[go: up one dir, main page]

WO2009090402A2 - Herbicidal compounds - Google Patents

Herbicidal compounds Download PDF

Info

Publication number
WO2009090402A2
WO2009090402A2 PCT/GB2009/000127 GB2009000127W WO2009090402A2 WO 2009090402 A2 WO2009090402 A2 WO 2009090402A2 GB 2009000127 W GB2009000127 W GB 2009000127W WO 2009090402 A2 WO2009090402 A2 WO 2009090402A2
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
formula
compound
substituted
aryl
Prior art date
Application number
PCT/GB2009/000127
Other languages
French (fr)
Other versions
WO2009090402A3 (en
Inventor
Matthew Robert Cordingley
Michael Drysdale Turnbull
Neil Brian Carter
Patrick Jelf Crowley
Original Assignee
Syngenta Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to BRPI0906794-9A priority Critical patent/BRPI0906794A2/en
Priority to AU2009204688A priority patent/AU2009204688B2/en
Priority to US12/863,286 priority patent/US8338598B2/en
Priority to JP2010542684A priority patent/JP5596556B2/en
Priority to CA2711920A priority patent/CA2711920C/en
Priority to CN200980105079.1A priority patent/CN101945581B/en
Priority to EA201070858A priority patent/EA017629B1/en
Application filed by Syngenta Limited filed Critical Syngenta Limited
Priority to EP09701563.0A priority patent/EP2254416B1/en
Priority to MX2010007679A priority patent/MX2010007679A/en
Publication of WO2009090402A2 publication Critical patent/WO2009090402A2/en
Publication of WO2009090402A3 publication Critical patent/WO2009090402A3/en
Priority to ZA2010/05096A priority patent/ZA201005096B/en
Priority to US13/723,270 priority patent/US8653078B2/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system

