GB2486717A - Substituted 4-aminopicolinate herbicides with safeners - Google Patents

Substituted 4-aminopicolinate herbicides with safeners Download PDF

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GB2486717A
GB2486717A GB1021899.8A GB201021899A GB2486717A GB 2486717 A GB2486717 A GB 2486717A GB 201021899 A GB201021899 A GB 201021899A GB 2486717 A GB2486717 A GB 2486717A
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optionally substituted
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alkyl
amino
co2me
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GB201021899D0 (en
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William Guy Whittingham
Christoph Weber
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Syngenta Ltd
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Syngenta Ltd
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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
    • A01N43/56—1,2-Diazoles; Hydrogenated 1,2-diazoles
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/48—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with two nitrogen atoms as the only ring hetero atoms
    • A01N43/60—1,4-Diazines; Hydrogenated 1,4-diazines
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
    • A01N47/08—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having one or more single bonds to nitrogen atoms
    • A01N47/10—Carbamic acid derivatives, i.e. containing the group —O—CO—N<; Thio analogues thereof
    • 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
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Dentistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Plant Pathology (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Pest Control & Pesticides (AREA)
  • Agronomy & Crop Science (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

The invention relates to compositions comprising for protecting crop plants from the harmful effects of substituted 4-aminopicoliniate herbicides of formula (I): wherein Q is a 3-10 membered ring system optionally containing up to 4 heteroatoms selected from O, S and N, the ring system optionally being substituted by up to 3 substituents R3, where R3 is halogen or other substituents ; A is halogen or other substituents; R1, R4 and R5 are hydrogen or substituents; X is hydrogen, halogen or other substituents; Y is halogen, optionally substituted C1-6alkyl, optionally substituted C2-6alkenyl or other substituents; Z is C(O)R6, C(S)R6 or C(=NR7)R8 where R6, R7 and R8 are hydrogen or substituents; and W is a bond or a linker group of formula (C1-3alkylene)0-1-L-(C1-3alkylene)0-1, wherein each alklylene group is optionally substituted and L is a direct single, double or triple bond, -S(O)0-2; -NH-, -N(C1-6alkyl)-, -O- or â C(O)O-; by providing a composition comprising a substituted 4-aminopicoliniate herbicide of formula (I) and a safener.(as listed in claim 1) as well as methods for protecting crop plants from the harmful effects of these herbicides. The most preferred safener is N-(2-methoxybenzoyl)-4-[(methylamino carbonyl)amino]benzenesulfonamide.

Description

I
CHEMICAL COMPOUNDS
The present invention relates to compositions comprising certain herbicidal 4-aminopicolinates and a safener and methods for protecting cultivated plants from the damaging effects of the herbicidal 4-aminopicolinates.
It is known that when herbicides are used to control the growth of undesired plants, there may be some damage to the cultivated plants. The amount of damage will depend on a number of factors but, in some cases, the cultivated plants can be protected from the effect of the herbicide by using a compound termed a safener.
As such, the present invention relates to a composition for protecting crop plants from the harmful effects of a 4-aminopicolinate herbicide of formula (I) (I) or a salt or N-oxide thereof, wherein: A is halogen, Cl -C6 alkyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, C1-C6 alkylthio optionally substituted by 1 to 3 groups R2, C6-C10 aryl optionally substituted by 1 to 3 groups R3 or a mono-or bicyclic beteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3; R' is hydrogen, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, Cl-C6 acyl optionally substituted by I to 3 groups R2, C6-C10 aryl optionally substituted by 1 to 3 groups R3, a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by I to 3 groups R3, Cl -C6 alkylsulphonyl optionally substituted by 1 to 3 groups 1(2, C2-C7 alkoxycarbonyl optionally substituted by 1 to 3 groups R2, aminocarbonyl, Cl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2 or diCl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2; R4 is hydrogen, cyano, nitro, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, Cl-C6 haloalkyl optionally substituted by 1 to 3 groups 1(2, C3-C6 cycloalkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups 1(2, C6-C10 aryl optionally substituted by 1 to 3 groups R3, a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups 1(3, Cl-GEl aeyl optionally substituted by 1 to 3 groups R2, Ci -C6 alkoxycarbonyl optionally substituted by 1 to 3 groups it2, carboxy, aminocarbonyl, Cl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2, diCi-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2 or diCl-C6 alkylphosphonyl optionally substituted by 1 to 3 groups it2; R5 is hydrogen, ChC6 alkyl optionally substituted by 1 to 3 groups 1(2 or C1-C6 haloalkyl; W is a direct bond or a linker group of the formula -(C1-C3 alkylene)-L-(C1-C3 alkylene)-wherein each alkylene group is optionally substituted by up to 3 groups 1(2, and t may each be independently 0 or 1, and L is a direct single, double or triple bond, -S(O)-wherein u isO, I or 2, -N(R")-wherein R" is H or C1-C6 alkyl, -0-or -C(O)O-; Q is a 3-10 membered ring system optionally containing up to 4 heteroatoms independently selected from 0, N or S. the ring system optionally substituted by up to X is hydrogen, halogen, cyano, nitro, bydroxyl, C1-C6 alkyl optionally substituted by I to 3 groups R2, Cl-C6 haloalkyl optionally substituted by i to 3 groups 2, C2-C6 alkenyl optionally substituted by 1 to 3 groups 2, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkoxy, C3-C8 cycloalkyl optionally substituted by ito 3 groups it2, C6-C10 aryl optionally substituted by 1 to 3 groups R3, a mono-or bieyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3, C1-C6 alkoxy optionally substituted by I to 3 groups R2, amino, Cl -C6 alkylamino optionally substituted by 1 to 3 groups R2, di(Cl-C6 alkyl)amino optionally substituted by 1 to 3 groups R2, Cl -C6 alkylthio optionally substituted by I to 3 groups R2, C1-C6 alkylsulphinyl optionally substituted by 1 to 3 groups R2, C1-C6 alkylsulphonyl optionally substituted by 1 to 3 groups R2, di(C 1 -C6 alkyl) phosphonyl or tri(C I -C6 alkyl)silyl; Y is halogen, cyano, nitro, hydroxyl, Cl -C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkoxy, C1-C6 alkoxy optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkoxy optionally substituted by 1 to 3 groups R2, C6-C10 aryl optionally substituted by 1 to 3 groups R3, a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3, amino, C1-C6 alkylamino, di(C1-C6 alkyl)amino, C1-C6 alkylthio, C1-C6 alkylsulphinyl, Cl-C6 alkylsulphonyl, di(C1-C6 alkyl) phosphonyl or tri(C1-C6 alkyl)silyl; Z is C(O)R6, C(S)R6 or C(NR7)R8; each R2 is independently halogen, hydroxyl, amino, C1-C3 alkylamino, di (Cl- C3alkyl)amino, carboxy, cyano, C1-C3 alkyl, Cl-C3 haloalkyl, C3-C6 cycloalkyl, Cl-C3 alkoxy, Cl-C3 haloalkoxy, Cl-C3 alkylthio, C1-C3 alkylsulphonyl, C2-C6 carboxyalkyl, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl or phenoxy; each ii is independently halogen, hydroxyl, nitro, amino, thiol, cyano, Cl -C3 alkyl, Cl -C3 haloalkyl, Cl -C3 alkoxy, Cl -C3 haloalkoxy, Cl -C3 alkylthio, Cl -C3 haloalkylthio, C2-C6 carboxyalkyl, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl, phenoxy, Cl -C3 alkylamino or di(C 1 -C3 alkyl)amino; R6 is hydrogen, hydroxyl, Cl-Cl 0 alkoxy optionally substituted by Cl-C6 alkoxy or phenyl, C3-C8 cycloalkoxy optionally substituted by Cl -C6 alkoxy or phenyl, Cl -C6 haloalkoxy, C2-C6 alkenyloxy, Cl -C6 alkylthio, amino, C1-C6 alkylamino or di(C 1 -C6 alkyl)amino; R7 is hydrogen, Cl -C6 alkyl, Cl -C6 alkoxy, C3-C8 cycloalkoxy, amino, Cl -C6 alkylamino or di(Cl-C6 alkyl)amino; R8 is hydrogen, C1-C6 alkoxy, C3-C8 cycloalkoxy, C1-C6 alkylthio, amino, C1-C6 alkylamino or di(Cl-C6 alkyl)amino.
wherein said composition comprises, in addition to the 4-aminopicolinate herbicide of formula (I), a safener selected from the group consisting of AD 67 (MON 4660), benoxacor, cloquintocet-mexyl, cyometrinil, the (Z) isomer or cyometrinil, cyprosulfamide (CAS RN 221667-31-8), dichiormid, fenchiorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, the R isomer of furilazole, isoxadifen-ethyl, mefenpyr- diethyl, oxabetrinil, naphthalic anhydride (CAS RN 8 1-84-5), N-isopropyl-4-(2- methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4) and N-(2-methoxybenzoyl)-4-[(methylaminoearbonyl)amino]benzenesulfonamide.
Accordingly, the present invention provides a composition for protecting crop plants from the harmful effects of a 4-aminopicolinate herbicide of formula (I) 1w, :x: (I) or a salt or N-oxide thereof, wherein: A is halogen, Cl -C6 alkyl optionally substituted by 1 to 3 groups R2, Cl -C6 haloalkyl optionally substituted by I to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, Cl-C6 alkylthio optionally substituted by 1 to 3 groups R2, C6-C10 aryl optionally substituted by 1 to 3 groups R3 or a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R' is hydrogen, Cl-C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl, C l-C6 acyl optionally substituted by 1 to 3 groups R2, Cl-C6 alkylsulphonyl optionally substituted by 1 to 3 groups R2, C2-C7 alkoxycarbonyl optionally substituted by 1 to 3 groups R2, aminocarbonyl, Cl -C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2 or diCl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2; R4 is hydrogen, cyano, nitro, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, Cl-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C3-C6 cycloalkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups 112, C6-C10 aryl optionally substituted by 1 to 3 groups R3, a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3, C1-C6 acyl optionally substituted by 1 to 3 groups R2, C1-C6 alkoxycarbonyl optionally substituted by 1 to 3 groups 112, carboxy, aminocarbonyl, C1-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2, diCl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups 112 or diCl-C6 alkylphosphonyl optionally substituted by 1 to 3 groups R5 is hydrogen, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, or Cl -C6 haloalkyl; W is a direct bond or a linker group of the formula -(C1-C3 alkylene%-L-(C1-C3 alkylene)-wherein each alkylene group is optionally substituted by up to 3 groups R2, s and t may each be independently 0 or 1, and L is a direct single, double or triple bond, -S(O)0-wherein u is 0, 1 or 2, -N(R")-wherein 11" is H or C1-C6 alkyl, -0-or -C(O)O-; Q is a 3-10 membered ring system optionally containing up to 4 heteroatoms independently selected from 0, N or S, the ring system optionally substituted by up to X is hydrogen, halogen, cyano, nitro, hydroxyl, C1-C6 alkyl optionally substituted by 1 to 3 groups 112, C1-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups 112, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkoxy, C3-C8 cycloalkyl optionally substituted by I to 3 groups 112, Cl-C6 alkoxy optionally substituted by 1 to 3 groups R2, amino, C1-C6 alkylamino optionally substituted by 1 to 3 groups R2, di(C1-C6 alkyl)amino optionally substituted by 1 to 3 groups R2, Cl-C6 alkylthio optionally substituted by 1 to 3 groups R2, C1-C6 alkylsulphinyl optionally substituted by 1 to 3 groups R2 or Cl-C6 alkylsulphonyl optionally substituted by 1 to 3 groups R2; Y is halogen, cyano, nitro, hydroxyl, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups 112, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkoxy, Cl -C6 alkoxy optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, C6-C10 aryl, amino, Cl-C6 alkylamino, di(C1-C6 alkyl)amino, C1-C6 alkylthio, C1-C6 alkylsulphinyl or C1-C6 alkylsuiphonyl; S Z is C(O)R6, C(S)R6 or C(NR7)R8; each R2 is independently halogen, hydroxyl, amino, Cl-C3 alkylamino, di(C1- C3alkyl)amino, carboxy, cyano, C1-C3 alkyl, C1-C3 haloalkyl, C3-C6 cycloalkyl, Cl-C3 alkoxy, C1-C3 haloalkoxy, Cl-C3 alkylthio, C1-C3 alkylsulphonyl, C2-C6 carboxyalkyl, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl or phenoxy; each R3 is independently halogen, hydroxyl, nitro, amino, thiol, cyano, C1-C3 alkyl, Cl-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C1-C3 alkylthio, C1-C3 haloalkylthio, C2-C6 carboxyalkyl, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl, phenoxy, C1-C3 alkylamino or di(C 1 -C3 alkyl)amino; R6 is hydrogen, hydroxyl, Cl-Cl 0 alkoxy optionally substituted by Cl-C6 alkoxy or phenyl, C3-C8 cycloalkoxy optionally substituted by Cl.-C6 alkoxy or phenyl, Cl -C6 haloalkoxy, C2-C6 alkenyloxy, Cl -C6 alkylthio, amino, CI -C6 alkylamino or di(Cl-C6 alkyl)amino; R7 is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, amino, Cl-C6 alkylamino or di(C1 -C6 alkyl)amino; R8 is hydrogen, Cl-C6 alkoxy, C3-C8 cycloalkoxy, C1-C6 alkylthio, amino, Cl-C6 alkylamino or di(C1 -C6 alkyl)amino.
wherein said composition comprises, in addition to the 4-aminopicolinate herbicide of formula (I), a safener selected from the group consisting of AD 67 (MON 4660), benoxacor, cloquintocet-mexyl, cyprosulfamide (CAS RN 22 1667-3 1-8), dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, the R isomer of furilazole, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, naphthalic anhydride (CAS RN 81-84-5), N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4) and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide.
In a further aspect, the present invention provides a method for protecting crop plants from the harmful effects of a herbicide of formula (I) as defined herein, which comprises applying to the locus of the crop plants a safener selected from the group comprising AD 67, benoxacor, cloquintocet-mexyl, cyprosulfamide, dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, the R isomer of furilazole, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, naphthalic anhydride, N- isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide.
The compounds of formula (I) may exist as different geometric isomers, or in different tautomeric forms. This invention covers all such isomers and tautomers, and mixtures thereof in all proportions, as well as isotopic forms such as deuterated compounds. Zwitterionic forms are also covered. For example, compounds of formula (II) may exist in equilibrium with the zwitterionic forms (III) and (IV).
Rc)CR, ___ Rc)CR, ___ Rç ActCCO2.. AX1c02..
(II) (III) (IV) The compounds of this invention may contain an asymmetric carbon atom and some of the compounds of this invention may contain one or more asymmetric centers and may thus give rise to optical isomers and diastcreomers. While shown without respect to stereochemistry, the present invention includes such optical isomers and diastereomers; as well as the racemic and resolved, enantiomerically pure R and S stereoisomers; as well as other mixtures of the R and S stereoisomers and agrochemically acceptable salts thereof It is recognized that one optical isomer, including diastereomer and enantiomer, or stercoisomer may have favorable properties over the other. Thus when disclosing and claiming the invention, when one racemic mixture is disclosed, it is clearly contemplated that both optical isomers, including diastereomers and enantiomers, or stereoisomers substantially free of the other arc disclosed and claimed as well.
Alkyl, as used herein refers to an aliphatic hydrocarbon chain and includes straight and branched chains e. g. of 1 to 6 carbon atoms such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl.
Aikenyl, as used herein, refers to an aliphatic hydrocarbon chain having at least one double bond, and preferably one double bond, and includes straight and branched chains e. g. of 2 to 6 carbon atoms such as ethenyl, propenyl, isopropenyl, but-i -enyl, but-2-enyl, but-3-enyl, 2-methypropenyl.
Alkynyl, as used herein, refers to an aliphatic hydrocarbon chain having at least one triple bond, and preferably one triple bond, and includes straight and branched chains e. g. of 2 to 6 carbon atoms such as ethynyl, propynyl, but-i-ynyl, but-2-ynyl and but-3-ynyl.
Cycloalkyl, as used herein, refers to a cyclic, saturated hydrocarbon group having from 3 to 8 ring carbon atoms. Examples of cycloalkyl groups are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.
Alkoxy as used herein refers to the group -0-alkyl, wherein alkyl is as defined above, Examples of alkoxy groups include methoxy, ethoxy, n-propoxy, isopropoxy, n- butoxy, isobutoxy, sec-butoxy, t-butoxy, n-pentoxy, isopentoxy, neo-pentoxy, n-hexyloxy, and isohexyloxy.
Cycloalkoxy as used herein refers to the group -0-cycloalkyl, wherein cycloalkyl is as defined above. Examples of cycloalkoxy groups are cyclopropoxy, cyclobutoxy, cyclopentoxy, cyclohexyloxy, cycloheptyloxy and cyclooctyloxy.
Alkylthio as used herein refers to the group -S-alkyl, wherein alkyl is as defined above, Examples of thioalkyl groups are methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, sec-butylthio, t-butyithio, n-pentylthio, isopentylthio, neo-pentylthio, n-hexylthio, and isohexylthio.
Alkylsuiphinyl as used herein refers to the group -S(O)-alkyl, wherein alkyl is as defined above.
Alkylsulphonyl as used herein refers to the group -S(O)2-alkyl, wherein alkyl is as defined above.
Halogen, halide and halo as used herein refer to iodine, bromine, chlorine and fluorine.
Haloalkyl as used herein refers to an alkyl group as defined above wherein at least one hydrogen atom has been replaced with a halogen atom as defined above.
Examples of haloalkyl groups include chloromethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl and trifluoromethyl. Preferred haloalkyl groups are fluoroalkyl groups (i.e. haloalkyl groups, containing fluorine as the only halogen). More highly preferred haloalkyl groups are perfluoroalkyl groups, (i.e. alkyl groups wherein all the hydrogen atoms are replaced with fluorine atoms).
Haloalkoxy as used herein refers to an alkoxy group as defined above wherein at least one hydrogen atom has been replaced with a halogen atom as defined above.
Acyl as used herein refers to the group -C(O)-alkyl or -C(O)H, wherein the alkyl group is as defined above. Examples of acyl groups are formyl, acetyl, pivaloyl etc. Alkoxycarbonyl as used herein refers to the group -C(O)-O-alkyl, wherein the alkyl group is as defined above. Examples of alkoxycarbonyl groups include methoxycarbonyl, ethoxycarbonyl, i-propoxycarbonyl, n-propoxycarbonyl, n-butoxycarbonyl and s-butoxycarbonyl etc. Aminocarbonyl as used herein refers to the group -C(O)NH2.
Alkylamino as used herein refers to the group -NH-alkyl, wherein alkyl is as defined above. Examples of alkylamino groups are methylamino, ethylamino, n-propylamino, i-propylamino etc. Alkylaminocarbonyl as used herein refers to the group -C(O)N1-I-alkyl, wherein alkyl is as defined above.
Dialkylamino as used herein refers to the group -N(alkyl)alkyl', wherein alkyl and alkyl' are both alkyl groups as defined above which may be the same or different.
Examples of dialkylamino groups are dimethylamino, diethylamino, di-n-propylamino, methylethylamino, methyisopropylamino, etc. Dialkylaminocarbonyl as used herein refers to the group -C(O)N(alkyl)alkyl', wherein alkyl and alkyl' are both alkyl groups as defined above which may be the same or different.
Dialkylphosphonyl as used herein refers to the group -P(O)(alkyl)(alkyl'), wherein alkyl and alkyl' are both alkyl groups as defined above which may be the same or different. Examples of dialkylphosphonyl groups are dimethylphosphonyl, diethylphosphonyl, ethyl methyl phosphonyl etc. Alkylcarbonyloxy as used herein refers to the group -OC(O)-alkyl wherein alkyl is as defined above.
Carboxyalkyl as used herein refers to the group -alkyl-C(O)OH, wherein alkyl is as defined above.
Alkylene as used herein refers to a branched or linear divalent hydrocarbon radical. Examples of alkylene are methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, 1,3-propylene and 2,2-propylene etc. Aryl as used herein refers to an unsaturated aromatic carbocyclic group of from 6 to 10 carbon atoms having a single ring (e. g., phenyl) or multiple condensed (fused) rings, at least one of which is aromatic (e.g., indanyl, naphthyl). Preferred aryl groups include phenyl, naphthyl and the like.
Aryloxy as used herein refers to the group -0-aryl, wherein aryl is as defined above. Preferred aryloxy groups include phenoxy, napbthyloxy and the like.
Heteroaryl as used herein refers to a ring system containing 3 to 10 ring atoms, and preferably 5 to 10 ring atoms, at least one ring heteroatom and consisting either of a single aromatic ring or of two or more fused rings, at least one of which is aromatic.
Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulfur. Examples of such groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl. Examples of bicyclic groups are benzothiophenyl, benzimidazolyl, benzothiadiazolyl, quinolinyl, cinnolinyl, quinoxalinyl and pyrazolo[l,5-a]pyrimidinyl.
1-leteroaryloxy as used herein refers to the group -0-heteroaryl, wherein heteroaryl is as defined above.
Heterocyclyl refers to a non-aromatic ring system containing 3 to 10 ring atoms, at least one ring heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings will contain up to three and bicyclic systems up to four heteroatoms which will preferably be chosen from nitrogen, oxygen and sulfur. Examples of such groups include pyrrolidinyl, imidazolinyl, pyrazolidinyl, piperidyl, piperazinyl, quinuclidinyl, morpholinyl, together with unsaturated or partially unsaturated analogues such as 4,5,6,7-tetrahydro-benzothiophenyl, chromen-4-onyl, 9F1-fluorenyl, 3,4-dihydro- 21-1-benzo-1,4-dioxepinyl, 2,3-dihydro-benzofuranyl, piperidinyl, 1,3-dioxolanyl, 1,3-dioxanyl, 4,5-dihydro-isoxazolyl, tetrahydrofuranyl and morpholinyl.
It is noted that, when the number of carbon atoms is specified for alkoxycarbonyl, carboxyalkyl and alkylcarbonyloxy groups, this number may include both the carbon atom associated with the carbonyl or carboxy group as well as the carbon atoms associated with the alkyl or alkoxy groups.
Optionally substituted as used herein means the group referred to can be substituted at one or more positions by any one or any combination of the radicals listed thereafter. For most groups, one or more hydrogen atoms are replaced by the radicals listed thereafter. For halogenated groups, for example, haloalkyl groups, one or more halogen atoms are replaced by the radicals listed thereafter.
Suitable salts include those derived from alkali or alkaline earth metals and those derived from ammonia and amines. Preferred cations include sodium, potassium, magnesium, and ammonium cations of the formula N+(R9RIORLIRI2) wherein R9, R'°, R' and R'2 are independently selected from hydrogen, C1-C6 alkyl and Cl-C6 hydroxyalkyl. Salts of the compounds of Formula I can be prepared by treatment of compounds of Formula I with a metal hydroxide, such as sodium hydroxide, or an amine, such as ammonia, trimethylamine, diethanolamine, 2-methylthiopropylamine, bisallylamine, 2-butoxyethylamine, morpholine, cyclododecylamine, or benzylamine.
Amine salts are often preferred forms of the compounds of Formula I because they are water-soluble and lend themselves to the preparation of desirable aqueous based herbicidal compositions.
Acceptable salts can be formed from organic and inorganic acids, for example, acetic, propionic, lactic, citric, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, phthalic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, methanesulfonic, naphthalenesulfonic, benzenesulfonic, toluenesulfonic, camphorsulfonic, and similarly known acceptable acids when a compound of this invention contains a basic moiety.
Preferred values of A, X, Y, Z, R' to R8, W and Q are set out below.
A is preferably halogen, C1-C6 alkyl, Cl-C6 haloalkyl, C2-C6 alkenyl, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, C6-C10 aryl optionally substituted by I to 3 groups R3, or a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3.
