2CF3). In one embodiment, R2 is amino. In one embodiment, R2 is C1-C4 alkylamino. In one embodiment, R2 is C2-C4 haloalkylamino. In one embodiment, R2 is . In one embodiment, R2 is (C1-C3 alkyl)carbonyl. In one embodiment, R2 is (C1-C3 haloalkyl)carbonyl. In one embodiment, R2 is cyano.
In one embodiment, R2 is -CR17=CR18-SiR19R20R21.
In one embodiment, R17 is hydrogen. In one ment, R17 is F. In one ment, R17 is Cl.
In one embodiment, R18 is hydrogen. In one embodiment, R18 is F. In one embodiment, R18 is Cl. In one embodiment, R18 is C1-C4 alkyl. In one embodiment, R18 is C1-Cdloalkyl.
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one embodiment, R19 is C1-C10 alkyl. In one embodiment, R19 is C3-C6 cycloalkyl. In one embodiment, R19 is C1-C10 haloalkyl. In one embodiment, R19 is C3-C6 halocycloalkyl. In one embodiment, R19 is phenyl. In one embodiment, R19 is tuted phenyl. In one embodiment, R19 is C1-C10 . In one embodiment, R19 is OH.
In one embodiment, R20 is C1-C10 alkyl. In one embodiment, R20 is C3-C6 lkyl. In one embodiment, R20 is C1-C10 haloalkyl. In one embodiment, R20 is C3-C6 cloalkyl. In one embodiment, R20 is phenyl. In one embodiment, R20 is substituted phenyl. In one embodiment, R20 is C1-C10 alkoxy. In one embodiment, R20 is OH.
In one embodiment, R21 is C1-C10 alkyl. In one embodiment, R21 is C3-C6 cycloalkyl. In one embodiment, R21 is C1-C10 haloalkyl. In one embodiment, R21 is C3-C6 halocycloalkyl. In one embodiment, R21 is phenyl. In one embodiment, R21 is substituted phenyl. In one embodiment, R21 is C1-C10 alkoxy. In one embodiment, R21 is OH.
In some embodiments, R2 is halogen, C2-C4 alkenyl, C2-C4 haloalkenyl, C1-C4 alkoxy, C1-C4 haloalkoxy, C1-C4 alkylthio, or C1-C4 haloalkylthio. In some embodiments, R2 is halogen, C2-C4 l, C2-C4 haloalkenyl, or C1-C4 alkoxy.
In some embodiments, R2 is halogen, C2-C4 alkenyl, or C1-C4 alkoxy. In some embodiments, R2 is Cl, Vinyl, or OCH3. In some embodiments, R2 is Cl. In some embodiments, R2 is Vinyl. In some embodiments, R2 is OCH3.
In one embodiment, R3 is hydrogen. In one embodiment, R3 is C1-C6 alkyl. In one embodiment, R3 is C1-C6 haloalkyl. In one embodiment, R3 is C3-C6 alkenyl. In one embodiment, R3 is C3-C6 haloalkenyl. In one embodiment, R3 is C3-C6 alkynyl. In one ment, R3 is hydroxy. In one embodiment, R3 is C1-C6 alkoxy. In one embodiment, R3 is C1-C6 haloalkoxy. In one embodiment, R3 is formyl. In one embodiment, R3 is (C1-C3 alkyl)carbonyl. In one embodiment, R3 is (C1-C3 kyl)carbonyl. In one embodiment, R3 is (C1-C6 alkoxy)carbonyl. In one embodiment, R3 is (C1-C6 alkyl)carbamyl. In one embodiment, R3 is C1-C6 alkylsulfonyl. In one embodiment, R3 is tri(C1-C6 alkyl)silyl. In one embodiment, R3 is di(C1-C6 alkyl)phosphonyl.
In one embodiment, R4 is hydrogen. In one embodiment, R4 is C1-C6 alkyl. In one embodiment, R4 is C1-C6 haloalkyl. In one embodiment, R4 is C3-C6 alkenyl. In one embodiment, R4 is C3-C6 haloalkenyl. In one embodiment, R4 is C3-C6 alkynyl. In one embodiment, R4 is hydroxy. In one embodiment, R4 is C1-C6 . In one ment, R4 is C1-C6 haloalkoxy. In one ment, R4 is formyl. In one embodiment, R4 is (C1-C3 alky bonyl. In one embodiment, R4 is (C1-C3 haloalkyl)carbonyl. In one embodiment, R4 ism-C6 )carbonyl. In one embodiment, R4 is (C1-C6 alkyl)carbamyl. In one [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel ment, R4 is C1-C6 alkylsulfonyl. In one embodiment, R4 is tri(C1-C6 silyl. In one embodiment, R4 is di(C1-C6 alkyl)phosphonyl.
In one embodiment, R3 and R4 together with the nitrogen atom to which they are attached form a 5-membered saturated ring. In one embodiment, R3 and R4 er with the en atom to which they are attached form a 6-membered saturated ring.
In one embodiment, R3 and R4 taken together represent =CR3[R41 In one embodiment, Ry is hydrogen. In one embodiment, Ry is C1-C6 alkyl. In one embodiment, Ry is C3-C6 alkenyl. In one embodiment, Ry is C3-C6 l. In one embodiment, Ry is C1-C6 alkoxy. In one embodiment, R3/ is C1-C6 alkylamino.
[0058] In one embodiment, R4/is hydrogen. In one ment, R4/is C1-C6 alkyl. In one embodiment, R4/is C3-C6 alkenyl. In one embodiment, R4/ is C3-C6 alkynyl. In one embodiment, R4/ is C1-C6 alkoxy. In one embodiment, R4/ is C1-C6 alkylamino.
In one embodiment, Ry and R4/together with the carbon atom to which they are attached form a 5- membered saturated ring. In one embodiment, Ry and R4/together with the carbon atom to which they are attached form a 6-membered saturated ring.
In some embodiments, R3 and R4 are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, formyl, (C1-C3 alkyl)carbonyl, (C1-C3 haloalkyl)carbonyl, (C1-C6 )carbonyl, (C1-C6 alkyl)carbamyl, tri(C1-C6 alkyl)silyl. In some embodiments, R3 and R4 taken together represent =CR3/R4/, wherein Ry and R4/ are each ndently hydrogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C1-C6 alkoxy, or C1-C6 alkylamino.
In some embodiments, R3 is H.
In some embodiments, R4 is H.
In one embodiment, Ar is Arl.
[0064] In one embodiment, provided herein is a compound of formula (1-1), or an N- oxide or agriculturally acceptable salt thereof: NR3R4 \\ R1 (1-1) wheI'DX, R1, R2, R3, R4, and X1 are defined herein elsewhere. ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] l None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one embodiment, in a compound of formula (I-l), R1 is OH and R2 is halogen.
In one embodiment, in a compound of formula (I-l), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-l), R1 is OH and R2 is C1-C4 alkoxy. In one ment, in a compound of formula (I-l), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-l), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-l), R1 is OH and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-l), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of a (I-l), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 . In one embodiment, in a compound of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-l), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-l), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, ed herein is a compound of a (I-la), (I-lb), (I-lc), (I-ld), or (I-le), or an N—oxide or agriculturally acceptable salt thereof: NR3R4 NR3R4 NR3R4 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel wherein R1, R2, R3 and X1 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-la), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula , R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-la), R1 is OH and R2 is C1-C4 . In one embodiment, in a compound of formula (I-la), R1 is OH and R2 is Cl. In one embodiment, in a compound of a , R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-la), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-la), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-la), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-la), R1 is -C4 alkyl) and R2 is l-propenyl. In one ment, in a compound of formula (I-la), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-la), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-la), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-la), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of a (I-la), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-la), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of a (I-la), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a nd of formula (I-lb), R1 is OH and R2 is n. In one embodiment, in a compound of formula (I-lb), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-lb), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a nd of formula , R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-lb), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-lb), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula , R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-lb), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of a (I-lb), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 R2alkerp In one embodiment, in a compound of formula (I-lb), R1 is —O—(C1-C4 alkyl) andis 1-C4 alkoxy. In one embodiment, in a compound of formula (I-lb), R1 is —O—(C1-C4 [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-lb), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-lb), R1 is - C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-lb), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula (I-lb), R1 is OCH3 and R2 is halogen. In one embodiment, in a nd of formula (I-lb), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-lb), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-lb), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-lb), R1 is OCH3 and R2 is OCH3. In one ment, in a compound of a (I-lb), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-lb), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-lc), R1 is OH and R2 is halogen. In one embodiment, in a nd of formula (I-lc), R1 is OH and R2 is C2-C4 alkenyl. In one ment, in a nd of formula (I-lc), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-lc), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-lc), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-lc), R1 is OH and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-lc), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-lc), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-lc), R1 is -C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-lc), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-lc), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a nd of formula (I-lc), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-lc), R1 is -C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-lc), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-lc), R1 is OCH3 and R2 isDropenyl.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one ment, in a compound of formula (I-ld), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-ld), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-ld), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-ld), R1 is OH and R2 is Cl. In one embodiment, in a nd of formula (I-ld), R1 is OH and R2 is OCH3. In one ment, in a compound of formula (I-ld), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-ld), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-ld), R1 is -C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-ld), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula , R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-ld), R1 is OCH3 and R2 is C2-C4 alkenyl. In one ment, in a nd of formula (I-ld), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-ld), R1 is OCH3 and R2 is Cl. In one ment, in a compound of a (I-ld), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-ld), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-ld), R1 is OCH3 and R2 is enyl.
In one ment, in a compound of formula (I-le), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-le), R1 is OH and R2 is C2-C4 l. In one embodiment, in a compound of formula (I-le), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-le), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-le), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-le), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-le), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-le), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-le), R1 is —O—(C1-C4 alkyl) and R2 is¢C4 alkoxy. In one embodiment, in a compound of formula (I-le), R1 is —O—(C1-C4 alkyl and R2 is Cl. In one embodiment, in a compound of formula (I-le), R1 is —O—(C1-C4 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-le), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-le), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-le), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-le), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a nd of formula (I-le), R1 is OCH3 and R2 is Cl. In one ment, in a compound of formula (I-le), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of a (I-le), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-le), R1 is OCH3 and R2 is enyl.
In one embodiment, Ar is Ar2.
In one embodiment, provided herein is a compound of formula (1-2), or an N- oxide or agriculturally acceptable salt thereof: NR3R4 \\ R1 (1-2) wherein X, R1, R2, R3 and X2 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is n.
In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (1-2), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-2), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embflent, in a compound of formula (I-2), R1 is -C4 alkyl) and R2 is OCH3. In one , in a compound of a (1-2), R1 is —O—(C1-C4 alkyl) and R2 is Vinyl (or [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ethenyl). In one embodiment, in a compound of formula (I-2), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula (1-2), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (1-2), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2), R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula (1-2), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of a (I-2), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of a (1-2), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, provided herein is a compound of formula (I-2a), (I-2b), (I-2c), (I-2d), or (I-2e), or an N—oxide or lturally acceptable salt thereof: NR3R4 NR3R4 NR3R4 (I-2d) wherein R1, R2, R3 and X2 are defined herein elsewhere.
, R4, In one embodiment, in a compound of a (I-2a), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-2a), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2a), R1 is OH and R2 is C1-C4 . In one embodiment, in a compound of formula (I-2a), R1 is OH and R2 is Cl. In one embodiment, in a nd of formula (I-2a), R1 is OH and R2 is OCH3. In one ment, in a compound of formula (I-2a), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2a), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2a), R1 is —O—(C1-C4 alkyl) and R2 is n. In one embodiment, in a compound of formula (I-2a), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-2a), R1 is —O—(C1-C4 alkyl) and R2 isDC4 alkoxy. In one embodiment, in a compound of formula (I-2a), R1 is —O—(C1-C4 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-2a), R1 is -C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-2a), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2a), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula (I-2a), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of a (I-2a), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2a), R1 is OCH3 and R2 is C1-C4 alkoxy. In one ment, in a compound of formula (I-2a), R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula (I-2a), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-2a), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2a), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-2b), R1 is OH and R2 is halogen. In one embodiment, in a nd of formula (I-2b), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2b), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of a (I-2b), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-2b), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula , R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2b), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is n. In one embodiment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one ment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one ment, in a compound of formula (I-2b), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2b), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula (I-2b), R1 is OCH3 and R2 is n. In one embodiment, in a nd of formula (I-2b), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2b), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2b), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-2b), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-2b), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-2b), R1 is OCH3 and R2 isDropenyl.
[Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by l In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula , R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2c), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2c), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-2c), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 l. In one embodiment, in a compound of formula (I-2c), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2c), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a nd of formula (I-2c), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-2c), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2c), R1 is -C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2c), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of a (I-2c), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2c), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a nd of formula (I-2c), R1 is OCH3 and R2 is Cl. In one ment, in a compound of formula (I-2c), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-2c), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula , R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-2d), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-2d), R1 is OH and R2 is C2-C4 l. In one embodiment, in a nd of formula (I-2d), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2d), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula , R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-2d), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2d), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2d), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-2d), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 l. In one embodiment, in a nd of formula (I-2d), R1 is —O—(C1-C4 alkyl) and R2 isalkylgd R2 is Cl.C4 alkoxy. In one embodiment, in a compound of formula (I-2d), R1 is -C4 In one embodiment, in a compound of formula (I-2d), R1 is —O—(C1-C4 ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l ation] chanmel Unmarked set by chanmel alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-2d), R1 is - C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2d), R1 is OCH3 and R2 is halogen. In one ment, in a compound of formula (I-2d), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2d), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2d), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of a (I-2d), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2d), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a nd of formula (I-2e), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2e), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2e), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2e), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-2e), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-2e), R1 is -C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-2e), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2e), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-2e), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-2e), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-2e), R1 is OCH3 and R2 is l-propenyl. [008b In one embodiment, Ar is Ar3.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel In one embodiment, provided herein is a compound of formula (1-3), or an N- oxide or agriculturally acceptable salt thereof: NR3R4 \\ R1 x3 F (1-3) wherein X, R1, R2, R3 and X3 are defined herein elsewhere.
, R4, In one ment, in a compound of formula (1-3), R1 is OH and R2 is halogen.
In one embodiment, in a compound of formula (I-3), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (1-3), R1 is OH and R2 is C1-C4 alkoxy. In one ment, in a nd of a (I-3), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-3), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-3), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-3), R1 is OH and R2 is l-propenyl. In one ment, in a compound of formula (I-3), R1 is -C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-3), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (1-3), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one ment, in a compound of formula (I-3), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-3), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (1-3), R1 is —O—(C1-C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-3), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one ment, in a compound of formula (1-3), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (1-3), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-3), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3), R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula (1-3), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-3), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (1-3), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, provided herein is a compound of formula (1-3 a), (I-3b), or (I-3c), or an N—oxide or agriculturally acceptable salt thereof: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel or (1-3 c) wherein R1, R2, R3 and X3 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-3a), R1 is OH and R2 is halogen. In one embodiment, in a compound of a (I-3a), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-3a), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3a), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-3a), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-3a), R1 is OH and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-3a), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-3a), R1 is —O—(C1-C4 alkyl) and R2 is n. In one embodiment, in a compound of a (I-3a), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 l. In one embodiment, in a compound of formula (I-3a), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3a), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (1-3 a), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-3a), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (1-3 a), R1 is —O—(C1-C4 alkyl) and R2 is enyl. In one embodiment, in a compound of formula (I-3a), R1 is OCH3 and R2 is halogen. In one embodiment, in a nd of formula (I-3a), R1 is OCH3 and R2 is C2-C4 alkenyl. In one ment, in a compound of formula (I-3a), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3a), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of a (I-3a), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-3a), R1 is OCH3 and R2 is ropenyl.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one ment, in a compound of formula , R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-3b), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-3b), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-3b), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-3b), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of a (I-3b), R1 is OH and R2 is l-propenyl. In one embodiment, in a nd of formula (I-3b), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-3b), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-3b), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3b), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-3b), R1 is -C4 alkyl) and R2 is OCH3. In one ment, in a compound of formula (I-3b), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-3b), R1 is —O—(C1-C4 alkyl) and R2 is enyl. In one embodiment, in a compound of formula (I-3b), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of a (I-3b), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of a (I-3b), R1 is OCH3 and R2 is C1-C4 . In one embodiment, in a compound of formula (I-3b), R1 is OCH3 and R2 is Cl. In one ment, in a compound of formula (I-3b), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-3b), R1 is OCH3 and R2 is Vinyl (or l). In one embodiment, in a compound of formula (I-3b), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is halogen. In one embodiment, in a nd of formula (I-3c), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-3c), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a nd of formula (I-3c), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-3c), R1 is —O—(C1-C4 alkyl) and R2 is¢C4 alkoxy. In one embodiment, in a compound of formula (I-3c), R1 is —O—(C1-C4 alkyl and R2 is Cl. In one embodiment, in a compound of formula (I-3 c), R1 is —O—(C1-C4 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel alkyl) and R2 is OCH3. In one embodiment, in a compound of formula , R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-3 c), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of a (I-3c), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of a (I-3c), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of a (I-3c), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-3c), R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula , R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-3c), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-3c), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, Ar is Ar4.
In one embodiment, provided herein is a compound of formula (1-4), or an N- oxide or agriculturally acceptable salt thereof: NR3R4 \ R1 x2 F (1-4) wherein X, R1, R2, R3 and X2 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (1-4), R1 is OH and R2 is halogen.
In one embodiment, in a compound of formula (I-4), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-4), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-4), R1 is OH and R2 is Vinyl (or ethenyl). In one ment, in a compound of formula (I-4), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a nd of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embflent, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one diment, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is Vinyl (or [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ethenyl). In one embodiment, in a compound of formula (I-4), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-4), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-4), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4), R1 is OCH3 and R2 is Cl. In one ment, in a compound of formula (I-4), R1 is OCH3 and R2 is OCH3. In one ment, in a compound of formula (I-4), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, ed herein is a compound of formula , (I-4b), or (I-4c), or an N—oxide or agriculturally acceptable salt thereof: NR3R4 NR3R4 or (I-4c) wherein R1, R2, R3 and X2 are defined herein ere.
, R4, In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula , R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4a), R1 is OH and R2 is l-propenyl. In one ment, in a compound of formula , R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-4a), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alken 1 In one embodiment, in a compound of formula (I-4a), R1 is —O—(C1-C4 alkyl) and R2 isbC4 alkoxy. In one embodiment, in a compound of formula (I-4a), R1 is —O—(C1-C4 [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-4a), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula , R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4a), R1 is —O—(C1-C4 alkyl) and R2 is enyl. In one embodiment, in a compound of formula (I-4a), R1 is OCH3 and R2 is n. In one embodiment, in a compound of formula (I-4a), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4a), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is OCH3. In one embodiment, in a nd of formula (I-4a), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4a), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-4b), R1 is OH and R2 is n. In one ment, in a compound of formula (I-4b), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4b), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4b), R1 is OH and R2 is Cl. In one embodiment, in a nd of a (I-4b), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-4b), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4b), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or l). In one embodiment, in a compound of formula (I-4b), R1 is —O—(C1-C4 alkyl) and R2 is enyl. In one embodiment, in a compound of formula (I-4b), R1 is OCH3 and R2 is halogen. In one ment, in a compound of formula (I-4b), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of a (I-4b), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4b), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-4b), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-4b), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4b), R1 is OCH3 and R2 isDropenyl.
[Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one embodiment, in a compound of formula , R1 is OH and R2 is halogen. In one embodiment, in a compound of a (I-4c), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of a (I-4c), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4c), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-4c), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-4c), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4c), R1 is OH and R2 is l-propenyl. In one ment, in a compound of formula (I-4c), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of a (I-4c), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4c), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-4c), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-4c), R1 is -C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-4c), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4c), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-4c), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, Ar is ArS.
In one ment, ed herein is a compound of formula (1-5), or an N- oxide or agriculturally acceptable salt f: NR3R4 F X \ R1 (1-5) wherEX, R1, R2, R3 , R4, and X3 are defined herein elsewhere.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one embodiment, in a compound of a (I-S), R1 is OH and R2 is halogen.
In one embodiment, in a compound of formula (I-S), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (1-5), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-S), R1 is OH and R2 is Cl. In one embodiment, in a compound of a (I-S), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-S), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-S), R1 is OH and R2 is l-propenyl. In one ment, in a compound of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one ment, in a compound of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (1-5), R1 is —O—(C1-C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-S), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (1-5), R1 is OCH3 and R2 is halogen. In one ment, in a compound of formula (1-5), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of a (I-S), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-S), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (1-5), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-S), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of a (1-5), R1 is OCH3 and R2 is enyl.
In one embodiment, provided herein is a compound of formula (1-5 a), (I-Sb), or (I-5c), or an N—oxide or agriculturally able salt thereof: ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel (I-5c) wherein R1, R2, R3 and X3 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-Sa), R1 is OH and R2 is n. In one embodiment, in a nd of formula (I-Sa), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-Sa), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-Sa), R1 is OH and R2 is Cl. In one embodiment, in a nd of formula (I-Sa), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-Sa), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-Sa), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-Sa), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-Sa), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-Sa), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-Sa), R1 is -C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (1-5 a), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-Sa), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (1-5 a), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-Sa), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-Sa), R1 is OCH3 and R2 is C2-C4 alkenyl. In one ment, in a compound of a (I-Sa), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-Sa), R1 is OCH3 and R2 is OCH3. In one ment, in a nd of formula (I-Sa), R1 is OCH3 and R2 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-Sa), R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-Sb), R1 is OH and R2 is halogen. In one ment, in a compound of formula (I-5b), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula , R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-Sb), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula , R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-Sb), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-Sb), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a nd of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-Sb), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of a (I-Sb), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-Sb), R1 is OCH3 and R2 is C1-C4 . In one embodiment, in a compound of formula (I-Sb), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is OCH3. In one embodiment, in a nd of formula (I-Sb), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-5b), R1 is OCH3 and R2 is l-propenyl.
[00101] In one embodiment, in a compound of a (I-Sc), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-5c), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-Sc), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-Sc), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-5c), R1 is OH and R2 is OCH3. In one embodiment, in a nd of formula (I-Sc), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-5c), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of a (I-5c), R1 is -C4 alkyl) and R2 is halogen. In one flodiment, in a compound of formula (I-5c), R1 is -C4 alkyl) and R2 is C2-C4 alke11y . In one embodiment, in a compound of formula (I-Sc), R1 is —O—(C1-C4 alkyl) and ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-5c), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-S c), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula , R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-S c), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is halogen. In one ment, in a compound of formula (I-5c), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-5c), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-5c), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-5c), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-5c), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-5c), R1 is OCH3 and R2 is l-propenyl.
In one ment, Ar is Ar6.
In one embodiment, provided herein is a compound of formula (1-6), or an N- oxide or agriculturally acceptable salt thereof: NR3R4 F X \N R1 X2 F (1-6) wherein X, R1, R2, R3 and X2 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-6), R1 is OH and R2 is halogen. In one ment, in a compound of a (I-6), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-6), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-6), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-6), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-6), R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-6), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (1-6), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 isalkeb In one ment, in a compound of a (I-6), R1 is —O—(C1-C4 alkyl) and R2C1 . In one embodiment, in a compound of formula (1-6), R1 is —O—(C1-C4 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel alkyl) and R2 is Cl. In one ment, in a compound of formula (I-6), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-6), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-6), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-6), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of a (I-6), R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula (I-6), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-6), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6), R1 is OCH3 and R2 is l-propenyl.
In one ment, provided herein is a compound of a (I-6a), (I-6b), or (I-6c), or an N—oxide or agriculturally acceptable salt thereof: NR3R4 NR3R4 F N / X2 F (I-6a) (I-6c) or F ; wherein R1, R2, R3 and X2 are defined herein elsewhere.
, R4, In one embodiment, in a compound of formula (I-6a), R1 is OH and R2 is halogen. In one embodiment, in a compound of a (I-6a), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a nd of formula (I-6a), R1 is OH and R2 is C1-C4 . In one embodiment, in a compound of formula (I-6a), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-6a), R1 is OH and R2 is OCH3. In one ment, in a compound of formula (I-6a), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6a), R1 is OH and R2 is l-propenyl. In one embcn1ent, in a nd of formula (I-6a), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel one embodiment, in a compound of formula (I-6a), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6a), R1 is -C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-6a), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one ment, in a compound of formula (I-6a), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-6a), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6a), R1 is -C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of a (I-6a), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-6a), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6a), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula , R1 is OCH3 and R2 is Cl. In one embodiment, in a nd of formula (I-6a), R1 is OCH3 and R2 is OCH3. In one embodiment, in a compound of formula (I-6a), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6a), R1 is OCH3 and R2 is l-propenyl.
[00107] In one embodiment, in a compound of formula , R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is C2-C4 l. In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is C1-C4 . In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6b), R1 is OH and R2 is l-propenyl. In one embodiment, in a nd of formula (I-6b), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-6b), R1 is -C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6b), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-6b), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one ment, in a compound of formula (I-6b), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-6b), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula (I-6b), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a compound of formula (I-6b), R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-6b), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a nd of a (I-6b), R1 is OCH3 and R2 is C1-C4 . In one embodiment, in a compound of formula (I-6b), R1 islfiHg and R2 is Cl. In one embodiment, in a compound of formula , R1 is OCH3 and 1s OCH3. In one embodiment, in a compound of formula (I-6b), R1 is OCH3 and R2 [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel is Vinyl (or ethenyl). In one embodiment, in a compound of formula , R1 is OCH3 and R2 is l-propenyl.
In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is halogen. In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is Cl. In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is OCH3. In one embodiment, in a compound of formula (I-6c), R1 is OH and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of formula , R1 is OH and R2 is l-propenyl. In one embodiment, in a compound of formula (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is halogen. In one embodiment, in a compound of formula (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is C1-C4 alkoxy. In one ment, in a compound of formula (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is Cl. In one embodiment, in a compound of formula (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is OCH3. In one embodiment, in a compound of formula (I-6c), R1 is —O—(C1- C4 alkyl) and R2 is Vinyl (or ethenyl). In one embodiment, in a compound of a (I-6c), R1 is —O—(C1-C4 alkyl) and R2 is l-propenyl. In one embodiment, in a nd of formula , R1 is OCH3 and R2 is halogen. In one embodiment, in a compound of formula (I-6c), R1 is OCH3 and R2 is C2-C4 alkenyl. In one embodiment, in a compound of formula (I-6c), R1 is OCH3 and R2 is C1-C4 alkoxy. In one embodiment, in a compound of formula (I-6c), R1 is OCH3 and R2 is Cl. In one embodiment, in a compound of formula (I-6c), R1 is OCH3 and R2 is OCH3. In one ment, in a compound of a (I-6c), R1 is OCH3 and R2 is Vinyl (or ethenyl). In one embodiment, in a nd of formula (I-6c), R1 is OCH3 and R2 is l-propenyl.
[00109] In one embodiment, X1 is H. In one embodiment, X1 is F. In one embodiment, X1 is Br. In one embodiment, X1 is I. In one embodiment, X1 is ethynyl. In one embodiment, X1 is CF2H. In one embodiment, X1 is OCF2H. In one embodiment, X1 is OCF3. In one embodiment, X1 is CN. In one embodiment, X1 is CONHz. In one embodiment, X1 is COZH. In one embodiment, X1 is COZCH3. In one embodiment, X1 is N02.
In some embodiments, X1 is H, F, Br, I, ethynyl, CF2H, OCF2H, OCF3, CN, CONH2, C02CH3, or N02. [001b In some embodiments, X1 is F. In some embodiments, X1 is Br or I.
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In one embodiment, X2 is H. In one embodiment, X2 is F. In one embodiment, X2 is C1. In one embodiment, X2 is Br. In one embodiment, X2 is I. In one embodiment, X2 is ethynyl. In one embodiment, X2 is CH3. In one embodiment, X2 is CFH2. In one embodiment, X2 is CF2H. In one embodiment, X2 is CF3. In one embodiment, X2 is OCF2H. In one ment, X2 is OCF3. In one embodiment, X2 is CN.
In one embodiment, X2 is CONH2. In one embodiment, X2 is CO2H. In one embodiment, X2 IS N02.
In some embodiments, X2 is H, Cl, Br, I, ethynyl, CH3, CF2H, CF3, OCF2H, or CN.
[00114] In some embodiments, X2 is H, F, Br, I, ethynyl, CH3, CF3, OCF2H, or CN.
In some embodiments, X2 is F or C1. In some embodiments, X2 is Br or I.
In one ment, X3 is H. In one embodiment, X3 is F. In one embodiment, X3 is Br. In one embodiment, X3 is I. In one ment, X3 is ethynyl. In one ment, X3 is CH3. In one embodiment, X3 is CFH2. In one ment, X3 is CF2H. In one embodiment, X3 is CF3. In one embodiment, X3 is OCF2H. In one ment, X3 is OCF3. In one embodiment, X3 is CN. In one embodiment, X3 is CONH2. In one embodiment, X3 is CO2H. In one embodiment, X3 is N02.
In some embodiments, X3 is H, Br, I, ethynyl, OCF2H, CN, or NO2.
In some embodiments, X3 is H, F, Br, I, CH3, CF2H, CF3, OCF2H, or CN.
[00119] In some embodiments, X3 is F or C1. In some embodiments, X3 is Br or I.
] In one embodiment, when Ar is X1 then X is N, CH, CF, CCl, or CCH3, with provisos that: i) R2 is not C1 or Vinyl, when X is N; ii) X1 is not H, F, OCF3, or CN, when R2 is C1 and X is CH; iii) X1 is not F, I, CN, or ethynyl, when R2 is OCH3 and X is CF; iV) X1 is not H, when X is CCl.
In one embodiment, when Ar is F then X is N, CH, CF, CCl, or CCH3, with provisos that: i) R2 is not C1, when X is N; D ii) X2 is not C1, when R2 is OCH3 or Vinyl and X is N; iii) X2 is not C1, when R2 is C1 and X is CH; and [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel iv) X2 is not Cl, Br, I, or CF3, when R2 is OCH3 and X is CF.
In one embodiment, when Ar is 3 F then X is N, CH, or CF, with provisos that: i) R2 is not Cl, when X is N; ii) X3 is not CH3, when R2 is OCH3 and X is N; iii) X3 is not H, F, or CH3, when R2 is Cl and X is CH; and iv) X3 is not Br or I, when R2 is OCH3 and X is CF.
Xz‘ ; F ] In one ment, when Ar is F then X is N, CH, or CF, with provisos that: i) R2 is not Cl, when X is N; ii) X2 is not Cl, when R2 is OCH3 or vinyl and X is N; iii) X2 is not F, when R2 is Cl and X is CH; and iv) X2 is not Cl, Br, I, or CF3, when R2 is OCH3 and X is CF.
In one ment, when Ar is F then X is N, CH, or CF, with proviso that: i) X3 is not CH3, when R2 is Cl and X is N; and ii) X3 is not Br or I, when X is CF and R2 is OCH3.
X2 F In one embodiment, when Ar is F then X is N, CH, or CF.
Any ofthe combinations ofAr, X, Y, R1, R2, R3, R4, R1, R1", R2", R17, R18, R19, R20, R21, R3, R4, Arl, Ar2, Ar3, Ar4, Ar5, Ar6, X1, X2, and/or X3, and/or other substituents described herein, are encompassed by this disclosure and specifically provided herein.
[Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by l METHODS OF PREPARING THE COMPOUNDS Exemplary procedures to synthesize the compounds of Formula (I) are provided below.
The 3,5-disubstitutedamino(optionally substituted phenyl)picolinic acids of Formula (I) can be prepared in a number of ways. As depicted in Scheme 1, the 4-amino picolinates of Formula (II) can be converted to the 4-aminosubstituted-picolinates of Formula (111), wherein Ar is as herein defined, via Suzuki coupling with a boronic acid or ester, in the presence of a base, such as potassium fluoride, and a st, such as bis(triphenylphosphine)-palladium(II) dichloride, in a polar, protic solvent mixture, such as acetonitrile-water, at a ature, such as 110 CC, 6.g. , in a microwave reactor (reaction (1;). 4-Aminosubstituted-picolinates of Formula (111) can be transformed into the 5-iodo- 4-aminosubstituted-picolinates of Formula (IV) via a reaction with iodinating reagents, such as periodic acid and iodine, in a polar, protic t, such as methyl alcohol (reaction [91). Stille coupling of the aminosubstituted-picolinates of Formula (IV) with a stannane, such as tetramethyltin, in the presence of a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in a non-reactive solvent, such as 1,2- dichloroethane, at a ature, such as 120-130 0C, e.g., in a microwave reactor, provides -(substituted)aminosubstituted-picolinates of Formula (I-A), wherein Z1 is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio (reaction 01).
[00129] Alternatively, 4-aminochloropicolinates of Formula (II) can be ormed into the 5-iodoaminochloropicolinates of Formula (V) via a reaction with iodinating reagents, such as periodic acid and iodine, in a polar, protic solvent, such as methyl alcohol (reaction [92). Stille coupling of the 5-iodoaminochloropicolinates of Formula (V) with a stannane, such as tetramethyltin, in the presence of a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in a active solvent, such as 1,2- dichloroethane, at a temperature, such as 120-130 0C, e.g., in a microwave reactor, provides -(substituted)aminochloropicolinates of Formula (VI), wherein Z1 is alkyl, alkenyl, alkynyl, haloalkenyl and hio (reaction Cg). The 5-substitutedamino picolinates of Formula (VI) can be converted to the 5-substitutedamino substituted-picolinates of Formula (I-A), n Ar is as herein defined, via Suzuki coupling with a boronic acid or ester, in the presence of a base, such as potassium fluoride, and a catalyst, such as bis(triphenylphosphine)—palladium(II) dichloride, in a polar, protic [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by l ation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel solvent mixture, such as acetonitrile-water, at a temperature, such as 110 CC, e.g., in a microwave reactor ion a2).
Schemel C1 C1 1 C1 \ [,1 \ z1 01 \ I I I / O / 0 \ \ Ar N/ 0\ Ar N Ar N O O O 111 IA_ a1 I “2 NH2 NH2 NH2 C1 b2 1 C1 CZ ZI C1 \ \ \ | _. | | 0\ / o / 0 C1 N \ C1 N/ C1 N \ o O O V VI
[00130] As depicted in Scheme 11, the 4,5,6-trichloropicolinate of Formula (VII) can be converted to the corresponding isopropyl ester of Formula (VIII), via a reaction with isopropyl alcohol and concentrated sulfuric acid, 6.g. , at reflux temperature under Dean- Stark conditions (reaction d). The isopropyl ester of a (VIII) can be reacted with a fluoride ion source, such as cesium fluoride, in a polar, aprotic solvent, such as dimethyl sulfoxide (DMSO), at a temperature, such as 80 CC, under Dean-Stark conditions, to yield the isopropyl trifluoropicolinate of a (IX) (reaction 6). The isopropyl 4,5,6- trifluoropicolinate of Formula (IX) can be aminated with a nitrogen source, such as ammonia, in a polar, aprotic solvent, such as DMSO, to produce a 4-amino-5,6- difluoropicolinate of Formula (X) (reactionf). The fluoro substituent in the 6-position of the 4-amino-5,6-difluoropicolinate of Formula (X) can be exchanged with a chloro substituent by ent with a chloride source, such as hydrogen chloride, e.g., in dioxane, in a Parr reactor, at a temperature, such as 100 CC, to produce a 4-aminofluorochloro-picolinate of Formula (XI) (reaction g). The 4-aminofluorochloropicolinate of Formula (XI) can be transesterified to the corresponding methyl ester of Formula (XII) by reaction with titanium(IV) isopropoxide in methyl alcohol at reflux temperature (reaction h).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Scheme II C1 C1 F C1 C1 F \ d \ e \ f | —> | —> | —> C1 N/ 0\ C1 N’ of F N’ of o o 0 VII VIII 1X NH2 NH2 NHz F F h F \\ 8' \\ \\ I I I , o / / N Y o o F C1 N Y C1 N \ O o O X XI XII As depicted in Scheme III, the 4-aminofluorochloropicolinate of Formula (XII) can be transformed into the 3-iodoaminofluorochloropicolinate of a (XIII) via reaction with iodinating reagents, such as periodic acid and iodine, in a polar, protic solvent, such as methyl alcohol (reaction [93). Stille coupling of the 3-iodoamino fluorochloropicolinates of Formula (XIII) with a stannane, such as tributyl(vinyl)stannane, in the presence of a catalyst, such as bis(triphenylphosphine)- palladium(II) dichloride, in a non-reactive solvent, such as chloroethane, at a temperature, such as 120-130 0C, e.g., in a microwave reactor, provides 3-(substituted)—4- aminofluorochloropicolinates of a (XIV), wherein R2 is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio ion 03). Alternatively, the 3-iodoaminofluoro picolinates of Formula (XIII) can be treated with cesium carbonate and a catalytic amount of both copper(I) iodide and l,lO-phenanthroline in the presence of a polar, protic solvent, such as methyl alcohol, at a temperature, such as 65 0C, to provide a 3-(substituted)— 4-aminofluorochloropicolinic acids of a (XIV), wherein R2 is alkoxy or haloalkoxy (reaction 2'1), which can be esterified to the methyl esters, e.g., by treatment with hydrogen de (gas) and methyl alcohol at 50 CC (reactionj1). The 3-(substituted)—4- aminofluorochloropicolinates of a (XIV) can be ted to the 4-amino substituted-picolinates of Formula (I-B), wherein Ar is as herein defined, via Suzuki coupn with a boronic acid or ester, in the presence of a base, such as potassium fluoride, ation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel and a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in a polar, protic solvent e, such as acetonitrile-water, at a temperature, such as 110 CC, e.g., in a microwave r (reaction a3).
Alternatively, the 4-aminofluorochloropicolinates of Formula (XII) can be converted to the 4-aminofluorosubstituted-picolinates of Formula (XV), wherein Ar is as herein defined, via Suzuki coupling with a boronic acid or ester, in the presence of a base, such as potassium fluoride, and a catalyst, such as bis(triphenylphosphine)-palladium(II) ride, in a polar, protic solvent mixture, such as itrile-water, at a temperature, such as 110 0C, e.g., in a microwave reactor (reaction a4). The 4-aminofluoro substituted-picolinates of Formula (XV) can be transformed into the 3-iodoamino fluorosubstituted-picolinates of Formula (XVI) Via reaction with iodinating ts, such as periodic acid and iodine, in a polar, protic t, such as methyl alcohol (reaction [94).
Stille coupling of the 3-iodoaminofluorosubstituted-picolinates of Formula (XVI) with a stannane, such as tributyl(Vinyl)stannane, in the presence of a catalyst, such as iphenylphosphine)-palladium(II) dichloride, in a non-reactive solvent, such as 1,2- dichloroethane, at a temperature, such as 120—130 0C, e.g., in a microwave reactor, provides 3-(substituted)—4-amino-5 -fluorosubstituted-picolinates of Formula (I-B), wherein R2 is alkyl, alkenyl, alkynyl, haloalkenyl and alkylthio (reaction C4). Alternatively, the 3-iodo aminofluorosubstituted-picolinates of Formula (XVI) can be treated with cesium carbonate and a catalytic amount of both copper(I) iodide and l,lO-phenanthroline in the presence of a polar, protic solvent, such as methyl alcohol, at a temperature, such as 65 CC, to e a 3-(substituted)—4-aminofluorosubstituted-picolinic acids of Formula (I-B), wherein R2 is alkoxy or haloalkoxy (reaction 2'2), which can be esterified to the methyl esters, e.g., by treatment with hydrogen chloride (gas) and methyl alcohol, at a temperature, such as 50 oC (reactionj2).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Scheme III | —> | / o , o —. | C1 N \ C1 N \ i1 thenjl C1 N O\ o O XII XIII NH2 NH2 F 1 \ b4 \ F R2 ' c4 01' \ | —> / —> / | \ Ar N o\ Ar N i2 thenj2 Ar N/ O\ As depicted in Scheme IV, the 4-acetamido(trimethylstannyl)picolinates of Formula (XVII) can be converted to the amidosubstituted-picolinates of Formula ), wherein Ar is as herein , Via Stille coupling with an aryl bromide or aryl , in the presence of a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in a solvent, such as l,2-dichloroethane, e.g., at reflux temperature (reaction k). osubstituted-picolinates of Formula (I-C), wherein Ar is as herein defined, can be synthesized from 4-acetamidosubstituted-picolinates of Formula (XVIII) Via standard deprotecting methods, such as hydrochloric acid gas in methanol (reaction 1).