Definitions

  • the present invention relates to novel herbicidal pyrido[2,3-b]pyrazines, to processes for their preparation, to compositions comprising these compounds, and to their use in controlling plants or in inhibiting plant growth.
  • Certain pyridopyrazines were disclosed as herbicidal compounds, for example, in WO 08/009908 and WO 08/071918. Certain pyridopyrazines were disclosed as intermediates in the synthesis of fungicidal compounds, for example, in WO 04/056825, WO 05/123698 and WO 05/123733. Certain pyridopyrazines were disclosed as fungicidal compounds, for example, in WO 05/010000. Certain pyridopyrazines were disclosed as pharmaceutical compounds, for example, in WO 96/22990 and WO 03/066630.
  • the present invention therefore provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I)
  • R 1 and R 2 are independently hydrogen, C]-C 4 alkyl, d-C 4 haloalkyl, halo, cyano, hydroxy, Ci-C 4 alkoxy, d-C 4 alkylthio, aryl or aryl substituted by one to five R 6 , which may be the same or different, or heteroaryl or heteroaryl substituted by one to five R 6 , which may be the same or different;
  • R 3 is hydrogen, d-C 1O alkyl, d-C 4 haloalkyl, C 2 -C]oalkenyl, C 2 -C4haloalkenyl, C 2 -C 10 alkynyl, C 2 -C 4 haloalkynyl, C 3 -C 10 cycloalkyl, C 3 -C 10 cycloalkyl-Ci-C 6 alkyl-, C 1 - C 10 alkoxy-Ci-C 6 alkyl-, Ci-Ciocyan
  • R 4 is heteroaryl or heteroaryl substituted by one to four R 8 , which may be the same or different;
  • R 5 is hydroxy or a group which can be metabolised to a hydroxy group;
  • each R 6 , R 7 and R 8 is independently halo, cyano, nitro, C 1 -C 1 QaIlCyI, d-C- t haloalkyl, C 2 - Cioalkenyl, C 2 -Cioalkynyl, hydroxy, Ci-C] 0 alkoxy, Ci-C 4 haloalkoxy, C 1 -C 1O aIkOXy-C 1 - C 4 alkyl-, C 3 -C 7 cycloalkyl, C 3 -C 7 cycloalkoxy, C 3 -C 7 cycloalkyl-Ci-C 4 alkyl-, C 3 - C 7 cycloalkyl-Ci-C 4 alkoxy-, Ci-C
  • the compounds of formula (I) may exist in different geometric or optical isomers or 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.
  • a compound of formula (Ia) i.e. a compound of formula (I) wherein R 3 is hydrogen and R 5 is hydroxy, can be drawn in at least five tautomeric forms.
  • a compound of formula (Ib) i.e. a compound of formula (I) wherein R 3 is hydrogen and R 5 is as defined for compounds of formula (I) other than hydroxy, can be drawn in at least two tautomeric forms.
  • a compound of formula (Ic), i.e. a compound of formula (I) wherein R 3 is as defined for compounds of formula (I) other than hydrogen and R 5 is as defined for compounds of formula (I) other than hydroxy, can be drawn in only one tautomeric form.
  • a compound of formula (Id), i.e. a compound of formula (I) wherein R 3 is as defined for compounds of formula (I) other than hydrogen and R 5 is hydroxy, can be drawn in three tautomeric forms.
  • Each alkyl moiety (either alone or as part of a larger group, such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, H-hexyl, MO-propyl, w-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl.
  • the alkyl groups are preferably C 1 to C 6 alkyl groups, more preferably C 1 -C 4 and most preferably C 1 -C 3 alkyl groups.
  • Alkenyl and alkynyl moieties can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl, allyl, prop-2-enyl and propargyl.
  • the alkenyl and alkynyl groups are preferably C 2 to C 6 alkenyl or alkynyl groups, more preferably C 2 -C 4 and most preferably C 2 -C 3 alkenyl or alkynyl groups.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Haloalkyl groups are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, -CF 3 , -CF 2 Cl, -CHF 2 , -CH 2 CF 3 or -CH 2 CHF 2 .
  • Cyanoalkyl groups are alkyl groups which are substituted with one or more cyano groups, for example, cyanomethyl or 1,3-dicyanopropyl.
  • Cycloalkyl groups can be in mono- or bi-cyclic form and may optionally be substituted by one or more methyl groups.
  • the cycloalkyl groups preferably contain 3 to 8 carbon atoms, more preferably 3 to 6 carbon atoms.
  • Examples of monocyclic cycloalkyl groups are cyclopropyl, 1 -methylcyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
  • aryl refers to a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl.
  • heteroaryl refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings contain up to three and bicyclic systems up to four heteroatoms which are preferably chosen from nitrogen, oxygen and sulfur.
  • Examples of monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl.
  • More preferred monocyclic groups are pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl and triazolyl, most preferably pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl and thiazolyl.
  • Examples of bicyclic groups are benzo thiophenyl, benzimidazolyl, benzoxazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl and pyrazolo[l,5- ajpyrimidinyl. More preferred bicyclic groups are benzoxazolyl, quinolinyl, isoquinolinyl and pyrazolo[l,5-a]pyrimidinyl, most preferably quinolinyl and isoquinolin
  • heterocyclyl is defined to include heteroaryl and in addition their unsaturated or partially unsaturated analogues such as 4,5,6,7-tetrahydro- benzothiophenyl, chromen-4-onyl, 9H-fluorenyl, 3,4-dihydro-2H-benzo-l,4-dioxepinyl, 2,3-dihydro-benzofuranyl, piperidinyl, 1,3-dioxolanyl, 1,3-dioxanyl, 4,5-dihydro- isoxazolyl, tetrahydrofuranyl and morpholinyl.
  • analogues such as 4,5,6,7-tetrahydro- benzothiophenyl, chromen-4-onyl, 9H-fluorenyl, 3,4-dihydro-2H-benzo-l,4-dioxepinyl, 2,3-dihydro-benzofuranyl, piperidiny
  • herbicide as used herein means a compound that controls or modifies the growth of plants.
  • herbicidally effective amount means the quantity of such a compound or combination of such compounds that is capable of producing a controlling or modifying effect on the growth of plants. Controlling or modifying effects include all deviation from natural development, for example: killing, retardation, leaf burn, albinism, dwarfing and the like.
  • plants refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.
  • locus is intended to include soil, seeds, and seedlings, as well as established vegetation.
  • the term “metabolism” as used herein means the conversion or breakdown of a substance from one form to another by a living organism, in particular in a plant (in planta).
  • salt means a compound of formula (I) which has a negative charge, for example, on an oxygen atom of a hydroxyl or of a carboxyl group, or a compound of formula (I) which has a positive charge, for example, on a nitrogen atom in a nitrogen-containing heteroaryl group, for example if a such a nitrogen is quarternised by alkylation.
  • the counter ion is necessarily of the opposite charge. Where the counter ion needs to be a cation the counter ion could be, for example, an alkali metal such as sodium or potassium, or an alkaline earth metal such as magnesium and calcium, or a quaternary ammonium base such as ammonium and tetramethylammonium. Where the counter ion needs to be a cation the counter ion could be, for example, hydroxide, or a halide such as chloride or bromide.
  • the compounds of formula (I) according to the invention also include hydrates which may be formed, for example, during salt formation.
  • R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are, in any combination, as set out below.
  • R 1 is hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, halo, cyano, hydroxy or C]-C 4 alkoxy.
  • R 1 is hydrogen, Ci-C 4 alkyl, halo, cyano or hydroxy. Even more preferably R 1 is hydrogen, methyl, chloro or bromo. Yet even more preferably R 1 is hydrogen or chloro.
  • R 1 is hydrogen
  • R 2 is hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, halo, cyano, hydroxy or d-C 4 alkoxy.
  • R 2 is hydrogen, C 1 -C 4 alkyl, halo, cyano or hydroxy. Even more preferably R 2 is hydrogen, methyl, chloro or bromo.
  • R 2 is hydrogen or chloro. Most preferably R 2 is hydrogen.
  • R 3 is hydrogen, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 2 -C 4 alkenyl, C 2 -C 4 haloalkenyl, C 2 -C 4 alkynyl or C 2 -C 4 haloalkynyl.
  • preferred groups for R 3 are hydrogen, methyl, ethyl, n-propyl, wo-propyl, ra-butyl, 2-methyl-propyl, 2- fluoro-ethyl, 2,2-difluoro-ethyl, 2,2,2-trifluoro-ethyl, allyl, but-3-en-l-yl or propargyl.
  • R 3 is hydrogen, Ci-C 2 alkyl, Ci-C 2 haloalkyl, C 2 -C 3 alkenyl or C 2 -C 3 alkynyl.
  • examples of such more preferred groups for R 3 are hydrogen, methyl, ethyl, 2,2-difluoro-ethyl, 2,2,2-trifluoro-ethyl, allyl or propargyl.
  • R 3 is hydrogen, C 1 -C 2 alkyl, Ci-C 2 haloalkyl or C 2 -C 3 alkynyl.
  • R 3 examples of such most preferred groups for R 3 are hydrogen, methyl, ethyl, 2,2-difluoro- ethyl or propargyl.
  • R 3 is 2,2-difluoro-ethyl.
  • R 4 is heteroaryl substituted by one to three R 8 , which may be the same or different.
  • R 4 is a monocyclic heteroaryl, containing up to two heteroatoms, substituted by one to three R 8 , which may be the same or different, or R 4 is a bicyclic heteroaryl, containing up to three heteroatoms, substituted by one to three R , which may be the same or different.
  • R 4 is pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl or triazolyl substituted by one to three R , which may be the same or different, or R 4 is benzoxazolyl, quinolinyl, isoquinolinyl or pyrazolo[l,5- a]pyrimidinyl substituted by one to three R 8 , which may be the same or different.
  • R 4 examples include 3,5-dichloro-pyrid-2-yl, 3,5- dichloro-pyrid-4-yl, 2,6-dichloro-pyrid-3-yl, 2,4-dichloro-pyrid-3-yl, 4,6-dichloro-pyrid- 3-yl, 2,5-dichloro-pyrid-4-yl, 3,6-dichloro-pyrid-2-yl, 3-chloro-5-fluoro-pyrid-2-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 3,5,6-trichloro-pyrid-2-yl, 2,5-dichloro-pyrid-3-yl, 2,3-dichloro-pyrid-4-yl, 2-chloro-4-trifluoromethyl-pyrid-3-yl, 2-chloro-6- trifluoromethyl-pyrid-3-yl, 3-chloro-5-trifluororor
  • R 4 is pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl or thiazolyl substituted by one to three R , which may be the same or different, or R is quinolinyl or isoquinolinyl substituted by one to three R 8 , which may be the same or different.
  • R 4 examples include 3,5-dichloro-pyrid-2-yl, 3,5-dichloro-pyrid-4-yl, 2,6-dichloro-pyrid-3-yl, 2,4-dichloro-pyrid-3-yl, 4,6-dich ⁇ oro- pyrid-3-yl, 2,5-dichloro-pyrid-4-yl, 3,6-dichloro-pyrid-2-yl, 3-chloro-5-fluoro-pyrid-2-yl, 3-chloro-5-trifiuoromethyl-pyrid-2-yl, 3,5,6-trichloro-pyrid-2-yl, 2,5-dichloro-pyrid-3-yl, 2,3-dichloro-pyrid-4-yl, 2-chloro-4-trifluoromethyl-pyrid-3-yl, 2-chloro-6- trifluoromethyl-pyrid-3-yl, 3-chloro
  • R 4 is 3,5-dichloro-pyrid-2-yl. In one preferred embodiment R 4 is 3,5-dichloro-pyrid-4-yl. In one preferred embodiment R 4 is 2,6-dichloro-pyrid-3-yl. In one preferred embodiment R 4 is 2,4-dichloro-pyrid-3-yl.
  • R 4 is 4,6-dichloro-pyrid-3-yl.
  • R 4 is 2,5-dichloro-pyrid-4-yl.
  • R 4 is 2,5-dichloro-thiophen-3-yl-. In one preferred embodiment R 4 is 3-trifiuoromethyl-isoxazol-5-yl.
  • R 4 is 3-methyl-l,2,4-oxadiazol-5-yl.
  • R 4 is 2-chloro-4-methyl-thiazol-5-yl.
  • R 4 is 2-chloro-4-trifluoromethyl-thiazol-5-yl-.
  • R 4 is 5-difluoromethoxy-l-methyl-3-trifiuoro- methyl- lH-pyrazol-4-yl.
  • R 4 is 2-methyl-5-trifluoromethyl-2H-l,2,3-triazol- 4-yl.
  • R 4 is 2-methyl-benzoxazol-5-yl.
  • R 4 is 2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl-.
  • R 5 is hydroxy, R 9 -oxy-, R 10 -carbonyloxy-, tri-R n -silyloxy- or R 12 - sulfonyloxy-, wherein
  • R 9 is Ci-doalkyl, C 2 -C 10 alkenyl, C 2 -Ci 0 alkynyl or aryl-Ci-C 4 alkyl- or aryl-C 1 -C 4 alkyl- wherein the aryl moiety is substituted by one to five substituents independently selected from halo, cyano, nitro, d-C 6 alkyl, d-C 6 haloalkyl or d-C 6 alkoxy;
  • R 10 is C-Cioalkyl, C 3 -Ci 0 cycloalkyl, Cj-Ciocycloalkyl-d-doalkyl-, Ci-C ]0 haloalkyl, C 2 - C 10 alkenyl, C 2 -C 10 alkynyl, Ci-C 4 alkoxy-C 1 -C 10 alkyl-, C 1 -C 4 alkylthio-C 1 -C 4 alkyl-,
  • R 12 is Ci-Cioalkyl, Ci-Ciohaloalkyl, or phenyl or phenyl substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C 6 alkyl, Ci-C 6 haloalkyl or Ci-C 6 alkoxy; and each R 14 is independently halo, cyano, nitro, Ci-Ci O alkyl, Ci-C 4 haloalkyl, Ci-C 10 alkoxy, Ci-dalkoxycarbonyl-, Ci-C 4 haloalkoxy, Ci-C 10 alkylthio-, Ci-C 4 haloalkylthio-, C 1 - Cioalkylsulfinyl-, Ci-C 4 haloalkylsulfmyl-, CrCi 0 alkylsulfonyl-, Ci-C 4 haloalkylsulfonyl-, aryl or aryl substituted by one
  • Ci-C 6 haloalkyl or d-C 6 alkoxy or heteroaryl or heteroaryl substituted by one to four substituents independently selected from halo, cyano, nitro, C 1 - C ⁇ alkyl, Ci-C 6 haloalkyl or Ci-C 6 alkoxy.
  • R 5 is hydroxy, R 9 -oxy- or R 10 -carbonyloxy-. Even more preferably R 5 is hydroxy, Ci-C 4 alkoxy, Ci-C 4 alkenyloxy, Ci-
  • R 5 examples of preferred groups for R 5 are hydroxy, methoxy, ethoxy, allyloxy, propargyloxy, benzyloxy, methylcarbonyloxy-, ethylcarbonyloxy-, /so-propylcarbonyl- oxy-, n-propylcarbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, tert- butylcarbonyloxy-, cyclopropylcarbonyloxy-, cyclopentyl-methylcarbonyloxy-, chloromethylcarbonyloxy-, trifluoromethylcarbonyloxy-, allylcarbonyloxy-, (E)-prop-l- en- 1 -ylcarbonyloxy-, 2-methyl-prop- 1 -en- 1 -ylcarbonyloxy-, methoxymethylcarbonyl- oxy-, ethoxycarbonyloxy-, tert-butoxycarbonyloxy-,
  • R 5 is hydroxy, Ci-Qalkylcarbonyloxy-, C 3 -C 6 cyclo- alkylcarbonyloxy-, C 2 -C 4 alkenylcarbonyloxy-, C 2 -C 4 alkynylcarbonyloxy-, C]- C 4 alkoxycarbonyloxy-, C 2 -C 4 alkenyloxycarbonyloxy-, C 2 -C 4 alkynyloxycarbonyloxy- or Ci-C/jalkylthiocarbonyloxy-.
  • R 5 examples of more preferred groups for R 5 are hydroxy, methylcarbonyloxy-, ethylcarbonyloxy-, zs ⁇ -propylcarbonyloxy-, w-propylcarbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, fert-butylcarbonyloxy-, cyclopropylcarbonyloxy-, allylcarbonyloxy-, (E)-prop-l -en- 1 -ylcarbonyloxy-, 2-methyl- prop- 1 -en- 1 -ylcarbonyloxy-, ethoxycarbonyloxy-, tert-butoxycarbonyloxy-, but-2-yn-l- yloxycarbonyloxy-, and ethylthiocarbonyloxy-.
  • R 5 is hydroxy, Ci-C 4 alkylcarbonyloxy-, Ci-C 4 alkoxycarbonyl- oxy- or Ci-C 4 alkylthiocarbonyloxy-.
  • Examples of most preferred groups for R 5 are hydroxy, methylcarbonyloxy-, ethylcarbonyloxy-, is ⁇ -propylcarbonyloxy-, n-propyl- carbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, tert-butylcarbonyl- oxy-, ethoxycarbonyloxy-, and ethylthiocarbonyloxy-.
  • R 5 is hydroxy.
  • R 5 is R 9 -oxy-, wherein R 9 is Ci-Cioalkyl, C 2 -
  • R 5 groups may be metabolised, preferably in planta, to give the corresponding compound wherein R 5 is hydroxy.
  • R 5 is R I0 -carbonyloxy-, wherein R 10 is Ci-doalkyl, C 3 -Ciocycloalkyl, C 3 -C t ocycloalkyl-C]-Cioalkyl-, Ci-Ciohaloalkyl, C 2 -C 10 alkenyl, C 2 - C 10 alkynyl, C r C 4 alkoxy-Ci-Ci 0 alkyl-, Ci-C 4 alkylthio-Ci-C 4 alkyl-, Ci-C 10 alkoxy, C 2 - C 10 alkenyloxy, d-doalkynyloxy, C)-C 10 alkylthio-, N-C 1 -C 4 alkyl-amino-, C 4 alkyl)-amino-, aryl or aryl substituted by one to three R 14 , which may be the same or different, heteroaryl or heteroaryl substituted by one to
  • each R 6 is independently halo, C 1 -C 4 alkyl, Cj-C 4 haloalkyl, Cj- C 4 alkoxy or Ci-C 4 haloalkoxy.
  • Examples of such preferred groups for R 6 are chloro, fluoro, methyl, ethyl, tr ⁇ fluoromethyl, methoxy or trifluoromethoxy.
  • each R 7 is independently halo, Ci-C 4 alkyl, Ci-C 4 haloalkyl, C 1 -
  • R 7 C 4 alkoxy or Ci-C 4 haloalkoxy.
  • preferred groups for R 7 are chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
  • each R 7 is independently halo, Ci-C 4 alkyl, Ci-C 4 haloalkyl or Q- C 4 alkoxy.
  • preferred groups for R 7 are chloro, fluoro, methyl, ethyl, trifluoromethyl and methoxy.
  • each R 8 is independently halo, cyano, nitro, Ci-Ci O alkyl, Ci- Qhaloalkyl, Ci-C 10 alkoxy, C]-C 4 alkoxycarbonyl-, Ci-C 4 haloalkoxy, Ci-C] 0 alkylthio-, Ci-C 4 haloalkylthio-, Ci-Cioalkylsulfinyl-, Ci-C 4 haloalkylsulfmyl-, Ci-Cioalkylsulfonyl- or Ci-C 4 haloalkylsulfonyl-.
  • each R 8 is independently halo, cyano, nitro, Ci-Cioalkyl, Ci- Qhaloalkyl, Ci-Ci 0 alkoxy, Ci-C 4 haloalkoxy, Ci-Cioalkylthio or Ci-C 4 haloalkylthio.
  • Examples of such more preferred groups for R 8 are iodo, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoromethylthio.
  • each R 8 is independently halo, Ci-Ci O alkyl, Ci-C 4 haloalkyl,
  • Ci-Ci 0 alkoxy or Ci-C 4 haloalkoxy examples of such even more preferred groups for R are bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy or trifluoromethoxy.
  • R 8 is independently halo, Ci-Cioalkyl, or Ci-C 4 haloalkyl.
  • R 8 examples of such even more preferred groups for R 8 are chloro, fluoro, methyl, or trifluoromethyl.
  • R 9 is C 2 -Cioalkenyl, C 2 -Ci 0 alkynyl, aryl-Ci-C 4 alkyl- or aryl-Q- Qalkyl- wherein the aryl moiety is substituted by one to three R 13 , which may be the same or different.
  • R 9 is C 3 -C 4 alkenyl, or C 3 -C 4 alkynyl, benzyl or benzyl wherein the phenyl moiety is substituted by one to three R 13 , which may be the same or different.
  • R 9 is allyl, propargyl or benzyl.
  • R 9 is allyl.
  • R 10 is C r C 4 alkyl, C 3 -C 6 cycloalkyl, C 3 -Ci 0 cycloalkyl-Ci-Ci 0 alkyl, Ci-
  • C 4 haloalkyl C 2 -C 4 alkenyl, C 2 -C 4 alkynyl, Ci-C 4 alkoxy-C r C 4 alkyl, C r C 4 alkylthio-Ci- C 4 alkyl, Ci-C 4 alkoxy, C 2 -C 4 alkenyloxy, C 2 -C 4 alkynyloxy, Ci-C 4 alkylthio, N-Ci-C 4 alkyl- amino, N,N-di-(C 1 -C 4 alkyl)-amino, aryl or aryl substituted by one to three R 14 , which may be the same or different, heteroaryl or heteroaryl substituted by one to three R , which may be the same or different, aryl-Ci-C 4 alkyl or aryl-Ci-C 4 alkyl wherein the aryl moiety is substituted by one to three R 14 , which may be the same or different, heteroaryl- Ci-
  • each R 11 is independently d-C 4 alkyl.
  • R 12 is Ci-C 4 alkyl or C 1 -C 4 haloalkyl.
  • each R 13 is independently halo, nitro, Ci-C 4 alkyl, Ci-C 4 haloalkyl or Ci-C 4 alkoxy.
  • Examples of such preferred groups are chloro, fluoro, nitro, methyl, ethyl, trifluoromethyl and methoxy.
  • each R 14 is independently halo, nitro, C]-C 4 alkyl, C 1 -C 4 haloalkyl, C 1 - C 4 alkoxy or C 1 -C 4 haloalkoxy.
  • Examples of such preferred groups are chloro, fluoro, nitro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
  • the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Ix)
  • R 1 , R 2 , R 4 and R 5 are as defined for a compound of formula (I) and R 3 is Ci-Cioalkyl, C 2 -C] 0 alkenyl, C 2 -C 10 alkynyl, C 3 -Ciocycloalkyl, C 3 -Ciocycloalkyl-d- C 6 alkyl-, d-doalkoxy-Ci-C ⁇ alkyl-, C]-C 10 cyanoalkyl-, d-doalkoxycarbonyl-d-
  • the preferences for R 1 , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I).
  • the preferences for R 3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 3 cannot be hydrogen.
  • the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Ic)
  • R 1 , R 2 and R 4 are as defined for a compound of formula (I) and R 3 is d-Cioalkyl, C 2 -C] 0 alkenyl, C 2 -Ci O alkynyl, C 3 -Ci 0 cycloalkyl, C 3 -Ciocycloalkyl-Ci- C 6 alkyl-, Q-Cioalkoxy-Ci-Cealkyl-, Ci-Qocyanoalkyl-, Ci-Cioalkoxycarbonyl-Ci- C 6 alkyl-, N-C 1 -Csalkyl-aminocarbonyl-Ci-C ⁇ alkyl-, N,N-di-(CrC 3 alkyl)-aminocarbonyl- C]-C 6 alkyl-, aryl-Ci-C 6 alkyl- or aryl-Ci-C 6 alkyl- wherein the aryl moiety is substituted
  • the preferences for R 1 , R 2 , R 4 , R 6 , R 7 , R 8 , R 9 , R 10 , R u , R 12 , R 13 and R 14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I).
  • the preferences for R 3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 3 cannot be hydrogen.
  • the preferences for R 5 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 5 cannot be hydroxy.
  • the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Id)
  • R 1 , R 2 and R 4 are as defined for a compound of formula (I) and R 3 is d-Cioalkyl, C 2 -C 10 alkenyl, C 2 -Ci 0 alkynyl, C 3 -Ci 0 cycloalkyl, C 3 -C 10 cycloalkyl-C]- C 6 alkyl-, Ci-C 10 alkoxy-Ci-C 6 alkyl-, Ci-Ciocyanoalkyl-, Ci-Ci 0 alkoxycarbonyl-Ci- C 6 alkyl-, N-Ci-C 3 alkyl-aminocarbonyl-Ci-C 6 alkyl-, iV,iV-di-(Ci-C 3 alkyl)-aminocarbonyl- C)-C 6 alkyl-, aryl-Ci-C 6 alkyl- or aryl-Ci-C 6 alkyl- wherein the aryl moiety is
  • R 1 , R 2 , R 4 , R 6 , R 7 , R 8 and R 13 are the same as the preferences set out for the corresponding substituents of a compound of formula (I).
  • the preferences for R 3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 3 cannot be hydrogen.
  • Certain compounds of formula (I) are novel and as such form a further aspect of the invention.
  • One group of novel compounds are compounds of formula (Ib)
  • R 1 , R 2 and R 4 are as defined for compounds of formula (I) and R 5 is a group which can be metabolised to a hydroxy group; or a salt or N-oxide thereof.
  • the preferences for R 1 , R 2 , R 4 , R 6 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are the same as the preferences set out for the corresponding substituents of compounds of the formula (I).
  • the preferences for R 5 are the same as the preferences set out for the corresponding substituents of compounds of formula (I) except that R 5 cannot be hydroxy.
  • Another group of novel compounds are compounds of formula (Ic)
  • R 1 , R 2 and R 4 are as defined for a compound of formula (I) and R 3 is
  • Ci-Cioalkyl C 2 -C 10 alkenyl, C 2 -C 10 alkynyl, C 3 -Ci 0 cycloalkyl, C 3 -C 10 cycloalkyl-d- C 6 alkyl-, Q-Cioalkoxy-Ci-Qalkyl-, CrQocyanoalkyl-, d-Cioalkoxycarbonyl-Ci- C 6 alkyl-, N-Ci-Caalkyl-aminocarbonyl-d-C ⁇ alkyl-, N,N-di-(Ci-C 3 alkyl)-aminocarbonyl- d-C 6 alkyl-, aryl-Ci-C 6 alkyl- or aryl-Ci-C 6 alkyl- wherein the aryl moiety is substituted by one to three R 7 , which may be the same or different, or heterocyclyl-Ci-C ⁇ alkyl- or hetero
  • R 1 , R 2 , R 4 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 and R 14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I).
  • the preferences for R 3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 3 cannot be hydrogen.
  • the preferences for R 5 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R 5 cannot be hydroxy.
  • a further group of novel compounds are compounds of formula (Id)
  • R 1 , R 2 and R 4 are as defined for a compound of formula (I) and R 3 is C]-Ci O alkyl, C 2 -Cioalkenyl, C 2 -Ci 0 alkynyl, C 3 -Ci 0 CyC loalkyl, C 3 -Ci 0 cycloalkyl-Ci- C 6 alkyl-, d-C t oalkoxy-Ci-Qalkyl-, Ci-Ciocyanoalkyl-, Ci-Cioalkoxycarbonyl-Ci- C 6 alkyl-, jV-Ci-Csalkyl-aminocarbonyl-Ci-C ⁇ alkyl-, N, ⁇ f-di-(Ci-C 3 alkyl)-aminocarbonyl- Ci-C 6 alkyl-, aryl-Ci-C 6 alkyl- or aryl-Ci-C 6 alkyl- wherein the
  • R 1 , R 2 , R 4 , R 6 , R 7 , R 8 and R 13 are the same as the preferences set out for the corresponding substituents of a compound of formula (I).
  • the preferences for R 3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R cannot be hydrogen.
  • Table 1 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3,5- dichloro-pyrid-2-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 2 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3,5- dichloro-pyrid-4-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 3 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2,6- dichloro-pyrid-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 4 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2,4- dichloro-pyrid-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 5 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 4,6- dichloro-pyrid-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 6 :
  • Table 6 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R is 2,5- dichloro-pyrid-4-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 7 Table 7 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3,6- dichloro-pyrid-2-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 8 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- chloro-5-fluoro-pyrid-2-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 9 :
  • Table 9 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- chloro-5-trifluoromethyl-pyrid-2-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 10 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3,5,6-trichloro-pyrid-2-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 11 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 12 Table 12 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 13 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R is 2- chloro-4-trifluoromethyl-pyrid-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 14 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2- chloro-6-trifluoromethyl-pyrid-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 15 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- chloro-5-trifluoromethyl-pyrid-4-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 16 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 17 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 5- chloro-pyrimidin-4-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 18 Table 18 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 19 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 20 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- trifluoromethyl-isoxazol-5-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 21 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- trifluoromethyl-4-chloro-isoxazol-5-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 22 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 23 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- methyl-l,2,4-oxadiazol-5-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 24 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 3- trifluoromethyl-l,2,4-oxadiazol-5-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 25 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 26 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2- chloro-4-methyl-thiazol-5-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 27 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 28 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2- chloro-4-trifluoromethyl-thiazol-5-yl-, and R 3 and R 5 have the values listed in Table 1.
  • Table 29 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R is 5- difluoromethoxy-l-methyl-3-trifluoromethyl-lH-pyrazol-4-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 30 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2- methyl-5-trifluoromethyl-2H-l,2,3-triazol-4-yl, and R 3 and R 5 have the values listed in
  • Table 31 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 2- methyl-benzoxazol-5-yl and R 3 and R 5 have the values listed in Table 1.
  • Table 32 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • Table 33 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is A- chloro-2-trifluoromethyl-quinolin-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 34 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is 1- chloro-isoquinolin-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 35 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is l,4-dichloro-isoquinolin-3-yl, and R 3 and R 5 have the values listed in Table 1.
  • Table 36 provides 70 compounds of formula (I), where R 1 and R 2 are hydrogen, R 4 is
  • reaction can conveniently be carried out optionally in the presence of a base, such as triethylamine or pyridine, in a suitable solvent, such as acetonitrile or dichloromethane, optionally using microwave heating.
  • a base such as triethylamine or pyridine
  • a suitable solvent such as acetonitrile or dichloromethane
  • microwave heating optionally using microwave heating.
  • (3) is a carboxylic acid (i.e.
  • the reaction can conveniently be carried out using an amide coupling method, for example by reaction with a coupling agent, such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride, in the presence of a base, such as triethylamine, in a suitable solvent, such as dichloromethane, or other amide coupling methods which have been reviewed in Tetrahedron (2005), 61(46), 10827-10852.
  • a coupling agent such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride
  • Compounds of formula (Ia) wherein R 1 , R 2 and R 4 are as defined for a compound of formula (I) can be prepared by treating a compound of formula (4) as defined in 1) with a base in a suitable solvent, such as potassium carbonate in N,N- dimethylformamide or lithium hexamethyldisilazide in tetrahydrofuran, optionally using microwave heating.
  • a suitable solvent such as potassium carbonate in N,N- dimethylformamide or lithium hexamethyldisilazide in tetrahydrofuran, optionally using microwave heating.
  • compounds of formula (Ie) as defined in 6) can also be formed by reaction of a compound of formula (Ia) as defined in 2) with at least two equivalents of a compound of formula R 3 LG as defined in 4), in the presence of a base, such as potassium carbonate, in a suitable solvent, such as N,7V-dimethylformamide, as shown in Scheme 3.
  • a base such as potassium carbonate
  • a suitable solvent such as N,7V-dimethylformamide
  • Compounds of formula (If) as defined in 4) can additionally be prepared in a shortened route directly from a compound of formula (4) as defined in 1) by reaction with a compound of formula R LG as defined in 4), in the presence of a base, such as sodium or potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating, followed by reaction with an acid chloride of formula R 10 COCl or an acid anhydride of formula (R 10 CO) 2 O as defined in 3), optionally in the presence of a base, such as triethylamine, in the same reaction pot, as shown in Scheme 4.
  • a base such as sodium or potassium hexamethyldisilazide
  • a suitable solvent such as tetrahydrofuran
  • Alternatively compounds of formula (If) as defined in 4) can be made from a compound of formula (Id) as defined in 5), by reaction with an acid chloride of formula R 10 COCl or an acid anhydride of formula (R 10 CO) 2 O as defined in 3), optionally in the presence of a base, such as triethylamine, optionally in a suitable solvent, such as dichloromethane.
  • a base such as triethylamine
  • Compounds of formula (Id) as defined in 5) can be made by reaction of a compound of formula (4) as defined in 1) with a compound of formula R 3 LG as defined in 4), in the presence of a base, such as potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating (Method 1).
  • a base such as potassium hexamethyldisilazide
  • a suitable solvent such as tetrahydrofuran
  • Compounds of formula (Ib) as defined in 5) can also be made by reaction of a compound of formula (4') with a compound of formula R 3 LG as defined in 4), in the presence of a base, such as sodium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating (Method 3).
  • a base such as sodium hexamethyldisilazide
  • a suitable solvent such as tetrahydrofuran
  • microwave heating Method 3
  • Compounds of formula (4') can be made from a compound of formula (4) by reaction with a base, such as lithium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran or N,N-dimethyl- formamide, optionally using microwave heating.
  • Silyl compounds of formula (Ig), i.e. a compound of formula (I) wherein R 3 is as defined for a compound of formula (I) other than hydrogen and R 5 is -0-Si(R 1 ') 3 can be made from a compound of formula (Id) as defined in 5), by reaction with a trialkylsilyl chloride of formula (R n ) 3 SiCl, in a suitable solvent, such as tetrahydrofuran or acetonitrile, in the presence of a base, such as triethylamine, as shown in Scheme 5.
  • a suitable solvent such as tetrahydrofuran or acetonitrile
  • r. 12 defined for a compound of formula (I) can be made from a compound of formula (Ia) as defined in 2) by reaction with a sulfonyl chloride of formula R 12 SO 2 Cl wherein R 12 is as defined for a compound of formula (I), in the presence of a base, such as triethylamine, in a suitable solvent, such as tetrahydrofuran or dichloromethane, as shown in Scheme 6.
  • Sulfonyl compounds of formula (Ih), i.e. a compound of formula (I) wherein R 3 is as defined for compounds of formula (I) other than hydrogen and R 5 is -0-SO 2 -R can be made by reaction of a compound of formula (Ik) as defined in 13), with a compound of formula R 3 LG as defined in 4), in the presence of a base, such as sodium or potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating.
  • a base such as sodium or potassium hexamethyldisilazide
  • compounds of formula (Ih) as defined in 14) can be made by reaction of a compound of formula (Id) as defined in 5) with a sulfonyl chloride of formula Ri 2 SO 2 Cl as defined in 13), in the presence of a base, such as triethylamine, in a suitable solvent, such as tetrahydrofuran or dichloromethane.
  • a base such as triethylamine
  • a N-halosuccinimide of formula chlorine, bromine or iodine in the presence of a radical initiator, such as benzoyl peroxide, in a suitable solvent, such as carbon tetrachloride, and optionally in the presence of a light source, such as a 500 watt tungsten halogen lamp, at reflux.
  • a radical initiator such as benzoyl peroxide
  • a suitable solvent such as carbon tetrachloride
  • a light source such as a 500 watt tungsten halogen lamp
  • Cyanomethyl-pyridines of formula (7) wherein R 8 is as defined for a compound of formula (I) can be made by reaction of a compound of formula (6) as defined in 17) with a metal cyanide, such as potassium cyanide, in a suitable solvent, such as ethanol, at reflux.
  • a metal cyanide such as potassium cyanide
  • Pyridyl acetic acids of formula (8) wherein R 8 is as defined for a compound of formula (I) can be made by reaction of a compound of formula (7) as defined in 18) by hydrolysis using aqueous acid or alkali, but preferably aqueous acid, such as aqueous sulfuric acid, at reflux.
  • Pyridyl acetic acids of formula (8) can be made by hydrolysis of pyridyl malonates of formula (9), in the presence of, for example, an alkali metal hydroxide MOH, where M is sodium or potassium, in the a suitable solvent, such as methanol or ethanol, optionally in the presence of water.
  • MOH alkali metal hydroxide
  • suitable solvent such as methanol or ethanol
  • R 16 is as defined in 1) and R 17 is hydrogen, Cj-C 6 alkyl, C 1 - C4haloalkyl, aryl or aryl substituted by one to five R 8 , which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R 8 , which may be the same or different, can be made by reacting a compound of formula (2) as defined in 1) with a compound of formula (10), wherein R 17 is hydrogen, C 1 -C 6 alkyl, Ci-C 4 haloalkyl, aryl or aryl substituted by one to five R , which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R 8 , which may be the same or different, in a suitable solvent, such as toluene, at a temperature range from 75 °C to 150°C, preferably at reflux, as shown
  • Compounds of formula (12), wherein R 1 and R 2 are as defined for a compound of formula (I), and R 17 is as defined in 21), can be made from a compound of formula (11) as defined in 21), by heating with a suitable base, such as an alkali metal alkoxide, for example sodium methoxide, in a suitable solvent, such as methanol, preferably at reflux.
  • a suitable base such as an alkali metal alkoxide, for example sodium methoxide
  • a suitable solvent such as methanol
  • Compounds of formula (14), wherein R 1 and R 2 are as defined for a compound of formula (I), R 17 is defined as in 21), and R 18 is defined as in 23), can be made from a compound of formula (13) as defined in 23) by heating with hydroxylamine or its salts, in a suitable solvent, such as ethanol, preferably at reflux.
  • Compounds of formula (20), wherein R 1 , R 2 and R 10 are as defined for a compound of formula (I) and R 19 is C]-C 6 alkyl can be made by reaction of a compound of formula (19) as defined in 28) with an acid chloride of formula R 10 COCl as defined in 3), in the presence of base, such as pyridine, in a suitable solvent, such as 1,2- dichloroethane, at a temperature range from 25 0 C to 100 0 C, preferably from 6O 0 C to 85 0 C.
  • the compounds of formula (I) according to the invention can be used as herbicides in unmodified form, as obtained in the synthesis, but they are generally formulated into herbicidal compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances.
  • formulation adjuvants such as carriers, solvents and surface-active substances.
  • the formulations can be in various physical forms, e.g.
  • the formulations 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 contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns.
  • the active ingredients 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 polymers that are known to the person skilled in the art in this connection.
  • 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. ⁇
  • 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, butyl ene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,7V-dimethylforrnamide, dimethyl sulfoxide, 1,4-dioxane,
  • 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 can advantageously be used in both solid and liquid formulations, especially in those formulations which can 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 nonylphenol 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; quaternary amines, such as lauryltrimethylammonium chloride, polyethylene glycol esters of fatty
  • Further adjuvants that can usually be used in pesticidal 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.
  • compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl 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.
  • 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® (Rh ⁇ ne-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 OfC 8 -C 22 fatty acids, especially the methyl derivatives OfC 12 -Ci 8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being of importance.
  • Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) 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.
  • 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.
  • surface-active substances such as non-ionic, anionic or cationic surfactants.
  • suitable anionic, non-ionic and cationic surfactants are listed on pages 7 and 8 of WO 97/34485.
  • 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 C 12 -C 22 fatty alcohols having a degree of ethoxylation of from 5 to 40.
  • Examples of commercially available surfactants are the Genapol types (Clariant AG).
  • silicone surfactants especially polyalkyl-oxide-modified heptamethyltriloxanes which are commercially available e.g. as Silwet L-77®, and also perfluorinated surfactants.
  • concentration of the surface-active substances in relation to the total additive is generally from 1 to 30 % by weight.
  • 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).
  • the mentioned surface-active substances may be used in the formulations on their own, that is to say without oil additives.
  • 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).
  • alkylpyrrolidones e.g. Agrimax®
  • formulations of alkylpyrrolidones e.g. Agrimax®
  • synthetic lattices e.g. polyacrylamide, polyvinyl compounds or poly-1-p-menthene (e.g. Bond®, Courier® or Emerald®)
  • propionic acid for example Eurogkem Pen-e-trate®
  • the herbicidal compositions 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.
  • a formulation adjuvant which preferably includes from 0 to 25 % by weight of a surface-active substance.
  • commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.
  • the rates of application of compounds of formula (I) 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, the grass 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 g/ha, especially from 50 to 1000 g/ha.
  • Emulsifiable concentrates active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 %
  • Dusts active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 %
  • Suspension concentrates active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 %
  • Wettable powders active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 %
  • Granules active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably
  • Emulsions of any desired concentration can be obtained from such concentrates by dilution with water.
  • the solutions are suitable for use in the form of microdrops.
  • Wettable powders a) b) c) d) active ingredient 5% 25% 50% 80% sodium lignosulfonate 4% - 3% - sodium lauryl sulfate 2% 3% - 4% sodium diisobutylnaphthalene- sulfonate - 6% 5% 6% octylphenol polyglycol ether - 1% 2% -
  • the active ingredient is mixed thoroughly with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of any desired concentration.
  • Coated granules a) b) c) active ingredient 0.1 % 5% 15% highly dispersed silicic acid 0.9 % 2% 2% inorganic carrier 99.0 % 93% 83% (diameter 0.1 - 1 mm) e.g. CaCO 3 or SiO 2
  • the active ingredient is dissolved in methylene chloride and applied to the carrier by spraying, and the solvent is then evaporated off in vacuo.
  • the finely ground active ingredient is uniformly applied, in a mixer, to the carrier moistened with polyethylene glycol.
  • Non-dusty coated granules are obtained in this manner.
  • the active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air.
  • F7. Dusts a) b) c) active ingredient 0.1 % 1 % 5 % talcum 39.9 % 49 % 35 % kaolin 60.0 % 50 % 60 %
  • Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
  • Suspension concentrates a) b) c) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether - 1 % 2 % -
  • the finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.
  • the invention relates to a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
  • the invention also relates to a method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
  • the invention also relates to a method of selectively controlling grasses and weeds in crops of useful plants which comprises applying to the useful plants or locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I).
  • Crops of useful plants in which the composition according to the invention can 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, maize and soy beans.
  • the grasses and weeds to be controlled may be both mono-'cotyledonous species, for example Agrostis, Alopecurus, Avena, Bromus, Cyperus, Digitaria, Echinochloa, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Chenopodium, Chrysanthemum, Galium, Ipomoea, Nasturtium, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.
  • Agrostis Alopecurus
  • Avena Bromus
  • Cyperus Digitaria
  • Echinochloa Lolium
  • Monochoria Rottboellia
  • Sagittaria Scirpus, Setaria
  • Sida and Sorghum and dicotyledonous species
  • dicotyledonous species for example Abutilon
  • Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. auxins or ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors) by conventional methods of breeding or by genetic engineering.
  • herbicides or classes of herbicides e.g. auxins or ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors
  • 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).
  • 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), Bt cotton (resistant to cotton boll weevil) and also Bt potatoes (resistant to Colorado beetle).
  • 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 transgenic plants able to synthesize such toxins are described in EP-A-451 878, EP-A-374 753, WO 93/07278, WO 95/34656, WO 03/052073 and EP-A-427 529.
  • 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), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® 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).
  • 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 flavor).
  • Areas under cultivation include land on which the crop plants are already growing and land intended for cultivation with those crop plants.
  • the compounds of the invention can be applied before weeds emerge (pre-emergence application) or after weeds emerge (post-emergence application), and are particularly effective when applied post- emergence.
  • the compounds of formula (I) according to the invention can also be used in combination with one or more further herbicides.
  • the following mixtures of the compound of formula (I) are important:
  • a compound of formula (I) with a synthetic auxin (e.g. compound of formula (I) + clopyralid (162), compound of formula (I) + 2,4-D (211), compound of formula (I) + dicamba (228), compound of formula (I) + diphenamid (274), compound of formula (I) + MCPA (499), compound of formula (I) + quinclorac (712), or compound of formula (I) + aminopyralid (CAS RN 150114-71-9)).
  • a synthetic auxin e.g. compound of formula (I) + clopyralid (162), compound of formula (I) + 2,4-D (211), compound of formula (I) + dicamba (228), compound of formula (I) + diphenamid (274), compound of formula (I) + MCPA (499), compound of formula (I) + quinclorac (712), or compound of formula (I) + aminopyralid (CAS RN 150114-71-9)).
  • the mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003.
  • the reference to glufosinate-ammonium also applies to glufosinate
  • the reference to cloransulam-methyl also applies to cloransulam
  • the reference to dimethenamid also applies to dimethenamid-P
  • the reference to flamprop-M also applies to flamprop
  • the reference to pyrithiobac-sodium also applies to pyrithiobac, etc.
  • the mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1: 100 to 1000:1.
  • mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient” relates to the respective mixture of compound of formula (I) with the mixing partner).
  • herbicides or plant growth regulators can be used in combination with a compound of formula (I) according to the invention or in combination with a mixture as described above: aclonifen (8), acrolein (10), alachlor (14), alloxydim (18), ametryn (20), amicarbazone (21), amidosulfuron (22), aminocyclopyrachlor (CAS RN 858956-08-8), amitrole (aminotriazole) (25), ammonium sulfamate (26), anilofos (31), asulam (36), aviglycine (39), azafenidin (CAS RN 68049- 83-2), azimsulfuron (43), BAS 800H (CAS RN 372137-35-4), beflubutamid (55), benazolin (57), bencarbazone (CAS RN 173980-17-1), benfluralin (59), benfuresate (61), bensulide (65
  • the mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003.
  • the reference to acifluorfen-sodium also applies to acifluorfen, and the reference to bensulfuron-methyl also applies to bensulfuron, etc.
  • the mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1 : 100 to 1000:1.
  • the mixtures can advantageously be used in the above-mentioned formulations
  • active ingredient relates to the respective mixture of compound of formula (I) with the mixing partner).
  • the compounds of formula (I) according to the invention can also be used in combination with one or more safeners.
  • mixtures of a compound of formula (I) according to the invention with one or more further herbicides can also be used in combination with one or more safeners.
  • safener as used herein means a chemical that when used in combination with a herbicide reduces the undesirable effects of the herbicide on non-target organisms, for example, a safener protects crops from injury by herbicides but does not prevent the herbicide from killing the weeds.
  • the safeners can be AD-67 (11), benoxacor (63), cloquintocet-mexyl (163), cyometrinil (CAS RN 78370-21-5), cyprosulfamide (CAS RN 221667-31-8), dichlormid (231), dicyclonon (CAS RN 79260-71-2), fenchlorazole-ethyl (331), fenclorim (332), flurazole (386), fluxofenim (399), furilazole (413) and the corresponding R isomer, isoxadifen- ethyl (478), mefenpyr-diethyl (506), 2-methoxy-N-[[4-[[(methylamino)carbonyl]amino]- phenyl] sulfonyl] -benzamide (CAS RN 129531 - 12-0), naphthalic anhydride (CAS RN 81 - 84-5), and oxabetrin
  • the safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003.
  • the reference to cloquintocet-mexyl also applies to cloquintocet, and the reference to fenchlorazole-ethyl also applies to fenchlorazole, etc.
  • 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 mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient” relates to the respective mixture of compound of formula (I) with the safener).
  • active ingredient relates to the respective mixture of compound of formula (I) with the safener.
  • the safener and a compound of formula (I) and one or more additional herbicide(s), if any are applied simultaneously.
  • the safener, a compound of formula (I) and one or more additional herbicide(s), if any might be applied to the locus pre-emergence or might be applied to the crop post- emergence.
  • the safener and a compound of formula (I) and one or more additional herbicide(s), if any, are applied sequentially.
  • the safener might be applied before sowing the seeds as a seed treatment and a compound of formula (I) and one or more additional herbicides, if any, might be applied to the locus pre- emergence or might be applied to the crop post-emergence.
  • Preferred mixtures of a compound of formula (I) with further herbicides and safeners include:
  • Mixtures of a compound of formula (I) with a triazine and a safener Mixtures of a compound of formula (I) with a triazine and isoxaflutole and a safener.
  • Example 1.3 Preparation of isobutyric acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6- dihvdro-pyridor2,3-blpyrazin-8-yl ester (Compound No. A5 of Table A)
  • Example 1.4 Preparation of isobutyric acid 7-( " 3,5-dichloro-pyrid-2-vD-5-ethyl-6-oxo- 5,6-dihydro-pyrido[ " 2,3-b1pyrazin-8-yl ester f Compound No. A6 of Table A)
  • Isobutyric acid 7-(3,5-dichloro-pyrid-2-yl)-5-methyl-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A7 of Table A) from isobutyric acid 7- (3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 1.3) using methyl iodide as reagent.
  • Carbonic acid 7-(3,5-dichloro-pyrid-2-yl)-5-methyl-6-oxo-5,6-dihydro-pyrido- [2,3-b]pyrazin-8-yl ester ethyl ester (Compound No. A2 of Table A) from carbonic acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester ethyl ester (Example 1.3) using methyl iodide as reagent.
  • (2,6-Dichloro-pyrid-3-yl)-acetyl chloride was formed by dropwise addition of oxalyl chloride to a solution of (2,6-dichloro-pyrid-3-yl)-acetic acid (Example 4.3) (1.174 g) in dichloromethane (10 ml) with two drops of N,N-dimethylformamide. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated to give the acid chloride as an oil, which used without purification in the next step.
  • 2,2-Dimethyl-propionic acid 7-(2,4-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A17 of Table A) from 7-(2,4-dichloro- pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6).
  • 2,2-Dimethyl-propionic acid 7-(4,6-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A27 of Table A) from 7-(4,6-dichloro- pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6).
  • 2-Chloro-4-methyl-thiazole acetic acid was prepared by hydrolysis of ethyl 2- chloro-4-methyl-thiazole acetate (which was made as described in EP27019), with aqueous sodium hydroxide (IM) in aqueous methanol (1:1), and was used without further purification.
  • the reaction was heated in a microwave to 85 0 C for 40 minutes and then cooled to ambient temperature.
  • the reaction mixture was diluted with ethyl acetate and washed with aqueous sodium hydrogen carbonate (saturated), water and aqueous hydrochloric acid (IM) and then water again.
  • the organic layer was dried over magnesium sulfate and concentrated.
  • the residue was purified using column chromatography on silica gel (eluent: hexane / ethyl acetate 1:1) to give 3-[2-(2-chloro-4- methyl-thiazol-5-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester (0.98 g).
  • Example 2.4 Preparation of isobutyric acid 7-(2-chloro-4-methyl-thiazol-5-yl)-6-oxo- 5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. B9 of Table B)
  • Example 2.5 Preparation of isobutyric acid 7-(2-chloro-4-methyl-thiazol-5-vD-5-methyl- 6-oxo-5,6-dihvdro-pyrido[2,3-blpyrazin-8-yl ester (Compound No. B2 of Table B)
  • Example 2.7 Preparation of isobutyric acid 7-(5-difluoromethoxy-l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl)-6-oxo-5,6-dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. B23 of Table B)
  • Example 2.8 Preparation of isobutyric acid 7-r5-difluoromethoxy-l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl)-5-( ' 2.2-difluoro-ethyl)-6-oxo-5,6-dihvdro-pyrido[2,3- bipyrazin-8-yl ester (Compound No. B24 of Table B)
  • Example 2.9 Preparation of 7-(5-difluoromethoxy-l-methyl-3-trifluoromethyl-lH- pwazol-4-yl)-5-(2,2-difluoro-ethyl)-8-hvdroxy-5H-pwido[2,3-b '
  • Compound No. B30 of Table B was made by a method analogous to the method set out in Example 2.9.
  • Potassium cyanide (1.0 g) was dissolved in water by heating to 4O 0 C.
  • a mixture of 3-bromomethyl-2,-6-dichloro-pyridine, 3,3-dibromomethyl-2,6-dichloro-pyridine, and 2,6-dichloro-3-methyl-pyridine (Example 4.1) (3.2 g) suspended in ethanol (20 ml) was added dropwise at 4O 0 C over a period of 30 minutes.
  • the reaction mixture was heated to reflux for 3 hours.
  • the reaction mixture was cooled to 40 0 C and another equivalent of potassium cyanide was added.
  • the reaction mixture was heated to reflux for a further 3 hours and then stored at ambient temperature for 16 hours.
  • reaction mixture was filtered to remove the solids and the solids were washed with ethyl acetate.
  • the combined filtrates were concentrated.
  • the residue was diluted with ethyl acetate.
  • the organic solution washed with aqueous sodium hydrogen carbonate (saturated) and brine, dried over magnesium sulfate, and concentrated.
  • This residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane from 3 : 100 to 1 : 1) to give slightly impure (2,6-dichloro-pyrid-3-yl)-acetonitrile (1.5 g) which solidified on standing. This material was used without further purification.
  • Example 6.6 Preparation of isobutyric acid 6-hvdroxy-7-(3-trifluoromethyl-isoxazol-5- yl)-pyridor2,3-b1pyrazin-8-yl ester (Compound No. B7 of Table B)
  • Example 6.7 Preparation of isobutyric acid 5-methyl-6-oxo-7-(3-trifluoromethyl- isoxazol-5-yl)-5,6-dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. B8 of Table B)
  • Example 7.4 Preparation of 8-hvdroxy-5-methyl-7-(3-methyl-l,2,4-oxadiazol-5-yr)-5H- Pyrido[2,3-blpyrazin-6-one (Compound No. B5 of Table 5)
  • Example 7.5 Preparation of isobutyric acid 5-methyl-7-(3-methyl-l,2,4-oxadiazol-5-yl)- 6-oxo-5,6-dihydro-pyridof2,3-b]pyrazin-8-yl ester (Compound No. B6 of Table B)
  • STEME Stellaria media
  • NAAOF Nasturtium officinale
  • AMARE Amaranthus retroflexus
  • SOLNI Solanum nigrum.
  • Example B2 Herbicidal action Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64- 5).
  • Tween 20 polyoxyethelyene sorbitan monolaurate
  • SOLNI Solanum nigrum
  • AMARE Amaranthus retroflexus
  • SETFA Setaria faberi
  • ECHCG Echinochloa crus-galli
  • IPOHE Ipomea hederaceae.
  • Table B Compound Nos. C5 and C6 of Table C, were tested using the same protocol and showed little or no damage to the test plants under the test conditions. Compound Nos. A22, A23, A24, A25, A26 and A27 of Table A were not tested under these protocols so no data is available for these compounds.
  • SOLNI Solanum nigrum
  • AMARE Amaranthus retroflexus
  • SETFA Setaria faberi
  • ECHCG Echinochloa crus-galli
  • IPOHE Ipomea hederaceae.
  • Compound No. C5 of Table C was tested using the same protocol and showed little or no damage to the test plants under the test conditions.
  • Compound Nos. A22, A23, A24, A25, A26 and A27 of Table A were not tested under these protocols so no data is available for these compounds.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Agronomy & Crop Science (AREA)
  • Pest Control & Pesticides (AREA)
  • Plant Pathology (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Dentistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Environmental Sciences (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

The present invention relates to a method of controlling plants or inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I) wherein R1, R2, R3, R4 and R5 are as defined in claim 1; or a salt or TV-oxide thereof. Furthermore, the present invention relates to processes for preparing compounds of formula (I), to intermediates used in the preparation of compounds of formula (I), to herbicidal compositions comprising compounds of formula (I) and to certain novel pyridopyridines.