Examples of group A include 2,3,4-trichlorophenyl, 2,4-dichloro-3-fluorophenyl, 2,4-dichiorophenyl, 2-ehloro-4-methylphenyl, 3,4-dichloro-2-fluorophenyl, 3,4- dichiorophenyl, 4,5-dichloro-2-fluorophenyl, 4-bromophenyl, 4-chloro-2,3- difluorophenyl, 4-chloro-2,5-difluorophenyl, 4-chloro-2-fluoro-3-methoxyphenyl, 4- chloro-2-fluorophenyl, 4-chloro-3-dimethylamino-2-tluorophenyl, 4-chloro-3- fluorophenyl, 4-chlorophenyl, 4-methyiphenyl, 4-trifluoromethylphenyl, 5-chlorothiophen-2-yl, 6-chloropyridin-3-yl, chloro, cyclopropyl and isopropyl.
More preferably, A is halogen, phenyl optionally substituted by 1 to 3 groups or C3-C6 cycloalkyl optionally substituted by 1 to 3 groups R2.
Very preferably, A is chlorine. In an alternative, very preferred embodiment, A is In an alternative, very preferred embodiment, A is trisubstituted phenyl, wherein the substituents are independently R3. More preferably, A is 2,3,4-trisubstituted phenyl, wherein the substituents are independently R3. More preferably, A is 4-chloro-2-fluoro- 3-methoxyphenyl, or 4-ehloro-3-dimethylamino-2-fluorophenyl.
Preferably, R' is hydrogen, Cl-C6 alkyl optionally substituted by 1 or 2 groups or C2-C6 alkenyl.
Examples of R' are hydrogen, methyl, ethyl and isopropyl.
More preferably, R' is hydrogen or C1-C6 alkyl. Most preferably, R' is hydrogen.
Preferably, X is hydrogen, halogen, Cl-C6 alkyl, C1-C6 haloalkyl, C1-C3 alkoxy(C 1 -C6)alkyl or C3-C6 cyeloalkyl.
More preferably, X is hydrogen, halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy(C 1 -C2)alkyl, or C3-C6 cycloalkyl.
Examples of X are hydrogen, fluoro, ehloro, bromo, methyl and cyclopropyl.
Most preferably, X is hydrogen, fluoro or chloro.
Preferably, Y is halogen, C1-C3 alkyl, Cl-C3 haloalkyl, C1-C2-alkoxy(C1-C2) alkyl, cyclopropyl, C2-C4 alkenyl or C2-C4 alkynyl.
More preferably, Y is halogen, Cl -C2 alkyl, Cl -C2 haloalkyl, Cl -C2 alkoxy(C 1-C2)alkyl, cyclopropyl, C2-C4 alkenyl or C2-C4 alkynyl.
Examples of Y are chlorine, bromine, methyl, vinyl, eyclopropyl and 1-propenyl.
More preferably, Y is chlorine, vinyl or cyclopropyl. Most preferably, Y is chlorine or vinyl.
Preferably, Z is C(O)R6, wherein R6 is hydroxyl, C1-C6 alkoxy, phenyl(Cl-C2)alkoxy, or (Cl -C3)alkoxy(C 1 -C6)alkoxy.
Examples of group Z are CO2CH2CH2OEt, CO2CH2Ph, CO2Et, CO2Me and CO2H.
More preferably, Z is C(O)R6 wherein R6 is hydroxyl, C1-C6 alkoxy or phenyl(C1-C2)alkoxy. More preferably, Z is CO2H or CO2Me.
Preferably, R4 is hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxyalkyl, Cl -C3 alkoxy(C 1 -C6)alkyl, C2-C6 alkoxycarbonyl or carboxyl. Most preferably, R4 is hydrogen.
Examples of R4 are hydrogen, methyl, CH2OH, CO2Et, CO2Me, CO2H.
Preferably, R5 is hydrogen or Cl-C6 alkyl. More preferably, R5 is hydrogen.
An example of R5 is hydrogen.
Preferably, W is a direct bond or a methylene group. More preferably, W is a direct bond.
Examples of W are CH(Oll), -CH(OH)Cl-120-, Cl-I2, and a direct bond.
In one preferred embodiment, Q is C6-C10 aryl optionally substituted by I to 3 groups independently selected from R3. More preferably, Q is phenyl or napthyl optionally substituted by 1 to 3 groups independently selected from R3. More preferably, Q is phenyl optionally substituted by 1 or 2 groups independently selected from R3.
In another preferred embodiment, Q is a heteroaryl ring system containing 3 to 10 ring atoms, with up to four ring heteroatoms independently selected from N, 0 or 5, consisting either of a single aromatic ring or of two or more fused rings, at least one of which is aromatic, optionally substituted by 1 to 3 groups independently selected from R3. Preferably, Q is a monocyclic heteroaryl ring with 5 to 7 ring members comprising 1 to 3 ring heteroatoms independently selected from N, 0 or S optionally substituted by 1 to 3 groups independently selected from R3. More preferably, Q is a monocyclic heteroaryl ring with 5 or 6 ring members comprising 1 to 3 ring heteroatoms independently selected from N, 0 or S optionally substituted by 1 to 3 groups independently selected from R3. More preferably, Q is pyridyl, furyl, thiophenyl, oxazolyl, or thiazolyl, optionally substituted by 1-2 groups R3. More preferably Q is furyl optionally substituted by 1-2 groups R3. More preferably, Q is unsubstituted furyl.
More preferably, Q is 2-furyl optionally substituted by 1-2 groups R3. More preferably, In another preferred embodiment, Q is C3-C8 cyeloalkyl optionally substituted by 1 or 2 groups It3.
Examples of Q are phenyl, naphthyl, pyridyl, pyrimidinyl, furanyl, benzofuranyl, thiophenyl, benzothiophenyl, pyrrolyl, indolyl, oxazolyl, oxadiazolyl, benzoxazolyl, pyrazolyl, thiazolyl, pyrrolidinyl, 1,3-dioxolanyl, morpholinyl, imidazolidinyl, 3,4-dihydro-2H-pyran-2-yl, benzothiazolyl, benzofuranyl, indanyl, tetrahydropyranyl, tetrahydrofuranyl, berrzo[1,3]dioxolyl each optionally substituted by 1 or 2 groups C3-8 cycloalkyl optionally substituted by I or 2 groups R3, C3-8 cycloalkenyl optionally substituted by I or 2 groups It3; wherein each It3 is independently halogen, hydroxyl, nitro, cyano, Cl -C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, CI-C3 alkoxycarbonyl, amino or di(C1-C2alkyl)amino.
It3 is preferably halogen, hydroxyl, nitro, Cl -C2 alkyl, Cl -C2 alkoxy, di(Cl-C2)alkylamino.
In a preferred embodiment, A is halogen, R' is hydrogen, X is hydrogen or halogen, Y is halogen, methyl or vinyl, Z is C(O)R6, wherein R6 is hydroxyl or C1-C6 alkoxy, R4 and It5 are both hydrogen, W is a direct bond and Q is a phenyl,furanyl, pyridyl or cyclopropyl ring optionally substituted by up to three substituents It3, wherein each R3 is independently halogen, hydroxyl, nitro, amino, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C1-C3 haloalkoxy, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, Cl-C3 alkylamino, or di(C 1 -C3 alkyl)amino.
The compounds described below are illustrative of compounds for use in the novel safened compositions of the invention. Table I below provides 467 compounds designated compounds 1-ito 1-467 respectively, of formula (I) wherein It' is H, R4 is H, It5 is H, W is a direct bond and Q is cyclopropyl.
TABLE 1
Number __________________________________________________________________________ ____ ______ -----±-------1 _x. Y z 1-1 CI I H I Cl CO2H 1-2 CI j H J CI CO2Me 1-3 Cl H -Cl CO2Et -1-4 Cl H Cl CO2CI-I2CH2OEt 1-5 Cl H Cl CO2CH2PIi 1-6 Cl_ H cyclopropyl CO2H 1-7 Cl H cycloprqpyj_ -CO2Me 1-8 -Cl -H cyclopropyl CO2Et 1-9 -Cl H cyclopropyl CO2CH2CH2OEt 1-10 Cl H _çyclopropyl -CO2CH2Ph 1-11 Cl H --vinyl CO2H 1-12 Cl H vinyl CO2Me 1-13 -Ci -H vinyl CO2Et 1-14 Cl H vinyl CO2CH2CH2OEt _1-15 Cl -H vinyl CO2CH2Ph 1-16 Cl H -Br CO2H 1-17 Cl H BrCO2Me - 1-18 Cl --H -Me CO2H 1-19 -H Me -CO2Me 1-20 Cl H hpropçnyj --CO2H 1-21 Cl H 1-propenyl CO2Me 1-22 Cl F Ci CO2H 1-23 Cl F Cl CO2Me 1-24 Cl F cyclopop CO2H - 1-25 Cl F cyclopropyl CO2Me 1-26 Cl F -yjny1__ _CO2H_ 1-27 Cl F vinyl CO2Me 1-28 Cl F _Br__ CO2H 1-29 Ci F Br CO2Me 1-30 Cl F Me CO2H 1-31 Cl F Me C2Me__ 1-32 -Cl -F 1 -propenyl C021-1 1-33 Cl F -p!opcnyl -CO2Me __1-34_ Cl Cl Cl CO2H 1-35 Cl Cl Cl CO2Me 1-36 ______________________ Cl c1opopyj CO2H 1-37 Cl Cl cyc1opop CO2Me 1-38 ci Cl vinyl CO2H 1-39 Cl Cl yiny_ _CO2Mc 1-40 -Cl Cl Br CO2H 1-41 -Cl Cl -_B_ CO2Me - 1-42 -Cl Ci Me CO2H 1-43 Cl Cl Me CO2Me 144 Cl --Cl 1-poppny1 CO2H 1-45 -Cl Ci 1-propenyl CO2Me 1-46 Cl -Br Cl CO2H 1-47 Cl Br Cl -CO2Me 1-48 C1_ Br çyplpprpyi CO2H 1-49 Cl -_Br cyciopropyl CO2Me 1-50 -Ci Br -vinyl -CO2H 1-51 Cl --Br vinyl -CO2Me -1-52 Cl Br Br CO2H -1-53 -Cl Br Br CO2Me 1-54 Cl Br Me CO2H -1--Cl Br Me CO2Me - -1-56 -Cl Br 1-propenyl CO2H 1-57 Cl Br 1-propenyl CO2M - -1-58 -Cl Me Cl CO2H - 1-59 Cl Me SL -CO2Me 1-60 Cl Me cyclopropyl CO2H -1-61 -_Cl_ Me çyclpprppyl CO2Me 1-62 Cl Me vinyl CO2H 1-63 Cl -_Me viyL CO2Me _1-64 C! Br -C0211 1-65 CI Me Br CO2Me -1-66 -Cl Me Me CO2H 1-67 Cl -Me Me CO2Me 1-68 Cl --Me jpjopyl _CO2H -1-69 -Cl_ Me I -propenyl CO2Me - 1-70 Cl cyjopppyl -Cl -CO2H -1-71 Cl_ çyclopropyj CI CO2Me -1-72 Cl cyclopropyl cyclopropyl -CO2H -1-73 Cl çyclopropy cycIprppyl CO2Me - 1-74_ Cl cyclopropyl vinyl CO2H 1-75 Cl çycloprop vinyl -CO2Me 1-76 -Cl cyclopropyl Br CO2H 1-77 Cl -çyclopropy -Br CO2Me 1-78 Cl cyclopropyl Me CO2H 1-79 Cl -çyclopropy Me CO2Me 1-80 Cl cyclopropyl 1-propenyl CO2H 1-81 Cl çyc1opropy 1-propy1 -CO2Me 1-82 -yc1opropy1 -H Cl CO2H 1-83 -çycpprppy1 H Cl CO2Me 1-84 cyclopropyl H Cl CO2Et - 1-85 çycçprppl -Fl Cl CO2CH2CH2OEt 1-86 cyclopropyl H Cl _CO2CJ-l2Ph -1-87 -cyclqpropyl -H cyclprpyl -CO2H 1-88 cyc1oprpyI H_ cyclopropyl CO2Me 1-89 --cyclopropyl -H cyclopropyl CO2Et 1-90 --çycjpprppyl -H çyclprppyl CO2CH2CH2OEt 1-91 cyclopropyl --H cyclopropyl CO2CH2Ph 1-92 çycpropy1 H --vil -CO2H 1-93 cyclopropyl H vinyl CO2Me 1-94 -cyclopropy4 --H vinyl CO2Et 1-95 cyclopropyl H -vinyl CO2CH2CH2OEt 1-96 -cyclopropyl H vinyl CO2CH2Ph 1-97 cyclopropyl H -Br -CO2H - 1-98 -cyclopropyl H -Br CO2Me - -1-99 cyclprqpy_ H -Me CO2H 1-100 cyclopropy -H Me CO2Me --i -101 -cyclqpropyl --H --I -propenyl CO2H 1-102 cy4propyl H -1-propeny CO2Me 1-103 -cyclopropyl -F Cl CO2H 1-104 cyc1prop --. F -Cl CO2Me 1-105 -cyclopropyl F cyclopropyl CO2H 1-106 --cycIpopy1 -F cyclopropyl CO2Me 1-107 cyclopropyl F -viny] CO2H _1-108 -cyclopropyl F vinyl CO2Me - 1-109 cyclopropyl -F -Br CO2H i-I 10 --cyclopropyl F Br -CO2Me 1-111 cyclopropyl -F -Me CO2H 1-112 cyclopropyl F_ -Me CO2Me 1-113 -cyclqpropyl -F I -propenyl CO2H - 1-1 14 cyclopropyl -F 1-propeny CO2Me 1-115 cyclopropyl Cl Cl ço2H - 1-116 cyç1qpropy -CL _C1 CO2Me 1-i 17 cyclopropyl -CI cyclopropyl CO2H 1-1 18 -cyçlçpropyl -CI -yc1opropy1 CO2Me 1-119 cyclopropy! CL viny! CO2H 1-120 -cyclçpropy Cl vinyl CO2Me 1-121 cycIopqpy_ Cl Br _COQ 1-122 cyclopropyl Cl Br CO2Me 1-123 -cyclopropyl Cl Me CO2H 1-124 cyclopropyl Cl Me CO2Me 1-125 cyclopropyl CI 1-propenyl CO2H 1-126 cyclopropyl Cl I -propenyl CO2Me 1-127 --cyclopropyl Br Cl CO2H 1-128 cyclopropyl Br CI CO2Me 1-129 --cyclopropyl Br cyclopropyl CO2H 1-130 cyclopropyl Br cyclopropyl CO2Me 1-131 --_çyclopropyl Br vinyl CO2FI 1-132 cyclopropyl Br vinyl CO2Me 1-133 -cyclopropyl Br Br CO2H 1-134 -cyçpropyj -Br -Br -CO2Me -1-135 -cyclopropyl Br Me CO2H 1-136 --_çycl9propyj Br Me CO2Me -1-137 cyclopropyl Br 1-propenyl CO2H 1-138 -cyçlppropyj Br 1-ppenyl CO2Me - 1-139 -cyclopropyl Me Cl CO2H 1-140 -cyç1qpqpyl Me Cl CO2Me 1-141 cyclopropyl Me -cyclopropyl CO2H - 1-142 -cyçlqpropyl Me cyclopropyl CO2Me -1-143 cyclopropyl ---Me -viny] CO2FI 1-144 cyçlopropyl Me vinyl CO2Me -1-145 cyclopropyl -Me --Br ço2H -1-146 -cyclopropyl Me -Br CO2Me 1-147 cyclopropyl -Me Me_ -CO2H 1-148 -cyc1oprqpy Me Me CO2Me - 1-149 cyclopropyl Me 1prpenyj -. CO2H 1-150 ypropyl Me!-procpyL CO2Me 1-151 cyclopropyl cyclopropy Cl CO2H 1-152 -cyclopropyl cyclopjopyl CI -CO2Me 1-153 cyclopropyl cyclopropyl cyclopropyl CO2H 1-154 cyclopropyl -cyclopropy cyclopropyl CO2Me - _*155 cyclojrqpyl -yclopropy1 _vjy[ CO2H 1-156 cyclopropyl -cyclopropyl vinyl CO2Me 1-157 cyc1opyl cyclopropy1 Br -CO2H 1-1 58 cyclopropyl cyclopropyl Br --CO2Me 1-159 cyclopropyl cyclopropyl Me CO2H - -1-160 -cyclqprqpyl cyc1oprqpy1 Me CO2Me -1-161 cycloprqpyt -cyclopropyl 1-ppyl _CO2H -1-162 cyclopropyl -cyclopropy1 1prppny -CO2Me 1-163 -4-chloro-2-fluoro-3-methoyieqyl H Cl CO2H_ 1-164 _4-chloro-2-fluoro-3-methoxyphenyl H CI CO2Me 1-165 4-chloro-2-fluoro-3-methoxyphenyj -H -Ci -CO2Et 1-166 _4ch1oro2fluor&3-methoxyphenyl H Cl CO2CH2CH2OEt 1-167 4-ch1oro-2-fluoro-3-methopey1 H Cl -CO2CH2Ph 1-168 --4-chloro-2-fluoro-3-methoxyphenyl H cyclopropyl CO2H 1-169 4-chloro-2-fluoro-3-methoxyphenyi --_H_ -clçppyL CO2Me 1-170 4-chloro-2-fluoro-3-tnethoxyphenyl -H cyclopropyl -_CO2Et 1-171 4-chloro-2-fluoro-3-methoxyphenyl H cyclopropyl CO2CH2CH2OEt 1-172 -H cyçlprqpy1 CO2CH2Ph 1-173 4-chloro-2-fluoro-3-methoxyphenyl H vinyl CO2H 1-174 4-chloro2-fluoro-3-methoyjLey1 H vinyl CO2Me 1-175 4-chloro-2-fluoro-3-methoxyphenyl H vinyl CO2Et 1-176 -H -vinyl CO2CH2CH2OEt 1-177 4-chloro-2-fluoro-3-methoxyphenyl H vinyl CO2CH2Ph 1-178 4-chloro-2-f1uoro-3-rnethoypçpy H Br -CO2H 1-179 4-chloro-2-fluoro-3-methoxypheyI H Br CO2Me 1-180 4-chloro-2-fluoro-3-rnethoçyphenyI H Me -02 1-181 4-chIoro-2-fluoro-3-methoxyphey1 H Me CO2Me 1-182 -4-chloro-241uoro-3-methoxypheyI --H 1-prony1 -CO2H 1-183 4-chloro-2-fluoro-3-methoxyphenyl H I -propenyl CO2Me 1-184 -4-chtoro-2-fluoro-3-methoxyp1hepyj F Cl -CO2H 1-185 4-chloro-2-fluoro-3-rnethoxyphenyl --F Cl CO2Me 1-186 4-chloro-2-fluoro-3-methoxypyl F cyclopropyl CO2H 1-187 4-chloro-2-fluoro-3-methoxyphenyl F cyçlqpr9pyl CO2Me -1-188 4-chloro-2-fluoro-3-methoxyphenyl F vinyl CO2H 1-189 4-chloro-2-fluoro-3-methoxyphenyl F -vinyl -CO2Me 1-190 4-chloro-2-fluoro-3-methoxyphenyl F Br -CO2H 1-191 -4-chloro-2-fluoro-3-rnethoynheiyl -F --Br CO2Me - 1-192 4-chloro-2-fluoro-3-methoxyphenyl F Me -CO2H 1-193 4-chIoro-2-fluoro-3-n1ethoypIyl F --Me CO2Me 1-194 4-chloro-2-fluoro-3-metlioçypheny1 F jpppenyl C021-l 1-195 4-chloro-2-fluoro-3-methoxypçy1 -F 1-propenyl CO2Me - 1-196 4-chloro-2-fluoro-3-methoxyphenyl Cl.C1 C0214 1-197 4-chioro-2-fluoro-3-methoxyheny1 -Cl Cl -CO2Me 1-198 -4-chloro-fiQrp-methoxyphen_ -Cl ycjppopy1_ CO2H -1-199 4-chloro-2-fluoro-3-methoxyphenyl Cl cyclopropyl CO2Me 1-200 4-chloro-2-fluoro-3-methoxyphenyl -CI vinyl -CO2H -1-201 4-chloro-2-fluoro-3-methoxyfthenyl CI_ vinyl CO2Me 1-202 -4-chIoro-2-fluoro-3-methoxyyl -Cl Br --CQ2H 1-203 4-chloro-2-fluoro-3-methoxyphenyl CI Br CO2Me 1-204 4-chtoro-2-fluoro-3-methoxyphenyl CI Me CO2H - 1-205 4-chloro-2-fluoro-3-methoxyphenyl CI -Me -CO2Me 1-206 4-chloro-2-uluoro-3-methoxyphenyi Ci l-propçnyl CO2H 1-207 4-chloro-2-fluoro-3-methoxyphenyl Cl I -propenyl CO2Me 1-208 4-chloro-2-fiuoro-3-methoxyphenyl Br Cl CO2H 1-209 4-chloro-2-f1uoro-3-meypjçpyl Br --Cl CO2Me - 1-210 4-chloro-2-tluoro-3-methoxyphenyl -Br cyclopropyl C021-l 1-211 4-chloro-2-fluoro-3-methoxypjienyl Br ylopropy1 CO2Me -1-212 -4-chloro-2-tluoro-3-methoxyphenyl Br vinyl CO2H 1-213 4-chloro-2-fluoro-3-niethoxyphenyl -Br vinyl* CO2Me 1-214 4-chloro-2-tluoro-3-methoxyphenyl Br --Br -CO2H - 1-215 4-chloro-2-fluoro-3-methoxyphenyl Br Br CO2Me 1-216 4-chloro-2-fluoro-3-methoxyphenyl Br -Me --CO2FI - 1-217 4-chloro-2-uluoro-3-methoxyphenyl Br Me CO2Me 1-218 4-chloro-2-fluoro-3-methoxyphenyl -Br -1-popçnyl CO2H 1-219 4-chloro-2-fluoro-3-methoxyphenyl Br I -propenyl CO2Me 1-220 4-chloro-2-f1uoro-3-methoyojienyl Me_ Cl CO2H 1-221 4-chloro-2-fluoro-3-methoxyphenyl Me Cl CO2Me - 1-222 4-chloro-2-fluoro-3-methoxyphenyl Me cyclopropyl CO2H 1-223 -4-chloro-2-fluoro-3-methoyphenyl Me çyc1oprpy -CO2Me 1-224 4-chloro-2-fluoro-3-methoxyphenyl Me* vinyl CO2H 1-225 -4-chloro-2-fluoro-3-methoypienyl Me vinyl CO2Me 1-226 4-chloro-2-fluoro-3-methoxyphenyl Me Br CO2H 1-227 4-ch1oro-2-f1uoro-3-methoypenyl Me ---Br CO2Me 1-228 4-chloro-2-fluoro-3-methoxyphenyl Me -Me CO2H - _-229 -4-ch1oro-2-fluoro-3-methoyp1enyl Me Me CO2Me 1-230 -4-chloro-2-f1uoro-3-methoynjwnyl Me -1 -propenyl CO2H 1-231 -4-chloro-2-fluoro-3-methoxyphenyl Me I -popenyI CO2Me -- 1-232 -4-chloro-2-t1uoro-3-methqyphenyl cyçIpropyl CI CO2FI 1-233 --4-chloro-2-f'luoro-3-methoxyphenyl cycloppy -CI CO2Me - 1-234 -4-chloro-2-fluoro-3-methoxyphenyl cyçlopropyl cyclopropyl --CO2FI 1-235 --4-chloro-2-fluoro-3-methoxyphenyl cyclopropyl cyclopropyl CO2Me 1-236 4-chloro-2-fluoro-3-niethoxyphenyl çyçjçprppyj vinyl CO2H 1-237 --4-chloro-2-f1uoro-3-nietlioypienyl cyclopropyl vinyl CO2Me 1-238 4-chloro-2-fluoro-3-methoxyphenyl cyclopropy Br C021-1 1-239 4-chloro-2-fluoro-3-methoxyphenyl cyclprpyl -Br CO2Me - 1-240 -4-ch1oro-2-fluoro-3-methqçypIeyI cyçlopropyl -Me --CO2H - 1-241 4-chloro-2-fluoro-3-methoxyphenyl cyclopropyl Me CO2Me 1-242 4-chloro-2-tluoro-3-methoxyphenyl yqprpy -ippçnyl CO2H 1-243 4-chloro-2-fluoro-3-methoxyphenyl yçjopropyI 1-propen>f 54e 1-244 4-chloro-3-dimethytamino-2-fluorophenyl H Cl CO2H 1-245 __ 4-chIoro-3-dimethytamino-2-fluorophen I-i * Cl CO2Me 1-246 4-chloro-3-dimethylamino-2-fluorpphenyl H C!_ CO2Et -1-247 4-chloro-3-diinethylamino-2-fluorophenyl H Cl CO2CI-12C1-I2OEt 1-248 4-chloro-3-dimethytamino-2-fluorpphenyl. H. Cl CO2CI-I2Ph I -249 4-chloro-3-dimethylamino-2-fluorqplienyl H çyc1oropyi CO2H 1-2L50 4-chIoro-3-dimethytamino-2-fluorqpheny H cyclopropyt CO2Me 1-25 1 4-chtoro-3-dimethylamino-2-fluorophenyl H cycIopjy CO2Et - -4-chloro-3-dimethylainino-2-fluorophenyj H cyclopropyL CO2CH2CH2QEt 1 -253 4-chloro-3-dimethylamino-2-fluorophenyl H cyclopropyl CO2CI-J2Ph 1-254 4-chtoro-3-dimethylamino-2-fluorophenyl H viflyl -C021-I 1-255 4-chloro-3-dimethylamino-2-fluorophenyl H vinyl CO2Me 1-256 4-chloro-3-dimethylamino-2-fluorophenyl H vinyl CO2Et 1-257 4-chtoro-3-dimy1ainino-2-fluorppheny1 H vinyl CO2CH2CL-I2OEt 1-25 8 4-chloro-3-dimethylamino-2-fluorophenyl H vinyl CO2CH2Ph 1-259 4-chloro-3-dimethy1amino-2-fluoropheny FL Br CO2H - 1-260 4-chloro-3-dimethylamino-2-fluorophenyl H Br CO2Me 1-261 4-chtoro-3-dimethylamino-2-fluorophenyl H Me CO2H 1-262 4-chloro-3-dimethylamino-2-fluorophenyl H Me CO2Me 1-263 4-chloro-3-dimethylamino-2-fluorophenyl H 1 -propenyl CO2H 1-264 4-chloro-3-dimethylamino-2-fluorophenyl H 1 -propenyl CO2Me 1-265 4-chloro-3-dimethylamino-2-fluorophenyl F Cl CO2H 1-266 4-cliloro-3-dirnethylamino-2-fluorophenyl F Cl CO2Me 1-267 4-chloro-3-dimethylamino-2-fluorpphenyl F cycloroyy1 CO2H -1-268 4-chloro-3-dimethylarnino-2-fluorophenyl F cyclopropyl CO2Me 1-269 4-chloro-3-dimethylamino-2-fluorqphenyl F viyI CO2H 1-270 4-ch1oro-3-dimethylamino-2-qpheqy F vinyl CO2Me 1-27 1 4-chloro-3-dimethylamino-2-fluorqphenyl F Br CO2H -1-272 4-chloro-3-dimethylarnino-2-fluorophenyl _F Br CO2Me 1-273 4-chloro-3-dimethylaniino-2-fluorpphenyl F Me -CO2H 1-274 _4jorp-3dmethyjmino-2-f1uorophenyI F Me CO2Me 1-275 4-chloro-3-dimethylamino-2-fluorophenyl F I.