Scheme IV 0 O )LNH )LNH NHz CI CI I C1 \ \ \ | | | \Sn N/ 0\ Ar N/ 0\ Ar N/ O\ XVIII 1-C XVII As depicted in Scheme V, chloromethoxypyrimidine (XIX) can be transned into 2,4-dichloromethoxyVinylpyrimidine (XX) Via a reaction with Vinyl [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel magnesium bromide, in a polar, aprotic solvent, such as tetrahydrofuran (reaction m). 2,4- ro-S-methoxyvinylpyrimidine (XX) can be transformed into 2,6-dichloro methoxypyrimidinecarboxaldehyde (XXI) via treatment with ozone, e.g., in a dichloromethane:methanol solvent mixture (reaction n). 2,6-Dichloro methoxypyrimidinecarboxaldehyde (XXI) can be transformed into methyl 2,6-dichloro methoxypyrimidinecarboxylate (XXII) via ent with bromine, e.g. , in a methanol:water solvent mixture (reaction 0). Methyl 2,6-dichloromethoxypyrimidine carboxylate (XXII) can be transformed into methyl 6-aminochloromethoxypyrimidine- 4-carboxylate (XXIII) via treatment with ammonia (e.g., 2 equivalents) in a solvent, such as DMSO ion [9). Finally, 6-aminosubstitutedmethoxypyrimidinecarboxylates of Formula (I-D), wherein Ar is as herein defined, can be prepared via Suzuki ng with a c acid or ester, with ochloromethoxypyrimidinecarboxylate (XXIII), in the presence of a base, such as potassium fluoride, and a catalyst, such as bis(triphenylphosphine)-palladium(II) dichloride, in a polar, protic solvent mixture, such as acetonitrile—water, at a temperature, such as 110 CC, e.g., in a microwave reactor (reaction a5).
SchemeV m O N \ n N \ 0 JL / c1 A / N C1 N C1 N I 5 XIX xx xx1 C1 | NH2 | (I) O p o a N \ , I 1x} \ / / O )NL \ ClxN/ 0\ O\ CIAN \ Ar N o 0 XXII XXIII ] The compounds of Formulae I-A, I-B, LC, and 1-D obtained by any of these processes, can be recovered by conventional means and purified by standard procedures, such as by recrystallization or chromatography. The compounds of a (I) can be prepared from compounds of Formulae I-A, I-B, LC, and 1-D using rd methods well knova the art.
[Annotation] l None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel COMPOSITIONS AND METHODS In some embodiments, the compounds provided herein are employed in mixtures containing a herbicidally effective amount of the compound along with at least one lturally acceptable adjuvant or carrier. Exemplary adjuvants or carriers include those that are not phytotoxic or significantly phytotoxic to valuable crops, 6.g. at the concentrations employed in applying the compositions for selective weed control in the presence of crops, and/or do not react or significantly react ally with the compounds provided herein or other composition ingredients. Such mixtures can be designed for application directly to weeds or their locus or can be concentrates or formulations that are diluted with additional carriers and adjuvants before ation. They can be solids, such as, for example, dusts, granules, water dispersible granules, or wettable powders, or liquids, such as, emulsif1able concentrates, solutions, emulsions or suspensions. They can also be provided as a pre-mix or tank-mixed.
Suitable agricultural adjuvants and carriers that are useful in preparing the herbicidal mixtures of the disclosure are well known to those skilled in the art. Some of these nts include, but are not limited to, crop oil trate al oil (85%) + emulsifiers (l 5 %)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary um salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and c surfactant; C9-C11 alkylpolyglycoside; ated alcohol ethoxylate; natural primary alcohol (Cu-C16) ethoxylate; di-sec-butylphenol EO-PO block copolymer; polysiloxane- methyl cap; nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8E0); tallow amine ethoxylate (15 E0); PEG(400) dioleate-99.
Liquid rs that can be employed include water and organic solvents. The organic solvents typically used include, but are not limited to, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraff1nic oils, and the like; vegetable oils such as soybean oil, ed oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; esters of cohols or dihydric, trihydric, or other lower polyalcohols (4-6 hydroxy ning), such as 2-ethylhexyl stearate, n-butyl oleate, isopropyl myristate, propylene glycol dioleate, di-octyl ate, di-butyl adipate, di-octyl phthalate and the like; esters of mono-, di- and poly-carboxylic acids and the like.
SpecDorganic solvents include toluene, xylene, petroleum naphtha, crop oil, acetone, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel methyl ethyl ketone, cyclohexanone, trichloroethylene, perchloroethylene, ethyl acetate, amyl e, butyl acetate, propylene glycol thyl ether and diethylene glycol monomethyl ether, methyl alcohol, ethyl alcohol, isopropyl alcohol, amyl alcohol, ethylene glycol, propylene glycol, glycerine, N—methylpyrrolidinone, N,N—dimethyl alkylamides, dimethyl sulfoxide, liquid fertilizers, and the like. In some embodiments, water is the carrier for the dilution of concentrates.
Suitable solid carriers include talc, pyrophyllite clay, silica, attapulgus clay, kaolin clay, kieselguhr, chalk, diatomaceous earth, lime, calcium carbonate, bentonite clay, 's earth, cottonseed hulls, wheat flour, soybean flour, pumice, wood flour, walnut shell flour, lignin, and the like.
In some embodiments, one or more surface-active agents are utilized in the compositions of the present disclosure. Such surface-active agents are, in some embodiments, employed in both solid and liquid compositions, e.g., those designed to be diluted with carrier before application. The surface-active agents can be anionic, cationic or nonionic in character and can be employed as emulsifying agents, wetting agents, suspending agents, or for other purposes. Surfactants conventionally used in the art of formulation and which may also be used in the present formulations are described, inter alia, in McCutcheon ’s Detergents and Emulsz'fiers Annual, MC hing Corp., Ridgewood, New Jersey, 1998, and in Encyclopedia ofSurfactants, Vol. I-III, Chemical Publishing Co., New York, 1980-81. l e-active agents include salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; alkylarylsulfonate salts, such as calcium dodecylbenzenesulfonate; alkylphenol-alkylene oxide addition ts, such as nonylphenol-Clg late; alcohol-alkylene oxide addition products, such as tridecyl alcohol-C16 ethoxylate; soaps, such as sodium stearate; alkylnaphthalene-sulfonate salts, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl) sulfosuccinate; ol , such as sorbitol oleate; quaternary , such as lauryl trimethylammonium chloride; polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and ene oxide; salts of mono- and dialkyl phosphate ; vegetable or seed oils such as n oil, rapeseed/canola oil, olive oil, castor oil, sunflower seed oil, coconut oil, corn oil, cottonseed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; and esters of the above vegetable oils, e.g., methyl esters.
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Oftentimes, some of these als, such as vegetable or seed oils and their esters, can be used interchangeably as an agricultural nt, as a liquid carrier or as a surface active agent.
] Other adjuvants commonly used in agricultural compositions include compatibilizing agents, am agents, sequestering agents, neutralizing agents and buffers, corrosion inhibitors, dyes, odorants, ing agents, penetration aids, sticking agents, dispersing agents, thickening agents, freezing point depressants, antimicrobial agents, and the like. The compositions may also contain other compatible components, for example, other herbicides, plant growth regulants, fungicides, insecticides, and the like and can be formulated with liquid fertilizers or solid, particulate fertilizer carriers such as ammonium nitrate, urea and the like.
The concentration of the active ients in the herbicidal compositions of this disclosure is generally from about 0.001 to about 98 percent by weight. Concentrations from about 0.01 to about 90 t by weight are often ed. In compositions designed to be employed as concentrates, the active ingredient is generally present in a concentration from about 5 to about 98 weight percent, preferably about 10 to about 90 weight percent. Such compositions are typically d with an inert carrier, such as water, before application. The d compositions usually applied to weeds or the locus of weeds generally contain about 0.0001 to about 1 weight percent active ingredient and preferably contain about 0.001 to about 0.05 weight percent.
The present compositions can be applied to weeds or their locus by the use of conventional ground or aerial dusters, sprayers, and granule applicators, by addition to irrigation or flood water, and by other conventional means known to those skilled in the art.
In some embodiments, the compounds and compositions described herein are applied as a post-emergence application, pre-emergence application, in-water application to flooded paddy rice or water bodies (e.g., ponds, lakes and streams), or bum-down application.
In some embodiments, the compounds and compositions ed herein are utilized to control weeds in crops, including but not limited to , apple, rubber, oil, palm, forestry, direct-seeded, water-seeded and transplanted rice, wheat, barley, oats, rye, m, aize, pastures, ands, rangelands, fallowland, turf, tree and vine orchards, aquatics, or row-crops, as well as non-crop settings, e.g., industrial vegetation man ent (IVM) or rights-of-way. In some embodiments, the compounds and compos1tions are used to control woody plants, broadleaf and grass weeds, or sedges. ation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel In some embodiments, the compounds and compositions provided herein are utilized to control rable vegetation in rice. In certain embodiments, the undesirable vegetation is Brachiarz'a platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitarz'a sanguinalz’s (L.) Scop. (large crabgrass, DIGSA), Echinochloa crus-gallz' (L.) P.
Beauv. rdgrass, ECHCG), Echinochloa colonum (L.) LINK (junglerice, ECHCO), Echinochloa oryzoz'des (Ard.) Fritsch (early watergrass, ECHOR), Echinochloa oryzz'cola (Vasinger) er (late watergrass, ECHPH), Ischaemum m Salisb. (saramollagrass, ISCRU), Leptochloa chinensz's (L.) Nees (Chinese sprangletop, LEFCH), Leptochloafascz’cularz’s (Lam.) Gray (bearded sprangletop, LEFFA), Leptochloa panicoz'des .) Hitchc. n sprangletop, LEFPA), Panicum dichotomz'florum (L.) MichX. (fall panicum, PANDI), um dilatatum Poir. (dallisgrass, PASDI), Cyperus dl'fi’orml's L. (smallflower flatsedge, CYPDI), Cyperus esculentus L. (yellow nutsedge, CYPES), Cyperus iria L. (rice flatsedge, CYPIR), Cyperus rotundus L. (purple nutsedge, CYPRO), Eleocharz’s species (ELOSS), Fimbrz’stylz’s miliacea (L.) Vahl (globe fringerush, FIMMI), Schoenoplectusjuncoides Roxb. (Japanese h, SCPJU), Schoenoplectus maritimus L. (sea sh, SCPMA), Schoenoplectus mucronatus L. (ricefield h, SCPMU), Aeschynomene species, (jointvetch, AESSS), Alternanthera philoxeroz'des (Mart) Griseb. (alligatorweed, ALRPH), Alisma plantago-aquatl'ca L. (common waterplantain, ALSPA), Amaranthus species, (pigweeds and amaranths, AMASS), ’a coccinea Rottb. (redstem, AMMCO), Eclipta alba (L.) Hassk. (American false daisy, ECLAL), Heteranthera limosa (SW.) Willd./Vahl (ducksalad, HETLI), Heteranthera remformis R. & P. (roundleaf mudplantain, HETRE), a hederacea (L.) Jacq. (ivyleaf glory, IPOHE), m'a dubia (L.) Pennell (low false pimpemel, LIDDU), Monochorz'a korsakowz'z' Regel & Maack (monochoria, MOOKA), Monochorz'a vaginalz's (Burm. F.) C.
Presl ex Kuhth, (monochoria, MOOVA), m'a nudz'flora (L.) Brenan (doveweed, MUDNU), Polygonum pensylvam’cum L. (Pennsylvania smartweed, POLPY), Polygonum persicarz'a L. (ladysthumb, POLPE), Polygonum hydropz'peroides MichX. (mild smartweed, POLHP), Rotala indica (Willd.) Koehne (Indian toothcup, ROTIN), Sagittaria species, (arrowhead, SAGSS), Sesbam'a exaltata (Raf) ydb. EX Hill (hemp sesbania, SEBEX), or Sphenoclea zeylam'ca Gaertn. weed, SPDZE).
In some embodiments, the nds and compositions provided herein are ed to control rable vegetation in cereals. In certain embodiments, the undesirable vegeBeaugwindgrass,n is Alopecurus myosuroz'des Huds. (blackgrass, ALOMY), Apera spica-ventz' (L.) APESV), Avenafatua L. (Wild oat, AVEFA), Bromus tectorum L.
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel (downy brome, , Loliam multifloram Lam. (Italian ryegrass, LOLMU), Phalaris minor Retz. (littleseed canarygrass, PHAMI), Poa annua L. (annual bluegrass, POAAN), Setaria pamila (Poir.) Roemer & J.A. es (yellow foxtail, SETLU), Setaria viridis (L.) Beauv. (green foxtail, SETVI), Cirsiam arvense (L.) Scop. (Canada thistle, , Galiam aparine L. (catchweed bedstraw, GALAP), Kochia scoparia (L.) Schrad. a, KCHSC), Lamium purpureum L. (purple deadnettle Matricaria recutita L. (wild , LAMPU), chamomile, MATCH), Matricaria arioides (Less.) Porter (pineappleweed, MATMT), Papaver rhoeas L. (common poppy, PAPRH), Polygonum convolvalus L. (wild buckwheat, POLCO), Salsola tragas L. (Russian thistle, , Stellaria media (L.) Vill. (common chickweed, STEME), Veronica persica Poir. (Persian speedwell, , Viola arvensis Murr. (field violet, VIOAR), or Viola tricolor L. (wild violet, VIOTR).
] In some embodiments, the compounds and compostions provided herein are utilized to control undesirable vegetation in range and pasture. In certain embodiments, the undesirable vegetation is ia artemisiifolia L. (common ragweed, AMBEL), Cassia obtusifolia (sickle pod, CASOB), Centaurea sa auct. non Lam. (spotted knapweed, CENMA), Cirsium arvense (L.) Scop. (Canada e, CIRAR), Convolvulus arvensis L. (field ed, CONAR), Eaphorbia esala L. (leafy spurge, EPHES), Lactaca serriola L./Tom. (prickly e, LACSE), Plantago lanceolata L. (buckhom plantain, PLALA), Rumex folias L. (broadleaf dock, RUMOB), Sida spinosa L. (prickly sida, SIDSP), Sinapis arvensis L. (wild mustard, SINAR), Sonchus arvensis L. nial sowthistle, SONAR), go species (goldenrod, , Taraxacam ofiicinale G.H. Weber ex Wiggers (dandelion, TAROF), Trifolium repens L. (white clover, , or Urtica dioica L. (common nettle, URTDI).
In some embodiments, the compounds and compositions ed herein are utilized to control rable tion found in row crops. In certain embodiments, the undesirable vegetation is Alopecaras myosaroides Huds. (blackgrass, ALOMY), Avena fataa L. (wild oat, AVEFA), Brachiaria platyphylla (Groseb.) Nash (broadleaf signalgrass, BRAPP), Digitaria sanguinalis (L.) Scop. (large crabgrass, , Echinochloa cras-galli (L.) P. Beauv. (bamyardgrass, ECHCG), Echinochloa colonam (L.) Link (junglerice, ECHCO), Loliam multifloram Lam. (Italian ryegrass, LOLMU), Panicam dichotomifloram Michx. (fall panicum, PANDI), Panicam miliaceum L. (wild-proso millet, PANMI), Setaria faberi Herrm. (giant foxtail, SETFA), Setaria viridis (L.) Beauv. (green foxtail, SETVI), ArangaceamSorg halepense (L.) Pers. (Johnsongrass, SORHA), Sorghum r (L.) Moench ssp. (shattercane, SORVU), Cyperus escalentus L. (yellow nutsedge, CYPES), [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] l Unmarked set by chanmel Cyperus rotundas L. (purple nutsedge, CYPRO), Abatz’lon theophrastz’ Medik. (velvetleaf, ABUTH), Amaranthas species (pigweeds and amaranths, AMASS), Ambrosia artemz’sz’z’folz’a L. (common ragweed, AMBEL), Ambrosia psilostachya DC. (western ragweed, AMBPS), Ambrosia trz'fida L. (giant ragweed, AMBTR), z’as syriaca L. (common milkweed, ASCSY), Chenopodz'am album L. (common lambsquarters, CHEAL), Cirsz'am arvense (L.) Scop. (Canada thistle, CIRAR), Commelz'na benghalensz’s L. (tropical spiderwort, COMBE), Datara stramom'um L. (jimsonweed, DATST), Daucus carota L. (wild carrot, , Euphorbz'a heterophylla L. (wild ttia, EPHHL), Erigeron bonariensis L. (hairy fleabane, ERIBO), Erigeron canadensz's L. (Canadian fleabane, ERICA), Helianthus annuus L. (common sunflower, HELAN), Jacqaemontz'a tamnz'folz'a (L.) Griseb. (smallflower momingglory, IAQTA), Ipomoea hederacea (L.) Jacq. (ivyleaf momingglory, IPOHE), Ipomoea lacanosa L. (white momingglory, , Lactaca serrz'ola L./Tom. (prickly lettuce, LACSE), Portulaca oleracea L. (common purslane, POROL), Sida spinosa L. (prickly sida, SIDSP), Sinapl's arvensis L. (wild mustard, SINAR), Solanum ptychanthum Dunal (eastern black nightshade, SOLPT), or Xanthz'um stramarz'am L. (common bur, XANST).
In some embodiments, application rates of about 1 to about 4,000 grams/hectare (g/ha) are employed in post-emergence operations. In some embodiments, rates of about 1 to about 4,000 g/ha are employed in pre-emergence operations.
[00152] In some ments, the compounds, compositions, and methods provided herein are used in conjunction with one or more other ides to control a wider variety of undesirable vegetation. When used in conjunction with other herbicides, the presently d compounds can be formulated with the other herbicide or herbicides, tank-mixed with the other herbicide or herbicides or applied tially with the other ide or herbicides. Some of the herbicides that can be employed in ction with the compounds of the present disclosure include: 4-CPA, 4-CPB, 4-CPP, 2,4-D, 2,4-D choline salt, 2,4-D esters and amines, 2,4-DB, 3,4-DA, 3,4-DB, 2,4-DEB, 2,4-DEP, 3,4-DP, TBA, 2,4,5- T, 2,4,5-TB, acetochlor, acifluorfen, aclonifen, in, alachlor, chlor, alloxydim, allyl alcohol, alorac, ametridione, ametryn, amibuzin, amicarbazone, amidosulfuron, aminocyclopyrachlor, aminopyralid, amiprofos-methyl, amitrole, ammonium ate, anilofos, anisuron, asulam, atraton, atrazine, azafenidin, azimsulfuron, aziprotryne, barban, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron- methguensulide, benthiocarb, bentazon-sodium, ox, benzfendizone, benzipram,benzo 1cyclon, benzofenap, benzofluor, benzoylprop, benzthiazuron, bicyclopyrone, ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel bifenox, bilanafos, bispyribac-sodiurn, borax, cil, brornobonil, brornobutide, fenoxirn, brornoxynil, brornpyrazon, butachlor, butafenacil, butarnifos, butenachlor, azole, ron, butralin, butroxydirn, buturon, butylate, cacodylic acid, trole, calcium chlorate, calcium cyanarnide, carnbendichlor, carbasularn, carbetarnide, carboxazole, chlorprocarb, carfentrazone-ethyl, CDEA, CEPC, chlornethoxyfen, chlorarnben, chloranocryl, chlorazifop, chlorazine, chlorbrornuron, chlorbufarn, chloreturon, chlorfenac, chlorfenprop, urazole, urenol, chloridazon, chlorirnuron, chlornitrofen, chloropon, toluron, chloroxuron, chloroxynil, chlorpropharn, chlorsulfuron, chlorthal, chlorthiarnid, n-ethyl, cinrnethylin, cinosulfuron, cisanilide, clethodirn, cliodinate, clodinafop-propargyl, clofop, clornazone, clorneprop, cloprop, cloproxydirn, clopyralid, cloransularn-rnethyl, CMA, copper sulfate, CPMF, CPPC, credazine, cresol, curnyluron, cyanatryn, ine, cycloate, cyclosulfarnuron, cycloxydirn, cycluron, cyhalofop-butyl, cyperquat, cyprazine, ole, cyprornid, dairnuron, dalapon, dazornet, delachlor, desrnedipharn, desrnetryn, di-allate, dicarnba, dichlobenil, dichloralurea, dichlorrnate, dichlorprop, dichlorprop-P, op, diclosularn, dietharnquat, diethatyl, difenopenten, difenoxuron, difenzoquat, diflufenican, diflufenzopyr, dirnefuron, dirnepiperate, dirnethachlor, dirnetharnetryn, dirnethenarnid, dirnethenarnid-P, dirnexano, dirnidazon, arnine, dinofenate, dinoprop, rn, dinoseb, rb, diphenarnid, dipropetryn, diquat, disul, dithiopyr, diuron, DMPA, DNOC, DSMA, EBEP, eglinazine, endothal, epronaz, EPTC, erbon, esprocarb, ethalfluralin, ethbenzarnide, etharnetsulfuron, ethidirnuron, ethiolate, ethobenzarnid, etobenzarnid, ethofilrnesate, fen, ethoxysulfiaron, etinofen, etniprornid, etobenzanid, EXD, fenasularn, fenoprop, fenoxaprop, fenoxaprop-P-ethyl, fenoxaprop-P-ethyl + isoxadifen-ethyl, fenoxasulfone, fenteracol, aprop, fentrazarnide, fenuron, ferrous sulfate, flarnprop, flarnprop-M, flazasulfuron, florasularn, op, fluazifop-P-butyl, fluazolate, azone, flucetosulfuron, fluchloralin, flufenacet, flufenican, flufenpyr-ethyl, flurnetsularn, flurnezin, flurniclorac- pentyl, flurnioxazin, flurnipropyn, fluorneturon, fluorodifen, fluoroglycofen, fluorornidine, fluoronitrofen, fluothiuron, flupoxarn, flupropacil, flupropanate, flupyrsulfilron, fluridone, flurochloridone, fluroxypyr, flurtarnone, fluthiacet, fornesafen, sulfuron, ine, furyloxyfen, glufosinate, glufosinate-arnrnoniurn, glyphosate, halosafen, halosulfuron- rnethyl, haloxydine, fop-rnethyl, haloxyfop-P-rnethyl, halauxifen-rnethyl, hexachloroacetone, hexaflurate, hexazinone, irnazarnethabenz, irnazarnox, irnazapic, imazq, irnazaquin, irnazethapyr, irnazosulfuron, indanofan, indaziflarn, iodobonil,iodorne ane, iodosulfuron, iofensulfiaron, ioxynil, ipazine, ipfencarbazone, ipryrnidarn, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel bamid, isocil, isomethiozin, isonoruron, isopolinate, isopropalin, isoproturon, isouron, en, isoxachlortole, utole, isoxapyrifop, karbutilate, ketospiradox, lactofen, lenacil, linuron, MAA, MAMA, MCPA esters and amines, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, medinoterb, mefenacet, mefluidide, mesoprazine, mesosulfuron, mesotrione, metam, fop, metamitron, metazachlor, metazosulfuron, metflurazon, methabenzthiazuron, methalpropalin, methazole, methiobencarb, methiozolin, methiuron, methometon, methoprotryne, methyl bromide, methyl ocyanate, methyldymron, metobenzuron, omuron, metolachlor, metosulam, metoxuron, metribuzin, metsulfuron, molinate, monalide, monisouron, loroacetic acid, monolinuron, monuron, morfamquat, MSMA, naproanilide, napropamide, amide-M, naptalam, neburon, lfuron, nipyraclofen, nitralin, nitrofen, nitrofluorfen, norflurazon, noruron, OCH, arb, ortho-dichlorobenzene, orthosulfamuron, oryzalin, oxadiargyl, oxadiazon, oxapyrazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraflufen-ethyl, parafluron, paraquat, pebulate, onic acid, pendimethalin, penoxsulam, pentachlorophenol, pentanochlor, pentoxazone, perfluidone, pethoxamid, phenisopham, phenmedipham, dipham-ethyl, phenobenzuron, phenylmercury acetate, picloram, picolinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, potassium e, pretilachlor, primisulfuron-methyl, procyazine, prodiamine, profluazol, alin, profoxydim, proglinazine, prohexadione-calcium, prometon, prometryn, propachlor, propanil, propaquizafop, propazine, propham, propisochlor, propoxycarbazone, propyrisulfilron, propyzamide, prosulfalin, prosulfocarb, furon, proxan, prynachlor, pydanon, pyraclonil, pyraflufen, pyrasulfotole, pyrazogyl, pyrazolynate, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyriclor, pyridafol, pyridate, pyriftalid, pyriminobac, pyrimisulfan, pyrithiobac-methyl, pyroxasulfone, pyroxsulam, quinclorac, quinmerac, quinoclamine, quinonamid, quizalofop, quizalofop-P-ethyl, rhodethanil, rimsulfuron, saflufenacil, lachlor, sebuthylazine, secbumeton, sethoxydim, siduron, simazine, simeton, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfallate, trazone, sulfometuron, sulfosate, sulfosulfuron, sulfuric acid, sulglycapin, swep, TCA, m, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbucarb, terbuchlor, eton, terbuthylazine, terbutryn, tetrafluron, thenylchlor, thiazafluron, thiazopyr, thidiazimin, zuron, thiencarbazone-methyl, thifensulfuron, thiobencarb, tiocarbazil, tioclorim, topramezone, tralkoxydim, triafamone, tri-alb triasulfuron, flam, tribenuron, tricamba, triclopyr esters and amines, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel tridiphane, zine, trifloxysulfuron, alin, ulfuron, trifop, trifopsime, trihydroxytriazine, trimeturon, tripropindan, tritac, tritosulfuron, vemolate and xylachlor.
The compounds and compositions of the present sure can lly be employed in combination with known herbicide safeners, such as benoxacor, ocarb, brassinolide, cloquintocet (e.g, mexyl), cyometrinil, daimuron, dichlormid, dicyclonon, dimepiperate, oton, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, filrilazole, harpin proteins, isoxadifen-ethyl, mefenpyr-diethyl, MG 191, MON 4660, naphthalic anhydride (NA), oxabetrinil, R29l48 and N—phenylsulfonylbenzoic acid amides, to enhance their selectivity.
[00154] The compounds, itions, and methods described herein be used to l undesirable vegetation on glyphosate-tolerant-, glufosinate-tolerant-, dicamba-tolerant-, phenoxy auxin-tolerant-, pyridyloxy auxin-tolerant-, aryloxyphenoxypropionate-tolerant-, acetyl CoA carboxylase (ACCase) tor-tolerant-, imidazolinone-tolerant-, acetolactate synthase (ALS) inhibitor-tolerant-, 4-hydroxyphenyl-pyruvate dioxygenase (HPPD) inhibitor -tolerant-, protoporphyrinogen oxidase (PPO) inhibitor ant-, triazine-tolerant-, and bromoxynil-tolerant- crops (such as, but not limited to, soybean, cotton, canola/oilseed rape, rice, cereals, corn, turf, etc), for example, in conjunction with glyphosate, glufosinate, dicamba, phenoxy auxins, pyridyloxy auxins, aryloxyphenoxypropionates, ACCase inhibitors, imidazolinones, ALS inhibitors, HPPD inhibitors, PPO inhibitors, triazines, and bromoxynil. The compositions and methods may be used in controlling undesirable vegetation in crops possessing multiple or stacked traits conferring nce to multiple chemistries and/or inhibitors of multiple modes-of-action.
The compounds and compositions provided herein may also be employed to control herbicide resistant or tolerant weeds. Exemplary resistant or tolerant weeds include, but are not limited to, biotypes resistant or tolerant to acetolactate synthase (ALS) inhibitors, photosystem II inhibitors, acetyl CoA carboxylase (ACCase) inhibitors, synthetic auxins, photosystem I inhibitors, 5-enolpyruvylshikimatephosphate (EPSP) synthase inhibitors, ubule assembly inhibitors, lipid synthesis inhibitors, orphyrinogen oxidase (PPO) inhibitors, carotenoid biosynthesis inhibitors, very long chain fatty acid (VLCFA) inhibitors, phytoene desaturase (PDS) inhibitors, ine synthetase inhibitors, 4- hydroxyphenyl-pyruvate-dioxygenase (HPPD) inhibitors, mitosis tors, cellulose biosynthesis inhibitors, herbicides with le of-action such as quinclorac, and uncl ' 1ed herbicides such as arylaminopropionic acids, difenzoquat, endothall, and organoarsenicals. Exemplary ant or tolerant weeds include, but are not limited to, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel es with resistance or tolerance to multiple herbicides, multiple chemical classes, and multiple herbicide modes-of—action.
The described embodiments and following examples are for illustrative purposes and are not intended to limit the scope of the claims. Other ations, uses, or ations with t to the compositions described herein will be nt to a person of ordinary skill in the art without departing from the spirit and scope of the claimed subject matter.
EXAMPLES lO SYNTHESIS OF PRECURSORS ] General Considerations: Fluorine spectra were acquired at 376 MHz on a Bruker DRX400 spectrometer. The spectra were referenced to trichlorofluoromethane (CFClg) as an external standard and were typically conducted with proton decoupling.
Example 1: Preparation of methyl 4-amin0-3,6-dichlor0picolinate (Head A) / 0 CI N \ Prepared as described in Fields et al., WO 2001051468 Al.
Example 2: Preparation of methyl 4-amin0-3,6-dichlor0flu0r0picolinate (Head B) F CI / 0\ CI N CH3 Prepared as described in Fields et al., Tetrahedron Letters 2010, 51, 79-81.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by l Example 3: Preparation of 2,6-dichloromethoxyvinyl dine CI C|3H3 CI (EH3 O O CI/kN/| CIANNI \/ To a solution of commercially available 2,6-dichlor0meth0xy pyrimidine (100 grams (g), 0.55 moles (mol) in dry tetrahydrofuran was added dropwise 1 molar (M) vinyl magnesium bromide in tetrahydrofuran solvent (124 g, 0.94 mol) over one hour (h) at room temperature. The mixture was then stirred for 4 h at room temperature. Excess Grignard reagent was quenched by addition of acetone (200 milliliters (mL)) while the temperature of the mixture was maintained at a temperature below 20 oC. Thereafter, 2,3-dichloro-5,6- dicyano-p-benzoquinone (DDQ; 151 g, 0.67 mol) was added at once and stirred overnight.
A yellow solid precipitated out. The solid was filtered and washed with ethyl e (500 mL). The filtrate was concentrated under reduced pressure and the resulting crude compound was diluted with ethyl acetate (2 liters (L)). The ing undissolved, dark, semi-solid was ted by filtration using ethyl e. It was further concentrated under reduced pressure to provide a crude compound, which was purified by column chromatography. The compound was eluted with 5% to 10% ethyl acetate in hexanes mixture to provide the title compound (70 g, 60%): mp 60 — 61 0C; 1H NMR(CDC13) 8 3.99 (s, 3H), 5.85 (d, 1H), 6.75 (d, 1H), 6.95 (dd, 1H). e 4: Preparation of 2,6-dichloromethoxy-pyrimidinecarbaldehyde CI 9H3 CI ('ng o O NI \ N \ CIAN/ | | CIAN/ CH2 0 A solution of 2,6-dichlor0meth0xyvinyl pyrimidine (50 g, 0.24 mol) in dichloromethane:methanol (4: 1, 2L) was cooled to -78 oC. Ozone gas was bubbled through for 5 h. The on was quenched with dimethyl sulfide (50 mL). The mixture was slowly warmed to room temperature and concentrated under reduced pressure at 40 0C to provide the title compound (50.5 g, 100%).
[Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Example 5: Preparation of methyl 2,6-dichloromethoxy-pyrimidinecarboxylate CI cH3 CI cH3 O O N \ N \ CI/kN| —> CIAN| / / O\ 0 0 A solution of chloromethoxy-pyrimidinecarbaldehyde (50 g, 0.24 mol) in methanol (1 L) and water (60 mL) was prepared. To the solution, sodium bicarbonate (400 g) was added. A 2 M solution of bromine (192 g, 1.2 mol) in methanol/water (600 mL, 9:1 v/v) was added dropwise to the pyrimidine on over 45 minutes (min) at 0 CC while stirring the mixture. The stirring was continued at the same temperature for 1 h. Later, the mixture was stirred at room temperature for 4 h. While stirring, the reaction mixture was thereafter poured onto a mixture of d ice (2 L), sodium bisulflte (50 g), and sodium chloride (NaCl; 200 g). The product was extracted with ethyl acetate (1 L x 2), and the combined organic layer was dried over sodium sulfate (NaZSO4) and d. Evaporation of the t under reduced pressure produced a thick material, which solidified on long standing to afford the title compound (50.8 g, 87%): ESIMS m/Z 238 ([M+H]+).
Example 6: Preparation of methyl 6-aminochloromethoxy-pyrimidine carboxylate (Head C) CI 9H3 NH2 9H3 O O N \\ ______, N \\ A / O\ A / 0\ CI N CH3 CI N CH3 0 0 A solution of methyl 2,6-dichloromethoxy-pyrimidinecarboxylate (25 g, 0.1 mol) and dimethyl sulfoxide (DMSO) was prepared. To this solution was added, at 0—5 c’C, a solution of ammonia (2 equivalents (equiv)) in DMSO. This mixture was stirred at the same 0—5 c’C temperature for 10 to 15 min. Later, the mixture was diluted with ethyl acetate, and the resulting solid was filtered off. The ethyl acetate e was washed with a brine solution and dried over NaZSO4. Upon concentration, the crude product was ed. The crude product was stirred in a minimum amount of ethyl acetate and filtered to obtain the pure npound. Additional pure compound was obtained from the filtrate which, after [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel concentration, was purified by flash chromatography. This produced the title compound (11 g, 50%): mp 158 0C; 1H NMR (DMSO-d6) 8 3.71 (s, 3H), 3.86 (s, 3H), 7.65 (br s, 1H), 8.01 (br s, 1H).
Example 7: Preparation of methyl 4-amin0-3,6-dichlor0i0d0picolinate \ I CI / O I C' N \CH3 CI N/ O\CH3 Methyl 4-amino-3,6-dichloropicolinate (10.0 g, 45.2 mmol), ic acid (3.93 g, 17.2 millimoles (mmol)), and iodine (11.44 g, 45.1 mmol) were dissolved in methanol (30 mL) and stirred at reflux at 60 CC for 27 h. The reaction e was concentrated, diluted with diethyl ether, and washed twice with saturated aqueous sodium bisulfite. The aqueous layers were extracted once with diethyl ether, and the combined organic layers were dried over anhydrous Na2S04. The t was trated and purified by flash chromatography a gel; 0—50% ethyl acetate/hexanes) to provide the title compound as a pale yellow solid (12.44 g, 79%): mp 315 0C; 1H NMR (400 MHz, CDC13)5 5.56 (s, 2H), 3.97 (s, 3H); 13C NMR (101 MHz, CDC13) 5 163.80, 153.00, 152.75, 145.63, 112.12, 83.91, 53.21; EIMS m/z 346.
Example 8: Preparation of methyl 0-3,6-dichloro-S-methylpicolinate (Head D) NH2 NH2 I CI H3C CI \ \ l l / O\ / 0\ CI N CH3 CI N CH3 0 0
[00165] A mixture of methyl 4-amino-3,6-dichloroiodopicolinate (8.1 g, 23.4 mmol), tetramethylstannane (8.35 g, 46.7 mmol), and bis(triphenylphosphine)palladium(H) chloride (2.5 g, 3.5 mmol) in 1,2-dichloroethane (40 mL) was irradiated in a Biotage InitiatorTM microwave at 120 CC for 30 min, with external infrared (IR)-sensor temperature ring from the side. The reaction mixture was loaded directly onto a silica gel cartridge and purified by flash chromatography (silica gel; 0—50% ethyl acetate/hexanes) to provide the title .pound as an orange solid (4.53 g, 83%): mp 133—136 0C; 1H NMR (400 MHz, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel CDClg) 5 4.92 (s, 2H), 3.96 (s, 3H), 2.29 (s, 3H); 13C NMR (101 MHz, CDC13)8 164.34, 150.24, 148.69, 143.94, , 114.60, 53.02, 14.40; ESIMS m/Z 236 ([M+H]+), 234 ([M- H]').
Example 9: Preparation of methyl 6-amino-2,5-dichloropyrimidinecarboxylate (Head E) CI O\CH3 Prepared as described in Epp et a1., WO 2007082076 A1. e 10: Preparation of methyl ochlorofluoromethoxypicolinate (Head F) NH2 C|3H3 F 0 CI N/ O\CH3 Prepared as described in Epp et a1., WO 2013003740 A1. e 11: Preparation of methyl 4-aminochlorofluorovinylpicolinate (Head NH2 NH2 CH2 F I I _> \ CI N/ O‘CHs CI N/ O\CH3 O 0 Methyl 4-aminochlorofluoroiodopicolinate (7.05 g, 21.33 mmol, prepared as described in Epp et a1., WO 2013003740 A1) and Vinyl tri-n-butyltin (7.52 mL, .6 mmol) were suspended in dichloroethane (71.1 mL) and the mixture was degassed with Argon for 10 min. Bis(triphenylphosphine)palladium(ll) chloride (1.497 g, 2.133 mmol) was 1D added, and the reaction mixture was stirred at 70 CC overnight (clear orange [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel solution). The reaction was red by gas tography-mass spectrometry (GC- MS). After 20 h, the reaction mixture was concentrated, adsorbed onto Celite®, and purified by column chromatography (silica gel (SiOz); s/ethyl acetate gradient) to afford the title compound as a light brown solid (3.23 g, : mp 99—100 0C; 1H NMR (400 MHz, CDCl3) 5 6.87 (dd, J: 18.1, 11.6 Hz, 1H), 5.72 (dd, J: 11.5, 1.3 Hz, 1H), 5.52 (dd, J: 18.2, 1.3 Hz, 1H), 4.79 (s, 2H), 3.91 (s, 3H); ”P NMR (376 C13)5 -138.79 (s); EIMS m/Z 230.
Example 12: Preparation of methyl 4-amin0-3,5,6-trichlor0picolinate (Head H) CI CI / 0 CI N \CH3 0 Prepared as described in Finkelstein et al., WO 2979 A1.
Example 13: Preparation of methyl 4-amin0br0m0chlor0fluoropicolinate (Head 1) F Cl Br N/ O\CH3 0 Prepared as described in Amdt et al., US 20120190857 A1.
Example 14: ation of methyl 4-amin0chlor0flu0r0 (trimethylstannyl)picolinate (Head J) F CI \ / 0\ Sn N Chg / \ 0 Methyl 4-aminobromochlorofluoropicolinate (500 milligrams (mg), 1.8 mmol), 1,1,1,2,2,2-hexamethyldistannane (580 mg, 1.8 mmol) and bis(triphenylphosphine)- pallannfll) chloride (120 mg, 0.18 mmol) were combined in dry dioxane (6 mL), sparged [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel with a stream of nitrogen for 10 min and then heated to 80 0C for 2 h. The cooled mixture was stirred with ethyl acetate (25 mL) and saturated NaCl (25 mL) for 15 min. The organic phase was ted, filtered through diatomaceous earth, dried (NaZSO4) and evaporated.
The residue was taken up in ethyl acetate (4 mL), stirred and treated in portions with hexanes (15 mL). The milky white solution was decanted from any solids ed, filtered through glass wool and evaporated to give the title compound as an off-white solid (660 mg, 100%): 1H NMR (400 MHz, CDClg) 8 4.63 (d, J = 29.1 Hz, 2H), 3.97 (s, 3H), 0.39 (s, 9H); ”P NMR (376 MHz, CDC13) 5 -130.28;EIMS m/Z 366.
Example 15: Preparation of methyl 4-acetamid0chlor0(trimethylstannyl)— picolinate (Head K) \ / 0 Sn N \CH / \ 3 Prepared as described in Balko et al., WO 2003011853 A1. e 16: ation of methyl amid0-3,6-dichlor0picolinate (Head L) H3CJL NH / 0\ CI N CH3 Prepared as described in Fields et al., WO 2001051468 A1.
Example 17: Preparation of methyl 4-amin0chloro-6—i0d0picolinate (Head M) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Prepared as bed in Balko et a1., WO 2007082098 A2.
Example 18: Preparation of methyl 4-acetamidochloroiodopicolinate (Head N) H3C NH / O\ | N CH3
[00175] ed as described in Balko et a1., WO 2007082098 A2. e 19: Preparation of methyl 4-aminobromo-3,S-difluoropicolinate (Head 0) F F / 0\ Br N CH3
[00176] Prepared as described in Fields et a1., WO 2001051468 A1.
Example 20: Preparation of methyl 6-aminochloroVinylpyrimidinecarboxylate (Head P) NH2 sz )L/ o\ CI N CH3
[00177] Prepared as described in Epp et a1., US 20090088322.