Description

HERBICIDAL COMPOUNDS
The present invention relates to novel herbicidal pyrido[2,3-b]pyrazines, to processes for their preparation, to compositions comprising these compounds, and to their use in controlling plants or in inhibiting plant growth.
Certain pyridopyrazines were disclosed as herbicidal compounds, for example, in WO 08/009908 and WO 08/071918. Certain pyridopyrazines were disclosed as intermediates in the synthesis of fungicidal compounds, for example, in WO 04/056825, WO 05/123698 and WO 05/123733. Certain pyridopyrazines were disclosed as fungicidal compounds, for example, in WO 05/010000. Certain pyridopyrazines were disclosed as pharmaceutical compounds, for example, in WO 96/22990 and WO 03/066630.
It has now surprisingly been found that certain pyrido[2,3-b]pyrazines display excellent herbicidal and growth-inhibiting properties. The present invention therefore provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I)
Figure imgf000002_0001
wherein R1 and R2 are independently hydrogen, C]-C4alkyl, d-C4haloalkyl, halo, cyano, hydroxy, Ci-C4alkoxy, d-C4alkylthio, aryl or aryl substituted by one to five R6, which may be the same or different, or heteroaryl or heteroaryl substituted by one to five R6, which may be the same or different; R3 is hydrogen, d-C1Oalkyl, d-C4haloalkyl, C2-C]oalkenyl, C2-C4haloalkenyl, C2-C10alkynyl, C2-C4haloalkynyl, C3-C10cycloalkyl, C3-C10cycloalkyl-Ci-C6alkyl-, C1- C10alkoxy-Ci-C6alkyl-, Ci-Ciocyanoalkyl-, d-dϋalkoxycarbonyl-d-Cealkyl-, N-C1- C3alkyl-aminocarbonyl-Ci-C6alkyl-, N.N-di^Ci-dalkyty-aminocarbonyl-d-Cealkyl-, aryl-Ci-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-d-C6alkyl- or heterocyclyl-Ci-C6alkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different;
R4 is heteroaryl or heteroaryl substituted by one to four R8, which may be the same or different; R5 is hydroxy or a group which can be metabolised to a hydroxy group; each R6, R7 and R8 is independently halo, cyano, nitro, C1-C1QaIlCyI, d-C-thaloalkyl, C2- Cioalkenyl, C2-Cioalkynyl, hydroxy, Ci-C]0alkoxy, Ci-C4haloalkoxy, C1-C1OaIkOXy-C1- C4alkyl-, C3-C7cycloalkyl, C3-C7cycloalkoxy, C3-C7cycloalkyl-Ci-C4alkyl-, C3- C7cycloalkyl-Ci-C4alkoxy-, Ci-Cόalkylcarbonyl-, formyl, CrC4alkoxycarbonyl-, Cj- C4alkylcarbonyloxy-, Ci-Ci0alkylthio-, Ci-C4haloalkylthio-, Ci-C10alkylsulfinyl-, Ci- C4haloalkylsulfinyl-, Ci-Cioalkylsulfonyl-, Ci-C4haloalkylsulfonyl-, amino, Ci- Cioalkylamino-, di-Ci-Ci0alkylamino-, Ci-Cioalkylcarbonylamino-, aryl or aryl substituted by one to three R13, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R13, which may be the same or different, aryl-Ci- C4alkyl- or aryl-Ci-C4alkyl- wherein the aryl moiety is substituted by one to three R13, which may be the same or different, heteroaryl-Ci-C4alkyl- or heteroaryl-Ci-C4alkyl- wherein the heteroaryl moiety is substituted by one to three R13, which may be the same or different, aryloxy- or aryloxy- substituted by one to three R13, which may be the same or different, heteroaryloxy- or heteroaryloxy- substituted by one to three R13, which may be the same or different, arylthio- or arylthio- substituted by one to three R13, which may be the same or different, or hetero arylthio- or heteroarylthio- substituted by one to three R13, which may be the same or different; and each R13 is independently halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy; or a salt or N-oxide thereof. The compounds of formula (I) may exist in different geometric or optical isomers or 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. For example, a compound of formula (Ia), i.e. a compound of formula (I) wherein R3 is hydrogen and R5 is hydroxy, can be drawn in at least five tautomeric forms.
Figure imgf000004_0001
Some of these compounds exhibit good herbicidal activity. Additionally, these compounds can be used as intermediates for the synthesis of compounds of the formula (Ib), (Ic) and (Id).
For example, a compound of formula (Ib), i.e. a compound of formula (I) wherein R3 is hydrogen and R5 is as defined for compounds of formula (I) other than hydroxy, can be drawn in at least two tautomeric forms.
Figure imgf000004_0002
(Ib)
Some of these compounds exhibit good herbicidal activity. Additionally, these compounds can be used as intermediates for the synthesis of compounds of the formula (Ia), (Ic) and (Id). - A -
A compound of formula (Ic), i.e. a compound of formula (I) wherein R3 is as defined for compounds of formula (I) other than hydrogen and R5 is as defined for compounds of formula (I) other than hydroxy, can be drawn in only one tautomeric form.
Figure imgf000005_0001
(Ic)
Most of these compounds exhibit excellent herbicidal activity. Additionally, these compounds can be used as intermediates for the synthesis of compounds of the formula (Ia), (Ib) and (Id).
A compound of formula (Id), i.e. a compound of formula (I) wherein R3 is as defined for compounds of formula (I) other than hydrogen and R5 is hydroxy, can be drawn in three tautomeric forms.
Figure imgf000005_0002
(Id)
Most of these compounds exhibit good herbicidal activity. Additionally, these compounds can be used as intermediates for the synthesis of compounds of the formula (Ia), (Ib) and (Ic).
Each alkyl moiety (either alone or as part of a larger group, such as alkoxy, alkoxycarbonyl, alkylcarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl) is a straight or branched chain and is, for example, methyl, ethyl, n-propyl, n-butyl, n-pentyl, H-hexyl, MO-propyl, w-butyl, sec-butyl, iso-butyl, tert-butyl or neo-pentyl. The alkyl groups are preferably C1 to C6 alkyl groups, more preferably C1-C4 and most preferably C1-C3 alkyl groups.
Alkenyl and alkynyl moieties (either alone or as part of a larger group, such as alkenyloxy or alkynyloxy) can be in the form of straight or branched chains, and the alkenyl moieties, where appropriate, can be of either the (E)- or (Z)-configuration. Examples are vinyl, allyl, prop-2-enyl and propargyl. The alkenyl and alkynyl groups are preferably C2 to C6 alkenyl or alkynyl groups, more preferably C2-C4 and most preferably C2-C3 alkenyl or alkynyl groups.
Halogen is fluorine, chlorine, bromine or iodine. Haloalkyl groups (either alone or as part of a larger group, such as haloalkoxy or haloalkylthio) are alkyl groups which are substituted with one or more of the same or different halogen atoms and are, for example, -CF3, -CF2Cl, -CHF2, -CH2CF3 or -CH2CHF2. Haloalkenyl and haloalkynyl groups (either alone or as part of a larger group, such as haloalkenyloxy or haloalkynyloxy) are alkenyl and alkynyl groups, respectively, which are substituted with one or more of the same or different halogen atoms and are, for example, -CH=CF2, -CF=CH2 or -C -CCl.
Cyanoalkyl groups are alkyl groups which are substituted with one or more cyano groups, for example, cyanomethyl or 1,3-dicyanopropyl.
Cycloalkyl groups can be in mono- or bi-cyclic form and may optionally be substituted by one or more methyl groups. The cycloalkyl groups preferably contain 3 to 8 carbon atoms, more preferably 3 to 6 carbon atoms. Examples of monocyclic cycloalkyl groups are cyclopropyl, 1 -methylcyclopropyl, 2-methylcyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.
In the context of the present specification the term "aryl" refers to a ring system which may be mono-, bi- or tricyclic. Examples of such rings include phenyl, naphthalenyl, anthracenyl, indenyl or phenanthrenyl. A preferred aryl group is phenyl. The term "heteroaryl" refers to an aromatic ring system containing at least one heteroatom and consisting either of a single ring or of two or more fused rings. Preferably, single rings contain up to three and bicyclic systems up to four heteroatoms which are preferably chosen from nitrogen, oxygen and sulfur. Examples of monocyclic groups include pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, furanyl, thiophenyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl and tetrazolyl. More preferred monocyclic groups are pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl and triazolyl, most preferably pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl and thiazolyl. Examples of bicyclic groups are benzo thiophenyl, benzimidazolyl, benzoxazolyl, benzothiadiazolyl, quinolinyl, isoquinolinyl, cinnolinyl, quinoxalinyl and pyrazolo[l,5- ajpyrimidinyl. More preferred bicyclic groups are benzoxazolyl, quinolinyl, isoquinolinyl and pyrazolo[l,5-a]pyrimidinyl, most preferably quinolinyl and isoquinolinyl.
The term "heterocyclyl" is defined to include heteroaryl and in addition their unsaturated or partially unsaturated analogues such as 4,5,6,7-tetrahydro- benzothiophenyl, chromen-4-onyl, 9H-fluorenyl, 3,4-dihydro-2H-benzo-l,4-dioxepinyl, 2,3-dihydro-benzofuranyl, piperidinyl, 1,3-dioxolanyl, 1,3-dioxanyl, 4,5-dihydro- isoxazolyl, tetrahydrofuranyl and morpholinyl.
The term "herbicide" as used herein means a compound that controls or modifies the growth of plants. The term "herbicidally effective amount" means the quantity of such a compound or combination of such compounds that is capable of producing a controlling or modifying effect on the growth of plants. Controlling or modifying effects include all deviation from natural development, for example: killing, retardation, leaf burn, albinism, dwarfing and the like. The term "plants" refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits. The term "locus" is intended to include soil, seeds, and seedlings, as well as established vegetation. The term "metabolism" as used herein means the conversion or breakdown of a substance from one form to another by a living organism, in particular in a plant (in planta).
The term "salt" as used herein means a compound of formula (I) which has a negative charge, for example, on an oxygen atom of a hydroxyl or of a carboxyl group, or a compound of formula (I) which has a positive charge, for example, on a nitrogen atom in a nitrogen-containing heteroaryl group, for example if a such a nitrogen is quarternised by alkylation. The counter ion is necessarily of the opposite charge. Where the counter ion needs to be a cation the counter ion could be, for example, an alkali metal such as sodium or potassium, or an alkaline earth metal such as magnesium and calcium, or a quaternary ammonium base such as ammonium and tetramethylammonium. Where the counter ion needs to be a cation the counter ion could be, for example, hydroxide, or a halide such as chloride or bromide.
The compounds of formula (I) according to the invention also include hydrates which may be formed, for example, during salt formation.
Preferred values of R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are, in any combination, as set out below. Preferably R1 is hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, halo, cyano, hydroxy or C]-C4alkoxy.
More preferably R1 is hydrogen, Ci-C4alkyl, halo, cyano or hydroxy. Even more preferably R1 is hydrogen, methyl, chloro or bromo. Yet even more preferably R1 is hydrogen or chloro.
Most preferably R1 is hydrogen.
Preferably R2 is hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, halo, cyano, hydroxy or d-C4alkoxy.
More preferably R2 is hydrogen, C1-C4alkyl, halo, cyano or hydroxy. Even more preferably R2 is hydrogen, methyl, chloro or bromo.
Yet even more preferably R2 is hydrogen or chloro. Most preferably R2 is hydrogen.
Preferably R3 is hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl or C2-C4haloalkynyl. Examples of such preferred groups for R3 are hydrogen, methyl, ethyl, n-propyl, wo-propyl, ra-butyl, 2-methyl-propyl, 2- fluoro-ethyl, 2,2-difluoro-ethyl, 2,2,2-trifluoro-ethyl, allyl, but-3-en-l-yl or propargyl. More preferably R3 is hydrogen, Ci-C2alkyl, Ci-C2haloalkyl, C2-C3alkenyl or C2-C3alkynyl. Examples of such more preferred groups for R3 are hydrogen, methyl, ethyl, 2,2-difluoro-ethyl, 2,2,2-trifluoro-ethyl, allyl or propargyl. Most preferably R3 is hydrogen, C1-C2alkyl, Ci-C2haloalkyl or C2-C3alkynyl.
Examples of such most preferred groups for R3 are hydrogen, methyl, ethyl, 2,2-difluoro- ethyl or propargyl.
In one preferred embodiment R3 is 2,2-difluoro-ethyl.
Preferably R4 is heteroaryl substituted by one to three R8, which may be the same or different.
More preferably R4 is a monocyclic heteroaryl, containing up to two heteroatoms, substituted by one to three R8, which may be the same or different, or R4 is a bicyclic heteroaryl, containing up to three heteroatoms, substituted by one to three R , which may be the same or different. Even more preferably R4 is pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl, thiazolyl, pyrazolyl or triazolyl substituted by one to three R , which may be the same or different, or R4 is benzoxazolyl, quinolinyl, isoquinolinyl or pyrazolo[l,5- a]pyrimidinyl substituted by one to three R8, which may be the same or different. Examples of such most preferred groups for R4 include 3,5-dichloro-pyrid-2-yl, 3,5- dichloro-pyrid-4-yl, 2,6-dichloro-pyrid-3-yl, 2,4-dichloro-pyrid-3-yl, 4,6-dichloro-pyrid- 3-yl, 2,5-dichloro-pyrid-4-yl, 3,6-dichloro-pyrid-2-yl, 3-chloro-5-fluoro-pyrid-2-yl, 3- chloro-5-trifluoromethyl-pyrid-2-yl, 3,5,6-trichloro-pyrid-2-yl, 2,5-dichloro-pyrid-3-yl, 2,3-dichloro-pyrid-4-yl, 2-chloro-4-trifluoromethyl-pyrid-3-yl, 2-chloro-6- trifluoromethyl-pyrid-3-yl, 3-chloro-5-trifluorornethyl-pyrid-4-yl, 2,3,5-trichloro-pyrid- 4-yl, 5-chloro-pyrimidin-4-yl, 3,4,5-trichloro-thiophen-2-yl, 2,5-dichloro-thiophen-3-yl, 3-trifluoromethyl-isoxazol-5-yl, 3-trifluoromethyl-4-chloro-isoxazol-5-yl, 3,4-dichloro- isoxazol-5-yl, 3-methyl-l,2,4-oxadiazol-5-yl, 3-trifluoromethyl-l,2,4-oxadiazol-5-yl, 2,4- dichloro-thiazol-5-yl, 2-chloro-4-methyl-thiazol-5-yl, 2,5-dichloro-thiazol-4-yl, 2-chloro- 4-trifluoromethyl-thiazol-5-yl-, 5-difluoromethoxy- 1 -methyl-3-trifluoromethyl- IH- pyrazol-4-yl, 2-methyl-5-trifluoromethyl-2H- 1 ,2,3 -triazol-4-yl, 2-methyl-benzoxazol-5 - yl, 2,4-dichloro-quinolin-3-yl, 4-chloro-2-trifluoromethyl-quinolin-3-yl, 1-chloro- isoquinolin-3-yl, and l,4-dichloro-isoquinolin-3-yl, 2,5-dimethyl-pyrazolo[l,5-a]- pyrimidin-7-yl-.
Most preferably R4 is pyridyl, pyrimidinyl, thiophenyl, isoxazolyl, oxadiazolyl or thiazolyl substituted by one to three R , which may be the same or different, or R is quinolinyl or isoquinolinyl substituted by one to three R8, which may be the same or different. Examples of such most preferred groups for R4 include 3,5-dichloro-pyrid-2-yl, 3,5-dichloro-pyrid-4-yl, 2,6-dichloro-pyrid-3-yl, 2,4-dichloro-pyrid-3-yl, 4,6-dichϊoro- pyrid-3-yl, 2,5-dichloro-pyrid-4-yl, 3,6-dichloro-pyrid-2-yl, 3-chloro-5-fluoro-pyrid-2-yl, 3-chloro-5-trifiuoromethyl-pyrid-2-yl, 3,5,6-trichloro-pyrid-2-yl, 2,5-dichloro-pyrid-3-yl, 2,3-dichloro-pyrid-4-yl, 2-chloro-4-trifluoromethyl-pyrid-3-yl, 2-chloro-6- trifluoromethyl-pyrid-3-yl, 3-chloro-5-trifluoromethyl-pyrid-4-yl, 2,3,5-trichloro-pyrid- 4-yl, 5-chloro-pyrimidin-4-yl, 3,4,5-trichloro-thiophen-2-yl, 2,5-dichloro-thiophen-3-yl, 3-trifiuoromethyl-isoxazol-5-yl, 3-trifluoromethyl-4-chloro-isoxazol-5-yl, 3,4-dichloro- isoxazol-5-yl, 3-methyl-l,2,4-oxadiazol-5-yl, 3-trifluoromethyl-l,2,4-oxadiazol-5-yl, 2,4- dichloro-thiazol-5-yl, 2-chloro-4-methyl-thiazol-5-yl, 2,5-dichloro-thiazol-4-yl, 2,4- dichloro-quinolin-3-yl, 4-chloro-2-trifluoromethyl-quinolin-3-yl, 1 -chloro-isoquinolin-3- yl, and l,4-dichloro-isoquinolin-3-yl.
In one preferred embodiment R4 is 3,5-dichloro-pyrid-2-yl. In one preferred embodiment R4 is 3,5-dichloro-pyrid-4-yl. In one preferred embodiment R4 is 2,6-dichloro-pyrid-3-yl. In one preferred embodiment R4 is 2,4-dichloro-pyrid-3-yl.
In one preferred embodiment R4 is 4,6-dichloro-pyrid-3-yl.
In one preferred embodiment R4 is 2,5-dichloro-pyrid-4-yl.
In one preferred embodiment R4 is 2,5-dichloro-thiophen-3-yl-. In one preferred embodiment R4 is 3-trifiuoromethyl-isoxazol-5-yl.
In one preferred embodiment R4 is 3-methyl-l,2,4-oxadiazol-5-yl.
In one preferred embodiment R4 is 2-chloro-4-methyl-thiazol-5-yl.
In one preferred embodiment R4 is 2-chloro-4-trifluoromethyl-thiazol-5-yl-.
In one preferred embodiment R4 is 5-difluoromethoxy-l-methyl-3-trifiuoro- methyl- lH-pyrazol-4-yl.
In one preferred embodiment R4 is 2-methyl-5-trifluoromethyl-2H-l,2,3-triazol- 4-yl.
In one preferred embodiment R4 is 2-methyl-benzoxazol-5-yl.
In one preferred embodiment R4 is 2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl-. Preferably R5 is hydroxy, R9-oxy-, R10-carbonyloxy-, tri-Rn-silyloxy- or R12- sulfonyloxy-, wherein
R9 is Ci-doalkyl, C2-C10alkenyl, C2-Ci0alkynyl or aryl-Ci-C4alkyl- or aryl-C1-C4alkyl- wherein the aryl moiety is substituted by one to five substituents independently selected from halo, cyano, nitro, d-C6alkyl, d-C6haloalkyl or d-C6alkoxy; R10 is C-Cioalkyl, C3-Ci0cycloalkyl, Cj-Ciocycloalkyl-d-doalkyl-, Ci-C]0haloalkyl, C2- C10alkenyl, C2-C10alkynyl, Ci-C4alkoxy-C1-C10alkyl-, C1-C4alkylthio-C1-C4alkyl-, C1- C10alkoxy, C2-Cioalkenyloxy, C2-C10alkynyloxy, d-doalkylthio-, N-d-C4alkyl-amino-, N,N-di-(Ci-C4alkyl)-amino-, aryl or aryl substituted by one to three R14, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R14, which may be the same or different, aryl-Ci-C4alkyl- or aryl-d-C4alkyl- wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl-d- C4alkyl- or heteroaryl-Ci-C4alkyl- wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, aryloxy- or aryloxy- substituted by one to three R14, which may be the same or different, heteroaryloxy- or heteroaryloxy- substituted by one to three R14, which may be the same or different, arylthio- or arylthio- substituted by one to three R14, which may be the same or different, or heteroarylthio- or heteroarylthio- substituted by one to three R14, which may be the same or different; each R1 ' is independently CpCioalkyl or phenyl or phenyl substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy;
R12 is Ci-Cioalkyl, Ci-Ciohaloalkyl, or phenyl or phenyl substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy; and each R14 is independently halo, cyano, nitro, Ci-CiOalkyl, Ci-C4haloalkyl, Ci-C10alkoxy, Ci-dalkoxycarbonyl-, Ci-C4haloalkoxy, Ci-C10alkylthio-, Ci-C4haloalkylthio-, C1- Cioalkylsulfinyl-, Ci-C4haloalkylsulfmyl-, CrCi0alkylsulfonyl-, Ci-C4haloalkylsulfonyl-, aryl or aryl substituted by one to five substituents independently selected from halo, cyano, nitro, C!-C6alkyl, Ci-C6haloalkyl or d-C6alkoxy, or heteroaryl or heteroaryl substituted by one to four substituents independently selected from halo, cyano, nitro, C1- Cβalkyl, Ci-C6haloalkyl or Ci-C6alkoxy.
More preferably R5 is hydroxy, R9-oxy- or R10-carbonyloxy-. Even more preferably R5 is hydroxy, Ci-C4alkoxy, Ci-C4alkenyloxy, Ci-
C4alkynyloxy, aryl-d-C4alkoxy or aryl-C1-C4alkoxy wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl-Ci- C4alkoxy or heteroaryl-Ci-C4alkoxy wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, Q-dalkylcarbonyloxy-, C3-C6cyclo- alkylcarbonyloxy-, d-Ciocycloalkyl-Ci-Cioalkylcarbonyloxy-, Ci-C4haloalkylcarbonyl- oxy-, C2-C4alkenylcarbonyloxy-, C2-C4alkynylcarbonyloxy-, C]-C4alkoxy-Ci-C4alkyl- carbonyloxy-, Ci-C4alkylthio-Ci-C4alkylcarbonyloxy-, C1-C4alkoxycarbonyloxy-, C2- C4alkenyloxycarbonyloxy-, C2-C4alkynyloxycarbonyloxy-, C \ -C4alkylthiocarbonyloxy-, N-C i -C4alkyl-aminocarbonyloxy-, N, JV-di-(C i -C4alkyl)-aminocarbonyloxy-, aryl- carbonyloxy- or arylcarbonyloxy- substituted by one to three R14, which may be the same or different, heteroarylcarbonyloxy- or heteroarylcarbonyloxy- substituted by one to three R14, which may be the same or different, aryl-Ci-C4alkylcarbonyloxy- or aryl-Cj- C4alkylcarbonyloxy- wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl-Ci-C4alkylcarbonyloxy- or heteroaryl-Ci- C4alkylcarbonyloxy- wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, aryloxycarbonyloxy- or aryloxycarbonyloxy- substituted by one to three R14, which may be the same or different, heteroaryloxy- carbonyloxy- or heteroaryloxycarbonyloxy- substituted by one to three R14, which may be the same or different, arylthiocarbonyloxy- or arylthiocarbonyloxy- substituted by one to three R14, which may be the same or different, or heteroarylthiocarbonyloxy- or heteroarylthiocarbonyloxy- substituted by one to three R14, which may be the same or different. Examples of preferred groups for R5 are hydroxy, methoxy, ethoxy, allyloxy, propargyloxy, benzyloxy, methylcarbonyloxy-, ethylcarbonyloxy-, /so-propylcarbonyl- oxy-, n-propylcarbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, tert- butylcarbonyloxy-, cyclopropylcarbonyloxy-, cyclopentyl-methylcarbonyloxy-, chloromethylcarbonyloxy-, trifluoromethylcarbonyloxy-, allylcarbonyloxy-, (E)-prop-l- en- 1 -ylcarbonyloxy-, 2-methyl-prop- 1 -en- 1 -ylcarbonyloxy-, methoxymethylcarbonyl- oxy-, ethoxycarbonyloxy-, tert-butoxycarbonyloxy-, but-2-yn-l-yloxycarbonyloxy-, ethylthiocarbonyloxy-, N.iV-diethylaminocarbonyloxy-, phenylcarbonyloxy-, 3-methoxy- phenylcarbonyloxy-, 4-nitro-phenylcarbonyloxy-, benzylcarbonyloxy-, furan-2-yl- carbonyloxy-, 2,5-dimethyl-furan-3-ylcarbonyloxy-, thiophen-2-ylcarbonyloxy-, 3,5- dimethyl-isoxazol-4-ylcarbonyloxy-, and 1 -phenyl -prop- 1 -ylcarbonyloxy-. Yet even more preferably R5 is hydroxy, Ci-Qalkylcarbonyloxy-, C3-C6cyclo- alkylcarbonyloxy-, C2-C4alkenylcarbonyloxy-, C2-C4alkynylcarbonyloxy-, C]- C4alkoxycarbonyloxy-, C2-C4alkenyloxycarbonyloxy-, C2-C4alkynyloxycarbonyloxy- or Ci-C/jalkylthiocarbonyloxy-. Examples of more preferred groups for R5 are hydroxy, methylcarbonyloxy-, ethylcarbonyloxy-, zsσ-propylcarbonyloxy-, w-propylcarbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, fert-butylcarbonyloxy-, cyclopropylcarbonyloxy-, allylcarbonyloxy-, (E)-prop-l -en- 1 -ylcarbonyloxy-, 2-methyl- prop- 1 -en- 1 -ylcarbonyloxy-, ethoxycarbonyloxy-, tert-butoxycarbonyloxy-, but-2-yn-l- yloxycarbonyloxy-, and ethylthiocarbonyloxy-.
Most preferably R5 is hydroxy, Ci-C4alkylcarbonyloxy-, Ci-C4alkoxycarbonyl- oxy- or Ci-C4alkylthiocarbonyloxy-. Examples of most preferred groups for R5 are hydroxy, methylcarbonyloxy-, ethylcarbonyloxy-, isø-propylcarbonyloxy-, n-propyl- carbonyloxy-, but-2-ylcarbonyloxy-, 2-methyl-propylcarbonyloxy-, tert-butylcarbonyl- oxy-, ethoxycarbonyloxy-, and ethylthiocarbonyloxy-. In one preferred embodiment R5 is hydroxy. In one preferred embodiment R5 is R9-oxy-, wherein R9 is Ci-Cioalkyl, C2-
C10alkenyl, C2-C10alkynyl or aryl-Ci-C4alkyl- or aryl-Ci-C4alkyl- wherein the aryl moiety is substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy. Such R5 groups may be metabolised, preferably in planta, to give the corresponding compound wherein R5 is hydroxy.
In one preferred embodiment R5 is RI0-carbonyloxy-, wherein R10 is Ci-doalkyl, C3-Ciocycloalkyl, C3-Ctocycloalkyl-C]-Cioalkyl-, Ci-Ciohaloalkyl, C2-C10alkenyl, C2- C10alkynyl, CrC4alkoxy-Ci-Ci0alkyl-, Ci-C4alkylthio-Ci-C4alkyl-, Ci-C10alkoxy, C2- C10alkenyloxy, d-doalkynyloxy, C)-C10alkylthio-, N-C1-C4alkyl-amino-,
Figure imgf000013_0001
C4alkyl)-amino-, aryl or aryl substituted by one to three R14, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R14, which may be the same or different, aryl-Ci-C4alkyl- or aryl-Ci-C4alkyl- wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl-Ci-C4alkyl- or heteroaryl-C|-C4alkyl- wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, aryloxy- or aryloxy- substituted by one to three R14, which may be the same or different, heteroaryloxy- or heteroaryloxy- substituted by one to three R14, which may be the same or different, arylthio- or arylthio- substituted by one to three R14, which may be the same or different, or heteroarylthio- or heteroarylthio- substituted by one to three R14, which may be the same or different; and each R14 is independently halo, cyano, nitro, Cj-Cioalkyl, Ci-C4haloalkyl, Ci-Cioalkoxy, Ci- Qalkoxycarbonyl-, Ci-C4haloalkoxy, Ci-Ci0alkylthio-, Q-Qhaloalkylthio-, Ci- Cioalkylsulfmyl-, Ci-C4haloalkylsulfinyl-, Ci-C10alkylsulfonyl-, Ci-C4haloalkylsulfonyl-, aryl or aryl substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy, or heteroaryl or heteroaryl substituted by one to four substituents independently selected from halo, cyano, nitro, C1- C6alkyl, Ci-C6haloalkyl or Q-Qsalkoxy. Such R5 groups may be metabolised, preferably in planta, to give the corresponding compound wherein R5 is hydroxy. In one preferred embodiment R5 is wo-propylcarbonyloxy- or tert-butyl- carbonyloxy-.
Preferably each R6 is independently halo, C1-C4alkyl, Cj-C4haloalkyl, Cj- C4alkoxy or Ci-C4haloalkoxy. Examples of such preferred groups for R6 are chloro, fluoro, methyl, ethyl, trϊfluoromethyl, methoxy or trifluoromethoxy. Preferably each R7 is independently halo, Ci-C4alkyl, Ci-C4haloalkyl, C1-
C4alkoxy or Ci-C4haloalkoxy. Examples of such preferred groups for R7 are chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy. Most preferably each R7 is independently halo, Ci-C4alkyl, Ci-C4haloalkyl or Q- C4alkoxy. Examples of such preferred groups for R7 are chloro, fluoro, methyl, ethyl, trifluoromethyl and methoxy.
Preferably each R8 is independently halo, cyano, nitro, Ci-CiOalkyl, Ci- Qhaloalkyl, Ci-C10alkoxy, C]-C4alkoxycarbonyl-, Ci-C4haloalkoxy, Ci-C]0alkylthio-, Ci-C4haloalkylthio-, Ci-Cioalkylsulfinyl-, Ci-C4haloalkylsulfmyl-, Ci-Cioalkylsulfonyl- or Ci-C4haloalkylsulfonyl-.
More preferably each R8 is independently halo, cyano, nitro, Ci-Cioalkyl, Ci- Qhaloalkyl, Ci-Ci0alkoxy, Ci-C4haloalkoxy, Ci-Cioalkylthio or Ci-C4haloalkylthio. Examples of such more preferred groups for R8 are iodo, bromo, chloro, fluoro, cyano, nitro, methyl, ethyl, trifluoromethyl, methoxy, trifluoromethoxy or trifluoromethylthio.
Even more preferably each R8 is independently halo, Ci-CiOalkyl, Ci-C4haloalkyl,
Ci-Ci0alkoxy or Ci-C4haloalkoxy. Examples of such even more preferred groups for R are bromo, chloro, fluoro, methyl, ethyl, trifluoromethyl, methoxy or trifluoromethoxy. Most preferably each R8 is independently halo, Ci-Cioalkyl, or Ci-C4haloalkyl.
Examples of such even more preferred groups for R8 are chloro, fluoro, methyl, or trifluoromethyl.
Preferably R9 is C2-Cioalkenyl, C2-Ci0alkynyl, aryl-Ci-C4alkyl- or aryl-Q- Qalkyl- wherein the aryl moiety is substituted by one to three R13, which may be the same or different.
More preferably R9 is C3-C4alkenyl, or C3-C4alkynyl, benzyl or benzyl wherein the phenyl moiety is substituted by one to three R13, which may be the same or different.
Even more preferably R9 is allyl, propargyl or benzyl.
Most preferably R9 is allyl. Preferably R10 is CrC4alkyl, C3-C6cycloalkyl, C3-Ci0cycloalkyl-Ci-Ci0alkyl, Ci-
C4haloalkyl, C2-C4alkenyl, C2-C4alkynyl, Ci-C4alkoxy-CrC4alkyl, CrC4alkylthio-Ci- C4alkyl, Ci-C4alkoxy, C2-C4alkenyloxy, C2-C4alkynyloxy, Ci-C4alkylthio, N-Ci-C4alkyl- amino, N,N-di-(C1-C4alkyl)-amino, aryl or aryl substituted by one to three R14, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R , which may be the same or different, aryl-Ci-C4alkyl or aryl-Ci-C4alkyl wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl- Ci-C4alkyl or heteroaryl-Ci-C4alkyl wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, aryloxy or aryloxy substituted by one to three R14, which may be the same or different, heteroaryloxy or heteroaryloxy substituted by one to three R14, which may be the same or different, arylthio or arylthio substituted by one to three R14, which may be the same or different, or heteroarylthio or heteroarylthio substituted by one to three R14, which may be the same or different. Most preferably R10 is iso-propyl or tert-butyl.
Preferably each R11 is independently d-C4alkyl.
Preferably R12 is Ci-C4alkyl or C1-C4haloalkyl.
Preferably each R13 is independently halo, nitro, Ci-C4alkyl, Ci-C4haloalkyl or Ci-C4alkoxy. Examples of such preferred groups are chloro, fluoro, nitro, methyl, ethyl, trifluoromethyl and methoxy.
Preferably each R14 is independently halo, nitro, C]-C4alkyl, C1-C4haloalkyl, C1- C4alkoxy or C1-C4haloalkoxy. Examples of such preferred groups are chloro, fluoro, nitro, methyl, ethyl, trifluoromethyl, methoxy and trifluoromethoxy.
In one embodiment the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Ix)
Figure imgf000015_0001
wherein R1, R2, R4 and R5 are as defined for a compound of formula (I) and R3 is Ci-Cioalkyl, C2-C]0alkenyl, C2-C10alkynyl, C3-Ciocycloalkyl, C3-Ciocycloalkyl-d- C6alkyl-, d-doalkoxy-Ci-Cόalkyl-, C]-C10cyanoalkyl-, d-doalkoxycarbonyl-d-
C6alkyl-, N-C \ -dalkyl-aminocarbonyl-C i-Cβalkyl-, N,N-di-(C \ -C3alkyl)-aminocarbonyl- d-Cβalkyl-, aryl-d-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-d-Cόalkyl- or heterocyclyl-d-C6alkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R5, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I). The preferences for R3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R3 cannot be hydrogen. In another embodiment the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Ic)
Figure imgf000016_0001
wherein R1, R2 and R4 are as defined for a compound of formula (I) and R3 is d-Cioalkyl, C2-C]0alkenyl, C2-CiOalkynyl, C3-Ci0cycloalkyl, C3-Ciocycloalkyl-Ci- C6alkyl-, Q-Cioalkoxy-Ci-Cealkyl-, Ci-Qocyanoalkyl-, Ci-Cioalkoxycarbonyl-Ci- C6alkyl-, N-C1 -Csalkyl-aminocarbonyl-Ci-Cόalkyl-, N,N-di-(CrC3alkyl)-aminocarbonyl- C]-C6alkyl-, aryl-Ci-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-C]-C6alkyl- or heterocyclyl-Ci-C6alkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; and R5 is a group which can be metabolised to a hydroxy group; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R6, R7, R8, R9, R10, Ru, R12, R13 and R14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I). The preferences for R3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R3 cannot be hydrogen. The preferences for R5 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R5 cannot be hydroxy. In another embodiment the invention provides a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (Id)
Figure imgf000016_0002
wherein R1, R2 and R4 are as defined for a compound of formula (I) and R3 is d-Cioalkyl, C2-C10alkenyl, C2-Ci0alkynyl, C3-Ci0cycloalkyl, C3-C10cycloalkyl-C]- C6alkyl-, Ci-C10alkoxy-Ci-C6alkyl-, Ci-Ciocyanoalkyl-, Ci-Ci0alkoxycarbonyl-Ci- C6alkyl-, N-Ci-C3alkyl-aminocarbonyl-Ci-C6alkyl-, iV,iV-di-(Ci-C3alkyl)-aminocarbonyl- C)-C6alkyl-, aryl-Ci-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Ci-Cόalkyl- or heterocyclyl-Ci-C6alkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R6, R7, R8 and R13 are the same as the preferences set out for the corresponding substituents of a compound of formula (I). The preferences for R3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R3 cannot be hydrogen. Certain compounds of formula (I) are novel and as such form a further aspect of the invention. One group of novel compounds are compounds of formula (Ib)
Figure imgf000017_0001
wherein R1, R2 and R4 are as defined for compounds of formula (I) and R5 is a group which can be metabolised to a hydroxy group; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R6, R8, R9, R10, R11, R12, R13 and R14 are the same as the preferences set out for the corresponding substituents of compounds of the formula (I). The preferences for R5 are the same as the preferences set out for the corresponding substituents of compounds of formula (I) except that R5 cannot be hydroxy. Another group of novel compounds are compounds of formula (Ic)