-propenyl_ C021-I 1-276 4-chloro-3-dimethylamino-2-fluorophenyi F 1-propenyl CO2Me 1-277 4-chloro-3-dimethylamino-2-fluorophenyl Cl Cl --CO2H_ 1-278 4-chloro-3-dimethylarnino-2-fluorophenyl -_Cj --Cl CO2Me - 1-279 4-cbloro-3-dimethylamino-2-fluorophenyl Cl cyclopropyl C021-1 1-280 4-chloro-3-dimethylarnino-2-fluorophenyl Cl cyc1oppyI -CO2Me 1-281 --4-chloro-3-dirnethylamino-2-tluorophenyl Cl vinyl CO2H 1-282 4-chloro-3-dimethylarnino-2-fluorophenyl Cl vinyl CO2Me 1-283 4-ch1oro-3-dimethylamino-2-fluoropheyl -Cl Br CO2H 1-284 4-chloro-3-dimethylamino-2-fluorophenyl Cl Br CO2Me -1-285 4-chloro-3-dimethylamino-2-fluorophenyl -Cl -Me CO2H 1-286 -4-chloro-3-dimethylamino-2-fluorophenyl Cl -Me --2Me -1-287 4-chloro-3-dimethyamino-2-fluorophenyl -Cl prqpenyl CO2H__ 1-288 4-chloro-3-diinethylamino-2-fluoropbenyl Cl 1-propenyl -_CQ2Me 1-289 4-ch1oro-3-thmethyjaniino-2-flgphenyl --Br CI CO2H - 1-290 4-chloro-3-dirnethylamino-2-fluorophenyl Br Cl CO2Me 1-291* -4-chloro-3-dimethylamino-2-fluorophenyl Br cyclopropyl C0211 1-292 -4-chloro-3-dimethylamino-2-fluorophenyl Br cypropyl -CO2Me 1-293 4-ch1oro-3-dimethy1amino-2fluorphen -Br vinyl CO2FI 1-294 -4-chloro-3-dimethylamino-2-fluorophenyl Br vinyl CO2Me -1-295 -4-ch1oro-3-dirnethylamino-2-fluorphenyl --Br -Br -C021-1 - -1-296 4-chloro-3-dimethylamino-2-fluorophenyi -Br Br CO2Me 1-297 -4-chloro-3-dirnethylamino-2-fluorophenyl Br -Me --CO2H 1-298 4-chloro-3-dirnethylamino-2-fluorpheny -Br Me CO2Me 1-299 4-chloro-3-dimethylamino-2-fluorophenyl Br 1-propenyl C0211 1-300 4-chloro-3-dimethylamino-2-fluorppheJy Br lpropeny CO2Me 1-301 4-chloro-3-dimethylamino-2-fluorophenyl Me CI C021-I 1-302 4-chloro-3-dimethylamino-2-fluorophenyl Me Cl CO2Me 1-303 4-chloro-3-dirnethylamino-2-fluorophenyl _Me cyclopropyl CO2FI - -1-304 4-chloro-3-dimethylamino-2-tluorophenyl Me cyclopropyl CO2Me 1-305 4-ch1oro-3-dimethylamino-2-fluorpheny1 Me viny CO2H - 1-306 -4-chloro-3-dimethylamino-2-fluorophenyl Me vinyl CO2Me 1-307 4-chloro-3-dimethylaniino-2-fluorophenyl Me Br CO2H 1-308 4-chloro-3-dirnethylamino-2-fluorophenyl -Me Br CO2Me 1-309 -4-chloro-3-dimethylamino-2-fluorophenyl Me Me CO2H 1-310 4-chloro-3-dimethylamino-2-fluorophenyl -Me Me CO2Me 1-31 1 4-chloro-3-dimethylamino-2-fluorophenyl Me 1-propenyl CO2H 1-3 12 4-chloro-3-dimethylamino-2-flupjçpyl --Me 1-propenyl CO2Me 1-313 4-chloro-3-dimethylamino-2-fluorophenyl cyclopropyl Cl CO2H 1-314 4-chloro-3-dimetliylamino-2-fluorophenyl cyclopropyl Cl CO2Me 1-315 4-chloro-3-dimethylamino-2-fluorophenyl cyclopropyl cyclopropyl CO2H - 1-316 4-ch1oro-3-dimey1amino-2-fluoropheny1 cyclopropyl cyclopropyl CO2Me 1-317 4-chloro-3-dimethylamino-2-fluorophenyl cyclopropyl vinyl C0211 - 1-3 18 4-cIiloro-3-diniethylamino-2-fluorophenyl cyclopropyl vinyl CO2Me 1-319 4-chloro-3-dimethylamino-2-fluorqphenyl cyclopropyl Br C0211 1-320 4-chloro-3-dirnethylamino-2-fluorophenyl cyclopropyl Br CO2Me 1-321 4-cbloro-3-dimethylamino-2-fluorophenyl cycloppy Me C0211 - 1-322 4-cbloro-3-dimethylamino-2-fluorophenyl cyclopropyl Me CO2Me 1-323 4-chloro-3-diinethylamino-2-fluorophenyl cyclopoy 1-prop)t CO2H 1-324 4-cbloro-3-diniethylamino-2-fluorophenyl cyclopropyl 1-propenyl CO2Me - 1-325 isopropyl H Cl -CO2H - 1-326 isopropyl H -Cl CO2Me - 1-327 isopropyl H cycloprqpyl --_CO2H 1-328 isopropyl -H cyçlopropyl -CO2Me 1-329 isopropyl H vinyl CO2H 1-330 isopropyl -H ___________ -CO2Me 1-331 4-ch1oropieny1 H Cl CO2H 1-332 4-chlorophenyl H Cl CO2Me 1-333 4-cb1or9Jpny1 -H cyclopropyl -CO2H 1-334 -4-chloropçpy1 H cyclopropyl CO2Me - 1-335 4-chlorophenyl -H viny! --CO2H 1-336 4-ch1oropieny1 -H vinyl CO2Me 1-337 4-bromophenyl -H Cl --CO2H 1-338 4-bromçpçnyl H Cl CO2Me 1-339 -4-bromophenyl H yclopropy CO2H 1-340 4-brompheny1 H çyclopropyl çgMe - 1-341_ 4-bromophenyl__ --H yJpy -CO2H 1-342 4-bromçphenyl H vinyl CO2Me 1-343 2,4-dichlorophenyl -H Cl --CO2H -1-344 2,4-dichlorophenyl H Cl -CO2Me 1-345 2,4-dichlorophenyl H çyclopropyl CO2H - __________ -2,4-dichlorophenyl H _çycIpqpyl -CO2Me - 1-347 2,4-dichlorophenyl H -vinyl CO2H 1-348 2,4-dichlorophenyl -H -vinyl CO2Me 1-349 3,4-dichlorophenyl H ci CO2H -1-350 3,4-dichlorophenyl -H -CI CO2Me 1-351 3,4-dichlorophenyl H _çyclopropyl -CO2H - 1-352 3,4-dichlorophenyl H çyclopropyl CO2Me 1-353 3,4-dichlorophenyl H --vinyl CO2H 1-354 3,4-dichlorophenyl H viflyl CO2Me 1-355 4-chloro-2-fluorophenyl H Cl CO2H -1-356 4-chloro-2-fluorophenyl H Cl CO2Me - 1-357 4-chloro-2-fluorophenyl H cyclopropyl CO2H 1-358 4-chloro-2-fluoroheny1 H --çyclopropyl CO2Me 1-359 4-chloro-2-fluorophenyt H vinyl CO2H 1-360 4-chloro-2-fluorophenyl H -viy1 --CO2Me 1-36 1 4-chloro-3-fluorophenyl H Cl CO2H 1-362 4-chloro-3-fluorophenyt H ---CO2Me 1-363 4-chloro-3-fluorophenyl H cyclopropyl CO2H 1-364 4-chloro-3-fluorophenyl H çyclopropyl CO2Me 1-365 --4-chloro-3-fluorophenyl H vinyl CO2H 1-366 -4-chloro-3-fluorophenyl H vinyl -co2Me -- 1-367 2,4-dichloro-3-fluorophenyi -H Cl CO2H 1-368 -2,4-dichloro-3-fluorophenyl H Cl CO2Me - -j39_ --H -cyclopropyl CO2H 1-370 2,4-dichloro-3-fluorophenyl H çyclopropyi -CO2Me 1-371 --2,4-dichloro-3-fluorophenyl H vinyl CO2H 1-372 -2,4-dichloro-3-fluorophenji H -vinyl -CO2Me 1-373 4-chloro-2,3-diuluorophenyi H Cl CO2H 1-374 4-chloro-2,3-clifluorophenj'l H --CO2Me 1-375 4-chloro-2,3-difluorophenyl --H cyclopropyl -CO2H 1-376 4-chloro-2,3-difluorophenyl H ylqppyl CO2Me 1-377 4-chloro-2,3-dit1uorophenl -H -vinyl -CO2H 1-378 4-chloro-2,3-difluorophenyl H vinyL -CO2Me -1-379 _3,4-dichloro-2-fluorophenj'i -H --CI -CO2H 1-380 3,4-dichloro-2-fluorophenyl H -Cl CO2Me 1-381 3,4-dicMoro-2-fluoropyl H cyclopropyl -CO2H 1-382 3,4-dichloro-2-fluorophenyl H -cyclopropyl CO2Me 1-383 --3,4-dicbloro-2-fluorophenyl H -vinyl CO2H - 1-384 -3,4-dichloro-2-fluorophenjd -H vinyl CO2Me 1-385 2,3,4-trich1oqphenyl H -C CO2H -1-386 --2,3,4-ichloropy H CI CO2Me - 1-387 -2,3,4-trichiorophenyl H CO2H _1-388 2,3,4-trichlorophenyl --H cyclopropyl CO2Me -1-3 89 -2,3,4-trichlorophenyl -_H -vinyj C0211 1-390 2,3,4-trichlorophenyl H --vini[ -CO2Me - 1-391 4-trifluoromethylphenyl -H -CI CO2H 1-392 -4-trit1uoromethyphenyI H -CI CO2Me - 1-393 4-trifluoromethylphenyl -H cyclopropyl CO2H 1-394 --4-trif1uoromethyphenyI -H cyclopropyl CO2Me -1-395 4-trifluoromethylphenyl H vinyj -CO2H 1-396 4-trifluoromethylphenyl H vinyl CO2Me 1-397 -4-methypheny1 --H -CI CO2H - 1-398 4-methylphenyl H CI CO2Me 1-399 4-methyeny1 -H cyclopropyl CO2H 1-400 --4-rnethylphenyl -H -çyclppropyj CO2Me - 1-401 4-methylphenyl H vinyl --CO2H 1-402 4-methyphenyl H -vixL. -_-- -_1403_ -chloro-4-methy1phenyl_ --H -CI CO2H J-404 2-chloro-4-methyjhenyl -_H_ CI CO2Me 1-405 2-chloro-4-methylphenyl H çyclppropyj --CO2H - 1-406 2-chloro-4-methyjpienyl -H cyclopropyl CO2Me _1-407 2-chloro-4-methylphenyl H vinyj CO2H --1-408 -2-chlp-4-rnethyphenyl__ H -vinyl CO2Me 1-409 4,5-dichloro-2-fluorqphenyl H Cl CO2H 1-410 4,5-dichloro-2-fluorophenyl H Cl CO2Me 1411 4,5-dichloro-2-fluorqphenyl H çyclppropyj --CO2H 1-412 4,5-dichloro-2-fluorophenyl H cyclopropyl CO2Me 1-413 -4,5-dich1oro-2-fluorppeny --__--vinyl --CO2H 1-414 4,5-dichloro-2-fluorophenyl H vinyl CO2Me 1-415 -4-chbro-Z5-thf1uorony H Cl CO2H 1-416 4-chloro-2,5-difluorophenyl H Cl CO2Me 1-417 -4-chIoro-Z5-dffluoropenyj -H cyclopropyl CO2H - 1-418 4-chloro-2,5-difluorophenyl H cyclopropyl CO2Me 1-4 19 4-chloro-2,5-difluorqphenyl H vinyi -CO2H 1-420 4-chloro-2,5-difhiorophenyl H vinyl CO2Me -1-421 -5-chbwthjpen-22yl H Cl CO2H 1-42_ -5-chlorothphen-2-y1 H Cl CO2Me 1-423 5-chlorothiophen-2-yl H cyclopropy CO2H 1-424 --5-chlorothiqphen-2-yl H cyclopropyl CO2Me 1-425 5-chlorothiophen-2-yl -H -vinyl -CO2H 1-426 5-chlorothiçphen-2-yl H -viny CO2Me 1-427 6-chloropyridin-3-yI H Cl CO2H - 1-428 -6-chlojppyjdin-3-yl --H -CI CO2Me 1-429 6-chloropyridin-3-yl H cyclopropyl CO2H 1-430 -6-chloropyridin-3-yI -H cyclopropyl CO2Me 1-431 6-chloropyidin-3-yI H vinyl --CO2H 1-432 6-chloropyridin-3-yI H vinyl CO2Me 1-433 rnetyIthio H Cl --CO2H 1-434 methylthio -H Cl CO2Me 1-435 -meyl1hio H cyc1orqpy1 CO2H - 1-436 methylthio H cyclopropyl CO2Me -1-437 methylthio H viy CO2H - 1-438 --methylthio H __viy1 CO2Me 1-439 Cl H -CF3 C021-1 -- 1-440 Cl H CF3 -CO2Me 1-441 C F_ CF3 CO2H 1-442 -Cl -F CF3 -CO2Me - -1-443 Cl Cl CF3 CO2H 1-444 _CL -Cl CF3 CO2Me 1-445 CI -H ethynyl CO2H 1-446 --CI --H -ethynyl CO2Me 1-447 -Cl F etyy CO2H 1-448 -C F ethynyl CO2Me 1-449 Cl CI ethynyl CO2H 1-450 Cl Cl -ethyy1 -CO2Me - 1-451 Cl H I -propynyl CO2H 1-452 C ---H ______ CO2Me 1-453 Cl F 1-propynyl CO2H 1-454 -C_ --F ppnyCO2Me 1-455 Cl CI 1-propynyl C0211 1-456 -CL_ C -J-propyy1 --CO2Me -- 1-457 Cl H phenyl C021-l 1-458 Cl H phenyl CO2Me 1-459 Cl F -_p1heny_ CQ2ft__ -1-460 Cl -F phenyl CO2Me 1-461 Cl Cl phenyl CO2H 1-462 Cl Cl phenyl CO2Me 1-463 4-chloro-2-fluoro-3-methoxyphenyl -Cl 2-ethoçyviny CO2Me -1-464 Me --Cl Me C0211 1-465 Me CI Me_ CO2Me 1-466 --Vinyl -F Vinyl CO2U 1-467 vinyl F viyI -_SQ2M - 467 compounds are described, designated compounds 2-1 to 2-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 3-1 to 3-467 respectively, of formula (I) wherein R' is H, R4 is H, B? is H, W is a direct bond and Q is 2-chiorophenyl, and the values of A, X, Y and Z are as defined in Table I. 467 compounds are described, designated compounds 4-1 to 4-467 respectively, of formula (I) wherein R' is H, R4 is H, B? is H, W is a direct bond and Q is 3-chlorophenyl, arid the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 5-I to 5-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-chlorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 6-1 to 6-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 7-1 to 7-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 8-i to 8-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 9-I to 9-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-methylphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 10-i to 10-467 respectively, of formula (I) wherein R' is H, R4 is H, is H, W is a direct bond and Q is 4-methyiphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 11-1 to 11-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-trifluoromethylphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 12-1 to 12-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-trifluoromethylphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 13-1 to 13-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-aminophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 14-1 to 14-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-dimethylaminophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 15-1 to 15-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-nitrophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 16-1 to 16-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-nitrophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 17-1 to 17-467 respectively, of formula (1) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-nitrophcnyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 18-1 to 18-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2,5-difluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 19-1 to 19-467 respectively, of formula (I) wherein R1 is H, R4 is H, R5 is H, W is a direct bond and Q is 2,6-difluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 20-1 to 20-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3,5-difluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 21-1 to 21-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2,6-dichlorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 22-1 to 22-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2,4-dimethoxyphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 23-1 to 23-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3,4-dimethoxyphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 24-1 to 24-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is benzo[1,3]dioxol-5-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 25-1 to 25-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-chloro-3-methoxyphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 26-1 to 26-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-furanyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 27-1 to 27-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-bromofuran-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 28-1 to 28-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 5-bromofuran-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 29-1 to 29-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 5-methylfuran-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 30-1 to 30-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 5-broniothiophen-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 31-1 to 31-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-pyridyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 32-1 to 32-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-chloropyrid-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 33-1 to 33-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 3-methylpyrid-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 34-1 to 34-467 respectively, of formula (I) wherein R' is H, R4 is methyl, R5 is H, W is a direct bond and Q is cyclopropyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 35-1 to 35-467 respectively, of formula (I) wherein R' is H, R4 is methyl, R5 is H, W is a direct bond and Q is 4-phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 36-1 to 36-467 respectively, of formula (I) wherein R' is H, R4 is methyl, R5 is H, W is a direct bond and Q is 4-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 37-1 to 37-467 respectively, of formula (I) wherein R1 is H, R4 is methyl, R5 is H, W is a direct bond and Q is 2-furanyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 38-1 to 3 8-467 respectively, of formula (I) wherein R' is H, R4 is methyl, R5 is methyl, W is a direct bond and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 39-1 to 39-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is CH2 and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 40-1 to 40-467 respectively, of formula (I) wherein R' is H, R4 is Fl, R5 is H, W is CH(OH) and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 41-1 to 4 1-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is CH(OH)CH2O and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 42-1 to 42-467 respectively, of formula (I) wherein R' is H, R4 is methyl, R5 is II, W is CH(OH) and Q is phenyl, and the values of A, X, Y and Z are as defined in Table I. 467 compounds are described, designated compounds 43-1 to 43-467 respectively, of formula (I) wherein R' is H, R4 is CH2OI-I, R5 is H, W is CH(Oll) and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 44-1 to 44-467 respectively, of formula (I) wherein R1 is H, R4 is CO2H, R5 is H, W is CH2OCH2 and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 45-1 to 45-467 respectively, of formula (I) wherein R' is H, R4 is CO2Me, R5 is 1-I, W is C1-1(OH) and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 46-1 to 46-467 respectively, of formula (I) wherein R' is H, R4 is CO2Et, R5 is H, W is a direct bond and Q is phenyl, and the values of A, X, Y and Z are as defined in Table I. 467 compounds are described, designated compounds 47-1 to 47-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is phenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 48-1 to 48-467 respectively, of formula (I) wherein R' is methyl, K4 is H, K5 is Fl, W is a direct bond and Q is 3-chlorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 49-1 to 49-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is 2-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 50-1 to 50-467 respectively, of formula (I) wherein R' is methyl, R4 is H, K5 is H, W is a direct bond and Q is 3-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 51-1 to 51-467 respectively, of formula (I) wherein K' is methyl, R4 is I-I, K5 is H, W is a direct bond and Q is 4-fluorophenyl, and the values of A, X, Y and Z arc as defined in Table 1.