Example 22: Preparation of 4-bromofluorophenyl)trimethylsilane M9381 [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l ed set by chanmel A 2.5 M solution of n-butyllithium in hexanes i; 900 microliters (uL), 2.2 mmol, 1.1 equiv) was added to a d solution of 1,4-dibromofluorobenzene (500 mg, 2.0 mmol, 1.0 equiv) in diethyl ether (10 mL) at -78 CC. The resulting pale yellow solution was stirred at -78 CC for 2 h. Chlorotrimethylsilane (300 uL, 2.4 mmol, 1.2 equiv) was added and the resulting pale yellow solution was allowed to slowly warm to 23 0C, by allowing the dry ice / acetone bath to melt, and was stirred for 72 h. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (3 x 50 mL). The combined organic layers were dried (magnesium sulfate (MgSO4)), gravity filtered, and concentrated by rotary evaporation to afford the title nd as a pale yellow oil (350 mg, 71%): IR (thin film) 3068 (w), 2955 (m), 2927 (m), 2855 (w), 1598 (w), 1567 (w) cm'1; 1H NMR (400 MHz, DMSO-d6) 5 7.38 — 7.49 (m, 3H), 0.30 (s, 9H).
Example 23: Preparation of (2—flu0r0(4,4,5,5—tetramethyl-1,3,2-di0xab0rolan yl)phenyl)trimethylsilane B\ ?)§<CH3CH3 0 CH3 Me3Si F A 2.5 M on of n-BuLi (8.5 mL, 21 mmol, 1.1 equiv) was added to a stirred solution of (4-bromofluorophenyl)trimethylsilane (4.8 g, 19 mmol, 1.0 equiv) in tetrahydrofuran (80 mL) at -78 CC. The resulting orange solution was stirred at -78 °C for min. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.4 mL, 21 mmol, 1.1 equiv) was added, and the cloudy orange solution was allowed to slowly warm to 23 0C, by allowing the dry ice / acetone bath to melt, and stirred for 20 h. The reaction mixture was diluted with water (200 mL), adjusted to approximately pH 4 using 1 M hloric acid (HCl), and extracted with dichloromethane (3 x 100 mL). The combined organic layers were dried (MgSO4), gravity filtered, and concentrated by rotary evaporation to afford the title compound as a pale yellow semi-solid (6.0 g, 99%): 1H NMR (400 MHz, CDClg) 8 7.55 (dt, .1: 7.5, 1 Hz, 1H), 7.38 — 7.42 (m, 2H), 1.34 (s, 12H), 0.29 (d, J: 1 Hz, 9H).
The following compounds were made in accordance with the procedures disclosed in Example 23: -62— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 2-(4-(Difluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane B\ 9A§<CH3CH3 0 CH3 1H NMR (400 MHz, CDC13)8 7.89 (br d, .1: 8 Hz, 2H), 7.50 (br d, .1: 8 Hz, 2H), 6.65 (t, .1: 56 Hz, 1H), 1.35 (s, 12H). 2-(4-(Difluoromethyl)fluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane B\ ?)§<CH3CH3 0 CH3 F F 1H NMR (400 MHz, CDClg) 8 7.51 — 7.68 (rn, 3H), 6.90 (t, J: 55 Hz, 1H), 1.35 (s, 12H).
Example 24: Preparation of (2,3-difluoro(4,4,5,5-tetramethyl—1,3,2-dioxaborolan yl)phenyl)trimethylsilane 8‘0 IOAS<CH3CH3 Me3Si F A 2.5 M solution of n-BuLi (9.5 rnL, 24 rnrnol, 1.1 equiv) was added to a stirred solution of (2,3-difluorophenyl)trirnethylsilane (4.0 g, 21 rnrnol, 1.0 equiv) in tetrahydrofuran (86 mL) at -78 oC. The ing very pale yellow solution was stirred at -78 CC for l h. 2-Is0pr0p0xy-4,4,5,5-tetrarnethyl-l,3,2-di0xab0rolane (4.8 rnL, 24 rnrnol, 1.1 equiv) was added, and the pale yellow solution was allowed to slowly warm to 23 0C, by allowing the dry ice / acetone bath to melt, and stirred for 20 h. The reaction mixture was rith water (200 rnL), adjusted to approximately pH 4 using lM HCl, and extracted [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel with dichloromethane (3 x 100 mL). The ed organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation to afford the title compound as a white powder (6.4 g, 96%): 1H NMR (400 MHz, CDClg) 8 7.42 (ddd, J: 7.5, 4.5, 0.5 Hz, 1H), 7.09 (ddd, J: 7.5, 4, 1 Hz, 1H), 1.34 (s, 12H), 0.29 (d, J: 1 Hz, 9H).
Example 25: Preparation of (3-flu0r0(4,4,5,5-tetramethyl-1,3,2-di0xab0rolan yl)phenyl)trimethylsilane 11 W B\9A§<CH3 Me3Si F A 2.5 M on of n-BuLi (3.5 mL, 8.5 mmol, 1.1 equiv) was added to a stirred solution of 1,4-dibromofluorobenzene (2.0 g, 7.9 mmol, 1.0 equiv) in tetrahydrofuran (THF; 26 mL) at -78 oC. The resulting bright yellow solution was stirred at -78 0C for 15 min. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.8 mL, 8.7 mmol, 1.1 equiv) was added and the resulting pale yellow solution was stirred at -78 0C for 30 min. A 2.5 M solution of n-BuLi (3.5 mL, 8.5 mmol, 1.1 equiv) was added and the ing yellow/brown solution was stirred at -78 CC for 15 min. Chlorotrimethylsilane (2.2 mL, 17 mmol, 2.2 equiv) was added, and the resulting pale yellow solution was allowed to slowly warm to 23 CC, by allowing the dry ice / e bath to melt, and stirred for 18 h. The reaction mixture was diluted with water (150 mL) and extracted with dichloromethane (2 x 100 mL). The combined organic layers were dried ( MgSO4), y d, and concentrated by rotary evaporation to afford the title compound as a pale yellow powder (2.3 g, 99%): IR (thin 111m) 3058 (w), 2981 (s), 2932 (m), 1615 (m) cm'l; 1H NMR (400 MHz, CDClg) 5 7.72 (dd, J: 7.5, 6 Hz, 1H), 7.26 (m, 1H), 7.16 (d, J: 7.5 Hz, 1H), 1.34 (s, 12H), 0.23 (s, 9H).
Example 26: Preparation of 2,3,5-triflu0r0i0d0aniline [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel To a stirred solution of 2,3,5-trifiuoroaniline (2.0 g, 13.605 mmol, 1.0 equiv) in dry THF (40 mL) at -78 0C, was added sec-butyllithium (10.88 mL, 13.6 mmol, 1.0 equiv) over 30 min. Stirring was continued at -78 CC for 2 h. A solution of iodine (4.14 g, 16.32 mmol, 1.2 equiv) was added dropwise, and reaction mixture was slowly warmed to 20 0C over 1 h. The reaction was quenched with 10% aqueous (aq) sodium thiosulfate (NaZSZOg) solution and extracted with methyl tert—butyl ether (MTBE; 3 x 50 mL). The combined c extracts were washed with saturated brine solution, dried over anhydrous Na2S04, filtered and evaporated to dryness under reduced pressure. The crude product was column purified over silica using 0—10% ethyl acetate (EtOAc) with hexanes as eluent to afford trifiuoroiodoaniline (1.3 g, 35%) as pink solid: 1H NMR (400 MHZ, CDClg) 5 6.43 — 6.39 (m, 1H), 3.99 (br s, 2H); ESIMS m/Z 274 ([M+H]+).
Example 27 : Preparation of 4-br0m0(difluoromethoxy)—2-fluorobenzene F O
[00186] To a 100 mL flask charged with N,N—dimethylformamide (DMF; 23 mL) were added sodium 2-chloro-2,2-difiuoroacetate (4.79 g, 31.4 mmol), ium carbonate (2.60 g, 18.85 mmol), 4-bromofluorophenol (3 g, 15.71 mmol). Water (5.75 mL) was added and the reaction mixture was heated to 100 0C for 3 h. Upon cooling to room temperature, the on mixture was diluted with diethyl ether (EtzO; 100 mL) and a 2 normal (N) sodium ide (NaOH) solution (100 mL). The c layer was removed and dried over anhydrous Na2SO4. Upon filtration the organic solution was concentrated on a rotary ator with the water bath at 4 CC to yield the title nd as a clear oil (1 g, 13%): 1H NMR (400 MHz, CDC13)5 7.35 (dd, J: 9.7, 2.3 Hz, 1H), 7.27 (ddd, J: 8.7, 2.3, 1.5 Hz, 1H), 7.19 — 7.04 (m, 1H), 6.53 (t, J: 73.0 Hz, 1H); ESIMS m/z 242([M+H]+).
[00187] The following compounds were made in accordance with the procedures disclosed in Example 27. 1-Bromo(difluor0methoxy)flu0r0benzene F £1 D F F [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l ation] chanmel Unmarked set by chanmel ] 1H NMR (400 MHz, CDC13)8 7.53 (dd, .1: 8.8, 7.7 Hz, 1H), 6.95 (dd, .1: 9.1, 2.7 Hz, 1H), 6.90 — 6.79 (m, 1H), 6.50 (t, .1: 72.8 Hz, 1H); IR (thin film) , 811.23, 856.78, 945.20, 1043.80, 977.35, 1141.65, 1113.50, 1174.18, 1260.90, 1285.55, 1382.78, 1423.39, 1487.03, 1593.17, 2847.53, 2927.91, 2992.21, 3112.78 cm'l; ESIMS m/Z 242([M+H]+). 1-Bromo(difluoromethoxy)-2,3-difluorobenzene F o F 1H NMR (400 MHz, CDC13)8 7.31 (ddd, .1: 9.2, 6.9, 2.5 Hz, 1H), 7.02 — 6.93 (111, 1H), 6.56 (t, .1: 72.4 Hz, 1H); IR (thin film) 776.30, 811.66, 884.39, 986.70, 1100.95, 1144.65, 5, 1241.96, 1266.36, 1297.59, 1383.98, 1494.35, 1474.47, 1600.40, 1679.63, 3038.31, 3103.90 cm'l; ESIMS m/Z 260 ([M+H]+).
Example 28: Preparation of 2-(4-(difluoromethoxy)fluorophenyl)-4,4,5,5- tetramethyl-1,3,2-dioxaborolane 9&CH3CH3 F B\O CH3 ] To DMSO (10 mL) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bi(1,3,2- dioxaborolane) (1.264 g, 4.98 mmol), PdC12(dpp1) (0.304 g, 0.415 mmol), ium acetate (1.222 g, 12.45 mmol), and 0(difluoromethoxy)—2-fluorobenzene (1 g, 4.15 11111101). The reaction was heated to an external temperature of 80 °C for 18 h. Upon cooling, the reaction mixture was poured into ice water (50 mL). The ice water mixture was transferred to a separatory funnel and two extractions with EtOAc (50 mL) were completed.
The organic layers were ed, dried over Na2S04, and filtered. The solution was concentrated onto Celite® (5 g) using EtOAc as solvent. The impregnated Celite® was purified by silica gel chromatography using 0—30% EtOAc:hexanes to yield the title comifiid as a yellow oil (773 mg, 64%): 1H NMR (400 MHz, CDClg) 8 7.61 — 7.53 (111, [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l 2H), 7.25 — 7.16 (m, 1H), 6.58 (t, J: 73.5 Hz, 1H), 1.34 (s, 12H); ESIMS m/z 289 ([M+H]+).
The following compounds were made in accordance with the procedures disclosed in Example 28: 2-(4-(Diflu0r0meth0xy)—2-flu0r0phenyl)—4,4,5,5-tetramethyl—1,3,2-di0xab0rolane F a‘0 CH3 Fxo F 1H NMR (400 MHz, CDC13)8 7.74 (dd, .1: 8.3, 6.8 Hz, 1H), 6.89 (dd, .1: 8.3, 2.2 Hz, 1H), 6.81 (dd, .1: 9.9, 2.2 Hz, 1H), 6.54 (t, .1: 73.2 Hz, 1H), 1.26 (s, 12H); IR (thin film) 848.53, 961.04, 1066.43, 1125.19, 1172.02, 1238.3, 7, 1, 1281.58, 1357.05, 1372.85, 1380.73, 1425.32, 1469.05, 1579.31, 1621.00, 2933.42, 2982.31 cm'l; ESIMS m/Z 289 ([M+H]+). 2-(4-(Diflu0r0meth0xy)—2,3-difluorophenyl)—4,4,5,5-tetramethyl-1,3,2-di0xab0rolane 9&0'13CH3 F I3\O CH3 Fxo F F 1H NMR (400 MHz, CDC13)8 7.46 (ddd, .1: 8.3, 5.8, 2.3 Hz, 1H), 7.05 — 6.95 (m, 1H), 6.59 (t, .1: 72.8 Hz, 1H), 1.35 (s, 12H); IR (thin film) 673.35, 851.08, 916.78, 965.07, 1123.87, 8, 1210.42, 1331.14, 3, 1362.56, 1392.44, 1467.32, 1507.77, 1589.62, 1629.61, 2935.00, 2982.70 cm'l; ESIMS m/Z 307 ([M+H]+). e 29: Preparation of 1,4-difluoro-Z-iodo-S-(triflu0r0methyl)benzene F | [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l N—(2,5-Difluoro(trifluoromethyl)phenyl)acetamide (950 mg, 4.0 mmol; Prepared according to Y. Tanabe et al, J. Org. Chem. 1988, 53, 4585-4587) was stirred in methanol (25 mL), treated with acetyl chloride (3 mL) and heated at reflux for 2 h. The volatiles were removed by evaporation, and the solid residue was dissolved in 6 N HCl (50 mL), cooled to 5 CC and treated in portions with a solution of sodium nitrite (410 mg, 6.0 mmol) in water (5 mL). After 30 min, this mixture was poured into a solution of sodium iodide (2.4 g, 16 mmol) in water (50 mL) and rapidly stirred with dichloromethane (50 mL).
After 30 min, solid sodium bisulfite was added to destroy the iodine color, and the separated organic phase was washed with saturated NaCl, dried (Na2SO4), and ated. The material was purified by flash chromatography (8102; eluting with hexanes) to provide the title compound as a volatile clear liquid (250 mg, 20%): 1H NMR (400 MHZ, CDClg) 5 7.64 (ddd, J: 8.8, 4.8, 0.4 Hz, 1H), 7.28 (dd, .1: 11.1, 4.7 Hz, 1H); ”P NMR (376 MHz, CDC13) -61.92, -97.64, -97.68, -118.59, -118.63, -118.64, -118.67; EIMS m/z 308.
Example 30: Preparation of 2-(2,5-diflu0r0(triflu0r0methyl)phenyl)—4,4,5,5- tetramethyl-1,3,2-di0xab0rolane 9&4.CH3 F B\o CH3 1,4-Difluoroiodo(trifluoromethyl)benzene (500 mg, 1.6 mmol) was ved in dry THF (7 mL), cooled to 0 OC and d in portions with isopropyl magnesium chloride-lithium chloride complex (1.3 M; 1.4 mL, 1.8 mmol) and stirred for 40 min at 5 OC. 2-Isopropoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (360 11L, 330 mg, 1.8 mmol) was added and stirring was continued for 1 h. After treating with saturated ammonium chloride ), the mixture was shaken with ethyl acetate. The c phase was washed with saturated NaCl, dried (Na2S04), and evaporated to give the title compound as a light brown oil (500 mg, 100%). The material was used without fiarther purification: 1H NMR (400 MHz, 5 7.54 (dd, J: 9.9, 4.3 Hz, 1H), 7.27 (dd, J: 8.0, 5.2 Hz, 2H), 1.37 (s, 12H); 19F NMR (376 MHz,CDC13)8 -62.10, -62.13, -106.85, 0, -121.81, - , -121.90.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 31: Preparation of 4-bromo-2,5-difluorobenzaldehyde ] To a on of 2,5-dibromo-1,4-difluorobenzene (10.0 g, 36.77 mmol) in diethyl ether (150 mL) at -78 CC was added n-butyl lithium (2.5 M in Hexanes, 14.86 mL, 37.15 mmol) dropwise under nitrogen. The reaction e was stirred at -78 0C for 30 min. Dry DMF (3.13 mL, 40.46 mmol) in diethyl ether (10 mL) was added dropwise and reaction was slowly warmed to room temperature over 2 h. The reaction was quenched with aqueous saturated NH4Cl solution (25 mL) and extracted with l ether. The organic phase was washed with saturated brine solution, dried (Na2S04), filtered, and concentrated under reduced pressure (Note: Product is highly volatile). The crude product was purified by flash chromatography (SiOz, eluting with 2-20% ethyl e in hexanes) to provide the title compound as a pale yellow solid (7.0 g, 86%): 1H NMR (400 MHz, CDClg) 8 7.50 (dd, J: 5.08, 8.92 Hz, 1H), 7.62 (dd, J: 5.80, 7.68 Hz, 1H), 10.30 (d, J: 2.76 Hz, 1H).
Example 32: Preparation of (E)bromo-2,S-difluorobenzaldehyde oxime HO’ N\ A solution of 4-bromo-2,5-difiuorobenzaldehyde (7.0 g, 31.67 mmol), hydroxyl amine hydrochloride (2.42 g, 34.84 mmol) in pyridine (35 mL) and l (35 mL) was stirred at room temperature for 30 min. The reaction mixture was diluted with saturated NH4Cl solution and extracted with ethyl acetate. The organic phase was washed with saturated brine solution, dried (Na2SO4), filtered, and concentrated under d re.
The crude product was purified by flash chromatography (SiOz; eluting with 5—100% ethyl acetate in hexanes) to provide the title compound as a yellow solid (4.0 g, 53%): ESIMS m/z 238 ([M+2H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 33: Preparation of 4-br0m0-2,5-diflu0robenzonitrile A solution of cyanuric de (3.12 g, 16.94 mmol) and dry DMF (8.5 mL) was stirred for 30 min or until the formation of white solid. earance of cyanuric chloride was confirmed by thin layer tography (TLC). Bromo-2,5- difluorobenzaldehyde oxime (4.0 g, 16.94 mmol) in DMF (26 mL) was added dropwise to the suspension and stirred for 1 h. The reaction mixture was diluted with water and extracted with hexanes. The organic extract was washed with water, washed with saturated brine solution, dried (Na2SO4), d, and evaporated to dryness under reduced pressure.
The crude product was purified by flash chromatography (SiOz; g with 2—20% ethyl acetate in hexanes) to provide the title compound as a white solid (2.5 g, 68%): 1H NMR (400 MHz, CDClg) 5 7.40 (dd, .1: 5.36, 7.10 Hz, 1H), 7.52 (dd, .1: 5.40, 7.66 Hz, 1H); EIMS m/z 218.
Example 34: Preparation of 1-br0m0(diflu0r0methyl)-2,5-diflu0robenzene F F To a on of 4-bromo-2,5-difluorobenzaldehyde (11.0 g, 49.77 mmol) in romethane (55 mL) was added (diethylamino)sulfur trifiuoride (DAST; 24.06 g, 0.15 mol) in dropwise manner at 0 CC. After the addition was complete, the cooling bath was removed and stirring was continued for 2 h at room temperature (rt). The reaction mixture was diluted with dichloromethane, washed with water, washed with saturated brine solution, dried (Na2S04), and evaporated under reduced pressure. The crude product was purified by flash chromatography (SiOz; g with 0—10% ethyl acetate in hexanes) to provide the title compound as a pale brown liquid (8.39 g, 69%): 1H NMR(400 MHz, CDC13 ) 8 6.58 (t, J: 72.32 Hz, 1H), 7.12 (t, J: 7.92 Hz, 1H), 7.44 (dd, J: 6.32, 9.18 Hz, 1H); EIMS m/z 244.
[Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 35: ation of 1-br0m0(diflu0r0meth0xy)—2,5-diflu0robenzene F F In a sealed tube, a solution of 4-bromo-2,5-difiuorophenol (5.0 g, 23.9 mmol) and ium hydroxide (26.8 g, 479 mmol) in a 1:1 mixture of acetonitrile and water (110 mL) at -78 °C was treated with bromo-difluoromethyl diethylphosphonate (12.8 g, 47.9 mmol) in one portion. The sealed tube was stirred at room temperature ght. The reaction mixture was diluted with diethyl ether and the organic phase was separated. The aqueous phase was extracted with diethyl ether twice. The combined organic extracts were washed with a saturated brine solution, dried (Na2SO4), filtered, and evaporated to dryness under reduced re. The crude product was purified by flash chromatography (SiOz; eluting with 0—10% ethyl acetate in s) to provide the title compound as a clear liquid (4.2 g, 67.8%): 1H NMR(300 MHz, CDC13)5 6.56 (t, .1: 72.36 Hz, 1H), 7.11 (t, .1: 7.32 Hz, 1H), 7.40 — 7.45 (m, 1H); EIMS m/z 259.
Example 36: General procedure for synthesis of boronic acids F oH R;\ \OH Argon was bubbled through a solution of the bromophenyl substrate (1.0 equiv), ium e (3.0 equiv), and bis-(pinacolato)diboron (1.1 equiv) in DMSO (enough volume to provide 0.1—0.2 M in substrate) for 15 min in a sealed tube. Pd(dppf)C12 (0.1 equiv) was added and the sealed tube was recapped. The reaction mixture was heated at 80 °C for 18 h. The cooled reaction mixture was diluted with water and extracted with methyl t—butyl ether. The organic extract was washed with water, washed with saturated brine solution, dried (Na2S04), filtered, and evaporated to dryness under reduced pressure. The crude boronate (1.0 equiv) was dissolved in diethyl ether (10 vol) and diethanolamine (1.1 equiv) was added. The reaction mixture was d at room ature for 30—45 min. A white solid precipitated out after 45 min. Stirring was stopped and the solvent was decanted.
Fresner was added to the solids followed by an excess of 1.5 N HCl . The resulting [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ic solution was stirred for 30 min. The organic phase was washed with saturated brine solution, dried (NaZSO4), filtered, and evaporated to dryness under d pressure. The boronic acids thus obtained were used in the next step without purification.
The following compounds were made in accordance with the procedures disclosed in Example 36: (4-(Difluoromethoxy)—2,5-difluorophenyl)b0r0nic acid F OH F OH F O 1H NMR(300 MHz, CDC13)8 6.59 (t, 8 Hz, 1H), 6.97 (dd, .1: 2.70, 9.14 Hz, 1H), 7.52 (dd, .1: 5.19, 10.29 Hz, 1H). (4-(Difluoromethyl)-2,5-difluorophenyl)b0r0nic acid F OH F F 1H NMR(400 MHz, CDClg) 8 6.87 (dt, .1: 8.48, 54.64 Hz, 1H), 7.25 — 7.32 (m, 1H), 7.49 (dd, .1: 4.08, 9.48 Hz, 1H), 7.59 — 7.60 (m, 1H). e 37: General procedure for synthesis of boronic acids (Method A) F (IDH R;\ OH To a solution of the appropriate henyl substrate (1.0 equiv) in dry THF (10 vol) at -78 0C, was added n-BuLi (2.5 M in hexanes; 1.2 equiv) dropwise. After on was complete, stirring was continued for 30 min. Trimethyl borate (l .5 equiv) was added in one portion and stirring was continued for l h at -78 CC. The reaction mixture was slowly warrgto room temperature, ed with 1.5 N HCl, and extracted with ethyl acetate.eTh nic extract was washed with water, washed with saturated brine solution, dried [Annotation] chanmel None set by chanmel ation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel (NaZSO4), filtered, and evaporated to dryness under d pressure. The boronic acids thus obtained were used in the next step without purification.
The following compound was made in accordance with the procedures disclosed in Example 37: iflu0r0methylphenyl)b0r0nic acid F (IJH B\OH ] 1H NMR(300 MHz, CDC13)5 2.30 (s, 3H), 5.03 (br s, 2H), 6.89 (dd, .1: 5.67, .25 Hz, 1H), 7.42 (dd, .1: 5.40, 9.19 Hz, 1H).
Example 38: General procedure for synthesis of c acids (Method B) F oH \ B‘OH To a on of the appropriate bromophenyl substrate (1.0 equiv) in dry THF (10 vol) at -40 0C was added isopropyl magnesium chloride lithium chloride complex solution (1.3 M solution in THF; 1.05 equiv) dropwise. After addition was complete, the reaction mixture was stirred at -40 CC for 45 min then slowly warmed to 0 °C.
Isopropoxyboronic acid pinacol ester (1.07 equiv) was added dropwise and stirring was continued at 0 0C for 2 h. The reaction e was warmed to room temperature, ed with aqueous saturated NH4Cl solution, and extracted with ethyl acetate. The organic extract was washed with saturated brine solution, dried (NaZSO4), filtered, and evaporated under reduced pressure. The boronic acids thus obtained were used in the next step without purification.
The following compound was made in accordance with the procedures disclosed in Example 38: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel (4-Cyano-2,5-difluorophenyl)boronic acid FCIJH 1H NMR(300 MHz, CDC13)8 5.15 (br s, 2H), 7.29 — 7.36 (m, 1H), 7.69 (dd, .1: 4.80, 8.28 Hz, 1H).
Example 39: Preparation of methyl 4-aminochloro(3-fluoro (trimethylsilyl)phenyl)picolinate H3C’Sl'i CH3 F To a 20-mL microwave vessel, equipped with a stir bar, Head A (500 mg, 2.262 mmol), (2-fluor0(4,4,5 ,5 -tetramethyl-l ,3 ,2-di0xaborolanyl)phenyl)trimethylsilane (997 mg, 3.39 mmol), bis(triphenylphosphine)palladium(ll) dichloride (203 mg, 3.39 mmol), and cesium fluoride (741 mg, 4.88 mmol) were charged. The vessel was placed under en (N2) atmosphere and acetonitrile (4.0 mL) and H20 (1 .0 mL) were added. The vessel was placed on a Biotage InitiatorTM microwave reactor for 30 min at 120 0C, with external lR-sensor temperature monitoring from the side of the vessel. The reaction was poured into brine solution and extracted with ethyl acetate (3 x 75 mL). The combined organic layers were dried over anhydrous MgSO4, d and concentrated. The resulting e was d via flash chromatography (Silica gel; 0—30% EtOAc in hexanes) to afford the title compound as a yellow solid (0.328 g, 41%): 1H NMR (400 MHZ, DMSO-d6) 5 7.68 (dd, J: 7.5, 1.4 Hz, 1H), 7.61 — 7.47 (m, 2H), 7.30 (s, 1H), 6.78 (s, 2H), 3.88 (s, 3H), 0.30 (d, .1: 0.8 Hz, 9H); 19F NMR (376 MHz, DMSO-d6) 5 -101.12;ESIMS m/Z 353 ([M+H1+).
The following compounds were prepared in ance with the procedures disclosed in Example 39: D ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by l ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-amin0-3,5-dichlor0(3-flu0r0(trimethylsilyl)phenyl)picolinate H3C I CH3 F The title compound was prepared as described in Example 39 with Head H (500 mg, 1.96 mmol) and isolated as a white solid (0.381 g, 50%): 1H NMR (400 MHZ, DMSO- d6) 5 7.52 (dd, J= 7.6, 5.9 Hz, 1H), 7.41 (dd, J= 7.5, 1.3 Hz, 1H), 7.30 (dd, J= 9.6, 1.4 Hz, 1H), 7.11 (s, 2H), 3.87 (s, 3H), 0.33 (d, J: 0.9 Hz, 9H); ”P NMR (376 MHz, DMSO-d6) 5 — 101.38; ESIMS m/Z 387 ([M+H]+).
Methyl 6-amin0(3-flu0r0(trimethylsilyl)phenyl)meth0xypyrimidine—4- carboxylate NH2 C|3H3 H3C\ _ 0\ ,SI CH3 H30 I CH3 F The title compound was prepared as described in Example 39 with Head C (0.510 g, 2.34 mmol) and isolated as a yellow solid (0.307 g, 38%): 1H NMR (400 MHz, DMSO-d6) 5 8.08 — 7.99 (m, 1H), 7.82 (dd, J: 10.3, 1.4 Hz, 1H), 7.60 — 7.27 (m, 3H), 3.91 (s, 3H), 3.74 (s, 3H), 0.32 (d, J: 0.9 Hz, 9H); ”P NMR (376 MHz, DMSO-d6) 5 401.73, ESIMS m/Z 350 ([M+H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Methyl 4-acetamid0chlor0(3-flu0r0(trimethylsilyl)phenyl)picolinate H3C I CH3 F ] The title nd was prepared as described in Example 39 with Head L (0.500 g, 1.90 mmol) in dioxane (7.0 mL) and H20 (2.0 mL) and isolated as a yellow solid (0.433 g, 58%): 1H NMR (400 MHz, DMSO-d6) 5 9.99 (s, 1H), 8.71 (s, 1H), 7.75 (dd, J: 7.6, 1.5 Hz, 1H), 7.63 (dd, J: 10.1, 1.5 Hz, 1H), 7.56 (dd, J: 7.7, 5.9 Hz, 1H), 3.94 (s, 3H), 2.24 (s, 3H), 0.30 (d, .1: 0.8 Hz, 9H); 19F NMR (376 MHz, DMSO-d6) 5 -100.78; ESIMS m/Z 396 ([M+H]+).
Methyl 4-amin0chloro(4-cyanofluorophenyl)flu0r0picolinate (Compound The title compound was prepared as described in Example 39 with Head B (400 mg, 1.673 mmol) and (4-cyanofluoropheny1)boronic acid (400 mg, 2.425 mmol) in dioxane (4.5 mL) and H20 (1.2 mL) and isolated as an off-white solid (0.451 g, 83%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Methyl o(3-fluoro(trifluoromethyl)phenyl)Vinylpyrimidine carboxylate (Compound 137) N \ \CHZ N CH3 F O F F The title compound was prepared as described in Example 39 with Head P (350 mg, 1.64 mmol) and (3-fluoro(trifluoromethyl)phenyl)b0ronic acid (445 mg, 2.14 mmol) in dioxane (5.0 mL) and H20 (1.0 mL) and isolated as a light tan solid (0.291 g, 52%).
Methyl 6-amino(4-cyanofluorophenyl)Vinylpyrimidinecarboxylate (Compound 98) NI \ \CHZ / O\ N CH3 / F N / The title compound was prepared as described in e 39 with Head P (350 mg, 1.638 mmol) and n0flu0r0phenyl)b0r0nic acid (375 mg, 2.27 mmol) in dioxane (4.5 mL) and H20 (1.2 mL) and isolated as a yellow solid (0.291 g, 60%).
Methyl 6-amino(4-aminophenyl)Vinylpyrimidinecarboxylate NI \ \CHZ / O\ N CH3 The title compound was prepared as described in Example 39 with Head P (0.800 g, 3.74 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-di0xaborolanyl)aniline (0.985 g, 4.49 mmol) in dioxane (15.6 mL) and H20 (3.12 mL) and isolated as a yellow solid (0.400 g, 40%3H),d (s, 2H), 5.49 — 5.30 (m, 2H), 3.81‘ NMR (400 MHz, DMSO-d6) 5 8.08 — 7.86 (m, 2H), 6.99 (s, 2H), 6.76 — 6.51 (m, (s, 3H); ESIMS m/z 271 ([M+H]+).
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l Methyl 6-amino(2,3,4-trifluorophenyl)vinylpyrimidinecarboxylate (Compound 197) NI \ \CH2 / O\ N CH3 The title compound was prepared as described in Example 39 with Head P (0.350 g, 1.64 mmol) and (2,3,4-trifluorophenyl)boronic acid (0.346 g, 1.97 mmol) in dioxane (5.0 mL) and H20 (1.0 mL) and isolated as a yellow solid (0.414 g, 82%).
Example 40. Preparation of methyl ochloro(3-fluoro (trifluoromethyl)phenyl)picolinate (Compound 29) / O\ N CH3 F O F F ] Methyl 4-amin0-3,6-dichlor0picolinate (630 mg, 2.85 mmol), 2-(3-flu0r0 (trifluoromethyl)phenyl)—4,4,5,5-tetramethyl-1,3,2-di0xab0rolane (1.06 g, 3.65 mmol, 1.3 equiv), bis(triphenylph0sphine)palladium(ll) chloride (209 mg, 0.30 mmol, 0.1 equiv), and potassium fluoride (510 mg, 8.8 mmol, 3 equiv) in acetonitrile/water (8 mL, 3:1) was capped in a 25-mL vial on a Biotage InitiatorTM microwave reactor for 20 min at 115 CC, with al lR-sensor temperature monitoring from the side of the vessel. The reaction mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were dried over anhydrous Na2S04, filtered, and concentrated. The crude compound was loaded onto a ® cartridge and dried in a vacuum oven. Purification by reverse-phase flash chromatography (0—60, 60, 60—100% acetonitrile/water) afforded the title compound as a white solid (0.57 g, 57%).
] The following compounds were prepared in accordance to the procedures sed in Example 40: [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel ation] chanmel Unmarked set by chanmel Methyl 4-aminochloro(4-cyanophenyl)methylpicolinate (Compound 83) The title compound was prepared as in Example 40 with Head D and isolated as an orange solid (180 mg, 55%).
Methyl 4-aminochloro(4-(difluoromethoxy)phenyl)methylpicolinate (Compound 1 1 1) The title compound was prepared as in Example 40 and isolated as a waxy yellow solid (120 mg, 32%).
Methyl ochloromethyl(4-(trimethylsilyl)phenyl)picolinate (H3C)3Si The title compound was prepared as in Example 40 with Head D and isolated as a yellow solid (1.11 g, 45%): mp 160—163 0C; 1H NMR (400 MHz,CDC13)5 7.57 (d, J: 8.2 Hz, 2H), 7.42 (d, .1: 8.2 Hz, 2H), 4.80 (s, 2H), 3.94 (s, 3H), 2.18 (s, 3H), 0.28 (s, 9H); 13C NMR (101 MHz, CDClg) 8 167.01, 157.65, 150.16, 146.19, 141.69, 141.24, 134.39, 129.61, 117.96, 114.49, 53.95, 15.86, 1.16; ESIMS m/Z 348 ([M]').
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Methyl 4-amin0chlor0(3-flu0r0(trimethylsilyl)phenyl)methylpicolinate ch I CH3 F The title nd was prepared as in Example 40 with Head D and ed as a yellow solid (346 mg, 27%): mp 167 oC (dec); 1H NMR (400 MHz, CDC13) 8 7.43 (dd, J = 7.4, 5.8 Hz, 1H), 7.20 (dd, J: 7.4, 0.9 Hz, 1H), 7.10 (dd, J: 9.2, 1.3 Hz, 1H), 4.83 (s, 2H), 3.95 (s, 3H), 2.18 (s, 3H), 0.33 (d, J: 0.8 Hz, 9H); ”P NMR (376 MHz, CDC13)8 —100.73; ESIMS m/Z 367 ([M+H]+).
Methyl 4-amin0chlor0(4-cyan0fluorophenyl)methylpicolinate (Compound 155) The title compound was prepared as in Example 40 with Head D and isolated as a white flaky solid (200 mg, 49%).
Methyl 4-amin0chlor0(3-flu0r0f0rmylphenyl)methylpicolinate The title compound was prepared as in Example 40 with Head D and isolated as an orange solid (747 mg, 65%): mp 114—120 c’C; 1H NMR (400 MHZ, CDC13) 5 10.40 (s, [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 1H), 7.92 (t, .1: 7.5 Hz, 1H), 7.38 — 7.29 (m, 2H), 4.97 (s, 2H), 3.97 (s, 3H), 2.18 (s, 3H); ”P NMR (376 MHz, CDC13) 5 421.53; ESIMS m/Z 323 ([M+H]+).
Methyl 4-aminochlorofluoro(2,4,5-trifluorophenyl)picolinate (Compound 200) The title compound was prepared as in Example 40 with Head B and isolated as a white powder (370 mg, 73%).
Example 41: ation of methyl 4-aminochlorofluoro(4- nitrophenyl)picolinate (Compound 95) To a suspension of Head B (250 mg, 1.05 mmol), (4-nitrophenyl)boronic acid (192 mg, 1.15 mmol), cesium fluoride (CsF; 315 mg, 2.09 mmol) and tris(3- sulfonatophenyl)ph0sphine e sodium salt (TPPTS, 60 mg, 0.11 mmol) in a water/acetonitrile mixture (2.8/0.7 mL) was added palladium acetate (12 mg, 0.05 mmol).
In a BiotageTM bench top microwave the mixture was heated at 150 CC for 5 min. The reaction e was then d through Celite®, diluted with EtOAc, washed with water and brine. The organics were then dried (NaZSO4), filtered, concentrated in vacuo, and then purified by silica gel chromatography eluting with 0—100% EtOAc in hexanes to afford a yellow solid (150 mg, 44%).
] The following compound was made in accordance with the procedures disclosed in Example 41: D [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Methyl 4-acetamidochloro(2,3-difluoro(trifluoromethyl)phenyl)picolinate 1H NMR (400 MHz, DMSO-d6) 8 10.03 (s, 1H), 8.79 (d, .1: 1.0 Hz, 1H), 7.93 — 7.84 (m, 1H), 7.75 (dd, .1: 8.3, 6.3 Hz, 1H), 3.96 (s, 3H), 2.26 (s, 3H); ESIMS m/Z 409 ([M+H]+).
Example 42: Preparation of methyl 4-aminochloro(4-cyanofluorophenyl)—5- fluoropicolinate (Compound 135) ] Head B (0.300 g, 1.255 mmol), 4-cyanofluorophenylboronic acid (0.248 g, 1.506 mmol), bis(tripheny1ph0sphine)palladium(ll) chloride (0.088 g, 0.126 mmol), and cesium fluoride (0.381 g, 2.51 mmol) were combined in 1,2-dimethoxyethane (2 mL) and water (2 mL) and heated in a microwave reactor at 110 CC for 20 min. The cooled reaction e was partitioned between ethyl acetate and water. The organic phase was dried and concentrated. The product was purified by flash chromatography (SiOz; eluting with 5—60% ethyl acetate in hexanes) to provide the title compound as a white solid (0.189 g, 46.5%). ation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 43: Preparation of methyl 4-aminochlorofluoro(4- (methoxycarbonyl)phenyl)picolinate (Compound 190) Head B (0.4 g, 1.673 mmol), 4-(methoxycarbony1)pheny1boronic acid (0.392 g, 2.175 mmol), potassium fluoride (0.253 g, 4.35 mmol), and bis(tripheny1phosphine)pa11adium(ll) chloride (0.059 g, 0.084 mmol) were ed in acetonitrile (3 mL) and water (1 mL). The reaction mixture was then irradiated in a microwave at 110 CC in a sealed vial for 20 min. The cooled reaction mixture was partitioned n ethyl acetate and water. The organic phase was dried and concentrated onto silica gel. This mixture was applied to the top of a silica gel column and the t was eluted with a 5—60% ethyl acetate in hexanes gradient solvent system. This process yielded the title compound as a white solid (0.230 g, 40.6%).
Example 44: Preparation of methyl 4-amino(4-bromo-2,3-difluorophenyl)—3- chloropicolinate (Compound 114) Step 1: Head N (0.600 g, 1.692 mmol), 4-bromo-2,3-difluoropheny1boronic acid (0.481 g, 2.031 mmol), cesium fluoride (0.617 g, 4.06 mmol), and bis(tripheny1phosphine)palladium(ll) de (0.119 g, 0.169 mmol) were combined in 1,2- dimethoxyethane (4 mL) and water (4 mL) and heated in a microwave reactor for 20 min at 110 CC. The cooled reaction mixture was partitioned between ethyl acetate and water. The organic phase was separated and concentrated onto silica gel. The product was eluted with an ethyl acetate/hexanes gradient to provide methyl 4-acetamido(4-bromo-2,3- difluunhenyl)chloropicolinate (0.515 g, 72.5%) as a white solid.
[Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ] Step 2: Methyl 4-acetamido(4-bromo-2,3-difluorophenyl)chloropicolinate (0.515 g, 1.227 mmol) was suspended in methanol (20 mL) and acetyl chloride (1.559 mL, 21.93 mmol) was added se. The reaction mixture was stirred overnight at room temperature and concentrated under vacuum. The residue was partitioned between ethyl acetate and 5% aqueous sodium bicarbonate solution. The organic phase was concentrated onto silica gel and purified by flash chromatography (8102; eluting with 5—60% ethyl acetate in hexanes) to provide the title compound as a white solid (0.231 g, 55.8%).