Figure imgf000017_0002
wherein R1, R2 and R4 are as defined for a compound of formula (I) and R3 is
Ci-Cioalkyl, C2-C10alkenyl, C2-C10alkynyl, C3-Ci0cycloalkyl, C3-C10cycloalkyl-d- C6alkyl-, Q-Cioalkoxy-Ci-Qalkyl-, CrQocyanoalkyl-, d-Cioalkoxycarbonyl-Ci- C6alkyl-, N-Ci-Caalkyl-aminocarbonyl-d-Cόalkyl-, N,N-di-(Ci-C3alkyl)-aminocarbonyl- d-C6alkyl-, aryl-Ci-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Ci-Cόalkyl- or heterocyclyl-Ci-Cόalkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; and R5 is a group which can be metabolised to a hydroxy group; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R6, R7, R8, R9, R10, R11, R12, R13 and R14 are the same as the preferences set out for the corresponding substituents of a compound of formula (I). The preferences for R3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R3 cannot be hydrogen. The preferences for R5 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R5 cannot be hydroxy.
A further group of novel compounds are compounds of formula (Id)
Figure imgf000018_0001
wherein R1, R2 and R4 are as defined for a compound of formula (I) and R3 is C]-CiOalkyl, C2-Cioalkenyl, C2-Ci0alkynyl, C3-Ci0CyC loalkyl, C3-Ci0cycloalkyl-Ci- C6alkyl-, d-Ctoalkoxy-Ci-Qalkyl-, Ci-Ciocyanoalkyl-, Ci-Cioalkoxycarbonyl-Ci- C6alkyl-, jV-Ci-Csalkyl-aminocarbonyl-Ci-Cόalkyl-, N,Λf-di-(Ci-C3alkyl)-aminocarbonyl- Ci-C6alkyl-, aryl-Ci-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Q-Cόalkyl- or heterocyclyl-Cj-Cealkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; or a salt or N-oxide thereof. The preferences for R1, R2, R4, R6, R7, R8 and R13 are the same as the preferences set out for the corresponding substituents of a compound of formula (I). The preferences for R3 are the same as the preferences set out for the corresponding substituents of a compound of formula (I) except that R cannot be hydrogen.
The compounds in Tables 1 to 36 below illustrate the compounds of the invention.
Table 1:
Table 1 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3,5- dichloro-pyrid-2-yl, and R3 and R5 have the values listed in Table 1.
Figure imgf000019_0001
Figure imgf000019_0002
Figure imgf000019_0003
Figure imgf000020_0002
Figure imgf000020_0001
Table 2:
Table 2 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3,5- dichloro-pyrid-4-yl, and R3 and R5 have the values listed in Table 1.
Table 3:
Table 3 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2,6- dichloro-pyrid-3-yl, and R3 and R5 have the values listed in Table 1.
Table 4:
Table 4 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2,4- dichloro-pyrid-3-yl, and R3 and R5 have the values listed in Table 1.
Table 5:
Table 5 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 4,6- dichloro-pyrid-3-yl, and R3 and R5 have the values listed in Table 1. Table 6:
Table 6 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R is 2,5- dichloro-pyrid-4-yl, and R3 and R5 have the values listed in Table 1.
Table 7: Table 7 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3,6- dichloro-pyrid-2-yl, and R3 and R5 have the values listed in Table 1.
Table 8:
Table 8 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- chloro-5-fluoro-pyrid-2-yl, and R3 and R5 have the values listed in Table 1. Table 9:
Table 9 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- chloro-5-trifluoromethyl-pyrid-2-yl, and R3 and R5 have the values listed in Table 1.
Table 10:
Table 10 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3,5,6-trichloro-pyrid-2-yl, and R3 and R5 have the values listed in Table 1.
Table 11:
Table 11 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,5-dichloro-pyrid-3-yl, and R3 and R5 have the values listed in Table 1.
Table 12: Table 12 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,3-dichloro-pyrid-4-yl, and R3 and R5 have the values listed in Table 1.
Table 13:
Table 13 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R is 2- chloro-4-trifluoromethyl-pyrid-3-yl, and R3 and R5 have the values listed in Table 1. Table 14:
Table 14 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2- chloro-6-trifluoromethyl-pyrid-3-yl, and R3 and R5 have the values listed in Table 1.
Table 15:
Table 15 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- chloro-5-trifluoromethyl-pyrid-4-yl, and R3 and R5 have the values listed in Table 1.
Table 16:
Table 16 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,3,5-trichloro-pyrid-4-yl, and R3 and R5 have the values listed in Table 1. Table 17
Table 17 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 5- chloro-pyrimidin-4-yl, and R3 and R5 have the values listed in Table 1.
Table 18: Table 18 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
3,4,5-trichloro-thiophen-2-yl, and R3 and R5 have the values listed in Table 1.
Table 19:
Table 19 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,5-dichloro-thiophen-3-yl, and R3 and R5 have the values listed in Table 1. Table 20:
Table 20 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- trifluoromethyl-isoxazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 21:
Table 21 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- trifluoromethyl-4-chloro-isoxazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 22;
Table 22 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
3,4-dichloro-isoxazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 23: Table 23 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- methyl-l,2,4-oxadiazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 24:
Table 24 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 3- trifluoromethyl-l,2,4-oxadiazol-5-yl, and R3 and R5 have the values listed in Table 1. Table 25:
Table 25 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,4-dichloro-thiazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 26:
Table 26 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2- chloro-4-methyl-thiazol-5-yl, and R3 and R5 have the values listed in Table 1.
Table 27:
Table 27 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,5-dichloro-thiazol-4-yl, and R3 and R5 have the values listed in Table 1. Table 28:
Table 28 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2- chloro-4-trifluoromethyl-thiazol-5-yl-, and R3 and R5 have the values listed in Table 1.
Table 29: Table 29 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R is 5- difluoromethoxy-l-methyl-3-trifluoromethyl-lH-pyrazol-4-yl, and R3 and R5 have the values listed in Table 1.
Table 30:
Table 30 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2- methyl-5-trifluoromethyl-2H-l,2,3-triazol-4-yl, and R3 and R5 have the values listed in
Table 1.
Table 31:
Table 31 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 2- methyl-benzoxazol-5-yl and R3 and R5 have the values listed in Table 1. Table 32:
Table 32 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,4-dichloro-quinolin-3-yl, and R3 and R5 have the values listed in Table 1.
Table 33:
Table 33 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is A- chloro-2-trifluoromethyl-quinolin-3-yl, and R3 and R5 have the values listed in Table 1.
Table 34:
Table 34 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is 1- chloro-isoquinolin-3-yl, and R3 and R5 have the values listed in Table 1.
Table 35: Table 35 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is l,4-dichloro-isoquinolin-3-yl, and R3 and R5 have the values listed in Table 1.
Table 36:
Table 36 provides 70 compounds of formula (I), where R1 and R2 are hydrogen, R4 is
2,5-dimethyl-pyrazolo[l,5-a]pyrimidin-7-yl-, and R3 and R5 have the values listed in Table 1.
The compounds of the invention may be made by a variety of methods, for example by the methods described in Schemes 1 to 10. Scheme 1
Figure imgf000024_0001
(3) method
Figure imgf000024_0002
1) Compounds of formula (4) wherein R1, R2 and R4 are as defined for a compound of formula (I) and R16 is Ci-Cόalkyl can be made by reaction of an amino- pyrazine ester of formula (2) wherein R1 and R2 are as defined for a compound of formula (I) and R16 is Ci-C6alkyl with an acid derivative of formula (3) wherein R4 is as defined for a compound of formula (I) and X is halogen or hydroxy, as shown in Scheme 1. For example, if (3) is an acid chloride (i.e. where X is chlorine) the reaction can conveniently be carried out optionally in the presence of a base, such as triethylamine or pyridine, in a suitable solvent, such as acetonitrile or dichloromethane, optionally using microwave heating. Alternatively, if (3) is a carboxylic acid (i.e. where X is hydroxy) the reaction can conveniently be carried out using an amide coupling method, for example by reaction with a coupling agent, such as bis(2-oxo-3-oxazolidinyl)phosphinic chloride, in the presence of a base, such as triethylamine, in a suitable solvent, such as dichloromethane, or other amide coupling methods which have been reviewed in Tetrahedron (2005), 61(46), 10827-10852.
2) Compounds of formula (Ia) wherein R1, R2 and R4 are as defined for a compound of formula (I) can be prepared by treating a compound of formula (4) as defined in 1) with a base in a suitable solvent, such as potassium carbonate in N,N- dimethylformamide or lithium hexamethyldisilazide in tetrahydrofuran, optionally using microwave heating. 3) Compounds of formula (Ij) wherein R1, R2, R4 and R10 are as defined for a compound of formula (I) can be prepared by reaction of a compound of formula (Ia) as defined in 2) with an acid chloride of formula R10COCl or an acid anhydride of formula (R10CO)2O wherein R10 is as defined for compounds of formula (I), optionally in the presence of a base, such as triethylamine or pyridine, optionally in a suitable solvent, such as dichloromethane.
Scheme 2
Figure imgf000025_0001
4) Compounds of formula (If), i.e. a compound of formula (I) wherein R3 is as defined for compound of formula (I) other than hydrogen and R5 is -O-CO-R10, can be prepared from a compound of formula (Ij) as defined in 3) by reaction with a compound of formula R3LG wherein R3 is as defined for a compound of formula (I) and LG is a leaving group such as a halide, for example bromide or iodide, or tosylate, mesylate or triflate, in the presence of a base, such as potassium carbonate, optionally in the presence of an activator / iodide, such as potassium iodide, in a suitable solvent, such as acetonitrile or N.N-dimethylformamide, optionally using microwave heating, as shown in Scheme 2.
5) Compounds of formula (Id), i.e. a compound of formula (I) wherein R3 is as defined for compounds of formula (I) other than hydrogen and R5 is hydroxy, can be prepared by treating a compound of formula (If) as defined in 4) with a base, such as sodium hydroxide or potassium carbonate, and water in a suitable solvent, such as methanol or N, N-dimethylformamide.
6) Compounds of formula (Ie), i.e. compounds of formula (I) wherein R3 is as defined for compound of formula (I) other than hydrogen and R5 is -O-R9, can be prepared from a compound of formula (Id) as defined in 5) by reaction with a compound of formula R9LG wherein R9 is as defined for compounds of formula (I) and LG is a leaving group such as halide, for example bromide or iodide, or tosylate, mesylate or triflate, in the presence of a base, such as potassium carbonate, in a suitable solvent, such as N,N-dimethylformamide.
Scheme 3
Figure imgf000026_0001
7) Where R3 and R9 happen to be identical, for example both are simple alkyl groups, compounds of formula (Ie) as defined in 6) can also be formed by reaction of a compound of formula (Ia) as defined in 2) with at least two equivalents of a compound of formula R3LG as defined in 4), in the presence of a base, such as potassium carbonate, in a suitable solvent, such as N,7V-dimethylformamide, as shown in Scheme 3.
Scheme 4
Figure imgf000027_0001
(4')
8) Compounds of formula (If) as defined in 4) can additionally be prepared in a shortened route directly from a compound of formula (4) as defined in 1) by reaction with a compound of formula R LG as defined in 4), in the presence of a base, such as sodium or potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating, followed by reaction with an acid chloride of formula R10COCl or an acid anhydride of formula (R10CO)2O as defined in 3), optionally in the presence of a base, such as triethylamine, in the same reaction pot, as shown in Scheme 4. 9) Alternatively compounds of formula (If) as defined in 4) can be made from a compound of formula (Id) as defined in 5), by reaction with an acid chloride of formula R10COCl or an acid anhydride of formula (R10CO)2O as defined in 3), optionally in the presence of a base, such as triethylamine, optionally in a suitable solvent, such as dichloromethane.
10) Compounds of formula (Id) as defined in 5) can be made by reaction of a compound of formula (4) as defined in 1) with a compound of formula R3LG as defined in 4), in the presence of a base, such as potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating (Method 1). 11) Compounds of formula (Id) as defined in 5) can also be made from a compound of formula (Ia) as defined in 2) by reaction with a compound of formula R3LG as defined in 4), in the presence of a base, such as potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating (Method 2). The synthesis of compounds of formula (Ia) was described under 2). 12) Compounds of formula (Ib) as defined in 5) can also be made by reaction of a compound of formula (4') with a compound of formula R3LG as defined in 4), in the presence of a base, such as sodium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating (Method 3). Compounds of formula (4') can be made from a compound of formula (4) by reaction with a base, such as lithium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran or N,N-dimethyl- formamide, optionally using microwave heating.
Scheme 5
Figure imgf000028_0001
13) Silyl compounds of formula (Ig), i.e. a compound of formula (I) wherein R3 is as defined for a compound of formula (I) other than hydrogen and R5 is -0-Si(R1 ')3, can be made from a compound of formula (Id) as defined in 5), by reaction with a trialkylsilyl chloride of formula (Rn)3SiCl, in a suitable solvent, such as tetrahydrofuran or acetonitrile, in the presence of a base, such as triethylamine, as shown in Scheme 5.
Scheme 6
Figure imgf000029_0001
I R3L.G, I base
Figure imgf000029_0002
(Id) (Ih) τ -.4 . „ , r. 12 defined for a compound of formula (I) can be made from a compound of formula (Ia) as defined in 2) by reaction with a sulfonyl chloride of formula R12SO2Cl wherein R12 is as defined for a compound of formula (I), in the presence of a base, such as triethylamine, in a suitable solvent, such as tetrahydrofuran or dichloromethane, as shown in Scheme 6.
15) Sulfonyl compounds of formula (Ih), i.e. a compound of formula (I) wherein R3 is as defined for compounds of formula (I) other than hydrogen and R5 is -0-SO2-R , can be made by reaction of a compound of formula (Ik) as defined in 13), with a compound of formula R3LG as defined in 4), in the presence of a base, such as sodium or potassium hexamethyldisilazide, in a suitable solvent, such as tetrahydrofuran, optionally using microwave heating.
16) Alternatively, compounds of formula (Ih) as defined in 14) can be made by reaction of a compound of formula (Id) as defined in 5) with a sulfonyl chloride of formula Ri2SO2Cl as defined in 13), in the presence of a base, such as triethylamine, in a suitable solvent, such as tetrahydrofuran or dichloromethane.
Scheme 7
Figure imgf000030_0001
17) In certain cases where pyridyl acetic acids of formula (8) are not commercially available it is necessary to make them. A typical synthesis is shown in Scheme 7. Pyridylmethyl halides of formula (6) wherein R8 is as defined for a compound of formula (I) and X is halogen, can be made by reaction of a substituted methyl-pyridine of formula (5) wherein R8 is as defined for a compound of formula (I), with a halogenation agent, such as the halogen of formula X2 wherein X is chlorine or bromine,
in the presence of light, or a N-halosuccinimide of formula
Figure imgf000030_0002
chlorine, bromine or iodine, in the presence of a radical initiator, such as benzoyl peroxide, in a suitable solvent, such as carbon tetrachloride, and optionally in the presence of a light source, such as a 500 watt tungsten halogen lamp, at reflux.
18) Cyanomethyl-pyridines of formula (7) wherein R8 is as defined for a compound of formula (I) can be made by reaction of a compound of formula (6) as defined in 17) with a metal cyanide, such as potassium cyanide, in a suitable solvent, such as ethanol, at reflux. 19) Pyridyl acetic acids of formula (8) wherein R8 is as defined for a compound of formula (I) can be made by reaction of a compound of formula (7) as defined in 18) by hydrolysis using aqueous acid or alkali, but preferably aqueous acid, such as aqueous sulfuric acid, at reflux.
Scheme 8
Figure imgf000031_0001
20) Pyridyl acetic acids of formula (8) can be made by hydrolysis of pyridyl malonates of formula (9), in the presence of, for example, an alkali metal hydroxide MOH, where M is sodium or potassium, in the a suitable solvent, such as methanol or ethanol, optionally in the presence of water.
Scheme 9
Figure imgf000032_0001
21) Diketo amides of formula (11), wherein R1 and R2 are as defined for a compound of formula (I), R16 is as defined in 1) and R17 is hydrogen, Cj-C6 alkyl, C1- C4haloalkyl, aryl or aryl substituted by one to five R8, which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R8, which may be the same or different, can be made by reacting a compound of formula (2) as defined in 1) with a compound of formula (10), wherein R17 is hydrogen, C1-C6 alkyl, Ci-C4haloalkyl, aryl or aryl substituted by one to five R , which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R8, which may be the same or different, in a suitable solvent, such as toluene, at a temperature range from 75 °C to 150°C, preferably at reflux, as shown in Scheme 9.
22) Compounds of formula (12), wherein R1 and R2 are as defined for a compound of formula (I), and R17 is as defined in 21), can be made from a compound of formula (11) as defined in 21), by heating with a suitable base, such as an alkali metal alkoxide, for example sodium methoxide, in a suitable solvent, such as methanol, preferably at reflux.
23) Compounds of formula (13), wherein R1 and R2 are as defined for a compound of formula (I), R17 is as defined in 21), and R18 is C]-C6 alkyl, Ci-C4haloalkyl, aryl or aryl substituted by one to five R8, which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R8, which may be the same or different, can be made from a compound of formula (12) as defined in 22) by reaction with an ester of formula R18COOR16, wherein R18 is C1-C6 alkyl, Ci-C4haloalkyl, aryl or aryl substituted by one to five R8, which may be the same or different, or heteroaryl or heteroaryl substituted by one to four R , which may be the same or different, and R is as defined in 1), with a suitable base, such as sodium or sodium hydride, in R COOR as solvent, or alternatively with a co-solvent, such as toluene, at a temperature range from 40°C to 100°C, preferably from 50°C to 75°C.
24) Compounds of formula (14), wherein R1 and R2 are as defined for a compound of formula (I), R17 is defined as in 21), and R18 is defined as in 23), can be made from a compound of formula (13) as defined in 23) by heating with hydroxylamine or its salts, in a suitable solvent, such as ethanol, preferably at reflux.
(25) Compounds of formula (15), wherein R1 and R2 are as defined for a compound of formula (I), R17 is defined as in 21), and R18 is defined as in 23), can be made from a compound of formula (14) as defined in 24) by heating with a a suitable acid, such as acetic acid or trifluoroacetic acid, preferably at reflux.
(26) Compounds of formula (16), wherein R1, R2 and R10 are as defined for a compound of formula (I), R17 is defined as in 21), and R18 is defined as in 23), can be made by reacting a compound of formula (15) as defined in 25) with an acid chloride of formula R10COCl as defined in 3) in the presence of base, such as pyridine, in a suitable solvent, such as dichloromethane, preferably at ambient temperature.
(27) Compounds of formula (17), wherein R1, R2 and R10 are as defined for a compound of formula (I), R3 is as defined for a compound of formula (I) other than hydrogen hydrogen, R17 is defined as in 21), and R18 is defined as in 23), can be made by reacting a compound of formula (16) as defined in 26) with a compound of formula R3LG as defined in 4), and suitable base, such as potassium carbonate, in a suitable solvent, such as iV,N-dimethylformamide, with heating, optionally in a microwave, at a temperature range from 50°C to 150°C, preferably from 80°C to 1200C.
Scheme 10
Figure imgf000034_0001
(23) (24)
28) Compounds of formula (19), wherein R1 and R2 are as defined for a compound of formula (I) and R19 is Ci-Cβalkyl, can be made by reaction of an aminopyrazine ester of formula (2) as defined under 1) with a dialkyl malonate of formula CH2(CO2R19)2 wherein R19 is Ci-C6alkyl, in the presence of a base, such as sodium methoxide, in a suitable solvent, such as methanol, at a temperature range from 250C to 8O0C, preferably from 400C to 65°C, as shown in Scheme 10. 29) Compounds of formula (20), wherein R1, R2 and R10 are as defined for a compound of formula (I) and R19 is C]-C6alkyl, can be made by reaction of a compound of formula (19) as defined in 28) with an acid chloride of formula R10COCl as defined in 3), in the presence of base, such as pyridine, in a suitable solvent, such as 1,2- dichloroethane, at a temperature range from 250C to 1000C, preferably from 6O0C to 850C.
30) Compounds of formula (21), wherein R1, R2 and R10 are as defined for a compound of formula (I), R3 is as defined for a compound of formula (I) other than hydrogen, and R19 is Ci-C6alkyl, can be made from a compound of formula (20) as defined in 29) by reaction with a compound of formula R3LG as defined in 4), in the presence of a suitable base, such as potassium carbonate, in a suitable solvent, such as N.N-dimethylformamide, at a temperature range from 5O0C to 15O0C, preferably from 8O0C to 1200C, optionally in a microwave.
31) Compounds of formula (23), wherein R1, R2 and R8 are as defined for a compound of formula (I), and R3 is as defined for a compound of formula (I) other than hydrogen, can be made from a compound of formula (21) as defined in 30) by heating with a hydroxy-amidine of formula (22), wherein R8 is as defined for a compound of formula (I), in a suitable solvent, such as toluene, preferably at reflux.
32) Compounds of formula (24), wherein R1, R2, R8 and R10 are as defined for a compound of formula (I), and R3 is as defined for a compound of formula (I) other than hydrogen, can be made by reacting a compound of formula (23) with an acid chloride of formula R10COCl as defined in 3), in the presence of a base, such as pyridine, in a suitable solvent, such as dichloromethane.
The compounds of formula (I) according to the invention can be used as herbicides in unmodified form, as obtained in the synthesis, but they are generally formulated into herbicidal compositions in various ways using formulation adjuvants, such as carriers, solvents and surface-active substances. The formulations 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, 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. Such formulations can either be used directly or they are diluted prior to use. The dilutions can be made, for example, with water, liquid fertilisers, micronutrients, biological organisms, oil or solvents.
The formulations 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 contain the active ingredients in a porous carrier. This enables the active ingredients to be released into the environment in controlled amounts (e.g. slow-release). Microcapsules usually have a diameter of from 0.1 to 500 microns. They 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 polymers that are known to the person skilled in the art in this connection. 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 the 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, butyl ene carbonate, chlorobenzene, cyclohexane, cyclohexanol, alkyl esters of acetic acid, diacetone alcohol, 1,2-dichloropropane, diethanolamine, p-diethylbenzene, diethylene glycol, diethylene glycol abietate, diethylene glycol butyl ether, diethylene glycol ethyl ether, diethylene glycol methyl ether, N,7V-dimethylforrnamide, dimethyl sulfoxide, 1,4-dioxane, dipropylene glycol, dipropylene glycol methyl ether, dipropylene glycol dibenzoate, diproxitol, alkylpyrrolidone, ethyl acetate, 2-ethylhexanol, ethylene carbonate, 1,1,1-trichloro ethane, 2-heptanone, 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, isoamyl acetate, isobornyl acetate, isooctane, isophorone, isopropylbenzene, isopropyl myristate, lactic acid, laurylamine, mesityl oxide, methoxy- propanol, methyl isoamyl ketone, methyl isobutyl ketone, methyl laurate, methyl octanoate, methyl oleate, methylene chloride, m-xylene, w-hexane, «-octylamine, octa- decanoic acid, octylamine acetate, oleic acid, oleylamine, o-xylene, phenol, polyethylene glycol (PEG400), 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, ethyl acetate, amyl acetate, butyl acetate, propylene glycol methyl ether, diethylene glycol methyl ether, methanol, ethanol, isopropanol, and alcohols of higher molecular weight, such as amyl alcohol, tetrahydrofurfuryl alcohol, hexanol, octanol, ethylene glycol, propylene glycol, glycerol, N-methyl-2-pyrrolidone 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 can advantageously be used in both solid and liquid formulations, especially in those formulations which can 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 nonylphenol 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; quaternary amines, such as lauryltrimethylammonium 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 pesticidal 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 compositions according to the invention can additionally include an additive comprising an oil of vegetable or animal origin, a mineral oil, alkyl 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® (Rhόne-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 OfC8-C22 fatty acids, especially the methyl derivatives OfC12-Ci8 fatty acids, for example the methyl esters of lauric acid, palmitic acid and oleic acid, being of importance. Those esters are known as methyl laurate (CAS-111-82-0), methyl palmitate (CAS-112-39-0) 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.
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 WO 97/34485. 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-C22 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 Pen-e-trate®, to be added to the spray mixture as action-enhancing agent. The herbicidal compositions 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 rates of application of compounds of formula (I) 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, the grass 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 g/ha, especially from 50 to 1000 g/ha.
Preferred formulations have especially the following compositions (% = percent by weight):
Emulsifiable concentrates: active ingredient: 1 to 95 %, preferably 60 to 90 % surface-active agent: 1 to 30 %, preferably 5 to 20 % liquid carrier: 1 to 80 %, preferably 1 to 35 % Dusts: active ingredient: 0.1 to 10 %, preferably 0.1 to 5 % solid carrier: 99.9 to 90 %, preferably 99.9 to 99 % Suspension concentrates: active ingredient: 5 to 75 %, preferably 10 to 50 % water: 94 to 24 %, preferably 88 to 30 % surface-active agent: 1 to 40 %, preferably 2 to 30 % Wettable powders: active ingredient: 0.5 to 90 %, preferably 1 to 80 % surface-active agent: 0.5 to 20 %, preferably 1 to 15 % solid carrier: 5 to 95 %, preferably 15 to 90 % Granules: active ingredient: 0.1 to 30 %, preferably 0.1 to 15 % solid carrier: 99.5 to 70 %, preferably 97 to 85 %
The following Examples further illustrate, but do not limit, the invention. Formulation Examples for herbicides of formula (I) (% = % by weight) Fl. Emulsifϊable concentrates a) b) c) d) active ingredient 5% 10% 25% 50% calcium dodecylbenzenesulfonate 6% 8% 6% 8% castor oil polyglycol ether 4% 4% 4% (36 mol of ethylene oxide) octylphenol polyglycol ether - 4 % - 2 %
(7-8 mol of ethylene oxide)
NMP " - - 10% 20% arom. hydrocarbon mixture 85% 78% 55% 16%
Emulsions of any desired concentration can be obtained from such concentrates by dilution with water.
F2. Solutions a) b) c) d) active ingredient ' 5% 10% 50% 90%
1 -methoxy-3 -(3 -methoxy- propoxy)-propane - 20 % 20 % polyethylene glycol MW 400 20% 10% NMP - - ' 30% 10% arom. hydrocarbon mixture 75 % 60 %
C9-C12
The solutions are suitable for use in the form of microdrops.
F3. Wettable powders a) b) c) d) active ingredient 5% 25% 50% 80% sodium lignosulfonate 4% - 3% - sodium lauryl sulfate 2% 3% - 4% sodium diisobutylnaphthalene- sulfonate - 6% 5% 6% octylphenol polyglycol ether - 1% 2% -
(7-8 mol of ethylene oxide) highly dispersed silicic acid 1% 3% 5% 10% kaolin 88 % 62 % 35 %
The active ingredient is mixed thoroughly with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of any desired concentration.
F4. Coated granules a) b) c) active ingredient 0.1 % 5% 15% highly dispersed silicic acid 0.9 % 2% 2% inorganic carrier 99.0 % 93% 83% (diameter 0.1 - 1 mm) e.g. CaCO3 or SiO2
The active ingredient is dissolved in methylene chloride and applied to the carrier by spraying, and the solvent is then evaporated off in vacuo.
F5. Coated granules a) b) c) active ingredient 0.1 % 5% 15% polyethylene glycol MW 200 1.0% 2% 3% highly dispersed silicic acid 0.9 % 1% 2% inorganic carrier 98.0 % 92% 80% (diameter 0.1 - 1 mm) e.g. CaCO3 or SiO2
The finely ground active ingredient is uniformly applied, in a mixer, to the carrier moistened with polyethylene glycol. Non-dusty coated granules are obtained in this manner.
F6. Extruder granules a) b) c) d) active ingredient 0.1 % 3% 5% 15% sodium lignosulfonate 1.5 % 2% 3% 4% carboxymethylcellulose 1.4 % 2% 2% 2% kaolin 97.0 % 93% 90% 79%
The active ingredient is mixed and ground with the adjuvants, and the mixture is moistened with water. The mixture is extruded and then dried in a stream of air. F7. Dusts a) b) c) active ingredient 0.1 % 1 % 5 % talcum 39.9 % 49 % 35 % kaolin 60.0 % 50 % 60 %
Ready-to-use dusts are obtained by mixing the active ingredient with the carriers and grinding the mixture in a suitable mill.
F8. Suspension concentrates a) b) c) d) active ingredient 3 % 10 % 25 % 50 % ethylene glycol 5 % 5 % 5 % 5 % nonylphenol polyglycol ether - 1 % 2 % -
(15 mol of ethylene oxide) sodium lignosulfonate 3 % 3 % 4 % 5 % carboxymethylcellulose 1 % 1 % 1 % 1 %
37 % aqueous formaldehyde 0.2 % 0.2 % 0.2 % 0.2 % solution silicone oil emulsion 0.8 % 0.8 % 0.8 % 0.8 % water 87 % 79 % 62 % 38 %