467 compounds are described, designated compounds 52-1 to 52-467 respectively, of formula (I) wherein K' is methyl, K4 is H, K5 is H, W is a direct bond and Q is 4-aminophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 53-I to 53-467 respectively, of formula (I) wherein R' is methyl, K4 is H, R5 is H, W is a direct bond and Q is 2-nitrophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 54-1 to 54-467 respectively, of formula (1) wherein K' is methyl, K4 is H, K5 is H, W is a direct bond and Q is 4-nitrophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 55-1 to 55-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is 2-fbranyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 56-1 to 5 6-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is 5-methylfiiran-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 57-1 to 57-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is 5-bromothiophen-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 58-1 to 58-467 respectively, of formula (I) wherein R' is methyl, R4 is H, R5 is H, W is a direct bond and Q is 4-pyridyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 59-1 to 59-467 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is phcnyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 60-1 to 60-46 7 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is 2-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 61-1 to 61-467 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is 3-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 62-1 to 62-467 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is 4-fluorophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 63-1 to 63-467 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is 2-furanyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 64-1 to 64-467 respectively, of formula (I) wherein R' is ethyl, R4 is H, R5 is H, W is a direct bond and Q is 5-methylfuran-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 65-1 to 65-467 respectively, of formula (I) wherein R' is isopropyl, R4 is H, R5 is H, W is a direct bond and Q is 2-furanyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 66-1 to 66-467 respectively, of formula (1) wherein R' is 2-hydroxyethyl, R4 is H, R5 is H, W is a direct bond and Q is 2-furanyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 67-1 to 67-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is cyclohexyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 68-1 to 68-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-hydroxycyclohexyl, and the values of A, X, Y and Z are as defined in Table I. 467 compounds are described, designated compounds 69-1 to 69-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is cyclooctyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 70-1 to 70-467 respectively, of formula (I) wherein B) is H, R4 is H, B) is H, W is a direct bond and Q is 2-tetrahydrofuranyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 71-1 to 71-467 respectively, of formula (I) wherein B) is H, R4 is H, B) is H, W is a direct bond and Q is N-ethyl-pyrrolidin-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 72-1 to 72-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-bromophenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 73-1 to 73-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-methoxyphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 74-1 to 74-467 respectively, of formula (I) wherein B) is H, R4 is H, R5 is H, W is a direct bond and Q is 2-trifluoromethylphenyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 75-1 to 75-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is thiophen-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 76-1 to 76-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 2-bromothiophen-3-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 77-1 to 77-467 respectively, of formula (I) wherein R' is H, jj4 is Fl, R5 is H, W is a direct bond and Q is 1,3-dimethyl-pyrazol-5-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 78-1 to 78-467 respectively, of formula (I) wherein R1 is H, R4 is H, R5 is H, W is a direct bond and Q is 3-pyridyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 79-1 to 79-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 6-trifluoromethylpyrid-3-yl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 80-1 to 80-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 4-pyridyl, and the values of A, X, Y and Z are as defined in Table 1.
467 compounds are described, designated compounds 81-1 to 8 1-467 respectively, of formula (I) wherein R' is H, R4 is H, R5 is H, W is a direct bond and Q is 5-methylpyrazin-2-yl, and the values of A, X, Y and Z are as defined in Table 1.
In particular, the present invention provides a composition comprising a compound of formula (I) as described above and AD 67 or a compound of formula (I) as described above and benoxacor or a compound of formula (I) as described above and cloquintocet-mexyl or a compound of formula (I) as described above and cyprosulfamide or a compound of formula (I) as described above and dichlormid or a compound of formula (I) as described above and fenchlorazole-ethyl or a compound of formula (I) as described above and fenclorim or a compound of formula (I) as described above and flurazole or a compound of formula (I) as described above and fluxofenim or a compound of formula (I) as described above and furilazole or a compound of formula (I) as described above and the R isomer of furilazole or a compound of formula (I) as described above and isoxadifen-ethyl or a compound of formula (I) as described above and mefenpyr-diethyl or a compound of formula (I) as described above and oxabetrinil or a compound of formula (I) as described above and naphthalic anhydride or a compound of formula (I) as described above and N-isopropyl-4-(2-methoxy-benzoylsulfanioyl)- benzamide or a compound of formula (I) as described above and N-(2-methoxybenzoyl)- 4-[(methylaminocarbonyl)amino]benzenesulfonamide. Particularly preferred safeners for use in the invention are cloquintocet-mexyl, cyprosulfamide, fenchiorazole-ethyl, mefenpyr-diethyl and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino}benzenesulfonamide.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-1 to 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 31-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 41-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with AD 67 (MON 4660).
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-i to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-i to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-i to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-ito 79-467, 80-ito 80-467 and 81-1 to 81-467 with benoxacor.
In particular, the present invention provides a compositions comprising any one of compounds 1-i to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-i to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, i7-i to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-i to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-i to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-i to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-i to 37-467, 38-1 to 38-467, 39-i to 39-467, 40-1 to 40-467, 41-i to 41-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-i to 47-467, 48-i to 48-467, 49-1 to 49-467, 50-i to 50-467, 51-i to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-i to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-i to 64-467, 65-i to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-i to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-i to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with cloquintocet-mexyl.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-i to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, li-ito 11-467, 12-i to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-i to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-i to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-i to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-i to 30-467, 31-1 to 3 1-467, 32-i to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 3 5-467, 36-1 to 36-467, 37-1 to 37-467, 38-i to 38-467, 39-1 to 39-467, 40-i to 40-467, 41-i to 41-467, 42-i to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-i to 45-467, 46-1 to 46-467, 47-i to 47-467, 48-i to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-i to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-i to 57-467, 58-1 to 58-467, 59-i to 59-467, 60-1 to 60-467, 61-i to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-ito 79-467, 80-ito 80-467 and 81-1 to 81-467 with cyprosuifamide (CAS RN 221667-31-8).
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-i to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-i to 10-467, 11-ito 11-467, 12-i to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-i to i6-467, 17-i to 17-467, 18-i to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-i to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-i to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-i to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 3 5-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-i to 43-467, 44-1 to 44-467, 45-! to 45-467, 46-1 to 46-467, 47-i to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-i to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-i to 57-467, 58-i to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 6 1-467, 62-i to 62-467, 63-1 to 63-467, 64-i to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-i to 68-467, 69-i to 69-467, 70-i to 70-467, 71-1 to 71-467, 72-i to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-i to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-i to 80-467 and 81-1 to 81-467 with dichiormid.
In particular, the present invention provides a compositions comprising any one of compounds i-i to 1-467, 2-i to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-i to 8-467, 9-i to 9-467, 10-i to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-i to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-i to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-i to 29-467, 30-i to 30-467, 31-1 to 3i-467, 32-i to 32-467, 33-1 to 33-467, 34-i to 34-467, 35-1 to 35-467, 36-i to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-i to 39-467, 40-i to 40-467, 41-1 to 41-467, 42-1 to 42-467, 43-i to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-i to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-i to 50-467, 51-i to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-i to 61-467, 62-i to 62-467, 63-i to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 7 1-467, 72-i to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-Ito 79-467, 80-1 to 80-467 and 81-1 to 81-467 with fenchiorazole-ethyl.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-i to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-I to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 31-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 7 1-467, 72-1 to 72-467, 73-I to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with fenclorim.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 31-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-! to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-i to 79-467, 80-i to 80-467 and 81-1 to 81-467 with flurazole.
In particular, the present invention provides a compositions comprising any one of compounds 1-i to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-i to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, Il-i to 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-i to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-i to 31-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-i to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-I to 41-467, 42-1 to 42-467, 43-i to 43-467, 44-1 to 44-467,45-Ito 45-467, 46-i to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-i to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-i to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-I to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 704 to 70-467, 71-1 to 7 1-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-i to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-i to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with uluxolenim.
In particular, the present invention provides a compositions comprising any one of compounds 1-i to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-i to 5-467, 6-i to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-i to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-i to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-i to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-i to 30-467, 31-i to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-i to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-i to 40-467, 41-i to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-i to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-i to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-i to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-i to 60-467, 61-i to 6 1-467, 62-i to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-! to 69-467, 70-1 to 70-467, 71-1 to 7 1-467, 72-1 to 72-467, 73-i to 73-467, 74-1 to 74-467, 75-i to 75-467, 76-1 to 76467,77-Ito 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81 -467 with furilazole.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 3 8-467, 39-1 to 39-467, 40-i to 40-467, 41-1 to 4 1-467, 42-1 to 42-467,43-ito 43-467, 44-1 to 44-467, 45-1 to iO 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-i to 48-467, 49-i to 49-467, 50-i to 50-467, 51-i to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-i to 54-467, 55-1 to 55-467, 56-i to 56-467, 57-i to 57-467, 58-1 to 58-467, 59-i to 59-467, 60-i to 60-467, 61-i to 6 1-467, 62-i to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-i to 65-467, 66-1 to 66-467, 67-i to 67-467, 68-i to 68-467, 69-1 to 69-467, 70-i to 70-467, 71-i to 71-467, 72-i to 72-467, 73-i to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-i to 76-467, 77-1 to 77-467, 78-i to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-i to 8 1-467 with the R isomer of furilazole.
In particular, the present invention provides a compositions comprising any one of compounds i-i to i-467, 2-i to 2-467, 3-1 to 3-467, 4-i to 4-467, 5-i to 5-467, 6-i to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, iO-1 to 10-467, il-ito 1 i-467, 12-i to 12-467, i3-i to i3-467, i4-i to i4-467, is-i to 15-467, 16-1 to 16-467, 17-i to i7-467, 18-1 to 18-467, 19-1 to 19-467, 20-i to 20-467, 21-i to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-i to 26-467, 27-i to 27-467, 28-i to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-i to 32-467, 33-i to 33-467, 34-i to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-i to 3 7-467, 38-1 to 3 8-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4i-467, 42-1 to 42-467,43-ito 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-i to 48-467, 49-i to 49-467, 50-1 to 50-467, 51-1 to 5i-467, 52-1 to 52-467, 53-i to 53-467, 54-i to 54-467, 55-i to 55-467, 56-1 to 56-467, 57-i to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-i to 6i-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-i to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-i to 68-467, 69-1 to 69-467, 70-i to 70-467, 71-i to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-i to 75-467, 76-i to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-i to 79-467, 80-1 to 80-467 and 81-i to 8 1-467 with isoxadifen-ethyl.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-1 to 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 31-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 3 5-467, 36-1 to 36-467, 37-1 to 3 7-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 41-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with mefenpyr-diethyl.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 81-467 with oxabetrinil.
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 3 5-467, 36-i to 36-467, 37-1 to 3 7-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 4 1-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 51-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-1 to 8 1-467 with naphthalic anhydride (CASRN81-84-5).
In particular, the present invention provides a compositions comprising any one of compounds 1-1 to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-1 to 34-467, 35-1 to 3 5-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 41-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 to 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-1 to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 71-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-1 to 79-467, 80-1 to 80-467 and 81-i to 8 1-467 with N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide (CAS RN 221668-34-4).
In particular, the present invention provides a compositions comprising any one of compounds i-i to 1-467, 2-1 to 2-467, 3-1 to 3-467, 4-1 to 4-467, 5-1 to 5-467, 6-1 to 6-467, 7-1 to 7-467, 8-1 to 8-467, 9-1 to 9-467, 10-1 to 10-467, 11-Ito 11-467, 12-1 to 12-467, 13-1 to 13-467, 14-1 to 14-467, 15-1 to 15-467, 16-1 to 16-467, 17-1 to 17-467, 18-1 to 18-467, 19-1 to 19-467, 20-1 to 20-467, 21-1 to 21-467, 22-1 to 22-467, 23-1 to 23-467, 24-1 to 24-467, 25-1 to 25-467, 26-1 to 26-467, 27-1 to 27-467, 28-1 to 28-467, 29-1 to 29-467, 30-1 to 30-467, 31-1 to 3 1-467, 32-1 to 32-467, 33-1 to 33-467, 34-i to 34-467, 35-1 to 35-467, 36-1 to 36-467, 37-1 to 37-467, 38-1 to 38-467, 39-1 to 39-467, 40-1 to 40-467, 41-1 to 41-467, 42-1 to 42-467, 43-1 to 43-467, 44-1 to 44-467, 45-1 to 45-467, 46-1 to 46-467, 47-1 to 47-467, 48-1 to 48-467, 49-1 to 49-467, 50-1 to 50-467, 51-1 to 5 1-467, 52-1 to 52-467, 53-1 to 53-467, 54-1 to 54-467, 55-1 to 55-467, 56-1 to 56-467, 57-1 lo 57-467, 58-1 to 58-467, 59-1 to 59-467, 60-1 to 60-467, 61-1 to 61-467, 62-1 to 62-467, 63-1 to 63-467, 64-1 to 64-467, 65-1 to 65-467, 66-i to 66-467, 67-1 to 67-467, 68-1 to 68-467, 69-1 to 69-467, 70-1 to 70-467, 71-1 to 7 1-467, 72-1 to 72-467, 73-1 to 73-467, 74-1 to 74-467, 75-1 to 75-467, 76-1 to 76-467, 77-1 to 77-467, 78-1 to 78-467, 79-ito 79-467, 80-ito 80-467 and 81-1 to 81-467 with N-(2-methoxybenzoyl)- 44(methylaminocarbonyl)amino]benzenesulfonamide.
General methods for the production of compounds of formula (I) are described below. Unless otherwise stated in the text, the substitutents A, R', R4, B?, W, Q, X, Y and Z are as defined hereinbefore. The abbreviation LG as used herein refers to any suitable leaving group. Preferred leaving groups are halogen, sulphonate (preferably tosylate), and sulphone groups.
Compounds of formula (I) may be prepared from compounds of formula (A) as shown in reaction scheme 1.
Reaction Scheme 1 R,Jc(5 RL.%N)CI :xc:x: (A) (I) For example (see reaction scheme 2) a compound of formula (I), in which Y is a group attached through a carbon atom, may be prepared by reacting a suitable metal or metalloid derivative Y-M (e.g. a boronic acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) with a compound of formula (A) in the presence of a suitable base (e.g. an inorganic base, such as potassium phosphate or eaesium fluoride), a metal source (e.g. a palladium source, such as Pd(OAc)2) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as PCy3.FIBF4) in a suitable solvent (e.g. a single solvent, such as dimethylformamide, or a mixed solvent system, such as a mixture of dimethoxyethane and water or toluene and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g. a palladiumlphosphine complex, such as bis(triphenylphosphine)palladium dichioride or [1,1 -bis(diphenylpbosphino)ferrocene] palladium dichloride dichloromethane adduct).
Reaction scheme 2 RL, ,JçR' Rc)CR5 :xc (A) (I) In a second example (see reaction scheme 3) a compound of formula (I), in which Y is a cyano group, may be prepared by reacting a metal cyanide (e.g. copper(I) cyanide) with a compound of formula (A) in a suitable solvent (e.g. dimethylformamide or N-methylpyrrolidone). This transformation may also be performed in the presence of a suitable metal (e.g. palladium) catalyst, optionally complexed by any suitable ligands (e.g. phosphine ligands, such as 1, 1'-bis(diphenylphosphino)ferrocene).
Reaction scheme 3 RL, ,JCR: WCN RL.%N)CRRS (A) (I) In a third example (see reaction scheme 4) a compound of formula (I), in which Y is a group attached through a nitrogen atom, may be prepared by reacting a suitable amine (e.g. propylaminc) with a compound of formula (A) in the presence of a suitable base (e.g. an inorganic base, such as sodium tert-butoxide), a metal source (e.g. a palladium source, such as Pd2(dba)3) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as Johnphos) in a suitable solvent (e.g. toluene).
In a fourth example (see reaction scheme 4) a compound of formula (I), in which Y is a group attached through a phosphorous atom, may be prepared by reacting a suitable phosphine or phosphonate (e.g. diphenyiphosphine or diethylphosphite) with a compound of formula (A) in the presence of a suitable base (e.g. triethylamine), and a metal source (e.g. a palladium source, such as Pd(OAc)2) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as triphenyiphosphine) in a suitable solvent (e.g. toluene).
Reaction scheme 4 Rç RLJcZ (A) (I) In a fifth example (see reaction scheme 5) a compound of formula (I), in which Y is a hydroxyl group, may be prepared by reacting a suitable organometallic reagent (e.g. n-butyllithium) with a compound of formula (A) in a suitable solvent (e.g. tetrahydrofuran) followed by a treatment with an alkylborane (e.g. tris-isopropoxyborane), and ultimately exposed to an oxidative work up (e.g. hydrogen peroxide in aqueous base, such as sodium hydroxide).
Reaction scheme 5 wee® wee®
RLJCR RLJCR
(A) (I) In a sixth example (see reaction scheme 6) a compound of formula (I) in which Y is an alkylthio group may be prepared by reacting a compound of formula (A) with a metal alkyithiolate (e.g. sodium methanethiolate) in a suitable solvent (e.g. methanol).
Reaction scheme 6 Rk Rk)CRS
N R M-SR R :xc
(A) (I) Compounds of formula (I) may be prepared from compounds of formula (B) as shown in reaction scheme 7.
Reaction scheme 7 RL Rc,JCR5 (B) (I) For example (see reaction scheme 8) a compound of formula (I), in which A is a group attached through a carbon atom, may be prepared by reacting a suitable metal or metalloid derivative A-M (e.g. a boronic acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) with a compound of formula (B) in the presence of a suitable base (e.g. an inorganic base, such as potassium phosphate or caesium fluoride), a metal source (e.g. a palladium source, such as Pd(OAc)2) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as PCy3.FIBF4) in a suitable solvent (e.g. a single solvent, such as dimethylformamide, or a mixed solvent system, such as a mixture of dimethoxyethane and water or toluene and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g. a palladiunVphosphine complex, such as bis(triphenylphosphine)palladium dichioride or [1,1'-bis(diphenylphosphino)ferrocene] palladium dichioride dichioromethane adduct).
Reaction scheme 8 W.M Rç A (B) (I) In a second example (see reaction scheme 9) a compound of formula (I), in which A is an alkylthio group, may be prepared by reacting a metal alkylthiolate (e.g. sodium methanethiolate) with a compound of formula (B) in a suitable solvent (e.g. methanol).
Reaction scheme 9 w,o Rç _JCR RSM RLS..N)CR:
LGXZ
(B) (I) In a third example (see reaction scheme 10) a compound of formula (I), in which A is a halogen, may be prepared by reacting a metal halide or metalloid derivative A-M (e.g. potassium fluoride, sodium iodide or bromotrimethylsilane) with a compound of formula (C) in a suitable solvent (e.g. acetonitrile or dimethyl sulfoxide).
Reaction scheme 10 wit® wit® R)CRS RLJCC LGXXZ MHaI (B) (I) Compounds of formula (I) may be prepared from compounds of formula (C) as shown in reaction scheme 11.
Reaction scheme 11 w,o Rç)CF, RkN,JC% :xc (C) (I) For example (sec reaction scheme 12) a compound of formula (1), in which X is a group attached through a carbon atom, may be prepared by reacting a suitable metal or metalloid derivative X-M (e.g. a boronic acid or ester, a trialkyltin derivative, a zinc derivative or a Grignard reagent) with a compound of formula (C) in the presence of a suitable base (e.g. an inorganic base, such as potassium phosphate or caesium fluoride), a metal source (e.g. a palladium source, such as Pd(OAc)2) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as PCy3.I-IBF4) in a suitable solvent (e.g. a single solvent, such as dimethylformamide, or a mixed solvent system, such as a mixture of dimethoxyethane and water or toluene and water). The metal catalyst and ligands may also be added as a single, pre-formed, complex (e.g. a palladiumlphosphirie complex, such as bis(triphenylphosphine)palladium dichloride or [1,1 -bis(diphenylphosphino)ferrocene] palladium dichloride dichloromethane adduct).
In a second example (see reaction scheme 12) a compound of formula (I), in which X is a cyano group, may be prepared by reacting a metal cyanide (e.g. copper(I) cyanide) with a compound of formula (C) in a suitable solvent (e.g. dimethylformamide or N-methylpyrrolidone). This transformation may also be performed in the presence of a suitable metal (e.g. palladium) catalyst, optionally complexed by any suitable ligands (e.g. phosphine ligands, such as 1,1 -bis(diphenylphosphino)ferrocene).
Reaction scheme 12 Rç X..M RLNN)CIS :xc (C) (I) In a third example (see reaction scheme 13) a compound of formula (I), in which X is a group attached through a nitrogen atom, may be prepared by reacting a suitable amine (e.g. propylamine) with a compound of formula (C) in the presence of a suitable base (e.g. an inorganic base, such as sodium tert-butoxide), a metal source (e.g. a palladium source, such as Pd2(dba)3) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as JohnPhos) in a suitable solvent (e.g. toluene).
In a fourth example (see reaction scheme 13) a compound of formula (I), in which X is a group attached through a phosphorous atom, may be prepared by reacting a suitable phosphine or phosphonate (e.g. diphenyiphosphine or diethylphosphite) with a compound of formula (C) in the presence of a suitable base (e.g. triethylamine), and a metal source (e.g. a palladium source, such as Pd(OAc)2) and, optionally, a ligand for the metal (e.g. a phosphine ligand, such as triphcnylphosphine) in a suitable solvent (e.g. toluene).
Reaction scheme 13 V® V® x..% U3xv H (C) (I) In a fifth example (see reaction scheme 14) a compound of formula (I), in which X is a hydroxyl group, may be prepared by reacting a suitable organometallic reagent (e.g. n-butyllithium) with a compound of formula (C) in a suitable solvent (e.g. tetrahydrofuran) followed by a treatment with an alkylborane (e.g. trisisopropoxyborane), and ultimately exposed to an oxidative work up (e.g. hydrogen peroxide in aqueous base, such as sodium hydroxide).
Reaction scheme 14 RcN)c (C) (I) Compounds of formula (C) may be prepared from compounds of formula (D) as shown in reaction scheme 15.
Reaction scheme 15 ws,o Rç R1.N.,JCR5 LG" (D) (C) For example a compound of formula (C) in which LG is a halogen may be prepared from a compound of formula (D) by reaction with a halogenating agent (e.g. Selectfluor®, an N-halosuccinimide such as N-chlorosuccinimide or N-iodosuccinimide, or an elemental halogen such as bromine) in a suitable solvent (e.g. acetonitrile). This transformation may also be performed by first deprotonating compound of formula (D) with a suitable base (e.g. LDA or ZnTMP), followed by a reaction with a halogenating agent (e.g. Selectfluor®, an N-halosuccinimide such as N-chlorosuccinimide or N-iodosuccinimide, or an elemental halogen such as bromine).
Compounds of formula (I) may be prepared from compounds of formula (E) as shown in reaction scheme 16.
Reaction scheme 16 w,o Rç,J<R5 (E) (I) For example, a compound of formula (I) may be prepared from a compound of formula (E) by reaction with a reagent R'(QWCR4R5)N-FI or its salt (e.g. a hydrogen halide salt, such as R'(QWCR4R5)NH2C1) in the presence of a suitable base (e.g. an organic base, such as triethylamine), in a suitable solvent (e.g. an organic solvent, such as dimethylformamide).
One skilled in the art will realise that it is often possible to alter the order in which the transformations described above are conducted, or to combine them in alternative ways to prepare a wide range of compounds of formula (I). All such variations are contemplated within the scope of the invention.
The skilled man will also be aware that some reagents will be incompatible with certain values or combinations of the substituents A, R', R4, R5, W, Q, X, Y and Z as defined herein, and any additional steps, such as protection andlor deprotection steps, which are necessary to achieve the desired transformation will be clear to the skilled man.
The safeners of the invention are described in The Pesticide Manual, l4ti Edition, 2006. It is noted that the safeners for use in the compositions of the invention may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 14th Edition supra. Thus, the reference to cloquintocet-mexyl also applies to a lithium, sodium, potassium, calcium, magnesium, aluminium, iron, ammonium, quatemary ammonium, sulfonium or phosphonium salt thereof as disclosed in W002/34048, and the reference to fenchiorazole-ethyl also applies to fenchlorazole, etc. Preferably the mixing ratio of compound of formula (I) to safener is from 100:1 to 1:10, especially from 20:1 to 1:1.