Example 45: Preparation of methyl 4-amin0chlor0(2,3-diflu0r0 (trimethylsilyl)phenyl)—5-flu0ropicolinate Head B (2.0 g, 8.37 mmol), (2,3-difluoro(4,4,5,5-tetramethyl-1,3,2- oro1any1)phenyl)trimethylsilane (3.40 g, 10.88 mmol), sodium carbonate (0.887 g, 8.37 mmol) and bis(triphenylphosphine)palladium(II) chloride (0.587 g, 0.837 mmol) were combined in acetonitrile (25 mL) and water (8 mL). The reaction mixture was then heated at reflux for 4 h. The cooled reaction mixture was partitioned between ethyl acetate and water.
The organic phase was washed twice more with water then concentrated onto silica gel.
This e was purified by silica gel tography and the product was eluted with a 7— 60% ethyl acetate in hexanes solvent system. This s yielded the title compound as a white solid (2.7 g, 83%): mp 160—162 0C; 1H NMR (300 MHz, CDC13) 8 7.37 — 7.28 (m, 1H), 7.21 (ddd, J: 7.7, 4.4, 1.3 Hz, 1H), 4.96 (br s, 2H), 3.97 (s, 3H), 0.35 (s, 9H).
[Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Example 46: Preparation of methyl 6-amino(3-fluoro(trifluoromethyl)phenyl) methoxypyrimidinecarboxylate (Compound 26) OCH3 / OCH3 To a microwave via1 were added Head C (184 mg, 0.846 mmol), uoro (trifluoromethy1)pheny1)-4,4,5,5-tetramethy1—1,3,2-dioxab0r01ane (270 mg, 0.930 mmol), potassium fluoride (128 mg, 2.198 mmol), and bis(triphenylphosphine)pa11adium(ll) chloride (59.3 mg, 0.085 mmol). Subsequently, acetonitrile (2.789 mL) and water (2.79 mL) were added. The reaction via1 was then capped and placed in a eTM Initiator ave reactor for 20 min at 115 CC, with external lR-sensor temperature monitoring from the side of the vessel. The reaction mixture was cooled to room temperature, diluted with EtOAc, and washed with H20. The organics were dried over , filtered, and concentrated in vacuo. The crude product was purified via flash chromatography (silica; Hexanes/EtOAc). This yielded the title compound (172 mg, 58.9%) as a white solid.
Example 47: Preparation of methyl 4-aminochlorofluoro(4- (trimethylsilyl)phenyl)picolinate Me3Si Head B (600 mg, 2.5 mmol, 1.0 equiv) and (4-(trimethy1si1y1)pheny1)b0r0nic acid (540 mg, 2.8 mmol, 1.1 equiv) were combined in a 20 mL via1 followed by cesium fluoride (420 mg, 2.8 mmol, 1.1 equiv), palladium acetate (28 mg, 0.13 mmol, 0.05 equiv), and sodium "-phosphinetriyltribenzenesulfonate (140 mg, 0.25 mmol, 0.10 equiv). A 3:1 mixture of water:acet0nitri1e (7.2 mL) was added and the resulting brown mixture was capped and placed in a Biotage InitiatorTM ave reactor for 5 min at 150 0C, with external IR-sensor temperature monitoring from the side of the vessel. The cooled reaction mixtDwas diluted with water (150 mL) and extracted with dichloromethane (5 x 60 mL).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel The combined organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (33% ethyl e in hexanes) to afford the title compound as a pale yellow powder (700 mg, 79%): mp 148—150 C’C; 1H NMR (300 MHz, CDC13)5 7.86 (m, 2H), 7.62 (m, 2H), 4.88 (br s, 2H), 3.98 (s, 3H), 0.29 (s, 9H); ESIMS m/Z 353 ([M+H]+).
The ing compounds were made in accordance with the ures disclosed in Example 47: Methyl 0chlor0flu0r0(2-flu0r0f0rmylphenyl)picolinate mp 151—154 0C; 1H NMR (400 MHz, CDC13)8 10.06 (d, .1: 2 Hz, 1H), 7.79 — 7.84 (m, 2H), 7.67 (dd, .1: 10, 1 Hz, 1H), 5.00 (br s, 2H), 3.99 (s, 3H); ESIMS m/Z 327 ([M+H]+).
Methyl 6-amin0(2-flu0r0f0rmylphenyl)methoxypyrimidine—4-carb0xylate \ OMe H O mp 176—178 0c; 1H NMR (400 MHz, CDC13)8 10.03 (d, .1: 2 Hz, 1H), 8.10 (t, .1 = 8 Hz, 1H), 7.73 (dd, .1: 8, 1.5 Hz, 1H), 7.65 (dd, .1: 8, 1.5 Hz, 1H), 5.45 (br s, 2H), 4.00 (s, 3H), 3.96 (s, 3H); ESIMS m/Z 306 ([M+H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-aminochlor0(2,3-diflu0r0f0rmylphenyl)flu0r0picolinate 1H NMR (400 MHz, CDC13) 8 10.40 (d, J: 1 Hz, 1H), 7.74 (m, 1H), 7.52 (m, 1H), 5.01 (br s, 2H), 3.97 (s, 3H).
Methyl 6-amin0(2,3-diflu0r0formylphenyl)meth0xypyrimidinecarb0xylate \ OMe H O O F mp 184—186 0c; 1H NMR (400 MHz, CDC13) 8 10.38 (d, .1: 0.5 Hz, 1H), 7.84 (m, 1H), 7.67 (ddd, .1: 8, 6, 2 Hz, 1H), 5.47 (br s, 2H), 4.01 (s, 3H), 3.96 (s, 3H); ESIMS m/z 324 ([M+H]+).
Methyl 6-amin0(4-formylphenyl)meth0xypyrimidine—4-carboxylate NH2 (EH3 mp 6 0C; 1H NMR (400 MHz, CDC13) 8 10.1 (s, 1H), 8.54 (d, 2H), 7.99 (d, 2H), 5.56 (s, 2H), 4.08(s, 3H), 3.99(s, 3H); ESIMS m/Z 288 ([M+H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-amino-3,5-dichloro(4-formylphenyl)picolinate mp 3 0c; 1H NMR (400 MHz, CDC13) 8 10.08 (s, 1H), 7.96 (d, 2H), 7.83 (d, 2H), 5.36 (s, 2H), 3.98 (s, 3H); ESIMS m/Z 325 ([M+H]+).
Example 48: Preparation of methyl 4-aminochlorofluoro(3-fluoro (trimethylsilyl)phenyl)picolinate M9381 ] Dichloro[bis(tripheny1phosphin0)]-pa11adium(ll) (150 mg, 0.21 mmol, 0.10 equiv) and sodium carbonate (270 mg, 2.5 mmol, 1.2 equiv) were sequentially added to a stirred mixture of crude (2-flu0r0(4,4,5,5-tetramethy1—1,3,2-dioxab0r01an y1)pheny1)trimethy1si1ane (990 mg, 2.5 mmol, 1.2 equiv) and Head B (500 mg, 2.1 mmol, 1.0 equiv) in a 1:1 mixture of water:acet0nitri1e (7.0 mL) at 23 CC. The resulting dark orange mixture was heated to 85 CC and stirred for 4 h. The cooled reaction mixture was diluted with water (150 mL) and extracted with dichloromethane (3 x 80 mL). The combined organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was d by silica gel column chromatography (25% ethyl acetate in hexanes) to afford the title compound as a pale yellow powder (500 mg, 65%): mp 125—127 0c; IR (thin film) 3481 (m), 3350 (s), 2952 (w), 1728 (m), 1610 (m) crn'lg 1H NMR (400 MHz, CDC13) 8 7.71 (dt, J: 6.5, 1 Hz, 1H), 7.59 (dt, J: 10, 1 Hz, 1H), 7.50 (dd, J: 8, 6.5 Hz, 1H), 4.91 (br s, 2H), 3.99 (s, 3H), 0.33 (d, 9H); ESIMS m/z 371 ([M+H]+).
The ing compounds were made in accordance with the procedures disclosed in Example 48: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-aminochloro(2,3-diflu0r0(trimethylsilyl)phenyl)flu0r0picolinate 1H NMR (400 MHz, CDC13)8 7.33 (ddd, .1: 8, 4.5, 1 Hz, 1H), 7.21 (ddd, .1: 8, , 1.5 Hz, 1H), 4.94 (br s, 2H), 3.96 (s, 3H), 0.33 (d, .1: 1 Hz, 9H); ESIMS m/Z 389 ([M+H]+).
Methyl 4-amin0chlor0flu0r0(2-flu0r0(trimethylsilyl)phenyl)picolinate Megsi mp 175—177 0C; 1H NMR (400 MHz, CDC13)8 7.58 (t, .1: 8 Hz, 1H), 7.39 (dd, .1 = 8, 1 Hz, 1H), 7.27 (m, 1H), 4.91 (br s, 2H), 3.96 (s, 3H), 0.26 (s, 9H); ESIMS m/Z 371 ([M+H]+).
Methyl 6-amino(2-flu0r0(trimethylsilyl)phenyl)meth0xypyrimidine—4- carboxylate \ OMe Megsi mp 140—142 0c; 1H NMR (400 MHz, 8 7.85 (t, .1: 8 Hz, 1H), 7.32 (dd, .1 = 8, 1 Hz, 1H), 7.26 (m, 1H), 5.38 (br s, 2H), 3.99 (s, 3H), 3.94 (s, 3H), 0.26 (s, 9H); ESIMS m/Z 348 ([M-H]').
D [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Methyl 4-acetamid0chlor0(2,3-diflu0r0(trimethylsilyl)phenyl)picolinate Me3Si 1H NMR (400 MHz, CDC13) 5 9.04 (d, .1: 1 Hz, 1H), 7.99 (br s, 1H), 7.65 (m, 1H), 7.18 (m, 1H), 4.00 (s, 3H), 2.31 (s, 3H), 0.33 (d, .1: 1 Hz, 9H); ESIMS m/Z 413 ([M- H]').
Methyl 6-aminometh0xy(4-(trimethylsilyl)phenyl)pyrimidinecarb0xylate NH2 (EH3 \N OMe Megsi 1H NMR (400 MHz, CDClg) 5 8.25 (m, 2H), 7.58 m, 2H), 5.35 (br s, 2H), 4.01 (s, 3H), 3.91 (s, 3H). 0.30 (s, 9H); ESIMS m/Z 330 ([M-H]').
Methyl 4-acetamid0chlor0(4-(trimethylsilyl)phenyl)picolinate \N OMe M93Si 1H NMR (400 MHz, CDClg) 5 9.00 (s, 1H), 7.98 (m, 2H), 7.61 (m, 2H), 7.25 (s, 1H), 4.01 (s, 3H), 2.32 (s, 3H), 0.29 (s, 9H); ESIMS m/Z 375 ([M-H]').
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 49: Preparation of methyl 4-acetamido(4-amin0-2,3,6-trifluorophenyl)—3- chloropicolinate A suspension of methyl 4-acetamidochloro(trimethylstannyl)picolinate (Head K; 0.502 g, 1.409 mmol, 1.0 equiv), 2,3,5-trifluoroiodoaniline (0.5 g, 1.831 mmol, 1.3 equiv), bis(triphenylphosphine)palladium(H) chloride (0.098 g, 0.1401 mmol, 0.1 equiv) and Cul (26 mg, 0.1401 mmol, 0.1 equiv) in dry DMF (3 mL) was irradiated with microwave at 120 CC for 1 h. The reaction e was cooled to 20 CC and stirred with aqueous potassium fluoride (KF) solution (20 mL) for 15 min and then extracted with ethyl acetate (3x100 mL). The combined organic layers were dried over anhydrous Na2S04, filtered and ated to dryness under reduced re. The crude product was purified on silica gel (60-120 mesh) using a gradient from 0—30% EtOAc in s yielded the title compound as a brown solid (280 mg, 44.8%): 1H NMR (400 MHz, DMSO-d6) 8 9.96 (s, 1H), 8.32 (s, 1H), 6.51 — 6.46 (m, 1H), 6.22 (br s, 2H), 3.92 (s, 3H), 2.23 (s, 3H); ESIMS m/Z 376 ]+).
Example 50: Preparation of methyl 4-amin0chloro(2,5-diflu0r0 (trimethylsilyl)phenyl)flu0ropicolinate ,Si F H3C | ] In a microwave vessel, a suspension of (2,5-difluoro(4,4,5,5-tetramethyl- 1,3,2-dioxaborolanyl)phenyl)trimethylsilane (see, e.g., WO 2013003740 A1; 0.6 g, 1.922 mmol methyl 4-amino-3,6-dichlorofluoropicolinate (Head B; 0.383 g, 1.601 mmol), bis(t nyl phosphine)palladium(ll) chloride (0.112 g, 0.160 mmol) and sodium carbonate [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] l Unmarked set by chanmel (0.204 g, 1.922 mmol) in a 3:1 mixture of acetonitrile (4.00 mL) and water (1.334 mL) was stirred under ave ation (120 CC, 20 min). The on mixture was poured into a half saturated brine solution and was extracted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title nd as a white solid (0.271 g, 43.5%): 1H NMR (400 MHz, CDClg) 8 7.23 (dd, J: 7.8, 5.1 Hz, 1H), 7.13 (dd, J: 9.3, 4.0 Hz, 1H), 4.95 (s, 2H), 3.98 (s, 3H), 0.33 (d, J: 0.8 Hz, 9H); ”P NMR (376 C13)8 -106.81, -106.87, -121.20, -121.25, -121.29, 5, -137.32, -137.41; ESIMS m/Z 389 ([M+H]+).
Example 51: Preparation of methyl 4-amin0chlor0(2,5-diflu0r0 (trimethylsilyl)phenyl)picolinate HSC,Sli F In a microwave vessel, a suspension of (2,5-difiuoro(4,4,5,5-tetramethyl- 1,3,2-dioxaborolanyl)phenyl)trimethylsilane (see, e.g., WO 2013003740 A1) (0.6 g, 1.922 mmol), methyl 4-amino-3,6-dichloropicolinate (Head A) (0.354 g, 1.601 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.112 g, 0.160 mmol) and sodium carbonate (0.204 g, 1.922 mmol) in a 3:1 mixture of acetonitrile (4.00 mL) and water (1.334 mL) was stirred under microwave irradiation (120 CC, 20 min). The reaction mixture was poured into a half saturated brine solution and was extracted with EtOAc (3x). The combined c layers were dried over Na2S04, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.234 g, 0.631 mmol, 39.4%): 1H NMR (400 MHz, CDClg) 8 7.66 (dd, J: 8.7, .8 Hz, 1H), 7.25 (d, J: 1.2 Hz, 1H), 7.09 (dd, J: 10.8, 4.1 Hz, 1H), 4.84 (s, 2H), 4.00 (s, 3H), 0.32 (d, .1: 0.7 Hz, 9H); 19F NMR (376 MHz, CDC13)8 6, -106.61, —124.00, -124.06; ESIMS m/Z 371 ([M+H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel e 52: Preparation of methyl 4-acetamidochloro(2,5-difluoro (trimethylsilyl)phenyl)picolinate /Si F H3C I In a microwave vessel, a suspension of (2,5-difluoro(4,4,5,5-tetramethyl- 1,3,2-di0xaborolanyl)phenyl)trimethylsilane (see, e.g., WO 2013003740 A1; 1 g, 2.56 mmol), methyl 4-acetamid0-3,6-dichloropicolinate (Head L; 0.562 g, 2.135 mmol), bis(triphenyl phosphine)palladium(ll) chloride (0.150 g, 0.214 mmol) and sodium carbonate (0.272 g, 2.56 mmol) in a 3:1 mixture of itrile (5.34 mL) and water (1.779 mL) was stirred under microwave irradiation (120 CC, 20 min). The reaction e was poured into a half saturated brine solution and was extracted with EtOAc (3x). The ed organic layers were dried over Na2S04, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.481 g, 54.6%): mp 135—137 c’C; 1H NMR (400 MHz, CDClg) 8 9.07 (d, J: 0.8 Hz, 1H), 7.96 (s, 1H), 7.62 (dd, J: 8.5, 5.7 Hz, 1H), 7.13 (dd, J: 10.5, 4.1 Hz, 1H), 4.02 (s, 3H), 2.33 (s, 3H), 0.33 (d, J: 0.8 Hz, 9H); ”P NMR (376 MHz, CDC13)8 -106.66, — 106.72, -l23.42, -l23.48; ESIMS m/z 411 ([M-H]'). e 53: Preparation of methyl 6-amino(2,5-difluoro(trimethylsilyl)phenyl)- -methoxypyrimidinecarboxylate N \ CH3 F / O\ N CH3 H3C\ 0 ,SI_ F H3C | CH3 In a microwave vessel, a suspension of ifluoro(4,4,5,5-tetramethyl- 1,3,2- ' xaborolanyl)phenyl)trimethylsilane (e.g., WO 2013003740 A1; 1.925 g, 5.05 , ethyl 6-aminochlor0meth0xypyrimidinecarboxylate (Head C; 1 g, 4.60 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel mmol), bis(triphenyl phosphine)palladium(II) chloride (0.323 g, 0.460 mmol) and sodium ate (0.584 g, 5.51 mmol) in a 3:1 mixture of acetonitrile (8.62 mL) and water (2.87 mL) was stirred under ave irradiation (120 CC, 20 min). The reaction mixture was poured into a half saturated brine solution and was ted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered and trated. The residue was d by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a white solid (0.994 g, 58.9%): mp 130—131 0C; 1H NMR (400 MHz, CDC13)5 7.53 (dd, J: 8.4, 5.6 Hz, 1H), 7.10 (dd, J: 10.2, 4.1 Hz, 1H), 5.44 (s, 2H), 4.00 (s, 3H), 3.94 (s, 3H), 0.32 (d, J: 0.9 Hz, 9H); ”P NMR (376 MHz, CDClg) 5 407.45, - 107.51, -122.32, -122.37; ESIMS m/Z 367 ([M]+).
Example 54: Preparation of methyl 4-amin0(2,3-diflu0r0 (trifluoromethyl)phenyl)fluorovinylpicolinate (Compound 53) F F ] In a microwave vessel, a suspension of 2-(2,3-difiuoro (trifiuoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (commercially available; 0.641 g, 2.081 mmol), methyl 4-aminochlorofiuorovinylpicolinate (Head G; 0.4 g, 1.734 mmol), bis(triphenyl phosphine)palladium(II) chloride (0.122 g, 0.173 mmol) and sodium ate (0.368 g, 3.47 mmol) in a 3:1 mixture of acetonitrile (3.25 mL) and water (1.084 mL) was stirred under microwave irradiation (120 CC, 20 min). The reaction mixture was poured into a half ted brine solution and was extracted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered and concentrated. The residue was purified by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a brown solid (0.163 g, 24.98%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Example 55: Preparation of methyl 4-amino(4-aminophenyl)fluoro vinylpicolinate In a microwave vessel, a suspension of 4-(4,4,5,5-tetramethyl-1 ,3,2- dioxaborolanyl)aniline (commercially ble; 0.617 g, 2.82 mmol), methyl o chlorofluorovinylpicolinate (Head G; 0.5 g, 2.168 mmol), bis(triphenyl phosphine)palladium(ll) chloride (0.152 g, 0.217 mmol) and potassium fluoride (0.327 g, .64 mmol) in a 1:1 mixture of acetonitrile (3.61 mL) and water (3.61 mL) was stirred under microwave irradiation (120 CC, 20 min). The reaction mixture was poured into a half saturated brine on and was extracted with EtOAc (3x). The combined organic layers were dried over , filtered and concentrated. The residue was purified by flash column chromatography (8102, 24 g; hexanes/EtOAc gradient) to afford the title compound as a yellow solid (0.552 g, 89%): 1H NMR (400 MHz, 6) 8 7.60 — 7.58 (m, 2H), 6.72 (dd, J: 17.7, 11.5 Hz, 1H), 6.65 — 6.58 (m, 2H), 6.24 (s, 2H), 5.47 (s, 2H), 5.45 (dd, J = 11.5, 1.2 Hz, 1H), 5.38 (dd, J: 17.7, 1.2 Hz, 1H), 3.77 (s, 3H); ”P NMR (376 MHz, DMSO-d6) 5 -146.62; ESIMS m/z 286 ([M-H]').
Example 56: Preparation of methyl 6-amino(4-(difluoromethoxy)phenyl) methoxypyrimidinecarboxylate (Compound 106) O—CH3 /©)\\N I F O‘CH3 F*0 To a 5-mL microwave safe vial were added potassium fluoride (0.151 g, 2.59 mmol), palladium (ll) acetate (0.012 g, 0.052 mmol), 2-(4-(diflu0r0methoxy)phenyl)- 4,4,5,5-tetramethyl-1,3,2-di0xab0rolane (0.28 g, 1.037 mmol), methyl 6-amin0chlor0 methoxypyrimidinecarb0xylate (0.226 g, 1.037 mmol), and "— phoSofietriyltribenzenesulfonate (0.052 g, 0.104 mmol). A mixture of water (1 mL) t ile (2 mL) was added, and the reaction was capped and placed in a Biotage [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l ation] chanmel Unmarked set by chanmel InitiatorTM microwave reactor for 6 min at 160 0C, with external IR-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with EtOAc (50 mL) and water (50 mL). An additional extraction using CHzClz (50 mL) was combined with the EtOAc and dried over ofNaZSO4 (50 g) after the CHzClz layer was filtered through a cotton plug. The combined organics were concentrated on a rotary evaporator and the e was purified using a ne ISCO purification system with a gradient eluent system of CHzClz and EtOAc to yield the title compound as a white solid (134.4 mg, 39.8%).
Example 57: ation of methyl 4-amin0(4-cyanophenyl)—5—flu0r0 vinylpicolinate (Compound 107) To a 5-mL microwave safe vial were added potassium fluoride (0.227 g, 3.90 mmol), methyl 4-aminochlorofluorovinylpicolinate (0.3 g, 1.301 mmol), bis- (triphenylphosphine)palladium (II) chloride (0.091 g, 0.130 mmol) and ,5,5- tetramethyl-1,3,2-dioxaborolanyl)benzonitrile (0.313 g, 1.366 mmol. A mixture of water (1 mL) and acetonitrile (2 mL) was added, and the reaction was capped and placed in a Biotage InitiatorTM microwave reactor for 20 min at 115 0C, with external IR-sensor temperature monitoring from the side of the vessel. Upon cooling to room temperature, the reaction mixture was diluted with CHzClz (25 mL) and water (25 mL), and the organic layer was filtered through a cotton plug. An additional extraction using EtOAc (25 mL) was combined with the CHzClz and dried over NaZSO4 (50 g). Following filtration of the ed organics through a cotton plug and concentration on a rotary evaporator, the e was purified using a Teledyne ISCO purification system with a gradient eluent system of CHzClz and EtOAc to yield the title compound as a tan solid (297 mg, 76%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by l Example 58: Preparation of methyl 4-aminofluoro(4-formylphenyl) vinylpicolinate To a 5-mL microwave safe vial were added potassium fluoride (0.378 g, 6.50 mmol), methyl 4-amin0chlor0fluorovinylpicolinate (0.5 g, 2.168 mmol), bis(triphenylph0sphine)palladium(ll) chloride (0.152 g, 0.217 mmol) and 4-(4,4,5,5- tetramethyl-l,3,2-dioxaborolanyl)benzaldehyde (0.528 g, 2.276 mmol). A e of water (1 mL) and itrile (2 mL) was added, and the reaction was capped and placed in a Biotage InitiatorTM microwave reactor for 20 min at 115 0C, with external lR-sensor temperature monitoring from the side of the vessel. Upon cooling to room ature, the reaction mixture was diluted with CHzClz (25 mL) and water (25 mL) and the organic layer was filtered through a cotton plug. An additional extraction using EtOAc (25 mL) was combined with the CHzClz and dried over Na2S04 (50 g). Following filtration of the combined organics through a cotton plug and concentration on a rotary evaporator, the residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CHzClz and EtOAc to yield the title compound as a white solid (635 mg, 98%): 1H NMR (400 MHz, CDC13)5 10.08 (s, 1H), 8.13 (dd, J: 8.3, 1.6 Hz, 2H), 8.03 — 7.93 (m, 2H), 6.91 (ddd, J: 18.1, 11.6, 0.5 Hz, 1H), 5.73 (dd, J: 11.5, 1.4 Hz, 1H), 5.60 (dd, J: 18.1, 1.4 Hz, 1H), 4.77 (s, 2H), 3.94 (s, 3H); ”P NMR (376 MHz, CDC13) 5 9;ESIMS m/Z 301 ([M+H]+).
Example 59: Preparation of methyl ochloro(2,5-difluoro (trifluoromethyl)phenyl)picolinate (Compound 70) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel 1,4-Difluoroiodo(trifluoromethyl)benzene (250 mg, 0.81 mmol), Head K (318 mg, 0.81 mmol), copper(I)iodide (0.08 mmol) and bis(triphenylphosphine)palladium(II) chloride (57 mg, 0.08 mmol) were combined in dry DMF (5 mL), deaerated with a stream of nitrogen for 10 min and heated to 75 CC. After 2 h, the mixture was cooled and partitioned between ethyl acetate and water. The organic phase was washed with ted NaCl, dried (Na2S04), and evaporated. The crude product was purified by flash chromatography (SiOz; eluting with 0—30% ethyl e in hexanes) to provide 100 mg of the acetamide intermediate. This material was taken up in methanol (20 mL), treated with acetyl chloride (3 mL) and stirred for 3 days at 20 CC. After removal of volatiles under vacuum, the e was stirred with saturated NaHC03 and ethyl acetate.
The organic phase was washed with ted NaCl, dried (Na2S04), and evaporated to provide the title compound as a white solid (77 mg, 24%).
Example 60: Preparation of methyl 6-amin0(2,5-diflu0r0 (trifluoromethyl)phenyl)methoxypyrimidinecarb0xylate (Compound 148) NH2 (IZH3 F N/ \ O F O H3C/ F F 2-(2,5 -Difluoro(trifluoromethyl)phenyl)-4,4,5 ,5 -tetramethyl- 1 ,3 ,2- dioxaborolane (400 mg, 1.2 mmol), Head C (250 mg 1.2 mmol), cesium fluoride (360 mg, 2.3 mmol) and bis(triphenylphosphine)palladium(II) chloride (82 mg, 0.12 mmol) were ed in 1:1 volume per volume (v/v) acetonitrile-water (4 mL) and heated at 115 0C for min in a microwave reactor. The mixture was partitioned between water and ethyl acetate. The organic phase was washed with saturated NaCl, dried (Na2S04), and evaporated. The al was purified by flash tography (SiOz; eluting with 0—30% ethyl acetate in hexanes) to provide a brown oil which was triturated with hexanes- dichloromethane to provide the title compound as a white solid (40 mg, 8.8%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Example 61: Preparation of methyl 6-amino(2,3-difluoro(trimethylsilyl)phenyl)- -methoxypyrimidinecarboxylate N \ CH3 / o \ ,0 H3C-Sli F H3C CH3 F (2,3-Diflu0r0(4,4,5,5-tetramethy1—1,3,2-di0xabor01an y1)pheny1)trimethy1si1ane(1.3 g, 4.2 mmol) (e.g., WO 2013003740 A1), Head C (750 mg, 3.5 mmol) and bis(tripheny1ph0sphine)pa11adium(ll) de (240 mg, 0.34 mmol) were combined in 1:1 v/v acetonitrile-water (10 mL) and heated to 115 CC for 30 min via microwave. The cooled mixture was partitioned n saturated NaCl and ethyl acetate.
The c phase was washed with saturated NaCl, dried (NaZSO4), and evaporated. The material was purified by flash chromatography (S102; e1uting with 0—20% ethyl acetate in hexanes) to provide the title compound as a white solid (330 mg, 26%): mp 157—1590 C; 1H NMR (400 MHz, CDC13) 5 7.60 (ddd, J: 7.5, 6.0, 1.2 Hz, 1H), 7.14 (ddd, J: 7.7, 4.5, 1.5 Hz, 1H), 5.48 (s, 2H), 4.00 (s, 3H), 3.95 (s, 3H), 0.34 (d, J: 0.7 Hz, 9H); ”P NMR (376 MHz, CDC13) 5 0 to -127.25 (m), -142.40 (dd, J: 22.6, 3.6 Hz); ESIMS m/z 368 ([M+H]+).
The following compound was made in accordance with the procedures disclosed in Example 61 from commercially available (4,4,5,5-tetramethy1—1,3,2-dioxab0r01an y1)pheny1)trimethy1si1ane: Methyl 4-amino-3,5-dichloro(4-(trimethylsilyl)phenyl)picolinate (prepared utilizing Head H) H30 I mp 171—174 0C; 1H NMR (400 MHz, CDClg) 5 6.36(rn, 4H), 533(2, 2H), 3.99(s, 3H),DH (s, 9H); ESIMS m/Z 369 ([M+H]+).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel The following nds were made in accordance with the procedures disclosed in e 61 from commercially available 2-fluoro(4,4,5,5-tetramethyl-l,3,2- dioxaborolanyl)phenyl)trimethylsilane (prepared according to WO 2013003740 Al): Methyl 4-amin0chlor0(2-flu0r0(trimethylsilyl)phenyl)picolinate (prepared utilizing Head A) ,Si F H30/ H30 1 mp 154—1560 C; 1H NMR (400 MHz, CDC13)8 7.97 (m, 1H), 7.30 (m, 3H), 4.84 (s, 2H), 4.01 (s, 3H), 0.293 (s, 9H); ESIMS m/Z 353 ([M+H]+).
Methyl 4-amin0-3,5-dichlor0(2-flu0r0(trimethylsilyl)phenyl)picolinate (prepared ing Head H) /Si F H30’ H30 1 mp 184—1850 C; 1H NMR (400 MHz, CDClg) 5 7.35 (m, 3H), 5.33 (s, 2H), 3.96 (s, 3H), 0.290 (s, 9H); ESIMS m/Z 387 )+).
Example 62: l procedure for Suzuki Coupling (Method A) Argon was bubbled through a solution of Head A, Head B, or Head C (1.0 equiv), a boronic acid (1.0 equiv), N32C03 (2.0 equiv) and Pd(PPh3)4 (0.1 equiv) in 1:1 toluene: ethanol (20 vol) for 15 min in a sealed tube. The reaction mixture was then heated in the sealed tube at 110°C for 18 h. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. (Note: The aqueous layer contained ylic acid products that were isolated as described below). The organic extracts was washed with water, washed with rated brine on, dried (NaZSO4), filtered, and evaporated to dryness under [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel reduced pressure. The crude product was purified by preparative TLC to get the pure esters.
The aqueous layer was acidified to pH 2 using 1.5 N HCl and extracted with ethyl acetate.
The organic extract was washed with saturated brine on, dried 4), filtered, and evaporated to dryness under reduced pressure. The crude product was purified by preparative TLC to get the pure carboxylic acid derivatives.
Example 63: General ure for Suzuki Coupling (Method B) Argon was bubbled through a solution of Head A, Head B or Head C (0.8 equiv), a boronic acid (1.0 equiv), NaHC03 (2 M solution, 1.0 equiv) and Pd(PPh3)4 (0.1 equiv) in dry dioxane (20 vol) for 15 min in a sealed tube. The sealed tube was heated at 80 0C for 18 h. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The organic extract was washed with water, washed with saturated brine solution, dried (Na2S04), filtered, and evaporated to dryness under reduced pressure. The crude t was purified by flash chromatography (8102; eluting with 5—40% ethyl acetate in hexanes) to provide the pure compound.
Example 64: Preparation of methyl 0chlor0(3-flu0r0 iodophenyl)picolinate (Compound 66) ] To a 250-mL round bottom flask, equipped with a stir bar, were added methyl 4- aminochloro(3-fiuoro(trimethylsilyl)phenyl)picolinate (0.328 g, 0.930 mmol), and dichloromethane (5.0 mL). To this solution iodine monochloride (0.141 mL, 2.79 mmol) was added. The reaction mixture was allowed to stir at room temperature for 18 h. Another portion of iodine monochloride (0.141 mL, 2.79 mmol) was added, and the reaction was allowed to stir at room ature for an additional 4.5 h. The reaction mixture was poured into 1 M Na2S03, and the layers were partitioned. The aqueous phase was extracted with onal ethyl acetate (2x 100 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and trated to afford the title compound as a brown solid (0.37:; 99%): [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel The following nds were made in accordance with the procedures disclosed in Example 64: Methyl 4-amino-3,5-dichloro(3-fluoroiodophenyl)picolinate (Compound 13) The title compound was prepared as described in Example 64 with methyl 4- amino-3,5-dichloro(3-fluoro(trimethylsilyl)phenyl)picolinate (0.381 g, 0.984 mmol) and isolated as a yellow solid (0.360 g, 83%).
Methyl 6-amin0(3-flu0r0i0dophenyl)meth0xypyrimidinecarb0xylate (Compound 27) N \ \CH3 / o The title compound was prepared as described in Example 64 with methyl 6- amino(3-fluoro(trimethylsilyl)phenyl)methoxypyrimidinecarboxylate (0.307 g, 0.879 mmol) and isolated as a yellow solid (0.368 g).
Example 65: Preparation of methyl ochloro(4—i0d0phenyl) methylpicolinate (Compound 136) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel ionNone set by l [Annotation] l Unmarked set by chanmel To methyl 4-aminochloromethyl(4-(trimethylsilyl)phenyl)picolinate (0.95 g, 2.72 mmol) in dichloromethane (9 mL) was added iodine monochloride (920 mg, .67 mmol) in dichloromethane (4.5 mL) dropwise. The reaction was stirred at room temperature for 4 h, then quenched with saturated aqueous sodium thiosulfate, diluted with water, and extracted with dichloromethane (3x). The organic layers were dried over anhydrous Na2S04, d and concentrated. Purification by flash chromatography (0—30% ethyl e/hexanes) afforded the title compound as a red-orange solid (618 mg, 56%).
The following compound was made in accordance with the procedures sed in Example 65: Methyl 4-amin0chloro(3-fluoroiodophenyl)methylpicolinate (Compound 79) The title compound was prepared as in Example 65 and isolated as an off-white solid (54 mg, 59%).
Example 66: Preparation of methyl 0(4-i0d0phenyl)—3-chlor0 fluoropicolinate (Compound 118) Iodine monochloride (280 mg, 1.7 mmol, 2.0 equiv) was added to a stirred solution of methyl 4-aminochlorofluoro(4-(trimethylsilyl)phenyl)picolinate (300 mg, 0.85 mmol, 1.0 equiv) in 1,2-dichloroethane (5.7 mL) at 23 0C. The resulting brown solution was stirred at 23 CC for 17 h. The reaction mixture was d with a saturated solution of sodium thiosulfate (100 mL) and extracted with dichloromethane (4 x 40 mL).
The combined organic layers were dried ( MgSO4), graVity filtered, and concentrated by rotarDaporation. The residue was purified by silica gel column chromatography (33% [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel ethyl acetate in hexanes) to afford the title compound as a pale purple powder (250 mg, 7 l %).
The ing compounds were made in accordance with the procedures disclosed in Example 66: Methyl amid0chlor0(2,3-diflu0r0i0dophenyl)picolinate MeJLNH 1H NMR (400 MHz, CDC13)8 9.06 (d, .1: 1.5 Hz, 1H), 7.98 (br s, 1H), 7.60 (ddd, .1: 9, 5, 2 Hz, 1H), 7.53 (ddd, .1: 9, 7, 2 Hz, 1H), 4.03 (s, 3H), 2.34 (s, 3H); ESIMS m/Z 467 ([M+H]+).
Methyl 4-acetamid0chlor0(4-i0d0phenyl)picolinate MeiNH \ OMe 1H NMR (400 MHz, CDClg) 5 9.00 (s, 1H), 7.77 (m, 4H), 7.25 (s, 1H), 4.03 (s, 3H), 2.33 (s, 3H); ESIMS m/Z 431 ([M+H]+). —104— [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel e 67: Preparation of methyl 4-aminochloro(2,5-difluoroiodophenyl)—5- fluoropicolinate (Compound 55) ] To a solution of methyl 4-amin0ch10ro(2,5-diflu0r0 (trimethylsilyl)phenyl)fluoropic01inate (0.280 g, 0.720 mmol) in CHZCIZ (2.88 mL) at 20 0C was added iodine monochloride (0.144 mL, 2.880 mmol). The reaction mixture was stirred at 20 OC overnight. The mixture was then poured into a 10% aqueous solution of N32803, extracted with EtOAc (3x), dried over Na2S04, filtered and concentrated. The residue was purified by flash column chromatography (SiOz; hexanes/EtOAc gradient) to afford the title compound as a white solid (0.237 g, 74.4%).
The following compound was made in accordance with the procedures disclosed in Example 67: Methyl 4-acetamidochloro(2,5-difluoroiodophenyl)picolinate ] 1H NMR (400 MHz, CDClg) 5 9.10 (d, .1: 0.7 Hz, 1H), 7.96 (s, 1H), 7.76 (dd, .1 = 8.4, 6.4 Hz, 1H), 7.57 (dd, J: 9.8, 5.0 Hz, 1H), 4.03 (s, 3H), 2.33 (s, 3H); ”P NMR (376 MHz, CDC13) 5 —99.95, 0, —119.90, —119.95; ESIMS m/z 465 ([M-H]'). ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel ation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 68: Preparation of methyl 6-amino(2,3-difluoroiodophenyl) ypyrimidinecarboxylate und 24) N \ CH3 F H3C Methyl 6-amin0(2,3-difiu0r0(trimethylsilyl)phenyl)-5 -meth0xypyrimidine- 0xylate (330 mg, 0.90 mmol) was stirred in 1,2-dichlor0ethane (5 mL), d with iodine monochloride (1.0 g, 6.9 mmol), and heated to 700 C for 21 h. After cooling, the mixture was diluted with ethyl acetate, washed with 15% sodium bisulfite, washed with saturated NaCl, dried (NaZSO4), and evaporated. The material was purified by RP-HPLC using 70% acetonitrile to provide the title compound as a white solid (250 mg, 66%).
Example 69: Preparation of methyl 4-acetamido(4-bromofluorophenyl) chloropicolinate To a 100-mL round bottom flask, equipped with a stir bar, were added methyl 4- acetamid0chlor0(3-fluor0(trimethylsilyl)phenyl)pic0linate (433 mg, 1.11 mmol), dichloromethane (10 mL) and bromine (0.225 mL, 4.39 mmol). The reaction mixture was allowed to stir at room temperature for 18 h. The reaction mixture was then poured into 1 N Na2803 and extracted with ethyl acetate (3 x 50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated. The resulting residue was purified by flash chromatography (0—50% EtOAc in Hexanes) to afford the title compound as a light tan solid (0.440 g, 100%): 1H NMR (400 MHz, DMSO-d6) 5 10.02 (s, 1H), 8.71 (s, 1H), 7.98 — 7.81 (m, 2H), 7.74 (dd, J: 8.4, 2.1 Hz, 1H), 3.94 (s, 3H), 2.23 (s, 3H); ”P NMR (376 MHzDVISO-d6) 5 407.44; ESIMS m/Z 402 ([M+H])+).
[Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel The following compounds were made in accordance with the procedures disclosed in Example 69: Methyl 4-amino(4-bromofluorophenyl)—3,5-dichlor0picolinate (Compound 73) CI CI / O\ N CH3 F The title compound was prepared as described in Example 69 with methyl 4- amino-3,5-dichloro(3-fluoro(trimethylsilyl)phenyl)picolinate (0.290 g, 0.749 mmol) and isolated as a white solid (0.250 g, 85%).
Methyl 6-amin0(4-br0m0flu0rophenyl)methoxypyrimidinecarb0xylate (Compound 171) N \ CH3 Br CH3 The title compound was prepared as bed in Example 69 with methyl 6- 2-(3-fluoro(trimethylsilyl)phenyl)methoxypyrimidinecarboxylate (0.250 g, 0.715 mmol) and isolated as a white solid (0.200 g, 78%).
Example 70: ation of methyl 4-amin0(4-br0mophenyl)chlor0 methylpicolinate (Compound 81) -lO7- [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel To methyl 4-aminochloromethyl(4-(trimethylsilyl)phenyl)picolinate (150 mg, 0.43 mmol) and potassium carbonate (215 mg, 1.56 mmol) in 1,2-dichloroethane (DCE, 2.9 mL) was added bromine (0.03 mL, 0.58 mmol) and stirred at room temperature for 18 h. The DCE was concentrated off under vacuum and the crude material was partitioned between ethyl acetate and aqueous potassium carbonate. The aqueous layer was extracted with ethyl e (3x), washed with water, dried over anhydrous MgSO4, filtered, and adsorbed onto silica gel. Purification by flash chromatography (0—40% ethyl acetate/hexanes) afforded the title compound as a pale orange powder (68 mg, 45%).