The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.
The invention relates to a method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
The invention also relates to a method of inhibiting plant growth which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I).
The invention also relates to a method of selectively controlling grasses and weeds in crops of useful plants which comprises applying to the useful plants or locus thereof or to the area of cultivation a herbicidally effective amount of a compound of formula (I). Crops of useful plants in which the composition according to the invention can 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, maize and soy beans.
The grasses and weeds to be controlled may be both mono-'cotyledonous species, for example Agrostis, Alopecurus, Avena, Bromus, Cyperus, Digitaria, Echinochloa, Lolium, Monochoria, Rottboellia, Sagittaria, Scirpus, Setaria, Sida and Sorghum, and dicotyledonous species, for example Abutilon, Amaranthus, Chenopodium, Chrysanthemum, Galium, Ipomoea, Nasturtium, Sinapis, Solanum, Stellaria, Veronica, Viola and Xanthium.
Crops are to be understood as also including those crops which have been rendered tolerant to herbicides or classes of herbicides (e.g. auxins or ALS-, GS-, EPSPS-, PPO- and HPPD-inhibitors) 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), Bt 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 transgenic plants able to synthesize such toxins, are described in EP-A-451 878, 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), NuCOTIN33B® (cotton), Bollgard® (cotton), NewLeaf® (potatoes), NatureGard® 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 flavor).
Areas under cultivation include land on which the crop plants are already growing and land intended for cultivation with those crop plants. The compounds of the invention can be applied before weeds emerge (pre-emergence application) or after weeds emerge (post-emergence application), and are particularly effective when applied post- emergence.
The compounds of formula (I) according to the invention can also be used in combination with one or more further herbicides. In particular, the following mixtures of the compound of formula (I) are important:
Mixtures of a compound of formula (I) with a synthetic auxin (e.g. compound of formula (I) + clopyralid (162), compound of formula (I) + 2,4-D (211), compound of formula (I) + dicamba (228), compound of formula (I) + diphenamid (274), compound of formula (I) + MCPA (499), compound of formula (I) + quinclorac (712), or compound of formula (I) + aminopyralid (CAS RN 150114-71-9)).
Mixtures of a compound of formula (I) with diflufenzopyr (252).
Mixtures of a compound of formula (I) with an acetanilide (e.g. compound of formula (I) + acetochlor (5), compound of formula (I) + dimethenamid (260), compound of formula (I) + metolachlor (548), compound of formula (I) + S-metolachlor (549), or compound of formula (I) + pretilachlor (656)).
Mixtures of a compound of formula (I) with flamprop-M (355).
Mixtures of a compound of formula (I) with flufenacet (BAY FOE 5043) (369).
Mixtures of a compound of formula (I) with pyroxasulfone (CAS RN 447399-55- 5).
Mixtures of a compound of formula (I) with an HPPD inhibitor (e.g. compound of formula (I) + isoxaflutole (479), compound of formula (I) + mesotrione (515), compound of formula (I) + pyrasulfotole (CAS RN 365400-11-9), compound of formula (I) + sulcotrione (747), compound of formula (I) + tembotrione (CAS RN 335104-84-2), compound of formula (I) + topramezone (CAS RN 210631 -68-8), compound of formula (I) + 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), or compound of formula (I) + 4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]- carbonyl]-bicyclo[3.2.1]oct-3-en-2-one (CAS RN 894355-80-7)).
Mixtures of a compound of formula (I) with a triazine (e.g. compound of formula (I) + atrazine (37), or compound of formula (I) + terbuthylazine (775)). Mixtures of a compound of formula (I) with a triazine and an HPPD inhibitor
(e.g. compound of formula (I) + triazine + isoxaflutole, compound of formula (I) + triazine + mesotrione, compound of formula (I) + triazine + pyrasulfotole, compound of formula (I) + triazine + sulcotrione, compound of formula (I) + triazine + tembotrione, compound of formula (I) + triazine + topramezone, compound of formula (I) + triazine + 4-hydroxy-3-[[2-[(2-methoxyethoxy)-imethyl]-6-(trifluoro-τnethyl)-3- pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, or compound of formula (I) + triazine + 4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoro-methyl)-3-pyridinyl]carbonyl]- bicyclo[3.2.1]oct-3-en-2-one).
Mixtures of a compound of formula (I) with glyphosate (419). Mixtures of a compound of formula (I) with glyphosate and an HPPD inhibitor
(e.g. compound of formula (I) + glyphosate + isoxaflutole, compound of formula (I) + glyphosate + mesotrione, compound of formula (I) + glyphosate + pyrasulfotole, compound of formula (I) + glyphosate + sulcotrione, compound of formula (I) + glyphosate + tembotrione, compound of formula (I) + glyphosate + topramezone, compound of formula (I) + glyphosate + 4-hydroxy-3-[[2-[(2-methoxyethoxy)methyl]-6- (trifluoromethyl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, or compound of formula (I) + glyphosate + 4-hydroxy-3-[[2-(3-methoxypropyl)-6-(difluoromethyl)-3- pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one).
Mixtures of a compound of formula (I) with glufosinate-ammonium (418). Mixtures of a compound of formula (I) with glufosinate-ammonium and an HPPD inhibitor (e.g. compound of formula (I) + glufosinate-ammonium + isoxaflutole, compound of formula (I) + glufosinate-ammonium + mesotrione, compound of formula (I) + glufosinate-ammonium + pyrasulfotole, compound of formula (I) + glufosinate- ammonium + sulcotrione, compound of formula (I) + glufosinate-ammonium + tembotrione, compound of formula (I) + glufosinate-ammonium + topramezone, compound of formula (I) + glufosinate-ammonium + 4-hydroxy-3-[[2-[(2-methoxy- ethoxy)methyl]-6-(trifluoromethyl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one, or compound of formula (I) + glufosinate-ammonium + 4-hydroxy-3-[[2-(3- methoxypropyl)-6-(difluoromethyl)-3-pyridinyl]carbonyl]-bicyclo[3.2.1]oct-3-en-2-one).
Mixtures of a compound of formula (I) with an ALS or an AHAS inhibitor (e.g. compound of formula (I) + bensulfuron-methyl (64), compound of formula (I) + chlorimuron-ethyl (135), compound of formula (I) + cloransulam-methyl (164), compound of formula (I) + florasulam (359), compound of formula (I) + flucarbazone- sodium (364), compound of formula (I) + imazamox (451), compound of formula (I) + imazapyr (453), compound of formula (I) + imazethapyr (455), compound of formula (I) + iodosulfuron-methyl-sodium (466), compound of formula (I) + mesosulfuron-methyl (514), compound of formula (I) + nicosulfuron (577), compound of formula (I) + penoxsulam (622), compound of formula (I) + pyroxsulam (triflosulam) (CAS RN 422556-08-9), compound of formula (I) + thifensulfuron-methyl (thiameturon-methyl) (795), compound of formula (I) + triasulfuron (817), compound of formula (I) + tribenuron-methyl (822), compound of formula (I) + trifloxysulfuron-sodium (833), compound of formula (I) + thiencarbazone (4-[(4,5-dihydro-3-methoxy-4-methyl-5-oxo- lH-l^^-triazol-l-ytycarbonylsulfamoy^-S-methylthiophene-S-carboxylic acid, BAY636)), or compound of formula (I) + thiencarbazone-methyl (methyl 4-[(4,5- dihydro-3-methoxy-4-methyl-5-oxo-lH-l,2,4-triazol-l-yl)carbonylsulfamoyl]-5- methylthiophene-3-carboxylate, CAS RN 317815-83-1, BAY636-methyl)). Mixtures of a compound of formula (I) with a PPO inhibitor (e.g. compound of formula (I) + acifluorfen-sodium (7), compound of formula (I) + butafenacil (101), compound of formula (I) + carfentrazone-ethyl (121), compound of formula (I) + cinidon-ethyl (152), compound of formula (I) + flumioxazin (376), compound of formula (I) + fomesafen (401), compound of formula (I) + lactofen (486), or compound of formula (I) + [3-[2-chloro-4-fluoro-5-(l-methyl-6-trifluoromethyl-2,4-dioxo-l,2,3,4- tetrahydropyrimidin-3-yl)phenoxy]-2-pyridyloxy] acetic acid ethyl ester) (CAS RN 353292-31-6)).
Mixtures of a compound of formula (I) with an ACCase inhibitor (e.g. compound of formula (I) + butroxydim (106), compound of formula (I) + clethodim (155), compound of formula (I) + clodinafop-propargyl (156), compound of formula (I) + cycloxydim (190), compound of formula (I) + cyhalofop-butyl (195), compound of formula (I) + diclofop-methyl (238), compound of formula (I) + fenoxaprop-P-ethyl (339), compound of formula (I) + fluazifop-butyl (361), compound of formula (I) + fluazifop-P-butyl (362), compound of formula (I) + haloxyfop (427), compound of formula (I) + haloxyfop-P (428), compound of formula (I) + propaquizafop (670), compound of formula (I) + quizalofop (717), compound of formula (I) + quizalofop-P (718), compound of formula (I) + sethoxydim (726), compound of formula (I) + tepraloxydim (771), compound of formula (I) + tralkoxydim (811)), or compound of formula (I) + pinoxaden (CAS RN 243973-20-8).
Mixtures of a compound of formula (I) with prosulfocarb (683), or a compound of formula (I) with tri-allate (816).
Mixtures of a compound of formula (I) with bromoxynil (95), a compound of formula (I) with chloridazon (134), a compound of formula (I) with chlorotoluron (143), a compound of formula (I) with diuron (281), or a compound of formula (I) with metribuzin (554).
Mixtures of a compound of formula (I) with clomazone (159), a compound of formula (I) with diflufenican (251), a compound of formula (I) with flurochloridone (389), or a compound of formula (I) with flurtamone (392).
Mixtures of a compound of formula (I) with pendimethalin (621) or a compound of formula (I) with trifluralin (836).
Mixtures of a compound of formula (I) with difenzoquat metilsulfate (248). Mixtures of a compound of formula (I) with diquat dibromide (276). Mixtures of a compound of formula (I) with paraquat dichloride (614).
The mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003. The reference to glufosinate-ammonium also applies to glufosinate, the reference to cloransulam-methyl also applies to cloransulam, the reference to dimethenamid also applies to dimethenamid-P, the reference to flamprop-M also applies to flamprop, and the reference to pyrithiobac-sodium also applies to pyrithiobac, etc.
The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1: 100 to 1000:1.
The mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the mixing partner).
Additionally, one or more of the following herbicides or plant growth regulators can be used in combination with a compound of formula (I) according to the invention or in combination with a mixture as described above: aclonifen (8), acrolein (10), alachlor (14), alloxydim (18), ametryn (20), amicarbazone (21), amidosulfuron (22), aminocyclopyrachlor (CAS RN 858956-08-8), amitrole (aminotriazole) (25), ammonium sulfamate (26), anilofos (31), asulam (36), aviglycine (39), azafenidin (CAS RN 68049- 83-2), azimsulfuron (43), BAS 800H (CAS RN 372137-35-4), beflubutamid (55), benazolin (57), bencarbazone (CAS RN 173980-17-1), benfluralin (59), benfuresate (61), bensulide (65), bentazone (67), benzfendizone (CAS RN 158755-95-4), benzobicyclon (69), benzofenap (70), bilanafos (bialaphos) (77), bispyribac-sodium (82), borax (86), bromacil (90), bromobutide (93), bromofenoxim (CAS RN 13181-17-4), butachlor (100), butamifos (102), butralin (105), butylate (108), cafenstrole (110), carbetamide (117), chlorbromuron (CAS RN 13360-45-7), chlorflurenol-methyl (133), chloroacetic acid (138), chlorpropham (144), chlorsulfuron (147), chlorthal-dimethyl (148), cinmethylin (153), cinosulfuron (154), clomeprop (160), cumyluron (180), cyanamide (182), cyanazine (183), cyclanilide (186), cycloate (187), cyclosulfamuron (189), daimuron (213), dalapon (214), dazomet (216), desmedipham (225), desmetryn (CAS RN 1014-69- 3), dichlobenil (229), dichlorprop (234), dichlorprop-P (235), diclosulam (241), dimefuron (256), dimepiperate (257), dimethachlor (258), dimethametryn (259), dimethipin (261), dimethylarsinic acid (264), dinitramine (268), dinoterb (272), dipropetryn (CAS RN 4147-51-7), dithiopyr (280), DNOC (282), DSMA (CAS RN 144- 21-8), endothal (295), EPTC (299), esprocarb (303), ethalfluralin (305), ethametsulruron- methyl (306), ethephon (307), ethofumesate (311), ethoxyfen (CAS RN 188634-90-4), ethoxyfen-ethyl (CAS RN 131086-42-5), ethoxysulfuron (314), etobenzanid (318), fentrazamide (348), ferrous sulfate (353), flazasulfuron (356), fluazolate (isopropazol) (CAS RN 174514-07-9), flucetosulfuron (CAS RN 412928-75-7), fluchloralin (365), flufenpyr-ethyl (371), flumetralin (373), flumetsulam (374), flumiclorac-pentyl (375), fiumipropyn (flumipropin) (CAS RN 84478-52-4), fluometuron (378), fluoroglyco fen- ethyl (380), flupoxam (CAS RN 119126-15-7), flupropacil (CAS RN 120890-70-2), flupropanate (383), flupyrsulfuron-methyl-sodium (384), flurenol (387), fluridone (388), fluroxypyr (390), fluthiacet-methyl (395), foramsulfuron (402), fosamine (406), halosulfuron-methyl (426), HC-252 (429), hexazinone (440), imazamethabenz-methyl (450), imazapic (452), imazaquin (454), imazosulfuron (456), indanofan (462), ioxynil (467), isoproturon (475), isouron (476), isoxaben (477), isoxachlortole (CAS RN 141112-06-3), isoxapyrifop (CAS RN 87757-18-4), karbutilate (482), lenacil (487), linuron (489), MCPA-thioethyl (500), MCPB (501), mecoprop (503), mecoprop-P (504), mefenacet (505), mefluidide (507), metam (519), metamifop (mefluoxafop) (520), metamitron (521), metazachlor (524), methabenzthiazuron (526), methazole (CAS RN 20354-26-1), methylarsonic acid (536), 1-methylcyclopropene (538), methyldymron (539), methyl isothiocyanate (543), metobenzuron (547), metobromuron (CAS RN 3060- 89-7), metosulam (552), metoxuron (553), metsulfuron-methyl (555), MK-616 (559), molinate (560), monolinuron (562), MSMA (CAS RN 2163-80-6), naproanilide (571), napropamide (572), naptalam (573), neburon (574), nipyraclofen (CAS RN 99662-11-0), n-methyl-glyphosate, nonanoic acid (583), norflurazon (584), oleic acid (fatty acids) (593), orbencarb (595), orthosulfamuron (CAS RN 213464-77-8), oryzalin (597), oxadiargyl (599), oxadiazon (600), oxasulfuron (603), oxaziclomefone (604), oxyfluorfen (610), pebulate (617), pentachlorophenol (623), pentanochlor (624), pentoxazone (625), pethoxamid (627), petrolium oils (628), phenmedipham (629), picloram (645), picolinafen (646), piperophos (650), primisulfuron-methyl (657), prodiamine (661), profluazol (CAS RN 190314-43-3), profoxydim (663), prohexadione calcium (664), prometon (665), prometryn (666), propachlor (667), propanil (669), propazine (672), propham (674), propisochlor (667), propoxycarbazone-sodium (procarbazone-sodium) (679), propyzamide (681), prosulfuron (684), pyraclonil (pyrazogyl) (CAS RN 158353-15-2), pyraflufen-ethyl (691), pyrazolynate (692), pyrazosulfuron-ethyl (694), pyrazoxyfen (695), pyribenzoxim (697), pyributicarb (698), pyridafol (CAS RN 40020-01-7), pyridate (702), pyriftalid (704), pyriminobac-methyl (707), pyrimisulfan (CAS RN 221205-90-9), pyrithiobac-sodium (709), quinmerac (713), quinoclamine (714), rimsulfuron (721), sequestrene, siduron (727), simazine (730), simetryn (732), sodium chlorate (734), sulfentrazone (749), sulfometuron-methyl (751), sulfosate (CAS RN 81591-81-3), sulfosulfuron (752), sulfuric acid (755), tar oils (758), TCA-sodium (760), tebutam (CAS RN 35256-85-0), tebuthiuron (765), tefuryltrione (CAS RN 473278-76-1), terbacil (772), terbumeton (774), terbutryn (776), thenylchlor (789), thidiazimin (CAS RN 123249-43-4), thiazafluron (CAS RN 25366-23-8), thiazopyr (793), thiobencarb (797), tiocarbazil (807), triaziflam (819), triclopyr (827), trietazine (831), triflusulfuron-methyl (837), trihydroxytriazine (CAS RN 108-80-5), trinexapac-ethyl (CAS RN 95266-40-3), tritosulfuron (843), N-[(lR,2S)-2,6-dimethyl- 2,3-dihydro- lH-inden- 1 -yl]-6-( 1 -fluoroethyl)- 1 ,3 ,5-triazine-2,4-diamine (C AS RN 950782-86-2), 1 -(2-chloro-6-proρylimidazo[ 1 ,2-b]pyridazin-3-ylsulfonyl)-3-(4,6- dimethoxypyrimidin-2-yl)urea (CAS RN 570415-88-2), and 5-(2,6-difluoro- benzyloxymethyl)-5-methyl-3-(3-methyl-thiophen-2-yl)-4,5-dihydro-isoxazole (CAS RN 403640-27-7).
The mixing partners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003. The reference to acifluorfen-sodium also applies to acifluorfen, and the reference to bensulfuron-methyl also applies to bensulfuron, etc.
The mixing ratio of the compound of formula (I) to the mixing partner is preferably from 1 : 100 to 1000:1. The mixtures can advantageously be used in the above-mentioned formulations
(in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the mixing partner).
The compounds of formula (I) according to the invention can also be used in combination with one or more safeners. Likewise, mixtures of a compound of formula (I) according to the invention with one or more further herbicides can also be used in combination with one or more safeners. The term "safener" as used herein means a chemical that when used in combination with a herbicide reduces the undesirable effects of the herbicide on non-target organisms, for example, a safener protects crops from injury by herbicides but does not prevent the herbicide from killing the weeds. The safeners can be AD-67 (11), benoxacor (63), cloquintocet-mexyl (163), cyometrinil (CAS RN 78370-21-5), cyprosulfamide (CAS RN 221667-31-8), dichlormid (231), dicyclonon (CAS RN 79260-71-2), fenchlorazole-ethyl (331), fenclorim (332), flurazole (386), fluxofenim (399), furilazole (413) and the corresponding R isomer, isoxadifen- ethyl (478), mefenpyr-diethyl (506), 2-methoxy-N-[[4-[[(methylamino)carbonyl]amino]- phenyl] sulfonyl] -benzamide (CAS RN 129531 - 12-0), naphthalic anhydride (CAS RN 81 - 84-5), and oxabetrinil (598). Particularly preferred are mixtures of a compound of formula (I) with benoxacor and a compound of formula (I) with cloquintocet-mexyl.
The safeners of the compound of formula (I) may also be in the form of esters or salts, as mentioned e.g. in The Pesticide Manual, 13th Edition (BCPC), 2003. The reference to cloquintocet-mexyl also applies to cloquintocet, and the reference to fenchlorazole-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 mixtures can advantageously be used in the above-mentioned formulations (in which case "active ingredient" relates to the respective mixture of compound of formula (I) with the safener). It is possible that the safener and a compound of formula (I) and one or more additional herbicide(s), if any, are applied simultaneously. For example, the safener, a compound of formula (I) and one or more additional herbicide(s), if any, might be applied to the locus pre-emergence or might be applied to the crop post- emergence. It is also possible that the safener and a compound of formula (I) and one or more additional herbicide(s), if any, are applied sequentially. For example, the safener might be applied before sowing the seeds as a seed treatment and a compound of formula (I) and one or more additional herbicides, if any, might be applied to the locus pre- emergence or might be applied to the crop post-emergence.
Preferred mixtures of a compound of formula (I) with further herbicides and safeners include:
Mixtures of a compound of formula (I) with S-metolachlor and a safener, particularly benoxacor.
Mixtures of a compound of formula (I) with isoxaflutole and a safener.
Mixtures of a compound of formula (I) with mesotrione and a safener.
Mixtures of a compound of formula (I) with sulcotrione and a safener.
Mixtures of a compound of formula (I) with a triazine and a safener. Mixtures of a compound of formula (I) with a triazine and isoxaflutole and a safener.
Mixtures of a compound of formula (I) with a triazine and mesotrione and a safener.
Mixtures of a compound of formula (I) with a triazine and sulcotrione and a safener.
Mixtures of a compound of formula (I) with glyphosate and a safener.
Mixtures of a compound of formula (I) with glyphosate and isoxaflutole and a safener.
Mixtures of a compound of formula (I) with glyphosate and mesotrione and a safener.
Mixtures of a compound of formula (I) with glyphosate and sulcotrione and a safener. Mixtures of a compound of formula (I) with glufosinate-ammonium and a safener.
Mixtures of a compound of formula (I) with glufosinate-ammonium and isoxaflutole and a safener. Mixtures of a compound of formula (I) with glufosinate-ammonium and mesotrione and a safener.
Mixtures of a compound of formula (I) with glufosinate-ammonium and sulcotrione and a safener.
Mixtures of a compound of formula (I) with florasulam and a safener, particularly cloquintocet-mexyl.
Mixtures of a compound of formula (I) with clodinafop-propargyl and a safener, particularly cloquintocet-mexyl.
Mixtures of a compound of formula (I) with pinoxaden and a safener, particularly cloquintocet-mexyl. Mixtures of a compound of formula (I) with bromoxynil and a safener, particularly cloquintocet-mexyl.
The following Examples further illustrate, but do not limit, the invention.
Preparation Examples
The following abbreviations were used throughout this section: s = singlet; bs = broad singlet; d = doublet; dd = double doublet; dt = double triplet; t = triplet, tt = triple triplet, q = quartet, sept = septet; m = multiplet; Me = methyl; Et = ethyl; Pr = propyl; Bu = butyl.
1. Reactions which are covered by Schemes 1 and 2 where R4 is a 6-membered ring Example 1.1 : Preparation of 3-[2-(3.5-dichloro-pyrid-2-vπ-acetylamino1-pyrazine-2- carboxylic acid methyl ester
Figure imgf000054_0001
To a solution of (3,5-dichloro-pyrid-2-yl)-acetic acid (Example 5.1) (5.7 g) and 3- amino-pyrazine-2-carboxylic acid methyl ester (4.65 g) in dichloromethane (120 ml) were added successively triethylamine (8.5 ml) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride ("BOP-Cl") (7.5 g). The reaction mixture was stirred at ambient temperature for 24 hours. The organic phase was washed successively with water, aqueous sodium hydrogen carbonate (IM), and brine. The organic phase was dried over magnesium sulfate and concentrated to give 3-[2-(3,5-dichloro-pyrid-2-yl)-acetylamino]-pyrazine-2- carboxylic acid methyl ester (6.37 g). 1H-NMR (400 MHz, CDCl3): 4.04 (s, 3H), 4.35 (s, 2H), 7.77 (s, IH), 8.39 (s, IH), 8.49 (s, IH), 8.56 (s, IH), 11.02 (s, IH) ppm.
Example 1.2: Preparation of 7-(3,5-dichloro-pyrid-2-yl)-pyrido[2,3-b]pyrazine-6,8-diol ("Compound No. Al of Table A)
Figure imgf000054_0002
A mixture of 3-[2-(3,5-dichloro-pyrid-2-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester (Example 1.1) (5.78 g) and potassium carbonate (2.4 g) in dry TV, N- dimethylformamide (100 ml) was heated to 100°C for 2 hours. The reaction mixture was cooled to ambient temperature and concentrated. The residue was triturated with diethyl ether and the organic phase decanted. The solid was dissolved in water and pH value adjusted to pH 5 by addition of aqueous hydrochloric acid (2M). The aqueous phase was concentrated. The residue was dissolved in methanol, the insoluble salts were removed by filtration and the filtrate was concentrated to give Compound No. Al of Table A (4.9 g)-
Example 1.3: Preparation of isobutyric acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6- dihvdro-pyridor2,3-blpyrazin-8-yl ester (Compound No. A5 of Table A)
Figure imgf000055_0001
pyridine
Figure imgf000055_0003
Figure imgf000055_0002
7-(3,5-Dichloro-pyrid-2-yl)-pyrido[2,3-b]pyrazine-6,8-diol (Example 1.2) (1.6 g) was dissolved in dichloromethane (50 ml) containing pyridine (0.445 g) and the reaction mixture stirred for 10 minutes. Isobutyryl chloride (0.556 g) was added dropwise over 5 minutes and the reaction mixture stirred for two hours. Water was added and the mixture extracted with ethyl acetate. The phases were separated and the organic fraction was washed with aqueous sodium carbonate (IM). The organic fraction was dried over sodium sulfate and concentrated to give a pale yellow solid which was recrystallized from ethyl acetate / hexane to give Compound No. A5 of Table A (1.02 g).
The following compound was made by an analogous method: Carbonic acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester ethyl ester (Compound No. A3 of Table A) from 7-(3,5-dichloro- pyrid-2-yl)-pyrido[2,3-b]pyrazine-6,8-diol (Example 1.2) using ethyl chloroformate as reagent.
Example 1.4: Preparation of isobutyric acid 7-("3,5-dichloro-pyrid-2-vD-5-ethyl-6-oxo- 5,6-dihydro-pyrido["2,3-b1pyrazin-8-yl ester f Compound No. A6 of Table A)
Figure imgf000056_0001
Isobutyric acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.3) (0.250 g) was dissolved in acetonitrile (2 ml) and potassium carbonate (0.138 g) and ethyl iodide (0.1 ml) were added successively. The reaction mixture was heated in a microwave at 1000C for 11 minutes, cooled to ambient temperature and concentrated. The residue was purified by column chromatography on silica gel (eluent: hexane / ethyl acetate 1 :1) to give Compound No. A6 of Table A as a yellow gum which solidified on standing (0.101 g).
The following compounds were made by analogous methods:
Isobutyric acid 7-(3,5-dichloro-pyrid-2-yl)-5-methyl-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A7 of Table A) from isobutyric acid 7- (3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 1.3) using methyl iodide as reagent.
Carbonic acid 7-(3,5-dichloro-pyrid-2-yl)-5-methyl-6-oxo-5,6-dihydro-pyrido- [2,3-b]pyrazin-8-yl ester ethyl ester (Compound No. A2 of Table A) from carbonic acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester ethyl ester (Example 1.3) using methyl iodide as reagent.
2,2-Dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-5-methyl-6-oxo-5,6- dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A9 of Table A) from 2,2- dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7) using methyl iodide as reagent. 2,2-Dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-5-ethyl-6-oxo-5,6- dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. AlO of Table A) from 2,2- dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7) using ethyl iodide as reagent.
2,2-Dimethyl-propionic acid 7-(2,6-dichloro-pyrid-3-yl)-5-methyl-6-oxo-5,6- dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. Al 5 of Table A) from 2,2- dimethyl-propionic acid 7-(2,6-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7) using methyl iodide as reagent.
Example 1.5 Preparation of 3-["2-(2,6-dichloro-pyrid-3-yl)-acetylamino]-pyrazine-2- carboxylic acid methyl ester
Figure imgf000057_0002
pyridine
Figure imgf000057_0001
Figure imgf000057_0003
(2,6-Dichloro-pyrid-3-yl)-acetyl chloride was formed by dropwise addition of oxalyl chloride to a solution of (2,6-dichloro-pyrid-3-yl)-acetic acid (Example 4.3) (1.174 g) in dichloromethane (10 ml) with two drops of N,N-dimethylformamide. The reaction mixture was stirred at ambient temperature for 2 hours. The reaction mixture was then concentrated to give the acid chloride as an oil, which used without purification in the next step. To a suspension of methyl 3-amino-pyrazine 2-carboxylate (0.870 g) in dichloromethane (20 ml) and pyridine (0.463 ml) was added dropwise a solution of the acid chloride in dichloromethane (10 ml). The reaction mixture was stirred for 20 hours at ambient temperature. The reaction mixture was then diluted with more dichloromethane (100 ml) and washed successively with water, aqueous hydrochloric acid (2M), and aqueous sodium hydrogen carbonate (saturated). The organic phase was dried over magnesium sulfate and concentrated to give 3-[2-(2,6-dichloro-pyrid-3-yl)- acetylamino]-pyrazine-2-carboxylic acid methyl ester (1.16 g). 1H-NMR (400 MHz, CDCl3): 4.04 (s, 3H), 4.12 (s, 2H), 7.30 (d, IH), 7.71 (d, IH), 8.42 (d, IH), 8.59 (d, IH), 10.91 (s, IH) ppm.
The following compounds were made by analogous methods:
3-[2-(3,5-Dichloro-pyrid-4-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester from (3,5-dichloro-pyrid-4-yl)-acetic acid (prepared according to WO 99/32449). 1H-NMR (400 MHz, CDCl3): 4.04 (s, 3H), 4.43 (s, 2H), 8.43 (d, IH), 8.55 (s, 2H), 8.60 (d, IH) ppm.
3-[2-(2,5-Dichloro-pyrid-4-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester from (2,5-dichloro-pyrid-4-yl)-acetic acid (prepared according to WO 99/32449). 1H-NMR (400 MHz, CDCl3): 4.07 (s, 3H), 4.17 (s, 2H), 8.37 (s, IH), 8.41 (s, IH), 8.44 (d, IH), 8.59 (d, IH) ppm.
3-[2-(2,4-Dichloro-pyrid-3-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester from (2,4-dichloro-pyrid-3-yl)-acetic acid (prepared according to WO 99/32449), was used without further purification.
3-[2-(4,6-Dichloro-pyrid-3-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester from (4,6-dichloro-pyrid-3-yl)-acetic acid (commercially available). 1H-NMR (400 MHz, CDCl3): 4.05 (s, 3H), 4.17 (s, 2H), 7.46 (s, IH), 8.37 (s, IH), 8.43 (d, IH), 8.60 (d, IH) ppm.
Example 1.6 Preparation of 7-(2,6-dichloro-pyrid-3-ylN)-8-hvdroxy-5H-pγridor2,3- blpyrazin-6-one (Compound No. Al 3 of Table A)
Figure imgf000058_0001
A mixture of 3-[2-(2,6-dichloro-pyrid-3-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester (Example 1.5) (1.16 g) and potassium carbonate (0.943 g) in dry N,N- dimethylformamide (20 ml) was heated to 100°C for 3 hours. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate. The mixture was filtered and the solid was washed with further ethyl acetate. The solid was then suspended in water and the pH of the suspension adjusted to pH 2 by addition of aqueous hydrochloric acid (2M). The aqueous phase was filtered to give Compound No. Al 3 of Table A as a beige solid which was washed with a small amount of water, followed by diethyl ether and allowed to dry (0.380 g).
The following compounds were made by analogous methods:
7-(3,5-Dichloro-pyrid-4-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. A25 of Table A) from 3-[2-(3,5-dichloro-pyrid-4-yl)-acetylamino]- pyrazine-2-carboxylic acid methyl (Example 1.5).
7-(2,5-Dichloro-pyrid-4-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. A22 of Table A) from 3-[2-(2,5-dichloro-pyrid-4-yl)-acetylamino]- pyrazine-2-carboxylic acid methyl (Example 1.5).
7-(2,4-Dichloro-pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. A24 of Table A) from 3-[2-(2,4-dichloro-pyrid-3-yl)-acetylamino]- pyrazine-2-carboxylic acid methyl ester (Example 1.5).
7-(4,6-Dichloro-pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. A26 of Table A) from 3-[2-(4,6-dichloro-pyrid-3-yl)-acetylamino]- pyrazine-2-carboxylic acid methyl ester (Example 1.5).
Compound Nos. A28, A29 and A31 of Table A were made by methods analogous to the methods set out in Examples 1.2 and 1.6.
Example 1.7 Preparation of 2,2-dimethyl-propionic acid 7-(2,6-dichloro-pyrid-3-yl)-6- oxo-5.6-dihvdro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. Al 4 of Table A)
Figure imgf000059_0001
pyridine
Figure imgf000059_0003
Figure imgf000059_0002