The safened compositions of the present invention are preferably formulated in any suitable manner using formulation adjuvants, such as carriers, solvents and surface.
active substances, for example, as described hereinafter. Accordingly, the present invention provides a composition of the invention which further comprises at least one agriculturally acceptable adjuvant or diluent.
The formulated compositions can be in various physical forms, e.g. in the form of dusting powders, gels, wettable powders, water-dispersible granules, water-dispersible tablets, effervescent pellets, emulsifiable concentrates, microemulsifiable concentrates, oil-in-water emulsions, oil-flowables, aqueous dispersions, oily dispersions, suspo-emulsions, capsule suspensions, suspension concentrates, emulsifiable granules, soluble liquids, water-soluble concentrates (with water or a water-miscible organic solvent as carrier), impregnated polymer films or in other forms known e.g. from the Manual on Development and Use of FAO Specifications for Plant Protection Products, 5th Edition, 1999. The formulated compositions can be in the form of concentrates which are diluted prior to use, although ready-to-use formulations can also be made. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
The formulated compositions can be prepared e.g. by mixing the active ingredient with the formulation adjuvants in order to obtain compositions in the form of finely divided solids, granules, solutions, dispersions or emulsions. The active ingredients can also be formulated with other adjuvants, such as finely divided solids, mineral oils, oils of vegetable or animal origin, modified oils of vegetable or animal origin, organic solvents, water, surface-active substances or combinations thereof The active ingredients can also be contained in very fine microcapsules consisting of a polymer.
Microcapsules usually have a diameter of from 0.1 to 500 microns. Typically, they will contain active ingredients in an amount of about from 25 to 95% by weight of the capsule weight. The active ingredients can be in the form of a monolithic solid, in the form of fine particles in solid or liquid dispersion or in the form of a suitable solution. The encapsulating membranes comprise, for example, natural or synthetic rubbers, cellulose, styrene/butadiene copolymers, polyacrylonitrile, polyacrylate, polyesters, polyamides, polyureas, polyurethane or chemically modified polymers and starch xanthates or other known polymers. Alternatively, very fine microcapsules can be formed in which the active ingredient is contained in the form of finely divided particles in a solid matrix of base substance, but the microcapsules are not themselves encapsulated.
The formulation adjuvants that are suitable for the preparation of compositions according to the invention are known per se. As liquid carriers there may be used: water, toluene, xylene, petroleum ether, vegetable oils, acetone, methyl ethyl ketone, cyclohexanone, acid anhydrides, acetonitrile, acetophenone, amyl acetate, 2-butanone, butylene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid (e.g. butyl acetate, ethyl acetate, isoamyl acetate, amyl acetate), diacetone alcohol, 1,2-S dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,N-.dimethylformamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, 2-ethylhexanol, ethylene carbonate, 1,1,1 -trichloroethane, 2-beptanone, alpha-pinene, d-limonene, ethyl lactate, ethylene glycol, ethylene glycol butyl ether, ethylene glycol methyl ether, gamma-butyrolactone, glycerol, glycerol acetate, glycerol diacetate, glycerol triacetate, hexadecane, hexylene glycol, , isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxypropanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, n-hexane, n-octylamine, octadecanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG), propionic acid, propyl lactate, propylene carbonate, propylene glycol, propylene glycol methyl ether, p-xylene, toluene, triethyl phosphate, triethylene glycol, xylenesulfonic acid, paraffin, mineral oil, trichloroethylene, perchloroethylene, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, N-methyl-2-pyrrotidone and the like. Water is generally the carrier of choice for diluting the concentrates. Suitable solid carriers are, for example, talc, titanium dioxide, pyrophyllite clay, silica, attapulgite clay, kieselguhr, limestone, calcium carbonate, bentonite, calcium montmorillonite, cottonseed husks, wheat flour, soybean flour, pumice, wood flour, ground walnut shells, lignin and similar substances, as described, for example, in CFR 180.1001. (c) & (d).
A large number of surface-active substances may advantageously be used in the formulations, especially in those formulations designed to be diluted with a carrier prior to use. Surface-active substances may be anionic, cationic, non-ionic or polymeric and they can be used as emulsifiers, wetting agents or suspending agents or for other purposes. Typical surface-active substances include, for example, salts of alkyl sulfates, such as diethanolammonium lauryl sulfate; salts of alkylarylsulfonates, such as calcium dodecylbenzenesulfonate; alkylphenol/alkylene oxide addition products, such as nonyiphenol ethoxylate; alcohol/alkylene oxide addition products, such as tridecylalcohol ethoxylate; soaps, such as sodium stearate; salts of alkylnaphthalenesulfonates, such as sodium dibutylnaphthalenesulfonate; dialkyl esters of sulfosuccinate salts, such as sodium di(2-ethylhexyl)sulfosuccinate; sorbitol esters, such as sorbitol oleate; quatemary amities, such as lauryltrimethylamnionium chloride, polyethylene glycol esters of fatty acids, such as polyethylene glycol stearate; block copolymers of ethylene oxide and propylene oxide; and salts of mono-and di-alkylphosphate esters; and also further substances described e.g. in "McCutcheon's Detergents and Emulsifiers Annual" MC Publishing Corp., Ridgewood New Jersey, 1981.
Further adjuvants that can usually be used in such formulations include crystallisation inhibitors, viscosity modifiers, suspending agents, dyes, anti-oxidants, foaming agents, light absorbers, mixing auxiliaries, antifoams, complexing agents, neutralising or pH-modifying substances and buffers, corrosion inhibitors, fragrances, wetting agents, take-up enhancers, micronutrients, plasticisers, glidants, lubricants, dispersants, thickeners, antifreezes, microbicides, and also liquid and solid fertilisers.
The formulated compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alky! esters of such oils or mixtures of such oils and oil derivatives. The amount of oil additive in the composition according to the invention is generally from 0.01 to 10%, based on the spray mixture. For example, the oil additive can be added to the spray tank in the desired concentration after the spray mixture has been prepared. Preferred oil additives comprise mineral oils or an oil of vegetable origin, for example rapeseed oil, olive oil or sunflower oil, emulsified vegetable oil, such as AMIGO® (Rhône-Poulenc Canada Inc.), alkyl esters of oils of vegetable origin, for example the methyl derivatives, or an oil of animal origin, such as fish oil or beef tallow. A preferred additive contains, for example, as active components essentially 80% by weight alkyl esters of fish oils and 15% by weight methylated rapeseed oil, and also 5% by weight of customary emulsifiers and pH modifiers. Especially preferred oil additives comprise alkyl esters of C8..22 fatty acids, especially the methyl derivatives of C12.18 fatty acids, for example the methyl esters of laurie acid, palmitic acid and oleic acid, being of importance. Those esters are known as methyl laurate (CAS-1 11-82-0), methyl palmitate (CAS-1 12-39-0) and methyl oleate (CAS-112-62-9). A preferred fatty acid methyl ester derivative is Emery® 2230 and 2231 (Cognis GmbH). Those and other oil derivatives are also known from the Compendium of Herbicide Adjuvants, 5th Edition, Southern Illinois University, 2000.
Another preferred adjuvant is Adigor® (Syngenta AG) which is a methylated rapeseed oil-based adjuvant.
The application and action of the oil additives can be further improved by combination with surface-active substances, such as non-ionic, anionic or cationic surfactants. Examples of suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of W097/34485. Preferred surface-active substances are anionic surfactants of the dodecylbenzylsulfonate type, especially the calcium salts thereof, and also non-ionic surfactants of the fatty alcohol ethoxylate type. Special preference is given to ethoxylated C12.22 fatty alcohols having a degree of ethoxylation of from 5 to 40.
Examples of commercially available surfactants are the Genapol types (Clariant AG).
Also preferred are silicone surfactants, especially polyalkyl-oxide-modified heptamethyltriloxanes which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants. The concentration of the surface-active substances in relation to the total additive is generally from 1 to 30% by weight. Examples of oil additives consisting of mixtures of oil or mineral oils or derivatives thereof with surfactants are Edenor ME SU®, Turbocharge® (Syngenta AG, CH) or ActipronC (BP Oil UK Limited, GB).
If desired, it is also possible for the mentioned surface-active substances to be used in the formulations on their own, that is to say, without oil additives.
Furthermore, the addition of an organic solvent to the oil additive/surfactant mixture may contribute to an additional enhancement of action. Suitable solvents are, for example, Solvesso® (ESSO) or Aromatic Solvent® (Exxon Corporation). The concentration of such solvents can be from 10 to 80% by weight of the total weight. Oil additives that are present in admixture with solvents are described, for example, in US-A- 4,834,908. A commercially available oil additive disclosed therein is known by the name MERGE® (BASF Corporation). A further oil additive that is preferred according to the invention is SCORE® (Syngenta Crop Protection Canada).
In addition to the oil additives listed above, for the purpose of enhancing the action of the compositions according to the invention it is also possible for formulations of alkylpyrrolidones (e.g. Agrimax®) to be added to the spray mixture. Formulations of synthetic lattices, e.g. polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®) may also be used. It is also possible for solutions that contain propionic acid, for example Eurogkem Penetrate®, to be added to the spray mixture as action-enhancing agent.
Formulated compositions of the invention generally comprise from 0.1 to 99% by weight, especially from 0.1 to 95% by weight, compounds of formula (I) and from 1 to 99.9% by weight of a formulation adjuvant which preferably includes from 0 to 25% by weight of a surface-active substance. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
The compositions of the present invention can also be used in combination with other active ingredients, e.g. other herbicides, and/or insecticides, andlor acaricides, and/or nematoeides, and/or molluscicides, and/or fungicides, and/or plant growth regulators. Such mixtures, and the use of such mixtures to control weeds and/or undesired plant growth form yet further aspects of the invention. For the avoidance of doubt, mixtures of invention also include mixtures of two or more different compounds of formula (I). In particular, the present invention also relates to a composition of the invention which comprises at least one further herbicide in addition to the compound of formula (I) and the safener.
Suitable further herbicides include, but are not limited to acetochlor, acifluorfen, acifluorfen-sodium, aclonifen, acrolein, alachlor, alloxydim, allyl alcohol, ametryn, amicarbazone, amidosulfuron, aminocyclopyrachior, aminopyralid, amitrole, anunonium sulfamate, anilofos, asulam, atrazine, aviglyeine, azafenidin, azimsulfuron, BCPC, beflubutamid, benazolin, bencarbazone, benfluralin, benfuresate, bensulfuron, bensulfuron-methyl, bensulide, bentazone, benzfendizone, benzobicyclon, benzofenap, bifenox, bilanafos, bispyribac, bispyribac-sodium, borax, bromacil, bromobutide, bromophenoxim, bromoxynil, butachlor, butafenacil, butamifos, butralin, butroxydim, butylate, cacodylic acid, calcium chlorate, cafenstrole, carbetamide, carfentrazone, carfentrazone-ethyl, CDEA, CEPC, chlorflurenol, ehlorflurenol-methyl, chloridazon, chlorimuron, ehiorimuron-ethyl, chloroacetic acid, chlorotoluron, chlorpropham, chlorsulfuron, chlorthal, chlorthal-dimethyl, cinidon-ethyl, cinmethylin, cinosulfuron, cisanilide, elethodim, clodinafop, clodinafop-propargyl, clomazone, clomeprop, clopyralid, cloransulam, eloransulam-methyl, CMA, 4-CPB, CPMF, 4-CPP, CPPC, cresol, cumyluron, cyanamide, eyanazine, cycloate, eyclosulfamuron, cycloxydim, cyhalofop, cyhalofop-butyl, 2,4-D, 3,4-DA, daimuron, dalapon, dazomet, 2,4-DB, 3,4-DB, 2,4-DEB, desmedipham, desmetryn, dieamba, dichlobenil, ortho-dichlorobenzene, para-dichlorobenzerie, dichiorprop, dichlorprop-P, diclofop, diclofop-methyl, diclosulam, difenzoquat, difenzoquat inetilsulfate, diflufenican, diflufenzopyr, dimefuron, dimepiperate, dimethachior, dimethatnetryn, dimethenamid, dimethenamid-P, dimethipin, dimethylarsinic acid, dinitramine, dinoterb, diphenamid, dipropetryn, diquat, diquat dibromide, dithiopyr, diuron, DNOC, 3,4-DP, DSMA, EBEP, endothal, EPTC, esprocarb, ethaifturalin, ethametsutfuron, ethametsulfuron-methyl, ethephon, ethofumesate, cthoxyfen, ethoxysulfuron, etobenzanid, fenoxaprop, fenoxaprop-P, fenoxaprop-ethyl, fenoxaprop-P-ethyl, fentrazamide, ferrous sulfate, flamprop-M, flazasulfuron, florasulam, fluazifop, fluazifop-butyl, fluazifop.-P, fluazifop-P-butyl, fluazolate, flucarbazone, flucarba.zone-sodium, flucetosulfüron, fluchioralin, flufenacet, flufenpyr, flufenpyr-ethyl, flumetralin, flumetsulam, flumictorac, flumiclorac-pentyl, flumioxazin, flumipropin, fluometuron, fluoroglycofen, fluoroglycofen-ethyl, fluoxaprop, flupoxam, flupropacit, flupropanate, flupyrsulfuron, flupyrsulfuron-methyl-sodium, flurenol, fluridone, flurochioridone, fluroxypyr, flurtamone, fluthiacet, fluthiacet-methyl, fomesafen, foramsulfuron, fosamine, glufosinate, glufosinate-ammonium, glyphosate, halosulfuron, halosulfuron-methyl, haloxyfop, haloxyfop-P, HC-252, hexazinone, imazamethabenz, imazamethabenz-methyl, imazamox, imazapic, imazapyr, imazaquin, imazethapyr, imazosulfuron, indanofan, iodomethane, iodosulfuron, iodosulfijron-methyl-sodium, ioxynil, isoproturon, isouron, isoxaben, isoxachiortole, isoxaflutole, isoxapyrifop, karbutilate, lactofen, lenacil, linuron, MAA, MAMA, MCPA, MCPA-thioethyl, MCPB, mecoprop, mecoprop-P, mefenacet, mefluidide, mesosulfuron, mesosutfuron-methyl, mesotrione, metam, metamifop, metainitron, metazachlor, methabenzthiazuron, methazole, methytarsonic acid, methyldymron, methyl isothiocyanate, metobenzuron, metobromuron, metolachior, S-metolachtor, metosutam, metoxuron, mctribuzin, metsulfuron, mctsutfuron-methyl, MK-616, molinate, monolinuron, MSMA, naproanitide, napropamide, naptalam, NDA-402989, neburon, nicosulfuron, nipyraclofen, n-methyl glyphosate, nonanoic acid, norfiurazon, oteic acid (fatty acids), orbencarb, orthosulfamuron, oryzalin, oxadiargyt, oxadiazon, oxasulfuron, oxaziclomefone, oxyfluorfen, paraquat, paraquat dichioride, pebulate, pendimethalin, penoxsulam, pentachiorophenol, pentanochlor, pentoxazone, pethoxamid, petrolium oils, phenmedipham, phenmedipham-ethyt, pictoram, picotinafen, pinoxaden, piperophos, potassium arsenite, potassium azide, pretilachior, primisulfuron, primisulfuron-methyl, prodiamine, profluazol, profoxydim, prohexadione-catcium, prometon, prometryn, propachtor, propanit, propaquizafop, propazine, propham, propisochtor, propoxycarbazone, propoxycarbazone-sodium, propyzamide, prosulfocarb, prosulfuron, pyraclonil, pyraflufen, pyraflufen-ethyt, pyrasulfotole, pyrazolynate, pyrazosulfuron, pyrazosulfuron-ethyl, pyrazoxyfen, pyribenzoxim, pyributicarb, pyridafol, pyridate, pyriftalid, pyriminobac, pyriminobac-methyl, pyrimisulfan, pyrithiobac, pyrithiobac-sodium, pyroxasulfone, pyroxulam, quinclorac, quinmerac, quinoclamine, quizalofop, quizalofop-P, quizalofop-ethyl, quizalofop-P-ethyl, rimsuifliron, saflufenacil, sethoxydim, siduron, simazine, simetryn, SMA, sodium arsenite, sodium azide, sodium chlorate, sulcotrione, sulfentrazone, sulfometuron, sulfometuron-methyl, sulfosate, sulfosulfuron, sulfuric acid, tar oils, 2,3,6-TBA, TCA, TCA-sodium, tebutam, tebuthiuron, tefuryltrione, tembotrione, tepraloxydim, terbacil, terbumeton, tcrbuthylazine, terbutryn, thenyichior, thiazafluron, thiazopyr, thifensulfuron, thiencarbazone, thifensulfuron-methyl, thiobencarb, tiocarbazil, topramezone, tralkoxydim, tri-allate, triasulfuron, triaziflam, tribenuron, tribenuron-methyl, tricamba, triclopyr, trietazine, trifloxysulfuron, trifloxysulfuron-sodium, trifluralin, triflusulfuron, triflusulfuron-methyl, trifop, trifop-methyl, trihydroxytriazinc, trinexapac-ethyl, tritosulfuron, [3-[2-chloro-4-fluoro-5-(l-methyl-6-trifluoromethyl-2,4-dioxo-1,2,3, 4-tetrahydropyrimidin-3-yl)phenoxy}-2-pyridyloxy]acetic acid ethyl ester (CAS RN 353292-31-6), 4-hydroxy-3-[2-[(2-methoxyethoxy)methyl]-6-(trifluoromethyl)-3- pyridinyl]carbonyl]-bicyclo[3.2. 1]oct-3-en-2-one (CAS RN 352010-68-5), 4-amino-3-chloro-6-(4-chloro-2-fluoro-3-methoxyphenyl) -2-pyridinecarboxylic acid (CAS RN 943832-60-8), and 4-hydroxy-3-[2-(3-methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]carbonyl] -bicyclo[3.2.1]oct-3-en-2-one.
Whilst compositions comprising a safcncr and a two-way mixture of a compound of formula (1) and another herbicide are explicitly disclosed above, the skilled man will appreciate that the invention extends to three-way, and further multiple combinations comprising the above two-way mixtures.
Particularly preferred mixture partners for use in the compositions of the invention are: florasulam, iodosulfi.iron-methyl-sodium, mesosulfuron-methyl, metsulfuron-methyl, nicosulfuron, prosulfuron, thifensulfuron, triasulfuron, tribenuron-methyl or pyroxsulam; dicamba, fluroxypyr, MCPA, mecoprop or mecoprop-P; clodinafop-propargyl, cyhalofop-butyl, diclofop-methyl, fenoxaprop-ethyl, fenoxaprop-P-ethyl, fluazifop-butyl, fluazifop-P-butyl, haloxyfop-methyl, haloxyfop-P-methyl, pinoxaden, propaquizafop, quizalofop-ethyl, quizalofop-P-ethyl, tralkoxydim, trifop-methyl, diflufenzopyr-Na, mesotrione, topramczone, naptalam, and glyphosate.
For the avoidance of doubt, even if not explicitly stated above, the mixing partners of may also be in the form of any suitable agrochemically acceptable ester or salt, as mentioned e.g. in The Pesticide Manual, Thirteenth Edition, British Crop Protection Council, 2003.
The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1: 100 to 1000:1.
The rates of application of compounds of formula (I) in the compositions of the invention may vary within wide limits and depend on the nature of the soil, the method of application (pre-or post-emergence; seed dressing; application to the seed furrow; no tillage application etc.), the crop plant, or weed to be controlled, the prevailing climatic conditions, and other factors governed by the method of application, the time of application and the target crop. The compounds of formula I according to the invention are generally applied at a rate of from 10 to 2000 gfha, especially from 25 to 1000 g/ha.
Any method of application to weeds/crop of useful plant, or locus thereof, which is routinely used in agriculture may be used, for example application by spray or broadcast method typically after suitable dilution of the composition of the invention.
The term "locus" as used herein includes not only areas where weeds may already be growing, but also areas where weeds have yet to emerge, and also to areas under cultivation with respect to crops of useful plants. Areas under cultivation include land on which the crop plants are already growing and land intended for cultivation with such crop plants.
The composition of the invention may be used in a pre-emergence application and/or in a post-emergence application in order to mediate its effect.
Crops of useful plants in which compositions of the invention may be used include perennial crops, such as citrus fruit, grapevines, nuts, oil palms, olives, pome fruit, stone fruit and rubber, and annual arable crops, such as cereals, for example barley and wheat, cotton, oilseed rape, maize, rice, soy beans, sugar beet, sugar cane, sunflowers, ornamentals and vegetables, especially cereals and maize.
Compositions of the invention may also be used on turf, pasture, rangeland, rights of way etc. In particular they may be used on golf-courses, lawns, parks, sports-fields, race-courses and the like.
Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. ALS-, GS-, EPSPS-, PPO-and FIPPD-inhibitors and synthetic auxins) by conventional methods of breeding or by genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding is Clearfield® summer rape (canola). Examples of crops that have been rendered tolerant to herbicides by genetic engineering methods include e.g. glyphosate-and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® and LibertyLink®.
Crops are also to be understood as being those which have been rendered resistant to harmful insects by genetic engineering methods, for example Bt maize (resistant to European corn borer), 13t cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle). Examples of Bt maize are the Bt 176 maize hybrids of NK® (Syngenta Seeds). The Bt toxin is a protein that is formed naturally by Bacillus thuringiensis soil bacteria. Examples of toxins, or transgcnic plants able to synthesise such toxins, are described in EP-A-45 1 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529. Examples of transgenic plants comprising one or more genes that code for an insecticidal resistance and express one or more toxins are KnockOut® (maize), Yield Gard® (maize), NuCOT[N33B® (cotton), Bollgard® (cotton), NewLear (potatoes), Natureoard® and Protexcta®. Plant crops or seed material thereof can be both resistant to herbicides and, at the same time, resistant to insect feeding ("stacked" transgenic events). For example, seed can have the ability to express an insecticidal Cry3 protein while at the same time being tolerant to glyphosate.
Crops are also to be understood as being those which are obtained by conventional methods of breeding or genetic engineering and contain so-called output traits (e.g. improved storage stability, higher nutritional value and improved flavour).
The term "weeds" as used herein means any undesired plant, and thus includes not only agronomically important weeds as described below, but also volunteer crop plants.
Compounds of formula (I) may be used against a large number of agronomically important weeds. The weeds that may be controlled include both monocotyledonous and dicotyledonous weeds, such as, for example, Alisma spp, Leptochloci chinensis, Stellaria, Nasturtium, Agrostis, Digitaria, Avena, Setaria, Sinapis, Lolium, Solanum, Echinochloa, Scirpus, Monochoria, Sagittaria, Bromus, Alopecurus, Sorghum, Rottboellia, Cyperus and especially Cyperus iria, Abutilon, Sida, Xanthium, Amaranthus, Chenopodium, Ipomoea, Chrysanthemum, Galium, Viola, Veronica, Bidens, Euphorbia,Ischaemum, Polygonum, Helianthus, Panicum, Eriochloa, Brachiaria, Cenchrus, Commelina, Spermacoce, Senna, Tridax, Richardia, Chamaesyce, and Conyza spp.
Various aspects and embodiments of the present invention will now be illustrated in more detail by way of example. It will be appreciated that modification of detail may be made without departing from the scope of the invention.
For the avoidance of doubt, where a literary reference, patent application, or patent, is cited within the text of this application, the entire text of said citation is herein incorporated by reference.
EXAMPLES
EXAMPLE 1
Synthesis of 3-bromo-6-chloro-pyridine-2-carboxylic acid methyl ester. Br Br cvH
3-Bromo-6-chloro-pyridine-2-carboxylic acid (50.00 g, 211.5 minol) was dissolved in methanol (235 mL), and concentrated sulphuric acid (5.6 mL) was added.