The following compound was made in accordance with the procedures disclosed in Example 70: Methyl 4-amino(4-brom0fluorophenyl)chloro-S-methylpicolinate (Compound 112)
[00296] The title compound was ed as in Example 70 and isolated as an off-white solid (96 mg, 52%).
Example 71: Preparation of methyl 4-amin0(4-br0m0-2,3-diflu0r0phenyl)—3-chlor0- -flu0r0picolinate (Compound 109) Methyl 4-aminochloro(2,3-difluoro(trimethylsilyl)phenyl) fluoropicolinate (2.5 g, 6.43 mmol) was dissolved in acetonitrile (32 mL) and bromine (3.31 mL, 64.3 mmol) was added. The reaction mixture was stirred at room temperature for 4 h at whicD'ne liquid tography-mass spectrometry (LC-MS) ted the reaction was [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel mostly complete. The on mixture was partitioned between dichloromethane and water and sodium lfate (10.17 g, 64.3 mmol) was added. The aqueous phase was extracted with dichloromethane and the organic ts were combined and concentrated under vacuum. The product was purified by flash chromatography (SiOz; eluting with 5—40% ethyl acetate in hexanes) to provide the title compound as a light yellow solid (1.62 g, 63.7%).
Example 72: Preparation of methyl 4-amin0(4-br0mophenyl)—3-chlor0 icolinate (Compound 138) Br Bromine (47 uL, 0.92 mmol, 1.2 equiv) was added to a stirred solution of methyl 4-aminochlorofiuoro(4-(trimethylsilyl)phenyl)picolinate (270 mg, 0.77 mmol, 1.0 equiv) in 1,2-dichloroethane (5.1 mL) at 23 0C. The resulting dark orange solution was stirred at 23 CC for 24 h. The reaction mixture was quenched with a saturated solution of sodium thiosulfate (5 mL) and then adjusted to pH 10 using 2 M sodium hydroxide. The reaction mixture was diluted with water (50 mL) and extracted with dichloromethane (3 x 30 mL). The combined organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary ation. The residue was purified by reverse phase column chromatography (5% acetonitrile to 100% acetonitrile gradient) to afford the title compound as a tan powder (160 mg, 57%).
The following nd was made in accordance with the procedures disclosed in Example 72.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-acetamido(4-bromophenyl)chloropicolinate MeJL NH \ OMe 1H NMR (400 MHz, CDClg) 5 9.01(s, 1H), 7.90 (m, 2H), 7.49 (m, 2H), 7.25 (s, 1H), 4.03 (s, 3H), 2.34 (s, 3H); ESIMS m/Z 385 ([M+H]+).
Example 73: Preparation of methyl 4-amino(4-bromo-2,5-difluorophenyl)chloro- -fluoropicolinate (Compound 51) To a solution of methyl ochloro(2,5-difluoro (trimethylsilyl)phenyl)flu0ropicolinate (0.240 g, 0.617 mmol) in CHzClz (2.469 mL) at 20 0C was added bromine (0.127 mL, 2.469 mmol). After 24 h, the on mixture was poured into a saturated aqueous solution ofNa28203 and was extracted with EtOAc (3x).
The combined organic layers were dried over NaZSO4, filtered and concentrated. The residue was purified by flash column chromatography (SiOz; hexanes/EtOAc nt) to afford the title compound as a white solid (0.187 g, 77%).
] The ing compound was made in accordance with the procedures disclosed in Example 73: -llO- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Methyl 4-acetamido(4-bromo-2,5-difluorophenyl)chloropicolinate HgCJLNH F / O\ N CH3 Br F mp 177—179 0C; 1H NMR (400 MHz, CDC13)8 9.10 (d, .1: 0.7 Hz, 1H), 7.97 (s, 1H), 7.85 (dd, .1: 9.1, 6.6 Hz, 1H), 7.40 (dd, .1: 9.9, 5.5 Hz, 1H), 4.03 (s, 3H), 2.33 (s, 3H); ”P NMR (376 MHz, CDC13) 5 6, -112.80, , -119.26; ESIMS m/Z 418 ([M-H]' Example 74: Preparation of methyl 6-amino(4-bromo-2,3-difluorophenyl) methoxypyrimidinecarboxylate und 122) N \ CH3 Br F H30 F Methyl 6-amino(2,3-diflu0r0(trimethy1silyl)pheny1)-5 -meth0xypyrimidine- 4-carb0xy1ate (350 mg, 0.95 mmol) was stirred in 1,2-dich10r0ethane (4 mL), d with bromine (1.0 g, 6.3 mmol) and heated to 60 0C for 6 h. After cooling, the mixture was d with 15% sodium bisulfite solution until negative to starch-iodine paper. The mixture was diluted with ethyl acetate, washed with saturated NaCl, dried (NaZSO4), and evaporated.
Purification by flash chromatography (8102; eluting with 0—30% ethyl acetate in hexanes) provided the title compound as white solid (75 mg, 23%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Example 75: Preparation of methyl 4-amino(4-bromofluorophenyl) chloropicolinate (Compound 115) / O\ N CH3 To a 100-mL round bottom flask, equipped with a stir bar, were added methyl 4- acetamido(4-bromofluorophenyl)chloropicolinate (0.411 g, 1.023 mmol), methanol (5.12 mL) and acetyl de (1.45 mL, 20.5 mmol). The reaction mixture was allowed to stir at room temperature for 18 h. The solvent was removed with a rotary evaporator. The resulting solid was dissolved in 1 N NaHC03 and extracted with ethyl e (3 x 75 mL).
The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated to afford the title compound as a white solid (0.324 g, 88%).
Example 76: Preparation of methyl 4-aminochloro(2,3-difluoro iodophenyl)picolinate (Compound 129)
[00305] Acetyl chloride (1.3 mL, 18 mmol, 10 equiv) was slowly added to methanol (12 mL) and stirred at 23 CC for 30 min. Methyl 4-acetamid0chlor0(2,3-diflu0r0 iodophenyl)picolinate (830 mg, 1.8 mmol, 1.0 equiv) was added and the heterogeneous white e was stirred at 23 CC for 18 h. The reaction mixture was trated by rotary evaporation. The residue was diluted with ted sodium onate (200 mL) and extracted with dichloromethane (3 x 75 mL). The organic layer was dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation to afford the title compound as a white powder (720 mg, 95%). -ll2- ation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Example 77: ation of methyl 4-amino(4-bromo-2,5-difluorophenyl)—3- chloropicolinate (Compound 127)
[00306] To a solution of methyl 4-acetamido(4-bromo-2,5-difiuorophenyl) chloropicolinate (0.300 g, 0.715 mmol) in a mixture of methanol (3.57 mL) and THF (3.57 mL) was slowly added acetyl chloride (1.017 mL, 14.30 mmol). The reaction mixture was stirred at 20 0C for 2 h. The mixture was then poured into a saturated aqueous solution of NaHC03 and ted with EtOAc (3x). The combined c layers were dried over NaZSO4, d, concentrated and dried in vacuo to afford methyl 4-amino(4-bromo-2,5- difiuorophenyl)—3-chloropicolinate (0.257 g, 95%) as a white solid.
Example 78: Preparation of methyl 4-(N-acetylacetamido)—3-chloro(2,5-difluoro (trimethylsilyl)phenyl)picolinate )L Elms H3C N HsC\ /S|_ F H30 | CH3 To a solution of methyl 4-aminochloro(2,5-difiuoro (trimethylsilyl)phenyl)picolinate (0.280 g, 0.755 mmol) in dichloroethane (3.02 mL) was added sopropylethylamine (0.396 mL, 2.265 mmol) and acetyl chloride (0.107 mL, 1.5 10 mmol). The reaction mixture was stirred at 20 CC for 4 h and then at 60 CC for 2 h.
The mixture was poured into a saturated aqueous solution ofNH4Cl and extracted with EtOAc (3x). The combined organic layers were washed with brine, dried over NaZSO4, filtered and concentrated. The residue was purified by flash column chromatography (SiOz; hexa EtOAc gradient) to afford the title compound as a light yellow solid (104 mg, .3 o . mp 121—123 c’C; 1H NMR (400 MHz, CDC13)5 7.88 (d, J: 0.7 Hz, 1H), 7.79 (dd, J -ll3- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel = 8.5, 5.8 Hz, 1H), 7.15 (dd, .1: 10.9, 4.1 Hz, 1H), 4.05 (s, 3H), 2.35 (s, 6H), 0.35 (d, .1: 0.8 Hz, 9H); ESIMS m/Z 455 ([M+H]+).
Example 79: Preparation of methyl 4-amino(4-bromophenyl)fluoro vinylpicolinate (Compound 57) To a 0 oC suspension of nitrosyl tetrafluoroborate (0.122 g, 1.044 mmol) in CHZClz (2 mL) was added a solution of methyl 4-amin0(4-aminophenyl)—5-flu0r0 vinylpicolinate (0.3 g, 1.044 mmol) in a 1:1 mixture of CHzClz and CH3CN (10 mL). The reaction mixture was stirred at 0 0C for 30 min, then was added se to a suspension of potassium e (0.497 g, 4.18 mmol),18-crown-6 (0.028 g, 0.104 mmol), copper(ll) bromide (0.023 g, 0.104 mmol), copper(l) bromide (0.015 g, 0.104 mmol), and 1,10- phenanthroline (0.019 g, 0.104 mmol). The mixture was stirred at 20 CC for 1 h. Additional copper (I) e (0.749 g, 5 equiv) was added and the reaction mixture was stirred at 20 CC for an additional 1 h. The reaction mixture was diluted with EtzO and filtered on a short pad of Celite®. The supernatant was concentrated and purified by flash column chromatography (SiOz; hexanes/EtOAc gradient) ed by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a light brown solid (130 mg, 35.5%).
] The following compound was made in accordance with the procedures sed in Example 79: Methyl 4-acetamido(4-bromo-2,3,6-trifluorophenyl)chloropicolinate —114— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 1H NMR (400 MHz, DMSO-d6) 8 10.08 (s, 1H), 8.48 (s, 1H), 7.87 — 7.84 (m, 1H), 3.93 (s, 3H), 2.25 (s, 3H); ESIMS m/Z 437 ([M+2H]+).
Example 80: Preparation of methyl 6-amino(4-iodophenyl)Vinylpyrimidine carboxylate (Compound 164) To a 50-mL round bottom flask, equipped with a stir bar, was added nitrosyl tetrafluoroborate (78 mg, 0.67 mmol) and dichloromethane (2.0 mL). The flask was cooled in a ice water bath and placed under N2 atmosphere. Then methyl 6-amino(4- lO aminophenyl)Vinylpyrimidinecarb0xylate (180 mg, 0.666 mmol) in dichloromethane (2.5 mL) was added dropwise. The reaction mixture was allowed to stir for 60 min. Then sodium iodide (499 mg, 3.33 mmol) in a l amount of H20 was added, followed by e (1.0 mL). The reaction was allowed to stir for 18 h at room temperature. The reaction mixture was poured into a ted Na2S03 solution and extracted with ethyl l5 acetate (3 x 50 mL). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated. The resulting residue was d by flash chromatography (Silica gel; 0—30% EtOAc in s) and reverse phase chromatography to afford the title compound as a light yellow solid (0.068 g, 27%).
Example 81: Preparation of methyl 4-aminofluoro(4-iodophenyl) icolinate (Compound 139) To a 0 oC suspension of nitrosyl tetrafluoroborate (0.041 g, 0.348 mmol) in CHZClz (1 mL) was added a solution of methyl 4-amin0(4-aminophenyl)—5-flu0r0 Vinylreactbrnixtureicolinate (0.1 g, 0.348 mmol) in a 1:1 mixture of CHzClz and CH3CN (4 mL). The was stirred at 0 0C for 30 min, then a solution of sodium iodide (0.261 g, -ll5- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 1.740 mmol) dissolved in a minimum of water was added and the reaction mixture was stirred at 20 0C for 30 min. The e was then poured into a 10% aqueous solution of sodium sulfite and ted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered and concentrated. The residue was purified by flash column chromatography (SiOz; hexanes/EtOAc gradient) followed by preparative reverse phase HPLC (water/acetonitrile nt) to afford the title compound as a white solid (32 mg, 23.09%).
The following compound was made in ance with the procedures disclosed in Example 81: Methyl 4-acetamid0chlor0(2,3,6-triflu0r0i0d0phenyl)picolinate 1H NMR (400 MHz, DMSO-d6) 8 10.07 (s, 1H), 8.46 (s, 1H), 7.89 — 7.85 (m, 1H), 3.93 (s, 3H), 2.25 (s, 3H); ESIMS m/z 487 ([M+3H]+).
Example 82. Preparation of methyl 4-amin0chlor0methyl(4- ((trimethylsilyl)ethynyl)phenyl)picolinate H3C\ ’9'". H3C A mixture of methyl 4-aminochloro(4-iodophenyl)methylpicolinate (264 mg, 0.66 mmol), hyl((tributylstannyl)ethynyl)silane (280 mg, 0.72 mmol), tetrakis(triphenylphosphine)palladium(0) (75 mg, 0.065 mmol) in anhydrous DMF (1.3 mL) was Ined at 90 0C for 16 h. The on mixture was cooled, diluted water, and extracted [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel with ethyl acetate (2x). The organic layers were dried over anhydrous MgSO4, filtered, and adsorbed onto silica gel. Purification by flash chromatography (0—100% ethyl acetate/hexanes) afforded the title compound as a brown solid (52 mg, 21%): mp 158—164 c’C; 1H NMR (400 MHz, CDC13)5 7.52 (d, J: 8.5 Hz, 2H), 7.40 (d, J: 8.5 Hz, 2H), 4.83 (s, 2H), 3.96 (s, 3H), 2.14 (s, 3H), 0.26 (s, 9H); IR (neat film) 3325, 3227, 2955, 2157, 1729, 1629, 1246 cm'l; ESIMS m/Z 372 ([M]+).
Example 83: Preparation of methyl 4-aminochloro(4-ethynylphenyl)—5- methylpicolinate (Compound 40) HC / ] To methyl 4-aminochloromethyl(4-((trimethylsilyl)ethynyl)phenyl)- picolinate (50 mg, 0.13 mmol) in methanol (0.7 mL) was added potassium carbonate (24 mg, 0.17 mmol). The reaction mixture was stirred at room temperature for 40 min, then d with water and extracted with dichloromethane (4x). The organic layers were dried over anhydrous MgSO4, filtered and concentrated to afford the title compound as a brown oil (34 mg, 84%).
Example 84: Preparation of methyl 4-amin0chlor0flu0r0(4- ((trimethylsilyl)ethynyl)phenyl)picolinate M9381 ] Trimethyl((tributylstannyl)ethynyl)silane (510 mg, 1.3 mmol, 1.1 equiv) was added to a stirred e of methyl ochlorofiuoro(4-iodophenyl)picolinate (490 mg, 1.2 mmol, 1.0 equiv) and is (triphenylphosphine)palladium(0) (140 mg, 0.12 mmoDlO equiv) in DMF (2.4 mL) at 23 OC. The on mixture was heated to 90 0C, [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel resulting in a homogeneous yellow solution, and stirred for 20 h. The cooled on mixture was d with water (200 mL) and extracted with diethyl ether (4 x 100 mL).
Hexanes (100 mL) was added to the combined c layers and the turbid solution was washed with water (200 mL). The organic layer was dried ( MgSO4), gravity filtered, and trated by rotary evaporation. The residue was purified by silica gel column chromatography (25% ethyl acetate in hexanes) to afford the title compound as a tan powder (330 mg, 73%): mp 83—86 0C; IR (thin film) 3487 (m), 3375 (s), 2958 (s), 2159 (m), 1739 (s), 1618 (s) cm'1; 1H NMR (300 MHz, CDC13)8 7.89 (m, 2H), 7.55 (m, 2H), 4.89 (br s, 2H), 3.99 (s, 3H), 0.26 (s, 9H); ESIMS m/z 377 ([M+H]+).
Example 85: Preparation of methyl 4-aminochloro(4-ethynylphenyl)—5- fluoropicolinate (Compound 7) HC// Potassium carbonate (100 mg, 0.74 mmol, 1.0 equiv) was added to a stirred mixture of methyl 4-aminochlorofiuoro(4-((trimethylsilyl)ethynyl)phenyl)picolinate (280 mg, 0.74 mmol, 0.10 equiv) in methanol (3.7 mL) at 23 oC. The heterogeneous pale yellow e was stirred at 23 CC for 30 min. The reaction mixture was diluted with water (200 mL) and extracted with dichloromethane (5 x 50 mL). The organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation to afford the title compound as a tan powder (220 mg, 96%).
Example 86: Preparation of methyl 4-amin0chlor0(4-ethynylflu0r0phenyl)—5— fluoropicolinate (Compound 133) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel ] yl 1-diazooxopropylphosphonate (290 mg, 1.5 mmol, 1.2 equiv) was added to a stirred mixture of methyl 4-aminochlorofluoro(3-fluoro formylphenyl)picolinate (410 mg, 1.3 mmol, 1.0 equiv) and solid potassium carbonate (350 mg, 2.5 mmol, 2.0 equiv) in methanol (12 mL) at 23 CC. The resulting cloudy pale yellow mixture was stirred at 23 CC for 2 h. The reaction mixture was d with water (150 mL) and extracted with dichloromethane (4 x 60 mL). The organic layers were dried ( MgSO4), gravity filtered, and concentrated by rotary evaporation. The residue was purified by silica gel column chromatography (33% ethyl acetate in hexanes) to afford the title compound as a white powder (150 mg, 38%).
Example 87. Preparation of methyl 4-amin0chlor0(4-ethynylflu0r0phenyl) methylpicolinate und 151) To a solution of methyl 4-aminochloro(3-fluoroformylphenyl) methylpicolinate (358 mg, 1.1 mmol) and potassium carbonate (537 mg, 3.9 mmol) in methanol (11 mL) at room temperature was added dimethyl (1-diazo oxopropyl)phosphonate (Bestmann-Ohira reagent, crude reagent; lmL), and the mixture was stirred for 3 h. The reaction was quenched with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3x). The ed organic layers were dried over anhydrous , filtered, and adsorbed onto silica gel. Purification by flash chromatography (0— 50% ethyl acetate/hexanes) provided the title compound as a yellow solid (245 mg, 69%).
Example 88: Preparation of methyl 4-amino(4-ethynylphenyl)—5-flu0r0 icolinate (Compound 60) -ll9- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel To a 20 mL reaction vial was added methyl 4-aminofluoro(4- formylphenyl)vinylpicolinate (0.41 g, 1.365 mmol), potassium carbonate (0.377 g, 2.73 mmol) and methanol (10 mL). Dimethyl (1-diazooxopropyl)phosphonate (0.315 g, 1.638 mmol) was added in one portion. After stirring for 4 h, the reaction mixture was diluted with EtzO (50 mL) and washed with a 5% on ofNaHC03 (25 mL). The organic layer was dried over MgSO4 (5 g), filtered, and concentrated on a rotary evaporator. The resulting residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CHZCIZ and EtOAc to yield the title compound as a white solid (250 mg, 61%).
Example 89: ation of methyl 4-((tert-but0xycarb0nyl)amin0)—3-chlor0(4- ch10r0flu0rophenyl)fluoropicolinate Step 1: Methyl 4-aminochloro(4-chlorofiuorophenyl)fiuoropicolinate (1.43 g, 4.29 mmol) was combined with di-tert—butyl onate (2.99 mL, 12.88 mmol) and N,N-dimethylpyridinamine (0.079 g, 0.644 mmol) in dichloromethane (30 mL). The reaction mixture was stirred overnight at rt. The reaction mixture was trated under a stream of nitrogen and applied directly to a column of silica gel. The compound was eluted with a 2—20% ethyl acetate/hexanes gradient solvent system to provide methyl 4-(bis(tert— butoxycarbonyl)amino)chloro(4-chlorofiuorophenyl)fluoropicolinate (2.1 g, 92%) as a white solid.
Step 2: Methyl 4-(bis(tert—butoxycarbonyl)amino)chloro(4-chloro fluorophenyl)fluoropicolinate (2.1 g, 3.94 mmol) was dissolved in dichloroethane (20 mL) and trifluoroacetic acid (0.598 mL, 7.76 mmol) was added at rt. The reaction mixture was stirred overnight at rt then concentrated under vacuum. The product was d by flash chromatography (SiOz; eluting with 2—20% ethyl acetate in dichloromethane) to e the title compound as a white solid (1.64 g, 98%): 1H NMR (300 MHz, CDClg) 8 7.80 J: 22.0, 8.5 Hz, 2H), 7.50 (dd, J: 8.3, 7.6 Hz, 1H), 6.51 (s, 1H), 4.02 (s, 3H), 1.56 QH); ESIMS m/z 431 ([M-H]'). ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 90: Preparation of methyl 4-amino(4-chlorofluorophenyl)fluoro vinylpicolinate (Compound 215) NH2 (le2 Step 1: Methyl 4-(tert—butoxycarbonylamin0)ch10ro(4-chlor0 fluorophenyl)fluor0picolinate (1.5 g, 3.46 mmol), tributy1(viny1)stannane (2.196 g, 6.92 mmol), and bis(triphenylphosphine)pa11adium(ll) chloride (0.365 g, 0.519 mmol) were combined in 1,2-dich10r0ethane (4.62 mL) and irradiated in a microwave at 130 CC in a sealed vial for 30 min. The cooled reaction mixture was applied directly to a silica gel column and eluted with a 5—40% ethyl acetate/hexanes gradient to provide methyl 4-(tert— butoxycarbonylamino)(4-chlorofluorophenyl)fluorovinylpicolinate (0.966 g, 65.7%) as a white solid.
Step 2: Methyl 4-(tert—butoxycarbonylamino)(4-ch10r0fluor0pheny1) fluoroviny1picolinate (0.966 g, 2.274 mmol) was dissolved in dichloroethane (11 mL) and trifluoroacetic acid (3.50 mL, 45.5 mmol) was added. After 4 h at rt, the reaction mixture was concentrated under vacuum then coevaporated with additional roethane twice more. The e was purified by flash chromatography (SiOz; eluting with 7—60% ethyl acetate in hexanes) to provide the title compound as a white solid (0.705 g, 95%). e 91: Preparation of methyl 4-aminobromochloro(2,5-difluoro (trimethylsilyl)phenyl)picolinate /Si F H3C | To a solution of methyl 4-amin0ch10ro(2,5-diflu0r0 thylsi1y1)phenyl)picolinate (0.210 g, 0.566 mmol) in CHZCIZ (2.265 mL) at 20 °C was addeDomine (0.117 mL, 2.265 mmol). The reaction mixture was stirred at 20 CC [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel overnight. The mixture was then poured into a saturated aqueous solution ofNa2S203 and extracted with EtOAc (3x). The combined organic layers were dried over Na2S04, filtered and concentrated. The residue was purified by flash column chromatography (SiOz; s/EtOAc gradient) to provide the title compound as a white solid (0.125 g, 49.1%): mp 165—166 c’C; 1H NMR (400 MHz, CDC13)5 7.10 (dd, J: 8.9, 4.0 Hz, 1H), 7.03 (dd, J: 7.6, 5.1 Hz, 1H), 5.43 (s, 2H), 3.96 (s, 3H), 0.33 (d, J: 0.7 Hz, 9H); ESIMS m/z 450 ([M+H]+).
Example 92: Preparation of 4-amin0chloro(3-flu0r0i0d0phenyl)picolinic acid (Compound 77) / O ] To a 100-mL round bottom flask, equipped with a stir bar, was added methyl 4- aminochloro(3-fiuoroiodophenyl)picolinate (0.284 g, 0.699 mmol), 1.0 N sodium hydroxide (2.79 mL, 2.79 mmol) and methanol (5.0 mL). The reaction mixture was allowed to stir for 18 h at rt. The t was then d with a rotary evaporator. The resulting solid was d with H20, which was adjusted to pH~3.0 with 1 N HCl, and extracted with ethyl acetate (3 x 50 mL). The combined c layers were dried over ous MgSO4, filtered and concentrated to afford the title compound as a white solid (0.056 g, 21%).
The following compounds were made in accordance with the procedures disclosed in Example 92: 4-Amino-3,5-dichloro(3-fluoroiod0phenyl)picolinic acid (Compound 145) CI CI [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel The title compound was prepared as described in Example 92 with methyl 4- amino-3,5-dichloro(3-fluoroiodophenyl)picolinate (0.197 g, 0.447 mmol) and isolated as a white solid (0.133 g, 70%). 6-Amin0(3-flu0r0i0d0phenyl)—5-methoxypyrimidine—4-carb0xylic acid (Compound 37) N \ O\CH3 / 0 The title compound was prepared as described in Example 92 with methyl 6- amino(3-fluoroiodophenyl)methoxypyrimidinecarboxylate (0.309 g, 0.766 mmol) and isolated as a white solid (0.065 g, 22%). 4-Amino(4-bromofluorophenyl)chloropicolinic acid und 110) / OH The title nd was prepared as described in Example 92 with methyl 4- amino(4-bromofluorophenyl)chloropicolinate (291 mg, 0.809 mmol) and isolated as an off-white solid (0.247 g, 88%). 4-Amino(4-bromofluorophenyl)—3,5-dichlor0picolinic acid (Compound 43) CI CI / OH [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel The title compound was prepared as described in Example 92 with methyl 4- 6-(4-bromofluorophenyl)-3,5-dichloropicolinate (225 mg, 0.571 mmol) and isolated as a white solid (0.219 g, 100%). 0(4-br0m0flu0rophenyl)methoxypyrimidine—4-carboxylic acid (Compound 113) N \ O\CH3 N/ OH The title compound was prepared as described in Example 92 with methyl 6- amino(4-bromofluorophenyl)methoxypyrimidinecarboxylate (166 mg, 0.466 mmol) and isolated as a white solid (0.056 g, 35%). 6-Amin0(4-cyan0flu0rophenyl)Vinylpyrimidine—4-carb0xylic acid (Compound N \ \CHZ / OH N// F
[00334] The title compound was prepared as described in Example 92 with methyl 6- amino(4-cyanofluorophenyl)Vinylpyrimidinecarboxylate (294 mg, 0.986 mmol) and isolated as a an orange solid (0.202 g, 72%). —124— ation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 6-Amino(3-fluoro(trifluoromethyl)phenyl)Vinylpyrimidinecarboxylic acid (Compound 32) N \\ \‘CFb / OH F O F F The title compound was prepared as described in Example 92 with methyl 6- 2-(3-fluoro(trifluoromethyl)phenyl)—5-Vinylpyrimidinecarboxylate (265 mg, 0.777 mmol) and isolated as a light yellow solid (0.234 g, 92%). 6-Amino(2,3,4-trifluorophenyl)Vinylpyrimidinecarboxylic acid (Compound 191) N ‘\ \‘CFb / OH F F F The title compound was prepared as described in Example 92 with methyl 6- amin0(2,3,4-triflu0rophenyl)—5-Vinylpyrimidinecarboxylate (335 mg, 1.08 mmol) and isolated as a yellow solid (0.275 g, 86%).
Example 93: Preparation of 4-aminochloro(4-cyanofluorophenyl)-5— fluoropicolinic acid (Compound 65) In a 50-mL round bottom flask, equipped with a stir bar, methyl 4-amin0 chloro(4-cyan0fluorophenyl)fluor0picolinate (351 mg, 1.084 mmol) and lithium hydrue hydrate (100 mg, 2.383 mmol) were ved in tetrahydrofuran (2.0 mL), [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel methanol (2.0 mL) and H20 (1.0 mL). The reaction was stirred at rt for 2 h. The solvent was then removed by rotary evaporator. The ing solid was treated with H20, which was then adjusted to pH~3.0 with 1 N HCl, and extracted with ethyl acetate (3 x 50 mL).
The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated.
The resulting residue was purified by reverse phase chromatography (150 g C18, 0—100% acetonitrile in H20), as needed, to afford the title compound as a brown solid (0.058 g, 20%).
The following compound was made in accordance with the procedures disclosed in Example 93: 6-Amin0(4-i0dophenyl)vinylpyrimidinecarboxylic acid (Compound 123) NH2 (3H2 / OH The title compound was prepared as described in Exampled 93 with methyl 6- amino(4-iodophenyl)vinylpyrimidinecarboxylate (65 mg, 0.177 mmol) and isolated as an off-white solid (60 mg, 92%).
Example 94. Preparation of 0chloro(3-flu0r0(triflu0r0methyl)phenyl)—5- methylpicolinic acid (Compound 161) ] To methyl ochloro(3-fiuoro(trifiuoromethyl)phenyl) picolinate (0.35 g, 0.96 mmol) in methanol (6.4 mL) was added 2 N NaOH (1.93 mL, 3.9 mmol), and the reaction mixture was stirred at rt for 18 h. The solution was acidified with 2 N HCl and the itate was vacuum filtered to afford the title compound as a white powder (199 mg, 59%). ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel The following compounds were made in accordance with the procedures disclosed in Example 94: 4-Amin0chlor0(4-(diflu0r0meth0xy)phenyl)—5-methylpicolinic acid und 94) The title compound was prepared as in e 94 and isolated as a yellow solid (36 mg, 68%). 4-Amino(4-bromophenyl)—3-chloro-S-methylpicolinic acid und 78) The title compound was prepared as in Example 94 and isolated as a white solid (24 mg, 71%). 4-Amin0chlor0(4-i0d0phenyl)—5-methylpicolinic acid (Compound 116) The title compound was prepared as in Example 94 and isolated as an orange powder (86 mg, 83%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 4-Aminochloro(3-fluoroiodophenyl)methylpicolinic acid (Compound 87) The title nd was prepared as in Example 94 and isolated as a white powder (120.5 mg, 88%). ochloro(4-ethynyl—3-fluorophenyl)methylpicolinic acid (Compound 6) The title compound was prepared as in Example 94 and isolated as a yellow powder (147 mg, 82%).
Example 95: Preparation of 4-aminochlorofluoro(4-nitrophenyl)picolinic acid und 31) To a solution of methyl 4-amin0chlorofluor0(4-nitr0phenyl)picolinate (88 mg, 0.27 mmol) in methanol (MeOH; 3 mL) was added 1 Normal (N) aqueous sodium hydroxide solution (NaOH; 3 mL, 3 mmol). The reaction mixture was stirred for 24 h at ambient temperature. The solution was then concentrated and acidified with 2 N aqueous HCl on. The desired product precipitated out of solution, was collected in a Biichner funnDnd allowed to dry overnight to afford a tan solid (84 mg, 100%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 96: Preparation of 4-aminochloro(2,3-difluoro (trifluoromethyl)phenyl)picolinic acid (Compound 172) To a mixture of methyl 4-acetamid0chlor0(2,3-diflu0r0 (trifluoromethyl)phenyl)picolinate (115 mg, 0.28 mmol) in ol (1 mL) was added 2 Normal (N) aqueous sodium ide solution (NaOH; 1.4 mL, 2.81 mmol). The reaction solution was stirred at ambient temperature for 15 h. The solution was then trated, and acidified with a 2 N aqueous HCl solution. The desired t precipitated out of solution. This mixture was extracted (3x) with dichloromethane, the organics were combined, dried 4), filtered and the concentrated in vacuo to afford a white solid (94 mg, 90%).
Example 97: Preparation of 4-aminochloro-S-fluoro(4-iodophenyl)picolinic acid (Compound 45) | A 2 M solution of sodium hydroxide (740 uL, 1.5 mmol, 4.0 equiv) was added to a stirred solution of methyl 4-amino(4-iodophenyl)—3-chlor0fluor0picolinate (150 mg, 0.37 mmol, 1.0 equiv) in methanol (3.7 mL) at 23 0C. The resulting pink solution was stirred at 23 CC for 3 h. The reaction mixture adjusted to pH 3, using concentrated HCl, and concentrated by rotary evaporation. The residue was ed in water and vacuum filtered to afford the title compound as a pale pink powder (110 mg, 79%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel e 98: Preparation of 4-aminochloro(2,3-difluoroiodophenyl)—5- fluoropicolinic acid (Compound 141) A 2 M solution of aqueous sodium hydroxide (270 ML, 0.54 mmol, 2.0 equiv) was added to a stirred suspension of methyl 4-aminochloro(2,3-difluoro i0dophenyl)flu0r0picolinate (120 mg, 0.27 mmol, 1.0 equiv) in methanol (2.7 mL) at 23 oC. The heterogeneous white mixture was stirred at 23 0C for 18 h. The reaction mixture was adjusted to approximately pH 4 via dropwise addition of concentrated HCl and concentrated via rotary evaporation. The residue was dissolved in dichloromethane (250 mL), passed through a hydrophobic membrane phase separator, dried ( , gravity filtered, and concentrated by rotary ation to afford the title compound as a white powder (110 mg, 92%).
Example 99: Preparation of o(4-bromo-2,3,6-trifluorophenyl) chloropicolinic acid (Compound 162) A solution of methyl 4-acetamid0(4-br0mo-2,3,6-triflu0r0phenyl) chloropicolinate (50 mg, 0.122 mmol, 1.0 equiv) and sodium hydroxide (14 mg, 0.366 mmol, 3.0 equiv) in OH:H20 .5; 2.5 mL) was stirred at 20 0C for 2 h. The reaction mixture was acidified to pH 4—5 using 1.5 N HCl and extracted with EtOAc (2x).
The combined organic extract was dried over anhydrous NaZSO4 and evaporated to dryness under reduced pressure to provide the title compound as a brown solid (30 mg, 65%). ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example 100: Preparation of 4-amino(4-bromo-2,5-difluorophenyl)chloro fluoropicolinic acid (Compound 42) To a solution of methyl 4-amino(4-br0m0-2,5-difluor0phenyl)chloro fluoropicolinate (0.160 g, 0.404 mmol) in a 1:1 mixture ofMeOH (0.674 mL) and acetone (0.674 mL) was added a 2 N aqueous solution of sodium hydroxide (0.607 mL, 1.213 mmol). The reaction mixture was stirred at 20 CC ght. The reaction mixture was concentrated, poured into a 2 N aqueous solution of HCl, and ted with EtOAc (3x).
The combined organic layers were dried over NaZSO4, filtered, concentrated and dried in vacuo to afford the title compound as a light brown solid (126 mg, 82%).
Example 101: Preparation of 4-aminochloro(4-(difluoromethoxy)—3- fluorophenyl)fluoropicolinic acid (Compound 92)
[00353] To a flask charged with MeOH (2 mL) was added methyl 4-aminochloro(4- (difluoromethoxy)—3-fiuor0phenyl)fiuor0picolinate (190 mg, 0.52 mmol) and 2 M sodium hydroxide solution (1 mL, 1 mmol). ing 12 h of mechanical stirring, the reaction mixture was trated using a rotary evaporator with a water bath temperature of 40 CC.
Water was added to the resulting oil and the solution was slowly acidified by the on of concentrated HCl until a tan precipitate formed. Filtration using filter paper and a Biichner funnel afforded the title compound as a tan solid (108 mg, 59%).