Pivaloyl chloride (0.096 ml) was added dropwise to a solution of 7-(2,6-dichloro- pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6) (0.20 g) and pyridine (0.068 ml) in dichloromethane (5 ml) at ambient temperature. The reaction mixture was stirred at ambient temperature for 1 hour and was then diluted with more dichloromethane. The organic phase was washed with aqueous sodium hydrogen carbonate (saturated) and brine, dried over magnesium sulfate, and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 2: 1) to give Compound No. A14 of Table A as a white solid (0.088 g).
The following compounds were made by analogous methods:
2,2-Dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A8 of Table A) from 7-(3,5-dichloro- pyrid~4-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6).
2,2-Dimethyl-propionic acid 7-(2,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A23 of Table A) from 7-(2,5-dichloro- pyrid-4-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6).
2,2-Dimethyl-propionic acid 7-(2,4-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A17 of Table A) from 7-(2,4-dichloro- pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6). 2,2-Dimethyl-propionic acid 7-(4,6-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro- pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A27 of Table A) from 7-(4,6-dichloro- pyrid-3-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Example 1.6).
Example 1.8 Preparation of 2,2-dimethyl-propionic acid 7-("2,6-dichloro-pyrid-3-yl)-5- (2,2-difluoro-ethyl)-6-oxo-5,6-dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. A16 ofTable A)
Figure imgf000060_0001
To s suspension of 2,2-dimethyl-propionic acid 7-(2,6-dichloro-pyrid-3-yl)-6- oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 1.7) (0.064 g) in dry N1N- dimethylformamide (3 ml) was added successively potassium carbonate (0.068 g) and difluoro-ethyl bromide (0.063 g). The reaction mixture was heated in a microwave for 20 minutes at 120°C. The reaction mixture was cooled to ambient temperature, and then diluted with ethyl acetate and water. The phases were separated and organic phase was washed with water and brine, dried over magnesium sulfate, and concentrated to give Compound No. A16 of Table A as a pale yellow solid (0.006 g).
The following compounds were made by analogous methods:
2,2-Dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-5-(2,2-difluoro-ethyl)-6- oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. Al 1 of Table A) from 2,2-dimethyl-propionic acid 7-(3,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7). 7-(3,5-Dichloro-ρyrid-4-yl)-5-(2,2-difluoro-ethyl)-8- hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. A12 of Table A) was obtained as a by-product.
7-(2,5-Dichloro-pyrid-4-yl)-5-(2,2-difluoro-ethyl)-8-hydroxy-5H-pyrido[2,3- b]pyrazin-6-one (Compound No. A21 of Table A) was obtained from 2,2-dimethyl- propionic acid 7-(2,5-dichloro-pyrid-4-yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 1.7) as the sole product.
2,2-Dimethyl-propionic acid 7-(2,4-dichloro-pyrid-3-yl)-5-(2,2-difluoro-ethyl)-6- oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. Al 8 of Table A) from 2,2-dimethyl-propionic acid 7-(2,4-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7).
2,2-Dimethyl-propionic acid 7-(4,6-dichloro-pyrid-3-yl)-5-(2,2-difluoro-ethyl)-6- oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. A20 of Table A) from 2,2-dimethyl-propionic acid 7-(4,6-dichloro-pyrid-3-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 1.7). 7-(4,6-Dichloro-pyrid-3-yl)-5-(2,2-difluoro-ethyl)-8- hydroxy-5//-pyrido[2,3-b]pyrazin-6-one (Compound No. Al 9 of Table A) was obtained as a by-product.
Compound No. A30 of Table A was made by a method analogous to the method set out in Examples 1.4 and 1.8. 2. Reactions which are covered by Schemes 1 and 2 where R4 is a 5-membered ring Example 2.1 : Preparation of 2-chloro-4-methyl-thiazole acetic acid
Figure imgf000062_0001
2-Chloro-4-methyl-thiazole acetic acid was prepared by hydrolysis of ethyl 2- chloro-4-methyl-thiazole acetate (which was made as described in EP27019), with aqueous sodium hydroxide (IM) in aqueous methanol (1:1), and was used without further purification.
Example 2.2: Preparation of 3-[2-(2-chloro-4-methyl-thiazol-5-yl)-acetylamino1- pyrazine-2-carboxylic acid methyl ester
Figure imgf000062_0002
2-Chloro-4-methyl-thiazole acetic acid (Example 2.1) (2.50 g) was dissolved in dichloromethane (70 ml) containing dry 7V,7V-dimethylformamide ("DMF") (3 drops). The reaction mixture was stirred until homogeneous and then cooled to 0°C. Oxalyl chloride (2.66 ml) was added dropwise at 0°C, the reaction mixture was stirred at ambient temperature for 4 hours and then evaporated. The reaction mixture was re- dissolved in acetonitrile (30 ml) and added to 3-amino-pyrazine-2-carboxylic acid methyl ester (1.82 g). The reaction was heated in a microwave to 850C for 40 minutes and then cooled to ambient temperature. The reaction mixture was diluted with ethyl acetate and washed with aqueous sodium hydrogen carbonate (saturated), water and aqueous hydrochloric acid (IM) and then water again. The organic layer was dried over magnesium sulfate and concentrated. The residue was purified using column chromatography on silica gel (eluent: hexane / ethyl acetate 1:1) to give 3-[2-(2-chloro-4- methyl-thiazol-5-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester (0.98 g). 1H- NMR (400 MHz, CDCl3): 2.40 (s, 3H), 4.05 (s, 3H, 4.10 (s, 2H), 8.45 (d, IH), 8.60 (d, IH), 10.9 (s, IH) ppm.
Example 2.3: Preparation of 7-(2-chloro-4-methyl-thiazol-5-yl)-8-hvdroxy-5H- pyrido[2,3-b1pyrazin-6-one (Compound No. Bl of Table B)
Figure imgf000063_0001
3-[2-(2-Chloro-4-methyl-thiazol-5-yl)-acetylamino]-pyrazine-2-carboxylic acid methyl ester (Example 2.2) (1.020 g) was heated to 110°C with potassium carbonate (1.08 g) in dry Λf,Λf-dimethylformamide (30 ml) for 3 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with water and the mixture extracted with ethyl acetate. The aqueous fraction was acidified to pH 3 by addition of concentrated hydrochloric acid (36% by weight in water) and then extracted again with ethyl acetate. The organic fraction was washed with water, dried over magnesium sulfate, and concentrated to give Compound No. Bl of Table B (0.6 Ig ).
Example 2.4: Preparation of isobutyric acid 7-(2-chloro-4-methyl-thiazol-5-yl)-6-oxo- 5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Compound No. B9 of Table B)
Figure imgf000063_0002
pyridine
Figure imgf000063_0004
Figure imgf000063_0003
7-(2-Chloro-4-methyl-thiazol-5-yl)-8-hydroxy-57/-pyrido[2,3-b]pyrazin-6-one (Example 2.3) (0.30 g), isobutyryl chloride (0.13 ml), and pyridine (0.10 ml) were stirred in dichloromethane (15 ml) at ambient temperature for 2 hours. The reaction mixture was washed successively with aqueous hydrochloric acid (IM), aqueous sodium hydrogen carbonate (saturated) and water. The organic fraction was dried over magnesium sulfate and concentrated to give Compound No. B9 of Table B (0.220 g). Example 2.5: Preparation of isobutyric acid 7-(2-chloro-4-methyl-thiazol-5-vD-5-methyl- 6-oxo-5,6-dihvdro-pyrido[2,3-blpyrazin-8-yl ester (Compound No. B2 of Table B)
Figure imgf000064_0001
Isobutyric acid 7-(2-chloro-4-methyl-thiazol-5-yl)-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-8-yl ester (Example 2.4) (0.10 g), methyl iodide (0.18 ml) and potassium carbonate (0.075 g) were heated in acetonitrile (4 ml) in a microwave to 100°C for 10 minutes. The reaction mixture was allowed to cool to ambient temperature and then diluted with ethyl acetate and water. The phases were separated and the organic phase was washed with water, aqueous sodium hydrogen carbonate (saturated) and brine, dried over magnesium sulfate and concentrated to give Compound No. B2 of Table B (0.078 g)-
Compound Nos. B3 and B4 of Table B were made by methods analogous to the method set out in Example 2.5.
Example 2.6: Preparation of 7-(5-difluoromethoxy-l-methyl-3-trifluoromethyl-lH- pyrazol-4-yl)-8-hydroxy-5H-pyrido[2,3-b]pyrazin-6-one (Compound No. B26 of Table B)
Figure imgf000064_0002
3-[2-(5-Difluoromethoxy-l-methyl-3-trifluoromethyl-lH-pyrazol-4-yl)- acetylamino]-pyrazine-2-carboxylic acid methyl ester (0.980 g) was heated to 100°C with potassium carbonate (0.662 g) in dry N,JV-dimethylformamide (10 ml) for 3 hours. The reaction mixture was allowed to cool to ambient temperature, diluted with water and the mixture extracted with ethyl acetate. The aqueous fraction was acidified to pH 1-2 by addition of aqueous hydrochloric acid (2M) and then extracted again with ethyl acetate. The organic fraction was washed with water, dried over sodium sulfate, and concentrated to give Compound No. B26 of Table B (0.805 g).
Example 2.7: Preparation of isobutyric acid 7-(5-difluoromethoxy-l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl)-6-oxo-5,6-dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. B23 of Table B)
Figure imgf000065_0001
pyridine
Figure imgf000065_0003
Figure imgf000065_0002
7-(5-Difiuoromethoxy-l-methyl-3-trifluoromethyl-lH-pyrazol-4-yl)-8-hydroxy- 5H-pyrido[2,3-b]pyrazin-6-one (Example 2.6) (0.34 g), isobutyryl chloride (0.11 ml), and pyridine (0.10 ml) were stirred in dichloromethane (10 ml) at ambient temperature for 2 hours. The reaction mixture was washed successively with aqueous hydrochloric acid (IM), aqueous sodium hydrogen carbonate (saturated) and water. The organic fraction was dried over sodium sulfate and concentrated to give Compound No. B23 of Table B (0.335 g).
Compound No. B28 of Table B and Compound No. C5 of Table C were made by methods analogous to the method set out in Example 2.7. Example 2.8: Preparation of isobutyric acid 7-r5-difluoromethoxy-l-methyl-3- trifluoromethyl-lH-pyrazol-4-yl)-5-('2.2-difluoro-ethyl)-6-oxo-5,6-dihvdro-pyrido[2,3- bipyrazin-8-yl ester (Compound No. B24 of Table B)
Figure imgf000066_0001
Ηunigs base
Figure imgf000066_0002
Figure imgf000066_0003
Isobutyric acid 7-(5-difluor6methoxy-l -methyl-S-trifluoromethyl-lH-pyrazol^- yl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 2.7) (0.335 g), 2,2- difluoroethyl triflate (0.32 g) and Ηunigs base (0.2 ml) were stirred in acetonitrile (12 ml) at ambient temperature for 30 minutes. The reaction mixture was poured into water and extracted with ethyl acetate. The phases were separated and the organic phase was washed with water, aqueous sodium hydrogen carbonate (saturated) and brine, dried over anhydrous sodium sulfate and concentrated to give Compound No. B24 of Table B (0.28O g).
Compound No. B29 of Table B and Compound No. C6 of Table C were made by methods analogous to the method set out in Example 2.8.
Example 2.9: Preparation of 7-(5-difluoromethoxy-l-methyl-3-trifluoromethyl-lH- pwazol-4-yl)-5-(2,2-difluoro-ethyl)-8-hvdroxy-5H-pwido[2,3-b'|pyrazin-6-one (Compound No. B25 of Table B)
Figure imgf000066_0004
A solution of isobutyric acid 7-(5-difluoromethoxy-l-methyl-3-trifluoromethyl- lH-pyrazol-4-yl)-5-(2,2-difluoroethyl)-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-8-yl ester (Example 2.8) (0.138 g), sodium hydroxide (0.022 g) in methanol (4 ml) and water (1 ml) were stirred at ambient temperature for 3 hours. The reaction mixture was poured into water and neutralised by addition of aqueous hydrochloric acid (2M). The mixture was extracted with ethyl acetate. The organic phase was washed with water, aqueous sodium hydrogen carbonate (saturated) and brine, dried over anhydrous sodium sulfate and concentrated to give Compound No. B25 of Table B (0.095 g).
Compound No. B30 of Table B was made by a method analogous to the method set out in Example 2.9.
3. Example of a reaction covered by Scheme 6 Example 3.1: Preparation of methanesulfonic acid 7-(3,5-dichloro-pyrid-2-yl)-6-oxo-5,6- dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. A4 of Table A)
Figure imgf000067_0001
To a suspension of 7-(3,5-dichloro-pyrid-2-yl)-pyrido[2,3-b]pyrazine-6,8-diol (Example 1.2) (0.20 g) and N-ethyl-diisopropylamine (0.126 g) in dry dichloromethane (15 ml) was added methane sulfonyl chloride (0.074 g). The reaction mixture was stirred at ambient temperature for one hour and then stored at ambient temperature for 16 hours. The reaction mixture was diluted with aqueous hydrochloric acid (IM). The phases were separated and the organic layer was concentrated. The residue was purified by reverse phase ΗPLC to give Compound No. A4 of Table A as a pale brown solid (0.055 g). 4. Examples of reactions covered by Scheme 7
Example 4.1 : Preparation of 3-bromomethyl-2,6-dichloro-pyridine
Figure imgf000068_0001
2,6-Dichloro-3-methyl-pyridine (3.6 g), N-bromosuccinimide ("ΝBS") (3.98 g), benzoyl peroxide (catalytic amount) and carbon tetrachloride (25 ml) were heated to reflux and a 500 watt tungsten halogen lamp was used to initiate the reaction. Reflux was continued for 8 hours. The reaction mixture was filtered to remove the solids and the filtrate concentrated to yield a mixture of 3-bromomethyl-2,6-dichloro-pyridine, 3,3- dibromomethyl-2,6-dichloro-pyridine, and 2,6-dichloro-3-methyl-pyridine (58:26:16). The mixture was used without purification for the next step.
Example 4.2: Preparation of (2,6-dichloro-pyrid-3-yl)-acetonitrile
Figure imgf000068_0002
Potassium cyanide (1.0 g) was dissolved in water by heating to 4O0C. A mixture of 3-bromomethyl-2,-6-dichloro-pyridine, 3,3-dibromomethyl-2,6-dichloro-pyridine, and 2,6-dichloro-3-methyl-pyridine (Example 4.1) (3.2 g) suspended in ethanol (20 ml) was added dropwise at 4O0C over a period of 30 minutes. The reaction mixture was heated to reflux for 3 hours. The reaction mixture was cooled to 400C and another equivalent of potassium cyanide was added. The reaction mixture was heated to reflux for a further 3 hours and then stored at ambient temperature for 16 hours. The reaction mixture was filtered to remove the solids and the solids were washed with ethyl acetate. The combined filtrates were concentrated. The residue was diluted with ethyl acetate. The organic solution washed with aqueous sodium hydrogen carbonate (saturated) and brine, dried over magnesium sulfate, and concentrated. This residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane from 3 : 100 to 1 : 1) to give slightly impure (2,6-dichloro-pyrid-3-yl)-acetonitrile (1.5 g) which solidified on standing. This material was used without further purification. 1H-NMR (400 MHz, CDCl3): 3.83 (s, 2H), 7.37 (d, IH), 7.85 (d, IH) ppm. Example 4.3: Preparation of (2,6-dichloro-pyrid-3-yl)-acetic acid
Figure imgf000069_0001
(2,6-Dichloro-pyrid-3-yl)-acetonitrile (Example 4.2) (1.5 g) was dissolved in a 1 : 1 mixture of water and concentrated sulfuric acid. The reaction mixture was heated to reflux for 3 hours, then allowed to cool to ambient temperature and stored at ambient temperature for 16 hours. The reaction mixture was diluted with dichloromethane and the phases were separated. The organic phase was dried over magnesium sulfate and concentrated to give (2,6-dichloro-pyrid-3-yl)-acetic acid as a cream-coloured solid (1.174 g). 1H-NMR (400 MHz, CDCl3): 3.78 (s, 2H), 7.40 (d, IH), 7.80 (d, IH) ppm.
5. Examples of reactions covered by Scheme 8
Example 5.1: Preparation of (3,5-dichloro-pyrid-2-ylVacetic acid
Figure imgf000069_0002
To a solution of 2-(3,5-dichloro-pyrid-2-yl)-malonic acid diethyl ester (118.5 g)
(prepared as described in WO 07/101859) in methanol (1 ml) was added aqueous sodium hydroxide (47 g dissolved in 300 ml water). The reaction mixture was heated to 80°C for 1 hour. The methanol was evaporated and the pH of the aqueous phase adjusted to pH 4 by addition of glacial acetic acid and then extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate and concentrated to give (3,5- dichloro-pyrid-2-yl)-acetic acid as an off-white solid (50 g). 1H-NMR (400 MHz, CDCl3): 4.04 (s, 2H), 7.81 (d, IH), 8.45 (d, IH) ppm. 6. Examples of reactions covered by Scheme 9
Example 6.1: Preparation of 3-(3-oxo-butyrylamino)-pyrazine-2-carboxylic acid methyl ester
Figure imgf000070_0001
3-Aminopyrazine-2-carboxylic acid methyl ester (12 g) and 2,2,6-trimethyl-
[l,3]dioxin-4-one (15.6 ml) were heated to reflux for 6 hours. The reaction mixture was concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 4:1, then ethyl acetate) to give 3-(3-oxo-butyrylamino)-pyrazine-2- carboxylic acid methyl ester as a beige solid (15 g). 1H-NMR (400 MHz, CDCl3): 2.33 (s, 3H), 3.91 (s, 2H), 4.05 (s, 3H), 8.40 (d, IH), 8.51 (d, IH), 10.06 (s, IH) ppm.
Example 6.2: Preparation of l-(6,8-dihvdroxy-pwido[2,3-b]pyrazin-7-yl)-ethanone
3-(3-Oxo-butyrylamino)-pyrazine-2-carboxylic acid methyl ester (Example 6.1) (15 g) in methanol (80 ml) was added to a suspension of sodium methoxide (7.2 g) in methanol (80 ml). The suspension was heated to reflux for 2 hours and then stored for 16 hours at ambient temperature. The mixture was filtered and the filtrate was acidified to pH 1 by addition of concentrated hydrochloric acid (36% by weight in water) and then filtered again. The solid was washed with water and then diethyl ether to give l-(6,8- dihydroxy-pyrido[2,3-b]pyrazin-7-yl)-ethanone (10.1 g). 1H-NMR (400 MHz, d6- DMSO): 2.70 (s, 3H), 8.60 (d, IH), 8.71 (d, IH), 12.2 (s, IH), 16.25 (s, IH) ppm. Example 6.3: Preparation of 8-hvdroxy-7-(fZV4A4-trifluoro-14lvdroxy-3-oxo-but-l- envD-5H-pyrido['2,3-b^pyrazin-6-one
Figure imgf000071_0001
To a suspension of l-(6,8-dihydroxy-pyrido[2,3-b]pyrazin-7-yl)-ethanone (Example 6.2) (1.0 g) in ethyl trifluoroacetate (14 ml) and was added sodium (0.56 g) in portions. The reaction mixture was heated to reflux for 4 hours. The reaction mixture was stored at ambient temperature for 16 hours and then poured into aqueous acetic acid (1 :1). The solid was isolated by filtration and washed with water, ethanol, ethyl acetate and diethyl ether and then dried to give a yellow solid (0.760 g). The solid was heated to reflux for a further two days in ethyl trifluoroacetate (14 ml) and sodium (0.56 g) and worked up similarly to give a darker yellow solid (0.515 g), which in turn was heated to reflux again in ethyl trifluoroacetate (7 ml) and sodium (0.290 g) and worked up similarly to give 8-hydroxy-7-(Z)-4,4,4-trifluoro-l-hydroxy-3-oxo-but-l-enyl)-5H- pyrido[2,3-b]pyrazin-6-one as a dark yellow solid (0.190 g). 1H-NMR (400 MHz, d6- DMSO): 7.30 (s, IH), 8.45 (d, IH), 8.51 (d, IH), 11.36 (s, IH), 11.97 (s, IH) ppm.
Example 6.4: Preparation of 4A4-trifluoro-l-(8-hvdroxy-6-oxo-5,6-dihvdro-pyrido[2,3- b1pyrazin-7-yl)-butane-l,3-dione 3-oxime
Figure imgf000071_0002
To a suspension of 4,4,4-trifluoro-l-(8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-7-yl)-butane-l,3-dione (Example 6.3) (0.170 g) in ethanol (2 ml) was added hydroxylamine hydrochloride (0.050 g). The reaction mixture was heated to reflux for 4 hours and was then stored at ambient temperature for 16 hours. The solid was isolated by filtration and washed with ethanol, ethyl acetate, and diethyl ether and dried to give 4,4,4-trifluoro-l-(8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazin-7-yl)-butane-l,3- dione 3-oxime as a brown solid (0.078 g). 1H-NMR (400 MHz, d6-DMSO): 3.61 (d, IH), 3.86 (d, IH), 8.57 (d, IH), 8.67 (d, IH), 12.35 (s, IH) ppm. Example 6.5: Preparation of 8-hydroxy-7-(3-trifluoromethyl-isoxazol-5-yl)-5H- Pyridor2,3-blpyrazin-6-one (Compound No. BlO of Table B)
Figure imgf000072_0001
A suspension of 4,4,4-trifluoro-l-(8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazin-7-yl)-butane-l,3-dione 3-oxime (Example 6.4) (0.068 g) in trifluoroacetic acid ("TFA") (0.5 ml) was heated to reflux for 7 hours. The solid was isolated by filtration and washed with diethyl ether and then dried. The solid was heated to reflux again in trifluoroacetic acid ("TFA") (2.0 ml) for 2 days and worked up similarly to give Compound No. BlO of Table B (0.050 g).
Compound Nos. B13, B14 and B15 of Table B and Compound No. Cl of Table C were made by methods analogous to the methods set out in Example 6.3, Example 6.4 and Example 6.5.
Example 6.6: Preparation of isobutyric acid 6-hvdroxy-7-(3-trifluoromethyl-isoxazol-5- yl)-pyridor2,3-b1pyrazin-8-yl ester (Compound No. B7 of Table B)
Figure imgf000072_0002
Figure imgf000072_0004
pyridine
Figure imgf000072_0003
To a solution of 8-hydroxy-7-(3-trifluoromethyl-isoxazol-5-yl)-5H-pyrido[2,3- b]pyrazin-6-one (Example 6.5) (0.037 g) and pyridine (0.1 ml) in dichloromethane (2 ml) was added dropwise isobutyryl chloride (0.05 ml). The reaction mixture was stirred at ambient temperature for 6 hours and stored at ambient temperature for 16 hours. The reaction mixture was diluted with ethyl acetate, and the organic phase was washed successively with water, aqueous sodium hydrogen carbonate (saturated) and brine. The organic phase was dried over magnesium sulfate and concentrated to give Compound No. B7 of Table B as a pale yellow solid (0.038 g).
Compound Nos. B 16, B 17, B18 and B19 of Table B and Compound Nos. C2 and C4 were made by methods analogous to the method set out in Example 6.6.
Example 6.7: Preparation of isobutyric acid 5-methyl-6-oxo-7-(3-trifluoromethyl- isoxazol-5-yl)-5,6-dihvdro-pyrido[2,3-b1pyrazin-8-yl ester (Compound No. B8 of Table B)
Figure imgf000073_0001
Potassium carbonate (0.023 g) and methyl iodide (0.01 ml) were added to isobutyric acid 6-hydroxy-7-(3-trifluoromethyl-isoxazol-5-yl)-pyrido[2,3-b]pyrazin-8-yl ester (Example 6.6) (0.030 g) in acetonitrile (1.5 ml). The reaction mixture was heated in a microwave to 100°C for 10 minutes. The reaction mixture was diluted with ethyl acetate and water. The phases were separated. The organic phase was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 1 :2 to 1 : 1) to give Compound No. B8 of Table B (0.025 g) as a colourless oil that solidified on standing.
Compound Nos. B20, B21 and B22 of Table B and Compound No. C3 of Table C were made by methods analogous to the method set out in Example 6.7. 7. Examples of reactions covered by Scheme 10
Example 7.1: Preparation of 8-hvdroxy-6-oxo-5,6-dihvdro-pyrido|"2.3-b1pyrazine-7- carboxylic acid methyl ester
Figure imgf000074_0001
Sodium methoxide (6.5 ml) (30% by weight in methanol) was dissolved in methanol (75 ml) at room temperature. Dimethyl malonate (3.7 ml) was added dropwise at ambient temperature over a period of 20 minutes and the reaction stirred at ambient temperature for 1 hour. Methyl 3-aminopyrazine-2-carboxylate (5.0 g) was added in portions at ambient temperature over a period of 40 minutes. The reaction mixture was heated to reflux for 3 days, and then allowed to cool. The solvent was concentrated. The residue was dissolved in water and acidified with concentrated hydrochloric acid (36% by weight in water). The precipitate was isolated, washed with water, methanol and ethyl acetate, and dried under high vacuum to give 8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazine-7-carboxylic acid methyl ester as a beige solid (4.16 g). 1H-NMR (d6- DMSO): 3.80 (s, 3H), 8.59 (s, IH), 8.70 (s, IH) ppm.
Example 7.2: Preparation of 8-isobutyryloxy-6-oxo-5,6-dihvdro-pyridor2,3-b1pyrazme-7- carboxylic acid methyl ester
Figure imgf000074_0002
Figure imgf000074_0004
molecular sieves
Figure imgf000074_0003
To a suspension of 8-hydroxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7- carboxylic acid methyl ester (Example 7.1) in 1,2-dichloro-ethane (9 ml) was added powdered molecular sieves (4A) followed by dropwise addition of isobutyryl chloride (0.048 ml). The reaction mixture was heated to reflux for 5 hours, cooled to ambient temperature and filtered. The filtrate was concentrated to give 8-isobutyryloxy-6-oxo- 5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester as a light brown solid (0.166 g) which was used without further purification.
Example 7.3: Preparation of 8-isobutyryloxy-5-methyl-6-oxo-5,6-dihvdro-pyrido|"2,3- bipyrazine-7-carboxylic acid methyl ester
Figure imgf000075_0001
To a suspension of 8-isobutyryloxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7- carboxylic acid methyl ester (0.422 g) (Example 7.2) in acetonitrile (12 ml) was added potassium carbonate (0.401 g) followed by methyl iodide (0.30 ml). The reaction mixture was heated to 100°C for 10 minutes in a microwave, and then cooled to ambient temperature. The reaction mixture was diluted with ethyl acetate and water. The phases were separated. The organic phase was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 1:2 to 1:1) to give 8- isobutyryloxy-5-methyl-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid ^ methyl ester as an orange oil (0.418 g). 1H-NMR (400 MHz, CDCl3): 1.36 (d, 6H), 2.95 (sept, IH), 3.79 (s, 3H), 3.94 (s, 3H), 8.49 (d, IH), 8.59 (d, IH) ppm.
Example 7.4: Preparation of 8-hvdroxy-5-methyl-7-(3-methyl-l,2,4-oxadiazol-5-yr)-5H- Pyrido[2,3-blpyrazin-6-one (Compound No. B5 of Table 5)
Figure imgf000075_0002
To a solution of 8-isobutyryloxy-5-methyl-6-oxo-5,6-dihydro-pyrido[2,3- b]pyrazine-7-carboxylic acid methyl ester (Example 7.3) (0.10 g) in toluene (4 ml) was added iV-hydroxy-acetamidine (0.025 g). The reaction mixture was heated to reflux for 16 hours. The reaction mixture was cooled to ambient temperature and the solid was isolated by filtration and dried to give Compound No. B5 of Table 5 (0.050 g).
Example 7.5: Preparation of isobutyric acid 5-methyl-7-(3-methyl-l,2,4-oxadiazol-5-yl)- 6-oxo-5,6-dihydro-pyridof2,3-b]pyrazin-8-yl ester (Compound No. B6 of Table B)
Figure imgf000076_0001
pyridine
Figure imgf000076_0003
Figure imgf000076_0002
To a solution of 8-hydroxy-5-methyl-7-(3-methyl-l,2,4-oxadiazol-5-yl)-5H- pyrido[2,3-b]pyrazin-6-one (Example 7.4) (0.044 g) and pyridine (0.018 ml) in dichloromethane (1 ml) was added dropwise isobutyryl chloride (0.022 ml). The reaction mixture was stirred at ambient temperature for 4 hours and then stored at ambient temperature for 16 hours. The reaction mixture was diluted with more dichloromethane and the mixture was washed successively with aqueous sodium hydrogen carbonate (saturated), aqueous ammonium chloride (saturated) and brine. The organic fraction was dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate / hexane 1 : 1) to give Compound No. B6 of Table 6 as a pale yellow solid (0.020 g).
Table A:
Compounds of formula (A), where R \ 3 , R Ti 4 a _ „nd j τ R> 5 have the values as described in the table below and R4 is a 6-membered ring.
(A)
Figure imgf000076_0004
Figure imgf000077_0001
Figure imgf000078_0001
Figure imgf000079_0002
Table B:
Compounds of formula (B), where R >3 , r R>4 and j r R> 5 have the values as described in the table below, and R4 is a 5-membered ring.
Figure imgf000079_0001
Figure imgf000079_0003
Figure imgf000080_0001
Figure imgf000081_0001
Figure imgf000082_0002
Table C:
Compounds of formula (C), where R > 3 , R and R have the values as described in the table below, and R4 is a bicyclic ring.
Figure imgf000082_0001
Figure imgf000082_0003
Figure imgf000083_0001
Biological Examples Example Bl: Herbicidal action
Seeds of a variety of test species were sown in sterilised standard soil in seed trays each having 96 cells. After cultivation for 8 to 9 days cultivation (post-emergence) under controlled conditions in a climatic chamber (cultivation at 23/170C, day/night; 13 hours light; 50-60% humidity), the plants were treated with an aqueous spray solution of 1000 mg/1 of the active ingredient dissolved in 10% DMSO (dimethyl sulfoxide, CAS RN 67-68-5) as a solvent, equivalent to 1000 g/ha. The plants were grown in the climatic chamber after application at (24/190C, day/night; 13 hours light; 50-60% humidity) and watered twice daily. After 9 days until the test was evaluated (10 = total damage to plant, 0 = no damage to plant)
Table Bl: Application post-emergence
Comp No. Rate (g/ha) STEME NAAOF AMARE SOLNI
A2 1000 5 5 0 0
A6 1000 3 5 2 0
A7 1000 7 7 7 0
B2 1000 0 5 0 0 B3 1000 2 6 0 0
B4 1000 2 8 0 3
B5 1000 0 0 3 0
B8 1000 0 2 0 2
BI l 1000 5 5 3 2
B12 1000 0 0 6 0
C4 1000 0 0 0 2
STEME = Stellaria media; NAAOF = Nasturtium officinale; AMARE = Amaranthus retroflexus ; SOLNI = Solanum nigrum.
Compound Nos. Al, A3, A4, A5, A17, A28 and A29 of Table A, Compound Nos. Bl, B6, B7, B13, B14, B15, B16, B17, B18, B19, B20, B21 and B22 of Table B and Compound Nos. Cl, C2 and C3 of Table 3 were tested using the same protocol and showed little or no damage to the test plants under the test conditions. Compound Nos. B9 and BlO of Table B were not tested under these protocols so no data is available for these compounds.
Example B2: Herbicidal action Seeds of a variety of test species were sown in standard soil in pots. After cultivation for one day (pre-emergence) or after 8 days cultivation (post-emergence) under controlled conditions in a glasshouse (at 24/16°C, day/night; 14 hours light; 65% humidity), the plants were sprayed with an aqueous spray solution derived from the formulation of the technical active ingredient in acetone / water (50:50) solution containing 0.5% Tween 20 (polyoxyethelyene sorbitan monolaurate, CAS RN 9005-64- 5). The test plants were then grown in a glasshouse under controlled conditions in a glasshouse (at 24/160C, day/night; 14 hours light; 65% humidity) and watered twice daily. After 13 days, the test was evaluated (10 = total damage to plant; 0 = no damage to plant).
Table B2: Application pre-emergence
Comp No. Rate (g/ha) SOLNI AMARE SETFA ECHCG IPOHE
A9 1000 1 0 0 5 5 AlO 1000 2 0 1 5 2
Al l 1000 8 8 7 8 5
A12 1000 2 4 4 6 5
A14 1000 0 0 2 4 0 A16 1000 5 0 0 2 2
A18 1000 9 6 5 7 6
A19 1000 0 7 0 5 1
A20 250 1 1 0 3 0
A21 1000 0 2 2 0 0 A30 250 1 1 0 3 0
B24 1000 8 10 7 8 5
B25 1000 7 10 8 8 6
B26 1000 0 1 0 1 0
B28 1000 0 7 0 0 0 B29 1000 2 4 3 1 1
B30 1000 2 7 2 1 3
SOLNI = Solanum nigrum; AMARE = Amaranthus retroflexus; SETFA = Setaria faberi; ECHCG = Echinochloa crus-galli; IPOHE = Ipomea hederaceae.
Compound Nos. A8, A13 and A15 of Table A, Compound Nos. B23 and B27 of
Table B, Compound Nos. C5 and C6 of Table C, were tested using the same protocol and showed little or no damage to the test plants under the test conditions. Compound Nos. A22, A23, A24, A25, A26 and A27 of Table A were not tested under these protocols so no data is available for these compounds.
Table B3: Application post-emergence
Comp No. Rate (g/ha) SOLNI AMARE SETFA ECHCG IP'
A8 1000 1 0 0 0 1
A9 1000 8 8 4 7 8
AlO 1000 9 9 6 7 8
Al l 1000 8 9 8 8 8
A12 1000 10 9 8 8 9 A13 1000 5 6 6 6 6
A14 1000 7 5 7 6 4
A15 250 4 2 0 3 4
A16 1000 9 10 6 6 7 A18 1000 9 10 7 7 9
A19 1000 10 10 4 6 8
A20 250 10 10 2 7 10
A21 1000 8 9 7 7 7
A30 250 6 9 4 1 6 B23 250 1 3 4 2 2
B24 1000 10 9 8 8 8
B25 1000 10 8 8 8 8
B26 1000 3 5 8 6 3
B27 1000 0 0 3 1 1 B28 1000 1 0 1 0 0
B29 1000 7 8 7 3 7
B30 1000 9 9 7 6 8
C6 1000 2 3 0 0 0
SOLNI = Solanum nigrum; AMARE = Amaranthus retroflexus; SETFA = Setaria faberi; ECHCG = Echinochloa crus-galli; IPOHE = Ipomea hederaceae.
Compound No. C5 of Table C was tested using the same protocol and showed little or no damage to the test plants under the test conditions. Compound Nos. A22, A23, A24, A25, A26 and A27 of Table A were not tested under these protocols so no data is available for these compounds.