The resulting reaction mixture was heated at reflux for 28 h. The reaction mixture was cooled to room temperature, and the resulting precipitate was recrystallized from methanol to give 3-bromo-6-chloro-pyridine-2-carboxylic acid methyl ester (54.38 g, quantitative) as a solid. Characterising data for the compound are as follows: II NMR (400 MHz, CDC13) 8 7.94 (d, IH), 7.34 (d, 1H) and 4.01 (s, 3H) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 2.
TABLE 2 Compounds made according to the method described in Example 1 above.
Name Structure -"EINMR (400 -MHz, CDCI3) 8 ppm 3,6---(#c(..CI 7.80 (d, 111), 7.40 Dichloropyridine-)J. .L (d, 1 H), 4.00 (s, CI N CO2Me 2-carboxylic acid 311) ppm methyl ester
EXAMPLE 2
Synthesis of 3-bromo-4,6-dichloro-pyridine-2-carboxylic acid methyl ester.
Urea hydrogen peroxide (65.32 g, 347.2 mmol) was added portionwise to a solution of trifluoroacetic anhydride (145.8 g, 694.4 mmol, 96.5 mL) in dichioromethane (577 mL) at 0 °C. 3-Bromo-6-chloro-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 1) (27.18 g, 108.5 mmol) was added to the mixture portionwise and the reaction mixture was stirred at room temperature for 19 h. The reaction was quenched by the addition of water, the phases separated and the organic layer washed with water and saturated aqueous potassium carbonate. The organic layer was dried over magnesium sulphate, filtered and concentrated under reduced pressure to give 3-bromo- 6-chloro-pyridine-2-earboxylic acid N-oxide as a yellow oil. Characterising data for the compound are as follows: H NMR (400 MHz, CD3OD) 8 7.77-7.75 (m, 211) arid 4.01 (s, 311) ppm.
3-Bromo-6-chloro-pyridine-2-carboxylic acid N-oxide was dissolved in phosphorus oxychloride (166 g, 1.085 mol, 101 mL) and stirred at room temperature for 2 h, then at reflux for 3 h. The reaction mixture was cooled, concentrated under reduced pressure, and purified by silica gel chromatography (gradient elution: 0-100% ethyl acetate in iso-hexane) followed by reverse phase silica gel chromatography (gradient elation: 0-100% methanol in water) to give 3-bromo-4,6-dichloro-pyridine-2-carboxylic acid methyl ester (9.45 g, 31%) as a solid. Characterising data for the compound are as follows: H NMR (400 MHz, CDCI3) 8 7.57 (s, 111) and 4.01 (s, 3H) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 3.
TABLE 3 Compounds made according to the method described in Example 2 above.
Name Structure H NMR (400 MHz, CDCI3) fippm 3,4,6-Trichioro-1 7.58 (s, 11-I), 3.99 pyridine-2-".. CI (s, 3H) carboxylic acid CI N CO2Me methyl ester
EXAMPLE 3
Synthesis of 3,6-dichloro-4-[(furan-2-ylmetbyl)-aminoj-pyridine-2-earboxylic acid methyl ester (Compound 26-2).
I HY
(L ______ CIN0 CIN7L(0 3,4,6-Trichloro-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 2) (0.500 g, 2.08 nimol) was dissolved in dimethylformamide (3 mL), and triethylamine (0.58 mL, 4.17 mmol) was added. Furfurylamine (0.202 g, 2.08 mmol) dissolved in dimethylformamidc (2 mL) was added to the solution, and the resulting reaction mixture was heated to 100 °C for 3 h. The reaction mixture was cooled to room temperature, poured into water and the aqueous layer was extracted with diethyl ether.
The combined organic layers were washed with brine, dried over magnesium sulphate and evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography (gradient elution: 0 -40% ethyl acetate in iso-hexane) to give 3,6-dichloro-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (221 mg, 35%) as a solid.
Characterising data for the compound are as follows: H NMR (400 MHz, CDC13) 5 7.42 (m, lI-I), 6.72 (s, 114), 6.37 (m, 1H), 6.32 (m, 114), 5.55 (br. s, IH), 4.44 (d, 214), 3.96 (s, 314) ppm.
Further examples of compounds that were prepared using this method are listed below in Table 4. Characteristic data provided is either H-nmr data (400 MHz, CDC13) OH ppm or LCMS [retention time (RT, recorded in minutes) and the molecular ion, typically the cation M+H]. Compounds characterised by HPLC-MS used a Waters 2777 injector with a 1525 micro pump HPLC equipped with a Waters Atlantis dCl8 IS column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron), Waters 2996 photodiode array, Waters 2420 ELSD and Micromass ZQ2000. The analysis was conducted using a three minute run time, according to the following
gradient table:
Time Solvent A Solvent B Flow (ml / (minutes) (%) (%) minute) 0.00 95 5 1.3 2.50 --0 -100 1.3 2.80 0 100 1.3 2.90 95 5 1.3 Solvent A: H20 with 0.05% TFA Solvent B: CH3CN with 0.05% TFA TABLE 4 Compounds made according to the method described in Example 3 above.
Compound Name Structure Characteristic Number data 33-2 3,6-Dichloro-4-[(3-8.49 (d, 114), 7.64 methyl-pyridin-2-NH (br. s, 114), 7.53 (d, ylmethyl)-amino]-,-N CI 1H), 7.22 (m, lH), pyridine-2-I 6.69 (s, 114), 4.35 carboxylic acid CI N CO2Me (d, 214), 3.98 (s, methyl ester 3H), 2.36 (s, 3H) 1-2 4-ç7YNH 6.50(s,111),5.31 -Cyclopropylmethyl amino-3,6-(br. s, 1H), 3.89 (s, 31-i), 3.00 (m, 2H), dichioro-pyridine-Cl N CO2Me 1.08 (m, 1H), 0.58 2-carboxylic acid (m, 2H), 0.25 (m, methyl ester 211) 2-2 3,6-Dichloro-4- 6.56 (s, 11-1), 5.76 phenylmethylamin 7.40-7.30 (m,SH), o-pyridine-2- (m, 111), 4.44 (d, carboxylic acid CIN"CO2Me 2H), 3.94 (s, 3H) methyl ester 5-2 4-[(4-Chlorophenylmeth 7.34 (d, 211), 7.24 ci (d, 2H), 6.50 (s, yl)-amino]-3,6-11-1), 6.02 (m, 1H), Ci N CO2Me dichloro-pyridine-4.44 (d, 211), 3.95 2-carboxylic acid (s, 311) methyl ester 6-2 3,6-Dichloro-4-[(2-7.37-7.24 (rn, 2H), fluorophenylmethyl 1jNH 7.17-7.08 (m, 2H), )-amino]-pyridine-ci 6.61 (s, 1Ff), 5.73 2-carboxylic acid (br. s, 1H), 4.51 (d, methyl ester Ci N CO2Me 211), 3.95 (s, 31-f) 7.35 (rn, 1H), 7.09 7-2 3,6-Dichloro-4-[(3-F ci (d, 111), 7.00 (m, fluorophenylmethyl 2H), 6.52 (s, 111), )-amino]-pyridine-,JJ L 2-carboxylic acid Ci N CO2Me 5.87 (br. s, 1H), methyl ester 4.47 (d, 211), 3.95 (s, 311) methyiphenylmeth NH 6.63 (s, 111), 5.36 9-2 -3,6-Dichloro-4-[(2-7.31-7.21 (m,4H), yl)-amino]-pyridine-2-,_L,,ci (m, 1H), 4.38 (d, 2H), 3.97 (s, 311), carboxylic acid CiNCO2Me 2.37 (s, 311) methyl ester 15-2 -3,6-Dichloro-4-[(2-NO2 -6.84 (s, 111), 6.78 nitrophenylmethyl) (m, 211), 6.62 (s, -amino]-pyridine-1H), 5.91 (s, 211), 2-carboxylic acid 4.36 (s, 211), 3.82 (s, 311) methyl ester CI N CO 19-2 3,6-Dichloro-4- RT 1.66, MFI 347, [(2,6-FJIIILF difluorophenylmeth NH yl)-amino]- pyridine-2-carboxylic acid N CO2Me methyl ester 22-2 3,6-Diehloro-4-OMe Used without - [(2,4-purification dimethoxyphenylm MeO I XLXcI ethyl)-amino]-Cl N CO pyridine-2-carboxylic acid methyl ester 24-2 3,6-Dichtoro-4- [(3,4-6.84 (s, 111), 6.78 methylenedioxyphe (m, 2H), 6.62 (s, Cr'N2CO2Me 1H), 5.91 (s, 211), nylmethyl)-amino]-4.36 (s, 2H), 382 pyridine-2-(s, 311) (Nil not carboxylie acid observed) methyl ester 31-2 3,6-Dichloro-4- 8.61 (m, 111), 7.72 (pyridin-2-c' (m, 111), 7.28 (m, ylmethylamino)- 211), 6.86 (m, lH), 6.61 (s, lH), 4.50 pyridine-2-CI N co carboxylic acid (d, 211), 3.96 (s, methyl ester 311) 7.36 (m, 111), 7.03 66-2 3,6-Dichloro-4-[ psi.. - (fiiran-2-ylmethyl)-1⁄4.2J#[JCl (s, 1H), 6.32 (m, N-(2-I 111), 6.22 (m, 11-I), hydroxyethyl)-ci N CO2Me 4.54 (s, 2H), 3.98 aminol-pyridine-2-(s, 311), 3.78 (in, carboxylic acid 211), 3.45 (t, 211), methyl ester 1.83 (br. s, 111) 67-2 4-Cyclohexylmethyla 6.51 (s, 111), 5.26 (in, 111), 3.90 (s, mino-3,6-dichloro- 311), 3.00 (t, 2H), pyridine-2-CINACO2Me 1.78-1.55 (in, 611), carboxylic acid 1.28-1.08 (in, 311), methyl ester 0.96 (m, 211) 68-2 (trans 3,6-Dichloro-OH 6.61 (s, 111), 6.50 isomer) pyridine-4-ftrans-á%%%SNH (s, 111), 3.86 (s, (2-hydroxycyclohexyl EjcI 311), 3.35 (m, 1Ff), 3.11 (m, 2H), 1.90 methyl)-amino]-2-CI N CO2Me (m, 111), 1.73-1.52 carboxylic acid (m, 411), 1.30-1.10 methyl ester (in, 311), 1.00 (m, 111) (OH not observed) 69-2 4-Cyclooctylmethyla 6.50 (s, 111), 5.27 (m, 111), 3.89 (s, mino-3,6-dichloro- 311), 2.98 (m, 211), pyridine-2-Ci N CO2Me 2.25 (br. s, 111), carboxylic acid 1.80 (m, 111), 1.70-methyl ester 1.40 (m, 1111), 1.30 (in, 2H) 70-2 3,6-Diehloro-4-6.56 (s, 111), 5.54 - (tetrahydrofuran-2- (m, 111), 4.07 (in, ylmethylamino)-I 111), 3.88 (s, 3H), N CO2MO 3.84 (m, 111), 3.74 pyridine-2-ci carboxylic acid (m, 111), 3.30 (in, methyl ester -111), 3.11 (m, 1H), 2.02 (in, 111), 1.89 (m, 2H), 1.57 (m, 111) ppm 71-2 3,6-Dichloro-4--( -6.51(s,1H), 6.16 [(N-ethyl-(m, 1 H), 3.92 (s, pyrrolidin-2- 3H), 3.27-3.07 (in, ylmethyl)-amino]-3H), 2.73 (in, 2H), pyridine-2-I 2.23 (m, 2H), 1.92 CI N CO2Me carboxylie acid (in, 1 H), 1.73 (m, methyl ester 211), 1.60 (in, 1 H), 1.07 (t, 311) 7.61 (dd, 1H), 72-2 4-[(2-Bromophenylmeth 7.34-7.19 (in, 3H), yl)-amino]-3,6- 6.53 (s, 111), 5.78 dichioro-pyridine- (m, 1H),4.51 (d, NCO2Me 211), 3.95 (s, 311) 2-carboxylic acid methyl ester 73-2 3,6-Dichloro-4-[(2-NH 7.31 (m, 111), 7.19 methoxyphenylmet (dd, 111), 6.94 (m, hyl)-aminoj-I.LJ K_Lt 211), 6.65 (s, 11-I), pyridine-2- 5.78 (m, 1H), 4.42 CINCO2Me (d, 2H), 3.94 (s, carboxylic acid methyl ester 31-1), 3.88 (s, 31-I) 74-2 3,6-Dichloro-4-[(2-F3 NH 7.62 (d, 111), 7.45 trifluoromethyiphe (t, 111), 7.32 (in, nylmethyl)-amino]-211), 6.33 (s, 111), pyridine-2- 6.29 (m, 1H), 4.58 carboxylic acid CI N CO2Me (d, 211), 3.85 (s, methyl ester 311) 75-2 3,6-Dichloro-4-/y"'NH 7.29 (dd, IFI), 7.04 (thiophen-2-%__.A,1111JtJCI (m, 111), 7.01 (m, ylmethylamino)-I IH), 6.67 (s, 1H), pyridine-2-N CO2Me 5.68 (m, 11-1), 4.62 carboxylic acid (d, 211), 3.96 (s, methyl ester 3H) 76-2 44(2-Br 7.32 (d, 1H), 6.99 Bromothiophen-3- NH (d, 111), 6.65 (s, ylmethyl)-amino]-1H), 5.52 (in, 111), 3,6-dichloro- 4.38 (d, 2H), 3.97 pyridine-2-CI N CO2Me (s, 311) carboxylic acid methyl ester 77-2 3,6-Dichloro-4-6.64 (s, 111), 6.00 (s, 1K), 5.39 (in, [(1,3-3.94(s, 3K), 3.79 dimethylpyrazol-5-ci 1H), 4.37 (d, 2H), ylmethyl)-amino]-pyridine-2-CI N CO2Me (s, 3H), 2.23 (s, carboxylic acid 311) methyl ester 78-2 3,6-Dichloro-4- 8.54 (m, 2H), 7.60 - (pyridin-3-LN_JJL (m, 111), 7.28 (m, ylmethylamino)-I 111), 6.51 (s, 1H),
I-
pyridine-2-ci N CO2Me 5.88 (m, 11-1), 4.46 carboxylic acid (d, 2H), 3.90 (s, methyl ester 3H) 79-2 3,6Dichloro4[(6: -8.74 (s, 111), 7.83 trifluoromethylpyri ci (d, 111), 7.74 (d, F,C N din-3-ylmethyl)- L 2Me 111), 6.54 (s, 111), Ci N Co amino]-pyridine-2-5.70 (m, 1Ff), 4.61 carboxylic acid (d, 2H), 3.98 (s, methyl ester 311) 80-2 3,6-Dichloro-4--NH 8.56 (d, 2H), 7.18 (pyridin-4-N' ,. ,,..L,,..,cI (d, 2H), 6.40 (s, ylmethylamino)-111), 6.02 (m, 1H), pyridine-2-cr"N'co2Me 4.49 (d, 2H), 3.92 carboxylic acid (s, 311) methyl ester 81-2 3,6-Dichloro-4-[(5-N NH 8.51 (s, 111), 8.47 methylpyrazin-2- _L._ci (s, 111), 6.66 (s, ylmethyl)-amino]-,Jj) 111), 6.48 (m, 1H), pyridine-2-CI N CO2Me 4.53 (d, 211), 3.96 carboxylic acid (s, 311), 2.60 (s, methyl ester 311)
EXAMPLE 4
Synthesis of 3-bromo-6-chloro-4-cyclopropylmethylamino-pyridine-2-carboxylic acid methyl ester (Compound 1-17).
CI NH
KJ<Br _______
CINO 0 0
A solution of 3-bromo-4,6-dichloro-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 2) (0.545 g, 1.91 mmol) in N-methylpyrrolidone (2 mL) was added to a mixture of cyclopropylmethylamine (136 mg, 1.91 mmol) and diisopropyethylamine (0.66 ml, 3.82 nimol) and the resulting mixture heated at 80 °C for 20 h. The reaction mixture was cooled to room temperature, water (2 ml) and dichloromethane (2 ml) added and the mixture stined for 5 mm. The phases were separated and the organic phase concentrated in vacuo. The residue was purified by reverse phase preparative HPLC, using FractionLynx (X Bridge column, ammonium acetate buffer) to give 3-bromo-6-chloro-4-cyclopropylamino-pyridine-2-carboxylic acid methyl ester. Characterising data for the compound is: H NMR (400 MHz, CDC13) & 6.50 (s, 111), 5.40 (m, 111), 4.00 (s, 311), 3.10 (m, 2H), 1.10 (m, 111), 0.70 (m, 2H), 0.30 (m, 211) ppm.
Other compounds made using this general method are listed in Table 5 below.
Characteristic data provided is either 1F1-nmr data (400 MHz, CDC13) 6H ppm or LCMS [retention time (RT, recorded in minutes) and the molecular ion, typically the cation M+l-lt]. Compounds characterised by HPLC-MS used a Waters 2777 injector with a 1525 micro pump HPLC equipped with a Waters Atlantis dCl8 IS column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron), Waters 2996 photodiode array, Waters 2420 ELSD and Micromass ZQ2000. The analysis was conducted using a three minute run time, according to the following gradient table: Time Solvent A Solvent B Flow (ml I (minutes) (%) (%) minute) 0.00 95 5 1.3 2.50 0 100 1.3 2.80 0 100 1.3 2.90 95 5 1.3 Solvent A: H20 with 0.05% TFA Solvent B: CFI3CN with 0.05% TFA TABLES Compounds made according to the method described in Example 4 above.
Compound Name Structure Characteristic Number data 2-17 3-Bromo-6-chloro-NH RT 1.64, MR 355, 4-I, ,,.J,,,Br phenylmethylamin I o-pyridine-2-C(' CO2Me carboxylic acid methyl ester 3-17 -3-Bromo-6-chloro-RT 1.76, Mr 389, 44(2-chiorophenylmethy 391, 393 l)-amino]-pyridine- 2-carboxylic acid N CO methyl ester RT 1.66, MIT 373, 44(2- 6-17 3-Bromo-6-chlro-fluorophenylmethyl )-amino]-pyridine- 2-carboxylic acid N CO2Me methyl ester 4-[(2-NH purification 9-17 3-Bromo-6-chloro-Used without methylphenylmeth yl)-amino]-
I-
pyridine-2-N CO2Me carboxylic acid methyl ester 14-17 3-Bromo-&chloro-RT 1.06, MI-t 398, Me,N' KL1,_Br 400, 402 dimethylaminophe CI N CO2Me nylmethyl)-aminoj- pyridine-2-earboxylic acid methyl ester 15-17 3-Bromo-6-chloro-NO2 8.21 (m, 111), 7.68 4-[(2-J"NH (m, 111), 7.55 (t, nitrophenylmethyl) 111), 7.46 (d, 111), 6.46 (s, 1H), 5.96 -aminoll-pyridine- 2-carboxylic acid N CO2Me (m, 111), 4.91 (d, methyl ester 211), 3.98 (s, 3H) 21-17 3-Bromo-6-chloro-RT 1.91, MR4 423, 4-[(2,6-425, 427, 429 dichiorophenylmet hyl)-amino]-NFl pyridine-2-xLxBr carboxylic acid I,, methyl ester CI N CO2Me 26-17 3-Bromo-6-chloro- 4-[(furan-2-7.43-7.42 (m, 111), Br 6.67 (s, 11-1), 6.39- ylmethyl)-amino]- 6.37 (m, 111), 6.33- pyridine-2-CI N CO2Me 6.31 (m, 111), 5.66-carboxylie acid 5.60 (m, 111), 4.44 methyl ester (d, 211), 3.97 (s, 3H) 8.50 (s, 111), 7.80 4-[(3-chloro- 32-17 3-Bromo-6-chloro-(m, 111), 7.40-7.20 pyridin-2-,-N (m, 211), 6.70 (s, ylmetbyl)-amino]-Jj 111), 4.50 (m,211), pyridine-2-CI N CO2Me 4.00 (s, 314) earboxylie acid methyl ester RT 0.97, MIt 370, 33-17 3-Brorno-6-chloro-372, 374 4-[(3-methyl-NH pyridin-2-Br ylmethyl)-amino]-Ac pyridine-2-CI N CO2Me earboxylic acid methyl ester RT1.94, MIt 361, 67-17 3-Bromo-6-chloro-cyclohexylmethyla --363, 365
H
mino-pyridine-2-CI N CO2Me carboxylic acid methyl ester 73-17 3-Bromo-6-chloro-Me RTL72, MH 385, 4-[(2-387,389 methoxyphenylmet Br hyl)-amino]-pyridine-2-N CO2Me carboxylic acid methyl ester 74-17 -3-Bromo-6-chloro-F3 RI 1.82, MI? 423, 4-[(2-J._7NNH 425, 427 trifluoromethyiphe Br nylmethyl)-aminoj-pyridine-2-N CO2Me carboxylic acid methyl ester RI 1.59, MI? 361, 75-17 3-Bromo-6-chloro-
NH
4-(thiophen-2--Br 363, 365 ylmethylamino)-pyridine-2-CI N CO2Me carboxylic acid methyl ester 80-17 3.-Bromo-6-chloro-358, 360 4-[(pyridin-4- RI 0.84, MI? 356, ylmethyl)-amino]- pyridine-2-N CO2Me carboxylic acid methyl ester
EXAMPLE S
Synthesis of 3-chloro-6-(4-cbloro-2-fluoro-3-methoxy-phcnyl)-4-[(furan-2-ylmethyl) -amino]-pyridine-2-carboxylic acid methyl ester (Compound 26-164). HN? B cIIO
3,6-Dichloro-4-[(ftiran-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 3) (0.500 g, 1.66 mmol), 2-(4-chloro-2-fluoro-3-methoxy-phenyl)-[l,3,2]dioxaborinane (0.446 g, 1.83 mmol), caesium fluoride (0.505 g, 3.32 mmol) and 11,1 -bis(diphenylphosphino)-ferrocene]dichloropalladium(II) dichioromethane adduct (0.068 g, 0.08 mmol) were suspended in a degassed mixture of dimethoxyethane (2.5 mL) and water (2.5 mL). After stirring the suspension under an atmosphere of nitrogen for 5 mm, the reaction mixture was heated under microwave irradiation to 140 °C for 15 mm. After cooling to room temperature, the reaction was poured into water and the aqueous layer was extracted with dichloromethane using a hydrophobic fit to collect the organic layer. The organic layer was evaporated under reduced pressure, and the resulting residue was purified by silica gel chromatography (gradient elution: 0 -40% ethyl acetate in iso-hexane). The resulting material was further purified by reverse phase preparative I-IPLC, using FractionLynx (XBridge column, 30 x 100 mm, 5 micron particles, 20 mM ammonium acetate buffer) to give 3-chloro-6-(4-chloro-2-fluoro-3-methoxy-phenyl)-4-[(furan-2-ylmethyl) -ainino-pyridine-2-carboxylic acid methyl ester (355 mg, 50%) as a solid.
Characterising data for the compound are as follows: II NMR (400 MHz, CDCI3) 7.63 (t, 1H), 7.40 (m, 1H), 7.24 (m, 111), 7.16 (d, lH), 6.35 (m, 111), 6.31 (m, 11-1), 5.50 (m, lH), 4.50 (d, 2H), 3.98 (s, 6H) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 6.
TABLE 6 Compounds made according to the method described in Example 5 above.