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Table 1. Compound Number, Structure, Preparation and ance compound Prepare(1 as Structure Appearance No. in Example: 1 White Solid 42 2 White Solid 73 3 White Solid 100 4 Brown Solid 97 Orange Solid 92 -l32- [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Appearance No. in Example: Yellow Powder Tan Powder 85 White solid 98 Off-White Powder White Solid 98 ll White Solid 100 -l33- [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Structure Appearance No. in Example: 12 Tan Solid 42 13 Yellow Solid 64 14 White Solid 98 Yellow Solid 42 Off-White 16 42 Solid 17 Yellow Solid 100 —134— [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Light Yellow 18 66 19 White Solid 101 Orange- Tinged White 97 Solid Off-White 21 97 Powder 22 White Powder 86 23 Yellow Solid 42 -l35- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel (?ompound Prepared as ure Appearance No inExmnpk: 24 White Solid 68 Yellow Solid 98 26 ohd 46 27 Yellow Solid 64 28 VVhfieSohd 98 29 VVhfieSohd 46 -l36- [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Com oundp Prepared as Structure ance N0. in Example: Yellow Solid 42 31 Tan Solid 95 Light Yellow 32 92 Solid 33 White Solid 98 34 Yellow Solid 86 Off-White 72 Powder -l37- [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Compound Prepared as No. in Example: Off-White 36 101 Solid 37 White Solid 92 38 White Powder 97 39 White Solid 98 40 Brown Oil 83 41 Tan Powder 98 -l38- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Light Brown 42 100 Solid 43 White Solid 92 Off-White 44 39 Solid Pale Pink 45 97 Powder Off-White 46 98 Powder 47 White Solid 74 -l39- [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Com oundp Prepared as ure Appearance N0. in Example: 48 White Solid 98 Off-White 49 72 Powder Off-White 50 98 Powder 51 White Solid 73 52 White Powder 72 53 Brown Solid 54 —140— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Structure ance No. in Example: 54 White Solid 97 55 White Solid 67 56 Orange Solid 77 Light Brown 57 79 Solid Off-White 58 46 Solid 59 White Powder 86 —141— [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Com oundp Prepared as Structure Appearance N0. in Example: Brown 61 100 Gummy Oil 62 97 63 White Solid 96 64 White Solid 41 65 Brown Solid 93 —142— [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: 66 Brown Solid 64 Dark Brown 67 76 Viscous Oil 68 100 Solid 69 White Solid 100 70 White Solid 59 Off-White 71 98 Powder —143— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Structure Appearance No. in Example: Yellow 72 98 Powder 73 White Solid 69 74 White Solid 98 76 White Solid 95 77 White Solid 92 78 White Solid 94 —144— [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Compound Prepared as No. in Example: Off-White 79 65 Solid 80 Yellow Solid 41 Pale Orange 81 70 Powder Yellow 82 66 Powder 83 Orange Solid 40 84 White Powder 86 —145— [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Structure Appearance No. in Example: 85 White Solid 42 86 White Solid 98 87 White Powder 94 88 White Solid 97 89 White Solid 98 90 White Solid 77 [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as ure Appearance No. in Example: 91 White Solid 97 92 Tan Solid 101 93 White Solid 74 94 Yellow Solid 94 95 Yellow Solid 41 96 Gray Solid 68 —147— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Off-White 97 72 Solid 98 Yellow Solid 39 99 White Powder 66 Light Brown 100 67 solid 101 White Solid 67 102 Yellow Solid 98 [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l Compound Prepared as Structure Appearance No. in Example: 103 Tan Solid 56 104 Yellow Solid 56 105 White Solid 98 106 White Solid 56 107 Tan Solid 57 Pale Orange 108 98 Powder —149— ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Light Yellow 109 71 Solid Off-White 110 92 Solid Waxy Yellow 111 40 Solid Off-White 112 70 Solid 113 White Solid 92 114 White Solid 44 [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel (?ompound Prepared as Structure Appearance Na inExmnpk: 115 ohd 75 1 16 I94 Light Brown 117 100 Solid 1 18 I66 119 ‘YEUOWISohd 100 12 1 White Powder 86 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Compound ed as Appearance No. in Example: 122 White Solid 74 Off-White 123 93 Solid 124 Yellow Solid 98 125 White Solid 98 126 Yellow Solid 86 127 White Solid 77 [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel (?ompound Prepared as Structure Appearance No pk: 128 VVhfieSohd 96 129 White Powder 76 130 VVhfieSohd 42 Light Brown 131 100 Solid 132 66 133 White Powder 86 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l Compound Prepared as No. in Example: 134 White Solid 95 135 White Solid 42 Red-Orange 136 65 Solid Light Tan 137 39 Solid 138 Tan Powder 72 139 White Solid 81 —154— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Com oundp Prepared as ure Appearance N0. in Example: Off-White 140 101 Solid 14 1 White Powder 98 142 42 143 White Solid 98 144 White Solid 60 145 White Solid 92 ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] l Unmarked set by chanmel (?ompound Prepared as Structure Appearance Na inExmnpk: 146 VVhfieSohd 96 147 Tan Solid 98 148 VVhfieSohd 60 149 VVhfieSohd 41 150 Tan Solid 101 151 Ybfloszohd 87 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel (?ompound Prepared as Structure Appearance Na inExmnpk: 152 VVhfieSohd 56 153 Sohd 98 154 98 White Flaky 155 40 Solid 156 VVhfieSohd 98 157 97 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Com oundp ed as Structure Appearance N0. in Example: Dark Brown 8 76 Semi-Solid 159 White Solid 68 160 White Solid 41 1 6 1 White Powder 94 162 Brown Solid 99 Off-White 163 98 Powder [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Light Yellow 164 80 Solid 165 White Solid 41 166 Yellow Solid 86 167 White Solid 95 168 Brown Solid 97 Off-White 169 98 Powder -lS9- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel Compound Prepared as Appearance No. in Example: 170 White Solid 42 171 White Solid 69 172 White Solid 96 173 Yellow Solid 98 Off White 174 62 Solid 175 Tan Solid 57 -l60- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: 176 White Solid 63 177 White Solid 63 Off-White 178 62 Solid 179 White Solid 63 180 White Solid 101 Off-White 181 57 Solid -l6l- [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: Pale Yellow 183 46 184 White Solid 63 185 White Solid 63 186 White Solid 41 187 White Solid 98 188 White Solid 62 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Compound Prepared as Appearance No. in Example: 189 White Solid 46 190 White Solid 43 191 Yellow Solid 92 192 White Solid 43 193 White Solid 63 194 White Solid 62 -l63- [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Compound Prepared as Structure Appearance No. in Example: 195 White Solid 98 196 White Powder 47 197 Yellow Solid 39 198 White Solid 63 199 Tan Solid 57 200 White Powder 40 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel (?ompound Prepared as Structure Appearance Na inExmnpk: 201 VVhfieSohd 62 202 White Solid 63 203 VVhfieSohd 62 204 White Solid 41 205 ohd 62 206 TanSohd 57 [Annotation] chanmel None set by chanmel [Annotation] l ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel (?ompound Prepared as Structure Appearance Na inExmnpk: 207 Tan Solid 101 208 VVhfieSohd 63 209 White Powder 47 210 I95 211 VVhfieSohd 41 212 I95 , [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Compound Prepared as No. in Example: 213 White Solid 41 214 White Solid 98 215 White Solid 90 216 White Solid 42 Off-White 217 97 Solid [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Table 2. Analytical Data for Compounds in Table 1 13C or 19F NMR 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.81 (m, ([M+H]+) 4H), 5.42 (s,2H), 4.02 (s,3H) 1H NMR (400 MHz, CDC13) 8 7.78 (dd, J 19F NMR (376 MHz, ESIMS m/z = 9.0, 6.5 Hz, 1H), CDC13) 8 -113.66, — 373 ([M-H]' 7.37 (dd, J = 9.6, 5.6 ) Hz, 1H), 5.43 (s, 2H), 4117.53, -117.58 4.01 (s, 3H), 3.95 (s, 1H NMR (400 MHz, 19F NMR (376 MHz, ESIMS m/z DMSO-dg) 8 7.894 DMSO-dg) 8 - 364 7.84 (m, 2H), 7.26 (d, ([M+H]+) 108.94, -108.99, J = 1.2 Hz, 1H), 6.85 8, —114.22 1H NMR (400 MHz, ESIMS m/z DMSO-d6) 8 7.85 (m, 375 2H), 7.69 (m, 2H), ([M+H]+) 7.24 (s, 1H), 6.73 (br s, 2H 1H NMR (400 MHz, DMSO-d6) 8 13.65 (s, 1H), 8.12 4 7.89 (m, 2H), 7.80 (dd, J 19F NMR (376 MHz, = 8.0, 1.6 Hz, 1H), DMSO-dg) 8 -111.46 7.32 (d, J = 4.8 Hz, 2H), 6.66 (dd, J = 17.7, 11.4 Hz, 1H), .75 4 5.41 m, 2H 1H NMR (400 MHz, DMSO-d6) 8 13.38 (s, 1H), 7.62 (t, J = ESIMS m/z 7.7 Hz, 1H), 7.40 19F NMR (376 MHz, 303 ([M-H]' (dd, J = 10.4, 1.5 Hz, DMSO-dé) 8 —111.32 ) 1H), 7.31 (dd, J = 7.9, 1.6 Hz, 1H), 6.51 (s, 2H), 4.59 (s, 1H), 1H NMR (300 MHz, IR (thin film) 3478 (s), ESIMS m/z CDC13) 8 7.91 (m, 3374 (s), 3239 (s), 2955 305 2H), 7.58 (m, 2H), (W), 1731 (m), 1624 (m) ([M+H]+) 4.90 (br s, 2H), 3.99 cm'1 (s, 3H), 3.16 (s, 1H) 1H NMR (400 MHz, 19F NMR (376 MHz, ESIMS m/z DMSO-dg) 8 13.64 DMSO-dg) 8 - 360 (s, 1H), 7.74 4 7.56 ([M+H]+) 131.53, -131.58, (m, 2H), 7.45 (s, 2H), -136.08, -136.14 3.76 (s, 3H) [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 7.88 (dd, J IR (thin film) 3489 (s), = 8, 1.5 Hz, 1H), 3381 (s), 3233 (m), 3199 ESIMS m/z 7.55 (dd, J =10, 1.5 (m), 3083 (w), 3000 (w), 425 Hz, 1H), 7.33 (dd,J 2954 (m), 2853 (w), +) = 8.5, 8 Hz, 1H), 1737 (s), 1622 (s) cm'1 4.94 (br s, 2H), 3.96 (s, 3H) 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.97(d, 2H), 7.30(m, 5H), ([M+H]+) 6.72(s, 2H) 1H NMR (400 MHz, 19F NMR (376 MHz, ESIMS m/z DMSO-d6) 6 7.86 4 DMSO-dg) 6 - 359 ([M-H]' 7.73 (m, 2H), 7.43 (s, 114.36, —114.40, 2H), 3.75 (s, 3H) —116.52, -116.57 1H NMR (400 MHz, CDC13) 6 7.86 (dd, J = 9.0, 6.9 Hz, 2H), 7.69 (t, J = 7.8 Hz, ESIMS m/z 1H), 6.90 (dd, J = 359 18.1,11.6 Hz, 1H), ([M+H]+) 5.74 (dd, J= 11.6, 1.3 Hz, 1H), 5.60 (dd, J= 18.1, 1.3 Hz, 1H), 4.78 (s, 2H), 3.94 (s, 3H) 1H NMR (400 MHz, DMSO-dé) 6 7.95 (dd, J = 8.1, 6.7 Hz, ESIMS m/z 1H), 7.47 (dd, J = 19F NMR (376 MHz, ([M+H]+) 9.1, 1.9 Hz, 1H), 7.22 DMSO-dg) 6 -95.18 (dd, J= 8.1,1.9 Hz, 1H), 7.14 (s, 2H), 1H NMR (400 MHz, ESIMS m/z g) 6 7.95 (d, ([M+H]+) 2H), 7.80 (d, 2H), 7.09 (s, 2H) 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.72 (d, 363 2H), 7.24 (d, 2H), ([M+H]+) 5.42 (s, 2H), 4.02 (s, 1H NMR (400 MHz, DMSO-dg) 6 8.01 (m, ESIMS m/z 2H), 7.79 (dd, J = 306 5 Hz, 1H), 7.30 ([M+H]+) (d, J= 1.5 Hz, 1H), 6.96 (s, 2H), 3.89 (s, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel ed set by chanmel 13C or 19F NMR 1H NMR (400 MHz, g) 8 13.12 (s, 1H), 7.87 (d, J= 8.4 Hz, 2H), 7.66 (d, ESIMS m/z J = 7.6 Hz, 2H), 6.75 19F NMR (376 MHz, 3 85 (dd,J=17.8,11.5 DMSO-dé) 8 5 ([M+H]+) Hz, 1H), 6.41 (s, 2H), .55 (dd, J= 14.2, 1.1 Hz, 1H), 5.52 (dd, J= 7.8, 1.1 Hz, 1H NMR (400 MHz, ESIMS m/z CDC13) 8 8.04 (m, 3 87 2H), 7.77 (m, 2H), ([M+H]+) 5.36 (br s, 2H), 4.01 (s, 3H), 3.91 (s, 3H) IR (thin film) 1025.80, 1H NMR (400 MHz, 1047.25, 1126.02, DMSO-dg) 8 13.70 1225.15, 1266.03, (s, 1H), 7.47 (ddd, J 1299.98, 1386.12, ESIMS m/z = 9.2, 7.2, 2.0 Hz, 1481.90,1515.13, 369 1585.75, 1633.93, ([M+H]+) 1H), 7.40 (d, J= 3.0 Hz, 1H), 7.37 (t, J = 1721.56, 2536.01, 72.3 Hz, 1H), 7.07 (s, 3199.39, 3331.39, 3471.03 cm‘1 NMR (400 MHz, ESIMS m/z 6) 8 7.85 4 347 7.77 (m, 2H), 7.75 4 ([M+H]+) 7.68 (m, 2H), 6.94 (s, 1H NMR (400 MHz, DMSO-dé) 8 7.88 IR (thin film) 3468 (s), ESIMS m/z (dd, J = 9, 8 Hz, 1H), 3334 (s), 3198 (s), 1717 365 7.82 (dd, J= 9,1.5 (w), 1629 (m), 1573 (w) 0111'1 ([M+H]+) Hz, 1H), 7.70 (d, J = 9 Hz, 1H), 6.73 (br s, 1H NMR (400 MHz, IR (thin film) 3512 (m), ESIMS m/z CDC13) 8 7.33 4 7.35 3411 (s), 3248 (s), 2954 341 (m, 2H), 4.98 (br s, (W), 1730 (m), 1616 (m) cm'1 ([M+H]+) 2H), 3.98 (s, 3H), 3.43 (s, 1H) 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.95 (d, 329 2H), 7.31 (m, 3H), ([M+H]+) 6.85 (s, 2H), 3.92 (s, 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.58 4 7.43 422 (m, 2H), 5.53 (s, 2H), ([M+H]+) 4.00 (s, 3H), 3.95 (s, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 8 13.6 (s, 271 1H), 8.40 (d, 2H), ([M+H]+) 7.96 (d, 2H), 7.46 (s, 2H), 3.79 (s, 3H) 1H NMR (400 MHz, DMSO-dg) 8 8.19 (t, J= 16.1 Hz, 1H), 19F NMR (376 MHz, ESIMS m/z IR (thin film) 3401, 8.11 (d, J= 12.3 Hz, g) 8 1739, 1638 cm‘1 ([M+H]+) 1H), 7.92 (t, J = 7.9 -59.9, -115.7, Hz, 1H), 7.74 4 7.46 -116.0 (m, 2H), 3.92 (s, 3H), 3.76 s, 3H 1H NMR (400 MHz, DMSO-d6) 8 8.00 4 ESIMS m/z 7.87 (m, 2H), 7.82 19F NMR (3 76 MHz, 403 (dd, J = 8.3, 1.8 Hz, ([M+H]+) DMSO-dé) 8 495.51 1H), 7.49 (s, 2H), 3.90 (s, 3H), 3.74 (s, 1H NMR (400 MHz, DMSO-dg) 8 13.6 (s, ESIMS m/z 1H), 8.25 (d, 2H), 7.59 (d, 2H), 7.36 (s, ([M+H]+) 2H), 4.35 (s, 1H), 3 77 s 3H 1H NMR (400 MHz, CDC13) 8 7.79 (dd, J ESIMS m/z = 15.8, 9.9 Hz, 2H), 19F NMR (376 MHz, 349 7.66 (t, J = 7.7 Hz, CDC13) 8 ([M+H]+) 1H), 7.12 (s, 1H), -61.3, 41139 4.90 (s, 2H), 4.02 (s, 1H NMR (400 MHz, ESIMS m/z CDC13) 8 8.33 (d, 343 2H), 7.27 (d, 2H), ([M+H]+) 5.84 (s, 2H), 4.03 (s, 3H), 3.95 (s, 3H) 1H NMR (400 MHz, DMSO-dg) 8 13.71 (s, 1H), 8.40 4 8.33 (m, 2H), 8.13 (d, J= 8.3, 2H), 7.07 (s, 2H) 1H NMR (400 MHz, DMSO-dg) 8 13.68 (s, 1H), 8.28 (d, J = 19F NMR (376 MHz, 8.2 Hz, 1H), 8.20 (d, ESIMS m/z g) 8 -59.97 J = 12.2 Hz, 1H), 328 (d, J = 12.2 Hz), — 7.94 ([M+H]+) (t, J = 7.9 Hz, 115.77 (q, J =12.2 1H), 7.35 (d, J = 27.9 Hz, 2H), 6.68 (dd, J = 17.7, 11.5 Hz, 1H), .75 4 5.46 (m, 2H) ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 13.7 (s, 349 1H), 7.68 (d, 2H), +) 7.32 (d, 2H), 6.96 (s, 1H NMR (300 MHz, ESIMS m/z CDC13) 6 6.30 (m, ([M+H]+) 5H), 5.35 (s, 2H), 1H NMR (400 MHz, IR (thin film) 3416 (s), CDC13) 6 7.84 (t, J = ESIMS m/z 3355 (w), 3300 (m), 9 Hz, 1H),7.314 U.) kl] 358 3162(s), 2957 (w), 1730 7.37 (m, 2H), 5.41 ([M+H]+) (s), 1637 (s) cm"1 (br s, 2H), 3.99 (s, 3H), 3.93 (s, 3H) 1H NMR (400 MHz, CDC13) 6 7.93 4 7.84 (m, 2H), 7.64 4 7.54 (m, 2H), 6.75 (dd, J ESIMS m/z 19F NMR (376 MHz, = 17.8, 11.5 Hz, 1H), U.) 282 CDC13) 6 6.36 (s, 2H), 5.57 ([M+H]') —141.43 (dd, J = 17.8, 1.4 Hz, 1H), 5.50 (dd, J = 11.5, 1.4 Hz, 1H), 4.31 s, 1H 1H NMR (400 MHz, DMSO-dg) 6 13.57 ESIMS m/z (s, 1H), 8.02 4 7.92 19F NMR (3 76 MHz, 390 (m, 2H), 7.85 (dd, J ([M+H]+) DMSO-dg) 6 -95.59. = 8.2, 1.8 Hz, 1H), 7.41 (s, 2H), 3.75 (s, 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.74 (m, IR (thin film) 3473 (s), 00 41 1 1H), 7.55 (m, 1H), 1588 (m) cm'1 ([M+H]+) 7.02 (d, J = 1.5 Hz, 1H), 6.30 (br s, 2H) 1H NMR (400 MHz, ESIMS m/z DMSO-d6) 6 8.08 4 O 292 7.92 (m, 4H), 7.03 ([M+H]+) (s, 13C NMR (101 MHz, 1H NMR (400 MHz, CDC13) 6 165.71, CDC13) 6 7.55 (d, J = 155.51,149.15, ESIMS m/z 8.4 Hz, 2H), 7.42 (d, ,140.11, J; O 301 J = 8.5 Hz, 2H), 4.83 ([M+H]+) 132.02, 129.34, (s, 2H), 3.96 (s, 3H), 122.02, 116.77, 3.12 (s, 1H), 2.16 (s, 113.59, 83.42, 77.90, 52.87, 14.65 [Annotation] l None set by chanmel ation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, IR (thin film) 3297 (s), DMSO-dé) 8 7.80 (t, ESIMS m/z 3218 (s), 2938 (w), 1618 J= 8 Hz, 1H), 7.35 , (s), 1576 (m) 7.40 (m, 2H), 6.66 0111'1 +) (br s, 2H), 4.41 (s, 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-dé) 8 13.63 DMSO-dé) 8 - ESIMS m/z (s, 1H), 7.92 (dd, J = 113.46, —113.50, 3 82 ([M+H]+) 9.0, 5.7 Hz, 1H), 7.61 —117.37, —117.41, (dd, J= 8.4, 6.3 Hz, —117.45, —117.49, 1H), 7.06 (s, 2H) —138.28, -138.36 1H NMR (400 MHz, DMSO-dg) 8 13.72 (s, 1H), 7.82 (dd, J = ESIMS m/z 8.3, 7.3 Hz, 1H), 7.60 19F NMR (376 MHz, 3 81 ([M+H]+) (dd, J = 9.8, 2.0 Hz, DMSO-dg) 8 —108.25 1H), 7.40 (dd, J = 8.3, 2.0 Hz, 1H), 7.06 (s, 2H) 1H NMR (400 MHz, DMSO-dg) 8 8.05 19F NMR (376 MHz, ESIMS m/z (dd, J = 10.0, 1.5 Hz, DMSO-d6) 8 —1 12.13 324 1H), 7.85 (dd, J = (d, J = 28.4 Hz), — ([M+H]+) 8.0, 1.5 Hz, 1H), 7.73 137.43 (d, J = 28.4 , 7.81 (m, 1H), 7.18 Hz) (s, 2H), 3.87 (s, 3H) 1H NMR (300 MHz, ESIMS m/z DMSO-dé) 8 7.87 (m, 2H), 7.62 (m, 2H), ([M+H]+) 6.91 (br s, 2H) 1H NMR (400 MHz, DMSO-dé) 8 13.60 (br s, 1H), 7.81 (t,J IR (thin film) 3490 (s), ESIMS m/z = 9 Hz, 1H), 7.63 3350 (s), 1753 (W), 1634 344 ([M+H]+) (dd, J= 11, 2 Hz, (m), 1607 (m) cm"1 1H), 7.52 (dd, J = 9, 2 Hz, 1H), 7.38 (br s, 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.58 (m, +) 4H), 5.36 (s,2H), 3.99 (s, 3H) 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 8 13.5 (s, 273 1H), 7.94 (d, 2H), ([M+H]+) 7.60 (d, 2H), 7.30 (s, 1H), 6.69 (s, 2H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l 13C or 19F NMR 1H NMR (300 MHz, IR (thin film) 3492 (s), ESIMS m/z CDC13) 6 7.76 (m, 3378 (s), 3235 (w), 2955 379 1H), 7.60 7 7.68 (m, (w), 2927 (w), 1736 (s), ([M+H]+) 2H), 4.94 (br s, 2H), 1621 (s)cm'1 3.99 (s, 3H) 1H NMR (400 MHz, DMSO-dg) 6 7.53 IR (thin film) 3305 (s), ESIMS m/z (dd, J = 8, 7 Hz, 1H), 1720 (w), 1634 (m), 327 7.41 (m, 1H), 6.93 1586 (w) cm‘l ([M+H]+) (br s, 2H), 4.81 (s, 19F NMR (376 MHz, 1H NMR (400 MHz, CDC13) 6 ESIMS m/z CDC13) 6 7.42 7 7.38 7112.74, 8, 394 ([M-H]' (m, 2H), 4.98 (s, 2H), 9, 7117.03, 3.99 (s, 3H) 7117.09, 7117.13, -137.28, -137.38 1H NMR (400 MHz, IR (neat film) 3519 (m), CDC13) 6 7.50 (dd, J 3473 (m), 3420 (s), 3379 ESIMS m/z = 8, 7 Hz, 1H), 7.42 (s), 3196 (w), 3075 (w), 379 (dd, J = 8, 2 Hz, 1H), 2955 (w), 2852 (w), ([M+H]+) 7.36 (dd, J= 10, 2 1736 (s), 1616 (s) cm'1 Hz, 1H), 4.93 (br s, 2H), 3.96 (s, 3H) 19F NMR (376 MHz, 1H NMR (400 MHz, CDC13) 6 CDC13) 6 7.53 7 7.45 -61.16, -61.20, (m ,2H), 6.91 (dd, J 7135.77, -135.83, ESIMS m/z =18.1, 11.6 Hz, 1H), -135.86, 7135.92, 377 5.76 (dd, J= 11.6, ([M+H]+) 1, -138.65, 1.3 Hz, 1H), 5.61 -138.67, -138.68, (dd,J=18.1, 1.3 Hz, -138.70, -138.72, 1H), 4.81 (s, 2H), -138.74, -138.77, 3.92 (s, 3H) 7140.73, -140.82. 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 8.15 (m, 326.07 2H), 7.67 (m, 2H), ([M+H]+) 7.45 (br s, 2H), 3.75 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 7.56 (dd, J CDC13) 6 ESIMS m/z = 8.5, 4.9 Hz, 1H), -99.87, -99.91, 7.32 (dd, J = 7.6, 5.8 7117.70, -117.74, ([M+H]+) Hz, 1H), 4.97 (s, 2H), 0, -117.84, 3.98 (s, 3H) 7137.25, 7137.35. 7174— [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 7.80 (dd, J 19F NMR (376 MHz, ESIMS m/z = 8.5, 6.5 Hz, 1H), CDC13) 6 —100.00, 425 7.53 (dd, J= 10.0, —100.05, ([M+H]+) 5.0 Hz, 1H), 7.25 (d, —120.62, J = 1.2 Hz, 1H), 4.86 —120.66. (s, 2H), 4.01 (s, 3H) 1H NMR (400 MHz, CDC13) 6 7.86 4 7.79 (m, 2H), 7.62 4 7.56 (m, 2H), 6.89 (dd, J ESIMS m/z 19F NMR (3 76 MHz, =18.1, 11.5 Hz, 1H), 352 CDC13) 6 .71 (dd, J= 11.6, ([M+H]+) —144.04 1.4 Hz, 1H), 5.58 (dd,J=18.1,1.4 Hz, 1H), 4.71 (s, 2H), 1H NMR (400 MHz, DMSO-dé) 6 7.91 (t, 19F NMR (376 MHz, ESIMS m/z J = 7.8 Hz, 1H), 7.74 IR (thin film) 3367, DMSO-dé) 6 3 81 (d, J = 11.6 Hz, 1H), 1735, 1608 cm'l. ([M+H]+) -59.9, -115.6, 7.62 (d, J = 8.1 Hz, -116.3 1H), 7.20 (d, J = 21.4 Hz, 2H), 3.87 (s, 3H) 1H NMR (400 MHz, CDC13) 6 7.91 (t, J = 8 Hz, 1H), 7.32 (dd, J IR (thin film) 3425 (m), ESIMS m/z = 8, 1.5 Hz, 1H), 3297 (m), 3245 (s), 3158 302 7.26 (dd, J = 12, 1.5 (m), 3008 (w), 2956 (w), ([M+H]+) Hz, 1H), 5.40 (br s, 1729 (m), 1637 (m) cm'1 2H), 3.99 (s, 3H), 3.93 (s, 3H), 3.15 (s, 1H NMR (400 MHz, CDC13) 6 7.93 (ddd, J = 8.2, 1.6, 0.7 Hz, 2H), 7.65 4 7.54 (m, ESIMS m/z 2H), 6.90 (ddd, J = 19F NMR (376 MHz, 297 18.1, 11.6, 0.5 Hz, CDC13) 6 ([M+H]+1) 1H),5.71(dd,J= -143.86 11.5, 1.4 Hz, 1H), .58(dd,J=18.1, 1.4 Hz, 1H), 4.71 (s, 19F NMR (376 MHz, 1H NMR (400 MHz, CDC13) 6 CDC13) 6 7.55 4 7.45 —61.22, —61.25, (m, 2H), 7.25 (dd, J -135.48, —135.54, ESIMS m/z =18.3,11.6 Hz, 1H), —135.57, —135.62, 361 ' .85 (dd, J= 11.7, —137.62, -137.66, 1.2 Hz, 1H), 5.64 -137.68, 9, (dd, J = 18.4, 1.2 Hz, —137.71,-137.73, 1H), 5.11 (s, 2H) 5, -137.78, -137.87, -137.95 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (300 MHz, IR (thin film) 3317 (s), ESIMS m/z DMSO-dé) 6 7.86 (m, 3199 (s), 2955 (w), 2924 291 2H), 7.61 (m, 2H), (w), 2870 (w), 2256 (w), ([M+H]+) 6.93 (br s, 2H), 4.33 1721 (m), 1634 (m) cm'1 (s, 1H) 1H NMR (400 MHz, DMSO-d6) 6 8.22 (t, J = 10.7 Hz, 1H), 19F NMR (376 MHz, ESIMS m/z IR (thin film) 2979, 1715 8.17 (d, J= 12.3 Hz, g) 6 -59.9, - 332 cm'1 ([M+H]+) 1H), 7.90 (dd, J = 115.3, 213,134 Hz, 1H), -116.7 7.56 (d, J= 44.0 Hz, 3H 3.77 , s, 3H 1H NMR (400 MHz, DMSO-dg) 6 7.87 (t, ESIMS m/z J = 7.5 Hz, 1H), 7.72 ([M+H]+) 4 7.66 (m, 1H), 7.58 (s, 2H), 3.90 (s, 3H), 3.78 (s, 3H) 1H NMR (400 MHz, DMSO-d6) 6 13.71 19F NMR (376 MHz, ESIMS m/z (s, 1H), 8.05 (dd, J = DMSO-dg) 6 411204 310 9.9, 1.4 Hz, 1H), 7.86 (d, J = 29.9 Hz), — +) (dd, J = 8.0, 1.5 Hz, 138.35 (d, J = 29.6 1H), 7.75 4 7.81 (m, Hz) 1H 7.09 , s, 2H 1H NMR (400 MHz, DMSO-dg) 6 7.95 ESIMS m/z (dd, 1H), 7.77 (dd, 19F NMR (3 76 MHz, ([M+H]+) 1H), 7.52 (dd, 1H), DMSO-dg) 6 495.03 7.32 (s, 1H), 6.81 (s, 2H), 3.89 (s, 3H) 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.77 (m, 341 2H), 7.55 (m, 2H), ([M-HT) 7.1 (s, 1H), 4.84 (br s, 2H), 4.00 (s, 3H) 1H NMR (400 MHz, ESIMS m/z é) 6 6.85 4 6.77 (m, 3H), 7.79 ([M+3H]+) (m, 1H) 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 11.14 (s, CDC13) 6 ESIMS m/z 1H), 7.63 (dd, J = , -99.20, ([M+H]+) 8.6, 4.9 Hz, 1H), 7.27 4117.70, -117.74, (dd, J = 7.5, 5.7 Hz, -117.79, -117.83, 1H), 5.21 (s, 2H) -134.64, 4134.71 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 5 7.97 (dd, J CDC13) 5 ESIMS m/z = 10.6, 6.3 Hz, 1H), -61.69, -61.73, 367 7.39 (dd, J= 10.5, ([M+H]+) —119.19,—119.22, .6 Hz, 1H), 7.30 (d, —119.24, —119.27, J = 1.2 Hz, 1H), 4.91 —120.01,—120.06 (s, 2H), 4.02 (s, 3H) 1H NMR (400 MHz, IR (thin film) 3400 (s), ESIMS m/z DMSO-d6) 5 7.68 4 3300 (s), 3200 (m), 1711 309 7.78 (m, 3H), 6.76 (W), 1630 (m) cm"1 ([M+H]+) (br s, 2H), 4.66 (s, 1H NMR (400 MHz, DMSO-dé) 5 13.67 (br s, 1H), 7.73 (dd,J IR (thin film) 3327 (s), ESIMS m/z = 11, 1.5 Hz, 1H), 2941 (w), 1718 (w), 390 7.68 (dd, J = 8.5, 1.5 1629 (m), 1603 (m)cm'1 ([M+H]+) Hz, 1H), 7.63 (t, J = 8.5 Hz, 1H), 7.33 (br s, 2H), 3.76 (s, 3H) 1H NMR (400 MHz, DMSO-dg) 5 7.82 (dd, J= 8.3, 7.3 Hz, ESIMS m/z 1H), 7.60 (dd, J = 19F NMR (3 76 MHz, ([M+H]+) 9.8, 2.0 Hz, 1H), 7.40 g) 5 108.20 (dd, J = 8.3, 2.0 Hz, 1H), 7.16 (s, 2H), 3.87 (s, 3H) 1H NMR (400 MHz, DMSO-dé) 5 13.6 (s, ESIMS m/z 1H), 7.87 (m, 1H), 7.72 (m, 1H), 7.57 ([M+H]+) (m,1H), 7.23 (s, 1H), 6.18 s, 2H 1H NMR (400 MHz, DMSO-dg) 5 13.63 ESIMS m/z (s, 1H), 7.89 (t, J = 7.5 Hz, 1H), 7.69 ([M+H]+) (t, J = 7.0 Hz, 1H), 7.48 (s, 2H), 3.79 (s, 3H) 1H NMR (400 MHz, DMSO-dé) 5 13.57 (s, 1H), 7.95 (dd, J = ESIMS m/z 8.2, 6.8 Hz, 1H), 7.74 19F NMR (3 76 MHz, ([M+H]+) (dd, J = 9.8, 2.0 Hz, DMSO-dg) 5 —95.12 1H), 7.53 (dd, J = 8.3, 2.0 Hz, 1H), 7.28 [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel 13C or 19F NMR 13C NMR (101 MHz, 1H NMR (400 MHz, DMSO-d6) 6 166.57, DMSO-dg) 6 7.64 (d, ESIMS m/z , 150.28, J = 8.5 Hz, 2H), 7.40 342 138.92,131.35, ([M+H]+) (d, J= 8.5 Hz, 2H), ,121.35, 6.47 (s, 2H), 2.07 (s, 115.84,109.91, 99.49, 14.91 1H NMR (400 MHz, CDC13) 6 7.80 (dd, J = 8.1, 6.5 Hz, 1H), ESIMS m/z 19F NMR (376 MHz, 7.19 (dd, J = 8.6, 1.9 421 CDC13) 6 ([M+H]+) Hz, 1H), 7.00 (dd, J -93.62 = 81,19 Hz, 1H), 4.86 (s, 2H), 3.96 (s, 3H 2.17 , s, 3H 1H NMR (400 MHz, DMSO-dg) 6 8.30 ESIMS m/z (dd, J = 9.8, 2.1 Hz, 344 1H), 8.22 (dd, J = ([M+H]+) 8.5, 2.2 Hz, 1H), 7.87 (m, 1H), 7.22 (s, 2H), 13C NMR (101 MHz, 1H NMR (400 MHz, CDC13) 6 , CDC13) 6 7.56 (d, J = ESIMS m/z 155.19,149.18, 8.5 Hz, 2H), 7.33 (d, 354 145.09, 138.57, J = 8.5 Hz, 2H), 4.84 ([M-HT) 131.42,131.00, (s, 2H), 3.96 (s, 3H), 122.60, 116.69, 2.15 (s, 3H) 113.59, 52.88, 14.65 1H NMR (400 MHz, IR (thin film) 3493 (s), CDC13) 6 7.68 (t, J = ESIMS m/z 3352 (s), 2943 (w), 2853 8 Hz, 1H), 7.50 4 (w), 1725 (m), 1602 (m) 7.58 (m, 2H), 5.40 -1 ([M+H]+) cm (br s, 2H), 4.00 (s, 3H), 3.94 (s, 3H) 13C NMR (101 MHz, 1H NMR (400 MHz, CDC13) 6 165.50, CDC13) 6 7.73 (d, J = 154.25, 149.37, ESIMS m/z 8.5 Hz, 2H), 7.58 (d, 145.36,144.19, J = 8.5 Hz, 2H), 4.90 ([M+H]+) 132.09,130.18, (s, 2H), 3.96 (s, 3H), 118.67,116.71, 2.16 (s, 3H) 114.01,112.06, 52.95, 14.58 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, IR (thin film) 3453 (m), CDC13) 5 7.69 (ddd, J 3302 (m), 3242 (s), 3170 ESIMS m/z = 9, 7, 2 Hz, 1H), (m), 2963 (w), 2852 (w), 320 7.27 (m, 1H), 5.42 2112 (w), 1732 (m), ([M+H]+) (br s, 2H), 4.00 (s, 1631 (m)cm'1 3H), 3.95 (s, 3H), 3.42 (s, 1H) 1H NMR (400 MHz, DMSO-dg) 5 7.88 ESIMS m/z (dd, J = 8.8, 1.3, 2H), 347 7.34 (t, J = 73.8, ([M+H]+) 1H), 7.31 (d, J = 8.9, 2H), 7.01 (br s, 2H), 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-dg) 5 13.22 CDC13) 5 ESIMS m/z (s, 1H), 8.02 4 7.94 -61.37, -61.41, 345 (m, 3H), 6.78 (dd, J 4114.17, 4114.20, ([M+H]+) = 17.7, 11.6 Hz, 1H), 4114.24, 4114.27, 6.56 (s, 2H), 5.65 4 -143.61 .52 (m, 2H) 1H NMR (400 MHz, DMSO-dg) 5 13.36 (s, 1H), 7.91 (dd, J= ESIMS m/z 8.0, 6.8 Hz, 1H), 7.35 19F NMR (3 76 MHz, ([M+H]+) (dd, J= 9.1,1.9 Hz, g) 5 495.45 1H), 7.10 (dd,J= 8.1, 1.9 Hz, 1H), 6.49 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 5 8.00 (m, 372 2H), 7.84 (m, 2H), ([M+H]+) 7.35 (br s, 2H), 3.11 (s, 3H) 1H NMR (400 MHz, DMSO-d6) 5 13.63 (s, 1H), 7.72 (ddd, J = 8.3, 5.7, 1.8 Hz, 1H), 7.51 (ddd, J= 8.6, 7.0, 1.8 Hz, 1H), 7.43 (s, 2H), 3.76 (s, 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 5 3.86 (s, 445 3H), 6.98 4 6.94 (m, ([M+2H]+) 3H), 7.89 4 7.85 (m, 1H NMR (300 MHz, ESIMS m/z DMSO-d6)8 7.76 4 363 7.56 (m, 2H), 7.22 (d, ([M-HT) J = 1.7, 1H), 6.84 (s, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR IR (thin film)778.80, 822.34, 879.66, 973.14, 0, 1026.12, 1H NMR (400 MHz, 1056.64, 1120.85, DMSO-dg) 6 13.63 1214.80, 1276.30, (s, 1H), 7.83 (dd, J = ESIMS m/z 1389.19, 8, 11.8, 2.1 Hz, 1H), 1459.47, 1496.89, 7.75 (t, J = 72.0 Hz, ([M+H]+) 1519.03, 1592.79, 1H), 7.52 (d, J= 8.0 1627.42, 1720.12, Hz, 1H), 7.50 4 7.14 1769.38, 2535.30, (m, 1H), 6.99 (s, 2H) 3199.10, 3386.23, 3501.86 cm‘1 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.93 (m, 359 1H), 7.34 (m, 2H), ([M+H]+) 7.22 (s, 1H), 4.85 (s, 2H), 4.00 (s, 3H) 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 7.51 (d, 19F NMR (376 MHz, 329 J = 8.6 Hz, 2H), 7.33 ([M+H]+) DMSO-dé) 6 -82.20 4 7.14 (m, 3H), 6.61 (s, 2H), 2.09 (s, 3H) 1H NMR (300 MHz, ESIMS m/z CDC13) 6 8.32 (d, J = 326 9.0, 2H), 8.13 (dd, J ([M+H]+) = 9.0, 1.4, 2H), 5.02 (s, 2H), 4.01 (s, 3H) 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.80 (d, 423 2H), 7.42 (d, 2H), ([M+H]+) 5.35 (s, 2H), 3.98 (s, 1H NMR (400 MHz, ESIMS m/z CDC13) 6 8.19 (m, 340 2H), 7.55 (m, 2H), ([M+H]+) 5.35 (br s, 2H), 4.01 s, 3H 3.92 , s, 3H 1H NMR (400 MHz, DMSO-d6) 6 8.13 4 7.90 (m, 2H), 7.80 ESIMS m/z (dd, J = 8.0, 1.6 Hz, 19F NMR (376 MHz, 299 1H), 7.46 (s, 2H), DMSO-dé) 6 4111.51 ([M+H]+) 6.66 (dd, J= 17.6, 11.5 Hz, 1H), 5.63 4 .43 (m, 2H), 3.82 (s, 1H NMR (400 MHz, IR (thin film) 3502 (m), CDC13) 6 7.62 (ddd, J ESIMS m/z 3378 (s), 2953 (w), 1739 = 9, 6, 2 Hz, 1H), (m), 1726 (m), 1617 (m) 7.16 (ddd, J = 9, 6.5, cm'1 ([M+H]+) 2 Hz, 1H), 4.97 (br s, 2H), 3.96 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 7.54 (dd, J 19F NMR (376 MHz, ESIMS m/z = 8.2, 4.9 Hz, 1H), CDC13) 6 7.12 (dd, J = 7.4, 5.8 -99.80, -99.84, ([M-HT) Hz, 1H), 5.44 (s, 2H), 4, -116.89 3.97 (s, 3H) 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 7.69 (dd, J CDC13) 6 ESIMS m/z = 8.3, 6.3 Hz, 1H), -100.82, 422 7.54 (dd, J = 9.5, 5.0 -100.86, ([M+H]+) Hz, 1H), 5.43 (s, 2H), —118.25, 4.00 (s, 3H), 3.94 (s, -118.29 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.35 (d, 330 2H), 7.47 (d, 2H), +) 7.39 (s, 2H), 3.78 (s, IR (thin film) , 786.89, 824.69, 939.95, 1032.81, 1120.09, 1H NMR (400 MHz, 1153.46, 1204.33, CDC13) 6 7.37 (ddd, J 1225.97, 1263.98, ESIMS m/z = 8.7, 7.0, 2.3 Hz, 1424.87, 1375.02, 3 83 1H), 7.19 4 7.11 (m, 1445.12,1481.84, ([M+H]+) 1H), 6.61 (t, J= 72.5 1518.14,1615.72, Hz, 1H), 4.99 (s, 2H), 1739.13, 2959.84, 3.98 (s, 3H) 3195.90, 3378.30, 3486.20 cm‘1 13C NMR (101 MHz, CDC13) 6 164.70, 161.50,158.98, IR (thin film) 758.08, 152.94, 152.84, 793.58, 824.98, 856.60, 1H NMR (400 MHz, 147.17, 144.60, 919.36, , 1014.89, CDC13) 6 7.61 (t, J = 143.59, 143.54, 1053.05, 1122.86, 8.3 Hz, 1H), 7.04 140.22, 140.08, 1162.89, 1203.20, ESIMS m/z (ddd, J = 8.6, 2.3, 0.8 137.91,137.78, 1241.89, 9, 366 Hz, 1H), 6.96 (dd, J 132.54, 132.53, 1369.66, 1439.27, +) = 10.5, 2.3 Hz, 1H), 132.49, , 1480.39, 6 6.55 (t, J = 73.0 Hz, 119.71,119.60, 1611.65,1732.10, 1H), 4.96 (s, 2H), , 118.02, 2957.77, 3021.70, 3.97 (s, 3H) 115.77,115.75, 3389.26, 3506.76 cm‘1 115.42,115.40, 115.37,112.81, 107.69, 107.43, 53.07 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 13.7 (s, 367 1H), 7.75 (d, 2H), ([M+H]+) 7.49 (d, 2H), 7.01 (s, [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR IR (thin film) 861.93, 886.37, 962.21, 984.56, 1035.97, 1010.25, 1113.86, 6, 1H NMR (400 MHz, 1173.58,1222.01, CDC13) 8 8.35 4 8.29 1251.67, 3, ESIMS m/z (m, 2H), 7.19 4 7.10 1438.95, 1397.88, 326 (m, 2H), 6.56 (t, J = 1514.76, 1486.42, ([M+H]+) 72 Hz, 1H), 5.33 (s, 7, 1568.01, 3H), 4.02 (s, 3H), 1608.88, 1645.71, 3.92 (s, 3H) 1735.15, 2693.18, 2860.72, 2960.57, 3179.92, 3320.20, 2 cm‘1 1H NMR (400 MHz, CDC13) 8 8.08 (dd, J = 8.6, 1.5 Hz, 2H), 7.78 4 7.71 (m, 2H), ESIMS m/z 6.89 (dd, J= 18.1, 19F NMR (376 MHz, 298 11.6 Hz, 1H), 5.73 CDC13) 8 ([M+H]+) (dd, J =11.6, 1.4 Hz, -143.64 1H), 5.59 (dd, J = 181,14 Hz, 1H), 4.78 (s, 2H), 3.93 (s, 1H NMR (400 MHz, DMSO-dg) 8 7.55 (t, ESIMS m/z J = 8 Hz, 1H), 7.50 IR (thin film) 3468 (s), 309 (dd, J= 11, 1.5 Hz, 1621 (rn)cm'1 ([M+H]+) 1H), 7.46 (dd, J = 8, 1.5 Hz, 1H), 6.47 (br 1H NMR (300 MHz, ESIMS m/z CDC13) 8 7.48 4 7.40 393 (m, 1H), 7.33 4 7.26 ([M-HT) (m, 1H), 4.99 (br s, 2H), 3.98 (s, 3H) 1H NMR (400 MHz, DMSO-dg) 8 13.33 ESIMS m/z (s, 1H), 7.70 4 7.52 19F NMR (376 MHz, 345 (m, 2H), 7.45 (dd, J DMSO-dg) 8 - ([M+H]+) = 8.4, 2.0 Hz, 1H), . 