Claims

CLAIMS:
1. A method of controlling plants which comprises applying to the plants or to the locus thereof a herbicidally effective amount of a compound of formula (I)
Figure imgf000087_0001
wherein R1 and R2 are independently hydrogen, CpQalkyl, C1-C4haloalkyl, halo, cyano, hydroxy, Ci-C4alkoxy, C1-C4alkylthio, aryl or aryl substituted by one to five R6, which may be the same or different, or heteroaryl or heteroaryl substituted by one to five R6, which may be the same or different; R3 is hydrogen, C]-CiOalkyl, Ci-C4haloalkyl, C2-Ci0alkenyl, C2-C4haloalkenyl, C2-C10alkynyl, C2-C4haloalkynyl, C3-C]0cycloalkyl, C3-Ciocycloalkyl-CrC6alkyl-, C1- Ci0alkoxy-Ci-C6alkyl-, Ci-Ciocyanoalkyl-, Ci-Cioalkoxycarbonyl-Ci-Cόalkyl-, N-C1- C3alkyl-aminocarbonyl-Ci-C6alkyl-, N,N-di-(Ci-C3alkyl)-aminocarbonyl-C]-C6alkyl-, aryl-C]-C6alkyl- or aryl-Ci-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Ci-Cόalkyl- or heterocyclyl-Ci-Cβalkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different;
R is heteroaryl or heteroaryl substituted by one to four R8, which may be the same or different; R5 is hydroxy or a group which can be metabolised to a hydroxy group; each R6, R7 and R8 is independently halo, cyano, nitro, C1-C1OaIlCyI, Q-C^aloalkyl, C2- Cioalkenyl, C2-Ci0alkynyl, hydroxy, C]-C10alkoxy, d-C4haloalkoxy, C]-Ci0alkoxy-Ci- Qalkyl-, C3-C7cycloalkyl, C3-C7cycloalkoxy, C3-C7cycloalkyl-C1-C4alkyl-, C3- C7cycloalkyl-C]-C4alkoxy-, Ci-C6alkylcarbonyl-, formyl, d-C4alkoxycarbonyl-, C1- C4alkylcarbonyloxy-, Ci-C10alkylthio-, Ci-C4haloalkylthio-, CrCiOalkylsulfinyl-, Ci- C4haloalkylsulfinyl-, Ci-Cioalkylsulfonyl-, Ci-C4haloalkylsulfonyl-, amino, C1- Cioalkylamino-, di-C]-Ci0alkylamino-, Ci-Cioalkylcarbonylamino-, aryl or aryl substituted by one to three R13, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R13, which may be the same or different, aryl-Ci- C4alkyl- or aryl-C i-C4alkyl- wherein the aryl moiety is substituted by one to three R13, which may be the same or different, heteroaryl-Ci-C4alkyl- or heteroaryl-Ci-C4alkyl- wherein the heteroaryl moiety is substituted by one to three R , which may be the same or different, aryloxy- or aryloxy- substituted by one to three R1 , which may be the same or different, heteroaryloxy- or heteroaryloxy- substituted by one to three R13, which may be the same or different, arylthio- or arylthio- substituted by one to three R13, which may be the same or different, or heteroarylthio- or heteroarylthio- substituted by one to three R13, which may be the same or different; and each R13 is independently halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or Ci-C6alkoxy; or a salt or N-oxide thereof.
2. A method according to claim 1 wherein R1 is hydrogen, C!-C4alkyl, C1- C4haloalkyl, halo, cyano, hydroxy or Ci-C4alkoxy.
3. A method according to claim 1 or claim 2 wherein R is hydrogen, Ci-C4alkyl, Ci-C4haloalkyl, halo, cyano, hydroxy or Ci-C4alkoxy.
4. A method according to any one of claims 1 to 3 wherein R3 is hydrogen, Ci-C4alkyl, Q-Qhaloalkyl, C2-C4alkenyl, C2-C4haloalkenyl, C2-C4alkynyl or C2-C4haloalkynyl .
5. A method according to any one of claims 1 to 4 wherein R4 is heteroaryl substituted by one to three R8, which may be the same or different.
6. A method according to any one of claims 1 to 5 wherein R5 is hydroxy, R9-oxy-,
R10-carbonyloxy-, tri-Rn-silyloxy- or R12-sulfonyloxy-, wherein
R9 is Ci-Cioalkyl, C2-C10alkenyl, C2-Ci0alkynyl or aryl-Ci-C4alkyl- or aryl-C]-C4alkyl- wherein the aryl moiety is substituted by one to five substituents independently selected from halo, cyano, nitro, Q-Cόalkyl, C]-C6haloalkyl or d-C6alkoxy; R10 is Ci-Cioalkyl, C3-C10cycloalkyl, C3-C10cycloalkyl-Ci-C10alkyl-, d-C10haloalkyl, C2- Cioalkenyl, C2-Ci0alkynyl, CrC4alkoxy-Ci-Ci0alkyl-, C1-C4alkylthio-C1-C4alkyl-, Ci- Ci0alkoxy, C2-Ci0alkenyloxy, C2-Cioalkynyloxy, Ci-Ci0alkylthio-, JV-d-Gjalkyl-amino-, N,N-di-(Ci-C4alkyl)-amino-, aryl or aryl substituted by one to three R14, which may be the same or different, heteroaryl or heteroaryl substituted by one to three R14, which may be the same or different, aryl-Ci-C4alkyl- or aryl-Ci-C4alkyl- wherein the aryl moiety is substituted by one to three R14, which may be the same or different, heteroaryl-Q- C4alkyl- or heteroaryl-Ci-C4alkyl- wherein the heteroaryl moiety is substituted by one to three R14, which may be the same or different, aryloxy- or aryloxy- substituted by one to three R14, which may be the same or different, heteroaryloxy- or heteroaryloxy- substituted by one to three R14, which may be the same or different, arylthio- or arylthio- substituted by one to three R14, which may be the same or different, or heteroarylthio- or heteroarylthio- substituted by one to three R14, which may be the same or different; each R1 ' is independently Ci-CiOalkyl or phenyl or phenyl substituted by one to five substituents independently selected from halo, cyano, nitro, C]-C6alkyl, Ci-C6haloalkyl or d-C6alkoxy;
R12 is Ci-C10alkyl, Ci-Qohaloalkyl, or phenyl or phenyl substituted by one to five substituents independently selected from halo, cyano, nitro, Ci-C6alkyl, Ci-C6haloalkyl or C!-C6alkoxy; and each R14 is independently halo, cyano, nitro, Ci-CiOalkyl, C1-C4haloalkyl, C]-C10alkoxy, Ci-dalkoxycarbonyl-, Ci-C4haloalkoxy, Ci-Ci0alkylthio-, Q-Gihaloalkylthio-, Ci- C]Oalkylsulfinyl-, Ci-C4haloalkylsulfinyl-, Ci-Cioalkylsulfonyl-, Ci-Gthaloalkylsulfonyl-, aryl or aryl substituted by one to five substituents independently selected from halo, cyano, nitro, d-C6alkyl, Ci-Cβhaloalkyl or Ci-Cβalkoxy, or heteroaryl or heteroaryl substituted by one to four substituents independently selected from halo, cyano, nitro, Q- C6alkyl, Ci-C6haloalkyl or d-C6alkoxy.
7. A compound of formula (Ib)
Figure imgf000089_0001
wherein R , R and R are as defined in claim 1 and R5 is a group which can be metabolised to a hydroxy group; or a salt or N-oxide thereof.
8. A compound of formula (Ic)
Figure imgf000090_0001
wherein R1, R2 and R4 are as defined in claim 1 and R3 is Ci-Cioalkyl, C2-Ci0alkenyl, C2-Cioalkynyl, C3-Ci0cycloalkyl, C3-Ci0cycloalkyl-Ci-C6alkyl-, C1-C1OaIkOXy-C1- C6alkyl-, CpCjocyanoalkyl-, C]-Cioalkoxycarbonyl-C]-C6alkyl-, Λ/-Ci-C3alkyl- aminocarbonyl-CrC6alkyl-, iV>Λr-di-(Ci-C3alkyl)-aminocarbonyl-Ci-C6alkyl-, aryl-Cr C6alkyl- or aryl-C]-C6alkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Ci-Cόalkyl- or heterocyc IyI-C1- C6alkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; and R5 is a group which can be metabolised to a hydroxy group; or a salt or iV-oxide thereof.
9. A compound of formula (Id)
Figure imgf000090_0002
wherein R1, R2 and R4 are as defined in claim 1 and R3 is CrC10alkyl, C2-C10alkenyl, C2-C1 oalkynyl, C3-Ci0cycloalkyl, Ca-docycloalkyl-d-Cόalkyl-, d-Cioalkoxy-Ci- C6alkyl-, Q-Ciocyanoalkyl-, Ci-doalkoxycarbonyl-Cj-Cόalkyl-, N-Ci-C3alkyl- aminocarbonyl-Ci-Coalkyl-, NN-di-^i-Csalky^-aminocarbonyl-CrCόalkyl-, aryl-Ci- C6alkyl- or aryl-Q-Cόalkyl- wherein the aryl moiety is substituted by one to three R7, which may be the same or different, or heterocyclyl-Ci-Cδalkyl- or heterocyc IyI-C i- Qalkyl- wherein the heterocyclyl moiety is substituted by one to three R7, which may be the same or different; or a salt or iV-oxide thereof.
10. A herbicidal composition which comprises a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 6 in addition to formulation adjuvants.
11. A herbicidal composition which comprises a herbicidally effective amount of a compound of formula (I) as defined in any one of claims 1 to 6, optionally one or more further herbicides, and optionally one or more safeners.
PCT/GB2009/000127 2008-01-17 2009-01-16 Herbicidal compounds WO2009090402A2 (en)