Name Ltuutt 1HNMR (400 Number -MHz, CDC13) öppm 26-245 -3-Chloro-6-(4-NH -7.56 (t,111), 7A0 chloro-3-ci (m, 111), 7.22 (dd, dimethylamino -2-1, 111), 7.12 (d, 111), fluoro-phenyl)-4-N CO2Me 6.36 (m, 111), 6.32 [(furan-2-Ci F (m, 111), 5.48 (m, NMe ylmethyl)-amino]-2 111), 4.50 (d, 2H), pyridine-2-3.98 (s, 311), 2.90 carboxylic acid (s, 611) methyl ester 22-164 3-Chloro-6-(4--7.61 (t, 111), 7.22 -chloro-2-fluoro-3-i NH (dd,111), 7.17 (d, methoxy-phenyl)-MeO -... Ci 111), 7.12 (m, 111), 4-[(2,4-N CO2Me 6.50 (d, 111), 6.47 dimethoxyphenyl-F (dd, 1H), 5.55 (m, methyl)-amino]-CM IH), 4.41 (d, 211), pyridine-2-3.98 (s, 611), 3.86 carboxylic acid (s, 3H), 3.81 (s, methyl ester 311)
EXAMPLES 6 AND 7
Synthesis of 3-ehloro-6-cycfopropyl-4-I(furan-2-ylmethyl)-amino-pyridine-2- carboxylic acid methyl ester (Compound 26-83) and 6-chloro-3-cyclopropyl-4- (furan-2-ylmethyl)-amino]-pyridine-2-earboxylic acid methyl ester (Compound 26-7).
3,6-Dichloro-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 3) (0.301 g, 1.00 mmol), cyclopropyl boronic acid (0.086 g, 1.00 mmol), potassium phosphate (0.637 g, 3.00 mmol), palladium acetate (0.011 g, 0.05 mmol) and tricyclohexyiphosphine tetrafluoroborate (0.037 g, 0.10 mmol) were suspended in a degassed mixture of toluene (3.6 mL) and water (0.4 mL). After stirring the suspension under an atmosphere of nitrogen for 5 mm, the reaction mixture was heated under microwave irradiation to 140 °C for 45 mm. After cooling to room temperature, the reaction mixture was poured into water and the aqueous layer was extracted with dichloromethane using a hydrophobic fit to collect the organic layer. The organic layer was evaporated under reduced pressure, arid the resulting material was purified by reverse phase preparative HPLC, using FractionLynx (XBridge column, 30 x 100 mm, 5 micron particles, 20 mM ammonium acetate buffer) to give two regioisomeric products. The two products were separately further purified by silica gel chromatography (gradient elution: 0 -40% ethyl acetate in iso-hexane) to give 3-chloro-6-cyclopropyl-4- [(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (72 mg, 23%) and 6-chloro-3-cyclopropyl-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (30 mg, 10%) as gums.
Characterising data for 3-chloro-6-cyclopropyl-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester are as follows: H NMR (400 MHz, CDC13) 8 7.40 (m, 111), 6.43 (s, 1H), 6.35 (m, 1H), 6.27 (m, iF!), 5.27 (m, iF!), 4.41 (d, 2H), 3.95 (s, 3H), 1.95 (m, 11-I), 0.95 (m, 4H) ppm.
Characterising data for 6-chloro-3..cyclopropyl-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester are as follows: H NMR (400 MHz, CDC13) 6 7.40 (m, 1H), 6.60 (s, 1H), 6.36 (m, iF!), 6.28 (m, Ill), 5.52 (m, iF!), 4.41 (d, 2H), 3.94 (s, 3H), 1.60 (m, lI-fl, 1.02 (m, 2H), 0.42 (m, 2H) ppm.
EXAMPLE 8
Synthesis of 6-(4-chloro-2-fluoro-3-methoxy-phenyl)-3-ethenyl-4-[(furan-2-ylmethyl) -aminol-pyridine-2-carboxylie acid methyl ester (Compound 26-174). N0 N°
HN HN
CI
3-Chloro-6-(4-chloro-2-fluoro..3-methoxy-phenyl)-4-[(furan-2-ylmethyl) -amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 5) (0.150 g, 0.35 mmol), 4,4,5,5-tetramethyl-2-vinyl-[ 1,3,2]dioxaborolane (0.082 g, 0.53 inrnol), caesium fluoride (0.107 g, 0.71 mmcl), and [1,l-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) dichioromethane adduct (0.029 g, 0.03 5 mmol) were suspended in a degassed mixture of dimethoxyethane (1.8 mL) and water (1.8 mL).
After stirring the suspension under an atmosphere of nitrogen for 5 mm, the reaction mixture was heated under microwave irradiation to 160 °C for 30 mm. After cooling to room temperature, the reaction mixture was poured into water and the aqueous layer was extracted with dichloromethane using a hydrophobic fit to collect the organic layer. The organic layer was evaporated under reduced pressure, and the resulting material was purified by reverse phase preparative IIPLC, using FractionLynx (XBridge column, 30 x mm, 5 micron particles, 20 mM ammonium acetate buffer) to give the desired product. The product was further purified by silica gel chromatography (gradient elution: 0 -30% ethyl acetate in iso-hexane) to give 6-(4-chloro-2-fluoro-3-methoxy-phenyl)-3-ethenyl-4-[(furan-2-ylmethyl) -amino]-pyridine-2-carboxylic acid methyl ester (13 mg, 9%) as a yellow gum.
Characterising data for the compound are as follows: 1-1 NMR (400 MHz, CDC13) 8 7.65 (t, 111), 7.39 (m, lH), 7.22 (dd, 111), 7.11 (d, 114), 6.80 (m, 111), 6.35 (m, lH), 6.29 (m, 111), 5.65 (dd, 114), 5.50 (dd, 111), 5.28 (m, 1H) 4.41 (U, 211), 3.98 (s, 311), 3.91 (s, 3H) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 7.
TABLE 7 Compounds made according to the method described in Example 8 above.
Compound Name Structure H NMR (400 -Number MHz, CDC13) öppm 26-255 6-(4-Chloro-3-NH - (t 11-1), 7.39 dimethylamino-2-(m, 111), 7.22 (dd, fluoro-phenyl)-3-I IH), 7.06 (d, 111), ethenyl-4-[(furan-I N CO2Me 6.80 (m, 1H), 6.35 2-ylmethyl)-CI F (m, 111), 6.28 (m, aminol-pyridine-2-NMe2 11-1), 5.65 (dd, 1H), carboxylic acid 5.50 (dd, 1H), 5.25 methyl ester (m, 111) 4.42 (d, 2H), 3.91 (s, 3F1), 2.90 (d, 6H)
EXAMPLE 9
Synthesis of (Z)-6-(4-chloro-2-fluoro-3-metboxy-pbenyl)-3-(2-ethoxyethenyl)-4- [(furan-2-yhuethyl)-aminoj-pyridine-2-carboxylic acid methyl ester (Compound 26-463). EtO
Q7çci cçz1) CI9FO CIFO 3-Chloro-6.{4-chloro-2-fluoro-3-methoxy-phenyl)-4-[(furan-2-yhnethyl) -amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 5) (0.20 g, 0.47 mmol), (Z)-1-ethoxy-2-(tributylstannyl)-ethene (0.21 g, 0.59 mniol), and bis(tri-t-butylphosphine)palladium (12 mg, 0.024 mmol) were suspended in degassed dimethylformamide (5 ml) and the resulting mixture heated under microwave irradiation to 160 °C for 15 mm. After cooling to room temperature, the reaction mixture was poured into water and the aqueous layer was extracted with dichioromethane. The organic extracts were evaporated under reduced pressure, and the residue purified by reverse phase preparative HPLC, using FractionLynx (XBridge column, 30 x 100 mm, 5 micron particles, 20 mM ammonium acetate buffer) to give (Z)-6-.(4-chloro-2-fluoro-3- methoxy-phenyl)-3-(2-ethoxyethenyl)-4-[(furan-2-ylmethyl)-amino] -pyridine-2-carboxylic acid methyl ester (23 mg, 11%) as a solid.
Characterising data for the compound are as follows: H NMR (400 MHz, CD3OD) 5 7.45-7.40 (m, 2H), 7.28 (dd, lIT), 7.01 (d, lH), 6.44 (d, 1H), 6.35 (m, 111), 6.29 (m, 1H), 5.25 (d, 1H), 4.48 (s, 2H), 3.96 (s, 3H), 3.91 (q, 21-I), 3.87 (s, 31-I), 1.21 (t, 3H) ppm (NH not observed).
EXAMPLE 10
Synthesis of 3-bromo-5,6-dicbloro-4-1(2-nitrophenyl-methyl) -aminoj-pyridine-2-carboxylie acid methyl ester (Compound 15-41) tNO2
NH NH
_______CK..LBr -ClN 0 0 N-Chlorosuccinimide (185 mg, 1.4 mmol) was added to a stirred solution of 3-bromo-6-chloro-4-[(2-nitrophenylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 4) (500 mg, 1.25 mmol) in acetonitrile (30 ml) and stirring continued at ambient temperature for 3 hours. The reaction mixture was then heated at reflux for 20 hours, with additional N-chlorosuccinimide (185 mg, 1.4 mmol) being added after 6 hours. The reaction mixture was allowed to cool and evaporated under reduced pressure. Water (40 ml) was added to the residue and the resulting mixture extracted with ethyl acetate (3 x 40 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide a yellow oil that was purified by silica gel chromatography (gradient elution: 0 - 50% ethyl acetate in iso-hexane) to provide 3-bromo-5,6-dichloro-4-[(2-nitrophenyl-methyl)-amino] -pyridine-2-carboxylic acid methyl ester (500 mg, 92%). Characterising data for the compound are as follows: H NMR (400 MHz, CDC13) 5 8.10 (m, 111), 7.60 (m, 111), 7.50 (m, 211), 5.90 (m, 111), 5.20 (m, 211), 4.00 (s, 311) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 8.
TABLE 8 Compounds made according to the method described in Example 10 above.
Compound Name Structure TH NMR (400 Number MHz, CDCI3) Sppm 1-41 3-Bromo-4-5.30 (m,1H), 3.90 cyclopropylmethyl J (s, 311), 3.50 (m, amino-5,6-NH 211), 1.10 (m, 1H), dichloro-pyridine-ci Br 0.60 (m, 211), 0.30 2-carboxylic acid (m, 211) methyl ester Ci N CO2Me 32-41 3-Bromo-4-[(3--8.60 (m, 111), 7.60 chloro-pyridin-2-(m, 211), 5.10 (m, ylmethyl)-amino]-Ci 2H), 4.00 (s, 311) 5,6-dichioro-NH (NH not observed) pyridine-2-ci Br carboxylic acid methyl ester CI N CO2Me
EXAMPLE 11
Synthesis of 3-bromo-6-chloro-5-t1uoro-4-(2-nitrophenyl-methyl)-aminoI-pyridine- 2-carboxylic acid methyl ester (Compound 15-29) T NO2 T NO2
NH
vL<Br ________ FzL.,Br CINL(O CIN0 Selectfluor® (660 mg, 1.9 mmol) was added to a stirred solution of 3-bromo-6-chloro-4-[(2-nitrophenylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 4) (500 mg, 1.25 mmol) in acetonitrile (30 ml) and the mixture heated at reflux for 16 hours. The reaction mixture was allowed to cool and evaporated under reduced pressure. Water (40 ml) was added to the residue and the resulting mixture extracted with ethyl acetate (3 x 40 ml). The combined organic extracts were dried over magnesium sulphate, filtered and evaporated under reduced pressure to provide a yellow oil that was purified by silica gel chromatography (gradient elution: 0 - 50% ethyl acetate in iso-hexane) to provide 3-bromo-6-chloro-5-fluoro-4-[(2-nitrophenyl-methyl)-amino] -pyridine-2-carboxylic acid methyl ester (440 mg, 84%).
Characterising data for the compound are as follows: H NMR (400 MHz, CDCI3) 8 8.20 (m, 111), 7.70 (m, 111), 7.50 (m, 211), 6.00 (m, 111), 5.10 (m, 211), 4.00 (s, 311) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 9.
TABLE 9 Compounds made according to the method described in Example 11 above.
Compound Name Structure JIINMR (400 Number MHz, CDCU3) öppm 1-29 3-Bromo-6-chloro-5.15 (br s, 1H), 4-J 3.96 (s, 3H), 3.43 cyclopropylmethyl NH (m, 2H), 1.13 (m, amino-5-fluoro-F Br 1H), 0.62 (m, 2H), pyridine-2-. I 0.30 (m, 2H) carboxylic acid CI N CO2Me methyl ester 32-29 3-Bromo-6-chloro-8.60 (m, lI-I), 7.70 4-[(3-chloro-(m, I H), 7.40 (m, pyridin-2-CI 111), 7.30 (m, 111), ylmethyl)-amino]-NH 5.00 (m, 211), 4.00 5-fluoro-pyridine-F Br (s, 3H) 2-carboxylic acid methyl ester CI N CO2Me
EXAMPLE 12
Synthesis of 6-ehloro-4-[(furan-2-ylmethy1)-amino-3-methyl-pyridine-2-carboxylie acid methyl ester (Compound 26-19).
cIo Clx(o 0 0 A mixture of 3-bromo-6-chloro-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid methyl ester repared as described in Example 4) (187 mg, 0.54 mmol), tetramethyltin (107 mg, 0.59 mmol) and bis(triphenylphosphine)palladitun(II) dichloride (19 mg, 0.03 mmol) in dimethylformamide (2 mL) was heated to 160 °C under microwave irradiation for 15 mm, then allowed to cool and poured into water. The mixture was extracted with dichioromethane, and the organic extracts concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC, using FractionLynx (X Bridge column, ammonium acetate buffer) followed by silica gel chromatography (gradient elution: 0 -60% ethyl acetate in iso-hexane) to give 6-chloro- 4-[(furan-2-ylmethyl)-aminoj-3-methyl-pyridine-2-carboxylic acid methyl ester (68 mg, 45%) as a white solid.
Characterising data for the compound are as follows: H NMR (400 MHz, CDCI3) 7.41 (d, 111), 6.65 (s, 111), 6.37 (m, 111), 6.30 (d, 1H), 4.73 (m, 11-I), 4.39 (d, 2H), 3.93 (s, 311), 2.24 (s, 311) ppm.
Further examples of compounds that were prepared using this method are listed
below in Table 10.
TABLE 10 Compounds made according to the method described in Example 12 above.
Compound Name Structure WNMR (400 Number MHz, CDC13) öppm 1-31 6-Chloro-4---3.90 (s, 311), 3.40 cyciopropylmethyl J (m, 2H), 2.30 (s, amino-5-fluoro-3-NH 311), 1.10 (m, 1H), methyl-pyridine-2-F 0.60 (m, 2H), 0.30 carboxylic acid I,, (m, 2H) (NH not methyl ester 2 8 observed) 1-43 4 -cç7 4.80 (m, 111), 3.90 Cyclopropylmethyl (s, 311), 3.30 (m, amino-5,6-NH 211), 2.50 (s, 31-1), dichloro-3-methyl-Ci 1.10 (m, 1H), 0.60 pyridine-2-I (m, 2H), 0.30 (m, carboxylic acid 2 8 211) methyl ester 15-31 6-Chloro-5-fluoro--8.10 (m, 111), 7.60 3-methyi-4-[(2-I (m, 111), 7.50 (m, nitrophenyl-NO2 211), 5.10 (m lI-I), methyl)-amino]-NH 5.00 (m, 2H), 4.00 pyridine-2-F (s, 311), 2.40 (s, carboxylic acid 311) methyl ester CI N CO2Me 1.10 (m, 1H), 7.60 15-43 5,6-Dichloro-3-methyl-4-[(2-NO (m, 111), 7.50 (m, 2 2H),5.20(m,1H), nitrophenyl-methyl)-amino]-NH carboxylic acid 4.80 (m, 211), 3.90 pyridine-2-ci (s, 311), 2.40 (s, )LJ 311) methyl ester Ci N CO2Me 8.10(m, 1H), 7.65 15-456 5,6-Dichloro-4-[(2-nitrophenyl-L'LNO (m, 111), 7.60 (m, 2 111), 7.50 (m, 1ff), methyl)-amino]-3-propyn-1-yl-LNH 6.10 (m, 111), 5.40 pyridine-2-ci (m, 211), 3.90 (s, carboxylic acid 3H), 1.95 (s, 311) methyl ester CiNCO2Me 26-458 6-Chloro-4-{(furan- 7.51-7.41 (m, 3H), 2-yl-methyl)-7.34 (m, 111), 7.25 amino]-3-phenyl- (m, 211), 6.72 (s, pyridine-2-Ci N CO2Me 1H), 6.31 (m, 111), carboxylic acid 6.17 (m, 111), 4.68 methyl ester (m, 11-1), 4.30 (d, 211), 3.63 (s, 311) 32-43 4-[(3-Chloro- 8.60 (m, 111), 7.70 pyridin-2-%%L.%..CI (m, 111), 7.30 (m, ylmethyl)-amino]- 4.90 (m, 211), 3.90 5,6-dichloro-3-NH carboxylic acid 111), 7.00 (m, 1ff), (s, 311), 2.50 (s, methyl-pyridine-2-ci 311) methyl ester Ci N CO2Me 32-465 5-Chloro-4-[(3--8.50 (in, 114), 7.70 chloro-pyridin-2-(m, 11-1), 7.20 (in, ylmethyl)-amino]-J CI 1H), 6.70 (m, lI-I), 3,6-dimethyl-1⁄4.NH 4.80 (m, 211), 4.00 pyridine-2-ci (s, 3H), 2.60 (s, carboxylic acid 3H), 2.50 (s, 3H) methyl ester N CO2Me
EXAMPLE 13
Synthesis of 5,6-dichloro-4-(2-nitrophenyl-methyl) -aminoJ-3-trifluorometby1-pyridine-2-carboxylic acid methyl ester (Compound 15-444) LcJNO
NH NH
CKvLBr _______ CIN° 0 0 A mixture of of 3-bromo-5,6-dichloro-4-[(2-nitrophenylmethyl)-amino]-pyridine- 2-carboxylic acid methyl ester (prepared as described in Example 10) (220 mg, 0.51 mmol), methyl 2,2-difluoro-2-ffluorosulphonyl)-acetate (71 Dl, 0.56 mmol)), copper (I) iodide (29 mg, 0.15 mmol) and dimethylformamide (1.5 ml) was heated under microwave irradiation at 150 °C for 1 hour, then cooled and filtered through Celite®.
The filtrate was purified by reverse phase preparative HPLC, using FractionLynx (X Bridge column, ammonium acetate buffer) to provide 5,6-dichloro-4-[(2-nitrophenyl-methyl)-amino] -3-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (52 mg, 24%).
The compound was characterised by HPLC-MS using a Waters Acquity HPLC equipped with a Waters Atlantis dCl 8 column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron, temperature 40 °C), Waters TUV detector, Waters 2777 Sample manager, ESI Corona CAD detector and Micromass ZQ2000 MS.
Standard MS conditions are ES+/-switching over mass range 130-700. The analysis is conducted using a two minute run time, according to the following gradient table: Time Solvent A Solvent B Flow (ml / (mins) (%) (%) mm) 0.00 90.0 10.0 2.00 1.50 10.0 90.0 2.00 1.75 10.0 90.0 2.00 1.90 90.0 10.0 2.00 2.00 90.0 10.0 2.00 SolventAH2Ocontaining 0.1% FICOOH Solvent B: CH3CN containing 0.1% UCOOM LCMS RT 1.10; MH 424, 426, 428.
Further examples of compounds that were prepared using this method are listed
belowinTablell.
TABLE 11 Compounds made according to the method described in Example 13 above.
Compound Name Structure 1H NMR (400 Number MHz, CDC13) bppm 1-444 4-5.50 (m, 111), 3.90 Cyclopropylmethyl (s, 3H), 3.60 (m, amino-5,6-FjJH 211), 1.10 (m, 111), dichloro-3-CK,,,L.<,CF3 0.70 (m, 2H), 0.30 trifluoromethyl-(m, 21-I) pyridine-2-CI N CO2Me carboxylic acid methyl ester 26-440 6-Chloro-4-[(furan--NH 7.43 (m, 1H), 6.77 2-yl-methyl)-\ CF3 (s, 111), 6.38 (m, amino]-3-I 111), 6.32 (m, 111), tnfluoromethyl-CI N CO2Me 5.50 (br. s, 111), -pyridine-2-4.44 (d,2H),3.94 carboxylic acid (s, 31-I) methyl ester
EXAMPLE 14
Synthesis of 6-chloro-4-cyclopropylmethylamino-3-ethenyl-pyridine-2-carboxylic acid methyl ester (Compound 1-12).
I
CINO CINO 0 0
A mixture of 3-bromo-6-chloro-4-cyclopropylmethylamino-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 4) (243 mg, 0.76 mmol), tributyl(vinyl)tin (265 mg, 0.84 mmol, 0.205 mL) and bis(triphenylphosphine)palladium(II) dichloride (27 mg, 0.04 mmol) in dimethylformamide (2 mL) was heated to 160 °C under microwave irradiation for 15 mm, then allowed to cool. Brine (2 ml) and dichloromethane (2 ml) were added, the phases separated and the organic phase concentrated under reduced pressure. The residue was purified by reverse phase preparative HPLC, using FractionLynx (X Bridge column, ammonium acetate buffer) followed by silica gel chromatography (gradient elution: 0 -50% ethyl acetate in iso-hexane) to give 6-chloro-4-cyclopropylmethylamino- 3-ethenyl-pyridine-2-carboxylic acid methyl ester (36 mg, 18%).
Characterising data for the compound are as follows: H NMR (400 MHz, CDC13) 66.75 (m, 1H), 6.52 (s, 111), 5.67 (dd, 1H), 5.46 (dd, 1H), 5.12 (br. s, 1H), 3.89 (s, 3H), 2.98 (m, 211), 1.09 (m, 111), 0.62 (m, 211), 0.27 (m, 2H) ppm.
Other compounds made using this general method are listed in Table 12 below.
Characteristic data provided is either H-nmr data (400 MHz, CDCI3) 8H ppm or LCMS [retention time (RT, recorded in minutes) and the molecular ion, typically the cation M+I-r]. Compounds eharacterised by HPLC-MS used a Waters Aequity FIPLC equipped with a Waters Atlantis dCl 8 column (column length 20 mm, internal diameter of column 3 mm, particle size 3 micron, temperature 40 °C), Waters TUV detector, Waters 2777 Sample manager, ESI Corona CAD detector and Micromass ZQ2000 MS. Standard MS conditions are ES+/-switching over mass range 130-700. The analysis is conducted using a two minute run time, according to the following gradient table: Time Solvent A Solvent B Flow (ml / (mins) (%) (%) mm) 0.00 90.0 10.0 2.00 1.50 10.0 90.0 2.00 1.75 10.0 90.0 2.00 1.90 90.0 10.0 2.00 2.00 90.0 10.0 2.00 Solvent A: H20 containing 0.1% HCOOFI Solvent B: CU3CN containing 0.1% I4COOH Table 12-Compounds made according to the general method described in
Example 14.