7.06 (s, 1H), 6.52 (s, 1H NMR (400 MHz, CDC13) 8 7.46 (d, J = ESIMS m/z 8.7 Hz, 2H), 7.18 (d, 19F NMR (376 MHz, 341 J = 8.7 Hz, 2H), 6.53 CDC13) 8 ([M-HT) (t, J= 73.8 Hz, 1H), -80.81 4.84 (s, 2H), 3.95 (s, 3H), 2.16 (s, 3H) ation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 7.61 (dd, J = 8.2, 7.1 Hz, 1H), ESIMS m/z 19F NMR (376 MHz, 7.27 4 7.25 (m, 1H), 375 CDC13) 6 7.13 (ddd, J = 8.2, ([M+H]+) —107.04 1.9, 0.6 Hz, 1H), 4.86 (s, 2H), 3.96 (s, 3H), 2.17 (s, 3H) 1H NMR (400 MHz, DMSO-dé) 6 13.63 (s, 1H), 8.07 (dd, J = ESIMS m/z 10.3, 1.9 Hz, 1H), 19F NMR (3 76 MHz, 344 8.01 (dd, J = 8.5, 2.0 ([M+H]+) DMSO-dg) 6 -108.44 Hz, 1H), 7.81 (dd,J = 8.4, 7.2 Hz, 1H), 7.40 (s, 2H), 3.76 (s, 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.78 4 379 7.58 (m, 2H), 7.26 (d, ([M+H]+) J = 1.6, 1H), 6.95 (s, 2H), 3.89 (s, 3H) 1H NMR (400 MHz, é) 6 7.91 4 ESIMS m/z 7.80 (m, 2H), 7.75 4 19F NMR (376 MHz, 7.67 (m, 1H), 7.35 (s, ([M+H]+) DMSO-dg) 6 -107.88 1H), 6.86 (s, 2H), 13C NMR (101 MHz, 1H NMR (400 MHz, DMSO-d6) 6 166.56, DMSO-dg) 6 7.81 (d, ESIMS m/z , 150.28, J= 8.3 Hz, 2H), 7.25 3 89 139.23, 136.72, ([M+H]+) (d, J= 8.3 Hz, 2H), 131.38,115.78, 6.46 (s, 2H), 2.07 (s, 109.86, 94.48, 48.57, 14.90 1H NMR (400 MHz, DMSO-dg) 6 13.13 (s, 1H), 7.82 (dd, J = 8.5, 0.9 Hz, 2H), 7.74 ESIMS m/z 4 7.66 (m, 2H), 6.75 19F NMR (376 MHz, 336 (dd, J =17.8,11.5 DMSO-dg) 6 -145.77 ([M-HT) Hz, 1H), 6.42 (s, 2H), .56 (dd, J= 12.8, 1.3 Hz, 1H), 5.52 (dd, J= 6.5, 1.3 Hz, 1H NMR (300 MHz, ESIMS m/z CDC13) 6 7.81 (m, 407 2H), 7.67 (m, 2H), ([M+H]+) 4.91 (br s, 2H), 3.99 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-dg) 6 7.83 DMSO-dg) 6 - ESIMS m/z (dd, J = 9.6, 5.1 Hz, 101.95, ([M+H]+) 1H), 7.66 (dd, J = 0, 8.5, 6.3 Hz, 1H), 7.42 -117.68, (s, 2H), 3.75 (s, 3H) 711772 1H NMR (400 MHz, IR (thin film) 3500 (w), CDC13) 6 7.58 (t, J = 3472 (m), 3370 (s), 3229 ESIMS m/z 8 Hz, 1H), 7.39 (dd, J (m), 2955 (w), 2921 (w), 323 = 8, 1.5 Hz, 1H), 2850 (w), 1728 (m), 7.28 (m, 1H), 4.94 1622 (m) cm'1 (br s, 2H), 3.97 (s, 3H), 3.17 (s, 1H) 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 7.65 (ddd, J CDC13) 6 ESIMS m/z = 9.0, 7.1, 2.1 Hz, —129.82 (s), 374 1H), 7.40 7 7.31 (m, —129.88 (s), 1H), 5.45 (s, 2H), 3 (s), 4.01 (s, 3H), 3.95 (s, —135.79 (s) 1H NMR (400 MHz, DMSO-d6) 6 8.01 7 8.09 (m, 2H), 7.82 7 7.90 (m, 2H), 7.16 (s, ESIMS m/z 1H), 6.65 (dd, J = 17.7, 11.5 Hz, 1H), .61 (dd, J= 17.7, 1.3 Hz, 1H), 5.49 (dd, J = 11.4, 1.3 Hz, 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 13.7 (s, 393 1H), 7.78 (m, 3H), 7.23 (s, 1H), 6.83 (s,2H) 1H NMR (400 MHz, ESIMS m/z DMSO-d6) 6 13.69 363 (s, 1H), 7.67 (d, 2H) 7.55 (d, 2H), 6.99 (s, 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.93 (d, 287 2H), 7.60 (d, 2H), 7.16 (s, 1H), 4.89 (s, 2H), 4.05 (s, 3H) 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 7.89 (dd, J CDC13) 6 ESIMS m/z = 9.2, 6.7 Hz, 1H), -112.80, 376 7.36 (dd, J= 10.2, -112.84, .5 Hz, 1H), 7.25 (d, -119.98, J = 1.2 Hz, 1H), 4.86 7120.02 (s, 2H), 4.01 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel . 13C or 19F NMR 1H NMR (400 MHz, DMSO-d6) 5 8.25 (d, 19F NMR (376 MHz, ESIMS m/z IR (thin film) 3334, 1722 J= 8.1 Hz, 2H), 8.17 DMSO) 5 —1 336 cm ([M+H]+) (d, J = 11.9 Hz, 2H), -60.0, —114.7, 7.95 (t, J = 7.9 Hz, -116.5 1H NMR (400 MHz, IR (thin film) 3481 (m), ESIMS m/z CDC13) 5 7.55 47.62 3338 (s), 3185 (w), 3096 425 (m, 2H), 7.21 (d, J = (w), 2963 (w), 1727 (m), ([M+H]+) 2 Hz, 1H), 4.86 (br s, 1608 (m) cm'1 2H), 3.99 (s, 3H) 1H NMR (400 MHz, ESIMS m/z CDC13) 5 8.45 (d, 285 2H), 7.75 (s, 2H), ([M+H]+) 5.84 (s, 2H), 4.03 (s, 3H), 3.96 (s, 3H) 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-dé) 5 7.90 ESIMS m/z DMSO-dg) 5 -96.56, (dd, J = 10.2, 5.1 Hz, 41 1 -96.61, ([M+H]+) 1H), 7.73 (dd, J = —115.34, 8.6, 6.6 Hz, 1H), 7.26 -115.38 (s, 1H), 6.83 (s, 2H) 1H NMR (400 MHz, CDC13) 5 7.88 (dd, J IR (thin film) 3437 (w), = 9, 7 Hz, 1H), 7.73 ESIMS m/z 3352 (s), 3197 (w), 2949 (ddd, J = 9, 2, 1 Hz, (w), 1737 (m), 1614 (m) 1H), 7.55 (dt, J= —1 ([M+H]+) cm 8.5, 2 Hz, 1H), 4.94 (br s, 2H), 4.00 (s, 1H NMR (400 MHz, IR (thin film) 3385 (s), CDC13) 5 7.75 (d, J = ESIMS m/z 3242 (m), 2955 (w), 9.5 Hz, 2H), 7.57 (t, 2918 (w), 2856 (w), J = 7 Hz, 1H), 4.93 ([M+H]+) 1734 (m), 1622 (m) cm'1 (br s, 2H), 3.98 (s, 3H), 3.37 (s, 1H) 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 5 7.92 (d, J = 12.8 Hz, 3H), ([M+H]+) 7.01 (s, 2H) 1H NMR (400 MHz, ESIMS m/z CDC13) 5 7.98 4 7.83 324 (m, 1H), 7.72 (dd, J ([M+H]+) = 8.4, 6.6, 1H), 5.01 (s, 1H), 4.01 (s, 2H) [Annotation] l None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 13C NMR (101 MHz, 1H NMR (400 MHz, CDC13) 5 165.69, CDC13) 5 7.77 (d, J = ESIMS m/z 155.29,149.17, 8.5 Hz, 2H), 7.20 (d, 403 145.12,139.19, J = 8.5 Hz, 2H), 4.83 ([M+H]+) 137.39,131.16, (s, 2H), 3.95 (s, 3H), 116.65,113.57, 2.15 (s, 3H) 94.30, 52.86, 14.64 1H NMR (400 MHz, DMSO-d6) 5 8.26 (d, J = 8.2 Hz, 1H), 8.17 19F NMR (376 MHz, ESIMS m/z (d, J = 12.2 Hz, 1H), g) 5 5999 342 7.94 (t, J = 7.9 Hz, (d, J = 12.2 Hz), ([M+H]+) 1H), 7.35 (s, 2H), —115.72 (d, J= 12.2 6.67 (dd, J= 17.7, Hz) 11.5 Hz, 1H), 5.52 (m, 2H), 3.85 (s, 3H) 1H NMR (400 MHz, CDC13) 5 7.81 (m, ESIMS m/z 2H), 7.60 (m, 2H), 7.40 (d, J= 2 Hz, ([M+H]+) 2H), 4.91 (br s, 2H), 3.99 s, 3H 1H NMR (400 MHz, CDC13) 5 7.84 4 7.75 (m, 2H), 7.73 4 7.66 (m, 2H), 6.89 (dd, J ESIMS m/z 19F NMR (376 MHz, =18.1, 11.6 Hz, 1H), 399 CDC13) 5 .71 (dd, J= 11.6, ([M+H]+) -143.98 1.4 Hz, 1H), 5.58 (dd, J= 18.1, 1.4 Hz, 1H), 4.71 (s, 2H), IR (thin film) 698.09, 825.26, 869.29, 998.15, 1H NMR (400 MHz, 1025.59, 1050.34, DMSO-dg) 5 18.40 1098.57, 1129.54, (s, 1H), 12.39 (t, J= 1167.58, 1246.97, ESIMS m/z 8.4 Hz, 1H), 12.16 (t, 1386.17,1435.44, 351 J = 72.0 Hz, 1H), 1481.70,1515.78, ([M+H]+) 12.05 (dd,J= 11.1, 1590.42, 1628.74, 2.4 Hz, 1H), 11.94 1720.93, 2535.45, (dd, J = 8.5, 2.4 Hz, 3198.03, 3327.36, 1H), 11.75 (s, 2H) 3469.29 cm‘1 1H NMR (400 MHz, IR (thin film) 3325 (s), ESIMS m/z DMSO-dg) 5 7.81 (br 3193 (s), 1625 (m) 429 1, J = 7 Hz, 1H), 7.20 cm'1 ([M+H]+) (br t, J = 7 Hz, 1H), 6.64 (br s, 2H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 8.06 4 306 7.94 (m, 4H), 7.12 ([M+H]+) (br s, 2H), 3.89 (s, 1H NMR (300 MHz, DMSO-dg) 6 7.90 ESIMS m/z (dd, J = 8.8, 1.3, 2H), 7.34 (t, J = 73.8, ([M+H]+) 1H), 7.30 (d, J = 8.8, 19F NMR (376 MHz, 1H NMR (400 MHz, CDC13) 6 CDC13) 6 7.50 (dd, J , -61.85, ESIMS m/z = 9.8, 5.3 Hz, 1H), —116.72, -116.76, 3 85 7.42 (dd, J = 8.9, 5.6 ([M+H]+) -116.81, -116.86, Hz, 1H), 5.03 (s, 2H), —119.30, —119.33, 3.99 (s, 3H) 5, -119.38, —137.15,—137.24 1H NMR (400 MHz, DMSO-d6) 6 13.75 (s, 1H), 7.95 (dd, J = ESIMS m/z 8.1, 6.7 Hz, 1H), 7.48 19F NMR (3 76 MHz, ([M+H]+) (dd, J= 9.1,1.9 Hz, DMSO-dg) 6 —95.25 1H), 7.25 (dd, J = 8.1, 1.9 Hz, 1H), 7.04 s, 2H 1H NMR (400 MHz, DMSO-dg) 6 7.90 (t, 19F NMR (376 MHz, ESIMS m/z IR (thin film) 3359, J = 7.9 Hz, 2H), 7.75 DMSO-dg) 6 -59.9, - 369 619 cm'l (d, J = 11.8 Hz, 2H), 115.3, ([M+H]+) 7.64 (d, J = 8.1 Hz, -116.6 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.74 4 381 7.65 (m, 1H), 7.43 4 ([M-HT) 7.32 (m, 1H), 7.00 1H NMR (400 MHz, 19F NMR (376 MHz, CDC13) 6 7.84 (dd, J CDC13) 6 ESIMS m/z = 10.6, 5.9 Hz, 1H), -61.73, -61.76, 364 7.39 (dd, J = 9.8, 5.6 ([M+H]+) —117.59, -117.64, Hz, 1H), 5.46 (s, 2H), —120.18,—120.21, 4.01 (s, 3H), 3.96 (s, —120.23, —120.26 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 7.77 (t, 385 J = 7.2, 1H), 7.63 (t, ([M+H]+) J = 7.0, 1H), 7.25 (s, 2H), 3.88 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 11.46 (s, 1H), 8.05 4 7.98 (m, 2H), 7.84 4 7.75 (m, ESIMS m/z 2H), 7.26 (ddd, J = 19F NMR (376 MHz, 284 18.4, 11.7, 1.4 Hz, CDC13) 6 ([M+H]+) 1H), 5.85 (dd, J = 4140.74 11.7, 1.4 Hz, 1H), .63 (dd, J = 18.4, 1.4 Hz, 1H), 5.06 (s, 1H NMR (400 MHz, CDC13) 6 7.53 (dd, J = 7.9, 7.3 Hz, 1H), ESIMS m/z 19F NMR (376 MHz, 7.22 (ddd, J = 7.3, 319 CDC13) 6 +) 6.7, 1.5 Hz, 2H), 4.87 4110.01 (s, 2H), 3.96 (s, 3H), 3.35 (s, 1H), 2.17 (s, IR (thin film) 751.85, 792.16, 879.37, 933.73, 1013.05,1094.15, 1H NMR (400 MHz, 1058.41,1117.03, CDC13) 6 7.86 4 7.68 ESIMS m/z 1200.23, 1247.75, (m, 2H), 7.36 4 7.29 1267.53, 1375.51, (m, 1H), 6.60 (t, J = ([M+H]+) 1432.34, 1476.69, 73.3 Hz, 1H), 4.95 (s, 1516.02,1611.65, 2H), 4.00 (s, 3H) 1725.02, 2961.33, 3378.00, 3505.09 cm‘1 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 13.72 ([M+H]+) (s, 1H), 7.61 (m, 5H), 1H NMR (400 MHz, IR (thin film) 3486 (m), ESIMS m/z DMSO-dg) 6 7.72 (m, 3378 (s), 3225 (s), 2940 306 1H), 7.46 (m, 1H), (w), 1768 (w), 1719 (w), ([M+H]+) 7.11 (br s, 2H), 4.80 1625 1 (s, 1H), 3.79 (m, 3H) 13C NMR (101 MHz, CDC13) 6 165.33, 1H NMR (400 MHz, 164.23,161.59, 152.85, 149.49, CDC13) 6 7.78 4 7.61 ESIMS m/z 145.46, 133.27, (m, 1H), 7.42 4 7.29 318 125.88, , (m, 2H), 4.92 (s, 2H), ([M-HT) ,116.64, 3.97 (s, 3H), 2.17 (s, 114.32,113.80, 53.01, 14.55; 19F NMR (376 MHz, CDC13) 6 -105.97 [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (300 MHz, ESIMS m/z DMSO-dg) 6 8.07 310 (dd, J = 8.1, 7.0, 1H), ([M+H]+) 7.96 4 7.85 (m, 2H), 7.08 s, 2H 1H NMR (400 MHz, DMSO-dg) 6 7.99 IR (thin film) 3462 (s), ESIMS m/z (dd, J = 8, 7 Hz, 1H), 3194 (s), 1610 (m) 41 1 7.68 (dd, J= 10,1 0111'1 ([M+H]+) Hz, 1H), 7.53 (dt, J = 9, 1.5 Hz, 1H), 6.39 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.75 (m, 387 2H), 7.63 (m, 2H), ([M-HT) 7.08 (s, 1H), 4.87 (br s, 2H 4.00 , s, 3H 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.60 (m, 407 3H), 7.39 (s, 1H), ([M+H]+) 5.53 (s, 2H), 4.04 (s, 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 7.90 (m, 342 1H), 7.59 (t, J = 6.8 ([M+H]+) Hz, 1H), 7.25 (s, 2H), 3.87 s, 3H 1H NMR (400 MHz, CDC13) 6 7.73 (t, J = 19F NMR (400 MHz, ESIMS m/z 7.7 Hz, 1H), 7.32 (t, CDC13) 6 349 ([M]+) J= 8.9 Hz, 2H), 5.15 -61.4, 4113.3 (s, 2H), 2.23 (s, 3H) 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 6.90 4 3 83 6.70 (br s, 3H), 7.88 ([M+2H]+) (d, J = 8.96 Hz, 1H) 1H NMR (400 MHz, DMSO-dg) 6 7.75 ESIMS m/z (dd, J = 10, 2 Hz, IR (thin film) 3467 (s), 365 1H), 7.60 (dd, J = 8, 1609 (m) cm'1 ([M+H]+) 2Hz, 1H), 7.52 (t, J = 8 Hz, 1H), 6.55 (br s, 1H NMR (400 MHz, g) 6 3.83 (s, 3H), 5.38 4 5.58 (m, ESIMS m/z 2H), 6.65 (dd, J = 3 82 17.6, 11.5 Hz, 1H), ([M+H]+) 6.98 4 7.65 (m, 2H), 7.86 (d, J = 8.5 Hz, 2H), 8.03 (d, J = 8.5 H 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 7.92 (m, 3H), 7.17 (s, 2H), ([M+H]+) 3.90 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 6 7.29(d, ESIMS m/z 2H), 7.56 (d, 2H), .37 (s,2H), 4.02 (s, ([M+H]+) 3H), 3.93 (s, 3H) 3.18 s,1H 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 13.75 369 (s, 1H), 7.77 (m, 1H), ) 7.64 (m, 1H), 7.16 (s, 1H NMR (400 MHz, ESIMS m/z g) 6 7.84 (m, 329 2H), 7.68 (m, 2H), ([M+H]+) 7.25 (s, 1H), 6.72 (br s, 2H) 1H NMR (400 MHz, g) 6 7.84 IR (thin film) 3470 (s), ESIMS m/z (dd, J= 10, 1.5 Hz, 1716 (w), 1629 (m), 41 1 1H), 7.76 (dd, J = 8, 1606 (m) cm'1 ([M+H]+) 1.5 Hz, 1H), 7.33 (t, J= 8 Hz, 1H), 6.61 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.75 (d, 3 81 2H), 7.32 (d, 2H), ([M+H]+) 5.40 (s, 2H), 4.02 (s, 1H NMR (400 MHz, DMSO-dg) 6 8.11 4 ESIMS m/z 7.90 (m, 2H), 7.82 19F NMR (376 MHz, 356 (dd, J = 8.3, 7.2 Hz, DMSO-dé) 6 -108.34 +) 1H), 7.67 4 7.39 (m, 2H), 3.91 (s, 3H), 3.75 s, 3H 1H NMR (400 MHz, DMSO-d6) 6 13.69 ESIMS m/z (s, 1H), 7.91 (t, J = 353 7.5 Hz, 1H), 7.71 (t, ([M+H]+) J = 7.2 Hz, 1H), 7.30 (d, J= 1.7 Hz, 1H), 6.93 s, 2H 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 6 13.79 409 (s, 1H), 7.87 (d,2H), ([M+H]+) 7.42 (d, 2H), 7.01 (s,2H) 1H-NMR(400 MHz, DMSO-d6) 6 6.91 (br s, 2H), 7.26 (t, J = ESIMS m/z 53.88 Hz, 1H), 7.45 4 337 7.47 (m, 1H), 7.68 [(M+3H)+] (dd, J = 5.60, 10.64 Hz, 1H), 7.87 (dd, J = 5.88, 10.74 Hz, [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, CDC13) 8 8.34 4 8.24 ESIMS m/z (m, 2H), 7.49 4 7.38 ([M+H]+) (m, 3H), 5.33 (s, 2H), 4.02 (s, 3H), 3.92 (s, 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.41 (m, 367 2H), 6.91 (t, 1H), ([M+H]+) 5.02 (s, 2H), 4.00 (s, 1H NMR (400 MHz, CDC13) 8 7.95 (m, ESIMS m/z 1H), 7.26 (s, 1H), 7.08 (m, 1H), 6.61 ([M+H]+) (t, 1H), 4.91 (s, 2H), 4.02 s, 3H 1H NMR(400 MHz, ESIMS m/z DMSO-dg) 8 6.99 (br 354 s, 2H), 7.28 (t, J = ([M+2H]+) 54.00 Hz, 1H), 7.60- 7.70 (m, 2H) 1H NMR (400 MHz, CDC13) 8 7.73 (m, ESIMS m/z 1H), 7.76 (s, 1H), 6.95 (m, 1H), 4.85 (s, ([M+H]+) 2H), 4.01 (s, 3H), 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 8 7.82 (m, ([M+H]+) 2H), 7.55 4 7.44 (m, 3H), 6.88 (s, 2H) 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 8 7.82 (m, 281 2H), 7.55 4 7.44 (m, ([M+H]+) 3H), 6.88 (s, 2H), 3.98 s, 3H 1H NMR (400 MHz, DMSO-dé) 8 7.68 19F NMR (376 MHz, ESIMS m/z (dq, J= 7.9, 1.3 Hz, DMSO-dé) 8 - 299 1H), 7.58 (m, 2H), 112.86, ([M+H]+) 7.33 (m, 1H), 7.06 (s, -140.06 2H 3.89 , s, 3H 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.26 (m, 331 1H), 6.99 (m, 1H), ([M+H]+) 4.95 (s, 2H), 3.99 (s, 3H 2.32 , s, 3H 1H NMR (400 MHz, CDC13) 8 7.62 (m, ESIMS m/z 1H), 6.97 (m, 1H), .45 (s, 2H), 4.01 ([M+H]+) (s, 3H), 3.95 (s, 3H), 2.30 (s, 3H) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, DMSO-dg) 8 7.46 (m, 2H), 7.17 (s, 2H), 3.87 s, 3H 1H NMR(400 MHz, CD3OD) 8 4.89 (s, 2H), 7.02 (t, J = ESIMS m/z 72.80 Hz, 1H), 7.33 (dd, J = 6.40, 10.80 ([M+H]+) Hz, 1H), 7.80 (dd, J = 7.20, 11.00 Hz, IH NMR(400 MHz, DMSO-dg) 8 2.28 (s, 3H), 6.80 (br s, 2H), ESIMS m/z 7.25 (s, 1H), 7.31 ([M+2H]+) (dd, J = 6.32, 11.58 Hz, 1H), 7.65 (dd,J = 6.60, 10.36 Hz, 1H), 13.54 (br s, 1H) 1H NMR (400 MHz, ESIMS m/z DMSO-d6) 8 7.50 4 IR (thin film) 3376, 317 7.32 (m, 3H), 7.13 (s, 1737,1615 cm‘1 ([M+H]+) 2H), 3.87 (d, J= 2.3 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 8 8.13 4 339 8.04 (m, 2H), 8.02 4 +) 7.92 (m, 2H), 7.08 (s, 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-d6) 8 7.86 4 DMSO-dg) 8 4132.72 7.70 (m, 1H), 7.41 (dd, J = 21.4, 8.8 ESIMS m/z (tdd, J= 9.5, 7.3, 2.1 HZ)? ([M+H]+) Hz, 3H), 6.66 (dd, J 9 (dd, J= = 17.6, 11.5 Hz, 1H), 21.0, 8.7 Hz), .63 4 5.38 (m, 2H), -161.04 (t, J = 21.3 3.82 (s, 3H) Hz) 1H NMR (400 MHz, DMSO-dg) 8 8.08 (br ESIMS m/z s, 1H), 7.99 (m, 2H), 7.87 (m, 2H), 7.47 ([M+H]+) (br s, 1H), 7.03 (br s, 2H 3.89 , s, 3H 1H NMR (400 MHz, CDC13) 8 7.77 (m, ESIMS m/z 1H), 7.39 (m, 1H), 6.89 +) (t, 1H), 5.49 (s, 2H), 4.02 (s, 3H), 3.97 (s, 3H) 1H NMR(400 MHz, ESIMS m/z DMSO-dg) 8 2.30 (s, 3H), 6.41 (br s, 2H), [(M+H)+] 7.28—7.45 (m, 2H) [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H-NMR(400 MHz, CDgOD) 6 4.90 (s, 2H), 7.01 (t, J = ESIMS m/z 72.72 Hz, 1H), 7.29 [(M+H)+] (dd, J = 6.52, 9.76 Hz, 1H), 7.55 (dd,J = 6.36, 10.52 Hz, 1H NMR (300 MHz, CDC13) 6 7.75 4 7.81 IR (thin film) 3480 (s), ESIMS m/z (m, 2H), 7.67 (t, J = 3345 (s), 3186 (w), 2961 331 8 Hz, 1H), 7.14 (s, (W), 1717 (s), 1614 (s) cm'1 ([M+H]+) 1H), 6.94 (t, J = 55 Hz, 1H), 4.90 (br s, 1H NMR (400 MHz, 19F NMR (376 MHz, DMSO-d6) 6 7.86 4 DMSO-dg) 6 4132.72 7.70 (m, 1H), 7.41 (dd, J = 21.4, 8.8 ESIMS m/z (tdd, J= 9.5, 7.3, 2.1 HZ)? ([M+H]+) Hz, 3H), 6.66 (dd, J 4135.29 (dd, J= = 17.6, 11.5 Hz, 1H), 21.0, 8.7 Hz), .63 4 5.38 (m, 2H), -161.04 (t, J = 21.3 3.82 (s, 3H) Hz) 19F NMR (376 MHz, 1H NMR (400 MHz, CDC13) 6 ESIMS m/z CDC13) 6 7.54(m, 4111.33, -111.38, 342 1H), , 1H), ([M+H]+) 4115.73, 4115.77, .06(s, 2H), 4.00(s, 3, -115.89, -136.82, —136.92 1H NMR (400 MHz, ESIMS m/z CDC13) 6 7.36 (n, J = 317 5.8, 1.7 Hz, 1H), 7.29 ([M+H]+) 4 7.15 (m, 2H), 4.97 1H NMR (400 MHz, 19F NMR (400 MHz, IR (thin film) 3498, ESIMS m/z CDC13) 6 7.57 4 7.39 CDC13) 6 3374,1731,1621,1520, 335 (m, 1H), 7.09 4 6.96 1232 cm‘1 ([M+H]+) -114.6, 4131.0, (m, 1H), 4.96 (s, 2H), 4137.5, 41420 4.00 (s, 3H) 1H-NMR(400 MHz, DMSO-dé) 6 2.28 (s, 3H), 3.75 (s, 3H), ESIMS m/z 7.24 (dd, J = 6.24, .98 Hz, 1H), 7.36 ([M+H]+) (br s, 2H), 7.58 (dd, J = 6.32, 10.20 Hz, 1H NMR (400 MHz, 19F NMR (376 MHz, ESIMS m/z CDC13) 6 8.03 (m, CDC13) 6 324 1H), 7.42 (m, 1H), ([M+H]+) 5, 7.32 (s, 1H), 4.96 (s, -119.08 2H), 4.03 (s, 3H) [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H-NMR(400 MHz, g) 8 3.76 (s, 3H), 7.24 (t, J = ESIMS m/z 54.00 Hz, 1H), 7.43 ([M+H]+) (br s, 2H), 7.59 (dd, J = 5.60, 10.00 Hz, 1H), 7.78 (dd, J = .60, 10.40 Hz, 1H) 1H NMR (400 MHz, DMSO-dg) 8 7.87 (m, 2H), 7.35 (m, 2H), 7.01 (s, 2H), 3.89 (s, 1H NMR (400 MHz, CDC13) 8 7.91(m, ESIMS m/z 1H), 7.38 (m, 1H), 7.35 ([M+H]+) (s, 1H), 6.90 (t, 1H), 4.90(s, 2H), 4.03 s, 3H 1H NMR (400 MHz, ESIMS m/z DMSO-dG) 8 7.55 (m, 299 2H), 7.39 4 7.30 (m, ([M+H]+) 2H), 7.05 (s, 2H), 3.86 (s, 3H) 1H NMR (400 MHz, ESIMS m/z CDC13) 8 8.29 4 8.21 246 (m, 2H), 7.48 (m, ([M+H]+) 3H), 5.66 (s, 2H), 4.06 (s, 3H) 1H NMR (400 MHz, ESIMS m/z CDC13) 8 7.88 (m, 321 1H), 7.42 (m, 1H), ([M+H]+) 5.51 (s, 2H), 4.03 (s, 3H), 3.98 (s, 3H) 1H NMR (300 MHz, CDC13) 8 8.01 (br d, IR (thin film) 3496 (s), ESIMS m/z J = 8 Hz, 2H), 7.61 3377 (s), 2954 (W), 1726 331 (br d, J = 8 Hz, 2H), (s), 1611 (s) cm'1 ([M+H]+) 6.70 (t, J= 56 Hz, 1H), 4.93 (br s, 2H), 3.99 s, 3H 1H NMR (400 MHz, ESIMS m/z DMSO-dg) 8 7.26 (m, 317 2H), 7.02 (s, 2H), ([M+H]+) 2.35 (d, J = 1.7 Hz, 1H NMR (300 MHz, ESIMS m/z g) 8 7.23 (m, 329 ([M-H]' 2H), 7.08 (s, 2H), ) 3.85 (s, 3H), 2.33 (d, J = 2.1 Hz, 3H) —194— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel 13C or 19F NMR 1H NMR (400 MHz, ESIMS m/z DMSO-dé) 6 13.59 299 (s, 1H), 7.60 (m, 2H), ([M+Hl+) 7.42 (m, 1H), 6.94 (s, 2H), 2.30 (s, 3H) 1H NMR (400 MHz, DMSO-dé) 6 7.57 ESIMS m/z (dd, J = 14.6, 9.7 Hz, 3 13 2H), 7.42 (t, J = 8.1 ([M+Hl+) Hz, 1H), 7.02 (s, 2H), 3.89 (s, 3H), 2.30 (s, 1H NMR (400 MHz, DMSO-dg) 6 7.87 (dd,J= 11.2, 1.6 Hz, ESIMS m/z 1H), 7.80 4 7.68 (m, 3 l l 2H), 6.76 (dd, J= ([M+Hl+) 17.6, 11.7 Hz, 1H), 6.50 (br s, 2H), 5.57 (dd, J = 7.3, 0.9 Hz, 1H 5.53 , s, 1H 1H NMR (300 MHz, CDC13) 6 7.83 4 7.77 (m, 1H), 7.76 4 7.69 (m, 1H), 7.48 (dd, J = 8.4, 7.6 Hz, 1H), ESIMS m/z 6.89 (dd, J= 18.0, 11.7 Hz, 1H), 5.73 ([M+Hl+) (dd,J=11.5, 1.4 Hz, 1H), 5.59 (dd, J= 18.1,1.4 Hz, 1H), 4.78 (br s, 2H), 3.93 1H NMR (400 MHz, CDC13) 6 7.80 (d, J = .4 Hz, 1H), 7.72 (d, J= 8.4 Hz, 1H), 7.48 (m, 1H), 4.93 (s, a Mass spectrometry data are electrospray ionization mass spectrometry (ESIMS) unless otherwise noted. b All 1H NMR data measured in CDC13 at 400 MHz unless otherwise noted.
Examples of Herbicidal Activities ] Herbicidal evaluations were made Visually on a scale of 0 to 100 where 0 represents no actiVity and 100 represents te plant death. The data are displayed as indich in Table A. -l95- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Table A: Percent Control Rating Conversion Table Rating.
Control -A 95-100 fl85-94 84 I. 60-74 -D1 45-59 -44 -C) 0-29 Example A. Evaluation of Postemergent Herbicidal Activity Post-Emergent Test 1: Seeds of test species were obtained from commercial suppliers and planted into a 13 centimeter (cm) er-round pot containing soil-less media mix (Metro-Mix 360®, Sun Gro ulture). Postemergence treatments were planted 8-12 days (d) prior to application and cultured in a greenhouse equipped with supplemental light sources to provide a 16 hour (h) photoperiod at 24—29 °C. All pots were surface irrigated.
[00356] A weighted , determined by the highest rate to be tested, of each compound was dissolved in 1.3 mL acetone-dimethyl sulfoxide (DMSO; 97:3, volume per volume (v/v)) and diluted with 4.1 mL water-isopropanol-crop oil concentrate :2, v/v/v) containing 0.02% Triton X-lSS to obtain concentrated stock solutions. Additional application rates were obtained by serial on of the high rate solution into a solution containing appropriate volume of 97:3 v/v mixture of e and DMSO and riate volume of an aqueous mixture of water, isopropyl l, crop oil concentrate (78:20:2, v/v/v) containing 0.02% Triton X-155.
Formulated compounds were applied using a DeVilbiss® compressed air sprayer at 2—4 pounds per square inche (psi). Following treatment, pots were ed to the greenhouse for the duration of the experiment. All pots were sub-irrigated as need to provide optimum growing conditions. All pots were fertilized one time per week by subirrigating with Peters Peat-Lite Special® fertilizer (2020). -l96- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel ] Phytotoxicity ratings were obtained 10 days after treatment postemergence applications. All tions were made visually on a scale of 0 to 100 Where 0 represents no activity and 100 represents complete plant death and is presented as indicated in Table A.
Some of the compounds tested, application rates ed, plant species tested, and results are given in Table 3. -l97- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Table 3. Post-Emergent Test I Herbicidal Activity on Key Broadleaf and Grass Weed as well as Crop Species Application Visual Growth Reduction (%) 14 Days After Application Compound Rate (kg AVEFA—!ECHCG HELAN IPOHE SETFA A A >D>D>D>D>D> I.—-C—nA—nA—-C—nF—nA >> —-A A —-A A —-E A >> t n—-A >D>D>D> -—nC-as C a A i I. > > n AMARE: redroot pigwseed nthus exus) AVEFA: wild oats (Avenafatua) ECHCG: barnyardgrass (Echinochloa crus-gallz') HELAN: sunflower (Helianthus ) IPOHE: ivyleaf morningglory (Ipomoea hederecea) SETFA: giant foxtail (Setarz'afaberz') kg ai/ha: kilograms active ingredient per hectare n/t: fiested -l98- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example B. Evaluation of Preemergent Herbicidal Activity Pre-Emergent Test 1: Seeds of test species were d into round plastic pots (5-inch diameter) containing sandy loam soil. After planting, all pots were sub-irrigated 16 h prior to compound application.
Compounds were dissolved in a 97:3 v/v mixture of acetone and DMSO and diluted to the appropriate concentration in a final application solution containing water, acetone, isopropanol, DMSO and Agri-dex (crop oil concentrate) in a 59:23:15:l.0: l .5 v/v ratio and 0.02% w/v (weight/volume) of Triton X-lSS to obtain the spray solution containing the t application rate. Additional application rates were obtained by serial dilution of the high rate solution with the above application solution.
Formulated nd (2.7 mL) was pipetted evenly over the soil e ed by incorporation with water (15 mL). Following treatment, pots were returned to the greenhouse for the duration of the experiment. The greenhouse was programmed for an imate 15 h photoperiod which was ined at about 23—290C during the day and 22—280C during the night. Nutrients and water were added on a regular basis through surface tion and supplemental lighting was provided with overhead metal halide 1000- Watt lamps as necessary.
Herbicidal effect ratings were obtained 14 days after treatment. All evaluations were made relative to appropriate controls on a scale of 0 to 100 where 0 represents no herbicidal effect and 100 represents plant death or lack of emergence from the soil and is presented as ted in Table A. Some of the compounds tested, application rates employed, plant species tested, and results are given in Table 4. -l99- ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Table 4. Pre-Eniergent Test 1 Herbicidal Activity on Key Broadleaf and Grass Weed as well as Crop Species Application Visual Growth ion (%) 14 Days After Application Compound Rate (kg AVEFA ECHCG HELAN IPOHE SETFA > >> >O>H10W > Q>>W>>W>OW>W>> aaa> 03C) > 03C) n/ >OUJD>D>UD>D>D>>D>D>>>>>>>> 03> >>D> i>>>w>>o>>w>>>m>>>>>> DJ > > > AMARE: redroot pigwseed (Amaranthus retroflexus) AVEFA: Wild oats (Avenafatua) ECHCG: barnyardgrass (Echinochloa crus-gallz') HELAN: sunflower (Helianthus ) IPOHE: ivyleaf morningglory (Ipomoea hederecea) SETFA: giant foxtail (Setarz'afaberz') kg ai/ha: kilograms active ingredient per hectare n/t: fiested [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Example C. Evaluation of Postemergent Herbicidal Activity Post-Emergent Test 11: Seeds or s of the desired test plant species were planted in Sun Gro Metro-Mix® 360 ng e, which typically has a pH of 6.0 to 6.8 and an c matter content of about 30 percent, in plastic pots with a surface area of 64 square centimeters. When required to ensure good germination and healthy plants, a ide treatment and/or other chemical or physical treatment was applied. The plants were grown for 7—21 d in a greenhouse with an approximate 15 h eriod which was maintained at about 23—29 c’C during the day and 22—28 c’C during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide lOOO-Watt lamps as necessary. The plants were employed for testing when they reached the first or second true leaf stage.
] A weighed amount, determined by the highest rate to be tested, of each test compound was placed in a 25 mL glass vial and was ved in 4 mL of a 97:3 v/v mixture of e and DMSO to obtain concentrated stock solutions. If the test compound did not dissolve readily, the e was warmed and/or sonicated. The concentrated stock solutions obtained were diluted with 20 mL of an aqueous mixture containing acetone, water, isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, and Triton® X-155 surfactant in a 48.5 :39: 10: 1 .5 : 1 .0:0.02 v/v ratio to obtain spray solutions containing the highest application rates. Additional application rates were obtained by serial dilution of 12 mL of the high rate solution into a solution containing 2 mL of 97:3 v/v mixture of acetone and DMSO and 10 mL of an aqueous mixture containing acetone, water, isopropyl alcohol, DMSO, Atplus 411F crop oil concentrate, and Triton X-155 surfactant in a 48.5:39:10:1.5:1.0:0.02 v/v ratio to obtain 1/2X, 1/4X, 1/8X and 1/16X rates ofthe high rate.
Compound requirements are based upon a 12 mL application volume at a rate of 187 liters per hectare (L/ha). Formulated compounds were applied to the plant material with an overhead Mandel track sprayer ed with 8002B nozzles calibrated to deliver 187 L/ha over an application area of 0.503 square meters at a spray height of 18 inches (43 cm) above the average plant canopy height. Control plants were sprayed in the same manner with the solvent blank.
[00366] The treated plants and control plants were placed in a greenhouse as described above and watered by subirrigation to prevent wash-off of the test compounds. After 14 d, the condition of the test plants as compared with that of the untreated plants was determined visu nd scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill and is ted as indicated in Table A. Some of the [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel compounds , application rates employed, plant species tested, and results are given in Table 5.