Priority Applications (11)

Application Number Priority Date Filing Date Title
EP09701563.0A EP2254416B1 (en) 2008-01-17 2009-01-16 Herbicidal compounds
US12/863,286 US8338598B2 (en) 2008-01-17 2009-01-16 Herbicidal pyrido[2,3-B]pyrazines and their use as herbicides
JP2010542684A JP5596556B2 (en) 2008-01-17 2009-01-16 Herbicidal compounds
CA2711920A CA2711920C (en) 2008-01-17 2009-01-16 Pyrido|2,3-b|pyrazines and their use as herbicidal compounds
CN200980105079.1A CN101945581B (en) 2008-01-17 2009-01-16 Herbicidal compounds
BRPI0906794-9A BRPI0906794A2 (en) 2008-01-17 2009-01-16 Method for controlling plants, compost, and herbicidal composition
AU2009204688A AU2009204688B2 (en) 2008-01-17 2009-01-16 Herbicidal compounds
EA201070858A EA017629B1 (en) 2008-01-17 2009-01-16 Herbicidal compounds
MX2010007679A MX2010007679A (en) 2008-01-17 2009-01-16 Herbicidal compounds.
ZA2010/05096A ZA201005096B (en) 2008-01-17 2010-07-16 Herbicidal compounds
US13/723,270 US8653078B2 (en) 2008-01-17 2012-12-21 Herbicidal pyrido[2,3-b]pyrazines

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0800856.7 2008-01-17
GBGB0800856.7A GB0800856D0 (en) 2008-01-17 2008-01-17 Herbicidal compounds

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/863,286 A-371-Of-International US8338598B2 (en) 2008-01-17 2009-01-16 Herbicidal pyrido[2,3-B]pyrazines and their use as herbicides
US13/723,270 Division US8653078B2 (en) 2008-01-17 2012-12-21 Herbicidal pyrido[2,3-b]pyrazines

Publications (2)

Publication Number Publication Date
WO2009090402A2 true WO2009090402A2 (en) 2009-07-23
WO2009090402A3 WO2009090402A3 (en) 2010-06-24

Family

ID=39165931

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2009/000127 WO2009090402A2 (en) 2008-01-17 2009-01-16 Herbicidal compounds

Country Status (14)

Country Link
US (2) US8338598B2 (en)
EP (1) EP2254416B1 (en)
JP (1) JP5596556B2 (en)
KR (1) KR20100105882A (en)
CN (1) CN101945581B (en)
AU (1) AU2009204688B2 (en)
BR (1) BRPI0906794A2 (en)
CA (1) CA2711920C (en)
CO (1) CO6280583A2 (en)
EA (1) EA017629B1 (en)
GB (1) GB0800856D0 (en)
MX (1) MX2010007679A (en)
WO (1) WO2009090402A2 (en)
ZA (1) ZA201005096B (en)

Cited By (55)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010139658A1 (en) * 2009-06-05 2010-12-09 Basf Se Substituted pyridopyrazines with a herbicidal action
DE102010042866A1 (en) 2009-10-30 2011-05-05 Basf Se New thioamide compounds, useful for controlling undesirable plant growth or weeds in cultural plants e.g. Arachis hypogaea, Allium cepa, Elaeis guineensis and Gossypium herbaceum
WO2011057942A1 (en) 2009-11-12 2011-05-19 Basf Se Insecticidal methods using pyridine compounds
WO2011057989A1 (en) 2009-11-11 2011-05-19 Basf Se Heterocyclic compounds having herbicidal action
WO2011058036A1 (en) 2009-11-13 2011-05-19 Basf Se Tricyclic compounds having herbicidal action
WO2011117273A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridazines having herbicidal action
WO2011117211A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridazines having herbicidal action
WO2011117195A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridines having herbicidal action
WO2011117210A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridines having herbicidal action
WO2012062531A1 (en) 2010-11-12 2012-05-18 Syngenta Limited Herbicidal compounds
US8338337B2 (en) 2008-10-29 2012-12-25 Basf Se Substituted pyridines having a herbicidal effect
WO2013039990A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013040021A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013040117A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013040049A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013040057A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
DE112011101566T5 (en) 2010-05-04 2013-05-08 Basf Se PLANTS WITH INCREASED HERBICID TOLERANCE
WO2014043435A1 (en) 2012-09-14 2014-03-20 Bayer Cropscience Lp Hppd variants and methods of use
AU2012284088A8 (en) * 2011-07-19 2014-05-01 Infinity Pharmaceuticals Inc. Heterocyclic compounds and uses thereof
WO2014151255A1 (en) 2013-03-15 2014-09-25 Monsanto Technology Llc Methods and compositions for weed control
WO2015108982A2 (en) 2014-01-15 2015-07-23 Monsanto Technology Llc Methods and compositions for weed control using epsps polynucleotides
US9121022B2 (en) 2010-03-08 2015-09-01 Monsanto Technology Llc Method for controlling herbicide-resistant plants
WO2015138394A2 (en) 2014-03-11 2015-09-17 Bayer Cropscience Lp Hppd variants and methods of use
US9416363B2 (en) 2011-09-13 2016-08-16 Monsanto Technology Llc Methods and compositions for weed control
US9422557B2 (en) 2011-09-13 2016-08-23 Monsanto Technology Llc Methods and compositions for weed control
US9540642B2 (en) 2013-11-04 2017-01-10 The United States Of America, As Represented By The Secretary Of Agriculture Compositions and methods for controlling arthropod parasite and pest infestations
WO2017042259A1 (en) 2015-09-11 2017-03-16 Bayer Cropscience Aktiengesellschaft Hppd variants and methods of use
US9777288B2 (en) 2013-07-19 2017-10-03 Monsanto Technology Llc Compositions and methods for controlling leptinotarsa
US9850496B2 (en) 2013-07-19 2017-12-26 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US10041068B2 (en) 2013-01-01 2018-08-07 A. B. Seeds Ltd. Isolated dsRNA molecules and methods of using same for silencing target molecules of interest
WO2018165091A1 (en) 2017-03-07 2018-09-13 Bayer Cropscience Lp Hppd variants and methods of use
US10240162B2 (en) 2012-05-24 2019-03-26 A.B. Seeds Ltd. Compositions and methods for silencing gene expression
WO2019083808A1 (en) 2017-10-24 2019-05-02 Basf Se Improvement of herbicide tolerance to hppd inhibitors by down-regulation of putative 4-hydroxyphenylpyruvate reductases in soybean
WO2019083810A1 (en) 2017-10-24 2019-05-02 Basf Se Improvement of herbicide tolerance to 4-hydroxyphenylpyruvate dioxygenase (hppd) inhibitors by down-regulation of hppd expression in soybean
US10294488B2 (en) 2012-12-18 2019-05-21 Basf Se Herbicide-metabolizing cytochrome P450 monooxygenases
US10378012B2 (en) 2014-07-29 2019-08-13 Monsanto Technology Llc Compositions and methods for controlling insect pests
US10557138B2 (en) 2013-12-10 2020-02-11 Beeologics, Inc. Compositions and methods for virus control in Varroa mite and bees
US10609930B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
US10612019B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
US10655136B2 (en) 2015-06-03 2020-05-19 Monsanto Technology Llc Methods and compositions for introducing nucleic acids into plants
US10683505B2 (en) 2013-01-01 2020-06-16 Monsanto Technology Llc Methods of introducing dsRNA to plant seeds for modulating gene expression
US10760086B2 (en) 2011-09-13 2020-09-01 Monsanto Technology Llc Methods and compositions for weed control
US10801035B2 (en) 2011-11-02 2020-10-13 Basf Se Plants having increased tolerance to herbicides
US10801028B2 (en) 2009-10-14 2020-10-13 Beeologics Inc. Compositions for controlling Varroa mites in bees
US10806146B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
US10829828B2 (en) 2011-09-13 2020-11-10 Monsanto Technology Llc Methods and compositions for weed control
US10829778B2 (en) 2013-04-30 2020-11-10 Basf Se Plants having increased tolerance to herbicides
US10883103B2 (en) 2015-06-02 2021-01-05 Monsanto Technology Llc Compositions and methods for delivery of a polynucleotide into a plant
US10888579B2 (en) 2007-11-07 2021-01-12 Beeologics Inc. Compositions for conferring tolerance to viral disease in social insects, and the use thereof
US10968449B2 (en) 2015-01-22 2021-04-06 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US10988764B2 (en) 2014-06-23 2021-04-27 Monsanto Technology Llc Compositions and methods for regulating gene expression via RNA interference
US11091770B2 (en) 2014-04-01 2021-08-17 Monsanto Technology Llc Compositions and methods for controlling insect pests
US11180770B2 (en) 2017-03-07 2021-11-23 BASF Agricultural Solutions Seed US LLC HPPD variants and methods of use
US11230717B2 (en) 2013-04-30 2022-01-25 Basf Se Plants having increased tolerance to herbicides
US11807857B2 (en) 2014-06-25 2023-11-07 Monsanto Technology Llc Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9493130B2 (en) * 2011-04-22 2016-11-15 Angel A. Penilla Methods and systems for communicating content to connected vehicle users based detected tone/mood in voice input
WO2024173781A1 (en) * 2023-02-16 2024-08-22 Ohio State Innovation Foundation Type ii topoisomerase inhibitors and methods of making and using thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003010145A1 (en) * 2001-07-20 2003-02-06 Bayer Cropscience Ag Biphenyl-substituted 4-hydroxy-quinolones and their use as pesticides and herbicides
WO2004056825A1 (en) * 2002-12-23 2004-07-08 Syngenta Limited Pyridodiazines as plant fungicides
WO2005123733A1 (en) * 2004-06-22 2005-12-29 Syngenta Participations Ag Pyridopyrazines for combatting phytopathogenic fungi

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0614471D0 (en) * 2006-07-20 2006-08-30 Syngenta Ltd Herbicidal Compounds

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003010145A1 (en) * 2001-07-20 2003-02-06 Bayer Cropscience Ag Biphenyl-substituted 4-hydroxy-quinolones and their use as pesticides and herbicides
WO2004056825A1 (en) * 2002-12-23 2004-07-08 Syngenta Limited Pyridodiazines as plant fungicides
WO2005123733A1 (en) * 2004-06-22 2005-12-29 Syngenta Participations Ag Pyridopyrazines for combatting phytopathogenic fungi

Cited By (85)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US10888579B2 (en) 2007-11-07 2021-01-12 Beeologics Inc. Compositions for conferring tolerance to viral disease in social insects, and the use thereof
US8338337B2 (en) 2008-10-29 2012-12-25 Basf Se Substituted pyridines having a herbicidal effect
WO2010139658A1 (en) * 2009-06-05 2010-12-09 Basf Se Substituted pyridopyrazines with a herbicidal action
US8841298B2 (en) 2009-06-05 2014-09-23 Basf Se Substituted pyrano[2,3-B]pyrazines as herbicides
US10801028B2 (en) 2009-10-14 2020-10-13 Beeologics Inc. Compositions for controlling Varroa mites in bees
DE102010042866A1 (en) 2009-10-30 2011-05-05 Basf Se New thioamide compounds, useful for controlling undesirable plant growth or weeds in cultural plants e.g. Arachis hypogaea, Allium cepa, Elaeis guineensis and Gossypium herbaceum
DE102010042864A1 (en) 2009-10-30 2011-06-01 Basf Se Substituted thioamides with herbicidal activity
WO2011057989A1 (en) 2009-11-11 2011-05-19 Basf Se Heterocyclic compounds having herbicidal action
WO2011057942A1 (en) 2009-11-12 2011-05-19 Basf Se Insecticidal methods using pyridine compounds
WO2011058036A1 (en) 2009-11-13 2011-05-19 Basf Se Tricyclic compounds having herbicidal action
US9121022B2 (en) 2010-03-08 2015-09-01 Monsanto Technology Llc Method for controlling herbicide-resistant plants
US9988634B2 (en) 2010-03-08 2018-06-05 Monsanto Technology Llc Polynucleotide molecules for gene regulation in plants
US11812738B2 (en) 2010-03-08 2023-11-14 Monsanto Technology Llc Polynucleotide molecules for gene regulation in plants
WO2011117211A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridazines having herbicidal action
JP2013522346A (en) * 2010-03-23 2013-06-13 ビーエーエスエフ ソシエタス・ヨーロピア Substituted pyridazines with herbicidal action
CN102858780A (en) * 2010-03-23 2013-01-02 巴斯夫欧洲公司 Substituted pyridazines having herbicidal action
US8921273B2 (en) 2010-03-23 2014-12-30 Basf Se Substituted pyridazines having herbicidal action
WO2011117210A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridines having herbicidal action
WO2011117195A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridines having herbicidal action
WO2011117273A1 (en) 2010-03-23 2011-09-29 Basf Se Substituted pyridazines having herbicidal action
CN102906088A (en) * 2010-03-23 2013-01-30 巴斯夫欧洲公司 Substituted pyridazines having herbicidal action
US8809535B2 (en) 2010-03-23 2014-08-19 Basf Se Substituted pyridines having herbicidal action
DE112011101566T5 (en) 2010-05-04 2013-05-08 Basf Se PLANTS WITH INCREASED HERBICID TOLERANCE
WO2012062531A1 (en) 2010-11-12 2012-05-18 Syngenta Limited Herbicidal compounds
AU2012284088A8 (en) * 2011-07-19 2014-05-01 Infinity Pharmaceuticals Inc. Heterocyclic compounds and uses thereof
US9718815B2 (en) 2011-07-19 2017-08-01 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
AU2012284088B2 (en) * 2011-07-19 2015-10-08 Infinity Pharmaceuticals Inc. Heterocyclic compounds and uses thereof
US8969363B2 (en) 2011-07-19 2015-03-03 Infinity Pharmaceuticals, Inc. Heterocyclic compounds and uses thereof
EP3296402A2 (en) 2011-09-13 2018-03-21 Monsanto Technology LLC Methods and compositions for weed control
WO2013040049A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013039990A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
US10760086B2 (en) 2011-09-13 2020-09-01 Monsanto Technology Llc Methods and compositions for weed control
US9416363B2 (en) 2011-09-13 2016-08-16 Monsanto Technology Llc Methods and compositions for weed control
US9422557B2 (en) 2011-09-13 2016-08-23 Monsanto Technology Llc Methods and compositions for weed control
US9422558B2 (en) 2011-09-13 2016-08-23 Monsanto Technology Llc Methods and compositions for weed control
EP3434779A1 (en) 2011-09-13 2019-01-30 Monsanto Technology LLC Methods and compositions for weed control
WO2013040021A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
EP3434780A1 (en) 2011-09-13 2019-01-30 Monsanto Technology LLC Methods and compositions for weed control
EP3382027A2 (en) 2011-09-13 2018-10-03 Monsanto Technology LLC Methods and compositions for weed control
US10829828B2 (en) 2011-09-13 2020-11-10 Monsanto Technology Llc Methods and compositions for weed control
US10808249B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
US10806146B2 (en) 2011-09-13 2020-10-20 Monsanto Technology Llc Methods and compositions for weed control
WO2013040057A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
WO2013040117A1 (en) 2011-09-13 2013-03-21 Monsanto Technology Llc Methods and compositions for weed control
US10801035B2 (en) 2011-11-02 2020-10-13 Basf Se Plants having increased tolerance to herbicides
US10240162B2 (en) 2012-05-24 2019-03-26 A.B. Seeds Ltd. Compositions and methods for silencing gene expression
US10934555B2 (en) 2012-05-24 2021-03-02 Monsanto Technology Llc Compositions and methods for silencing gene expression
US10240161B2 (en) 2012-05-24 2019-03-26 A.B. Seeds Ltd. Compositions and methods for silencing gene expression
WO2014043435A1 (en) 2012-09-14 2014-03-20 Bayer Cropscience Lp Hppd variants and methods of use
EP3173477A1 (en) 2012-09-14 2017-05-31 Bayer Cropscience LP Hppd variants and methods of use
EP3683307A2 (en) 2012-09-14 2020-07-22 BASF Agricultural Solutions Seed US LLC Hppd variants and methods of use
US10294488B2 (en) 2012-12-18 2019-05-21 Basf Se Herbicide-metabolizing cytochrome P450 monooxygenases
US10041068B2 (en) 2013-01-01 2018-08-07 A. B. Seeds Ltd. Isolated dsRNA molecules and methods of using same for silencing target molecules of interest
US10683505B2 (en) 2013-01-01 2020-06-16 Monsanto Technology Llc Methods of introducing dsRNA to plant seeds for modulating gene expression
US10612019B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
US10609930B2 (en) 2013-03-13 2020-04-07 Monsanto Technology Llc Methods and compositions for weed control
US10568328B2 (en) 2013-03-15 2020-02-25 Monsanto Technology Llc Methods and compositions for weed control
WO2014151255A1 (en) 2013-03-15 2014-09-25 Monsanto Technology Llc Methods and compositions for weed control
US10829778B2 (en) 2013-04-30 2020-11-10 Basf Se Plants having increased tolerance to herbicides
US11230717B2 (en) 2013-04-30 2022-01-25 Basf Se Plants having increased tolerance to herbicides
US9856495B2 (en) 2013-07-19 2018-01-02 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US11377667B2 (en) 2013-07-19 2022-07-05 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US10597676B2 (en) 2013-07-19 2020-03-24 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US9850496B2 (en) 2013-07-19 2017-12-26 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US9777288B2 (en) 2013-07-19 2017-10-03 Monsanto Technology Llc Compositions and methods for controlling leptinotarsa
US10100306B2 (en) 2013-11-04 2018-10-16 Monsanto Technology Llc Compositions and methods for controlling arthropod parasite and pest infestations
US10927374B2 (en) 2013-11-04 2021-02-23 Monsanto Technology Llc Compositions and methods for controlling arthropod parasite and pest infestations
US9540642B2 (en) 2013-11-04 2017-01-10 The United States Of America, As Represented By The Secretary Of Agriculture Compositions and methods for controlling arthropod parasite and pest infestations
US10557138B2 (en) 2013-12-10 2020-02-11 Beeologics, Inc. Compositions and methods for virus control in Varroa mite and bees
US10334848B2 (en) 2014-01-15 2019-07-02 Monsanto Technology Llc Methods and compositions for weed control using EPSPS polynucleotides
WO2015108982A2 (en) 2014-01-15 2015-07-23 Monsanto Technology Llc Methods and compositions for weed control using epsps polynucleotides
WO2015138394A2 (en) 2014-03-11 2015-09-17 Bayer Cropscience Lp Hppd variants and methods of use
US11091770B2 (en) 2014-04-01 2021-08-17 Monsanto Technology Llc Compositions and methods for controlling insect pests
US10988764B2 (en) 2014-06-23 2021-04-27 Monsanto Technology Llc Compositions and methods for regulating gene expression via RNA interference
US11807857B2 (en) 2014-06-25 2023-11-07 Monsanto Technology Llc Methods and compositions for delivering nucleic acids to plant cells and regulating gene expression
US11124792B2 (en) 2014-07-29 2021-09-21 Monsanto Technology Llc Compositions and methods for controlling insect pests
US10378012B2 (en) 2014-07-29 2019-08-13 Monsanto Technology Llc Compositions and methods for controlling insect pests
US10968449B2 (en) 2015-01-22 2021-04-06 Monsanto Technology Llc Compositions and methods for controlling Leptinotarsa
US10883103B2 (en) 2015-06-02 2021-01-05 Monsanto Technology Llc Compositions and methods for delivery of a polynucleotide into a plant
US10655136B2 (en) 2015-06-03 2020-05-19 Monsanto Technology Llc Methods and compositions for introducing nucleic acids into plants
WO2017042259A1 (en) 2015-09-11 2017-03-16 Bayer Cropscience Aktiengesellschaft Hppd variants and methods of use
WO2018165091A1 (en) 2017-03-07 2018-09-13 Bayer Cropscience Lp Hppd variants and methods of use
US11180770B2 (en) 2017-03-07 2021-11-23 BASF Agricultural Solutions Seed US LLC HPPD variants and methods of use
WO2019083808A1 (en) 2017-10-24 2019-05-02 Basf Se Improvement of herbicide tolerance to hppd inhibitors by down-regulation of putative 4-hydroxyphenylpyruvate reductases in soybean
WO2019083810A1 (en) 2017-10-24 2019-05-02 Basf Se Improvement of herbicide tolerance to 4-hydroxyphenylpyruvate dioxygenase (hppd) inhibitors by down-regulation of hppd expression in soybean

Also Published As

Publication number Publication date
WO2009090402A3 (en) 2010-06-24
KR20100105882A (en) 2010-09-30
CA2711920C (en) 2016-03-22
CO6280583A2 (en) 2011-05-20
EP2254416B1 (en) 2016-09-07
ZA201005096B (en) 2011-03-30
US8653078B2 (en) 2014-02-18
CN101945581B (en) 2015-01-07
EP2254416A2 (en) 2010-12-01
JP5596556B2 (en) 2014-09-24
MX2010007679A (en) 2010-08-09
US20130137574A1 (en) 2013-05-30
BRPI0906794A2 (en) 2015-07-14
JP2011511765A (en) 2011-04-14
AU2009204688B2 (en) 2013-09-26
US20110021351A1 (en) 2011-01-27
EA201070858A1 (en) 2011-02-28
CN101945581A (en) 2011-01-12
GB0800856D0 (en) 2008-02-27
US8338598B2 (en) 2012-12-25
AU2009204688A1 (en) 2009-07-23
CA2711920A1 (en) 2009-07-23
EA017629B1 (en) 2013-01-30

Similar Documents

Publication Publication Date Title
US8338598B2 (en) Herbicidal pyrido[2,3-B]pyrazines and their use as herbicides
US8987455B2 (en) Herbicidal compounds
US8217055B2 (en) Pyrido-pyrazine derivatives useful as herbicidal compounds
AU2010247237B2 (en) Herbicidal compounds
US8133847B2 (en) Pyrido[2,3-B]pyrazine derivatives useful as herbicidal compounds
AU2011328418B2 (en) Herbicidal compounds

Legal Events

Date Code Title Description
WWE Wipo information: entry into national phase

Ref document number: 200980105079.1

Country of ref document: CN

121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 09701563

Country of ref document: EP

Kind code of ref document: A2

WWE Wipo information: entry into national phase

Ref document number: 2009204688

Country of ref document: AU

WWE Wipo information: entry into national phase

Ref document number: 2711920

Country of ref document: CA

WWE Wipo information: entry into national phase

Ref document number: MX/A/2010/007679

Country of ref document: MX

WWE Wipo information: entry into national phase

Ref document number: 5106/DELNP/2010

Country of ref document: IN

WWE Wipo information: entry into national phase

Ref document number: 2010542684

Country of ref document: JP

NENP Non-entry into the national phase

Ref country code: DE

ENP Entry into the national phase

Ref document number: 2009204688

Country of ref document: AU

Date of ref document: 20090116

Kind code of ref document: A

ENP Entry into the national phase

Ref document number: 20107018184

Country of ref document: KR

Kind code of ref document: A

REEP Request for entry into the european phase

Ref document number: 2009701563

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: PI 2010003312

Country of ref document: MY

Ref document number: 2009701563

Country of ref document: EP

Ref document number: 201070858

Country of ref document: EA

WWE Wipo information: entry into national phase

Ref document number: 10100435

Country of ref document: CO

WWE Wipo information: entry into national phase

Ref document number: 12863286

Country of ref document: US

ENP Entry into the national phase

Ref document number: PI0906794

Country of ref document: BR

Kind code of ref document: A2

Effective date: 20100716