Compound Name Structure Characteristic No. data 1-27 6-Chloro-4-ç7 6.80 (m, 1H), 5.80 cyclopropylmet J (m, 1fl), 5.50 (m, hylamino-3-1H), 4.80 (m, 1H), ethenyl-5-F 3.90 (s, 3H), 3.40 fluoro-pyridine-I (m, 2H), 1.10 (m, 2-carboxylic ci CO2Me 11-1), 0.60 (m, 2H), acid methyl 0.30 (m, 2F1) ester Cyclopropylmet (m, 111), 5.60 (m, hylamino-5,6-1H), 5.10 (m, 111), 1-39 - 6.90(m, 11-1), SM dichloro-3-3.90 (s, 3H), 3.40 ethenyl-(m, 211), 1.10 (m, pyridine-2-N CO2Me 1H), 0.60 (m, 2H), carboxylic acid 0.30 (m, 211) methyl ester 2-12 6-Chloro-3- 7.40-7.25 (m, 5H), ethenyl-4-6.76 (m, 1H), 6.56 (s, 1H), 5.64 (dd, phenylmethyla mino-pyridine-CO2Me 111), 5.47 (dd, 1H), 2-carboxylic 5.39 (m, 111), 4.36 acid methyl (d, 2H), 3.89 (s, ester 311) 3-12 6-Chloro-4-[(2-NH 7.43 (m, 111), 7.28 chlorophenylme (m, 311), 6.79 (m, thyl)-amino]-3-1H), 6.54 (s, 1H), ethenyl-5.68 (dd, 111), 5.50 pyridine-2-CO2Me (dd, 1H), 5.48 (m, carboxylic acid 1H), 4.47 (d, 2H), methyl ester 3.91 (s, 3H) ethenyl-4-f(2-(m, 111), 7.15 (m, 6-12 6-Chloro-3-7.33 (m, 1H),7.25 fluorophenylme 2H), 6.77 (m, 1H), thyl)-amino]-6.59 (s, 1H), 5.67 pyridine-2-CO2Me (dd, 111), 5.48 (dcl, carboxylic acid I H), 5.41 (m, 1 H), methyl ester 4.43 (d, 2H), 3.90 (s, 3H) 9-12 6-Chloro-3--NH 7.28-7.18 (in, 411), ethenyl-4-[(2-6.74 (in, IF), 6.58 methylphenylm (s, 111), 5.62 (dd, 111), 5.44 (dd, 111), ethyl)-amino]-pyridine-2-CI N CO2Me 5.15 (in, 1H), 4.29 carboxylic acid (d, 211), 3.90 (s, methyl ester 31-1), 2.34 (s, 311) 7.16 (d, 211), 6.72 14-12 6-Chloro-4-[(4- (in, 3H), 6.61 (s, dimethylaminop Me2NC 111), 5.60 (dd, 111), heriylniethyl)-amino]-3-CI N CO2Me 5.45 (dd, 1H), 5.22 ethenyl-(in, lH), 4.21 (d, pyridine-2-211), 3.89 (s, 311), carboxylic acid 2.97 (s, 611) methyl ester 15-12 -6-Chloro-3-NO2 8.14 (dd, 111), 7.68 ethcnyl-4-[(2-1J0__NH (in, 111), 7.53 (m, nitrophenylmet 211), 6.73 (in, 1H), hyl)-amino]-6.48 (s, 111), 5.64 pyridine-2-CI N CO2Me (dd, 1H), 5.50 (dd, carboxylic acid 111), 4.85 (s, 211), methyl ester 3.86 (s, 311) (NH not observed) (CD3OD) 15-27 6-Chloro-3-8.10 (in, 111), 7.60 ethenyl-5-(in, 111), 7.50 (m, fluoro-4-ft2-NO2 211), 6.70 (in, 111), nitrophenylmet hyl)-amino]-F NH 5.70 (in, 211), 5.40 (in, 111), 4.90 (m, pyridine-2-211), 3.90 (s, 311) carboxylic acid CrN"CO2Me methyl ester 1-39 5,6-Dichloro-3- 8.10 (m, 111), 7.60 ethenyl-4-[(2-L1L (m, 111), 7.50-7.40 nitrophenylmet NO (m, 2H), 6.70 (m, hyl)-amino]-LNH 1H), 5.30 (m, 111), 5.50-5.30 (m, 211), pyridine-2-ci carboxylic acid 5.00 (m, 2H), 3.90 methyl ester ci N CO2Me (s, 311) 2 1-12 6-Chloro-4-7.37(m, 211), 7.25 [(2,6-cr'-c (m, 111), 6.88 (s, dichlorophenyl 111), 6.73 (m, 111), methyl)-LNH 5.62 (d, 111), 5.42 amino]-3-ethenyl-,J%%j(%.%% (d, 111), 5.40 (m, 111), 4.61 (d, 211), pyridine-2-Ci N CO2Me 3.88 (s, 311) carboxylic acid methyl ester 26-12 -6-Chloro-3- 7.40 (d, 111), 6.77 ethenyl-4-(m, 111), 6.67 (s, 111), 6.37 (m, 111), [(furan-2-ylmethyl)-Ci N CO2Me 6.27 (d, 111), 5.67 amino]-(dd, 111), 5.47 (dd, pyridine-2-lI-I), 5.37 (m, 111), carboxylic acid 4.36 (d, 211), 3.90 methyl ester (s, 311) 26-21 (mix 6-Chloro-4-<"J-'NH -of E and Z [(furan-2-\ isomers A+B), 6.65 isomers) ylmethyl)-(s, 0.7511, isomer COMe A), 6.62 (s, 0.2511, amino]-3-c (propen-1-yl)-isomer B), 6.38-pyridine-2-6.23 (m, 311, carboxylic acid isomers A+B), methyl ester 6.08-6.00 (m, 0.7511, isomer A), 5.92-5.83 (m, ____________ -0.2511, isomer B), 5.27 (m, 0.2511, isomer B), 5.15 (m, 0.7511, isomer A), 4.36 (m, 211, isomers A+B), 3.87 (s, 311, isomers A+B), 1.90 (dd, 0.75H, isomer B), 1.49 (dd, 2.25 H, isomer A) 8.50 (d, 111), 7.75 - 32-12 6-Chloro-4-[(3- (d, 111), 7.27 (m, chioro-pyridin- 2-ylmethyfl- 111), 7.06 (m, 1H), 6.85 (m, 111), 6.69 amino]-3-ethenyl-CINCO2Me (m, 111), 5.76 (dd, pyridine-2-111), 5.60 (dd, 111), carboxylic acid 4.45 (d, 2H), 3.91 methyl ester (s, 311) 32-39 4-[(3-Chloro--RT 1.12; Mr 372, ylmethyl)-amino] -5,6-I
KNH
dichloro-3- ethenyl-pyridine-2-CI carboxylic acid methyl ester CIANACO2Me pyridin-2-(m, 211), 7.00-6.70 32-467 4-[(3-Chloro--EL 8.50 (m, 1H), 7.70 ylmethyl)-CI (m, 211), 6.70 (m, 111), 6.40 (m, 1H), amino]-3,6-(di- ethenyl)-5- 5.80 (m, 111), 5.60 fluoro-pyridine-(m, 211), 4.80 (m, N CO2Me 211), 3.90 (s, 31-1) 2-carboxylic acid methyl ester 33-12 6-Chloro-3-NH 8.44 (m, 111), 7.53 ethenyl-4-[(3-(_L1!=._t%%. (d, 111), 7.42 (br. s, methyl-pyridin- 111), 7.20 (m, 111), 2-ylmethyl)-6.87 (m, 111), 6.65 amino]-CI N CO2Me (s, 111), 5.77 (dd, pyridine-2-1H), 5.62 (dd, 111), carboxylic acid 4.29 (d, 211), 3.92 methyl ester (s, 311), 2.35 (s, 3H) 67-12 6-Chloro-4-- (s, 1Ff), 5.66 (d, cyclohexylmeth 6.74 (m, 111), 6.5 ylamino-3- 111), 5.43 (d, 111), ethenyl-CI N CO2Me 5.08 (m, 111), 3.89 pyridine-2-(s, 3H), 2.97 (t, carboxylic acid 211), 1.82-1.68 (m, methyl ester 411), 1.62-1.54 (m, 211), 1.34-1.13 (m, 311), 1.05-0.93 (m, 111), 0.90-0.82 (m, 111) 73-12 6-Chloro-3-OMe 7.31 (m, 111), 7.19 ethenyl-4-[(2-(dd, 111), 6.94 (m, methoxyphenyl 211), 6.75 (m, 111), methyl)- 6.63 (s, 111), 5.64 amino]-CI N CO2Me (dd, 111), 5.54 (m, -pyridine-2-11113, 5.45 (dd, I H), carboxylic acid 4.35 (d, 211), 3.89 methyl ester (s, 3H), 3.88 (s, 311) 74-12 6-Chloro-3--7.73 (d, IH),7.55 ethenyl-4-[(2-/v"NH (m, 111), 7.45-7.37 :::: WfllflO] N COMe 5.68 (dd, IH), pyridine-2-(dd, I H), 5.47 (m, carboxylic acid 111), 4.59 (d, 211), methyl ester 3.90 (s, 3H) 75-12 6-Chloro-3-NH 717(m, 111), 7.01 ethenyl-4-\ I (m, 211), 6.74 (m, (thiophen-2-ii j" 111), 6.64 (s, 1 H), ylmethylamino) CI-''N'-CO2Me 5.65 (dd, 1H), 5.47 -pyridine-2-(dd, 1 H), 5.40 (m, carboxylic acid 111), 4.54 (d, 2H), methyl ester 3.89 (s, 3H)
EXAMPLE 15
Synthesis of 6-ch1oro-3-etheny1-4-(furan-2-ylmetby1)-amino-pyridine-2-carboxy1ic acid (Compound 26-11).
S
cO CIA Nff OH 0 0 A mixture of 3-bromo-6-chloro-4-cyclopropylmethylamino-pyridine-2-carboxylic acid methyl ester (prepared as described in Example 4) (200 mg, 0.58 mmol), tributyl(vinyl)tin (202 mg, 0.64 mmol) and bis(triphenylphosphine)palladium(II) dichioride (20 mg, 0.03 mmol) in dimethylformamide (2 ml) was heated to 160 °C under microwave irradiation for 15 mm, then allowed to cool. Water (2 ml) and dichloromethane (2 ml) were added, the phases separated and the organic phase concentrated under reduced pressure. The residue was dissolved in methanol (10 ml) and aqueous sodium hydroxide (2N; 5 ml) added. The resulting solution was stirred at ambient temperature for 8 hours, then acidified by the addition of hydrochloric acid (lN) and extracted with dichioromethane. The combined organic extracts were evaporated under reduced pressure and the resulting yellow oil was purified by reverse phase preparative HPLC, using FractionLynx (X Bridge column, ammonium acetate buffer) to give 6-chloro-3-ethenyl-4-[(furan-2-ylmethyl)-amino]-pyridine-2-carboxylic acid (30 mg, 19%) as a white solid.
Characterising data for the compound are as follows: H NMR (400 MHz, CDC13) 3 7.40 (br. s, 1H), 7.37 (s, 1H), 6.79 (m, IH), 6.46 (s, 1H), 6.33 (m, IH), 6.24 (m, 1H), 5.55 (m, 2H), 5,40 (d, lH), 4.28 (d, 2H) ppm.
EXAMPLE 16 Safening on Corn Maize seeds were sown into standard soil in pots and cultivated under controlled conditions in a glasshouse (at 24/18 °C day/night; 16 hours light; 65% humidity).
When the plants were at the vegetative stage of 3 leaves they were sprayed with an aqueous spray solution containing the components of the invention alone and where appropriate the herbicide safener (N-(2-methoxybenzoyl)-4- [(methylaminocarbonyl)amino]benzenesulfonamide). All the compounds used for the spray solution were present as an BC or SC formulation respectively. In addition a non-ionic surfactant (X-77 Spreader) was added to form a 0.2% v/v solution.
The spray solution was applied with a cabinet tracksprayer with a flat fan nozzle (Teejet 1 1002VS) and an application volume of 200L/ha (at 2 bar).
The test plants were then grown on in a glasshouse under controlled conditions (at 24/18 °C day/night; 16 hours light; 65% humidity) and watered twice a day. After 7 days the test was evaluated for general crop injury (100% equals total damage to plant; 0% equals no damage to plant).
Results are shown below in Table 13.
TABLE 13 Percentage damage caused to corn by the compositions of the invention alone and in the presence of a safener (N-(2- methoxyhenzoyl)-4-I(methylaminocarhonyl)amino]benzcnesulfonamide).
Compound Rate 7 days after application Number (gaifha) Maize cv --Maize cv
GARLAND CLAXXON
1-27 50 -0 -0 -0 0 0 0 10 0 1-27&Safener 200+200 0 0 5-2 50 0 0 0 0 5 0 --10 10 5-2 & Safener 200+200 0 0 -6-2 50 0 0 0 0 0 0 5 0 6-2 & Safener 200+200 0 0 -26-11 50 0 0 _0 --0 0 5 5 26-11&Safener 200+200 -0 0 Although the invention has been described with reference to preferred embodiments and examples thereof, the scope of the present invention is not limited only to those described embodiments. As will be apparent to persons skilled in the art, modifications and adaptations to the above-described invention can be made without departing from the spirit and scope of the invention, which is defined and circumscribed by the appended claims. All publications cited herein are hereby incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were specifically and individually indicated to be so incorporated by reference.

Claims (15)

  1. CLAIMSA composition for protecting crop plants from the harmful effects of a 4-aminopicolinate herbicide of formula (I) (I) or a salt or N-oxide thereof, wherein: A is halogen, Cl-C6 alkyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, Cl -C6 alkylthio optionally substituted by I to 3 groups R2, C6-C1O aryl optionally substituted by 1 to 3 groups or a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R' is hydrogen, C l-C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl, Cl-C6 acyl optionally substituted by 1 to 3 groups R2, C1-C6 alkylsulphonyl optionally substituted by 1 to 3 groups R2, C2-C7 alkoxycarbonyl optionally substituted by 1 to 3 groups R2, aminocarbonyl, Cl -C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups or diCl -C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R4 is hydrogen, cyano, nitro, Cl-C6 alkyl optionally substituted by 1 to 3 groups B.2, Cl -C6 haloalkyl optionally substituted by 1 to 3 groups R2, C3-C6 cycloalkyl optionally substituted by I to 3 groups R2, C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C6-Cl 0 aryl optionally substituted by 1 to 3 groups R3, a mono-or bicyclic heteroaryl group having 3 to 10 ring atoms and at least one ring atom which is nitrogen, oxygen or sulfur optionally substituted by 1 to 3 groups R3, Cl-C6 acyl optionally substituted by 1 to 3 groups R2, C1-C6 alkoxycarbonyl optionally substituted by 1 to 3 groups R2, carboxy, aminocarbonyl, Cl -C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2, diCl-C6 alkylaminocarbonyl optionally substituted by 1 to 3 groups R2 or diCl-C6 alkyiphosphonyl optionally substituted by 1 to 3 groups R2; R5 is hydrogen, C1-C6 alkyl optionally substituted by 1 to 3 groups R2 or Cl -C6 haloalkyl; W is a direct bond or a linker group of the formula -(C1-C3 alkylene)-L-(C1-C3 alkylene)r wherein each alkylene group is optionally substituted by up to 3 groups s and t may each be independently 0 or 1, and L is a direct single, double or triple bond, -S(O)-wherein u is 0, 1 or 2, -N(R")-wherein R" is H or Cl-C6 alkyl, -0-or -C(0)0-; Q is a 3-10 membered ring system optionally containing up to 4 heteroatoms independently selected from 0, N or S, the ring system optionally substituted by up X is hydrogen, halogen, cyano, nitro, hydroxyl, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkyl optionally substituted by 1 to 3 groups C2-C6 alkenyl optionally substituted by 1 to 3 groups R2, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, C1-C6 haloalkoxy, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, Cl-C6 alkoxy optionally substituted by 1 to 3 groups R2, amino, C1-C6 alkylamino optionally substituted by I to 3 groups di(C1-C6 alkyl)amino optionally substituted by 1 to 3 groups R2, C1-C6 alkylthio optionally substituted by 1 to 3 groups R2, C1-C6 alkylsulphinyl optionally substituted by I to 3 groups R2 or C1-C6 alkylsulphonyl optionally substituted by I to 3 groups Y is halogen, cyano, nitro, hydroxyl, C1-C6 alkyl optionally substituted by 1 to 3 groups R2, C2-C6 alkenyl optionally substituted by I to 3 groups R2, C2-C6 alkynyl optionally substituted by 1 to 3 groups R2, Cl -C6 haloalkyl optionally substituted by 1 to 3 groups R2, Cl-C6 haloalkoxy, C1-C6 alkoxy optionally substituted by 1 to 3 groups R2, C3-C8 cycloalkyl optionally substituted by 1 to 3 groups R2, C6-C 10 aryl, amino, Cl -C6 alkylamino, di(C 1 -C6 alkyl)amino, Cl -C6 alkylthio, Cl -C6 alkylsulphinyl or Cl -C6 alkytsuiphonyl,; Z is C(O)R6, C(S)R6 or C(=NR7)R8; each R2 is independently halogen, hydroxyl, amino, Cl-C3 alkylamino, di (Cl-C3alkyl)amino, carboxy, cyano, Cl-C3 alkyl, Cl-C3 haloalkyl, C3-C6 cycloalkyl, Cl-C3 alkoxy, C1-C3 haloalkoxy, Cl-C3 alkylthio, C1-C3 alkylsulphonyl, C2-C6 carboxyalkyl, carboxy, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl or phenoxy; each R3 is independently halogen, hydroxyl, nitro, amino, thiol, cyano, Cl-C3 alkyl, C1-C3 haloalkyl, Cl-C3 alkoxy, C1-C3 haloalkoxy, Cl-C3 alkylthio, Cl-C3 haloalkylthio, C2-C6 carboxyalkyl, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, phenyl, phenoxy, Cl-C3 alkylamino or di(Cl -C3 alkyl)amino; R6 is hydrogen, hydroxyl, Cl-Cl 0 alkoxy optionally substituted by Cl -C6 alkoxy or phenyl, C3-C8 cycloalkoxy optionally substituted by Cl-C6 alkoxy or phenyl, Cl-C6 haloalkoxy, C2-C6 alkenyloxy, Cl-C6 alkylthio, amino, C1-C6 alkylamino or di(Cl-C6 alkyl)amino; R7 is hydrogen, Cl-C6 alkyl, C1-C6 alkoxy, C3-C8 cycloalkoxy, amino, Cl-C6 alkylamino or di(Cl-C6 alkyl)amino; R8 is hydrogen, C1-C6 alkoxy, C3-C8 cycloalkoxy, C1-C6 alkylthio, amino, Cl-C6 alkylamino or di(Cl-C6 alkyl)amino; wherein said composition comprises, in addition to the herbicide of formula (I), a safener selected from the group comprising AD 67, benoxacor, cloquintocet-mexyl, cyprosulfamide, dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, the R isomer of furilazole, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, naphthalic anhydride, N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)- benzamide and N-(2-methoxybenzoyl)-4- [(methylaminocarbonyflamino]benzenesulfonaniide.
  2. 2. A composition according to claim I wherein A is halogen, phenyl optionally substituted by 1 to 3 groups R3 or C3-C6 cycloalkyl optionally substituted by 1 to 3 groups R2.
  3. 3. A composition according to claim 1 or 2 wherein R' is hydrogen or C1-C6 alkyl.
  4. 4. A composition according to any preceding claim wherein X is hydrogen, halogen, CI-C6 alkyl, Cl-C6 haloalkyl, C1-C3 alkoxy(C1-C6)alkyl or C3-C6 cycloalkyl.
  5. 5. A composition according to any preceding claim wherein Y is halogen, Cl-C3 alkyl, Cl -C3 haloalkyl, Cl -C2 alkoxy(C I -C2)alkyl, cyclopropyl, C2-C4 alkenyl or C2-C4 alkynyl.
  6. 6. A composition according to any preceding claim wherein R4 is hydrogen, Cl -C6 alkyl, CI -C6 haloalkyl, Cl -C6 hydroxyalkyl, C1.-C3 alkoxy(Cl -C6)alkyl, C2-C6 alkoxycarbonyl or carboxyl.
  7. 7. A composition according to any preceding claim wherein R5 is hydrogen or Cl-C6 alkyl.
  8. 8. A composition according to any preceding claim wherein W is a direct bond or a methylene group.
  9. 9. A composition according to any preceding claim, wherein Q is phenyl, pyridyl, fury!, thiophenyl, oxazolyl, thiazolyl, each optionally substituted by 1 or 2 groups R3, or C3-C8 cycloalkyl optionally substituted by 1 or 2 groups R3; wherein each R3 is independently halogen, nitro, cyano, C1-C2 alkyl, Cl-C2 haloalkyl, C1-C2 alkoxy, C1-C2 haloalkoxy, C2-C3 alkoxycarbonyl, amino or di(C1 -C2alkyl)amino.
  10. 10. A composition according to any preceding claim, wherein X is hydrogen, halogen, Cl -C2 alkyl, Cl -C2 haloalkyl, Cl -C2 alkoxy(C 1 -C2)alkyl or C3-C6 cycloalkyl.
  11. 11. A composition according to any preceding claim, wherein Y is halogen, C1-C2 alkyl, C1-C2 haloalkyl, C1-C2 alkoxy(C1-C2)alkyl or C2-4 alkenyl.
  12. 12. A composition according to any preceding claim wherein Z is C(O)R6, wherein R6 is hydroxyl, C1-C6 alkoxy, phenyl(C1-C2)alkoxy or (C1-C3)alkoxy(C1.-C6)alkoxy.
  13. 13. A composition according to claim 1, wherein A is halogen, R' is hydrogen, X is hydrogen or halogen, Y is halogen, methyl or vinyl, Z is C(O)R6, wherein R6 is hydroxyl or Cl-C6 alkoxy, R4 and R5 are both hydrogen, W is a direct bond and Q is a phenyl, fUranyl, pyridyl or cyclopropyl ring optionally substituted by up to three substituents R3, wherein each R3 is independently halogen, hydroxyl, nitro, amino, Cl -C3 alkyl, Cl -C3 haloalkyl, C1-C3 alkoxy, Cl -C3 haloalkoxy, C2-C6 alkoxycarbonyl, C2-C7 alkylcarbonyloxy, Cl -C3 alkylamino or di(C 1 -C3 alkyl)amino.
  14. 14. The composition according to any one of the preceding claims, wherein the safener is cloquintocet-mexyl, cyprosulfamide, fenchlorazole-ethyl, mefenpyr-diethyl or N- (2-methoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.
  15. 15. A method for protecting crop plants from the harmful effects of a herbicide of formula (I) as defined in any one of the preceding claims, which comprises applying to the locus of the crop plants a safener selected from the group comprising AD 67, benoxacor, cloquintocet-mexyl, cyprosulfamide, dichlormid, fenchlorazole-ethyl, fenclorim, flurazole, fluxofenim, furilazole, the R isomer of furilazole, isoxadifen-ethyl, mefenpyr-diethyl, oxabetrinil, naphthalic anhydride, N-isopropyl-4-(2-methoxy-benzoylsulfamoyl)-benzamide and N-(2-mcthoxybenzoyl)-4-[(methylaminocarbonyl)amino]benzenesulfonamide.
GB1021899.8A 2010-12-22 2010-12-22 Substituted 4-aminopicolinate herbicides with safeners Withdrawn GB2486717A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0365484A1 (en) * 1988-10-20 1990-04-25 Ciba-Geigy Ag Sulfamoyl phenyl ureas
WO2009056333A2 (en) * 2007-11-01 2009-05-07 Syngenta Participations Ag Method of protecting rice crops
WO2010060579A2 (en) * 2008-11-29 2010-06-03 Bayer Cropscience Ag Herbicide-safener combination
WO2010149956A1 (en) * 2009-06-22 2010-12-29 Syngenta Limited 4 -aminopicolinates and their use as herbicides
WO2011144891A1 (en) * 2010-05-18 2011-11-24 Syngenta Limited Chemical compounds

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0365484A1 (en) * 1988-10-20 1990-04-25 Ciba-Geigy Ag Sulfamoyl phenyl ureas
WO2009056333A2 (en) * 2007-11-01 2009-05-07 Syngenta Participations Ag Method of protecting rice crops
WO2010060579A2 (en) * 2008-11-29 2010-06-03 Bayer Cropscience Ag Herbicide-safener combination
WO2010149956A1 (en) * 2009-06-22 2010-12-29 Syngenta Limited 4 -aminopicolinates and their use as herbicides
WO2011144891A1 (en) * 2010-05-18 2011-11-24 Syngenta Limited Chemical compounds

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