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GO G G v—1 V3 W :r mg ation] l None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MHOUV sogosmga Z<Amfl m.“I Ho¢< 995 Aflflmm -SN- AAXVV I'll.mA<mEU souogom Zmem 8x580 mm<§< <1: < I.< 35m; I0 .0 III.EHDm< "E -mozmg< San on o: on C: on o: on o: O o: O [\ o: on so: I 930mg mg of I'llN O '13 00 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel IllllllllllllMHOC/ sogosmga In <IIHIIIIIIHZ<Amfl 4.) Ho¢< IAflflmm < 995 -NMN- AAXVV IlllllllllllA<mEU souogom Zmem 8x580 mm<2< m 35m; EHDm< < < < -mozmg< 3mm o o: O o: O ow O [\ [\ [\ o: [\ o: [\ on 930mg 0 fi' fl. 00 v.2 as IIm mwfi ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MHOC/ sogosmga 23mm o <<E< Ho¢< IIIII.Aflflmm 00 995 -mfiN- AAXVV Ill.A<mEU souogom 2295 I 8x580 6232 (D 35m; UII” Im< Im< 53m? o CD<CII -mozmg< 03m 3% E o: E o: on ow O O O [\ o: o: 2 o: [\ o: so: 3 H vasomnu a 0 m N N 0 mg mm o: ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel MHOC/ o o Ill-IllllllE sogosmga Z<Amm < < HIIIIIHIII Ho¢< 995 I.OAmflmm -EN- AAXVV A<mEU < < < llllll souogom Zmem 8x580 mm<2< <1: 35m; <I<<II< EHDm< -mozmg< San on o: on o: O O [\ o: [\ o: [\ o: 930mg 32 com II 05 I [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel lllllllMHOUV sogosmga Z<Amfl Ho¢< 995 I'llllllllllAflflmm HEN- AAXVV I'llllllllllA<mEU souogom IIIIIIIII“Zmem 8x580 mm<§< (D 35m; 0' IIIIIIIHII.EHDm< -mozmg< San C: o: o: o: o: O o: O ow O O [\ [\ [\ o: [\ o: [\ o: on 930mg o: .2: fl. v—1 N W v—1 W V I03 [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel “I.<MHOUV sogosmga .0Z<Amfl Q <Imm Ho¢< 995 I'llllllllllAflflmm -SN- AAXVV Ill.<A<mEU souogom Ill.Zmem ”ll. 8x580 mm<§< (3 < < 35m; 0' EHDm< -mozmg< 3mm o: o: o: on o: O o: O ow O [\ [\ [\ o: on 0: on o: 930mg om NS .nN 55 IIIO'13 fimfi a: vs I [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Ill-IllMHOTV E: < sogosmga Z<Amfl II.<< Ho¢< O 995 Aflflmm -EN- AAXVV A<mEU < souogom Zmem 8x580 mm<2< m < I.< :25; EHDm< “ -mozmg< 3mm 0 o: 0: o: on 0: O o: O o: o o: O o: o: O [\ [\ [\ [\ [\ 930mg m: mm 02 EM m m '13 0 l\ \o Homfi [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel Ill-IllllllllMHOH> sogosmga Z<Amfl < all.
Ho¢< 995 Aflflmm -wfim- AAXVV A<mEU m m m M souogom Zmem m < 8x580 mm<2< m 35m; <I I< I'llll<EHDm< -mozmg< 3mm on o: 0: 0 on on 0: on 0: on 0: on V so: v—1 930mg mm o: II 2: : a: [Annotation] chanmel None set by l [Annotation] l MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MHOH> sogosmga Z<Amfl m U H. ll. Damiano Ho¢< 995 I00Aflflmm -SN- AAXVV A<mEU U U souogom Zmem 8x580 mm<§< (D < .IO 0 (DU-1CD 35m; UI EHDm< -mozmg< 3mm on o: 0 ow O O [\ [\ o: [\ o: on 930mg 0 [\ m Ln —1 5: mw [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MHOC/ OO< sogosmga Z<Amfl Ho¢< 995 Aflflmm -ONN- AAXVV ImA<mEU m <<C <<C<C m 2295 m I!van <<C<C 8x580 6232 < < 35m; QI<C<C U<m 53m? < LUQLT-l -mozmm< 03m 3% o on o: N2 O ow O o: o: O o: 0 O [\ [\ [\ [\ [\ [\ E E so: 3 vasomnu N: [\ [\ m2 N R m: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] l ed set by chanmel .-59> sogosmga 72qu < < <<E<.“ll.
Ho¢< 995 I.E95 ANN- AAXVV immo m m < souogom 2295 < 8x580 6232 < < 35m; 53m? m mI Illll -mozmm< 03m 3% E o: o: O O O O [\ o: o: [\ [\ [\ o: 2 o: [\ o: so: 3 H vasomnu m M: IIm m: m: o: 53 E [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MHOH> sogosmga Z<Amfl O O HIE. .Im < H< m Ho¢< (30 995 Aflflmm -NNN- AAXVV A<mEU souogom Ill.Zmem (DO om 8x580 mm<§< (3 (D C.) IO E {a E §< <<C U<E<C 35m; EHDm< O -mozmg< 3mm 0 o: 0 0 O O [\ o: ow 2 o: [\ o: [\ [\ o: 930mg N m 72 00 mg [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel Ill-IIIHII.MHOUV sogosmga Z<Amfl m <1: momma.“ll.
Ho¢< U m < 995 Aflflmm -mNN- AAXVV A<mEU m < souogom IllZmem I<I.< 8x580 mm<§< <1: <I < 35m; I< I< Ill.EHDm< -mozmg< San on 0: on 0: on 0: on 0: O [\ o: on C: on so: H 930mg w: NS NON mg mg [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Ill-IllllllllMHOTV sogosmga Z<Amfl < Ho¢< < 995 Aflflmm I!"H -VNN- AAXVV A<mEU m souogom Zmem < I 8x580 mm<2< 35m; EHDm< < III -mozmg< 3mm 3% E o: o: O o: O o: O O [\ [\ [\ o: 2 o: [\ [\ o: so: 3 H 930mg me b: a: 32 .92 v: w: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel MHOTV (30 Ila sogosmga Z<Amm m D H. C.) Ho¢< << mm 995 Ammmm -mNN- AAXVV A<mEU C.) < C.) souogom Zmem D U m 8x580 mm<§< < < QESKE‘SKN 35m; .IQ @362 3:33 ASEQENE 888: EHDm< Lu llQ $36386: figfifitfifivo 3.2%ka Efiwomosgbv $33223 SEES C883 Mom -mozmm< 3mm 3% on C: on 0: on 0: on 0: on 0: 29:8 39$ EBUSmE so: m3§2§§5 3 cougwa “85 58 @385 .oZ Emswrszoz? 252:3 8968 33:0 muotmswgfifl BE Hogomqsm 9:5 2E 32 mg wwfi v3 95% 3:9 mg ”EDEN ME<§< ”Zmem HA<mEU SEE HZ<AmE HEOE 68% “on m ”t: .n S [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN 380 <””m<ooomo 330 sogosmga mmNmrw U I U m I U m I m Q I m O III mm Ho¢< <m>MO QHIIIIOUOOOOO V683 mth E D>m0m oonm AAXVV a all -omm- was souogom <nEme so 8x580 OUEUM <<om<mfl bfi>uo< 35m; <mOHQ < I m U $205“on mmEflu “SE ga Sam 3% Hombfiméom 3 6859800 ON 2an n [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel N§<MN U U I“. mim (D sogosmga mmNmrw Im m Im m IO IIU U m m m Q O Ho¢< <m>MO (30 E D>m0m AAXVV I -hNN- souogom <mHMm m .mII 8x580 OUEUm <1: <<C I .< 35m; <mOHQ m m mmeU sogosmga O O O [\ [\ [\ 2 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel X2<MN III.”mD U U sogosmga mmNmrw 0 O Ho¢< <m>m0 (30 O O m H O O E D>m0m AAXVV Imm -wNN- souogom <nEme U O O 8x580 OUEUm m H.<C<C<C O O :25; <mOHQ m III O O mmeU H O O cosmozmovfl Sam 3% O [\ C: [\ C: 2 o: [\ o: o: E E o: on E 22:39 am mg of vow 32 mom IIIIIIIHH ma [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l N§<MN Ill0O IIm m m H m < sogosmga mmNMH ll0O I!ll0O o U a (D (D H Ho¢< <m>MO O (DIOQ E D>m0m < AAXVV OmH<< -mNN- souogom <mHMm (DO 8x580 OUEUm I 35m; <mOHQ O LLII mmeU sogosmga O O O O [\ [\ [\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] l Unmarked set by chanmel N§<MN IO IIm IIm IIO lU m l < O sogosmga mmNMH O LLLULU Ho¢< <m>MO O (DUO E D>m0m AAXVV -omN- souogom <mHMm U Q<C<C<C LT-‘QLT-l 8x580 OUEUm QLJI.0I Lumen 35m; <mOHQ mmeU U sogosmga O O 0 O O [\ [\ [\ [\ [\ 22:39 IINO O [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN I< IIO lI< lI< l< < I O < sogosmga mmNMH Lu Q O m O O {DOLL} Ho¢< <m>MO (3 0 III.0 O llI.0 IIllm0 HI 0 O (DUO E D>m0m AAXVV Imm OU< 4mm- m <mHMm OU< 8x580 OUEUm 4.) < < mI E: 35m; <mOHQ mmeU ILu sogosmga O O O O O [\ [\ [\ [\ [\ [\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN lO I!ll0m I I< < < O sogosmga mmNMH O 0 IImU IIIn<m m O O an D D Ho¢< <m>MO 00I. (3'00 E D>m0m m m Q AAXVV II. II.m -NmN- souogom <mHMm (30 .< H 8x580 OUEUm m H 35m; <mOHQ D D mmeU <<I.0I m m sogosmga O O o O o [\ [\ l\ [\ l\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN II<m IIll<m lI!m I!ll0O IU m l < < sogosmga mmNMH m 0 m m m m O Ho¢< <m>MO mth D>m0m <mm AAXVV m <mHMm DUI.(DILULL 8x580 OUEUm 35m; <mOHQ O mmeU sogosmga O 0 0 O O [\ [\ [\ [\ [\ 22:39 [\ GO V GO 0 v—1 G W GO V3 <1- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel ed set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel X2<MN D < sogosmga mmNmrw Ho¢< <m>m0 (D (3 IO (3 mNAmQ E D>m0m AAXVV -VmN- souogom <m a Ema E O O D O 8x580 OUEUM m m < m :25; <mOHQ O O D m mmeU < < < < < cosmozmovfl Sam 3% o O 0 O O O O [\ o: o: ow [\ [\ [\ o: o: [\ o: [\ o: on E 22:39 Nm m3 of IIIWN N N 00 IIHIHH mm [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN Im II< IO HI O O H sogosmga mmNMH (3 IOI'-(3 Ho¢< <m>MO O IO 0 E D>m0m AAXVV .I.< -mmN- souogom <mHMm U Ill-I 8x580 OUEUm m IE E 35m; <mOHQ (30 mmeU sogosmga o O O 0 l\ l\ [\ [\ [\ 22:39 0 q. 00 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN O Hal H sogosmga mmNMH O .I LL] Ho¢< <m>MO IIIII(30 I0 l0 O O O (DUO mth D>m0m U E (DILULU Lumen AAXVV .08. souogom <mHMm (DUO .0 E1 E: m 8x580 OUEUm O II LUCDU omen 35m; <mOHQ mmeU 00I< Illg 4.) E ©l<< sogosmga O 0 O O [\ [\ [\ [\ [\ 22:39 0 G m v—1 N N 0 [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel N§<MN I O Im HIO IIQ IO D H sogosmga mmNmrw (D Ho¢< <m>MO E D>m0m AAXVV a -th- souogom <nEme U 8x580 OUEUM “E a a E C.) :25; <mOHQ mmEflu cosmozmovfl O O [\ [\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN Im HI?IU D H sogosmga mmNMH <H Ho¢< <m>MO (D (3 IO (3 LUCDCD mth 4.; E D>m0m AAXVV -me- m <mHMm 8x580 OUEUm O O 0II< 35m; <mOHQ EU mml<©©mm mmeU <<CI<C<C I00 sogosmga O O O [\ [\ [\ [\ 22:39 v—1 N V3 V3 <1- W ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel N§<MN m m UUIUU sogosmga mmNMH O O O D U Q U D m Ho¢< <m>MO (D (3 IO (3 U m .I0 m LLOCD mth D>m0m U U AAXVV I<< <mm -mmN- souogom <mHMm l< <00 8x580 OUEUm <1: m 35m; <mOHQ mmeU <<C<C sogosmga 0 O 0 [\ [\ [\ [\ [\ 22:39 IIIOW [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l ation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN Q IO HIU I I sogosmga mmNMH I” Ho¢< <m>MO (30 (DUO E D>m0m LL] D AAXVV -ovm- souogom <mHMm (D 8x580 OUEUm 35m; <mOHQ Q mmeU 4.) CD<C<C sogosmga O O 0 [\ [\ [\ [\ 22:39 m fl' V3 G [\ [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel X§<mN IO IIU H H sogosmga mmNmrw m m IIIIM0 IIIHHHHHm llmU l Ho¢< <m>mo U U 0 o IIDO (30 mth D>m0m (D AAXVV -ZVN- souogom <5me Q H 8x580 Oomom O O II 35m; <mOHQ E! ll. mmeU sogosmga 0 O [\ [\ [\ mg II [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN ll00 I!IIMm IIIDm I!IIDO IO O I O O sogosmga mmNMH 0 O O (300 Ho¢< <m>MO (DO III(3'00 (300 EAIQ (300 E D>m0m AAXVV ll.0 -NVN- souogom <mHMm (300 8x580 OUEUm O (3'00 (300 35m; <mOHQ (300 mmeU (300 sogosmga O 0 0 0 O O [\ [\ [\ [\ [\ [\ 22:39 O [\ m V3 v—1 G [Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN O IO HID IO O I U U sogosmga mmNmrw (3'00.I-m Lu mam Lu Ho¢< <m>MO III (3'00 '00 mth D>m0m m LLLULU E m AAXVV HI Emu souogom <mHMm .0 I .m 8x580 OUEUm I! IDU 35m; <mOHQ fl (Dom mmeU .< l sogosmga O O O [\ E [\ 22:39 [\ [\ v—1 N [\ ation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN HIU IIm IIm H IQED sogosmga mmNMH m. " (DU (DLLCD Ho¢< <m>MO QI (3'00 (DUO E D>m0m AAXVV II“ souogom <mHMm 8x580 OUEUm 35m; <mOHQ U ULUQ mmeU sogosmga O 0 [\ E [\ [\ [\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN IQ IH< < I0 O mmNMH ll0O I!I.DO sogosmga (3'00I om LLLLCD Ho¢< <m>MO l0 IlO O IO O (3 IO (3 (300 (300 E D>m0m AAXVV ll.0 I IIM -mvm- m <mHMm I (300 8x580 OUEUm (30 35m; <mOHQ (300 mmeU I Om<< LLLUCD sogosmga O 0 O 0 [\ [\ E [\ E [\ 22:39 N O q. m GO [\ q. ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN l0Q IIIIIID H IO O I U m sogosmga mmNMH D m o m m Ho¢< <m>MO O 0 m IIIQmm IIIIll0mm o U O E D>m0m AAXVV souogom <mHMm Doll III 8x580 OUEUm II 35m; <mOHQ UII mmeU m sogosmga O O O O [\ [\ [\ [\ 22:39 [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN ll0m I!ll0m I m IO O I O sogosmga mmNMH ll0O I!ll0O m o O O m m O Ho¢< <m>MO (DUO E D>m0m AAXVV -DVN- souogom <mHMm HHIIIm 8x580 OUEUm .IIII”O (D 35m; <mOHQ mmeU m O sogosmga O O O O [\ [\ [\ [\ 22:39 [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel N§<MN (DO III sogosmga mmNmrw (D Lu III Ho¢< <m>MO (D (3 I (D (D E D>m0m AAXVV II -wvm- souogom <nEme D 0 Ilv I 8x580 OUEUM IIO H. 35m; <mOHQ wll O 33%-385 mmEflu (3 m0Ill-IO @Emmguzm 888: mEmQADV ENEENQMEQ $§m§> Q3353» ESIBQEIBWV Mom A33: cosmozmovfl Sam 3% on C: on 0: on 0: on 0: on 0: EKSNMNQV C253 Smfixgsfi ENIINMKQWV ENSEEBV 3603:: EmNV EBUSmE 3 mmfiwuhwbims wqtgm €00 @385 302% mmfiwsfio 355V swim 22%? 8: “new mmfimqo‘mqaoh 53:3 “ONES SS mg wwfi v3 95% 3:9 ”OUEUm ”mme0 H<mOHQ ”<m>m0 HEEm HD>MOm Hm<Nmrw ”N§<MN 68% “on m Ht: .n S [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Example D. Evaluation of Postemergent Herbicidal Activity in Wheat and Barley Post-Emergent Test 111. Seeds of the desired test plant species were planted in Sun Gro MetroMix® 306 ng mixture, which typically has a pH of 6.0 to 6.8 and an organic matter content of about 30 percent, in plastic pots with a surface area of 103.2 square centimeters (cmz). When required to ensure good germination and healthy plants, a fimgicide treatment and/or other chemical or physical treatment was applied. The plants were grown for 7-36 d in a greenhouse with an approximate 14 h photoperiod which was ined at about 18 CC during the day and 17 CC during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide lOOO-Watt lamps as necessary. The plants were employed for testing when they reached the second or third true leaf stage.
A weighed amount, determined by the highest rate to be , of each test compound was placed in a 25 mL glass vial and was dissolved in 4 mL of a 97:3 v/v e of e and DMSO to obtain concentrated stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or sonicated. The concentrated stock solutions ed were diluted with 20 mL of an aqueous e ning acetone, water, isopropyl alcohol, DMSO, Agri-Dex crop oil concentrate, and X-77 surfactant in a 48:39: 10: l .5 : l .5 :0.02 v/v ratio to obtain spray solutions containing the highest application rates. Additional application rates were obtained by serial dilution of 12 mL of the high rate solution into a solution ning 2 mL of 97:3 v/v mixture of e and DMSO and 10 mL of an aqueous mixture containing acetone, water, isopropyl alcohol, DMSO, Agri-Dex crop oil trate, and X-77 surfactant in a 48:39: 10: l .5:l.5:0.02 v/v ratio to obtain l/2X, l/4X, 1/8X and l/16X rates of the high rate. Compound requirements are based upon a 12 mL application volume at a rate of 187 liters per hectare (L/ha). Formulated nds were applied to the plant material with an overhead Mandel track sprayer equipped with 8002E nozzles ated to deliver 187 L/ha over an application area of 0.503 square meters at a spray height of 18 inches (43 cm) above the average plant canopy height. Control plants were sprayed in the same manner with the solvent blank.
The treated plants and l plants were placed in a ouse as described above and watered by subirrigation to prevent wash-off of the test nds. After 21 d, the condition of the test plants as compared with that of the untreated plants was determined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresnds to complete kill and is presented as indicated in Table A. —249— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel By ng the well-accepted probit analysis as described by J. Berkson in Journal oft/w American Statistical Society, 48, 565 (1953) and by D. Finney in “Probit Analysis” dge University Press (1952), herbicidal injury of a specific compound at various rates can be used to ate GRZO, GRSO, GRgo and GR90 values, which are defined as growth ion factors that correspond to the ive dose of herbicide ed to provide plant growth reduction (GR) of 20 percent, 50 percent, 80 percent and 90 percent, respectively. Probit analysis was applied to data collected from multiple dose rates of individual compounds utilizing the procedures explained in the following examples. The data for some of the dose rates and analysis of all of the dose rates are captured in the following tables.
Some of the compounds tested, application rates employed, plant species tested, and results are given in Tables 7 through ll.
[Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel noumommmxw Hum/w fish. nofloswum -EN- €386 knotmm Esmt/ 3055 mussomfioo $205“on >mmE< mo MCZOQ ~33ro [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel mmNMH fl -- mmmom -- m mm -- mmMmC/ oEA m m Ila mzmrflm oEA O O -- hm ms H>Hmm oEA O O -- noumommmxw H2<Em oEA O O -- oEA Hum/w fish. §m<m fl m < -- fl nofloswum mmH<2 oEA Ifiaafilafilfiaaa O O HHHIIIIIIHIIIIE O -- mm aalafilfiaaaa' -NmN- €386 meOA oEA O O -- oEA Esmt/ mmzaofi m m -- 30.0 UmEUM O O -- oEA mELOMm oEA O O -- oEA >mmE< oEA O O -- oEA >EOQ< oEA 0 O -- oEA 239$ 3 Ba. EMU 3H0 0% mm on 8M0 3M0 .Z mw [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel mmNMH mmmom O O mmMmC/ m I: m mzmrflm O O I: oEA H>Hmm O O I: O m noumommmxw H2<Em O O I: oEA O Q Hum/w fish. §m<m m < I: fl < < nofloswum mmH<2 O O IHIIIIIIHHIIIE I: oEA Iafiaalaalaaaa Q U -mmN- €386 meOA O O I: oEA m Q Esmt/ mmzaofi m m I: m; < < UmEUM m D I: S m m mELOMm O O I: oEA >mmE< O O I: oEA D U >EOQ< O O I: oEA Q U 239$ 3 Ba. on ommo 3H0 35 mm .Z m: [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel mmNMH mmmom U U H -- m m M: -- mmMmC/ m m -- mg no m m -- M mzmrflm U m -- 03A 03A U m -- M: H>Hmm Q U Nm m m noumommmxw H2<Em m m -- 03A m -- w: Hum/w fish. §m<m < < -- fl < < -- M nofloswum mmH<2 D D HIIIIIHIIHIHIE -- 2 aalaaaa Iaaaaafialaa O < HIIHIIIHIHIHIE < -- M -VmN- €386 meOA O O -- 03A 9: m m -- Nw Esmt/ mmzafi < < -- M < < -- M UmEUM D m -- N 03A U m -- m mHomm m m -- am mm U U -- 03A >mmE< m m -- no § m m -- on >EOQ< m 3 5 0 m -- M: 239$ 3 Ba. mm on 2mm ommmu 35 mm ommo ommmu So mm on 2mm ommmu .Z m: am [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l mmmom S -- -- m Q mmMmC/ -- ON Nw D U ON ow mzmrflm U U -- 5 92A O m 03A oEA H>Hmm O m -- 03A O O 92A m m mo oEA noumommmxw H2<Em O m -- o3 92A O O 03A oEA Hum/w awn. §m<m m m -- m fl < < N m nofloswum mmH<2 O O HHHIHIIIIIIHIE -- 03A Iaafifiaaaaiaaa 92A O O HIIIIIIIIIIIIE 03A oEA -mmN- €386 meOA O O -- 03A 92A O m mm oEA Esmt/ mmzafi m < -- M M m m 5 mm UmEUM m < -- N M NM 9 mHomm O O -- 03A 92A 0 m ww oEA >mmE< O m -- 03 O 92A O O 03A oEA >EOQ< O m -- .2: 0 92A 0 O 03A oEA 239$ 3 Ba. on 2mm OWMO 35 mm ONMU OWMO mm on OWMO owmo .Z 32 8N [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l mmNMH Q U m Q E -- mmmom U m m m D Q -- mEMm; m < IIIIIIIIIIIIIIE' N Q U D mv oEA < -- N mzmrflm M M oEA E oEA m -- oEA H>Hmm D D .n M NV m m S 3 D -- om noumommmxw Max/Ema < < o 3 < < v E in Hum/w fish. EMA/Vi < < M fl < < M M < -- M nofloswum mmH<2 m m Nb oEA IHlIHIIIIHHIH-iaa m < < o E wv -omN- €386 mmAOA m m Vm oEA m D 3 oEA O -- oEA Esmt/ mmzafi < < M fl m m M w < -- fl UmEUM m m m 3 < m v a D -- Nm mHOMm U m E in m m o wN D -- 3w >mmE< m m M o m m .n S ov >EOA< D D NN ww m m om Eu a: 239$ nous- 3Ba. as?» .n m on OWMO 3&0 on o: OWMO 3&0 on EMU 3&0 ,.Z Q: HIIIIIIIIIHIIIHE [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel mmNMH mmmom VN -- mmMmC/ m Q -- No mzmrflm O m -- K H>Hmm O m -- 03A mmxw H2<Em O O -- 03A Hum/w fish. §m<m < < -- v nofloswum mmH<2 D m -- v -th- €386 meOA m m -- mm.
Esmt/ mmzaofi U U -- NM UmEUM m -- 5 mELOMm O U -- 03A >mmE< O m -- o: >EOQ< m -- mm 239$ 3 Ba. on EMU OWMO .Z HHIIIIIHHHHIIIE' [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel '55!a2% sogosmga w AAXVV souogom 5255 -me- knotmm :25; UmEUM U 3055 m<A<O D E II mussomfioo MEMO m $205“on Sam mo qofiwmosmm‘a bfi>uo< ”w USS [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel :EEEEEEEEEE U m Illllllllllg IIIIIIIIIIII'MM IIHIHIEIHIH%IIlllllllllllflNMNV0:fl92A3E.nNon9&0 IIHIHHI m M -- M < -- oEA oEA -- m -- 9% sogosmga < -- S E¢< 3 AAXVV -- < -- M souogom -- < -- S 5255 < -mmN- :25; -- D -- N: < -- E -- < -- 5 qofiwmosmm‘a 3M0 owMO amo o: 2mm 3mm 6859800 [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel m -- sogosmga mm E¢< m AAXVV M souogom m 5255 :EEEEEEEEEE U M -oom- :25; qofiwmosmm‘a 6859800 [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel :EEEEEEEEEE m m sogosmga AAXVV souogom 5255 -EN- :25; qofiwmosmm‘a 6859800 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Table 9: Activity of Herbicidal Compounds in Wheat and Barley Application Visual Growth Reduction (%) 21 Days After Application Rate (g No. APESV KCHSC a1/ha)_ \10 b.) m \1O 030 WC) mamam??? mana??? DJ £11 DJ £11 \1o "UCD 030 CDC)5°? J; O\ mCDC) 03030 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Application Visual Growth Reduction (%) 21 Days After Application Compound Rate (g No. APESV KCHSC 211/ha)_ DJ £11 \1o CDCDC) CDCDC) DJ £11 moma??? 4; \l b.) m 03 \10 >>> >0 12U1 mooEUPEBILG‘J??? [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Application Visual Growth ion (%) 21 Days After Application Compound Rate (g No. APESV KCHSC 211/ha)_ IILN DJ £11 DJ CDCDC) 592656 \1 01 m \IUJ OU‘I >0 UJUJH moma??? L L N)—A DJ £11 \10 >03 >03 Q0 DJ U1 \10 mmm com CDC)5“? :5 >140 b.) 01 OD mm CDCDC)0???? \1 O\o [Annotation] chanmel None set by l ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Application Visual Growth Reduction (%) 21 Days After Application Compound Rate (g No. APESV KCHSC LOLSS SETVI HORSS TRZSS ai/ha) N 00 03 £11 \10 CDC) mo ° ——-— >140 --— CC C) "I CDCDC)55656 \lJ; b.) £11 \103 om CDC) DU 7 --— >140 --— DJ 0 CDC) CDC) “I. ° ——- >140 >140 --— [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel Application Visual Growth Reduction (%) 21 Days After Application Compound Rate (g APESV KCHSC LOLSS SETVI HORSS TRZSS —---E D [Annotation] chanmel None set by l [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Table 10: Activity of Herbicidal Compounds in Wheat and Barley Compd. Application Visual Gorowth Reduction (%) 21 days After Application -—n-nn—n -__——--- -—----—— -_----I-- -—---—-n -_-““_E -__——--- -—----_— -—mn -_-—--—- -—----_— -—--—nn— -——————- -—---— -—n-nn—n -:l_----_- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l Compd. Application Visual Gorowth Reduction (%) 21 days After ation -_----_- 108 _---n -—---—-n -__——--n 6-_- -_----_- ”2 _n-_- -_---n -__——--- -_----_- -_----_- -_”-_fl -_“-_nfl -__——--- -_----_- -_----_- -_--_-flfl -__——--- -—---—n— -_----_- 169um- -—---—nn - 149 “mu" -__——--- -—---—n— -_----_- “In“ -—--—nnn —__——--- -:l_-_- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by l Compd. Application Visual Gorowth Reduction (%) 21 days After Application N“ -TRZSS -_105 106 n—- “—__—n“ -—nnn-—fl -__——- -_"-_- -_n_- ”9 _“-_ -_”-_fl -__——- -_-I“n_- -_-131 - ”m"n -——nnnnn -__-—- -_---_- -_m“2 - “nil-“m -_”-_fl -__——- -_---_- -_--_n- n—n-nn—n -——“nnn -__-—- -_---_- -_---I-- m—-nnn—I. -—--—nnn -__-—- —_---_- u_”-_- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Table 11: Activity of Herbicidal Compounds in Wheat and Barley Application Visual Growth Reduction (%) 21 Days After Application Compound I." D -n ll NO 24 " ->140 100 El-—C F El-m n-—4 55 ALOMY: blackgrass curus myosuroides) APESV: bentgrass (Apera spica-venti) BROTE: downy brome (Bromas tectoram) HORSS: barley, including spring and winter (Hordeam valgare) TRZSS: wheat, including spring and winter (Triticam aestivam) LOLSS: ryegrass including, Italian ryegrass (Loliam maltifloram), rigid ryegrass (Loliam rigidam), annual ryegrass m maltifloram sabsp. Gaadini) PHAMI: lesser canary grass (Phalaris minor) SETVI: green foxtail (Setaria viridis) KCHSC: kochia (Kochia scoparia) LAMSS: including purple deadnettle (Lamiam parpaream) and henbit (Lamiam amplexicaule) GALAP: rs (Galiam aparine) VERPE: bird’s-eye ell (veronica persica) PAPRH: common poppy er rhoeas) SASKR: n thistle (Salsola iberica) VIOSCIRAgfanada thistle (Cirsium arvense). ild pansy (Viola tricolor), field Violet (Viola arvensis) [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel MATSS: scented mayweed (Matricarz'a chamomilla), pineappleweed (Matricarz'a matricarz'oz'des) STEME: common chickweed (Stellarz'a media). g ai/ha: grams active ient per e nt: Not tested GRzo: Growth reduction of 20% of plant growth GRso: Growth reduction of 50% of plant growth GRgo: Growth reduction of 80% of plant growth GR90: Growth ion of 90% of plant growth e E. Evaluation of Preemergent Herbicidal Activity Pre-Emergent Test 111. Seeds of test species were planted into square plastic pots (10 cm wide) containing sandy loam soil. After planting, all pots were sub-irrigated 16 h prior to compound application.
[00373] A weighed amount, determined by the highest rate to be tested, of each test compound was placed in a 25 mL glass vial and was ved in 4 mL of a 97:3 v/v mixture of acetone and DMSO to obtain concentrated stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or sonicated. The concentrated stock solutions obtained were d with 20 mL of an aqueous e containing water and 0.02% w/v (weight/volume) of Triton X-l55 to obtain spray solutions containing the highest application rates. Additional application rates were obtained by serial dilution of 12 mL of the high rate solution into a solution containing 2 mL of 97:3 v/v mixture of acetone and DMSO and 10 mL of an s mixture containing water and 0.02% w/v (weight/volume) of Triton X-l55 to obtain l/2X, l/4X, 1/8X and l/16X rates of the high rate. Compound requirements are based upon a 12 mL application volume at a rate of 187 liters per hectare (L/ha). Formulated compounds were applied to the soil surface with an overhead Mandel track sprayer equipped with 8002E nozzles ated to deliver 187 L/ha over an application area of 0.503 square meters. Control pots were sprayed in the same manner with the solvent blank.
The treated pots and control pots were placed in a greenhouse as described above and watered through surface irrigation. After 21 d, the condition of the test pots as compared with that of the untreated pots was ined visually and scored on a scale of 0 to 100 percent where 0 ponds to no herbicidal effect and 100 corresponds to plant death or lack ofiiergence from the soil and is presented as indicated in Table A. -27l- [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel By applying the well-accepted probit analysis as described by J. Berkson in l oft/w American Statistical Society, 48, 565 (1953) and by D. Finney in “Probit is” Cambridge University Press (1952), herbicidal injury of a specific compound at various rates can be used to calculate GRZO, GRSO, GRgo and GR90 , which are defined as growth reduction factors that correspond to the effective dose of herbicide required to provide plant growth reduction (GR) of 20 percent, 50 percent, 80 percent and 90 percent, respectively. Probit analysis was applied to data collected from multiple dose rates of individual compounds utilizing the procedures ned in the following examples. The data for some of the dose rates and analysis of all of the dose rates are captured in the following tables.
Some of the compounds tested, ation rates employed, plant species tested, and results are given in Table 12.
Table 12: Preemergent ty of idal Compounds in Wheat and Barley Application Visual Growth Reduction (%) 21 Days After Application Rate (g No. APESV LAMSS LOLSS SETVI HORSS TRZSS ai/ha) NO 35 > 03m m \1o > mm D1 C)5° j—A \] 10 IC)2° V\1o b.) N C)708 y—A O\ V\lO \] y—A 147 b.) 01 0 C) m ‘ DJ C) "11 O 00¢)a??? IIIIEIIIIIIHIIII \lO NDJ E £11 N )—A \l 0.) b.) V\lO V\l0 214 b.) 01 O C) C) \1o > m C) moma??? l N 00 S IIIEIIIIEIIIIIII\om V\lO V\lO N 00 V\lO V\lO [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] l None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel Application Visual Growth Reduction (%) 21 Days After Application Compound 1:33;; ——— s APESV: ass (Apera spica-ventz') LAMPU: purple deadnettle (Lamium purpureum) LOLSS: ryegrass including, Italian ryegrass (Lolium multz’florum), rigid ryegrass (Lolium rigidum), annual ryegrass (Lolium multz’florum subsp. m') SETVI: green foxtail (Setarl'a viridz's) HORSS: barley, including spring and winter (Hordeum vulgare) TRZSS: wheat, including spring and winter (Tritz’cum vum) g ai/ha: grams active ingredient per e nt: Not tested GRzo: Growth reduction of 20% of plant growth GR50: Growth reduction of 50% of plant growth GRgo: Growth reduction of 80% of plant growth GR90: Growth reduction of 90% of plant growth Example F. Evaluation of Postemergence Herbicidal Activity in Direct Seeded Rice Seeds or nutlets of the d test plant species were planted in a soil matrix prepared by mixing a loam soil (43 percent silt, 19 percent clay, and 38 percent sand, with a pH of about 8.1 and an organic matter content of about 1.5 percent) and river sand in an 80 to 20 ratDThe soil matrix was contained in plastic pots with a surface area of 139.7 cmz.
[Annotation] chanmel None set by chanmel ation] chanmel ionNone set by l [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel When required to ensure good ation and healthy , a fungicide treatment and/or other chemical or physical treatment was d. The plants were grown for 10—17 d in a greenhouse with an approximate 14-h photoperiod which was maintained at about 29 CC during the day and 26 CC during the night. Nutrients and water were added on a regular basis and supplemental lighting was provided with overhead metal halide att lamps as ary. The plants were employed for testing when they reached the second or third true leaf stage.
A weighed amount, determined by the highest rate to be tested, of each test compound was placed in 25 mL glass vials and dissolved in a volume of 97:3 v/v acetone— DMSO to obtain 12X stock solutions. If the test compound did not dissolve readily, the mixture was warmed and/or ted. The concentrated stock solutions were added to the spray solutions so that the final acetone and DMSO concentrations were 16.2% and 0.5%, respectively. Spray solutions were diluted to the riate final concentrations with the addition of 10 mL of an aqueous mixture of 1.5% (v/v) ex crop oil concentrate. The final spray solutions contained 1.25% (v/v) Agri-dex crop oil concentrate. Compound requirements are based upon a 12 mL application volume at a rate of 187 L/ha. Formulated compounds were applied to the plant material with an overhead Mandel track sprayer equipped with 8002E nozzles calibrated to deliver 187 L/ha over an application area of 0.503 square meters (m2) at a spray height of 18 inches (43 cm) above average plant canopy height.
Control plants were d in the same manner with the solvent blank.
The treated plants and control plants were placed in a greenhouse as described above and watered by sub-irrigation to prevent wash-off of the test compounds. After 20—22 d, the condition of the test plants, compared with that of the untreated plants, was determined visually and scored on a scale of 0 to 100 percent where 0 corresponds to no injury and 100 corresponds to complete kill and is presented as indicated in Table A.
By applying the well-accepted probit is as described by J. Berkson in Journal oft/w American Statistical Society, 48, 565 (1953) and by D. Finney in “Probit Analysis” Cambridge University Press (1952), herbicidal injury of a c compound at various rates can be used to calculate GRZO, GRSO, GRgo and GR90 values, which are defined as growth reduction factors that correspond to the effective dose of herbicide required to provide plant growth reduction (GR) of 20 percent, 50 percent, 80 percent and 90 percent, respectively. Probit analysis was applied to data collected from multiple dose rates of indivibl compounds ing the procedures explained in the ing examples. The —274— [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel data for some of the dose rates and analysis of all of the dose rates is captured in the following .
Some of the application rates and ratios employed, plant species tested, and results are given in Table 13.
[Annotation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel sogosmga Ho¢< 8E AAXVV 330m souofiuom E 8x580 mussomfioo 35m; II II IIII $205“on mo sogosmga 38an am: ”I“m bfi>uo< II IHII . 6859800 [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] l Unmarked set by chanmel [Annotation] l None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel sogosmga Ho¢< 995 -hbm- AAXVV souogom 8x580 35m; sogosmga 6859800 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l mm>m0 O IIIO o GO sogosmga XmmMm Ho¢< 995 330m AAXVV mmmm: souogom mmEUm II 8x580 mmeU 35m; mmém sogosmga IIIIIIH<<O<<< 6859800 :5 V" [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel ed set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel ation] chanmel Unmarked set by chanmel sogosmga Ho¢< AAXVV souogom 8x580 35m; sogosmga 38an 3: 6859800 ation] chanmel None set by chanmel [Annotation] l MigrationNone set by chanmel [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel sogosmga Ho¢< 995 -owN- AAXVV souogom 8x580 35m; sogosmga 6859800 [Annotation] chanmel None set by chanmel [Annotation] chanmel MigrationNone set by l [Annotation] chanmel Unmarked set by l [Annotation] chanmel None set by chanmel ation] chanmel MigrationNone set by chanmel [Annotation] chanmel Unmarked set by chanmel [Annotation] chanmel None set by chanmel [Annotation] chanmel ionNone set by chanmel [Annotation] chanmel Unmarked set by chanmel ESSQADV oonflmm 8: 35% “$3333.08 EEDSQSV sogosmga nEmQADV 35:88 mBBwqfimm Ho¢< oonmfia 58m 995 Egfiofifirfl Bozo» AflfiSEfi -SN- AAXVV Aflfiésfiw 60:2qu souogom EQEBSRSV 8x580 AENASENQEQ 3:333 “SEMQED 35m; oonmEm mowofiwqfimm EEEQDEMV Eqfixuofifirfl 888: Hogomfimfim 36:15 mmNfiowminEumngmguh A5332» 3532th Sm EBUSmE sogosmga 33%?qu @3932: @3932: gficms “€339 2:3QO $53 $32385 960$ noonm wEUEQE “982%quon 36:33 980: 355 6859800 H H 3:9 95% ”mmém ”mmeU ”mmEUm NmmMm mm>m0 H ”mmmm: ”Emom “oz 58% ”E m 6613

Claims (12)

WHAT IS CLAIMED IS:
1. A compound of Formula (I): wherein X is CH, CF, CCl, or CCH3; R1 is OR1′,wherein R1′ is H, C1-C8 alkyl, or C7-C10 arylalkyl; R2 is Cl; R3 and R4 are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 l, C3-C6 haloalkenyl, C3-C6 alkynyl, hydroxy, C1-C6 alkoxy, C1-C6 haloalkoxy, formyl, (C1-C3 alkyl)carbonyl, (C1-C3 haloalkyl)carbonyl, (C1-C6 alkoxy)carbonyl, or (C1-C6 alkyl)carbamyl; Ar is Ar1: wherein X1 is Br, I, ethynyl, CF2H, OCF2H, CN, CO2H, or NO2; with provisos that X1 is not CN, when X is CH; or an N-oxide or agriculturally acceptable salt thereof.
2. The compound of claim 1, n R1’ is H or C1-C8 alkyl.
3. The compound of claim 1 or 2, wherein R1’ is H or methyl.
4. The compound of claim 1, wherein R3 and R4 are each independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl. 1003086613
5. The compound of claim 4, wherein R3 and R4 are hydrogen.
6. The compound of claim 1, wherein X1 is Br, I, ethynyl, CF2H, OCF2H, or CN.
7. The compound of claim 1, n X1 is Br or I.
8. The compound of claim 1 or an N-oxide or agriculturally acceptable salt thereof, wherein the compound is: 6613 1003086613
9. A idal composition comprising the compound of any one of claims 1-8 or an N- oxide or agriculturally acceptable salt thereof, and an agriculturally acceptable adjuvant or carrier.
10. The composition of claim 9, further comprising at least one additional herbicidal compound.
11. The composition of claim 9 or 10, further comprising a safener.
12. A method for controlling undesirable vegetation, which comprises applying the nd of any one of claims 1-8, or the composition of any one of claims 9-11.
NZ712512A 2013-03-15 2014-03-12 4-amino-6-(4-substituted-phenyl)-picolinates and 6-amino-2-(4-substituted-phenyl)-pyrimidine-4-carboxylates and their use as herbicides NZ712512B2 (en)

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